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  • Temporal Trends in Contemporary Use of Ventricular Assist Devices by Race and Ethnicity
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-08-01
    Khadijah Breathett, Larry A. Allen, Laura Helmkamp, Kathryn Colborn, Stacie L. Daugherty, Irene V. Blair, Jacqueline Jones, Prateeti Khazanie, Sula Mazimba, Marylyn McEwen, Jeff Stone, Elizabeth Calhoun, Nancy K. Sweitzer, Pamela N. Peterson

    Background The proportion of racial/ethnic minorities receiving ventricular assist devices (VADs) has previously been less than expected. It is unclear if trends have changed since the broadening of access to insurance in 2014 and the rapid adoption of VAD technology. Methods and Results Using the Interagency Registry of Mechanically Assisted Circulatory Support, we analyzed time trends by race/ethnicity for 10 795 patients (white, 67.4%; African-American, 24.8%; Hispanic, 6.3%; Asian, 1.5%) who had a VAD implanted between 2012 and 2015. Linear models were fit to the annual census-adjusted rate of VAD implantation for each racial/ethnic group, stratified by sex and age group. From 2012 to 2015, African-Americans had an increase in the census-adjusted annual rate of VAD implantation per 100 000 (0.26 [95% confidence interval, 0.17–0.34]) while other ethnic groups exhibited no significant changes (white: 0.06 [−0.03 to 0.14]; Hispanic: 0.04 [−0.05 to 0.12]; Asian: 0.04 [−0.04 to 0.13]). Stratified by sex, rates increased in both African-American men and women (P<0.05), but the change in rate was highest among African-American men (men 0.37 [0.28–0.46]; women 0.16 [0.07–0.25]; interaction with sex P=0.004). Stratified by age group, rates increased in African-Americans aged 40 to 69 years and Asians aged 50 to 59 years (P<0.05). The observed differential change in VAD implantation rate by age group was significant among African-Americans (interaction with age, P<0.01) and Asians (interaction with age, P=0.02). Conclusions From 2012 to 2015, VAD implantation rates increased among African-Americans but not other racial/ethnic groups. The greatest increase in rate was observed among middle-aged African-American men, suggesting a decline in racial disparities. Further investigation is warranted to reduce disparities among women and older racial/ethnic minorities.

    更新日期:2018-07-19
  • Left Ventricular Mass Change After Anthracycline Chemotherapy
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Jennifer H. Jordan, Sharon M. Castellino, Giselle C. Meléndez, Heidi D. Klepin, Leslie R. Ellis, Zanetta Lamar, Sujethra Vasu, Dalane W. Kitzman, William O. Ntim, Peter H. Brubaker, Nathaniel Reichek, Ralph B. D’Agostino, W. Gregory Hundley

    Background: Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment. Methods and Results: We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non–Anth-bC (n=15), and in 24 cancer-free controls using paired t and χ2 tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF (P<0.0001) and LV mass (P=0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups (P=0.11–0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines (r=−0.27; P<0.01) but not with LVEF declines (r=0.11; P=0.45). Moreover, this finding was independent of LVEF changes and body weight. Conclusions: Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.

    更新日期:2018-07-18
  • Anthracycline Cardiomyopathy
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Amanda J. Favreau-Lessard, Douglas B. Sawyer, Sanjeev A. Francis

    See Article by Jordan et al Anthracycline-based chemotherapy regimens remain in wide use for treatment of many malignancies, despite the rapid growth and development of targeted pathway inhibitors and immunotherapies (both of which can be associated with a variety of cardiovascular toxicities). Discovered in the late 1960s and commonly used as a chemotherapeutic in the early 1970s, anthracycline cardiotoxicity was quickly recognized as a serious complication1,2 and served as the canonical example of chemotherapy-associated cardiomyopathy, spurring the development of the field of cardio-oncology. The observation that left ventricular (LV) mass and growth potential are reduced after exposure to anthracycline chemotherapy was first observed in survivors of childhood cancer and the term Grinch Syndrome was coined by Lipshultz et al3 to describe the potential evolution of reduced LV mass after anthracycline therapy to a restrictive cardiomyopathy in some patients. In adults, a reduction in LV mass has been observed several years after anthracycline-based chemotherapy and is associated with increased cardiac events.4 In this issue of Circulation: Heart Failure , Jordan et al5 provide further details to our understanding of how anthracycline chemotherapy alters cardiac structure and function, using serial cardiac magnetic resonance imaging in a cohort of …

    更新日期:2018-07-18
  • Data-Driven Approach to Identify Subgroups of Heart Failure With Reduced Ejection Fraction Patients With Different Prognoses and Aldosterone Antagonist Response Patterns
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    João Pedro Ferreira, Kevin Duarte, John J.V. McMurray, Bertram Pitt, Dirk J. van Veldhuisen, John Vincent, Tariq Ahmad, Jasper Tromp, Patrick Rossignol, Faiez Zannad

    Background: Patients with heart failure with reduced ejection fraction have a poor prognosis. The identification of subgroups with different outcomes and treatment response patterns may help to tailor strategies to each individual patient. We present an exploratory study of patients enrolled in the EMPHASIS-HF trial (Eplerenone in Patients With Systolic Heart Failure and Mild Symptoms) using latent class analysis with validation using the EPHESUS trial (Eplerenone, a Selective Aldosterone Blocker, in Patients With Left Ventricular Dysfunction After Myocardial Infarction) to identify subgroups of patients with different prognosis and response to eplerenone therapy. Methods and Results: Latent class analysis identifies mutually exclusive groups of individuals maximizing within-group similarities and between-group differences. In the EMPHASIS-HF trial, 2279 heart failure with reduced ejection fraction patients were randomized to eplerenone or placebo and were characterized according to 18 clinical features. Subgroup definitions were applied to 6472 patients enrolled in the EPHESUS trial to validate observations. Event-free survival and effect of eplerenone on the composite of cardiovascular death and heart failure hospitalization were determined for each subgroup. Four subgroups were identified with significant differences in event-free survival (P=0.002). The subgroup C had the worst event-free survival in both studies and was characterized by older age, lower body mass index, worse renal function, higher baseline potassium levels, high prevalence of anemia, diabetes mellitus, previous revascularization and higher rates of eplerenone discontinuation, and hyperkalemia during follow-up. Two subgroups (B and C) showed a poorer response to eplerenone in both studies and these groups shared common features such as lower body mass index and high prevalence of anemia. Clinical profiles, prognosis, and treatment response patterns of the 4 subgroups applied in EPHESUS trial presented similarities to those observed in EMPHASIS. Conclusions: Using a data-driven approach, we identified heart failure with reduced ejection fraction subgroups with significantly different prognoses and potentially different responses to eplerenone. However, these data should be regarded as hypothesis-generating and prospective validation is warranted, to assess the potential clinical implications of these subgroups. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00232180.

    更新日期:2018-07-18
  • Embracing the Long Road to Precision Medicine
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Julio A. Chirinos, David E. Lanfear

    See Article by Ferreira et al In classic cardiovascular phase III trials, individuals satisfying a well-defined set of inclusion and exclusion criteria are randomly assigned to receive one of 2 or more treatments in a nonadaptive parallel-arm design. If the trial is positive, for example in favor of treatment A (a new treatment) over treatment B (standard of care), it is concluded that the new treatment benefits such a patient population. A more concrete hypothetical trial may demonstrate that treatment A significantly reduces the composite end point of death or heart failure–related hospitalizations by 20% relative to treatment B. A subjective interpretation that may follow such trial results is that a patient that meets trial criteria will experience a benefit from the treatment (ie, a reduction in adverse outcomes). This interpretation is flawed. In reality, some individuals benefit, some individuals are harmed, and some individuals experience neither benefit nor harm, but the number of individuals who benefit exceeds the number of those who are harmed, such that the net rate of the end point is ≈20% lower in a group of patients receiving treatment A relative to treatment B (for the purposes of our discussion, we will ignore the confidence interval). Explicitly acknowledging this difference in interpretations has increasingly important implications in the era of precision medicine. Implantable cardioverter defibrillator (ICD) trials can further illustrate these concepts. Consider the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial),1 which demonstrated that among patients with heart failure with reduced ejection fraction (HFrEF), New York Heart Association class II or III symptoms, and a left ventricular ejection fraction ≤35%, ICD therapy decreased the risk of death by 23%. Patients who meet indications for ICDs based on well-designed phase III trials may experience infection, bleeding, or mechanical complications as a direct consequence of …

    更新日期:2018-07-18
  • HeartLogic Multisensor Algorithm Identifies Patients During Periods of Significantly Increased Risk of Heart Failure Events
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Roy S. Gardner, Jagmeet P. Singh, Branislav Stancak, Devi G. Nair, Michael Cao, Christopher Schulze, Pramodsingh H. Thakur, Qi An, Scott Wehrenberg, Eric F. Hammill, Yi Zhang, John P. Boehmer

    Background: Care of heart failure (HF) patients results in a high burden on healthcare resources, and estimating prognosis is becoming increasingly important to triage resources wisely. Natriuretic peptides are recommended prognosticators in chronic HF. Our objective was to evaluate whether a multisensor HF index and alert algorithm (HeartLogic) replaces or augments current HF risk stratification. Methods and Results: MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) enrolled 900 patients with cardiac resynchronization therapy defibrillators enabled for collection of heart sounds, respiration, thoracic impedance, heart rate, and activity data. The HeartLogic algorithm automatically calculated a daily HF index and identified periods IN or OUT of an active alert state relative to a configurable threshold. Patients experienced 192 independently adjudicated HF events (average rate, 0.20/patient-year [pt-yr]) during 1 year of follow-up. HF event rates while IN alert was 10-fold higher than OUT of alert (0.80 versus 0.08 events/pt-yr). Combined with NT-proBNP (N-terminal pro-B-type natriuretic peptide) at enrollment (relative to 1000 pg/mL threshold, event rate was 0.42 [HIGH] versus 0.07 [LOW] events/pt-yr), substratification found the lowest risk group (LOW NT-proBNP and OUT of alert) experienced 0.02 events/pt-yr, whereas the highest risk group (HIGH NT-proBNP and IN alert) was associated with a 50-fold increased risk of an HF event (1.00 events/pt-yr) relative to the lowest risk group. Conclusions: Dynamic assessment using implantable device sensors within HeartLogic by itself or in conjunction with NT-proBNP measurements can identify time-intervals when patients are at significantly increased risk of worsening HF and potentially better triage resources to this vulnerable patient population. Clinical Trial Registration: https://www.clinicaltrials.gov. Unique identifier: NCT01128166.

    更新日期:2018-07-18
  • The Luck of Having a Cardiac Implantable Electronic Device
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Maria Rosa Costanzo

    See Article by Gardner et al > Shallow men believe in luck or in circumstance. > > Strong men believe in cause and effect. > > —Ralph Waldo Emerson The principle aims of the post hoc analysis by Gardner et al1 were to use data from the MultiSENSE study (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) to further stratify the 1-year risk of heart failure events (HFE) based on different thresholds of the HeartLogic alert algorithm, compare their prognostic power to that of different NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, and assess whether the combination of algorithm and biomarker values stratified the risk of an HFE better than each measure alone.2 To develop the HeartLogic alert algorithm, data collected from multiple device sensors were used in combination with clinical baseline and HFE data. Initial analyses evaluated the performance of each sensor parameter to predict an HFE. Heart sounds (S1 and S3), thoracic impedance, respiration, heart rate, and activity emerged as variables detectable by device sensors that are predictive of an HFE. Changes in these features from each patient’s baseline were aggregated and weighted based on an individual’s daily risk for worsening HF. The HeartLogic index value is updated daily, and an alert is issued when the index crosses the nominal threshold of 16. In the MultiSENSE study, this alert index predicted the occurrence of HFE with a 70% sensitivity and a median of 34-day warning.2 The findings of the analysis by Gardner et al1 are undoubtedly impressive. Among 900 patients (average event rate: 0.20/patient-year), 145 HFE occurred over 1 year in 88 patients with evaluable HeartLogic alert algorithm. The risk of a HFE during periods in alert status was 10-fold that occurring during periods out of alert status (0.80 versus 0.08/patient-year).2 Substratification showed that, compared with the lowest risk …

    更新日期:2018-07-18
  • Baseline Characteristics of Patients With Heart Failure and Preserved Ejection Fraction in the PARAGON-HF Trial
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Scott D. Solomon, Adel R. Rizkala, Martin P. Lefkowitz, Victor C. Shi, JianJian Gong, Nagesh Anavekar, Stefan D. Anker, Juan L. Arango, Jose L. Arenas, Dan Atar, Turia Ben-Gal, Sergey A. Boytsov, Chen-Huan Chen, Vijay K. Chopra, John Cleland, Josep Comin-Colet, Hans-Dirk Duengen, Luis E. Echeverría Correa, Gerasimos Filippatos, Andreas J. Flammer, Michel Galinier, Armando Godoy, Eva Goncalvesova, Stefan Janssens, Tzvetana Katova, Lars Køber, Małgorzata Lelonek, Gerard Linssen, Lars H. Lund, Eileen O’Meara, Béla Merkely, Davor Milicic, Byung-Hee Oh, Sergio V. Perrone, Naresh Ranjith, Yoshihiko Saito, Jose F. Saraiva, Sanjiv Shah, Petar M. Seferovic, Michele Senni, Antonio S. Sibulo, David Sim, Nancy K. Sweitzer, Jyrki Taurio, Dragos Vinereanu, Bojan Vrtovec, Jiří Widimský, Mehmet B. Yilmaz, Jingmin Zhou, Robert Zweiker, Inder S. Anand, Junbo Ge, Carolyn S.P. Lam, Aldo P. Maggioni, Felipe Martinez, Milton Packer, Marc A. Pfeffer, Burkert Pieske, Margaret M. Redfield, Jean L. Rouleau, Dirk J. Van Veldhuisen, Faiez Zannad, Michael R. Zile, John J.V. McMurray

    Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality. Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464–1610), and structural heart disease. Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711.

    更新日期:2018-07-18
  • Dermal Interstitial Alterations in Patients With Heart Failure and Reduced Ejection Fraction
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Petra Nijst, Mikhail Olinevich, Petra Hilkens, Pieter Martens, Matthias Dupont, W.H. Wilson Tang, Ivo Lambrichts, Jean-Paul Noben, Wilfried Mullens

    Background: Large networks of interstitial glycosaminoglycans help to regulate water and electrolyte homeostasis. The relation between dermal interstitial alterations and occurrence of edema in heart failure patients with reduced ejection fraction (HFrEF) is unknown. We hypothesize that in HFrEF patients (1) interstitial glycosaminoglycan density is increased, (2) changes in the interstitial glycosaminoglycan network are associated with interstitial fluid accumulation, and (3) there is a link between the interstitial glycosaminoglycan network and the renin-angiotensin-aldosterone system. Methods and Results: Two punch biopsies of the skin were obtained in healthy subjects (n=18) and HFrEF patients (n=29). Alcian blue staining and immunostaining for the angiotensin II type 1 receptor was performed. After obtaining tissue water content, total interstitial glycosaminoglycan (uronic acid) and sulfated glycosaminoglycan were quantified. A venous blood sample, clinical examination, and echocardiography were obtained. A significantly higher interstitial glycosaminoglycan content was observed in HFrEF patients compared with healthy subjects (uronic acid: 13.0±4.2 versus 9.6±1.6 μg/mg; P=0.002; sulfated glycosaminoglycan: 14.1 [11.7; 18.1] versus 10.0 [9.1; 10.8] μg/mg; P<0.001). Uronic acid and sulfated glycosaminoglycan density were strongly associated with tissue water content and peripheral edema (uronic acid: ρ=0.66; P<0.0001 and sulfated glycosaminoglycan: τ=0.58; P<0.0001). Expression of the angiotensin II type 1 receptor was found on dermal cells, although use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker was associated with significantly lower levels of interstitial glycosaminoglycans in HFrEF patients. Conclusions: Interstitial glycosaminoglycan concentration is significantly increased in HFrEF patients compared with healthy subjects and correlated with tissue water content and clinical signs of volume overload. A better appreciation of the interstitial compartment might improve management of volume overload in HF.

    更新日期:2018-07-18
  • Regulation of Fluid Volume From the Outside
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Helge Wiig

    See Article by Nijst et al Few will argue against the central role of salt in fluid volume and blood pressure homeostasis—a role that has passed the test of time through classical studies linking blood pressure and Na+ balance,1 also placing the kidney in the very center of extracellular fluid volume and blood pressure homeostasis.2 This fact notwithstanding, a role for other tissues like the interstitium, mostly in skin, has more recently been suggested in an increasing number of studies.3 Indeed, already Guyton et al4 proposed that strongly negatively charged mucopolysaccharides (now named glycosaminoglycans [GAGs]) could attract and thereby generate a higher density of cations, notably Na+, and that “tissue fluids, pressures, and gel” could influence overall regulation of circulation.5 There are 2 major types of GAGs, hyaluronan having 1 charge and sulfated GAGs having ≤3 charges per disaccharide unit.6 At physiological pH, GAGs have a net negative charge, thus attracting counterions. Although there existed data showing Na+ accumulation in skin, thus challenging the commonly accepted sodium homeostasis principle,7 this challenge was brought to a new level by Titze et al who introduced a new paradigm with regard to salt handling in the body. In studies from humans, rats, and mice, they showed that Na+ can be buffered in the body in kidney-independent reservoirs. This occurs without commensurate water retention, thereby making the Na+ osmotically inactive by association with negatively charged GAGs and thereby invisible to the kidney. In a series of studies, they demonstrated that the skin acts as kidney-independent regulator of the release and storage of Na+, for example,8 making the interstitium and its extracellular matrix and gel phase an additional player in Na+ homeostasis. Without questioning the undisputed role of …

    更新日期:2018-07-18
  • Sarcomeric Auto-Oscillations in Single Myofibrils From the Heart of Patients With Dilated Cardiomyopathy
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Tatsuya Kagemoto, Kotaro Oyama, Mitsunori Yamane, Seiichi Tsukamoto, Fuyu Kobirumaki-Shimozawa, Amy Li, Cristobal Dos Remedios, Norio Fukuda, Shin’ichi Ishiwata

    Background: Left ventricular wall motion is depressed in patients with dilated cardiomyopathy (DCM). However, whether or not the depressed left ventricular wall motion is caused by impairment of sarcomere dynamics remains to be fully clarified. Methods and Results: We analyzed the mechanical properties of single sarcomere dynamics during sarcomeric auto-oscillations (calcium spontaneous oscillatory contractions [Ca-SPOC]) that occurred at partial activation under the isometric condition in myofibrils from donor hearts and from patients with severe DCM (New York Heart Association classification III-IV). Ca-SPOC reproducibly occurred in the presence of 1 μmol/L free Ca2+ in both nonfailing and DCM myofibrils, and sarcomeres exhibited a saw-tooth waveform along single myofibrils composed of quick lengthening and slow shortening. The period of Ca-SPOC was longer in DCM myofibrils than in nonfailing myofibrils, in association with prolonged shortening time. Lengthening time was similar in both groups. Then, we performed Tn (troponin) exchange in myofibrils with a DCM-causing homozygous mutation (K36Q) in cTnI (cardiac TnI). On exchange with the Tn complex from healthy porcine ventricles, period, shortening time, and shortening velocity in cTnI-K36Q myofibrils became similar to those in Tn-reconstituted nonfailing myofibrils. Protein kinase A abbreviated period in both Tn-reconstituted nonfailing and cTnI-K36Q myofibrils, demonstrating acceleration of cross-bridge kinetics. Conclusions: Sarcomere dynamics was found to be depressed under loaded conditions in DCM myofibrils because of impairment of thick-thin filament sliding. Thus, microscopic analysis of Ca-SPOC in human cardiac myofibrils is beneficial to systematically unveil the kinetic properties of single sarcomeres in various types of heart disease.

    更新日期:2018-07-18
  • Unmasking Early Wild-Type Transthyretin Amyloidosis Cardiomyopathy in a Patient With Refractory Atrial Fibrillation and Unremarkable Cardiac Imaging
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Danny Varedi, Tibor Kovacsovics, Erinn Downs Kelly, Jo Abraham, Jared Cowley, Kelsey Barrell, Monica P. Revelo, Josef Stehlik, Stavros Drakos, Nassir Marrouche, Brent Wilson, Eric A. Swanson, James Fang, Jose Nativi-Nicolau

    A 78-year-old man with atrial flutter/fibrillation unresponsive to 3 cardioversions, 1 flutter, and 2 left atrial ablations, myocardial infarction in 2000 treated with a stent to the left anterior descending coronary, hypertension, bilateral carpal tunnel surgery (15 years before), and lumbar spinal stenosis presented with anemia in March 2015. He also complained of dysphagia and was referred for an esophagogastroduodenoscopy. Esophageal biopsies revealed esophagitis. The submucosal vessels in both the duodenal and gastric biopsies showed the presence of a slight thickening by acellular eosinophilic material that raised the possibility of amyloid on routine hematoxylin and eosin–stained slides (Figure [A] and [B]). This finding prompted investigation with Congo red stain, which demonstrated gastric and duodenal amyloid deposition within the submucosal blood vessels. Figure. Patient with wild-type cardiac amyloidosis. A , Duodenal submucosa with abnormal vessels that appear thickened by waxy, eosinophilic amorphous material suggestive of amyloid. B , Gastric biopsy with abnormal vessels within the muscularis mucosae wherein the vessels appear thickened by waxy, eosinophilic amorphous material suggestive of amyloid. C , Transthoracic echocardiogram in the parasternal view demonstrates septal thickness of 1.1 cm and posterior wall thickness of 0.9 cm. D , Cardiac magnetic resonance with septal thickness of 1.4 cm. E , 12-lead ECG shows atrial fibrillation, mild criteria for left ventricular hypertrophy, and nonspecific …

    更新日期:2018-07-18
  • Cardiac Shock Revealing Systemic Lupus Erythematosus
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-07-01
    Kevin Bouiller, Pauline Naudion, Sébastien Humbert, Helder Gil, Nadine Meaux-Ruault, Maxime Cravat, Lucie Revel, Chloé Molimard, Marie-France Seronde, Nadine Magy-Bertrand

    Pericarditis is the most commonly recognized cardiac complication in systemic lupus erythematosus (SLE). However, myocarditis with cardiac shock as the initial manifestation of SLE is uncommon. We describe a case of a 28-year-old man who presented cardiogenic shock revealing SLE. A 28-year-old man, white, with a history of smoking, presented to the emergency department in December 2016 with dyspnea. Blood pressure was 165/75 mm Hg, pulse rate 113 beats per minute, body temperature 36°C, and oxygen saturation 100%. Cardiovascular examination was remarkable for signs of congestion with edemas of lower limbs. Skin examination revealed livedo on both feet (Figure 1). Initial laboratory data on admission showed the following: Troponin I 0.053 μg/L (N<0.034 μg/L), brain natriuretic peptide 3342 pg/mL (N<100 pg/mL), aspartate transaminases 2334 IU/L (N<34 IU/L) and alanine transaminases 1120 IU/L (N<55 IU/L), white blood cell count 3700/mm3, hemoglobin 10.4 g/dL, platelet count 206 000/mm3, serum creatinine 84.9 μmol/L. Urine dipstick was negative for protein and blood. The ECG showed sinus tachycardia, negative T wave in V4 through V6 leads, and incomplete right bundle branch block. The chest radiograph revealed cardiomegaly. Echocardiography demonstrated a dilated cardiomyopathy and a biventricular edema, with a left ventricle ejection fraction evaluated at 15% to 20% without pericardial effusion and no significant valvulopathy. Two days …

    更新日期:2018-07-18
  • Reduced Myocardial Flow Reserve by Positron Emission Tomography Predicts Cardiovascular Events After Cardiac Transplantation
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-06-01
    Matthew C. Konerman, John J. Lazarus, Richard L. Weinberg, Ravi V. Shah, Michael Ghannam, Scott L. Hummel, James R. Corbett, Edward P. Ficaro, Keith D. Aaronson, Monica M. Colvin, Todd M. Koelling, Venkatesh L. Murthy

    Background: We evaluated the diagnostic and prognostic value of quantification of myocardial flow reserve (MFR) with positron emission tomography (PET) in orthotopic heart transplant patients. Methods and Results: We retrospectively identified orthotopic heart transplant patients who underwent rubidium-82 cardiac PET imaging. The primary outcome was the composite of cardiovascular death, acute coronary syndrome, coronary revascularization, and heart failure hospitalization. Cox regression was used to evaluate the association of MFR with the primary outcome. The relationship of MFR and cardiac allograft vasculopathy severity in patients with angiography within 1 year of PET imaging was assessed using Spearman rank correlation and logistic regression. A total of 117 patients (median age, 60 years; 71% men) were identified. Twenty-one of 62 patients (34%) who underwent angiography before PET had cardiac allograft vasculopathy. The median time from orthotopic heart transplant to PET imaging was 6.4 years (median global MFR, 2.31). After a median of 1.4 years, 22 patients (19%) experienced the primary outcome. On an unadjusted basis, global MFR (hazard ratio, 0.22 per unit increase; 95% confidence interval, 0.09–0.50; P<0.001) and stress myocardial blood flow (hazard ratio, 0.48 per unit increase; 95% confidence interval, 0.29–0.79; P=0.004) were associated with the primary outcome. Decreased MFR independently predicted the primary outcome after adjustment for other variables. In 42 patients who underwent angiography within 12 months of PET, MFR and stress myocardial blood flow were associated with moderate–severe cardiac allograft vasculopathy (International Society of Heart and Lung Transplantation grade 2–3). Conclusions: MFR assessed by cardiac rubidium-82 PET imaging is a predictor of cardiovascular events after orthotopic heart transplant and is associated with cardiac allograft vasculopathy severity.

    更新日期:2018-06-20
  • Predicting the Future of Cardiac Allograft Vasculopathy With Cardiac Positron Emission Tomography
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-06-01
    Eugene C. DePasquale

    See Article by Konerman et al Over the last 5 decades, significant advances in the care of heart transplant recipients have improved long-term survival. However, cardiac allograft vasculopathy (CAV) remains a significant problem with incidence varying from 30% at 5 years to 50% at 10 years. CAV is one of the leading causes of death after heart transplantation and accounts for ≈12% of deaths starting at 1 to 3 years posttransplant.1 CAV affects both epicardial and microvascular coronary vasculature. The microvascular dysfunction associated with CAV can result in early endothelial vasoreactive abnormalities which can reduce myocardial flow reserve (MFR). The pathogenesis of CAV is multifactorial and is influenced by both alloimmune dependent and independent factors.2 Because of denervation of the transplanted heart and absence of typical anginal symptoms, surveillance coronary angiography is recommended for CAV surveillance. Periodic screening is important for prognosis and management (ie, adjustment of cardiovascular and immunosuppressive therapies).3 Coronary angiography may not identify early small vessel or advanced diffuse CAV.4 Intravascular ultrasonography (IVUS) is more sensitive than angiography for CAV detection and has prognostic value with >0.5 mm intimal thickening in the first year posttransplant associated with increased risk of death and angiographic CAV development.5 Although considered the gold standard, IVUS has limitations. It is only able to image larger epicardial vessels and is better at identifying focal eccentric narrowing of the vessel lumen rather than the more diffuse pattern typically found in CAV. Invasive methods, in general, have significant limitations associated with procedural- and contrast-related complications as well as reduced …

    更新日期:2018-06-20
  • Expression and Implication of Clusterin in Left Ventricular Remodeling After Myocardial Infarction
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-06-01
    Annie Turkieh, Marie Fertin, Marion Bouvet, Paul Mulder, Hervé Drobecq, Gilles Lemesle, Nicolas Lamblin, Pascal de Groote, Sina Porouchani, Maggy Chwastyniak, Olivia Beseme, Philippe Amouyel, Frédéric Mouquet, Jean-Luc Balligand, Vincent Richard, Christophe Bauters, Florence Pinet

    Background: Left ventricular remodeling (LVR) after myocardial infarction is associated with an increased risk of heart failure and death. In spite of a modern therapeutic approach, LVR remains relatively frequent and difficult to predict in clinical practice. Our aim was to identify new biomarkers of LVR and understand their involvement in its development. Methods and Results: Proteomic analysis of plasma from the REVE-2 study (Remodelage Ventriculaire)—a study dedicated to the analysis of LVR which included 246 patients after a first anterior myocardial infarction—identified increased plasma levels of CLU (clusterin) in patients with high LVR. We used a rat model of myocardial infarction to analyze CLU expression in the LV and found a significant increase that was correlated with LVR parameters. We found increased CLU expression and secretion in primary cultures of rat neonate cardiomyocytes hypertrophied by isoproterenol. Silencing of CLU in hypertrophied neonate cardiomyocytes induced a significant decrease in cell size, ANP (atrial natriuretic peptide), and BNP (B-type natriuretic peptide) expression, associated with a decreased ERK (extracellular signal-regulated kinase) 1/2 activity, suggesting a prohypertrophic role of CLU. We then confirmed a significant increase of both intracellular p-CLU (precursor form of CLU) and m-CLU (mature form of CLU) in failing human hearts. Finally, the circulating levels of CLU (secreted form) were increased in patients with chronic heart failure who died from cardiovascular cause during a 3-year follow-up (n=99) compared with survivors (n=99). Conclusions: Our results show for the first time that plasma CLU levels are associated with LVR post–myocardial infarction, have in part a cardiac origin, and are a predictor of early death in heart failure patients.

    更新日期:2018-06-20
  • Intake of Different Dietary Proteins and Risk of Heart Failure in Men
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-06-01
    Heli E.K. Virtanen, Sari Voutilainen, Timo T. Koskinen, Jaakko Mursu, Tomi-Pekka Tuomainen, Jyrki K. Virtanen

    Background: Animal and plant protein intakes have indicated opposite associations with cardiovascular mortality risk. Whether dietary proteins are associated with risk of heart failure (HF) is unclear. Thus, we examined the associations of proteins from different food sources with risk of HF. Methods and Results: The study included 2441 men aged 42 to 60 years at the baseline examinations in 1984 to 1989 in the Kuopio Ischaemic Heart Disease Risk Factor Study. Protein intakes at baseline were assessed with 4-day dietary records. Data on incident HF cases were obtained from national registers. HF risk according to protein intake was estimated by Cox proportional hazard ratios. During the mean follow-up of 22.2 years, 334 incident HF cases occurred. Higher intake of total protein indicated a trend toward increased risk of HF (multivariable-adjusted hazard ratio in the highest versus lowest quartile=1.33; 95% confidence interval: 0.95–1.85; P-trend=0.05). The associations between specific types and sources of protein with incident HF were consistent with this overall finding although not all associations reached statistical significance. For example, the hazard ratio in the highest versus lowest quartile was 1.43 (95% confidence interval: 1.00–2.03; P-trend=0.07) for total animal protein and 1.17 (95% confidence interval: 0.72–1.91; P-trend=0.35) for total plant protein. Conclusions: In middle-aged men, higher protein intake was marginally associated with increased risk of HF. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03221127

    更新日期:2018-06-20
  • Trends in Noncardiovascular Comorbidities Among Patients Hospitalized for Heart Failure
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-06-01
    Abhinav Sharma, Xin Zhao, Bradley G. Hammill, Adrian F. Hernandez, Gregg C. Fonarow, G. Michael Felker, Clyde W. Yancy, Paul A. Heidenreich, Justin A. Ezekowitz, Adam D. DeVore

    Background: The increase in medical complexity among patients hospitalized with heart failure (HF) may be reflected by an increase in concomitant noncardiovascular comorbidities. Among patients hospitalized with HF, the temporal trends in the prevalence of noncardiovascular comorbidities have not been well described. Methods and Results: We used data from 207 984 patients in the Get With The Guidelines–Heart Failure registry (from 2005 to 2014) to evaluate the prevalence and trends of noncardiovascular comorbidities (chronic obstructive pulmonary disorder/asthma, anemia, diabetes mellitus, obesity [body mass index ≥30 kg/m2], and renal impairment) among patients hospitalized with HF. Medicare beneficiaries aged ≥65 years were used to assess 30-day mortality. The prevalence of 0, 1, 2, and ≥3 noncardiovascular comorbidities was 18%, 30%, 27%, 25%, respectively. From 2005 to 2014, there was a decline in patients with 0 noncardiovascular comorbidities (22%–16%; P<0.0001) and an increase in patients with ≥3 noncardiovascular comorbidities (18%–29%; P<0.0001). Among Medicare beneficiaries, there was an increased 30-day adjusted mortality risk among patients with 1 noncardiovascular comorbidity (hazard ratio, 1.16; 95% confidence interval, 1.09–1.24; P<0.0001), 2 noncardiovascular comorbidities (hazard ratio, 1.34; 95% confidence interval, 1.25–1.44; P<0.0001), and ≥3 noncardiovascular comorbidities (hazard ratio, 1.63; 95% confidence interval, 1.51–1.75; P<0.0001). Similar trends were seen for in-hospital mortality. Conclusions: Patients admitted in hospital for HF have an increasing number of noncardiovascular comorbidities over time, which are associated with worse outcomes. Strategies addressing the growing burden of noncardiovascular comorbidities may represent an avenue to improve outcomes and should be included in the delivery of in-hospital HF care.

    更新日期:2018-06-20
  • Sex Differences at the Time of Myectomy in Hypertrophic Cardiomyopathy
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-06-01
    Louise L.A.M. Nijenkamp, Ilse A.E. Bollen, Hannah G. van Velzen, Jessica A. Regan, Marjon van Slegtenhorst, Hans W.M. Niessen, Arend F.L. Schinkel, Martina Krüger, Corrado Poggesi, Carolyn Y. Ho, Diederik W.D. Kuster, Michelle Michels, Jolanda van der Velden

    Background: One of the first clinically detectable alterations in heart function in hypertrophic cardiomyopathy (HCM) is a decline in diastolic function. Diastolic dysfunction is caused by changes in intrinsic properties of cardiomyocytes or an increase in fibrosis. We investigated whether clinical and cellular parameters of diastolic function are different between male and female patients with HCM at the time of myectomy. Methods and Results: Cardiac tissue from the interventricular septum of patients with HCM (27 women and 44 men) was obtained during myectomy preceded by echocardiography. At myectomy, female patients were 7 years older than male patients and showed more advanced diastolic dysfunction than men evident from significantly higher values for E/e′ ratio, left ventricular filling pattern, tricuspid regurgitation velocity, and left atrial diameter indexed for body surface. Whereas most male patients (56%) showed mild (grade I) diastolic dysfunction, 50% of female patients showed grade III diastolic dysfunction. Passive tension in HCM cardiomyocytes was comparable with controls, and myofilament calcium sensitivity was higher in HCM compared with controls, but no sex differences were observed in myofilament function. In female patients with HCM, titin was more compliant, and more fibrosis was present compared with men. Differences between female and male patients with HCM remained significant after correction for age. Conclusions: Female patients with HCM are older at the time of myectomy and show greater impairment of diastolic function. Furthermore, left ventricular and left atrial remodeling is increased in women when corrected for body surface area. At a cellular level, HCM women showed increased compliant titin and a larger degree of interstitial fibrosis.

    更新日期:2018-06-20
  • Living Without a Pulse
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-06-01
    Suneet N. Purohit, William K. Cornwell, Jay D. Pal, JoAnn Lindenfeld, Amrut V. Ambardekar

    Pulsatility seems to have a teleological role because evolutionary hierarchy favors higher ordered animals with more complex, multichamber circulatory systems that generate higher pulse pressure compared with lower ordered animals. Yet despite years of such natural selection, the modern generation of continuous-flow left ventricular assist devices (CF-LVADs) that have been increasingly used for the last decade have created a unique physiology characterized by a nonpulsatile, nonlaminar blood flow profile with the absence of the usual large elastic artery Windkessel effect during diastole. Although outcomes and durability have improved with CF-LVADs, patients supported with CF-LVADs have a high rate of complications that were not as frequently observed with older pulsatile devices, including gastrointestinal bleeding from arteriovenous malformations, pump thrombosis, and stroke. Given the apparent fundamental biological role of the pulse, the purpose of this review is to describe the normal physiology of ventricular-arterial coupling from pulsatile flow, the effects of heart failure on this physiology and the vasculature, and to examine the effects of nonpulsatile blood flow on the vascular system and potential role in complications seen with CF-LVAD therapy. Understanding these concomitant vascular changes with CF-LVADs may be a key step in improving patient outcomes as modulation of pulsatility and flow characteristics may serve as a novel, yet simple, therapy for reducing complications.

    更新日期:2018-06-20
  • Eosinophilic Myocarditis With Rapid Progression to Cardiogenic Shock, Managed With Mechanical Support and High-Dose Corticosteroids
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-06-01
    Samvit Tandan, Seth N. Meltzer, Carlos D. Davila, Marvin A. Konstam, Martin M. LeWinter

    A 19-year-old woman with no significant medical history was admitted to the University of Vermont Medical Center with 3 weeks of abdominal pain, vomiting, and diarrhea, as well as 2 to 3 days of chest pain. Her only medication was oral contraceptives, which she had taken for the past 2 years. At presentation, her blood pressure was 97/78 mm Hg and heart rate 107 beats per minute and regular. Physical examination was remarkable for mild generalized pallor, diffuse abdominal tenderness, elevated jugular venous pressure, and a gallop rhythm. Laboratory results revealed a total white blood cell count count of 16.6 K/mm3 (Reference, 4.0-10.4 K/mm3), absolute eosinophil count of 8.52 (Reference, 0.03–0.61 K/mm3), troponin I of 9.99 (Reference, <0.034 ng/mL), and IgE of 241 (Reference, <158 IU/mL). Initial ECG revealed ST-segment elevation in leads I, II, III, aVF, and V4 through V6, ST depression in leads V1 through V3, and mild PR-segment depression (Figure 1A). A chest computed tomographic scan was negative for pulmonary embolism. ECG at presentation (A) and 2 week after recovery with medical therapy (B). Within a few hours of admission, the patient’s condition deteriorated rapidly, with development of worsening hypotension and tachycardia (blood pressure, 86/42 mm Hg; heart rate 134 beats per minute). Echocardiography revealed a trivial pericardial effusion, left ventricular (LV) ejection fraction of 30% to 35% with diffuse hypokinesis and marked thickening of the septum and posterior wall consistent with intramyocardial edema, and reduced LV cavity size (Figure 2A and 2B). Because of worsening hemodynamics, the patient was emergently transferred to the Tufts Medical …

    更新日期:2018-06-20
  • Coronary Artery Remodeling and Fibrosis With Continuous-Flow Left Ventricular Assist Device Support
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Amrut V. Ambardekar, Mary C.M. Weiser-Evans, Marcella Li, Suneet N. Purohit, Muhammad Aftab, T. Brett Reece, Karen S. Moulton

    Background: Coronary artery fluid dynamics may be altered because of the nonphysiological flow seen in continuous-flow left ventricular assist devices (CF-LVADs). Our aim was to study the structure and composition of coronary vessels after CF-LVAD. Methods and Results: Coronary arteries were collected from patients with heart failure (HF) at the time of transplantation, of whom 15 were supported with a CF-LVAD before transplant (HF+LVAD group) and 9 were not (HF non-LVAD group). In addition, coronary samples were obtained from 5 nonfailing age-matched donors (nonfailing group). Histological analysis was performed to quantify coronary morphology, composition, vascular fibrosis, and vasa vasorum density. The age and sex mix of the 3 groups were similar, and the mean duration of LVAD support was 213 days. Compared with patients with HF and nonfailing donors, the arteries from patients with HF+LVAD had expansion of the adventitia, breakdown of the internal elastic lamina, and increased adventitial collagen deposition and density of vasa vasorum. Conclusions: Among patients supported with CF-LVADs, the coronary arteries develop marked remodeling with increased adventitial fibrosis. The physiological consequences of these structural changes are unknown, but it is possible that arterial contractility may be impaired, thus limiting coronary flow reserve and promoting myocardial ischemia. This may contribute to CF-LVAD complications, such as ventricular arrhythmias and right ventricular failure. As more patients receive CF-LVADs and new pump technology attempts to modulate flow profiles and pulsatility, further research is needed to understand the mechanisms and long-term sequela of these changes in coronary arteries and other vascular beds.

    更新日期:2018-05-16
  • Prognostic Significance of Creatinine Increases During an Acute Heart Failure Admission in Patients With and Without Residual Congestion
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Marco Metra, Gad Cotter, Stefanie Senger, Christopher Edwards, John G. Cleland, Piotr Ponikowski, Guillermo C. Cursack, Olga Milo, John R. Teerlink, Michael M. Givertz, Christopher M. O’Connor, Howard C. Dittrich, Daniel M. Bloomfield, Adriaan A. Voors, Beth A. Davison

    Background: The importance of a serum creatinine increase, traditionally considered worsening renal function (WRF), during admission for acute heart failure has been recently debated, with data suggesting an interaction between congestion and creatinine changes. Methods and Results: In post hoc analyses, we analyzed the association of WRF with length of hospital stay, 30-day death or cardiovascular/renal readmission and 90-day mortality in the PROTECT study (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). Daily creatinine changes from baseline were categorized as WRF (an increase of 0.3 mg/dL or more) or not. Daily congestion scores were computed by summing scores for orthopnea, edema, and jugular venous pressure. Of the 2033 total patients randomized, 1537 patients had both available at study day 14. Length of hospital stay was longer and 30-day cardiovascular/renal readmission or death more common in patients with WRF. However, these were driven by significant associations in patients with concomitant congestion at the time of assessment of renal function. The mean difference in length of hospital stay because of WRF was 3.51 (95% confidence interval, 1.29–5.73) more days (P=0.0019), and the hazard ratio for WRF on 30-day death or heart failure hospitalization was 1.49 (95% confidence interval, 1.06–2.09) times higher (P=0.0205), in significantly congested than nonsignificantly congested patients. A similar trend was observed with 90-day mortality although not statistically significant. Conclusions: In patients admitted for acute heart failure, WRF defined as a creatinine increase of ≥0.3 mg/dL was associated with longer length of hospital stay, and worse 30- and 90-day outcomes. However, effects were largely driven by patients who had residual congestion at the time of renal function assessment. Clinical Trial Registration : URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00328692 and NCT00354458.

    更新日期:2018-05-16
  • Independent Prognostic Value of Serum Soluble ST2 Measurements in Patients With Heart Failure and a Reduced Ejection Fraction in the PARADIGM-HF Trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure)
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Eileen O’Meara, Margaret F. Prescott, Brian Claggett, Jean L. Rouleau, Lu-May Chiang, Scott D. Solomon, Milton Packer, John J.V. McMurray, Michael R. Zile

    Background: Soluble ST2 (sST2) is associated with cardiac remodeling and fibrosis. In chronic heart failure, the predictive value of sST2 has not been evaluated in a model that includes both NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-TnT (high-sensitivity cardiac troponin T), in a trial in which treatment had a major impact. Therefore, the effects of treatment on sST2 levels in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the relationships between sST2 and outcomes, and the prognostic utility of various sST2 partition values were examined. Methods and Results: Baseline (n=2002), 1-month (n=1936), and 8-month postrandomization (n=1758) sST2 levels were compared between treatment groups (sacubitril/valsartan versus enalapril). Relationships between baseline sST2 and (1) heart failure hospitalization, (2) cardiovascular death, and (3) combined heart failure hospitalization and cardiovascular death were assessed using restricted cubic spline models. Adjusted Cox proportional hazards models were used to examine the impact of sST2 change from baseline to 1 month on the hazard of experiencing each outcome. Sacubitril/valsartan led to more reductions and fewer increases in sST2 levels versus enalapril. After adjusting for other predictors, including NT-proBNP and hs-TnT, baseline sST2 remained an independent predictor of outcomes. Associations between baseline sST2 and outcomes were linear. sST2 increases at 1 month were associated with worse subsequent outcomes and decreased with better outcomes (P=0.001, 0.012, and 0.009 for the 3 outcomes, respectively). Conclusions: Sacubitril/valsartan resulted in greater reductions and less increases in sST2 levels than enalapril. No specific threshold was associated with risk, as linear relationships between baseline sST2 and outcomes were observed. Changes in sST2 from baseline to 1 month were independently associated with the risk of outcomes. Clinical Trial Registration : URL: https://www.clinicaltrials.gov. Unique identifier: NCT01035255.

    更新日期:2018-05-16
  • Pulmonary Capillary Wedge Pressure Patterns During Exercise Predict Exercise Capacity and Incident Heart Failure
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Aaron S. Eisman, Ravi V. Shah, Bishnu P. Dhakal, Paul P. Pappagianopoulos, Luke Wooster, Cole Bailey, Thomas F. Cunningham, Kathryn M. Hardin,, Aaron L. Baggish, Jennifer E. Ho, Rajeev Malhotra, Gregory D. Lewis

    Background: Single measurements of left ventricular filling pressure at rest lack sensitivity for identifying heart failure with preserved ejection fraction (HFpEF) in patients with dyspnea on exertion. We hypothesized that exercise hemodynamic measurements (ie, changes in pulmonary capillary wedge pressure [PCWP] indexed to cardiac output [CO]) may more sensitively differentiate HFpEF and non-HFpEF disease states, reflect aerobic capacity, and forecast heart failure outcomes in individuals with normal PCWP at rest. Methods and Results: We studied 175 patients referred for cardiopulmonary exercise testing with hemodynamic monitoring: controls (n=33), HFpEF with resting PCWP≥15 mm Hg (n=32), and patients with dyspnea on exertion with normal resting PCWP and left ventricular ejection fraction (DOE-nlrW; n=110). Across 1835 paired PCWP-CO measurements throughout exercise, we used regression techniques to define normative bounds of “PCWP/CO slope” in controls and tested the association of PCWP/CO slope with exercise capacity and composite cardiac outcomes (defined as cardiac death, incident resting PCWP elevation, or heart failure hospitalization) in the DOE-nlrW group. Relative to controls (PCWP/CO slope, 1.2±0.4 mm Hg/L/min), patients with HFpEF had a PCWP/CO slope of 3.4±1.9 mm Hg/L/min. We used a threshold (2 SD above the mean in controls) of 2 mm Hg/L/min to define abnormal. PCWP/CO slope >2 in DOE-nlrW patients was common (n=45/110) and was associated with reduced peak Vo2 (P<0.001) and adverse cardiac outcomes after adjustment for age, sex, and body mass index (hazard ratio, 3.47; P=0.03) at a median 5.3-year follow-up. Conclusions: Elevated PCWP/CO slope during exercise (>2 mm Hg/L/min) is common in DOE-nlrW and predicts exercise capacity and heart failure outcomes. These findings suggest that current definitions of HFpEF based on single measures during rest are insufficient and that assessment of exercise PCWP/CO slope may refine early HFpEF diagnosis.

    更新日期:2018-05-16
  • Risk Factor Burden, Heart Failure, and Survival in Women of Different Ethnic Groups
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Khadijah Breathett, Iris Leng, Randi E. Foraker, William T. Abraham, Laura Coker, Keith E. Whitfield, Sally Shumaker, JoAnn E. Manson, Charles B. Eaton, Barbara V. Howard, Nkechinyere Ijioma, Crystal W. Cené, Lisa W. Martin, Karen C. Johnson, Liviu Klein

    Background: The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups. Methods and Results: In the WHI (Women’s Health Initiative; 1993–2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased (P<0.0001, interaction of race/ethnicity and RF number P=0.18)—African-Americans 1 RF: 1.80 (1.01–3.20), 2 RFs: 3.19 (1.84–5.54), 3+ RFs: 7.31 (4.26–12.56); Whites 1 RF: 1.27 (1.04–1.54), 2 RFs: 1.95 (1.60–2.36), 3+ RFs: 4.07 (3.36–4.93); Hispanics 1 RF: 1.72 (0.68–4.34), 2 RFs: 3.87 (1.60–9.37), 3+ RFs: 8.80 (3.62–21.42). Risk of death before developing HF increased with subsequent RFs (P<0.0001) but differed by racial/ethnic group (interaction P=0.001). The number of RFs was not associated with the risk of death after developing HF in any group (P=0.25; interaction P=0.48). Conclusions: Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups.

    更新日期:2018-05-16
  • Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Keita Saku, Takamori Kakino, Takahiro Arimura, Genya Sunagawa, Takuya Nishikawa, Takafumi Sakamoto, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa

    Background: Acute myocardial infarction remains a leading cause of chronic heart failure. Excessive myocardial oxygen demand relative to supply is the fundamental mechanism of myocardial infarction. We thus hypothesized that left ventricular (LV) mechanical unloading by the total support of transvascular LV assist device Impella could minimize oxygen demand, thereby reducing infarct size and preventing subsequent heart failure. Methods and Results: In 20 dogs, we ligated the left anterior descending coronary artery for 180 minutes and then reperfused. We introduced Impella from 60 minutes after the onset of ischemia to 60 minutes after reperfusion. In the partial support group, Impella supported 50% of total cardiac output. In the total support group, systemic flow totally depends on Impella flow. Four weeks after ischemia/reperfusion (I/R), we compared LV function and infarct size among 4 groups: sham (no I/R), I/R (no Impella support), partial support, and total support. Compared with I/R, total support lowered LV end-diastolic pressure (15.0±3.5 versus 4.7±1.7 mm Hg; P<0.001), increased LV end-systolic elastance (4.3±0.8 versus 13.9±5.1 mm Hg/mL; P<0.001), and decreased NT-proBNP (N-terminal pro-B-type natriuretic peptide) level (4081±1123 versus 1773±390 pg/mL; P<0.05). Furthermore, total support markedly reduced infarct size relative to I/R, whereas partial support decreased infarct size to a lesser extent (I/R, 16.3±2.6; partial support, 8.5±4.3; and total support, 2.1±1.6%; P<0.001). Conclusions: LV mechanical unloading by the total support of Impella during the acute phase of myocardial infarction reduced infarct size and prevented subsequent heart failure in dogs.

    更新日期:2018-05-16
  • Dog Model Holds Promise for Early Mechanical Unloading in Patients With Acute Myocardial Infarction
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Cesar Y. Guerrero-Miranda, Shelley A. Hall

    See Article by Saku et al Myocardial infarction (MI) and ischemic heart disease are leading causes of morbidity and mortality. Globally, 110 million people live with ischemic heart disease,1 and >8 million per year die secondary to ischemic heart disease.2 As for MI, the 2018 Heart and Disease Stroke Statistics update of the American Heart Association reported a prevalence of 7.9 million adults in the United States alone. In 2015, >110 000 patients died because of MI, with 30-day in-hospital mortality of 15%.3 Both of these conditions combine as the most common cause of heart failure (HF), either from chronic ischemia or from resultant injury after MI. Up to 40% of individuals with MI develop left ventricular (LV) dysfunction.4 The infarct size with resultant adverse ventricular remodeling is directly associated with the development of HF after MI.4 Cardiogenic shock, the worst expression of HF, in the setting of acute myocardial dysfunction is preceded by myocardial contractile dysfunction, which leads to inadequate tissue perfusion and, in turn, can result in multiorgan failure. Although the prevalence of cardiogenic shock among patients with MI is relatively low (5%–10%),5 cardiogenic shock has historically had an early mortality rate as high as 80%, whereas recent studies have suggested a decline in mortality to ≈40%,6 which is nevertheless still too high. Traditionally, coronary artery reperfusion using percutaneous intervention has been the cornerstone therapy to reduce myocardial damage and subsequent HF. Moreover, early percutaneous coronary intervention, using the latest generation of drug-eluted stents and novel antithrombotics and pharmacological therapies, has significantly reduced mortality in MI-related cardiogenic …

    更新日期:2018-05-16
  • Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Carla J. Weinheimer, Attila Kovacs, Sarah Evans, Scot J. Matkovich, Philip M. Barger, Douglas L. Mann

    Background: To better understand reverse left ventricular (LV) remodeling, we developed a murine model wherein mice develop LV remodeling after transverse aortic constriction (TAC) and a small apical myocardial infarct (MI) and undergo reverse LV remodeling after removal of the aortic band. Methods and Results: Mice studied were subjected to sham (n=6) surgery or TAC+MI (n=12). Two weeks post-TAC+MI, 1 group underwent debanding (referred to as heart failure debanding [HF-DB] mice; n=6), whereas the aortic band remained in a second group (heart failure [HF] group; n=6). LV remodeling was evaluated by 2D echocardiography at 1 day, 2 weeks and 6 weeks post-TAC+MI. The hearts were analyzed by transcriptional profiling at 4 and 6 weeks and histologically at 6 weeks. Debanding normalized LV volumes, LV mass, and cardiac myocyte hypertrophy at 6 weeks in HF-DB mice, with no difference in myofibrillar collagen in the HF and HF-DB mice. LV ejection fraction and radial strain improved after debanding; however, both remained decreased in the HF-DB mice relative to sham and were not different from HF mice at 6 weeks. Hemodynamic unloading in the HF-DB mice was accompanied by a 35% normalization of the HF genes at 2 weeks and 80% of the HF genes at 4 weeks. Conclusions: Hemodynamic unloading of a pathophysiologically relevant mouse model of HF results in normalization of LV structure, incomplete recovery of LV function, and incomplete reversal of the HF transcriptional program. The HF-DB mouse model may provide novel insights into mechanisms of reverse LV remodeling.

    更新日期:2018-05-16
  • Internal Versus External Compression of a Left Ventricular Assist Device Outflow Graft
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Cory R. Trankle, Mohammed A. Quader, John D. Grizzard, Daniel G. Tang, Keyur B. Shah, Kendall Paris, Christina K. Shepard, Zachary M. Gertz

    Obstruction within the circuit of a left ventricular assist device (LVAD) is a challenging situation for clinicians to definitively diagnose and manage. Available diagnostic tools are limited in their ability to visualize large portions within the device and cannulas, often leading to uncertainty as to whether redo surgery is required or if there are feasible medical or percutaneous alternatives. Here, we report a case of LVAD outflow graft obstruction, which by computed tomographic angiography (CTA) appeared to be intramural thrombus, but by intravascular ultrasound (IVUS) was shown to be compression external to the graft. A 62-year-old female with a continuous flow LVAD (HeartMate II Abbott, IL) 5 years prior presented to the emergency department with frequent low-flow alarms and syncope. The patient’s post-LVAD course had been complicated by outflow graft infection 1 year after initial implantation, necessitating an outflow graft replacement. She had also experienced multiple bleeding events for which her warfarin therapeutic goal was lowered. In the preceding year, her LVAD flows had steadily declined from 4.5 to 5.0 L/min to 2.7 to 2.8 L/min with an increasing frequency of low-flow alarms not responsive to the intravenous fluid administration or changes in LVAD …

    更新日期:2018-05-16
  • Correction to: 2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant): A Report of the ACC Competency Management Committee
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-05-01
    Lippincott Williams & Wilkins

    In the article by Jessup et al, “2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant): A Report of the ACC Competency Management Committee,” which published ahead of print …

    更新日期:2018-05-16
  • When the VEST Does Not Fit
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Larry A. Allen, Eric D. Adler, Antoni Bayés-Genis, Meredith A. Brisco-Bacik, Julio A. Chirinos, Brian Claggett, Jennifer L. Cook, James C. Fang, Finn Gustafsson, Carolyn Y. Ho, Navin K. Kapur, Scott E. Klewer, Robb D. Kociol, David E. Lanfear, Orly Vardeny, Nancy K. Sweitzer

    Sudden cardiac death (SCD) prevention in patients with newly diagnosed ventricular dysfunction or heart failure with reduced ejection fraction is an important clinical issue. A lack of strong evidence has led to uncertainty in medical decision making and variable clinical practice in the use of wearable cardioverter-defibrillators (WCDs). In this context, the results of VEST (Vest Prevention of Early Sudden Death Trial)1 at the American College of Cardiology Scientific Sessions on March 10, 2018, in Orlando, FL were highly anticipated. However, interpretations of the trial results have been presented that we find difficult to reconcile. We wish to call attention to what we think is the most rigorous interpretation of VEST: the primary results were negative. The WCD is designed for patients at risk of SCD who are not immediate candidates for implantable cardioverter-defibrillator (ICD) therapy. This is most commonly because of a new diagnosis of left ventricular dysfunction, often after acute myocardial infarction (MI).2 Although ICDs improve survival over years of treatment in appropriately selected patients, reductions in the first 40 days postinfarction have not been conclusively demonstrated.3,4 Despite this lack of evidence, the Food and Drug Administration approved the WCD for use in 2002, primarily because of the ability of this noninvasive technology to deliver appropriate shocks in laboratory settings and case series.5 Although the WCD may seem benign—prompting a philosophy among some of why not, or better safe than sorry—there are reasons its efficacy and value should be …

    更新日期:2018-04-18
  • Ventricular Assist Device Utilization in Heart Transplant Candidates
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Lauren K. Truby, A. Reshad Garan, Raymond C. Givens, Koji Takeda, Hiroo Takayama, Pauline N. Trinh, Melana Yuzefpolskaya, Maryjane A. Farr, Yoshifumi Naka, Paolo C. Colombo, Veli K. Topkara

    Background: Continuous-flow left ventricular assist devices (CF-LVADs) have become a standard treatment choice in advanced heart failure patients. We hypothesized that practice patterns with regards to CF-LVAD utilization vary significantly among transplant centers and impact waitlist outcomes. Methods and Results: The United Network for Organ Sharing registry was queried to identify adult patients who were waitlisted for heart transplantation (HT) between 2008 and 2015. Each patient was assigned a propensity score based on likelihood of receiving a durable CF-LVAD before or while waitlisted. The primary outcomes of interest were death or delisting for worsening status and HT at 1 year. A total of 22 863 patients from 92 centers were identified. Among these, 9013 (39.4%) were mechanically supported. CF-LVAD utilization varied significantly between and within United Network for Organ Sharing regions. Freedom from waitlist death or delisting was significantly lower in propensity-score–matched patients who were mechanically supported versus medically managed (83.5% versus 79.2%; P<0.001). However, cumulative incidence of HT was also lower in mechanically supported patients (53.3% versus 63.6%; P<0.001). Congruous mechanical and medical bridging strategies based on clinical risk profile were associated with lower risk of death or delisting (hazard ratio, 0.88; P=0.027) and higher likelihood of HT (hazard ratio, 1.14; P<0.001). Conclusions: CF-LVAD utilization may lower waitlist mortality at the expense of lower likelihood of HT. Decision to use CF-LVAD and timing of transition should be individualized based on patient-, center-, and region-level risk factors to achieve optimal outcomes.

    更新日期:2018-04-18
  • TTR (Transthyretin) Stabilizers Are Associated With Improved Survival in Patients With TTR Cardiac Amyloidosis
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Hannah Rosenblum, Adam Castano, Julissa Alvarez, Jeff Goldsmith, Stephen Helmke, Mathew S. Maurer

    Background: TTR (transthyretin) cardiac amyloidosis is caused by dissociation of TTR into monomers, which misassemble into amyloid fibrils. TTR stabilizers act at the dimer–dimer interface to prevent dissociation. We investigated differences in survival among patients with TTR cardiac amyloidosis on stabilizer medications compared with those not on stabilizers. Methods AND RESULTS: A retrospective study of patients with TTR cardiac amyloidosis presenting to a single center was conducted. Baseline characteristics were compared between those treated with stabilizers and those not treated with stabilizers. Cox proportional hazards modeling assessed for univariate predictors of the composite outcome of death or orthotopic heart transplant (OHT). Multivariable Cox proportional hazards assessed whether stabilizer treatment was independently associated with improved death or OHT after controlling for significant univariate predictors. One hundred twenty patients (mean age, 75±8, 88% male) were included: 29 patients who received stabilizers and 91 patients who did not. Stabilizer use was associated with a lower risk of the combined end point of death or OHT (hazard ratio, 0.32; 95% confidence interval, 0.18–0.58; P<0.0001). Subjects treated with stabilizers were more likely to be of White race (93% versus 55%; P<0.001), classified as New York Heart Association classes I and II (79% versus 38%; P=0.002), less likely to have a mutation (10% versus 36%; P=0.010), have lower troponin I (median 0.06 versus 0.12 ng/mL; P=0.002), and higher left ventricular ejection fraction (49% versus 40%; P=0.011), suggesting earlier stage of disease. In multivariable Cox analysis, the association between stabilizer and death or OHT persisted when adjusted for all noncollinear univariate predictors with P<0.05 (hazard ratio, 0.37; 95% confidence interval, 0.19–0.75; P=0.003). Conclusions: TTR stabilizers are associated with decreased death and OHT in TTR cardiac amyloidosis. These results need to be confirmed by ongoing randomized clinical trials.

    更新日期:2018-04-18
  • Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Orly Vardeny, Brian Claggett, Jessica Kachadourian, Scott M. Pearson, Akshay S. Desai, Milton Packer, Jean Rouleau, Michael R. Zile, Karl Swedberg, Martin Lefkowitz, Victor Shi, John J.V. McMurray, Scott D. Solomon

    Background: In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients. Methods and Results: We characterized patients in PARADIGM-HF by whether they reported hypotension during study run-in periods (enalapril, followed by sacubitril/valsartan) and after randomization and assessed whether hypotension modified the efficacy of sacubitril/valsartan. Of the 10 513 patients entering the enalapril run-in, 136 (1.3%) experienced hypotension and 93 (68%) were unable to continue to the next phase; of 9419 patients entering the sacubitril/valsartan run-in period, 228 (2.4%) patients experienced hypotension and 51% were unable to successfully complete the run-in. After randomization, 388 (9.2%) participants had 501 hypotensive events with enalapril, and 588 (14.0%) participants had 803 hypotensive events with sacubitril/valsartan (P<0.001). There was no difference between randomized treatment groups in the number of participants who discontinued therapy because of hypotension. Individuals with a hypotensive event in either group were older, had lower blood pressure at randomization, and were more likely to have an implantable cardioverter defibrillator. Participants with hypotensive events during run-in who were ultimately randomized derived similar efficacy from sacubitril/valsartan compared with enalapril as those without hypotensive events (P interaction>0.90). Conclusions: Hypotension was more common with sacubitril/valsartan relative to enalapril in PARADIGM-HF but did not differentially affect permanent discontinuations. Patients with hypotension during run-in derived similar benefit from sacubitril/valsartan compared with enalapril as those who did not experience hypotension.

    更新日期:2018-04-18
  • Left Ventricular Assist Device Inflow Cannula Angle and Thrombosis Risk
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Venkat Keshav Chivukula, Jennifer A. Beckman, Anthony R. Prisco, Todd Dardas, Shin Lin, Jason W. Smith, Nahush A. Mokadam, Alberto Aliseda, Claudius Mahr

    Background: As heart failure prevalence continues to increase in the setting of a static donor supply, left ventricular assist device (LVAD) therapy for end-stage heart failure continues to grow. Anecdotal evidence suggests that malalignment of the LVAD inflow cannula may increase thrombosis risk, but this effect has not been explored mechanistically or quantified statistically. Our objective is to elucidate the impact of surgical angulation of the inflow cannula on thrombogenicity. Methods and Results: Unsteady computational fluid dynamics is used in conjunction with computational modeling and virtual surgery to model flow through the left ventricle for 5 different inflow cannula angulations. We use a holistic approach to evaluate thrombogenicity: platelet-based (Lagrangian) metrics to evaluate the platelet mechanical environment, combined with flow-based (Eulerian) metrics to investigate intraventricular hemodynamics. The thrombogenic potential of each LVAD inflow cannula angulation is quantitatively evaluated based on platelet shear stress history and residence time. Intraventricular hemodynamics are strongly influenced by LVAD inflow cannula angulation. Platelet behavior indicates elevated thrombogenic potential for certain inflow cannula angles, potentially leading to platelet activation. Our analysis demonstrates that the optimal range of inflow angulation is within 0±7° of the left ventricular apical axis. Conclusions: Angulation of the inflow cannula >7° from the apical axis (axis connecting mitral valve and ventricular apex) leads to markedly unfavorable hemodynamics as determined by computational fluid dynamics. Computational hemodynamic simulations incorporating Lagrangian and Eulerian metrics are a powerful tool for studying optimization of LVAD implantation strategies, with the long-term potential of improving outcomes.

    更新日期:2018-04-18
  • Pulmonary Effective Arterial Elastance as a Measure of Right Ventricular Afterload and Its Prognostic Value in Pulmonary Hypertension Due to Left Heart Disease
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Emmanouil Tampakakis, Sanjiv J. Shah, Barry A. Borlaug, Peter J. Leary, Harnish H. Patel, Wayne L. Miller, Benjamin W. Kelemen, Brian A. Houston, Todd M. Kolb, Rachel Damico, Stephen C. Mathai, Edward K. Kasper, Paul M. Hassoun, David A. Kass, Ryan J. Tedford

    Background: Patients with combined post- and precapillary pulmonary hypertension due to left heart disease have a worse prognosis compared with isolated postcapillary. However, it remains unclear whether increased mortality in combined post- and precapillary pulmonary hypertension is simply a result of higher total right ventricular load. Pulmonary effective arterial elastance (Ea) is a measure of total right ventricular afterload, reflecting both resistive and pulsatile components. We aimed to test whether pulmonary Ea discriminates survivors from nonsurvivors in patients with pulmonary hypertension due to left heart disease and if it does so better than other hemodynamic parameters associated with combined post- and precapillary pulmonary hypertension. Methods and Results: We combined 3 large heart failure patient cohorts (n=1036) from academic hospitals, including patients with pulmonary hypertension due to heart failure with preserved ejection fraction (n=232), reduced ejection fraction (n=335), and a mixed population (n=469). In unadjusted and 2 adjusted models, pulmonary Ea more robustly predicted mortality than pulmonary vascular resistance and the transpulmonary gradient. Along with pulmonary arterial compliance, pulmonary Ea remained predictive of survival in patients with normal pulmonary vascular resistance. The diastolic pulmonary gradient did not predict mortality. In addition, in a subset of patients with echocardiographic data, Ea and pulmonary arterial compliance were better discriminators of right ventricular dysfunction than the other parameters. Conclusions: Pulmonary Ea and pulmonary arterial compliance more consistently predicted mortality than pulmonary vascular resistance or transpulmonary gradient across a spectrum of left heart disease with pulmonary hypertension, including patients with heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, and pulmonary hypertension with a normal pulmonary vascular resistance.

    更新日期:2018-04-18
  • Association of Biomarker Clusters With Cardiac Phenotypes and Mortality in Patients With HIV Infection
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Rebecca Scherzer, Sanjiv J. Shah, Eric Secemsky, Javed Butler, Carl Grunfeld, Michael G. Shlipak, Priscilla Y. Hsue

    Background: Although individual cardiac biomarkers are associated with heart failure risk and all-cause mortality in HIV-infected individuals, their combined use for prediction has not been well studied. Methods and Results: Unsupervised k-means cluster analysis was performed blinded to the study outcomes in 332 HIV-infected participants on 8 biomarkers: ST2, NT-proBNP (N-terminal pro-B-type natriuretic peptide), hsCRP (high-sensitivity C-reactive protein), GDF-15 (growth differentiation factor 15), cystatin C, IL-6 (interleukin-6), D-dimer, and troponin. We evaluated cross-sectional associations of each cluster with diastolic dysfunction, pulmonary hypertension (defined as echocardiographic pulmonary artery systolic pressure ≥35 mm Hg), and longitudinal associations with all-cause mortality. The biomarker-derived clusters partitioned subjects into 3 groups. Cluster 3 (n=103) had higher levels of CRP, IL-6, and D-dimer (inflammatory phenotype). Cluster 2 (n=86) displayed elevated levels of ST2, NT-proBNP, and GDF-15 (cardiac phenotype). Cluster 1 (n=143) had lower levels of both phenotype-associated biomarkers. After multivariable adjustment for traditional and HIV-related risk factors, cluster 3 was associated with a 51% increased risk of diastolic dysfunction (95% confidence interval, 1.12–2.02), and cluster 2 was associated with a 67% increased risk of pulmonary hypertension (95% confidence interval, 1.04–2.68), relative to cluster 1. Over a median 6.9-year follow-up, 48 deaths occurred. Cluster 3 was independently associated with a 3.3-fold higher risk of mortality relative to cluster 1 (95% confidence interval, 1.3–8.1), and cluster 2 had a 3.1-fold increased risk (95% confidence interval, 1.1–8.4), even after controlling for diastolic dysfunction, pulmonary hypertension, left ventricular mass, and ejection fraction. Conclusions: Serum biomarkers can be used to classify HIV-infected individuals into separate clusters for differentiating cardiopulmonary structural and functional abnormalities and can predict mortality independent of these structural and functional measures.

    更新日期:2018-04-18
  • Early Ambulation Among Hospitalized Heart Failure Patients Is Associated With Reduced Length of Stay and 30-Day Readmissions
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Lisa M. Fleming, Xin Zhao, Adam D. DeVore, Paul A. Heidenreich, Clyde W. Yancy, Gregg C. Fonarow, Adrian F. Hernandez, Robb D. Kociol

    Background: Early ambulation (EA) is associated with improved outcomes for mechanically ventilated and stroke patients. Whether the same association exists for patients hospitalized with acute heart failure is unknown. We sought to determine whether EA among patients hospitalized with heart failure is associated with length of stay, discharge disposition, 30-day post discharge readmissions, and mortality. Methods and Results: The study population included 369 hospitals and 285 653 patients with heart failure enrolled in the Get With The Guidelines-Heart Failure registry. We used multivariate logistic regression with generalized estimating equations at the hospital level to identify predictors of EA and determine the association between EA and outcomes. Sixty-five percent of patients ambulated by day 2 of the hospital admission. Patient-level predictors of EA included younger age, male sex, and hospitalization outside of the Northeast (P<0.01 for all). Hospital size and academic status were not predictive. Hospital-level analysis revealed that those hospitals with EA rates in the top 25% were less likely to have a long length of stay (defined as >4 days) compared with those in the bottom 25% (odds ratio, 0.83; confidence interval, 0.73–0.94; P=0.004). Among a subgroup of fee-for-service Medicare beneficiaries, we found that hospitals in the highest quartile of rates of EA demonstrated a statistically significant 24% lower 30-day readmission rates (P<0.0001). Both end points demonstrated a dose–response association and statistically significant P for trend test. Conclusions: Multivariable-adjusted hospital-level analysis suggests an association between EA and both shorter length of stay and lower 30-day readmissions. Further prospective studies are needed to validate these findings.

    更新日期:2018-04-18
  • Causes and Predictors of 30-Day Readmission in Patients With Acute Myocardial Infarction and Cardiogenic Shock
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Mahek Shah, Shantanu Patil, Brijesh Patel, Manyoo Agarwal, Carlos D. Davila, Lohit Garg, Sahil Agrawal, Navin K. Kapur, Ulrich P. Jorde

    Background: Acute myocardial infarction (AMI) occurs as a result of irreversible damage to cardiac myocytes secondary to lack of blood supply. Cardiogenic shock complicating AMI has significant associated morbidity and mortality, and data on postdischarge outcomes are limited. Methods and Results: We derived the study cohort of patients with AMI and cardiogenic shock from the 2013 to 2014 Healthcare Cost and Utilization Project National Readmission Database. Incidence, predictors, and causes of 30-day readmissions were analyzed. From 43 212 index admissions for AMI with cardiogenic shock, 26 016 (60.2%) survived to discharge and 5277 (20.2% of survivors) patients were readmitted within 30 days. More than 50% of these readmissions occurred within first 10 days. Cardiac causes accounted for 42% of 30-day readmissions (heart failure 20.6%; acute coronary syndrome 11.6%). Among noncardiac causes, respiratory (11.4%), infectious (9.4%), medical or surgical care complications (6.3%), gastrointestinal/hepatobiliary (6.5%), and renal causes (4.8%) were most common. Length of stay ≥8 days (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.70–2.44; P<0.01), acute deep venous thrombosis (OR, 1.26; 95% CI, 1.08–1.48; P<0.01), liver disease (OR, 1.25; 95% CI, 1.03–1.50; P=0.02), systemic thromboembolism (OR, 1.21; 95% CI, 1.02–1.44; P=0.02), peripheral vascular disease (OR, 1.16; 95% CI, 1.07–1.27; P<0.01), diabetes mellitus (OR, 1.16; 95% CI, 1.08–1.24; P<0.01), long-term ventricular assist device implantation (OR, 1.77; 95% CI, 1.23–2.55; P<0.01), intraaortic balloon pump use (OR, 1.10; 95% CI, 1.02–1.18; P<0.01), performance of coronary artery bypass grafting (OR, 0.85; 95% CI, 0.77–0.93; P<0.01), private insurance (OR, 0.72; 95% CI, 0.64–0.80; P<0.01), and discharge to home (OR, 0.85; 95% CI, 0.73–0.98; P=0.03) were among the independent predictors of 30-day readmission. Conclusions: In-hospital mortality and 30-day readmission in cardiogenic shock complicating AMI are significantly elevated. Patients are readmitted mainly for noncardiac causes. Identification of high-risk factors may guide interventions to improve outcomes within this population.

    更新日期:2018-04-18
  • Incidence, Risk Factors, and Clinical Characteristics of Peripartum Cardiomyopathy in South Korea
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Sunki Lee, Geum Joon Cho, Geun U. Park, Log Young Kim, Tae-Seon Lee, Do Young Kim, Suk-Won Choi, Jong-Chan Youn, Seong Woo Han, Kyu-Hyung Ryu, Jin Oh Na, Cheol Ung Choi, Hong Seog Seo, Eung Ju Kim

    Background: Peripartum cardiomyopathy (PPCM) is a rare disorder associated with pregnancy that can lead to life-threatening conditions. The incidence and clinical characteristics of this condition remain poorly understood. Methods and Results: We aimed to perform the first population-based study of PPCM in South Korea, using the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Patients who fulfilled predefined diagnostic criteria for PPCM from January 1, 2010, to December 31, 2012, were identified from International Classification of Diseases, Tenth Revision, Clinical Modification codes. To discriminate PPCM from other causes of heart failure, we excluded subjects who already had heart failure-related International Classification of Diseases, Tenth Revision, Clinical Modification codes at least 1 year before delivery. During the study period, there were 1 404 551 deliveries in South Korea, and we excluded 20 159 patients who already had heart failure. In those, a total of 795 cases were identified as PPCM. Patients with PPCM were older, had a higher prevalence of preeclampsia and gestational diabetes mellitus, and were more likely to be primiparous and have multiple pregnancies. Moreover, cesarean section and pregnancy-related complications and in-hospital death were also more common in patients with PPCM. Intriguingly, a considerable number of heart failure cases (n=64; 8.1% of total PPCM) were noted between 5 and 12 months after delivery. Conclusions: The incidence of PPCM was 1 in 1741 deliveries in South Korea. Patients with PPCM were older, were more associated with primiparity and multiple pregnancy, had more pregnancy-related complications, and revealed higher in-hospital mortality than controls. The number of cases diagnosed as PPCM were decreased over time after delivery; however, a large number of patients were still noted through 12 months after delivery.

    更新日期:2018-04-18
  • Devil in Disguise
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Johann Bauersachs, Tobias Koenig

    See Article by S. Lee et al Pregnancy-associated heart diseases substantially contribute to maternal morbidity and mortality. Among these, peripartum cardiomyopathy (PPCM), an idiopathic cardiomyopathy that causes heart failure with reduced left ventricular ejection fraction, represents one of the major life-threatening diseases in previously healthy women. The clinical course ranges from milder forms with slightly depressed left ventricular ejection fraction to severe forms with cardiogenic shock.1,2 Although greater awareness and understanding of PPCM have developed over recent years, major gaps remain about epidemiology, risk factors, pathophysiology, and targeted therapy. As such, the exact diagnosis of PPCM remains a fundamental challenge in both clinical practice and scientific analysis. In this issue of Circulation: Heart Failure, Lee et al3 present important data on the incidence and risk factors of PPCM in South Korea. The authors retrospectively analyzed a nationwide database that covers a total of 97% of the Korean population, hence expanding the knowledge of PPCM in Asian countries. The estimated incidence of PPCM in South Korea is 1:1741 (795 cases in 1 384 449 pregnancies; Figure). This compares well to the incidences reported in the United States and Germany but is markedly higher than those previously described in an analysis from Japan.4–6 The incidence of PPCM differs widely depending on the ethnic/racial and regional background of women. Interestingly, Africans and African Americans are at a higher risk for developing PPCM, with an estimated incidence of 1:100 in Nigeria and 1:299 in Haiti,1,3,7–9 whereas incidences in Caucasian populations range from 1:1000 in Germany to 1:10149 in Denmark.1,5,6,10 In a Japanese cohort, the incidence was as low as 1:20 00011; however, these results should be interpreted with caution because of methodological aspects, and …

    更新日期:2018-04-18
  • Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Yu Nakagama, Ryo Inuzuka, Kayoko Ichimura, Munetoshi Hinata, Hiroki Takehara, Norihiko Takeda, Satsuki Kakiuchi, Kazuhiro Shiraga, Hiroko Asakai, Takahiro Shindo, Yoichiro Hirata, Makiko Saitoh, Akira Oka

    LEOPARD syndrome (LS) is a form of RASopathy caused by mutations in the PTPN11 gene an upstream regulator of RAS/MAPK signaling. Although hypertrophic cardiomyopathy (HCM) is a shared cardiac phenotype among RASopathies, HCM complicating patients with LS is characteristic for its unique early-onset and progressive features. We herein report a neonate with LS who presented with an extremely severe form of HCM. Autopsy revealed remarkable evidence of active cardiomyocyte proliferation contributing to the overt cardiomegaly. The case suggests an intriguing association between the observed dramatic increase in cardiomyocyte mitotic activity and the fatal clinical course of LS-associated HCM. The patient was the second daughter born to nonconsanguineous parents with no significant family history. Marked biventricular hypertrophy was noted on fetal echocardiography at the 28th week of gestation. After an uneventful delivery, the patient was immediately admitted to the neonatal intensive care unit. Physical examination at birth revealed multiple dysmorphic features, including a wide forehead, low set ears, hypertelorism, and wide set nipples. No skin lesions, such as café-au-lait spots or lentigines, were noticed, whereas mild hearing loss was detected by newborn screening. The findings were suggestive of LS. Imaging studies were remarkable for cardiomegaly (Figure …

    更新日期:2018-04-18
  • Advanced Dilated Cardiomyopathy in a Patient With Hutterite Limb-Girdle Muscular Dystrophy
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-04-01
    Bailey Miskew Nichols, Anish Nikhanj, Faqi Wang, Darren H. Freed, Gavin Y. Oudit

    A 39-year-old male was diagnosed with Hutterite hereditary limb-girdle muscular dystrophy subtype 2I (LGMD2I), complicated by a secondary cardiomyopathy, ventricular arrhythmias, and heart failure. He had mild muscle weakness and independent mobility. Medical therapy included diuretic, amiodarone, angiotensin-converting enzyme inhibitor, β-blocker, and mineralocorticoid receptor antagonist and had an implanted cardiac device inserted for secondary prophylaxis. Twelve-lead ECG showed premature ventricular complexes, first-degree atrioventricular block, and a nonspecific intraventricular conduction delay (Figure [A]). Transthoracic echocardiogram showed a severely dilated left ventricle (LV), with an LV end-diastolic internal diameter of 8.6 cm, eccentric left ventricular hypertrophy with markedly reduced ejection fraction (26%), and severe mitral regurgitation. Heart catheterization showed a wedge pressure of 30 mm Hg, mean pulmonary arterial pressure of 51 mm Hg, and a transpulmonary gradient of 21 mm Hg indicative of left-sided heart failure and pulmonary hypertension. Coronary angiogram revealed normal origin, course, and lumen of the coronary arteries. Given his advanced heart failure, he was admitted and given intravenous inotropic support. He required an LV assist device (LVAD) as a bridge-to-transplant which was successfully inserted using a minimally invasive technique (Figure [A]). The patient was discharged in stable condition on appropriate …

    更新日期:2018-04-18
  • Apophenia and the Crafting of a Circulation: Heart Failure Issue
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Nancy K. Sweitzer

    > Apophenia: the spontaneous perception of connections and meaningfulness in unrelated phenomena It is our nature as human beings to look for connections—and often to discern them where none actually exist, something known as illusory correlation. This is wired into our brains, for a number of reasons. The ability to discern a true pattern quickly can be a time saver—and one would expect evolutionarily that it may have been a life saver as well. Apophenia exists in many species. Skinner1 demonstrated the existence of illusory correlation or superstition in pigeons. In a series of experiments, pigeons apparently associated a food reward with unusual behavior (for a pigeon), such as bowing, scraping, dancing, or neck turns. The bird would then begin repeating that motion, and every subsequent food reward would further reinforce the behavior. Apophenia is a tool humans use to exert control over a chaotic world. Research has shown that doing relaxation exercises can lower the chances of succumbing to such illusory pattern perception.2 Apophenia is an important force to acknowledge in scientific research and publishing. Many of the papers we receive report associations between two phenomena, such as a biomarker and heart failure events. It is in our nature as humans to infer causality in these associations, and as journal editors, we often require authors to propose a potentially causal mechanism when describing such associations. It is important to recognize that while this is natural and important as it imparts scientific rigor to the work we publish, we are likely often fooling …

    更新日期:2018-03-22
  • Mechanical Circulatory Support Device Utilization and Heart Transplant Waitlist Outcomes in Patients With Restrictive and Hypertrophic Cardiomyopathy
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Lakshmi Sridharan, Brian Wayda, Lauren K. Truby, Farhana Latif, Susan Restaino, Koji Takeda, Hiroo Takayama, Yoshifumi Naka, Paolo C. Colombo, Mathew Maurer, Maryjane A. Farr, Veli K. Topkara

    Background: Patients with restrictive cardiomyopathy (RCM) and hypertrophic cardiomyopathy (HCM) generally are considered poor candidates for mechanical circulatory support devices (MCSDs) and often not able to be bridged mechanically to heart transplantation. This study characterized MCSD utilization and transplant waitlist outcomes in patients with RCM/HCM under the current allocation system and discusses changes in the era of the new donor allocation system. Methods and Results: Patients waitlisted from 2006 to 2016 in the United Network for Organ Sharing registry were stratified by RCM/HCM versus other diagnoses. MCSD utilization and waitlist duration were analyzed by propensity score models. Waitlist outcomes were assessed by cumulative incidence functions with competing events. Predictors of waitlist mortality or delisting for worsening status in patients with RCM/HCM were identified by proportional hazards model. Of 30 608 patients on the waitlist, 5.1% had RCM/HCM. Patients with RCM/HCM had 31 fewer waitlist days (P<0.01) and were ≈26% less likely to receive MCSD (P<0.01). Cumulative incidence of waitlist mortality was similar between cohorts; however, patients with RCM/HCM had higher incidence of heart transplantation. Predictors of waitlist mortality or delisting for worsening status in patients with RCM/HCM without MCSD support included estimated glomerular filtration rate <60 mL/min per 1.73 m2, pulmonary capillary wedge pressure >20 mm Hg, inotrope use, and subjective frailty. Conclusions: Patients with RCM/HCM are less likely to receive MCSD but have similar waitlist mortality and slightly higher incidence of transplantation compared with other patients. The United Network for Organ Sharing RCM/HCM risk model can help identify patients who are at high risk for clinical deterioration and in need of expedited heart transplantation.

    更新日期:2018-03-22
  • Outcomes in Patients With Hypertrophic Cardiomyopathy Awaiting Heart Transplantation
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Julio Zuñiga Cisneros, Josef Stehlik, Craig H. Selzman, Stavros G. Drakos, Stephen H. McKellar, Omar Wever-Pinzon

    Background: Current organ allocation policy and the rapid growth of mechanical support favor heart transplant (HT) candidates on left ventricular assist devices. HT candidates with hypertrophic cardiomyopathy (HCM) are usually not left ventricular assist device candidates and may have a disadvantage compared with dilated forms of cardiomyopathy. Methods and Results: Adult HT candidates registered in the Scientific Registry of Transplant Recipients database between 1999 and 2016 were included. HCM candidates were compared with ischemic cardiomyopathy (ICM) and non-ICM patients. Two eras were defined on the basis of the approval date of the first continuous-flow left ventricular assist device for bridge-to-transplant in the United States (2008). Patients outcomes were evaluated while on the waitlist and after HT. The proportion of patients with HCM listed for HT increased by 44% in era 2 compared with era 1. Waitlist mortality in patients with ICM (15.5%–8.7%) and non-ICM (14.2%–8.2%) declined across eras, but minimal decline was observed in HCM patients (11.7%–9.6%; P=0.06). In era 2, the 12-month rate of HT in HCM (64.8%) was comparable to that of ICM (60.9%) and non-ICM (62.7%) patients (P=0.06). Post-transplant survival in HCM patients was the most favorable in the most recent era (1 year: 91.6% and 5 years: 82.5%; P<0.05 for all comparisons). Conclusions: The number of patients with HCM in need of HT is increasing. Although post-transplant survival in HCM is excellent, waitlist mortality is substantial and with minimal decline in the most recent era, despite the frequent use of listing status upgrade by exception in this patient cohort. Different strategies to improve the performance of the organ allocation system in patients with HCM are needed.

    更新日期:2018-03-22
  • Thirty-Day Readmissions After Left Ventricular Assist Device Implantation in the United States
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Sahil Agrawal, Lohit Garg, Mahek Shah, Manyoo Agarwal, Brijesh Patel, Amitoj Singh, Aakash Garg, Ulrich P. Jorde, Navin K. Kapur

    Background: Early readmissions contribute significantly to heart failure–related morbidity and negatively affect quality of life. Data on left ventricular assist device (LVAD)–related 30-day readmissions are scarce and limited to small studies. Methods and Results: Patients undergoing LVAD implantation between January 2013 and November 2014 who survived the index hospitalization were identified in the Nationwide Readmissions Database. We analyzed the incidence, predictors, causes, and costs of 30-day readmissions. Of 2510 LVAD recipients, 788 (31%) were readmitted within 30 days. Length of index hospitalization ≥31 days (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.07–1.50) and female sex (HR, 1.19; 95% CI, 1.01–1.42) were associated with a higher risk of 30-day readmission, whereas private insurance (HR, 0.83; 95% CI, 0.70–0.99), pre-LVAD use of short-term mechanical circulatory support (HR, 0.53; 95% CI, 0.29–0.98), and discharge to a short-term hospital facility (HR, 0.41; CI, 0.21–0.78) were associated with a lower risk. Cardiac causes accounted for 23.8% of readmissions: heart failure (13.4%) and arrhythmias (8.1%). Noncardiovascular causes accounted for 76.2% of readmissions: infection (30.2%), bleeding (17.6%), and device-related causes (8.2%). Mean length of stay for readmission was 10.7 days (median, 6 days), and average hospital cost per readmission was $34 948±2457. Conclusions: Early readmissions are frequent after LVAD implantation even in contemporary times. Preimplant identification of high-risk patients, and a protocol-driven follow-up using a multidisciplinary approach will be needed to reduce readmissions and improve outcomes.

    更新日期:2018-03-22
  • Outcomes After Continuous-Flow Left Ventricular Assist Device Implantation as Destination Therapy at Transplant Versus Nontransplant Centers
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    D. Marshall Brinkley, David DeNofrio, Robin Ruthazer, Amanda R. Vest, Navin K. Kapur, Gregory S. Couper, Michael S. Kiernan

    Background: Since Food and Drug Administration’s approval of the HeartMate II left ventricular assist device (LVAD) as destination therapy, the number of hospitals offering LVAD therapy has grown rapidly. A rising number are performed at centers without internal transplant programs. We sought to determine whether outcomes after destination therapy LVAD implantation are similar at transplant and nontransplant centers. Methods and Results: Adult recipients of a primary, continuous-flow LVAD as destination therapy between January 2012 and March 2014 from the Interagency Registry for Mechanically Assisted Circulatory Support were included. Subjects were classified by implanting center as transplant (n=3323) or nontransplant (n=260). Center volume before 2012 was categorized as <15 or ≥15 implants. Outcomes included overall survival, freedom from death or major adverse event, rates of individual adverse events, rehospitalization, and health-related quality of life. Patients treated at nontransplant centers were generally less sick, with higher Interagency Registry for Mechanically Assisted Circulatory Support patient profiles and more normal laboratory and hemodynamic values. One-month (94.2% [95% confidence interval {CI}, 95.0–93.4] versus 94.2% [95% CI, 97.1–91.4]) and 12-month (76.4% [95% CI, 77.9–74.8] versus 71.3% [95% CI, 77.4–65.2]) survival were similar at transplant and nontransplant centers, respectively (hazard ratio, 0.88 [95% CI, 0.70–1.12]). Risk remained similar after adjustment for baseline characteristics (hazard ratio, 0.88 [95% CI, 0.69–1.12]). Freedom from death or major adverse event at 12 months (29.0% [95% CI, 30.6–27.3] versus 29.8% [95% CI, 36.0–23.6]) was similar at transplant and nontransplant centers (adjusted hazard ratio, 1.01 [95% CI, 0.87–1.18]). Individual adverse event rates, rehospitalization, and postimplant health-related quality of life were also similar. Conclusions: In a large, modern cohort of destination therapy LVAD recipients, outcomes after implantation were similar at transplant and nontransplant centers.

    更新日期:2018-03-22
  • Socioeconomic Disparities in Adherence and Outcomes After Heart Transplant
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Brian Wayda, Autumn Clemons, Raymond C. Givens, Koji Takeda, Hiroo Takayama, Farhana Latif, Susan Restaino, Yoshifumi Naka, Maryjane A. Farr, Paolo C. Colombo, Veli K. Topkara

    Background: There is mixed evidence of racial and socioeconomic disparities in heart transplant outcomes. Their underlying cause—and whether individual- or community-level traits are most influential—remains unclear. The current study aimed to characterize socioeconomic disparities in outcomes and identify time trends and mediators of these disparities. Methods and Results: We used United Network for Organ Sharing registry data and included 33 893 adult heart transplant recipients between 1994 and 2014. Socioeconomic status (SES) indicators included insurance, education, and neighborhood SES measured using a composite index. Black race and multiple indicators of low SES were associated with the primary outcome of death or retransplant, independent of baseline clinical characteristics. Blacks had lower HLA and race matching, but further adjustment for these and other graft characteristics only slightly attenuated the association with black race (HR, 1.25 after adjustment). This and the associations with neighborhood SES (HR, 1.19 for lowest versus highest decile), Medicare (HR, 1.17), Medicaid (HR, 1.29), and college education (HR, 0.90) remained significant after full adjustment. When comparing early (1994–2000) and late (2001–2014) cohorts, the disparities associated with the middle (second and third) quartiles significantly decreased over time, but those associated with lowest SES quartile and black race persisted. Low neighborhood SES was also associated with higher risks of noncompliance (HR, 1.76), rejection (HR, 1.28), hospitalization (HR, 1.13), and infection (HR, 1.10). Conclusions: Racial and socioeconomic disparities exist in heart transplant outcomes, but the latter may be narrowing over time. These disparities are not explained by differences in clinical or graft characteristics.

    更新日期:2018-03-22
  • Same Story, Different Disease
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Khadijah Breathett

    See Article by Wayda et al Heart failure disproportionately affects African-Americans and individuals of lower socioeconomic status (SES).1,2 African-Americans have 2× to 3× higher prevalence of heart failure than Caucasians before the age of 75.1 African-Americans have more hospitalizations for heart failure1 and receive fewer advanced therapies for heart failure than expected.3 Similarly, individuals of lower SES have a 30% to 50% higher risk of developing heart failure2 and lower likelihood of receiving heart transplant compared with individuals of higher SES.4 Furthermore, as illustrated in this issue of Circulation: Heart Failure in the article by Wayda et al,5 African-Americans and individuals of lower SES have worse outcomes post heart transplant. Using the United Network for Organ Sharing database, Wayda et al5 studied the impact of race and SES on risk of composite death or retransplant after initial heart transplant. SES was measured by patient insurance, education, and neighborhood-level SES index. Results were adjusted for donor and graft characteristics. They found that African-Americans and individuals of lower SES have higher risk of composite death or retransplant after initial …

    更新日期:2018-03-22
  • Donation After Cardiac Death Heart Transplantation in America Is Clinically Necessary and Ethically Justified
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Taufiek Konrad Rajab, Steve K. Singh

    Many patients die on American transplant waiting lists because there are far fewer hearts donated after brain death than patients who would benefit from transplantation. For this reason, extended criteria donation after brain death hearts, which would otherwise be considered inferior, are routinely transplanted. Examples for extended criteria donation after brain death hearts include older donors, from further distances, with lower cardiac function, and higher risk features, such as hepatitis C. In response to the dire need for donor hearts, a small number of transplant centers in Australia and Europe have pushed the envelope further still by pioneering heart transplantation following donation after cardiac death (DCD).1 Death of DCD donors is declared on the basis of irreversible cardiac arrest rather than irreversible loss of all functions of the entire brain.2 However, because of unique ethical and legal concerns that arise from the surgical techniques for DCD heart procurement, there are no clinically active DCD heart transplantation programs in America. The first human heart transplant, performed by Christiaan Barnard in 1967, was made possible by a DCD donor and a recipient who was located in an operating room adjacent to the donor.3 This seminal medical achievement was marred in ethical controversy, which led to the Harvard criteria for brain death in 1968.4 DCD heart transplantation was subsequently abandoned in favor of donation after brain death heart transplantation because DCD hearts were considered inferior out of concern for ischemic injury to the donor heart. Interest in DCD heart …

    更新日期:2018-03-22
  • Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Anna B. Catino, Rebecca A. Hubbard, Julio A. Chirinos, Ray Townsend, Stephen Keefe, Naomi B. Haas, Igor Puzanov, James C. Fang, Neeraj Agarwal, David Hyman, Amanda M. Smith, Mary Gordon, Theodore Plappert, Virginia Englefield, Vivek Narayan, Steven Ewer, Chantal ElAmm, Daniel Lenihan, Bonnie Ky

    Background: Sunitinib, used widely in metastatic renal cell carcinoma, can result in hypertension, left ventricular dysfunction, and heart failure. However, the relationships between vascular function and cardiac dysfunction with sunitinib are poorly understood. Methods and Results: In a multicenter prospective study of 84 metastatic renal cell carcinoma patients, echocardiography, arterial tonometry, and BNP (B-type natriuretic peptide) measures were performed at baseline and at 3.5, 15, and 33 weeks after sunitinib initiation, correlating with sunitinib cycles 1, 3, and 6. Mean change in vascular function parameters and 95% confidence intervals were calculated. Linear regression models were used to estimate associations between vascular function and left ventricular ejection fraction, longitudinal strain, diastolic function (E/e′), and BNP. After 3.5 weeks of sunitinib, mean systolic blood pressure increased by 9.5 mm Hg (95% confidence interval, 2.0–17.1; P=0.02) and diastolic blood pressure by 7.2 mm Hg (95% confidence interval, 4.3–10.0; P<0.001) across all participants. Sunitinib resulted in increases in large artery stiffness (carotid–femoral pulse wave velocity) and resistive load (total peripheral resistance and arterial elastance; all P<0.05) and changes in pulsatile load (total arterial compliance and wave reflection). There were no statistically significant associations between vascular function and systolic dysfunction (left ventricular ejection fraction and longitudinal strain). However, baseline total peripheral resistance, arterial elastance, and aortic impedance were associated with worsening diastolic function and filling pressures over time. Conclusions: In patients with metastatic renal cell carcinoma, sunitinib resulted in early, significant increases in blood pressure, arterial stiffness, and resistive and pulsatile load within 3.5 weeks of treatment. Baseline vascular function parameters were associated with worsening diastolic but not systolic function.

    更新日期:2018-03-22
  • Long-Term Cognitive Decline After Newly Diagnosed Heart Failure
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Christa A. Hammond, Natalie J. Blades, Sarwat I. Chaudhry, John A. Dodson, W.T. Longstreth, Susan R. Heckbert, Bruce M. Psaty, Alice M. Arnold, Sascha Dublin, Colleen M. Sitlani, Julius M. Gardin, Stephen M. Thielke, Michael G. Nanna, Rebecca F. Gottesman, Anne B. Newman, Evan L. Thacker

    Background: Heart failure (HF) is associated with cognitive impairment. However, we know little about the time course of cognitive change after HF diagnosis, the importance of comorbid atrial fibrillation, or the role of ejection fraction. We sought to determine the associations of incident HF with rates of cognitive decline and whether these differed by atrial fibrillation status or reduced versus preserved ejection fraction. Methods and Results: Participants were 4864 men and women aged ≥65 years without a history of HF and free of clinical stroke in the CHS (Cardiovascular Health Study)—a community-based prospective cohort study in the United States, with cognition assessed annually from 1989/1990 through 1998/1999. We identified 496 participants with incident HF by review of hospital discharge summaries and Medicare claims data, with adjudication according to standard criteria. Global cognitive ability was measured by the Modified Mini-Mental State Examination. In adjusted models, 5-year decline in model-predicted mean Modified Mini-Mental State Examination score was 10.2 points (95% confidence interval, 8.6–11.8) after incident HF diagnosed at 80 years of age, compared with a mean 5-year decline of 5.8 points (95% confidence interval, 5.3–6.2) from 80 to 85 years of age without HF. The association was stronger at older ages than at younger ages, did not vary significantly in the presence versus absence of atrial fibrillation (P=0.084), and did not vary significantly by reduced versus preserved ejection fraction (P=0.734). Conclusions: Decline in global cognitive ability tends to be faster after HF diagnosis than without HF. Clinical and public health implications of this finding warrant further attention.

    更新日期:2018-03-22
  • Racial Differences in Characteristics and Outcomes of Patients With Heart Failure and Preserved Ejection Fraction in the Treatment of Preserved Cardiac Function Heart Failure Trial
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Eldrin F. Lewis, Brian Claggett, Amil M. Shah, Jiankang Liu, Sanjiv J. Shah, Inder Anand, Eileen O’Meara, Nancy K. Sweitzer, Jean L. Rouleau, James C. Fang, Akshay S. Desai, Tamrat M. Retta, Scott D. Solomon, John F. Heitner, Thomas D. Stamos, Robin Boineau, Bertram Pitt, Marc A. Pfeffer

    Background: Black patients have been shown to have different baseline characteristics and outcomes compared with nonblack patients in cohort studies. However, few studies have focused on heart failure (HF) with preserved ejection fraction (HFpEF) patients. We aimed to determine the difference in cardiovascular outcomes in black and nonblack patients with HFpEF and to determine the relative efficacy and safety of spironolactone in black and nonblack patients. Methods and Results: Patients with HFpEF, randomized to spironolactone versus placebo in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) in North and South America, were grouped according to self-described black and nonblack race. Black HFpEF patients (n=302) were younger and were more likely to have diabetes mellitus and hypertension than nonblack patients but had similar HFpEF severity. Black patients had higher risk for the primary outcome (hazard ratio [HR], 1.34; 95% confidence interval, 1.06–1.71; P=0.02) and first HF hospitalization (HR, 1.51; 95% confidence interval, 1.167–1.97; P=0.002)], but no significant difference in cardiovascular mortality risk (HR, 0.78; 95% confidence interval, 0.51–1.20; P=0.326). In black and nonblack patients, randomization to spironolactone conferred similar efficacy in the primary outcome (HR, 0.83 versus 0.79; P for interaction=0.49), HF hospitalization (HR, 0.67 versus 0.82; P for interaction=0.76), and cardiovascular mortality (P for interaction=0.19). The risk of hyperkalemia and worsening renal function with spironolactone and study drug adherence were also similar. Conclusions: Black patients with HFpEF have a higher HF hospitalization risk than nonblack patients, but spironolactone is similarly effective and safe in both groups. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00094302.

    更新日期:2018-03-22
  • Prevention of PKG-1α Oxidation Suppresses Antihypertrophic/Antifibrotic Effects From PDE5 Inhibition but not sGC Stimulation
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Taishi Nakamura, Guangshuo Zhu, Mark J. Ranek, Kristen Kokkonen-Simon, Manling Zhang, Grace E. Kim, Kenichi Tsujita, David A. Kass

    Background: Stimulation of sGC (soluble guanylate cyclase) or inhibition of PDE5 (phosphodiesterase type 5) activates PKG (protein kinase G)-1α to counteract cardiac hypertrophy and failure. PKG1α acts within localized intracellular domains; however, its oxidation at cysteine 42, linking homomonomers, alters this localization, impairing suppression of pathological cardiac stress. Because PDE5 and sGC reside in separate microdomains, we speculated that PKG1α oxidation might also differentially influence the effects from their pharmacological modulation. Methods and Results: Knock-in mice expressing a redox-dead PKG1α (PKG1αC42S) or littermate controls (PKG1αWT) were subjected to transaortic constriction to induce pressure overload and treated with a PDE5 inhibitor (sildenafil), sGC activator (BAY602770 [BAY]), or vehicle. In PKG1αWT controls, sildenafil and BAY similarly enhanced PKG activity and reduced pathological hypertrophy/fibrosis and cardiac dysfunction after transaortic constriction. However, sildenafil failed to protect the heart in PKG1αC42S, unlike BAY, which activated PKG and thereby facilitated protective effects. This corresponded with minimal PDE5 activation in PKG1αC42S exposed to transaortic constriction versus higher activity in controls and little colocalization of PDE5 with PKG1αC42S (versus colocalization with PKG1αWT) in stressed myocytes. Conclusions: In the stressed heart and myocytes, PKG1α C42-disulfide formation contributes to PDE5 activation. This augments the pathological role of PDE5 and so in turn enhances the therapeutic impact from its inhibition. PKG1α oxidation does not change the benefits from sGC activation. This finding favors the use of sGC activators regardless of PKG1α oxidation and may help guide precision therapy leveraging the cyclic GMP/PKG pathway to treat heart disease.

    更新日期:2018-03-22
  • Exploring New Cardiovascular Pathways
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Marek Michalak, Paul W. Armstrong

    See Article by Nakamura et al Acting is very start and stop. —Estelle Parsons Despite major therapeutic advances in the treatment of heart failure (HF), this syndrome continues to extract an oppressive clinical penalty of morbidity and mortality. Moreover, the increased prevalence of HF also imposes a major health system economic burden. Hence, this rising cascade of unmet health needs has generated intense interest in discovering novel therapeutic solutions. In this context, NO occupies central stage given its fundamental role in activating soluble guanylate cyclase (sGC).1 In turn, sGC generates cyclic GMP (cGMP)—a potent activator of the PKG1α (protein kinase G1α), which plays an essential and pleiotropic role in normal cardiovascular function by inhibiting vasoconstriction, inflammation, hypertrophy, and fibrosis.2 Hence, reduced sGC activity is an important contributor to coronary microvascular impairment, cardiomyocyte stiffness, and interstitial fibrosis.3 It is now recognized that oxidative stress is a key feature of the HF syndrome as reflected by excess production of reactive oxygen species (ROS) which reduce NO bioavailability.4 In cardiovascular disease, the most important sources of ROS are the mitochondrial respiratory chain, various oxidases, uncoupled NO synthase, and MPO (myeloperoxidase) from infiltrating monocytes and neutrophils.5 Clinically, there are several ways to enhance NO availability. These include inhalation of NO and the addition of nitrate therapy, but both have significant limitations.6 Reducing degradation of cGMP offers an additional therapeutic option. A variety of cyclic nucleotide PDEs (phosphodiesterases) break down cGMP into GMP, a process sensitive to inhibitors currently in clinical use, such as milrinone and theophylline. This alternative approach also led to rediscovery of the PDE5 inhibitor sildenafil for applications in cardiovascular medicine. Retarding catabolism of cGMP through PDE5 inhibition with sildenafil appeared a potentially attractive way to mitigate the …

    更新日期:2018-03-22
  • Long-Term Caloric Restriction Improves Cardiac Function, Remodeling, Adrenergic Responsiveness, and Sympathetic Innervation in a Model of Postischemic Heart Failure
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Claudio de Lucia, Giuseppina Gambino, Laura Petraglia, Andrea Elia, Klara Komici, Grazia Daniela Femminella, Maria Loreta D’Amico, Roberto Formisano, Giulia Borghetti, Daniela Liccardo, Maria Nolano, Steven R. Houser, Dario Leosco, Nicola Ferrara, Walter J. Koch, Giuseppe Rengo

    Background: Caloric restriction (CR) has been described to have cardioprotective effects and improve functional outcomes in animal models and humans. Chronic ischemic heart failure (HF) is associated with reduced cardiac sympathetic innervation, dysfunctional β-adrenergic receptor signaling, and decreased cardiac inotropic reserve. We tested the effects of a long-term CR diet, started late after myocardial infarction on cardiac function, sympathetic innervation, and β-adrenergic receptor responsiveness in a rat model of postischemic HF. Methods and Results: Adult male rats were randomly assigned to myocardial infarction or sham operation and 4 weeks later were further randomized to a 1-year CR or normal diet. One year of CR resulted in a significant reduction in body weight, heart weight, and heart weight/tibia length ratio when compared with normal diet in HF groups. At the end of the study period, echocardiography and histology revealed that HF animals under the CR diet had ameliorated left ventricular remodeling compared with HF rats fed with normal diet. Invasive hemodynamic showed a significant improvement of cardiac inotropic reserve in CR HF rats compared with HF-normal diet animals. Importantly, CR dietary regimen was associated with a significant increase of cardiac sympathetic innervation and with normalized cardiac β-adrenergic receptor levels in HF rats when compared with HF rats on the standard diet. Conclusions: We demonstrate, for the first time, that chronic CR, when started after HF established, can ameliorate cardiac dysfunction and improve inotropic reserve. At the molecular level, we find that chronic CR diet significantly improves sympathetic cardiac innervation and β-adrenergic receptor levels in failing myocardium.

    更新日期:2018-03-22
  • Caloric Restriction as a Therapeutic Approach to Heart Failure
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Pratik B. Sandesara, Laurence S. Sperling

    See Article by de Lucia et al Caloric restriction (CR) is a dietary intervention that involves reduction of total calories below ad libitum intake without nutritional insufficiency or malnutrition. A form of CR, intermittent fasting (IF), involves significant energy restriction on alternate days or 2 days a week (5:2 diet) with ad libitum consumption on nonfasting days.1 In the mid-1930s, McCay and colleagues first described the potential benefits of CR when they demonstrated prolongation of the mean and maximal lifespan of rats.2 Since then, CR has been the subject of considerable investigation across a spectrum of species including yeast, worms, flies, fish, rodents, and nonhuman primates to better understand possible biological and molecular benefits on aging and longevity. Perhaps the most well-known studies of CR were initiated in the late 1980s involving rhesus monkeys at the National Institute on Aging and the University of Wisconsin Madison.3 Rhesus monkeys are a useful model as their anatomy, physiology, eating patterns, and aging processes are similar to humans. The University of Wisconsin Madison study reported a positive impact on survival, but the National Institute on Aging study did not find a similar benefit. Significant differences in the 2 study designs likely contributed to the observed mortality differences.3 Other nonhuman studies over the past decade support the potential for CR to delay the onset of age-related chronic diseases, protect against cancer and neurodegenerative diseases, and exert direct cardioprotective effects.4 CR may have a favorable impact on the cardiovascular system, mediated by improvement in cardiovascular risk factors such as obesity, hypertension, and diabetes mellitus. As well, CR may reduce inflammation, myocardial fibrosis, oxidative stress, and development of atherosclerosis, and improve myocardial ischemic tolerance.4 The …

    更新日期:2018-03-22
  • Prevalence of Pathogenic Gene Mutations and Prognosis Do Not Differ in Isolated Left Ventricular Dysfunction Compared With Dilated Cardiomyopathy
    Circ. Heart Fail. (IF 5.684) Pub Date : 2018-03-01
    Mark R. Hazebroek, Ingrid Krapels, Job Verdonschot, Arthur van den Wijngaard, Els Vanhoutte, Marije Hoos, Luc Snijders, Lieke van Montfort, Maryvonne Witjens, Robert Dennert, Harry J.G.M. Crijns, Hans-Peter Brunner-La Rocca, Han G. Brunner, Stephane Heymans

    Background: Genetic evaluation is recommended in patients with unexplained dilated cardiomyopathy (DCM), but its diagnostic yield and prognostic relevance in unexplained isolated left ventricular dysfunction (LVdys) is unknown. Methods and Results: A total of 127 LVdys and 262 DCM patients underwent genetic screening. Long-term outcome consisted of a combined end point of life-threatening arrhythmia, heart transplantation, and death. At baseline, LVdys patients were younger and had less frequently New York Heart Association class ≥3 when compared with DCM (55±13 versus 58±12; P=0.019 and 21% versus 36%; P=0.003, respectively). The prevalence of familial disease and pathogenic mutations was similar in LVdys and DCM (45% versus 40%; P=0.37 and 19% versus 17%; P=0.61, respectively). After a follow-up of 56 (31–82) months, outcome did not differ in LVdys compared with DCM patients (hazard ratio, 0.83; 95% confidence interval, 0.47–1.45; P=0.51). Overall, outcome was less favorable in patients with a genetic mutation or familial disease when compared with those without (hazard ratio, 2.7; 95% confidence interval, 1.07–7.7; P=0.048 and hazard ratio, 2.2; 95% confidence interval, 1.2–4.2; P=0.013, respectively). Thus, the diagnostic yield of genetic testing in LVdys and DCM is similarly high. The presence of a gene mutation or familial predisposition results in an equally worse prognosis. Conclusions: Genetic evaluation is advised in LVdys patients and should not merely be restricted to DCM.

    更新日期:2018-03-22
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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