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  • Immunosuppressive Therapy Improves Both Short- and Long-Term Prognosis in Patients With Virus-Negative Nonfulminant Inflammatory Cardiomyopathy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Jort Merken, Mark Hazebroek, Pieter Van Paassen, Job Verdonschot, Vanessa Van Empel, Christian Knackstedt, Myrurgia Abdul Hamid, Michael Seiler, Julian Kolb, Philipp Hoermann, Christian Ensinger, Hans-Peter Brunner-La Rocca, Gerhard Poelzl, Stephane Heymans

    Background: Inflammatory cardiomyopathy (infl-CMP) is characterized by increased cardiac inflammation in the absence of viruses, ischemia, valvular disease, or other apparent causes. Studies addressing the efficacy of immunosuppressive therapy in patients with infl-CMP are sparse. This study retrospectively investigates whether immunosuppressive agents on top of heart failure therapy according to current guidelines improves cardiac function and long-term outcome in patients with infl-CMP. Methods and Results: Within the Innsbruck and Maastricht Cardiomyopathy Registry, a total of 209 patients fulfilled the criteria for infl-CMP using endomyocardial biopsy (≥14 infiltrating inflammatory cells/mm2). A total of 110 (53%) patients received immunosuppressive therapy and 99 (47%) did not. To correct for potential selection bias, 1:1 propensity score matching was used on all significant baseline parameters, resulting in a total of 90 patients per group. Baseline characteristics did not significantly differ between both patient groups, reflecting optimal propensity score matching. After a median follow-up of 31 (15–47) months, immunosuppressive therapy resulted in an improved long-term outcome (eg, heart transplantation–free survival) as compared with standard heart failure therapy alone (Log-rank P=0.043; hazard ratio, 0.34 [95% CI, 0.17–0.92]) and in a significant larger increase of left ventricular ejection fraction after a mean of 12 months follow-up, as compared with patients receiving standard heart failure treatment only (12.2% versus 7.3%, respectively; P=0.036). Conclusions: To conclude, this study suggests that immunosuppressive therapy in infl-CMP patients results in an improved heart transplantation–free survival as compared with standard heart failure therapy alone, underscoring the urgent need for a large prospective multicenter trial.

    更新日期:2018-02-21
  • Adoption of Sacubitril/Valsartan for the Management of Patients With Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Lindsey R. Sangaralingham, S. Jeson Sangaralingham, Nilay D. Shah, Xiaoxi Yao, Shannon M. Dunlay

    Background: The US Food and Drug Administration approved the use of sacubitril/valsartan in patients with heart failure with reduced ejection fraction in July 2015. We aimed to assess the adoption and prescription drug costs of sacubitril/valsartan in its first 18 months after Food and Drug Administration approval. Methods and Results: Using a large US insurance database, we identified privately insured and Medicare Advantage beneficiaries who filled a first prescription for sacubitril/valsartan between July 1, 2015, and December 31, 2016. We compared them to patients treated with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Outcomes included adoption, prescription drug costs, and 180-day adherence, defined as a proportion of days covered ≥80%. A total of 2244 patients initiated sacubitril/valsartan. Although the number of users increased over time, the proportion of heart failure with reduced ejection fraction patients taking sacubitril/valsartan remained low (<3%). Patients prescribed sacubitril/valsartan were younger, more often male, with less comorbidity than those taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Although a majority of prescription costs were covered by the health plan (mean, $328.37; median, $362.44 per 30-day prescription), out-of-pocket costs were still high (mean, $71.16; median, $40.27). By comparison, median out-of-pocket costs were $2 to $3 for lisinopril, losartan, carvedilol, and spironolactone. Overall, 59.1% of patients were adherent to sacubitril/valsartan. Refill patterns suggested that nearly half of nonadherent patients discontinued sacubitril/valsartan within 180 days of starting. Conclusions: Adoption of sacubitril/valsartan after Food and Drug Administration approval has been slow and may be associated with the high cost.

    更新日期:2018-02-21
  • From Molecules to Markets
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Nalini A. Colaco, Dhruv S. Kazi

    See Article by Sangaralingham et al On July 7, 2015, sacubitril/valsartan became the first angiotensin receptor-neprilysin inhibitor approved by the US Food and Drug Administration for use among patients with symptomatic heart failure with reduced ejection fraction (HFrEF). This expedited approval was based on the results of the PARADIGM-HF trial (Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure) that showed that among patients with New York Heart Association class II–IV heart failure and ejection fraction ≤40%, treatment with sacubitril/valsartan rather than 10 mg twice daily of enalapril produced a 17.7% reduction in the composite end point of cardiovascular mortality and hospitalizations for heart failure. The study demonstrated a remarkable 19.4% reduction in death from cardiovascular causes and 17.9% reduction in heart failure hospitalizations among patients receiving sacubitril/valsartan compared with those receiving enalapril.1 Sacubitril/valsartan is the first new-in-class medication to demonstrate a mortality benefit in patients with HFrEF since the early 2000s.2 In this issue of Circulation: Heart Failure, Sangaralingham et al3 describe the early experience with sacubitril/valsartan among patients enrolled in private or Medicare Advantage insurance plans. Although slow uptake is par for the course for a first-in-class drug, this study reveals a disappointingly low prescription rate of sacubitril/valsartan among patients with HFrEF in the first 18 months after approval, and a high discontinuation rate among patients who initiate the drug. This disconnect between strong clinical data and low real-world uptake warrants further exploration. Sangaralingham et al analyzed the OptumLabs database, a large collection of medical and pharmaceutical claims data, to evaluate prescription practices, drug costs, and medication use in individuals with HFrEF. In their cohort of 102 247 individuals with HFrEF (identified by International Classification of Diseases, Ninth Revision, codes), only 2244 (2.2%) filled a …

    更新日期:2018-02-21
  • Load-Independent Systolic and Diastolic Right Ventricular Function in Heart Failure With Preserved Ejection Fraction as Assessed by Resting and Handgrip Exercise Pressure–Volume Loops
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Karl-Philipp Rommel, Maximilian von Roeder, Christian Oberueck, Konrad Latuscynski, Christian Besler, Stephan Blazek, Thomas Stiermaier, Karl Fengler, Volker Adams, Marcus Sandri, Axel Linke, Gerhard Schuler, Holger Thiele, Philipp Lurz

    Background: Although systolic right ventricular (RV) dysfunction has been shown to be a potent predictor for adverse outcomes in patients with heart failure with preserved ejection fraction (HFpEF), RV functional abnormalities in the course of the syndrome are not well characterized. We, therefore, sought to assess load-independent and load-dependent systolic and diastolic characteristics of RV function in stable outpatients with HFpEF. Methods and Results: We invasively obtained RV and left ventricular pressure–volume loops in 24 HFpEF patients and 9 patients without heart failure symptoms with a conductance catheter during basal conditions and handgrip exercise. Transient preload reduction was used to extrapolate the RV end-systolic elastance and diastolic stiffness constant. HFpEF patients and controls showed similar left ventricular and RV dimensions and ejection fractions with elevated left ventricular filling pressures. In HFpEF patients, invasively determined load-independent RV contractility (P=0.04) and load-independent passive RV stiffness constant β (P<0.01) were elevated. Although RV relaxation and cardiac output were similar at baseline, HFpEF patients demonstrated a blunted increase in cardiac output under exercise (P=0.01) associated with prolonged RV relaxation (P=0.01), decrease in stroke volume (P<0.01), higher RV-filling pressures (P<0.01), and a marked increase in the end-diastolic pressure–volume relationship (P<0.01). Conclusions: In compensated stages of the HFpEF syndrome, systolic RV function is preserved, but diastolic abnormalities with intrinsic RV stiffness and prolonged RV relaxation are already present. Impaired diastolic RV reserve contributes to a blunted increase in cardiac output during exertion. Because impairments in diastolic function seem to be a biventricular phenomenon, RV diastolic dysfunction warrants further consideration when characterizing HFpEF patients. Clinical Trial Registration: https://www.clinicaltrials.gov. Unique identifier: NCT02459626.

    更新日期:2018-02-21
  • Definition of Iron Deficiency Based on the Gold Standard of Bone Marrow Iron Staining in Heart Failure Patients
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Niels Grote Beverborg, IJsbrand T. Klip, Wouter C. Meijers, Adriaan A. Voors, Eline L. Vegter, Haye H. van der Wal, Dorine W. Swinkels, Joost van Pelt, Andre B. Mulder, Sjoerd K. Bulstra, Edo Vellenga, Massimo A. Mariani, Rudolf A. de Boer, Dirk J. van Veldhuisen, Peter van der Meer

    Background The most commonly used definition of iron deficiency (ID; ferritin <100 ng/mL or ferritin 100–300 ng/mL and transferrin saturation [TSAT] <20%) has not been validated in patients with heart failure (HF). We aimed to define and validate the biomarker-based definition of ID in HF, using bone marrow iron staining as the gold standard. Second, we aimed to assess the prognostic value of the optimized definition. Methods and Results Bone marrow aspiration with iron staining was performed in 42 patients with HF and a reduced left ventricular ejection fraction (≤45%) undergoing median sternotomy for coronary artery bypass grafting. Patients were mostly male (76%) with mild-to-moderate HF and a mean age of 68±10 years. Bone marrow ID was found in 17 (40%) of the HF patients. The most commonly used definition of ID had a sensitivity of 82% and a specificity of 72%. A definition solely based on TSAT ≤19.8% or serum iron ≤13 µmol/L had a sensitivity of 94% and specificity of 84% and 88%, respectively (P<0.05 compared with the former definition). Subsequently, we assessed the incidence of all-cause mortality in 387 consecutive outpatient HF patients (left ventricular ejection fraction ≤45%). In these patients, TSAT ≤19.8% and serum iron ≤13 µmol/L, and not ferritin, were independently associated with mortality. Conclusions A TSAT ≤19.8% or a serum iron ≤13 µmol/L shows the best performance in selecting patients with ID and identifies HF patients at the highest risk of death. Our findings validate the currently used TSAT cutoff of <20% for the identification of ID in HF patients, but question the diagnostic value of ferritin.

    更新日期:2018-02-21
  • MicroRNAs Associated With Reverse Left Ventricular Remodeling in Humans Identify Pathways of Heart Failure Progression
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Ravi Shah, Olivia Ziegler, Ashish Yeri, Xiaojun Liu, Venkatesh Murthy, Dustin Rabideau, Chun Yang Xiao, Kristina Hanspers, Arianna Belcher, Michael Tackett, Anthony Rosenzweig, Alexander R. Pico, James L. Januzzi, Saumya Das

    Background: Plasma extracellular RNAs have recently garnered interest as biomarkers in heart failure (HF). Most studies in HF focus on single extracellular RNAs related to phenotypes and outcomes, and few describe their functional roles. We hypothesized that clusters of plasma microRNAs (miRNAs) associated with left ventricular (LV) remodeling in human HF would identify novel subsets of genes involved in HF in animal models. Methods and Results: We prospectively measured circulating miRNAs in 64 patients with systolic HF (mean age, 64.8 years; 91% men; median LV ejection fraction, 26%) with serial echocardiography (10 months apart) during medical therapy. We defined LV reverse remodeling as a 15% reduction in LV end-systolic volume index. Using principal components analysis, we identified a component associated with LV reverse remodeling (odds ratio=3.99; P=0.01) that provided risk discrimination for LV reverse remodeling superior to a clinical model (C statistic, 0.58 for a clinical model versus 0.71 for RNA-based model). Using network bioinformatics, we uncovered genes not previously widely described in HF regulated simultaneously by >2 miRNAs. We observed increased myocardial expression of these miRNAs during HF development in animals, with downregulation of target gene expression, suggesting coordinate miRNA–mRNA regulation. Target mRNAs were involved in autophagy, metabolism, and inflammation. Conclusions: Plasma miRNAs associated with LV reverse remodeling in humans are dysregulated in animal HF and target clusters of genes involved in mechanisms implicated in HF. A translational approach integrating human HF, bioinformatics, and model systems may uncover novel pathways involved in HF. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00351390

    更新日期:2018-02-21
  • Plasma MicroRNA Clusters in Human Left Ventricular Remodeling
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Arun Padmanabhan, Saptarsi M. Haldar

    See Article by Shah et al Impaired cardiac function results in increased neurohormonal activity, a stress response initially mounted to augment cardiac output. However, chronic or excessive activity of the neurohormonal response contributes to progressive myocardial damage and the clinical manifestations of the heart failure (HF) syndrome.1 This myocardial injury leads to a vicious cycle of organ remodeling, wherein the shape, thickness, volume of the ventricular cavity, and the functional state of the cells populating the stressed heart are adversely altered in a manner that further compromises cardiac performance.1,2 Early work in animal models of myocardial infarction demonstrated the pathophysiologic significance of cardiac remodeling and a role for neurohormonal blockade in its prevention and reversal.2 These findings were subsequently extended to humans with myocardial infarction–associated HF and cardiac dilation in the absence of HF, with the severity of remodeling serving as a poor prognostic indicator.3,4 Current guideline-directed medical therapy for HF is associated with regression of ventricular dilation and improvement of ejection fraction in a subset of patients, a process called left ventricular reverse remodeling (LVRR). As LVRR has emerged as a strong predictor of improved outcomes in HF patients,5,6 understanding the molecular determinants of LVRR in humans and developing improved molecular biomarkers that predict LVRR are of great clinical interest. In this issue of Circulation: Heart Failure, Shah et al7 implicate a panel of plasma microRNAs (miRNAs) as predictors of LVRR in a cohort of patients with HF with reduced ejection fraction, findings which may point to novel …

    更新日期:2018-02-21
  • Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Jacquelyn L.S. Hanson, Marios Arvanitis, Clarissa M. Koch, John L. Berk, Frederick L. Ruberg, Tatiana Prokaeva, Lawreen H. Connors

    Background: Wild-type transthyretin amyloidosis (ATTRwt), an underappreciated cause of heart failure in older adults, is challenging to diagnose and monitor in the absence of validated, disease-specific biomarkers. We examined the prognostic use and survival association of serum TTR (transthyretin) concentration in ATTRwt. Methods and Results: Patients with biopsy-proven ATTRwt were retrospectively identified. Serum TTR, cardiac biomarkers, and echocardiographic parameters were assessed at baseline and follow-up evaluations. Statistical analyses included Kaplan–Meier method, Cox proportional hazard survival models, and receiver-operating characteristic curve analysis. Median serum TTR concentration at presentation was 23 mg/dL (n=116). Multivariate predictors of shorter overall survival were decreased TTR, left ventricular ejection fraction and elevated cTn-I (cardiac troponin I); an inclusive model demonstrated superior accuracy in 4-year survival prediction by receiver-operating characteristic curve analysis (area under the curve, 0.77). TTR values lower than the normal limit, <18 mg/dL, were associated with shorter survival (2.8 versus 4.1 years; P=0.03). Further, TTR values at 1- and 2-year follow-ups were significantly lower (P<0.001) in untreated patients (n=23) compared with those treated with TTR stabilizer, diflunisal (n=12), after baseline evaluation. During 2-year follow-up, unchanged TTR corresponded to increased cTn-I (P=0.006) in untreated patients; conversely, the diflunisal-treated group showed increased TTR (P=0.001) and stabilized cTn-I and left ventricular ejection fraction at 1 year. Conclusions: In this series of biopsy-proven ATTRwt, lower baseline serum TTR concentration was associated with shorter survival as an independent predictor of outcome. Longitudinal analysis demonstrated that decreasing TTR corresponded to worsening cardiac function. These data suggest that TTR may be a useful prognostic marker and predictor of outcome in ATTRwt.

    更新日期:2018-02-21
  • Serum Transthyretin
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Jose Nativi-Nicolau

    See Article by Hanson et al The future depends on what you do today. ―Mahatma Gandhi A biomarker is defined by the National Institutes of Health Biomarkers Definitions Working Group as “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”1 Several biomarkers have been studied in recent years; however, few are used in clinical practice. According to the US Preventive Services Task Force, the potential impact of a novel risk factor is based on the following: (1) its predictive ability, (2) its prevalence in the target population, (3) the number of intermediate-risk individuals who are reclassified as high risk when the risk factor is applied, and (4) the net benefit (benefits minus harms) that would accrue to these high-risk individuals if they were managed according to guidelines for high-risk patients.2 Amyloidosis involves the transformation of a precursor protein into an insoluble extracellular fibril that interferes with the function of the organs affected (Figure). The most common precursors include immunoglobulin light chains (AL amyloidosis), wild-type transthyretins (ATTRwt), and genetically mutated transthyretins (ATTRm). The field of amyloidosis continues to develop, and biomarkers have been used to estimate prognosis, guide management, and assess response to treatment. In AL amyloidosis, serum cTn (cardiac troponins) and NT-proBNP (N-terminal pro-brain natriuretic peptide) are the most studied biomarkers. In combination with other hematologic markers, they are used to classify patients into prognostic stages and to determine eligibility for stem cell transplantation, resulting in …

    更新日期:2018-02-21
  • Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure)
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Peter van der Meer, Niels Grote Beverborg, Marc A. Pfeffer, Kurt Olson, Inder S. Anand, B. Daan Westenbrink, John J.V. McMurray, Karl Swedberg, James B. Young, Scott D. Solomon, Dirk J. van Veldhuisen

    Background: A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear. Methods and Results: We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0–12.0 g/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was −0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02–1.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04–1.63) than responders. Conclusions: A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00358215.

    更新日期:2018-02-21
  • Percutaneous Occlusion of Patent Ductus Arteriosus for an Elderly Patient With Refractory Congestive Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Satoshi Shoji, Hideaki Kanazawa, Ryo Yanagisawa, Makoto Tanaka, Ryoma Fukuoka, Keitaro Akita, Mai Kimura, Takahide Arai, Takashi Kawakami, Kentaro Hayashida, Shinsuke Yuasa, Hikaru Tsuruta, Yuji Itabashi, Mitsushige Murata, Takahiko Nishiyama, Takashi Kohno, Yuichiro Maekawa, Keiichi Fukuda

    A 92-year-old woman with a history of patent ductus arteriosus (PDA) was referred to our hospital because of worsening dyspnea, with New York Heart Association classification IV. She had 3 admissions because of congestive heart failure within a year. A 12-lead ECG showed atrial fibrillation, and a chest radiograph showed severe pulmonary congestion and cardiomegaly (Figure [A]). The plasma B-type natriuretic peptide level was 4527.9 pg/mL. The echocardiogram showed a reduced ejection fraction of 39% and moderate to severe aortic valve stenosis (peak velocity=3.9 m/s; mean pressure gradient=29 mm Hg; aortic valve area=0.83 cm2). The reconstructed 3-dimensional computed tomography (CT; Ziostation2; Ziosoft Inc, Tokyo, Japan) revealed a 50-mm thoracic aortic aneurysm and a large PDA (Krichenko type A, 4.7 mm of the pulmonary artery side) with severe calcifications surrounding it (Figure B–D; Movies I and II in the Data Supplement). Because of her refractory heart failure despite treatment with intravenous furosemide and dobutamine, we decided to perform a transcatheter occlusion of PDA 8 days after her admission to the hospital. For the transcatheter occlusion procedure, we …

    更新日期:2018-02-21
  • Intracardiac Echinococcal Cyst Causing Biventricular Cavity Obliteration
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-02-01
    Haider J. Warraich, Jennifer A. Rymer, Jacob N. Schroder, Han W. Kim, Mark E. Leithe, John Kevin Harrison

    A 47-year-old male presented to the emergency room after an episode of exertional syncope. He denied palpitations, incontinence, dyspnea, or any prior syncope. An ECG and serum cardiac enzymes were normal. A computed tomographic angiogram performed to rule out pulmonary embolism revealed an intracardiac mass in the ventricular septum, measuring 5.0×5.0×4.7 cm (Figure [A]). Subsequent transthoracic echocardiography demonstrated cavity obliteration of the right ventricle from the mass. Intracardiac echinococcal cyst. A, Computed tomographic angiogram shows an intracardiac mass within the interventricular septum between the right …

    更新日期:2018-02-21
  • Editorial Board
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Lippincott Williams & Wilkins

    ![Figure][1] [1]: pending:yes

    更新日期:2018-01-17
  • Exercise Hemodynamic and Functional Capacity After Mitral Valve Replacement in Patients With Ischemic Mitral Regurgitation
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Carlo Fino, Attilio Iacovoni, Philippe Pibarot, John R. Pepper, Paolo Ferrero, Maurizio Merlo, Lorenzo Galletti, Massimo Caputo, Paolo Ferrazzi, Constantinos Anagnostopoulos, Diego Cugola, Michele Senni, Diego Bellavia, Julien Magne

    Background In patients with ischemic mitral regurgitation requiring mitral valve replacement (MVR), the choice of the prosthesis type is crucial. The exercise hemodynamic and functional capacity performance in patients with contemporary prostheses have never been investigated. To compare exercise hemodynamic and functional capacity between biological (MVRb) and mechanical (MVRm) prostheses. Methods and Results We analyzed 86 consecutive patients with ischemic mitral regurgitation who underwent MVRb (n=41) or MVRm (n=45) and coronary artery bypass grafting. All patients underwent preoperative resting echocardiography and 6-minute walking test. At follow-up, exercise stress echocardiography was performed, and the 6-minute walking test was repeated. Resting and exercise indexed effective orifice areas of MVRm were larger when compared with MVRb (resting: 1.30±0.2 versus 1.19±0.3 cm2/m2; P=0.03; exercise: 1.57±0.2 versus 1.18±0.3 cm2/m2; P=0.0001). The MVRm had lower exercise systolic pulmonary arterial pressure at follow-up compared with MVRb (41±5 versus 59±7 mm Hg; P=0.0001). Six-minute walking test distance was improved in the MVRm (pre-operative: 242±43, post-operative: 290±50 m; P=0.001), whereas it remained similar in the MVRb (pre-operative: 250±40, post-operative: 220±44 m; P=0.13). In multivariable analysis, type of prosthesis, exercise indexed effective orifice area, and systolic pulmonary arterial pressure were joint predictors of change in 6-minute walking test (ie, difference between baseline and follow-up). Conclusions In patients with ischemic mitral regurgitation, bioprostheses are associated with worse hemodynamic performance and reduced functional capacity, when compared with MVRm. Randomized studies with longer follow-up including quality of life and survival data are required to confirm these results.

    更新日期:2018-01-17
  • Novel Wearable Seismocardiography and Machine Learning Algorithms Can Assess Clinical Status of Heart Failure Patients
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Omer T. Inan, Maziyar Baran Pouyan, Abdul Q. Javaid, Sean Dowling, Mozziyar Etemadi, Alexis Dorier, J. Alex Heller, A. Ozan Bicen, Shuvo Roy, Teresa De Marco, Liviu Klein

    Background Remote monitoring of patients with heart failure (HF) using wearable devices can allow patient-specific adjustments to treatments and thereby potentially reduce hospitalizations. We aimed to assess HF state using wearable measurements of electrical and mechanical aspects of cardiac function in the context of exercise. Methods and Results Patients with compensated (outpatient) and decompensated (hospitalized) HF were fitted with a wearable ECG and seismocardiogram sensing patch. Patients stood at rest for an initial recording, performed a 6-minute walk test, and then stood at rest for 5 minutes of recovery. The protocol was performed at the time of outpatient visit or at 2 time points (admission and discharge) during an HF hospitalization. To assess patient state, we devised a method based on comparing the similarity of the structure of seismocardiogram signals after exercise compared with rest using graph mining (graph similarity score). We found that graph similarity score can assess HF patient state and correlates to clinical improvement in 45 patients (13 decompensated, 32 compensated). A significant difference was found between the groups in the graph similarity score metric (44.4±4.9 [decompensated HF] versus 35.2±10.5 [compensated HF]; P<0.001). In the 6 decompensated patients with longitudinal data, we found a significant change in graph similarity score from admission (decompensated) to discharge (compensated; 44±4.1 [admitted] versus 35±3.9 [discharged]; P<0.05). Conclusions Wearable technologies recording cardiac function and machine learning algorithms can assess compensated and decompensated HF states by analyzing cardiac response to submaximal exercise. These techniques can be tested in the future to track the clinical status of outpatients with HF and their response to pharmacological interventions.

    更新日期:2018-01-17
  • Efficacy of Ranolazine in Patients With Symptomatic Hypertrophic Cardiomyopathy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Iacopo Olivotto, Paolo G. Camici, Piera Angelica Merlini, Claudio Rapezzi, Monica Patten, Vicent Climent, Gianfranco Sinagra, Benedetta Tomberli, Francisco Marin, Philipp Ehlermann, Lars S. Maier, Alessandra Fornaro, Claudius Jacobshagen, Antonello Ganau, Luciano Moretti, Antonio Hernandez Madrid, Raffaele Coppini, Giorgio Reggiardo, Corrado Poggesi, Francesco Fattirolli, Luiz Belardinelli, Gianfranco Gensini, Alessandro Mugelli

    Background The late sodium current inhibitor ranolazine reverses the main electrophysiological and mechanical abnormalities of human hypertrophic cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical benefit. We aimed to assess the effect of ranolazine on functional capacity, symptomatic status, diastolic function, and arrhythmias in HCM. Methods and Results In this multicenter, double-blind, phase 2 study, 80 adult patients with nonobstructive HCM (age 53±14 years, 34 women) were randomly assigned to placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months. The primary end point was change in peak VO2 compared with baseline using cardiopulmonary exercise test. Echocardiographic lateral and septal E/E′ ratio, prohormone brain natriuretic peptide levels, 24-hour Holter arrhythmic profile, and quality of life were assessed. Ranolazine was safe and well tolerated. Overall, there was no significant difference in VO2 peak change at 5 months in the ranolazine versus placebo group (delta 0.15±3.96 versus −0.02±4.25 mL/kg per minute; P=0.832). Ranolazine treatment was associated with a reduction in 24-hour burden of premature ventricular complexes compared with placebo (>50% reduction versus baseline in 61% versus 31%, respectively; P=0.042). However, changes in prohormone brain natriuretic peptide levels did not differ in the ranolazine compared with the placebo group (geometric mean median [interquartile range], −3 pg/mL [−107, 142 pg/mL] versus 78 pg/mL [−71, 242 pg/mL]; P=0.251). Furthermore, E/E′ ratio and quality of life scores showed no significant difference. Conclusions In patients with nonobstructive HCM, ranolazine showed no overall effect on exercise performance, plasma prohormone brain natriuretic peptide levels, diastolic function, or quality of life. The drug showed an excellent safety profile and was associated with reduced premature ventricular complex burden. Late sodium current inhibition does not seem to improve functional capacity in HCM. Clinical Trial Registration: URL: https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004507-20

    更新日期:2018-01-17
  • Evolving Story of Clinical Trials in Hypertrophic Cardiomyopathy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Perry M. Elliott

    See Article by Olivotto et al Our greatest glory is not in never falling, but in rising every time we fall. —Attributed to Confucius Thousands of papers on hypertrophic cardiomyopathy have been published since Donald Teare’s landmark description of the disease in 1958, but in spite of considerable advances in its management, clinicians still struggle with the treatment of symptoms in people afflicted by the condition. Patients with hypertrophic cardiomyopathy often complain of exertional chest pain, dyspnea, and fatigue.1 The underlying mechanisms are complex and vary between patients; in some, heart failure symptoms are caused by diastolic dysfunction with preserved ejection fraction and in others by systolic left ventricular dysfunction or left ventricular outflow tract obstruction (with or without mitral insufficiency). Atrial fibrillation is frequent in both scenarios and often exacerbates symptoms. When caused by dynamic left ventricular outflow tract obstruction, exertional symptoms can be managed effectively with drugs or interventions, such as surgical septal myectomy and alcohol septal ablation. However, treatment options in nonobstructive patients are usually much less successful and are often associated with side effects. In this issue of Circulation: Heart Failure, Olivotto et al2 report a multicenter, double-blind, phase 2 study of ranolazine—an inhibitor of the cardiac late sodium current (INaL)—in 80 adult patients with …

    更新日期:2018-01-17
  • Heart Failure in Pregnant Women
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Mulubrhan F. Mogos, Mariann R. Piano, Barbara L. McFarlin, Jason L. Salemi, Kylea L. Liese, Joan E. Briller

    Background Heart failure (HF) is a leading cause of maternal morbidity and mortality in the United States, but prevalence, correlates, and outcomes of HF-related hospitalization during antepartum, delivery, and postpartum periods remain unknown. The objective was to examine HF prevalence, correlates, and outcomes among pregnancy-related hospitalizations among women 13 to 49 years of age. Methods and Results We used the 2001 to 2011 Nationwide Inpatient Sample. Rates of HF were calculated by patient and hospital characteristics. Survey logistic regression was used to estimate adjusted odds ratios representing the association between HF and each outcome, stratified by antepartum, delivery, and postpartum periods. Joinpoint regression was used to describe temporal trends in HF and in-hospital mortality. Over 50 million pregnancy-related hospitalizations were analyzed. The overall rate of HF was 112 cases per 100 000 pregnancy-related hospitalizations. Although postpartum encounters represented only 1.5% of pregnancy-related hospitalizations, ≈60% of HF cases occurred postpartum, followed by delivery (27.3%) and antepartum (13.2%). Among postpartum hospitalizations, there was a significant 7.1% (95% confidence interval, 4.4–9.8) annual increase in HF from 2001 to 2006, followed by a steady rate through 2011. HF rates among antepartum hospitalizations increased on average 4.9% (95% confidence interval, 3.0–6.8) annually from 2001 to 2011. Women with a diagnosis of HF were more likely to experience adverse maternal outcomes, as reflected by outcome-specific adjusted odds ratios during antepartum (2.7–25), delivery (6–195), and postpartum (1.5–6.6) periods. Conclusions HF is associated with increased risk of maternal mortality and morbidities. During hospitalization, high-risk mothers need to be identified and surveillance programs developed before discharge.

    更新日期:2018-01-17
  • Acute and Chronic Increases of Circulating FSTL1 Normalize Energy Substrate Metabolism in Pacing-Induced Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Mitsuru Seki, Jeffery C. Powers, Sonomi Maruyama, Maria A. Zuriaga, Chia-Ling Wu, Clara Kurishima, Lydia Kim, Jesse Johnson, Anthony Poidomani, Tao Wang, Eric Muñoz, Sudarsan Rajan, Joon Y. Park, Kenneth Walsh, Fabio A. Recchia

    Background FSTL1 (follistatin-like protein 1) is an emerging cardiokine/myokine that is upregulated in heart failure (HF) and is found to be cardioprotective in animal models of cardiac injury. We tested the hypothesis that circulating FSTL1 can affect cardiac function and metabolism under baseline physiological conditions and in HF. Methods and Results FSTL1 was acutely (10 minutes) or chronically (2 weeks) infused to attain clinically relevant blood levels in conscious dogs with cardiac tachypacing-induced HF. Dogs with no cardiac pacing and FSTL1 infusion served as control. 3H-oleate and 14C-glucose were infused to track the metabolic fate of free fatty acids and glucose. Cardiac uptake of lactate and ketone bodies and systemic respiratory quotient were also measured. HF caused a shift from prevalent cardiac and systemic fat to carbohydrate oxidation. Although acute FSTL1 administration caused minimal hemodynamic changes at baseline, in HF dogs it enhanced cardiac oxygen consumption and transiently reversed the changes in free fatty acid and glucose oxidation and systemic respiratory quotient. In HF, chronic FSTL1 infusion stably normalized cardiac free fatty acid, glucose, ketone body consumption, and systemic respiratory quotient, while moderately improving diastolic and contractile function. Consistently, FSTL1 prevented the downregulation of medium-chain acyl-CoA dehydrogenase—a representative enzyme of the free fatty acid oxidation pathway. Complementary in vitro experiments in primary cardiac and skeletal muscle myocytes showed that FSTL1 stimulated oxygen consumption through AMPK (AMP-activated kinase) activation. Conclusions These findings support a novel function for FSTL1 and provide the first direct evidence that a circulating cardiokine/myokine can alter myocardial and systemic energy substrate metabolism, in vivo.

    更新日期:2018-01-17
  • Intersection of Pulmonary Hypertension and Right Ventricular Dysfunction in Patients on Left Ventricular Assist Device Support
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Christopher T. Sparrow, Shane J. LaRue, Joel D. Schilling

    Left ventricular assist devices (LVADs) improve survival and quality of life in patients with advanced heart failure. Despite these benefits, combined post- and precapillary pulmonary hypertension can be particularly problematic in patients on LVAD support, often exacerbating right ventricular (RV) dysfunction. Both persistently elevated pulmonary vascular resistance and RV dysfunction are associated with adverse outcomes, including death after LVAD. These observations have led to significant interest in the use of pulmonary vasodilators to treat pulmonary hypertension and preserve RV function among LVAD-supported patients. Although pulmonary vasodilators are commonly used for the treatment of pulmonary hypertension and RV dysfunction in LVADs, the benefits of this practice remain unclear. The purpose of this review is to highlight the current challenges in managing pulmonary vascular disease and RV dysfunction in patients with heart failure on LVAD support.

    更新日期:2018-01-17
  • Skeletal Muscle Compensation for Cardiac Muscle Insufficiency in Heart Failure and Reduced Ejection Fraction
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-01-01
    Yogesh N. V. Reddy, Masaru Obokata, Mark J. Haykowsky, Barry A. Borlaug

    Patients with heart failure (HF) and reduced ejection fraction (HFrEF) display exercise intolerance measured objectively as decreased peak oxygen uptake (VO2).1 In accordance with Fick’s principal and law of diffusion, reduced peak VO2 is the result of impaired convective and diffusive O2 transport.2,3 Endurance training improves peak VO2 in clinically stable HFrEF patients secondary to central and peripheral adaptations that result in increased cardiac output and O2 distribution and extraction in skeletal muscle.1 We report, using invasive hemodynamic and pulmonary gas exchange measures, exercise changes in VO2 and its determinants in an avid cyclist with severe cardiac limitation because of advanced HFrEF. A 55-year-old male patient who had been a lifelong marathon runner was diagnosed with idiopathic nonischemic dilated cardiomyopathy 5 years before evaluation. He had a history of atrial fibrillation and was on optimal doses of carvedilol, lisinopril, and spironolactone. His ejection fraction was 20% to 25%, but he had remained in New York Heart Association class I and was able to continue cycling and intense daily exercise. In the past year, he was hospitalized twice for acutely decompensated HF, with gradually worsening effort intolerance. Given the increasing need for hospitalization, he was referred for invasive exercise testing as part of a transplant evaluation workup. Laboratories revealed hemoglobin 13.3 g/dL, creatinine 1.5 mg/dL, sodium 132 mmol/L, troponin 0.06 ng/mL, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) 14 080 pg/mL. Echocardiography showed ejection …

    更新日期:2018-01-17
  • Novel Mitochondria-Targeting Peptide in Heart Failure Treatment
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Melissa A. Daubert, Eric Yow, Gary Dunn, Sotir Marchev, Huiman Barnhart, Pamela S. Douglas, Christopher O’Connor, Sidney Goldstein, James E. Udelson, Hani N. Sabbah

    Background Mitochondrial dysfunction and energy depletion in the failing heart are innovative therapeutic targets in heart failure management. Elamipretide is a novel tetrapeptide that increases mitochondrial energy; however, its safety, tolerability, and therapeutic effect on cardiac structure and function have not been studied in heart failure with reduced ejection fraction. Methods and Results In this double-blind, placebo-controlled, ascending-dose trial, patients with heart failure with reduced ejection fraction (ejection fraction, ≤35%) were randomized to either a single 4-hour infusion of elamipretide (cohort 1 [n=8], 0.005; cohort 2 [n=8], 0.05; and cohort 3 [n=8], 0.25 mg·kg−1·h−1) or placebo control (n=12). Safety and efficacy were assessed by clinical, laboratory, and echocardiographic assessments performed at pre-, mid- and end-infusion and 6-, 8-, 12- and 24-hours postinfusion start. Peak plasma concentrations of elamipretide occurred at end-infusion and were undetectable by 24 hours postinfusion. There were no serious adverse events. Blood pressure and heart rate remained stable in all cohorts. Compared with placebo, a significant decrease in left ventricular end-diastolic volume (−18 mL; P=0.009) and end-systolic volume (−14 mL; P=0.005) occurred at end infusion in the highest dose cohort. Conclusions This is the first study to evaluate elamipretide in heart failure with reduced ejection fraction and demonstrates that a single infusion of elamipretide is safe and well tolerated. High-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations, supporting a temporal association and dose–effect relationship. Further study of elamipretide is needed to determine long-term safety and efficacy. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02388464.

    更新日期:2017-12-20
  • Targeting Myocardial Energetics in the Failing Heart
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Douglas L. Mann

    See Article by Daubert et al It has long been recognized that key components of the cardiac energetic system are downregulated in the failing heart. Under normoxic conditions, mitochondrial oxidative phosphorylation generates ≈95% of the ATP content in the heart,1 which is essential for the process of excitation contraction, as well as maintenance of membrane transport systems. Studies in patients with end-stage cardiomyopathy have shown that the total adenine nucleotide pool (ATP, ADP, and AMP), creatine kinase activity (required for ATP synthesis), creatine phosphate concentration, and the Cr/ATP ratio (a marker of impaired energy metabolism) are all decreased in the failing heart, which has given rise to the notion that the failing heart is an engine out of fuel.1,2 Although multiple mechanisms have been proposed to explain the profoundly abnormal energetics in the failing heart, recent advances in our understanding of mitochondrial biology3 have raised the intriguing possibility that mitochondria-targeted therapeutics may lead to improved energy production in the heart.4 Accordingly, a study in this issue of the Circulation: Heart Failure by Daubert et al,5 which evaluates the safety of elamipretide, a novel mitochondria-targeted peptide, in heart failure patients with a reduced ejection fraction (HFrEF) is of considerable interest.5 Daubert et al5 conducted a double-blind placebo-controlled ascending-dose trial with elamipretide in patients with HFrEF (<35%) who were receiving evidence-based medical therapies for heart failure. Patients were randomized to a single 4-hour intravenous infusion of …

    更新日期:2017-12-20
  • Trends in the Use of Inotropes to List Adult Heart Transplant Candidates at Status 1A
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    William F. Parker, Edward R. Garrity, Savitri Fedson, Matthew M. Churpek

    Background The number of adult heart transplant candidates waiting at the most urgent status 1A has increased over time despite the expansion of geographic sharing of hearts in 2006. We aimed to determine whether candidates listed with inotropes contribute to the excess status 1A candidates. Methods and Results The initial registrations of all adult heart-only candidates listed from 2000 to 2015 were analyzed using the Scientific Registry of Transplant Recipients data set. Trends in listing status, justifications, and candidate factors were measured. Adjusted trends in listing status pre- and post–geographic sharing were estimated using multilevel logistic regression. Competing risks models provided trends in transplant-free waitlist survival. There were 46 853 adult heart-alone listings during 2000 to 2015. Pre-sharing, status 1A listing was unchanged over time (adjusted odds ratio, 0.98; 95% confidence interval, 0.78–1.23). Post-sharing, the adjusted odds of status 1A listing increased 117% over 9 years (adjusted odds ratio 2.17, 95% confidence interval, 1.82–2.58). The number of candidates listed as status 1A with inotropes increased by 193 a year, whereas the dobutamine, dopamine, and milrinone doses used decreased 49%, 55%, and 29% (P<0.001). The risk of waitlist death or deterioration of status 1A inotrope candidates relative to status 2 candidates decreased 62% for 2006 to 2010 and 70% for 2011 to 2015 compared with that for 2003 to 2006. Conclusions After the wider geographic sharing of hearts in 2006, transplant programs used multiple inotropes to list candidates at status 1A more frequently with progressively lower doses. Concurrently, the status 1A inotrope candidate waitlist outcomes improved substantially. These trends suggest that overtreatment with multiple inotropes contributes to the current critical excess of status 1A candidates.

    更新日期:2017-12-20
  • The Heart Transplant Waiting List and the Interplay of Policy and Practice
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Josef Stehlik, Omar Wever-Pinzon

    See Article by Parker et al The national heart allograft allocation algorithm established by the Organ Procurement and Transplantation Network has undergone several major changes over the years. The main goals of these policy modifications have been to respond to the evolving treatment options for advanced heart failure patients, minimize the risk of death on the waiting list, and maximize the benefit of transplant.1 An aspirational goal has also been to achieve as much uniformity as possible in the practical application of the allocation algorithm. Every modification of the allocation policy in the past has been met with a good dose of anxiety in anticipation of what the implemented change will mean. Will the benefits to transplant candidates predicted by the statistical modeling of waiting list events be realized? Will the change affect the required level of staffing or the established process logistics of organizations participating in donation, procurement, and transplantation? Will the change alter transplant volumes at one’s transplant center? Yet, the more contentious aspect has typically been the issue of uniform application of the policy from one transplant program to another and from patient to patient—a subject matter that can be best characterized as fairness. In this issue of Circulation: Heart Failure, Parker et al2 present their evaluation of one aspect of the fairness of the current heart allocation in the United States. They hypothesized that changes have taken place over time in the listing practices under the current Organ Procurement and Transplantation Network allocation …

    更新日期:2017-12-20
  • Short-Term Outcomes and Factors Associated With Adverse Events Among Adults Discharged From the Emergency Department After Treatment for Acute Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Dana R. Sax, Dustin G. Mark, Renee Y. Hsia, Thida C. Tan, Grace H. Tabada, Alan S. Go

    Background Although 80% of patients with heart failure seen in the emergency department (ED) are admitted, less is known about short-term outcomes and demand for services among discharged patients. Methods and Results We examined adult members of a large integrated delivery system who visited an ED for acute heart failure and were discharged from January 1, 2013, through September 30, 2014. The primary outcome was a composite of repeat ED visit, hospital admission, or death within 7 days of discharge. We identified multivariable baseline patient-, provider-, and facility-level factors associated with adverse outcomes within 7 days of ED discharge using logistic regression. Among 7614 patients, mean age was 77.2 years, 51.9% were women, and 28.4% were people of color. Within 7 days of discharge, 75% had outpatient follow-up (clinic, telephone, or e-mail), 7.1% had an ED revisit, 4.7% were hospitalized, and 1.2% died. Patients who met the primary outcome were more likely to be older, smokers, have a history of hemorrhagic stroke, hypothyroidism, and dementia, and less likely to be treated in a facility with an observation unit. In multivariable analysis, higher comorbidity scores and history of smoking were associated with a higher odds of the primary outcome, whereas treatment in a facility with an observation unit and presence of outpatient follow-up within 7 days were associated with a lower odds. Conclusions We identified selected hospital and patient characteristics associated with short-term adverse outcomes. Further understanding of these factors may optimize safe outpatient management in ED-treated patients with heart failure.

    更新日期:2017-12-20
  • Breaking the Law of Small Numbers
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Peter S. Pang, Christopher S. Weaver

    See Article by Sax et al I always avoid prophesying beforehand because it is much better to prophesy after the event has already taken place. —Winston Churchill Over 50% of all hospital admissions originate from the emergency department (ED), supporting the popular belief that the ED admits too many patients. Although the ED is the source of most admissions,1 the truth is most patients seen in the ED actually go home. Of 141 million annual visits to EDs in the United States, only 12.6% result in admission.2 When it comes to acute heart failure (AHF), however, the perceived reality is in fact true. The ED admits ≈85% of patients who present with AHF, accounting for ≈80% of the >1 million AHF hospitalizations per year.3,4 Many patients with AHF clearly require acute care; but is it truly 8 of every 10 patients? What do the data tell us? Unfortunately, little. Despite countless assertions that more patients with AHF should be sent home, supporting evidence is lacking.5,6 The most robust data come from our Canadian colleagues7,8; perhaps, we should simply extrapolate their data to the US setting. However, this highlights the surprising paucity of US data on outcomes of patients discharged from the ED with AHF. If we do extrapolate, current data suggest that patients discharged from the ED have worse outcomes than hospitalized patients!7 Our clinical gestalt to discriminate high from low risk seems poor. Unlike chest pain and the rule-out risk-scores or risk-stratification instruments for acute coronary syndromes, no universally accepted tools exist for AHF.9 Several promising ED-based AHF risk instruments have been proposed both outside and within the United States8,9 but are not ready for prime time. They either (1) have …

    更新日期:2017-12-20
  • Predicting Risk in Patients Hospitalized for Acute Decompensated Heart Failure and Preserved Ejection Fraction
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Tonje Thorvaldsen, Brian L. Claggett, Amil Shah, Susan Cheng, Sunil K. Agarwal, Lisa M. Wruck, Patricia P. Chang, Wayne D. Rosamond, Eldrin F. Lewis, Akshay S. Desai, Lars H. Lund, Scott D. Solomon

    Background Risk-prediction models specifically for hospitalized heart failure with preserved ejection fraction are lacking. Methods and Results We analyzed data from the ARIC (Atherosclerosis Risk in Communities) Study Heart Failure Community Surveillance to create and validate a risk score predicting mortality in patients ≥55 years of age admitted with acute decompensated heart failure with preserved ejection fraction (ejection fraction ≥50%). A modified version of the risk-prediction model for acute heart failure developed from patients in the EFFECT (Enhanced Feedback for Effective Cardiac Treatment) study was used as a composite predictor of 28-day and 1-year mortalities and evaluated together with other potential predictors in a stepwise logistic regression. The derivation sample consisted of 1852 hospitalizations from 2005 to 2011 (mean age, 77 years; 65% women; 74% white). Risk scores were created from the identified predictors and validated in hospitalizations from 2012 to 2013 (n=821). Mortality in the derivation and validation sample was 11% and 8% at 28 days and 34% and 31% at 1 year. The modified EFFECT score, including age, systolic blood pressure, blood urea nitrogen, sodium, cerebrovascular disease, chronic obstructive pulmonary disease, and hemoglobin, was a powerful predictor of mortality. Another important predictor for both 28-day and 1-year mortalities was hypoxia. The risk scores were well calibrated and had good discrimination in the derivation sample (area under the curve: 0.76 for 28-day and 0.72 for 1-year mortalities) and validation sample (area under the curve: 0.73 and 0.71, respectively). Conclusions Mortality after acute decompensation in patients with heart failure with preserved ejection fraction is high, with one third of patients dying within a year. A prediction tool may allow for greater discrimination of the highest risk patients.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005131

    更新日期:2017-12-20
  • Hemodynamics of Fontan Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Alexander C. Egbe, Heidi M. Connolly, William R. Miranda, Naser M. Ammash, Donald J. Hagler, Gruschen R. Veldtman, Barry A. Borlaug

    Background Nonpulsatile pulmonary blood flow in Fontan circulation results in pulmonary vascular disease, but the potential relationships between pulmonary vascular resistance index (PVRI) and Fontan failure have not been studied. The objective was to determine whether the absence of subpulmonary ventricle in the Fontan circulation would make patients more vulnerable to even low-level elevations in PVRI, and when coupled with low cardiac index, this would identify patients at increased risk of Fontan failure. Methods and Results Two hundred sixty-one adult Fontan patients underwent cardiac catheterization; age 26±3 years, men 146 (56%), atriopulmonary Fontan 144 (55%). Patients were divided into 2 groups: those with high PVRI (>2 WU·m2) and low cardiac index <2.5 L min−1 m−2 (group 1, n=70, 30%), and those with normal PVRI and normal cardiac index (group 2, n=182, 70%). Fontan failure was defined by the composite of all-cause mortality, listing for heart transplantation, or initiation of palliative care. There were 68 (26%) cases of Fontan failure during a mean follow-up of 8.6±2.4 years. When compared with group 2, freedom from Fontan failure was significantly lower in group 1: 66% versus 89% at 5 years. The combination of high PVRI and low cardiac index was an independent risk factor for Fontan failure (hazard ratio, 1.84; 95% confidence interval, 1.09–2.85). Conclusions When coupled with low cardiac index, even mild elevations in PVRI identify patients at high risk of Fontan failure. This suggests that pulmonary vascular disease is a key mechanism underlying Fontan failure and supports further studies to understand the pathophysiology and target treatments to pulmonary vascular tone in this population.

    更新日期:2017-12-20
  • Impaired Protein Quality Control During Left Ventricular Remodeling in Mice With Cardiac Restricted Overexpression of Tumor Necrosis Factor
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Justin Hartupee, Gabor D. Szalai, Wei Wang, Xiucui Ma, Abhinav Diwan, Douglas L. Mann

    Background: Sustained inflammation in the heart is sufficient to provoke left ventricular dysfunction and left ventricular remodeling. Although inflammation has been linked to many of the biological changes responsible for adverse left ventricular remodeling, the relationship between inflammation and protein quality control in the heart is not well understood. Methods and Results: To study the relationship between chronic inflammation and protein quality control, we used a mouse model of dilated cardiomyopathy driven by cardiac restricted overexpression of TNF (tumor necrosis factor; Myh6-sTNF). Myh6-sTNF mice develop protein aggregates containing ubiquitin-tagged proteins within cardiac myocytes related to proteasome dysfunction and impaired autophagy. The 26S proteasome was dysfunctional despite normal function of the core 20S subunit. We found an accumulation of autophagy substrates in Myh6-sTNF mice, which were also seen in tissue from patients with end-stage heart failure. Moreover, there was evidence of impaired autophagosome clearance after chloroquine administration in these mice indicative of impaired autophagic flux. Finally, there was increased mammalian target of rapamycin complex 1 (mTORC1) activation, which has been linked to inhibition of both the proteasome and autophagy. Conclusions: Myh6-sTNF mice with sustained inflammatory signaling develop proteasome dysfunction and impaired autophagic flux that is associated with enhanced mTORC1 activation.

    更新日期:2017-12-20
  • Cardiac-Specific Bdh1 Overexpression Ameliorates Oxidative Stress and Cardiac Remodeling in Pressure Overload–Induced Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Motoki Uchihashi, Atsushi Hoshino, Yoshifumi Okawa, Makoto Ariyoshi, Satoshi Kaimoto, Shuhei Tateishi, Kazunori Ono, Ryoetsu Yamanaka, Daichi Hato, Yohei Fushimura, Sakiko Honda, Kuniyoshi Fukai, Yusuke Higuchi, Takehiro Ogata, Eri Iwai-Kanai, Satoaki Matoba

    Background Energy starvation and the shift of energy substrate from fatty acids to glucose is the hallmark of metabolic remodeling during heart failure progression. However, ketone body metabolism in the failing heart has not been fully investigated. Methods and Results Microarray data analysis and mitochondrial isobaric tags for relative and absolute quantification proteomics revealed that the expression of D-β-hydroxybutyrate dehydrogenase I (Bdh1), an enzyme that catalyzes the NAD+/NADH coupled interconversion of acetoacetate and β-hydroxybutyrate, was increased 2.5- and 2.8-fold, respectively, in the heart after transverse aortic constriction. In addition, ketone body oxidation was upregulated 2.2-fold in transverse aortic constriction hearts, as determined by the amount of 14CO2 released from the metabolism of [1-14C] β-hydroxybutyrate in isolated perfused hearts. To investigate the significance of this augmented ketone body oxidation, we generated heart-specific Bdh1-overexpressing transgenic mice to recapitulate the observed increase in basal ketone body oxidation. Bdh1 transgenic mice showed a 1.7-fold increase in ketone body oxidation but did not exhibit any differences in other baseline characteristics. When subjected to transverse aortic constriction, Bdh1 transgenic mice were resistant to fibrosis, contractile dysfunction, and oxidative damage, as determined by the immunochemical detection of carbonylated proteins and histone acetylation. Upregulation of Bdh1 enhanced antioxidant enzyme expression. In our in vitro study, flow cytometry revealed that rotenone-induced reactive oxygen species production was decreased by adenovirus-mediated Bdh1 overexpression. Furthermore, hydrogen peroxide–induced apoptosis was attenuated by Bdh1 overexpression. Conclusions We demonstrated that ketone body oxidation increased in failing hearts, and increased ketone body utilization decreased oxidative stress and protected against heart failure.

    更新日期:2017-12-20
  • Peer Review of a Manuscript Submission
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Larry A. Allen, P. Michael Ho

    Scientific publication is fundamentally based on peer review—a process whereby reviewers are asked to evaluate the scientific merits of the submitted manuscript contents and provide feedback.1 It is hoped that through this peer review process, good science is enhanced and bad science is dismissed.2 Journal editors will discuss the merits of a manuscript critically informed by the reviews provided.3 An invitation to conduct peer review is a chance to serve as the arbiter of scientific quality and an opportunity to participate directly in the dissemination of new knowledge. Unfortunately, many reviewers never receive formal guidance or mentorship on how best to review an original research manuscript. With the growth of academic medicine and the proliferation of open-access journals, high-quality peer reviews have …

    更新日期:2017-12-20
  • Detection of Urinary Mulberry Bodies Leads to Diagnosis of Fabry Cardiomyopathy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Toshiyuki Yano, Ryo Takahashi, Tomohisa Yamashita, Nobutaka Nagano, Aki Ishikawa, Akihiro Sakurai, Hiroki Maruyama, Tetsuji Miura

    Fabry disease is an X-linked lysosomal storage disease characterized by globotriaosyceramide accumulation because of genetic loss/deficiency of α-galactosidase A (α-Gal A) activity. Clinical symptoms of classic Fabry disease, such as acroparethesia and neuropathic pain, typically become apparent in childhood and adolescence. Clinical manifestations in adulthood include cardiac and renal diseases, which are the main causes of death. Life expectancy of untreated Fabry males is ≈50 years. Myocardial involvement in Fabry disease is potentially misdiagnosed as hypertrophic cardiomyopathy unless careful workup of the patient, including pathological and genetic tests, is performed. The presence of chronic kidney disease with proteinuria in patients with ventricular hypertrophy leads to further analyses for diagnosis of Fabry disease. Although deterioration of renal function, leading to end-stage renal disease, is a typical manifestation of classical Fabry disease, a cardiac variant of Fabry disease, often accompanied by mild proteinuria, has also been reported. A 52-year-old man with ventricular hypertrophy and a history of acroparethesia during childhood was referred …

    更新日期:2017-12-20
  • Correction to: Symptom Diary Use and Improved Survival for Patients With Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-12-01
    Lippincott Williams & Wilkins

    In the article by Park et al, “Symptom Diary Use and Improved Survival for Patients With Heart Failure,” …

    更新日期:2017-12-20
  • Cardiac Magnetic Resonance Imaging in Myocarditis Reveals Persistent Disease Activity Despite Normalization of Cardiac Enzymes and Inflammatory Parameters at 3-Month Follow-Up
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Jan Berg, Jan Kottwitz, Nora Baltensperger, Christine K. Kissel, Marina Lovrinovic, Tarun Mehra, Frank Scherff, Christian Schmied, Christian Templin, Thomas F. Lüscher, Bettina Heidecker, Robert Manka

    Background: There is a major unmet need to identify high-risk patients in myocarditis. Although decreasing cardiac and inflammatory markers are commonly interpreted as resolving myocarditis, this assumption has not been confirmed as of today. We sought to evaluate whether routine laboratory parameters at diagnosis predict dynamic of late gadolinium enhancement (LGE) as persistent LGE has been shown to be a risk marker in myocarditis. Methods and Results: Myocarditis was diagnosed based on clinical presentation, high-sensitivity troponin T, and cardiac magnetic resonance imaging, after exclusion of obstructive coronary artery disease by angiography. Cardiac magnetic resonance imaging was repeated at 3 months. LGE extent was analyzed with the software GT Volume. Change in LGE >20% was considered significant. Investigated cardiac and inflammatory markers included high-sensitivity troponin T, creatine kinase, myoglobin, N-terminal B-type natriuretic peptide, C-reactive protein, and leukocyte count. Twenty-four patients were enrolled. Absolute levels of cardiac enzymes and inflammatory markers at baseline did not predict change in LGE at 3 months. Cardiac and inflammatory markers had normalized in 21 patients (88%). LGE significantly improved in 16 patients (67%); however, it persisted to a lesser degree in 17 of them (71%) and increased in a small percentage (21%) despite normalization of cardiac enzymes. Conclusions: This is the first study reporting that cardiac enzymes and inflammatory parameters do not sufficiently reflect LGE in myocarditis. Although a majority of patients with normalizing laboratory markers experienced improved LGE, in a small percentage LGE worsened. These data suggest that cardiac magnetic resonance imaging might add value to currently existing diagnostic tools for risk assessment in myocarditis.

    更新日期:2017-12-14
  • Pathogenic Role of the Damage-Associated Molecular Patterns S100A8 and S100A9 in Coxsackievirus B3–Induced Myocarditis
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Irene Müller, Thomas Vogl, Kathleen Pappritz, Kapka Miteva, Konstantinos Savvatis, David Rohde, Patrick Most, Dirk Lassner, Burkert Pieske, Uwe Kühl, Sophie Van Linthout, Carsten Tschöpe

    Background: The alarmins S100A8 and S100A9 are damage-associated molecular patterns, which play a pivotal role in cardiovascular diseases, inflammation, and viral infections. We aimed to investigate their role in Coxsackievirus B3 (CVB3)–induced myocarditis. Methods and Results: S100A8 and S100A9 mRNA expression was 13.0-fold (P=0.012) and 5.1-fold (P=0.038) higher in endomyocardial biopsies from patients with CVB3-positive myocarditis compared with controls, respectively. Elimination of CVB3 led to a downregulation of these alarmins. CVB3-infected mice developed an impaired left ventricular function and displayed an increased left ventricular S100A8 and S100A9 protein expression versus controls. In contrast, CVB3-infected S100A9 knockout mice, which are also a complete knockout for S100A8 on protein level, showed an improved left ventricular function, which was associated with a reduced cardiac inflammatory and oxidative response, and lower CVB3 copy number compared with wild-type CVB3 mice. Exogenous application of S100A8 to S100A9 knockout CVB3 mice induced a severe myocarditis similar to wild-type CVB3 mice. In CVB3-infected HL-1 cells, S100A8 and S100A9 enhanced oxidative stress and CVB3 copy number compared with unstimulated infected cells. In CVB3-infected RAW macrophages, both alarmins increased MIP-2 (macrophage inflammatory protein-2) chemokine expression, which was reduced in CVB3 S100A8 knockdown versus scrambled siRNA CVB3 cells. Conclusions: S100A8 and S100A9 aggravate CVB3-induced myocarditis and might serve as therapeutic targets in inflammatory cardiomyopathies.

    更新日期:2017-12-14
  • The Changing Face of Cardiac Inflammation
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Leslie T. Cooper

    See Articles by Berg et al and Müller et al The search for noninvasive tests to diagnose myocardial inflammation has developed from the use of 67Gallium through antimyosin antibodies to the current standards of 18fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging (CMR).1,2 In CMR, a combination of 2 of 3 signal intensity measurements from native T2-weighted images and T1-weighted images obtained before and after gadolinium contrast provides a reasonable diagnostic performance with an estimated sensitivity of 67% and specificity of 91%.3 Since these original Lake Louise criteria were published, newer mapping techniques that quantify T1 and T2 relaxation times have significantly improved the performance of CMR for the diagnosis of inflammation.4 Early in the course of suspected myocarditis, CMR can predict meaningful clinical outcomes. In most but not all studies, the risk of ventricular arrhythmias is increased in patients with delayed gadolinium enhancement.5–7 CMR sequences that estimate extracellular volume and edema can also inform management decisions. For example, an increase in T2 relaxation time may suggest greater myocardial water content and a greater likelihood of improved cardiac function.8 Because exercise can trigger arrhythmias in the setting of acute myocarditis, current American Heart Association scientific and European Society of Cardiology position …

    更新日期:2017-12-14
  • Interleukin-1 Blockade in Recently Decompensated Systolic Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Benjamin W. Van Tassell, Justin Canada, Salvatore Carbone, Cory Trankle, Leo Buckley, Claudia Oddi Erdle, Nayef A. Abouzaki, Dave Dixon, Dinesh Kadariya, Sanah Christopher, Aaron Schatz, Jessica Regan, Michele Viscusi, Marco Del Buono, Ryan Melchior, Pranav Mankad, Juan Lu, Robin Sculthorpe, Giuseppe Biondi-Zoccai, Edward Lesnefsky, Ross Arena, Antonio Abbate

    Background An enhanced inflammatory response predicts worse outcomes in heart failure (HF). We hypothesized that administration of IL-1 (interleukin-1) receptor antagonist (anakinra) could inhibit the inflammatory response and improve peak aerobic exercise capacity in patients with recently decompensated systolic HF. Methods and Results We randomly assigned 60 patients with reduced left ventricular ejection fraction (<50%) and elevated C-reactive protein levels (>2 mg/L), within 14 days of hospital discharge, to daily subcutaneous injections with anakinra 100 mg for 2 weeks, 12 weeks, or placebo. Patients underwent measurement of peak oxygen consumption (Vo2 [mL/kg per minute]) and ventilatory efficiency (the VE/Vco2 slope). Treatment with anakinra did not affect peak Vo2 or VE/Vco2 slope at 2 weeks. At 12 weeks, patients continued on anakinra showed an improvement in peak Vo2 from 14.5 (10.5–16.6) mL/kg per minute to 16.1 (13.2–18.6) mL/kg per minute (P=0.009 for within-group changes), whereas no significant changes occurred within the anakinra 2-week or placebo groups. The between-groups differences, however, were not statistically significant. The incidence of death or rehospitalization for HF at 24 weeks was 6%, 31%, and 30%, in the anakinra 12-week, anakinra 2-week, and placebo groups, respectively (log-rank test P=0.10). Conclusions No change in peak Vo2 occurred at 2 weeks in patients with recently decompensated systolic HF treated with anakinra, whereas an improvement was seen in those patients in whom anakinra was continued for 12 weeks. Additional larger studies are needed to validate the effects of prolonged anakinra on peak Vo2 and rehospitalization for HF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01936909.

    更新日期:2017-12-14
  • Impact of Diabetes Mellitus on Outcomes in Patients Supported With Left Ventricular Assist Devices
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Rabea Asleh, Alexandros Briasoulis, Sarah D. Schettle, Vakhtang Tchantchaleishvili, Naveen L. Pereira, Brooks S. Edwards, Alfredo L. Clavell, Simon Maltais, David L. Joyce, Lyle D. Joyce, Richard C. Daly, Sudhir S. Kushwaha, John M. Stulak

    Background Diabetes mellitus (DM) is a risk factor for morbidity and mortality in patients with heart failure. The effect of DM on post–left ventricular assist device (LVAD) implantation outcomes is unclear. This study sought to investigate whether patients with DM had worse outcomes than patients without DM after LVAD implantation and whether LVAD support resulted in a better control of DM. Methods and Results We retrospectively reviewed 341 consecutive adults who underwent implantation of LVAD from 2007 to 2016. Patient characteristics and adverse events were studied and compared between patients with and without DM. One hundred thirty-one patients (38%) had DM. Compared with patients without DM, those with DM had higher rates of ischemic cardiomyopathy, LVAD implantation as destination therapy, and increased baseline body mass index. In a proportional hazards (Cox) model with adjustment for relevant covariates and median follow-up of 16.1 months, DM was associated with increased risk of all-cause mortality (hazard ratio, 1.73; 95% confidence interval: 1.18–2.53; P=0.005) and increased risk of nonfatal LVAD-related complications, including a composite of stroke, pump thrombosis, and device infection (hazard ratio, 2.1; 95% confidence interval: 1.35–3.18; P=0.001). Preoperative hemoglobin A1c was not significantly associated with mortality or adverse events among patients with DM. LVAD implantation resulted in a remarkable decrease in hemoglobin A1c levels (7.4±1.9 pre-LVAD versus 6.0±1.5 and 6.3±1.4 after 3 and 12 months post-LVAD, respectively; P<0.0001) and a significant reduction in requirements of DM medications. Conclusions DM is associated with increased rates of all-cause mortality and major adverse events despite favorable glycemic control after LVAD implantation.

    更新日期:2017-12-14
  • Is There a Sweet Spot for Left Ventricular Assist Devices and Diabetes Mellitus?
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    James B. Young, Amanda R. Vest

    See Article by Asleh et al As outcomes of left ventricular assist device (LVAD) therapy for advanced systolic heart failure (HF) have improved, focus shifts from identification and exclusion of patients with high-risk features toward finding opportunities to modify such risks and maximize event-free survival on LVAD support. Diabetes mellitus (DM) is one such feature, but existing literature has neither fully defined the risk presented by this comorbidity nor the best strategies for management. This is critical because DM is a common problem and HF pathogenesis. Independent of coronary artery disease and hypertension, DM may cause cardiomyopathy, and >40% of patients hospitalized for decompensated HF have DM.1 We are challenged when we consider these patients for advanced HF therapies. In this issue of Circulation: Heart Failure, Asleh et al2 present a detailed analysis of their single-center experience with DM and LVAD outcomes. They have added to the literature evidence that DM is associated with an increased rate of all-cause mortality and major adverse events during LVAD support. Specifically, a retrospective analysis of 341 consecutive adult patients undergoing predominantly destination therapy LVAD implant from 2007 to 2016 was performed. This experience totaled almost a decade and thus saw changes in devices, changes in device implant philosophy, and undoubtedly, changes in patient selection. Although the study experienced all the usual limitations of a retrospective cohort design, including incomplete evaluation of the impact of type 1 versus type 2 DM, duration of DM, short- and long-term treatment strategies, and the role of micro- and macrovascular DM complications, these real-world studies can provide valuable insight into optimal patient selection and management practices. The authors remind us that the International Society for Heart and Lung Transplantation patient selection guidelines considers DM presence to be important but focuses on patients with poor glycemic …

    更新日期:2017-12-14
  • Multicenter Evaluation of Octreotide as Secondary Prophylaxis in Patients With Left Ventricular Assist Devices and Gastrointestinal Bleeding
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Keyur B. Shah, Sampath Gunda, Sitaramesh Emani, Manreet K. Kanwar, Nir Uriel, Paolo C. Colombo, Patricia A. Uber, Melissa L. Sears, Joyce Chuang, David J. Farrar, Donald F. Brophy, George B. Smallfield

    Background Gastrointestinal (GI) bleeding is one of the most common complications after continuous-flow left ventricular assist device implantation. More than one third of patients with incident bleed go on to develop recurrent GI bleeding. Octreotide, a somatostatin analog, is proposed to reduce the risk of recurrent GI bleeding in this population. Methods and Results This multicenter, retrospective analysis evaluated 51 continuous-flow left ventricular assist device patients who received secondary prophylaxis with octreotide after their index GI bleed from 2009 to 2015. All patients had a hospitalization for GI bleed and received octreotide after discharge. Patient demographics, medical and medication history, and clinical characteristics of patients who rebled after receiving octreotide were compared with non–rebleeders. These data were also compared with matched historical control patients previously enrolled in the HMII (HeartMate II) clinical trials, none of whom received octreotide, to provide a context for the bleeding rates. Twelve patients (24%) who received secondary octreotide prophylaxis developed another GI bleed, whereas 39 (76%) did not. There were similar intergroup demographics; however, significantly more bleeders had a previous GI bleeding history before left ventricular assist device placement (33% versus 5%; P=0.02) and greater frequency of angiodysplasia confirmed during endoscopy (58% versus 23%; P=0.03). Fewer patients in this study experienced a recurrent GI bleed compared with a matched historical control group that did not receive octreotide (24% versus 43%; P=0.04). Conclusions Patients with continuous-flow left ventricular assist device receiving secondary prophylaxis with octreotide had a significantly lower GI bleed recurrence compared with historical controls not treated with octreotide. Additional prospective studies are needed to confirm these data.

    更新日期:2017-12-14
  • Sildenafil Is Associated With Reduced Device Thrombosis and Ischemic Stroke Despite Low-Level Hemolysis on Heart Mate II Support
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Omar Saeed, Sabarivinoth Rangasamy, Ibrahim Selevany, Shivank Madan, Jeremy Fertel, Ruth Eisenberg, Mohammad Aljoudi, Snehal R. Patel, Julia Shin, Daniel B. Sims, Morayma Reyes Gil, Daniel J. Goldstein, Marvin J. Slepian, Henny H. Billett, Ulrich P. Jorde

    Background: Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support. Methods and Results: A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5–50; P<0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2–16.1; P=0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, P<0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil (P<0.001). Conclusions: Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support.

    更新日期:2017-12-14
  • Contemporary Epidemiology of Heart Failure in Fee-For-Service Medicare Beneficiaries Across Healthcare Settings
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Rohan Khera, Ambarish Pandey, Colby R. Ayers, Vijay Agusala, Sandi L. Pruitt, Ethan A. Halm, Mark H. Drazner, Sandeep R. Das, James A. de Lemos, Jarett D. Berry

    Background To assess the current landscape of the heart failure (HF) epidemic and provide targets for future health policy interventions in Medicare, a contemporary appraisal of its epidemiology across inpatient and outpatient care settings is needed. Methods and Results In a national 5% sample of Medicare beneficiaries from 2002 to 2013, we identified a cohort of 2 331 939 unique fee-for-service Medicare beneficiaries ≥65-years-old followed for all inpatient and outpatient encounters over a 10-year period (2004–2013). Preexisting HF was defined by any HF encounter during the first year, and incident HF with either 1 inpatient or 2 outpatient HF encounters. Mean age of the cohort was 72 years; 57% were women, and 86% and 8% were white and black, respectively. Within this cohort, 518 223 patients had preexisting HF, and 349 826 had a new diagnosis of HF during the study period. During 2004 to 2013, the rates of incident HF declined 32%, from 38.7 per 1000 (2004) to 26.2 per 1000 beneficiaries (2013). In contrast, prevalent (preexisting + incident) HF increased during our study period from 162 per 1000 (2004) to 172 per 1000 beneficiaries (2013) (Ptrend <0.001 for both). Finally, the overall 1-year mortality among patients with incident HF is high (24.7%) with a 0.4% absolute decline annually during the study period, with a more pronounced decrease among those diagnosed in an inpatient versus outpatient setting (Pinteraction <0.001) Conclusions In recent years, there have been substantial changes in the epidemiology of HF in Medicare beneficiaries, with a decline in incident HF and a decrease in 1-year HF mortality, whereas the overall burden of HF continues to increase.

    更新日期:2017-12-14
  • Contemporary Characteristics and Outcomes in Chagasic Heart Failure Compared With Other Nonischemic and Ischemic Cardiomyopathy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Li Shen, Felix Ramires, Felipe Martinez, Luiz Carlos Bodanese, Luis Eduardo Echeverría, Efraín A. Gómez, William T. Abraham, Kenneth Dickstein, Lars Køber, Milton Packer, Jean L. Rouleau, Scott D. Solomon, Karl Swedberg, Michael R. Zile, Pardeep S. Jhund, Claudio R. Gimpelewicz, John J.V. McMurray, on behalf of the PARADIGM-HF and ATMOSPHERE Investigators and Committees

    Background Chagas’ disease is an important cause of cardiomyopathy in Latin America. We aimed to compare clinical characteristics and outcomes in patients with heart failure (HF) with reduced ejection fraction caused by Chagas’ disease, with other etiologies, in the era of modern HF therapies. Methods and Results This study included 2552 Latin American patients randomized in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and ATMOSPHERE (Aliskiren Trial to Minimize Outcomes in Patients With Heart Failure) trials. The investigator-reported etiology was categorized as Chagasic, other nonischemic, or ischemic cardiomyopathy. The outcomes of interest included the composite of cardiovascular death or HF hospitalization and its components and death from any cause. Unadjusted and adjusted Cox proportional hazards models were performed to compare outcomes by pathogenesis. There were 195 patients with Chagasic HF with reduced ejection fraction, 1300 with other nonischemic cardiomyopathy, and 1057 with ischemic cardiomyopathy. Compared with other etiologies, Chagasic patients were more often female, younger, and had lower prevalence of hypertension, diabetes mellitus, and renal impairment (but had higher prevalence of stroke and pacemaker implantation) and had worse health-related quality of life. The rates of the composite outcome were 17.2, 12.5, and 11.4 per 100 person-years for Chagasic, other nonischemic, and ischemic patients, respectively—adjusted hazard ratio for Chagasic versus other nonischemic: 1.49 (95% confidence interval, 1.15–1.94; P=0.003) and Chagasic versus ischemic: 1.55 (1.18–2.04; P=0.002). The rates of all-cause mortality were also higher. Conclusions Despite younger age, less comorbidity, and comprehensive use of conventional HF therapies, patients with Chagasic HF with reduced ejection fraction continue to have worse quality of life and higher hospitalization and mortality rates compared with other etiologies. Clinical Trial Registration PARADIGM-HF: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01035255; ATMOSPHERE: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00853658.

    更新日期:2017-12-14
  • Symptom Diary Use and Improved Survival for Patients With Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Linda G. Park, Kathleen Dracup, Mary A. Whooley, Charles McCulloch, Chengshi Jin, Debra K. Moser, Robyn A. Clark, Michele M. Pelter, Martha Biddle, Jill Howie Esquivel

    Background: Attention to symptoms of weight gain and dyspnea are central tenets of patient education in heart failure (HF). However, it is not known whether diary use improves patient outcomes. The aims of this study were to compare mortality among rural patients with HF who completed versus did not complete a daily diary of weight and symptom self-assessment and to identify predictors of diary use. Methods and Results: This is a secondary analysis of a 3-arm randomized controlled trial on HF education of self-care with 2 intervention groups versus control who were given diaries for 24 months to track daily weight, HF symptoms, and response to symptom changes. Mean age was 66±13, 58% were men, and 67% completed diaries (n=393). We formed 5 groups (no use, low, medium, high, and very high) based on the first 3 months of diary use and then analyzed time to event (cardiac mortality, all-cause mortality, and HF-related readmission) starting at 3 months. Compared with patients with no diary use, high and very high diary users were less likely to experience all-cause mortality (P=0.02 and P=0.01, respectively). Self-reported sedentary lifestyle was associated with less diary use in an adjusted model (odds ratio, 0.66; 95% confidence interval, 0.46–0.95; P=0.03). Depression and sex were not significant predictors of diary use in the adjusted model. Conclusions: In this study of 393 rural patients with HF, we found that greater diary use was associated with longer survival. These findings suggest that greater engagement in self-care behaviors is associated with better HF outcomes. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00415545.

    更新日期:2017-12-14
  • Waiting Period Before Implantable Cardioverter-Defibrillator Implantation in Newly Diagnosed Heart Failure With Reduced Ejection Fraction
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Ersilia M. DeFilippis, Javed Butler, Muthiah Vaduganathan

    A critical waiting period of ≈3 months is generally accepted in patients with newly diagnosed heart failure with reduced ejection fraction (HFrEF) outside the context of an acute myocardial infarction before reassessing left ventricular (LV) ejection fraction and considering implantable cardioverter-defibrillator (ICD) therapy. This time window is offered to allow optimization of guideline-directed medical therapy (GDMT) to promote LV reverse remodeling, which if above a certain threshold, would render the need for an ICD unnecessary. Consideration for an ICD after this time-frame is endorsed by major professional groups,1 serves as a key quality and performance measure, and is deemed appropriate by the Appropriate Use Criteria for ICD therapy.2 This duration also guides reimbursement schema, for example, the Centers for Medicare & Medicaid Services limit coverage for ICDs in nonischemic dilated cardiomyopathy to after this 3-month waiting period. Perhaps it is time to lengthen this time-frame before ICD decision making in newly diagnosed patients with HFrEF. In many cases, 3 months are not sufficient to truly optimize GDMT and allow adequate chance for LV recovery. Evolving risks of sudden cardiac death (SCD), recent expansion of the heart failure (HF) therapeutic armamentarium, and greater focus on shared decision making all support extension of this time window. We summarize these converging lines of evidence and critically appraise the merits of extending this traditional waiting period. We contend that consideration for ICD implantation should only occur once GDMT has been achieved at target doses and may be deferred up to 1 year after diagnosis in appropriately selected patients. As the Centers for Medicare & Medicaid Services plan to update the national coverage determination regarding ICD implantation over the next year, we believe this issue is timely and topical to address. Epidemiological studies3 and clinical trials4 during the past several decades …

    更新日期:2017-12-14
  • Unique Pattern of Aortic Regurgitation Caused by Rupture Into the Left Ventricular Interleaflet Triangle of a Sinus Valsalva Aneurysm Involving the Left Coronary Cusp
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Yasuhide Mochizuki, Kazuhiko Iwahashi, Keitaro Nakagiri, Junya Shite

    A 43-year-old man with a primary complaint of prolonged paroxysmal coughing was admitted to our hospital for evaluation of a to-and-fro heart murmur. When he initially visited our hospital, his heart failure symptom was classified as New York Heart Association functional classification III. His upper limb blood pressure was 129/52 mm Hg and, pulse rate was 95 beats/min. He had a normal respiratory rate with an O2 saturation of 98% on room air. Moreover, his lower limb blood pressure was 190/48 mm Hg. Hence, transthoracic echocardiography was performed for suspected severe aortic regurgitation based on physical findings. However, transthoracic echocardiography showed a flattened, saccular aneurysm originating in the right sinus of Valsalva, which enlarged at the septum of the left ventricle and appeared to rupture into the left ventricular outflow tract (Figure, A and B). After this, cardiac computed …

    更新日期:2017-12-14
  • Notice of Retraction
    Circ. Heart Fail. (IF 6.372) Pub Date : 2017-11-01
    Lippincott Williams & Wilkins

    The authors of the following article have requested that it be retracted from publication in Circulation: Heart Failure: Liu W, Deng J, Ding W, Wang G, Shen Y, Zheng J, Zhang X, Luo Y, Lv …

    更新日期:2017-12-14
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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