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  • Trends in Noncardiovascular Comorbidities Among Patients Hospitalized for Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-06-01
    Abhinav Sharma, Xin Zhao, Bradley G. Hammill, Adrian F. Hernandez, Gregg C. Fonarow, G. Michael Felker, Clyde W. Yancy, Paul A. Heidenreich, Justin A. Ezekowitz, Adam D. DeVore

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

    更新日期:2018-05-23
  • Coronary Artery Remodeling and Fibrosis With Continuous-Flow Left Ventricular Assist Device Support
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Amrut V. Ambardekar, Mary C.M. Weiser-Evans, Marcella Li, Suneet N. Purohit, Muhammad Aftab, T. Brett Reece, Karen S. Moulton

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

    更新日期:2018-05-16
  • Prognostic Significance of Creatinine Increases During an Acute Heart Failure Admission in Patients With and Without Residual Congestion
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Marco Metra, Gad Cotter, Stefanie Senger, Christopher Edwards, John G. Cleland, Piotr Ponikowski, Guillermo C. Cursack, Olga Milo, John R. Teerlink, Michael M. Givertz, Christopher M. O’Connor, Howard C. Dittrich, Daniel M. Bloomfield, Adriaan A. Voors, Beth A. Davison

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

    更新日期:2018-05-16
  • Independent Prognostic Value of Serum Soluble ST2 Measurements in Patients With Heart Failure and a Reduced Ejection Fraction in the PARADIGM-HF Trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure)
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Eileen O’Meara, Margaret F. Prescott, Brian Claggett, Jean L. Rouleau, Lu-May Chiang, Scott D. Solomon, Milton Packer, John J.V. McMurray, Michael R. Zile

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

    更新日期:2018-05-16
  • Pulmonary Capillary Wedge Pressure Patterns During Exercise Predict Exercise Capacity and Incident Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Aaron S. Eisman, Ravi V. Shah, Bishnu P. Dhakal, Paul P. Pappagianopoulos, Luke Wooster, Cole Bailey, Thomas F. Cunningham, Kathryn M. Hardin,, Aaron L. Baggish, Jennifer E. Ho, Rajeev Malhotra, Gregory D. Lewis

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

    更新日期:2018-05-16
  • Risk Factor Burden, Heart Failure, and Survival in Women of Different Ethnic Groups
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Khadijah Breathett, Iris Leng, Randi E. Foraker, William T. Abraham, Laura Coker, Keith E. Whitfield, Sally Shumaker, JoAnn E. Manson, Charles B. Eaton, Barbara V. Howard, Nkechinyere Ijioma, Crystal W. Cené, Lisa W. Martin, Karen C. Johnson, Liviu Klein

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

    更新日期:2018-05-16
  • Left Ventricular Mechanical Unloading by Total Support of Impella in Myocardial Infarction Reduces Infarct Size, Preserves Left Ventricular Function, and Prevents Subsequent Heart Failure in Dogs
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Keita Saku, Takamori Kakino, Takahiro Arimura, Genya Sunagawa, Takuya Nishikawa, Takafumi Sakamoto, Takuya Kishi, Hiroyuki Tsutsui, Kenji Sunagawa

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

    更新日期:2018-05-16
  • Dog Model Holds Promise for Early Mechanical Unloading in Patients With Acute Myocardial Infarction
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Cesar Y. Guerrero-Miranda, Shelley A. Hall

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

    更新日期:2018-05-16
  • Load-Dependent Changes in Left Ventricular Structure and Function in a Pathophysiologically Relevant Murine Model of Reversible Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Carla J. Weinheimer, Attila Kovacs, Sarah Evans, Scot J. Matkovich, Philip M. Barger, Douglas L. Mann

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

    更新日期:2018-05-16
  • Internal Versus External Compression of a Left Ventricular Assist Device Outflow Graft
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Cory R. Trankle, Mohammed A. Quader, John D. Grizzard, Daniel G. Tang, Keyur B. Shah, Kendall Paris, Christina K. Shepard, Zachary M. Gertz

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

    更新日期:2018-05-16
  • Correction to: 2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant): A Report of the ACC Competency Management Committee
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-05-01
    Lippincott Williams & Wilkins

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

    更新日期:2018-05-16
  • When the VEST Does Not Fit
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Larry A. Allen, Eric D. Adler, Antoni Bayés-Genis, Meredith A. Brisco-Bacik, Julio A. Chirinos, Brian Claggett, Jennifer L. Cook, James C. Fang, Finn Gustafsson, Carolyn Y. Ho, Navin K. Kapur, Scott E. Klewer, Robb D. Kociol, David E. Lanfear, Orly Vardeny, Nancy K. Sweitzer

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

    更新日期:2018-04-18
  • Ventricular Assist Device Utilization in Heart Transplant Candidates
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Lauren K. Truby, A. Reshad Garan, Raymond C. Givens, Koji Takeda, Hiroo Takayama, Pauline N. Trinh, Melana Yuzefpolskaya, Maryjane A. Farr, Yoshifumi Naka, Paolo C. Colombo, Veli K. Topkara

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

    更新日期:2018-04-18
  • TTR (Transthyretin) Stabilizers Are Associated With Improved Survival in Patients With TTR Cardiac Amyloidosis
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Hannah Rosenblum, Adam Castano, Julissa Alvarez, Jeff Goldsmith, Stephen Helmke, Mathew S. Maurer

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

    更新日期:2018-04-18
  • Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Orly Vardeny, Brian Claggett, Jessica Kachadourian, Scott M. Pearson, Akshay S. Desai, Milton Packer, Jean Rouleau, Michael R. Zile, Karl Swedberg, Martin Lefkowitz, Victor Shi, John J.V. McMurray, Scott D. Solomon

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

    更新日期:2018-04-18
  • Left Ventricular Assist Device Inflow Cannula Angle and Thrombosis Risk
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Venkat Keshav Chivukula, Jennifer A. Beckman, Anthony R. Prisco, Todd Dardas, Shin Lin, Jason W. Smith, Nahush A. Mokadam, Alberto Aliseda, Claudius Mahr

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

    更新日期:2018-04-18
  • Pulmonary Effective Arterial Elastance as a Measure of Right Ventricular Afterload and Its Prognostic Value in Pulmonary Hypertension Due to Left Heart Disease
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Emmanouil Tampakakis, Sanjiv J. Shah, Barry A. Borlaug, Peter J. Leary, Harnish H. Patel, Wayne L. Miller, Benjamin W. Kelemen, Brian A. Houston, Todd M. Kolb, Rachel Damico, Stephen C. Mathai, Edward K. Kasper, Paul M. Hassoun, David A. Kass, Ryan J. Tedford

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

    更新日期:2018-04-18
  • Association of Biomarker Clusters With Cardiac Phenotypes and Mortality in Patients With HIV Infection
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Rebecca Scherzer, Sanjiv J. Shah, Eric Secemsky, Javed Butler, Carl Grunfeld, Michael G. Shlipak, Priscilla Y. Hsue

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

    更新日期:2018-04-18
  • Early Ambulation Among Hospitalized Heart Failure Patients Is Associated With Reduced Length of Stay and 30-Day Readmissions
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Lisa M. Fleming, Xin Zhao, Adam D. DeVore, Paul A. Heidenreich, Clyde W. Yancy, Gregg C. Fonarow, Adrian F. Hernandez, Robb D. Kociol

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

    更新日期:2018-04-18
  • Causes and Predictors of 30-Day Readmission in Patients With Acute Myocardial Infarction and Cardiogenic Shock
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Mahek Shah, Shantanu Patil, Brijesh Patel, Manyoo Agarwal, Carlos D. Davila, Lohit Garg, Sahil Agrawal, Navin K. Kapur, Ulrich P. Jorde

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

    更新日期:2018-04-18
  • Incidence, Risk Factors, and Clinical Characteristics of Peripartum Cardiomyopathy in South Korea
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Sunki Lee, Geum Joon Cho, Geun U. Park, Log Young Kim, Tae-Seon Lee, Do Young Kim, Suk-Won Choi, Jong-Chan Youn, Seong Woo Han, Kyu-Hyung Ryu, Jin Oh Na, Cheol Ung Choi, Hong Seog Seo, Eung Ju Kim

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

    更新日期:2018-04-18
  • Devil in Disguise
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Johann Bauersachs, Tobias Koenig

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

    更新日期:2018-04-18
  • Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Yu Nakagama, Ryo Inuzuka, Kayoko Ichimura, Munetoshi Hinata, Hiroki Takehara, Norihiko Takeda, Satsuki Kakiuchi, Kazuhiro Shiraga, Hiroko Asakai, Takahiro Shindo, Yoichiro Hirata, Makiko Saitoh, Akira Oka

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

    更新日期:2018-04-18
  • Advanced Dilated Cardiomyopathy in a Patient With Hutterite Limb-Girdle Muscular Dystrophy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-04-01
    Bailey Miskew Nichols, Anish Nikhanj, Faqi Wang, Darren H. Freed, Gavin Y. Oudit

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

    更新日期:2018-04-18
  • Apophenia and the Crafting of a Circulation: Heart Failure Issue
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Nancy K. Sweitzer

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

    更新日期:2018-03-22
  • Mechanical Circulatory Support Device Utilization and Heart Transplant Waitlist Outcomes in Patients With Restrictive and Hypertrophic Cardiomyopathy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Lakshmi Sridharan, Brian Wayda, Lauren K. Truby, Farhana Latif, Susan Restaino, Koji Takeda, Hiroo Takayama, Yoshifumi Naka, Paolo C. Colombo, Mathew Maurer, Maryjane A. Farr, Veli K. Topkara

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

    更新日期:2018-03-22
  • Outcomes in Patients With Hypertrophic Cardiomyopathy Awaiting Heart Transplantation
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Julio Zuñiga Cisneros, Josef Stehlik, Craig H. Selzman, Stavros G. Drakos, Stephen H. McKellar, Omar Wever-Pinzon

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

    更新日期:2018-03-22
  • Thirty-Day Readmissions After Left Ventricular Assist Device Implantation in the United States
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Sahil Agrawal, Lohit Garg, Mahek Shah, Manyoo Agarwal, Brijesh Patel, Amitoj Singh, Aakash Garg, Ulrich P. Jorde, Navin K. Kapur

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

    更新日期:2018-03-22
  • Outcomes After Continuous-Flow Left Ventricular Assist Device Implantation as Destination Therapy at Transplant Versus Nontransplant Centers
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    D. Marshall Brinkley, David DeNofrio, Robin Ruthazer, Amanda R. Vest, Navin K. Kapur, Gregory S. Couper, Michael S. Kiernan

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

    更新日期:2018-03-22
  • Socioeconomic Disparities in Adherence and Outcomes After Heart Transplant
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Brian Wayda, Autumn Clemons, Raymond C. Givens, Koji Takeda, Hiroo Takayama, Farhana Latif, Susan Restaino, Yoshifumi Naka, Maryjane A. Farr, Paolo C. Colombo, Veli K. Topkara

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

    更新日期:2018-03-22
  • Same Story, Different Disease
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Khadijah Breathett

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

    更新日期:2018-03-22
  • Donation After Cardiac Death Heart Transplantation in America Is Clinically Necessary and Ethically Justified
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Taufiek Konrad Rajab, Steve K. Singh

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

    更新日期:2018-03-22
  • Longitudinal Assessment of Vascular Function With Sunitinib in Patients With Metastatic Renal Cell Carcinoma
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Anna B. Catino, Rebecca A. Hubbard, Julio A. Chirinos, Ray Townsend, Stephen Keefe, Naomi B. Haas, Igor Puzanov, James C. Fang, Neeraj Agarwal, David Hyman, Amanda M. Smith, Mary Gordon, Theodore Plappert, Virginia Englefield, Vivek Narayan, Steven Ewer, Chantal ElAmm, Daniel Lenihan, Bonnie Ky

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

    更新日期:2018-03-22
  • Long-Term Cognitive Decline After Newly Diagnosed Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Christa A. Hammond, Natalie J. Blades, Sarwat I. Chaudhry, John A. Dodson, W.T. Longstreth, Susan R. Heckbert, Bruce M. Psaty, Alice M. Arnold, Sascha Dublin, Colleen M. Sitlani, Julius M. Gardin, Stephen M. Thielke, Michael G. Nanna, Rebecca F. Gottesman, Anne B. Newman, Evan L. Thacker

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

    更新日期:2018-03-22
  • Racial Differences in Characteristics and Outcomes of Patients With Heart Failure and Preserved Ejection Fraction in the Treatment of Preserved Cardiac Function Heart Failure Trial
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Eldrin F. Lewis, Brian Claggett, Amil M. Shah, Jiankang Liu, Sanjiv J. Shah, Inder Anand, Eileen O’Meara, Nancy K. Sweitzer, Jean L. Rouleau, James C. Fang, Akshay S. Desai, Tamrat M. Retta, Scott D. Solomon, John F. Heitner, Thomas D. Stamos, Robin Boineau, Bertram Pitt, Marc A. Pfeffer

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

    更新日期:2018-03-22
  • Prevention of PKG-1α Oxidation Suppresses Antihypertrophic/Antifibrotic Effects From PDE5 Inhibition but not sGC Stimulation
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Taishi Nakamura, Guangshuo Zhu, Mark J. Ranek, Kristen Kokkonen-Simon, Manling Zhang, Grace E. Kim, Kenichi Tsujita, David A. Kass

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

    更新日期:2018-03-22
  • Exploring New Cardiovascular Pathways
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Marek Michalak, Paul W. Armstrong

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

    更新日期:2018-03-22
  • Long-Term Caloric Restriction Improves Cardiac Function, Remodeling, Adrenergic Responsiveness, and Sympathetic Innervation in a Model of Postischemic Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Claudio de Lucia, Giuseppina Gambino, Laura Petraglia, Andrea Elia, Klara Komici, Grazia Daniela Femminella, Maria Loreta D’Amico, Roberto Formisano, Giulia Borghetti, Daniela Liccardo, Maria Nolano, Steven R. Houser, Dario Leosco, Nicola Ferrara, Walter J. Koch, Giuseppe Rengo

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

    更新日期:2018-03-22
  • Caloric Restriction as a Therapeutic Approach to Heart Failure
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Pratik B. Sandesara, Laurence S. Sperling

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

    更新日期:2018-03-22
  • Prevalence of Pathogenic Gene Mutations and Prognosis Do Not Differ in Isolated Left Ventricular Dysfunction Compared With Dilated Cardiomyopathy
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Mark R. Hazebroek, Ingrid Krapels, Job Verdonschot, Arthur van den Wijngaard, Els Vanhoutte, Marije Hoos, Luc Snijders, Lieke van Montfort, Maryvonne Witjens, Robert Dennert, Harry J.G.M. Crijns, Hans-Peter Brunner-La Rocca, Han G. Brunner, Stephane Heymans

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

    更新日期:2018-03-22
  • Robotically Guided Left Ventricular Biopsy to Diagnose Cardiac Sarcoidosis
    Circ. Heart Fail. (IF 6.372) Pub Date : 2018-03-01
    Arvind Bhimaraj, Barry Trachtenberg, Miguel Valderrábano

    Sarcoidosis may affect the heart in ≤25% of patients with known involvement of other organs.1 Because of the patchy and unpredictable nature of the infiltrate location, traditional endomyocardial biopsy of the right ventricular septum lacks sensitivity, and imaging and electroanatomic mapping (EAM) guidance can increase sensitivity.2,3 Involved areas may be difficult to reach with standard bioptome. We present a case using robotic assistance to overcome such limitation. A 44-year-old healthy white female presented with syncope and dyspnea on exertion. Her electrocardiogram showed complete atrioventricular block with ventricular escape rhythm. Echocardiogram was normal, but cardiac magnetic resonance showed hypokinesis and hyperenhancement post-gadolinium in the basal anterior septum, right ventricle free wall, and mid anterolateral left ventricular (LV) wall suspicious for infiltrative cardiomyopathy. An electrophysiological study was performed showing inducible monomorphic ventricular tachycardia (VT) leading to a defibrillator placement. Standard biopsy, angiogram, and contrast chest computed tomography were noncontributory. She represented within 2 weeks with multiple defibrillator shocks because of multiple VT episodes, failed amiodarone, and hence an ablation was planned. Empirical …

    更新日期:2018-03-22
  • 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
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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