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  JACC : Heart Failure
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   Full-text available via subscription Subscription journal
   ISSN (Online) 2213-1779
   Published by American College of Cardiology Foundation Homepage  [1 journal]
  • Baroreflex Activation Therapy for the Treatment of Heart Failure With a
           Reduced Ejection Fraction
    • Authors: Abraham WT; Zile MR, Weaver FA, et al.
      Abstract: ObjectivesThe objective of this clinical trial was to assess the safety and efficacy of carotid BAT in advanced HF.BackgroundIncreased sympathetic and decreased parasympathetic activity contribute to heart failure (HF) symptoms and disease progression. Baroreflex activation therapy (BAT) results in centrally mediated reduction of sympathetic outflow and increased parasympathetic activity.MethodsPatients with New York Heart Association (NYHA) functional class III HF and ejection fractions ≤35% on chronic stable guideline-directed medical therapy (GDMT) were enrolled at 45 centers in the United States, Canada, and Europe. They were randomly assigned to receive ongoing GDMT alone (control group) or ongoing GDMT plus BAT (treatment group) for 6 months. The primary safety end point was system- and procedure-related major adverse neurological and cardiovascular events. The primary efficacy end points were changes in NYHA functional class, quality-of-life score, and 6-minute hall walk distance.ResultsOne hundred forty-six patients were randomized, 70 to control and 76 to treatment. The major adverse neurological and cardiovascular event–free rate was 97.2% (lower 95% confidence bound 91.4%). Patients assigned to BAT, compared with control group patients, experienced improvements in the distance walked in 6 min (59.6 ± 14 m vs. 1.5 ± 13.2 m; p = 0.004), quality-of-life score (–17.4 ± 2.8 points vs. 2.1 ± 3.1 points; p < 0.001), and NYHA functional class ranking (p = 0.002 for change in distribution). BAT significantly reduced N-terminal pro–brain natriuretic peptide (p = 0.02) and was associated with a trend toward fewer days hospitalized for HF (p = 0.08).ConclusionsBAT is safe and improves functional status, quality of life, exercise capacity, N-terminal pro–brain natriuretic peptide, and possibly the burden of heart failure hospitalizations in patients with GDMT-treated NYHA functional class III HF. (Barostim Neo System in the Treatment of Heart Failure; NCT01471860; Barostim HOPE4HF [Hope for Heart Failure] Study; NCT01720160)
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • In Search of New Targets and Endpoints in Heart Failure With Preserved
           Ejection Fraction ∗
    • Authors: Borlaug BA.
      Abstract: In Search Of… was an American television series broadcast in the early 1980s that tackled various unsolved mysteries and paranormal phenomena. The show’s stated goal was to “suggest some possible explanations, but not necessarily the only ones, to the mysteries” examined in each episode. Around this very time in the world of medicine, cardiologists began to appreciate that many patients presenting with heart failure (HF) had a relatively preserved ejection fraction (HFpEF) (1). Seminal studies over the past 3 decades have shown us that diastolic dysfunction plays a central role in HFpEF, at least partially “de-mystifying” things, but we continue to search for and suggest other possible explanations. In this light, it has recently been established that many patients with HFpEF develop pulmonary hypertension (PH) and right ventricular dysfunction, and that these abnormalities independently contribute to adverse outcomes in this cohort (2–4). Perhaps novel therapies that target these abnormalities may hold promise in HFpEF.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Relative Importance of History of Heart Failure Hospitalization and
           N-Terminal Pro–B-Type Natriuretic Peptide Level as Predictors
           of Outcomes in Patients With Heart Failure and
           Preserved Ejection Fraction
    • Authors: Kristensen SL; Jhund PS, Køber L, et al.
      Abstract: ObjectivesThe aim of this study was to investigate N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels and recent heart failure (HF) hospitalization as predictors of future events in heart failure – preserved ejection fraction (HF-PEF).BackgroundRecently, doubt has been expressed about the value of a history of HF hospitalization as a predictor of adverse cardiovascular outcomes in patients with HF and HF-PEF.MethodsWe estimated rates and adjusted hazard ratios (HRs) for the composite endpoint of cardiovascular death or HF hospitalization, according to history of recent HF hospitalization and baseline NT-proBNP level in the I-PRESERVE (Irbesartan in Heart Failure with Preserved systolic function) trial.ResultsRates of composite endpoints in patients with (n = 804) and without (n = 1,963) a recent HF hospitalization were 12.78 (95% confidence interval [CI]: 11.47 to 14.24) and 4.49 (95% CI: 4.04 to 4.99) per 100 person-years, respectively (HR: 2.71; 95% CI: 2.33 to 3.16). For patients with NT-proBNP concentrations >360 pg/ml (n = 1,299), the event rate was 11.51 (95% CI: 10.54 to 12.58) compared to 3.04 (95% CI: 2.63 to 3.52) per 100 person-years in those with a lower level of NT-proBNP (n = 1468) (HR: 3.19; 95% CI: 2.68 to 3.80). In patients with no recent HF hospitalization and NT-proBNP ≤360 pg/ml (n = 1,187), the event rate was 2.43 (95% CI: 2.03 to 2.90) compared with 17.79 (95% CI: 15.77 to 20.07) per 100 person-years when both risk predictors were present (n = 523; HR: 6.18; 95% CI: 4.96 to 7.69).ConclusionsRecent hospitalization for HF or an elevated level of NT-proBNP identified patients at higher risk for cardiovascular events, and this risk was increased further when both factors were present.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Hospitalizations and Prognosis in Elderly Patients With Heart Failure
           and Preserved Ejection Fraction Time to Treat the Whole Patient
    • Authors: Kitzman DW; Upadhya B, Reeves G.
      Abstract: In the comic strip Peanuts, Charlie Brown allows his optimism and narrow focus to override his repeated objective experiences. He rushes at the football, only to have Lucy yank it away while he is in perfect midkick. Charlie launches into the air and falls, defeated again. This could be an appropriate metaphor for our approach to date to heart failure (HF) with preserved ejection fraction (HFpEF), the dominant form of HF in elderly persons. It seemed logical to assume that in patients selected for HF, cardiac factors would be the dominant if not the sole contributor to pathophysiology and the key to effective therapy. However, after more than 2 decades of research pursuing this paradigm, the objective evidence suggests that HFpEF is far more complex and that a broader view is needed.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Time for Recognition
    • Authors: O’Connor CM.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Correction
    • Abstract: Kiernan MS, Gregory D, Sarnak MJ, Rossignol P, Massaro J, Kociol R, Zannad F, Konstam MA.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Cardiac Resynchronization Therapy in the Autumn of Life ∗
    • Authors: Al-Khatib SM.
      Abstract: To implant or not to implant a primary prevention implantable-cardioverter defibrillator (ICD) in older patients is a question that has challenged clinicians for years. On the one hand, the ICD is a highly effective therapy for the prevention of sudden cardiac death. On the other hand, there are no definitive data regarding the benefit of the ICD in older patients. Indeed, in the pivotal randomized clinical trials that demonstrated the efficacy of the ICD, the mean or median age of enrolled patients was well below 75 years of age (1–4). There are reasons why older patients may not derive survival benefit from the ICD. Such patients typically have heart failure along with other comorbidities that may attenuate the efficacy of the ICD. Older patients may also be frail, and this, along with the coexisting diseases, may make the device implantation risky and negatively impact their quality of life, raising concerns about therapies, like the ICD, that prolong life but do not necessarily improve its quality. However, when the ICD is coupled with cardiac resynchronization therapy (CRT), there is potential for improved quality of life and reduced heart failure hospitalizations, 2 important goals in the care of heart failure patients.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Does Age Influence Cardiac Resynchronization Therapy Use
           and Outcome'
    • Authors: Heidenreich PA; Tsai V, Bao H, et al.
      Abstract: ObjectivesThis study sought to describe the use of CRT-D and its association with survival for older patients.BackgroundMany patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) in practice are older than those included in clinical trials.MethodsWe identified patients undergoing ICD implantation in the National Cardiovascular Disease Registry (NCDR) ICD registry from 2006 to 2009, who also met clinical trial criteria for CRT, including left ventricular ejection fraction (LVEF) ≤35%, QRS ≥120 ms, and New York Heart Association (NYHA) functional class III or IV. NCDR registry data were linked to the social security death index to determine the primary outcome of time to death from any cause. We identified 70,854 patients from 1,187 facilities who met prior trial criteria for CRT-D. The mean age of the 58,147 patients receiving CRT-D was 69.4 years with 6.4% of patients age 85 or older. CRT use was 80% or higher among candidates in all age groups. Follow-up was available for 42,285 patients age ≥65 years at 12 months.ResultsReceipt of CRT-D was associated with better survival at 1 year (82.1% vs. 77.1%, respectively) and 4 years (54.0% vs. 46.2% , respectively) than in those receiving only an ICD (p < 0.001). The CRT association with improved survival was not different for different age groups (p = 0.86 for interaction).ConclusionsMore than 80% of older patients undergoing ICD implantation who were candidates for a CRT-D received the combined device. Mortality in older patients undergoing ICD implantation was high but was lower for those receiving CRT-D.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Predict, Protect, Prevent Working Toward a Personalized Approach
           to Heart Failure Prevention ∗
    • Authors: McDonald K; Murphy T.
      Abstract: The growing prevalence of heart failure (HF) poses a significant health and economic challenge (1). Although there are have been significant improvements in therapy, the outlook for patients with established HF remains poor. Therefore, a change in strategy is required, directing attention to prevention of symptomatic HF.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Prognostic Significance and Determinants of the 6-Min Walk Test
           in Patients With Heart Failure and Preserved
           Ejection Fraction
    • Authors: Zotter-Tufaro C; Mascherbauer J, Duca F, et al.
      Abstract: ObjectivesThis study sought to define the prognostic significance and clinical determinants of the 6-min walk distance (6-MWD) in affected patients.BackgroundSymptoms of exertional fatigue and dyspnea, as well as a reduced exercise tolerance, are cardinal features of pulmonary hypertension associated with heart failure and preserved ejection fraction (PH-HFpEF). Mechanisms limiting exercise capacity in this specific entity remain incompletely understood.MethodsConsecutive patients with PH-HFpEF, as confirmed by right heart catheter, were enrolled in our prospective registry. Hospitalization for HF and/or death for cardiac reasons were defined as primary outcome. Multiple regression models were constructed to establish determinants of the 6-MWD. For quantification of left ventricular (LV) extracellular matrix (ECM), myocardial biopsies were taken from 18 patients.ResultsBetween December 2010 and July 2013, 142 PH-HFpEF patients were included in the study. After a mean follow-up of 14.0 ± 10.0 months, 43 patients (30.3%) reached the combined endpoint. The 6-MWD was found to be an independent predictor of outcome and was influenced by a variety of clinical, echocardiographic, hemodynamic, laboratory, and pulmonary parameters. There was a significant inverse correlation between the 6-MWD and the extent of ECM in the LV myocardium.ConclusionsImpaired exercise capacity in PH-HFpEF patients is explained by cardiac and noncardiac factors. The 6-MWD predicts outcome and may be a useful endpoint in clinical trials.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Pulmonary Arterial Capacitance Is an Important Predictor of Mortality in
           Heart Failure With a Preserved Ejection Fraction
    • Authors: Al-Naamani N; Preston IR, Paulus JK, et al.
      Abstract: ObjectivesThe purpose of this study was to determine the predictors of mortality in patients with pulmonary hypertension (PH) associated with heart failure with preserved ejection fraction (HFpEF).BackgroundPH is commonly associated with HFpEF. The predictors of mortality for patients with these conditions are not well characterized.MethodsIn a prospective cohort of patients with right heart catheterization, we identified 73 adult patients who had pulmonary hypertension due to left heart disease (PH-LHD) associated with HFpEF (left ventricular ejection fraction ≥50% by echocardiography); hemodynamically defined as a mean pulmonary artery pressure ≥25 mm Hg and pulmonary artery wedge pressure >15 mm Hg. PH severity was classified according to the diastolic pressure gradient (DPG). Cox proportional hazards ratios were used to estimate the associations between clinical variables and mortality. Receiver-operating characteristic curves were used to evaluate the ability of hemodynamic measurements to predict mortality.ResultsThe mean age for study subjects was 69 ± 12 years and 74% were female. Patients classified as having combined post-capillary PH and pre-capillary PH (DPG ≥7) were not at increased risk of death as compared to patients with isolated post-capillary PH (DPG 
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Older Adults, “Malignant” Left Ventricular Hypertrophy,
           and Associated Cardiac-Specific Biomarker Phenotypes to Identify the
           Differential Risk of New-Onset Reduced Versus
           Preserved Ejection Fraction Heart Failure CHS
           (Cardiovascular Health Study)
    • Authors: Seliger SL; de Lemos J, Neeland IJ, et al.
      Abstract: ObjectivesThis study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart failure (HF) risk among older adults with left ventricular hypertrophy (LVH).BackgroundThe natural history of LVH, an important risk factor for HF, is heterogeneous.MethodsNT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression.ResultsPrevalence of LVH was 12.5% among 2,347 participants with complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers.ConclusionsThe combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH to HF and suggest modifiable targets for prevention.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • Inside This Issue
    • PubDate: Mon, 01 Jun 2015 00:00:00 GMT
  • The Hospitalization Burden and Post-Hospitalization Mortality Risk in
           Heart Failure With Preserved Ejection Fraction Results From the
           I-PRESERVE Trial (Irbesartan in Heart Failure and Preserved
           Ejection Fraction)
    • Authors: Carson PE; Anand IS, Win S, et al.
      Abstract: ObjectivesThe aim of this study was to investigate prognosis in patients with heart failure (HF) with preserved ejection fraction and the causes of hospitalization and post-hospitalization mortality.BackgroundAlthough hospitalizations in patients with HF with preserved ejection fraction are common, there are limited data from clinical trials on the causes of admission and the influence of hospitalizations on subsequent mortality risk.MethodsPatients (n = 4,128) with New York Heart Association functional class II to IV HF and left ventricular ejection fractions >45% were enrolled in I-PRESERVE (Irbesartan in Heart Failure and Preserved Ejection Fraction). A blinded events committee adjudicated cardiovascular hospitalizations and all deaths using predefined and standardized definitions. The risk for death after HF, any-cause, or non-HF hospitalization was assessed using time-dependent Cox proportional hazard models.ResultsA total of 2,278 patients had 5,863 hospitalizations during the 49 months of follow-up, of which 3,585 (61%) were recurrent hospitalizations. For any-cause hospitalizations, 26.5% of patients died during follow-up, with an incident mortality rate of 11.1 deaths per 100 patient-years (PYs) and an adjusted hazard ratio of 5.32 (95% confidence interval: 4.21 to 6.23). Overall, 53.6% of hospitalizations were classified as cardiovascular and 43.7% as noncardiovascular, with 2.7% not classifiable. HF was the largest single cause of initial (17.6%) and overall (21.1%) hospitalizations, although, after HF hospitalization, a substantially higher proportion of readmissions were due to primary HF causes (40%). HF hospitalization occurred in 685 patients, with 41% deaths during follow-up, an incident mortality rate of 19.3 deaths per 100 PYs. The adjusted hazard ratio was 2.93 (95% confidence interval: 2.40 to 3.57) relative to patients who were not hospitalized for HF and was greater in those with longer durations of hospitalization. There were 1,593 patients with only non-HF hospitalizations, 21% of whom died during follow-up, with an incident mortality rate of 8.7 deaths per 100 PYs and an adjusted hazard ratio of 4.25 (95% confidence interval: 3.27 to 5.32). The risk for death was highest in the first 30 days and declined over time for all hospitalization categories. Patients not hospitalized for HF or for any cause had observed incident mortality rates of 3.8 and 1.3 deaths per 100 PYs, respectively.ConclusionsIn I-PRESERVE, HFpEF patients hospitalized for any reason, and especially for HF, were at high risk for subsequent death, particularly early. The findings support the need for careful attention in the post-discharge time period including attention to comorbid conditions. Among those hospitalized for HF, the high mortality rate and increased proportion of readmissions due to HF (highest during the first 30 days), suggest that this group would be an appropriate target for investigation of new interventions.
      PubDate: Mon, 01 Jun 2015 00:00:00 GMT
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