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Heart Failure

Effect of caloric restriction on heart failure with preserved ejection fraction

2 Feb, 16 | by flee

Therapies that improve outcomes are lacking for heart failure with preserved ejection fraction (HFpEF). The impact of exercise and diet interventions on HFpEF patients has not been studied.  In this single center study of 100 patients,  the effect of caloric restriction (~400 kcal/day) and or aerobic exercise training (3x a week hour long supervised sessions) on co-primary outcomes of exercise capacity (measured by peak oxygen consumption) and quality of life (QOL) (measured by the Minnesota Living with Heart Failure Questionnaire) were evaluated using a 2×2 factorial design,.  Additional exploratory outcomes included: exercise time, 6-minute walk distance, ventilator anaerobic threshold, ventilation/carbon dioxide output slope, other QOL measures (Kansas City Cardiomyopathy Questionnaire, 36-item Short-Form Health Survey), and left ventricular mass and volume. Patient included were obese (BMI >30) with HFpEF (EF ≥ 50%) without segmental wall motion abnormalities, significant valvular or ischemic disease, or pulmonary disease.  The majority of patients in this trial were female, NYHA class II or III, hypertensive, and on diuretic therapy.Both diet and exercise interventions significantly increased exercise capacity (peak VO2, diet 1.3ml/kg body mass/min, 95% CI 0.8-1.8, P <0.001 and exercise, 1.2ml/kg body mass/min, 95% CI, 0.7-1.7, p <0.001) and had an additive effect with improvement in peak VO2 of 2.5ml/kg/min.  There was no difference in QOL by MLHF with either diet or exercise (exercise, -1 unit, 95% -8-5, p 0.7; diet -6 unit, -12-1, p 0.08).


Conclusion: Although the 20-week diet and exercise interventions improved peak VO2 amongh patients with HFpEF, the lack of improvement in QOL scores raise questions about the clinical significance of these findings.  While diet and exercise may not significantly impact HRpEF symptoms, optimizing diet and exercise remains central to cardiovascular health.


Summarized by Lauren E. Thompson and Steven M. Bradley


Kitzman DW, et al. Effect of Caloric Restriction or Aerobic Exercise Training
on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction
A Randomized Clinical Trial. JAMA. 2016 Jan 5;315(1):36-46

Adaptive servo-ventilation increases mortality in systolic heart failure

22 Oct, 15 | by flee

Central sleep-apnea (CSA) with associated Cheyne-Stokes breathing patterns effects up to 40% of patients with low ejection fraction heart failure.   Given that CSA is an independent marker for poor prognosis and mortality, treatment of CSA has been identified as a potential target to improve heart failure outcomes.  This study randomized 1325 patients with low ejection fraction heart failure (mean EF 32%) and a diagnosis of CSA to either overnight adaptive servo-ventilation or guideline directed medical therapy alone. Adaptive servo-ventilation (ASV) is a noninvasive therapy that provides inspiratory pressure support in addition to expiratory positive airway pressure.  Trial patients were followed for a mean of 31 months, with a primary composite end-point of all-cause mortality, hospitalization for heart failure or life-saving cardiac intervention.  Although ASV resulted in a significant decrease in the apnea-hypopnea index among patients in the intervention arm, suggesting the treatment was effective in alleviating CSA.  However, ASV treatment of CSA resulted in increased all-cause mortality (hazard ratio, 1.28; 95% CI, 1.06 to 1.55; P=0.01) and cardiovascular mortality (hazard ratio, 1.34; 95% CI, 1.09 to 1.65; P=0.006) in this population of patients with low ejection fraction. more…

Quality of Life following Coronary Artery Bypass Graft Surgery versus Guideline-based Medical Therapy in Ischemic Cardiomyopathy  

14 Oct, 14 | by Alistair Lindsay

It remains uncertain if surgical revascularization improves patient outcomes in the setting of coronary artery disease with reduced systolic function. This is particularly true in light of the STICH trial, a contemporary randomized control trial of coronary artery bypass graft surgery (CABG) with optimal medical therapy compared to optimal medical therapy alone in patients with ischemic left ventricular dysfunction. The primary results of the STICH trial demonstrated no overall mortality benefit to CABG with medical therapy compared to medical therapy alone. In this study, the trial authors report quality of life outcomes from the STICH trial. The trial randomized 1212 patients with an ejection fraction ≤35% with coronary anatomy suitable for surgical revascularization to either CABG with medical therapy or medical therapy alone. more…

Beta-blockers in heart failure – what is the impact of concurrent atrial fibrillation?            

14 Oct, 14 | by Alistair Lindsay

Beta-blockers form an essential cornerstone of therapy for heart failure with reduced ejection fraction. However, the benefits of beta-blockade for heart failure in patients with concurrent atrial fibrillation are less certain. In this meta-analysis of individual-patient data from 10 randomized control trials comparing beta-blockers to placebo for systolic heart failure, investigators assessed the impact of beta-blockade by the presence of sinus rhythm or atrial fibrillation at baseline. Of the 18,254 patients assessed, 76% were in sinus rhythm and 17% were in atrial fibrillation at baseline. Over 1.5 years of mean follow-up, beta-blocker therapy was associated with a significant mortality benefit in sinus rhythm patients (HR 0.73, 0.67-0.80; p<0.001) but not in patients with atrial fibrillation (HR 0.97, 0.83-1.14; p=0.73). Results did not vary by subgroup of patients with atrial fibrillation or for secondary outcomes which included cardiovascular death, cardiovascular hospital admission, and non-fatal stroke. more…

A new PARADIGM in heart failure treatment?

14 Oct, 14 | by Alistair Lindsay

Natriuretic peptides are released in response to cardiac-wall stress and other stimuli of heart failure. These potent natriuretic and vasodilatory peptides also inhibit the renin-angiotensin system and sympathetic drive. The neutral endopeptidase neprilysin is responsible for the degradation of several of these natriuretic peptides. Inhibition of neprilysin increases the level of these natriuretic peptides, thus potentially enhancing the beneficial effects of standard therapies to suppress the renin angiotensin system. In the PARADIGM-HF randomized controlled trial, the ACE inhibitor enalapril at a dose of 10mg twice a day was compared with the experimental drug LCZ696, which was a combination of the ARB valsartan and the neprilysin inhibitor sacubitril. This combination was chosen in response to prior studies that demonstrated combining a neprilysin inhibitor with an ARB reduced the risk of angioedema. more…

Spironolactone for heart failure with preserved ejection fraction

8 Jun, 14 | by Alistair Lindsay

Nearly half of all patients presenting with heart failure have normal or near normal left ventricular systolic function.  Optimal treatment strategies for this large patient group remain unclear.  Small mechanistic studies have suggested diastolic function may be improved by mineralocorticoid-receptor antagonists.  Whether this mechanistic benefit translates into better patient outcomes is not known.  In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, 3445 patients with heart failure and an ejection fraction of 45% or more were randomised in a double-blind fashion to either spironolactone (15 to 45 mg daily) or placebo.  The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure with patients.  Over a mean follow-up period of 3.3 years, the primary outcome occurred in 18.6% of the spironolactone group and 20.4% of the placebo group (HR, 0.89; 95% CI, 0.77 to 1.04; P=0.14).  Compared with placebo, spironolactone resulted in a statistically significant reduction in hospitalizations for heart failure (206 patients vs. 245 patients, HR, 0.83; 95% CI, 0.69 to 0.99, P=0.04).  Use of spironolactone came at a cost of increased rates of hyperkaliemia (18.7%, vs. 9.1%), but no differences in serious adverse events. more…

Mesenchymal stem cells may improve quality of life for patients with ischemic cardiomyopathy

13 Apr, 14 | by Alistair Lindsay

In this study, patients with chronic ischemic cardiomyopathy and EF <50% on optimal medical therapy were randomized to autologous culture expanded mesenchymal cells (=22), autologous bone marrow mononuclear cells (n=22) or placebo vehicle (n=21) delivered by transendocardial stem cell injection (TESI). There were no serious adverse events among any patients undergoing a TESI procedure. Rates of major adverse cardiovascular events did not vary between groups. A possible signal of improved quality of life was observed following treatment with either of the cell types.  At one year, a repeated measures model demonstrated the Minnesota Living with Heart Failure score had improved following treatment with mesenchymal (-6.3; 95% CI -15.0 to 2.4, P=.02) or bone marrow cells (-8.2; 95% CI -17.4 to 0.97, P=.005) but not in the placebo group (0.4; 95% CI -9.45 to 10.25, P=.38). Only mesenchymal cells decreased scar size as a percentage of the LV mass (-18.9%; 95% CI  -30.4 to -7.4, P=.004). more…

No renal protection with low-dose dopamine or nesiritide in acute heart failure

13 Apr, 14 | by Alistair Lindsay

Diuresis to decongest patients with acute heart failure (AHF) is particularly challenging in the setting of renal dysfunction, as these patients are at risk of worsening renal function.  Small studies have suggested that low-dose dopamine or nesiritide may increase urine output and maintain renal function in such patients. The Renal Optimization Strategies Evaluation (ROSE) trial randomized 360 patients with AHF and renal dysfunction (GFR 15-60ml/min/1.73m2) to nesiritide, low-dose dopamine, or placebo in addition to an intravenous loop diuretic. Primary outcomes included urine volume and change in cystatin C at 72-hours post-randomization. Compared to placebo, patients randomized to low-dose dopamine had similar 72-hour urine volumes (8524mL vs. 8296mL, p=0.59) and cystatin C levels (0.12 vs. 0.11mg/L, p=0.72). In addition, there was no change in weight or creatinine at 72 hours. Similarly, patients randomized to low-dose nesiritide demonstrated no better 72-hour urine volumes (8574 mL vs. 8296 mL, p=0.49), cystatin C levels (0.07 vs. 0.11 mg/L, p=0.36), weight or creatinine. more…

Sudden increase in LVAD thrombosis rates

13 Apr, 14 | by Alistair Lindsay

The left ventricular assist device (LVAD) has rapidly been incorporated into the management of patients with advanced heart failure.  In response to an internal audit demonstrating a rapid increase in the incidence of pump thrombosis following implantation of HeartMate II LVADs, the authors pooled data from additional centers to investigate this trend.  The resultant retrospective analysis of 895 HeartMate II LVADs implanted in 837 patients identified 72 confirmed pump thrombosis in 66 patients and an additional 36 suspected thrombosis. Starting in the spring of 2011, the incidence of thrombosis at 3 months from implant rose from 2.2% to 8.4% by early 2013.  Levels of LDH and in particular a doubling in levels in the previous week were highly predictive of thrombosis.  Thrombosis was associated with substantial morbidity and mortality with 11 patients receiving urgent transplantation and a further 20 requiring pump replacement.  Mortality in those not undergoing a surgical procedure was 48.2% in the following 6 months.  more…

No Benefit from Cardiac Resynchronization Therapy in Patients with a Narrow QRS Complex

28 Nov, 13 | by Alistair Lindsay

Cardiac-resynchronization therapy (CRT) has known benefits in patients with severe left ventricular systolic dysfunction and prolonged QRS duration (>120 ms).  However, up to half of patients with systolic dysfunction appear to have left ventricular dyssynchrony by echocardiographic measures, despite a QRS duration of less than 120 ms.  As a result, CRT is often used for patients with echocardiographic evidence of dyssynchrony and a narrow QRS complex, despite a lack of clear benefit to this approach.  The Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) study sought to determine the effect of CRT on patient outcomes in the setting of symptomatic heart failure, echocardiographic findings of dyssynchrony, and QRS duration <120 ms. more…

Highlighted articles from non-cardiological journals relevant to cardiology.


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