Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial

Yusuf, Salim; Pfeffer, Marc A.; Swedberg, Karl; Granger, Christopher B.; Held, Peter; McMurray, John J.V.; Michelson, Eric L.; Olofsson, Bertil; Östergren, Jan

doi:10.1016/s0140-6736(03)14285-7

Cited by 2,637 publications

(1,844 citation statements)

References 15 publications

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“…Lowering neurohormonal activation has unexpectedly failed to improve clinical outcome in large, placebo‐controlled, randomized HFpEF trials 20, 21, 22, 23, 24. Diagnostic uncertainties may partially account for the lack of therapeutic benefit 29, 76, 77.…”

Section: Aging Phenotypementioning

confidence: 99%

“…The large, all‐inclusive, randomized, placebo‐controlled therapeutic trials approach that led to great therapeutic progress in HFrEF has not worked so far in HFpEF 20, 21, 22, 23, 24, 25, 26, 27. Such discrepancy is, in part, attributable to overt differences in the pathogenesis and progression of HFpEF and HFrEF.…”

Section: Future Directionsmentioning

confidence: 99%

“…However, little therapeutic progress was made 20, 21, 22, 23, 24, 25, 26, 27. Among the issues that may account for the modest therapeutic progress, one appears to be overwhelming: HFpEF is not a well‐defined clinical entity: It is an amalgam of cardiovascular, metabolic, renal, and geriatric conditions 28, 29.…”

Section: Introductionmentioning

confidence: 99%

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Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

Samson

Jaiswal

Ennezat

et al. 2016

JAHA

109

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Section: Aging Phenotypementioning

confidence: 99%

Section: Future Directionsmentioning

confidence: 99%

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Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

Samson

Jaiswal

Ennezat

et al. 2016

JAHA

109

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“…Although substantial progress has been made in the management and outcomes of heart failure with reduced ejection fraction (HFREF), outcomes associated with HFPEF remain unchanged 1, 2. Well‐established pharmacological therapies for HFREF have failed to improve prognosis in HFPEF 3, 4, 5, 6. This has largely been attributed to the phenotypic variability and the complex pathophysiological mechanisms underlying the development of HFPEF 7…”

mentioning

confidence: 99%

Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta‐Analysis and Systematic Review

Pandey

Garg

Matulevicius

et al. 2015

JAHA

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BackgroundThere has been an increasing interest in use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure with preserved ejection fraction (HFPEF). However, a comprehensive evaluation of MRA effects on left ventricular (LV) structure and function in these patients is lacking. In this meta‐analysis, we evaluated the effects of MRAs on LV structure and function among patients with diastolic dysfunction or HFPEF.Methods & ResultsRandomized, controlled clinical trials evaluating the efficacy of MRAs in patients with diastolic dysfunction or HFPEF were included. The primary outcome was change in E/e’, a specific measure of diastolic function. Secondary outcomes included changes in other measures of diastolic function, LV structure, surrogate markers for myocardial fibrosis (carboxy‐terminal peptide of procollagen type I [PICP] and amino‐terminal peptide of pro‐collagen type‐II [PIIINP]), blood pressure, and exercise tolerance. In the pooled analysis, MRA use was associated with significant reduction in E/e’ (weighted mean difference [WMD] [95% confidence interval {CI}]: −1.68 [−2.03 to −1.33]; P<0.0001) and deceleration time (WMD [95% CI]: −12.0 ms [−23.3 to −0.7]; P=0.04) as compared with control, suggesting and improvement in diastolic function. Furthermore, blood pressure and levels of PIIINP and PICP were also significantly reduced with MRA therapy with no significant change in LV mass or dimensions.Conclusion MRA therapy in patients with asymptomatic diastolic dysfunction or HFPEF is associated with significant improvement in diastolic function and markers of cardiac fibrosis without a significant change in LV mass or dimensions.

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“…The prevalence of HF with preserved ejection fraction (HFpEF) is high and increasing, making HFpEF a continuously growing public health problem 1, 2. Morbidity and mortality in HFpEF are quite similar to HF with reduced ejection fraction (HFrEF), but no effective pharmacological treatment has been identified so far3, 4, 5, 6 and a successful management of the disease remains elusive 2. Therefore, an intensified search for prevention and treatment strategies in HFpEF is of global interest.…”

Section: Introductionmentioning

confidence: 99%

Amount or intensity? Potential targets of exercise interventions in patients with heart failure with preserved ejection fraction

et al. 2017

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AimsHeart failure with preserved ejection fraction (HFpEF) remains a common condition with no pharmacological treatment. Physical activity (PA) improves symptoms and quality of life (QoL), but no clear recommendations exist on PA in HFpEF patients. We investigated the association of PA (amount/intensity) on clinical phenotype in HFpEF.Methods and resultsThe Aldosterone in Diastolic Heart Failure trial investigated spironolactone vs. placebo in stable HFpEF patients. At baseline, all patients underwent detailed phenotypization including echocardiography, cardiopulmonary exercise testing, 6 minute walking test (6MWT), and QoL assessment (36‐item Short‐Form questionnaire). PA was assessed by a self‐report questionnaire, classified in metabolic equivalents of task (MET) and analysed with regard to exercise capacity, diastolic function, and QoL. Four hundred twenty‐two patients (52% women, age 67 ± 8 years, New York Heart Association II and III) were classified by weekly MET hours into a low (<70), middle (70–140), or high (>140) level of PA. Total PA correlated positively with 6MWT distance (r = 0.17; P = 0.002) and physical function of QoL (r = 0.10; P = 0.05), but not with peak oxygen uptake (peakVO2). In contrast, both 6MWT distance and peakVO2 were significantly higher in patients who performed high‐intensity PA for >8 h/week (P < 0.001, P = 0.02, respectively). Time of high‐intensity PA was related to higher 6MWT distance (r = 0.21, P < 0.001), peakVO2, and better physical function of QoL (both r = 0.13, P = 0.01), whereas low‐intensity PA did not show significant associations. Interestingly, PA was not related to any measure of diastolic function.ConclusionsA higher amount of PA is related to higher submaximal exercise capacity and physical function of QoL. Regarding maximal exercise capacity, only high‐intensity PA showed significant association in HFpEF patients.

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Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial

Cited by 2,637 publications

References 15 publications

Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

Effect of Mineralocorticoid Receptor Antagonists on Cardiac Structure and Function in Patients With Diastolic Dysfunction and Heart Failure With Preserved Ejection Fraction: A Meta‐Analysis and Systematic Review

Amount or intensity? Potential targets of exercise interventions in patients with heart failure with preserved ejection fraction

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