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Spironolactone and preserved heart failure

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https://www.readbyqxmd.com/read/29709099/biomarker-based-phenotyping-of-myocardial-fibrosis-identifies-patients-with-heart-failure-with-preserved-ejection-fraction-resistant-to-the-beneficial-effects-of-spironolactone-results-from-the-aldo-dhf-trial
#1
Susana Ravassa, Tobias Trippel, Doris Bach, Diana Bachran, Arantxa González, Begoña López, Rolf Wachter, Gerd Hasenfuss, Christian Delles, Anna F Dominiczak, Burkert Pieske, Javier Díez, Frank Edelmann
BACKGROUND: Myocardial fibrosis is characterized by excessive cross-linking and deposition of collagen type I and is involved in left ventricular stiffening and left ventricular diastolic dysfunction (LVDD). We investigated whether the effect of spironolactone on LVDD in patients with heart failure with preserved ejection fraction (HFpEF) depends on its effects on collagen cross-linking and/or deposition. METHODS AND RESULTS: We investigated 381 HFpEF patients from the multicentre, randomized, placebo-controlled Aldo-DHF trial with measures of the E:e' ratio...
April 30, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29664406/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
#2
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...
March 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29572190/incident-hyperkalemia-hypokalemia-and-clinical-outcomes-during-spironolactone-treatment-of-heart-failure-with-preserved-ejection-fraction-analysis-of-the-topcat-trial
#3
Akshay S Desai, Jiankang Liu, Marc A Pfeffer, Brian Claggett, Jerome Fleg, Eldrin F Lewis, Sonja McKinlay, Eileen O'Meara, Sanjiv J Shah, Nancy K Sweitzer, Scott Solomon, Bertram Pitt
BACKGROUND: In patients with heart failure and preserved ejection fraction (HF-PEF) randomized in the Americas (but not Russia and Georgia) as part of the TOPCAT trial, treatment with spironolactone enhanced the risk of hyperkalemia but reduced the risk of hypokalemia. We examined the clinical correlates and prognostic implications of incident hypo- and hyperkalemia during study follow up. METHODS: We defined the region-specific incidence of hypokalemia (potassium [K+ ]<3...
March 20, 2018: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/29501806/sudden-death-in-heart-failure-with-preserved-ejection-fraction-a-competing-risks-analysis-from-the-topcat-trial
#4
Muthiah Vaduganathan, Brian L Claggett, Neal A Chatterjee, Inder S Anand, Nancy K Sweitzer, James C Fang, Eileen O'Meara, Sanjiv J Shah, Sheila M Hegde, Akshay S Desai, Eldrin F Lewis, Jean Rouleau, Bertram Pitt, Marc A Pfeffer, Scott D Solomon
BACKGROUND: Sudden death (SD) may be an important mode of death in heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: To investigate rates and predictors of SD or aborted cardiac arrest (ACA) in HFpEF. METHODS: We studied 1,767 patients with HFpEF (EF≥45%) enrolled in the Americas region of the TOPCAT trial. We identified independent predictors of composite SD/ACA with step-wise backward selection using competing risks regression analysis accounting for non-sudden causes of death...
March 4, 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29493068/derangements-in-adrenergic-adipokine-signalling-establish-a-neurohormonal-basis-for-obesity-related-heart-failure-with-a-preserved-ejection-fraction
#5
REVIEW
Milton Packer
Among patients with heart failure and a preserved ejection (HFpEF), obesity is associated with a distinct phenotype that is characterized by adiposity-driven plasma volume expansion and cardiac overfilling, which is coupled with an impairment of ventricular distensibility. These pathophysiological abnormalities may be related to the increased actions of specific adipocyte-derived signalling molecules (aldosterone, neprilysin and leptin) that work in concert with increased renal sympathetic nerve traffic and activated beta2 -adrenergic receptors to promote sodium retention, microvascular rarefaction, cardiac fibrosis and systemic inflammation...
May 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29411216/pharmacological-treatments-for-heart-failure-with-preserved-ejection-fraction-a-systematic-review-and-indirect-comparison
#6
REVIEW
Kwadwo Osei Bonsu, Poukwan Arunmanakul, Nathorn Chaiyakunapruk
Pharmacological interventions for heart failure with preserved ejection fraction (HFpEF) have failed to reduce mortality and hospitalization. Evidence for mineralocorticoid antagonists (MRAs), β-adrenoceptor blockers (β-blockers), and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs)-to reduce clinical outcomes in HFpEF remains unclear. We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Clinical Trials.gov for randomized controlled trials (RCTs) assessing pharmacological treatments in HFpEF diagnosed according the recommendations of the European Society of Cardiology (ESC) 2016 guidelines from inception to August, 2017...
March 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29248640/association-of-active-and-passive-components-of-lv-diastolic-filling-with-exercise-intolerance-in-heart-failure-with-preserved-ejection-fraction-mechanistic-insights-from-spironolactone-response
#7
Wojciech Kosmala, Monika Przewlocka-Kosmala, Thomas H Marwick
OBJECTIVES: This study sought to investigate the association of left ventricular (LV) untwisting rate (UT) and E/e' ratio with the response of exercise capacity to spironolactone in heart failure with preserved ejection fraction (HFpEF). BACKGROUND: In most patients with HFpEF, LV filling abnormalities represent a central component in the development of dyspnea. LV diastolic filling is determined by the interplay of passive (LV stiffness and myocardial collagen content, reflected by E/e' ratio) and active myocardial properties (UT, a precursor to isovolumic pressure decay and contributor to diastolic suction)...
December 8, 2017: JACC. Cardiovascular Imaging
https://www.readbyqxmd.com/read/29228101/spironolactone-and-resistant-hypertension-in-heart-failure-with-preserved-ejection-fraction
#8
Patrick Rossignol, Brian Lee Claggett, Jiankang Liu, Orly Vardeny, Bertram Pitt, Faiez Zannad, Scott Solomon
BACKGROUND: Recent evidence suggests that the mineralocorticoid receptor antagonist spironolactone should be the preferred fourth-line antihypertensive treatment in resistant hypertension (RHTN). Whether spironolactone improves blood pressure (BP) control in heart failure with preserved ejection fraction (HFpEF) and RHTN is unknown. METHODS: We identified patients with RHTN, defined as baseline systolic blood pressure (SBP) between 140 and 160 mm Hg on 3 or more medications, in the Americas cohort of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial, in which patients with HFpEF were randomized to spironolactone vs...
March 10, 2018: American Journal of Hypertension
https://www.readbyqxmd.com/read/29210202/amount-or-intensity-potential-targets-of-exercise-interventions-in-patients-with-heart-failure-with-preserved-ejection-fraction
#9
Anna Bobenko, Inke Bartels, Marlene Münch, Tobias Trippel, Ruhdja Lindhorst, Kathleen Nolte, Christoph Herrmann-Lingen, Martin Halle, André Duvinage, Hans-Dirk Düngen, Götz Gelbrich, Carsten Tschöpe, Gerd Hasenfuss, Rolf Wachter, Burkert Pieske, Frank Edelmann
AIMS: Heart 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 RESULTS: The Aldosterone in Diastolic Heart Failure trial investigated spironolactone vs. placebo in stable HFpEF patients...
February 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29148144/systolic-blood-pressure-and-cardiovascular-outcomes-in-heart-failure-with-preserved-ejection-fraction-an-analysis-of-the-topcat-trial
#10
Senthil Selvaraj, Brian Claggett, Sanjiv J Shah, Inder Anand, Jean L Rouleau, Akshay S Desai, Eldrin F Lewis, Bertram Pitt, Nancy K Sweitzer, Marc A Pfeffer, Scott D Solomon
AIMS: Recent guidelines have advocated for stricter systolic blood pressure (SBP) control in heart failure with preserved ejection fraction (HFpEF), though data regarding the optimal SBP in HFpEF are sparse. METHODS AND RESULTS: We analysed participants from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study with available baseline and 8-week visit SBP data (n = 1645). We related baseline SBP to several efficacy and safety outcomes...
March 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29034087/spironolactone-in-cardiovascular-disease-an-expanding-universe
#11
REVIEW
John W Funder
Spironolactone has been marketed for over half a century as a 'potassium-sparing diuretic', used primarily in patients with ascites. With the realization that primary aldosteronism is the most common (5-13%) form of secondary hypertension, it has become widely used as a mineralocorticoid receptor antagonist. More recently, in the wake of the RALES trial, spironolactone in addition to standard therapy has been shown to be very beneficial in heart failure with a reduced ejection fraction. Despite the failure of the TOPCAT trial, spironolactone is being increasingly used in diastolic heart failure (i...
2017: F1000Research
https://www.readbyqxmd.com/read/28768320/effects-of-sodium-glucose-cotransporter-2-inhibitors-for-the-treatment-of-patients-with-heart-failure-proposal-of-a-novel-mechanism-of-action
#12
Milton Packer, Stefan D Anker, Javed Butler, Gerasimos Filippatos, Faiez Zannad
Importance: Only 1 class of glucose-lowering agents-sodium-glucose cotransporter 2 (SGLT2) inhibitors-has been reported to decrease the risk of cardiovascular events primarily by reducing the risk of the development or progression of heart failure. In a landmark trial called Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes [EMPA-REG Outcomes], long-term treatment with empagliflozin prevented fatal and nonfatal heart failure events but did not reduce the risk of myocardial infarction or stroke in diabetic patients...
September 1, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28647918/designing-future-clinical-trials-in-heart-failure-with-preserved-ejection-fraction-lessons-from-topcat
#13
REVIEW
Ravi B Patel, Sanjiv J Shah, Gregg C Fonarow, Javed Butler, Muthiah Vaduganathan
PURPOSE OF REVIEW: Spironolactone did not demonstrate benefit with respect to the primary composite endpoint in the global TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial in patients with chronic heart failure with preserved ejection fraction (HFpEF). We identify key lessons from the TOPCAT experience that can be applied to future HFpEF trials. RECENT FINDINGS: Subsequent analyses of TOPCAT have revealed marked regional heterogeneity in patient profiles, event rates, drug adherence, and treatment effects...
August 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28579091/characteristics-and-outcomes-of-heart-failure-hospitalization-before-implementation-of-a-heart-failure-clinic-the-precic-study
#14
Irene Marques, Sara Abreu, Manuela V Bertão, Betânia Ferreira, Raquel Lopes Ramos, Juliana Lopes, Sandra Nunes, Denisa Mendonça, Laetitia Teixeira
OBJECTIVE: This study aims to characterize patients hospitalized for acute heart failure (HF) in an internal medicine department and their one-year mortality and rate of rehospitalization for decompensated HF. METHODS: This retrospective observational study enrolled all patients discharged in 2012 after hospitalization for acute HF. Discharge summaries, clinical records and telephone interviews were analysed. The data reports to the year before implementation of a heart failure clinic...
June 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/28542926/effect-of-spironolactone-on-exercise-tolerance-and-arterial-function-in-older-adults-with-heart-failure-with-preserved-ejection-fraction
#15
RANDOMIZED CONTROLLED TRIAL
Bharathi Upadhya, William G Hundley, Peter H Brubaker, Timothy M Morgan, Kathryn P Stewart, Dalane W Kitzman
OBJECTIVES: To evaluate the effects of an aldosterone antagonist on exercise intolerance in older adults with heart failure and preserved ejection fraction (HFpEF). DESIGN: Randomized, placebo-controlled, double-blind trial. SETTING: Academic medical center, Winston-Salem, North Carolina. PARTICIPANTS: Older adults (N = 80, aged 71 ± 1; 80% female) with stable compensated HFpEF and controlled blood pressure (BP)...
November 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28460827/heart-failure
#16
REVIEW
Marco Metra, John R Teerlink
Heart failure is common in adults, accounting for substantial morbidity and mortality worldwide. Its prevalence is increasing because of ageing of the population and improved treatment of acute cardiovascular events, despite the efficacy of many therapies for patients with heart failure with reduced ejection fraction, such as angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), β blockers, and mineralocorticoid receptor antagonists, and advanced device therapies. Combined angiotensin receptor blocker neprilysin inhibitors (ARNIs) have been associated with improvements in hospital admissions and mortality from heart failure compared with enalapril, and guidelines now recommend substitution of ACE inhibitors or ARBs with ARNIs in appropriate patients...
October 28, 2017: Lancet
https://www.readbyqxmd.com/read/28451445/who-are-patients-classified-within-the-new-terminology-of-heart-failure-from-the-2016-esc-guidelines
#17
Benoit Delepaul, Guillaume Robin, Clément Delmas, Thomas Moine, Adrien Blanc, Pauline Fournier, Aénora Roger-Rollé, Guillaume Domain, Clémence Delon, Charles Uzan, Rabah Boudjellil, Didier Carrié, Jérôme Roncalli, Michel Galinier, Olivier Lairez
AIMS: The main terminology used to describe heart failure (HF) is based on measurement of the left ventricular ejection fraction (LVEF). LVEF in the range of 40-49% was recently defined as HF with mid-range EF (HFmrEF) by the 2016 European Society of Cardiology guidelines. The purpose of our study was to assess the clinical profile and prognosis of patients with HF according to this new classification. METHODS AND RESULTS: A total of 482 patients referred for HF were retrospectively included over a period of 1 year...
May 2017: ESC Heart Failure
https://www.readbyqxmd.com/read/28401618/tailoring-mineralocorticoid-receptor-antagonist-therapy-in-heart-failure-patients-are-we-moving-towards-a-personalized-approach
#18
REVIEW
João Pedro Ferreira, Robert J Mentz, Anne Pizard, Bertram Pitt, Faiez Zannad
The aim of personalized medicine is to offer a tailored approach to each patient in order to provide the most effective therapy, while reducing risks and side effects. The use of mineralocorticoid receptor antagonists (MRAs) has demonstrated major benefits in heart failure with reduced ejection fraction (HFrEF), results with challenging inconsistencies in heart failure with preserved ejection fraction (HFpEF), and 'neutral' preliminary results in acute heart failure. Data derived from landmark trials are generally applied in a 'one size fits all' manner and the development and implementation of more personalized MRA management would offer the potential to improve outcomes and reduce side effects...
April 12, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/28359411/interaction-between-spironolactone-and-natriuretic-peptides-in-patients-with-heart-failure-and-preserved-ejection-fraction-from-the-topcat-trial
#19
Inder S Anand, Brian Claggett, Jiankang Liu, Amil M Shah, Thomas S Rector, Sanjiv J Shah, Akshay S Desai, Eileen O'Meara, Jerome L Fleg, Marc A Pfeffer, Bertram Pitt, Scott D Solomon
OBJECTIVES: The aims of this study were to explore the relationship of baseline levels of natriuretic peptides (NPs) with outcomes and to test for an interaction between baseline levels of NPs and the effects spironolactone. BACKGROUND: Plasma NPs are considered to be helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF), and elevated levels are associated with adverse outcomes. Levels of NPs higher than certain cutoffs are often used as inclusion criteria in clinical trials of HFpEF to increase the likelihood that patients have HF and to select patients at higher risk for events...
April 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28247180/registry-based-pragmatic-trials-in-heart-failure-current-experience-and-future-directions
#20
REVIEW
Lars H Lund, Jonas Oldgren, Stefan James
PURPOSE OF REVIEW: Randomized controlled trials (RCTs) in heart failure (HF) are becoming increasingly complex and expensive to conduct and if positive deliver expensive therapy tested only in selected populations. RECENT FINDINGS: Electronic health records and clinical cardiovascular quality registries are providing opportunities for pragmatic and registry-based prospective randomized clinical trials (RRCTs). Simplified regulatory, ethics, and consent procedures; recruitment integrated into real-world care; and simplified or automated baseline and outcome collection allow assessment of study power and feasibility, fast and efficient recruitment, delivery of generalizable findings at low cost, and potentially evidence-based and novel use of generic drugs with low costs to society...
April 2017: Current Heart Failure Reports
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