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https://www.readbyqxmd.com/read/27900610/novel-sgc-stimulators-and-sgc-activators-for-the-treatment-of-heart-failure
#1
Stefanie Breitenstein, Lothar Roessig, Peter Sandner, Kelly S Lewis
The burden of heart failure (HF) increases worldwide with an aging population, and there is a high unmet medical need in both, heart failure with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). The nitric oxide (NO) pathway is a key regulator in the cardiovascular system and modulates vascular tone and myocardial performance. Disruption of the NO-cyclic guanosine monophosphate (cGMP) signaling axis and impaired cGMP formation by endothelial dysfunction could lead to vasotone dysregulation, vascular and ventricular stiffening, fibrosis, and hypertrophy resulting in a decline of heart as well as kidney function...
November 30, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27868321/dementia-related-adverse-events-in-paradigm-hf-and-other-trials-in-heart-failure-with-reduced-ejection-fraction
#2
Jane A Cannon, Li Shen, Pardeep S Jhund, Søren L Kristensen, Lars Køber, Fabian Chen, Jianjian Gong, Martin P Lefkowitz, Jean L Rouleau, Victor C Shi, Karl Swedberg, Michael R Zile, Scott D Solomon, Milton Packer, John J V McMurray
AIMS: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials...
November 20, 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27867532/left-ventricular-ejection-fraction-recovery-in-patients-with-heart-failure-treated-with-intravenous-iron-a-pilot-study
#3
Julio Núñez, José Vicente Monmeneu, Anna Mollar, Eduardo Núñez, Vicent Bodí, Gema Miñana, Sergio García-Blas, Enrique Santas, Jaume Agüero, Francisco J Chorro, Juan Sanchis, Maria Pilar López-Lereu
AIMS: In patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency, treatment with intravenous iron has shown a clinical improvement regardless of anaemic status. Cardiac magnetic resonance (CMR) T2* sequence has shown a potential utility for evaluating myocardial iron deficiency. We aimed to evaluate whether T2* sequence significantly changes after ferric carboximaltose (FCM) administration, and if such changes correlate with changes in left ventricle ejection fraction (LVEF)...
December 2016: ESC Heart Failure
https://www.readbyqxmd.com/read/27867524/varying-effects-of-recommended-treatments-for-heart-failure-with-reduced-ejection-fraction-meta-analysis-of-randomized-controlled-trials-in-the-esc-and-accf-aha-guidelines
#4
REVIEW
Marius Mark Thomsen, Christian Lewinter, Lars Køber
The aim of this paper is to evaluate the treatment effects of recommended drugs and devices on key clinical outcomes for patients with heart failure with reduced ejection fraction (HFREF). Randomized controlled trials (RCTs) listed in the 2012 HF guideline from the European Society of Cardiology as well as the 2013 HF guideline from the American College of Cardiology Foundation and American Heart Association were evaluated for use in the meta-analysis. RCTs written in English evaluating recommended drugs and devices for the treatment of patients with HFREF were included...
December 2016: ESC Heart Failure
https://www.readbyqxmd.com/read/27858191/focus-on-the-novel-cardiovascular-drug-lzc696-from-evidence-to-clinical-consideration
#5
L M Lin, Y Wu, M F Wu, J X Lin
LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is comprised of the angiotensin receptor blocker valsartan and the neprilysin inhibitor pro-drug sacubitril (AHU377). After oral administration, AHU377 is rapidly metabolized to the active neprilysin inhibitor LBQ657. LCZ696 exerts its effects of diuresis, natriuresis, vasodilation and aldosterone secretion inhibition through simultaneous renin-angiotensin-aldosterone system (RAAS) blockade and natriuretic peptides system (NPS) enhancement...
November 18, 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27858115/-the-new-esc-guidelines-for-acute-and-chronic-heart-failure-2016
#6
C U Oeing, C Tschöpe, B Pieske
The new guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) were presented in May 2016 during the congress of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in Florence. An important amendment affects the classification of HF which now differentiates between HF with preserved ejection fraction (HFpEF) and left ventricular EF (LVEF) > 50%, HF with reduced ejection fraction (HFrEF, LVEF < 40%) and the new entity HF with mid-range ejection fraction (HFmrEF, LVEF 40-49%)...
December 2016: Herz
https://www.readbyqxmd.com/read/27824422/-sacubitril-valsartan-in-patients-with-diabetes-and-heart-failure
#7
Vincent Matthias Brandenburg, Hans-Peter Brunner-La Rocca, Nikolaus Marx
Sacubitril / Valsartan proofed to be an effective treatment compared to enalapril in reducing heart failure hospitalisations and mortality in patients with severe "Heart failure with reduced ejection fraction" (HFREF). Recent European cardiology guidelines attributed a class IB recommendation for Sacubitril / Valsartan in HFREF patients who remain symptomatic despite optimal treatment with ACE-I, a beta-blocker, and a mineralocorticoid receptor antagonist. There is a significant overlap between diabetic and HFREF patients and thus, efficacy assessment of Sacubitril / Valsartan is a clinically meaningful issue in the large subgroup of HFREF patients with diabetes...
October 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27754187/sp-04-2-lcz-696-a-new-paradigm-shift-for-the-treatment-of-heart-failure
#8
ByungSu Yoo
Heart failure (HF) represents a significant healthcare issue because of its ever-increasing prevalence, poor prognosis and complex pathophysiology. The cornerstone of modern drug therapy in chronic HF is the inhibition of neurohormonal activation that plays a crucial role in the pathophysiology of HF development and progression and, more specifically, of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. LCZ696 is a first-in-class, angiotensin receptor NEP inhibitor (ARNI) that consists of a supramolecular complex of a molecule of the ARB valsartan in combination with a molecule of the NEP inhibitor prodrug AHU377 (also known as sacubitril)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27747488/angiotensin-neprilysin-inhibition-as-a-paradigm-for-all
#9
Muthiah Vaduganathan, Akshay S Desai
Composite angiotensin receptor-neprilysin inhibition (ARNi) represents a novel pharmacologic strategy for treatment of heart failure with reduced ejection fraction (HFrEF). In the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial of 8399 subjects with HFrEF, treatment with the ARNi LCZ696 (sacubitril/valsartan) was associated with statistically important reductions in cardiovascular death, all-cause mortality, and the composite of cardiovascular death or heart failure hospitalization in comparison with enalapril...
November 2016: Current Cardiology Reports
https://www.readbyqxmd.com/read/27725624/a-treatment-approach-for-patients-with-chronic-systolic-heart-failure
#10
Barry H Greenberg
The treatment of heart failure with reduced ejection (HFrEF) is changing rapidly. Advances over the past several decades have focused on blocking the adverse effects of neurohormonal activation. This approach has resulted in marked improvement in outcomes in the HFrEF population. Despite these advances, however, mortality and morbidity remain high and HFrEF patients have poor quality of life. New approaches to therapy now offer additional benefits. Combined neprilysin inhibition and angiotensin receptor blockade using sacubitril-valsartan (LCZ696) has been shown to be superior to an angiotensin-converting enzyme inhibitor in HFrEF patients...
2016: Reviews in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27690339/echo-and-natriuretic-peptide-guided-therapy-improves-outcome-and-reduces-worsening-renal-function-in-systolic-heart-failure-an-observational-study-of-1137-outpatients
#11
Anca Simioniuc, Erberto Carluccio, Stefano Ghio, Andrea Rossi, Paolo Biagioli, Gianpaolo Reboldi, Gian Giacomo Galeotti, Fei Lu, Cornelia Zara, Gillian Whalley, Pier Luigi Temporelli, Frank Lloyd Dini
BACKGROUND: B-type natriuretic peptide (BNP) and echocardiography are potentially useful adjunct to guide management of patients with chronic heart failure (HF).Thus, the aim of this retrospective, multicenter study was to compare outcomes and renal function in outpatients with chronic HF with reduced ejection fraction (HFrEF) who underwent an echo and BNP guided or a clinically driven protocol for follow-up. METHODS AND RESULTS: In 1137 consecutive outpatients, management was guided according to echo-Doppler signs of elevated left ventricular filling pressure and BNP levels conforming to the protocol of the Network Labs Ultrasound (NEBULA) in HF Study Group in 570 (mean EF=30%), while management was clinically driven based on the institutional protocol of the HF Unit of the Cardiovascular and Thoracic Department in 567 (mean EF=33%)...
September 18, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27643144/sp-04-2-lcz-696-a-new-paradigm-shift-for-the-treatment-of-heart-failure
#12
ByungSu Yoo
Heart failure (HF) represents a significant healthcare issue because of its ever-increasing prevalence, poor prognosis and complex pathophysiology. The cornerstone of modern drug therapy in chronic HF is the inhibition of neurohormonal activation that plays a crucial role in the pathophysiology of HF development and progression and, more specifically, of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. LCZ696 is a first-in-class, angiotensin receptor NEP inhibitor (ARNI) that consists of a supramolecular complex of a molecule of the ARB valsartan in combination with a molecule of the NEP inhibitor prodrug AHU377 (also known as sacubitril)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27630137/could-modification-of-titin-contribute-to-an-answer-for-heart-failure-with-preserved-ejection-fraction
#13
EDITORIAL
Martin M LeWinter, Michael R Zile
No abstract text is available yet for this article.
October 11, 2016: Circulation
https://www.readbyqxmd.com/read/27624622/safety-and-tolerability-of-neladenoson-bialanate-a-novel-oral-partial-adenosine-a1-receptor-agonist-in-patients-with-chronic-heart-failure
#14
Adriaan Alexander Voors, Hans-Dirk Düngen, Michele Senni, Savina Nodari, Piergiuseppe Agostoni, Piotr Ponikowski, Jeroen J Bax, Javed Butler, Raymond J Kim, Bernard Dorhout, Wilfried Dinh, Mihai Gheorghiade
We studied safety and tolerability of neladenoson bialanate, a novel oral selective partial adenosine A1 receptor agonist that maintains the cardioprotective effects of adenosine without the undesired side effects of a full agonist, in 2 pilot studies in patients with heart failure with reduced ejection fraction (HFrEF). The β-blocker interaction study was a single-blind, placebo-controlled study on the effects of a 30-mg single dose of neladenoson bialanate on atrioventricular (AV) conduction in 11 patients with HFrEF treated with β-blockers...
September 14, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27620301/should-mras-be-at-the-front-row-in-heart-failure-a-plea-for-the-early-use-of-mineralocorticoid-receptor-antagonists-in-medical-therapy-for-heart-failure-based-on-clinical-experience
#15
Ward A Heggermont, Marc Goethals, Riet Dierckx, Sofie Verstreken, Jozef Bartunek, Marc Vanderheyden
The brand new 2016 ESC guidelines for the treatment of acute and chronic heart failure continue to give a prominent place to mineralocorticoid receptor antagonists in the treatment of chronic heart failure with reduced ejection fraction (HFrEF). In the prevention of HF hospitalization and death, a class I, level of recommendation A, is given to MRAs for patients with HFrEF, who remain symptomatic despite treatment with an ACE-inhibitor and a beta-blocker and have an LVEF below 35 %. This recommendation is primarily based on two landmark trials, the RALES trial (for spironolactone) and the EMPHASIS-HF trial (for eplerenone)...
September 12, 2016: Heart Failure Reviews
https://www.readbyqxmd.com/read/27609832/skeletal-muscle-alterations-are-exacerbated-in-heart-failure-with-reduced-compared-with-preserved-ejection-fraction-mediated-by-circulating-cytokines
#16
Martin Seiler, T Scott Bowen, Natale Rolim, Maja-Theresa Dieterlen, Sarah Werner, Tomoya Hoshi, Tina Fischer, Norman Mangner, Axel Linke, Gerhard Schuler, Martin Halle, Ulrik Wisloff, Volker Adams
BACKGROUND: A greater understanding of the different underlying mechanisms between patients with heart failure with reduced (HFrEF) and with preserved (HFpEF) ejection fraction is urgently needed to better direct future treatment. However, although skeletal muscle impairments, potentially mediated by inflammatory cytokines, are common in both HFrEF and HFpEF, the underlying cellular and molecular alterations that exist between groups are yet to be systematically evaluated. The present study, therefore, used established animal models to compare whether alterations in skeletal muscle (limb and respiratory) were different between HFrEF and HFpEF, while further characterizing inflammatory cytokines...
September 2016: Circulation. Heart Failure
https://www.readbyqxmd.com/read/27592224/mechanisms-underlying-increased-mortality-risk-in-patients-with-heart-failure-and-reduced-ejection-fraction-randomly-assigned-to-adaptive-servoventilation-in-the-serve-hf-study-results-of-a-secondary-multistate-modelling-analysis
#17
Christine Eulenburg, Karl Wegscheider, Holger Woehrle, Christiane Angermann, Marie-Pia d'Ortho, Erland Erdmann, Patrick Levy, Anita K Simonds, Virend K Somers, Faiez Zannad, Helmut Teschler, Martin R Cowie
BACKGROUND: A large randomised treatment trial (SERVE-HF) showed that treatment of central sleep apnoea with adaptive servoventilation in patients with heart failure and reduced ejection fraction (HFREF) increased mortality, although the analysis of the composite primary endpoint (time to first event of death from any cause, life-saving cardiovascular intervention, or unplanned hospital admission for worsening heart failure) was neutral. This secondary multistate modelling analysis of SERVE-HF data investigated associations between adaptive servoventilation and individual components of the primary endpoint to try to better understand the mechanisms underlying the observed increased mortality...
August 31, 2016: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/27591220/heart-rate-induced-modifications-of-concentric-left-ventricular-hypertrophy-exploration-of-a-novel-therapeutic-concept
#18
Franziska J Klein, Stephen Bell, K Elisabeth Runte, Robert Lobel, Takamuru Ashikaga, Lilach O Lerman, Martin M LeWinter, Markus Meyer
Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy...
October 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/27574931/limitations-of-sacubitril-valsartan-in-the-management-of-heart-failure
#19
Srikanth Yandrapalli, Wilbert S Aronow, Pratik Mondal, David R Chabbott
BACKGROUND: The PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial was a double-blind trial that randomized 8442 patients with heart failure (HF) with reduced ejection fraction (HFrEF) to receive twice daily dosing of either 200 mg of LCZ696 or 10 mg of enalapril in addition to standard medical therapy for HF. AREAS OF UNCERTAINTY: Limitations of this trial include (1) sacubitril has not been tested by itself in the treatment of HFrEF; (2) the maximum recommended dose of valsartan for the treatment of HFrEF was used in this trial, but the maximum recommended dose of enalapril for the treatment of HFrEF was not used; (3) a run-in phase was used in this trial to test the tolerability of LCZ696, and patients who had adverse effects in this period were excluded from randomization; (4) the percent of blacks enrolled in this trial was only 5%; (5) LCZ696 caused a 14% incidence of hypotension; (6) neprilysin inhibition might favor the development of Alzheimer dementia, which was not assessed in the PARADIGM-HF trial; (7) patients with severe symptomatic HF were underrepresented in this trial; (8) major exclusions from this trial included an acute coronary event in the last 3 months, severe pulmonary disease, hepatic impairment, and an estimated glomerular filtration rate <30 mL per minute per 1...
August 17, 2016: American Journal of Therapeutics
https://www.readbyqxmd.com/read/27573608/practical-considerations-on-the-introduction-of-sacubitril-valsartan-in-clinical-practice-current-evidence-and-early-experience
#20
Dimitrios Farmakis, Vassiliki Bistola, Apostolos Karavidas, John Parissis
The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients...
November 15, 2016: International Journal of Cardiology
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