Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM-HFpEF study.

BackgroundApproximately half of the patients presenting with new-onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid-range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta-blockers and angiotensin-converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease.MethodsThe Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM-HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post-titration follow-up period of at least 12 months.ConclusionsThe ANTHEM-HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF

Research Needed to Support Clinical Use of Biomarkers as Prognostic Indicators for Patients with Heart Failure

Despite extensive research and numerous publications biomarkers have yet to fulfill their promise as prognostic indicators that can be widely used in the care of patients with heart failure. Specific clinical applications need to be identified for informative analyses of data that emphasize the most directly applicable measures of predictive performance

Comparison of once-daily versus twice-daily dosing of valsartan in patients with chronic stable heart failure

Inder S Anand1, Anita Deswal2, Dean J Kereiakes3, Das Purkayastha4, Dion H Zappe41Veterans Administration Medical Center, Minneapolis, MN, USA; 2Michael E DeBakey VA Medical Center, Houston, TX, USA; 3The Christ Hospital Heart and Vascular Center, Cincinnati, OH, USA; 4Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; Clinical trial registration information: www.clinicaltrials.gov/ct2/show/NC T00294086 Unique identification number: NC T00294086Background: The safety of once-daily (qd) dosing of valsartan in heart failure (HF) patients is not known. Hypothesis: This 10-week, double-blind trial examined the relative safety and efficacy of valsartan administered qd versus twice-daily (bid).Methods: HF patients (NYHA class II–III) receiving diuretics (87%), angiotensin-converting enzyme inhibitors (98%), beta-blockers (92%), aldosterone antagonists (25%), or digoxin (32%) were randomized to valsartan 40 mg bid (n = 60) or 80 mg qd (n = 55) and titrated to a maximum dose of 320 mg/day; doubling the dose every 2 weeks. Clinical and biochemical parameters were measured at Weeks 2, 4, 6, and 10.Results: The average dose of valsartan at the end of study was 245 mg in the bid group vs 256 mg in the qd group (P = NS). Similar proportions of patients tolerated qd vs bid dosing (bid 67% vs qd 68%). Outcome measures including reduction in blood pressure, incidence of hypotension, renal impairment, orthostatic dizziness or fatigue, changes in serum K+, creatinine, cystatin-C, and estimated glomerular filtration rate were similar between the 2 groups at all time-points. Brain natriuretic peptide levels decreased and plasma renin activity increased from baseline by the same amount in both groups at all time-points.Conclusion: Valsartan administered qd has a similar safety and tolerability profile with comparable 24-hour RAAS blockade, as assessed by increases in PRA, as bid dosing in patients with moderate to severe (NYHA class II–III) heart failure.Keywords: heart failure, angiotensin receptor blocker, valsarta

Spironolactone for heart failure with preserved ejection fraction

BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive 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. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P = 0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P = 0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 μmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure

Prognostic importance of left ventricular mechanical dyssynchrony in heart failure with preserved ejection fraction

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138381/1/ejhf789.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138381/2/ejhf789_am.pd

Field Bund & Border as Alternative Land Use for Forage Production: A Case of Marginal Farmer in Bundelkhand Region of India

In India, if marginal farmers are approached for production of forage grasses in their agricultural lands, the response of the farmers would be straight forward „NO‟ to the forage crops on agricultural lands. The reason is that food grains (cereals & pulses), vegetables, oilseeds, fruits, etc. are grown on agricultural land and get the first preference for family members, while the forage grasses are least preferred, as crops residues are being fed to livestock. More than 60% of the farm produce come from the small farms only. The productivity of the marginal and small farmers is the solution for growing population food needs. Most of the marginal and small farmers cultivate the farm land with the support of their family members and local labour which the quality of the work is higher. They grow multiple crops and sow as soon as they harvest. The last four decades has witnessed a sharp decline in the average size of operational land holdings in India. The average size of operational land holdings has reduced by half from 2.28 ha in 1970-71 to 1.6 ha in 2010-11. Land holdings in the marginal category (less than 1 ha) constitute 67% of the operational holdings in India (2010-11). Marginal and small holdings together, constitute 85% in terms of number of operational holdings and 44% of the operated area in the country. Thus, over the period, the marginal category has emerged as a distinct and dominant class by itself with its average size dwindling to a mere 0.38 ha. (NABARD, 2014). This is the case study of an illiterate & marginal farmer, Shri Vijay Singh Kushwaha (37) S/o shri Dhan Singh resides in Kushwaha Dera at village Parasai (under Babina development block) in Jhansi district of Uttar Pradesh, Bundelkhand region of central India. He used to cultivate only monsoon crops, was the target of an extension programme initiated by ICAR-Central Agroforestry Research Institute, Jhansi in 2011 under the project “Enhancing groundwater recharge and water use efficiency in Semi-Arid Tropics region through watershed interventions, Parasai-Sindh watershed, Jhansi”. The watershed is being developed in consortia mode with ICAR-Central Agroforestry Research Institute, Jhansi, and International Crop Research Institute for Semi-Arid Tropics (ICRISAT), Hyderabad. The watershed comprises three villages namely Parasai, Chhatpur and Bachhauni and located between 250 23‟56‟‟ to 250 27‟ 9.34‟‟ N latitude and 780 19‟ 45.71‟‟ to 780 22‟ 42.57‟‟E longitude. The watershed is about 35 km in the West of the district headquarter. Bundelkhand is prone to severe drought leading to huge migration towards cities in search of livelihoods and the scarcity of green fodder posed as one of the major hindrances for dairy and livestock production activity in the region

A Systematic Review and Network Meta-Analysis of Pharmacological Treatment of Heart Failure With Reduced Ejection Fraction

Objectives: This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. Background: The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized. Methods: We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor–neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]). Results: We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses. Conclusions: In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i

Readmissions, death and its associated predictors in heart failure with preserved versus reduced ejection fraction

BACKGROUND: Data on rehospitalizations for heart failure (HF) in Asia are scarce. We sought to determine the burden and predictors of HF (first and recurrent) rehospitalizations and all‐cause mortality in patients with HF and preserved versus reduced ejection fraction (preserved EF, ≥50%; reduced EF, <40%), in the multinational ASIAN‐HF (Asian Sudden Cardiac Death in Heart Failure) registry. METHODS AND RESULTS: Patients with symptomatic (stage C) chronic HF were followed up for death and recurrent HF hospitalizations for 1 year. Predictors of HF hospitalizations or all‐cause mortality were examined with Cox regression for time to first event and other methods for recurrent events analyses. Among 1666 patients with HF with preserved EF (mean age, 68±12 years; 50% women), and 4479 with HF with reduced EF (mean age, 61±13 years; 22% women), there were 642 and 2302 readmissions, with 28% and 45% attributed to HF, respectively. The 1‐year composite event rate for first HF hospitalization or all‐cause death was 11% and 21%, and for total HF hospitalization and all‐cause death was 17.7 and 38.7 per 100 patient‐years in HF with preserved EF and HF with reduced EF, respectively. In HF with preserved EF, consistent independent predictors of these clinical end points included enrollment as an inpatient, Southeast Asian location, and comorbid chronic kidney disease or atrial fibrillation. The same variables were predictive of outcomes in HF with reduced EF except atrial fibrillation, and also included Northeast Asian location, older age, elevated heart rate, decreased systolic blood pressure, diabetes, smoking, and non‐usage of beta blockers. CONCLUSIONS: One‐year HF rehospitalization and mortality rates were high among Asian patients with HF. Predictors of outcomes identified in this study could aid in risk stratification and timely interventions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01633398

Impact of pulmonary disease on the prognosis in heart failure with preserved ejection fraction: the TOPCAT trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154618/1/ejhf1593_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154618/2/ejhf1593.pd