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

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

Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction. A report from the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial (I-Preserve)

Background—In patients with HF and preserved ejection fraction (HFpEF), little is known about the characteristics of and outcomes in those with and without diabetes. Methods—We examined clinical and echocardiographic characteristics and outcomes in the Irbesartan in Heart Failure with Preserved Ejection Fraction trial (I-Preserve), according to history of diabetes. Cox regression models were used to estimate hazard ratios (HR) for cardiovascular outcomes adjusted for known predictors, including age, sex, natriuretic peptides, and comorbidity. Echocardiographic data were available in 745 patients and were additionally adjusted for in supplementary analyses. Results—Overall, 1134 of 4128 patients (27%) had diabetes. Compared to those without diabetes, they were more likely to have a history of myocardial infarction (28% vs. 22%), higher BMI (31kg/m2 vs. 29kg/m2), worse Minnesota living with HF score (48 vs. 40), higher median NT-proBNP concentration (403 vs 320 pg/ml; all p<0.01), more signs of congestion but no significant difference in LVEF. Patients with diabetes had a greater left ventricular (LV) mass and left atrial area than patients without diabetes. Doppler E wave velocity (86 vs 76 cm/sec, p<0.0001) and the ratio of E/e' (11.7 vs 10.4, p=0.010) were higher in patients with diabetes. Over a median follow-up of 4.1 years, cardiovascular death or HF hospitalization occurred in 34% of patients with diabetes vs. 22% of those without diabetes; adjusted HR 1.75 (95% CI 1.49-2.05) and 28% vs. 19% of patients with and without diabetes died; adjusted HR 1.59 (1.33-1.91). Conclusions—In HFpEF, patients with diabetes have more signs of congestion, worse quality of life, higher NT-proBNP levels, and a poorer prognosis. They also display greater structural and functional echocardiographic abnormalities. Further investigation is needed to determine the mediators of the adverse impact of diabetes on outcomes in HFPEF, and whether they are modifiable

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

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

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

Association of diabetes mellitus on cardiac remodeling, quality of life, and clinical outcomes in heart failure with reduced and preserved ejection fraction

Background: Diabetes mellitus frequently coexists with heart failure (HF), but few studies have compared the associations between diabetes mellitus and cardiac remodeling, quality of life, and clinical outcomes, according to HF phenotype. Methods and Results: We compared echocardiographic parameters, quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire), and outcomes (1‐year all‐cause mortality, cardiovascular mortality, and HF hospitalization) between HF patients with and without type 2 diabetes mellitus in the prospective ASIAN‐HF (Asian Sudden Cardiac Death in Heart Failure) Registry, as well as community‐based controls without HF. Adjusted Cox proportional hazards models were used to assess the association of diabetes mellitus with clinical outcomes. Among 5028 patients with HF and reduced ejection fraction (HFrEF; EF <40%) and 1139 patients with HF and preserved EF (HFpEF; EF ≥50%), the prevalences of type 2 diabetes mellitus were 40.2% and 45.0%, respectively (P=0.003). In both HFrEF and HFpEF cohorts, diabetes mellitus (versus no diabetes mellitus) was associated with smaller indexed left ventricular diastolic volumes and higher mitral E/e′ ratio. There was a predominance of eccentric hypertrophy in HFrEF and concentric hypertrophy in HFpEF. Patients with diabetes mellitus had lower Kansas City Cardiomyopathy Questionnaire scores in both HFpEF and HFrEF, with more prominent differences in HFpEF (Pinteraction<0.05). In both HFpEF and HFrEF, patients with diabetes mellitus had more HF rehospitalizations (adjusted hazard ratio, 1.27; 95% CI, 1.05–1.54; P=0.014) and higher 1‐year rates of the composite of all‐cause mortality/HF hospitalization (adjusted hazard ratio, 1.22; 95% CI, 1.05–1.41; P=0.011), with no differences between HF phenotypes (Pinteraction>0.05). Conclusions: In HFpEF and HFrEF, type 2 diabetes mellitus is associated with smaller left ventricular volumes, higher mitral E/e′ ratio, poorer quality of life, and worse outcomes, with several differences noted between HF phenotypes

Influence of Blood Pressure on the Effectiveness of a Fixed-Dose Combination of Isosorbide Dinitrate and Hydralazine in the African-American Heart Failure Trial

OBJECTIVES: This study sought to assess the effect of baseline systolic blood pressure (SBP) and changes in SBP on the effectiveness of treatment with fixed-dose combination of isosorbide dinitrate and hydralazine (FDC I/H) in patients with heart failure (HF). BACKGROUND: Low SBP is a risk factor for adverse outcomes in patients with HF. However, FDC I/H lowered SBP in the A-HeFT (African-American Heart Failure Trial) and yet prolonged survival. Whether blood pressure (BP) lowering is critical to the efficacy of FDC I/H and whether a low BP limits its effectiveness is unclear. METHODS: The effects of FDC I/H on SBP and on mortality and hospitalization were compared in patients with a low or high baseline SBP using multivariable Cox regression models. The interaction between the effect of treatment and baseline SBP was examined. RESULTS: Mean +/- SD baseline SBP in all of the patients was 126 +/- 18 mm Hg. Patients with baseline SBP equal to or below the median (126 mm Hg) had features of more severe HF. Baseline SBP equal to or below the median was an independent risk factor for death (hazard ratio [HR] 2.09; 95% confidence interval [CI] 1.02 to 4.29) or first hospitalization for HF (HR 1.66; 95% CI 1.18 to 2.34). The FDC I/H treatment reduced BP in patients with SBP above the median but not in patients with SBP below 126 mm Hg. The FDC I/H treatment was associated with a similar decrease in mortality or hospitalization for HF in patients with SBP below the median and above the median. The effects of FDC I/H on mortality alone were also similar. CONCLUSIONS: In A-HeFT, patients with lower SBP had a greater risk but a similar relative benefit from the use of FDC I/H as those with higher SBP. The FDC I/H treatment did not reduce SBP in patients with low SBP. An asymptomatic low SBP should not be considered a contraindication to use of FDC I/H in patients with HF