Aims We aimed to explore the heterogeneous treatment effects (HTEs) for spironolactone treatment in patients with Heart failure with preserved ejection fraction (HFpEF) and examine the efficacy and safety of spironolactone medication, ensuring a better individualized therapy. Methods and results We used the causal forest algorithm to discover the heterogeneous treatment effects (HTEs) from patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Cox regressions were performed to assess the hazard ratios (HRs) of spironolactone medication for cardiovascular death and drug discontinuation in each group. The causal forest model revealed three representative covariates and participants were partitioned into four subgroups which were Group 1 (baseline BMI ≤ 31.71 kg/m 2 and baseline ALP ≤ 80 U/L, n = 759); Group 2 (BMI ≤ 31.71 kg/m 2 and ALP > 80 U/L, n = 1088); Group 3 (BMI > 31.71 kg/m 2 , and WBC ≤ 6.6 cells/μL, n = 633); Group 4 (BMI > 31.71 kg/m 2 and WBC > 6.6 cells/μL, n = 832), respectively. In the four subgroups, spironolactone therapy reduced the risk of cardiovascular death in high‐risk group (Group 4) with both high BMI and WBC count (HR: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in low‐risk group (Group 1) with both low BMI and ALP (HR: 1.45; 95% CI 1.02 to 2.07; P = 0.041; P for interaction = 0.020) but showed similar risk of drug discontinuation ( P for interaction = 0.498). Conclusion Our study manifested the HTEs of spironolactone in patients with HFpEF. Spironolactone treatment in HFpEF patients is feasible and effective in patients with high BMI and WBC while harmful in patients with low BMI and ALP. Machine learning model could be meaningful for improved categorization of patients with HFpEF, ensuring a better individualized therapy in the clinical setting.

Background It is well established that obesity is associated with the risk of heart failure (HF). However, the data about relationship between visceral fat and the risk of HF are limited. Aim We aim to evaluate the association between visceral obesity assessed by visceral adiposity index (VAI) and incident HF and left ventricular (LV) structure and function in Atherosclerosis Risk in Communities (ARIC) Study. Methods We included 12,161 participants (aged 54.1 ± 5.8years) free of history of HF and coronary heart disease at baseline (1987–1989) in ARIC Study. We used multivariable Cox hazard regression models to assess the association between the VAI and incident HF. We further explored the effects of the VAI on LV geometry and function among 4,817 participants with echocardiographic data using multivariable linear regression analysis and multinomial logistic regression. Results During a median follow-up of 22.5 years, a total of 1,904 (15.7%) participants developed HF. After adjustment for traditional HF risk factors, one unit increase in the baseline VAI was associated with an 8% higher risk of incident HF [hazard ratio (HR): 1.08, 95% confidence interval (CI):1.06–1.11]. Results were similar when participants were categorized by VAI tertiles. Compared with participants in the lowest tertile of VAI, those in the second tertile and third tertile had a greater risk of incident HF [HR (95%CI) :1.19 (1.05–1.34), 1.42 (1.26–1.61), respectively]. For the analyses of the HF subtypes, the higher VAI was only associated with the risk of HF with preserved ejection fraction, not with HF with reduced ejection fraction. In addition, the greater VAI was associated with worse LV diastolic function and abnormal LV geometry including concentric remodeling, concentric hypertrophy and eccentric Hypertrophy. Conclusion This study shows that higher VAI was independently associated with the increased risk of incident HF and abnormal LV geometry and LV diastolic dysfunction.

adjusted life years annually. Although antihypertension treatment reduces the incidence of major adverse cardiovascular events (MACEs), a substantial proportion of treated patients still have uncontrolled BP. 9,10 Most importantly, the optimal BP treatment target remains controversial due to discordant findings from the latest observational studies and randomized controlled trials (RCTs). 11The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated the benefits of an intensive SBP treatment target (<120 mmHg) vs. a standard target (<140 mmHg) in reducing cardiovascular events and all-cause death in adults without diabetes. 12 However, other studies have reported no benefit or increased risk of CVD death. [13][14][15] The Action to Control Cardiovascular Risk in Diabetes H ypertension (HTN) is the leading preventable cause of cardiovascular disease (CVD), chronic kidney disease (CKD) and dementia. 1-3 With population aging, severe COVID-19 complications, 4 and worsening trends in HTN control, 5 the health burden of HTN will remain a global social challenge worldwide. In 2015, the number of all-cause deaths attributable to systolic blood pressure (SBP) ≥140 mmHg was estimated at 7.8 million (14.0% of all deaths) and the number for SBP ≥110-115 mmHg was 10.7 million (19.2% of all deaths). 6,7 According to the Global Burden of Disease Study, 8 nonoptimal BP has been and continues to be the most prominent risk factor for disease and all-cause deaths globally, resulting in 9.4 million deaths and 212 million disability-