Background: Neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) are novel inflammation markers. Their combined usefulness for estimating the prognosis of patients with heart failure with preserved ejection fraction (HFpEF) admitted for acute decompensated heart failure remains elusive. Methods and Results: We investigated 1026 patients registered in the Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction. Both NLR and PLR values were measured at the time of admission. Comorbidity burden was defined as the number of occurrences of 8 common comorbidities of HFpEF. The primary end point was cardiac death. The patients were stratified into 3 groups based on the optimal cut‐off values of NLR and PLR on the receiver operating characteristic curve analysis for predicting cardiac death (low NLR and PLR, either high NLR or PLR, and both high NLR and PLR). After a median follow‐up of 429 days, 195 patients died, with 85 of these deaths attributed to cardiac causes. An increased comorbidity burden was significantly associated with a higher proportion of patients with high NLR (>4.5) or PLR (>193), or both. High NLR and PLR values were independently associated with cardiac death, and a combination of both values was the strongest predictor (hazard ratio, 2.66 [95% CI, 1.51–4.70], P =0.0008). A significant difference was found in the rate of cardiac death among the 3 groups stratified by NLR and PLR values. Conclusions: The combination of NLR and PLR is useful for the prediction of postdischarge cardiac death in patients with acute HFpEF. Registration: URL: ClinicalTrials.gov ; Unique identifier: UMIN000021831.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a phenotype primarily reported in patients carrying genetic mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) which releases long chain fatty acid (LCFA) as a major energy source by the intracellular TG hydrolysis. These patients suffered from intractable heart failure requiring cardiac transplantation. Moreover, we identified TGCV patients without PNPLA2 mutations based on pathological and clinical studies. We provided the diagnostic criteria, in which TGCV with and without PNPLA2 mutations were designated as primary TGCV (P-TGCV) and idiopathic TGCV (I-TGCV), respectively. We hereby report clinical profiles of TGCV patients. Between 2014 and 2018, 7 P-TGCV and 18 I-TGCV Japanese patients have been registered in the International Registry. Patients with I-TGCV, of which etiologies and causes are not known yet, suffered from adult-onset severe heart disease, including heart failure and coronary artery disease, associated with a marked reduction in ATGL activity and myocardial washout rate of LCFA tracer, as similar to those with P-TGCV. The present first registry-based study showed that TGCV is an intractable, at least at the moment, and heterogeneous cardiovascular disorder.

Objective Our previously established machine learning-based clustering model classified heart failure with preserved ejection fraction (HFpEF) into four distinct phenotypes. Given the heterogeneous pathophysiology of HFpEF, specific medications may have favourable effects in specific phenotypes of HFpEF. We aimed to assess effectiveness of medications on clinical outcomes of the four phenotypes using a real-world HFpEF registry dataset. Methods This study is a posthoc analysis of the PURSUIT-HFpEF registry, a prospective, multicentre, observational study. We evaluated the clinical effectiveness of the following four types of postdischarge medication in the four different phenotypes: angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB), beta blockers, mineralocorticoid-receptor antagonists (MRA) and statins. The primary endpoint of this study was a composite of all-cause death and heart failure hospitalisation. Results Of 1231 patients, 1100 (83 (IQR 77, 87) years, 604 females) were eligible for analysis. Median follow-up duration was 734 (398, 1108) days. The primary endpoint occurred in 528 patients (48.0%). Cox proportional hazard models with inverse-probability-of-treatment weighting showed the following significant effectiveness of medication on the primary endpoint: MRA for phenotype 2 (weighted HR (wHR) 0.40, 95% CI 0.21 to 0.75, p=0.005); ACEi or ARB for phenotype 3 (wHR 0.66 0.48 to 0.92, p=0.014) and statin therapy for phenotype 3 (wHR 0.43 (0.21 to 0.88), p=0.020). No other medications had significant treatment effects in the four phenotypes. Conclusions Machine learning-based clustering may have the potential to identify populations in which specific medications may be effective. This study suggests the effectiveness of MRA, ACEi or ARB and statin for specific phenotypes of HFpEF. Trial registration number UMIN000021831.

Background: An optimal strategy for left atrial ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not been determined. Methods and Results: We conducted an extended follow‐up of the multicenter randomized controlled EARNEST‐PVI (Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial, which compared 12‐month rhythm outcomes in patients with persistent AF between patients randomized to a PVI‐alone strategy (n=248) or PVI‐plus strategy (n=248; PVI followed by left atrial additional ablation, including linear ablation or ablation targeting areas with complex fractionated electrograms). The present study extended the follow‐up period to 3 years after enrollment. Outcomes were compared not only between randomly allocated groups but also between on‐treatment groups categorized by actually created ablation lesions. Recurrence rate of AF or atrial tachycardia (AT) was lower in the randomly allocated to PVI‐plus group than the PVI‐alone group (29.0% versus 37.5%, P =0.036). On‐treatment analysis revealed that patients with PVI+linear ablation (n=205) demonstrated a lower AF/AT recurrence rate than those with PVI only (26.3% versus 37.8%, P =0.007). In contrast, patients with PVI+complex fractionated electrograms ablation (n=37) had an AF/AT recurrence rate comparable to that of patients with PVI only (40.5% versus 37.8%, P =0.76). At second ablation in 126 patients with AF/AT recurrence, ATs excluding common atrial flutter were more frequent in patients with PVI+linear ablation than in those with PVI only (32.6% versus 5.7%, P <0.0001). Conclusions: Left atrial ablation in addition to PVI was efficacious during 3‐year follow‐up. Linear ablation was superior to other ablation strategies but may increase iatrogenic ATs. Registration: URL: http://www.umin.ac.jp/ctr/index‐j.htm ; Unique identifier: UMIN000019449.