Quantitative flow ratio versus fractional flow reserve for Heart Team decision-making in multivessel disease: the randomised, multicentre DECISION QFR trial.

BACKGROUND: Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time. AIMS: The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated. METHODS: Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa. RESULTS: The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00]). CONCLUSIONS: QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

Impact of left atrial appendage flow velocity on thrombus resolution and clinical outcomes in patients with atrial fibrillation and silent left atrial thrombi: insights from the LAT study.

AIMS: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear. METHODS AND RESULTS: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005). CONCLUSION: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes.

Relationship of interleukin-16 with different phenogroups in acute heart failure with preserved ejection fraction.

AIMS: Interleukin-16 (IL-16) has been reported to mediate left ventricular myocardial fibrosis and stiffening in patients with heart failure with preserved ejection fraction (HFpEF). We sought to elucidate whether IL-16 has a distinct impact on pathophysiology and prognosis across different subphenotypes of acute HFpEF. METHODS AND RESULTS: We analysed 211 patients enrolled in a prospective multicentre registry of acute decompensated HFpEF for whom serum IL-16 levels after stabilization were available (53% female, median age 81 [interquartile range 75-85] years). We divided this sub-cohort into four phenogroups using our established clustering algorithm. The study endpoint was all-cause death. Patients were subclassified into phenogroup 1 ('rhythm trouble' [n = 69]), phenogroup 2 ('ventricular-arterial uncoupling' [n = 49]), phenogroup 3 ('low output and systemic congestion' [n = 41]), and phenogroup 4 ('systemic failure' [n = 52]). After a median follow-up of 640 days, 38 patients had died. Among the four phenogroups, phenogroup 2 had the highest IL-16 level. The IL-16 level showed significant associations with indices of cardiac hypertrophy, diastolic dysfunction, and congestion only in phenogroup 2. Furthermore, the IL-16 level had a significant predictive value for all-cause death only in phenogroup 2 (C-statistic 0.750, 95% confidence interval 0.606-0.863, P = 0.017), while there was no association between the IL-16 level and the endpoint in the other phenogroups. CONCLUSIONS: Our results indicated that the serum IL-16 level had a significant association with indices that reflect the pathophysiology and prognosis of HFpEF in a specific phenogroup in acute HFpEF.

Low-density lipoprotein cholesterol, erythrocyte, and platelet in heart failure with preserved ejection fraction.

AIMS: Low-density lipoprotein cholesterol (LDL-C), anaemia and low platelets have been associated with worse clinical outcomes in heart failure patients. We investigated the relationship between the combination of these three components and clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We examined the data of 1021 patients with HFpEF hospitalized with acute decompensated heart failure (HF) from the PURSUIT-HFpEF registry, a prospective, multicenter observational study. The enrolled patients were classified into four groups by an LEP (LDL-C, Erythrocyte, and Platelet) score of 0 to 3 points, with 1 point each for LDL-C, erythrocyte and platelet values less than the cut-off values as calculated by receiver operating characteristic curve analysis. The endpoint, a composite of all-cause death and HF readmission, was evaluated among the four groups. Median follow-up duration was 579 [300, 978] days. Risk of the composite endpoint significantly differed among the four groups (P < 0.001). Kaplan-Meier analysis showed that the groups with an LEP score of 2 had higher risk of the composite endpoint than those with an LEP score of 0 or 1 (P < 0.001, and P = 0.013, respectively), while those with an LEP score of 3 had higher risk than those with an LEP score of 0, 1 or 2 (P < 0.001, P < 0.001 and P = 0.020, respectively). Cox proportional hazards analysis showed that an LEP score of 3 was significantly associated with the composite endpoint (P = 0.030). Kaplan-Meier analysis showed that risk of the composite of all-cause death and HF readmission was significantly higher in low LDL values (less than the cut-off values as calculated by receiver operating characteristic curve analysis) patients with statin use than in those without statin use (log rank P = 0.002). CONCLUSIONS: LEP score, which comprehensively reflects extra-cardiac co-morbidities, is significantly associated with clinical outcomes in HFpEF patients.

Duration of atrial fibrillation persistence: implications for recurrence risk after catheter ablation and efficacy of additional substrate ablation.

BACKGROUND: The optimal duration of atrial fibrillation (AF) persistence for predicting poor outcomes after catheter ablation of long-standing AF (LsAF) and the best ablation strategy for these patients remain unclear. OBJECTIVE: We aimed to assess the impact of the duration of AF persistence on outcomes after catheter ablation of AF. METHODS: We analyzed the Efficacy of Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation (EARNEST-PVI) trial data comparing pulmonary vein isolation (PVI) alone (PVI-alone) with additional linear ablation or defragmentation (PVI-plus) in persistent AF (PerAF). Patients who received catheter ablation by contact force-sensing catheter were enrolled in the study. In patients with LsAF, the optimal cutoff duration of AF persistence was evaluated. With use of the threshold, patients with LsAF were divided into 2 groups and compared with PerAF <1 year for arrhythmia-free survival after a 3-month blanking period. RESULTS: The optimal cutoff duration was 2.4 years. Of 458 patients, arrhythmia-free survival rates for LsAF 1-2.4 years were comparable to those of PerAF (hazard ratio [HR], 1.01; 95% CI, 0.67-1.52). However, LsAF >2.4 years had a higher recurrence risk than PerAF (HR, 2.22; 95% CI, 1.42-3.47). In LsAF >2.4 years, the PVI-plus strategy showed advantages over the PVI-alone strategy (HR, 0.36; 95% CI, 0.14-0.89). However, the interaction effect between LsAF 1-2.4 years and LsAF >2.4 years did not reach statistical significance (P = .116). CONCLUSION: Whereas LsAF 1-2.4 years has similar outcomes to those of PerAF, LsAF >2.4 years was linked to higher arrhythmia recurrence risks. For LsAF >2.4 years, the PVI-plus strategy showed a potential to be superior to the PVI-alone strategy.

Uplift modeling to identify patients who require extensive catheter ablation procedures among patients with persistent atrial fibrillation.

Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19-0.84; P-value = 0.015). In contrast, among patients with an uplift score < 0.0124, recurrence of AF did not significantly differ between PVI-plus and PVI-alone (HR 1.17; 95% CI 0.57-2.39; P-value = 0.661). By employing uplift modeling, we could effectively identify a subset of patients with persistent AF who would benefit from PVI-plus. This model could be valuable in stratifying patients with persistent AF who need extensive catheter ablation before the procedure.

The WATCH-DM risk score estimates clinical outcomes in type 2 diabetic patients with heart failure with preserved ejection fraction.

The coexistence of heart failure is frequent and associated with higher mortality in patients with type 2 diabetes (T2DM), and its management is a critical issue. The WATCH-DM risk score is a tool to predict heart failure in patients with type 2 diabetes mellitus (T2DM). We investigated whether it could estimate outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF). The WATCH-DM risk score was calculated in 418 patients with T2DM hospitalized for HFpEF (male 49.5%, age 80 ± 9 years, HbA1c 6.8 ± 1.0%), and they were divided into the "average or lower" (≤ 10 points), "high" (11-13 points) and "very high" (≥ 14 points) risk groups. We followed patients to observe all-cause death for 386 days (median). We compared the area under the curve (AUC) of the WATCH-DM score for predicting 1-year mortality with that of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and of the Barcelona Bio-Heart Failure Risk (BCN Bio-HF). Among the study patients, 108 patients (25.8%) had average or lower risk scores, 147 patients (35.2%) had high risk scores, and 163 patients (39.0%) had very high risk scores. The Cox proportional hazard model selected the WATCH-DM score as an independent predictor of all-cause death (HR per unit 1.10, 95% CI 1.03 to 1.19), and the "average or lower" risk group had lower mortality than the other groups (p = 0.047 by log-rank test). The AUC of the WATCH-DM for 1-year mortality was 0.64 (95% CI 0.45 to 0.74), which was not different from that of the MAGGIC score (0.72, 95% CI 0.63 to 0.80, p = 0.08) or that of BCN Bio-HF (0.70, 0.61 to 0.80, p = 0.25). The WATCH-DM risk score can estimate prognosis in T2DM patients with HFpEF and can identify patients at higher risk of mortality.

The Prognostic Impact of In-Hospital Major Bleeding and Recurrence of Myocardial Infarction during Acute Phase after Percutaneous Coronary Intervention for Acute Myocardial Infarction.

AIM: Both recurrent myocardial infarction (ReMI) and bleeding events after acute myocardial infarction (AMI) were reportedly associated with increased mortality. To date, the prognostic impact of these events on subsequent outcomes in East Asians is still unclear. In this study, we aimed to investigate the impact of bleeding or thrombotic events during acute phase on subsequent mortality and time-dependent change of the impact in patients with AMI undergoing percutaneous coronary intervention (PCI). METHOD: We conducted a prospective, multicenter, observational study of patients with AMI (n=12,093). The patients who did not undergo emergent PCI were excluded. In addition, the patients registered before 2003 were excluded because the data of bleeding severity was not obtained. Eligible patients were divided into two groups based on the occurrence of major bleeding within 7 days of PCI, and the same approach was performed for ReMI within 7 days of PCI. The endpoint of this study was all-cause death. We assessed the impact of major bleeding and ReMI, which occurred within 7 days of index PCI, on the subsequent clinical outcomes up to 5 years. RESULTS: A total of 6,769 patients were found to be eligible. All-cause death occurred in 898 (13.3%) patients during a median follow-up period of 1,726 [511-1,840] days. After adjustment for multiple confounders, major bleeding in 7 days from index PCI was independently associated with higher 30-day and 30-day to 1-year mortality (odds ratio [OR]: 2.06 [1.45-2.92] p＜0.001, OR: 2.03 [1.28-3.15] p=0.002), whereas ReMI was not (OR: 1.93 [0.92-3.80] p=0.07, OR: 0.81 [0.24-2.03] p=0.68). Major bleeding and ReMI did not affect mortality between 1 and 5 years (hazard ratio [HR]: 1.32 [0.77-2.26] p=0.31, HR: 0.48 [0.12-1.94] p=0.30). CONCLUSION: Major bleeding in 7 days from admission was independently associated with higher 30-day and 1-year mortality but not during 1-5 years. ReMI did not affect mortality in all phases. We should be more concerned about bleeding event during acute phase after PCI.

Pathophysiological insights into machine learning-based subphenotypes of acute heart failure with preserved ejection fraction.

OBJECTIVE: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology. METHODS: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated. RESULTS: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15. CONCLUSIONS: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy. TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.

Preprocedural physiological assessment of coronary disease patterns to predict haemodynamic outcomes post-PCI.

BACKGROUND: Even with intracoronary imaging-guided stent optimisation, suboptimal haemodynamic outcomes post-percutaneous coronary intervention (PCI) can be related to residual lesions in non-stented segments. Preprocedural assessment of pathophysiological coronary artery disease (CAD) patterns could help predict the physiological response to PCI. AIMS: The aim of this study was to assess the relationship between preprocedural pathophysiological haemodynamic patterns and intracoronary imaging findings, as well as their association with physiological outcomes immediately post-PCI. METHODS: Data from 206 patients with chronic coronary syndrome enrolled in the ASET-JAPAN study were analysed. Pathophysiological CAD patterns were characterised using Murray law-based quantitative flow ratio (µQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the pullback pressure gradient (PPG) index. Intracoronary imaging in stented segments after stent optimisation was also analysed. RESULTS: In the multivariable analysis, diffuse disease - defined by the pre-PCI µQFR-PPG index - was an independent factor for predicting a post-PCI µQFR <0.91 (per 0.1 decrease of PPG index, odds ratio 1.57, 95% confidence interval: 1.07-2.34; p=0.022), whereas the stent expansion index (EI) was not associated with a suboptimal post-PCI µQFR. Among vessels with an EI ≥80% and post-PCI µQFR <0.91, 84.0% of those vessels had a diffuse pattern preprocedure. There was no significant difference in EI between vessels with diffuse disease and those with focal disease. The average plaque burden in the stented segment was significantly larger in vessels with a preprocedural diffuse CAD pattern. CONCLUSIONS: A physiological diffuse pattern preprocedure was an independent factor in predicting unfavourable immediate haemodynamic outcomes post-PCI, even after stent optimisation using intracoronary imaging. Preprocedural assessment of CAD patterns could identify patients who are likely to exhibit superior immediate haemodynamic outcomes following PCI.

ß-blockers may be detrimental in frail patients with heart failure with preserved ejection fraction.

BACKGROUND: The effectiveness of ß-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of ß-blocker and prognosis according to the status of frailty. METHODS: We compared prognosis between HFpEF patients with and without ß-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831). RESULTS: Among 1159 patients enrolled in the analysis (median age, 81.4 years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of ß-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10-1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71-1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05-1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60-1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5. CONCLUSIONS: Use of ß-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of ß-blockers in HFpEF patients with frailty may need careful attention.

Impact of Structural Abnormalities in Left Ventricle and Left Atrium on Clinical Outcomes in Heart Failure with Preserved Ejection Fraction.

Two key echocardiographic parameters, left ventricular mass index (LVMI) and left atrial volume index (LAVI), are important in assessing structural myocardial changes in heart failure (HF) with preserved ejection fraction (HFpEF). However, the differences in clinical characteristics and outcomes among groups classified by LVMI and LAVI values are unclear.We examined the data of 960 patients with HFpEF hospitalized due to acute decompensated HF from the PURSUIT-HFpEF registry, a prospective, multicenter observational study. Four groups were classified according to the cut-off values of LVMI and LAVI [LVMI = 95 g/m2 (female), 115 g/m2 (male) and LAVI = 34 mL/m2]. Clinical endpoints were the composite of HF readmission and all-cause death. Study endpoints among the 4 groups were evaluated. The composite endpoint occurred in 364 patients (37.9%). Median follow-up duration was 445 days. Kaplan-Meier analysis revealed significant differences in the composite endpoint among the 4 groups (P < 0.001). Cox proportional hazards analysis demonstrated that patients with increased LAVI alone were at significantly higher risk of HF readmission and the composite endpoints than those with increased LVMI alone (P = 0.030 and P = 0.024, respectively). Age, male gender, systolic blood pressure at discharge, atrial fibrillation (AF) hemoglobin, renal function, and LAVI were significant determinants of LVMI and female gender, AF, hemoglobin, and LVMI were significant determinants of LAVI.In HFpEF patients, increased LAVI alone was more strongly associated with HF readmission and the composite of HF readmission and all-cause death than those with increased LVMI alone.

The efficacy and safety of adaptive servo-ventilation therapy for heart failure with preserved ejection fraction.

It is unclear whether adaptive servo-ventilation (ASV) therapy for heart failure with preserved ejection fraction (HFpEF) is effective. The aim of this study was to investigate the details of ASV use, and to evaluate the effectiveness and safety of ASV in real-world HFpEF patients. We retrospectively enrolled 36 HFpEF patients at nine cardiovascular centers who initiated ASV therapy during hospitalization or on outpatient basis and were able to continue using it at home from 2012 to 2017 and survived for at least one year thereafter. The number of hospitalizations for heart failure (HF) during the 12 months before and 12 months after introduction of ASV at home was compared. The median number of HF hospitalizations for each patient was significantly reduced from 1 [interquartile range: 1-2] in the 12 months before introduction of ASV to 0 [0-0] in the 12 months after introduction of ASV (p < 0.001). In subgroup analysis, reduction in heart failure hospitalization was significantly greater in female patients, patients with a body mass index < 25, and those with moderate or severe tricuspid valve regurgitation. In patients with HFpEF, the number of HF hospitalizations was significantly decreased after the introduction of ASV. HFpEF patients with female sex, BMI < 25, or moderate to severe tricuspid valve regurgitation are potential candidates who might benefit from ASV therapy.

P2Y12 inhibitor monotherapy after complex percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials.

It remains unknown whether the recent trend of short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy can simply be applied to patients undergoing complex percutaneous coronary intervention (PCI). We performed a systematic review and meta-analysis to evaluate P2Y12 inhibitor monotherapy vs. conventional DAPT in patients undergoing complex PCI and non-complex PCI (PROSPERO: CRD42022335723). Primary endpoint was the 1-year Net Adverse Clinical Event (NACE). Among 5,323 screened studies, six randomized trials fulfilled the eligibility criteria. A total of 10,588 complex PCI patients (5,269 vs. 5,319 patients) and 25,618 non-complex PCI patients (12,820 vs 12,798 patients) were randomly assigned to P2Y12 inhibitor monotherapy vs. conventional DAPT. In complex PCI patients, P2Y12 inhibitor monotherapy was associated with a lower risk of NACE than conventional DAPT [Odds ratio (OR) 0.76, 95% confidence interval (CI) 0.63-0.91, P = 0.003], whereas in non-complex PCI patients, P2Y12 inhibitor monotherapy was associated with a trend toward lowering the risk of NACE (OR 0.86, 95% CI 0.72-1.02, P = 0.09). This meta-analysis across randomized trials demonstrated that a strategy of short DAPT followed by P2Y12 inhibitor monotherapy reduces the risk of 1-year NACE in patients undergoing complex PCI.

Long-Term Impact of Additional Ablation After Pulmonary Vein Isolation: Results From EARNEST-PVI Trial.

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.

Prognostic impact of cardiovascular polypharmacy on octogenarians with heart failure with preserved ejection fraction.

BACKGROUNDS: Drug treatments of heart failure with preserved ejection fraction (HFpEF) have a little clinical benefit, but cardiovascular polypharmacy (CP) trend is observed in elderly HFpEF. We investigated the impact of CP on octogenarian with HFpEF. METHODS: We examined 783 consecutive octogenarians (≥80 years) enrolled in the PURSUIT-HFpEF registry. We defined medications for hypertension, dyslipidemia, heart failure (HF), coronary artery disease, stroke, peripheral artery disease, and atrial fibrillation as cardiovascular medications (CM). In this study, we defined CP as ≥5 CM. We investigated whether CP was correlated with the composite end point (CE) of all-cause mortality and HF rehospitalization. RESULTS: The proportion with CP was 51.9% (n = 406). Background characteristics correlated with CP were frailty, history of coronary artery disease, atrial fibrillation and left atrial dimension. Multivariable Cox proportional hazards analysis showed CP was significantly and independently correlated with CE (hazard ratio (HR): 1.31; 95% confidence Interval (CI): 1.01-1.70) in addition to age, clinical frailty scale, history of HF admission and N-terminal pro brain natriuretic peptide. Kaplan-Meier curve analysis showed that, compared with the non-CP group, the CP group had significantly higher risk of CE and HF (HR: 1.27; 95%CI: 1.04-1.56; P = 0.02 and HR: 1.46; 95%CI: 1.13-1.88; P < 0.01, respectively), but not any-cause death. In addition, diuretics were correlated with CE (HR: 1.61; 95%CI: 1.17-2.22; P < 0.01), but antithrombotic drugs and HFpEF medications were not. CONCLUSIONS: CP at discharge is a prognostic factor driven by HF rehospitalization in octogenarians with HFpEF. In these patients, diuretics may be correlated with the prognosis.

Medications for specific phenotypes of heart failure with preserved ejection fraction classified by a machine learning-based clustering model.

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.

The clinical relevance of quality of life in heart failure patients with preserved ejection fraction.

AIMS: Patient reported outcomes (PROs) are gradually being incorporated into daily practice to assess individual health-related quality of life (QOL). However, despite accumulating evidence of the prognostic utility of heart failure (HF)-specific QOL indices, evidence on the generic QOL score is scarce, especially in patients with HF with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Patient data were extracted from the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study. EuroQol 5 dimensions 5-level (EQ-5D-5L) data were obtained at discharge to evaluate patients' health-related QOL. The study population (n = 864) was divided into tertiles based on their EQ-5D-5L index as follows: low EQ-5D-5L 0.038-0.664 (n = 287), middle EQ-5D-5L 0.665-0.867 (n = 293), and high EQ-5D-5L 0.871-1.000 (n = 284). A total of 206 patients died over a mean follow-up period of 2.0 ± 1.2 years. Kaplan-Meier analysis revealed that the risk of mortality increased with the tertile of the EQ-5D-5L index (34% vs. 23% vs. 14%, P < 0.001). Cox multivariable analysis revealed that patients with EQ-5D-5L index in the low and middle tertiles had a significantly greater risk of mortality than those with EQ-5D-5L index in the high tertile [low EQ-5D-5L: adjusted hazard ratio (HR): 1.81 (1.12-2.92), P = 0.002, middle EQ-5D-5L: adjusted HR 1.91 (1.21-3.03), P = 0.006]. Among the dimensions of EQ-5D-5L, mobility (P = 0.014), self-care (P = 0.023) and usual activities (P = 0.008) were significant factors associated with all-cause mortality after multivariable adjustment. CONCLUSIONS: EQ-5D-5L is useful tool for risk stratification in patients with HFpEF.