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.

Comparison of Postprocedural P-Wave Vector Magnitude on 12-Lead Electrocardiogram Between Cryoballoon and Radiofrequency Ablation.

Pulmonary vein isolation (PVI) causes changes in P-wave parameters. However, the difference in changes in P-wave parameters including P-wave vector magnitude (Pvm) between radiofrequency catheter ablation (RFCA) and cryoballoon ablation (CBA) remains unknown. Paroxysmal atrial fibrillation (PAF) patients who underwent only PVI were enrolled. Pvm was calculated by the square root of the sum of the squared P-wave amplitude in leads II and V6 and one-half of the P-wave amplitude in V2. The patients were divided into 2 groups: RFCA and CBA. ΔPvm was calculated as ΔPvm (mV) = (Pvm at pre-PVI)-(Pvm at post-PVI). The following factors were evaluated: (1) differences in the ΔPvm between the 2 groups, (2) relation between late arrhythmia recurrence and ΔPvm in RFCA and CBA groups, and (3) the impact of relevant factors on ΔPvm. The study population included a total of 426 patients with PAF (RFCA, 167 patients; CBA, 259 patients). ΔPvm was significantly larger in CBA than in RFCA (p <0.001). Kaplan-Meier analysis showed late arrhythmia recurrence was significantly higher in patients with low ΔPvm (<0.019 mV) than high ΔPvm (≥0.019 mV) in RFCA (Log-rank p <0.001), and low ΔPvm (<0.033 mV) than high ΔPvm (≥0.033 mV) in CBA (Log-rank p <0.001). Multiple regression analysis showed that CBA and heart rate change were independently and significantly associated with ΔPvm (p <0.001 and p <0.001, respectively). In conclusion, ΔPvm was significantly larger in CBA than RFCA during procedure. Low ΔPvm had a higher risk of late arrhythmia recurrence in RFCA and CBA.

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.

Impact of left ventricular inflow-outflow angle on heart failure readmission post-transcatheter aortic valve implantation.

Heart failure (HF) readmission post-transcatheter aortic valve implantation (TAVI) is common; however, its anatomical predictors remain unclear. This study identified a small systolic left ventricular inflow-outflow (LVIO) angle, evaluated using computed tomography, as a potential anatomical predictor associated with HF readmission post-TAVI. Patients with a small systolic LVIO angle may require close follow-up post-TAVI.

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.

Predictors of 30-day survival after emergent percutaneous coronary intervention following ventricular tachyarrhythmias complicating acute myocardial infarction.

BACKGROUND: Little has been reported on the predictors of 30-day survival after emergent percutaneous coronary intervention (PCI) following life-threatening ventricular tachyarrhythmias associated with acute myocardial infarction (AMI). METHODS: We analyzed 55 consecutive patients who underwent an emergent PCI after ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) complicating AMI between September 2014 and March 2023 in our hospital. These patients were categorized into two groups: survival group (S group) who survived >30 days after the emergent PCI and death group (D group) who died by 30 days after the emergent PCI. We compared the patient characteristics, coronary angiographic findings, and PCI procedures between the two groups. RESULTS: S group consisted of 40 patients. In the univariate analysis, absence of diabetes mellitus, presence of immediate cardiopulmonary resuscitation (CPR), low arterial lactate, and single-vessel coronary artery disease (CAD) were associated with 30-day survival after the emergent PCI (P = 0.048, P < 0.001, P = 0.009, and P = 0.003, respectively). In the multivariate analysis, presence of immediate CPR and single-vessel CAD were independently associated with 30-day survival after the emergent PCI (P = 0.023 and P = 0.032, respectively). CONCLUSIONS: Immediate CPR and single-vessel CAD were significant predictors of 30-day survival after the emergent PCI following VF or pulseless VT complicating AMI. Absence of diabetes mellitus and low arterial lactate were associated with 30-day survival in the univariate analysis.

Ratio of P-Wave Duration to P-Wave Amplitude and Left Atrial Remodeling: Insights from Electrophysiological Findings and Myocardial Injury After Cryoballoon Ablation.

The impact of the P-wave morphology on clinical outcomes postcatheter ablation (post-CA) and recurrent arrhythmia characteristics or electrophysiologic findings in patients with paroxysmal atrial fibrillation (PAF) remains unclear. Patients with PAF who underwent cryoballoon ablation were enrolled. In 12-lead electrocardiography recorded within 1 month before CA, the P-wave duration (Pd) and P-wave vector magnitude (Pvm) (square root of the sum of the squared P-wave amplitude in leads II, V6, and one-half of the P-wave amplitude in V2) were measured and divided into 2 groups: patients with high and low Pd/Pvm based on a statistically calculated cut-off value. We evaluated the incidence of late recurrence of atrial fibrillation (LRAF), myocardial injury (high-sensitive troponin I), and the electrophysiologic findings in repeat ablation sessions. This study included 269 patients with PAF. The median follow-up duration was 697 days. The cut-off value of the Pd/Pvm for predicting LRAF was 740.7 ms/mV (area under the curve = 0.81, sensitivity = 58.2%, and specificity = 89.6%). Multivariable Cox proportional hazards analysis showed that high Pd/Pvm (>740.7 ms/mV) was significantly associated with LRAF (p <0.001). The high-sensitive troponin I level was significantly lower, and the ratio of DR-FLASH score >3 was significantly higher in those with high than low Pd/Pvm (p = 0.044 and p = 0.002, respectively). In the repeat ablation sessions, the Pd/Pvm in patients with atrial tachycardia-induced or spontaneously occurring during the repeat CA sessions was significantly higher than in those without (p = 0.009). There was a significant difference between the Pd/Pvm and low-voltage area (p <0.001). In conclusion, the Pd/Pvm is significantly associated with LRAF after cryoballoon ablation in patients with PAF and predicts left atrial low-voltage areas and atrial tachycardia inducibility.

Difference between antegrade and retrograde orbital atherectomy system debulking using an artificial pulsatile heart model.

BACKGROUND: Debulking devices are necessary to treat severe calcified lesions. OAS has a unique characteristic that the burr moves forward and backward. There are few studies reporting the differences of ablation style between only-antegrade and only-retrograde OAS. AIMS: The aim of this study was to evaluate the difference of ablation style between only-antegrade and only-retrograde orbital atherectomy system (OAS) using an artificial pulsatile heart model (HEARTROID system®) and optical coherence tomography (OCT). METHODS: The calcified lesion model was inserted into the mid of left anterior descending in the HEARTROID®. Only-antegrade and only-retrograde ablation of OAS were conducted for each five lesions. Pre-OCT, OCT after low speed debulking and OCT after high speed debulking were conducted. The width and the depth of debulked area, the debulked area and the direction of debulked area were investigated. RESULTS: In all of 210 cross-sections, 91 debulked cross sections were chosen for analysis. Only-antegrade group had 47 debulked cross-sections, and only-retrograde group 44 cross-sections. In the evaluation of OCT after high speed debulking, the debulked area (0.76 mm2 [0.58-0.91] vs. 0.53 mm2 [0.36-0.68], p < 0.001) and the depth of debulked area (0.76 mm [0.58-0.91] vs. 0.53 mm [0.36-0.68], p < 0.001) were significantly higher in only-antegrade group compared to only-retrograde group. The debulked bias and the width of debulked area are not significantly different between the two groups. CONCLUSIONS: Compared to only-retrograde debulking, only-antegrade debulking acquired larger debulked area because of larger cutting depth, although the debulked bias and the width of debulked area were comparable between the two groups.

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.

Left atrial appendage peak flow velocity predicts improvement in mitral regurgitation after atrial fibrillation ablation.

BACKGROUND: Mitral regurgitation (MR) is associated with an increased risk of developing atrial fibrillation (AF) and high AF recurrence ratio after ablation. Left atrial appendage (LAA) is involved in left atrium (LA) pressure modulation and LAA peak flow velocity (LAAV) is validated as an indicator of LA contractile and reservoir function. LA function is related to the MR pathology, but the relationship between LAAV and improvement in MR after ablation remains unknown. METHODS: The present study included AF patients with moderate or severe MR from the Osaka Rosai Atrial Fibrillation ablation (ORAF) registry. We evaluated MR severity one-year post-ablation and assigned the patients based on MR improvement (at least a one-grade improvement in MR over one year) and investigated the impact of the relevant factors, including LAAV, on MR improvement. RESULTS: This study population included a total of 289 patients [paroxysmal AF (PAF), 112 patients; persistent AF (PerAF), 177 patients]. Kaplan-Meier analysis demonstrated that the patients with MR improvement had a significantly lower risk of late arrhythmia recurrence than those without (log-rank p < 0.001). MR improvement was observed in 56.3 % (63/112) of PAF patients and 55.4 % (98/177) of PerAF patients. Multiple regression analysis showed that LAAV was an independent and significant determinant of MR improvement post-ablation in both PAF and PerAF patients (p = 0.037 and p = 0.018, respectively), in addition to age and hemoglobin in PerAF patients (p = 0.045 and p = 0.048, respectively). CONCLUSION: LAAV can predict an improvement in MR after catheter ablation in both PAF and PerAF patients.

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.

Prognostic Comparison of Octogenarian vs. Non-Octogenarian With Acute Decompensated Heart Failure　- AURORA Study.

BACKGROUND: Acute decompensated heart failure (ADHF) is the main cause of hospitalization and death of octogenarians, but no data on the 1-year post-discharge mortality rate. We evaluated the clinical status and predictors of 1-year mortality in octogenarians with ADHF.Methods and Results: From the AURORA (Acute Heart Failure Registry in Osaka Rosai Hospital) study, we examined 1,246 hospitalized ADHF patients. We compared the in-hospital mortality rate and the proportion of heart failure (HF) with preserved ejection fraction (HFpEF) between octogenarians and non-octogenarians. After discharge we compared the 1-year mortality rate between these groups, and we also evaluated the predictors of death in both groups. The proportion of HFpEF among the in-hospital deaths of octogenarians was significantly higher than in non-octogenarians (46.2% vs. 15.0%, P=0.031). The 1-year mortality rate after discharge was significantly higher in the octogenarians than non-octogenarians (P=0.014). Multivariable Cox regression analysis revealed that albumin ≤3.0 g/dL and antiplatelet agents were useful predictors of 1-year death after discharge of octogenarians whereas chronic kidney disease was a predictor in the non-octogenarians. CONCLUSIONS: The proportion of HFpEF among in-hospital deaths of octogenarians with ADHF was high as compared with non-octogenarians. When octogenarians with ADHF have severe hypoalbuminemia and antiplatelet agents, early nutritional and medical interventions after discharge may be important to improve the 1-year prognosis.

Clinical Impact of Cryoballoon Ablation for Paroxysmal Atrial Fibrillation in Patients With Enlarged Left Atrium.

The impact of cryoballoon ablation (CBA) for atrial fibrillation (AF) in patients with enlarged left atrium (E-LA) has not been sufficiently clarified. A total of 306 patients underwent an initial CBA for paroxysmal AF between February 2017 and March 2022 in our hospital. These patients were categorized into 2 groups according to the preprocedural left atrium (LA) diameter (LAD): E-LA group with LAD ≥40 mm and normal LA (N-LA) group with LAD <40 mm. We compared late recurrence (LR, defined as a recurrence of atrial tachyarrhythmia more than 3 months after the ablation) between the 2 groups. In addition, we made a further classification of the E-LA group into a severely E-LA (SE-LA) group with LAD ≥50 mm and mildly enlarged LA (ME-LA) group with LAD <50 mm and compared LR in the SE-LA, ME-LA, and N-LA groups. In the patients who experienced a second ablation procedure owing to LR, subsequent recurrences were also evaluated. After initial CBA, there was no significant difference in recurrence-free survival between E-LA and N-LA groups (p = 0.447). In contrast, the SE-LA group showed the lowest incidence of recurrence-free survival in the SE-LA, ME-LA, and N-LA groups (p = 0.012). However, when we analyzed recurrences after the ablation including second ablation procedure, there were no significant differences in recurrence-free survival among these 3 groups (p = 0.103). In conclusion, patients with paroxysmal AF with enlarged LA showed favorable outcomes compared with those with N-LA after CBA.

Direct Comparison of Rotational vs Orbital Atherectomy for Calcified Lesions Guided by Optical Coherence Tomography.

BACKGROUND: There are several retrospective studies comparing rotational atherectomy (RA) and orbital atherectomy (OA), but all percutaneous coronary interventions (PCIs) in those studies were not performed under intracoronary imaging guidance. OBJECTIVES: This study sought to compare the efficacy and safety of optical coherence tomography (OCT)-guided PCI with RA vs OA. METHODS: The DIRO (To directly compare RA and OA for calcified lesions, a prospective randomized trial) trial was conducted. We enrolled patients with de novo calcified lesions (arc >180°) assessed by OCT or angiographically moderate or severe calcifications if the OCT catheter could not cross the lesion before any intervention. Eligible patients were randomly 1:1 allocated to lesion preparation with RA vs OA. Stent expansion was defined as the minimum stent area divided by the distal reference area multiplied by 100. Tissue modification was assessed using preatherectomy and postatherectomy OCT images. Procedural outcomes including periprocedural myocardial infarctions were evaluated. Furthermore, clinical events and vascular healing evaluated by OCT at 8 months postprocedure were assessed. RESULTS: The stent expansion was significantly greater in the RA group vs the OA group (99.5% vs 90.6%; P = 0.02). The maximum atherectomy area was significantly larger in the RA group than in the OA group (1.34 [IQR: 1.02-1.89] mm2 vs 0.83 [IQR: 0.59-1.11] mm2; P = 0.004). The procedural outcomes and clinical events at 8 months did not differ between the groups. The vascular healing was sufficient in both groups. CONCLUSIONS: The prospective randomized DIRO trial revealed that RA could produce a more favorable tissue modification, which may lead to a larger stent expansion than OA in heavily calcified lesions.