York Heart Association Functional Class Research Articles

Ertugliflozin for Functional Mitral Regurgitation Associated With Heart Failure: EFFORT Trial.

The morbidity and mortality rates of patients with heart failure (HF) and functional mitral regurgitation (MR) remain substantial despite guideline-directed medical therapy for HF. We evaluated the efficacy of ertugliflozin for reduction of functional MR associated with HF with mild to moderately reduced ejection fraction. The EFFORT trial (Ertugliflozin for Functional Mitral Regurgitation) was a multicenter, double-blind, randomized trial to examine the hypothesis that the sodium-glucose cotransporter 2 inhibitor ertugliflozin is effective for improving MR in patients with HF with New York Heart Association functional class II or III, 35%≤ejection fraction<50%, and effective regurgitant orifice area of chronic functional MR >0.1 cm2 on baseline echocardiography. We randomly assigned 128 patients to receive either ertugliflozin or placebo in addition to guideline-directed medical therapy for HF. The primary end point was change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, left ventricular (LV) volume indices, left atrial volume index, LV global longitudinal strain, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). The treatment groups were generally well-balanced with regard to baseline characteristics: mean age, 66±11 years; 61% men; 13% diabetes; 51% atrial fibrillation; 43% use of angiotensin receptor-neprilysin inhibitor; ejection fraction, 42±8%; and effective regurgitant orifice area, 0.20±0.12 cm2. The decrease in effective regurgitant orifice area was significantly greater in the ertugliflozin group than in the placebo group (-0.05±0.06 versus 0.03±0.12 cm2; P<0.001). Compared with placebo, ertugliflozin significantly reduced regurgitant volume by 11.2 mL (95% CI, -16.1 to -6.3; P=0.009), left atrial volume index by 6.0 mL/m2 (95% CI, -12.16 to 0.15; P=0.005), and LV global longitudinal strain by 1.44% (95% CI, -2.42% to -0.46%; P=0.004). There were no significant between-group differences regarding changes in LV volume indices, ejection fraction, or NT-proBNP levels. Serious adverse events occurred in one patient (1.6%) in the ertugliflozin group and 6 (9.2%) in the placebo group (P=0.12). Among patients with functional MR associated with HF, ertugliflozin significantly improved LV global longitudinal strain and left atrial remodeling, and reduced functional MR. Sodium-glucose cotransporter 2 inhibitors may be considered for patients with functional MR. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04231331.

Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.

Evaluation of mavacamten in patients with hypertrophic cardiomyopathy.

We aimed to comprehensively assess the safety and efficacy of mavacamten in hypertrophic cardiomyopathy (HCM) patients. A systematic review and meta-analysis was conducted, and efficacy [changes in postexercise left ventricular outflow tract (LVOT) gradient, left ventricular ejection fraction (LVEF), peak oxygen consumption (pVO 2 ), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS), and the proportion of patients exhibiting an improvement of at least one New York Heart Association (NYHA) functional class from baseline)], safety (total count of treatment-emergent adverse events and SAEs, as well as the proportion of patients experiencing at least one adverse event or SAE), and cardiac biomarkers (NT-proBNP and cTnI) outcomes were evaluated. We incorporated data from four randomized controlled trials, namely EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and EXPLORER-CN. Mavacamten demonstrated significant efficacy in reducing the postexercise LVOT gradient by 49.44 mmHg ( P = 0.0001) and LVEF by 3.84 ( P < 0.0001) and improving pVO 2 by 0.69 ml/kg/min ( P = 0.4547), KCCQ CSS by 8.11 points ( P < 0.0001), and patients with at least one NYHA functional class improvement from baseline by 2.20 times ( P < 0.0001). Importantly, mavacamten increased 1.11-fold adverse events ( P = 0.0184) 4.24-fold reduced LVEF to less than 50% ( P = 0.0233) and 1.06-fold SAEs ( P = 0.8631). Additionally, mavacamten decreased NT-proBNP by 528.62 ng/l ( P < 0.0001) and cTnI by 8.28 ng/l ( P < 0.0001). Mavacamten demonstrates both safety and efficacy in patients with HCM, suggesting its potential as a promising therapeutic strategy for this condition. Further research is warranted to confirm these results and explore its long-term effects.

Left bundle branch vs biventricular pacing for cardiac resynchronization therapy

Abstract Background/Introduction Left bundle branch pacing (LBBP) has emerged as a predominant conduction system pacing technique for reducing QRS duration in patients with intrinsic left bundle branch block (LBBB). It represents a potentially optimal alternative to cardiac resynchronization therapy (CRT) through biventricular pacing (BiVP). Purpose This study aims to compare the efficacy of LBBP-CRT with BiVP-CRT in patients experiencing heart failure with reduced left ventricular ejection fraction. Methods This single-center prospective study involved patients with heart failure and reduced ventricular ejection fraction, encompassing both ischemic and nonischemic cardiomyopathy. LBBP-CRT was employed when BiVP was unsuccessful for any reason, with LBBP-CRT implanted during the same procedure. After 3 and 6 months of preplanned follow-up, comparisons were made between the New York Heart Association (NYHA) functional class and QRS duration in the BiVP-CRT and LBBP-CRT groups. Results Sixty consecutive patients were included in the study (39 males, mean age 64.1 ± 10.6 years, LVEF 29.6% ± 5.6%). All patients completed follow-up, with 32 receiving LBBP-CRT and 28 receiving BiVP-CRT. All 32 LBBP-CRT patients achieved LBB capture, with 14 undergoing selective LBBP and 18 undergoing nonselective LBBP. The LBBP-CRT group exhibited shorter procedure and x-ray exposure times ((11.95 ± 5.77 vs 18.66 ± 10.12). The LBBP lead demonstrated a lower LBB capture threshold at implantation (0.7 ± 0.26 V vs. 1.1 ± 0.40 V; p= 0.039) compared to the CS LV lead in the BiVP-CRT group. Pacing parameters remained stable at the 6-month follow-up (0.72 ± 0.20 V vs. 1.1 ± 0.57 V; p=0.07). During the 3 and 6-month follow-up, pacing parameters remained stable in both groups. Only one patient in the LBBP-CRT group experienced dislodgment of the CS LV lead two days after the procedure, while no patients in the LBBP-CRT group had lead dislodgment. QRS duration significantly shortened in LBBP (171.6 ± 14.3 ms to 131.5 ± 12.5 ms; p=0.047) and remained not significantly shortened in BiVP (174.7 ± 14.1 ms to 150.6 ± 12.9 ms; p=0.06). Both LBBP and BiVP demonstrated improvement in NYHA functional class at the 3 and 6-month follow-up, with statistically significant differences observed between the two groups (change in NYHA functional class from baseline to 6 months -1.2 ± 0.1 vs -0.94 ± 0.11 p=0.047). Throughout the 6-month follow-up, neither the LBBP-CRT nor BiVP-CRT groups experienced rehospitalizations for heart failure, ventricular arrhythmia events, or all-cause death. Conclusions In this series, LBBP-CRT exhibited improvements in NYHA functional class and significantly shortened QRS duration when compared to BiVP-CRT in patients with reduced left ventricular ejection fraction and LBBB.

Effects of hemodynamic support on arrhythmia-free survival following catheter ablation of ventricular arrhythmias

Abstract Background Radiofrequency-guided catheter ablation is an established therapy for ventricular tachycardia (VA). Hemodynamic support (HS) is often required for patients suffering from incessant VA to guide ablation. Data on the outcome of patients receiving HS during VA ablation procedures are lacking. Purpose The aim of this observational study was to analyze the acute procedural success as well as long-term 36-month-VA-recurrence rates and mortality in patients requiring HS during VA ablation procedures. Methods Data from consecutive patients receiving HS during VA ablation procedures between 2015-2023 were analyzed. HS was defined as the use of an Impella, an extracorporeal membrane oxygenation (ECMO) or a left ventricular assist device (LVAD). HS-group patients were compared to patients that underwent VA ablation procedures without HS. All patients were continuously followed up in our outpatient clinic. Data on procedural parameters, acute success and complications as well as long-term VA-free survival and mortality were analyzed. Results A total of 95 consecutive patients (mean age 60.9 ± 11.0 years, 15% female) were included. 62 patients (65%, mean age 60.4±9.4 years, 16% female) receiving HS (ECMO or Impella: n=26, 42%; ECMO+Impella: n=7, 11%; LVAD: n=29, 47%) were compared to those without (mean age 61.7±13.5 years, 12 % female). In the HS-cohort a significantly lower left ventricular ejection fraction (LVEF) (p&amp;lt;0.001), a higher New York Heart Association (NYHA) functional class (p=0.013) and a more frequent antiarrhythmic drug use (p=0.045) was documented. Fluoroscopy times were significantly longer in the HS-group (HS: 10:22 ± 07:04 vs. no HS: 05:52 ± 02:50 minutes, p&amp;lt;0.001). Acute procedural success (HS: n=59, 95% vs. no HS: n=33, 100%, p=0.549) and major procedure complications (HS: n=4. 6% vs. no HS: n=4. 6%, p=1.000) were comparable between the two groups. Nevertheless, patients receiving HS had a significantly higher in-hospital mortality (HS: n=20, 32 % vs. no HS: n=2, 6%, p=0.004). The estimated 36-month-VA-free survival was comparable between the groups (Log-rank p=0.114). But Kaplan-Meier-plot analyses revealed a significantly higher estimated mortality in patients receiving HS (Log-rank p=0.002) (Figure 1). Between the subgroups (ECMO or Impella vs. LVAD) no statistically relevant differences were observed (Log-rank p=0.466). Multivariate analyses revealed HS as an independent predictor for mortality (Hazard ratio (HR) 3.259, Confidence Interval (CI) 1.060-10.015, p=0.039), but not for VA-recurrence. Conclusion In the specific cohort of patients receiving HS, VA ablation procedures seem to be safe and effective with comparable acute and long-term success- and complication-rates. The need for HS seems to be associated with an increased risk for mortality. Further studies are required to validate our initial observations.Kaplan-Meier-plot on 36-month survival

The effect of cardiac resynchronisation therapy upgrade from right ventricular pacing on symptoms and functional clinical outcomes, results from the BUDAPEST-CRT Upgrade trial

Abstract Background Based on the results of the BUDAPEST-CRT Upgrade trial, in patients with intermittent or permanent right ventricular (RV) pacing and reduced left ventricular ejection fraction (HFrEF) upgrade to cardiac resynchronization therapy (CRT) reduces morbidity and mortality. Purpose Whether the substantial treatment effect of the CRT upgrade could also be detected in a better functional and exercise capacity is scarcely investigated. We examined the changes of the prespecified tertiary endpoints such as symptoms, quality of life (QoL), exercise capacity and natriuretic peptide measurement from baseline to 12 months. Methods In the BUDAPEST CRT Upgrade trial 360 HFrEF patients with a priorly implanted PM or ICD and &amp;gt;20% of RV pacing burden were randomly assigned to CRT-D upgrade (n=215) or ICD (n=145) in a 3:2 ratio. The prespecified tertiary endpoints were changes in quality of life measured by EQ-5D-3L, New York Heart Association (NYHA) functional class, 6-minute walk test (6-MWT), and NT-proBNP. When data of trial patients were unavailable due to death at 12 months, imputed values were used as 0 (6MWT) and 0 score (EQ-5D-3L) or a 5th grade (NYHA class). Responders were defined as &amp;gt;15% change of left ventricular end-systolic volume at 12 months. Results From baseline to 12 months, NYHA functional class improved in the CRT-D upgrade arm compared with the ICD only group [adjusted odds ratio (OR) 0.50; 95% CI 0.32-0.80; P=0.003]. According to the adjusted model there was a statistically significant decrease in the NT-proBNP [adjusted difference -1257 pg/mL; 95% CI -2287 – (-228); P=0.017]. In responders, the changes in NT-proBNP levels were significantly greater than in non-responders [adjusted difference -1635 pg/mL; 95% CI -2811 - (-459); P=0.007]. The progression of worsening of QoL attributed to ageing was moderated only by CRT-D upgrade [EQ-5D-3L difference by age -0.01; 95% CI -0.02 - (-0.003); P=0.004; interaction P=0.003]. 6MWT did not improve significantly in either group. Conclusions Patients receiving CRT upgrade showed a substantial improvement in symptoms and a significant decrease in natriuretic peptide levels, as compared to ICD alone, which was more pronounced in responders. Moreover, CRT-D upgrade could moderate the progression of worsening of quality of life attributed to ageing in this vulnerable, older patient population.

A machine learning approach to classifying New York Heart Association (NYHA) heart failure

According to the European Society of Cardiology, globally the number of patients with heart failure nearly doubled from 33.5 million in 1990 to 64.3 million in 2017, and is further projected to increase dramatically in this decade, still remaining a leading cause of morbidity and mortality. One of the most frequently applied heart failure classification systems that physicians use is the New York Heart Association (NYHA) Functional Classification. Each NYHA class describes a patient’s symptoms while performing physical activities, delivering a strong indicator of the heart performance. In each case, a NYHA class is individually determined routinely based on the subjective assessment of the treating physician. However, such diagnosis can suffer from bias, eventually affecting a valid assessment. To tackle this issue, we take advantage of the machine learning approach to develop a decision-tree, along with a set of decision rules, which can serve as additional blinded investigator tool to make unbiased assessment. On a dataset containing 434 observations, the supervised learning approach was initially employed to train a Decision Tree model. In the subsequent phase, ensemble learning techniques were utilized to develop both the Voting Classifier and the Random Forest model. The performance of all models was assessed using 10-fold cross-validation with stratification.The Decision Tree, Random Forest, and Voting Classifier models reported accuracies of 76.28%, 96.77%, and 99.54% respectively. The Voting Classifier led in classifying NYHA I and III with 98.7% and 100% accuracy. Both Random Forest and Voting Classifier flawlessly classified NYHA II at 100%. However, for NYHA IV, Random Forest achieved a perfect score, while the Voting Classifier reported 90%. The Decision Tree showed the least effectiveness among all the models tested. In our opinion, the results seem satisfactory in terms of their supporting role in clinical practice. In particular, the use of a machine learning tool could reduce or even eliminate the bias in the physician’s assessment. In addition, future research should consider testing other variables in different datasets to gain a better understanding of the significant factors affecting heart failure.

New York Heart Association functional class and implantable cardioverter-defibrillator in non-ischaemic heart failure with reduced ejection fraction: Extended follow-up of the DANISH trial.

Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure, a left ventricular ejection fraction of ≤35%, and New York Heart Association (NYHA) class II-III. However, the evidence regarding the benefit of primary prevention ICD is less consistent in patients with NYHA class III. We investigated the long-term effects of primary prevention ICD implantation according to NYHA class in an extended follow-up study of the DANISH trial. The DANISH trial randomized 1116 patients with non-ischaemic heart failure with reduced ejection fraction (HFrEF) to ICD implantation or usual care. Outcomes were analysed according to NYHA class at baseline (NYHA class II and III/IV). The primary outcome was all-cause mortality. Of the 1116 patients randomized in the DANISH trial, 597 (53.5%) were in NYHA class II at baseline, 505 (45.3%) in NYHA class III, and 14 (1.3%) in NYHA class IV. During a median follow-up of 9.5 years, NYHA class III/IV, compared with NYHA class II, were associated with a greater long-term rate of all-cause mortality (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.20-1.93) and cardiovascular death (HR 1.95 [1.47-2.60]). ICD implantation, compared with usual care, did not reduce the long-term rate of all-cause mortality (all participants: HR 0.89 [95% CI 0.74-1.08]; NYHA class II: HR 0.85 [0.64-1.13]; NYHA class III/IV: HR 0.89 [0.69-1.14]; pinteraction = 0.78) or cardiovascular death (all participants: HR 0.87 [95% CI 0.70-1.09]; NYHA class II: HR 0.78 [0.54-1.12]; NYHA class III/IV: HR 0.89 [0.67-1.19]; pinteraction = 0.58), irrespective of NYHA class. Similarly, NYHA class did not modify the beneficial effects of ICD implantation on sudden cardiovascular death (all participants: HR 0.60 [95% CI 0.40-0.92]; NYHA class II: HR 0.73 [0.40-1.36]; NYHA class III/IV: HR 0.52 [0.29-0.94]; pinteraction = 0.39). In patients with non-ischaemic HFrEF, ICD implantation, compared with usual care, did not reduce the overall mortality rate, but it did reduce sudden cardiovascular death, regardless of baseline NYHA class. ClinicalTrials.gov NCT00542945.

Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

Impact of heart failure hospitalizations on clinical outcomes after mitral transcatheter edge-to-edge repair: Results from the EXPAND study.

This analysis aimed to compare the clinical outcomes associated with heart failure (HF) readmissions and to identify associations with HF hospitalizations (HFH) in patients treated with the MitraClip™ NTR/XTR System in the EXPAND study. The global, real-world EXPAND study enrolled 1041 patients with primary or secondary mitral regurgitation (MR) treated with the MitraClip NTR/XTR System. Echocardiograms were analysed by an independent echocardiographic core laboratory. The study population was stratified into HFH and No-HFH groups based on the occurrence of HFH 1 year post-index procedure. Clinical outcomes including MR severity, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and all-cause mortality were compared (HFH: n = 181; No-HFH: n = 860). Both groups achieved consistent 1-year MR reduction to ≤1+ (HFH vs. No-HFH: 87.3% vs. 89.5%, p = 0.6) and significant 1-year improvement in KCCQ scores (+16.5 vs. +22.3, p = 0.09) and NYHA functional class. However, more patients in the No-HFH group had 1-year NYHA class ≤II (HFH vs. No-HFH: 67.9% vs. 81.9%, p < 0.01). All-cause mortality at 1 year was 36.8% in the HFH group versus 10.4% in the No-HFH group (p < 0.001). The HFH rate decreased by 63% at 1 year post-M-TEER versus 1 year pre-treatment (relative risk 0.4, p < 0.001). Independent HFH associations were MR ≥2+ at discharge, HFH 1 year prior to treatment, baseline NYHA class ≥III, baseline tricuspid regurgitation ≥2+, and baseline left ventricular ejection fraction ≤40%. This study reports the impact of HFH on clinical outcomes post-treatment in the EXPAND study. Results demonstrate that the occurrence of HFH was associated with worse 1-year survival, and treatment with the MitraClip system substantially reduced HFH and improved patient symptoms and quality of life.

Low irisin levels predict acutely decompensated heart failure in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements None. Background Acutely decompensated heart failure (ADHF) continues to be associated with unacceptably increasing in-hospital mortality rates and one-year mortality rates. Distinct scenarios of the natural course of ADHF relate to clinical heterogeneity among patients admitted to hospitals, cardiac dysfunction etiology, precipitating factors contributing to heart failure (HF) decompensation including type 2 diabetes mellitus (T2DM). The aim of this study was to determine the discriminative value of irisin for ADHF in T2DM patients with hemodynamically stable chronic HF. Methods A total of 738 patients with T2DM were prescreened using the local database of "Vita Center" (Ukraine). Using criteria of inclusion (male/female with age of ≥18 years, established T2DM with hemodynamically stable chronic HF, glycosylated hemoglobin &amp;lt; 6.9%, informed consent to participate in the study), we enrolled 489 patients with T2DM with concomitant chronic HF I-IV New York Heart Association (NYHA) functional classes. We enrolled 480 T2DM patients with any phenotype of HF and followed them for 52 weeks. Hemodynamic performances and the serum levels of biomarkers were detected at the study entry. The primary clinical end-point was ADHF that led to urgent hospitalization. Results We found that the serum levels of N-terminal natriuretic pro-peptide (NT-proBNP) were higher (1719 [980-2457] pmol/mL vs. 1057 [570-2607] pmol/mL, respectively) and the levels of irisin were lower (4.96 [3.14-6.85] ng/mL vs. 7.95 [5.73-9.16] ng/mL) in ADHF patients than in those without ADHF. The ROC curve analysis showed that the estimated cut-off point for serum irisin levels (ADHF versus non-ADHF) was 7.85 ng/mL (area under curve [AUC] = 0.869 (95% CI = 0.800-0.937), sensitivity = 82.7%, specificity = 73.5%; p = 0.0001). The multivariate logistic regression yielded that the serum levels of irisin &amp;lt; 7.85 ng/mL (OR = 1.20; p = 0.001) and NT-proBNP &amp;gt; 1215 pmol/mL (OR = 1.18; p = 0.001) retained the predictors for ADHF. Kaplan-Meier plots (Figure) showed a significant difference of clinical end-point accumulations in patients with HF depending on irisin levels (&amp;lt;7.85 ng/mL versus ≥7.85 ng/mL). The intra-class correlation coefficient for inter-observer reproducibility of LV dimensions was 0.88 (95% CI = 0.83–0.92), of LVEF was 0.93 (95% CI = 0.90–0.97), of LAVI was 0.92 (95% CI = 0.89–0.94), and of E/e’ was 0.90 (95% CI = 0.87–0.94). Along with it, the intra-class correlation coefficient for the intra-observer reproducibility of LV dimensions was 0.91 (95% CI = 0.88–0.95), of LVEF was 0.94 (95% CI = 0.90–0.98), of LAVI was 0.95 (95% CI = 0.93–0.97), and of E/e’ was 0.92 (95% CI = 0.90–0.95). In conclusion, we established that decreased levels of irisin were associated with ADHF presentation in chronic HF patients with T2DM independently from NT-proBNP.Flow chart of the study designThe Kaplan–Meier analysis of ADHF

Characteristics Associated with Ventricular Tachyarrhythmias and Their Prognostic Impact in Heart Failure with Mildly Reduced Ejection Fraction.

Background: The occurrence of ventricular tachyarrhythmias represents an established risk factor of mortality in heart failure (HF). However, data concerning their prognostic impact in heart failure with mildly reduced ejection fraction (HFmrEF) is limited. Therefore, the present study aims to investigate patient characteristics associated with ventricular tachyarrhythmias and their prognostic impact in patients with HFmrEF. Methods: Consecutive patients hospitalized with HFmrEF (i.e., left ventricular ejection fraction 41-49% and signs and/or symptoms of HF) were retrospectively included at one institution from 2016 to 2022. The prognosis of patients with HFmrEF and different types of ventricular tachyarrhythmias (i.e., non-sustained ventricular tachycardia (nsVT), sustained VT (sVT), and ventricular fibrillation (VF) was investigated for the primary endpoint of long-term all-cause mortality at 30 months. Secondary endpoints included in-hospital all-cause mortality and long-term HF-related rehospitalization at 30 months. Results: From a total of 2184 patients with HFmrEF, 4.4% experienced ventricular tachyarrhythmias (i.e., 2.0% nsVT, 0.7% sVT, and 1.6% VF). The occurrence of nsVT was associated with higher New York Heart Association (NYHA) functional class, whereas the incidence of sVT/VF was associated with acute myocardial infarction and ischemic heart disease. However, nsVT (25.0%; HR = 0.760; 95% CI 0.419-1.380; p = 0.367) and sVT/VF (28.8%; HR = 0.928; 95% CI 0.556-1.549; p = 0.776) were not associated with a higher risk of long-term all-cause mortality compared to patients with HFmrEF without ventricular tachyarrhythmias (31.5%). In-hospital cardiovascular mortality was more frequently observed in patients with HFmrEF and sVT/VF compared to those with HFmrEF but without sustained ventricular tachyarrhythmias (7.7% vs. 1.5%; p = 0.004). Finally, the risk of rehospitalization for worsening HF was not affected by the presence of ventricular tachyarrhythmias. Conclusions: The occurrence of ventricular tachyarrhythmias in patients hospitalized with HFmrEF was low and not associated with long-term prognosis.

Clinical and Electrophysiological Outcomes of Left Bundle Area Pacing Compared to Biventricular Pacing: An Updated Meta-analysis.

Left bundle branch area pacing (LBBAP) is a novel pacing strategy that uses the conduction system distal to the left bundle branch block level for direct activation of the left bundle and right ventricular myocardium. Our meta-analysis compared the structural, electrophysiological, clinical, and procedural outcomes of LBBAP and biventricular pacing (BVP). The meta-analysis included two randomized controlled trials and showed significant reductions in the left ventricular (LV) systolic and diastolic volumes with LBBAP compared to BVP, together with statistically significant reductions in the QRS duration, New York Heart Association (NYHA) functional class, and heart failure (HF) hospitalizations. The fluoroscopic time was also significantly shorter in the LBBAP group. However, no significant change in the LV ejection fraction was noted. Procedural complications were slightly higher in the LBBAP group, albeit not to a statistically significant degree. Our findings suggest that LBBAP may be a superior alternative to standard BVP in improving the structural, electrophysiological, and clinical components of cardiomyopathy, including the NYHA class and HF hospitalizations. LBBAP is a more physiological pacing strategy that results in normal ventricular activation and may be a viable alternative to BVP for cardiac synchronization therapy.

Effects of trimetazidine on heart failure with reduced ejection fraction and associated clinical outcomes: a systematic review and meta-analysis

BackgroundDespite maximal treatment, heart failure (HF) remains a major clinical challenge. Besides neurohormonal overactivation, myocardial energy homoeostasis is also impaired in HF. Trimetazidine has the potential to restore myocardial energy...

Evaluating haemodynamic changes: vericiguat in patients with heart failure with reduced ejection fraction.

Vericiguat has been used to treat patients with heart failure with reduced ejection fraction (HFrEF) who demonstrated worsening heart failure despite treatment with other guideline-directed medical therapies. The haemodynamic effects of vericiguat remain unclear. This study enrolled 12 patients (median age, 63 [quartiles 53.5, 70] years; 16.7%(N=2) women) with symptomatic HFrEF (New York Heart Association functional class II-IV) who demonstrated worsening heart failure despite treatment with the four foundational guideline-recommended therapies between March and December 2022, with follow-ups completed in June 2023. A balloon-tipped pulmonary artery thermodilution catheter was placed in the right internal jugular vein to perform right heart catheterisation (RHC) on day 1. Haemodynamic data were acquired before and after vericiguat intake (2.5mg) on days 2 and 3. The data on days 2 and 3 were averaged. RHC was repeated on day 105 (37, 168). Oral intake of vericiguat 2.5mg decreased mean pulmonary artery pressure (19.3 [14.3, 26.8] mmHg) and pulmonary artery wedge pressure (PAWP) (11 [7.5, 15] mmHg) before the intake to mean pulmonary artery pressure (17.5 [12.5, 24] mmHg) and PAWP (9.3 [6.8, 14] mmHg) at 30min after (both P<0.05). Reduction in PAWP was also found from 14.5 [9.5, 19.5] mmHg on day 1 to 9.5 [6.5, 12.5] mmHg on day 105 (37, 168) (P<0.05), when vericiguat was titrated to 2.5mg 25% (N=3), 5mg 50% (N=6), and 10mg 25% (N=3). The consistent reduction in PAWP underscores the well-tolerated nature of vericiguat and its potential to enhance cardiac performance in patients with HFrEF.

Implication of geriatric nutritional risk index on treatment response and long-term prognosis in patients with cardiac resynchronization therapy

PurposeGeriatric Nutritional Risk Index (GNRI) is a simple tool for assessing the nutritional status of the aging population. This study aims to explore the clinical implication of GNRI on treatment response and long-term clinical outcomes in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). MethodsPatients who underwent CRT implantation or upgrade at our hospital were retrospectively included. The association of GNRI and its tertiles with the echocardiographic response, all-cause mortality or heart transplantation, and the first hospitalization due to HF were investigated. ResultsTotally, 647 patients were enrolled, with a median age of 60 [Interquartile Range (IQR): 52–67] years and mean score of GNRI at 107.9 ± 23.7. Super-response rates increased significantly among the GNRI T1, T2, and T3 groups (25.1%, 29.8% vs. 41.1%, P = 0.002). Patients with higher GNRI were more likely to have better LVEF improvement after multiple adjustments (OR = 1.13, 95% CI: 1.04–1.23, P = 0.010). Higher GNRI was independently associated with a lower risk of all-cause mortality or heart implantation (HR = 0.95, 95% CI: 0.93–0.96, P < 0.001) and HF hospitalization (HR = 0.96, 95% CI: 0.95–0.98, P < 0.001). The inclusion of GNRI enhanced the predictability of all-cause mortality based on traditional model, including sex, New York Heart Association functional class, left bundle branch block, QRS reduction, and N-terminal pro-B-type natriuretic peptide level (C statistics improved from 0.785 to 0.813, P = 0.007). ConclusionHigher GNRI was associated with better treatment response and long-term prognosis in HF patients with CRT. Evaluation of nutritional status among CRT population is necessary for individualized choice of potential responders.

Incidence of Hospitalization-Associated Disability in Older Patients With Heart Failure.

This study determined the incidence of hospitalization-associated disability (HAD) and its characteristics in older patients with heart failure in Japan.Methods and Results: Ninety-six institutions participated in this nationwide multicenter registry study (J-Proof HF). From December 2020 to March 2022, consecutive heart failure patients aged ≥65 years who were prescribed physical rehabilitation during hospitalization were enrolled. Of the 9,403 patients enrolled (median age 83.0 years, 50.9% male), 3,488 (37.1%) had HAD. Compared with the non-HAD group, the HAD group was older and had higher rates of hypertension, chronic kidney disease, and cerebrovascular disease comorbidity. The HAD group also had a significantly lower Barthel Index score and a significantly higher Kihon checklist score before admission. Of the 9,403 patients, 2,158 (23.0%) had a preadmission Barthel Index score of <85 points. Binomial logistic analysis revealed that age and preadmission Kihon checklist score were associated with HAD in patients with a preadmission Barthel Index score of ≥85, compared with New York Heart Association functional classification and preadmission cognitive decline in those with a Barthel Index score <85. This nationwide registry survey found that 37.1% of older patients with HF had HAD and that these patients are indicated for convalescent rehabilitation. Further widespread implementation of rehabilitation for older patients with heart failure is expected in Japan.

Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction

Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.

Prognostic performance of pulmonary effective arterial elastance in patients with heart failure

Objective: To explore the predictive value of pulmonary effective arterial elastance (Ea) in patients with heart failure (HF). Methods: This is a retrospective cohort study, which retrospectively included 284 patients with HF who underwent right heart catheterization at Heart Failure Center in Fuwai Hospital between September 2013 and February 2022. Data regarding baseline clinical characteristics, hemodynamic profiles, and prognosis were collected. Ea was calculated as mean pulmonary arterial pressure/stroke volume. Patients were divided into Ea<0.555 group and Ea≥0.555 group according to the median value of Ea (0.555 mmHg/ml, 1 mmHg=0.133 kPa). The primary outcome was the primary clinical event, set as the first occurrence of a series of composite events, including all-cause death, heart transplantation, left ventricular assist device implantation, and HF rehospitalization. Event-free survival was defined as the absence of primary clinical events. Spearman correlation analysis was used to calculate the correlation coefficient between Ea and parameters reflective of right heart function. The Kaplan-Meier analysis was used to compare the different groups for the estimation of outcomes with the log-rank test. We used Cox proportional-hazards regression models to estimate hazard ratios (HR) for primary clinical event. Subgroup analysis was performed based on the age, gender, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, presence of pulmonary hypertension, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values. We used receiver operating characteristic (ROC) curve to calculate the area under the curve (AUC) of Ea for predicting event-free survival in patients with HF. Results: The median age was 51 years, and 206 (72.5%) patients were male. Ea and pulmonary vascular resistance (PVR) were significantly correlated (r=0.698, P<0.001). The correlation between Ea and pulmonary arterial elastance (PAC) were even more significant (r=-0.888, P<0.001). Compared with Ea<0.555 group, Ea≥0.555 group presented with higher serum NT-proBNP values (4 443 (1 792, 8 554) ng/L vs. 1 721 (480, 4 528)ng/L,P<0.001), higher PVR (3.4 (2.5, 4.7) Wood vs. 1.4 (0.9, 2.2) Wood, P<0.001), lower cardiac output (3.0 (2.3, 3.9) L/min vs. 4.3 (3.8, 4.9) L/min, P<0.001), and lower PAC (1.6 (1.3, 2.0) ml/mmHg vs. 4.0 (3.0, 6.0) ml/mmHg, P<0.001). The median follow-up time was 392 (166, 811) days. The Kaplan-Meier survival curve demonstrated a lower event-free survival rate in the Ea≥0.555 group compared to the Ea<0.555 group (Plog-rank<0.001). After multivariate adjustment, Ea (HR=1.734, P<0.001) remained significantly associated with the primary outcome. Subgroup analysis indicated that Ea was associated with the primary outcome across all subgroups. The AUC was 0.724 (P<0.001) for Ea to predict event-free survival calculated from ROC analysis. Conclusions: Ea is closely related to parameters reflective of right ventricular afterload. Increased Ea is an independent predictor of adverse outcomes in patients with HF.

Simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction: initial experience.

Simultaneous transcatheter mitral valve in valve (VIV) replacement and aortic valve replacement experience is limited. We report our initial experience with simultaneous transapical transcatheter aortic and mitral valve replacement in patients with severe valve dysfunction. A total of 8 patients had simultaneous transcatheter heart valve implants for severe mitral bioprosthesis failure (VIV), with a second valve procedure that included native aortic regurgitation (n = 3) or degenerated bioprostheses in the aortic position (n = 5). All patients were treated with a self-expandable J-valve transcatheter valve, using the transapical approach. The mean age of the patients was 73.1 ± 6.2years. The mean Society of Thoracic Surgeons score was 13.8 ± 6.3%. Device success was 100% according to Valve Academic Research Consortium-2 criteria. No other procedure-associated complications occurred, including left ventricular outflow tract obstruction and valve migration. The mean hospital lengths of stay after the procedure were 11.5 ± 8.0days. No deaths occurred at 30days. At a median follow-up period of 28.7 ± 22.3months, no patients died. All patients were in New York Heart Association functional classes I-II. Echocardiographic parameters at follow-up showed a normofunctioning J valve in the mitral position and a mean max mitral flow velocity of 2.0 ± 0.5m/s; the J valve in the aortic position was also normofunctioning, and the mean max aortic flow velocity was 2.3 ± 0.5m/s. Simultaneous transapical transcatheter aortic and mitral valve replacement using the self-expandable J valve appears to be a feasible and effective alternative to redo surgery.