York Heart Association Class Research Articles

Discordance between symptomatic response and changes in cardiac structure and function one year after transcatheter aortic valve implantation

Abstract Background Symptomatic improvement is one of the main goals of transcatheter aortic valve implantation (TAVI) in patients with severe symptomatic aortic stenosis. We hypothesized that the degree of symptomatic response after TAVI is associated with improvement in cardiac structure and function after TAVI. Purpose We aimed to evaluate 1) the change in symptomatic burden measured by New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) functional class after TAVI, 2) the change in echocardiographic structural and functional parameters after TAVI, and 3) the association of symptomatic response with echocardiographic response as well as long-term survival. Methods In patients undergoing TAVI, we assessed New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) functional class at 12 months. Symptomatic response was defined as NYHA/CCS class I or ≥ 1 improvement in NYHA/CCS class compared to baseline at 12 months. Echocardiographic images at baseline and 6-18 months post-TAVI were analysed using an automated, validated, deep-learning workflow. Logistic regression was used to assess association between change in echocardiographic parameters and symptomatic change at 12 months. The association of symptomatic response and echocardiographic changes in the first 12 months after TAVI with survival beyond 12 months, was evaluated by landmark analysis using Kaplan-Meier analysis. Results Among 868 TAVI patients (median age 80 years, 53% female), the majority (74%) had NYHA/CCS class III at baseline and 77% of patients experienced improvement in symptoms at 12 months post-TAVI (Figure 1). Patients without an improvement in symptoms more often had COPD, atrial fibrillation and more heart failure medications compared to responders. Left ventricular systolic function did not show improvement compared to baseline, whereas a modest improvement in left atrial volume index, left ventricular mass index, E/A ratio, E/e’ ratio, mean e’ and tricuspid regurgitation peak jet velocity was observed. Symptomatic response was not associated with echocardiographic response. Beyond 12 months, patients with symptomatic improvement had lower mortality than those without symptomatic improvement (1.5 vs. 2.4 per 10 patient years; p = .001), whereas changes in echocardiographic parameters were not associated with subsequent mortality (Figure 2). Conclusion Patients undergoing TAVI for symptomatic severe aortic stenosis, showed substantial symptomatic improvement at one year after the procedure, whereas only a modest improvement in echocardiographic parameters was observed. Improvement in symptoms was not associated with improvement in echocardiographic measures of cardiac structure and function. Symptomatic improvement, but not improvement in cardiac structure and function at 12 months, was a strong predictor of subsequent survival.Change in NYHA/CCS class after TAVISymptoms and echo versus mortality

Long-term safety and efficacy of mavacamten in obstructive hypertrophic cardiomyopathy: up to 3.5-year follow-up results of the EXPLORER cohort of MAVA-Long-Term Extension study

Abstract Introduction Mavacamten safety and efficacy in patients with obstructive hypertrophic cardiomyopathy (HCM) was demonstrated in the phase 3 EXPLORER-HCM trial. Long-term safety and efficacy of mavacamten in patients with obstructive HCM is being studied in the MAVA-Long-Term Extension (LTE) study (NCT03723655). Purpose To present long-term safety and efficacy data from the EXPLORER cohort of MAVA-LTE up to week 180 (data cutoff: August 31, 2023). Methods Patients who completed EXPLORER-HCM could enroll in MAVA-LTE following washout. All patients received mavacamten 5 mg at baseline; dose titration to 2.5, 10, or 15 mg was based on site-read echocardiographic evaluation of Valsalva left ventricular outflow tract (LVOT) gradient and left ventricular ejection fraction (LVEF). Following titration, patients were assessed at 12-week intervals between weeks 24 to 156; week 180 was the first visit following a 24-week interval. Results At the data cutoff, 211 of 231 patients who enrolled in MAVA-LTE were on treatment; 185 and 99 patients had reached week 156 and 180, respectively (median [interquartile range (IQR)] time on study: 166 [160–189] weeks; total exposure: 739 patient-years). Sustained improvements from baseline to weeks 156 and 180 were observed in mean (standard deviation [SD]) resting LVOT gradient (−40.2 [32.8] mmHg, n=187; and −40.3 [32.7] mmHg, n=94; respectively), Valsalva LVOT gradient (−55.3 [37.3] mmHg, n=184; and −55.3 [33.7] mmHg, n=91) (Figure 1), and median (IQR) N-terminal pro B-type natriuretic peptide levels (−504 [−1160, −143] ng/L, n=179; and −562 [−1162.5, −209] ng/L, n=88). Improvements from baseline to weeks 144 and 180 were sustained in mean (SD) left atrial volume index (−3.5 [10.4] mL/m2, n=193; and −5.5 [9.7] mL/m2, n=62; respectively). At week 156 and 180, 53.5% and 66.3% of patients, respectively, were in New York Heart Association class I. Mean (SD) LVEF decreased from baseline to week 180 (−11.0% [8.9%]; n=93) but the mean (63.9%) remained within normal range. Overall, 33 patients (14.3%) experienced atrial fibrillation, 14 patients (6.1%) experienced cardiac failure episodes, 13 patients (5.6%) permanently discontinued treatment owing to adverse events and 20 patients (8.7%) experienced transient reductions in LVEF < 50% (range: 30–48%), of whom 6 (2.6%) experienced LVEF < 40% (Figure 2). Of these 20 patients (13 from the placebo group in EXPLORER-HCM), all recovered LVEF ≥ 50% following treatment interruption and 14 reinitiated medication. In total, 5 patients died during the study (all deaths unrelated to mavacamten). Conclusions Long-term mavacamten treatment in patients with obstructive HCM resulted in sustained improvements in echocardiographic measures, symptoms, and biomarkers. Treatment was well-tolerated; no new safety signals were observed. Transient and reversible reductions in LVEF were observed in a small proportion of patients during long-term therapy.

Adverse prognostic implications of increased left ventricular force in hypertrophic cardiomyopathy

Abstract Background The left ventricular (LV) force, also known as elastance, serves as a load-independent indicator of contractility and can be noninvasively assessed through echocardiography. In hypertrophic cardiomyopathy (HCM), the heightened presence of the active state of myosin heads results in an increased LV force. Purpose To assess the prognostic value of increased LV elastance at rest in patients with HCM. Methods We enrolled 1420 HCM patients (age 50±16 years, 907 males, 64%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 10 quality-controlled labs from 7 countries. TTE assessment included peak left ventricular outflow tract gradient (LVOTG), EF, and LV force (systolic blood pressure + LVOTG/LV end-systolic volume assessed with 2-D, mmHg/mL). All patients were followed up. All-cause death was the outcome measure. Results At a median follow-up of 83 months, 150 deaths occurred (Group 1). At study entry, Group 1 patients had the same ESC-Sudden cardiac death score compared to survivors (Group 2). In Group 1 compared to Group 2, TTE showed higher values of MR severity, E/e’ , left atrial volume index, estimated systolic pulmonary artery pressure, and force (see table). At multivariable Cox analysis, only age (HR =1.08, 95% CI=1.03-1.14, p=0.001) and force > median value of 5.3 mmHg/mL (HR = 2.14, 95% CI 1.53-2.99, p=0.020) were independent predictors of mortality. Ten-year survival was 95% in the pooled first (<3.8 mmHg/mL) and second (3.8-5.2 mmHg/mL) quartiles vs 80% in the pooled third (5.3-7.8 mmHg/mL) and fourth quartiles (>7.8 mmHg/mL), see figure. Conclusion HCM patients with higher values of resting LV elastance show a worse survival, highlighting the dark prognostic side of an excess of force in these patients. Table Legends E/e’, early mitral inflow to early mitral annulus motion ratio, EF, left ventricular ejection fraction, LAVI, left atrial volume index; LVOTG, left ventricular outflow tract peak gradient, MR, mitral regurgitation; MWT, maximal wall thickness, NYHA, New York Heart Association classification, RWT, relative wall thickness; SCD risk, risk score for sudden cardiac death in hypertrophic cardiomyopathy, SPAP, systolic pulmonary arterial pressure.Table.Clinical and TTE findingsFigure.Survival in the force quartiles

Association between self-care behaviour and multiple frailty domains in older patients with heart failure

Abstract Background/Introduction Heart failure (HF) self-care is important for the effective management of HF, reducing clinical events such as all-cause mortality and hospitalizations. HF self-care behaviours encompass comply with a regimen involving medication, diet, and exercise, symptom monitoring, and seeking assistance when symptoms occur. Frailty, prevalent among older patients with HF, involves physical, social, and cognitive domains. Identified factors influencing self-care behaviours in patients with HF include age, social support, and knowledge of the condition. Despite research on the association between self-care behaviours and frailty, there is a notable gap in studies that explore the relationship between self-care behaviour and multiple domains of frailty, particularly with adjustments for clinical characteristics. Purpose The aim of this study was to assess the association between self-care behaviour and multiple domains of frailty in older patients with HF. Methods The study included 182 patients with HF who were aged 65 years or older. Self-care behaviour was assessed 5 months after their discharge using the European Heart Failure Self-Care Behaviour Scale (EHFScBS), a self-report questionnaire. Frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria (J-CHS) for physical frailty, and using Makizako’s five items for social frailty, and using Mini-Cog for cognitive decline. We used multiple regression analysis to assess the association between self-care score and multiple frailty domains and the number of frailty domains. The adjusted model was constructed based on age, gender, body mass index, New York Heart Association Classification, left ventricular ejection fraction, log-transformed B-type natriuretic peptide, estimated glomerular filtration rate and history of HF. In addition, we used multiple regression analysis to assess the association between the EHFScBS subitems score complying with regimen, asking for help, and adapting activities and multiple frailty domains and the number of frailty domains. Results According to the results of a multiple regression analysis, poor self-care behaviour was significantly associated with physical and social frailty and the number of frailty domains (all p < 0.05), even after adjusting for clinical characteristics. Poor complying with regimen was also significantly associated with physical and social frailty and the number of frailty domains (all p < 0.05). Poor asking for help was significantly associated with social frailty and the number of frailty domains (all p < 0.05). Conclusion The study indicates that poor self-care behaviour is linked to physical and social frailty, in addition to the cumulative number of frailty domains in older patients with HF, even when clinical characteristics are taken into consideration. This underscores the importance of factoring in the frailty status when guiding patients with HF in disease management.

Smaller intrinsic QRS area and smaller reduction of QRS area during cardiac resynchronisation therapy are associated with higher risk of ventricular arrhythmias and appropriate ICD therapy

Abstract Background Cardiac resynchronisation therapy (CRT) patients are at high risk for ventricular arrhythmias (VAs), and little is known about which characteristics are associated with an increased risk for arrhythmic events. Purpose To investigate the association between QRS area parameters and the risk for VAs in patients with heart failure undergoing primary preventive CRT with defibrillator (CRT-D) implantation. Methods All patients receiving CRT-D between 2015 and 2020 at a large-volume tertiary care center were retrospectively evaluated. Digital 12-lead electrocardiograms (ECGs) were collected before and after CRT implantation. Patients were included if they had native LBBB and were implanted with a primary preventive CRT-D. Kors’ regression transformation was used to derive vectorcardiographic QRS area from the 12-lead ECGs. QRS area parameters were analysed in relation to a primary endpoint of first appropriate ICD therapy, i.e., ATP or shock therapy. Results 177 patients with LBBB (68.9 years [60.7–73.8]; 21.5% female; 52.9% New York Heart Association (NYHA) class III-IV; LVEF 25.9±6.3%) were followed over a median follow-up time of 2.5 years [1.6–3.0] after CRT-D implantation. 27 patients reached the primary endpoint. The median pre-CRT QRS area was 134.5 μVs [102.3–163.8]. Multivariable Cox regression identified a small pre-CRT QRS area (HR, per 10 μVs decrease, 1.30; [1.12–1.51]; p=<.001) and a small post-CRT reduction in QRS area (HR, per 10 μVs decrease, 1.30; [1.13–1.49]; p=<.001) as independent predictors of an increased risk of appropriate ICD therapy. In analyses with a scoring variable combining pre-CRT QRS area and QRS area reduction both above or below median, the combination of a small pre-CRT QRS area and a small QRS area reduction was strongly associated with an increased risk of reaching the endpoint (HR, per point increase, 2.47; [1.2–4.9]; p=0.01). Conclusion A small intrinsic QRS area, by itself or in combination with a small reduction of post-CRT QRS area, was strongly associated with a higher risk of ventricular arrhythmias in this cohort of CRT-D treated patients. In conjunction with other parameters, further risk stratification for arrhythmic events could be achieved by assessing QRS area data pre- and post-CRT.Figure 1.K-M pre-CRT QRS area quartilesFigure 2.K-M QRS area score

Conduction system pacing and atrioventricular node ablation for atrial fibrillation - a systematic review and meta-analysis

Abstract Background/Introduction Biventricular pacing (BVP) has been shown to reduce the risk of heart failure following atrioventricular node ablation (AVNA) for the management of medically refractory atrial fibrillation (AF) when compared with conventional right ventricular pacing.[1] Conduction system pacing (CSP) is an emerging cardiac synchronization alternative to BVP[2], however, its evidence in AVNA for AF is limited. Purpose To evaluate the effect of CSP on left ventricular ejection fraction (LVEF), QRS duration (QRSd), pacing threshold and New York Heart Association (NYHA) class score following AVNA for AF. Methods We conducted a literature review of PUBMED, MEDLINE, EMBASE, Cochrane Library, and Web of Science for randomized clinical trials (RCTs) and observational studies evaluating CSP (His bundle pacing and left bundle branch pacing) post AVNA for AF. Out of 14 studies comprising 1112 patients, we conducted meta-analyses evaluating the impact of CSP on LVEF and QRS. Ten studies were pooled to assess outcomes pre- and post-implantation of CSP following AVNA. Three observational studies and one RCT were included in the meta-analysis comparing outcomes in CSP versus BVP post AVNA. Results CSP resulted in a significant QRSd reduction (-11.01 ms, 95% CI 5.07 - 16.95, p <0.01), improved LVEF (+10.28%, 95% CI 7.03 - 13.52; p <0.01) and improved NYHA score (-1.09; 95% CI -1.41 - -0.78; p <0.01) during follow-up of 6-36 months (Figure 1) from baseline (peri-implantation). There was no significant pacing threshold rise (0.11V; 95% CI -0.14 - 0.36; p= 0.39) observed during the same period. CSP was associated with statistically significant shorter QRSd (-49.81ms; 95% CI, -70.57 - -29.06; p <0.01) when compared to BVP. For LVEF, there was a statistically significant improvement of +8.96% (95% CI 2.55 - 15.37%; p <0.01) with CSP versus BVP. Limited data prohibited comparison of threshold and NYHA outcomes between CSP and BVP. Conclusion Conduction system pacing appears effective in improving baseline LVEF, QRSd and NYHA score in AVNA for AF, and may be a viable alternative to further optimising LVEF and QRSd in comparison to BVP. Further studies are required to evaluate the long-term impact and clinical outcomes of CSP in post AVNA patients.

Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking. Purpose Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF. Methods TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis < 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. Results Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported. Conclusions SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.

Prognostic impact of symptom relief under low and normal physical performance in patients hospitalized for worsening heart failure

Abstract Background Subjective symptoms, represented by the New York Heart Association (NYHA) class, are well-established prognostic indicators and treatment goals of heart failure (HF). However, older patients may be less likely to develop subjective symptoms due to an impaired physical performance. Purpose To evaluate the prognostic impact of symptom relief under low and normal physical performance in patients hospitalized for worsening HF. Methods We carried out a sub-analysis of FRAGILE-HF, a prospective multicenter study, including 1272 consecutive older (>=65 years) hospitalized patients with HF (median age 80; 57.2% male; left ventricular ejection fraction 46±17%). NYHA class and gait speed were documented before discharge. The patients were prospectively followed-up for two years after discharge. Results At the time of discharge, 715 patients (56%) remained symptomatic (NYHA2-4) whereas 557 patients (44%) were asymptomatic (NYHA1). Patients were classified into 4 groups according to symptom relief and physical performance represented by slow (<0.8 m/s) or normal (>=0.8 m/s) gait speed: 279 slow-asymptomatic, 278 normal-asymptomatic, 402 slow-symptomatic, and 313 normal-symptomatic patients, respectively. During the follow-up period, 266 patients (20.9%) died. Slow-asymptomatic (hazard ratio (HR) 1.72[1.09-2.72], p=0.019 in comparison with normal-asymptomatic patients as a reference) and slow-symptomatic (HR 1.85[1.21-2.82], p=0.004) status was associated with high mortality in a Cox regression analysis adjusted for the Meta-analysis Global Group in Chronic Heart Failure score and B-type natriuretic peptide level (Figure). Furthermore, the combined endpoint of HF rehospitalization and all-cause death within 90 days were more frequently observed in slow-asymptomatic (HR 1.94[1.05-3.60], p=0.034), normal-symptomatic (HR 1.89[1.06-3.36], p=0.031), and slow-symptomatic (HR 1.97[1.10-3.52], p=0.022) patients than normal-asymptomatic patients (Figure). Conclusions Symptom relief achieved at the time of discharge was not associated with a lower mortality in patients with low physical performance, for whom careful follow-up may be needed especially in the early period after discharge because the symptoms may be masked due to low physical performance.

Tafamidis treatment for transthyretin amyloid cardiomyopathy: results from an open-label, early-access, long-term study extension in an all-comers population

Abstract Background In the pivotal Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT NCT01994889), tafamidis significantly reduced mortality and cardiovascular hospitalization in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Given the high clinical unmet need and the favorable benefit-to-risk profile of tafamidis, there was a justification to provide patients with an option for early access to treatment as part of the ATTR-ACT long-term extension study (LTE; NCT02791230). Purpose To assess long-term safety in an all-comers population receiving early access to tafamidis. Methods Following protocol amendment (20 July 2018), patients with ATTR-CM, not previously enrolled in ATTR-ACT, and without commercial access to tafamidis, were enrolled in the LTE early-access study arm in 13 countries. Patients received open-label, once-daily tafamidis free acid 61 mg for up to 60 months, until they gained product access by prescription or study discontinuation by the sponsor. All-cause and cardiovascular (CV)-related mortality, CV-related hospitalization, and treatment-emergent adverse events (TEAEs) were assessed. Results Of 1481 patients enrolled in the early-access cohort, 1476 received at least one dose of tafamidis and were included in the analysis. Mean (SD) age at enrollment was 76.5 (7.8) years old, 37.5% were ≥80 years old, and 88.8% were male. Most patients (85.6%) had wild-type ATTR-CM, and 14.9%, 52.9%, 30.8%, and 1.3% were in New York Heart Association (NYHA) Class I, II, III, and IV, respectively. Over a mean (SD) follow-up period of 17.7 (13.8) months, all-cause and CV-related mortality rates were 23.4% and 13.8%, respectively (Table). Mean frequency of CV-related hospitalization per year was 0.28 (0.60). Serious TEAEs and TEAEs leading to discontinuation of the study were observed in 0.6% of patients (both); no new safety signals were identified. Conclusions Findings from the early-access cohort of the ATTR-ACT LTE highlight the safety of tafamidis treatment in an all-comers ATTR-CM patient population.

Coronary microvascular dysfunction in patients with heart failure with reduced and mildly reduced ejection fraction: results from the PANACEA study

Abstract Aims Coronary microvascular dysfunction (CMD) is common and associated with impaired survival in patients with heart failure with preserved ejection fraction (HFpEF). In patients with heart failure with reduced ejection fraction (HFrEF) and mildly reduced ejection fraction (HFmrEF) the impact of CMD is not fully known. Purpose We aimed to investigate the prevalence of CMD and its association with phenotype, biomarkers, endothelial function and echocardiographic measurements in patients with HFrEF or HFmrEF. Method A prospective, exploratory bi-center study in patients with chronic stable heart failure, New York Heart Association (NYHA) Class II-IV, and ejection fraction (EF) <50% was performed. Study procedures included echocardiography, adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR), physical examination, fasting blood and urine sample, pulse wave velocity (PWV) and hemodynamic measurements. The cutoff of CFR<2.5 was used to diagnose CMD. A multivariable linear regression analysis with CFR as dependent variable, adjusted for age, sex, body mass index, smoking, atrial fibrillation and left ventricular mass, was performed to explore biomarkers, endothelial function, and echocardiographic measurements associated with CMD. Results Of 112 included patients, 87 (78%) were men, with a mean age of 73.3 (±7.5) years. Among patients with a successful CFR measurement (n=62), CMD was present in 40 (65%), mean age of 75.4 (±5.8) years (Table 1). Patients with CMD had higher N-terminal pro B-type natriuretic peptide (NTproBNP) and Troponin T (p<0.05), and more often HFrEF ( p=0.06). Patients with CMD had larger ventricles with greater left ventricular mass and larger end-diastolic volumes (p<0.05). In a linear regression analysis CMD was associated with higher NTproBNP, lower EF, PWV and global strain (table 2). Conclusion CMD was common and present in two thirds of patients with HFrEF or HFmrEF. Further CMD was associated with markers of more severe heart failure and systemic endothelial dysfunction indicating that CMD may be an important predictor of outcome in patients with HFrEF and HFmrEF.

Influence of prior heart valve intervention on treatment and disease trajectory after diagnosis of heart failure with reduced ejection fraction

Abstract Background and aim Among patients with heart failure with reduced ejection fraction (HFrEF), knowledge is scarce on whether patients with prior valvular heart disease (VHD) intervention are distinct regarding clinical characteristics, treatment, and prognosis. Methods Using the Danish Heart Failure Registry and nationwide administrative registries, we identified patients with new-onset HFrEF from 2008 to 2021. Within this cohort, patients with a prior VHD intervention were identified and matched 1:5 on age-, sex-, in/outpatient presentation, and year of HFrEF diagnosis with remaining patients (controls). Outcomes were 1) baseline use and up-titration of guidelines-directed medical therapy (GDMT) and implementation of implantable cardioverter-defibrillator or cardiac resynchronization therapy with pacemaker/defibrillator (ICD/CRT-P/D) at 6 months follow-up, and 2) a composite of HF hospitalization or all-cause death at 3 years follow-up. The Kaplan-Meier estimator and Cox regression models, adjusted for HF severity, socioeconomic status, and major comorbidities, were used to compare the composite outcome, with patients without prior heart valve intervention as reference. Results The study cohort comprised 32,713 patients, of whom 1196 (3.6%) underwent a prior VHD intervention (median time since intervention 10 months). After matching, the study population were 1151 cases (median age 74 years, 82% men), and 3769 matched controls. Among cases and controls, median left ventricular ejection fraction was similar (30% vs. 30%) and the proportion in New York Heart Association (NYHA) class II was alike (82% vs 83%). At the time of HFrEF diagnosis, numerically more cases were on a beta-blocker (62% vs. 53%), ACEi/ARB/ARNI (48% vs. 44%), MRA (19% vs. 14%), and more had an implementation of (ICD/CRT-P/D) (17 % vs. 7%) (Figure 1). At 6 months, ≥ 50% of the daily target dose was achieved in (46% vs. 46%) for beta-blockers, (47% vs. 47%) for ACEi/ARBs/ARNI, (31% vs. 33%) for MRA, and implementation of ICD/CRT-P/D was attained in (28% vs. 18%), among cases and controls, respectively (Figure 1). The 3-year risk of HF hospitalization or all-cause death was 25% in cases and 24% in controls (Figure 2) with no significant differences (hazard ratio (HR) 0.95 , 95% confidence interval (CI) 0.84-1.08) compared to controls. Conclusions Patients with new-onset HFrEF and prior VHD interventions received more GDMT and had a higher implementation of ICD/CRT-P/D at the time of HFrEF diagnosis. However, following diagnosis, no major differences in GDMT initiation and up-titration, implementation of ICD/CRT-P/D, and the adjusted rates of HF hospitalization or all-cause death were observed among patients with and without prior heart valve intervention.Figure 1 Guideline-directed medicationFigure 2 Crude cumulative risk

A larger reduction of spatial mean QRS-T angle during cardiac resynchronisation therapy is associated with a lower risk of mortality and heart failure hospitalisation

Abstract Background Predicting clinical outcome in heart failure patients undergoing cardiac resynchronization therapy (CRT) remains challenging, necessitating improved risk stratification for CRT recipients. Previous studies have shown an association between large spatial peak and mean QRS-T angles and cardiovascular disease. Little is known, however, about their relation to clinical outcome following CRT. Purpose To investigate the association between spatial peak and mean QRS-T angles and long-term clinical outcome following CRT initiation. Methods All patients with native LBBB receiving CRT at a large-volume tertiary care center between 2015 and 2020 were retrospectively evaluated. Spatial peak and mean QRS-T angles were derived from digital pre- and post-CRT 12-lead ECGs that were processed using Glasgow algorithm and Kors’ regression transformation. The QRS-T angles and their change after CRT were analyzed in relation to the primary composite endpoint of heart failure hospitalisation or all-cause mortality using Cox regression analysis adjusted for clinical covariates (age, gender, CRT-P or CRT-D, secondary ICD indication, ischemic etiology, NYHA class, LVEF, diabetes, atrial fibrillation, baseline QRS duration, NT-proBNP, and eGFR). Results The study group comprised 250 patients (a median age [Q1–Q3] of 72.2 years [64.5–76.3]; 22% female; 58% New York Heart Association (NYHA) class III-IV; LVEF 27% [22–30]) who were followed over a median follow-up time of 4.5 years [3.2–5.8] after CRT implantation. The median post-CRT spatial peak and mean QRS-angles were 142° [116–160] and 152° [127–166], and the median angle was decreased by 16° [-0.6–41] and 14° [-0.4–38], respectively. Both a larger post-CRT mean QRS-T angle (HR 1.20, 95%CI 1.08-1.33, p=<.001) and peak QRS-T angle (HR 1.08, 95%CI 1.01-1.17, p=0.046) were associated with the primary endpoint. A larger reduction of mean QRS-T angle, but not peak QRS-T angle, was associated with a risk reduction (HR 0.87, 95%CI 0.79-0.95, p<0.003). In Kaplan-Meier analysis, patients with a post-CRT mean QRS-T angle above median had a higher risk of reaching the endpoint (log-rank p=0.002, Figure 1). Conclusion Our results show that a larger magnitude of the post-CRT spatial peak and mean QRS-T angles, and a larger reduction of the latter, are associated with long-term heart failure hospitalisation and death. These findings suggest that spatial QRS-T angle may have a potential role in refined risk stratification of CRT patients.Figure 1.K-M curve spatial mean QRS-T

HFpEF is associated with a higher risk of hospitalization or death in men undergoing transcatheter edge-to-edge tricuspid valve repair

Abstract Aims There are fundamental differences between women and men regarding the pathophysiology and etiology of tricuspid regurgitation (TR) as well as underlying comorbidities. The aim of this study was to analyze differences between female and male patients undergoing transcatheter edge-to-edge tricuspid valve repair for TR (T-TEER) and to identify gender-specific predictors of adverse outcome. Methods and Results In this monocentric study 197 consecutive patients (96 women and 101 men) undergoing T-TEER at our university heart center were included. Prevalence of heart failure with preserved ejection (HFpEF) was higher in women than in men (63% vs. 37.3%; p=0.001) whereas men more often had heart failure with reduced ejection fraction (HFrEF; 62.7% vs. 37%; p=0.001). Women had more severe symptoms (86.2% in New York Heart Association (NYHA) class III-IV vs. 72.3% in men; p=0.022). Device success rates (p=0.64), procedural characteristics (e.g. number of clips, p=0.17) and postprocedural results (TR grade post clip, p=0.1) were comparable. One-year mortality did not differ between genders (5.9% in women, 8.6% in men; p=0.53). Likewise, no significant difference could be found with regard to heart failure hospitalizations within one year after T-TEER (20.3% in women, 18.8% in men, p=0.82). Strikingly, prevalence of HFpEF was substantially higher than of HFrEF in men that reached the combined endpoint of one-year mortality or rehospitalization for heart failure (61.5% vs. 38.5%; p = 0.08). In women, no relevant difference could be found (27.0% vs. 32.4%; p=0,623). To identify gender-specific predictors of the combined endpoint, a cox regression analysis was performed. In men, HFpEF emerged as an independent predictor (HR 2.703; 95% CI 1.069 – 6.837; p = 0.036). In women, NYHA functional class proved to be an independent risk factor (Hazard Ratio (HR) 3.362; 95% confidence interval (CI) 1.085 – 10.415; p=0.036) for the combined endpoint whereas HFpEF was not associated with adverse outcome (HR 0.865, 95% CI 0.259 – 2.885, p=0.81). Conclusions Women undergoing T-TEER were more symptomatic and had higher prevalence of HFpEF compared to men. Nevertheless, HFpEF emerged as an independent predictor of the combined endpoint of one-year mortality or rehospitalization for heart failure only in men. NYHA functional class independently predicted adverse outcome in women.

Development and validation of a predicting model for risk of rehospitalization within 30 days in heart failure patients with preserved ejection fraction

Abstract Objective This study aimed to develop and validate a predicting model for risk of rehospitalization within 30 days post discharge in patients diagnosed with Heart Failure with Preserved Ejection Fraction (HFpEF). Methods Clinical data of 9555 HFpEF patients registered in the heart failure registry from 2014 to 2022 at our hospital were analyzed. A total of 8160 patients (from 2014-2021) were designated as the training set, and 1395 patients (from 2022) as the validation set. A predictive model was established based on risk factors associated with 30-day rehospitalization due to heart failure identified by the Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression analysis. The model's stability was ensured through Bootstrap internal validation and Temporal validation external validation. Results LASSO and logistic regression analyses identified eight risk factors associated with increased risk of 30-day rehospitalization, including New York Heart Association (NYHA) classification, albumin, c-reactive protein, N-terminal pro b-type natriuretic peptide (NT-proBNP) divided by 100, anemia, pleural effusion, atrial fibrillation, and pulmonary hypertension. The established predictive model demonstrated good discriminative ability in the internal validation with an Area Under the Curve (AUC) value of 0.714, and a 95% confidence interval (CI) of 0.693-0.736 after 500 Bootstrap replicates. In the Temporal validation external validation, the model exhibited robust stability with an AUC value of 0.740 and a 95% CI of 0.693-0.781. When compared to analogous models from prior studies, present model showcased superior predictive accuracy in that both Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) values were positive and within their respective 95% confidence intervals (P-values <0.05). Conclusion This study successfully developed and validated a predictive model for 30-day rehospitalization due to heart failure in patients diagnosed with HFpEF. This model might allow the timely identification of high-risk HFpEF patients for 30-day rehospitalization due to heart failure and optimizes the patient management accordingly.

Angina pectoris after coronary angiography or revascularization in pre- and postmenopausal women with coronary artery disease

Abstract Background Menopause is a known risk factor of coronary artery disease (CAD) in women. Earlier studies indicate that the incidence of angina pectoris (AP) increases with age. Some studies suggest that menopause would be a risk factor for AP in women with history of myocardial infarction (MI). However, the evidence is still incomplete. Purpose The aim of this study was to determine whether pre- or postmenopausal women are more symptomatic after revascularization using Canadian Cardiovascular Society (CCS) grading and New York Heart Association (NYHA) classification. We also wanted to evaluate whether the presence of type two diabetes (T2D) had an impact of the volume of the symptoms of CAD. Methods ARTEMIS Study contains 1,947 subjects with angiographically documented CAD with or without T2D (women 31.8%). Nondiabetic patients were matched with T2D patients for age, sex, prior MI and revascularization. Information of the menopause was from 610 women. Results Total of 584 women were at postmenopausal stage and only 26 were at premenopausal stage. The mean age of the premenopausal women was 57.5±10.8 years (P<0.001) and 69.4±7.5 years in postmenopausal women (P<0.001). Among premenopausal women 46.2% were active or ex-smokers and 26.8% of postmenopausal women still smoked or had smoked in the past (P=0.031). There was not statistically significant difference in other baseline characteristics: BMI, LDL or BNP levels, systolic or diastolic blood pressure, syntax score prior or after the revascularization and prevalence of prior MI. Over half of the postmenopausal women (57.4%, p<0.001) reported to suffer chest pain CCS grade ≥ 2 after the revascularization whereas only one fifth of the premenopausal women (23.1%, P<0.001) reported the same level of AP. T2D seemed to increase the symptoms of CAD as 33.3% of the premenopausal and 61.7% of the postmenopausal women with T2D reported AP with severity of CCS grade ≥ 2 (P=0.050). CCS 2 symptoms were reported by 45.7% of the postmenopausal and 19.2% of the premenopausal women, and CCS 3 symptoms by 11.6% of the postmenopausal women, yet only 3.8% of the premenopausal women (p=0.001 for both, respectively). Three quarter of the premenopausal women reported CCS 1 level of symptoms but only 42.6% of the postmenopausal women (P=0.003). Prevalence of each of CCS grade reported within pre- and postmenopausal women with and without T2D are shown in the Table 1. None of the premenopausal women reported NYHA ≥ 2 dyspnea, and the same level of shortness of breath was reported also only from 4.3 % of the postmenopausal women (p=0.005). Among postmenopausal women with T2D, NYHA ≥ 2 symptoms were more common, though statistical significance was not obtained (9.2%, P=0.196). Conclusion Postmenopausal women seem to experience more CAD-related symptoms after angiography or revascularization compared premenopausal women. Presence of T2D seems to associate with higher CCS grade after revascularization.

Characterizing disease burden and health care resource utilization in patients with hypertrophic cardiomyopathy: a nationwide real-world study in Finland

Abstract Background Hypertrophic cardiomyopathy (HCM) is an often hereditary myocardial disease with an estimated prevalence of 1:500 in the general population. Purpose This study aimed to investigate healthcare resource utilization (HCRU) and associated costs in patients diagnosed with HCM (and the associated subtypes: obstructive or non-obstructive) in a nationwide cohort in Finland. Methods This retrospective, registry-based cohort study included all Finnish patients diagnosed with HCM between 2000 and 2021, who were 12+ years old at the time of diagnosis, as identified from the national care registers for healthcare. HCRU data were collected between 2014 and 2021 from the Finnish national care registers for health care and the social insurance institution. Data pertaining to New York Heart Association (NYHA) classification were collected from three Finnish university hospitals. Results The study cohort comprised 5,834 patients with an HCM diagnosis; obstructive HCM accounted for 34% of cases. Mean per patient-year costs were €6638, 95% confidence interval (CI) €6472-€7415, and €6112, 95% CI €5957-€6560 for those with obstructive and non-obstructive HCM respectively. All-cause hospitalizations at specialized care were the most prominent cost associated with patients with obstructive and non-obstructive HCM equating to 46.3% and 46.1% of the total cost respectively (Fig 1.). Comorbidity burden, as measured by Charlson comorbidity index (CCI) score, was greater in patients with the obstructive than non-obstructive phenotype of the disease (CCI ≥4: 2.2 and 1.8, p<0.01, respectively). The highest utilization of invasive procedures was found for patients with NYHA class III-IV. Conclusion This population-based study, utilizing real-world data, provides novel insights into HCRU and related costs among Finnish patients with HCM (and associated subtypes). HCRU appears to be primarily driven by hospitalizations at specialized care. Furthermore, the data indicate that patients with obstructive HCM are likely to have a more severe disease, with higher comorbidity burden and requiring more invasive procedures than patients with the non-obstructive form of the disease. However, there were no statistically significant differences in health care costs between those with obstructive and non-obstructive HCM.

Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis

Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis. To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis. This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia. Asymptomatic patients with severe aortic stenosis and myocardial fibrosis were included. The final date of follow-up was July 26, 2024. Early valve intervention with transcatheter or surgical aortic valve replacement or guideline-directed conservative management. The primary outcome was a composite of all-cause death or unplanned aortic stenosis-related hospitalization in a time-to-first-event intention-to-treat analysis. There were 9 secondary outcomes, including the components of the primary outcome and symptom status at 12 months. The trial enrolled 224 eligible patients (mean [SD] age, 73 [9] years; 63 women [28%]; mean [SD] aortic valve peak velocity of 4.3 [0.5] m/s) of the originally planned sample size of 356 patients. The primary end point occurred in 20 of 113 patients (18%) in the early intervention group and 25 of 111 patients (23%) in the guideline-directed conservative management group (hazard ratio, 0.79 [95% CI, 0.44-1.43]; P = .44; between-group difference, -4.82% [95% CI, -15.31% to 5.66%]). Of 9 prespecified secondary end points, 7 showed no significant difference. All-cause death occurred in 16 of 113 patients (14%) in the early intervention group and 14 of 111 (13%) in the guideline-directed group (hazard ratio, 1.22 [95% CI, 0.59-2.51]) and unplanned aortic stenosis hospitalization occurred in 7 of 113 patients (6%) and 19 of 111 patients (17%), respectively (hazard ratio, 0.37 [95% CI, 0.16-0.88]). Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70]). In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis-related hospitalization. The trial had a wide 95% CI around the primary end point, with further research needed to confirm these findings. ClinicalTrials.gov Identifier: NCT03094143.

Prognostic implications and alterations in left atrial deformation following transcatheter aortic valve implantation for severe aortic stenosis

Abstract Background Left atrial reservoir strain (LARS) as a single parameter estimate of left ventricular (LV) diastolic dysfunction (DD), may provide important prognostic insights into patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Purpose To evaluate the prognostic implications of pre- and post TAVI LARS-defined DD (LARS-DD) grade in patients undergoing TAVI for severe AS and its association with new-onset atrial fibrillation. Methods Pre-TAVI LARS-DD was evaluated by speckle-tracking echocardiography and was assigned as grade 0 to 1 (LARS ≥24%), grade 2 (LARS ≥19 to <24%) and grade 3 (LARS <19%). Patients were followed-up for the primary endpoint of all-cause mortality from the date of TAVI. For the secondary endpoint, patients with pre- and post-TAVI LARS measurements, no history of atrial fibrillation and with clinical/ECG follow-up following the post-TAVI follow-up echocardiogram were evaluated for the occurrence of new-onset atrial fibrillation. Results A total of 601 patients (median age 81 [76-85] years, 53% male) undergoing TAVI for severe AS were included. Overall, 169 patients (28%) were LARS-DD grade 0/1, 96 patients (16%) were LARS-DD grade 2 and 336 (56%) were LARS-DD grade 3. Over a median follow-up of 40 (IQR 26 to 58) months, a total of 258 (43%) patients died (Figure 1). In a comprehensive multivariable Cox regression model adjusted for age, sex, EuroSCORE II, New York Heart Association class III to IV symptoms, LV ejection fraction, atrial fibrillation, LA volume index and LV stroke volume index, LARS-DD grade was independently associated with all-cause mortality (adjusted HR 1.28 per one grade increase above LARS-DD grade 0/1, 95% CI 1.07 to 1.53, P=0.007). For the secondary endpoint of new-onset atrial fibrillation, a total of 285 patients were evaluated (Figure 2). On multivariable Fine and Gray regression analyses adjusting for age and LA volume index, post-TAVI LARS (SDHR 1.14 per 1% <20%, 95% CI 1.05 to 1.23, P=0.0009), rather than pre-TAVI LARS (SDHR 1.00 per 1% <20%, 95% CI 0.91 to 1.11, P=0.93) was associated with the occurrence of new-onset atrial fibrillation. Conclusions Increasing LARS-DD grade was independently associated with long-term post-TAVI survival in patients with severe AS and may enhance risk stratification. In addition, post-TAVI LARS, but not pre-TAVI LARS, was closely related to the occurrence of new-onset atrial fibrillation, likely better reflecting intrinsic LA dysfunction.Figure 1:All-Cause MortalityFigure 2:New-Onset Atrial Fibrillation

Long-term outcomes of patients with apical hypertrophic cardiomyopathy: incorporation of a novel risk score

Abstract Background Apical hypertrophic cardiomyopathy (aHCM) is a subtype of HCM characterized by left ventricular hypertrophy predominantly in the apex. There is still limited data on factors associated with adverse outcomes in patients with aHCM. Objectives To a) describe the characteristics and b) develop a novel risk score associated with outcomes in aHCM patients. Methods A total of 462 patients (mean age 58±15 years, 68% male and 70% white) diagnosed with aHCM based on clinical, echocardiographic, and cardiac magnetic resonance (CMR) evaluation were included. The primary endpoint was all-cause death or aborted sudden cardiac death. Using the cox regression analysis, variables showing potential association with the composite endpoint were considered to develop an aHCM specific risk score. Results On echocardiography, the mean LV ejection fraction (LVEF) was 64±8%, and the mean LV mass was 223±72 g. A baseline CMR was performed in 246 (53%) patients, with delayed gadolinium enhancement in 170 (71%) patients with a mean percentage of 5±7%. Patients were followed-up for a mean of 68 months (range 1-248), with composite events occurring in 80 (17%) patients (death in 62 [13%] patients). Univariate Cox regression analysis identified age hazard ratio (HR) 1.06 (95% Confidence Interval or CI 1.04-1.08; p< 0.001), apical aneurysm HR 2.32 (95% CI 1.24-4.34 p=0.008), lower LVEF HR 0.96 (95% CI 0.94-0.99 p=0.002), higher right ventricular systolic pressure (RVSP) HR 1.04 (95% CI 1.02-1.06 p< 0.001), New York Heart Association Class IV HR 11.69 (95% CI 3.59-38.08 p< 0.001) and the presence of Atrial fibrillation HR 1.77 (95% CI 1.14-2.76 p=0.012). An aHCM specific risk score was subsequently created (Figure 1), with good discrimination (c-statistic=0.75) and good calibration with expected to observed ratio of 1.02 and a calibration slope of 0.91 (p-value for difference between expected and observed probabilities =0.22). The risk score ranges between 0 and 8 points, with higher score associated with a higher rate of composite events (Figure 2). Conclusion We developed a novel risk score which demonstrated incremental prognostic value for hard events in aHCM patients.Risk prediction modelKaplan Meier event-free survival curves

Long-term efficacy of cardiac resynchronization therapy with triple-site ventricular stimulation in heart failure patients

Abstract Background Cardiac resynchronization therapy (CRT) reduces cardiac electrical dyssyncrhony and improves clinical outcomes in selected symptomatic patients with left ventricular (LV) systolic dysfunction. However, patients after conventional CRT (Bi-V) have residual cardiac electrical dyssynchrony. CRT with multi-site pacing has gained attention to improve short-term outcome refractory to BiV. However, long-term follow up outcome is still uncertain. We evaluated the efficacy of CRT with triple-site ventricular stimulation (Tri-V), involving 2 LV lead in 2 anatomically separated veins and a single RV lead in RV apex for long-term follow up period. Methods Ninety-two consecutive patients with New York Heart Association class II-IV heart failure, LV ejection fraction <0.35, and QRS interval >120ms, who underwent CRT implantation between 2010 and 2016, were enrolled. Acute hemodynamic responses to temporary dual-site and triple-site ventricular pacing were evaluated, and patients were assigned to either the Bi-V or Tri-V group based on the results. The primary endpoint was the HF clinical composite score, which scores patients as improved, unchanged, or worsened. The secondary endpoint included cumulative survival from any cause of death and HF hospitalization. Results Tri-V was successfully implanted in 32 patients. Five patients were excluded during follow-up because of uncaptured pacing in one of the LV leads. One year post-implantation, the clinical composite score significantly improved in 84% of Tri-V patients compared to 57% in the Bi-V group (p=0.026). After a median follow-up of 12.0 years, there was no significant difference about all-cause mortality between Tri-V and Bi-V (p=0.147). However, Tri-V group showed significant lower HF hospitalization (p=0.005) than Bi-V group. The number of battery exchange was not significantly different between Tri-V than Bi-V group (1.4±0.7 vs. 1.2±0.8, p=0.361). Conclusion CRT with Tri-V, characterized by stable lead parameters, appears to offer greater long-term benefits than Bi-V in terms of clinical status without excessive battery exchanges.figure