Improvement In NYHA Functional Class Research Articles

Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.

Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined. This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten. Patients who were symptomatic of oHCM were randomized to aficamten (n=142) or placebo (n=140) daily for 24weeks. Outcomes assessed included the proportion of patients with complete hemodynamic response (rest and Valsalva gradient<30mmHg and<50mmHg, respectively), relief in limiting symptoms (≥1 improvement in NYHA functional class and/or≥10-point change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score), enhanced exercise capacity (≥1.5mL/kg/min change in peak oxygen uptake), and≥50% reduction in N-terminal pro-B-type natriuretic peptide. Eligibility for septal reduction therapy was also evaluated. At 24weeks, patients treated with aficamten vs placebo showed significant improvement in limiting symptoms (71% vs 42%), were more likely to have complete hemodynamic response (68% vs 7%), demonstrated enhanced exercise capacity (47% vs 24%), and showed a decrease≥50% in N-terminal pro-B-type natriuretic peptide (84% vs 8%) (P≤ 0.002 for all). An improvement in≥1 of these outcome measures was achieved in 97% of patients treated with aficamten (vs 59% placebo), including 23% on aficamten who achieved all 4 outcomes compared with none in placebo. Among 32 patients receiving aficamten and 29 patients receiving placebo who were eligible for septal reduction therapy, 28 (88%) from the aficamten group were no longer eligible at 24weeks compared with 15 (52%) from the placebo group (P=0.002). Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures. These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with oHCM [SEQUOIA-HCM]; NCT05186818).

Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program

BackgroundIn the Semaglutide Treatment Effect in People with obesity and HFpEF (STEP-HFpEF) program, semaglutide improved heart failure (HF)-related symptoms, physical limitations, and exercise function, and reduced bodyweight in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Whether semaglutide improves functional status, as assessed by NYHA functional class, is unknown. ObjectivesThe goal of this study was to examine the effects of semaglutide on change in NYHA functional class over time. We also investigated the effects of semaglutide on HF-related symptoms, physical limitations, and bodyweight and other trial endpoints across baseline NYHA functional class categories. MethodsThis was a prespecified analysis of pooled data from 2 international, double-blind, randomized trials (STEP-HFpEF and STEP-HFpEF type 2 diabetes [STEP-HFpEF DM], comprising the STEP-HFpEF program), which collectively randomized 1,145 participants with obesity-related HFpEF to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. The outcome of interest for this analysis was the change in NYHA functional class (baseline to 52 weeks). We also investigated the effects of semaglutide on the dual primary, confirmatory secondary, and selected exploratory endpoints according to baseline NYHA functional class. ResultsMore semaglutide-treated than placebo-treated patients had an improvement in NYHA functional class (32.6% vs 21.5%, respectively; OR: 2.20 [95% CI: 1.62-2.99; P < 0.001]) and fewer semaglutide-treated patients experienced deterioration in NYHA functional class (2.09% vs 5.24%, respectively; OR: 0.36 [95% CI: 0.19-0.70; P = 0.003]) at 52 weeks. Semaglutide (vs placebo) improved the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CCS) across NYHA functional class categories; this was especially pronounced in those in NYHA functional classes III/IV (10.5 points [95% CI: 6.6-14.4 points]) vs NYHA functional class II (6.0 points [95% CI: 3.4-8.6 points]) (P interaction = 0.06). By contrast, the degree of reduction in bodyweight was similar with semaglutide vs placebo regardless of baseline NYHA functional class category (NYHA functional class II, −8.4% [95% CI: −9.4% to −7.3%]; NYHA functional classes III/IV, −8.3% [95% CI: −9.9% to −6.8%]; P interaction = 0.96). Semaglutide consistently improved 6-minute walking distance (6MWD), the hierarchical composite endpoint (death, HF events, differences in KCCQ-CSS, and 6MWD changes), and reduced C-reactive protein and N-terminal prohormone of brain natriuretic peptide across NYHA functional class categories (all P interactions = NS). ConclusionsIn patients with obesity-related HFpEF, fewer semaglutide-treated than placebo-treated patients had a deterioration, and more had an improvement, in NYHA functional class at 52 weeks. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced bodyweight and biomarkers of inflammation and congestion in all NYHA functional class categories. Semaglutide-mediated improvements in health status were especially large in patients with NYHA functional classes III/IV. (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure and Obesity; NCT04788511) (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes; NCT04916470)

Personalized Guidance of Edge-to-Edge Transcatheter Tricuspid Valve Repair by Multimodality Imaging.

Background: Transcatheter edge-to-edge tricuspid valve repair (T-TEER) for tricuspid regurgitation (TR) is always guided by transesophageal echocardiography (TEE). As each patient has unique anatomy and acoustic window, adding transthoracic echocardiography (TTE) and cardiac CT could improve procedural planning and guidance. Objectives: We aimed to assess T-TEER success and outcomes of a personalized guidance approach, based on multimodality imaging (MMI) of patient-tailored four right-sided chamber views (four-right-ch), as depicted by CT, TTE, TEE and fluoroscopy. Methods: Patients were assigned to MMI or classical TEE guidance, depending on TTE acoustic window. In MMI patients, planning included cardiac CT, which determined the fluoroscopic angulations of the specific four-right-ch, while guidance relied heavily on TTE, with minimal intermittent TEE for leaflet grasping and result confirmation. Both TTE and TEE were matched to respective CT and fluoroscopy four-right-ch. TR severity and quality of life (QoL) parameters were assessed from baseline to 12 months. Results: A total of 40 T-TEER patients were included, with 17 procedures guided by MMI and 23 solely by TEE. Baseline characteristics were similar between groups, e.g., age (83.1 ± 4.1 vs. 81 ± 5.3, p = 0.182) or STS-Score (11.1 ± 7.4% vs. 10.6 ± 5.9%, p = 0.813). The primary efficacy endpoint of ≥one-grade TR reduction at 30 days was 94% (16/17) in MMI vs. 91% (21/23) in TEE patients, with two or more TR grade reduction in 65% vs. 52% (p = 0.793). Device success was overall 100%, with no device-related complications, but three TEE-associated cases of gastrointestinal bleeding in the TEE-only group. By 12 months, all 15 MMI and 19 TEE survivors improved NYHA functional class and QoL, e.g., Kansas City Cardiomyopathy Questionnaire Score Δ29.6 ± 6.7 vs. 21.9 ± 5.8 (p = 0.441) pts., 6-min walk distance Δ101.5 ± 36.4 vs. 85.7 ± 32.1 (p = 0.541) meters. Conclusions: In a subset of patients with good TTE acoustic window, MMI guidance of T-TEER is effective and seems to avoid gastroesophageal injuries caused by TEE probe manipulation. TR reduction, irrespective of guidance method, impacts long-term QoL.

2-Year Clinical and Echocardiography Follow-Up of Transcatheter Mitral Valve Replacement With the Transapical Intrepid System

BackgroundThirty-day outcomes with the investigational Intrepid transapical (TA) transcatheter mitral valve replacement (TMVR) system have previously demonstrated good technical success, but longer-term outcomes in larger cohorts need to be evaluated. ObjectivesThe authors sought to evaluate the 2-year safety and performance of the Intrepid TA-TMVR system in patients with symptomatic, ≥moderate-severe mitral regurgitation (MR) and high surgical risk. MethodsPatient eligibility was determined by local heart teams and approved by a central screening committee. Clinical events were adjudicated by an independent clinical events committee. Echocardiography was evaluated by an independent core laboratory. ResultsThe cohort included 252 patients that were enrolled at 58 international sites before February 2021 as part of the global Pilot Study (n = 95) or APOLLO trial (primary cohort noneligible + TA roll-ins, n = 157). Mean age was 74.2 years, mean STS-PROM was 6.3%, 60.3% were male, and 80.6% were in NYHA functional class III/IV. Most presented with secondary MR (70.1%), and nearly all had ≥moderate-severe MR (98.4%). All-cause mortality was 13.1% (30-day), 27.3% (1-year), and 36.2% (2-year). The 30-day ≥major bleeding event rate was 22.3%. Heart failure rehospitalization was 9.6% (30-day) and 36.2% (2-year). At 2 years, >50% of patients were alive with improvement in NYHA functional class (82.1%, class I/II), and all patients with available echocardiograms had ≤mild MR. ConclusionsThis analysis represents the largest reported TA-TMVR experience with the longest follow-up in high-risk ≥moderate-severe MR patients. Early mortality and heart failure rehospitalizations were significant, exacerbated by early TA-related bleeding events; however, meaningful improvements in clinical outcomes and marked reductions in MR severity were observed through 2 years.

Echocardiographic parameters associated with less reverse left ventricular remodeling after transcatheter aortic valve implant in subjects with prosthesis patient mismatch.

Transaortic valve implant (TAVI) is the treatment of choice for severe aortic stenosis (AS). Some patients develop prosthesis patient mismatch (PPM) after TAVI. It is challenging to determine which patients are at risk for clinical deterioration. We retrospectively measured echocardiographic parameters of left ventricular (LV) morphology and function, prosthetic aortic valve effective orifice area (iEOA) and hemodynamics in 313 patients before and 1year after TAVI. Our objective was to compare the change in echocardiographic parameters associated with left ventricular reverse modeling in subjects with and without PPM. Our secondary objective was to evaluate echo parameters associated with PPM and the relationship to patient functional status and survival post-TAVI. We found that 82 (26.2%) of subjects had moderate and 37 (11.8%) had severe PPM post-TAVI. There was less relative improvement in LVEF with PPM (1.9±21.3% vs. 8.2+30.1%, p=.045). LV GLS also exhibited less relative improvement in those with PPM (13.4+34.1% vs. 30.9+73.3%, p=.012). NYHA functional class improved in 84.3% of subjects by one grade or more. Echocardiographic markers of PPM were worse in those without improvement in NYHA class (mean AT/ET was .29 vs. .27, p=.05; DVI was .46 vs. .51, p=.021; and iEOA was .8cm/m2 vs. .9cm/m2 , p=.025). There was no association with PPM and survival. There was no improvement in LVEF and less improvement in LV GLS in those with PPM post-TAVI. Echocardiographic markers of PPM were present in those with lack of improvement in NYHA functional class.

Applying the TRILUMINATE Eligibility Criteria to Real-World Patients Receiving Tricuspid Valve Transcatheter Edge-to-Edge Repair

BackgroundAccording to the TRILUMINATE (Clinical Trial to Evaluate Cardiovascular Outcomes in Patients Treated With the Tricuspid Valve Repair System) trial, transcatheter tricuspid edge-to-edge repair (T-TEER) improves quality of life beyond medical treatment, while no effects on heart failure hospitalization (HFH) and survival were observed at 1 year. However, the generalizability of the TRILUMINATE trial to real-world conditions remains a subject of discussion. ObjectivesThe aim of this study was to apply the clinical TRILUMINATE inclusion and exclusion criteria to a real-world T-TEER patient group and evaluate symptomatic and survival outcome in TRILUMINATE-eligible and TRILUMINATE-ineligible patients. MethodsClinical TRILUMINATE inclusion and exclusion criteria were applied to a cohort of patients who underwent T-TEER at 5 European centers from 2016 to 2022. Study patients were compared regarding baseline characteristics, survival, HFH, and symptomatic outcomes as measured by NYHA functional class, a quality-of-life questionnaire and 6-minute walk distance. ResultsOf 962 patients, 54.8% were classified as TRILUMINATE eligible, presenting with superior left ventricular function and fewer comorbidities compared with the ineligible population. Tricuspid regurgitation reduction, improvement in NYHA functional class, quality of life, and exercise capacity were comparable in both groups. However, the 1-year survival and HFH rates significantly differed (tricuspid regurgitation ≤2+ at discharge, 82% vs 85%; survival, 85% vs 75%; HFH, 14% vs 22% for eligible vs ineligible patients). ConclusionsThe observed differences in survival and HFH outcomes suggest a limited generalizability of TRILUMINATE to real-world conditions and indicate the need for additional studies evaluating the outcomes after T-TEER in less selected patient populations.

Impact of transcatheter edge-to-edge repair (TEER) of mitral valve on the clinical outcomes in the management of atrial functional mitral regurgitation

Abstract Background Atrial functional mitral regurgitation (aFMR) has become a novel topic of interest. Data on the safety and efficacy of transcatheter edge-to-edge repair (TEER) of mitral valve among patients with aFMR and ventricular functional mitral regurgitation (vFMR) is scarce and limited to single center studies. Purpose We conducted a systematic review and meta-analysis to assess the safety and efficacy of TEER in the management of aFMR vs vFMR and its impact on clinical outcomes. Methods PubMed/MEDLINE, Cochrane Library and EMBASE databases were queried to identify studies comparing the efficacy of TEER between aFMR and vFMR. The primary outcome of interest was mortality at 1 year and composite of all-cause mortality and heart failure (HF) hospitalizations. Secondary outcomes included mitral regurgitation (MR) reduction, presence of residual MR, improvement in NYHA functional class, postoperatively and at 1-year. Risk ratios (RR’s) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects model. Results We included a total of 3,314 patients from 6 observational studies which met the inclusion criteria (mean age 63.8 ± 3.8 years, 43% male). There were 443 aFMR patients and 2871 vFMR patients with an average follow-up of 12 months. Mortality at 1-year and the composite outcome of all-cause mortality and heart failure hospitalizations were comparable between aFMR and vFMR groups (RR 1.06; 95% CI 0.64 - 1.75; p = 0.81 and RR 0.92; 95% CI 0.75 - 1.14; p = 0.47, respectively). There were no significant differences between aFMR and vFMR groups in terms of MR reduction postoperatively (RR 0.99; 95% CI 0.96 - 1.02; p = 0.53) or at 1-year (RR 1.15; 95% CI 0.96 - 1.38; p = 0.14). Moreover, the presence of residual MR grade ≥ 3+ postoperatively (RR 1.31; 95% CI 0.83 - 2.08; p = 0.25) and at 1-year (RR 0.96; 95% CI 0.44 - 2.11; p = 0.92) was similar between aFMR and vFMR cohorts. Overall, although there was a clinical improvement in symptoms in terms of NYHA functional class at 1 year (grade ≤ 2), there was no statistical significance between the two groups (RR 1.02; 95% CI 0.93 - 1.11; p = 0.74). Conclusion This meta-analysis suggests that transcatheter edge-to-edge repair is likely to be an efficacious and safe option in patients with aFMR and vFMR. Future randomized control trials are needed to fully assess the clinical impact of this procedure in the two MR etiologies.Figure 1Figure 2

Abstract P2138: Long-Term Clinical Value And Impact Of Mavacamten In Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Systematic Review And Meta-Analysis

Introduction: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder involving the cardiac sarcomere. Mavacamten is the first-in-class oral cardiac myosin inhibitor approved for treating HCM in adults targeting sarcomere hypercontractility. We aimed to evaluate the efficacy and safety of mavacamten in symptomatic obstructive HCM. Methods: We conducted a systematic literature search in Embase, PubMed, Scopus, and Web of Science databases from inception until March 05, 2023. Results: After screening 349 studies, our final analysis included 5 studies with 843 obstructive HCM patients and an average follow-up of 27.2 weeks. A fixed effects model was used to calculate risk ratios (RRs). Our meta-analysis revealed a significant improvement in NYHA functional class from baseline in patients on mavacamten compared to placebo [RR, 4.59 (95% CI: 2.94-7.16), p&lt;0.00001]. Mavacamten use in obstructive HCM patients also resulted in significantly lower rates of septal reduction therapy (SRT) or patients who were guideline-eligible for SRT versus placebo [RR, 0.29 (95% CI: 0.22-0.39), p&lt;0.00001]. There was no significant effect of mavacamten use on the Kansas City Cardiomyopathy Questionnaire (KCCQ) score (p = 0.22). Also, no significant difference was observed in the occurrence of ≥1 serious adverse event (p = 0.77), atrial fibrillation (p = 0.98), and non-sustained ventricular tachycardia (p = 0.44) between mavacamten and placebo group. Conclusions: A substantial improvement in NYHA functional class without any serious adverse events, and a significant reduction in the number of patients requiring SRT, makes mavacamten a promising drug for obstructive HCM.

Abstract P3118: Gender Differences In The Efficacy Of A Mobile-based Self-management Program For Patients With Heart Failure

Background: This study was to develop a mobile application (App) program, presenting educational materials and giving interactive feed-backs on self-management for heart failure patients and to evaluate the gender differences in the efficacy of the program. Methods: We developed a mobile App program for heart failure patients’ self-management, which included comprehensive educational materials and daily record logs for the patients. Also, it took into account the mobile use characteristics and convenience of aged heart failure patients, as well as active and instant interactions and feedback via group chat among the patients and healthcare providers. Regarding the experimental study, we employed a randomized controlled trial to evaluate the effects of the program in 66 heart failure patients. The intervention group was guided to use the mobile App program in their daily life at home for 3 months. Results: Male patients in the experimental group exhibited significantly decreased waist circumference and improved NYHA functional class than the control group after 3 months. As for female patients in the experimental group, they showed significantly improved NYHA functional class, depressive symptoms, and quality of life than the control group after 3 months. Conclusion: This mobile App program showed effective improvements in heart failure patients' symptom classes for both men and women. Also, it showed that women had overall higher positive outcomes in psychosocial aspects, such as depressive symptoms and quality of life than men. Future study is needed to develop self-management programs considering gender differences and also to understand their effectiveness according to gender.

Left ventricular global strain and duration of QRS complex as predictors of prognosis after cardiac resynchronization therapy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National heart institute and Menoufia university, Egypt. Background cardiac resynchronization therapy is effective for patients with chronic heart failure with reduced left ventricular ejection fraction and wide QRS (≥120 ms). We aimed to verify that a baseline left ventricular global longitudinal strain(LVGLS) and qrs duration may be beneficial as predictors of prognosis of CRT response. purpose We aimed to evaluate if LVGLS &amp; QRS duration may be of additive prognostic value in CRT response. Methods Transthoracic echocardiography was performed prior to and 6 months after CRT implantation. Echocardiography was performed to assess left ventricular function as LVGLS. The response to CRT was defined as improvement in NYHA functional class (at least one class) and ≥ 15% reduction in the left ventricular end-systolic volume or improvement in left ventricular ejection fraction &amp;gt; 10. Comparison between responders and not responders was done using the appropriate test, and ROC analyses were done for QRS duration and LVGLS to predict CRT response. Results fifty-five HF patients (age 58 ±8 years, LVEF 23 ±5%, QRS duration 159 ±8ms, 30.9% ischemic aetiology of HF) underwent CRT implantation. The percentage of responders was 72.72% (Table). Baseline LVGLS differed significantly according to CRT response (P &amp;lt; 0.019). The best cutoff for LVGLS to predict response was 6.2, at which sensitivity and specificity were 70% and 73.3%, respectively with AUC of 0.793, with a 95% confidence interval (CI) of 0.651 - 0.936 (P = 0.001). Also, there was a statistically significant difference of the baseline QRS duration between the patients who had and hadn’t CRT response (P &amp;lt;0.001). The best cutoff was &amp;gt;154 ms,at which sensitivity and specificity were 87.5% and 86.7%, respectively. (AUC was of 0.793, with a 95% CI ranging from 0.651 - 0.936 (P = 0.001). Conclusion Baseline LVGLS and QRS duration may have a prognostic value in prediction CRT response. Baseline LVGLS (&amp;gt;6.2) and QRS duration (&amp;gt;154ms) may help to select CRT responders.

Clinical, hemodynamic and biochemical improvement related to left bundle branch area pacing.

Right ventricular pacing is associated with risk of heart failure and left ventricular dysfunction. Left bundle branch area pacing (LBBP) has emerged as an alternative method for delivering physiological pacing. The effect of LBBP on N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been investigated. Finally, 50 patients referred for pacemaker implantation were included. LBBP was performed as described previously by Huang et al. Transthoracic echocardiogram and NT-proBNP were performed before and four weeks after the procedure. 50 patients were analyzed. There were not differences between ventricular thresholds during the procedure and 3 months later, LBBP significantly reduced QRS complex duration (148 ± 21 vs. 107 ± 11 ms; p = 0.029). LBBP significantly improved NYHA functional class and reduced NT-proBNP concentration (2888.2 ± 510 vs. 1181 ± 130 pg/ml; p = 0.04). In patients showing left ventricular ejection fraction (LVEF) < 50% and ventricular desynchrony LBBP showed a significant LVEF increase (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). LBBP was feasible and safe in most of patients. LBBP was associated with reduction in QRS width and with increase in LVEF in patients with ventricular desynchrony, while in patients with normal LVEF it remained unchanged during follow-up.

Evaluation of Angiotensin Receptor and Neprlysin Inhibition (ARNI) in Patients of Heart Failure with Reduced Ejection Fraction (HFrEF) - a real-world study

Objectives: This is a real world prospective study to evaluate the effects of Neprlysin Inhibition (ARNI) using sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). Methodology: This was an outpatient study on patients of HFrEF (EF&lt;40%) and stable blood pressure after obtaining informed consent. Consecutive patients were enrolled and followed at 6 and 12 weeks. Detailed clinical and echocardiographic examinations were performed on all visits. Biochemistry evaluating ProBNP, renal profile, HbA1C and electrolytes were performed in 24 patients at baseline and follow-up. Results: We enrolled 80 patients, but 63 patients could be followed. Mean age was 53.54±13.32 years and 55% were males. After 12 weeks treatment improvement in NYHA functional class was seen in 66% and improvement by more than one grade in 31% (p&lt;0.01). Pro-BNP reduced from 3552.71±1804.74 at the baseline to 723±930 on the second FU visit (p&lt;0.002). Structural improvement was seen in 33% of patients. Left ventricular (LV) end-diastolic diameter (EDD) reduced by 3.49 mm and LV end systolic diameter (ESD) by 3.97 mm (p&lt;0.014). Fractional shortening (FS) increased by 2.07% and EF by 3.52 (p&lt;0.01). Patients tolerated the drug well, but most could not tolerate the higher recommended dosage. Renal status, electrolytes, and HbA1C did not alter significantly. Conclusion: Treatment with sacubitril/valsartan in addition to the guideline directed medical therapy (GDMT) resulted in marked reduction in ProBNP, significant improvement in functional class and enhancement of cardiac pumping activity with reduction in LVEDD and LVESD and improvement in FS and EF.

Percutaneous Transmitral Commissurotomy - Clinical and Echocardiographic Follow-up in Severe Mitral Stenosis

Objectives: To study the long term clinical and echocardiographic outcomes of percutaneous Trans mitral balloon commissurotomy (PTMC) performed in patients with severe mitral stenosis. Methodology: Total 103 patients were enrolled in this study. Their PTMC procedure was performed between the years 2015 to 2019. Those patients who returned for follow-up in the year 2021 were enrolled. At the time of follow-up their clinical and echocardiographic parameters were recorded. Results: The mean age was 27.44±6.26 years and 97 (94.2%) of them were female. Mitral valve area was improved significantly, planimetry; 0.813±1.39 vs. 1.288±0.21cm2 and PHT; 0.871±0.13 vs. 1.336±0.19 cm2 between baseline and follow-up, respectively. Pressure gradient across mitral valve also improved 7.233±2.81 vs. 14.407±0.92 mmHg between baseline and follow-up, respectively. Pulmonary artery pressures were also reduced significantly 24±0.27 vs. 55±2.41 mmHg as well as the right ventricular systolic pressures 24.4±2.94 vs. 62.34±10.98 mmHg between baseline and follow-up, respectively. At follow-up, 70.9% had NYHA I class, 16.5% had NYHA II class, 11.7% had NYHA III class, and 1% had NYHA IV class compared to 6.8%, 5.8%, 33.9%, and 53.4% pre-procedure, respectively. Conclusion: Long term follow-up of patients after PTMC showed satisfactory outcomes both clinically, as evident from improvement in NYHA functional class, and from echocardiographic stand point with sustained increase in mitral valve area over the period of years. Overall the results of PTMC performed in patients with severe mitral stenosis are satisfactory.

Benefits and Harms of Continuous Intravenous Inotropic Support as Palliative Therapy: A Single-Institution, Retrospective Analysis.

Use of continuous intravenous inotropic support (CIIS) strictly as palliative therapy for patients with ACC/AHA Stage D (end-stage) Heart Failure (HF) has increased significantly. The harms of CIIS therapy may detract from its benefits. To describe benefits (improvement in NYHA functional class) and harms (infection, hospitalization, days-spent-in-hospital) of CIIS as palliative therapy. Methods: Retrospective analysis of patients with end-stage HF initiated on CIIS as palliative therapy at an urban, academic center in the United States between 2014-2016. Clinical outcomes were extracted, and data were analyzed using descriptive statistics. Seventy-five patients, 72% male, 69% African American/Black, with a mean age 64.5 years (SD = 14.5) met study criteria. Mean duration of CIIS was 6.5 months (SD = 7.7). Most patients (69.3%) experienced improvement in NYHA functional class from class IV to class III. Sixty-seven patients (89.3%) were hospitalized during their time on CIIS, with a mean of 2.7 hospitalizations per patient (SD = 3.3). One-third of patients (n = 25) required at least one intensive care unit (ICU) admission while on CIIS therapy. Eleven patients (14.7%) experienced catheter-related blood stream infection. Patients spent an average of 20.6% (SD = 22.8), approximately 40 days, of their time on CIIS admitted to the study institution. Patients on CIIS as palliative therapy report improvement in functional class, survive 6.5 months following initiation, but spend a significant number of days in the hospital. Prospective studies quantifying the symptomatic benefit and the direct and indirect harms of CIIS as palliative therapy are warranted.

Pulmonary vasodilator therapies in pulmonary arterial hypertension associated with CHD: a systematic review and network meta-analysis.

The optimal treatment strategy using pulmonary vasodilators in pulmonary arterial hypertension associated with CHD (PAH-CHD) remains controversial. We aimed to compare the efficacy and safety of pulmonary vasodilators in PAH-CHD. PubMed and EMBASE databases were searched through May 2022 and a network meta-analysis was conducted. The primary outcomes were mean difference of changes in 6-minute walk distance, NYHA functional class, and N-terminal pro-brain natriuretic peptide. The secondary outcomesincluded pulmonary vascular resistance, mean pulmonary arterial pressure, and resting oxygen saturation. We identified 14 studies, yielding 807 patients with PAH-CHD. Bosentan and sildenafil were associated with a significant increase in 6-minute walk distance from baseline compared with placebo (MD 48.92 m, 95% CI 0.32 to 97.55 and MD 59.70 m, 95% CI 0.88 to 118.53, respectively). Bosentan, sildenafil, and combination of bosentan and sildenafil were associated with significant improvement in NYHA functional class compared with placebo (MD -0.33, 95% CI -0.51 to -0.14, MD -0.58, 95% CI -0.75 to -0.22 and MD -0.62, 95% CI -0.92 to -0.31, respectively). Bosentan and sildenafil were also associated with significant improvements in secondary outcomes. These findings were largely confirmed in the subgroup analysis. Various adverse events were reported; however, serious adverse event rates were relatively low (4.8-8.7%), including right heart failure, acute kidney injury, respiratory failure, hypotension, and discontinuation of pulmonary vasodilators. In conclusion, bosentan and sildenafil were the most effective in improving prognostic risk factor such as 6-minute walk distance and NYHA class. Overall, pulmonary vasodilators were well tolerated in PAH-CHD.

Transcatheter valve-in-valve or valve-in-ring implantation with a novel balloon-expandable device in patients with bioprosthetic left side heart valves failure: 1-year follow-up from a multicenter experience

BackgroundTranscatheter aortic and mitral valve-in-valve (ViV) or valve-in-ring (ViR) implantation into failed bioprosthetic heart valves (BHVs) or rings represents an appealing, less invasive, treatment option for patients at high surgical risk. Nowadays, few data have been reported on the use of balloon-expandable Myval (Meril Life Science, Vapi, India) transcatheter heart valve (THV) for the treatment of degenerated BHVs or rings. We aimed at evaluating the early and mid-term clinical outcomes of patients with left side heart bioprosthesis deterioration treated with transcatheter ViV/ViR implantation using Myval THV. Methods97 consecutive patients with symptomatic, severe aortic(n=33) and mitral(n=64) BHVs/ring dysfunction underwent transcatheter aortic ViV and mitral ViV/ViR implantation with Myval THV. ResultsTechnical success was achieved in 95 (98%) of the patients. Two cases of acute structural trans-catheter mitral ViV/ViR dysfunction requiring a second THV implantation were reported. At 30-day, a significant reduction in prosthetic trans-valvular pressure gradients and increase in valve areas were seen following both aortic and mitral ViV/ViR implantation. Overall survival at 15 months (IQR 8-21) was 92%. Patients undergoing mitral ViV/ViR had a relatively worse survival compared with those undergoing aortic ViV implantation (89% vs. 97% respectively; HR:2.7,CI:0.33-22.7;p=0.34). At longest follow-up available a significant improvement in NYHA functional class I and II was observed in patients with aortic and mitral ViV/ViR implantation(93.8% and 92.1%). ConclusionsDespite high surgical risk, transcatheter ViV/ViR implantation for failed left side heart bioprosthesis can be performed safely using Myval THV with a high success rate and low early and mid-term mortality and morbidity.

Effects of Sacubitril/Valsartan on left ventricular pressure-volume relationship in heart failure

Abstract Background In patients with heart failure (HF) and reduced ejection fraction, Sacubitril/Valsartan (S/V) reduces the risk for death and hospitalisations. However, the underlying mechanism for these beneficial effects of S/V, is still lacking. Methods Consecutive patients with symptomatic HF and LV ejection fraction (EF) ≤40% who were assigned to S/V were prospectively included in this study (n=117). Non-invasive pressure volume loops were obtained from echocardiography with simultaneous arm-cuff blood pressure measurement. By this method, LV end-systolic elastance (Ees), effective arterial elastance (Ea) and ventricular-arterial coupling (Ea/Ees) were calculated. LV end-diastolic pressure was derived from the E/e' ratio. This is a prespecified interim analysis of 50 patients with completed 6 months of follow-up. The study is registered with ClinicalTrials.gov, NCT04498780. Results Mean age was 61.8±18.6 years and 12 (24%) patients were females. Ischaemic heart failure was present in 22 (44%), non-ischaemic aetiology in 24 (48%), and myocarditis in 4 (8%) patients. 34 (68%) patients were on the target dose of S/V after 6 months of treatment. At 6 months, LV end-diastolic volume (110±28 ml/m2 vs. 87±31 ml/m2, p&amp;lt;0.0001) and end-systolic volume (78±26 ml/m2 vs. 52±26 ml/m2, p&amp;lt;0.0001) were reduced, hence mean LVEF increased (30±7% vs. 42±11%, p&amp;lt;0.0001). LV end-diastolic pressure was significantly reduced (21±3.9 mmHg vs. 18±2.7 mmHg, p&amp;lt;0.0001). These hemodynamic changes were associated with improved NYHA functional class (8% class III vs. 20% at baseline), reduced median NT-proBNP level (2398 pg/ml, interquartile range [IQR]: 1185–6034 to 813 pg/ml, IQR: 299–1971, p&amp;lt;0.001) and increased mean six-minute walk test (6MWT) distance (356.8m (±150.5) at baseline to 415.0m (±397.0) at six months, p=0.003). LV end-systolic elastance (Ees), arterial elastance (Ea) and the ventricular-arterial coupling ratio Ea/Ees remained similar at 6 months of follow-up compared to baseline (p=ns). Conclusion After 6 months of treatment with Sacubitril/Valsartan, LV remodelling and reduced LV filling pressures were observed. These changes were associated with improvements in functional capacity, natriuretic peptide levels and NYHA functional class. Thus, the study provides important mechanistic insides into the hemodynamics of angiotensin–neprilysin inhibition in heart failure which might help to individualize therapy. Funding Acknowledgement Type of funding sources: None.

EFFECT OF ALLOPURINOL TREATMENT ON CARDIAC FUNCTION AND LONG-TERM DISEASE PROGNOSIS IN PATIENTS WITH CHRONIC HEART FAILURE AND HYPERURICEMIA

Hyperuricemia (HU) is important and common comorbidity that often coexist in patients with heart failure (HF). High values of serum uric acid are associated to severe heart failure. The purpose of the present study was to evaluate a UA-lowering and prognostic effects of allopurinol in patients with chronic HF and hyperuricemia.We studied 75 patients (50 men and 25 women) with HF and increased UA levels, who have been admitted to hospital since September 2019; All patients aged 18&nbsp;years and older were eligible, provided a left ventricular ejection fraction of 45% or less was documented on echocardiography during the enrolment visit and signs and symptoms of chronic heart failure were present. Patient baseline assessment included a standardized HF history regarding HF aetiology (classified as ischemic or non-ischemic) and co-morbidities. All patients underwent a standardized clinical evaluation, including physical examination, determination of NYHA class, determination of body weight. Blood samples were drawn from an antecubital vein in the morning for the assessment of a full blood count and clinical chemistry. Echocardiographic parameters included interventricular septum thickness, left ventricular dimension, left ventricular diastolic function, posterior wall thickness, left ventricular mass index, LVEF. Hyperuricemia was defined according to World Health Organization criteria as uric acid level &gt;5.7&nbsp;mg/dl in women and &gt;7 mg/dl in men. Patients were divided into two groups: 50 patients (group 1) received allopurinol. The initial dose of in most patients was 200 mg/day and it was reduced according to their renal function or UA level. 25 patients (group 2) – controlled group. Treatment duration was 6 and 12 months.Repeated studies after 12 months showed the following results: Uric acid treatment improved the echocardiographic parameters LVEF (38.5± 3.7 and 43.4± 2.4) LV mass index, IVS, PW, stroke volume), reduced NT-proBNP, improved renal function, Improved NYHA functional class; We studied the frequency of cardiovascular events 24-30 months after the start of treatment. Of the 50 patients treated with allopurinol, 11 patients (22%) required rehospitalisation and 9 patients (36%) in the control group;

URIC ACID LOWERING TREATMENT OF PATIENTS WITH CHRONIC HEART FAILURE

Hyperuricemia (HU) is important and common comorbidity that often coexist in patients with heart failure (HF). High values of serum uric acid are associated to severe heart failure. The purpose of the present study was to evaluate a UA-lowering and prognostic effects of allopurinol in patients with chronic HF and hyperuricemia.We studied 75 patients with HF and increased UA levels, who have been admitted to hospital. All patients aged 18&nbsp;years and older were eligible, provided a left ventricular ejection fraction of 45% or less was documented on echocardiography during the enrolment visit and signs and symptoms of chronic heart failure were present. Patient baseline assessment included a standardized HF history regarding HF aetiology (classified as ischemic or non-ischemic) and co-morbidities. All patients underwent a standardized clinical evaluation, including physical examination, determination of NYHA class, determination of body weight. Blood samples were drawn from an antecubital vein in the morning for the assessment of a full blood count and clinical chemistry. Patients were divided in to two groups:&nbsp; 50 patients (group 1) received allopurinol. The initial dose of in most patients was 200 mg/day and it was reduced according to their renal function or UA level. 25 patients (group 2) – controlled group. Treatment duration was 6 months.Repeated studies after 3 months showed the following results: Uric acid treatment improved the echocardiographic parameters (LVEF, LV mass index, IVS, PW, stroke volume), reduced NT- proBNP, improved renal function, Improved NYHA functional class;6-minute walking test distance improved significantly in the UA- treatment group and quality of life. The QoL parameters that was improved included reduced physical limitation, improved mobility, selfcare, increased daily activities and reduced discomfort, anxiety and depression.Among patients with HF and elevated serum uric acid levels, allopurinol use was safe and strongly associated with improved outcomes.

Spanish registry of cardiac resynchronization therapy in adults with congenital heart disease (RETRACCA): clinical outcomes at one year follow-up

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Spanish Society of Cardiology Background There are limited data about the impact of cardiac resynchronization therapy (CRT) in adults with congenital heart disease (CHD) with conflicting results in patients (P) with systemic right ventricle (SRV). Objectives We analyzed the one-year outcomes of adults with CHD implanted with CRT and the impact of CRT in P with SRV as compared with systemic left ventricle (SLV). Methods Data were analyzed from the Spanish Registry of CRT in adults with CHD (RETRACCA). This is an observational, ambispective (66 % retrospective), multicenter Registry, including 74 adults with CHD implanted with a CRT device from 6 Spanish centers from 2007 to 2021. Ventricular function was assessed by echocardiography and graded on a four-point ordinal scale. Response to CRT was defined as an improvement in NYHA functional class and/or systemic ventricular ejection fraction by at least one category. In addition to changes in functional class and ventricular function, other outcomes analyzed included mortality, heart transplantation and CRT-related complications. Results 68 P completed one year of follow-up. Table 1 shows the baseline characteristics of the P prior to CRT. The two main indications for CRT were depressed systolic function of the systemic ventricle with more than 40 % ventricular pacing (69 %) and severely depressed systolic function of systemic ventricle, NYHA FC II-IV and QRS &amp;gt; 150 (18 %). Sixty percent of P received a CRT-ICD, whereas 40 % received a CRT-pacemaker. The approach for CRT system implantation was transvenous in 70 % of the patients, mixed in 21 % and fully epicardial in 9 %. Overall, 43 out of 68 patients (75 %) responded to CRT either by improvement of NYHA FC (56 %) and/or systemic ventricular function (41 %). Compared with baseline, CRT was associated with significant improvement in NYHA FC (p&amp;lt;0.001; figure 1), QRS duration (169±31 vs 150±29; p=0.005), and systemic ventricle systolic function (severe or moderate 80 % vs 58 %; p=0.04). Percentage of responders was similar among patients with a SLV (73 %) and with SRV (81 %; p=0.51). Only pre-implant NYHA FC III-IV was predictive of a positive response in the univariate analysis (OR 3.82; 95 % CI 1.03-14.18). Seven complications occurred at implant (10 %). During the follow-up, there were 8 complications in 7 P: 2 P had heart transplantation, 3 P required hospital admission for decompensation of heart failure, 2 P presented pocket infections and 1 lead malfunction. No differences in complication rates were observed between the systemic LV and systemic RV subgroups. Conclusions In this series, at one-year follow-up, CRT resulted in improvement in functional class and/or systemic ventricular function in 75 % of P with adult CHD. The percentages of responders and complications were similar among patients with SLV or SRV.