KCCQ Score Research Articles

Disease-modifying treatments in transthyretin amyloid cardiomyopathy: a meta-analysis of randomized controlled trials

Abstract Background and Aims Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and life-threatening disease. With advancements in pharmacology, numerous novel medications are currently under investigation. However, the effects of these treatments on long-term outcomes remain elusive and inconclusive. Methods PubMed, MEDLINE, Embase, and the Cochrane Library were searched for literature inclusion until January 2024. Only phase 3, high-quality, randomized controlled trials related to ATTR-CM were considered for enrolment. Endpoints included all-cause mortality, six-minute walk distance, Kansas City Cardiomyopathy Questionnaire–Overall Summary Score, and serum N-terminal pro-B-type natriuretic peptide (NTproBNP) levels. A random-effects model was applied for meta-analysis. Results Three landmark trials (ATTR-ACT, APOLLO-B, ATTRibute-CM) comprising 866 patients with ATTR-CM were pooled. 66.6% of the subjects were administered with medical treatment. Consistent improvements in all-cause mortality (P=0.001), 6-minute walk distance (P=0.045), Kansas City Cardiomyopathy Questionnaire–Overall Summary Score (P<0.001), and serum NTproBNP level (P=0.002) were present by medical treatment. At 12 months, only NT-proBNP showed significant improvement in the pooled analysis of the APOLLO-B and ATTRibute-CM results. At 30 months, the pooled analysis of ATTR-ACT and ATTRibute-CM demonstrated significantly better all-cause mortality and KCCQ scores in patients received mediation. Conclusions Disease-modifying Treatments is associated with better survival, functional capacity, quality of life, and NTproBNP level in patients with ATTR-CM. Extended follow-up duration might be needed to demonstrate efficacies.

Right ventricular to pulmonary artery coupling credicts poor outcomes after interatrial shunting in heart failure

Abstract Background Left atrial decompression is under investigation for heart failure (HF) with the potential to improve symptoms and potentially clinical outcomes. However, heterogeneous outcomes have been observed in randomized controlled studies. Purpose This study aimed to explore whether right ventricular (RV) -pulmonary artery (PA) coupling, as assessed from the tricuspid annular plane systolic excursion (TAPSE) /systolic PA pressure ratio, can be useful in predicting outcomes after implantation of the interatrial shunting device. Methods A total of 106 HF patients, n=62 with reduced ejection fraction (HFrEF), n=44 with preserved ejection fraction (HFpEF), were prospectively enrolled in the PRELIEVE registry with the Atrial Flow Regulator (AFR) implantation. Serious adverse events included cardiovascular mortality and HF worsening (W). Results Serious adverse events (SAEs) occurred in a total of 19 (18%) patients. There were no differences in baseline comorbidities, KCCQ scores, the 6-minute walking distance between patients with and without SAEs (Table). Patients with SAEs showed higher systolic pulmonary arterial pressure, NT-proBNP, serum creatinine and lower TAPSE/PASP ratio. Incidence of SAEs was higher in patients within the first TAPSE/PASP vs the third tertile (59% vs 12%, p=0.026), respectively. A TAPSE/PASP of <0.55 was identified to bear the most optimal sensitivity to predict the event (AUC=0.683, CI95% (0.533-0.833). Conclusion The reduced TAPSE/PASP ratio was associated with higher rates of serious adverse events in patients with heart failure undergoing controlled inter-atrial shunting. The hypothesis generating finding that reduced RV-PA coupling may identify potential clinical non-responders to left atrial decompression should be further prospectively validated.

Edge-to-edge repair for tricuspid valve regurgitation: 1-year follow up and clinical implications from the TR- Interventional Study (TRIS)

Abstract Background Tricuspid regurgitation (TR) affects 7% of the population, contributing significantly to heart failure-related hospitalizations. Traditional treatments have several limitations, prompting the exploration of innovative interventions. Purpose The present study aims to investigate the efficacy of tricuspid valve transcatheter edge-to-edge repair (T-TEER) in real-world patients with severe and symptomatic TR deemed at high surgical risk. Primary objectives focus on assessing T-TEER-induced TR reduction and reverse structural remodeling of the RV. Secondary objectives include assessment of functional status, quality of life, and residual regurgitation during the 12-month follow-up period. Methods The TR-Interventional study (TRIS) is a prospective, single-arm study. From January 2021 to December 2023, we enrolled 44 symptomatic patients with at least severe TR referred for TEER. Outcomes included safety and effectiveness along with assessment of clinical status. Results The study cohort had a mean age of 78.3±7 years, with 77.3% women and a mean TRISCORE of 5.1±1.9. Seventeen patients (38.6%) had massive, 7 (15.9%) had torrential, and 20 (45.5%) patients had severe TR. Etiologies included functional (40.9%), degenerative (13.64%), lead-induced (15.9%), and mixed (29.54%) origin. The primary efficacy endpoint, which assesses the successful implantation and performance of the device at the 30-day mark, was attained in 82.9% of patients. The secondary efficacy endpoint, assessing the stability of TR reduction at the 12-month, was achieved in 82,3% of patients. Post-procedural TR reduction of at least 2 degrees was achieved in 84% of patients. Echocardiographic assessments indicate ongoing beneficial remodeling over the one-year follow-up (Figure 1). Effects on RV remodeling also became apparent at the one-year follow-up, including reductions in the RV end-diastolic basal (p<0.01) and medium (p= 0.04) diameters of the TA septal-lateral diameter (p< 0.01). Significant reduction in vena contracta width (9 mm to 3 mm; p=<0.01), regurgitant volume (58 ml to 30 ml; p<0.01), and effective regurgitant orifice area (EROA) (0.6 cm2 to 0.3 cm2; p<0.01), occurred between baseline and one-year follow-up (Figure 2). The NYHA Functional Class and KCCQ scores were improved from 30 days to 1 year (Figure 2). Conclusion TRIS suggests that T-TEER is a durable, effective, and safe therapeutic option for high-risk patients with severe TR. The enduring nature of TR reduction at one year correlates with sustained clinical benefits and reverse structural remodeling of the right ventricle.TR reductionNYHA and functional status

Obesity and renal impairment in patients with heart failure and reduced ejection fraction: another obesity paradox?

Abstract Background Obesity is associated with poor cardiovascular outcomes in patients with HF and reduced ejection fraction (HFrEF). However, whether obesity is associated with worse kidney outcomes in HFrEF has not been evaluated. Purpose To estimate the association between obesity and change in estimated glomerular filtration rate (eGFR) over time in patients with HFrEF. Methods In this post hoc analysis of the PARADIGM-HF trial, body mass index (BMI) and eGFR was collected in 8,389 patients. Change in eGFR over time was assessed according to baseline BMI (normal weight: BMI <25.0, overweight: BMI 25-29.9, and obesity: BMI ≥30). Results The number of patients in each BMI category was: 2,421 (BMI <25.0), 3,249 (BMI 25-29.9), and 2,719 (BMI ≥30), respectively. Patients with obesity were younger but had worse health status (worse NYHA class and KCCQ scores) and had more comorbidities including diabetes mellitus and hypertension. At baseline, eGFR was lower in patients who were overweight (BMI 25-29.9) and obese (BMI ≥30), compared to those with normal weight. Urine albumin-creatinine ratio (UACR) and kidney injury molecule-1 (KIM-1) were also higher in patients with obesity. However, the rate of change in eGFR per year (eGFR "slope") in the overall cohort did not differ according to BMI: change in eGFR per year was -1.8 [-2.1, -1.6] mL/min/1.73m2 for the normal weight category, -1.6 [-1.8, -1.3] mL/min/1.73m2 for those who were overweight, and -1.5 [-1.8, -1.3] mL/min/1.73m2 for those with obesity; P=0.21) (Figure 1). Among those without diabetes at baseline, those who were obese had a significantly less steep eGFR slope compared to patients in the other BMI categories. In those with diabetes at baseline, the eGFR slope was steeper than in patients without diabetes but was similar across all three BMI categories (Figure 2). Conclusions Although baseline kidney function was more impaired in HFrEF patients with obesity, high BMI was not associated with a more rapid subsequent rate of decline in eGFR. Figure 1. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF Figure 2. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF with and without diabetes at baselineFigure 1Figure 2-A and 2-B

Empowering patients with heart failure: a digital health solution improved self-care and metabolic outcomes in a randomized controlled trial

Abstract Background/Introduction Heart failure is a common cause of morbidity and mortality and poses a significant burden on patients and healthcare providers. Purpose The aim of the study was to evaluate whether a digital health program improves quality of life and clinical outcomes for patients with heart failure. Methods A single-center, randomized controlled trial (RCT) was conducted with patients receiving standard of care (SoC) at a heart failure outpatient clinic. Patients were randomized (1:1) to receive either SoC alone or SoC with an additional six-month digital health program. The program consisted of remote patient monitoring (RPM) with symptom tracking, disease-specific education, and lifestyle coaching, designed to empower patients with heart failure. After the main program concluded, a six-month maintenance program was initiated, consisting of recurrent educational materials, with reduced coaching- and RPM frequency. The primary endpoint was the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at six months. Secondary endpoints included the European Heart Failure Self-care Behaviour Scale-9 (EHFScB-9), 6-question heart failure knowledge questionnaire, and metabolic outcomes. Here we report on the Intention-to-Treat (ITT) population analysis for the primary and significant secondary endpoints at six and 12 months. Results The ITT included 175 participants, 86 in the program group and 89 in the control. Program group: mean age (SD) 64.7 (13.2), 66.3% male, 87.2% with NYHA stages I-II. Control group: mean age (SD) 66.2 (11.1) years, 69.7% male, 87.6% with NYHA stages I-II. Median compliance with RPM was 93% and in-app retention was 80% at six months. Results for primary and secondary endpoints are presented in Table 1 and Figure 1. No statistical difference was observed in the KCCQ score between groups at six or 12 months. The program group had statistically significant improvements in EHFScB-9 score at six and 12 months and in heart failure knowledge at 12 months compared to the control group. Metabolic outcomes: a significant difference in glucose levels was also observed between groups at six months, and in HbA1c and triglycerides levels at 12 months. Conclusions The difference between groups in the primary endpoint of heart failure symptoms and quality of life, as measured by the KCCQ-12, was not statistically significant. However, significant differences were observed in self-care behaviour and heart failure knowledge, as well as metabolic outcomes at six and 12 months, when compared with standard care alone. These findings, along with good retention and engagement, indicate the value to patients of digital health interventions in the management of heart failure.

Effect of alcohol septal ablation on exercise hemodynamics, symptoms and quality of life in patients with obstructive hypertrophic cardiomyopathy

Abstract Background The comprehensive impact of septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy (HCM), including exercise hemodynamics and quality of life (QoL), remains poorly understood. Purpose The aim of this study was to evaluate the effect of alcohol septal ablation (ASA) in mitigating left ventricular outflow tract (LVOT) obstruction, reducing filling pressures during exercise, and the effect on QoL in patients with obstructive HCM. Methods This prospective study enrolled 24 patients with obstructive HCM referred for ASA. Evaluations included right-heart catheterization and echocardiography performed at rest and during exercise, before and approximately six months post-ASA. The primary outcome was the difference in filling pressures assessed by pulmonary capillary wedge pressure (PCWP) at 75 Watt (W). Secondary outcome assessed LVOT gradients, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and exercise capacity. Results ASA significantly reduced PCWP at 75 W (24 ± 10 mmHg vs 33 ± 9 mmHg; P = 0.0001) (Figure 1), decreased LVOT gradients at rest (49 mmHg (24-90) vs 17 mmHg (14-27); P=0.002), at peak exercise (45 mmHg (29-90) vs 32 mmHg (21-61); P = 0.02), and post-exercise (96 mmHg (34-161) vs 28 mmHg (21-62); P=0.004). The KCCQ-OSS score was also significantly reduced (75.6 ± 18.8 vs 64.7 ± 16; P = 0.006), without affecting peak oxygen consumption (19.9 ± 4.8 ml/kg/min vs 18.7 ± 3.6 ml/kg/min; P = 0.26). The improvement in the KCCQ score was confirmed by changes in NYHA functional class. Before ASA treatment, 54% of patients were in NYHA functional class III compared to 13% after ASA (P < 0.0005). Conclusion ASA substantially reduces exercise-induced filling pressures, reduces LVOT obstruction, and improves symptoms and QoL in obstructive HCM, without impacting maximal exercise capacity.

Effects of dapagliflozin in heart failure according to duration of type 2 diabetes: a patient-level meta-analysis of DAPA-HF and DELIVER

Abstract Introduction Type 2 diabetes (T2D) is a common comorbidity in heart failure (HF), and long-standing T2D is associated with worse outcomes. Purpose To investigate the efficacy and safety of dapagliflozin, compared with placebo, according to duration of T2D in patients with HF and established T2D. Methods We conducted a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which evaluated the effects of dapagliflozin, compared with placebo, in patients with HF with reduced ejection fraction and HF with mildly reduced/preserved ejection fraction, respectively. T2D duration was categorized as <5 years, 6-10 years, and >11 years. The primary outcome was a composite of worsening HF or cardiovascular death. Results Of the 4,784 patients with a history of T2D, 1,879 (39.3%) had a T2D duration of <5 years, 1,074 (22.4%) 5-10 years, and 1,831 (38.3%) >11 years. Patients with longer-duration T2D were older, more often female, and White, and had a higher HbA1c, body mass index, and left ventricular ejection fraction. They were more likely to have ischaemic heart disease, peripheral artery disease, hypertension, and chronic kidney disease, but were less likely to have atrial fibrillation/flutter. Although patients with longer-duration T2D had longer duration of HF, they were not more likely to have a prior HF hospitalization or worse New York Heart Association functional class. Despite similar N-terminal pro-B-type natriuretic peptide levels, patients with longer-duration T2D had a higher risk of the primary outcome, even after adjustment for potential confounders (<5 years, reference; 6-10 years, HR 1.25 [95% CI, 1.06-1.46]; >11 years, HR 1.33 [1.15-1.54]). The benefit of dapagliflozin on the primary outcome was consistent across T2D duration category: <5 years, HR 0.85 (95% CI, 0.69-1.04); 5-10 years, HR 0.65 (0.51-0.83); >11 years, HR 0.84 (0.70-1.01) (Pinteraction=0.18). Dapagliflozin reduced the risk of secondary clinical outcomes and increased (improved) mean KCCQ scores from baseline to 8 months, regardless of T2D duration (Table). Adverse events and treatment discontinuation were not more frequent with dapagliflozin than with placebo irrespective of T2D duration. Conclusions Dapagliflozin reduced the risk of worsening HF or cardiovascular death, and improved symptoms, in patients with HF and T2D, irrespective of T2D duration.

Safety and quality of life assessment at 6 months follow-up of the valvosoft pivotal study

Abstract Background Calcific Aortic stenosis (CAS) is currently the most common heart valve disease. Patients suffering from severe CAS are treated with invasive surgeries based on valve replacement. Symptoms heavily impact quality of life, including chest pain, shortness of breath, dizziness, fatigue, and major risks as heart failure or sudden death, and daily activities might also be strongly impacted. Purpose A prospective, multi-centre, single-arm, pivotal study (NCT05235568) was initiated in 2021 to treat severe CAS patients with Valvosoft, a medical device based on Non-Invasive Ultrasound Therapy (NIUT) intended to treat CAS in patients not eligible for immediate aortic valve replacement (SAVR/TAVR) or refusing such a treatment, to confirm safety and performance at 1-, 3-, 6- and 12 months. We present here the safety and quality of life results at 6M follow-up. Methods Valvosoft NIUT procedure is based on a trans-thoracic delivery of focused, high intensity short therapeutic ultrasound pulses, to precisely generate a cavitation bubble cloud on the aortic valve. Echocardiographic imaging enables to monitor the valve in real-time while cavitation causes both non-thermal tissue softening and calcification fractionation of the diseased valve. 60 planned subjects, suffering from severe calcific aortic stenosis, not recommended for aortic valve replacement or refusing such a procedure, were enrolled in 11 centres in Europe. Patients were awake or lightly sedated, NIUT was delivered during up to 70 minutes per patient per procedure. DSMB and CEC were installed to monitor safety, performance and effectiveness of Valvosoft device, and safety related to participation in the clinical investigation. Results Sixty high-risk patients advanced in age (85.2 ± 9.1) with multiple severe comorbidities were included. Primary safety endpoint (less than 25% MACE) was met at 30D (p=0.002). Furthermore patients experienced an overall quality of life improved. 6 minutes’ walk test increases from baseline towards 6 months with 10 %. At 6M follow-up, no stroke was reported, an average KCCQ score improvement of 17% was noticed, and NYHA class improved or stabilized for 78% of patients. The calcium score or volume on the aortic did not change pre- and post-procedure. Conclusion Valvosoft NIUT safety and quality of life improvement are proven at 6MFU, and the technology is presented as potentially disruptive, in the treatment of severe calcific aortic stenosis.

One-year outcomes of transcatheter mitral valve replacement in patients with severe mitral regurgitation

Abstract Background Mitral valve regurgitation (MR) is a prevalent valvular heart disease, and a subset of patients face challenges in undergoing surgical treatment. Transcatheter mitral valve replacement (TMVR) has emerged as a viable option for selected patients with severe MR deemed unsuitable for traditional valve surgery. Purpose This study aims to evaluate the feasibility, safety, durability, and clinical outcomes of a novel transapical mitral valve system (MitraFix valve) in treating moderate to severe MR patients. Methods The early feasibility study of the MitraFix TMVR transapical system is a multicenter, prospective, nonrandomized study. All patients underwent evaluation by a multidisciplinary heart team and were deemed suitable for mitral valve intervention. Clinical events were adjudicated by an independent clinical events committee. Results From June 2021 to July 2022, 10 patients (mean age: 71.2 ± 7.4 years, 40% male) were enrolled. The mean Society of Thoracic Surgeons(STS) predicted risk of mortality was 7.5 ± 2.7%. All implants were successful, with a mean operational time of 45.2 ± 25.9 min. One patient was converted to open cardiac surgery after successfully implanting the valve due to persistent apical bleeding. At 1-year follow-up, all-cause mortality was 20%, with a cardiovascular mortality at 10.0%. Among survival patients, 87.5% of surviving patients had MR ≤1+ and 75% patients were in NYHA functional class I or II at 1 year. The overall KCCQ score significantly increased from 55.8 (42.9, 72.9) points at baseline to 77.5 (73.7, 88.6) points at 1-year follow up (P = 0.012). Left ventricular ejection fraction showed no significant change from basline (51.5%) to 1 year (50.0%) (P=0.799). No evidence of mitral stenosis or left ventricular outflow tract (LVOT) obstruction was observed. Conclusions The MitraFix TMVR transapical system demonstrated excellent valve function, low mortality, sustained MR elimination and clinical improvement up to one year in this study. Further studies, encompassing a larger cohort of patients and an extended follow-up duration, are needed to confirm these findings.Change in MR and NYHA functional classChange in Quality-of-Life Assessment

REDUCE-HF: a stronger heart go a long way

Abstract Introduction/Purpose Heart failure (HF) is a serious cardiovascular condition with a significant global health concern. The risk of heart failure rehospitalisation is high globally and locally, the 30-day HF readmission was about 32% from a local study (1). The study aims to adopt an intensive treatment strategy similar to Strong-HF trial (2) and evaluate rapid up-titration of guideline directed medical therapy (GDMT) and close follow-up will improve patients' outcomes after acute heart failure (AHF). Objectives The Reduction of Decompensation and Unnecessary Cardiac failure Emergency admissions: ambulatory Heart Failure service model (REDUCE-HF) is a non-randomised prospective study evaluating clinical outcome of patients discharged from AHF. Exclusion criteria included primary valvular disorders, end-stage renal failure and metastatic cancer. After HF discharge, eligible patients were recruited into our REDUCE-HF program irrespective of LVEF. They were subsequently managed in our ambulatory HF centre within two weeks, where intensive up-titration of GDMT and close follow-up would be proceeded. The data of our service model will be compared with our 5-year historical cohort. Primary outcome comprised of all-cause mortality and heart failure hospitalisation. Secondary outcome will be comparison of clinical and functional status at baseline and 3-month on follow up. Results Between October 2022, and December 2023, 245 patients were successfully recruited into our REDUCE-HF service model. Historical cohort of 6867 patients with primary diagnosis of acute heart failure were served as control (usual care pathway), data extracted from 2018 to 2022. Their mean age was 67.8+/-12.2 and 72.2%were male. 60% of them were HFrEF (EF<=40%) and 28% were ischaemic cardiomyopathy. The mean follow up period was 3 months. At 90 days, REDUCE-HF cohort group has shown much lower all-cause mortality than usual care group (2.5% vs 9.3%, HR 0.26, 95% CI 0.18-0.41, p<0.001). There was a much lower incidence of heart failure hospitalisation in REDUCE-HF group as compared to control (8.6% vs 13.1%, HR 0.65; 95% CI 0.55 to 0.74, p<0.01). In secondary outcome, there was significant reduction of NT-ProBNP of 45.2% (from 4229 to 2319pg/m, p<0.001), tremendous increment of 6-minute walk test (from 211 to 250m, p<0.001) and remarkable improvement of KCCQ score from 55.1 to 86.7, p<0.001. The overall LVEF was significantly increased from 39% to 44%, p<0.05. The positive outcome were attributed to good adherence to GDMT: ACEi/ARB/ARNI 91%, Betablocker 90.3%, MRA 72.4% and SGLT2i 95.5%. Conclusion The REDUCE-HF ambulatory service model has been proven effective in reducing mortality, decompensation and preventing unnecessary heart failure hospitalisation in this prospective study. By intervening proactively, this model not only enhances the quality of life but also hold promise in alleviating the burden of in-patient services on heart failure.

The Management Outcome of Heart Failure Reduced Ejection Fraction with or without Angiotensin Receptor Neprilysin Inhibitor

INTRODUCTION: Heart failure is associated with recurrent admission, higher mortality and low quality of life. Angiotensin receptor neprilysin inhibitor (ARNI) is a novel agent that has been used for treating heart failure reduced ejection fraction (HFrEF) patients. Thus, it is interesting to evaluate the effect of ARNI on the reverse cardiac remodelling, rehospitalization, cardiac biomarker and quality of life in HFrEF patients. MATERIALS AND METHODS: A case controlled study was conducted to assess the treatment outcome of HFrEF with or without ARNI. During the study, the patients’ basic demography, co-morbidities, baseline echocardiography (ECHO) findings, NYHA classification, NT-pro BNP levels and KCCQ score were evaluated. The patients’ admission history within 90 days from initiation of ARNI or non ARNI were obtained retrospectively. A follow up ECHO was obtained after at least 3 months of intervention. RESULTS: A total of 81 patients were recruited in which 54 patients were on ARNI and 27 were on non ARNI treatment. There was a statistically significant improvement of ejection fraction, left ventricular internal diameter end diastole and systole, and left ventricular end-systolic volume in ARNI group. The NYHA class was also noted to improve after ARNI treatment. The NT-proBNP value was lower whereas the KCCQ score was higher in ARNI group compared to non ARNI group. CONCLUSION: HFrEF patients with ARNI treatment had better reverse cardiac remodelling effect, cardiac biomarker and quality of life compared to non ARNI treatment. Furthermore, patient received ARNI demonstrated improved heart failure classification after treatment

Remote, Smart Device-Based Cardiac Rehabilitation After Myocardial Infarction: A Pilot, Randomized Cross-Over SmartRehab Study

ObjectiveTo evaluate the effect of smart device-based telerehabilitation on Vo2peak in patients after myocardial infarction. Patients and MethodsThis was a pilot, single-center, randomized, cross-over study with a 3-month intervention. One month after myocardial infarction, patients had cardiopulmonary exercise testing and a 6-minute walking test (6MWT) and were randomly assigned 1:1. In the intervention group, patients received a smartwatch to track the recommended number of steps, which was individualized and derived from the 6MWT. A study nurse telemonitored adherence to the recommended number of steps a day. In the control group, 150 minutes a week of moderate-intensity physical activity was recommended. After 3 months study arms were crossed over, and study procedures were repeated after 3 months. ResultsBetween June 1, 2019, and February 28, 2023, 64 patients were randomized, of which 61 (aged 51±10 years, 10% women) completed the study. Overall, the smart device-based telerehabilitation led to 2.31 mL/kg/min (95% CI, 1.25-3.37; P<.001) Vo2peak increase compared with the control treatment. Furthermore, there was a significant effect on weight (−1.50 kg; 95% CI, −0.39 to −2.70), whereas the effect on the 6MWT distance (4.7 m; 95% CI, −11.8 to 21.1) or Kansas City Quality of Life questionnaire score (0.98; 95% CI, −1.38 to 3.35) was not significant. ConclusionSmart device-based cardiac rehabilitation may be a promising alternative for patients unable or unwilling to attend in-person cardiac rehabilitation. Trial Registrationclinicaltrials.gov Identifier: NCT03926312

TELECUORE: FEASIBILITY OF A HOSPITAL–TERRITORIAL TELEMEDICINE PROJECT IN CHRONIC HEART FAILURE

Abstract Background Since February 2023, Cardiology department of AUSL Piacenza has started a telemedicine project named “TeleCuore,” aimed at exploring the impact of a multiparametric telemonitoring system on the management of patients affected by chronic heart failure (CHF). OBJECTIVES assess organizational sustainability, satisfaction among involved figures, and the clinical impact at 9 months of an extensive telemonitoring project targeting patients with CHF. Materials and Methods 250 patients with CHF and recent clinical instability were recruited and equipped with the Adilife device to monitor and transmit weight, temperature, blood pressure, heart and respiratory rate, oxygen saturation, and single–lead ECG. These data are managed by case manager (CM), cardiologists, respiratory and perfusion pathophysiology technicians (TFCPC), general practitioner to optimize patient therapy, empowerment, and reduce acute admissions through timely teleconsultations/televisits. Every 6 months, patients are asked to complete a Quality of Life questionnaire (KCCQ–23) and a satisfaction questionnaire regarding the project, which is also administered to healthcare professionals. Results Over 9 months, positive patient engagement is confirmed, with over 92,000 total transmitted measurements. The most monitored parameter is heart rate (4 times/week). At questionnaire analysis, 80% of patients believes TeleCuore helps them remember parameter measurements, and 70% adopt a correct lifestyle through phone conversations with CM. For over 50%of them the project contributes improving their relationship with healthcare professionals. For 90%of healthcare professionals there is better team collaboration and patient education. Both clinicians and patients (100%) believe that TeleCuore improves the effectiveness of follow–up visits: patients arrive more prepared (30%), and staff can dedicate more time to patients (30%) and access information before the visit (10%). The patients KCCQ score varies from a medium of 71 at baseline to a medium of 78 at 6 months analisys. Conclusions TeleCuore project demonstrates that telemedicine can facilitate patient management and empowerment. Professional figures (CM and TFCPC) are crucial for project execution, working alongside clinical cardiologists for proper alert management, patient education on therapy adherence, and correct lifestyle. An ongoing analysis aims to quantify whether TeleCuore can reduce hospitalizations related to acute heart failure.

SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure

The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported. To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF. The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023. Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO2] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included. Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted. Outcomes of interest included changes in peak VO2, 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS). In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes. These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients' everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.

The Role of Comorbidities in Predicting Functional Improvement After Transcatheter Aortic Valve Implantation

Patients undergoing transcatheter aortic valve implantation (TAVI) have a high comorbidity burden. We sought to stratify patients into functional outcomes using the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), a patient-reported outcome with benefits over both the New York Heart Association (NYHA) classification and the original 23-item KCCQ, and to evaluate the importance of comorbidities in predicting failure of functional improvement post-TAVI in a contemporary cohort. In total, 366 patients with severe aortic stenosis undergoing TAVI with baseline KCCQ-12 were retrospectively analysed and divided into two groups. Failure to improve was defined as a score <60 and a change in score <10 at 1 year in either overall score (KCCQ-OS) or clinical summary score (KCCQ-CSS). Failure to improve was noted in 13% of patients, who were more likely to have lower KCCQ-OS at baseline (47 [35-59] vs 56 [42-74]), chronic obstructive pulmonary disease (COPD) (19% vs 8%), severe chronic kidney disease (CKD) (13% vs 2%), a clinical frailty score (CFS) ≥5 (41% vs 14%), and lower serum albumin (36 g/L [34-38] vs 38 g/L [35-40]). On multivariate analysis, with an area under the curve of 0.71 (0.63-0.78), baseline KCCQ-OS (adjusted odds ratio [aOR] 0.3 [0.1-0.6], p=0.04), COPD (aOR 2.8 [1.2-6.5], p=0.02), and severe CKD (aOR 5.7 [1.7-18.5], p=0.004) remained independent predictors. CFS alone had a similar predictive value as the multivariable model (OR 2.0 [1.3-3.4], area under the curve 0.69 [0.59-0.80], p<0.001). KCCQ scores were effective in delineating functional outcomes, with most patients in our relatively lower surgical risk cohort showing significant functional improvements post-TAVI. Low baseline KCCQ, moderate or worse COPD, and severe CKD were associated with failure of improvement post-TAVI. Baseline CFS appears to be a good screening tool to predict poor improvement. These factors should be evaluated and weighted accordingly in pre-TAVI assessments and decision-making.

Effects of dapagliflozin and empagliflozin on 6-min walk distance in heart failure with preserved and reduced ejection fraction: A systematic review and meta-analysis of randomized controlled trials involving 2624 patients.

Dapagliflozin and empagliflozin are antidiabetic medications. They are the first two sodium-glucose cotransporter-2 inhibitors (SGLT2i) to receive the US Food and Drug Administration approval to manage heart failure. Emerging new trials have examined changes in the 6-min walk distance as a clinically significant response to dapagliflozin and empagliflozin in patients with heart failure with reduced ejection fraction (HFpEF) and heart failure with preserved ejection fraction (HFrEF). This meta-analysis aims to evaluate the effects of dapagliflozin and empagliflozin on the 6-min walk distance in patients with HFpEF and HFrEF. To our knowledge, no such meta-analysis has been published. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched four electronic databases (PubMed, EMBASE, Cochrane Library, and Web of Science) to identify eligible studies reported up to December 16, 2023. Using Review Manager software, we reported outcomes as risk ratios (RRs) or mean difference (MD) and confidence intervals (CIs). A p-value ≤ 0.05 is considered as statistically significant. The meta-analysis included a total of 8 studies with 2624 patients. Overall, the results showed insignificant differences in the 6-min walk between the SGLT2i and placebo (MD 24, 95% CI -0.30 to 18.78, p = 0.06). Results became significant after resolving the heterogeneity (MD 6.72, 95% CI 0.13 to 13.31, p = 0.05). Notably, the results of each drug separately were insignificant. More robust observations occurred in the HFpEF group (MD 10.73, 95% CI 1.08 to 20.39, p = 0.03). Compared to placebo, patients on dapagliflozin reported significant improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary (KCCQ-CS) and Overall Summary (KCCQ-OS) with values of MD 5.18 (95% CI 2.80 to 7.57, p < 0.0001) and MD 4.06 (95% CI 1.66 to 6.46, p = 0.0009), respectively. The dapagliflozin group and patients with HFpEF had reported a significant reduction in their weight compared with the control group (MD -0.59 CI -1.09 to -0.08, p = 0.02) and (MD -0.80 CI -1.47 to -0.13, p = 0.02), respectively. No significant side effects were observed for dapagliflozin or empagliflozin. Patients with HFpEF experienced benefits from SGLT2i administration, as evidenced by improved 6-min walk distances and weight reduction. Dapagliflozin demonstrated clinical and overall improvements in KCCQ scores and was more effective in reducing weight than the placebo. Both Dapagliflozin and Empagliflozin were well-tolerated and exhibited favorable safety profiles. Future studies could benefit from a larger patient population, a longer follow-up period, and a broader range of SGLT2i.

Evaluating the efficacy and safety of mavacamten in hypertrophic cardiomyopathy: A systematic review and meta-analysis focusing on qualitative assessment, biomarkers, and cardiac imaging.

Hypertrophic Cardiomyopathy (HCM) is a complex cardiac condition characterized by hypercontractility of cardiac muscle leading to a dynamic obstruction of left ventricular outlet tract (LVOT). Mavacamten, a first-in-class cardiac myosin inhibitor, is increasingly being studied in randomized controlled trials. In this meta-analysis, we aimed to analyse the efficacy and safety profile of Mavacamten compared to placebo in patients of HCM. We carried out a comprehensive search in PubMed, Cochrane, and clinicaltrials.gov to analyze the efficacy and safety of mavacamten compared to placebo from 2010 to 2023. To calculate pooled odds ratio (OR) or risk ratio (RR) at 95% confidence interval (CI), the Mantel-Haenszel formula with random effect was used and Generic Inverse Variance method assessed pooled mean difference value at a 95% CI. RevMan was used for analysis. P<0.05 was considered significant. We analyzed five phase 3 RCTs including 609 patients to compare mavacamten with a placebo. New York Heart Association (NYHA) grade improvement and KCCQ score showed the odds ratio as 4.94 and 7.93 with p<0.00001 at random effect, respectively. Cardiac imaging which included LAVI, LVOT at rest, LVOT post valsalva, LVOT post-exercise, and reduction in LVEF showed the pooled mean differences for change as -5.29, -49.72, -57.45, -36.11, and -3.00 respectively. Changes in LVEDV and LVMI were not statistically significant. The pooled mean difference for change in NT-proBNP and Cardiac troponin-I showed 0.20 and 0.57 with p<0.00001. The efficacy was evaluated in 1) A composite score, which was defined as either 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction, or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening and 2) changes in pVO2, which was not statistically significant. Similarly, any treatment-associated emergent adverse effects (TEAE), treatment-associated serious adverse effects (TSAE), and cardiac-related adverse effects were not statistically significant. Mavacamten influences diverse facets of HCM comprehensively. Notably, our study delved into the drug's impact on the heart's structural and functional aspects, providing insights that complement prior findings. Further large-scale trials are needed to evaluate the safety profile of Mavacamten.

Short-term study of atrial shunt and improvement of functional mitral regurgitation

BackgroundThis study used an atrial septal shunt to compare the treatment progress and prognosis for patients with heart failure (HF) who have different ejection fractions.MethodsTwenty HF patients with pulmonary hypertension, who required atrial septal shunt therapy, were included in this study. The patients underwent surgery between December 2012 and December 2020. They were divided into two groups based on their ejection fraction: a group with reduced ejection fraction (HFrEF) and a group with preserved ejection fraction(HFpEF) + mid-range ejection fraction (HfmrEF). Echocardiography was utilized to evaluate parameters such as left ventricular dimension (LVD), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume (LVEDV). Hemodynamic parameters were measured using cardiac catheterization. The patient's cardiac function was assessed using the six-minute walking test (6MWT), KCCQ score, NYHA classification, and the degree of functional mitral regurgitation (FMR). Followed-up visits were conducted at 1, 3, and 6 months, and any adverse effects were recorded.ResultsThe LVEF values were consistently higher in the HFpEF+HFmrEF group than HFrEF group at all periods (P < 0.05). Differences in LVD were observed between the two groups before the surgery. Statistically, significant differences were found at the preoperative stage, 1 month, and 3 months (P < 0.05, respectively). However, the LVEDV showed a significant difference between the two groups only at 3 months (P = 0.049). Notably, there were notable variations in LAPm, LAPs, and the pressure gradient between the LA-RA gradient at baeline, after implantation, and during the 6 months follow-up (all P < 0.05).ConclusionFollowing treatment, the HFpEF+HFmrEF group exhibited more significant improvements in echocardiographic and cardiac catheterization indices than the HFrEF group. However, there was no statistically significant difference between the two groups regarding the 6MWT and KCCQ scores. It is important to note that the findings of this study still require further investigation in a large sample size of patients.

Transcatheter endomyocardial alginate-hydrogel injection for treatment of heart failure

Abstract Background and Aim Intramyocardial injection of alginate-hydrogel, an emerging and promising strategy for patients with advanced heart failure (HF), is limited by the paucity of commercially available intramyocardial delivery methods. This study investigates the feasibility and safety of a novel X-DROP catheter injection system (Figure 1) for delivery of the alginate-hydrogel to pre-defined target areas in the treatment of HF with reduced ejection fraction. Methods and results Prior to the First-in-man, we demonstrated that transcatheter endo-myocardial alginate-hydrogel implantation (TEAi) was successfully and precisely performed with the X-DROP catheter system under TEE and fluoroscopy guidance in a healthy porcine model (Figure 2). Acute animal results (n = 15) showed no mortality, perforation, and sustained ventricular arrhythmias. Gross examination revealed the retention of the alginate-hydrogel in the pre-defined endocardial area at six months post-procedure (n = 4, Figure 2). The histological assessment showed that alginate-hydrogel was encapsulated by multiple layers of fibrosis without causing damage to the nearby myocardium. Expanding from the animal result, we conducted a first-in-human trial to evaluate the TEAi in patients with heart failure. Ten patients with NYHA class III-IV were enrolled, and all patients were successfully treated with TEAi without the device or procedure-related complications. At the 30-day follow-up, there were no serious adverse device events. One death occurred at a 3-month follow-up. The mean LVEF evaluated by MRI improved from 17.7±3.82 % at baseline to 24.94±11.15 % at 6 months post-procedure (p = 0.046). Also, ESV (297.50±67.85 vs 264.79±101.41, p = 0.029), EDV (359.5±71.92 vs 341.56±67.85, p = 0.105), six minutes walking test (339.7±37.6 m vs 370.4±64.8 m, p = 0.184), NYHA functional class (30% Class III and 70% Class IV vs 100% Class II), and KCCQ score (49.7±3.91 vs 79.0±8.1) were improved at 6-month follow-up. Holter monitor data showed no sustained ventricular arrhythmia during the TEAi or follow-up. Conclusions Our results established the safety and feasibility of TEAi using a novel platform, the X-DROP system and paved the way for the clinical application of intramyocardial injection of alginate-hydrogel in patients with HF.Figure 1Figure 2

The PRELIEVE trial:Final 1-year outcomes of the prospective atrial flow regulator study

Abstract Background Implantation of the Atrial Flow Regulator (AFR) with an 8 or 10mm interatrial fenestration reduces left sided filling pressures in symptomatic heart failure (HF). Here, we report the final one-year results on safety and efficacy of the AFR in HF patients. Methods PRELIEVE is a prospective, non-randomized, multi-center, single-arm study in HF patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction. Patients with elevated fillings pressure at rest received an 8mm shunt device while those with exercise-induced rise in filling pressure received a 10mm AFR shunt device. Results Out of 109 enrolled patients 106 patients (n=62 HFrEF and n=44 HFpEF) received a successful device implantation (n=86 8mm AFR and n=20 10mm AFR). All-cause and cardiovascular mortality were 21% and 14% respectively in HFrEF and 7% and 0% respectively in HFpEF. HF hospitalization rate was 19% in HFrE and 9% in HFpEF. In 85 patients (n=44 HFrEF and n=41 HFpEF) with completed follow-up, device patency was documented in all patients having adequate image quality at 1-year follow-up (n=78). NYHA class &amp;gt;1 increase was noted in 67.5% HFrEF and 63.7% HFpEF patients. Quality of life assessed from the KCCQ score (overall summary score) increased from 49 + 23 to 72+24 in HFrEF and from 41+20 to 55+26 in HFpEF patients. Improved KCCQ&amp;gt;5 points was noted in 67.4% HFrEF and 44.7% in HFpEF patients. Six minute walking distance increased from 203+101m to 269+108m in HFrEF and from 228+121 m to 253+109m in HFpEF. Improved walking distance by either 50 m or by 50% was noted in 59.5% in HFrEF and 41.2% in HFpEF patients. Among echocardiography parameters, right ventricular diameter tended to increase in patients receiving 10 mm shunt device (Delta 1year vs. baseline 3.1 +11.2 mm), no changes were observed in patients treated with 8 mm shunt device. Note, pacemaker presence or resting pulmonary vascular resistance were similar. Conclusions Implantation of AFR device with either 8 or 10 mm shunt size in HF patients was safe and feasible irrespective of baseline ejection fraction. Signals of clinical efficacy were observed in the majority of patients. This study warrants further clinical evaluation of the AFR device in HF.Clinical efficacy parameters