York Heart Association Functional Class Research Articles

Predictive factors of right heart catheterization to diagnose pulmonary arterial hypertension using least absolute shrinkage selection operator (LASSO) regression

Objective This study involved an analysis of a real world, international survey where physicians provided cross-sectional, retrospective data for patients with pulmonary arterial hypertension (PAH) to determine predictive factors of right heart catheterization (RHC) to confirm their PAH diagnosis. Methods Data were sourced from the Adelphi PAH Disease Specific Programme (DSP) in the United States (US), France, Germany, Italy, Spain, United Kingdom, and Japan, between March and August 2022. Results Overall, 75% (n = 395) of patients with PAH (n = 529) underwent RHC at diagnosis; this varied by country, ranging from 64% in the US to 92% in France. RHC was more likely to be performed in patients with a higher New York Heart Association Functional Class, with key PAH symptoms (dyspnea, palpitations, and cyanosis), and diagnosed at PH specialist centers. Conclusion By understanding the factors associated with RHC utilization at PAH diagnosis, more targeted approaches for improving the diagnosis for patients with suspected PAH may be pursued.

Clinical Implications of Left Ventricular Apex Mechanics in Patients With Apical Hypertrophic Cardiomyopathy

Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathologic hypertrophy mainly at the left ventricular (LV) apex. Although previous studies have indicated apical dysfunction in ApHCM, how apical mechanics change during disease progression has not been thoroughly examined. The aims of this study were to characterize the mechanics of the LV apex in patients with ApHCM at different disease stages and to explore the clinical significance of these alterations. One hundred four patients with ApHCM were divided into three subtypes on the basis of LV apical maximum wall thickness (AMWT) and extent of hypertrophy: relative type (isolated apical hypertrophy with AMWT<15mm), pure type (isolated apical hypertrophy with AMWT≥15mm), and mixed type (both apical and midventricular hypertrophy with AMWT≥15mm). Two-dimensional speckle-tracking echocardiography was used to analyze LV segmental strain, global strain, and twist. Comparisons of these parameters were performed among ApHCM subtypes and 30 healthy control subjects. Logistic regression and Cox proportional-hazards regression analyses were used to explore associations between myocardial mechanics and clinical indicators. A composite outcome of new-onset atrial fibrillation, heart failure hospitalization, myectomy, and all-cause mortality was assessed. Even in relative ApHCM patients, apical longitudinal strain (LS), circumferential strain, and radial strain (RS) were significantly impaired compared with control subjects (LS: -14.6±4.1% vs -20.0±1.7% [P=.001]; circumferential strain: -19.6±2.5% vs -25.6±3.7% [P=.002]; RS: 26.6±7.4% vs 35.6± 11.1% [P=.026]), while apical rotation and LV twist remained unchanged. In patients with greater apical hypertrophy (mixed and pure patients), apical LS and RS were more abnormal. Moreover, apical rotation showed significant reductions compared with relative-type patients. After adjusting for clinical and myocardial mechanical parameters, apical rotation was independently associated with New York Heart Association functional class≥II (odds ratio, 0.81; 95% CI, 0.66-0.99; P=.036) and the composite outcome (hazard ratio, 0.82; 95% CI, 0.73-0.91; P=.001). Relative ApHCM demonstrates apical dysfunction but sparing of apical rotation, which was abnormal in more extensive phenotypes. LV apex mechanics were closely related to clinical patterns, with apical rotation correlated with both New York Heart Association functional class≥II and clinical events.

Outcomes of mitral transcatheter edge to edge repair with MitraClip™ – An Indian single center experience

ObjectiveTo evaluate the outcomes of transcatheter edge-to-edge repair (TEER) with MitraClip™ (Abbott Vascular) in symptomatic high surgical risk Indian patients with significant mitral regurgitation (MR). MethodsPatients with moderately severe or severe primary or secondary MR and deemed high surgical risk were treated with MitraClip™. The data were collected retrospectively from medical records. The primary outcome was technical success, and secondary outcomes were ≤2+ MR reduction and improvement in functional capacity at 30 days. ResultsBetween November 2018 and August 2023, 64 patients were treated with MitraClipTM. The mean age was 70.0 ± 12.1 years and 64 % were males. The mean EuroScore II and STS score predicted mortality for mitral valve repair were 5.8 ± 4.5 % and 4.0 ± 3.8 % respectively. MR etiology was primary in 56.3 %, secondary in 40.6 % and mixed in 3.1 %. The device was implanted successfully in all but one patient with technical success rate of 98.4 %. The average number of clips per patient was 1.5 ± 0.6 and 42.2 % patients received more than one clip. The mean mitral valve gradient was 3.5 ± 1.6 mmHg. The MR severity of ≤2+ was achieved in 91.8 % of the subjects and similar proportion were in New York Heart Association Functional Class I or II at 30 days. ConclusionIn high-risk Indian patients with symptomatic significant MR, TEER with MitraClip™ was achieved with a high technical success rate. It was associated with significant reduction in MR severity and improvement in functional capacity in >90 % of the subjects.

Qiliqiangxin Alleviates Imbalance of Inflammatory Cytokines in Patients with Dilated Cardiomyopathy: A Randomized Controlled Trial.

Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM. The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment. At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant. QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.

Transthyretin cardiac amyloid: Broad heart failure phenotypic spectrum and implications for diagnosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is most often associated with heart failure with preserved ejection fraction (HFpEF). However, patients may present with impaired systolic function at the time of diagnosis, which has not been widely investigated. We sought to explore the prevalence of various heart failure (HF) phenotypes and their associated clinical characteristics at the time of ATTR-CA diagnosis. We performed a single-centre retrospective cohort study of consecutive patients with ATTR-CA evaluated between February 2016 and December 2022. Data on patient demographics, comorbidities, imaging and laboratory findings were compared across HF phenotypes (age: 78.1±8.6years, with 91.1% male). A total of 21.6% (n=46) presented with heart failure with reduced ejection fraction (HFrEF), 17.8% (n=38) with heart failure with mildly reduced ejection fraction (HFmrEF) and 60.6% (n=129) with HFpEF at the time of diagnosis with ATTR-CA. Those presenting with HFrEF or HFmrEF were more likely to be African American and had significantly worse New York Heart Association (NYHA) functional class, higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and higher serum creatinine levels as compared with those with HFpEF. Although ATTR-CA is traditionally thought to be seen primarily among patients with HFpEF, our data suggest that ATTR-CA has a higher prevalence among patients with HFrEF, which underscores the importance of heightened clinical suspicion regardless of ejection fraction when considering ATTR-CA. Furthermore, although comorbidities are similar, patients with HFmrEF and HFrEF had a worse symptom burden.

Transcatheter aortic valve implantation for combined aortic and mitral stenoses: Insights from the OCEAN-TAVI Registry.

Mitral stenosis (MS) occasionally coexists with aortic stenosis (AS). Limited data are available regarding the functional class and clinical outcomes of patients who undergo transcatheter aortic valve implantation (TAVI) for combined AS and MS. This study compared the clinical outcomes in patients with and without MS who underwent TAVI for severe AS and assessed the impact of mitral annulus calcification (MAC) severity, transmitral gradient (TMG) and mitral valve area (MVA) on outcomes in patients with combined AS and MS. We investigated patients in the OCEAN-TAVI registry who underwent TAVI. MS was defined as an MVA≤1.5cm2 or TMG≥5mmHg. The composite of all-cause death and admission for heart failure was compared between patients with and without MS. The impact of MAC, TMG and MVA on outcomes was assessed in patients with combined AS and MS. We identified 106 patients with MS (MAC 84%; TMG 6.4±2.6mmHg; MVA 1.10±0.31cm2) and 6570 without MS as controls. The MS group was older (85±5 vs. 84±5years, P=0.033), more of women (85 vs. 67%, P<0.01), and had a higher risk of surgery (the Society of Thoracic Surgeons Mortality Score 8.7±5.1 vs. 7.6±5.9, P=0.047) than the controls. In the MS group, the New York Heart Association Functional Class was 3 or 4 in 56% of the patients at baseline and 6% at 1year after TAVI. Thirty-day mortality (2.8% vs. 1.3%, P=0.18) and early composite outcomes (17% vs. 15%, P=0.56) were comparable between patients with and without MS. During a median follow-up of 2.1years, the presence of MS was associated with a higher incidence of adverse events compared with controls (adjusted hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.34-2.51, P<0.01), even on propensity score matched analysis (adjusted HR 1.91; 95% CI 1.14-3.22, P<0.01). Moderate or severe MAC contributed to increased risk of adverse events in patients with MS (adjusted HR 2.89; 95% CI 1.20-6.99, P=0.018), but TMG and MVA did not. In patients undergoing TAVI for severe AS, those with moderate or severe MS experienced worse outcomes after TAVI compared with those without MS. Patients with combined AS and MS sustained symptom improvement at 1-year post-TAVI. MAC severity was a useful predictor of adverse events compared with MS haemodynamics such as TMG and MVA in patients with combined AS and MS.

Comparable efficacy and safety for bicuspid aortic valve stenosis patients undergoing transcatheter aortic valve replacement with balloon-expandable or self-expanding valves using Wei's sizing method.

The present study aimed to investigate whether proper sizing can improve the procedural and clinical outcomes of transcatheter aortic valve replacement (TAVR) with new-generation self-expanding valves (SEVs) and balloon-expandable valves (BEVs) for treating bicuspid aortic stenosis (BAS). We retrospectively evaluated consecutive patients who underwent TAVR with Sapien 3 valves (Edwards Lifesciences, Irvine, CA) or Evolut R/PRO valves (Medtronic, Minneapolis, MN) for severe BAS from 2017 to 2022. The primary endpoints were device success rate and major adverse cardiac and cerebral events (MACCEs), including mortality, non-fatal myocardial infarction or disabling stroke, transcatheter heart valve failure, or clinically relevant valve thrombosis during follow-up. Our team employed a complementary approach of supra-annular sizing in addition to the conventional annular sizing method (Wei's method) to guide the TAVR procedures. We recruited a total of 75 consecutive patients, of whom 43 (57%) were treated with BEVs from October 2017 to June 2021, and 32 (43%) were treated with SEVs from July 2021 to December 2022. Device success was similar between the BEV and SEV groups (93% vs. 94%; p > 0.99), and no cases of annular rupture occurred in either group. Similar rates of moderate-to-severe paravalvular leak were observed in the BEV and SEV groups (5% vs. 6%, p > 0.99). At a median follow-up of 464 days, the MACCE rates were comparable between the two groups. In multivariate analysis, the presence of previous percutaneous coronary interventions (hazard ratio: 5.43; p = 0.039) and New York Heart Association functional class III/IV heart failure at 30 days of follow-up after TAVR (hazard ratio: 9.90; p = 0.037) were independently associated with long-term MACCEs. Our results demonstrated comparable efficacy and safety for BAS patients undergoing TAVR using either BEVs or SEVs when using Wei's sizing method.

Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: A Randomized Controlled Phase 3 Study.

We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension. In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline. Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P=0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P=0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group. The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points. URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595.

Clinical profile, associated events and safety of vericiguat in a real-world cohort: The VERITA study.

The aim of this study was to determine the clinical profile, associated events and safety of vericiguat in a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF). This study is a prospective and observational cohort study of patients with HFrEF and recent HF worsening episodes requiring intravenous therapy who initiated vericiguat in an HF outpatient clinic. A subanalysis of patients with ≥6months' follow-up was performed separately. Out of 103 patients initially included, 52 had a follow-up of at least 6months (median follow-up of 303days). At baseline, the mean age was 71.3±9.4years, 27.2% were women, the median left ventricular ejection fraction was 34% (28%-39%) and 99% were taking beta-blockers, 96.1% sodium-glucose cotransporter-2 (SGLT2) inhibitors, 95.1% sacubitril-valsartan, 90.3% aldosterone antagonists and 93.2% loop diuretics. During follow-up, New York Heart Association (NYHA) functional class improved (from 67.3% and 32.7% in classes III and II, respectively, to 22.4% and 75.5% at study end; P<0.001), as did the EuroQol-5D (EQ-5D) and visual analogue scale (VAS) scores (from 0.83±0.13 to 0.87±0.12, P=0.032, and from 60 to 79, P=0.005, respectively). Vericiguat was well tolerated (13.5% had symptomatic hypotension, and 11.5% had discontinued treatment), and 78.8% of patients achieved the target dose of 10mg. The number of HF-related hospitalizations/decompensations within the previous 12months was 2.3±1.4 and decreased with vericiguat to 0.79±1.14 (P<0.001). At study end, 7.7% died (50% for HF). In clinical practice, treatment with vericiguat is associated with substantial improvements in functional class and quality of life and a reduction in hospitalizations for HF, with a low risk of adverse effects.

Sweat lactate sensor for detecting anaerobic threshold in heart failure: a prospective clinical trial (LacS-001)

A simple method for determining the anaerobic threshold in patients with heart failure (HF) is needed. This prospective clinical trial (LacS-001) aimed to investigate the safety of a sweat lactate-monitoring sensor and the correlation between lactate threshold in sweat (sLT) and ventilatory threshold (VT). To this end, we recruited 50 patients with HF and New York Heart Association functional classification I–II (mean age: 63.5 years, interquartile range: 58.0–72.0). Incremental exercise tests were conducted while monitoring sweat lactate levels using our sensor. sLT was defined as the first steep increase in lactate levels from baseline. Primary outcome measures were a correlation coefficient of ≥ 0.6 between sLT and VT, similarities as assessed by the Bland–Altman analysis, and standard deviation of the difference within 15 W. A correlation coefficient of 0.651 (95% confidence interval, 0.391–0.815) was achieved in 32/50 cases. The difference between sLT and VT was −4.9 ± 15.0 W. No comparative error was noted in the Bland–Altman plot. No device-related adverse events were reported among the registered patients. Our sweat lactate sensor is safe and accurate for detecting VT in patients with HF in clinical settings, thereby offering valuable additional information for treatment.

A prospective analysis of the correlation between ultrasonic B-lines, cardiac tissue doppler signals and left ventricular end-diastolic pressure in patients with severe aortic stenosis

BackgroundThe development of heart failure is a turning point in the natural course of aortic stenosis (AS). Pulmonary oedema and elevated left ventricular pressure (LVP) are cardinal features of heart failure. Evaluating pulmonary oedema by lung ultrasound involves taking the upper hand with a bedside noninvasive tool that may reflect LVP.AimWe sought to assess the correlation between sonographic pulmonary congestion, invasive LV pre-A pressure, and echocardiographic LV end-diastolic pressure (LVEDP) in symptomatic AS patients receiving transcatheter aortic valve replacement.MethodsForty-eight consecutive patients with severe AS and planned transcatheter aortic valve implantation (TAVI) were enrolled. LVEDP was estimated to be normal or elevated using the ASE/EACVI algorithm and transmitral Doppler indices, the E/A ratio, the E/e′, and the left atrial volume index. Invasive LV pre-A pressure was used as a reference, with > 12 mm Hg defined as elevated.ResultsForty-eight patients (25 women (52%), mean age 75 years, standard deviation (SD) ± 7.7 years) were enrolled in the study. We detected severe B-lines (≥ 30) in 13 (27%) patients and moderate B-lines (15–30) in 33 (68.6%) patients. The number of B-lines increased significantly with the severity of New York Heart Association (NYHA) functional classes (Fig. 1). The B-line count was 14 ± 13 in NYHA class I patients, 20 ± 20 in class II patients, and 44 ± 35 in class III patients (p < 0.05, rho = 0.384). The number of B-lines was correlated with the E/E’ ratio (R = 0.664, p < 0.0001) and the proBNP level (R = 0. 882, p < 0.008). We found no significant correlation with the LVEDP or LVEF. The LVEDP correlated well with the E/E’ ratio (R = 0.491, p < 0.001) but not at all with E/A, DT, or LAVI. All patients had an elevated LVEDP > 12, with a mean pressure of 26 mmHg, a minimum of 13 mmHg, and a maximum of 45 mmHg, with an SD of 7.85.ConclusionAssessing lung ultrasonic B-lines is a straightforward and practical approach to identifying pulmonary oedema in AS patients. The number of B-lines correlated with the E/E’ ratio and the functional status of patients but did not correlate with invasive LVEDP or LVEF. All patients had elevated LVEDP that correlated with E/E’.

Midterm Outcomes of Percutaneous Intramyocardial Septal Radiofrequency Ablation for Hypertrophic Cardiomyopathy: A Single-Center, Observational Study.

Percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported to be safe and effective at midterm follow-up to treat drug-refractory hypertrophic obstructive cardiomyopathy in a single center. However, data from other centers are lacking. This retrospective cohort study aimed to investigate the efficacy and safety of PIMSRA from another independent center. PIMSRA was performed in 76 patients with hypertrophic obstructive cardiomyopathy in our center from April 2020 to June 2023. The primary outcome was the reduction of left ventricular outflow tract gradient after 6 months or more post-PIMSRA. Secondary outcomes were periprocedural major adverse clinical events. Sixty-one patients returned to the hospital for follow-up 6 to 30 (median, 14) months after the procedure. At the last follow-up of the 61 patients, the maximum septal thickness decreased from a median of 23.6 (interquartile range, 20.5-26.4) to 19.1 (interquartile range, 16.0-22.1) mm (P<0.001) and the left ventricular outflow tract peak gradient at rest decreased from a median of 70.0 (interquartile range, 29.1-107.5) to 20.0 (interquartile range, 10.8-48.8) mm Hg (P<0.001). The percentage of patients with symptoms of New York Heart Association functional class III/IV decreased from 51% to 0%. Of all 76 patients, there was no in-hospital or 30-day death, no right or left branch block, and no permanent pacemaker implantation. Six (8%) patients had pericardial effusion, with 1 experiencing cardiac tamponade and ventricular fibrillation, and 1 (1%) patient developed septal branch aneurysm that was treated with coil occlusion. PIMSRA allows for the reduction in the left ventricular outflow tract gradient and enhances symptomatic improvement, with a limited incidence of adverse events and complications among patients with hypertrophic obstructive cardiomyopathy.

Symptom perception, health-related quality of life and predicted survival in heart failure patients

BackgroundHeart failure (HF) is a chronic and progressive condition that significantly impacts patients’ lives, necessitating a comprehensive understanding of the factors influencing their health outcomes. Among these factors, symptom perception, health-related quality of life (HRQoL), and predicted survival are paramount. This study aimed to assess symptom perception, HRQoL and predictive survival among HF patients. MethodsA baseline analysis was carried out in a randomized controlled trial involving patients with HF. Heart Failure Somatic Perception Scale to assess symptom perception, Kansas City Cardiomyopathy Questionnaire-12 to assess HRQoL and Seattle Heart Failure Model to assess predicted survival were used. ResultsAmong the 160 patients, 62.5 % were between 36 and 59 years of age and were married (88 %). Hypertension and diabetes were reported in 104 and 94 participants respectively, and among them, 65 participants had both hypertension and diabetes. The mean left ventricular ejection fraction was 33(%), and 56.5 % of the participants were in New York Heart Association functional class III and IV. The average symptom perception score was 27.4 ± 18.3, while the mean HRQoL score was 37.2 ± 14.2. The predicted one-year survival score was 80 ± 11.5, and the predicted five-year survival score was 38.5 ± 21.3. HRQoL showed a significant negative correlation with symptom perception (r = −0.75; p = 0.001) and a positive correlation with one-year survival (r = 0.53; p = 0.001), and five-year survival (r = 0.56; p = 0.001). ConclusionPatients with HF experience persistent symptoms and poor HRQoL. Symptom severity decreases HRQoL. Understanding HRQoL and symptom perception is crucial for developing effective self-care interventions, which are vital for improving patient outcomes and managing HF effectively.

Efficacy and safety of macitentan in Fontan-palliated patients: 52-week randomized, placebo-controlled RUBATO Phase 3 trial and open-label extension

ObjectivesThe efficacy and safety of macitentan, an endothelin receptor antagonist, were assessed in a 52-week, prospective, multicenter, double-blind, randomized, placebo-controlled, parallel-group study assessing the efficacy and safety of macitentan in Fontan-palliated adult and adolescent patients (RUBATO-DB) and an open-label extension trial (RUBATO-OL). MethodsPatients aged 12 years and older with New York Heart Association functional class II or III underwent total cavopulmonary connection more than 1 year before screening and showed no signs of Fontan failure/clinical deterioration. In RUBATO-DB, the primary efficacy end point was change in peak oxygen consumption from baseline to week 16; secondary end points were change from baseline over 52 weeks in peak oxygen consumption and change in mean count/minute of daily physical activity via accelerometer from baseline to week 16. Safety was assessed throughout both studies. ResultsIn RUBATO-DB, 137 patients were randomized to macitentan 10 mg (n = 68) or placebo (n = 69); 92.7% completed 52-week double-blind treatment. At week 16, mean ± SD change in peak oxygen consumption was −0.16 ± 2.86 versus −0.67 ± 2.66 mL/kg/minute with macitentan versus placebo (median unbiased treatment difference estimate, 0.62 mL/kg/minute [99% repeated CI, −0.62 to 1.85]; P = .19). No treatment effect was observed in either of the secondary end points. During RUBATO-DB, most common adverse events with macitentan were headache, nasopharyngitis, and pyrexia. Across RUBATO-DB and RUBATO-OL, most common adverse events were COVID-19, headache, and fatigue. RUBATO-OL was prematurely discontinued because RUBATO-DB did not meet its primary or secondary end point. ConclusionsThe primary end point of RUBATO-DB was not met; macitentan did not improve exercise capacity versus placebo in patients with Fontan palliation. Macitentan was generally well tolerated over long-term treatment.

Sex-related differences among patients undergoing surgical aortic valve replacement-a propensity score matched study.

We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM). Data from 2 prospective registries, the INSPIRIS RESILIA Durability Registry (INDURE) and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. The PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics. Females had a lower body mass index (median 27.1 vs 28.0 kg/m2; P = 0.008), fewer bicuspid valves (52% vs 59%; P = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; P < 0.001) and Society of Thoracic Surgeons score (mean 1.6 vs 0.9%; P < 0.001), were more often in New York Heart Association functional class III/IV (47% vs 30%; P < 0.001) and angina Canadian Cardiovascular Society III/IV (8.2% vs 4.4%; P < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; P = 0.028) compared to males. These differences vanished after PSM, except for the EuroSCORE II and Society of Thoracic Surgeons scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, P < 0.001). There were no differences in the length of hospital stay (median 8 days) or intensive care unit stay (median 24 vs 25 hours) between the 2 sexes. At 2 years, post-SAVR outcomes were comparable between males and females, even after PSM. Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females.

Early left atrial reverse remodelling in patients with hypertrophic obstructive cardiomyopathy receiving transapical beating-heart septal myectomy.

This study aims to investigate the short-term effects of transapical beating-heart septal myectomy (TA-BSM) on left atrial (LA) anatomy and function and its association with clinical indicators in patients with hypertrophic obstructive cardiomyopathy (HOCM). A total of 105 HOCM patients who received TA-BSM were included. Clinical and comprehensive echocardiographic data were obtained before surgery, at discharge, and 3 months after myectomy. LA reverse remodelling was defined as LA maximum volume index (LAVI) ≤34 ml/m2 and a change of ≥10%. At 3 months after TA-BSM, New York Heart Association (NYHA) functional class and 6-min walking test were significantly improved, N-terminal pro-B-type natriuretic peptide (NT-proBNP) decreased, left ventricular outflow tract (LVOT) peak gradient and mitral regurgitation were significantly reduced. LAVI decreased in 76%, with a median change of 20%, and the criteria for LA reverse remodelling were met in 48%. LA strain parameters were improved at 3 months after TA-BSM. Moreover, left ventricular (LV) diastolic function was significantly improved, but LV global longitudinal strain was not significantly changed at 3 months after operation. Improvement in LVOT peak gradient, LAVI, LA reservoir strain (LASr) and conduit strain (LAScd) were associated with reduction in NT-proBNP. Along with effectively relieving the obstruction of the LVOT and mitral regurgitation, TA-BSM could significantly improve LA size and function during the short-term follow-up for HOCM patients. The indicators of LA reverse remodelling were associated with reduction in a biomarker of myocardial wall stress, indicating the early recovery of LV relaxation and clinical status for patients.

The Predictive Role of Cardiac Troponin Elevation Ratio Combined With Heart Function Index Model in the Prognosis of Non-ST-Segment Elevation Myocardial Infarction Patients.

Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of coronary artery disease, and its prognosis is influenced by multiple factors. This study aimed to analyze the predictive role of the combined application of cardiac troponin and cardiac function indices in NSTEMI patients' prognosis. NSTEMI patients were screened and included in the study. Cardiac troponin elevation ratio (cardiac troponin I (cTnI)/upper limit of normal (ULN)) was measured upon admission, and cardiac function was assessed. General clinical data, laboratory parameters, Grace score, New York Heart Association (NYHA) functional class, complications, and mortality data were collected. The correlation between mortality in NSTEMI patients and clinical parameters was analyzed, and a nomogram prediction model for NSTEMI patient mortality was established. A total of 252 NSTEMI patients were included. Female gender, elevated high-sensitivity C-reactive protein (H-CRP), left ventricular ejection fraction (LVEF) < 50%, NYHA class III and IV, and cTnI/ULN elevation by 36.25-fold were significantly independently associated with mortality outcomes. Multifactorial logistic analysis indicated that these indices remained associated with mortality. A nomogram model predicting NSTEMI patient mortality was constructed using these indices, with an area under the curve (AUC) of 0.911, sensitivity of 97.5%, and specificity of 72.8%. This predictive model outperformed the Grace score (AUC = 0.840). In NSTEMI patients, a 36.25-fold increase in cTnI/ULN, coupled with NYHA class III and IV, independently predicted prognosis. We developed a nomogram model integrating cTnI/ULN and cardiac function indices, aiding clinicians in assessing risk and implementing early interventions for improved outcomes.

Cardiac sympathetic activity and lethal arrhythmic events: insight into bell-shaped relationship between 123I-meta-iodobenzylguanidine activity and event rates

Background123I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between 123I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts.ResultsWe calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar 123I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I.ConclusionsThe relationship between cardiac 123I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs.

IL-17 is associated with disease severity and targetable inflammatory processes in heart failure.

Heart failure (HF) is recognized as an inflammatory disease in which cytokines play an important role. In animal HF models, interleukin-17A (IL-17) has been linked to deterioration of cardiac function and fibrosis, whereas knock-out of IL-17 showed beneficial cardiac effects. However, there is limited evidence of IL-17 involvement in patients with HF. This study aims to investigate the clinical characteristics, outcomes, and pathophysiological processes associated with circulating IL-17 concentrations in patients with HF. IL-17 was measured by ELISA in 2082 patients diagnosed with HF along with 363 circulating proteins using proximity extension assay technology for differential expression and pathway analysis. Data were validated in an independent cohort of 1737 patients with HF. Patients with elevated IL-17 concentrations had more severe HF, as reflected by more frequent current or previous hospitalizations for HF, higher New York Heart Association functional class (NYHA) and higher levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). High IL-17 concentrations were independently associated with an increased risk of hospitalization for HF and mortality. In both cohorts, the most strongly up-regulated proteins in patients with high IL-17 were fibroblast growth factor 21 (FGF-21), interleukin-6 (IL-6), C-X-C motif chemokine ligand 13 (CXCL13), tumour necrosis factor receptor superfamily member 6B (TNFRSF6B) and interleukin-1 receptor antagonist (IL-1RA). Pathway over-representation analysis showed increased activity of pathways related to lymphocyte-mediated immunity, leukocyte activation and regulation of the immune response. In patients with HF, elevated IL-17 concentrations indicate more severe HF and increased activity of inflammatory processes known to be involved in the pathophysiology of HF. IL-17 might hold potential for identifying and targeting inflammation in HF.

Effects of a video-viewing intervention with positive word stimulation on the depressive symptoms of older patients with cardiac disease and subthreshold depression: a pilot randomized controlled trial protocol

BackgroundIntervention for older patients with cardiac disease and subthreshold depression (StD) may be an effective strategy to prevent the development of major depressive disorder. The subliminal priming with supraliminal reward stimulation (SPSRS) website developed by us is an advanced intervention that can improve depressive symptoms in individuals with StD by presenting positive word stimuli in videos. However, its efficacy for treating depressive symptoms in older patients with cardiac disease and StD has not been investigated. Here, we present a pilot randomized controlled trial protocol to investigate the preliminary efficacy of an intervention for older patients with cardiac disease with StD.MethodsThe study was designed as a single-center, open-label, pilot, randomized, parallel-group trial. The participants will include 30 older patients with cardiac disease and StD who are hospitalized in acute wards. The Experimental group received the SPSRS intervention (video viewing with positive word stimuli; n = 15) and the Control group will receive the YouTube intervention (video viewing without positive word stimuli; n = 15). In both groups, the intervention will be administered for 10 min per day, five times per week for 1 week. The primary outcome will be the change in the scores on the Japanese version of the Beck Depression Inventory-II at 1 week after the baseline assessment. The secondary outcomes will be the changes in the Specific Activity Scale, New York Heart Association functional classification, as well as grip strength at 1 week after the baseline assessment.DiscussionThis pilot randomized controlled trial will be the first to evaluate the SPSRS intervention for depressive symptoms in older patients with cardiac disease and StD who are admitted to acute wards. The results will provide tentative indications regarding the impact of the intervention on depressive symptoms among older patients with cardiac disease and StD who are admitted to acute wards, and will contribute to the planning of a full-scale study.Trial registrationUMIN, UMIN000052155. Registered September 8, 2023, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000059526. This study was registered with the University Hospital Medical Information Network (UMIN) (UMIN000052155) in Japan.