Class Of Functions Research Articles

Clinical experience of transapical off-pump mitral valve repair with NeoChord implantation

Abstract Introduction Transapical off-pump mitral valve repair with NeoChord implantation is a novel minimally invasive surgical procedure to treat degenerative mitral valve regurgitation (MR). has gained widespread application for patients presenting with severe mitral regurgitation caused by leaflet prolapse or flail. However, there is a scarcity of data concerning the clinical experience with this device. Purpose This prospective study aims to assess 1-year clinical results of the Neochord Procedure in a consecutive cohort of patients. Methods Between March 2018 and December 2023, 38 patients with severe symptomatic degenerative MR were enrolled in the study. All patients presented with severe MR due to flail of 1 or both leaflets and they all completed postoperative echocardiographic assessment up to 1 year. We identified the primary endpoint as composed of procedural success , freedom from mortality, reintervention, recurrence of severe MR , and decrease of at least 1 New York Heart Association (NYHA) functional class at 1-year follow- up. Results Median age was 59 years (21% female). Acute procedure success (defined as successful placement of at least 3 neochords with reduction of residual MR to less than 2+) was achieved in all patients. The intraoperative and in-hospital mortality rate was 0%. At 1-year overall survival was 97% with the one reported death attributed to other causes. Following the procedure, almost all patients (94%) reported a decrease in NYHA functional class at 1-year follow-up along with a reduction in diuretic usage (18% of patients presented with NYHA Class I, while 76% of them presented with NYHA Class II). Moreover, 18% of patients exhibited mild MR, while 63% presented with moderate MR, and 10% had no detectable mitral leakage. Conclusion Transapical off-pump mitral valve repair with NeoChord implantation seem to be a safe procedure for patients. However, further investigations with a larger sample size and longer follow-up periods are warranted.

Utilization and safety of digoxin in patients with chronic heart failure and atrial fibrillation with rapid ventricular rate

Abstract Background Digoxin can reduce symptoms and the risk of tachycardia-induced cardiomyopathy in patients with heart failure (HF) and concomitant atrial fibrillation (AF) with rapid ventricular rate. The effect of digoxin in HF and AF has not been tested in randomized controlled trials, and observational data have shown conflicting results linking digoxin to increased mortality in AF, though the nature of observational data makes it prone to bias and results difficult to interpret. Purpose To assess the utilization of digoxin in patients with HF and AF, and its association with New York Heart Association (NYHA) functional class and survival. Methods We used data from the Norwegian HF registry that collected data from all Norwegian HF clinics between 2013-2022. Data was collected from the first and last visit during optimizization of HF medical therapy. Associations with mortality status from Statistics Norway were assessed in unadjusted time-to-event analysis, and after adjustment for age, sex, body mass index, estimated glomerular filtration rate, aldosterone antagonists, renin-angiotensin-aldosterone system inhibitors, and beta blockers. Results The study included 4,877 HF patients, consisting of 4,067 (83.4%) with ejection fraction (EF) ≤40% and 810 (16.6%) with EF >40%.. The mean age was 67.7±12.0 years; 25.1% were women, and 27.3% had NYHA functional class III/IV. At the first visit, 1,339 (27.5%) patients had AF and 829 (61.9%) of these were treated with ≥50% of the beta-blocker target dose. AF with a ventricular rate ≥100 bpm was present in 277 (20.1%) patients, and 188 (67.9%) of these were on ≥50% beta-blocker target dose. Similarly, 262 (19.6%) of all AF patients and 44 (15.9%) of those with a ventricular rate ≥100 bpm were treated with digoxin. After optimization of HF medical therapy (median duration 140 [Q1–Q3 82–237] days), 1,039 (21.3%) patients had AF. Among these, 227 (21.9%) were treated with digoxin, including 9 (18.0%) patients with ventricular rate ≥100 bpm. Patients with AF who were started on digoxin experienced during the optimization period a larger decline in heart rate compared to those who were not (mean change -23.7±17.2 vs. -5.7±16.7 bpm, p=0.001), and more often an improvement in NYHA functional class (45% vs 30%, p=0.018). During median 779 [Q1–Q3 386–1,334)] days of follow-up after the last optimization visit, digoxin use was associated with lower mortality in HF patients with AF in unadjusted analysis (HR 0.67 [0.46–0.97]). After adjustment for baseline characteristics and other HF medical therapies, the association with mortality was attenuated and no longer significant (HR 0.96 [0.65–1.42]). Conclusion Digoxin was infrequently used in patients with HF and AF with rapid ventricular rate but was associated with a greater decrease in heart rate and improvement in NYHA functional class. The use of digoxin appears safe and was not associated with increased mortality.

Continuous heart monitoring to evaluate treatment effects in pulmonary hypertension

Abstract Background The treatment of pulmonary hypertension (PH) has improved rapidly in recent years, and there is increasing evidence to support the role of early intervention. However, studies demonstrate that timely intervention is often still lagging which affects clinical outcomes in patients with PH. Purpose To assess treatment effects after escalation of specific PH treatments using continuous heart monitoring via a Reveal LINQ loop recorder. Methods The patients change in heart rate variability (HRV), heart rate (HR), and physical activity were assessed before and after treatment escalation. Treatment escalation was defined as an additional PAH drug, pulmonary endarterectomy (PEA), percutaneous balloon angioplasty (PBA), or bilateral lung transplantation (BLTX). Results In this prospective study, 41 patients (27 with PAH and 14 with chronic thromboembolic pulmonary hypertension) were enrolled. Among them, 15 patients (36.6%) underwent PH treatment escalation. Prior to escalation, patients were monitored for a median of 100 (range: 68–100) days and after therapy escalation for a median duration of 165 (range: 89–308) days. In the escalation group, a significant increase in HRV (Figure), physical activity indexed by daytime HR was observed, while a significant decrease was seen in nighttime HR assessed at baseline and after treatment escalation. These changes were found both in the PAH and CTEPH group. In parallel a significant improvement in WHO functional class, 6-minute walking distance, and N-terminal pro-b-type natriuretic peptide (NT-proBNP) was observed. Conclusions This is the first study to demonstrate a direct association between specific PH therapies and changes in HRV, HR nighttime and physical activity in patients with PAH and CTEPH. Continuous monitoring allows for an early intervention with supplementary treatment for PH. This is especially relevant considering the increasing availability of wearables that allow for a convenient measurement of relevant prognostic parameters in PH.

Identification of Aberrant Expression of Gemcitabine-Targeting Proteins in Drug-Resistant Cells Using an Activity-Based Gemcitabine Probe.

Gemcitabine-based monotherapy or combination therapy has become the standard treatment for locally advanced and metastatic pancreatic cancer. However, the emergence of resistance within weeks of treatment severely compromises therapeutic efficacy. The intricate biological process of gemcitabine resistance in pancreatic cancer presents a complex challenge, as the underlying mechanisms remain unclear. Identifying the target protein of gemcitabine is crucial for studying its drug-resistance mechanism. An activity-based probe is a powerful tool for studying drug target proteins, but the current lack of activity-based gemcitabine probes with robust biological activity hinders research on gemcitabine. In this study, we developed three active probes based on gemcitabine, among which Gem-3 demonstrated excellent stability and labeling efficacy. We utilized Gem-3 in conjunction with chemical proteomics to identify intracellular target proteins. We identified 79 proteins that interact with gemcitabine, most of which were previously unknown and represented various functional classes. Additionally, we validated the increased expression of IFIT3 and MARCKS in drug-resistant cells, along with the activation of the NF-κB signaling pathway. These findings substantially contribute to our comprehension of gemcitabine's target proteins and further our understanding of the mechanisms driving gemcitabine resistance in pancreatic cancer cells.

Functional status is associated with mean right atrial pressure derived from cardiac MRI

Abstract Background Right atrial pressure (RAP) is a key metric in haemodynamic assessment. Elevated RAP is associated with poor prognosis in heart failure and pulmonary hypertension and physiologically with fluid overload. RAP can be measured invasively or non-invasively, but Cardiac MRI (CMR) currently cannot estimate RAP. Purpose To develop a model to estimate RAP from CMR from paired right heart catheter (RHC) and CMR assessments. Assess correlation to WHO functional status prior to prospective clinical validation studies. Methods Patients were recruited to a registry of those referred for assessment of dyspnoea between 2012 and 2020. Inclusion criteria were age >18 years, signs and symptoms of heart failure and adequate CMR image quality. Patients diagnosed with pulmonary arterial hypertension were excluded. RHC and CMR were performed on the same day. CMR 2- and 4- chamber cines were used to measure chamber dimensions, strain, ejection fraction and stroke volume with operator reviewed AI contours in MASS research software. Pearson’s product-moment correlation coefficient (r ) was used to assess relationships between CMR metrics and invasive mRAP. Variables were then included in stepwise multiple linear regression models to predict mRAP. These were compared with receiver-operator curve analysis and DeLong’s test. Kruskal-Wallis test compared median mRAP between WHO functional class groups. Results The cohort of 672 patients was divided based upon invasive mRAP ≤ 8mmHg (44%) and mRAP > 8mmHg (56%). Higher mRAP was associated with increased age, male sex and a higher diastolic blood pressure but there was no difference in rates of heart failure types although the majority had preserved ejection fraction (51% vs 52%) with few having reduced ejection fraction (4.1% vs 8%). Right atrial (RA) dimensions, strain and ejection fraction had the strongest correlation with mRAP with moderate correlation to right ventricular (RV) measurements. Multivariable models contained simple RA dimensions (model 1), RA dimensions and strain (model 2), RA and RV dimensions (model 3) and RA end systolic volume corrected for body mass index and sex (model 4). All models had similar predictive capability (Figure 1 Panel A). RA end systolic volume was isolated in model 1 as the only variable required for mRAP prediction (coefficient = 0.06, p < 0.001). Using a threshold of mRAP >8mmHg ROC analysis demonstrated an area under the curve of 0.78 (95% Confidence interval 0.75 to 0.81) (Figure 1 Panel B). Worse WHO functional Class at time of assessment was significantly associated with increased CMR derived mRAP (P<0.001) (Figure 2). Conclusions mRAP can be estimated with moderate confidence from CMR RA end systolic volume. Limited available clinical data suggest functional status may be predicted by CMR derived mRAP. Further studies on wider populations are required to validate this model externally, refine it and determine its prognostic clinical significance.

Efficacy of specific drug class therapy in pulmonary arterial hypertension associated with HIV, portal hypertension or both: a single Center experience

Abstract Background Pulmonary arterial hypertension (PAH) is a rare complication of both HIV infection (HIV-PAH) and portal hypertension (Po-PAH); it can occur in patients with both diseases (HIV/Po-PAH). The use of the PAH-specific drug classes (prostanoids, endothelin-1 receptor antagonists [ERA] and phosphodiesterase-5 inhibitors [PDE5-i]) is largely justified by retrospective and observational case reports since, to date, there are no randomized clinical trials except for the PORTICO trial which demonstrated the efficacy of macitentan in Po-PAH. Purpose the aim of the study was to evaluate the efficacy of PAH-specific drugs, both monotherapy and dual oral upfront therapy (ERA + PDE5i started within 1 month apart), in patients with Po-PAH, HIV/Po-PAH and HIV-PAH. Methods Between 1998 and 2023 we enrolled patients with Po-PAH, HIV-PAH and HIV/Po-PAH referred to our Center and undergoing monotherapy with prostanoid, ERA and PDE5-I or dual upfront oral therapy. The efficacy of the drugs was assessed by comparing clinical parameters (NYHA functional class), exercise capacity (six-minute walking test) and hemodynamic parameters at baseline and after a treatment period of 3-6 months. The data are expressed as mean and standard deviation and were compared with Student's t-test for paired data. Results 128 patients were enrolled (83 Po-PAH, 23 HIV/Po-PAH and 22 HIV-PAH). 20 were treated with ERA monotherapy, 90 with PDE5-I, 13 with prostanoids and 5 treated with dual oral upfront therapy. Conclusions Prostanoids, ERAs and PDE5-Is, both in monotherapy and as dual upfront oral therapy, are associated with a significant improvement in functional class, exercise capacity and hemodynamic parameters. The effect of such drugs is similar to patients suffering from other forms of PAH.

Sotatercept: The First FDA-Approved Activin A Receptor IIA Inhibitor Used in the Management of Pulmonary Arterial Hypertension.

This report illustrates the Food and Drug Administration (FDA) approval of first-in-its-class activin A receptor IIA inhibitor, sotatercept (Winrevair™), for the treatment of pulmonary arterial hypertension (PAH). Sotatercept is used to increase exercise capacity, improve WHO functional class, and decrease the risk of clinical worsening events in adults with PAH. One phase 2 trial, one phase 3 trial, and an ongoing open-label extension study is described in detail within the current text. Sotatercept significantly improved the 6-min walk distance in patients with PAH after 24 weeks with a mean change increase of 40.1 meters in the experimental group versus 1.4 meters decrease in the placebo group. Epistaxis, telangiectasia, increased hemoglobin, hematocrit, red blood cell levels, and dizziness were adverse events more frequently observed in the sotatercept group than in the placebo group. Sotatercept has shown significant benefits in the reduction of pulmonary vascular resistance and N-terminal pro b-type natriuretic peptide in patients with PAH. However, more studies are needed to evaluate the reduction in mortality. Limitations in practice include high cost and unknown long-term effects.

Residual tricuspid regurgitation after transcatheter tricuspid valve edge-to-edge repair: the EuroTR Registry

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

The trajectory of self-care over a 12-month period in patients with heart failure, comparing those with consistently good and poor self-care

Abstract Background Self-care behaviour plays a pivotal role in enhancing the quality of life for patients with heart failure (HF) and reducing mortality and morbidity rates, but many patients struggle with suboptimal self-care behaviours. It is crucial to understand the factors influencing long-term self-care management. Purpose To assess the trajectory of self-care over a 12-month period and assess differences between patients who have constantly good self-care over a 12-month period compared to constantly poor self-care. Method This study use data from a randomised controlled intervention study, called the HF-Wii study. We included patients who had complete data on self-care during on baseline, 3, 6 and 12 months. Self-care was measured with the European Heart Failure Self-care Behaviour scale (EHFSBs). A threshold score of equal or higher than 70 was used to define self-care behaviour as good and a score lower than 70 as poor self-care. Based on literature, the following characteristics (collected from questionnaires and medical records at baseline) were considered in the analysis: age, sex, marital status, education, history of myocardial infarction, duration of HF, New York Heart Association (NYHA) functional class, LVEF, comorbidity. Other factors assessed were Health-related Quality of Life (HrQoL, Minnesota living with HF questionnaire), depressive symptoms (Hospital Anxiety and Depression scale), cognition (Montreal Cognitive Assessment), sleep (Minimal Insomnia Symptom Scale) and level of HF knowledge (Dutch HF knowledge scale). Logistic regression was performed with backwards elimination of the factors considered associated with the differences between patients who have constantly good self-care at baseline, 3, 6 and 12 months compared to constantly poor self-care. Results In total, 407 patients were included in this study. At baseline, the mean self-care was 65±21, with 41% of the patients (n=245) performing good self-care. In total, 126 patients had a constantly good self-care over 12 month (31%), 120 patients had a constantly bad self-care over 12 months (30%) and 161 (39%) fluctuated in their self-care (Figure). In the multivariate analysis, patients that had continuously good self-care over 12-months were of older age (68±10 vs. 64±12, odds ratio (OR) 1.061, P-value<0.001), had higher HF knowledge (score 13±2 vs. 12±2, OR 1.439, P-value<0.001) and had higher HrQoL (score 28±20 vs 36±22, OR 0.984, P-value=0.022). compared to patients with consistently poor self-care. The variance was explained by 20%. Conclusion Younger patients with HF tend to struggle with consistent self-care over a year, underscoring the necessity for tailored interventions for this group. Conversely, patients with greater HF knowledge and higher HrQoL maintained good self-care habits.

Metoprolol therapy in patients with Eisenmenger syndrome (MINES) study. A single-centre, double-blinded, randomised, placebo-controlled trial

Abstract Background Prevalence of Eisenmenger syndrome is still common in developing countries where early neonatal screening and referral for surgery is seldom possible. Limited number of drugs are available for treatment of this condition. Beta-blockers may improve functional status in these patients. Observational study has shown beta blockers to be safe and effective in improving effort intolerance in patients with Eisenmenger syndrome. Purpose To study the safety and efficacy of metoprolol succinate therapy in patients with Eisenmenger syndrome. Methods In this double-blind, placebo-controlled study, we randomly assigned 60 patients with Eisenmenger syndrome to receive placebo or to receive 25 mg of metoprolol succinate once daily for 2 weeks followed by 25 mg twice daily for 14 weeks (total of 16 weeks). The primary outcome was mean difference in 6-minute walk test (6MWT) distance. Secondary outcomes were clinical composite outcome (all-cause death, heart failure hospitalization, worsening of heart failure, change in WHO functional class, and new onset syncope), change in resting saturation, Tricuspid Annular Plane Systolic Excursion (TAPSE) and NT Pro BNP level at 16 weeks. Results At 16 weeks, the mean difference in 6MWT distance between treatment group and placebo group as per protocol analysis was 6 meters (95% confidence interval, - 7.43 to 19.49; P 0.37), and the mean difference in 6MWT distance as per intention to treat analysis was -1.1 meters (95% confidence interval, - 16.97 to 14.77; P 0.89). Clinical composite outcome occurred more in the treatment group 5(17%) as compared to the placebo group 1(3%) (P 0.197) though it did not reach statistical significance. This was primarily driven by worsening of heart failure in the treatment group. Compared to baseline metoprolol group had 37% increase in NT pro BNP level while placebo group had 13% (-313.69, 88.80) reduction in NT Pro BNP level. There was no difference in TAPSE 0.05 (95% confidence interval -0.62 to 0.72; P 0.88) or resting saturation -0.06 (95% confidence interval -0.88 to 0.75; P 0.87) between the two groups at 16 weeks Conclusion Metoprolol succinate therapy did not improve 6-minute walk distance at 16 weeks among patients with Eisenmenger syndrome compared to placebo. Metoprolol succinate therapy was associated with increased clinical composite outcomes, primarily driven by worsening of heart failure.Graphic Abstract of MINES study

Idiopathic pulmonary arterial hypertension, associated with connective tissue disease and comorbidities: prognostic differences? Results the Spanish Registry of pulmonary hypertension (REHAP Registry)

Abstract Introduction Idiopathic pulmonary arterial hypertension (iPAH) and associated with connective tissue disease (PAH-SSc) are the most frequent groups of pulmonary arterial hypertension (PAH) but their long-term survival is usually unequal. Comorbidities, increasing in frequency in these patients, show prognostic influences but it is not known whether these differ in both groups of patients. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classifies into iPAH and PAH-SSc. We analyzed baseline characteristics and the distribution of the different comorbidities in the two groups. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test were done according to PAH etiology and comorbidities and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results Seven hundred and fifty-seven patients were selected for this study. The characteristics of the patients are shown in Table 1. Patients with PAH-SSc compared to iPAH were older (62 vs 56 years), more female (81.8% vs 62.4%), had a more favorable hemodynamic profile, TAPSE/sPAP ratio and lower NT-proBNP levels. No differences were found in functional class or 6MWT. We found a higher proportion of patients in a low and intermediate risk profile, according to ESC, in patients with PAH-SSC as opposed to PAHi (46.8/50.9% vs. 29.3/64.5%; p<0.001). Regarding comorbidities, history of smoking (27.1 vs 54%; p<0-001), obesity (17.1 vs 20.7%; p<0.001) and diabetes (9.4 vs 22.1%; p<0.001) are less frequent in PAH-SSc than in iPAH. There are no differences in the rest of the comorbidities studied in the two groups of patients. In a survival analysis, we found no differences between patients with iPAH and PAH-SSc at 7-year follow-up. Patients with ≥ 3 comorbidities had statistically significantly higher mortality (p<0.001) compared to those with 0 or 1-2 comorbidities in both etiologies. There were no differences between 0 and 1-2 comorbidities. (Figure 1). Variables associated with mortality were male sex (HR 1.9, 95% CI 1,28 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06), the intermediate risk profile (HR 2.64, 95% CI 1.62 – 4.32) and high risk profile (HR 9.97, 95% CI 4.36 – 18.47), but not etiology. The presence of connective tissue diseases, were not associated with increased mortality. Conclusions Patients with PAH-SSc show lower comorbidities, better hemodynamic profile, RV-PA coupling and risk profile than those with iPAH. Comorbidity has a great relevance in survival but without differences according to etiology. The presence of male sex, age, the intermediate and high risk profile is associated with worse survival, but not the connective tissue diseases.

The prognostic impact of intra-procedural mitral valve gradient following transcatheter edge-to-edge repair for primary mitral regurgitation

Abstract Background/Introduction The impact of intra-procedural mitral valve gradient following transcatheter edge-to-edge repair (TEER) in primary mitral regurgitation (MR) is a matter of controversial debates. Purpose The aim of this study was to investigate the prognostic impact of intra-procedural mean mitral valve gradient (MPG) in patients with primary MR undergoing TEER. Methods The PRIME-MR registry included consecutive patients with primary MR undergoing TEER from 2008-2022 at 27 international sites. Clinical outcomes were assessed according to intra-procedural mean MPG measured at the end of the procedure by transesophageal echocardiography. The evolution of mean MPG from intra-procedural to discharge and follow-up was documented. Baseline characteristics and clinical outcomes of patients were investigated according to intra-procedural mean MPG using a cut-off of 5mmHg (low MPG: ≤5mmHg, high MPG: >5mmHg). The prognostic impact of intra-procedural mean MPG was evaluated in multivariable Cox regression analysis. The primary endpoint was 2-year all-cause mortality or heart failure (HF) hospitalization. Results Intra-procedural MPG was available in 1,516 patients (median age 82 years [IQR 76.0, 86.0], 55.1% male). Patients with high intra-procedural MPG presented with less atrial fibrillation and less severe MR but were more symptomatic at baseline than patients with low MPG. Moreover, patients with high intra-procedural MPG had higher baseline MPG and smaller LV dimensions (LVEDV and LVESV). The rate of patients with mean MPG >5mmHg increased from intra-procedural (18.3%) to discharge (31.3%), while remaining stable thereafter (1-year follow-up: 30.9%; last follow-up: 29.6%). At 1-year follow-up the rate of patients presenting with New York Heart Association (NYHA) functional class I or II did not differ between patients with low (82.3%) and high MPG (83.6%, p=0.93). Kaplan-Meier analysis according to mean MPG showed no difference between patients with low and high MPG for the primary endpoint (32.4% vs. 42.1%, p=0.12), as well as for the single endpoints of all-cause mortality (22.3% vs. 27.7%, p=0.47) and HF hospitalization (17.6% vs. 27.5%, p=0.087) through 2 years (Figure 1). Unadjusted spline analyses were provided to depict the prognostic impact of continuous intra-procedural MPG (Figure 2). Following multivariable Cox regression neither MPG >5mmHg (HR 0.91, 95%-CI 0.56-1.49, p=0.72), nor continuous MPG (HR 1.05, 95% CI 0.96-1.15, p=0.28) were independently associated with adverse clinical outcomes. Conclusions Based on a large international cohort of patients with primary MR undergoing TEER, intra-procedural mean MPG did not significantly affect clinical and functional outcomes at 2 years. The long-term impact of elevated post-procedural MPG warrants further investigation.Figure 1Figure 2

Magnetic resonance lymphangiography abnormalities as extracardiac biomarkers of pulmonary hypertension and functional phenotype in Fontan-Kreutzer univentricular circulation.

Lymphatic abnormalities have been documented on magnetic resonance lymphangiography in patients with functionally univentricular circulation. The aim of this study is to evaluate associations between findings on magnetic resonance lymphangiography, cardiac catheterisation and functional phenotype in patients with Fontan-Kreutzer circulation. Between January 2017 and October 2019, seven patients with Fontan-Kreutzer circulation (16.57 ± 7.10 years) were enrolled following ethical committee approval and attainment of informed consent. Clinical data, consecutive magnetic resonance imaging and cardiac catheterisation findings were reviewed. Qualitative lymphatic abnormality types were defined as: 1 - Little or none; 2 - Localised to the supraclavicular region; 3 - Extending into the mediastinum; and 4 - Extending into the lung. Pulmonary hypertension was defined as a transpulmonary gradient > 6 mmHg. Quantitative data were assessed using Mann-Whitney U tests, and p < 0.05 was considered statistically significant. Patients with lymphatic abnormalities categorised type 1 or 2 and transpulmonary gradient ≤ 6 mmHg had a normal functional phenotype, while those with type 3 or 4 and transpulmonary gradient > 6 mmHg had a failing functional phenotype. Magnetic resonance lymphangiography in patients with Fontan-Kreutzer circulation and pulmonary hypertension revealed lymphatic abnormalities types 3-4, indicative of a failing functional phenotype compared to patients without pulmonary hypertension. If validated in larger studies, these results suggest the potential utility of this extracardiac biomarker for improving risk stratification. Integration of lymphangiography and transpulmonary gradient with functional class, atrioventricular valve function, and ejection fraction allowed for the categorisation of three distinct functional phenotypes, which may be valuable for future analyses.

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 &amp;lt; 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.

May right heart failure cause pulmonary congestion in pulmonary arterial hypertension?

Abstract Aims Recent studies have shown that lung ultrasound-assessed pulmonary congestion is worse in heart failure when pulmonary vascular resistance (PVR) is increased, suggesting a paradoxical relationship between right heart failure and increased lung water content. Accordingly, we wondered if lung ultrasound would reveal otherwise clinically silent pulmonary congestion in patients with pulmonary arterial hypertension (PAH). Methods and results All patients referred for suspicion of PAH in a tertiary center from January 2020 to December 2022 underwent a complete diagnostic work-up including echocardiography, lung ultrasound and right heart catheterization. Pulmonary congestion was identified by lung ultrasound B-lines using an 8-site scan. The study enrolled 102 patients with idiopathic PAH (mean age 53±13; 71% female). WHO functional classes I, II and III were found respectively in 2, 52 and 46% of them. The N-terminal-pro-brain natriuretic peptide (NT-proBNP) was 377 pg/mL [interquartile range, IQR 218, 906]. B-lines were identified in 77 out of 102 patients (75%), with a median of 3 [IQR: 1-5]. At univariable analysis B-lines were positively correlated to male sex, age, NT-proBNP, systolic PA pressure (sPAP), right atrial pressure (RAP), PVR, left ventricular end-diastolic volume and tricuspid annulus plane systolic excursion (TAPSE), and negatively to cardiac output and stroke volume. At multivariable analysis, RAP (p&amp;lt;0.001; Fig 1), TAPSE/sPAP (p=0.001), and NT-proBNP (p=0.04) were independent predictors of B-lines. Conclusion Lung ultrasound commonly discloses pulmonary congestion in PAH. This finding is related to right ventricle to pulmonary artery uncoupling, and may tentatively be explained by increased central venous pressure impeding lymphatic outflow.Figure 1

Multiparametric risk predictions for morbidity and mortality in patients with pulmonary arterial hypertension: insights from a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we aimed to evaluate risk predictions for morbidity and mortality. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). ESC/ERS 2022 risk scoring, COMPERA 2.0 and REVEAL lite 2 models were used for baseline risk predictions, and COMPERA 2.0 model was used for risk evaluation at follow-up. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age (mean +SD) was 51.27 + 21.37 years, and 72 % of patients were female. Incident cases were noted in 65.9 % of overall study group. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of overall patients, respectively. Background mono and dual targeted combinations, and sequential dual or triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. According to the ESC/ERS 2022 baseline risk scoring, low-, intermediate-, and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time was 867 (412-1667) days. Overall rates of mortality and CEP were 26 % and 39%, respectively. Prevalent versus incident cases were associated signifinatly lower mortality and CEP ( p=0.028 and p=0.024, respectively). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. Baseline high versus intermediate /low risk status were associated with a lower survival estimates for mortality and CEP in patients with PAH ( p=0.03 and p=0.003, respectively). Baseline COMPERA 2.0 risk status revealed significant differences in overall survival and CEP-free survival among risk groups ( p&amp;lt;0.0001 for both), but 1st year COMPERA 2.0 score did not (p=0.39 and p=0.06, respectively) . As compared to baseline, 1st year COMPERA 2.0 score decreased in 31 %, and remained unchanged in 34 % of patients. Baseline REVEAL lite 2.0 score was associated with mortality (hazard ratio (HR): 1.14;1.08-1.2, p&amp;lt;0.0001) and CEP (HR:1.17;1.1-1.25, p&amp;lt;0.0001) risks. Male sex (HR: 1.73; 1.2-2.51, p = 0.004), six-minute walk distance (p&amp;lt;0.001), functional class III/IV (HR: 2.52;1.47-4.32, p&amp;lt;0.001) and baseline low-risk status (HR:0.37;0.21-0.65, p&amp;lt;0.001) were independent predictors of mortality. Conclusions Our nation-wide data revealed current insights concerning the multiparametric risk predictions for morbidity and mortality in PAH.

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 &amp;lt;5 years, 6-10 years, and &amp;gt;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 &amp;lt;5 years, 1,074 (22.4%) 5-10 years, and 1,831 (38.3%) &amp;gt;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 (&amp;lt;5 years, reference; 6-10 years, HR 1.25 [95% CI, 1.06-1.46]; &amp;gt;11 years, HR 1.33 [1.15-1.54]). The benefit of dapagliflozin on the primary outcome was consistent across T2D duration category: &amp;lt;5 years, HR 0.85 (95% CI, 0.69-1.04); 5-10 years, HR 0.65 (0.51-0.83); &amp;gt;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.

Acetazolamide for patients with acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials

Abstract Background The role of acetazolamide as an adjunct to standard loop diuretic therapy in patients with acute decompensated heart failure (ADHF) remains uncertain. Purpose We undertook a systematic review and meta-analysis to ascertain the efficacy and safety of acetazolamide plus standard of care (SOC) in patients with ADHF. Methods In January 2024, we systematically searched PubMed, Embase, and Cochrane for randomised controlled trials (RCTs) comparing acetazolamide plus SOC versus SOC alone in patients with ADHF. Effective decongestion was defined as per the definition of each individual study. We pooled risk ratios (RR) and standardized mean difference (SMD) with 95% confidence intervals (CI) for binary and continuous outcomes, respectively. Statistical analyses were performed using Review Manager version 5.4.1. Results We included 4 RCTs comprising 634 patients, of whom 318 (50.1%) were randomised to acetazolamide plus SOC. The mean age was 77.1 years and 64.2% were male. Nearly half of the patients (n=320; 50.5%) had impaired left ventricular ejection fraction at baseline. Most patients had a New York Heart Association functional class III or higher, ranging from 75 to 91% in each study. In the pooled analysis, acetazolamide plus SOC significantly increased the proportion of patients with clinical decongestion at day 3 compared with SOC alone (RR 1.36; 95% CI 1.10 to 1.68; p=0.005; Figure 1A). There was no significant difference between groups in natriuresis at day 1 (SMD 0.46; 95% CI -0.01 to 0.94; p=0.06; Figure 1B) or worsening renal function (RR 1.71; 95% CI 0.73 to 3.98; p=0.22; Figure 1C). Conclusion In this meta-analysis of RCTs among patients admitted with ADHF, acetazolamide plus SOC significantly improved the proportion of patients with clinical decongestion at day 3 relative to SOC alone, without significantly affecting renal function or natriuresis.Figure 1

Impact of dapagliflozin on cardiometabolic outcomes after myocardial infarction according to baseline left ventricular ejection fraction: a DAPA-MI substudy

Abstract Background Dapagliflozin improved cardiometabolic outcomes compared with placebo following acute myocardial infarction (MI) in participants without prior diabetes mellitus (DM) or chronic heart failure (HF) in the DAPA-MI trial. Purpose Cardiometabolic outcomes were assessed in the DAPA-MI trial according to left ventricular ejection fraction (EF) at randomisation. Methods Participants were categorised according to whether baseline EF was ≥50 or &amp;lt;50%. Those without a baseline EF result and those who did not receive a dose of study drug were excluded. The primary objective was to determine the clinical effect of dapagliflozin 10 mg versus placebo assessed using a hierarchical composite outcome and analysed by the win ratio method. The primary outcome was the hierarchical composite, by order of perceived clinical importance, of death, hospitalization for HF (HHF), nonfatal MI, atrial fibrillation/flutter event, new diagnosis of type 2 DM, NYHA functional class at the last trial visit, and body weight decrease of ≥5% from baseline to the last trial visit. Time to first event of NYHA class II-IV or HHF and time to first event of NYHA class III-IV or HHF were assessed as endpoints of special interest. Hazard ratios (HR) with 95% confidence intervals (CI) were determined using Cox proportional hazards models. The main subgroup variable (baseline EF ≥50 or &amp;lt;50) and its interaction with treatment (P int) were included. Results 838 participants had EF≥50 and 2913 had EF&amp;lt;50 at baseline. The primary hierarchical composite outcome resulted in a win ratio for those with EF≥50 of 1.32 (CI 1.00-1.73) and 1.38 for those with EF&amp;lt;50 (CI 1.21-1.57; P int 0.8) (Figures). There were no significant interactions by EF for any of the secondary outcomes. In those with EF&amp;lt;50, a first event of NYHA class II-IV or HHF occurred in 435 (29.4%) participants in the dapagliflozin group and 485 (33.8%) in the placebo group (absolute risk difference [ARD] 4.4%; HR 0.83, CI 0.73-0.94, P&amp;lt;0.01). In those with EF≥50, this occurred in 81 (19.7%) and 93 (21.8%), respectively (ARD 2.1%; HR 0.96, CI 0.65-1.41, P=0.7; P int 0.47). In those with EF&amp;lt;50, a first event of NYHA class III-IV or HHF occurred in 77 (5.2%) in the dapagliflozin and 115 (8.0%) in the placebo groups (ARD 2.2%; HR 0.64, CI 0.48-0.85, P&amp;lt;0.01). In those with EF≥50, this occurred in 14 (3.4%) and 19 (4.4%), respectively (ARD 1.0%; HR 0.80, CI 0.40-1.60, P=0.5; P int 0.55). There was no significant effect of dapagliflozin on death/MI/stroke in either subgroup (EF&amp;lt;50: HR 0.96, CI 0.65-1.41; EF≥50: HR 0.83, CI 0.38-1.84; P int 0.75). Dapagliflozin increased the incidence of 5% weight loss in both of the EF subgroups with no significant interaction. Conclusions Dapagliflozin resulted in significant benefit in cardiometabolic outcomes compared with placebo regardless of baseline EF. The absolute reduction in HF symptoms or HHF with dapagliflozin, compared with placebo, was greatest in those with baseline EF&amp;lt;50.Figures

Importance of cardiac rehabilitation on cardiorrespiratory fitness in patients undergoing percutaneous aortic valve replacement

Abstract Background Percutaneous Aortic Valve Replacement (TAVR) significantly improves cardiac function in patients with severe aortic stenosis. However, the vast majority of these patients do not reach an adequate functional class despite the valve change, due to the deterioration of hemodynamic function and the repercussions of afterload over time. Cardiac rehabilitation (CR) program is an interdisciplinary intervention aimed at restoring functionality in Post-TAVR patients and the key to optimizing the recovery and enhancing cardiorrespiratory fitness (CRFit). The Purpose of the study is to provide an analysis of the effects of CR on exercise capacity and CRFit in TAVR patients. Methods Quasi-experimental study in TAVR patients that underwent a 4-6 week CR program, including personalized aerobic and strength training. Outcomes assessed pre- and post-rehabilitation included VO2 max, ventilatory thresholds (VT1 and VT2), and exercise capacity. The study also evaluated METs efficiency by comparing actual to predicted METs values before and after the therapy, alongside expired gas analysis test to examine exercise tolerance and its relation to VO2max gains. Results A total of 28 patients were analyzed, with an average age of 73 years (±8.1), initial weight of 68 kg (±12.32), and final weight of 65 kg (±11.13). The average ejection fraction (EF) from echocardiographic parameters was 62% (±10.1). All patients underwent cardiopulmonary exercise testing (CPET) after post-TAVR with improvements in CRFit. Initial exercise test parameters showed an average METs-load at 8.1 (±1.98), VO2max at 4.75 (±1.86), VT1 at 3.05 (±1.86), VAT at 3.85 (±1.62), VT2 at 4.5 (±2.28), and VE/VCO2 at 38 (±5.32). Final test parameters revealed VO2max at 5.8 (±2.09), VT1 at 3.2 (±1.33), VAT at 4.65 (±1.60), VT2 at 5.15 (±2.3), and VE/VCO2 at 36.4 (±69.95). Pearson's correlation analysis between CPET variables and the percentage improvement of various exercise test parameters found no statistically significant correlation. Except for METs-load and final time in Bruce, which show a significant and inversely proportional correlation (r=-0.67, p&amp;lt; 0.001). Conclusions The study demonstrates the effect of cardiac rehabilitation program in enhancing cardiorespiratory fitness and exercise capacity in post-TAVR patients. Notably, improvements in VO2max and ventilatory thresholds highlight the program's efficacy in promoting cardiovascular health. The inverse correlation between initial time in Bruce and METs improvement underscores the importance of baseline exercise capacity in predicting rehabilitation outcomes. Our results allow us to conclude that training volume is not the only variable to consider for proper CR. This insight could guide personalized rehabilitation strategies, making a significant contribution to the field of cardiac recovery post-TAVR.Measured METsBruce time - METs correlation