Combined Primary Endpoint Research Articles

Prognostic value of exercise right ventricular pulmonary arterial coupling in severe primary mitral regurgitation: new atrial fibrilation and unplanned cardiovascular hospitalization

Abstract Background Exercise-induced pulmonary hypertension, characterized by mean pulmonary artery pressure over cardiac output slope (mPAP/CO slope) > 3mmHg/L/min is associated with worse outcome in greater than moderate primary mitral regurgitation (PMR). However, the prognostic value of right ventricle to pulmonary artery coupling (RVPAc) is unknown. Purpose Assess the prognostic value of RVPAc; determine the additional value of exercise over rest RVPAc and compare these findings to the mPAP/CO slope. Methods The single center study included consecutive patients with greater than moderate PMR, no/discordant symptoms, left ventricular ejection fraction >60% and absence of concomitant valvular disease greater than moderate or permanent atrial fibrillation (AF) referred to simultaneous CPET and exercise echocardiography (CPET-echo). A thorough echocardiographic assessment of right ventricle (RV) systolic function and RVPAc (TAPSE/sPAP, ratio of tricuspid annular plane systolic excursion over systolic pulmonary artery pressure) was performed using a dedicated RV window. mPAP and CO were obtained by Doppler echocardiography. Primary outcome was the composite of cardiovascular mortality, unplanned cardiovascular hospitalization and new AF episodes. Results A total of 159 consecutive patients (64±11 years, 59% men) were included. The event-free survival rate was 84% at 1 year and 78% at 2 years. Patients who fulfilled the primary combined endpoint had significantly larger left atrium indexed volumes (LAVi), lower left atrial strain and strain rate at rest and strain at intermediate exercise, lower absolute and normalized peak oxygen uptake (VO2peak), and a significantly higher mPAP/CO slope. They had significantly lower TAPSE, RV free wall S’ and TAPSE/sPAP. Sequentially adding intermediate or high exercise TAPSE/sPAP and percent-predicted VO2peak to the baseline predictive model (age, LAVi, mitral regurgitation grade and TAPSE/sPAP at rest) significantly improved the area under the curve (AUC) of the baseline logistic regression model (AUC: 0.71 vs. 0.80 and 0.71 vs. 0.81, p<0.05, respectively), with LAVi and TAPSE/sPAP at intermediate or high exercise remaining as significant independent variables (although coupling assessment at high exercise technically less feasible). Replacing exercise TAPSE/sPAP with mPAP/CO yields models with comparable accuracy (Figure 1). Exercise TAPSE/sPAP <0,6 was related to a higher event rate (Figure 2) Conclusion Decreased rest or exercise TAPSE/sPAP are single point measures of RVPAc, associated with adverse outcome in patients with greater than moderate PMR and no or discordant symptoms. Exercise TAPSE/sPAP has independent additional value over rest TAPSE/sPAP in predicting adverse events, with a similar accuracy as mPAP/CO slope. Exercise TAPSE/sPAP represents a potential alternative to mPAP/CO slope in this population, being readily available and simpler to adopt in clinical practice.

Tremelimumab plus durvalumab prior to chemoradiotherapy in unresectable, locally advanced non-small cell lung cancer: the Induction trial.

The phase I Induction trial (NCT04287894) assessed the feasibility and safety of induction immunotherapy (IIT) prior to concurrent chemoradiotherapy (cCRT) in patients with locally advanced non-small cell lung cancer (NSCLC). Patients with unresectable stage II/III NSCLC were eligible for inclusion. Patients received either one cycle of tremelimumab (75mg) with two cycles of durvalumab (1500mg) in cohort I, one cycle of tremelimumab (300mg) with two cycles of durvalumab in cohort II or one cycle of tremelimumab (300mg) with one cycle of durvalumab in cohort III. After IIT, a comprehensive radiological and pathological restaging was performed followed by cCRT. The combined primary endpoint was feasibility and safety of IIT-cCRT. Fifteen of seventeen included patients were treated per-protocol. IIT-cCRT was completed in 13/15 of the patients within the predefined feasibility criteria. Grade ≥3 immune-related adverse events (irAEs) occurred in 7/15 patients, of which 6 were treated in the high-dose tremelimumab cohorts, thereby violating the safety criteria in cohorts II and III. The low-dose tremelimumab cohort (I) complied with safety criteria. Eleven patients had multilevel N2 or N3 disease at baseline, eight of these patients were downstaged to either N0/1 or single level N2 after IIT. Multiparametric MRI accurately identified nodal downstaging in 7/7 patients. Induction with high-dose tremelimumab plus durvalumab prior to cCRT in unresectable locally advanced NSCLC was associated with unacceptable toxicity, although ITT resulted in clinically relevant nodal downstaging in 8/11 of patients with baseline multilevel N2 or N3 disease. Multiparametric MRI showed potential evaluating treatment response.

Impact of porcelain aorta on outcomes in transfemoral aortic valve implantation (TAVI) with balloon-expandable valves

BackgroundCurrent guidelines recommend transcatheter aortic valve implantation (TAVI) for patients with aortic stenosis and porcelain aorta (PA). Neurological outcomes of patients with PA undergoing TAVI with modern valves require clarification...

Guideline-directed medical therapy for heart failure in arrhythmia-induced cardiomyopathy with improved left ventricular ejection fraction.

No study has analyzed the impact of guideline-directed medical therapy in preventing heart failure (HF) relapse in patients with arrhythmia-induced cardiomyopathy (AiCM) following left ventricular ejection fraction (LVEF) improvement. We analyzed data from a single-center cohort of 200 patients admitted for HF, LVEF <50% and cardiac arrhythmia considered by cardiologists to be the precipitating cause of the episode. The primary endpoint was time-to-HF relapse, defined as the composite of readmission for HF, Emergency Department (ED) visit for HF, or significant decline in LVEF. Changes in medication were recorded and a time-varying multivariate Cox regression was performed. After a median follow-up period of 6.14 years, diagnostic confirmation was achieved in 188 out of the initial 200 patients with suspected AiCM. A total of 89 patients (47.3%) met the primary endpoint. RAS inhibitors (adjusted hazard ratio (HR) 0.50 [0.31-0.81]; p = 0.005) and beta-blockers (adjusted HR 0.48 [0.28-0.81]; p = 0.006) were associated with a lower incidence of relapse. Mineralocorticoid receptor antagonists were associated with a significantly lower incidence of ED visits for HF (adjusted HR 0.38 [0.15-0.95]; p = 0.038), but did not achieve statistical significance for the combined primary endpoint. Antiarrhythmic drugs did not show a significant impact on the primary endpoint. Maintaining RAS inhibitors and beta-blockers was associated with a significantly lower incidence of relapse in the setting of AiCM with improved LVEF.

Curricular Self-management for patients on ventricular assist device support decreases depression: A multicenter randomized controlled trial.

Utilization of ventricular assist device (VAD) support in patients with end-stage heart failure is well advanced. Recent studies emphasize the need to develop and evaluate evidence-based psychosocial support interventions for patients following VAD implantation. A national, multi-center study in four established German heart centers was initiated. An evidence-based VAD curriculum was developed; a randomized controlled trial evaluated the impact of the interprofessional intervention over time. Primary combined endpoint was the occurrence of adverse events (thromboembolic events, driveline infections, bleeding, rehospitalization, and death); secondary endpoints were psychosocial outcomes (anxiety, depression [HADS], quality of life [QoLVAD], social support [FSoZu], and self-management [SELMA]). A total of 140 patients were randomized block-wise to intervention (IG n = 70) or control (CG n = 70). Center-effects were considered. Instruments were completed at four time points (T0-T3). At baseline, intervention group (IG) patients were 19% female (control group [CG] 19%; p = 0.982); 58 ± 11 years. (CG 58 ± 11 years.; p = 0.966); 80% were implanted electively (CG 79%; p = 0.968). No significant difference in primary endpoint was found between IG versus CG (p > 0.05). For secondary endpoints, mixed linear regression revealed a significant reduction in depression scores in IG compared to CG (est. 1.18; 95% CI -2.17 to -0.18; p = 0.021). Clinically significant reductions in anxiety were greater in IG patients between T0 and T3 (IG 51.9%; CG 40.7%); increased anxiety was reported in 3.7% IG (11.1% CG). Mixed linear regression analyses favored IG (all >0.05) for QoL, social support, and self-management. A comprehensive curricular VAD intervention has potential to decrease depression levels and improve psychosocial outcomes of patients on VAD support.

Prospective randomized evaluation of transcutaneous carbon dioxide monitoring during complex electrophysiological procedures under deep sedation: the TRACES trial.

The field of interventional electrophysiology is rapidly growing. For safe and efficient procedures sedation is needed for patient comfort and immobility. However, sedative and analgesic agents can induce respiratory depression, risking hypercapnia, hypoxia, and hypotension. This study evaluates the impact of adding transcutaneous carbon-dioxide (CO2) monitoring to standard monitoring practices in electrophysiological procedures under deep sedation. This prospective, randomized study at Ulm University Heart Center included 726 patients undergoing treatment under deep sedation between August 2019 and October 2023. Patients were randomly assigned to standard monitoring or standard monitoring with continuous transcutaneous CO2 monitoring (TCM-group). Standard monitoring involved non-invasive blood pressure, oxygen saturation (SpO2), and frequent peripheral venous blood gas analysis. The primary composite endpoint was SpO2 dips below 90% and pathological changes in venous blood gas analysis. The TCM-group included 357 patients, and the standard group had 348. The primary composite endpoint was reached by 195 patients (54.8%) in the TCM-group and 195 patients (56.5%) in the standard group (p = 0.642). However, peripheral venous CO2 partial pressure increased by more than 30% from baseline more often in the standard group than in the TCM-group (p = 0.005). Additionally, a venous pH below 7.25 was more common in the standard group (p = 0.047). While transcutaneous CO2 monitoring offers no significant benefit for the primary combined endpoint over standard monitoring during electrophysiological procedures, it helps mitigate significant CO2 elevations and respiratory acidosis. ClinicalTrials.gov, NCT04038476, 29 July 2019.

Combined Assessment of Function and Survival to Demonstrate the Effect of Treatment on Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) is a rare and fatal neurodegenerative disorder for which there are currently no disease-modifying treatments. Recent trials of potential therapies had durations of 12 months, which may be insufficient because of nonrandom missingness due to death. Longer durations, incorporating PSP Rating Scale and survival, can reduce the potential for type II error. Selecting efficacy measures more sensitive to disease modification may facilitate identification of treatment effect. The objective of this study was to evaluate the simulated phase 3 PSP trial assessing the effect of disease-modifying intervention on a novel combined primary endpoint comprising function (PSP Rating Scale) and survival, the Combined Assessment of Function and Survival (CAFS), and to determine operating characteristics of the CAFS. To simulate PSP progression in the trial population, we developed models of PSP Rating Scale and survival using data from published clinical studies. These models were used to define operating characteristics of the CAFS for use in a phase 3 trial. The sample size determined (N = 384; 1:1 randomization) would provide >80% power to detect significant treatment effects on the CAFS compared with placebo. The CAFS provides good operating characteristics and increased power to detect moderate treatment effects on the PSP Rating Scale. We propose a trial design allowing potential detection of treatment effects at a preplanned interim analysis after participants complete 12 months of treatment, with assessment of effects of treatment (≤24 months) on survival. Use of the CAFS could provide a comprehensive and robust estimate of the clinical benefit of future therapies. © 2024 UCB. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prognostic value of exercise right ventricular-pulmonary arterial coupling in primary mitral regurgitation

Abstract Background Exercise-induced pulmonary hypertension (mPAP/CO slope &amp;gt;3mmHg/L/min) was recently associated with worse outcome in &amp;gt;moderate PMR. However, the prognostic value of right ventricle to pulmonary artery coupling (RVPAc) is unknown. Purpose Assess the prognostic value of RVPAc; determine the additional value of exercise over rest RVPAc and compare these findings to the mPAP/CO slope. Methods Cohort study including consecutive pts submitted to CPET-echo with &amp;gt;moderate PMR, no/discordant symptoms, preserved LV function and without &amp;gt;moderate concomitant valvular disease or atrial fibrillation (AF). Thorough assessment of RV systolic function and RVPAc (TAPSE/sPAP ratio) was obtained by echocardiography using a dedicated RV window. mPAP and CO were obtained by Doppler echocardiography. Primary outcome was the composite of all-cause mortality, cardiovascular hospitalization (CVH), new-onset AF and valvular intervention; secondary outcome was the composite of CVH and new-onset AF. Results A total of 128 consecutive pts (64±11 years, 61% men) underwent CPET-echo. Event-free survival rate was 55% and 46% at 1 and 2 years. Pts that reached the primary combined endpoint were significantly older, had larger left atrium indexed volumes (LAVi), higher proportion of grade 4 MR, lower absolute and normalized peak VO2, and a significantly higher mPAP/CO slope (2,1±0,8 vs.3,7±2,6). They had a significantly lower rest and exercise TAPSE/sPAP, RV global and free wall longitudinal strain, rest and exercise TAPSE and exercise RV free wall S’. Rest and low exercise TAPSE/sPAP scored the highest accuracy in predicting the primary combined endpoint among variables statistically significant in the univariate analysis and therefore were used in the multivariate model. Sequentially adding rest and low exercise TAPSE/sPAP significantly improved the baseline predictive model (age, LAVi and MR grade). Low exercise TAPSE/sPAP and LAVi remained as significant independent variables in the multivariate model. They also correlated with new-onset AF and CVH; with rest and low exercise TAPSE/sPAP constituting significant steps (Fig 2). Replacing low exercise TAPSE/sPAP for mPAP/CO slope in the proposed model only slightly improved its accuracy in predicting the primary and secondary composite outcomes. Adding predicted peak VO2 (≥80% vs &amp;lt;80%) did not significantly improve the accuracy of any of the multivariate models. Low exercise TAPSE/sPAP and mPAP/CO slope both correlated well with peak VO2 and VE/VCO2 slope. Conclusion Decreased rest or exercise TAPSE/sPAP are single point measures of RVPAc, associated with adverse outcome in pts with &amp;gt;moderate PMR and no/discordant symptoms. Low exercise TAPSE/sPAP has independent additional value over rest TAPSE/sPAP in predicting adverse events, with a similar accuracy as mPAP/CO slope. Low exercise TAPSE/sPAP is a potential alternative to mPAP/CO slope in this population and it may be simpler to adopt in clinical practice.Central Illustration

Right ventricular-pulmonary artery coupling and clinical outcomes after mitral transcatheter edge-to-edge repair: A meta-analysis

Abstract Introduction Mitral transcatheter edge-to-edge repair (TEER) has gained prominence in the realm of cardiovascular care, as it has been proven to improve patient prognosis and quality of life. While the primary focus of such interventions is the mitral valve itself, understanding the broader impact of right ventricular function and pulmonary artery dynamics is crucial for a comprehensive assessment of clinical efficacy and patient outcomes. A newly recognized index, right ventricular-pulmonary artery (RV-PA) coupling, reflects the RV's ability to handle pulmonary afterload and is associated with adverse outcomes. Purpose This meta-analysis consolidates findings from diverse studies to systematically evaluate the association between RV-PA coupling parameters and the success of mitral TEER. Methods We conducted a systematic literature search for studies assessing RV-PA coupling indices at baseline in patients undergoing mitral TEER. We recorded the year of publication, method of RV-PA assessment, and the proposed cutoffs. The primary outcome of interest was the combined primary endpoint of included studies at maximal follow-up and the adjusted hazard ratios of RV-PA uncoupling were extracted if they were available. Secondary outcomes included mortality and post-operative mitral regurgitation at follow-up. Pooling of the hazard ratios was conducted according to a random effects model. I2 was chosen as the measure of between-study heterogeneity, with values exceeding 50% being significant. Results We identified a total of 316 studies, of which 8 were ultimately selected for data extraction and inclusion in the meta-analysis after screening of title/abstract/full-text. All but one study utilized the Tricuspid Annular Plane Systolic Excursion/Pulmonary artery systolic pressure (TAPSE/PASP) as the method of RV-PA assessment. According to the results of the meta-analysis, the presence of baseline RV-PA uncoupling was associated with a 2.3-fold increased risk of facing the combined primary endpoint at maximal follow-up (Figure, Panel A). All-cause mortality was also approximately 2.2-fold higher in cases of RV-PA uncoupling (Figure, Panel B). Finally, post-operative MR was 1.4-fold higher in cases of RV-PA uncoupling (Figure, Panel C). Significant between-study heterogeneity was detected in all the examined endpoints. Conclusion: This meta-analysis indicates that RV-PA uncoupling at baseline represents an important prognostic marker in patients undergoing mitral TEER.Figure

Left atrioventricular coupling index is an independent associate of new-onset AF and stroke in hypertrophic cardiomyopathy: a CMR study

Abstract Background Left atrial (LA) dysfunction is an important marker of disease progression in hypertrophic cardiomyopathy (HCM). LA volumes and functional parameters are associated with new-onset atrial fibrillation (AF) and its complications including stroke. The association between left atrioventricular coupling (LACI), a parameter reflecting the contribution of the left ventricular and LA remodeling to LA dysfunction, with the occurrence of new-onset AF and stroke has not been evaluated. Aim To investigate the association between LACI and the occurrence of new-onset AF or stroke in patients with HCM. Methods In patients with an established diagnosis of HCM and cardiac magnetic resonance (CMR) data, LACI was calculated as the ratio between the LA and the LV end-diastolic volumes. New-onset AF or occurrence of stroke comprised the primary combined endpoint. Cumulative event-free survival rates for the occurrence of the primary endpoint were estimated with the population divided according to a LACI cut-off value of 40%. The association between clinical and CMR variables and the primary endpoint was assessed with univariable and multivariable Cox proportional hazard regression models. Results Of 114 patients with HCM, (mean age 54±16 years, 33 (29%) female, LV ejection fraction 67.0±8.4%), 71 patients (49%) had a LACI &amp;gt; 40% (left atrioventricular uncoupling). During a median follow-up of 4.1 (1.8-6.4) years, 19 (16.7%) patients experienced new-onset AF or stroke. Patients with preserved left atrioventricular coupling (LACI ≤ 40%) had a lower cumulative rate of events compared to those with left atrioventricular uncoupling (log-rank p=0.031, Fig. 1). LACI was independently associated with new-onset AF or stroke after adjusting by the presence of late gadolinium enhancement (LGE) sex and age (HR=23.27, p=0.016). Conclusions In patients with HCM, the presence of left atrioventricular uncoupling is independently associated with the occurrence of new-onset AF or stroke.

Do CYP2D6 polymorphisms affect the efficacy and toxicity of flecainide? A cohort study

Abstract Background The CYP2D6 enzyme, coded by the CYP2D6 gene, is the primary metabolic pathway for flecainide.(1,2) Over the years, studies on how different variants of this gene affect flecainide metabolism and efficacy have yielded contradictory results.(3–7) This is likely due to the fact that CYP2D6 pharmacogenetic classifications were not standardized until 2017.(8,9) Purpose To date, there has been no published study using a standardized classification to assess the efficacy and toxicity of flecainide across different CYP2D6 phenotypes; therefore, we decided to study this. Methods We conducted a cohort study with data collected through indirect methods, blinding all parties involved except the statistician. We identified patients with flecainide prescriptions (100 mg/12 h) and follow-up in our health area (n=450,136 people) between 2017 and 2021. A primary combined endpoint composed of initial inefficacy and early toxicity was pre-set, and a secondary combined endpoint of toxicity or inefficacy during follow-up. Results 104 patients met the criteria and agreed to participate: 38 (36.5%) intermediate metabolizers, 52 (50%) normal metabolizers, 2 (1.9%) could not be classified with certainty (compatible with intermediate or normal metabolizers), 7 (6.7%) poor metabolizers, 4 (3.8%) ultra-rapid metabolizers, and 1 (1%) possible hybrid. Intermediate and normal metabolizers showed an almost superimposable incidence of the primary endpoint (28,9% vs 28,8%, p=0.99), early inefficacy (21,6% vs 17,4%, p=0.97) and early toxicity (13,2% vs 13,3%, p=0.72). No significant differences were observed in multivariate analysis (p=0.76, picture 1) or in a combined endpoint of toxicity or inefficacy during follow-up (p=0.58, Kaplan-Meier in picture 2). Differences were seen in the primary endpoint when comparing poor metabolizers to the rest of the sample, although they did not reach statistical significance (p=0.07), likely due to the small number of patients in this group (n=7, absolute risk reduction -32%; 95% confidence interval: -41% to -23%). Conclusions Using the standardized classification for CYP2D6 pharmacogenetics, no statistically significant differences were detected between the two largest groups, intermediate and normal metabolizers. It is possible that better results are achieved in poor metabolizers. Based on these results, it is worth questioning whether, in an attempt to minimize the risk of flecainide toxicity, doses that are subtherapeutic in all groups except slow metabolizers have been used unknowingly.

Lack of incremental prognostic value of triglyceride glucose index beyond coronary computed tomography angiography features for major events

This study was aim to determine the prognostic value of triglyceride-glucose (TyG) index and coronary computed tomography angiography (CTA) features for major adverse cardiovascular events (MACE). In addition, we investigate the incremental prognostic value of TyG index beyond coronary CTA features in patients with suspected or known coronary artery disease (CAD). The present study ultimately includes 3528 patients who met the enrollment criteria. The TyG index was calculated based on measured levels of triglycerides and fasting blood glucose. Primary combined endpoint consisted of MACE, which defined as myocardial infraction (MI), all-cause mortality and stroke. Three multivariate Cox proportional hazard regression models were performed to assess the association between TyG index and MACE. C-statistic was performed to assess the discriminatory value of models. 212 (6.0%) patients developed MACE during a median follow-up of 50.4 months (IQR, 39.4–55.1). TyG index remained to be a significantly and independent risk factors for predicting MACE after adjusting by different models (clinical variables alone or plus coronary CTA features) in multivariable analysis. Both the addition of TyG index to clinical model plus Coronary Artery Disease Reporting and Data System (CAD-RADS) and to clinical model plus CAD-RADS 2.0 slightly but not significantly increased the C-statistic index (0.725 vs. 0.721, p = 0.223; 0.733 vs. 0.731, p = 0.505). TyG index was associated with an increased risk of MACE. However, no incremental prognostic benefit of TyG index over CAD-RADS or CAD-RADS 2.0 was detected for MACE in patients with suspected or known CAD.

The Use of Short Dilator Tip in Endovascular Branched Arch Repair: A Case Series.

The aim of the study was to investigate the safety and feasibility of branched endovascular arch repair (b-TEVAR) with a custom-made double or triple inner branched arch endograft using a short dilator tip (35 mm) in patients with aortic arch pathologies. Retrospective analysis of all consecutive patients undergoing b-TEVAR with a short dilator tip for the treatment of aortic arch pathologies in a high-volume tertiary center between January 2019 and July 2023. The combined primary endpoint was technical success and perioperative complications caused by the endograft, including tip-induced cardiac injury and trackability issues. Secondary endpoints were major adverse events (MAE), including morbidity, mortality, and reinterventions within 30 days. During a 4-year period, 22 patients (median age 72 years, 16 males) were treated with a custom-made double or triple inner-branched TEVAR for different aortic arch pathologies using a short dilator tip (35 mm). After initial exclusive treatment of patients with previous valve replacement, the use of a short dilator tip became standard. Eighteen patients received a triple- and 4 patients received a double-branched endograft. Seventeen patients (77.3%) underwent elective treatment, while 5 patients underwent urgent repair due to contained rupture or symptomatic aneurysms. The technical success was 100%. No tip-induced cardiac mortality and morbidity occurred perioperatively. The trackability of the device was in no case affected by the short tip. Within 30 days, the MAE rate was 45%, including one death. No re-intervention had to be performed. Endovascular aortic arch repair with inner-branched arch endografts using a short dilator tip (35 mm) appears to be safe and technically feasible and could potentially reduce the risk of fatal myocardial injuries. Due to safe and stable maneuverability and deployment of endograft in zone 0 the use of short dilator tip might have the potential to become standard in endovascular branched arch repair. This is one of the first reports on the use of short dilator tip and associated complications in endovascular branched arch repair.

Incidence and clinical impact of inappropriate periprocedural and perioperative management of antiplatelet therapy

Background and aimsThere is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in “real life” in Spain. MethodsA prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy. ResultsWe included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents. ConclusionsDespite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the “real world” remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic.

Remote monitoring of patients with chronic heart failure: A prospective randomized study

BACKGROUND: Chronic heart failure is one of the key problems of the Russian domestic healthcare system. E-health can be used to improve medical care quality and reduce the of hospitalizations and mortality. AIM: To examine the effect of telemedicine monitoring on mortality, frequency of hospitalizations, and clinical and functional states of patients with chronic heart failure. MATERIALS AND METHODS: A prospective, controlled, randomized study was conducted in the Central City Hospital No. 20 in Ekaterinburg (Russia), covering the period from December 2020 to December 2022. Patients with a confirmed diagnosis of chronic heart failure were randomized using the envelope method into three groups: group 1, a telephone control group (n=58); group 2, a remote control group using a Russian medical platform Medsenger (n=52); and group 3, the standard control group (n=103). All patients were examined, including NT-proBNP measurement and echocardiography on the first day of the study and at 3, 6, and 12 months. The occurrence of primary and secondary outcomes was evaluated at these reference points. Stata14 and jamovi software were used for statistical processing. RESULTS: The study involved 213 participants, and all three groups were comparable in terms of basic demographic and clinical characteristics. The advantage of remote control (groups 1 and 2) over face-to-face observation in reducing cardiovascular mortality was observed after 3 (odds ratio 2.73, 95% confidence interval 1.1–7.39; p=0.042) and 12 (odds ratio 2.1, 95% confidence interval 1.1–3.7; p=0.027) months and that in reducing the occurrence of the combined primary endpoint (odds ratio 2.1, 95% confidence interval 1.1–5.6; p=0.015) after 12 months. The use of the Medsenger platform also demonstrated an advantage over face-to-face observation in the development of the combined secondary endpoint (odds ratio 1.39, 95% confidence interval 0.19–0.81; p=0.011) after 3 months and over telephone control by a nurse after 12 months in reducing cardiovascular mortality (odds ratio 0.177, 95% confidence interval 0.06–0.487; p=0.021) and development of the combined secondary endpoint (odds ratio 0.427, 95% confidence interval 0.189–0.964; p=0.041). When using the Medsenger platform, the ejection fraction increased from 47% initially to 55% after 12 months (p=0.004). The NT-proBNP level decreased from 817 to 582 pg/mL (p 0.001) after 3 months and then to 233 pg/mL after 12 months (p 0.001). CONCLUSION: Remote monitoring protocols can be a good alternative to the traditional face-to-face monitoring of patients with chronic heart failure, which may improve clinical and functional health indicators.

Diabetes mellitus in stable chronic heart failure and the combination with humoral activation, their association, and prediction of 2-year adverse outcomes. Data from the FAR NHL registry.

The study aims to describe the role of diabetes in patients with heart failure. In all, 1052 chronic heart failure patients were included in the FARmacology and NeuroHumoral Activation (FAR NHL) multicenter prospective registry. They had ejection fraction below 50% and were on stable medication for at least 1 month. More than one-third (38.9%) of the patients had diabetes mellitus (DM). Diabetic patients (N = 409) were older (median 67 vs. 64, p < 0.001), had higher body mass index (BMI) (30 vs. 28 kg/m2, p < 0.001), much more frequently had ischemic heart disease (71 vs. 47%, p < 0.001), hypertension (80 vs. 67%, p < 0.001), dyslipidemia (89 vs. 69%, p < 0.001), worse renal function (estimated glomerular filtration rate [eGFR] median 63 vs. 73 mL/min/1.73 m2, p < 0.001), and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) (median 681 vs. 463 pg/mL, p = 0.003). All-cause death, left ventricle assist device implantation, and orthotopic heart transplantation were set as the combined primary end point, which was present in 15.5% (163 patients) within the 2-year follow-up. In the 2-year follow-up, 81.0% of patients with diabetes survived without a primary end point, while 85.4% of the patients without diabetes survived, the difference being on the verge of statistical significance (p = 0.089). DM is a statistically significant predictor of NT-proBNP value in univariate analysis, but it is not an independent predictor in a multivariate analysis. When the NT-proBNP level was high, the presence of DM did not influence the prognosis. The combination of diabetes and NT-proBNP levels may better stratify the prognosis of patients with chronic heart failure.

Clinical trials in pulmonary sarcoidosis; what is needed, what is happening and what is next?

There is a clinical unmet need to improve treatment for patients with pulmonary sarcoidosis. Both retrospective and prospective drug trials are hampered by the fact that patients with sarcoidosis are characterized by a heterogeneous presentation and disease course. In this review, an overview is given of different drug trials in pulmonary sarcoidosis with an emphasis on different primary endpoints and the problems related to them. In recent years, using significant input from patients with sarcoidosis, different task-forces/studies tried to develop a core set of most important outcomes to measure in future studies on treatment of sarcoidosis. Furthermore, at present, three major clinical trials are being conducted on new drugs for treatment of pulmonary sarcoidosis. Progress has been made to develop a core set of outcomes measures that can be used in making a combined primary endpoint in future drug trials in sarcoidosis.

Heart failure risk assessment in patients with hypertrophic cardiomyopathy based on the H2FPEF score.

The aim of this study was to investigate whether the H2FPEF score, which was developed to improve the diagnosis of heart failure (HF) with preserved ejection fraction, is associated with HF outcomes in patients with hypertrophic cardiomyopathy (HCM). Patients with HCM and preserved left ventricular ejection fraction (LVEF ≥50%) were included from a multicentre registry and the H2FPEF score was calculated. Patients were divided into three groups: low (0-1), intermediate (2-5) and high (6-9) H2FPEF score. The primary combined endpoint was a composite of all-cause death and HF admissions, while the secondary endpoints were all-cause death and HF admissions separately. A total of 955 patients were included (age 51 ± 17 years, 310 [32.5%] female). Patients with a high H2FPEF score (n = 105) were more often female, and presented with more symptoms and comorbidities. On echocardiography, patients with a high H2FPEF score had lower LVEF, more impaired diastolic function and more frequently left ventricular outflow tract obstruction. During follow-up (median 90 months [interquartile range 49-176]), 103 (11%) patients died and 57 (6%) patients had a first HF hospitalization. Event-free survival rate for the primary combined and secondary endpoints was lower for patients with an intermediate and high H2FPEF score. On multivariate Cox regression analysis, female sex (hazard ratio [HR] 1.670, 95% confidence interval [CI] 1.157-2.410; p = 0.006), Asian ethnicity (HR 6.711, 95% CI 4.076-11.048; p < 0.001), ischaemic heart disease (HR 1.732, 95% CI 1.133-2.650; p = 0.011), left atrial diameter (HR 1.028, 95% CI 1.005-1.051; p = 0.016) and intermediate (HR 2.757, 95% CI 1.612-4.713; p < 0.001) or high H2FPEF score (HR 3.689, 95% CI 1.908-7.134; p < 0.001) were independently associated with the primary combined endpoint. The H2FPEF score is independently associated with HF outcome in patients with HCM and may be considered for risk stratification.

Acute post-procedural inducibility is a poor predictor of clinical outcomes in high-risk patients (PAINESD > 17) undergoing scar-related ventricular tachycardia ablation.

Ventricular tachycardia (VT) non-inducibility in response to programmed ventricular stimulation (PVS) is a widely used procedural endpoint for VT ablation despite inconclusive evidence with respect to clinical outcomes in high-risk patients. The aim is to determine the utility of acute post-ablation VT inducibility as a predictor of VT recurrence, mortality, or mortality equivalent in high-risk patients. We conducted a retrospective analysis of high-risk patients (defined as PAINESD > 17) who underwent scar-related VT ablation at our institution between July 2010 and July 2022. Patients' response to PVS (post-procedure) was categorized into three groups: Group A, no clinical VT or VT with cycle length > 240 ms inducible; Group B, only non-clinical VT with cycle length > 240 ms induced; and Group C, all other outcomes (including cases where no PVS was performed). The combined primary endpoint included death, durable left ventricular assist device placement, and cardiac transplant (Cox analysis). Ventricular tachycardia recurrence was considered a secondary endpoint (competing risk analysis). Of the 1677 VT ablation cases, 123 cases met the inclusion criteria for analysis. During a 19-month median follow-up time (interquartile range 4-43 months), 82 (66.7%) patients experienced the composite primary endpoint. There was no difference between Groups A and C with respect to the primary [hazard ratio (HR) = 1.21 (0.94-1.57), P = 0.145] or secondary [HR = 1.18 (0.91-1.54), P = 0.210] outcomes. These findings persisted after multivariate adjustments. The size of Group B (n = 13) did not permit meaningful statistical analysis. The results of post-ablation PVS do not significantly correlate with long-term outcomes in high-risk (PAINESD > 17) VT ablation patients.

Effects of tele-yoga on physical and psychological outcomes in patients living with ICD, a randomised controlled trial

Abstract Background Patients with long-term illness, including those living with an implantable cardioverter defibrillator (ICD), often suffer from symptoms of anxiety and depression, decreased health-related quality-of-life (HRQOL), and impaired functional capacity. Yoga, being a mind-body intervention, may improve all these outcomes. Purpose To determine effects of tele-yoga on exercise capacity and patient-reported outcome measures. Methods A single-blind (evaluator blinded) parallel two-arm RCT with 1:1 distribution. Participants were recruited from four hospitals in Sweden. Inclusion criteria: &amp;gt;18 years, admitted to a cardiology or intensive care units &amp;gt;48 hours during the last 36 months due to ICD implantation or ventricular arrhythmias, heart failure, or conditions in need of intensive care and now clinically stable. The participants were randomised to a control group receiving individual exercise advice or to the intervention group (tele-yoga). The intervention included performing live-streamed group-yoga for 60 min twice/week for 3 months and practicing yoga individually for a minimum of 10 min/day using an app. The group-sessions with approximately 10 participants were led by certified Mediyoga-instructors via the virtual video-platform ZOOM. The yoga form was Kundalini adapted to individuals with health conditions (Mediyoga). Two standardised yoga-programmes including different postures, breathing exercises and meditations were rotated. The primary endpoint of the study after 3 months was a combined endpoint consisting of change in functional capacity measured by 6-min walk test (6MWT), HRQOL (EQ-5D index/VAS) and symptoms of anxiety and depression (HADS). The used cut offs for change were 30 meters for 6MWT, a score &amp;gt;11 for EQ-5D VAS and ≥8 for anxiety/depression in HADS. Secondary endpoints included separate analysis of functional capacity, HRQOL and symptoms of anxiety/depression. Results In total, 311 participants were randomized to tele-yoga (n=156) and control (n=155), mean age 65.8 years, 30% women, 38% living with an ICD (whereof 62% had a primary preventive indication). Median attendance to yoga-sessions was 20 sessions for 12 weeks and 74% of the study participants were adherent to &amp;gt;16 tele-yoga sessions. There were no adverse events reported during yoga sessions or app usage. In this sub-group analysis involving the ICD cohort (n=118), there was a significant improvement in favour of the tele-yoga group in the combined primary endpoint (p=.011). When analysing them separately, there was a significant improvement in 6MWT (p=.002), but not in HRQOL in EQ-5D VAS or symptoms of anxiety and depression. No adverse events were reported during yoga sessions or app usage. Conclusion Digitally delivered mind-body training such as tele-yoga showed a significant improvement in the combined endpoint consisting of physical function, HRQOL and mental health. Tele-yoga may be a promising new form of rehabilitation for patients living with ICD.