Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

AIM: The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. METHODS AND RESULTS: The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. CONCLUSION: Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

Impact of lead position on tricuspid regurgitation, ventricular function, and heart failure exacerbation and mortality after cardiac implantable electronic device implantation. Preliminary results from the PACE-RVTR Registry.

BACKGROUND: The most frequent mechanism of lead-related tricuspid regurgitation (LRTR), which occurs in 7.2% to 44.7% of patients implanted with a cardiac implantable electronic device (CIED), is leaflet impingement or the restriction of its movement by a ventricular lead. It is unclear if the position of the lead tip - in the right ventricular apex (RVA) or other location (non-RVA) - has any influence on the development of LRTR. The study aimed to determine the impact of the CIED lead tip position on the development or progression of tricuspid regurgitation (TR) and its potential impact on heart failure exacerbation and mortality. METHODS: One hundred and two consecutive patients who received CIEDs between March 2020 and October 2021 were included in the prospective registry (PACE-RVTR). Patients were assigned to two groups depending on the lead position - the RVA group and the non-RVA group. All patients underwent echocardiographic evaluation before implantation and one year later. RESULTS: In terms of baseline clinical characteristics, the two groups did not differ. Before CIED implantation, patients in the non-RVA group had better left ventricular systolic function (P = 0.004). Pacemakers were implanted more often in the non-RVA group (P = 0.001) while implantable cardioverter-defibrillators in the RVA group (P = 0.008). Progression to severe or massive TR was more common in the non-RVA group (P = 0.005). CONCLUSION: Severe and massive TR occurred more often in patients with the non-RVA position of the lead. The right ventricular lead position did not impact heart failure progression or all-cause mortality at two-year follow-up.

Does atrial fibrillation still increase the risk of death? One-year follow-up results of the NOMED-AF study.

INTRODUCTION: Although atrial fibrillation (AF) is a well­known risk factor for ischemic stroke and hospitalization, its effect on mortality has not been clearly established. OBJECTIVES: We aimed to assess whether AF is an independent risk factor for death. A secondary objective was to evaluate the role of oral anticoagulation in the prevention of stroke and death in 1­year follow­up of patients included in the NOMED­AF (Noninvasive Monitoring for Early Detection of Atrial Fibrillation) study. PATIENTS AND METHODS: The NOMED­AF study included 3014 patients. The participants underwent continuous long­term electrocardiographic monitoring using a wearable vest for up to 30 days. The present analysis involved 2795 patients who completed the 1­year follow­up. The median (interquartile range) follow­up time was 365 (365-365) days. AF was diagnosed in 617 participants. RESULTS: Independent risk factors for death in the patients who completed the 1­year follow­up were AF, age equal to or above 65 years, and chronic kidney disease. The individuals with diagnosed AF had an almost 2­fold higher risk of death (odds ratio [OR], 1.7; 95% CI, 1.18-2.44; P <0.001) and a 2.5­fold higher risk of stroke (OR, 2.53; 95% CI, 1.41-4.44; P <0.001), as compared with those without an AF diagnosis. The participants with AF who received oral anticoagulants had an almost 5­fold lower risk of death than those who were not on anticoagulation (2.9% vs 14.2%, respectively; P <0.001). CONCLUSIONS: AF is an independent risk factor for death and cardiovascular hospitalization. The risk of death and stroke in patients with AF is significantly higher than in the patients without this arrhythmia. Oral anticoagulation in patients with AF significantly reduces the rates of death and stroke; however, its use is suboptimal in this group of patients.

Echocardiographic predictors of positive left ventricular remodeling in patients with a history of active myocarditis.

INTRODUCTION: Myocarditis may be difficult to diagnose because of the variety of its clinical manifestations, and the clinical course of the disease can be unpredictable. Nevertheless, some patients may exhibit partial or full contractile recovery following myocarditis. Standard and speckle-tracking echocardiography may serve as tools to follow this recovery. OBJECTIVES: We aimed to evaluate predictors of positive left ventricular (LV) remodeling after active myocarditis (AM). PATIENTS AND METHODS: A database of a high­volume, tertiary cardiology center was searched for patients with AM hospitalized between 2016 and 2019. They were included in the analysis based on clinical manifestations and presence of at least 1 of the following diagnostic criteria: positive findings on electrocardiography / Holter monitoring, echocardiography, elevated troponin T/I levels, functional or structural abnormalities on cardiac imaging, or tissue characterization by cardiac magnetic resonance. LV global longitudinal strain and mechanical dispersion (MD; defined as SD of the time to peak longitudinal strain derived from all LV segments in 3 apical views) were determined. Echocardiographic response (positive LV remodeling measured by transthoracic echocardiography) was defined as end­systolic volume (ESV) reduction by 15% or greater or end-diastolic volume (EDV) reduction by 15% or greater from the baseline values. RESULTS: A total of 61 consecutive patients were recruited. The median follow­up was 1.4 years (range, 0.3-4). The mortality rate was 1.6%. Echocardiographic response was noted in 24 patients (39.4%). A multivariable Cox regression model including significant baseline differences as covariates showed that QRS duration (hazard ratio [HR], 1.31; 95% CI, 1.17-1.57; P = 0.049), MD (HR, 1.03; 95% CI, 1.01-1.07; P = 0.04), and mineralocorticoid receptor antagonist [MRA] use (HR, 8.60; 95% CI, 1.50-46.49; P = 0.01) were independently associated with positive LV remodeling with ESV reduction. MD (HR, 1.04; 95% CI, 1.02-1.06; P = 0.04) was also independently associated with positive LV remodeling with EDV reduction. CONCLUSIONS: Mechanical dispersion, QRS duration, and MRA use are independent predictors of positive LV remodeling in individuals with a history of AM.

Antithrombotic Usage, Including Three-Year Outcomes With Dabigatran and Vitamin K Antagonists for Atrial Fibrillation, in Eastern Europe: A Descriptive Analysis From Phase 3 of the GLORIA-AF Registry.

BACKGROUND: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective registry of outcomes from patients with newly diagnosed AF at risk of stroke. In the propensity score (PS)-matched global population of phase 3 GLORIA-AF, at 3 years, dabigatran-treated patients experienced reduced risk for major bleeding, and similar risk for stroke and myocardial infarction, compared with vitamin K antagonist (VKA)-treated patients. STUDY QUESTION: Do patients in Eastern Europe benefit from treatment with dabigatran versus VKA? STUDY DESIGN: Descriptive analysis, without PS matching. To contextualize the Eastern Europe results of GLORIA-AF phase 3, we also descriptively analyzed the global population without PS matching. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc-score ≥1 were enrolled until December 2016 in 38 countries (9 in Eastern Europe). MEASURES AND OUTCOMES: Three-year outcomes with dabigatran and VKA. RESULTS: In Eastern Europe, 1341 patients were eligible (6% of patients globally), and incidence rates (per 100 patient-years) for the following outcomes were numerically lower with dabigatran (N = 498) versus VKA (N = 466): major bleeding (0.26 vs. 0.90), all-cause death (2.04 vs. 3.50), and a composite of stroke, systemic embolism, myocardial infarction, life-threatening bleeding, and vascular death (1.37 vs. 1.92); stroke was comparable (0.51 vs. 0.50). All incidence rates were numerically lower in Eastern Europe versus the global population for both treatments. Chronic concomitant use of high bleeding risk medications (eg, nonsteroidal anti-inflammatories) was lower in Eastern Europe (dabigatran 3.8%, VKA 9.3%) than globally (dabigatran 14.8%, VKA 20.6%) and persistence with dabigatran was higher in Eastern Europe (76%) than globally (64%). CONCLUSIONS: Dabigatran was associated with numerically reduced major bleeding, all-cause death, and cardiovascular (CV) composite, with comparable risk of stroke versus VKA, in Eastern Europe. Limitations of this descriptive analysis include few CV events (n = 11 for stroke, in the dabigatran and VKA groups combined) and a lack of statistical analysis and PS matching, which precludes definitive conclusions; however, the CV outcomes in Eastern Europe were consistent with the beneficial impact of dabigatran versus VKA in the statistically analyzed global population with PS matching.

The Influence of Hybrid Comprehensive Telerehabilitation on Anxiety in Heart Failure Patients: The TELEREH-HF Randomized Clinical Trial.

Telerehabilitation for heart failure (HF) patients is beneficial for physical functioning, prognosis, and psychological status. The study aimed at evaluating the influence of hybrid comprehensive telerehabilitation (HCTR) on the level of anxiety in comparison to usual care (UC). The TELEREH-HF study was a multicenter prospective RCT in 850 clinically stable HF participants. Patients underwent clinical examinations, including the assessment of anxiety, at entry and after the 9-week training program (HCTR) or observation (UC). The State-Trait Anxiety Inventory (STAI) was used. 20.3% HCTR and 20.1% UC patients reported high level of anxiety as a state at baseline, with higher STAI results in younger participants (< 63 y.o.) (p = .048 for HCTR; p = .026 for UC). At both stages of the study, patients with lower level of physical capacity (measured by a peak VO2) had shown significantly higher level of anxiety. There were no significant changes in anxiety levels during the 9-week observation for the entire study population, although there were different patterns of change in anxiety (both trait and state) in younger and older groups,with the decrease in younger patients, and the increase-in the older group.Trial registry number NCT02523560 (Clinical Trials.gov), date of registration: August 14, 2015.

Anticoagulants versus Left Atrial Appendage Occlusion in Patients with Atrial Fibrillation and Co-Morbid Thrombocytopenia.

Left atrial appendage closure (LAAC) is an alternative approach to anticoagulants. Nonetheless, data regarding the outcomes of LAAC procedures in patients with thrombocytopenia remain lacking. The primary objective was to determine the incidence of the composite endpoint comprising ischemic stroke, intracranial hemorrhage, major bleeding, and cardiac cause of death among patients with atrial fibrillation (AF) and thrombocytopenia who were either undergoing LAAC or receiving oral anticoagulants. The secondary endpoint was the determination of total mortality. Data from a prospective, single-center registry of patients undergoing LAAC procedures were analyzed. A subset of 50 consecutive patients with thrombocytopenia were selected. Thrombocytopenia was defined as a thrombocyte count below 150,000. Subsequently, from patients hospitalized with AF receiving oral anticoagulants, 50 patients were further chosen based on propensity score matching, ensuring comparability with the study group. The primary endpoint occurred in 2% of patients in the LAAC group and 10% of patients in the non-LAAC group (p = 0.097). Additionally, a significant difference was noted in the occurrence of the secondary endpoint, which was observed in 0% of patients in the LAAC group and 10% of patients in the non-LAAC group (p = 0.025). In patients with thrombocytopenia the LAAC procedure improves prognosis compared with continued anticoagulant treatment.

Predictors of ventricular tachyarrhythmia in patients with implantable cardioverter-defibrillator and non-ischemic systolic heart failure.

BACKGROUND: The benefit derived from implantable cardioverter-defibrillators (ICD) in subjects with non-ischemic systolic HF (NICM) is less well-established. AIM: The study aimed to determine the incidence, predictors, and prognostic impact of ventricular arrhythmias in patients with ICD and NICM. METHODS: The study sample included 377 consecutive patients with ICD or cardiac resynchronization cardioverter-defibrillators (CRT-D, 74% of patients) and NICM implanted and monitored remotely in a university hospital. RESULTS: During the median (interquartile range [IQR]) follow-up of 1645 (960-2675) days, sustained ventricular arrhythmia occurred in 92 patients (24.4%). Of those, ventricular fibrillation (VF), ventricular tachycardia (VT), and both VT and VF occurred in 10 (10.9%), 72 (78.3%), and 10 (10.9%) patients, respectively. Patients with vs. those without ventricular arrhythmia differed concerning sex, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular ejection fraction (LVEF), post-inflammatory etiology, atrial fibrillation/flutter occurrence, and supraventricular arrhythmia (SVT) other than AF/AFL during follow-up. In multivariable Cox regression, LVEDD (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.003-1.09; P = 0.03), AF/AFL (HR, 1.86; 95% CI, 1.21-2.85; P = 0.004), and SVT (HR, 1.77; 95% CI, 1.10-2.87; P = 0.02) were independent predictors of sustained VT, while AF/AFL (HR, 1.65; 95% CI, 1.07-2.56; P = 0.02) was independent predictor of VF. All-cause mortality in patients with VT/VF was significantly higher than in subjects without sustained ventricular arrhythmias (35.9% vs. 22.4%; P = 0.01). CONCLUSIONS: Ventricular arrhythmia occurred in every fourth patient with NICM and ICD during 4.5 years of observation and was associated with significantly worse prognosis than in subjects free of VT/VF. Higher LVEDD, atrial fibrillation/atrial flutter, and supraventricular tachycardia flag patients at risk of ventricular arrhythmia.

Rationale and design of a randomized clinical trial evaluating the efficacy of mechanical neuroprotection in reducing the risk of silent brain infarcts associated with percutaneous left atrial appendage closure: study protocol for a LAAC-SBI trial.

BACKGROUND: Left atrial appendage closure (LAAC) procedures prevent cardioembolic stroke in patients with atrial fibrillation who have contraindications to oral anticoagulant medications. However, these procedures carry certain risks of peri-procedural complications. One such complication is silent brain infarcts (SBI), which can lead to cognitive impairment and mood disturbances. The implementation of mechanical neuroprotection systems during LAAC procedures may reduce the risk of SBI and associated cognitive and mood disorders. METHODS: The LAAC-SBI trial is a prospective, multicenter, randomized, and double-blind interventional study. The study aims to enroll a total of 240 patients, with 120 patients allocated to each group. The study group will evaluate the use of the Sentinel CPS during LAAC, while the control group will undergo LAAC procedures without the Sentinel CPS. The primary endpoint of the study is the number of new SBIs or stroke foci detected by diffusion-weighted magnetic resonance imaging (DW MRI). Secondary endpoints include deterioration of cognitive function, development of dementia syndrome, and occurrence of depressive disorders. These endpoints will be assessed using questionnaire tools such as the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), Controlled Oral Word Association Test (COWAT), and Hospital Anxiety and Depression Scale (HADS). The observational period for patients in the study is 2 years. DISCUSSION: If the study demonstrates a favorable outcome with reduced incidence of SBI and improved cognitive and mood outcomes in patients receiving cerebral protection devices during LAAC, it will have significant implications for clinical management standards. This would support the use of neuroprotection devices not only for LAAC but also in procedures such as atrial fibrillation ablation or transcatheter mitral valve interventions, where the risk of embolic events and subsequent brain injury may also be present. TRIAL REGISTRATION: ClinicalTrials.gov NCT05369195. Registration on 11.05.2022.

Impact of diabetes mellitus severity, treatment regimen and glycaemic control on atrial fibrillation prevalence in the Polish population aged ≥ 65.

Diabetes mellitus (DM) is a well-known risk factor for atrial fibrillation (AF), but the mechanism(s) by which DM affects AF prevalence remains unclear. This study aims to evaluate the impact of diabetes mellitus severity (expressed as its known duration), antihyperglycemic treatment regimen and glycaemic control on AF prevalence. From the representative sample of 3014 participants (mean age 77.5, 49.1% female) from the cross-sectional NOMED-AF study, 881 participants (mean age 77.6 ± 0.25, 46.4% female) with concomitant DM were involved in the analysis. AF was screened using a telemonitoring vest for a mean of 21.9 ± 9.1 days. The mean DM duration was 12 ± 0.35 years, but no significant impact of DM timespan on AF prevalence was observed. No differences in the treatment pattern (oral medication vs insulin vs both oral + insulin) among the study population with and without AF were shown (p = 0.106). Metabolic control reflected by HbA1c levels showed no significant association with AF and silent AF prevalence (p = 0.635; p = 0.094). On multivariate analyses, age (Odds Ratio (OR) 1.35, 95%CI: 1.18-1.53, p < 0.001), p = 0.042), body mass index (BMI; OR 1.043, 95%CI: 1.01-1.08, p = 0.027) and LDL < 100 mg/dl (OR 0.64, 95%CI: 0.42-0.97, p = 0.037) were independent risk factors for AF prevalence, while age (OR 1.45, 95%CI: 1.20-1.75, p < 0.001), LDL < 100 mg/dl (OR 0.43, 95%CI 0.23-0.82, p = 0.011), use of statins (OR 0.51, 95%CI: 0.28-0.94, p = 0.031) and HbA1c ≤ 6.5 (OR 0.46, 95%CI: 0.25-0.85, p = 0.013) were associated with silent AF prevalence. Diabetes duration, diabetic treatment pattern or metabolic control per se did not significantly impact the prevalence of AF, including silent AF detected by prospective continuous monitoring. Independent predictors of AF were age, BMI and low LDL levels, with statins and HbA1c ≤ 6.5 being additional independent predictors for silent AF.Trial registration: NCT03243474.

Predictive factors of left ventricular ejection fraction improvement after myocardial infarction treated invasively.

Introduction: One indication for the implantation of a cardioverter-defibrillator is a reduction in the left ventricular ejection fraction (LVEF) ≤ 35%. However, in certain patients following an acute myocardial infarction (AMI) a gradual improvement in LVEF has been observed. The factors determining this increase in LVEF have not been conclusively determined. Aim: To ascertain the independent predictors associated with the improvement of LVEF in patients following AMI who underwent invasive treatment, while observing their progress over a 6-month follow-up period. Material and methods: Among 665 patients with AMI, a population with LVEF ≤ 35% was selected. After 6 months, a follow-up echocardiogram was performed. Further analysis compared patients with at least 5% improvement in LVEF (Group I) with those without an increase (Group II). Results: Group I consisted of 34 individuals out of 80 patients (43%) with LVEF ≤ 35%. The factors linked to a reduced probability of LVEF improvement were: higher levels of cardiac troponin T (cTnT) (OR 0.841 for 1 ng/ml increase in cTnT, CI 0.715-0.989; p = 0.037), presence of diabetes mellitus (OR = 0.217, 95% CI: 0.058-0.813, p = 0.023) and moderate or severe mitral regurgitation (OR = 0.178, 95% CI: 0.053-0.597; p = 0.005). Conclusions: The study findings indicate that the presence of severe or moderate mitral regurgitation is the most significant factor contributing to the lack of LVEF improvement following AMI. Moreover, the extent of myocardial damage, as indicated by elevated cTnT values, along with compromised adaptation to hypoxia in patients with diabetes, are identified as independent factors associated with reduced chances of an increase in LVEF.

Tricuspid Regurgitation (TR) after Implantation of a Cardiac Implantable Electronic Device (CIED)-One-Year Observation of Patients with or without Left Ventricular Dysfunction.

The frequency of tricuspid regurgitation (TR) progression after cardiac implantable electronic devices (CIEDs) implantation varies from 7.2% to 44.7%. TR is associated with increased mortality and hospitalizations due to heart failure (HF) decompensation. The aim of this study was to assess the rate of early TR progression after CIED implantation and the frequency of HF decompensation and mortality. The 101 patients, who received a CIED between March 2020 and October 2021, before the procedure were divided into two groups-one with left ventricle ejection fraction (LVEF) ≥ 40% (n = 60) and one with LVEF < 40% (n = 41). Lead-related tricuspid regurgitation (LRTR) was defined as an increase of TR by at least one grade. The follow-up period was similar between both groups and was on average 13 (12-16) months. In the whole study group, TR progression by one grade was 34.6% and by two or more grades 15.8%. The significant changes in the dynamic of TR degree were as follows before and after implantation: none/trivial TR in group 1 (61.7% vs. 28.3%, p = 0.01) and severe/massive TR in group 2 (0.0% vs. 14.6%, p = 0.03). The groups did not differ from each other in terms of survival from decompensation of HF (18.3% vs. 36.6%, p = 0.70) and survival from death (1.7% vs. 4.9%, p = 0.16). At the one-year follow-up, the baseline LVEF did not affect the survival rate from death or HF decompensation among patients with a progression of TR after CIED implantation. In this study, a progression by one grade was more common in group 1, but the occurrence of severe/massive TR after implantation was more specific for group 2.

Double protection in patients with a massive thrombus in the infarct-related artery - a single-center retrospective study.

Introduction: ST-segment elevation myocardial infarction (STEMI) is associated with thrombus formation on a ruptured or ulcerated atherosclerotic plaque. The consequences of a massive thrombus (MT) may include lack of reperfusion, extensive myocardial infarction (MI) and its complications. Although there are various treatment options for patients with coronary thrombi, double protection (DP) - manual thrombectomy (MTH) with a distal protection device (DPD) - has not been tested yet. Aim: To present DP outcomes in the treatment of patients with STEMI and MT patients. Material and methods: Fourteen patients with STEMI and MT were included in the study. Those patients underwent primary percutaneous coronary intervention (PPCI) with DP. Results: Inferior MI was found in 12 (85.8%) patients. Stents were implanted in 13 (92.8%) patients. Thrombolysis In Myocardial Infarction (TIMI) Thrombus Grade 5 was present in 11 (78.6%) patients and Grade 4 in 3 (21.4%) patients. The median thrombus length was 39.1 mm. Complete reperfusion (TIMI flow 3) was observed in 11 (78.6%) patients and TIMI flow 2 in 3 (21.4%) patients. Myocardial Blush Grade (MBG) was used in patients with TIMI flow 3 and Grade 3 was found in 5 (35.7%) patients. Resolution in ST-segment elevation > 50% was obtained in 13 (92.8%) patients. No myocardial rupture, stroke, or death occurred during hospitalization. Conclusions: DP in MT patients is a safe and feasible procedure. However, further observations and studies are needed to assess the efficacy of this method.

Predictors of long-term prognosis based on clinical status and measurements obtained in heart failure patients after 9-week hybrid comprehensive telerehabilitation: A subanalysis of the TELEREH-HF randomized clinical trial.

BACKGROUND: Assessing prognosis in heart failure (HF) is of major importance. AIMS: The study aimed to define predictors influencing long-term cardiovascular mortality or HF hospitalization ("composite outcome") based on clinical status and measurements obtained after a 9-week hybrid comprehensive telerehabilitation (HCTR) program. METHODS: This analysis is based on the TELEREH-HF (TELEREHabilitation in Heart Failure) multicenter randomized trial that enrolled 850 HF patients (left ventricular ejection fraction [LVEF] ≤40%). Patients were randomized 1:1 to 9-week HCTR plus usual care (experimental arm) or usual care only (control arm) and followed for median (interquartile range [IQR]) 24 (20-24) months for development of the composite outcome. RESULTS: Over 12-24 months of follow-up, 108 (28.1%) patients experienced the composite outcome. The predictors of our composite outcome were: nonischemic etiology of HF, diabetes, higher serum level of N-terminal prohormone of brain natriuretic peptide, creatinine, and high-sensitivity C-reactive protein; low carbon dioxide output at peak exercise; high minute ventilation and breathing frequency at maximum effort in cardiopulmonary exercise tests; increase in delta of average heart rate in 24-hour Holter ECG monitoring, lower LVEF, and patients' non-adherence to HCTR. The model discrimination C-index was 0.795 and decreased to 0.755 on validation conducted in the control sample which was not used in derivation. The 2-year risk of the composite outcome was 48% in the top tertile versus 5% in the bottom tertile of the developed risk score. CONCLUSION: Risk factors collected at the end of the 9-week telerehabilitation period performed well in stratifying patients based on their 2-year risk of the composite outcome. Patients in the top tertile had an almost ten-fold higher risk compared to patients in the bottom tertile. Treatment adherence, but not peak VO2 or quality of life, was significantly associated with the outcome.