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.

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.

Predictors of proarrhythmic effect in heart failure patients after 9-week hybrid comprehensive telerehabilitation and their influence on cardiovascular mortality in long-term follow-up: Subanalysis of the TELEREH-HF randomized clinical trial.

BACKGROUND: Regular exercise training is beneficial in heart failure (HF) patients. However, its potential proarrhythmic effect is possible but has not been sufficiently investigated. OBJECTIVE: To identify patients at risk for proarrhythmic effect after the 9-week of hybrid comprehensive telerehabilitation (HCTR) program vs the 9-week of usual care (UC) and to investigate its predictors and impact on cardiovascular mortality based on data from the TELEREH-HF RCT. METHODS: Proarrhythmic effect, strictly defined on the basis of available standards was evaluated by comparing 24-h Holter ECG before and after 9-week of HCTR or UC of 773 HF patients (The New York Heart Association class I-III, left ventricular ejection fraction ≤40%). RESULTS: The proarrhytmic effect was found in 78 (20.4%) and in 61 (15.6%) patients in the HCTR and UC group respectively, and the difference between groups was not statistically significant (p = 0.081). However, univariate analysis identified several statistically significant predictors of proarrhythmia in HCTR only vs the UC group. After a multivariate analysis ischaemic aetiology of HF (OR = 2.27, p = 0.008), peak oxygen consumption at baseline <14 ml/kg/min (OR = 2.03, p = 0.012) and level of N-terminal-pro B-type natriuretic peptide (NT-proBNP) in the first and the second tercile (OR = 1.85, p = 0.043) were identified to be independent predictors of proarrhytmic effect of exercise training among the HF patients in HCTR group only. CONSLUSIONS: Patients who underwent a 9-week HCTR were not at a higher risk of proarrhythmic effect after its completion compared to UC. However, predictors of proarrhythmia such as ischemic aetiology of HF, poor physical capacity, lower NT-proBNP level were discovered in the HCTR group only, yet it does not cause a significant risk of cardiovascular mortality including sudden cardiac death in long-term follow-up.

Prognostic Impact of Hybrid Comprehensive Telerehabilitation Regarding Diastolic Dysfunction in Patients with Heart Failure with Reduced Ejection Fraction-Subanalysis of the TELEREH-HF Randomized Clinical Trial.

AIMS: The objective of the study was to evaluate the effects of individually prescribed hybrid comprehensive telerehabilitation (HCTR) implemented at patients' homes on left ventricular (LV) diastolic function in heart failure (HF) patients. METHODS AND RESULTS: The Telerehabilitation in Heart Failure Patients trial (TELEREH-HF) is a multicenter, prospective, randomized (1:1), open-label, parallel-group, controlled trial involving HF patients assigned either to HCTR involving a remotely monitored home training program in conjunction with usual care (HCTR group) or usual care only (UC group). The patient in the HCTR group underwent a 9-week HCTR program consisting of two stages: an initial stage (1 week) conducted in hospital and the subsequent stage (eight weeks) of home-based HCTR five times weekly. Due to difficulties of proper assessment and differences in the evaluation of diastolic function in patients with atrial fibrillation, we included in our subanalysis only patients with sinus rhythm. Depending on the grade of diastolic dysfunction, patients were assigned to subgroups with mild diastolic (MDD) or severe diastolic dysfunction (SDD), both in HCTR (HCTR-MDD and HCTR-SDD) and UC groups (UC-MDD and UC-SDD). Changes from baseline to 9 weeks in echocardiographic parameters were seen only in A velocities in HCTR-MDD vs. UC-MDD; no significant shifts between groups of different diastolic dysfunction grades were observed after HCTR. All-cause mortality was higher in UC-SDD vs. UC-MDD with no difference between HCTR-SDD and HCTR-MDD. Higher probability of HF hospitalization was observed in HCTR-SDD than HCTR-MDD and in UC-SDD than UC-MDD. No differences in the probability of cardiovascular mortality and hospitalization were found. CONCLUSIONS: HCTR did not influence diastolic function in HF patients in a significant manner. The grade of diastolic dysfunction had an impact on mortality only in the UC group and HF hospitalization over a 12-24-month follow-up in HCTR and UC groups.

Antiarrhythmic effect of 9-week hybrid comprehensive telerehabilitation and its influence on cardiovascular mortality in long-term follow-up - subanalysis of the TELEREHabilitation in Heart Failure Patients randomized clinical trial.

Introduction: Cardiac rehabilitation is a component of heart failure (HF) management, but its effect on ventricular arrhythmias is not well understood. We analyzed the antiarrhythmic effect of a 9-week hybrid comprehensive telerehabilitation (HCTR) program and its influence on long-term cardiovascular mortality in HF patients taken from the TELEREHabilitation in Heart Failure Patients (TELEREH-HF) trial. Material and methods: We evaluated the presence of non-sustained ventricular tachycardia (nsVT) and frequent premature ventricular complexes ≥ 10 beats/hour (PVCs ≥ 10) in 24-hour ECG monitoring at baseline and after 9-week HCTR or usual care (UC) of 773 HF patients (NYHA I-III, LVEF ≤ 40%). Functional response for HCTR was assessed by changes - delta (Δ) - in peak oxygen consumption (pVO2) as a result of comparing pVO2 from the beginning and the end of the program. Results: Among 143 patients with nsVT, arrhythmia subsided in 30.8% after HCTR. Similarly, among 165 patients randomized to UC who had nsVT 34.5% did not show it after 9 weeks (p = 0.481). There was no significant difference in the decrease in PVC ≥ 10 over 9 weeks between randomization arms (14.9% vs. 17.8%, respectively p = 0.410). Functional response for HCTR in ΔpVO2 > 2.0 ml/kg/min did not affect occurrence of arrhythmias. Multivariable analysis did not identify HCTR as an independent factor determining improvement of nsVT or PVCs ≥ 10. However, only in the HCTR group, the achievement of the antiarrhythmic effect significantly reduced the cardiovascular mortality in 2-year follow-up (p < 0.001). Conclusions: Significant improvement in physical capacity after 9 weeks of HCTR did not correlate with the antiarrhythmic effect in terms of incidence of nsVT or PVCs ≥ 10. An antiarrhythmic effect after the 9-week HCTR affected long-term cardiovascular mortality in HF patients.

Relationship between physical capacity and depression in heart failure patients undergoing hybrid comprehensive telerehabilitation vs. usual care: subanalysis from the TELEREH-HF Randomized Clinical Trial.

AIMS: The hybrid comprehensive telerehabilitation (HCTR) consisting of telecare (with psychological telesupport), telerehabilitation, and remote monitoring of cardiovascular implantable electronic devices might be an option to improve both physical capacity and depressive symptoms. The aim of the study was to investigate the influence of HCTR on depressive symptoms and physical capacity in heart failure (HF) patients in comparison with usual care (UC). METHODS AND RESULTS: The present analysis formed part of a multicentre, randomized trial that enrolled 850 HF patients (New York Heart Association I-III, left ventricular ejection fraction ≤ 40%). Patients were randomized 1:1 to HCTR or UC. Patients underwent an HCTR programme (1 week in hospital and 8 weeks at home; exercise training 5 times weekly) or UC with observation. The Beck Depression Inventory II (BDI-II) score (cut point for depression ≥ 14) was used to assess depression and the physical capacity was measured by peak oxygen consumption (peak VO2; mL/kg/min). Measurements were made before and after 9-week intervention/observation (HCTR/UC group). Both groups were comparable in terms of demographic and clinical characteristics. In HCTR group, at entry, 23% of the sample obtained BDI-II scores ≥14 vs. 27.5% in UC group. There were no significant differences between groups regarding ΔBDI-II score (P = 0.992) after 9-week HCTR/UC. There was a significant improvement in physical capacity only in the HCTR group in both patients with (P = 0.033) and without (P < 0.001) depression. CONCLUSIONS: In HF patients, HCTR provided similar reduction of depressive symptoms as UC. HCTR resulted in a significant improvement in physical capacity in patients with and without depression.

Quality of life in heart failure patients undergoing hybrid comprehensive telerehabilitation versus usual care - results of the Telerehabilitation in Heart Failure Patients (TELEREH-HF) Randomized Clinical Trial.

INTRODUCTION: Hybrid comprehensive telerehabilitation (HCTR) consisting of telecare (with psychological telesupport), telerehabilitation and remote monitoring of implantable devices might be an innovative option improving heart failure (HF) patients' quality of life (QoL) and emotional health. The aim of the study was to investigate the influence of HCTR on various facets of QoL in HF patients in comparison with usual care (UC) alone. MATERIAL AND METHODS: The present analysis formed part of a multicenter, randomized trial that enrolled 850 HF patients (NYHA I-III, LVEF ≤ 40%). Patients were randomized 1 : 1 to HCTR plus UC or UC only. Patients underwent either an HCTR program or UC with observation. The psychological intervention in the HCTR group included supportive psychological counseling via mobile phone. The Medical Outcome Survey Short Form 36 Questionnaire was used to assess QoL. Measurements were made before and after a 9-week intervention (HCTR group)/observation (UC group). RESULTS: After the intervention, the HCTR group showed significant improvement in overall QoL, physical domain (PD) of QoL, and 4 areas of QoL (physical functioning (PhF), role functioning related to physical state (RF), general health (GH), vitality (VI)). A significant positive change in QoL in the UC group was observed only in VI and social functioning. There were also significant differences in QoL after 9-week intervention/observation between the two groups. The results showed greater improvement in HCTR for overall QoL (p = 0.009), PD of QoL (p = 0.0003) and three specific areas of QoL: PhF (p = 0.001), RF (p = 0.003), bodily pain (BP) (p = 0.015). CONCLUSIONS: In comparison to UC, HCTR resulted in improvement in overall QoL, PD of QoL and 3 specific areas of QoL: PhF, RF and BP.

Assessment of ECG during hybrid comprehensive telerehabilitation in heart failure patients-Subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH-HF) randomized clinical trial.

BACKGROUND: Exercise training in heart failure (HF) patients should be monitored to ensure patients' safety. Electrocardiographic (ECG) telemonitoring was used to assess the safety of hybrid comprehensive telerehabilitation (HCTR). OBJECTIVE: Analysis of ECG recorded during HCTR in HF patients. METHODS: The TELEREH-HF multicenter, randomized, controlled trial enrolled 850 HF patients with New York Heart Association class I-III and left ventricular ejection fraction of ≤40%. This subanalysis focuses on 386 patients (aged 62 ± 11 years, LVEF 31 ± 7%) randomized to HCTR. HCTR was telemonitored with a device allowing to record 16-s fragments of ECG and to transmit the data via mobile phone network to the monitoring center. ResultsIn 386 patients, 16,622 HCTR sessions were recorded and 66,488 ECGs fragments were evaluated. Sinus rhythm was present in 320 (83%) and permanent atrial fibrillation (AF) in 66 (17%) patients, respectively. The most common arrhythmias were ventricular and atrial premature beats, recorded in 76.4% and 27.7% of the patients, respectively. Non-sustained ventricular tachycardia (21 episodes in 8 patients) and paroxysmal AF episodes (6 in 4 patients) were rare. None of the analyzed demographic and clinical characteristics was predictive for onset of the new arrhythmias on exercise. CONCLUSION: Telerehabilitation in HF patients was safe without the evidence for symptomatic arrhythmias requiring discontinuation of telerehabilitation. Only one mildly symptomatic paroxysmal AF episode led to the short-term suspension of the training program. The most common arrhythmias were atrial and ventricular premature beats. These arrhythmias did not result in any changes in rehabilitation and therapy regimens.

Pacemaker-Based Cardiac Neuromodulation Therapy in Patients With Hypertension: A Pilot Study.

Background In prior unblinded studies, cardiac neuromodulation therapy (CNT) employing a sequence of variably timed short and longer atrioventricular intervals yielded sustained reductions of systolic blood pressure (SBP) in patients with hypertension. The effects of CNT on SBP were investigated in this double-blind randomized pilot study. Methods and Results Eligible patients had daytime ambulatory SBP (aSBP) ≥130 mm Hg and office SBP ≥140 mm Hg despite taking ≥1 antihypertensive medication, and an indication for a dual-chamber pacemaker. Patients underwent Moderato device implantation, which was programmed as a standard pacemaker during a 1-month run-in phase. Patients whose daytime aSBP was ≥125 mm Hg at the end of this period were randomized (1:1, double blind) to treatment (CNT) or control (CNT inactive). The primary efficacy end point was the between-group difference of the change in 24-hour aSBP at 6 months. Of 68 patients initially enrolled and who underwent implantation with the Moderato system, 47 met criteria for study continuation and were randomized (26 treatment, 21 control). The mean age was 74.0±8.7 years, 64% were men, left ventricular ejection fraction was 59.2%±5.7%, and aSBP averaged 141.0±10.8 mm Hg despite the use of 3.3±1.5 antihypertensive medications; 81% had isolated systolic hypertension. Six months after randomization, aSBP was 11.1±10.5 mm Hg (95% CI, -15.2 to -8.1 mm Hg) lower than prerandomization in the treatment group compared with 3.1±9.5 mm Hg (-7.4 to 1.2 mm Hg) lower in controls, yielding a net treatment effect of 8.1±10.1 mm Hg (-14.2 to -1.9 mm Hg) (P=0.012). There were no Moderato device- or CNT-related adverse events. Conclusions CNT significantly reduced 24-hour aSBP in patients with hypertension with a clinical indication for a pacemaker. The majority of patients had isolated systolic hypertension, a particularly difficult group of patients to treat. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02837445.

Effects of hybrid comprehensive telerehabilitation on cardiopulmonary capacity in heart failure patients depending on diabetes mellitus: subanalysis of the TELEREH-HF randomized clinical trial.

BACKGROUND: Type 2 diabetes mellitus (DM) is one of the most common comorbidities among patients with heart failure (HF) with reduced ejection fraction (HFrEF). There are limited data regarding efficacy of hybrid comprehensive telerehabilitation (HCTR) on cardiopulmonary exercise capacity in patients with HFrEF with versus those without diabetes. AIM: The aim of the present study was to analyze effects of 9-week HCTR in comparison to usual care on parameters of cardiopulmonary exercise capacity in HF patients according to history of DM. METHODS: Clinically stable HF patients with left ventricular ejection fraction [LVEF] < 40% after a hospitalization due to worsening HF within past 6 months were enrolled in the TELEREH-HF (The TELEREHabilitation in Heart Failure Patients) trial and randomized to the HCTR or usual care (UC). Cardiopulmonary exercise tests (CPET) were performed on treadmill with an incremental workload according to the ramp protocol. RESULTS: CPET was performed in 385 patients assigned to HCTR group: 129 (33.5%) had DM (HCTR-DM group) and 256 patients (66.5%) did not have DM (HCTR-nonDM group). Among 397 patients assigned to UC group who had CPET: 137 (34.5%) had DM (UC-DM group) and 260 patients (65.5%) did not have DM (UC-nonDM group). Among DM patients, differences in cardiopulmonary parameters from baseline to 9 weeks remained similar among HCTR and UC patients. In contrast, among patients without DM, HCTR was associated with greater 9-week changes than UC in exercise time, which resulted in a statistically significant interaction between patients with and without DM: difference in changes in exercise time between HCTR versus UC was 12.0 s [95% CI - 15.1, 39.1 s] in DM and 43.1 s [95% CI 24.0, 63.0 s] in non-DM, interaction p-value = 0.016. Furthermore, statistically significant differences in the effect of HCTR versus UC between DM and non-DM were observed in ventilation at rest: - 0.34 l/min [95% CI - 1.60, 0.91 l/min] in DM and 0.83 l/min [95% CI - 0.06, 1.73 l/min] in non-DM, interaction p value = 0.0496 and in VE/VCO2 slope: 1.52 [95% CI - 1.55, 4.59] for DM vs. - 1.44 [95% CI - 3.64, 0.77] for non-DM, interaction p value = 0.044. CONCLUSIONS: The benefits of hybrid comprehensive telerehabilitation versus usual care on the improvement of physical performance, ventilatory profile and gas exchange parameters were more pronounced in patients with HFrEF without DM as compared to patients with DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02523560. Registered 3rd August 2015. https://clinicaltrials.gov/ct2/show/NCT02523560?term=NCT02523560&draw=2&rank=1 . Other Study ID Numbers: STRATEGME1/233547/13/NCBR/2015.

An aetiology-based subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH-HF) trial.

AIMS: The aim of our study was to analyse the benefits of a 9 week hybrid comprehensive telerehabilitation (HCTR) programme in heart failure (HF) patients according to aetiology, as a subanalysis of the Telerehabilitation in Heart Failure Patients (TELEREH-HF) trial. METHODS AND RESULTS: Overall, 555 (65.3%) patients with ischaemic (IS) and 295 (34.7%) patients with non-ischaemic (NIS) HF aetiology were randomized. There were no differences between the effect of HCTR and usual care (UC) on the primary outcome of number of days alive and out of the hospital in 26 months from the time of randomization in either aetiology (Wilcoxon-Mann-Whitney test), and no heterogeneity of effect between the aetiologies was noted (van Elteren test, P = 0.746). In Cox proportional hazards regression analysis, treatment was not independently associated with the secondary outcomes. For all-cause mortality, the adjusted hazard ratio for HCTR vs. UC was 0.90 (95% confidence interval, 0.54-1.51) in IS and 1.42 (95% confidence interval, 0.69-2.94) in NIS (P interaction = 0.316). Differences between HCTR and UC in terms of change in the 6 min walk test distance and cardiopulmonary exercise test time after 9 weeks reached statistical significance in the IS arm (P = 0.015 and P < 0.001, respectively), but not in the NIS arm; however, tests of heterogeneity indicated no statistically significant differences. CONCLUSIONS: The trial showed no difference between HCTR and UC in the primary outcome of percentage of days alive and out of the hospital for either IS or NIS aetiology. Moreover, the magnitude of changes in the clinical and functional statuses of the HF patients did not differ by aetiology. HCTR might have had beneficial effects on the 6 min walk test distance and cardiopulmonary exercise test time after 9 weeks in the IS patients; however, the effect was not statistically significantly different from that observed in the NIS patients.

Remote Monitoring of Cardiac Implantable Electronic Devices in Patients Undergoing Hybrid Comprehensive Telerehabilitation in Comparison to the Usual Care. Subanalysis from Telerehabilitation in Heart Failure Patients (TELEREH-HF) Randomised Clinical Trial.

BACKGROUND: The impact of cardiac rehabilitation on the number of alerts in patients with remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is unknown. We compared alerts in RM and outcomes in patients with CIEDs undergoing hybrid comprehensive telerehabilitation (HCTR) versus usual care (UC). METHODS: Patients with heart failure (HF) after a hospitalization due to worsening HF within the last 6 months (New York Heart Association (NYHA) class I-III and left ventricular ejection fraction (LVEF) ≤40%) were enrolled in the TELEREH-HF study and randomised 1:1 to HCTR or UC. Patients with HCTR and CIEDs received RM (HCTR-RM). Patients with UC and CIEDs were offered RM optionally (UC-RM). Data from the initial 9 weeks of the study were analysed. RESULTS: Of 850 enrolled patients, 208 were in the HCTR-RM group and 62 in the UC-RM group. The HCTR-RM group was less likely to have alerts of intrathoracic impedance (TI) decrease (p < 0.001), atrial fibrillation (AF) occurrence (p = 0.031) and lower mean number of alerts per patient associated with TI decrease (p < 0.0001) and AF (p = 0.019) than the UC-RM group. HCTR significantly decreased the occurrence of alerts in RM of CIEDs, 0.360 (95%CI, 0.189-0.686; p = 0.002), in multivariable regression analysis. There were two deaths in the HCTR-RM group (0.96%) and no deaths in the UC-RM group (p = 1.0). There were no differences in the number of hospitalised patients between the HCTR-RM and UC-RM group (p = 1.0). CONCLUSIONS: HCTR significantly reduced the number of patients with RM alerts of CIEDs related to TI decrease and AF occurrence. There were no differences in mortality or hospitalisation rates between HCTR-RM and UC-RM groups.

Effects of a 9-Week Hybrid Comprehensive Telerehabilitation Program on Long-term Outcomes in Patients With Heart Failure: The Telerehabilitation in Heart Failure Patients (TELEREH-HF) Randomized Clinical Trial.

Importance: Guidelines recommend exercise training as a component of heart failure management. There are large disparities in access to rehabilitation, and introducing hybrid comprehensive telerehabilitation (HCTR) consisting of remote monitoring of training at patients' homes might be an appealing alternative. Objective: To assess whether potential improvements in quality-of-life outcomes after a 9-week HCTR intervention in patients with heart failure translate into improvement in clinical outcomes during extended 12 to 24 months of follow-up, compared with usual care. Design, Setting, and Participants: The Telerehabilitation in Heart Failure Patients (TELEREH-HF) trial is a multicenter, prospective, open-label, parallel-group randomized clinical trial that enrolled 850 patients with heart failure up to 6 months after a cardiovascular hospitalization with New York Heart Association levels I, II, or III and left ventricular ejection fraction of 40% or less. Patients from 5 centers in Poland were randomized 1:1 to HCTR plus usual care or usual care only and followed up for 14 to 26 months after randomization. Interventions: During the first 9 weeks, patients underwent either an HCTR program (1 week in hospital and 8 weeks at home) or usual care with observation. The HCTR intervention encompassed telecare, telerehabilitation, and remote monitoring of implantable devices. No intervention occurred in the remaining study period. Main Outcomes and Measures: The percentage of days alive and out of the hospital from randomization through the end of follow-up at 14 to 26 months. Results: A total of 850 patients were enrolled, with 425 randomized to the HCTR group (377 male patients [88.7%]; mean [SD] age, 62.6 [10.8] years) and 425 randomized to usual care (376 male patients [88.5%]; mean [SD] age, 62.2 [10.2] years). The HCTR intervention did not extend the percentage of days alive and out of the hospital. The mean (SD) days were 91.9 (19.3) days in the HCTR group vs 92.8 (18.3) days in the usual-care group, with the probability that HCTR extends days alive and out of the hospital equal to 0.49 (95% CI, 0.46-0.53; P = .74) vs usual care. During follow-up, 54 patients died in the HCTR arm and 52 in the usual-care arm, with mortality rates at 26 months of 12.5% vs 12.4%, respectively (hazard ratio, 1.03 [95% CI, 0.70-1.51]). There were also no differences in hospitalization rates (hazard ratio, 0.94 [95% CI, 0.79-1.13]). The HCTR intervention was effective at 9 weeks, significantly improving peak oxygen consumption (0.95 [95% CI, 0.65-1.26] mL/kg/min vs 0.00 [95% CI, -0.31 to 0.30] mL/kg/min; P < .001) and quality of life (Medical Outcome Survey Short Form-36 questionnaire score, 1.58 [95% CI, 0.74-2.42] vs 0.00 [95% CI, -0.84 to 0.84]; P = .008), and it was well tolerated, with no serious adverse events during exercise. Conclusions and Relevance: In this trial, the positive effects of a 9-week program of HCTR in patients with heart failure did not lead to the increase in percentage of days alive and out of the hospital and did not reduce mortality and hospitalization over a follow-up period of 14 to 26 months. Trial Registration: ClinicalTrials.gov identifier: NCT02523560.

Ferritin as a potential biomarker of efficacy of treatment of atrial fibrillation - preliminary report.

BACKGROUND: Complex mechanisms of responsible for originating and maintaining of atrial fibrillation (AF) are involved in pathophysiology of this arrhythmia. Inflammation substantially contribute to arrhythmic remodelling of atrial tissue.The aim of the present study is to assess an applicability of ferritin and high sensitive C-reactive protein (hs-CRP) as biomarkers of atrial fibrillation and their usefulness in evaluation of efficacy of cryoablation. MATERIALS AND METHODS: The study population consisted of 40 patients who underwent first AF cryoablation procedure. The whole follow-up time was for 6 months. The efficacy of cryoablation was defined as lack of episodes of AF longer than 30 s reported either in patient's medical documentation or present in standard or Holter ECG records. Concentrations of hs-CRP (latex method ) and ferritin (immunochemical method) were determined in standard way in hospital laboratory. RESULTS: The recurrence of atrial fibrillation during follow-up was detected in 7 of 40 patients (efficacy 82.5%). Basal concentrations of hs-CRP and ferritin were significantly higher in patients who underwent ablation during AF. Ablation resulted in an increase of either hs-CRP or ferritin concentrations. After seven days, both hs-CRP and ferritin concentrations returned to basal level. The trend toward the higher concentration of hs-CRP was observed in AF recurrence subgroup in 30th and the 90th day after the procedure. Ferritin concentrations were significantly higher in recurrence subgroup after 30 and 90 days. CONCLUSION: Our results suggest that the evaluation of ferritin serum level can be a potential tool for assessment of AF treatment efficacy.

Do we need to monitor the percentage of biventricular pacing day by day?

BACKGROUND: Incidence and clinical significance of transient, daily fluctuations of biventricular pacing percentage (CRT%) remain unknown. We assessed the value of daily remote monitoring in identifying prognostically critical burden of low CRT%. METHODS AND RESULTS: Prospective, single-centre registry encompassed 304 consecutive heart failure patients with cardiac resynchronization therapy defibrillators (CRT-D). Patients with 24-h episodes of CRT% loss<95% were assigned to quartiles depending on cumulative time spent in low CRT%: quartile 1 (1-8days), 2 (9-20days), 3 (21-60days) and quartile 4 (>60days). During median follow-up of 35months 51,826 transmissions were analysed, including 15,029 in 208 (68.4%) patients with episodes of low CRT%. Overall, mean CRT%≥95% vs. <95% resulted in a 4-fold lower mortality (17.3 vs. 68.2%; p<0.001). Fifty-four percent of patients experienced episodes of CRT% loss, despite 85.6% having mean CRT%≥95%. Mortality was lowest in quartile 1 (7.7%), while longer periods of CRT% loss resulted in significantly higher death rates (25.0 vs. 34.6 vs. 57.7%; quartiles 2-4 respectively, p<0.001), despite mean CRT% still being ≥95% in quartiles 1-3. Cumulative low CRT% burden was the independent risk factor for death (HR 1.013; 95% CI 1.006-1.021; p<0.001). Mortality rose by 1.3 and 49% with every additional day and quartile of CRT% loss, respectively. CONCLUSIONS: Daily remote monitoring allows one to detect 24-h episodes of CRT% loss<95% in over two-thirds of CRT-D recipients during median observation of 3years. Cumulative low CRT% burden (in days) independently predicts mortality before mean CRT% drop.

Day by day telemetric care of patients treated with cardiac resynchronisation therapy: first Polish experience.

BACKGROUND: Due to the recent rapid increase in the number of patients implanted with pacemakers, cardioverter-defibrillators (ICD), and cardiac resynchronisation therapy devices (CRT), conventional monitoring at specialist clinics is becoming increasingly difficult. The development of technology has enabled remote device monitoring with the use of teletransmission systems. AIM: To assess the effectiveness of transmission and the possibility of using telemetric data for further clinical management of patients with heart failure (HF) treated with CRT-D. METHODS: The analysis included 305 consecutive patients with chronic HF, New York Heart Association functional classes II-IV, treated with the use of CRT-D by Biotronik or Medtronic in the years 2006-2012. The patients received transmitters, enabling the remote monitoring of the implanted device from the patients' houses. Scheduled reports were automatically sent every month. The triggers for pre-specified emergency alert transmissions were as follows: ventricular tachycardia (VT) or ventricular fibrillation (VF) episodes, CRT-D intervention, ventricular extrasystoles > 110/h, any episode of atrial fibrillation (AF), atrial flutter (AFL) or supraventricular tachycardia, mean heart rate (HR) during, mean 24-h HR, CRT pacing < 95%, Elective Replacement Indicator, or End Of Service and device malfunction. The all-cause mortality of the study population has been assessed at the end of the follow-up period (mean of 20.5 months). RESULTS: Devices manufactured by Biotronik were provided to 71% of the study population, while 29% received devices by Medtronic. In 97.3% of cases, the monitors were wireless, fully automatic, and capable of immediate data transmission whenever a pre-specified alert notification was fulfilled. The analysis of long-term outcomes revealed that all-cause mortality of the whole study population was 13%. The effectiveness of report transmission was 98%. During follow-up a total of 31,198 transmissions were received and analysed, which constituted, on average, 4.9 transmissions per patient per month. Among analyses, 30% were reports generated by scheduled remote follow-ups, and 70% were caused by unscheduled device alerts. Correct functioning of the system was confirmed; the quality of the received data was 100%. In 63.9% of patients, decisions based on the information obtained from telemonitoring reports were made to modify the therapy, refer the patients to cardiology or electrophysiology clinics, or hospitalise them urgently. The most common medical reaction was device reprogramming (46.8%). Pharmacotherapy was modified in 33.7% of patients: beta-blocker dose increase (25.9%), anticoagulant treatment inclusion (15.7%), amiodarone inclusion (1.9%), or digoxin inclusion (4.5%). The remaining medical responses were referring patients for atrioventricular junction ablation (8.1%), VT ablation (2.9%), or AF/AFl ablation (1.6%). CONCLUSIONS: Remote monitoring of implantable devices is feasible, safe, and effective in supervising patients with CRT-D devices. Daily-based remote monitoring of a large population of HF patients allows continuous "triage" of high-risk patients and selection of individuals who require urgent intervention.

Prognostic value of collagen turnover biomarkers in cardiac resynchronization therapy: A subanalysis of the TRUST CRT randomized trial population.

BACKGROUND: A substantial proportion of patients do not respond to cardiac resynchronization therapy (CRT). Various echocardiographic and biochemical markers including collagen turnover biomarkers were suggested to predict CRT results. However, pathological significance of collagen turnover biomarkers in CRT remains controversial. OBJECTIVE: The aim of the present study was to evaluate the relationship between levels of collagen turnover biomarkers (amino-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III [PIIINP]), N-terminal of the prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein, and matrix metalloproteinases (metalloproteinase-2 and metalloproteinase-9) and echocardiographic response to CRT and clinical outcomes. METHODS: The study population consisted of patients enrolled in the Triple Site Versus Standard Cardiac Resynchronization Therapy trial. Blood samples were obtained before implantation of a CRT with defibrillator. The levels of PIIINP, amino-terminal propeptide of procollagen type I, metalloproteinase-2, and metalloproteinase-9 were determined using commercially available ELISA kits. High-sensitivity C-reactive protein and NT-proBNP levels were determined in a standard way. RESULTS: Samples were collected from 74 of 100 enrolled patients. The multivariate logistic regression analysis demonstrated that low PIIINP levels (odds ratio [OR] 3.56; 95% confidence interval [CI] 1.23-10.24; P = .017) and baseline ejection fraction (OR 2.14; 95% CI 1.11-4.11; P = .02) were favorably associated with echocardiographic response. PIIINP and NT-proBNP levels appeared to be independent predictors of all-cause mortality (PIIINP: OR 3.11; 95% CI 1.21-7.89; P = .033; NT-proBNP: OR 2.05; 95% CI 1.11-4.96; P = .039) and risk of major cardiac adverse event (PIIINP: OR 3.56; 95% CI 1.53-9.15; P = .007; NT-proBNP: OR 4.51; 95% CI 1.75-11.6; P = .001). PIIINP levels showed significant additive value in predicting mortality as compared with NT-proBNP levels, but they were not superior to ejection fraction in predicting response. Survival analysis with cutoff values identified by receiver operating characteristic analysis confirmed a significant benefit associated with low baseline PIIINP levels. CONCLUSION: Low PIIINP levels are associated with favorable echocardiographic response and long-term survival in CRT recipients.

Efficacy of cardiac resynchronisation therapy in the treatment of end-stage inotrope-dependent heart failure patients.

BACKGROUND AND AIM: Currently, cardiac resynchronisation therapy (CRT) is recommended only for New York Heart Association (NYHA) class IV ambulatory patients. However, some recent reports have suggested that CRT could also be beneficial for end-stage inotrope-dependent heart failure (HF) NYHA class IV patients. In this report, we summarise the results of CRT implantation in a group of 11 HF inotrope-dependent patients who were not candidates for urgent orthotopic heart transplantation (OHT). METHODS AND RESULTS: Between August 2006 and June 2011, 11 end-stage inotrope-dependent HF patients with wide QRS complex, ineligible for urgent OHT, were implanted with CRT in the Silesian Centre for Heart Diseases in Zabrze. Dependence on inotropic therapy was defined as an inability to stop the infusion of the drug without the occurrence of hypotension, oligooranuria and/or hypoxaemia. All patients were successfully implanted with CRT and subsequently weaned from inotropes in a median time of two (1-17) days. Mean QRS duration shortened from 190 ± 34 ms at baseline to 142 ± 25 ms (p < 0.001) after the procedure. Average left ventricular ejection fraction increased from 19 ± 4% to 25 ± 4% (p < 0.001). All patients were discharged from hospital. Median hospital stay after the procedure was ten (5-56) days. During the median follow-upof 1,212 (182-2,048) days, four patients died (one due to arrhythmic storm, three others due to progressive pump failure). During that period, 57 adequate device interventions occurred in three patients, including 52 therapies in one fatal case. CONCLUSIONS: CRT can be an alternative for end-stage inotrope-dependent HF patients with wide QRS who are ineligible for urgent heart transplantation.

Long-term outcomes of cardiac resynchronization therapy are worse in patients who require atrioventricular junction ablation for atrial fibrillation than in those with sinus rhythm.

BACKGROUND: The aim of the study was to assess the impact of atrial fibrillation (AF) with and without the need for atrioventricular junction (AVJ) ablation on outcomes in patients undergoing cardiac resynchronization therapy (CRT). METHODS: A single center cohort of 200 consecutive CRT patients was divided into three groups: 1) AF with CRT pacing < 95% in which AVJ ablation was performed (AF-ABL, n = 40; 20%), 2) AF without the need for AVJ ablation (AF-non ABL, n = 40; 20%), 3) sinus rhythm (SR, n = 120; 60%). All patients were assessed before CRT implantation and at 6-month follow-up. Positive clinical response to CRT was considered alive status without the need for heart transplantation and improvement ≥ 1 NYHA after 6 months. The comparative analysis among all study groups with respect to response-rate and long-term survival was performed. RESULTS: The 6-month response-rate in both AF-ABL and AF-nonABL was significantly lower than in SR (52.5 and 50 vs.77.5%, respectively; both p < 0.017), though there were no differences in baseline characteristics among study groups apart from higher baseline NT-proBNP levels in AF-ABL. However, after adjustment for this confounder, and despite optimal CRT pacing burden in study groups, the remote all-cause mortality during median follow-up of 36.1 months was significantly higher in AF-ABL than in SR (adjusted HR = 2.57, 95% CI 1.09-6.02, p = 0.03). What is more, no difference in long-term survival between SR and AF-nonABL was observed. CONCLUSIONS: Despite the improvement of CRT pacing burden and thus response-rate up to the level of AF subjects without the need for ablation, the long-term survival of AF patients requiring AVJ ablation remains still worse than in SR.

[Atrial fibrillation in patient with concealed Wolff-Parkinson-White syndrome]. / Migotanie przedsionków u chorej z utajonym zespolem Wolffa-Parkinsona-White'a.

We present a case of 33-year-old woman suffered from palpitations and syncope. ECG was normal at the rest and showed irregular tachycardia with wide QRS complex (HR > 300/min) during the effort. The patient was admitted to our department in order to perform detailed diagnostics and therapy. Based on electrophysiological study we found and ablated numerous concealed accessory pathways. During 1 year observation patient stay assymptomatic.