Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).

Diagnostic electrocardiographic trap: A case of conduction system pacing.

His-bundle pacing (HBP) is a relatively new method of cardiac pacing, with recent studies showing an association between HBP and a lower risk of developing right ventricular heart failure compared to classical pacing methods. However, HBP is also associated with a higher risk of lead dislodgement, undersensing, and loss of capture. As such, a detailed assessment of pacing effectiveness in pacemaker patients is vital. In the presented case, an electrocardiogram (ECG) recording seems to present successful selective His-bundle pacing, while pacemaker follow-up demonstrated the loss of ventricular capture. In conclusion, patients receiving HBP should undergo ECG alongside pacing parameter analysis and pacing electrograms, as differences in successful and unsuccessful pacing ECG can be very subtle.

Rate-Responsive Cardiac Pacing: Technological Solutions and Their Applications.

Modern cardiac pacemakers are equipped with a function that allows the heart rate to adapt to the current needs of the patient in situations of increased demand related to exercise and stress ("rate-response" function). This function may be based on a variety of mechanisms, such as a built-in accelerometer responding to increased chest movement or algorithms sensing metabolic demand for oxygen, analysis of intrathoracic impedance, and analysis of the heart rhythm (Q-T interval). The latest technologies in the field of rate-response functionality relate to the use of an accelerometer in leadless endocavitary pacemakers; in these devices, the accelerometer enables mapping of the mechanical wave of the heart's work cycle, enabling the pacemaker to correctly sense native impulses and stimulate the ventricles in synchrony with the cycles of atria and heart valves. Another modern system for synchronizing pacing rate with the patient's real-time needs requires a closed-loop system that continuously monitors changes in the dynamics of heart contractions. This article discusses the technical details of various solutions for detecting and responding to situations related to increased oxygen demand (e.g., exercise or stress) in implantable pacemakers, and reviews the results of clinical trials regarding the use of these algorithms.

Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. METHODS: In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II-III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2-4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. FINDINGS: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (-36 mm Hg, 95% CI -43·2 to -28·1; p<0·0001), greater increase in pVO2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB -1·8, -2·4 to -1·2; p<0·0001). 34% more patients in the mavacamten group improved by at least one NYHA class (80 of 123 patients in the mavacamten group vs 40 of 128 patients in the placebo group; 95% CI 22·2 to 45·4; p<0·0001). Safety and tolerability were similar to placebo. Treatment-emergent adverse events were generally mild. One patient died by sudden death in the placebo group. INTERPRETATION: Treatment with mavacamten improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive hypertrophic cardiomyopathy. The results of this pivotal trial highlight the benefits of disease-specific treatment for this condition. FUNDING: MyoKardia.

Safety and efficacy of aficamten in patients with non-obstructive hypertrophic cardiomyopathy: A 36-week analysis from FOREST-HCM.

AIMS: The aim of this study was to report safety and efficacy of aficamten in patients with non-obstructive hypertrophic cardiomyopathy (nHCM) over 36 weeks in the ongoing FOREST-HCM trial. METHODS AND RESULTS: Patients were started on aficamten 5 mg daily, with doses adjusted in 5-mg increments (5-20 mg) at ≥2-week intervals according to site-read left ventricular ejection fraction (LVEF). Aficamten dose was increased if LVEF ≥55%, maintained if LVEF 50-54%, decreased if LVEF 40-<50%, and temporarily interrupted if LVEF <40%. Safety and efficacy were assessed over 36 weeks. Overall, 34 patients were enrolled (mean age 57.2 ± 15.3 years, 62% female, 41% in New York Heart Association [NYHA] class III). Over 36 weeks, 82.3% achieved 15-20 mg daily dose and there was a modest reduction in LVEF by -4.3% ± 5.2 from 70% ± 6.1 (p < 0.0001). At Week 36, NYHA class improved by ≥1 class in 27 (79.4%) patients. Mean Kansas City Cardiomyopathy Questionnaire clinical summary score improved by 13.8 ± 12.5 points relative to baseline. Median (interquartile range) levels of N-terminal pro-B-type natriuretic peptide were significantly improved from baseline (-665.5 pg/ml [-1244.0, -232.0]; p < 0.0001), while high-sensitivity cardiac troponin I was unchanged (-2.7 ng/L [-11.3, 1.6]; p = 0.25). There were no drug discontinuations due to adverse events. LVEF <50% occurred in 2 (5.9%) patients, one following pulmonary vein isolation and one associated with atrial fibrillation. CONCLUSIONS: Over 36 weeks, aficamten appeared safe and effective in the studied patients with nHCM.

Mavacamten Treatment for Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results From the MAVA-LTE Study, EXPLORER-LTE Cohort.

BACKGROUND: Data assessing the long-term safety and efficacy of mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy are needed. OBJECTIVES: The authors sought to evaluate interim results from the EXPLORER-Long Term Extension (LTE) cohort of MAVA-LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM; NCT03723655). METHODS: After mavacamten or placebo withdrawal at the end of the parent EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545), patients could enroll in MAVA-LTE. Patients received mavacamten 5 mg once daily; adjustments were made based on site-read echocardiograms. RESULTS: Between April 9, 2019, and March 5, 2021, 231 of 244 eligible patients (94.7%) enrolled in MAVA-LTE (mean age: 60 years; 39% female). At data cutoff (August 31, 2021) 217 (93.9%) remained on treatment (median time in study: 62.3 weeks; range: 0.3-123.9 weeks). At 48 weeks, patients showed improvements in left ventricular outflow tract (LVOT) gradients (mean change ± SD from baseline: resting: -35.6 ± 32.6 mm Hg; Valsalva: -45.3 ± 35.9 mm Hg), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (median: -480 ng/L; Q1-Q3: -1,104 to -179 ng/L), and NYHA functional class (67.5% improved by ≥1 class). LVOT gradients and NT-proBNP reductions were sustained through 84 weeks in patients who reached this timepoint. Over 315 patient-years of exposure, 8 patients experienced an adverse event of cardiac failure, and 21 patients had an adverse event of atrial fibrillation, including 11 with no prior history of atrial fibrillation. Twelve patients (5.2%) developed transient reductions in site-read echocardiogram left ventricular ejection fraction of <50%, resulting in temporary treatment interruption; all recovered. Ten patients discontinued treatment due to treatment-emergent adverse events. CONCLUSIONS: Mavacamten treatment showed clinically important and durable improvements in LVOT gradients, NT-proBNP levels, and NYHA functional class, consistent with EXPLORER-HCM. Mavacamten treatment was well tolerated over a median 62-week follow-up.

Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design.

Patients with obstructive hypertrophic cardiomyopathy (oHCM) have increased risk of arrhythmia, stroke, heart failure, and sudden death. Contemporary management of oHCM has decreased annual hospitalization and mortality rates, yet patients have worsening health-related quality of life due to impaired exercise capacity and persistent residual symptoms. Here we consider the design of clinical trials evaluating potential oHCM therapies in the context of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). This large, phase 3 trial is now fully enrolled (N = 282). Baseline characteristics reflect an ethnically diverse population with characteristics typical of patients encountered clinically with substantial functional and symptom burden. The study will assess the effect of aficamten vs placebo, in addition to standard-of-care medications, on functional capacity and symptoms over 24 weeks. Future clinical trials could model the approach in SEQUOIA-HCM to evaluate the effect of potential therapies on the burden of oHCM. (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM [SEQUOIA-HCM]; NCT05186818).

Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial.

Importance: Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten's effects on exercise performance remains unclear. Objective: To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET). Design, Setting, and Participants: Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled. Interventions: Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo. Main Outcomes and Measures: The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO2), and VO2/workload slope. Results: Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak VE/VCO2 ratio (least squares [LS] mean difference, -2.2; 95% CI, -3.05 to -1.26; P < .001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60; P < .001), peak circulatory power (LS mean difference, 372.9 mL/kg/min × mm Hg; 95% CI, 153.12-592.61; P = .001), and peak PETCO2 (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79; P < .001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24; P = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as VE/VCO2 slope (LS mean difference, -2.6; 95% CI, -3.58 to -1.52; P < .001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90; P < .001) favoring mavacamten vs placebo. Conclusions and Relevance: Mavacamten improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM. Trial Registration: ClinicalTrials.gov Identifier: NCT03470545.

Sudden Cardiac Death Risk over Time in HCM Patients with Implantable Cardioverter-Defibrillator.

Background: In patients with HCM at high risk of SCD, an ICD should be considered as a standard of care. Current risk approximation algorithms recommended by ESC 2014 criteria indicate that SCD risk is not stable. The aim of the study was to investigate how the calculated SCD risk in HCM patients with an ICD implanted in the past changed over time. Methods: We analyzed 64 HCM patients with ICD for primary prevention, referred for ICD re-implantation, and 32 HCM patients referred for a first-time ICD placement during the same period. The 5-year-SCD risk was assessed for suitable patients using the recommended ESC calculator. Results: The first-time group had a higher 5-year-SCD risk than those referred for ICD re-implantation: 7.50 (IQR 5.98−10.46) vs. 4.88 (IQR 3.42−7.25), p < 0.05. Out of the patients with an initial calculated risk below 4%, the risk increased in 22% of cases, reaching the 4−6% range. In 78% of patients, the risk remained stable and low. In 31% of patients with an initial calculated SCD risk ≥ 6%, the risk decreased over time to below 6%, and in 14% of the cases, below 4%. Conclusions: SCD risk in HCM patients is usually stable or gets lower. Our data suggest it is important to re-evaluate the risk profile for patients with HCM when ICD re-implantation is considered.

Titin-Related Dilated Cardiomyopathy: The Clinical Trajectory and the Role of Circulating Biomarkers in the Clinical Assessment.

Titin truncating variants (TTNtv) are known as the leading cause of inherited dilated cardiomyopathy (DCM). Nevertheless, it is unclear whether circulating cardiac biomarkers are helpful in detection and risk assessment. We sought to assess 1) early indicators of cardiotitinopathy including the serum biomarkers high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in clinically stable patients, and 2) predictors of outcome among TTNtv carriers. Our single-center cohort consisted of 108 TTNtv carriers (including 70 DCM patients) from 43 families. Clinical, laboratory and follow-up data were analyzed. The earliest abnormality was left ventricular dysfunction, present in 8, 26 and 47% of patients in the second, third and fourth decade of life, respectively. It was followed by symptoms of heart failure, linked to NT-proBNP elevation and severe left ventricular systolic dysfunction, and later by arrhythmias. Hs-cTnT serum levels were increased in the late stage of the disease only. During the median follow-up of 5.2 years, both malignant ventricular arrhythmia (MVA) and end-stage heart failure (esHF) occurred in 12% of TTNtv carriers. In multivariable analysis, NT-proBNP level ≥650 pg/mL was the best predictor of both composite endpoints (MVA and esHF) and of MVA alone. In conclusion, echocardiographic abnormalities are the first detectable anomalies in the course of cardiotitinopathies. The assessment of circulating cardiac biomarkers is not useful in the detection of the disease onset but may be helpful in risk assessment.

Predictors of successful defibrillation threshold test during CRT-D implantation.

BACKGROUND: The assessment of defibrillation energy requirement (DER) is a standard practice during cardioverter-defibrillator (ICD) implantation. It is recommended to assure that the energy at least 10 J below the maximal energy deliverable by the implanted device successfully converts the induced ventricular fibrillation (VF). The cardiac resynchronisation therapy with defibrillator (CRT-D) recipients are at increased risk of developing serious complications due to repeated VF induction. AIM: To define the prevalence of high DER among CRT-D recipients and to determine the factors which allow to obtain defibrillation safety margin. METHODS: We examined all patients who underwent CRT-D implantation between June 2006 and June 2009 in our institution. The verification of the DER required at least one termination of the induced VF with the energy at least 10 J below the maximal energy deliverable by the implanted device. RESULTS: The CRT-D was implanted in 65 patients. The first defibrillation test was successful in 57 (88%) patients. In the remaining 8 patients (12%), the defibrillation test was unsuccessful. These patients required system revision: reprogramming shocking polarity (2), reversing polarity and adjusting waveform (3), lead repositioning (1) and adding a subcutaneous lead (2). The use of high output devices (maximal energy > 30 J) and dual-coil leads was associated with a significantly (p < 0.05) lower rate of high DER, although high DER occurred in one patient implanted with the high output device. There was a correlation between the probability of successful defibrillation and renal function. It was less likely to obtain successful defibrillation safety margin in patients with creatinine > 175 micromol/L. During the follow up, ventricular tachyarrhythmia detected in the VF detection zone occurred in 13 (20%) patients, including two patients, who required system modification during implantation. In both cases, VF was terminated by the first defibrillation with the maximal energy of the implanted devices. CONCLUSIONS: High DER occurred in a significant number of CRT-D recipients. There is a correlation between high DER and impaired renal function. The use of high output devices significantly decreases the number of patients who required system modification in order to obtain an adequate defibrillation safety margin.

Patient perspective and safety of remote monitoring of implantable cardioverter-defibrillators in the Polish Nationwide Multicenter Registry: the Medtronic CareLink network evaluation.

BACKGROUND: Remote monitoring of cardiovascular implantable electronic devices allows the assessment of system effectiveness, arrhythmia occurrence, and indirectly, clinical changes. Medical interventions can be performed earlier because of a faster transfer of information to the monitoring site, even in the case of asymptomatic arrhythmias or abnormalities in the operation of the system. AIMS: The aim of the study was to assess the effectiveness of remote monitoring of implantable cardioverter-defibrillators and evaluation in an outpatient setting during 12-month follow -up. METHODS: We analyzed 176 patients at 10 sites (men, 84.1%). The mean (SD) age of the patients was 60.7 (12.5) years (range, 20-86 years), and mean (SD) follow -up period was 405 (70) days (range, 131-723 days). RESULTS: A total of 354 outpatient and 514 remote follow -up visits were conducted. Episodes of arrhythmias and device malfunctions were detected with similar frequency in outpatient visits and in remote visits. During the study period, patient sense of safety increased. More patients preferred joined remote and outpatient visits as the optimal healthcare model. As the patient survey showed, the greatest benefit of the CareLink network was fast intervention and an increased sense of safety. CONCLUSIONS: The strategy of remote monitoring appeared to be feasible, safe, and patient friendly, demonstrating that the majority of patients do not require an additional in -person visit within 1 year from the device implantation just to confirm the proper functioning of the implantable cardioverter--defibrillators.

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.

Can Circulating Cardiac Biomarkers Be Helpful in the Assessment of LMNA Mutation Carriers?

Mutations in the lamin A/C gene are variably phenotypically expressed; however, it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment of cardiolaminopathies. We sought to assess (1) clinical characteristics including serum biomarkers: high sensitivity troponin T (hsTnT) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in clinically stable cardiolaminopathy patients, and (2) outcome among pathogenic/likely pathogenic lamin A/C gene (LMNA) mutation carriers. Our single-centre cohort included 53 patients from 21 families. Clinical, laboratory, follow-up data were analysed. Median follow-up was 1522 days. The earliest abnormality, emerging in the second and third decades of life, was elevated hsTnT (in 12% and in 27% of patients, respectively), followed by the presence of atrioventricular block, heart failure, and malignant ventricular arrhythmia (MVA). In patients with missense vs. other mutations, we found no difference in MVA occurrence and, surprisingly, worse transplant-free survival. Increased levels of both hsTnT and NT-proBNP were strongly associated with MVA occurrence (HR > 13, p ≤ 0.02 in both) in univariable analysis. In multivariable analysis, NT-proBNP level > 150 pg/mL was the only independent indicator of MVA. We conclude that assessment of circulating cardiac biomarkers may help in the detection and risk assessment of cardiolaminopathies.

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.

Unsuccessful left ventricular lead implantation in two first-degree relatives. Is the coronary venous anatomy similar in both cases?

We reported on two unsuccessful implantations of the left ventricular lead in two first-degree relatives due to inability to cannulate the coronary sinus (CS). The anatomy of the coronary venous system investigated by means of dual source computed tomography showed several similarities in both patients: narrowing of the proximal part of CS and a small number of CS tributaries.

[Ventricular bigeminy as a cause of CRT inefficacy and inappropriate cardioverter-defibrillator intervention]. / Bigeminia komorowa jako przyczyna nieskutecznosci terapii resynchronizujacej i nieadekwatnych interwencji kardiowertera-defibrylatora.

Double counting of ventricular beats is not only one of the cause of an inappropriate detection of ventricular arrhythmias but a reason of lost of resynchronisation therapy. Sensing disturbances often creates the need for reprogramming of the device or additional pharmacotherapy and procedures. We present a case of 76-year-old man with CRT-D and inappropriate detection and intervention due to ventricular bigeminy. Fortunately, change of device program, potassium and magnesium supplementation was successful, without necessity of RF ablation of the ventricular ectopic beats.

Experts of the Heart Rhythm Section of the Polish Cardiac Society: opinion on the use of wearable cardioverter-defibrillators in Poland.

Sudden cardiac death (SCD) is one of the main causes of mortality in developed countries. Implantable cardioverter-defibrillators (ICDs) have become a widely used and efficient method for SCD prevention in high-risk populations. Nevertheless, there are clinical situations in which the benefit of ICD is uncertain, such as: early postinfarction left ventricular dysfunction, reversible causes of cardiomyopathy, presence of temporary or permanent ICD contraindications in high-risk populations, or when ICD is not accepted by SCD prevention candidates. Wearable cardioverter-defibrillator (WCD) can be an alternative option in these clinical circumstances. However, even though WCDs are available in the United States and many countries of Western Europe, they are still not available in Poland. The authors present clinical and organisational recommendations for WCD use in Poland, with respect to medical evidence.

Patients with cardiac implantable electronic devices undergoing radiotherapy in Poland. Expert opinion of the Heart Rhythm Section of the Polish Cardiac Society and the Polish Society of Radiation Oncology.

Older age and high morbidity of the society contribute to a growing number of patients with cardiac implantable electronic devices (CIEDs) requiring effective cancer treatment, including radiotherapy (RT). The effect of RT on a CIED may vary depending on the type and physical parameters of radiation, location of the treated lesion, indications for electrotherapy, and the type of CIED. In the most dramatic scenarios, it may cause an irreversible damage to the CIED, with serious clinical consequences. The lack of precise guidelines may limit the access to RT for many patients with CIEDs who would otherwise benefit from the therapy or may lead to a therapy without taking the necessary precautions, which may worsen the prognosis. Therefore, clear and unequivocal recommendations for assessing patient eligibility for RT are aimed at ensuring that adequate precautions are taken as well as at providing patients with concomitant cardiovascular and oncologic diseases with access to safe and effective RT.