Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy.

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.

Investigating the Cost-Effectiveness of Telemonitoring Patients With Cardiac Implantable Electronic Devices: Systematic Review.

BACKGROUND: Telemonitoring patients with cardiac implantable electronic devices (CIEDs) can improve their care management. However, the results of cost-effectiveness studies are heterogeneous. Therefore, it is still a matter of debate whether telemonitoring is worth the investment. OBJECTIVE: This systematic review aims to investigate the cost-effectiveness of telemonitoring patients with CIEDs, focusing on its key drivers, and the impact of the varying perspectives. METHODS: A systematic review was performed in PubMed, Web of Science, Embase, and EconLit. The search was completed on July 7, 2022. Studies were included if they fulfilled the following criteria: patients had a CIED, comparison with standard care, and inclusion of health economic evaluations (eg, cost-effectiveness analyses and cost-utility analyses). Only complete and peer-reviewed studies were included, and no year limits were applied. The exclusion criteria included studies with partial economic evaluations, systematic reviews or reports, and studies without standard care as a control group. Besides general study characteristics, the following outcome measures were extracted: impact on total cost or income, cost or income drivers, cost or income drivers per patient, cost or income drivers as a percentage of the total cost impact, incremental cost-effectiveness ratios, or cost-utility ratios. Quality was assessed using the Consensus Health Economic Criteria checklist. RESULTS: Overall, 15 cost-effectiveness analyses were included. All studies were performed in Western countries, mainly Europe, and had primarily a male participant population. Of the 15 studies, 3 (20%) calculated the incremental cost-effectiveness ratio, 1 (7%) the cost-utility ratio, and 11 (73%) the health and cost impact of telemonitoring. In total, 73% (11/15) of the studies indicated that telemonitoring of patients with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs was cost-effective and cost-saving, both from a health care and patient perspective. Cost-effectiveness results for telemonitoring of patients with pacemakers were inconclusive. The key drivers for cost reduction from a health care perspective were hospitalizations and scheduled in-office visits. Hospitalization costs were reduced by up to US $912 per patient per year. Scheduled in-office visits included up to 61% of the total cost reduction. Key drivers for cost reduction from a patient perspective were loss of income, cost for scheduled in-office visits and transport. Finally, of the 15 studies, 8 (52%) reported improved quality of life, with statistically significance in only 1 (13%) study (P=.03). CONCLUSIONS: From a health care and patient perspective, telemonitoring of patients with an ICD or a cardiac resynchronization therapy ICD is a cost-effective and cost-saving alternative to standard care. Inconclusive results were found for patients with pacemakers. However, telemonitoring can lead to a decrease in providers' income, mainly due to a lack of reimbursement. Introducing appropriate reimbursement could make telemonitoring sustainable for providers while still being cost-effective from a health care payer perspective. TRIAL REGISTRATION: PROSPERO CRD42022322334; https://tinyurl.com/puunapdr.

Lifelong endurance exercise and its relation with coronary atherosclerosis.

AIMS: The impact of long-term endurance sport participation (on top of a healthy lifestyle) on coronary atherosclerosis and acute cardiac events remains controversial. METHODS AND RESULTS: The Master@Heart study is a well-balanced prospective observational cohort study. Overall, 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile, were included. Peak oxygen uptake quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on computed tomography coronary angiography. Analyses were corrected for multiple cardiovascular risk factors. The median age was 55 (50-60) years in all groups. Lifelong and late-onset athletes had higher peak oxygen uptake than non-athletes [159 (143-177) vs. 155 (138-169) vs. 122 (108-138) % predicted]. Lifelong endurance sports was associated with having ≥1 coronary plaque [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.17-2.94], ≥ 1 proximal plaque (OR 1.96, 95% CI 1.24-3.11), ≥ 1 calcified plaques (OR 1.58, 95% CI 1.01-2.49), ≥ 1 calcified proximal plaque (OR 2.07, 95% CI 1.28-3.35), ≥ 1 non-calcified plaque (OR 1.95, 95% CI 1.12-3.40), ≥ 1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39-5.65), and ≥1 mixed plaque (OR 1.78, 95% CI 1.06-2.99) as compared to a healthy non-athletic lifestyle. CONCLUSION: Lifelong endurance sport participation is not associated with a more favourable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum.

Regional beat-to-beat variability of repolarization increases during ischemia and predicts imminent arrhythmias in a pig model of myocardial infarction.

Ventricular arrhythmia (VT/VF) can complicate acute myocardial ischemia (AMI). Regional instability of repolarization during AMI contributes to the substrate for VT/VF. Beat-to-beat variability of repolarization (BVR), a measure of repolarization lability increases during AMI. We hypothesized that its surge precedes VT/VF. We studied the spatial and temporal changes in BVR in relation to VT/VF during AMI. In 24 pigs, BVR was quantified on 12-lead electrocardiogram recorded at a sampling rate of 1 kHz. AMI was induced in 16 pigs by percutaneous coronary artery occlusion (MI), whereas 8 underwent sham operation (sham). Changes in BVR were assessed at 5 min after occlusion, 5 and 1 min pre-VF in animals that developed VF, and matched time points in pigs without VF. Serum troponin and ST deviation were measured. After 1 mo, magnetic resonance imaging and VT induction by programmed electrical stimulation were performed. During AMI, BVR increased significantly in inferior-lateral leads correlating with ST deviation and troponin increase. BVR was maximal 1 min pre-VF (3.78 ± 1.36 vs. 5 min pre-VF, 1.67 ± 1.56, P < 0.0001). After 1 mo, BVR was higher in MI than in sham and correlated with the infarct size (1.43 ± 0.50 vs. 0.57 ± 0.30, P = 0.009). VT was inducible in all MI animals and the ease of induction correlated with BVR. BVR increased during AMI and temporal BVR changes predicted imminent VT/VF, supporting a possible role in monitoring and early warning systems. BVR correlated to arrhythmia vulnerability suggesting utility in risk stratification post-AMI.NEW & NOTEWORTHY The key finding of this study is that BVR increases during AMI and surges before ventricular arrhythmia onset. This suggests that monitoring BVR may be useful for monitoring the risk of VF during and after AMI in the coronary care unit settings. Beyond this, monitoring BVR may have value in cardiac implantable devices or wearables.

Effectiveness of the risk stratification proposed by the 2022 European Heart Rhythm Association Expert Consensus statement on arrhythmic mitral valve prolapse.

BACKGROUND: Recently, an expert consensus statement proposed indications where implantation of a primary prevention implantable cardioverter-defibrillator (ICD) may be reasonable in patients with mitral valve prolapse (MVP). The objective was to evaluate the proposed risk stratification by the expert consensus statement. METHODS: Consecutive patients with MVP without alternative arrhythmic substrates with cardiac magnetic resonance imaging (CMR) were included in a single-center retrospective registry. Arrhythmic MVP (AMVP) was defined as a total premature ventricular complex burden ≥5%, non-sustained ventricular tachycardia (VT), VT, or ventricular fibrillation. The end point was a composite of SCD, VT, inducible VT, and appropriate ICD shocks. RESULTS: In total, 169 patients (52.1% male, median age 51.4 years) were included and 99 (58.6%) were classified as AMVP. Multivariate logistic regression identified the presence of late gadolinium enhancement (OR 2.82, 95%CI 1.45-5.50) and mitral annular disjunction (OR 1.98, 95%CI 1.02-3.86) as only predictors of AMVP. According to the EHRA risk stratification, 5 patients with AMVP (5.1%) had a secondary prevention ICD indication, while in 69 patients (69.7%) the implantation of an ICD may be reasonable. During a median follow-up of 8.0 years (IQR 5.0-15.6), the incidence rate for the composite arrhythmic end point was 0.3%/year (95%CI 0.1-0.8). CONCLUSION: More than half of MVP patients referred for CMR met the AMVP diagnostic criteria. Despite low long-term event rates, in 70% of patients with AMVP the implantation of an ICD may be reasonable. Risk stratification of SCD in MVP remains an important knowledge gap and requires urgent investigation.

Evolution of ventricular and valve function in patients with right ventricular pacing - A randomized controlled trial comparing leadless and conventional pacing.

BACKGROUND: Leadless pacemakers (PMs) were recently introduced to overcome lead-related complications. They showed high safety and efficacy profiles. Prospective studies assessing long-term safety on cardiac structures are still missing. OBJECTIVE: The purpose of this study was to compare the mechanical impact of Micra with conventional PM on heart function. METHODS: We conducted a non-inferiority trial in patients with an indication for single chamber ventricular pacing. Patients were 1:1 randomized to undergo implantation of either Micra or conventional monochamber ventricular pacemaker (PM). Patients underwent echocardiography at baseline, 6 and 12 months after implantation. Analysis included left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and valve function. N-terminal-pro hormone B-type natriuretic peptide (NT-pro-BNP) levels were measured at baseline and 12 months. RESULTS: Fifty-one patients (27 in Micra group and 24 in conventional group) were included. Baseline characteristics were similar for both groups. At 12 months, (1) the left ventricular function as assessed by LVEF and GLS worsened similarly in both groups (∆LVEF -10 ± 7.3% and ∆GLS +5.7 ± 6.4 in Micra group vs. -13.4 ± 9.9% and +5.2 ± 3.2 in conventional group) (p = 0.218 and 0.778, respectively), (2) the severity of tricuspid valve regurgitation was significantly lower with Micra than conventional pacing (p = 0.009) and (3) median NT-pro-BNP was lower in Micra group (970 pg/dL in Micra group versus 1394 pg/dL in conventional group, p = 0.041). CONCLUSION: Micra is non inferior to conventional PMs concerning the evolution of left ventricular function at 12-month follow-up. Our data suggest that Micra has a comparable mechanical impact on the ventricular systolic function but resulted in less valvular dysfunction.

Exercise-induced myocardial T1 increase and right ventricular dysfunction in recreational cyclists: a CMR study.

PURPOSE: Although cardiac troponin I (cTnI) increase following strenuous exercise has been observed, the development of exercise-induced myocardial edema remains unclear. Cardiac magnetic resonance (CMR) native T1/T2 mapping is sensitive to the pathological increase of myocardial water content. Therefore, we evaluated exercise-induced acute myocardial changes in recreational cyclists by incorporating biomarkers, echocardiography and CMR. METHODS: Nineteen male recreational participants (age: 48 ± 5 years) cycled the 'L'étape du tour de France" (EDT) 2021' (175 km, 3600 altimeters). One week before the race, a maximal graded cycling test was conducted to determine individual heart rate (HR) training zones. One day before and 3-6 h post-exercise 3 T CMR and echocardiography were performed to assess myocardial native T1/T2 relaxation times and cardiac function, and blood samples were collected. All participants were asked to cycle 2 h around their anaerobic gas exchange threshold (HR zone 4). RESULTS: Eighteen participants completed the EDT stage in 537 ± 58 min, including 154 ± 61 min of cycling time in HR zone 4. Post-race right ventricular (RV) dysfunction with reduced strain and increased volumes (p < 0.05) and borderline significant left ventricular global longitudinal strain reduction (p = 0.05) were observed. Post-exercise cTnI (0.75 ± 5.1 ng/l to 69.9 ± 41.6 ng/l; p < 0.001) and T1 relaxation times (1133 ± 48 ms to 1182 ± 46 ms, p < 0.001) increased significantly with no significant change in T2 (p = 0.474). cTnI release correlated with increase in T1 relaxation time (p = 0.002; r = 0.703), post-race RV dysfunction (p < 0.05; r = 0.562) and longer cycling in HR zone 4 (p < 0.05; r = 0.607). CONCLUSION: Strenuous exercise causes early post-race cTnI increase, increased T1 relaxation time and RV dysfunction in recreational cyclists, which showed interdependent correlation. The long-term clinical significance of these changes needs further investigation. TRIAL REGISTRATION NUMBERS AND DATE: NCT04940650 06/18/2021. NCT05138003 06/18/2021.

Relating QRS voltages to left ventricular mass and body composition in elite endurance athletes.

PURPOSE: Electrocardiogram (ECG) QRS voltages correlate poorly with left ventricular mass (LVM). Body composition explains some of the QRS voltage variability. The relation between QRS voltages, LVM and body composition in endurance athletes is unknown. METHODS: Elite endurance athletes from the Pro@Heart trial were evaluated with 12-lead ECG for Cornell and Sokolow-Lyon voltage and product. Cardiac magnetic resonance imaging assessed LVM. Dual energy x-ray absorptiometry assessed fat mass (FM) and lean mass of the trunk and whole body (LBM). The determinants of QRS voltages and LVM were identified by multivariable linear regression. Models combining ECG, demographics, DEXA and exercise capacity to predict LVM were developed. RESULTS: In 122 athletes (19 years, 71.3% male) LVM was a determinant of the Sokolow-Lyon voltage and product (ß = 0.334 and 0.477, p < 0.001) but not of the Cornell criteria. FM of the trunk (ß = - 0.186 and - 0.180, p < 0.05) negatively influenced the Cornell voltage and product but not the Sokolow-Lyon criteria. DEXA marginally improved the prediction of LVM by ECG (r = 0.773 vs 0.510, p < 0.001; RMSE = 18.9 ± 13.8 vs 25.5 ± 18.7 g, p > 0.05) with LBM as the strongest predictor (ß = 0.664, p < 0.001). DEXA did not improve the prediction of LVM by ECG and demographics combined and LVM was best predicted by including VO2max (r = 0.845, RMSE = 15.9 ± 11.6 g). CONCLUSION: LVM correlates poorly with QRS voltages with adipose tissue as a minor determinant in elite endurance athletes. LBM is the strongest single predictor of LVM but only marginally improves LVM prediction beyond ECG variables. In endurance athletes, LVM is best predicted by combining ECG, demographics and VO2max.

QRS micro-fragmentation as a mortality predictor.

AIMS: Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. METHODS AND RESULTS: A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS-µf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS-µf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS-Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS-µf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS-µf prospectively at 3.5%. When QRS-µf was used in multivariable analyses, QRS-Mf and QRS duration lost their predictive value. CONCLUSION: In three populations with different clinical characteristics, QRS-µf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS-µf values are likely responsible for the predictive power of visible QRS-Mf.

Oxygen Pathway Limitations in Patients With Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the pathogenesis has been attributed to central factors, including ventilation/perfusion mismatch, increased pulmonary vascular resistance, and right heart dysfunction and uncoupling. Pulmonary endarterectomy and balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. However, despite normalization of pulmonary hemodynamics, exercise capacity often does not return to age-predicted levels. By systematically evaluating the oxygen pathway, we aimed to elucidate the causes of functional limitations in patients with CTEPH before and after pulmonary vascular intervention. METHODS: Using exercise cardiac magnetic resonance imaging with simultaneous invasive hemodynamic monitoring, we sought to quantify the steps of the O2 transport cascade from the mouth to the mitochondria in patients with CTEPH (n=20) as compared with healthy participants (n=10). Furthermore, we evaluated the effect of pulmonary vascular intervention (pulmonary endarterectomy or balloon angioplasty) on the individual components of the cascade (n=10). RESULTS: Peak Vo2 (oxygen uptake) was significantly reduced in patients with CTEPH relative to controls (56±17 versus 112±20% of predicted; P<0.0001). The difference was attributable to impairments in multiple steps of the O2 cascade, including O2 delivery (product of cardiac output and arterial O2 content), skeletal muscle diffusion capacity, and pulmonary diffusion. The total O2 extracted in the periphery (ie, ΔAVo2 [arteriovenous O2 content difference]) was not different. After pulmonary vascular intervention, peak Vo2 increased significantly (from 12.5±4.0 to 17.8±7.5 mL/[kg·min]; P=0.036) but remained below age-predicted levels (70±11%). The O2 delivery was improved owing to an increase in peak cardiac output and lung diffusion capacity. However, peak exercise ΔAVo2 was unchanged, as was skeletal muscle diffusion capacity. CONCLUSIONS: We demonstrated that patients with CTEPH have significant impairment of all steps in the O2 use cascade, resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increased peak Vo2 by partly correcting O2 delivery but had no effect on abnormalities in peripheral O2 extraction. This suggests that current interventions only partially address patients' limitations and that additional therapies may improve functional capacity.

Q waves are the strongest electrocardiographic variable associated with primary prophylactic implantable cardioverter-defibrillator benefit: a prospective multicentre study.

AIM: The association of standard 12-lead electrocardiogram (ECG) markers with benefits of the primary prophylactic implantable cardioverter-defibrillator (ICD) has not been determined in the contemporary era. We analysed traditional and novel ECG variables in a large prospective, controlled primary prophylactic ICD population to assess the predictive value of ECG in terms of ICD benefit. METHODS AND RESULTS: Electrocardiograms from 1477 ICD patients and 700 control patients (EU-CERT-ICD; non-randomized, controlled, prospective multicentre study; ClinicalTrials.gov Identifier: NCT02064192), who met ICD implantation criteria but did not receive the device, were analysed. The primary outcome was all-cause mortality. In ICD patients, the co-primary outcome of first appropriate shock was used. Mean follow-up time was 2.4 ± 1.1 years to death and 2.3 ± 1.2 years to the first appropriate shock. Pathological Q waves were associated with decreased mortality in ICD patients [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.35-0.84; P < 0.01] and patients with pathological Q waves had significantly more benefit from ICD (HR 0.44, 95% CI 0.21-0.93; P = 0.03). QTc interval increase taken as a continuous variable was associated with both mortality and appropriate shock incidence, but commonly used cut-off values, were not statistically significantly associated with either of the outcomes. CONCLUSION: Pathological Q waves were a strong ECG predictor of ICD benefit in primary prophylactic ICD patients. Excess mortality among Q wave patients seems to be due to arrhythmic death which can be prevented by ICD.

Behavior of AV synchrony pacing mode in a leadless pacemaker during variable AV conduction and arrhythmias.

INTRODUCTION: MARVEL 2 assessed the efficacy of mechanical atrial sensing by a ventricular leadless pacemaker, enabling a VDD pacing mode. The behavior of the enhanced MARVEL 2 algorithm during variable atrio-ventricular conduction (AVC) and/or arrhythmias has not been characterized and is the focus of this study. METHODS: Of the 75 patients enrolled in the MARVEL 2 study, 73 had a rhythm assessment and were included in the analysis. The enhanced MARVEL 2 algorithm included a mode-switching algorithm that automatically switches between VDD and ventricular only antibradycardia pacing (VVI)-40 depending upon AVC status. RESULTS: Forty-two patients (58%) had persistent third degree AV block (AVB), 18 (25%) had 1:1 AVC, 5 (7%) had variable AVC status, and 8 (11%) had atrial arrhythmias. Among the 42 patients with persistent third degree AVB, the median ventricular pacing (VP) percentage was 99.9% compared to 0.2% among those with 1:1 AVC. As AVC status changed, the algorithm switched to VDD when the ventricular rate dropped less than 40 bpm. During atrial fibrillation (AF) with ventricular response greater than 40 bpm, VVI-40 mode was maintained. No pauses longer than 1500 ms were observed. Frequent ventricular premature beats reduced the percentage of AV synchrony. During AF, the atrial signal was of low amplitude and there was infrequent sensing. CONCLUSION: The mode switching algorithm reduced VP in patients with 1:1 AVC and appropriately switched to VDD during AV block. No pacing safety issues were observed during arrhythmias.

Left ventricular regional glucose metabolism in combination with septal scar extent identifies CRT responders.

BACKGROUND: Cardiac resynchronization therapy (CRT) is effective in selective heart failure (HF) patients, but non-response rate remains high. Positron emission tomography (PET) may provide a better insight into the pathophysiology of left ventricular (LV) remodeling; however, its role for evaluating and selecting patients for CRT remains uncertain. PURPOSE: We investigated if regional LV glucose metabolism in combination with myocardial scar could predict response to CRT. METHODS: Consecutive CRT-eligible HF patients underwent echocardiography, cardiac magnetic resonance (CMR), and 18F-fluorodeoxyglucose (FDG) PET within 1 week before CRT implantation. Echocardiography was additionally performed 12 months after CRT and end-systolic volume reduction ≥ 15% was defined as CRT response. Septal-to-lateral wall (SLR) FDG uptake ratio was calculated from static FDG images. Late gadolinium enhancement (LGE) CMR was analyzed semi-quantitatively to define scar extent. RESULTS: We evaluated 88 patients (67 ± 10 years, 72% males). 18F-FDG SLR showed a linear correlation with volumetric reverse remodeling 12 months after CRT (r = 0.41, p = 0.0001). In non-ischemic HF patients, low FDG SLR alone predicted CRT response with sensitivity and specificity of more than 80%; however, in ischemic HF patients, specificity decreased to 46%, suggesting that in this cohort low SLR can also be caused by the presence of a septal scar. In the multivariate logistic regression model, including low FDG SLR, presence and extent of the scar in each myocardial wall, and current CRT guideline parameters, only low FDG SLR and septal scar remained associated with CRT response. Their combination could predict CRT response with sensitivity, specificity, negative, and positive predictive value of 80%, 83%, 70%, and 90%, respectively. CONCLUSIONS: FDG SLR can be used as a predictor of CRT response and combined with septal scar extent, CRT responders can be distinguished from non-responders with high diagnostic accuracy. Further studies are needed to verify whether this imaging approach can prospectively be used to optimize patient selection.

Clinical characterization of the first Belgian SCN5A founder mutation cohort.

AIMS: We identified the first Belgian SCN5A founder mutation, c.4813 + 3_4813 + 6dupGGGT. To describe the clinical spectrum and disease severity associated with this mutation, clinical data of 101 SCN5A founder mutation carriers and 46 non-mutation carrying family members from 25 Belgian families were collected. METHODS AND RESULTS: The SCN5A founder mutation was confirmed by haplotype analysis. The clinical history and electrocardiographic parameters of the mutation carriers and their family members were gathered and compared. A cardiac electrical abnormality was observed in the majority (82%) of the mutation carriers. Cardiac conduction defects, defined as PR or QRS prolongation on electrocardiogram (ECG), were most frequent, occurring in 65% of the mutation carriers. Brugada syndrome (BrS) was the second most prevalent phenotype identified in 52%, followed by atrial dysrythmia in 11%. Overall, 33% of tested mutation carriers had a normal sodium channel blocker test. Negative tests were more common in family members distantly related to the proband. Overall, 23% of the mutation carriers were symptomatic, with 8% displaying major adverse events. As many as 13% of the patients tested with a sodium blocker developed ventricular arrhythmia. One family member who did not carry the founder mutation was diagnosed with BrS. CONCLUSION: The high prevalence of symptoms and sensitivity to sodium channel blockers in our founder population highlights the adverse effect of the founder mutation on cardiac conduction. The large phenotypical heterogeneity, variable penetrance, and even non-segregation suggest that other genetic (and environmental) factors modify the disease expression, severity, and outcome in these families.

Development and external validation of prediction models to predict implantable cardioverter-defibrillator efficacy in primary prevention of sudden cardiac death.

AIMS: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation. METHODS AND RESULTS: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality. CONCLUSION: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed.

Quality of life outcomes in cryoablation of atrial fibrillation-A literature review.

BACKGROUND: Cryoballoon ablation (CRYO) for pulmonary vein isolation (PVI) in atrial fibrillation (AF) has become an established treatment option as alternative for radiofrequency catheter ablation (RFCA). As symptom relief is still the main indication for PVI, quality of life (QoL) is a key outcome parameter. This review summarizes the evidence about the evolution of QoL after CRYO. METHODS: A search for clinical studies reporting QoL outcomes after CRYO was performed on PUBMED and COCHRANE. A total of 506 publications were screened and 10 studies met the in- and exclusion criteria. RESULTS: All studies considered QoL as a secondary endpoint and reported significant improvement in QoL between baseline and 12 months follow-up, independent of the QoL instruments used. The effect size of CRYO on QoL was comparable between studies and present in both paroxysmal and persistent AF. Direct comparison between CRYO and RFCA was limited to two studies, there was no difference between ablation modalities after 12 months FU. Two studies in paroxysmal AF reported outcome beyond 12 months follow-up and QoL improvement was maintained up to 36 months after ablation. There were no long-term data available for persistent AF. CONCLUSION: CRYO of AF significantly improves QoL. The scarce amount of data with direct comparison between subgroups limits further exploration. Assessment of QoL should be considered a primary outcome parameter in future trials with long-term follow-up.

The effect of posture on maximal oxygen uptake in active healthy individuals.

PURPOSE: Semi-supine and supine cardiopulmonary exercise testing (CPET) with concurrent cardiac imaging has emerged as a valuable tool for evaluating patients with cardiovascular disease. Yet, it is unclear how posture effects CPET measures. We aimed to discern the effect of posture on maximal oxygen uptake (VO2max) and its determinants using three clinically relevant cycle ergometers. METHODS: In random order, 10 healthy, active males (Age 27 ± 7 years; BMI 23 ± 2 kg m2) underwent a ramp CPET and subsequent constant workload verification test performed at 105% peak ramp power to quantify VO2max on upright, semi-supine and supine cycle ergometers. Doppler echocardiography was conducted at peak exercise to measure stroke volume (SV) which was multiplied by heart rate (HR) to calculate cardiac output (CO). RESULTS: Compared to upright (46.8 ± 11.2 ml/kg/min), VO2max was progressively reduced in semi-supine (43.8 ± 10.6 ml/kg/min) and supine (38.2 ± 9.3 ml/kg/min; upright vs. semi-supine vs. supine; all p ≤ 0.005). Similarly, peak power was highest in upright (325 ± 80 W), followed by semi-supine (298 ± 72 W) and supine (200 ± 51 W; upright vs. semi-supine vs. supine; all p < 0.01). Peak HR decreased progressively from upright to semi-supine to supine (186 ± 11 vs. 176 ± 13 vs. 169 ± 12 bpm; all p < 0.05). Peak SV and CO were lower in supine relative to semi-supine and upright (82 ± 22 vs. 92 ± 26 vs. 91 ± 24 ml and 14 ± 3 vs. 16 ± 4 vs. 17 ± 4 l/min; all p < 0.01), but not different between semi-supine and upright. CONCLUSION: VO2max is progressively reduced in reclined postures. Thus, posture should be considered when comparing VO2max results between different testing modalities.

Clinical effectiveness of primary prevention implantable cardioverter-defibrillators: results of the EU-CERT-ICD controlled multicentre cohort study.

AIMS: The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy. METHODS AND RESULTS: We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537-0.865, P = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class

Supervised SVM Transfer Learning for Modality-Specific Artefact Detection in ECG.

The electrocardiogram (ECG) is an important diagnostic tool for identifying cardiac problems. Nowadays, new ways to record ECG signals outside of the hospital are being investigated. A promising technique is capacitively coupled ECG (ccECG), which allows ECG signals to be recorded through insulating materials. However, as the ECG is no longer recorded in a controlled environment, this inevitably implies the presence of more artefacts. Artefact detection algorithms are used to detect and remove these. Typically, the training of a new algorithm requires a lot of ground truth data, which is costly to obtain. As many labelled contact ECG datasets exist, we could avoid the use of labelling new ccECG signals by making use of previous knowledge. Transfer learning can be used for this purpose. Here, we applied transfer learning to optimise the performance of an artefact detection model, trained on contact ECG, towards ccECG. We used ECG recordings from three different datasets, recorded with three recording devices. We showed that the accuracy of a contact-ECG classifier improved between 5 and 8% by means of transfer learning when tested on a ccECG dataset. Furthermore, we showed that only 20 segments of the ccECG dataset are sufficient to significantly increase the accuracy.

Artefact Detection in Impedance Pneumography Signals: A Machine Learning Approach.

Impedance pneumography has been suggested as an ambulatory technique for the monitoring of respiratory diseases. However, its ambulatory nature makes the recordings more prone to noise sources. It is important that such noisy segments are identified and removed, since they could have a huge impact on the performance of data-driven decision support tools. In this study, we investigated the added value of machine learning algorithms to separate clean from noisy bio-impedance signals. We compared three approaches: a heuristic algorithm, a feature-based classification model (SVM) and a convolutional neural network (CNN). The dataset consists of 47 chronic obstructive pulmonary disease patients who performed an inspiratory threshold loading protocol. During this protocol, their respiration was recorded with a bio-impedance device and a spirometer, which served as a gold standard. Four annotators scored the signals for the presence of artefacts, based on the reference signal. We have shown that the accuracy of both machine learning approaches (SVM: 87.77 ± 2.64% and CNN: 87.20 ± 2.78%) is significantly higher, compared to the heuristic approach (84.69 ± 2.32%). Moreover, no significant differences could be observed between the two machine learning approaches. The feature-based and neural network model obtained a respective AUC of 92.77±2.95% and 92.51±1.74%. These findings show that a data-driven approach could be beneficial for the task of artefact detection in respiratory thoracic bio-impedance signals.