Risk of Cardiac Arrhythmias Among Climbers on Mount Everest.

Importance: Arterial hypoxemia, electrolyte imbalances, and periodic breathing increase the vulnerability to cardiac arrhythmia at altitude. Objective: To explore the incidence of tachyarrhythmias and bradyarrhythmias in healthy individuals at high altitudes. Design, Setting, and Participants: This prospective cohort study involved healthy individuals at altitude (8849 m) on Mount Everest, Nepal. Recruitment occurred from January 25 to May 9, 2023, and data analysis took place from June to July 2023. Exposure: All study participants underwent 12-lead electrocardiogram, transthoracic echocardiography, and exercise stress testing before and ambulatory rhythm recording both before and during the expedition. Main Outcome: The incidence of a composite of supraventricular (>30 seconds) and ventricular (>3 beats) tachyarrhythmia and bradyarrhythmia (sinoatrial arrest, second- or third-degree atrioventricular block). Results: Of the 41 individuals recruited, 100% were male, and the mean (SD) age was 33.6 (8.9) years. On baseline investigations, there were no signs of exertional ischemia, wall motion abnormality, or cardiac arrhythmia in any of the participants. Among 34 individuals reaching basecamp at 5300 m, 32 participants climbed to 7900 m or higher, and 14 reached the summit of Mount Everest. A total of 45 primary end point-relevant events were recorded in 13 individuals (38.2%). Forty-three bradyarrhythmic events were documented in 13 individuals (38.2%) and 2 ventricular tachycardias in 2 individuals (5.9%). Nine arrhythmias (20%) in 5 participants occurred when climbers were using supplemental bottled oxygen, whereas 36 events (80%) in 11 participants occurred at lower altitudes when no supplemental bottled oxygen was used. The proportion of individuals with arrhythmia remained stable across levels of increasing altitude, while event rates per 24 hours numerically increased between 5300 m (0.16 per 24 hours) and 7300 m (0.37 per 24 hours) before decreasing again at higher altitudes, where supplemental oxygen was used. None of the study participants reported dizziness or syncope. Conclusion and Relevance: In this study, more than 1 in 3 healthy individuals experienced cardiac arrhythmia during the climb of Mount Everest, thereby confirming the association between exposure to high altitude and incidence of cardiac arrhythmia. Future studies should explore the potential implications of these rhythm disturbances.

Supervised exercise training in patients with cancer during anthracycline-based chemotherapy to mitigate cardiotoxicity: a randomized-controlled-trial.

Background: Exercise training (ET) has been shown to mitigate cardiotoxicity of anthracycline-based chemotherapies (AC) in animal models. Data from randomized controlled trials in patients with cancer are sparse. Methods: Patients with breast cancer or lymphoma receiving AC were recruited from four cancer centres and randomly assigned to 3 months supervised ET. Primary outcome was change in left ventricular global longitudinal strain (GLS) from baseline (before AC) to post AC (AC-end) compared between the EXduringAC group, who participated in an exercise intervention during AC including the provision of an activity tracker, and the control group EXpostAC, who received an activity tracker only. Secondary outcome parameters were changes in high sensitivity Troponin T (hsTnT), NT-pro-brain natriuretic peptide (NT-proBNP), peak oxygen consumption (peak VO2) and objectively measured physical activity (PA) during this same time-period. All assessments were repeated at a 12-week follow-up from AC-end, when also the EXpostAC group had completed the ET, that started after AC. In exploratory analyses, robust linear models were performed to assess the association of PA with changes in echocardiographic parameters and biomarkers of LV function. Results: Fifty-seven patients (median age 47 years; 95% women) were randomized to EXduringAC (n = 28) and EXpostAC (n = 29) group. At AC-end, GLS deteriorated in both study groups (albeit insignificantly) with 7.4% and 1.0% in EXduringAC (n = 18) and EXpostAC (n = 18), respectively, and hsTnT and NT-proBNP significantly increased in both groups, without difference between groups for any parameter. Change in peak VO2 (-1.0 and -1.1 ml/kg/min) at AC-end was also similar between groups as was duration of moderate-to-vigorous PA (MVPA) with a median of 33 [26, 47] min/day and 32 [21, 59] min/day in the EXduringAC and EXpostAC group, respectively. In the robust linear model including the pooled patient population, MVPA was significantly associated with a more negative GLS and lesser increase in hsTnT at AC-end. Conclusion: In this small scale RCT, supervised ET during AC was not superior to wearing a PA tracker to mitigate cardiotoxicity. The dose-response relationship between PA and cardioprotective effects during AC found in our and previous data supports the notion that PA should be recommended to patients undergoing AC. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03850171.

Impact of COVID-19 Surge Periods on Clinical Outcomes of Transcatheter Aortic Valve Implantation.

Healthcare systems adopted various strategies to minimize the impact of the COVID-19 pandemic on clinical outcomes of patients with symptomatic severe aortic stenosis referred for transcatheter aortic valve implantation (TAVI). We aimed to compare baseline characteristics and procedural and clinical outcomes of patients who underwent TAVI during COVID-19 surge periods with those of patients who underwent TAVI during the nonsurge and prepandemic periods. In the prospective Bern TAVI registry, the pandemic period was divided into surge and nonsurge periods on the basis of the mean number of occupied beds in the intensive care unit in each month and matched with 11 months immediately preceding the pandemic. A total of 1,069 patients underwent TAVI between April 1, 2019 and December 31, 2021. Patients who underwent TAVI during surge periods had a higher surgical risk (Society of Thoracic Surgeons predicted risk of mortality) than that of patients who underwent TAVI during nonsurge and prepandemic periods. Diagnosis-to-procedure time (in days) was longer for patients who underwent TAVI during the surge period than during the nonsurge and prepandemic periods (95.20 ± 121.07 vs 70.99 ± 72.25 and 60.46 ± 75.43, both p <0.001). At 30 days, all-cause mortality was higher in the surge than in the nonsurge group (4.9 vs 1.1%, hazard ratio 4.68, 95% confidence interval 1.55 to 14.10, p = 0.006), and in the surge than in the prepandemic group (4.9 vs 1.3%, hazard ratio 3.67, 95% confidence interval 1.34 to 10.11, p = 0.012). In conclusion, TAVI during COVID-19 surge periods was associated with higher Society of Thoracic Surgeons predicted risk of mortality score, delayed procedure scheduling, and increased 30-day mortality than that of TAVI during nonsurge and prepandemic periods.

Transcatheter aortic valve implantation in patients with rheumatic aortic stenosis.

BACKGROUND: Rheumatic heart disease (RHD) accounts for the highest number of deaths from valvular heart disease globally. Yet, rheumatic aortic stenosis (AS) was excluded from landmark studies investigating the safety and efficacy of transcatheter aortic valve implantation (TAVI). We aimed to describe the clinical and anatomical characteristics of patients with rheumatic AS undergoing TAVI, and to compare procedural and clinical outcomes with patients undergoing TAVI for degenerative AS. METHODS: In a prospective TAVI registry, patients with rheumatic AS were identified based on International Classification of Diseases version 10 codes and/or a documented history of acute rheumatic fever and/or the World Heart Federation criteria for echocardiographic diagnosis of RHD, and were propensity score-matched in a 1:4 ratio to patients with degenerative AS. RESULTS: Among 2329 patients undergoing TAVI, 105 (4.5%) had rheumatic AS. Compared with patients with degenerative AS, patients with rheumatic AS were more commonly female, older, had higher surgical risk and more commonly suffered from multivalvular heart disease. In the unmatched cohort, both technical success (85.7% vs 85.9%, p=0.887) and 1-year cardiovascular mortality (10.0% vs 8.6%; HR 1.16, 95% CI 0.61 to 2.18, p=0.656) were comparable between patients with rheumatic and degenerative AS. In contrast, patients with rheumatic AS had lower rates of 30-day and 1-year cardiovascular mortality compared with matched patients with degenerative AS (1.9% vs 8.9%, adjusted HR (HRadj) 0.18, 95% CI 0.04 to 0.80, p=0.024; and 10.0% vs 20.3%, HRadj 0.44, 95% CI 0.24 to 0.84, p=0.012, respectively). CONCLUSION: TAVI may be a safe and effective treatment strategy for selected elderly patients with rheumatic AS. TRIAL REGISTRATION NUMBER: NCT01368250.

Young endurance training starting age in non-elite athletes is associated with higher proximal aortic distensibility.

OBJECTIVE: Decreased proximal aortic distensibility (AD) is known to significantly predict all-cause mortality and cardiovascular events among individuals without overt cardiovascular disease. This cross-sectional study investigated the association of endurance training (ET) parameters, namely, ET starting age, ET years and yearly ET volume with AD in non-elite endurance athletes. METHODS: Healthy, normotensive, male Caucasian participants of a 10-mile race were assessed with a 2D echocardiogram and comprehensive interview. Ascending aortic diameters were measured simultaneously with pulse pressure. Aortic strain, AD and aortic stiffness index were calculated. Predictors of AD were investigated among training parameters by linear regression models corrected for age, resting heart rate, stroke volume index and mean blood pressure. RESULTS: Ninety-two of 121 athletes (aged 42±8 years) had sufficient echocardiogram quality and were used for analysis. ET starting age (range 6-52 years) and years of ET (range 2-46 years) were highly collinear and used in two separate models for AD. Significant factors for AD were ET starting age, 10-mile race time and resting heart rate in model I, and age, years of ET, 10-mile race time and heart rate in model II (all p<0.01). CONCLUSIONS: In our cohort of healthy, non-elite, middle-aged runners, AD was significantly higher in athletes with younger ET starting age or more years of ET (in the model adjusted for confounders). In the model with years of ET, age had a negative contribution to AD, suggesting that with older age, the benefit of more years of ET on AD decreased. Future studies assessing the effect of exercise training on arterial properties should include training starting age.

Permanent pacemaker implantation late after transcatheter aortic valve implantation.

BACKGROUND: Impairment of atrioventricular (AV) conduction may occur late after transcatheter aortic valve implantation (TAVI), and progression to complete AV block is a matter of concern. OBJECTIVE: The purpose of this study was to describe the incidence of permanent pacemaker (PPM) implantation late after TAVI. METHODS: In a prospective TAVI registry, we retrospectively identified patients with PPM implantation after hospital discharge for TAVI and analyzed serial electrocardiograms for AV conduction impairment before PPM implantation. RESULTS: Among 1059 patients discharged after TAVI without PPM between January 2012 and December 2017, 62 patients (5.9%) underwent PPM implantation at a median of 305 days after discharge for TAVI. Indications for PPM implantation late after TAVI were AV conduction impairment in 46 patients (74.2%); sick sinus syndrome in 10 (16.1%); cardiac resynchronization or implantable cardioverter-defibrillator indication in 2 (3.2%); and a pace and ablate strategy in 4 (6.5%). Clinical symptoms leading to PPM implantation late after TAVI included syncope in 19 patients (30.7%), presyncope in 7 (11.3%), and dyspnea in 8 (12.9%). First-degree AV block and new left bundle branch block (LBBB) after TAVI as well as valve-in-valve procedure during follow-up were independent predictors of PPM implantation late after TAVI due to AV conduction impairment. CONCLUSION: PPM implantation late after TAVI is infrequent and is associated with clinical symptoms in half of patients. Impairment of AV conduction was the indication in three-quarters of patients. First-degree AV block and new LBBB after TAVI as well as valve-in-valve procedure during follow-up emerged as independent predictors.

The impact of obesity on left ventricular hypertrophy and diastolic dysfunction in children and adolescents.

Childhood obesity continues to escalate worldwide and may affect left ventricular (LV) geometry and function. The aim of this study was to investigate the impact of obesity on prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction in children. In this analysis of prospectively collected cross-sectional data of children between 5 and 16 years of age from randomly selected schools in Peru, parameters of LV geometry and function were compared according to presence or absence of obesity (body mass index z-score > 2). LVH was based on left ventricular mass index (LVMI) adjusted for age and sex and defined by a z-score of > 2. LV diastolic function was assessed using mitral inflow early-to-late diastolic flow (E/A) ratio, peak early diastolic tissue velocities of the lateral mitral annulus (E'), early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity (E/E') ratio, and left atrial volume index (LAVI). Among 1023 children, 681 children (mean age 12.2 ± 3.1 years, 341 male (50.1%)) were available for the present analysis, of which 150 (22.0%) were obese. LVH was found in 21 (14.0%) obese and in 19 (3.6%) non-obese children (padjusted < 0.001). LVMI was greater in obese than that in non-obese children (36.1 ± 8.6 versus 28.7 ± 6.9 g/m2.7, p < 0.001). The mean mitral E/E' ratio and LAVI were significantly higher in obese than those in non-obese individuals (E/E': 5.2 ± 1.1 versus 4.9 ± 0.8, padjusted = 0.043; LAVI 11.0 ± 3.2 versus 9.6 ± 2.9, padjusted = 0.001), whereas E' and E/A ratio were comparable. Childhood obesity was associated with left ventricular hypertrophy and determinants of diastolic dysfunction.ClinicalTrials.gov Identifier: NCT02353663.

Validation of the 2019 Expert Consensus Algorithm for the Management of Conduction Disturbances After TAVR.

OBJECTIVES: The aim of this study was to validate the 2019 consensus algorithm in a large cohort of contemporary transcatheter aortic valve replacement (TAVR) patients. BACKGROUND: The optimal management of patients with atrioventricular conduction disturbances after TAVR is unknown. Guidance was consolidated in an expert consensus algorithm in 2019. METHODS: In a retrospective analysis of a prospective registry, patients were classified according to the 2019 consensus algorithm as eligible for early discharge (day 1 or 2 after TAVR), higher risk for high-degree atrioventricular block (HAVB) or complete heart block (CHB) or in need for a permanent pacemaker (PPM). The primary endpoint was the incidence of PPM implantation for HAVB or CHB within 30 days after TAVR. Patients with prior PPM or implantable cardioverter-defibrillator implantation, valve-in-valve procedures, or incomplete electrocardiographic data were excluded. RESULTS: Among 1,439 patients undergoing TAVR between January 2014 and December 2019, the 2019 consensus algorithm classified 73% as eligible for early discharge, 21% as at higher risk for HAVB or CHB, and 6% as in need of PPM. PPM implantation for HAVB or CHB occurred in 234 patients (16%) within 30 days after TAVR. The incidence of PPM implantation was 2.7% in the early discharge group, 41% in the group with higher risk for HAVB or CHB, and 100% in the PPM group. CONCLUSIONS: The 2019 consensus algorithm safely identifies patients with no need for PPM implantation. This strategy allows more uniform management of TAVR patients and facilitates early discharge of low-risk patients without prolonged monitoring in 3 of 4 patients. However, the algorithm is less precise in the identification of high-risk patients.

Valvular and Nonvalvular Atrial Fibrillation in Patients Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVES: The aim of this study was to investigate the impact of valvular and nonvalvular atrial fibrillation (AF) in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: AF has been associated with adverse clinical outcomes after TAVR. However, the differential impact of valvular as opposed to nonvalvular AF has not been investigated. METHODS: In a retrospective analysis of a prospective registry, valvular AF was defined as AF in the setting of concomitant mitral stenosis or the presence of a mitral valve prosthesis. The presence of mitral stenosis was determined by pre-procedural echocardiography. The primary endpoint was a composite of cardiovascular death or disabling stroke at 1 year after TAVR. RESULTS: Among 1,472 patients undergoing TAVR between August 2007 and June 2018, AF was recorded in 465 patients (31.6%) and categorized as nonvalvular in 376 (25.5%) and valvular in 89 (6.0%). AF scores including HAS-BLED, CHADS2, and CHA2DS2-VASc were comparable between patients with nonvalvular and valvular AF. The primary endpoint occurred in 9.3% of patients with no AF, in 14.5% of patients with nonvalvular AF (hazard ratio: 1.57; 95% confidence interval: 1.12 to 2.20; p = 0.009), and in 24.2% of patients with valvular AF (hazard ratio: 2.75; 95% confidence interval: 1.71 to 4.41; p < 0.001). Valvular AF conferred an increased risk for cardiovascular death or disabling stroke compared with nonvalvular AF (hazard ratio: 1.77; 95% confidence interval: 1.07 to 2.94; p = 0.027). CONCLUSIONS: The presence of valvular AF in patients undergoing TAVR increased the risk for cardiovascular death or disabling stroke compared with both no AF and nonvalvular AF. (SWISS TAVI Registry; NCT01368250).

Age at start of endurance training is associated with patterns of left ventricular hypertrophy in middle-aged runners.

BACKGROUND: Left ventricular hypertrophy (LVH) is a physiological adaptation to long-term endurance training. We investigated the impact of age at start of endurance training on LV geometry in a cohort of male, middle-aged, non-elite endurance athletes. METHODS: A total of 121 healthy, normotensive, Caucasian participants of a 10-mile race were recruited and assessed with an echocardiogram and a comprehensive interview. Athletes were classified based on patterns of LVH. RESULTS: Thirty-five athletes (31%) had LVH. Athletes with eccentric LVH (16%) were significantly younger at start of endurance training compared to athletes with concentric LVH (15%, 14 ±â€¯5 years vs. 31 ±â€¯8 years; P < 0.001). Although the yearly volume of endurance training was comparable between athletes with eccentric and concentric LVH, athletes with eccentric LVH had shorter race times. All athletes with an increased LV end diastolic volume index (LVEDVI; ≥74 ml/m2) started endurance training before or at age 25. CONCLUSIONS: In our cohort of non-elite middle-aged runners, eccentric LVH was found only in athletes with an early start of endurance training. In case of a mature starting age, endurance training may, contrary to what is commonly assumed, also lead to concentric LVH. The consideration of endurance training starting age may lead to a better understanding of morphological adaptations of the heart.

Exercise-induced cardiac remodeling in non-elite endurance athletes: Comparison of 2-tiered and 4-tiered classification of left ventricular hypertrophy.

BACKGROUND: Long-term endurance sport practice leads to eccentric left ventricular hypertrophy (LVH). We aimed to compare the new 4-tiered classification (4TC) for LVH with the established 2-tiered classification (2TC) in a cohort of normotensive non-elite endurance athletes. METHODS: Male participants of a 10-mile race were recruited and included when blood pressure (BP) was normal (<140/90 mmHg). Phenotypic characterization of LVH was based on relative wall thickness (2TC), and on LV concentricity2/3 (LV mass/end-diastolic volume [LVM/EDV]2/3) plus LVEDV index (4TC). Parameters of LV geometry, BP, cumulative training hours, and race time were compared between 2TC and 4TC by analysis of variance, and post-hoc analysis. RESULTS: Of 198 athletes recruited, 174 were included. Mean age was 41.6±7.5 years. Forty-two (24%) athletes had LVH. Allocation in the 2TC was: 32 (76%) eccentric LVH and 10 (24%) concentric LVH. Using the 4TC 12 were reclassified to concentric LVH, and 2 to eccentric LVH, resulting in 22 (52%) eccentric LVH (7 non-dilated, 15 dilated), and 20 (48%) concentric LVH (all non-dilated). Based on the 2TC, markers of endurance training did not differ between eccentric and concentric LVH. Based on the 4TC, athletes with eccentric LVH had more cumulative training hours and faster race times, with highest values thereof in athletes with eccentric dilated LVH. CONCLUSIONS: In our cohort of normotensive endurance athletes, the new 4TC demonstrated a superior discrimination of exercise-induced LVH patterns, compared to the established 2TC, most likely because it takes three-dimensional information of the ventricular geometry into account.