Exercise Test Predicts Both Noncardiovascular and Cardiovascular Death in a Primary Prevention Population.

OBJECTIVE: To identify specific causes of death and determine the prevalence of noncardiovascular (non-CV) deaths in an exercise test referral population while testing whether exercise test parameters predict non-CV as well as CV deaths. PATIENTS AND METHODS: Non-imaging exercise tests on patients 30 to 79 years of age from September 1993 to December 2010 were reviewed. Patients with baseline CV diseases and non-Minnesota residents were excluded. Mortality through January 2016 was obtained through Mayo Clinic Records and the Minnesota Death Index. Exercise test abnormalities included low functional aerobic capacity (ie, less than 80%), heart rate recovery (ie, less than 13 beats/min), low chronotropic index (ie, less than 0.8), and abnormal exercise electrocardiogram (ECG) of greater than or equal to 1.0 mm ST depression or elevation. We also combined these four abnormalities into a composite exercise test score (EX_SCORE). Statistical analyses consisted of Cox regression adjusted for age, sex, diabetes, hypertension, obesity, current and past smoking, and heart rate-lowering drug. RESULTS: The study identified 13,382 patients (females: n=4736, 35.4%, 50.5±10.5 years of age). During 12.7±5.0 years of follow-up, there were 849 deaths (6.3%); of these 162 (19.1%) were from CV; 687 (80.9%) were non-CV. Hazard ratios for non-CV death were significant for low functional aerobic capacity (HR, 1.42; 95% CI, 1.19 to 1.69; P<.0001), abnormal heart rate recovery (HR, 1.36; 95% CI, 1.15 to 1.61; P<.0033), and low chronotropic index (HR, 1.49; 95% CI, 1.26 to 1.77; P<.0001), whereas abnormal exercise ECG was not significant. All exercise test abnormalities including EX_SCORE were more strongly associated with CV death versus non-CV death except abnormal exercise ECG. CONCLUSION: Non-CV deaths predominated in this primary prevention cohort. Exercise test abnormalities not only predicted CV death but also non-CV death.

Iron deficiency in young basketball players: Is a 100 µg/L ferritin cut-off appropriate for iron supplementation?: Results of a randomized placebo-controlled study.

BACKGROUND: Iron deficiency (ID) is one of the most common factors that may reduce sports performance, supplementation forms and doses are still not standardized in athletes. Our aim was to assess the iron status of young male basketball players and to study the effect of iron supplementation in a randomized placebo-controlled study. HYPOTHESIS: We hypothesized that due to the higher iron demand of athletes, the 100 µg/L ferritin cut-off may be appropriate to determine the non-anemic ID. METHODS: During a sports cardiology screening, questionnaires, laboratory tests, electrocardiograms, echocardiography exams, and cardiopulmonary exercise tests were performed. Athletes with ID (ferritin <100 µg/L) were randomized into iron and placebo groups. Ferrous sulfate (containing 100 mg elemental iron [II] and 60 mg ascorbic acid) or placebo (50 mg vitamin C) was administered for 3 months. All exams were repeated after the supplementation period. RESULTS: We included 65 (age 15.8 ± 1.7 years) basketball players divided into four age groups. Non-anemic ID was observed in 60 (92%) athletes. After supplementation, ferritin levels were higher in the iron group (75.5 ± 25.9 vs. 54.9 ± 10.4 µg/L, p < .01). Ferritin >100 µg/L level was achieved only in 15% of the athletes. There were no differences in performance between the groups (VO2 max: 53.6 ± 4.3 vs. 54.4 ± 5.7 mL/kg/min, p = .46; peak lactate: 9.1 ± 2.2 vs. 9.1 ± 2.6 mmol/L, p = .90). CONCLUSIONS: As a result of the 3-month iron supplementation, the ferritin levels increased; however, only a small portion of the athletes achieved the target ferritin level, while performance improvement was not detectable.

Cardiopulmonary examinations of athletes returning to high-intensity sport activity following SARS-CoV-2 infection.

After SARS-CoV-2 infection, strict recommendations for return-to-sport were published. However, data are insufficient about the long-term effects on athletic performance. After suffering SARS-CoV-2 infection, and returning to maximal-intensity trainings, control examinations were performed with vita-maxima cardiopulmonary exercise testing (CPET). From various sports, 165 asymptomatic elite athletes (male: 122, age: 20y (IQR: 17-24y), training:16 h/w (IQR: 12-20 h/w), follow-up:93.5 days (IQR: 66.8-130.0 days) were examined. During CPET examinations, athletes achieved 94.7 ± 4.3% of maximal heart rate, 50.9 ± 6.0 mL/kg/min maximal oxygen uptake (V̇O2max), and 143.7 ± 30.4L/min maximal ventilation. Exercise induced arrhythmias (n = 7), significant horizontal/descending ST-depression (n = 3), ischemic heart disease (n = 1), hypertension (n = 7), slightly elevated pulmonary pressure (n = 2), and training-related hs-Troponin-T increase (n = 1) were revealed. Self-controlled CPET comparisons were performed in 62 athletes: due to intensive re-building training, exercise time, V̇O2max and ventilation increased compared to pre-COVID-19 results. However, exercise capacity decreased in 6 athletes. Further 18 athletes with ongoing minor long post-COVID symptoms, pathological ECG (ischemic ST-T changes, and arrhythmias) or laboratory findings (hsTroponin-T elevation) were controlled. Previous SARS-CoV-2-related myocarditis (n = 1), ischaemic heart disease (n = 1), anomalous coronary artery origin (n = 1), significant ventricular (n = 2) or atrial (n = 1) arrhythmias were diagnosed. Three months after SARS-CoV-2 infection, most of the athletes had satisfactory fitness levels. Some cases with SARS-CoV-2 related or not related pathologies requiring further examinations, treatment, or follow-up were revealed.

Prognosis and clinical characteristics of patients with early ventricular fibrillation in the 6-week guideline-offered time period: is it safe to wait 6 weeks with the assessment? (results from the VMAJOR-MI Registry).

BACKGROUND: The most common, potentially fatal complication following an acute myocardial infarction (AMI) is early ventricular fibrillation (EVF). According to the guidelines, the assessment of implanting an implantable cardioverter defibrillator (ICD) is sufficient 6 weeks after the event, in patients with reduced left ventricular ejection fraction (LVEF), regardless of VF. The present study aimed to evaluate the 6-week prognosis of patients surviving an EVF. We divided the patients in two group based on their general condition at the time they left the hospital. We investigated the clinical characteristics of patients discharged in good general health but still dying within 6 weeks. METHODS: The present study comprised 12,270 patients with AMI following their primary revascularization in the first 12 h of symptom onset. Five hundred and forty-seven of them suffered EVF due to the AMI. Clinical and 6-week mortality data were examined. RESULTS: Poor general condition correlates with multiple comorbidities, higher troponin levels, more severe complications after the event. Patients leaving in good condition thought to be low risk, from dying. But low LVEF, high blood sugar, high cardiac biomarker level, poor renal function elevates the risk of dying within 6 weeks. However, there is no difference in clinical characteristics between EVF- cases and EVF+ cases in good condition who dies within 6 weeks. CONCLUSIONS: According to our study we can select patients who are safe in the critical 6-week period and those who need closer follow-up despite leaving in good general condition.

Relationship between Cardiac Remodeling and Exercise Capacity in Elite Athletes: Incremental Value of Left Atrial Morphology and Function Assessed by Three-Dimensional Echocardiography.

BACKGROUND: Data are scarce regarding left atrial (LA) adaptation to regular physical exercise. The aim of this study was to examine left ventricular (LV) and also LA morphologic and functional remodeling in elite athletes using three-dimensional (3D) echocardiography. METHODS: In this retrospective analysis, the study group consisted of 138 elite athletes (mean age, 20 ± 4 years; 62% men) and 50 sedentary control subjects. Electrocardiographically gated full-volume 3D data sets were obtained for offline analysis using dedicated software for 3D LA and LV measurements. Body surface area-indexed LA maximal volume (LAVmax) and LV end-diastolic volume were determined. LA total emptying fraction, LA passive and LA active emptying fraction, and LV global longitudinal strain were also calculated. Athletes also underwent cardiopulmonary exercise testing to determine peak oxygen uptake. RESULTS: Athletes demonstrated higher 3D LAVmax (32 ± 6 vs 26 ± 8 mL/m2) and indexed LV end-diastolic volume (85 ± 12 vs 62 ± 10 mL/m2) compared with control subjects (P < .001 for both). Functional measures of the left ventricle and left atrium, such as the absolute value of 3D LV global longitudinal strain (19 ± 2% vs 22 ± 2%), LA total emptying fraction (58 ± 6% vs 64 ± 6%), and active emptying fraction (24 ± 10% vs 32 ± 10%) were lower in athletes (P < .001 for all). Male athletes had higher indexed LV end-diastolic volume compared with female athletes (89 ± 13 vs 80 ± 8 mL/m2, P < .001), but LAVmax did not differ between genders (32 ± 6 vs 33 ± 5 mL/m2, P = .18). Besides heart rate, gender, and body surface area, 3D LAVmax, LV global longitudinal strain, and LA passive emptying fraction were independent predictors of peak oxygen uptake. CONCLUSIONS: Regular physical exercise results in marked LA and LV remodeling with considerable gender differences as explored by 3D echocardiography. In contrast with various cardiovascular diseases, more pronounced LA dilation and lower resting functional measures are associated with better exercise performance.

Effect of Cardiorespiratory Fitness on Co-Morbidities and Mortality in Never, Past, and Current Smokers.

Smoking is a strong risk factor for cardiovascular (CV) disease and mortality, but quitting may cause weight gain and increase the risk of co-morbidities. Our aim was to investigate the effect of smoking and exercise on weight-associated co-morbidities and mortality. We included Minnesota residents without baseline CV disease who underwent exercise testing from 1993 to 2010. Mortality was determined from Mayo Clinic records and Minnesota Death Index. Total, CV and cancer mortality by smoking status and cardiorespiratory fitness (CRF): (1) <80%, (2) 80% to 99%, (3) ≥100%. Differences were tested using logistic and Cox regression adjusting for age and gender. A total of 21,981 patients (7,090 past, 2,464 current smokers) were included. Past smokers had more obesity, hypertension, diabetes, and low CRF compared with never smokers. Current smokers did not show increased risk factor prevalence compared with never smokers but had higher rates of low CRF. There were 1,749 deaths; mean follow-up was 12 ± 5 years. Mortality was only slightly increased in past versus never smokers (Hazard Ratio: 1.2; 95% confidence interval 1.12 to 1.38) but was much higher in current smokers (Hazard Ratio 2.4; 95% confidence interval 2.05 to 2.80). Mortality in never, past, and current smokers was inversely related to CRF level. In conclusion, past smokers showed higher rates of co-morbidities and low CRF, but mortality was only mildly increased versus never smokers, whereas current smokers carried a high mortality risk. Our data suggest that quitting smoking is beneficial despite the increased co-morbidities. Exercise may potentially mitigate the risk of co-morbidities and death in those who quit smoking.

Significance of an Increase in Diastolic Blood Pressure During a Stress Test in Terms of Comorbidities and Long-Term Total and CV Mortality.

BACKGROUND: A decrease in diastolic blood pressure (DBP) with exercise is considered normal, but the significance of an increase in DBP has not been validated. Our aim was to determine the relationship of DBP increasing on a stress test regarding comorbidities and mortality. METHODS: Our database was reviewed from 1993 to 2010 using the first stress test of a patient. Non-Minnesota residence, baseline cardiovascular (CV) disease, rest DBP <60 or >100 mm Hg, and age <30 or ≥80 were exclusion criteria. DBP response was classified: normal if peak DBP-rest DBP < 0, borderline 0-9, and abnormal ≥10 mm Hg. Mortality was determined from Mayo Clinic records and Minnesota Death Index. Logistic regression was used to determine the relationship of DBP response to the presence of comorbidities. Cox regression was used to determine total and CV mortality risk by DBP response. All analyses were adjusted for age, sex, and resting DBP. RESULTS: Twenty thousand seven hundred sixty patients were included (51 ± 11 years, female n = 7,314). Rest/peak averaged DBP 82 ± 8/69 ± 15 mm Hg in normal vs. 79 ± 9/82 ± 9 mm Hg in borderline vs. 76 ± 9/92 ± 11 mm Hg in abnormal DBP response. There were 1,582 deaths (8%) with 557 (3%) CV deaths over 12 ± 5 years of follow-up. In patients with borderline and abnormal DBP response, odds ratios for obesity, hypertension, diabetes, and current smoking were significant, while hazard ratios for total and CV death were not significant compared with patients with normal DBP response. CONCLUSIONS: DBP response to exercise is significantly associated with important comorbidities at the time of the stress test but does not add to the prognostic yield of stress test.

Prognostic Performance of Heart Rate Recovery on an Exercise Test in a Primary Prevention Population.

BACKGROUND: Heart rate (HR) recovery has been investigated in specific patient cohorts, but there is less information about the role of HR recovery in general populations. We investigated whether HR recovery has long-term prognostic significance in primary prevention. METHODS AND RESULTS: Exercise tests performed between 1993 and 2010 on patients aged 30 to 79 years without cardiovascular disease were included. Mortality was determined from Mayo Clinic records and Minnesota Death Index. Total, cardiovascular, and non-cardiovascular mortality was reported according to HR recovery <13 bpm using Cox regression. 19 551 patients were included, 6756 women (35%), age 51±10 years. There were 1271 deaths over follow-up of 12±5 years. HR recovery declined after age 60, and was also lower according to diabetes mellitus, hypertension, obesity, current smoking, and poor cardiorespiratory fitness but not sex or ß-blockers. Adjusting for these factors, abnormal HR recovery was a significant predictor of total (hazard ratio [95% confidence interval]=1.56 [1.384-1.77]), cardiovascular (1.95 [1.57-2.42]), and non-cardiovascular death (1.41 [1.22-1.64]). Hazard ratios for cardiovascular death according to abnormal HR recovery were significant in all age groups (30-59, 60-69, 70-79), in both sexes, in patients with and without hypertension, obesity, and diabetes mellitus, but not in patients taking ß-blockers, current smokers, and patients with normal cardiorespiratory fitness. CONCLUSIONS: HR recovery is a powerful prognostic factor predicting total, cardiovascular, and non-cardiovascular death in a primary prevention cohort. It performs consistently well according to sex, age, obesity, hypertension, and diabetes mellitus but shows diminished utility in patients taking ß-blockers, current smokers, and patients with normal cardiorespiratory fitness.

Relationship between exercise heart rate and age in men vs women.

OBJECTIVE: To analyze a large cohort of patients who underwent exercise testing and also report sex differences in other exercise heart rate (HR) parameters to determine whether separate sex-based equations to predict peak HR are indicated. PATIENTS AND METHODS: Patients aged 40 to 89 years who performed treadmill exercise tests (Bruce protocol) from September 21, 1993, to December 20, 2010, were included. Patients with cardiovascular disease or taking HR-attenuating drugs were excluded. After analyses on preliminary cohort, peak HR-modifying factors were eliminated to obtain a pure data set. Analysis of variance was used to test difference in HR responses by sex with age adjustment. RESULTS: A total of 37,010 patients (67.3% men) were included in the preliminary cohort. Men had higher peak HR (166±17 vs 163±16 beats/min [bpm]; P<.001), HR reserve (90±19 vs 84±17 bpm; P<.001), and HR recovery (19±8 vs 18±9 bpm; P<.03). Poor exercise capacity, current smoking, diabetes, and obesity had significant peak HR-lowering effects (all P<.001). In a pure cohort of 19,013 patients (51.3% of full cohort) without these factors, regression lines approximated more closely the traditional line of 220 - age. For men, the regression line in our final cohort was peak HR = 220 - 0.95 × age. For women, both slope (0.79 bpm/y) and intercept (210 bpm) were still substantially different from those obtained with the traditional formula. CONCLUSION: The HR responses to exercise are different in men and women. The HR response of men was close to that obtained with the traditional formula, but peak HR in women had a lower intercept and decreased more slowly with age. A separate formula for peak HR in women appears to be appropriate.