Accelerated Aging in LMNA Mutations Detected by Artificial Intelligence ECG-Derived Age.

OBJECTIVE: To demonstrate early aging in patients with lamin A/C (LMNA) gene mutations after hypothesizing that they have a biological age older than chronological age, as such a finding impacts care. PATIENT AND METHODS: We applied a previously trained convolutional neural network model to predict biological age by electrocardiogram (ECG) [Artificial Intelligence (AI)-ECG age] to LMNA patients evaluated by multiple ECGs from January 1, 2003, to December 31, 2019. The age gap was the difference between chronological age and AI-ECG age. Findings were compared with age-/sex-matched controls. RESULTS: Thirty-one LMNA patients who had a total of 271 ECGs were studied. The median age at symptom onset was 22 years (range, <1-53 years; n=23 patients); eight patients were asymptomatic family members carrying the LMNA mutation. Cardiac involvement was detected by ECG and echocardiogram in 16 patients and consisted of ventricular arrhythmias (13), atrial fibrillation (12), and cardiomyopathy (6). Four patients required cardiac transplantation. Fourteen patients had neurological manifestations, mainly muscular dystrophy. LMNA mutation carriers, including asymptomatic carriers, were 16 years older by AI-ECG than non-LMNA carriers, suggesting accelerated biological age. Most LMNA patients had an age gap of more than 10 years, compared with controls (P<.001). Consecutive AI-ECG analysis showed accelerated aging in the LMNA group compared with controls (P<.0001). There were no significant differences in age-gap among LMNA patients based on phenotype. CONCLUSION: AI-ECG predicted that LMNA patients have a biological age older than chronological age and accelerated aging even in the absence of cardiac abnormalities by traditional methods. Such a finding could translate into early medical intervention and serve as a disease biomarker.

Predictors of Changes in Peak Oxygen Uptake After Outpatient Cardiac Rehabilitation: Importance of Cardiac Rehabilitation Attendance.

Objective: To determine whether the number of cardiac rehabilitation (CR) sessions attended and selected clinical characteristics were predictive of patients who exhibited improvement in peak oxygen uptake (VO2peak) after CR. Patients and Methods: Using the Rochester Epidemiology Project records-linkage system, we identified all consecutive patients aged 18 years or older from Olmsted County, Minnesota, who underwent cardiopulmonary exercise testing before and after CR from 1999 to 2017. Regression models were created to assess the clinical predictors of VO2peak improvement (>0% baseline) after CR. Results: The analysis included 671 patients, of which 524 (78%) patients exhibited VO2peak improvement after CR. The significant univariate predictors of VO2peak improvement included younger age (odds ratio [OR], 0.98; 95% CI, 0.96-0.99), lower pre-CR VO2peak (OR, 0.96; 95% CI, 0.94-0.99), and no history of peripheral artery disease (OR, 0.50; 95% CI, 0.31-0.81) (all, P<.005). The significant independent predictors of VO2peak improvement from the multivariable analysis included the number of CR sessions (OR, 1.04; 95% CI, 1.02-1.05), younger age (OR, 0.96; 95% CI, 0.94-0.98), lower pre-CR VO2peak (OR, 0.92; 95% CI, 0.89-0.95), and no history of peripheral artery disease (OR, 0.47; 95% CI, 0.28-0.78) (all, P<.005). Conclusion: These findings highlight the importance of patient participation in CR sessions and individual clinical characteristics in influencing VO2peak improvement after CR in patients with cardiovascular disease.

Age-Related Differences for Cardiorespiratory Fitness Improvement in Patients Undergoing Cardiac Rehabilitation.

Objective: We investigated age-related differences for peak oxygen uptake (peak VO2) improvement with exercise training during cardiac rehabilitation (CR). Patients and Methods: This was a retrospective cohort study of the Mayo Clinic Rochester CR program including adult patients who attended CR (≥1 session) for any eligible indication between 1999 and 2017 and who had a cardiopulmonary exercise test pre and post CR with VO2 data (peak respiratory exchange ratio ≥1.0). Younger (20-49 yrs), midlife (50-64 yrs), and older adults (≥65 yrs) were compared using ANOVA for delta and percent change in peak VO2; and percentage of peak VO2 responders (>0% change). Results: 708 patients (age: 60.8 ± 12.1 years; 24% female) met inclusion criteria. Delta and percent change in peak VO2 was lower for older adults (1.6 ± 3.2 mL.kg.min-1; 12 ± 27%) compared with younger (3.7 ± 4.0 mL.kg.min-1, p < 0.001; 23 ± 28%, p = 0.002) and midlife adults (2.8 ± 3.8 mL.kg.min-1, p < 0.001; 17 ± 28%, p = 0.04). For midlife, delta change, but not percent change in peak VO2 was significantly lower (p = 0.02) compared with younger. Percentage of responders was only different between older and younger (72 vs. 86%; p = 0.008). Sensitivity analyses in non-surgical patients showed similar differences for delta change, and differences in percent change remained significant between older and younger adults (10 ± 20% vs. 16 ± 18%; p = 0.04). Conclusions: In CR patients, older adults had lower improvement in cardiorespiratory fitness than younger and midlife adults. While excluding surgical patients reduced age-related differences, older adults still had lower cardiorespiratory fitness improvement during CR. These findings may have implications for individualizing CR programming in aging populations to reduce future cardiovascular risk.

Physical Activity and Exercise Patterns After Spontaneous Coronary Artery Dissection: Insights From a Large Multinational Registry.

Objective: The objective of the study was to assess the physical activity (PA) and exercise patterns among participants in a large multinational spontaneous coronary artery dissection (SCAD) registry. Patients and Methods: Participants with SCAD enrolled from March 2011 to November 2019 completed surveys including details regarding PA and exercise habits prior to SCAD, and PA counseling received from their provider after SCAD. Demographics and clinical characteristics were collected by electronic record review. Exercise prescribed to patients after SCAD was categorized according to exercise components: type, intensity, frequency, time/session, and extreme environmental conditions. Results: We included 950 participants; mean ± age was 46.8 ± 9.5 years old at the time of first SCAD; most (96.3%) were women and (77.0%) attended ≥1 cardiac rehabilitation session. Hyperlipidemia (34.3%), hypertension (32.8%), and elevated body weight (overweight = 27.0%; obesity = 20.0%) were the most common comorbidities. Prior to SCAD, 48.5% performed aerobic exercise ≥3 times/week, and only 32.0% performed strength-building exercise regularly. PA counseling details after SCAD in 299/950 participants showed that most (93.3%) patients received some form of counseling including exercise prescription (EXP), non-specific recommendations, and discouraged from any exercise. Limits regarding exercise type and intensity were the most common advice among participants who received EXP. Conclusion: Insights from our study suggest that only 48% of the patients performed some aerobic exercise three or more times per week, and 32.0% performed strength-building exercises, which suggest that most of them may not be as active as assumed. Furthermore, 70% of the SCAD patients have ≥1 cardiovascular risk factors. We suggest guiding patients based on individual assessment, taking into consideration baseline PA habits, treatment, and risk factors. SCAD-tailored PA guidelines are needed for optimal EXP without compromising patient safety.

Body Mass Index, Multi-Morbidity, and COVID-19 Risk Factors as Predictors of Severe COVID-19 Outcomes.

PURPOSE: The purpose of the present study was to investigate body mass index, multi-morbidity, and COVID-19 Risk Score as predictors of severe COVID-19 outcomes. PATIENTS: Patients from this study are from a well-characterized patient cohort collected at Mayo Clinic between January 1, 2020 and May 23, 2020; with confirmed COVID-19 diagnosis defined as a positive result on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays from nasopharyngeal swab specimens. MEASURES: Demographic and clinical data were extracted from the electronic medical record. The data included: date of birth, gender, ethnicity, race, marital status, medications (active COVID-19 agents), weight and height (from which the Body Mass Index (BMI) was calculated, history of smoking, and comorbid conditions to calculate the Charlson Comorbidity Index (CCI) and the U.S Department of Health and Human Services (DHHS) multi-morbidity score. An additional COVID-19 Risk Score was also included. Outcomes included hospital admission, ICU admission, and death. RESULTS: Cox proportional hazards models were used to determine the impact on mortality or hospital admission. Age, sex, and race (white/Latino, white/non-Latino, other, did not disclose) were adjusted for in the model. Patients with higher COVID-19 Risk Scores had a significantly higher likelihood of being at least admitted to the hospital (HR = 1.80; 95% CI = 1.30, 2.50; P < .001), or experiencing death or inpatient admission (includes ICU admissions) (HR = 1.20; 95% CI = 1.02, 1.42; P = .028). Age was the only statistically significant demographic predictor, but obesity was not a significant predictor of any of the outcomes. CONCLUSION: Age and COVID-19 Risk Scores were significant predictors of severe COVID-19 outcomes. Further work should examine the properties of the COVID-19 Risk Factors Scale.

Cardiac rehabilitation availability and characteristics in Latin America and the Caribbean: A Global Comparison.

BACKGROUND: This study aimed to establish availability and characteristics of cardiac rehabilitation (CR) in Latin America and the Caribbean (LAC), where cardiovascular disease is highly prevalent. METHODS: In this cross-sectional sub-analysis focusing on the 35 LAC countries, local cardiovascular societies identified CR programs globally. An online survey was administered to identified programs, assessing capacity and characteristics. CR need was computed relative to ischemic heart disease (IHD) incidence from the Global Burden of Disease study. RESULTS: ≥1 CR program was identified in 24 LAC countries (68.5% availability; median = 3 programs/country). Data were collected in 20/24 countries (83.3%); 139/255 programs responded (54.5%), and compared to responses from 1082 programs in 111 countries. LAC density was 1 CR spot per 24 IHD patients/year (vs 18 globally). Greatest need was observed in Brazil, Dominican Republic and Mexico (all with >150,000 spots needed/year). In 62.8% (vs 37.2% globally P < .001) of CR programs, patients pay out-of-pocket for some or all of CR. CR teams were comprised of a mean of 5.0 ± 2.3 staff (vs 6.0 ± 2.8 globally; P < .001); Social workers, dietitians, kinesiologists, and nurses were significantly less common on CR teams than globally. Median number of core components offered was 8 (vs 9 globally; P < .001). Median dose of CR was 36 sessions (vs 24 globally; P < .001). Only 27 (20.9%) programs offered alternative CR models (vs 31.1% globally; P < .01). CONCLUSION: In LAC countries, there is very limited CR capacity in relation to need. CR dose is high, but comprehensiveness low, which could be rectified with a more multidisciplinary team.

A Midwest COVID-19 Cohort for the Evaluation of Multimorbidity and Adverse Outcomes from COVID-19.

OBJECTIVE: To describe the process and outcome of creating a patient cohort in the early stages of the COVID-19 pandemic in order to better understand the process of and predict the outcomes of COVID-19. PATIENTS AND METHODS: A total of 1169 adults aged 18 years of age or older who tested positive in Mayo Clinic Rochester or the Mayo Clinic Midwest Health System between January 1 and May 23 of 2020. RESULTS: Patients were on average 43.9 years of age and 50.7% were female. Most patients were white (69.0%), and Blacks (23.4%) and Asians (5.8%) were also represented in larger numbers. Hispanics represented 16.3% of the sample. Just under half of patients were married (48.4%). Common comorbid conditions included: cardiovascular diseases (25.1%), dyslipidemia (16.0%), diabetes mellitus (11.2%), chronic obstructive pulmonary disease (6.6%), asthma (7.5%), and cancer (5.1%). All other comorbid conditions were less the 5% in prevalence. Data on 3 comorbidity indices are also available including the: DHHS multi-morbidity score, Charlson Comorbidity Index, and Mayo Clinic COVID-19 Risk Factor Score. CONCLUSION: In addition to managing the ever raging pandemic and growing death rates, it is equally important that we develop adequate resources for the investigation and understanding of COVID-19-related predictors and outcomes.