A New Era in Cardiac Rehabilitation Delivery: Research Gaps, Questions, Strategies, and Priorities.

Cardiac rehabilitation (CR) is a guideline-recommended, multidisciplinary program of exercise training, risk factor management, and psychosocial counseling for people with cardiovascular disease (CVD) that is beneficial but underused and with substantial disparities in referral, access, and participation. The emergence of new virtual and remote delivery models has the potential to improve access to and participation in CR and ultimately improve outcomes for people with CVD. Although data suggest that new delivery models for CR have safety and efficacy similar to traditional in-person CR, questions remain regarding which participants are most likely to benefit from these models, how and where such programs should be delivered, and their effect on outcomes in diverse populations. In this review, we describe important gaps in evidence, identify relevant research questions, and propose strategies for addressing them. We highlight 4 research priorities: (1) including diverse populations in all CR research; (2) leveraging implementation methodologies to enhance equitable delivery of CR; (3) clarifying which populations are most likely to benefit from virtual and remote CR; and (4) comparing traditional in-person CR with virtual and remote CR in diverse populations using multicenter studies of important clinical, psychosocial, and cost-effectiveness outcomes that are relevant to patients, caregivers, providers, health systems, and payors. By framing these important questions, we hope to advance toward a goal of delivering high-quality CR to as many people as possible to improve outcomes in those with CVD.

A MUC5B Gene Polymorphism, rs35705950-T, Confers Protective Effects Against COVID-19 Hospitalization but Not Severe Disease or Mortality.

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is unclear. Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP). Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects. Measurements and Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (Ncases = 4,325; Ncontrols = 507,640; OR = 0.89 [0.82-0.97]; P = 6.86 × 10-3) and joint meta-analyses with the HGI (Ncases = 13,320; Ncontrols = 1,508,841; OR, 0.90 [0.86-0.95]; P = 8.99 × 10-5). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (Ncases = 19,168/Ncontrols = 492,854; OR, 0.98 [0.95-1.01]; P = 0.06) but was nominally significant (P < 0.05) in the joint meta-analysis with the HGI (Ncases = 44,820; Ncontrols = 1,775,827; OR, 0.97 [0.95-1.00]; P = 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 [0.72-0.93]; P = 0.001). Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations.

Cardiac Rehabilitation and the COVID-19 Pandemic: Persistent Declines in CR Participation and Access Among US Medicare Beneficiaries.

Background: The impact of the COVID-19 pandemic on participation in and availability of cardiac rehabilitation (CR) is unknown. Methods: Among eligible Medicare fee-for-service beneficiaries, we evaluated, by month, the number of CR sessions attended per 100,000 beneficiaries, individuals eligible to initiate CR, and centers offering in-person CR between January 2019 and December 2021. We compared these outcomes between two periods: December 1, 2019 through February 28, 2020 (period 1, prior to declaration of the pandemic-related national emergency) and October 1, 2021 through December 31, 2021 (period 2, the latest period for which data are currently available). Results: In period 1, Medicare beneficiaries participated in (mean ± SD) 895 ± 84 CR sessions per 100,000 beneficiaries each month. After the national emergency was declared, CR participation sharply declined to 56 CR sessions per 100,000 beneficiaries in April 2020. CR participation recovered gradually through December 2021, but remained lower than pre-pandemic levels (Period 2: 698 ± 29 CR sessions per month per 100,000 beneficiaries, p=.02). Declines in CR participation were most marked among dual Medicare and Medicaid enrollees, and patients residing in rural areas or socially vulnerable communities. There was no statistically significant change in CR eligibility between the two periods. Compared with 2,618 ± 5 CR centers in period 1, there were 2,464 ± 7 in period 2 (p<0.01). Compared with CR centers that survived the pandemic, 220 CR centers that closed were more likely to be affiliated with public hospitals, located in rural areas, and serve the most socially vulnerable communities. Conclusions: The COVID-19 pandemic was associated with a persistent decline in CR participation and the closure of CR centers, which disproportionately affected rural and low-income patients and the most socially vulnerable communities. Innovation in CR financing and delivery is urgently needed to equitably enhance CR participation among Medicare beneficiaries.

Association between median household income, state Medicaid expansion status, and COVID-19 outcomes across US counties.

OBJECTIVE: To study the relationship between county-level COVID-19 outcomes (incidence and mortality) and county-level median household income and status of Medicaid expansion of US counties. METHODS: Retrospective analysis of 3142 US counties was conducted to study the relationship between County-level median-household-income and COVID-19 incidence and mortality per 100,000 people in US counties, January-20th-2021 through December-6th-2021. County median-household-income was log-transformed and stratified by quartiles. Multilevel-mixed-effects-generalized-linear-modeling adjusted for county socio-demographic and comorbidities and tested for Medicaid-expansion-times-income-quartile interaction on COVID-19 outcomes. RESULTS: There was no significant difference in COVID-19 incidence-rate across counties by income quartiles or by Medicaid expansion status. Conversely, for non-Medicaid-expansion states, counties in the lowest income quartile had a 41% increase in COVID-19 mortality-rate compared to counties in the highest income quartile. Mortality-rate was not related to income in counties from Medicaid-expansion states. CONCLUSIONS: Median-household-income was not related to COVID-19 incidence-rate but negatively related to COVID-19 mortality-rate in US counties of states without Medicaid-expansion.

Long-term Cardiovascular Manifestations and Complications of COVID-19: Spectrum and Approach to Diagnosis and Management.

Survivors of coronavirus disease 2019 (COVID-19) may experience persistent symptoms, abnormal diagnostic test findings, incident disease in specific organ systems, or progression of existing disease. Post-acute COVID-19 syndrome (PACS) is defined by persistent, recurrent, or new symptoms, findings, or diagnoses beyond four weeks after the initial infection. PACS has been characterized as a multi-organ syndrome, often with cardiopulmonary symptoms that include fatigue, dyspnea, chest pain, and palpitations. Cardiovascular pathologies in PACS include new-onset arrhythmia, myocarditis, unmasked coronary artery disease, and diastolic dysfunction as well as abnormal findings on electrocardiogram, troponin testing, and cardiac magnetic resonance imaging. In this review, we discuss the cardiovascular symptoms, pathophysiology, clinical investigation, and management strategies for cardiopulmonary symptoms of PACS. We offer a treatment algorithm for primary care clinicians encountering patients with cardiopulmonary PACS and discuss ongoing research on this topic.

Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

Importance: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear. Objective: To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19. Design, Setting, and Participants: COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129 848 SCT-negative individuals, of whom 13 488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021. Exposures: The hemoglobin beta S (HbS) allele (rs334-T). Main Outcomes and Measures: This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records. Results: Of the 132 577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P = .01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure. Conclusions and Relevance: In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity.

Genetic Loci Associated With COVID-19 Positivity and Hospitalization in White, Black, and Hispanic Veterans of the VA Million Veteran Program.

SARS-CoV-2 has caused symptomatic COVID-19 and widespread death across the globe. We sought to determine genetic variants contributing to COVID-19 susceptibility and hospitalization in a large biobank linked to a national United States health system. We identified 19,168 (3.7%) lab-confirmed COVID-19 cases among Million Veteran Program participants between March 1, 2020, and February 2, 2021, including 11,778 Whites, 4,893 Blacks, and 2,497 Hispanics. A multi-population genome-wide association study (GWAS) for COVID-19 outcomes identified four independent genetic variants (rs8176719, rs73062389, rs60870724, and rs73910904) contributing to COVID-19 positivity, including one novel locus found exclusively among Hispanics. We replicated eight of nine previously reported genetic associations at an alpha of 0.05 in at least one population-specific or the multi-population meta-analysis for one of the four MVP COVID-19 outcomes. We used rs8176719 and three additional variants to accurately infer ABO blood types. We found that A, AB, and B blood types were associated with testing positive for COVID-19 compared with O blood type with the highest risk for the A blood group. We did not observe any genome-wide significant associations for COVID-19 severity outcomes among those testing positive. Our study replicates prior GWAS findings associated with testing positive for COVID-19 among mostly White samples and extends findings at three loci to Black and Hispanic individuals. We also report a new locus among Hispanics requiring further investigation. These findings may aid in the identification of novel therapeutic agents to decrease the morbidity and mortality of COVID-19 across all major ancestral populations.

Cardiovascular Outcomes of Patients Referred to Home Based Cardiac Rehabilitation.

BACKGROUND: Home Based Cardiac Rehabilitation (HBCR) has been considered a reasonable alternative to Center-based Cardiac Rehabilitation (CBCR) in patients with established cardiovascular disease, especially in the midst of COVID-19 pandemic. However, the long-term cardiovascular outcomes of patients referred to HBCR remains unknown. OBJECTIVES: To compare outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR). METHODS: We performed a retrospective study of 269 patients referred to HBCR at Providence Veterans Affairs Medical Center (PVAMC). From November 2017 to March 2020, 427 patients were eligible and referred for Cardiac Rehabilitation (CR) at PVAMC. Of total patients, 158 patients were referred to CBCR and 269 patients to HBCR based on patient and/or clinician preference. The analysis of outcomes was focused on HBCR patients. We compared outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR) from 3 to 12 months of the referral date. HBCR consisted of face-to-face entry exam with exercise prescription, weekly phone calls for education and exercise monitoring, with adjustments where applicable, for 12-weeks and an exit exam. Primary outcome was composite of all-cause mortality and hospitalizations. Secondary outcomes were all-cause hospitalization, all-cause mortality and cardiovascular hospitalizations, separately. We used cox proportional methods to calculate hazard ratios (HR) and 95% CI. We adjusted for imbalanced characteristics at baseline: smoking, left ventricular ejection fraction and CABG status. RESULTS: A total of 269 patients (mean age: 72, 98% Male) were referred to HBCR, however, only 157 (58%) patients attended HBCR. The primary outcome occurred in 30 patients (19.1%) in the HBCR group and 30 patients (30%) in the Non-HBCR group (adjusted HR=0.56, CI 0.33-0.95, P=.03). All-cause mortality occurred in 6.4% of patients in the HBCR group and 13% patients in the Non-HBCR group 3 to 12 months after HBCR referral (adjusted HR=0.43, CI 0.18-1.0, P= .05). There was no difference in cardiovascular hospitalizations (HBCR: 5.7% vs Non-HBCR: 10%, adjusted HR 0.57, CI 0.22-1.4, P= .23) or all cause hospitalizations at 3 to 12 months between the groups (HBCR: 12.7% vs Non-HBCR: 21%, adjusted HR 0.53, CI 0.28-1.01, P= .05). CONCLUSION: Completion of HBCR among referred patients was associated with a lower risk of the combined all-cause mortality and all-cause hospitalizations up to 12 months. Based on the outcomes, HBCR is a reasonable option that can improve access to CR for patients who are not candidates of or cannot attend CBCR. Randomized-controlled studies are needed to confirm these findings.

Early vs. Late Onset Cardiac Injury and Mortality in Hospitalized COVID-19 Patients in Wuhan.

Background: Increasing evidence points to cardiac injury (CI) as a common coronavirus disease 2019 (COVID-19) related complication. The characteristics of early CI (occurred within 72 h of admission) and late CI (occurred after 72 h of admission) and its association with mortality in COVID-19 patients is unknown. Methods: This retrospective study analyzed patients confirmed with COVID-19 in Union Hospital (Wuhan, China) from Jan 29th to Mar 15th, 2020. Clinical outcomes (discharge, or death) were monitored to April 15, 2020, the latest date of follow-up. Demographic, clinical, laboratory, as well as treatment and prognosis were collected and analyzed in patients with early, late CI and without CI. Results: A total of 196 COVID-19 patients were included for analysis. The median age was 65 years [interquartile range (IQR) 56-73 years], and 112 (57.1%) were male. Of the 196 COVID-19 patients, 49 (25.0%) patients had early and 20 (10.2%) patients had late CI, 56.6% developed Acute-Respiratory-Distress-Syndrome (ARDS) and 43 (21.9%) patients died. Patients with any CI were more likely to have developed ARDS (87.0 vs. 40.2%) and had a higher in-hospital mortality than those without (52.2 vs. 5.5%, P < 0.001). Among CI subtypes, a significantly higher risk of in-hospital death was found in patients with early CI with recurrence [19/49 patients, adjusted odds ratio (OR) = 7.184, 95% CI 1.472-35.071] and patients with late CI (adjusted OR = 5.019, 95% CI 1.125-22.388) compared to patients with early CI but no recurrence. Conclusions: CI can occur early on or late after, the initial 72 h of admission and is associated with ARDS and an increased risk of in-hospital mortality. Both late CI and recurrent CI after the initial episode were associated with worse outcomes than patients with early CI alone. This study highlights the importance of early examination and periodical monitoring of cardiac biomarkers, especially for patients with early CI or at risk of clinical deterioration.

Outcomes of coronavirus disease-2019 among veterans with pre-existing diagnosis of heart failure.

AIMS: Pre-existing cardiovascular disease in general and related risk factors have been associated with poor coronavirus disease-2019 (COVID-19) outcomes. However, data on outcomes of COVID-19 among people with pre-existing diagnosis of heart failure (HF) have not been studied in sufficient detail. We aimed to perform detailed characterization of the association of pre-existing HF with COVID-19 outcomes. METHODS AND RESULTS: A retrospective cohort study based on Veterans Health Administration (VHA) data comparing 30 day mortality and hospital admission rates after COVID-19 diagnosis among Veterans with and without pre-existing diagnosis of HF. Cox-regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for covariates. Among 31 051 veterans (97% male) with COVID-19, 6148 had pre-existing diagnosis of HF. The mean (SD) age of patients with HF was 70 (13) whereas the mean (SD) age of patients without HF was 57 (17). Within the HF group with available data on left ventricular ejection fraction (EF), 1844 patients (63.4%) had an EF of >45%, and 1063 patients (36.6%) had an EF of ≤45%. Patients in the HF cohort had higher 30 day mortality (5.4% vs. 1.5%) and admission (18.5% vs. 8.4%) rates after diagnosis of COVID-19. After adjustment for age, sex, and race, HRs (95% CIs) for 30 day mortality and for 30 day hospital admissions were 1.87 (1.61-2.17) and 1.79 (1.66-1.93), respectively. After additional adjustment for medical comorbidities, HRs for 30 day mortality and for 30 day hospital admissions were 1.37 (1.15-1.64) and 1.27 (1.16-1.38), respectively. The findings were similar among HF patients with preserved vs. reduced EF, among those taking vs. not taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, and among those taking vs. not taking anticoagulants. CONCLUSIONS: Patients with COVID-19 and pre-existing diagnosis of HF had a higher risk of 30 day mortality and hospital admissions compared to those without history of HF. The findings were similar by EF categories and by angiotensin-converting enzyme inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitors or anticoagulant use.

Association of poor housing conditions with COVID-19 incidence and mortality across US counties.

OBJECTIVE: Poor housing conditions have been linked with worse health outcomes and infectious disease spread. Since the relationship of poor housing conditions with incidence and mortality of COVID-19 is unknown, we investigated the association between poor housing condition and COVID-19 incidence and mortality in US counties. METHODS: We conducted cross-sectional analysis of county-level data from the US Centers for Disease Control, US Census Bureau and John Hopkins Coronavirus Resource Center for 3135 US counties. The exposure of interest was percentage of households with poor housing conditions (one or greater of: overcrowding, high housing cost, incomplete kitchen facilities, or incomplete plumbing facilities). Outcomes were incidence rate ratios (IRR) and mortality rate ratios (MRR) of COVID-19 across US counties through 4/21/2020. Multilevel generalized linear modeling (with total population of each county as a denominator) was utilized to estimate relative risk of incidence and mortality related to poor housing conditions with adjustment for population density and county characteristics including demographics, income, education, prevalence of medical comorbidities, access to healthcare insurance and emergency rooms, and state-level COVID-19 test density. We report incidence rate ratios (IRRs) and mortality ratios (MRRs) for a 5% increase in prevalence in households with poor housing conditions. RESULTS: Across 3135 US counties, the mean percentage of households with poor housing conditions was 14.2% (range 2.7% to 60.2%). On April 21st, the mean (SD) number of cases and deaths of COVID-19 were 255.68 (2877.03) cases and 13.90 (272.22) deaths per county, respectively. In the adjusted models standardized by county population, with each 5% increase in percent households with poor housing conditions, there was a 50% higher risk of COVID-19 incidence (IRR 1.50, 95% CI: 1.38-1.62) and a 42% higher risk of COVID-19 mortality (MRR 1.42, 95% CI: 1.25-1.61). Results remained similar using earlier timepoints (3/31/2020 and 4/10/2020). CONCLUSIONS AND RELEVANCE: Counties with a higher percentage of households with poor housing had higher incidence of, and mortality associated with, COVID-19. These findings suggest targeted health policies to support individuals living in poor housing conditions should be considered in further efforts to mitigate adverse outcomes associated with COVID-19.

Transition to Home-Based Treatment Plans for Center-Based Cardiac, Pulmonary, and Vascular Rehabilitation during COVID-19.

BACKGROUND: Traditional rehabilitation services, whether they are cardiac, pulmonary, or vascular, consist of 6-36 center-based, supervised sessions; however, due to COVID-19, in-person visits were suspended. This study sought to implement a transitional home-based treatment plan (HBTP) to patients. METHOD: Patients enrolled in a rehabilitation service at the Miriam Hospital during the time of temporary closure were provided with a HBTP that was individualized to their needs and multi-disciplinary in nature. Patients were called weekly for continual guidance and support. RESULTS: Of the 129 patients that received a HBTP, 115 (89%) participated in follow-up correspondence (63±12 years, 83% white, 66% male, 81% enrolled in cardiac rehab). Nearly 70% of patients continued to participate in regular exercise and upon re-opening, 69 (60%) of patients returned to center-based care. Psychosocial factors appeared to inhibit treatment adherence. CONCLUSIONS: Patients are receptive to an HBTP and subsequent follow-up throughout temporary closure of rehabilitation services.