Complex Percutaneous Coronary Intervention Outcomes in Older Adults.

Background Complex percutaneous coronary intervention (PCI) is increasingly performed in older adults (age ≥75 years) with stable ischemic heart disease. However, little is known about clinical outcomes. Methods and Results We derived a cohort of older adults undergoing elective PCI for stable ischemic heart disease across a large health system. We compared 12-month event-free survival (freedom from all-cause death, nonfatal myocardial infarction, stroke, and major bleeding), all-cause death, target lesion revascularization, and bleeding events for patients receiving complex versus noncomplex PCI and derived risk estimates with Cox regression models. We included 513 patients (mean age, 81±5 years). Patients receiving complex PCI versus noncomplex PCI did not significantly differ across a host of clinical characteristics including cardiovascular disease features, noncardiac comorbidities, guideline-directed medical therapy use, and frailty. Patients receiving complex PCI versus noncomplex PCI experienced worse event-free survival (80.4% versus 86.8%), which was not significant in adjusted analyses (hazard ratio [HR], 1.38 [95% CI, 0.88-2.16]). All-cause death at 1 year for patients undergoing complex PCI was nearly double that seen for patients receiving noncomplex PCI (10.2% versus 5.9%), and the risk was significant in models adjusted for clinical characteristics (HR, 1.97 [95% CI, 1.02-3.79]). Target lesion revascularization risk was lower for patients receiving complex PCI (2.2% versus 3.5%, adjusted HR), but bleeding events were not statistically different between groups (25.3% versus 20.5%; P=0.19). Conclusions Complex PCI in older adults with stable ischemic heart disease was associated with lower risk of target lesion revascularization but higher all-cause death compared with noncomplex PCI.

Management of Stable Angina in the Older Adult Population.

As society ages, the number of older adults with stable ischemic heart disease continues to rise. Older adults exhibit the greatest morbidity and mortality from stable angina. Furthermore, they suffer a higher burden of comorbidity and adverse events from treatment than younger patients. Given that older adults were excluded or underrepresented in most randomized controlled trials of stable ischemic heart disease, evidence for management is limited and hinges on subgroup analyses of trials and observational studies. This review aims to elucidate the current definitions of aging, assess the overall burden and clinical presentations of stable ischemic heart disease in older patients, weigh the available evidence for guideline-recommended treatment options including medical therapy and revascularization, and propose a framework for synthesizing complex treatment decisions in older adults with stable angina. Due to evolving goals of care in older patients, it is paramount to readdress the patient's priorities and preferences when deciding on treatment. Ultimately, the management of stable angina in older adults will need to be informed by dedicated studies in representative populations emphasizing patient-centered end points and person-centered decision-making.

Readmission rates and risk factors for readmission after transcatheter aortic valve replacement in patients with end-stage renal disease.

OBJECTIVES: We sought to examine readmission rates and predictors of hospital readmission following TAVR in patients with ESRD. BACKGROUND: End-stage renal disease (ESRD) is associated with poor outcomes following transcatheter aortic valve replacement (TAVR). METHODS: We assessed index hospitalizations for TAVR from the National Readmissions Database from 2017 to 2018 and used propensity scores to match those with and without ESRD. We compared 90-day readmission for any cause or cardiovascular cause. Length of stay (LOS), mortality, and cost were assessed for index hospitalizations and 90-day readmissions. Multivariable logistic regression was performed to identify predictors of 90-day readmission. RESULTS: We identified 49,172 index hospitalizations for TAVR, including 1,219 patients with ESRD (2.5%). Patient with ESRD had higher rates of all-cause readmission (34.4% vs. 19.2%, HR 1.96, 95% CI 1.68-2.30, p<0.001) and cardiovascular readmission (13.2% vs. 7.7%, HR 1.85, 95% CI 1.44-2.38, p<0.001) at 90 days. During index hospitalization, patients with ESRD had longer length of stay (mean difference 1.9 days), increased hospital cost (mean difference $42,915), and increased in-hospital mortality (2.6% vs. 0.9%). Among those readmitted within 90 days, patients with ESRD had longer LOS and increased hospital charge, but similar in-hospital mortality. Diabetes (OR 1.86, 95% CI 1.31-2.64) and chronic pulmonary disease (OR 1.51, 95% CI 1.04-2.18) were independently associated with higher odds of 90-day readmission in patients with ESRD. CONCLUSION: Patients with ESRD undergoing TAVR have higher mortality and increased cost associated with their index hospitalization and are at increased risk of readmission within 90 days following TAVR.

Measures of Financial Hardship From Health Care Expenses Among Families With a Member With Atherosclerotic Cardiovascular Disease in the US.

Importance: Patients with atherosclerotic cardiovascular disease (ASCVD) face substantial financial burden from health care costs as assessed by many disparate measures. However, evaluation of the concordance of existing measures and the prevalence of financial burden based on these measures is lacking. Objective: To compare subjectively reported and objectively measured financial burden from health care in families of patients with ASCVD. Design Setting and Participants: This cross-sectional study used data from the Medical Expenditure Panel Survey, a nationally representative survey of individuals and families in the US, and included all families with 1 or more members with ASCVD from 2014 to 2018. Analyses were conducted from October 2021 to April 2022. Main Outcomes and Measures: Using accepted definitions, objective financial hardship represented annual out-of-pocket medical expenses exceeding 20% of annual postsubsistence income, and subjective financial hardship represented self-reported problems paying medical bills or paying them over time. Prevalence of financial hardship was identified based on individual definitions and their concordance was assessed. Factors associated with each type of financial hardship were examined using risk-adjusted survey logistic regression. Multivariable logistic regression was used to model the odds of subjective financial hardship vs objective financial hardship across subgroups. The association between measures of financial hardship and self-reported deferral of care was also assessed. Results: Among 10 975 families of patients with ASCVD, representing 22.5 million families nationally (mean [SD] age of index individual, 66 [24] years; estimated 54% men]), 37% experienced either objective or subjective financial hardship. This group included 11% (95% CI, 10%-11%) with objective financial hardship, 21% (95% CI, 20%-22%) with subjective financial hardship, and 5% (95% CI, 5%-6%) with both objective and subjective financial hardship. Mean age was 70 (95% CI, 68-71) years vs 61 (95% CI, 60-62) years for index patients in families reporting objective financial hardship only vs subjective financial hardship only, with no difference in sex (50% [95% CI, 46%-54%] of men vs 49% [95% CI, 47%-52%] of women). In risk-adjusted analyses, among families of patients with ASCVD, patient age of 65 years or older was associated with lower odds of subjective financial hardship than objective financial hardship (odds ratio [OR], 0.39; 95% CI, 0.20-0.76), whereas higher income (OR, 6.08; 95% CI, 3.93-9.42 for an income of >100%-200% of the federal poverty level [FPL] vs ≤100% of the FPL and OR, 20.46; 95% CI, 11.45-36.56 for >200% of FPL vs ≤100% of FPL), public insurance (OR, 6.60; 95% CI, 4.20-10.37), and being uninsured (OR, 5.36; 95% CI, 2.61-10.98) were associated with higher odds of subjective financial hardship than objective financial hardship. Subjective financial hardship alone was associated with significantly higher adjusted odds of self-reporting deferred or forgone care compared with objective financial hardship alone (OR, 2.69; 95% CI, 1.79-4.06). Conclusions and Relevance: In this cross-sectional study of US adults, 2 in 5 families of patients with ASCVD experienced health care-related financial hardship, but a focus on objective or subjective measures alone would have captured only half the burden and not identified those deferring health care. The findings suggest that a comprehensive framework that evaluates both objective and subjective measures is essential to monitor financial consequences of health care.

Choice of antihypertensive agent in isolated systolic hypertension and isolated diastolic hypertension: A secondary analysis of the ALLHAT trial.

Despite broad treatment recommendations, there are limited published reports comparing the efficacy of different antihypertensive agents in patients with isolated systolic hypertension or isolated diastolic hypertension. This study was a secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We compared the use of chlorthalidone, amlodipine, or lisinopril on the primary outcome of combined coronary heart disease, stroke, or all-cause mortality in patients with isolated systolic hypertension or isolated diastolic hypertension.

Characteristics of patients referred to a cardiovascular disease clinic for post-acute sequelae of SARS-CoV-2 infection.

Introduction: There is limited literature on cardiovascular manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC). Methods: This observational study aimed to describe the characteristics, diagnostic evaluations, and new cardiac diagnoses in patients referred to a cardiovascular disease clinic designed for patients with PASC, and to identify factors associated with cardiovascular symptoms with no identifiable cardiac pathology. Results: Of 126 patients, average age was 46 years, and 34 % were male. Patients presented on average five months after COVID-19 diagnosis. The most common symptoms were dyspnea (52 %), chest pain/pressure (48 %), palpitations (44 %), and fatigue (42 %), commonly associated with exertion or exercise intolerance. New cardiovascular diseases were present in 23 % of cases. The remainder exhibited common symptoms which we termed "cardiovascular PASC syndrome." Discussion: We found that only one in four patients had a new cardiovascular diagnosis, but most displayed a pattern of symptoms associated with exercise intolerance.

Subjective Financial Hardship due to Medical Bills Among Patients With Heart Failure in the United States: The 2014-2018 Medical Expenditure Panel Survey.

BACKGROUND: Heart failure (HF) poses a substantial economic burden on the United States (US) health care system. In contrast, little is known about the financial challenges faced by patients with HF. In this study, we examined the scope and sociodemographic predictors of subjective financial hardship due to medical bills incurred by patients with HF. METHODS: In the Medical Expenditure Panel Survey (MEPS; years 2014--2018), a US nationally representative database, we identified all patients who reported having HF. Any subjective financial hardship due to medical bills was assessed based on patients' reporting either themselves or their families (1) having difficulties paying medical bills in the past 12 months, (2) paying bills late or (3) being unable to pay bills at all. Logistic regression was used to evaluate independent predictors of financial hardship among patients with HF. All analyses took into consideration the survey's complex design. RESULTS: A total of 116,563 MEPS participants were included in the analysis, of whom 858 (0.7%) had diagnoses of HF, representing 1.8 million (95% CI 1.6-2.0) patients annually. Overall, 33% (95% CI 29%-38%) reported any financial hardship due to medical bills, and 13.2% were not able to pay bills at all. Age ≤ 65 years and lower educational attainment were independently associated with higher odds of subjective financial hardship due to medical bills. CONCLUSION: Subjective financial hardship is a prevalent issue for patients with HF in the US, particularly those who are younger and have lower educational attainment. There is a need for policies that reduce out-of-pocket costs for the care of HF, an enhanced identification of this phenomenon in the clinical setting, and approaches to help minimize financial toxicity in patients with HF while ensuring optimal quality of care.

Challenges in interpreting cytokine data in COVID-19 affect patient care and management.

Challenges in using cytokine data are limiting Coronavirus Disease 2019 (COVID-19) patient management and comparison among different disease contexts. We suggest mitigation strategies to improve the accuracy of cytokine data, as we learn from experience gained during the COVID-19 pandemic.

Association of obesity with venous thromboembolism and myocardial injury in COVID-19.

INTRODUCTION: Although both obesity and coronavirus disease 2019 (COVID-19) independently induce inflammation and thrombosis, the association between obesity class and risk of thrombosis in patients with COVID-19 remains unclear. METHODS: This retrospective cohort study included consecutive patients hospitalized with COVID-19 at a single institution. Patients were categorized based on obesity class. The main outcomes were venous thromboembolism (VTE) and myocardial injury, a marker of microvascular thrombosis in COVID-19. Adjustments were made for sociodemographic variables, cardiovascular disease risk factors and comorbidities. RESULTS: 609 patients with COVID-19 were included. 351 (58%) patients were without obesity, 110 (18%) were patients with class I obesity, 76 (12%) were patients with class II obesity, and 72 (12%) were patients with class III obesity. Patients with class I and III obesity had significantly higher risk-adjusted odds of VTE compared to patients without obesity (OR = 2.54, 95% CI: 1.05-6.14 for class I obesity; and OR = 3.95, 95% CI: 1.40-11.14 for class III obesity). Patients with class III obesity had significantly higher risk-adjusted odds of myocardial injury compared to patients without obesity (OR = 2.15, 95% CI: 1.12-4.12). Both VTE and myocardial injury were significantly associated with greater risk-adjusted odds of mortality. CONCLUSION: This study demonstrates that both macrovascular and microvascular thromboses may contribute to the elevated morbidity and mortality in patients with obesity and COVID-19.

Out-of-Pocket Annual Health Expenditures and Financial Toxicity From Healthcare Costs in Patients With Heart Failure in the United States.

Background Heart failure (HF) poses a major public health burden in the United States. We examined the burden of out-of-pocket healthcare costs on patients with HF and their families. Methods and Results In the Medical Expenditure Panel Survey, we identified all families with ≥1 adult member with HF during 2014 to 2018. Total out-of-pocket healthcare expenditures included yearly care-specific costs and insurance premiums. We evaluated 2 outcomes of financial toxicity: (1) high financial burden-total out-of-pocket healthcare expense to postsubsistence income ratio of >20%, and (2) catastrophic financial burden with the ratio of >40%-a bankrupting expense defined by the World Health Organization. There were 788 families in the Medical Expenditure Panel Survey with a member with HF representing 0.54% (95% CI, 0.48%-0.60%) of all families nationally. The overall mean annual out-of-pocket healthcare expenses were $4423 (95% CI, $3908-$4939), with medications and health insurance premiums representing the largest categories of cost. Overall, 14% (95% CI, 11%-18%) of families experienced a high burden and 5% (95% CI, 3%-6%) experienced a catastrophic burden. Among the two-fifths of families considered low income, 24% (95% CI, 18%-30%) experienced a high financial burden, whereas 10% (95% CI, 6%-14%) experienced a catastrophic burden. Low-income families had 4-fold greater risk-adjusted odds of high financial burden (odds ratio [OR] , 3.9; 95% CI, 2.3-6.6), and 14-fold greater risk-adjusted odds of catastrophic financial burden (OR, 14.2; 95% CI, 5.1-39.5) compared with middle/high-income families. Conclusions Patients with HF and their families experience large out-of-pocket healthcare expenses. A large proportion encounter financial toxicity, with a disproportionate effect on low-income families.

Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis.

Thrombotic complications occur at high rates in hospitalized patients with COVID-19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. We examined in-hospital mortality with intermediate- compared to prophylactic-dose anticoagulation, and separately with in-hospital aspirin compared to no antiplatelet therapy, in a large, retrospective study of 2785 hospitalized adult COVID-19 patients. In this analysis, we established two separate, nested cohorts of patients (a) who received intermediate- or prophylactic-dose anticoagulation ("anticoagulation cohort", N = 1624), or (b) who were not on home antiplatelet therapy and received either in-hospital aspirin or no antiplatelet therapy ("aspirin cohort", N = 1956). To minimize bias and adjust for confounding factors, we incorporated propensity score matching and multivariable regression utilizing various markers of illness severity and other patient-specific covariates, yielding treatment groups with well-balanced covariates in each cohort. The primary outcome was cumulative incidence of in-hospital death. Among propensity score-matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate- compared to prophylactic-dose anticoagulation was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.518 [0.308-0.872]). Among propensity-score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in-hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in-hospital death (hazard ratio 0.522 [0.336-0.812]). In this propensity score-matched, observational study of COVID-19, intermediate-dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in-hospital death.

Non-Vitamin K Antagonist Oral Anticoagulant for Atrial Fibrillation in Obese Patients.

Four non-vitamin K antagonist oral anticoagulants (NOACs) are approved for use to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation (AF). However, data are limited regarding the use of NOACs in the obese population. This manuscript summarizes current concepts regarding obesity in patients with AF and reviews in depth the data on the efficacy and safety of NOACs in obese patients with AF. The Pubmed database was searched for relevant articles. When evaluating obese patients with AF, weight loss is important to reduce disease burden. Recent analyses of the four NOAC versus warfarin trials (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48) stratified by body mass index (BMI) demonstrate preserved efficacy with NOACs versus warfarin in obese patients, with similar risk of major bleeding. Although the data are limited in class III obese patients (body mass index ≥40kg/m2), the efficacy and safety of apixaban or edoxaban appears to be similar to warfarin in patients with BMI 40-50kg/m2. In conclusion, these new data should be considered in updated guidelines, which currently provide limited, and sometimes conflicting recommendations regarding the use of NOACs in obese patients, particularly in severely obese patients.

Changes in inflammatory and immune drivers in response to immunomodulatory therapies in COVID-19.

As the global community strives to discover effective therapies for COVID-19, immunomodulatory strategies have emerged as a leading contender to combat the cytokine storm and improve clinical outcomes in patients with severe disease. Systemic corticosteroids and selective cytokine inhibitory agents have been utilized both as empiric therapies and in clinical trials. While multiple randomized, placebo controlled trials have now demonstrated that corticosteroids improve survival in patients with COVID-19,1, 2 IL-6 inhibition, which gained significant early interest based on observational studies, has not demonstrated reliable efficacy in randomized, placebo controlled trials.3, 4 To better understand the mechanistic basis of immunomodulatory therapies being implemented for treatment of COVID-19, we assessed longitudinal biochemical changes in response to such approaches in hospitalized patients with COVID-19. We demonstrate broad suppression of multiple immunomodulatory factors associated with adverse clinical outcomes in COVID-19 in patients who received corticosteroids, but no such response was seen in patients who either received tocilizumab or no immunomodulatory therapy. Our findings provide early insights into molecular signatures that correlate with immunomodulatory therapies in COVID-19 which may be useful in understanding clinical outcomes in future studies of larger patient cohorts.

Longitudinal Associations Between Income Changes and Incident Cardiovascular Disease: The Atherosclerosis Risk in Communities Study.

Importance: Higher income is associated with lower incident cardiovascular disease (CVD). However, there is limited research on the association between changes in income and incident CVD. Objective: To examine the association between change in household income and subsequent risk of CVD. Design, Setting, and Participants: The Atherosclerosis Risk In Communities (ARIC) study is an ongoing, prospective cohort of 15 792 community-dwelling men and women, of mostly black or white race, from 4 centers in the United States (Jackson, Mississippi; Washington County, Maryland; suburbs of Minneapolis, Minnesota; and Forsyth County, North Carolina), beginning in 1987. For our analysis, participants were followed up until December 31, 2016. Exposures: Participants were categorized based on whether their household income dropped by more than 50% (income drop), remained unchanged/changed less than 50% (income unchanged), or increased by more than 50% (income rise) over a mean (SD) period of approximately 6 (0.3) years between ARIC visit 1 (1987-1989) and visit 3 (1993-1995). Main Outcomes and Measures: Our primary outcome was incidence of CVD after ARIC visit 3, including myocardial infarction (MI), fatal coronary heart disease, heart failure (HF), or stroke during a mean (SD) of 17 (7) years. Analyses were adjusted for sociodemographic variables, health behaviors, and CVD biomarkers. Results: Of the 8989 included participants (mean [SD] age at enrollment was 53 [6] years, 1820 participants were black [20%], and 3835 participants were men [43%]), 900 participants (10%) experienced an income drop, 6284 participants (70%) had incomes that remained relatively unchanged, and 1805 participants (20%) experienced an income rise. After full adjustment, those with an income drop experienced significantly higher risk of incident CVD compared with those whose incomes remained relatively unchanged (hazard ratio, 1.17; 95% CI, 1.03-1.32). Those with an income rise experienced significantly lower risk of incident CVD compared with those whose incomes remained relatively unchanged (hazard ratio, 0.86; 95% CI, 0.77-0.96). Conclusions and Relevance: Income drop over 6 years was associated with higher risk of subsequent incident CVD over 17 years, while income rise over 6 years was associated with lower risk of subsequent incident CVD over 17 years. Health professionals should have greater awareness of the influence of income change on the health of their patients.

Utility of the Cardiovascular Physical Examination and Impact of Spironolactone in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The prognostic value of physical examination, its relation to quality of life, and influence of therapy in heart failure with preserved ejection fraction is not well known. METHODS AND RESULTS: We studied participants from the Americas with available physical examination (jugular venous distention, rales, and edema) at baseline in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist). The association of the number of signs of congestion with the primary outcome (cardiovascular death or heart failure hospitalization), its individual components, and all-cause mortality was assessed using time-updated, multivariable-adjusted Cox regression analyses. We evaluated whether spironolactone improved congestion at 4 months and whether improvement in congestion was related to quality of life as assessed by Kansas City Cardiomyopathy Questionnaire overall summary scores and to outcomes. Among 1644 participants, 22%, 54%, 20%, and 4% had 0, 1, 2, and 3 signs of congestion, respectively, at baseline. After multivariable adjustment, each additional increase in sign of congestion was associated with a 30% to 60% increased risk of each outcome ( P<0.001). Spironolactone reduced the total number of signs of congestion by -0.10 ( P=0.005) signs, jugular venous distention (odds ratio, 0.60; P=0.01), and edema (odds ratio, 0.74; P=0.006) at 4 months compared with placebo. Each reduction in sign of congestion was independently associated with a 4.0 (95% CI, 2.4-5.6) point improvement in Kansas City Cardiomyopathy Questionnaire overall summary score. When assessed simultaneously, time-updated, but not baseline congestion, predicted outcomes. CONCLUSIONS: In heart failure with preserved ejection fraction, the physical exam provides independent prognostic value for adverse outcomes. Spironolactone improved congestion compared with placebo. Reducing congestion was independently associated with improved quality of life and outcomes and is a modifiable risk factor. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00094302.

The Beyond the Books Program: Improving Medical Student Attitudes Toward the Underserved.

Purpose: To determine the impact of the Beyond the Books (BTB) program, a short-term pre-clinical intervention, on medical student attitudes toward the underserved (MSATU). Methods: BTB was evaluated through a prospective cohort study using the validated MSATU questionnaire. Results: There were no significant MSATU total score differences between BTB students (n=13) and student controls (n=29) at the beginning of the program. At the program's conclusion, BTB participant MSATU total scores were significantly higher than those of controls (p<0.001). Conclusion: Although limited by selection methods, our MSATU data support the capability of short-term pre-clinical interventions to significantly improve medical student attitudes toward underserved communities.

Dofetilide-Associated QT Prolongation: Total Body Weight Versus Adjusted or Ideal Body Weight for Dosing.

Dofetilide is an antiarrhythmic drug with dosing based on the Cockcroft-Gault formula using total body weight (TBW). We investigated the impact of calculating dofetilide dose using adjusted body weight (ABW) or ideal body weight (IBW) on subsequent dose reduction or discontinuation. We conducted a retrospective review of 265 patients admitted to an academic medical center for initiation of dofetilide using TBW. Dosing was recalculated using ABW or IBW. Patients who would have received a reduced dose using ABW or IBW (reduced dose group) were compared with patients whose dose would not have changed (same dose group). Manual measurement of QT intervals was performed. We found that Forty-one of 265 patients (15%) would have received a lower initial dose of dofetilide based on ABW. Patients in this reduced dose group had 2.95 times greater odds of drug discontinuations or dose reductions due to QTc prolongation (95% confidence interval, 1.47-5.90; P < 0.01) compared with the same dose group. Seventy-seven of 265 patients (29%) would have received a lower initial dose of dofetilide based on IBW. Patients in this reduced dose group had 1.78 times greater odds of drug discontinuations or dose reductions due to QTc prolongation (95% confidence interval, 0.98-3.21; P = 0.056) compared with the same dose group. These data suggest that caution should be used when dosing dofetilide using TBW, as it may lead to a greater frequency of dose reduction or discontinuation compared with dosing using ABW or IBW.

Spontaneous Closure of a Secundum Atrial Septal Defect.

Spontaneous closure of an atrial septal defect (ASD) is well described in pediatric cardiology but may be less familiar to adult internists and cardiologists. We report a moderately sized 6-mm ASD that closed spontaneously without intervention. A literature review found that a smaller defect size and an early age of diagnosis are the most important predictors of closure. Possible mechanisms of a spontaneous ASD closure include adaptive endothelial migration, limited myocardial proliferation, and fibroblast migration with extracellular matrix deposition.