Induction immunosuppression and post-transplant diabetes mellitus: a propensity-matched cohort study.

Introduction: Post-transplant diabetes mellitus (PTDM) is a common complication among cardiac transplant recipients, causing diabetes-related complications and death. While certain maintenance immunosuppressive drugs increase PTDM risk, it is unclear whether induction immunosuppression can do the same. Therefore, we evaluated whether induction immunosuppression with IL-2 receptor antagonists, polyclonal anti-lymphocyte antibodies, or Alemtuzumab given in the peri-transplant period is associated with PTDM. Methods: We used the Scientific Registry of Transplant Recipients database to conduct a cohort study of US adults who received cardiac transplants between January 2008-December 2018. We excluded patients with prior or multiple organ transplants and those with a history of diabetes, resulting in 17,142 recipients. We created propensity-matched cohorts (n=7,412) using predictors of induction immunosuppression and examined the association between post-transplant diabetes and induction immunosuppression by estimating hazard ratios using Cox proportional-hazards models. Results: In the propensity-matched cohort, the average age was 52.5 (SD=13.2) years, 28.7% were female and 3,706 received induction immunosuppression. There were 867 incident cases of PTDM during 26,710 person-years of follow-up (32.5 cases/1,000 person-years). There was no association between induction immunosuppression and post-transplant diabetes (Hazard Ratio= 1.04, 95% confidence interval 0.91 - 1.19). Similarly, no associations were observed for each class of induction immunosuppression agents and post-transplant diabetes. Conclusion: The use of contemporary induction immunosuppression in cardiac transplant patients was not associated with post-transplant diabetes.

Outcomes With Peripheral Venoarterial Extracorporeal Membrane Oxygenation for Suspected Acute Myocarditis: 10-Year Experience From the Extracorporeal Life Support Organization Registry.

BACKGROUND: Acute myocarditis can result in severe hemodynamic compromise requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). Outcomes and factors associated with mortality among myocarditis patients are not well described in the modern ECMO era. METHODS: We queried the Extracorporeal Life Support Organization registry from 2011 to 2020 for adults with suspected acute myocarditis undergoing peripheral VA-ECMO support. The primary outcome was in-hospital mortality and was compared to all-comers receiving VA-ECMO in the registry over the same period. Secondary outcomes were rates of bridging to advanced therapies and ECMO complications. We used multivariable logistic regression to examine factors associated with in-hospital mortality. RESULTS: Among 850 patients with suspected acute myocarditis receiving peripheral VA-ECMO, the mean age was 41 years, 52% were men, 39% Asian race, and 14.8% underwent extracorporeal cardiopulmonary resuscitation. During the study period, in-hospital mortality steadily declined and was 58.3% for all all-comers receiving VA-ECMO compared with 34.9% for patients with myocarditis (P<0.001). After multivariable modeling, risk factors for mortality were earlier year of support, older age, higher weight, Asian race, need for extracorporeal cardiopulmonary resuscitation, sepsis, and lower mean arterial pressure and pH prior to ECMO initiation. ECMO complications including bleeding, limb ischemia, infections and ischemic stroke were more common among nonsurvivors and significantly declined during the study period. CONCLUSIONS: Compared with all-comers supported with VA-ECMO, in-hospital mortality for patients with acute myocarditis is significantly lower, with nearly two-thirds of patients surviving to discharge. Major modifiable risk factors for mortality were ongoing cardiopulmonary resuscitation requiring ECMO and markers of illness severity prior to ECMO.

Cardiogenic shock related cardiovascular disease mortality trends in US population: Heart failure vs. acute myocardial infarction as contributing causes.

BACKGROUND: Observational and trial data have revealed significant improvement in cardiogenic shock (CS) mortality due to acute myocardial infarction (AMI) after introducing early coronary revascularization. Less is known about CS mortality due to heart failure (HF), which is increasingly recognized as a distinct entity from AMI-CS. METHODS AND RESULTS: In this nationwide observational study, the CDC WONDER database was used to identify national trends in age-adjusted mortality rates (AAMR) due to CS (HF vs. AMI related) per 100,000 people aged 35-84. AAMR from AMI-CS decreased significantly from 1999 to 2009 (AAPC: -6.9% [95%CI -7.7, -6.1]) then stabilized from 2009 to 2020. By contrast, HF-CS associated AAMR rose steadily from 2009 to 2020 (AAPC: 13.3% [95%CI 11.4,15.2]). The mortality rate was almost twice as high in males compared to females in both AMI-CS and HF-CS throughout the study period. HF-CS mortality in the non-Hispanic Black population is increasing more quickly than that of the non-Hispanic White population (AAMR in 2020: 4.40 vs. 1.97 in 100,000). The AMI-CS mortality rate has been consistently higher in rural than urban areas (30% higher in 1999 and 28% higher in 2020). CONCLUSIONS: These trends highlight the fact that HF-CS and AMI-CS represent distinct clinical entities. While mortality associated with AMI-CS has primarily declined over the last two decades, the mortality related to HF-CS has increased significantly, particularly over the last decade, and is increasing rapidly among individuals younger than 65. Accordingly, a dramatic change in the demographics of CS patients in modern intensive care units is expected.

Post-transplant mortality and graft failure after induction immunosuppression among Black heart transplant recipients in the United States.

Black heart transplant recipients are more likely to receive induction immunosuppression compared to other races because of higher rates of acute rejection, graft failure, and mortality. However, it is not known whether contemporary induction immunosuppression improves their post-transplant outcomes. To evaluate whether Black patients who were prescribed induction immunosuppression therapy have lower all-cause mortality or graft-failure rates compared to those who were not, we studied Black U.S. adult heart transplant recipients in the Scientific Registry of Transplant Recipients database (2008-2018). We used multivariable Cox proportional hazards regression analysis to compare the hazards of all-cause mortality or graft failure as a composite, for patients who were prescribed induction immunosuppression and those who were not. Among 5160 recipients, 2787 (54.0%) were prescribed induction immunosuppression and 2373 (46.0%) were not. There was no evidence of survival differences according to induction immunosuppression for the composite of all-cause mortality or graft failure (aHR = 1.13, 95% CI 0.96-1.32), mortality (aHR = 1.14, 95% CI 0.97-1.34), graft failure (aHR = 1.05, 95% CI 0.82-1.34) and acute rejection (aHR = 1.00, 95% CI 0.89-1.12). Given the side effects of treatment, future guidelines should reconsider the recommendation for induction immunosuppression among Black patients.

A clinical and proteomics approach to predict the presence of obstructive peripheral arterial disease: From the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) Study.

BACKGROUND: Peripheral arterial disease (PAD) is a global health problem that is frequently underdiagnosed and undertreated. Noninvasive tools to predict the presence and severity of PAD have limitations including inaccuracy, cost, or need for intravenous contrast and ionizing radiation. HYPOTHESIS: A clinical/biomarker score may offer an attractive alternative diagnostic method for PAD. METHODS: In a prospective cohort of 354 patients referred for diagnostic peripheral and/or coronary angiography, predictors of ≥50% stenosis in ≥1 peripheral vessel (carotid/subclavian, renal, or lower extremity arteries) were identified from >50 clinical variables and 109 biomarkers. Machine learning identified variables predictive of obstructive PAD; a score derived from the final model was developed. RESULTS: The score consisted of 1 clinical variable (history of hypertension) and 6 biomarkers (midkine, kidney injury molecule-1, interleukin-23, follicle-stimulating hormone, angiopoietin-1, and eotaxin-1). The model had an in-sample area under the receiver operating characteristic curve of 0.85 for obstructive PAD and a cross-validated area under the curve of 0.84; higher scores were associated with greater severity of angiographic stenosis. At optimal cutoff, the score had 65% sensitivity, 88% specificity, 76% positive predictive value (PPV), and 81% negative predictive value (NPV) for obstructive PAD and performed consistently across vascular territories. Partitioning the score into 5 levels resulted in a PPV of 86% and NPV of 98% in the highest and lowest levels, respectively. Elevated score was associated with shorter time to revascularization during 4.3 years of follow-up. CONCLUSIONS: A clinical/biomarker score demonstrates high accuracy for predicting the presence of PAD.

Single-Molecule Counting of High-Sensitivity Troponin I in Patients Referred for Diagnostic Angiography: Results From the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) Study.

BACKGROUND: The meaning of high-sensitivity troponin I (hsTnI) concentrations in patients without acute myocardial infarction (MI) requires clarity. We hypothesized that among patients referred for diagnostic coronary angiography without acute MI, hsTnI concentrations would correlate with prevalent coronary artery disease (CAD) and predict incident cardiovascular events and mortality. METHODS AND RESULTS: We measured hsTnI using a single-molecule counting assay (99th percentile, 6 ng/L) in samples from 991 patients obtained at the time of angiography. Concentrations of hsTnI were assessed relative to the severity of CAD and prognosis during mean follow-up of 3.7 years. Median hsTnI concentration was 4.19 ng/L; 38% of patients had hsTnI concentrations ≥99th percentile. Across increasing hsTnI quartiles, patients had higher prevalence of angiographic CAD; in multivariate models, hsTnI ≥99th percentile independently predicted obstructive CAD (odds ratio: 2.57; P<0.001) and incident MI (hazard ratio [HR]: 2.68; P<0.001), cardiovascular death (HR: 2.29; P=0.001), and all-cause death (HR: 1.84; P=0.004). In those with >70% coronary stenosis, hsTnI ≥99th percentile independently predicted incident MI (HR: 1.87; P=0.01), cardiovascular mortality (HR: 2.74; P=0.001), and the composite end point of MI and all-cause death (HR: 2.06; P<0.001). In participants with coronary stenosis <70%, hsTnI ≥99th percentile even more strongly predicted incident MI (HR: 8.41; P<0.001), cardiovascular mortality (HR: 3.60; P=0.03), and the composite end point of MI and all-cause death (HR: 3.62; P<0.001). CONCLUSIONS: In a large prospective cohort of patients who were free of prevalent MI and undergoing diagnostic coronary angiography, hsTnI concentrations were associated with higher prevalence of CAD and predicted incident MI, cardiovascular death, and all-cause death. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868.

Predicting new-onset HF in patients undergoing coronary or peripheral angiography: results from the Catheter Sampled Blood Archive in Cardiovascular Diseases (CASABLANCA) study.

AIMS: Methods to identify patients at risk for incident HF would be welcome as such patients might benefit from earlier interventions. METHODS AND RESULTS: From a registry of 1251 patients referred for coronary and/or peripheral angiography, we sought to identify independent predictors of incident HF during follow-up and develop a clinical and biomarker strategy to predict this outcome. There were 991 patients free of prevalent HF at baseline. Cox proportional hazard models were developed to predict adjudicated diagnosis of incident HF. Model discrimination and reclassification were evaluated. At follow-up, 177 (18%) developed new-onset HF. Independent predictors of new-onset HF included five clinical variables (age, male sex, heart rate, history of atrial fibrillation/flutter, and history of hypertension) and two biomarkers (amino-terminal pro-B type natriuretic peptide and ST2). The c-statistic for the model without biomarkers was 0.69; including biomarkers increased the c-statistic to 0.76 (P < 0.001). A score was developed from the model. Patients in the highest score quintile had shortest time to incident HF compared with lower quintiles (log-rank P < 0.001). Following 100 bootstrap iterations, internal validation was confirmed with Harrell's c-statistic of 0.77. Use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers at enrollment was associated with substantial attenuation of predictive value of the risk score. CONCLUSIONS: Patients undergoing coronary/peripheral angiographic procedures are a population at high risk for incident HF. We describe an accurate clinical and biomarker strategy for predicting incident HF and possibly intervening in such patients (NCT00842868).

Usefulness of Multiple Biomarkers for Predicting Incident Major Adverse Cardiac Events in Patients Who Underwent Diagnostic Coronary Angiography (from the Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA] Study).

We sought to develop a multiple biomarker approach for prediction of incident major adverse cardiac events (MACE; composite of cardiovascular death, myocardial infarction, and stroke) in patients referred for coronary angiography. In a 649-participant training cohort, predictors of MACE within 1 year were identified using least-angle regression; over 50 clinical variables and 109 biomarkers were analyzed. Predictive models were generated using least absolute shrinkage and selection operator with logistic regression. A score derived from the final model was developed and evaluated with a 278-patient validation set during a median of 3.6 years follow-up. The scoring system consisted of N-terminal pro B-type natriuretic peptide (NT-proBNP), kidney injury molecule-1, osteopontin, and tissue inhibitor of metalloproteinase-1; no clinical variables were retained in the predictive model. In the validation cohort, each biomarker improved model discrimination or calibration for MACE; the final model had an area under the curve (AUC) of 0.79 (p <0.001), higher than AUC for clinical variables alone (0.75). In net reclassification improvement analyses, addition of other markers to NT-proBNP resulted in significant improvement (net reclassification improvement 0.45; p = 0.008). At the optimal score cutoff, we found 64% sensitivity, 76% specificity, 28% positive predictive value, and 93% negative predictive value for 1-year MACE. Time-to-first MACE was shorter in those with an elevated score (p <0.001); such risk extended to at least to 4 years. In conclusion, in a cohort of patients who underwent coronary angiography, we describe a novel multiple biomarker score for incident MACE within 1 year (NCT00842868).

Systematic Evaluation of Endothelin 1 Measurement Relative to Traditional and Modern Biomarkers for Clinical Assessment and Prognosis in Patients With Chronic Systolic Heart Failure: Serial Measurement and Multimarker Testing.

OBJECTIVES: To define the role of single or serial measurement of endothelin 1 (ET-1) for prognostication beyond traditional and modern markers of risk in heart failure (HF). METHODS: In total, 115 patients with chronic systolic HF were followed for 10 months. Clinical assessment and ET-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP), highly sensitive troponin I (hsTnI), soluble ST2 (sST2), and galectin 3 were measured at each visit. RESULTS: Elevated ET-1 was associated with worse HF, lower right ventricular function, higher pulmonary pressure, and higher left atrial volume index despite similar left ventricular function. ET-1 correlated with angiotensin-converting enzyme inhibitor use. A model containing traditional risk factors, ET-1, NT-proBNP, hsTnI, and sST2 best predicted cardiovascular events, and ET-1 improved reclassification. In an adjusted time-integrated model, percent time spent with ET-1 of 5.90 pg/mL or less was predictive of fewer cardiovascular events (odds ratio, 0.75; 95% confidence interval, 0.62-0.91). ET-1 reduction over time was associated with a lower rate of cardiovascular events compared with increasing or stable ET-1 (24.4% vs 50.0%). CONCLUSIONS: ET-1 may be a unique predictor of HF prognosis, complementing other biomarkers in a multimarker profile. Serial measurement of ET-1 may provide additional prognostic information.

A Clinical and Biomarker Scoring System to Predict the Presence of Obstructive Coronary Artery Disease.

BACKGROUND: Noninvasive models to predict the presence of coronary artery disease (CAD) may help reduce the societal burden of CAD. OBJECTIVES: From a prospective registry of patients referred for coronary angiography, the goal of this study was to develop a clinical and biomarker score to predict the presence of significant CAD. METHODS: In a training cohort of 649 subjects, predictors of ≥70% stenosis in at least 1 major coronary vessel were identified from >200 candidate variables, including 109 biomarkers. The final model was then validated in a separate cohort (n = 278). RESULTS: The scoring system consisted of clinical variables (male sex and previous percutaneous coronary intervention) and 4 biomarkers (midkine, adiponectin, apolipoprotein C-I, and kidney injury molecule-1). In the training cohort, elevated scores were predictive of ≥70% stenosis in all subjects (odds ratio [OR]: 9.74; p < 0.001), men (OR: 7.88; p <0.001), women (OR: 24.8; p < 0.001), and those with no previous CAD (OR: 8.67; p < 0.001). In the validation cohort, the score had an area under the receiver-operating characteristic curve of 0.87 (p < 0.001) for coronary stenosis ≥70%. Higher scores were associated with greater severity of angiographic stenosis. At optimal cutoff, the score had 77% sensitivity, 84% specificity, and a positive predictive value of 90% for ≥70% stenosis. Partitioning the score into 5 levels allowed for identifying or excluding CAD with >90% predictive value in 42% of subjects. An elevated score predicted incident acute myocardial infarction during 3.6 years of follow up (hazard ratio: 2.39; p < 0.001). CONCLUSIONS: We described a clinical and biomarker score with high accuracy for predicting the presence of anatomically significant CAD. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases; NCT00842868).

Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction.

PURPOSE: To compare remote myocardium native T1 in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T1 in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI. MATERIALS AND METHODS: A total of 41 chronic MI (18 anterior MI) patients and 15 age-matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T1 map was performed using a slice interleaved T1 mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass. RESULTS: The remote myocardium native T1 time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P < 0.05). Remote myocardium native T1 moderately correlated with LV volume, mass index, and ejection fraction (r = 0.38, 0.50, -0.49, respectively, all P < 0.05). LGE infarct size had a moderate correlation with reduced LV ejection fraction (r = -0.33, P < 0.05), but there was no significant association between native T1 and infarct size. Native T1 time in the remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (ß = -0.34, P = 0.03). CONCLUSION: In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T1 in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post-MI LV dysfunction. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1073-1081.

Associations Between Psychological Constructs and Cardiac Biomarkers After Acute Coronary Syndrome.

OBJECTIVE: Psychological constructs are associated with cardiovascular health, but the biological mechanisms mediating these relationships are unknown. We examined relationships between psychological constructs and markers of inflammation, endothelial function, and myocardial strain in a cohort of post-acute coronary syndrome (ACS) patients. METHODS: Participants (N = 164) attended study visits 2 weeks and 6 months after ACS. During these visits, they completed self-report measures of depressive symptoms, anxiety, optimism, and gratitude; and blood samples were collected for measurement of biomarkers reflecting inflammation, endothelial function, and myocardial strain. Generalized estimating equations and linear regression analyses were performed to examine concurrent and prospective relationships between psychological constructs and biomarkers. RESULTS: In concurrent analyses, depressive symptoms were associated with elevated markers of inflammation (interleukin-17: ß = .047; 95% confidence interval [CI] = .010-.083]), endothelial dysfunction (endothelin-1: ß = .020; 95% [CI] = .004-.037]), and myocardial strain (N-terminal pro-B-type natriuretic peptide: ß = .045; 95% [CI] = .008-.083]), independent of age, sex, medical variables, and anxiety, whereas anxiety was not associated with these markers in multivariable adjusted models. Optimism and gratitude were associated with lower levels of markers of endothelial dysfunction (endothelin-1: gratitude: ß = -.009; 95% [CI] = -.017 to - .001]; optimism: ß = -.009; 95% [CI] = -.016 to - .001]; soluble intercellular adhesion molecule-1: gratitude: ß = -.007; 95% [CI] = -.014 to - .000]), independent of depressive and anxiety symptoms. Psychological constructs at 2 weeks were not prospectively associated with biomarkers at 6 months. CONCLUSIONS: Depressive symptoms were associated with more inflammation, myocardial strain, and endothelial dysfunction in the 6 months after ACS, whereas positive psychological constructs were linked to better endothelial function. Larger prospective studies may clarify the directionality of these relationships. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01709669.

Incident Type 2 Myocardial Infarction in a Cohort of Patients Undergoing Coronary or Peripheral Arterial Angiography.

BACKGROUND: Despite growing recognition of type 2 myocardial infarction (T2MI; related to supply/demand mismatch), little is known about its risk factors or its association with outcome. METHODS: A single-center cohort of patients undergoing coronary or peripheral angiography with or without intervention was prospectively enrolled and followed for incident type 1 and T2MI, and major adverse cardiovascular events (MACE, a composite of all-cause death, nonfatal myocardial infarction [MI], heart failure, stroke, transient ischemic attack, peripheral arterial complication, and cardiac arrhythmia), as well. T2MI was adjudicated using criteria from the Third Universal Definition of MI. Baseline characteristics, blood samples, and angiography information were obtained. Major end points subsequent to first MI were assessed using landmark analyses to compare the rates of first events only where everyone with a prior history of any MACE before MI were censored and adjusted for follow-up times. Cox proportional hazard models were used for time-to-event analyses with age and sex forced into all models and additional covariates evaluated by using the stepwise option for the selection. RESULTS: One thousand two hundred fifty-one patients were enrolled and followed for a median of 3.4 years. Of these patients, 152 (12.2%) had T2MI during follow-up; T2MI was frequently recurrent. Multivariable predictors of T2MI were older age, lower systolic blood pressure, history of coronary artery disease, heart failure, chronic obstructive pulmonary disease, diabetes mellitus, nitrate use, and elevated concentrations of glucose, N-terminal pro-B type natriuretic peptide, and cystatin C. Patients with T2MI had higher rates of subsequent adverse events than those without T2MI (per 100 person-years: MACE, 53.7 versus 21.1, P<0.001; all-cause death, 23.3 versus 3.3, P<0.001; cardiovascular death, 17.5 versus 2.6, P<0.001; heart failure events, 22.4 versus 7.4, P<0.001); these rates are similar to those seen in patients with type 1 MI. Incident diagnosis of T2MI strongly predicted risk for subsequent MACE (adjusted hazard ratio, 1.90; 95% confidence interval, 1.46-2.48; P<0.001), all-cause death (adjusted hazard ratio, 2.96; 95% confidence interval, 2.01-4.36; P<0.001), and cardiovascular death (adjusted hazard ratio, 2.16; 95% confidence interval, 1.36-3.43; P=0.001). CONCLUSIONS: T2MI is common and associated with poor prognosis. Studies evaluating treatment strategies for management of T2MI are needed. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842868.

Biomarkers to Predict Reverse Remodeling and Myocardial Recovery in Heart Failure.

Left ventricular remodeling appears to be a critical link between cardiac injury and the development and progression of heart failure with reduced ejection fraction (HFrEF). Several drug and device therapies that modify and reverse the remodeling process in patients with HFrEF are closely associated with improvement in clinical outcomes. Reverse remodeling, including partial or complete recovery of systolic function and structure, is possible but its determinants are incompletely understood. Methods to predict reverse remodeling in response to therapy are not well defined. Though non-invasive imaging techniques remain the most widely used methods of assessing reverse remodeling, serum biomarkers are now being investigated as more specific, mechanistically driven, and clinically useful predictors of reverse remodeling. Biomarkers that reflect myocyte stretch and stress, myocyte injury and necrosis, inflammation and fibrosis, and extracellular matrix turnover may be particularly valuable for predicting pathophysiologic changes and prognosis in individual patients. Their use may ultimately allow improved application of precision medicine in chronic HF.

Effects of Optimism and Gratitude on Physical Activity, Biomarkers, and Readmissions After an Acute Coronary Syndrome: The Gratitude Research in Acute Coronary Events Study.

BACKGROUND: Positive psychological constructs, such as optimism, are associated with beneficial health outcomes. However, no study has separately examined the effects of multiple positive psychological constructs on behavioral, biological, and clinical outcomes after an acute coronary syndrome (ACS). Accordingly, we aimed to investigate associations of baseline optimism and gratitude with subsequent physical activity, prognostic biomarkers, and cardiac rehospitalizations in post-ACS patients. METHODS AND RESULTS: Participants were enrolled during admission for ACS and underwent assessments at baseline (2 weeks post-ACS) and follow-up (6 months later). Associations between baseline positive psychological constructs and subsequent physical activity/biomarkers were analyzed using multivariable linear regression. Associations between baseline positive constructs and 6-month rehospitalizations were assessed via multivariable Cox regression. Overall, 164 participants enrolled and completed the baseline 2-week assessments. Baseline optimism was significantly associated with greater physical activity at 6 months (n=153; ß=102.5; 95% confidence interval, 13.6-191.5; P=0.024), controlling for baseline activity and sociodemographic, medical, and negative psychological covariates. Baseline optimism was also associated with lower rates of cardiac readmissions at 6 months (n=164), controlling for age, sex, and medical comorbidity (hazard ratio, 0.92; 95% confidence interval, [0.86-0.98]; P=0.006). There were no significant relationships between optimism and biomarkers. Gratitude was minimally associated with post-ACS outcomes. CONCLUSIONS: Post-ACS optimism, but not gratitude, was prospectively and independently associated with superior physical activity and fewer cardiac readmissions. Whether interventions that target optimism can successfully increase optimism or improve cardiovascular outcomes in post-ACS patients is not yet known, but can be tested in future studies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01709669.