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.

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.

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.

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.

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.

Galectin-3 and mineralocorticoid receptor antagonist use in patients with chronic heart failure due to left ventricular systolic dysfunction.

BACKGROUND: Galectin-3 is a prognostic heart failure biomarker associated with aldosterone-induced myocardial fibrosis; mineralocorticoid receptor antagonists (MRAs) may reduce such fibrosis. We sought to examine outcomes of patients with heart failure with reduced ejection fraction (HFrEF) as a function of galectin-3 and MRA therapy. METHODS: A total of 151 patients with chronic HFrEF were categorized by baseline galectin-3 and subsequent MRA therapy trends with regard to cardiovascular (CV) events, left ventricular remodeling, safety, and quality of life, over a mean of 10 months. RESULTS: Although galectin-3 >20 ng/mL was associated with doubling in adjusted risk for CV events, regardless of MRA treatment, there was no difference in CV event rates with regard to MRA use patterns, independent of galectin-3 concentrations. Specifically, in patients with elevated galectin-3 treated with intensified MRA therapy, a significant difference was not detected in CV event rates (P = .79) or the cumulative number of such events (P = .76). Adjusted analysis revealed no difference in time to first CV event if MRA was added/intensified in those with elevated galectin-3 (hazard ratio 0.99, 95% CI 0.97-1.02, P = .74); similarly, cumulative MRA dose was not a specific predictor of benefit. In those with elevated galectin-3, MRA therapy did not affect left ventricular remodeling indices or quality of life at follow-up; these patients had the highest rates of treatment-related adverse events with intensified MRA use. Regardless of MRA use, elevated galectin-3 was associated with more significant renal dysfunction. CONCLUSIONS: Among patients with chronic HFrEF and elevated galectin-3 concentrations, we found no specific benefit from addition or intensification of MRA therapy.

Characterization and prediction of adverse events from intensive chronic heart failure management and effect on quality of life: results from the pro-B-type natriuretic peptide outpatient-tailored chronic heart failure therapy (PROTECT) study.

BACKGROUND: Serious adverse events (SAEs) from heart failure (HF) therapy are frequent; however, techniques to identify at-risk patients are inadequate. Furthermore, the relationship between SAEs, quality of life (QOL), and cardiac structure are unknown. METHODS AND RESULTS: 151 symptomatic patients with systolic HF were followed for a mean of 10 months. In this post hoc analysis, treatment-related SAEs included acute renal failure, dizziness, hypo/hyperkalemia, hypotension, and syncope. At 1 year, 21 treatment-related SAEs occurred. No difference in SAEs existed between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided arm and the standard of care arm (P = .20). At baseline, patients who suffered SAEs were less likely to be receiving beta-blockers (85.7% vs 97.7%; P = .009) and had worse functional class and lower chloride levels. Patients who experienced SAEs had less improvement in their Minnesota Living With Heart Failure Questionnaire scores and had a trend toward reduced echocardiographic reverse remodeling over the follow-up period. Univariable and multivariable analyses were conducted to develop a risk score for SAE prediction; patients in the highest risk quartile had the shortest time to first cardiovascular event (P = 0.01). CONCLUSIONS: NT-proBNP-guided HF care is safe. Experiencing treatment-related SAEs is associated with worse QOL and potentially reduced reverse remodeling. A risk score to prospectively predict SAEs in aggressive HF management was developed.

ST2 pathogenetic profile in ambulatory heart failure patients.

BACKGROUND: Soluble ST2 is involved in multiple pathogenic pathways, including cardiac strain, inflammation, and myocardial necrosis with remodeling. The relative weight of ST2 and the point at which its prognostic value in heart failure (HF) is affected by different degrees of myocardial strain, inflammation, necrosis, and remodeling is unknown. METHODS AND RESULTS: We examined whether soluble ST2 levels improves HF risk stratification relative to other biomarkers representative of multiple pathogenic pathways-N-terminal pro-B-type natriuretic peptide (NT-proBNP; strain), high-sensitivity C-reactive protein (hsCRP; inflammation), and galectin-3 and high-sensitivity troponin T (hsTnT; necrosis and remodeling)-in 1,015 patients with mean left ventricular ejection fraction (LVEF) 33.5%. Mean follow-up was 4.2 ± 2.1 years. The correlation with soluble ST2 was highest with NT-proBNP (r = 0.32; P < .001) and lowest with galectin-3 (r = 0.15; P < .001). ST2 levels increased with increasing concentrations of the other biomarkers (P < .001 in all cases). During follow-up, 467 patients died. Soluble ST2 remained an independent prognosticator of risk at every tertile of each biomarker. This was observed even after adjusting for clinical parameters. CONCLUSIONS: Soluble ST2 may be regarded as a 3-in-1 prognosis biomarker in HF. ST2 provides valuable long-term risk stratification information in HF beyond that reported by other biomarkers of stretch, inflammation, necrosis, and remodeling.

Comparison between admission natriuretic peptides, NGAL and sST2 testing for the prediction of worsening renal function in patients with acutely decompensated heart failure.

BACKGROUND: In order to predict the occurrence of worsening renal function (WRF) and of WRF plus in-hospital death, 101 emergency department (ED) patients with acute decompensated heart failure (ADHF) were evaluated with testing for amino-terminal pro-B-type natriuretic peptide (NT-proBNP), BNP, sST2, and neutrophil gelatinase associated lipocalin (NGAL). METHODS: In a prospective international study, biomarkers were collected at the time of admission; the occurrence of subsequent in hospital WRF was evaluated. RESULTS: In total 26% of patients developed WRF. Compared to patients without WRF, those with WRF had a longer in-hospital length of stay (LOS) (mean LOS 13.1±13.4 days vs. 4.8±3.7 days, p<0.001) and higher in-hospital mortality [6/26 (23%) vs. 2/75 (2.6%), p<0.001]. Among the biomarkers assessed, baseline NT-proBNP (4846 vs. 3024 pg/mL; p=0.04), BNP (609 vs. 435 pg/mL; p=0.05) and NGAL (234 vs. 174 pg/mL; p=0.05) were each higher in those who developed WRF. In logistic regression, the combination of elevated natriuretic peptide and NGAL were additively predictive for WRF (ORNT-proBNP+NGAL=2.79; ORBNP+NGAL=3.11; both p<0.04). Rates of WRF were considerably higher in patients with elevation of both classes of biomarker. Comparable results were observed in a separate cohort of 162 patients with ADHF from a different center. CONCLUSIONS: In ED patients with ADHF, the combination of NT-proBNP or BNP plus NGAL at presentation may be useful to predict impending WRF (Clinicaltrials.gov NCT#0150153).

Biomarkers in ACS and heart failure: should men and women be interpreted differently?

BACKGROUND: Sex-based differences exist in the circulating concentrations of certain novel and established biomarkers in patients with acute coronary syndromes (ACS) and heart failure (HF). However, to date, few studies have compared the diagnostic and prognostic utility of these markers in men vs women. CONTENT: This mini-review contains a discussion of the published reports of studies that have explored whether differences in biomarker concentrations exist between men and women with ACS or HF. It also examines those studies that have compared the utility of biomarkers for diagnosis or risk stratification in women vs men. Because biomarkers are often used to make therapeutic and triage decisions in patient care, the potential clinical implications for any observed differences in biomarker reference limits for men and women is discussed. SUMMARY: Although the concentration distributions may differ between men and women for certain biomarkers in clinical use, the clinical implications of these observations remain unclear. Because elements of the pathophysiology of ACS and HF may differ between the sexes, further research is needed to better evaluate the diagnostic and prognostic utility of biomarkers in men vs women.

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.

Vitamin D and cardiovascular risk.

Vitamin D deficiency is a common condition that has well-documented effects on musculoskeletal health. A growing body of literature has related vitamin D deficiency to other chronic disorders, including cardiovascular disease. Several plausible biological mechanisms have been postulated to explain this association, including the effect of poor vitamin D status on intermediate risk factors (eg, hypertension and diabetes), neurohormonal activation, inflammation, and cardiac remodeling. These mechanisms have been explored in experimental and animal studies, as well as several small interventional studies. The results of the controlled trials have not been conclusive to date. In this review, we summarize the existing studies investigating the effects of vitamin D on cardiovascular health, and propose that additional well-designed, prospective, randomized controlled trials are necessary to delineate the appropriate role of vitamin D supplementation in reducing the burden of cardiovascular disease.

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.

Vitamin D and cardiovascular disease.

PURPOSE OF REVIEW: Vitamin D plays a role in many biochemical pathways outside of bone and calcium metabolism, including the cardiovascular system. Prior studies have linked vitamin D deficiency to hypertension, dyslipidemia, diabetes mellitus, and coronary artery disease. In this review, we summarize existing studies investigating these associations, specifically those addressing potential mechanisms, epidemiologic associations, and possible benefits of supplementation. RECENT FINDINGS: Experimental studies have demonstrated that activated vitamin D reduces neurohormonal activation, inhibits inflammation, and suppresses ventricular hypertrophy. Both retrospective and prospective observational studies have related vitamin D levels with cardiometabolic risk factors and outcomes. To date, there have been a small number of randomized controlled trials investigating the effects of vitamin D supplementation on cardiovascular structure and function, but results have been inconclusive or conflicting. SUMMARY: Experimental and clinical evidence suggests a link between vitamin D deficiency and cardiovascular disease. Nonetheless, it remains unclear how many of the reported associations are causal. Well designed prospective randomized controlled trials are necessary to further investigate the appropriate role of vitamin D supplementation for cardiovascular risk reduction.

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).

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.