Long-Term Prognosis After Coronary Artery Calcification Testing in Asymptomatic Patients: A Cohort Study.

BACKGROUND: The extent of coronary artery calcification (CAC) and near-term adverse clinical outcomes are strongly related through 5 years of follow-up. OBJECTIVE: To describe the ability of CAC scores to predict long-term mortality in persons without symptoms of coronary artery disease. DESIGN: Observational cohort. SETTING: Single-center, outpatient cardiology laboratory. PATIENTS: 9715 asymptomatic patients. MEASUREMENTS: Coronary artery calcification scoring and binary risk factor data were collected. The primary end point was time to all-cause mortality (median follow-up, 14.6 years). Univariable and multivariable Cox proportional hazards models were used to compare survival distributions. The net reclassification improvement statistic was calculated. RESULTS: In Cox models adjusted for risk factors for coronary artery disease, the CAC score was highly predictive of all-cause mortality (P < 0.001). Overall 15-year mortality rates ranged from 3% to 28% for CAC scores from 0 to 1000 or greater (P < 0.001). The relative hazard for all-cause mortality ranged from 1.68 for a CAC score of 1 to 10 (P < 0.001) to 6.26 for a score of 1000 or greater (P < 0.001). The categorical net reclassification improvement using cut points of less than 7.5% to 22.5% or greater was 0.21 (95% CI, 0.16 to 0.32). LIMITATIONS: Data collection was limited to a single center with generalizability limitations. Only binary risk factor data were available, and CAC was only measured once. CONCLUSION: The extent of CAC accurately predicts 15-year mortality in a large cohort of asymptomatic patients. Long-term estimates of mortality provide a unique opportunity to examine the value of novel biomarkers, such as CAC, in estimating important patient outcomes. PRIMARY FUNDING SOURCE: None.

Team-Based Care for Managing Cardiac Comorbidities in Heart Failure.

The need for HF management is predicted to increase as the HF population ages. Balancing HF and the multiple cardiac comorbidities remains difficult for any single provider, but becomes Fig. 6. Five-year rates of death or urgent heart transplantation by deciles of total cholesterol in heart failure. (From Horwich TB, Fonarow GC, Hamilton MA, et al. Low serum total cholesterol is associated with marked increase in mortality in advanced heart failure. J Card Fail 2002;8(4):222; with permission.) easier with the involvement of a team. Collaboration between physicians, nurses, nurse practitioners, physician assistants, pharmacists, and other health care workers reduces the burden of care coordination and simultaneously improves delivery of care. Team-based approaches increase cost-effectiveness, reduce hospitalization rates, and equally important, give patients more resources and support, which research shows may ultimately improve compliance and outcomes.

Prognostic significance of impaired chronotropic response to pharmacologic stress Rb-82 PET.

BACKGROUND: An impaired chronotropic response to exercise is an accepted risk marker but the relationship between heart rate reserve (HRR) with pharmacologic stress is less well-established. The primary aim of this analysis was to evaluate the prognostic significance of HRR in patients undergoing rest/stress myocardial perfusion positron emission tomography (PET) in estimating coronary artery disease (CAD) mortality. METHODS: This subset analysis from the PET Prognosis Multicenter Registry includes a total of 2,398 patients undergoing rest/stress Rb-PET from three participating sites. The HRR from rest to peak stress was categorized into tertiles of ≤ 4, 5-14, and ≥ 15 beats per minute (bpm). At stress, the % abnormal myocardium was categorized as <5%, 5-9.9%, and ≥ 10%. We estimated CAD mortality using univariable and multivariable Cox proportional hazard models. RESULTS: CAD mortality was 12.8%, 3.4%, and 0.8%, respectively, for HRR measurements of ≤ 4, 5-14, and ≥ 15 bpm (P < 0.0001). In a multivariable model, the HRR was independently predictive of CAD mortality (P < 0.0001) with adjusted hazard ratios elevated 3.5- and 8.4-fold for HRR of 5-14 and ≤ 4 versus ≥ 15 bpm. In a multivariable model, both the HRR and stress MPI % abnormal myocardium were independently and highly predictive of CAD mortality. Moreover, the net reclassification improvement was 0.18 for the HRR when compared to a model including risk factors, symptoms, rest HR, and PET variables (P = 0.0008). For those with ≥ 10% abnormal myocardium on stress PET, there was a graded relationship between HRR and CAD mortality with adjusted hazards exceeding 50-fold for measurements of 5-14 and ≤ 4 bpm (P < 0.0001) compared to stress MPI with <5% abnormal myocardium and a HRR ≥ 15 bpm. CONCLUSION: A diminished HRR to vasodilator stress is a novel but increasingly important predictor of CAD mortality. HRR measurements of ≤ 4, 5-14, and ≥ 15 bpm were independently predictive of CAD mortality and underscore the importance of optimizing readily available novel markers of risk as highly relevant to identifying high and low risk patient subsets.

Prognostic significance of calcified plaque among symptomatic patients with nonobstructive coronary artery disease.

BACKGROUND: Coronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD. METHODS: From the COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with nonobstructive CAD (<50% coronary stenosis) on coronary-computed tomographic angiography were prospectively enrolled and followed for a median of 2.1 years. Patients were categorized as without (0% stenosis) or with (>0% but <50% coronary stenosis) a luminal stenosis. CAC scores were calculated using the Agatston method. Univariable and multivariable Cox proportional hazard models were employed to estimate all-cause mortality and/or myocardial infarction (MI). Four-year death and death or MI rates were 1.9% and 3.3%. RESULTS: Of the 4,380 patients with no luminal stenosis, 86% had CAC scores of <10 while those with a luminal stenosis had more prevalent and extensive CAC with 31.9% having a CAC score of ≥100. Among patients with no luminal stenosis, CAC was not predictive of all-cause mortality (P = .44). However, among patients with a luminal stenosis, 4-year mortality rates ranged from 0.8% to 9.8% for CAC scores of 0 to ≥400 (P < .0001). The mortality hazard was 6.0 (P = .004) and 13.3 (P < .0001) for patients with a CAC score of 100-399 and ≥400. In patients with a luminal stenosis, CAC remained independently predictive in all-cause mortality (P < .0001) and death or MI (P < .0001) in multivariable models containing CAD risk factors and presenting symptoms. CONCLUSIONS: CAC allows for the identification of those at an increased hazard for death or MI in symptomatic patients with nonobstructive disease. From the CONFIRM registry, the extent of CAC was an independent estimator of long-term prognosis among symptomatic patients with luminal stenosis and may further define risk and guide preventive strategies in patients with nonobstructive CAD.

Influence of race/ethnic differences in pre-transplantation panel reactive antibody on outcomes in heart transplant recipients.

OBJECTIVES: This study sought to investigate post-transplantation outcomes as a function of race and panel reactive antibody (PRA). BACKGROUND: PRA screening is used to determine the presence of pre-formed antibodies to population-wide human leukocyte antigens (HLAs) in patients being evaluated for heart transplantation (HT). Racial/ethnic differences in long-term survival after HT have been described. However, whether there are significant racial/ethnic differences in PRA among adults awaiting HT is poorly characterized. METHODS: We identified patients age ≥18 years in the Organ Procurement and Transplantation database with race/ethnicity of white, black, Hispanic, or Asian and listed for HT between 2000 and 2012 (N = 19,704). A PRA value of ≥10% was used to define clinically meaningful sensitization. RESULTS: Blacks had a higher peak PRA than did all other groups and were more likely to be sensitized. Black HT recipients were more likely to experience graft failure than were Hispanic, white, and Asian recipients (31% vs. 27%, 26%, and 21%, respectively; p < 0.001). The median follow-up was 1,207 days (interquartile range: 373 to 2,364 days), with a trend toward a shorter median time to graft failure in the Asian group than in the black, Hispanic, and white groups (p = 0.065). Sensitized blacks had the lowest rate of allograft survival, whereas nonsensitized Asians had the highest survival. Using Cox proportional regression to adjust for other clinical variables, black race (HR: 1.3; 95% confidence interval [CI]: 1.2 to 1.5), Hispanic ethnicity (HR: 1.2; 95% CI: 1.0 to 1.5), and sensitization (HR: 1.2; 95% CI: 1.1 to 1.4) remained predictors of higher rates of graft failure. CONCLUSIONS: Race/ethnicity and level of sensitization are important predictors of graft survival.

Influence of sex on risk stratification with stress myocardial perfusion Rb-82 positron emission tomography: Results from the PET (Positron Emission Tomography) Prognosis Multicenter Registry.

OBJECTIVES: The aim of the current analysis was to compare sex differences in the prognostic accuracy of stress myocardial perfusion rubidum-82 (Rb-82) positron emission tomography (PET). BACKGROUND: The diagnostic evaluation of women presenting with suspected cardiac symptoms is challenging with reported reduced accuracy, attenuation artifact, and more recent concerns regarding radiation safety. Stress myocardial perfusion Rb-82 PET is a diagnostic alternative with improved image quality and radiation dosimetry. Currently, the prognostic accuracy of stress Rb-82 PET in women has not been established. METHODS: A total of 6,037 women and men were enrolled in the PET Prognosis Multicenter Registry. Patients were followed for the occurrence of coronary artery disease (CAD) mortality, with a median follow-up of 2.2 years. Cox proportional hazards modeling was used to estimate CAD mortality. The net re-classification improvement index (NRI) was calculated. RESULTS: The 5-year CAD mortality was 3.7% for women and 6.0% for men (p < 0.0001). Unadjusted CAD mortality ranged from 0.9% to 12.9% for women (p < 0.0001) and from 1.5% to 17.4% for men (p < 0.0001) for 0% to ≥15% abnormal myocardium at stress. In multivariable models, the percentage of abnormal stress myocardium was independently predictive of CAD mortality in women and men. An interaction term of sex by the percentage of abnormal stress myocardium was nonsignificant (p = 0.39). The categorical NRI when Rb-82 PET data was added to a clinical risk model was 0.12 for women and 0.17 for men. Only 2 cardiac deaths were reported in women <55 years of age; accordingly the percentage of abnormal myocardium at stress was of borderline significance (p = 0.063), but it was highly significant for women ≥55 years of age (p < 0.0001), with an increased NRI of 0.21 (95% confidence interval: 0.09 to 0.34), including 17% of CAD deaths and 3.9% of CAD survivors that were correctly re-classified in this older female subset. CONCLUSIONS: Stress Rb-82 PET provides significant and clinically meaningful effective risk stratification of women and men, supporting this modality as an alternative to comparative imaging modalities. Rb-82 PET findings were particularly helpful at identifying high-risk, older women.