Preoperative Noncoronary Cardiovascular Assessment and Management of Kidney Transplant Candidates.

The pretransplant risk assessment for patients with ESKD who are undergoing evaluation for kidney transplant is complex and multifaceted. When considering cardiovascular disease in particular, many factors should be considered. Given the increasing incidence of kidney transplantation and the growing body of evidence addressing ESKD-specific cardiovascular risk profiles, there is an important need for a consolidated, evidence-based model that considers the unique cardiovascular challenges that these patients face. Cardiovascular physiology is altered in these patients by abrupt shifts in volume status, altered calcium-phosphate metabolism, high-output states (in the setting of arteriovenous fistulization), and adverse geometric and electrical remodeling, to name a few. Here, we present a contemporary review by addressing cardiomyopathy/heart failure, pulmonary hypertension, valvular dysfunction, and arrhythmia/sudden cardiac death within the ESKD population.

Assessment and management of coronary artery disease in kidney and pancreas transplant candidates.

: Patients with end-stage renal disease (ESRD) undergoing evaluation for kidney and/or pancreas transplantation represent a population with unique cardiovascular (CV) profiles and unique therapeutic needs. Coronary artery disease (CAD) is common in patients with ESRD, mediated by both the overrepresentation and higher prognostic value of traditional CV risk factors amongst this population, as well as altered cardiovascular responses to failing renal function, likely mediated by dysregulation of the renin-angiotensin-aldosterone system (RAAS) and abnormal calcium and phosphate metabolism. Within the ESRD population, obstructive CAD correlates highly with adverse coronary events, including during the peri-transplant period, and successful revascularization may attenuate some of that increased risk. Accordingly, peri-transplant coronary risk assessment is critical to ensuring optimal outcomes for these patients. The following provides a review of CAD in patients being evaluated for kidney and/or pancreas transplantation, as well as evidence-based recommendations for appropriate peri-transplant evaluation and management.

10-Year Resource Utilization and Costs for Cardiovascular Care.

BACKGROUND: Cardiovascular disease (CVD) imparts a heavy economic burden on the U.S. health care system. Evidence regarding the long-term costs after comprehensive CVD screening is limited. OBJECTIVES: This study calculated 10-year health care costs for 6,814 asymptomatic participants enrolled in MESA (Multi-Ethnic Study of Atherosclerosis), a registry sponsored by the National Heart, Lung, and Blood Institute, National Institutes of Health. METHODS: Cumulative 10-year costs for CVD medications, office visits, diagnostic procedures, coronary revascularization, and hospitalizations were calculated from detailed follow-up data. Costs were derived by using Medicare nationwide and zip code-specific costs, inflation corrected, discounted at 3% per year, and presented in 2014 U.S. dollars. RESULTS: Risk factor prevalence increased dramatically and, by 10 years, diabetes, hypertension, and dyslipidemia was reported in 19%, 57%, and 53%, respectively. Self-reported symptoms (i.e., chest pain or shortness of breath) were common (approximately 40% of enrollees). At 10 years, approximately one-third of enrollees reported having an echocardiogram or exercise test, whereas 7% underwent invasive coronary angiography. These utilization patterns resulted in 10-year health care costs of $23,142. The largest proportion of costs was associated with CVD medication use (78%). Approximately $2 of every $10 were spent for outpatient visits and diagnostic testing among the elderly, obese, those with a high-sensitivity C-reactive protein level >3 mg/l, or coronary artery calcium score (CACS) ≥400. Costs varied widely from <$7,700 for low-risk (Framingham risk score <6%, 0 CACS, and normal glucose measurements at baseline) to >$35,800 for high-risk (persons with diabetes, Framingham risk score ≥20%, or CACS ≥400) subgroups. Among high-risk enrollees, CVD costs accounted for $74 million of the $155 million consumed by MESA participants. CONCLUSIONS: Longitudinal patterns of health care resource use after screening revealed new evidence on the economic burden of treatment and testing patterns not previously reported. Maintenance of a healthy population has the potential to markedly reduce the economic burden of CVD among asymptomatic individuals.

Long-Term Prognosis After Coronary Artery Calcium Scoring Among Low-Intermediate Risk Women and Men.

BACKGROUND: Cardiovascular screening of women using traditional risk factors has been challenging, with results often classifying a majority of women as lower risk than men. The aim of this report was to determine the long-term prognosis of asymptomatic women and men classified at low-intermediate risk undergoing screening with coronary artery calcium (CAC) scoring. METHODS AND RESULTS: A total of 2363 asymptomatic women and men with traditional risk factors aggregating into a low-intermediate Framingham risk score (6%-9.9%; 10-year predicted risk) underwent CAC scanning. Individuals were followed up for a median of 14.6 years. We estimated all-cause mortality using Cox proportional hazards models; hazard ratios with 95% confidence intervals were calculated. The area under the curve from a receiver operating characteristics curve analysis was calculated. There were 1072 women who were older (55.6 years) when compared with the 1291 men (46.7 years; P<0.0001), resulting in a greater prevalence and extent of CAC; 18.8% of women and 15.1% of men had a CAC score ≥100 (P=0.029). This older group of women had a 1.44-fold higher 15-year adjusted mortality hazard when compared with men (P=0.022). For women, the 15-year mortality ranged from 5.0% for those with a CAC score of 0 to 23.5% for those with a CAC score ≥400 (P<0.001). For men, the 15-year mortality ranged from 3.5% for those with a CAC score of 0 to 18.0% for those with a CAC score ≥400 (P<0.001). Women with CAC scores >10 had a higher mortality risk when compared with men. CONCLUSIONS: Our findings extend previous work that CAC effectively identifies high-risk women with a low-intermediate risk factor burden. These data require validation in external cohorts but lend credence to the use of CAC in women to improve risk detection algorithms that are currently based on traditional risk factors.

15-Year prognostic utility of coronary artery calcium scoring for all-cause mortality in the elderly.

INTRODUCTION: Prior studies have demonstrated a decline in the predictive ability of conventional risk factors (RF) with advancing age, emphasizing the need for novel tools to improve risk stratification in the elderly. Coronary artery calcification (CAC) is a robust predictor of adverse cardiovascular events, but its long-term prognostic utility beyond RFs in elderly persons is unknown. METHODS: A consecutive series of 9715 individuals underwent CAC scoring and were followed for a mean of 14.6 ± 1.1 years. Multivariable Cox proportional hazards regression (HR) with 95% confidence intervals (95% CI) was employed to assess the independent relationship of CAC and RFs with all-cause death. The incremental value of CAC, stratified by age, was examined by using an area under the receiver operator characteristic curve (AUC) and category-free net reclassification improvement (NRI). RESULTS: Of the overall study sample, 728 (7.5%) adults (mean age 74.2 ± 4.2 years; 55.6% female) were 70 years or older, of which 157 (21.6%) died. The presence of any CAC was associated with a >4-fold (95% CI = 2.84-6.59) adjusted risk of death for those over the age of 70, which was higher compared with younger study counterparts, or other measured RFs. For individuals 70 years or older, the discriminatory ability of CAC improved upon that of RFs alone (C statistics 0.764 vs. 0.675, P < 0.001). CAC also enabled improved reclassification (category-free NRI = 84%, P < 0.001) when added to RFs. CONCLUSION: In a large-scale observational cohort registry, CAC improves prediction, discrimination, and reclassification of elderly individuals at risk for future death.

Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality: A 15-Year Follow-Up Study of 9715 Patients.

BACKGROUND: Data regarding coronary artery calcification (CAC) prognosis in diabetic individuals are limited to 5-years follow-up. We investigated the long-term risk stratification of CAC among diabetic compared with nondiabetic individuals. METHODS AND RESULTS: Nine thousand seven hundred and fifteen asymptomatic individuals undergoing CAC scoring were followed for a median (interquartile range) of 14.7 (13.9-15.6) years. The incidence density rate and hazard ratios with 95% confidence intervals were used to calculate all-cause mortality. Incremental prognostic utility of CAC was evaluated using the area under the receiver operator characteristic curve and net reclassification improvement. Diabetics (54.7±10.8 years; 59.4% male) comprised 8.3% of the cohort (n=810), of which 188 (23.2%) died. For CAC=0, the rate of mortality was similar between diabetic and nondiabetic individuals for the first 5 years (P>0.05), with a nonlinear increased risk of mortality for diabetics after 5 years (P<0.05). The adjusted risk of death for those in the highest (CAC>400) versus the lowest (CAC=0) category of CAC increased by a hazards of 4.64 (95% confidence interval =3.74-5.76) and 3.41 (95% confidence interval =2.22-5.22) for nondiabetic and diabetic individuals, respectively. The presence of CAC improved discrimination (area under the receiver operator characteristic curve range: 0.73-0.74; P<0.01) and reclassification (category-free net reclassification improvement range: 0.53-0.50; P<0.001) beyond conventional risk factors in nondiabetic and diabetic individuals, respectively. CONCLUSIONS: CAC=0 is associated with a favorable 5-year prognosis for asymptomatic diabetic and nondiabetic individuals. After 5 years, the risk of mortality increases significantly for diabetic individuals even in the presence of a baseline CAC=0.

Coronary calcium scoring for long-term mortality prediction in patients with and without a family history of coronary disease.

OBJECTIVE: Minimal data are available regarding the long-term mortality risk of subclinical atherosclerosis using coronary artery calcium (CAC) scoring among patients with a family history (FH) of coronary artery disease (CAD). The aim of the present analysis was to assess the prognostic utility of CAC scoring among cohorts of young and older patients with and without a FH of CAD. METHODS: A total of 9715 consecutive asymptomatic patients, free of known CAD, underwent CAC scoring for cardiovascular risk assessment. The primary end point was all-cause mortality, with a median follow-up of 14.6 years. Unadjusted and risk-factor adjusted Cox proportional hazard modelling was employed. We calculated the area under the curve (AUC) from receiver operating characteristics analysis. RESULTS: 15-year all-cause mortality rates ranged from 4.7% to 25.0% for FH patients and from 5.0% to 38.0% for non-FH patients with CAC scores of 0 to >400 (p<0.0001). Effect modification by age altered the mortality risk of CAC among FH patients. For patients aged >60 years with FH of CAD, there was a significant improvement in the AUC with CAC over CAD risk factors (AUC: 0.539 vs 0.725, p<0.001). No such improvement was observed in FH patients aged <60 years (AUC: 0.636 vs 0.626, p=0.67). CONCLUSION: CAC effectively stratified mortality risk of patients with and without FH of CAD. However, for younger and lower-risk FH cohorts, CAC screening did not provide additive prognostic information beyond that of the traditional cardiac risk factors.

Time to Change Our Focus: Defining, Promoting, and Impacting Cardiovascular Population Health.

Despite numerous groundbreaking advances in the field, cardiovascular disease remains the leading cause of mortality in the United States, accounting for more than 787,000 deaths per year. Already leading the world in per capita healthcare expenditure, U.S. medical costs related to cardiovascular disease are projected to triple by 2030, to over $800 billion annually. The medical community's traditional disproportionate focus on treating cardiovascular disease, relative to promoting cardiovascular health, is an important contributor to these expenses. To ensure continued reductions in the burden of cardiovascular disease, as well as the overall sustainability of the healthcare system, a paradigm shift that places more emphasis on cardiovascular health promotion throughout the life course is required. This review will discuss the current definitions of cardiovascular health, as well as strategies for promoting and impacting cardiovascular health at both the local and national level.

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.

A 15-Year Warranty Period for Asymptomatic Individuals Without Coronary Artery Calcium: A Prospective Follow-Up of 9,715 Individuals.

OBJECTIVES: The aim of this study was to examine the long-term prognosis in asymptomatic individuals with a coronary artery calcium (CAC) score of 0 and its associated warranty period. BACKGROUND: Emerging evidence supports a CAC score of 0 as a favorable cardiovascular short-to intermediate-term prognostic factor. METHODS: A total of 9,715 individuals undergoing CAC imaging were stratified by age, Framingham risk score (FRS), and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) categories and followed for a mean of 14.6 years (range 12.9 to 16.8 years). Cox regression, area under the receiver-operating characteristic curve, and net reclassification information were used to assess all-cause mortality, discrimination, and reclassification of a CAC score of 0 compared with the FRS and NCEP ATP III, respectively. A warranty period was pre-defined as <1% annual mortality rate. Vascular age was estimated by linear regression. RESULTS: In 4,864 individuals with a baseline CAC score of 0 (mean age, 52.1 ± 10.8 years; 57.9% male), 229 deaths occurred. The warranty period of a CAC score of 0 was almost 15 years for individuals at low and intermediate risk with no significant differences regarding age and sex. A CAC score of 0 was associated with a vascular age of 1, 10, 20, and 30 years less than the chronological age of individuals between 50 and 59, 60 and 69, 70 and 79, and 80 years of age and older, respectively. The CAC score was the strongest predictor of death (hazard ratio: 2.67, 95% confidence interval: 2.29 to 3.11) that enabled discrimination and consistent reclassification beyond the FRS (area under the receiver-operating characteristic curve: 0.71 vs. 0.64, p < 0.001) and NCEP ATP III (area under the receiver-operating characteristic curve: 0.72 vs. 0.64, p < 0.001). CONCLUSIONS: A CAC score of 0 confers a 15-year warranty period against mortality in individuals at low to intermediate risk that is unaffected by age or sex. Furthermore, in individuals considered at high risk by clinical risk scores, a CAC score of 0 confers better survival than in individuals at low to intermediate risk but with any CAC score.

Cardiac platypnea-orthodeoxia syndrome: an often unrecognized malady.

Platypnea-orthodeoxia syndrome (POS) is a rare but clinically important form of dyspnea. The syndrome is characterized by dyspnea and arterial oxygen desaturation that occurs in the upright position and improves with recumbency. In cardiac POS, an atrial septal defect or patent foramen ovale allows communication between the right- and left-sided circulations. A second defect, such as a dilated aorta, prominent eustachian valve, or pneumonectomy, then contributes to right-to-left shunting through the interatrial connection. Diagnosis is made through pulse oximetry to confirm orthodeoxia and through transesophageal echocardiography with bubble study to visualize the shunt. Although data are limited for this rare syndrome, percutaneous closure has thus far proven safe and effective.