Parag C. Patel

Left atrial structure and function and clinical outcomes in the general population

AIMS Left atrial (LA) structural and functional abnormalities may be subclinical phenotypes, which identify individuals at increased risk of adverse outcomes. METHODS AND RESULTS Maximum LA volume (LAmax) and LA emptying fraction (LAEF) were measured via cardiac magnetic resonance imaging in 1802 participants in the Dallas Heart Study. The associations of LAEF and LAmax indexed to body surface area (LAmax/BSA) with traditional risk factors, natriuretic peptide levels, and left ventricular (LV) structure [end-diastolic volume (EDV) and concentricity(0.67) (mass/EDV(0.67))] and function (ejection fraction) were assessed using linear regression analysis. The incremental prognostic value of LAmax/BSA and LAEF beyond traditional risk factors, LV ejection fraction, and LV mass was assessed using the Cox proportional-hazards model. Both increasing LAmax/BSA and decreasing LAEF were associated with hypertension and natriuretic peptide levels (P < 0.05 for all). In multivariable analysis, LAmax/BSA was most strongly associated with LV end-diastolic volume/BSA, while LAEF was strongly associated with LV ejection fraction and concentricity(0.67). During a median follow-up period of 8.1 years, there were 81 total deaths. Decreasing LAEF [hazard ratio (HR) per 1 standard deviation (SD) (8.0%): 1.56 (1.32-1.87)] but not increasing LAmax/BSA [HR per 1 SD (8.6 mL/m(2)): 1.14 (0.97-1.34)] was independently associated with mortality. Furthermore, the addition of LAEF to a model adjusting Framingham risk score, diabetes, race, LV mass, and ejection fraction improved the c-statistic (c-statistics: 0.78 vs. 0.77; P < 0.05, respectively), whereas the addition of LAmax/BSA did not (c-statistics: 0.76, P = 0.20). CONCLUSION In the general population, both LAmax/BSA and LAEF are important subclinical phenotypes but LAEF is superior and incremental to LAmax/BSA.

Association of cystatin C with left ventricular structure and function: The Dallas Heart Study

Background—Cystatin C, a novel marker of renal function, has been associated with heart failure and cardiovascular mortality in older individuals. We tested the hypothesis that cystatin C is associated with preclinical cardiac structural and functional abnormalities in a younger population-based sample. Methods and Results—The study included participants in the Dallas Heart Study (ages 30 to 65 years) who had measurements of cystatin C and cardiac MRI. The associations of cystatin C with left ventricular (LV) mass, LV end-systolic and -diastolic volumes, concentricity (LV mass/LV end-diastolic volume), LV wall thickness, and LV ejection fraction were evaluated. Cystatin C levels ranged from 0.46 to 6.55 mg/L. In univariable analyses, increasing levels of cystatin C correlated with higher LV mass, concentricity, and wall thickness (P<0.001), but not with LV end-systolic volume, LV end-diastolic volume, or LV ejection fraction. After adjustment with traditional covariates and estimated glomerular filtration rate by the modification of diet in renal disease formula, log-transformed cystatin C remained independently associated with LV mass (P<0.001), concentricity (P=0.027), and wall thickness (P<0.001). These associations persisted when creatinine or estimated glomerular filtration rate by the Cockcroft-Gault formula were included in the models. Conclusions—Higher levels of cystatin C were associated with increased LV mass and a concentric LV hypertrophy phenotype. These findings were independent of potential confounding variables including standard measurements of renal function, supporting the hypothesis that cystatin C may be useful to identify individuals with preclinical structural heart abnormalities.

Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population: observations from the Dallas Heart Study.

BACKGROUND Growth differentiation factor 15 (GDF-15) is produced by cardiomyocytes and atherosclerotic lesions under stress conditions. Although higher circulating GDF-15 concentrations are associated with mortality across a spectrum of cardiovascular conditions, the relationship of GDF-15 with atherosclerosis and mortality in the general population remains undefined. METHODS We measured plasma GDF-15 in 3219 participants of the Dallas Heart Study, a population sample of adults ages 30-65 years (55% women, 49% black). GDF-15 was analyzed in prespecified categories (<1200; 1200-1799; and ≥1800 ng/L) and continuously. End points included prevalent coronary artery calcium (CAC>10 Agatston units), increased CAC (CAC≥100 Agatston units) by electron beam computed tomography, and mortality through a median 7.3 years of follow-up (120 deaths, 48 cardiovascular deaths). RESULTS Increasing GDF-15 associated with older age, black race, hypertension, diabetes, smoking, left ventricular (LV) mass/body surface area, and worse renal function (P<0.0001 for each). In multivariable models adjusted for traditional risk factors, renal function, and LV mass/body surface area, GDF-15≥1800 ng/L was associated with CAC>10 (odds ratio 2.1; 95% CI 1.2-3.7; P=0.01), CAC≥100 (odds ratio 2.6; 95% CI 1.4-4.9; P=0.002), all-cause mortality (hazard ratio 3.5; 95% CI 2.1-5.9, P<0.0001), and cardiovascular mortality (hazard ratio 2.5; 95% CI 1.1-5.8, P=0.03). Adding log GDF-15 to fully adjusted models modestly improved the c statistic (P=0.025), the integrated discrimination index (0.028; P<0.0001) and the category-less net reclassification index (0.42; P=0.002). These findings remained significant with further adjustment for high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and cardiac troponin T. CONCLUSIONS GDF-15 is independently associated with subclinical coronary atherosclerosis and mortality, and its potential role for risk stratification in the general population merits further evaluation.

Allocating scarce resources in real-time to reduce heart failure readmissions: a prospective, controlled study

Objective To test a multidisciplinary approach to reduce heart failure (HF) readmissions that tailors the intensity of care transition intervention to the risk of the patient using a suite of electronic medical record (EMR)-enabled programmes. Methods A prospective controlled before and after study of adult inpatients admitted with HF and two concurrent control conditions (acute myocardial infarction (AMI) and pneumonia (PNA)) was performed between 1 December 2008 and 1 December 2010 at a large urban public teaching hospital. An EMR-based software platform stratified all patients admitted with HF on a daily basis by their 30-day readmission risk using a published electronic predictive model. Patients at highest risk received an intensive set of evidence-based interventions designed to reduce readmission using existing resources. The main outcome measure was readmission for any cause and to any hospital within 30 days of discharge. Results There were 834 HF admissions in the pre-intervention period and 913 in the post-intervention period. The unadjusted readmission rate declined from 26.2% in the pre-intervention period to 21.2% in the post-intervention period (p=0.01), a decline that persisted in adjusted analyses (adjusted OR (AOR)=0.73; 95% CI 0.58 to 0.93, p=0.01). In contrast, there was no significant change in the unadjusted and adjusted readmission rates for PNA and AMI over the same period. There were 45 fewer readmissions with 913 patients enrolled and 228 patients receiving intervention, resulting in a number needed to treat (NNT) ratio of 20. Conclusions An EMR-enabled strategy that targeted scarce care transition resources to high-risk HF patients significantly reduced the risk-adjusted odds of readmission.

Association of Cystatin C With Left Ventricular Structure and FunctionCLINICAL PERSPECTIVE

Background—Cystatin C, a novel marker of renal function, has been associated with heart failure and cardiovascular mortality in older individuals. We tested the hypothesis that cystatin C is associated with preclinical cardiac structural and functional abnormalities in a younger population-based sample. Methods and Results—The study included participants in the Dallas Heart Study (ages 30 to 65 years) who had measurements of cystatin C and cardiac MRI. The associations of cystatin C with left ventricular (LV) mass, LV end-systolic and -diastolic volumes, concentricity (LV mass/LV end-diastolic volume), LV wall thickness, and LV ejection fraction were evaluated. Cystatin C levels ranged from 0.46 to 6.55 mg/L. In univariable analyses, increasing levels of cystatin C correlated with higher LV mass, concentricity, and wall thickness (P<0.001), but not with LV end-systolic volume, LV end-diastolic volume, or LV ejection fraction. After adjustment with traditional covariates and estimated glomerular filtration rate by the modification of diet in renal disease formula, log-transformed cystatin C remained independently associated with LV mass (P<0.001), concentricity (P=0.027), and wall thickness (P<0.001). These associations persisted when creatinine or estimated glomerular filtration rate by the Cockcroft-Gault formula were included in the models. Conclusions—Higher levels of cystatin C were associated with increased LV mass and a concentric LV hypertrophy phenotype. These findings were independent of potential confounding variables including standard measurements of renal function, supporting the hypothesis that cystatin C may be useful to identify individuals with preclinical structural heart abnormalities.

Clinical outcomes after cardiac transplantation in muscular dystrophy patients

BACKGROUND Patients with muscular dystrophy are at risk of developing a dilated cardiomyopathy and can progress to advanced heart failure. At present, it is not known whether such patients can safely undergo cardiac transplantation. METHODS This was a retrospective review of the Cardiac Transplant Research Database, a multi-institutional registry of 29 transplant centers in the United States, from the years 1990 to 2005. The post-cardiac transplant outcomes of 29 patients with muscular dystrophy were compared with 275 non-muscular dystrophy patients with non-ischemic cardiomyopathy, matched for age, body mass index, gender, and race. RESULTS Beckers muscular dystrophy was present in 52% of the patients. Survival in the muscular dystrophy patients was similar to the controls at 1 year (89% vs 91%; p = 0.5) and at 5 years (83% vs 78%; p = 0.5). The differences in rates of cumulative infection, rejection, or allograft vasculopathy between the 2 groups were not significant (p > 0.5 for all comparisons). CONCLUSIONS Recognizing the limitations of the present investigation (ie, selection bias and data lacking in the functional capacity of the muscular dystrophy patients), the current study suggests that the clinical outcomes after cardiac transplantation in selected patients with muscular dystrophy are similar to those seen in age-matched patients with non-ischemic cardiomyopathy.

Left ventricular hypertrophy, aortic wall thickness, and lifetime predicted risk of cardiovascular disease:the Dallas Heart Study.

OBJECTIVES To examine whether individuals with low short-term risk of coronary heart disease but high lifetime predicted risk of cardiovascular disease (CVD) have greater prevalence of left ventricular (LV) hypertrophy and increased aortic wall thickness (AWT) than those with low short-term and low lifetime risk. BACKGROUND Lifetime risk prediction can be used for stratifying individuals younger than 50 years of age into 2 groups: low short-term/high lifetime and low short-term/low lifetime predicted risk of CVD. Individuals with low short-term/high lifetime risk have a greater burden of subclinical atherosclerosis as measured by coronary artery calcium and carotid intima-media thickness. However, >75% of individuals with low short-term/high lifetime risk do not have detectable coronary artery calcium, suggesting the presence of alternative subclinical abnormalities. METHODS We stratified 1,804 Dallas Heart Study subjects between the ages of 30 and 50 years who had cardiac magnetic resonance into 3 groups: low short-term (<10% 10-year risk of coronary heart disease)/low lifetime predicted risk (<39% lifetime risk of CVD), low short-term (<10%)/high lifetime risk (> or =39%), and high short-term risk (> or =10%, prevalent diabetes, or previous stroke, or myocardial infarction). In those with low short-term risk, we compared measures of LV hypertrophy and AWT between those with low versus high lifetime risk. RESULTS Subjects with low short-term/high lifetime risk compared with those with low short-term/low lifetime risk had increased LV mass (men: 95 +/- 17 g/m(2) vs. 90 +/- 12 g/m(2) and women: 75 +/- 14 g/m(2) vs. 71 +/- 10 g/m(2), respectively; p < 0.001 for both). LV concentricity (mass/volume), wall thickness, and AWT were also significantly greater in those with high lifetime risk in this comparison (p < 0.001 for all), but LV end-diastolic volume was not (p > 0.3). These associations persisted among participants without detectable coronary artery calcium. CONCLUSIONS Among individuals 30 to 50 years of age with low short-term risk, a high lifetime predicted risk of CVD is associated with concentric LV hypertrophy and increased AWT.

Utility of the Cylex Assay in Cardiac Transplant Recipients

BACKGROUND Although the Cylex immune assay has been proposed as a means of tailoring immunosuppression after organ transplantation, there are limited data regarding its utility in cardiac transplant recipients. Therefore, we sought to determine the utility of the Cylex assay in assessing the risk of infection or rejection in cardiac transplant recipients. METHODS This study is a retrospective review of the clinical course of all adult cardiac transplant recipients who underwent a Cylex assay at UT Southwestern Medical Center between January 2004 and September 2007. RESULTS One hundred eleven patients were free of significant rejection or infection at the time of the first Cylex assay. Most patients (92%) were >1 year post-transplant. Over the next 157 +/- 41 (mean +/- SD) days, 2 patients had 3 episodes of rejection requiring therapy and 7 patients had 8 infections requiring therapy. The Cylex responses ranged from 17 to 894 ng/ml. No correlation was observed between the baseline Cylex response and subsequent risk of either infection or rejection within 6 months. Lower white blood cell count and African American ethnicity were correlated with a lower Cylex response. CONCLUSIONS In this study, the Cylex assay had limited utility as an adjunct to routine clinical evaluation in assessing risk of infection or rejection in cardiac transplant recipients.

High Incidence of Cytomegalovirus Disease in D+/R-Heart Transplant Recipients Shortly After Completion of 3 Months of Valganciclovir Prophylaxis

BACKGROUND Cytomegalovirus (CMV) infection remains a serious problem after heart transplantation. Recipients with D(+)/R(-) CMV serostatus often receive prophylaxis with valganciclovir, but the optimal duration of such therapy after heart transplant is unknown. METHODS We retrospectively reviewed the clinical course of all adult cardiac transplant recipients with D(+)/R(-) CMV serostatus at the UT Southwestern Medical Center between January 2003 and December 2006. Standard immunosuppression included basiliximab induction therapy and the CMV prophylaxis included CMV hyperimmune globulin, 2 weeks of intravenous ganciclovir and 3 months of oral valganciclovir. RESULTS Seven patients met the study criteria. Six of the 7 patients (86%) developed CMV disease. Five of these 6 patients presented with CMV disease within 3 months of the cessation of valganciclovir prophylaxis. CONCLUSIONS There was a high incidence of CMV disease in D(+)/R(-) heart transplant recipients despite CMV hyperimmune globulin, 2 weeks of intravenous ganciclovir and 3 months of valganciclovir prophylaxis. CMV infection occurred consistently within 2 to 3 months of cessation of valganciclovir. Alternative strategies for CMV prophylaxis, including an extension of valganciclovir prophylaxis to 6 months after heart transplantation, needs to be investigated.

Utilization of Cardiac Computed Tomography Angiography for the Diagnosis of Left Ventricular Assist Device Thrombosis

The use of left ventricular assist devices (LVADs) in the management of advanced heart failure has grown substantially in recent years, with implantation of these devices increasing 10-fold since the approval of a continuous-flow device for destination therapy in January 2010. With the significant increase in use of this technology comes the potential for an increased incidence of complications associated with these devices. One such complication that can be fatal if not urgently recognized is device thrombosis, which has been reported to occur in approximately 1% of patients receiving the HeartMate II LVAD.1 Cardiologists, radiologists, and other health care professionals must become increasingly more adept …