Sirolimus Adverse Event Profile in a Non-Clinical Trial Cohort of Heart Transplantation Patients.

BACKGROUND Sirolimus has been used increasingly in heart transplantation for its ability to reduce acute rejection, prevent the progression of cardiac allograft vasculopathy (CAV), and preserve renal function. We sought to assess the adverse reactions associated with the use of sirolimus compared to mycophenolate mofetil (MMF). MATERIAL AND METHODS We retrospectively reviewed the charts of 221 adult heart transplant patients who received either sirolimus or MMF as part of their immunosuppression from June 1, 2001 to April 1, 2005. Patients were assigned to 2 groups based upon immunosuppression use. The prevalence and types of complications were recorded in each group. RESULTS Sirolimus was received by 109 patients and 112 patients received MMF during the study period. Seventy-seven patients (71%) in the sirolimus group experienced adverse reactions compared to 45 patients (40%) in the MMF group (P<0.01). Compared to MMF, the use of sirolimus was associated with a higher prevalence of elevated triglyceride levels, lower-extremity edema, and oral ulcerations. Sirolimus was discontinued due to adverse reactions in 22% of patients, whereas no patients in the MMF group experienced adverse effects requiring drug discontinuation. CONCLUSIONS Compared to MMF, sirolimus use is associated with a higher prevalence of adverse reactions requiring drug discontinuation, but most patients were able to stay on therapy despite adverse effects.

Prevalence and Prognostic Significance of Left Ventricular Noncompaction in Patients Referred for Cardiac Magnetic Resonance Imaging.

BACKGROUND: Presence of prominent left ventricular trabeculation satisfying criteria for left ventricular noncompaction (LVNC) on routine cardiac magnetic resonance examination is frequently encountered; however, the clinical and prognostic significance of these findings remain elusive. This registry aimed to assess LVNC prevalence by 4 current criteria and to prospectively evaluate an association between diagnosis of LVNC by these criteria and adverse events. METHODS AND RESULTS: There were 700 patients referred for cardiac magnetic resonance: 42% were women, median age was 70 years (range, 45-71 years), mean left ventricular ejection fraction was 51% (±17%), and 32% had late gadolinium enhancement on cardiac magnetic resonance. The cohort underwent diagnostic assessment for LVNC by 4 separate imaging criteria-referenced by their authors as Petersen, Stacey, Jacquier, and Captur, with LVNC prevalence of 39%, 23%, 25% and 3%, respectively. Primary clinical outcome was combined end point of time to death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, and heart failure hospitalization. Secondary clinical outcomes were (1) all-cause mortality and (2) time to the first occurrence of any of the following events: cardiac death, ischemic stroke, ventricular tachycardia/ventricular fibrillation, or heart failure hospitalization. During a median follow-up of 7 years, there were no statistically significant differences in assessed outcomes noted between patients with and without LVNC irrespective of the applied criteria. CONCLUSIONS: Current criteria for the diagnosis of LVNC leads to highly variable disease prevalence in patients referred for cardiac magnetic resonance. The diagnosis of LVNC, by any current criteria, was not associated with adverse clinical events on nearly 7 years of follow-up. Limited conclusions can be made for Captur criteria due to low observed prevalence.

Clinical application of cine-MRI in the visual assessment of mitral regurgitation compared to echocardiography and cardiac catheterization.

BACKGROUND: Detecting and quantifying the severity of mitral regurgitation is essential for risk stratification and clinical decision-making regarding timing of surgery. Our objective was to assess specific visual parameters by cine-magnetic resonance imaging (MRI) in the determination of the severity of mitral regurgitation and to compare it to previously validated imaging modalities: echocardiography and cardiac ventriculography. METHODS: The study population consisted of 68 patients who underwent a cardiac MRI followed by an echocardiogram within a median time of 2.0 days and 49 of these patients who had a cardiac catheterization, median time of 2.0 days. The inter-rater agreement statistic (Kappa) was used to evaluate the agreement. RESULTS: There was moderate agreement between cine MRI and Doppler echocardiography in assessing mitral regurgitation severity, with a kappa value of 0.47, confidence interval (CI) 0.29-0.65. There was also fair agreement between cine MRI and cardiac catheterization with a kappa value of 0.36, CI of 0.17-0.55. CONCLUSION: Cine MRI offers a reasonable alternative to both Doppler echocardiography and, to a lesser extent, cardiac catheterization for visually assessing the severity of mitral regurgitation with specific visual parameters during routine clinical cardiac MRI.

The accuracy of the electrocardiogram during exercise stress test based on heart size.

BACKGROUND: Multiple studies have shown that the exercise electrocardiogram (ECG) is less accurate for predicting ischemia, especially in women, and there is additional evidence to suggest that heart size may affect its diagnostic accuracy. HYPOTHESIS: The purpose of this investigation was to assess the diagnostic accuracy of the exercise ECG based on heart size. METHODS: We evaluated 1,011 consecutive patients who were referred for an exercise nuclear stress test. Patients were divided into two groups: small heart size defined as left ventricular end diastolic volume (LVEDV) <65 mL (Group A) and normal heart size defined as LVEDV ≥65 mL (Group B) and associations between ECG outcome (false positive vs. no false positive) and heart size (small vs. normal) were analyzed using the Chi square test for independence, with a Yates continuity correction. LVEDV calculations were performed via a computer-processing algorithm. SPECT myocardial perfusion imaging was used as the gold standard for the presence of coronary artery disease (CAD). RESULTS: Small heart size was found in 142 patients, 123 female and 19 male patients. There was a significant association between ECG outcome and heart size (χ(2) = 4.7, p = 0.03), where smaller hearts were associated with a significantly greater number of false positives. CONCLUSIONS: This study suggests a possible explanation for the poor diagnostic accuracy of exercise stress testing, especially in women, as the overwhelming majority of patients with small heart size were women.

The aorta wall of patients presenting to the emergency department with acute myocardial infarction by cardiac magnetic resonance.

BACKGROUND: Inflammation has been shown to be a major component in the pathophysiology of acute coronary syndrome (ACS). In patients presenting with acute myocardial infarction (AMI), a critical component of the ACS spectrum, multiple coronary arteries are involved during this inflammatory process. In addition to the coronary vasculature, the inflammatory cascade has also been shown to affect the carotid arteries and possibly the aorta. PURPOSE: To assess the involvement of the aorta during AMI by cardiac magnetic resonance (CMR). METHODS: We prospectively evaluated the aortic wall by CMR in 123 patients. 78 patients were enrolled from the emergency department (ED), who presented with chest pain and were classified as either: (1) AMI: elevated troponin levels and typical chest pain or (2) non-cardiac chest pain (CP): negative troponins and a normal stress test or normal cardiac catheterization. We compared these 2 groups to a group of 45 asymptomatic diabetic patients. The descending thoracic aortic wall area (AWA) and maximal aortic wall thickness (AWT) were measured using a double inversion recovery T-2 weighted, ECG-gated, spin echo sequence by CMR. RESULTS: Patients with AMI were older, more likely to smoke, had a higher incidence of claudication, and had higher CRP levels. The AWA and maximal AWT were greater in patients who presented to the ED with ACS (2.11+/-0.17 mm(2), and 3.17+/-0.19 mm, respectively) than both patients presenting with non-cardiac CP (1.52+/-0.58 mm(2), p<0.001; and 2.57+/-0.10 mm, p<0.001) and the diabetic patients (1.38+/-0.58 mm(2), p<0.001; and 2.30+/-0.131 mm, p<0.001). The difference in the aortic wall characteristics remained significant after correcting for body mass index, hyperlipidemia, statins and C-reactive protein. There was no difference in maximal AWT or AWA between patients with non-cardiac CP and patients with diabetes. CONCLUSION: Patients with AMI have a significantly greater maximal aortic wall thickness and area compared to patients with non-cardiac CP. Longitudinal studies are needed to assess whether this increase is due to inflammation or a higher atherosclerotic burden.