Faculty Bibliography

BACKGROUND:Stress cardiac magnetic resonance imaging (CMR) has demonstrated excellent diagnostic and prognostic value in single-center studies. OBJECTIVES:This study sought to investigate the prognostic value of stress CMR and downstream costs from subsequent cardiac testing in a retrospective multicenter study in the United States. METHODS:In this retrospective study, consecutive patients from 13 centers across 11 states who presented with a chest pain syndrome and were referred for stress CMR were followed for a target period of 4 years. The authors associated CMR findings with a primary outcome of cardiovascular death or nonfatal myocardial infarction using competing risk-adjusted regression models and downstream costs of ischemia testing using published Medicare national payment rates. RESULTS:In this study, 2,349 patients (63 ± 11 years of age, 47% female) were followed for a median of 5.4 years. Patients with no ischemia or late gadolinium enhancement (LGE) by CMR, observed in 1,583 patients (67%), experienced low annualized rates of primary outcome (<1%) and coronary revascularization (1% to 3%), across all years of study follow-up. In contrast, patients with ischemia+/LGE+ experienced a >4-fold higher annual primary outcome rate and a >10-fold higher rate of coronary revascularization during the first year after CMR. Patients with ischemia and LGE both negative had low average annual cost spent on ischemia testing across all years of follow-up, and this pattern was similar across the 4 practice environments of the participating centers. CONCLUSIONS:In a multicenter U.S. cohort with stable chest pain syndromes, stress CMR performed at experienced centers offers effective cardiac prognostication. Patients without CMR ischemia or LGE experienced a low incidence of cardiac events, little need for coronary revascularization, and low spending on subsequent ischemia testing. (Stress CMR Perfusion Imaging in the United States [SPINS]: A Society for Cardiovascular Resonance Registry Study; NCT03192891).

BACKGROUND:Patients with chronic kidney disease are at increased risk of cardiovascular disease (CVD). Even after kidney transplant, the rate of CVD events and death remain elevated. Early detection of patients at risk would be helpful for guiding aggressive preventive therapy. The purpose of this study was to evaluate global longitudinal strain (GLS) as a predictor of CVD events and death after kidney transplant. METHOD/METHODS:Among patients with successful kidney transplant between 3/2009 and 12/2012 at our institution, 111 individuals had an echocardiogram within 6 months of the transplant. Medical records were evaluated for demographics and patient characteristics. Echocardiograms were analyzed for conventional measurements, and GLS was assessed using speckle-tracking analysis. RESULTS:The median age of the study sample was 54 years. Overall, 60% were men; 35% were non-Hispanic black, and 50% Hispanic. After a mean follow-up of 3.8 ± 0.5 years, there were 21 cardiovascular events or deaths. Patients who experienced an event were older, more frequently had a history of coronary artery disease, and had higher LV filling/longitudinal diastolic annular velocity (E/e') than those who did not. GLS was significantly associated with event-free survival even after adjusting for age, sex, race-ethnicity, hypertension, diabetes, history of coronary artery disease or heart failure, and E/e'. CONCLUSION/CONCLUSIONS:Reduced GLS peri-transplant is significantly associated with increased CVD events or death after kidney transplant. Larger studies are required to determine the incremental predictive value of GLS over clinical and other echocardiographic parameters for adverse CVD events following renal transplantation.

Tissue transglutaminase (tTG) is a multifunctional protein with a wide range of enzymatic and non-enzymatic functions. We have recently demonstrated that tTG expression is upregulated in the pressure-overloaded myocardium and exerts fibrogenic actions promoting diastolic dysfunction, while preventing chamber dilation. Our current investigation dissects the in vivo and in vitro roles of the enzymatic effects of tTG on fibrotic remodeling in pressure-overloaded myocardium. Using a mouse model of transverse aortic constriction, we demonstrated perivascular and interstitial tTG activation in the remodeling pressure-overloaded heart. tTG inhibition through administration of the selective small molecule tTG inhibitor ERW1041E attenuated left ventricular diastolic dysfunction and reduced cardiomyocyte hypertrophy and interstitial fibrosis in the pressure-overloaded heart, without affecting chamber dimensions and ejection fraction. In vivo, tTG inhibition markedly reduced myocardial collagen mRNA and protein levels and attenuated transcription of fibrosis-associated genes. In contrast, addition of exogenous recombinant tTG to fibroblast-populated collagen pads had no significant effects on collagen transcription, and instead increased synthesis of matrix metalloproteinase (MMP)3 and tissue inhibitor of metalloproteinases (TIMP)1 through transamidase-independent actions. However, enzymatic effects of matrix-bound tTG increased the thickness of pericellular collagen in fibroblast-populated pads. tTG exerts distinct enzymatic and non-enzymatic functions in the remodeling pressure-overloaded heart. The enzymatic effects of tTG are fibrogenic and promote diastolic dysfunction, but do not directly modulate the pro-fibrotic transcriptional program of fibroblasts. Targeting transamidase-dependent actions of tTG may be a promising therapeutic strategy in patients with heart failure and fibrosis-associated diastolic dysfunction.

A 66-year-old woman presented with frequent premature ventricular contractions (PVC) and akinesis of the basal septum on echocardiography. Coronary angiography was normal. Cardiac magnetic resonance showed mid-wall enhancement. Positron emission tomography showed a perfusion defect at the same location using 13N-ammonia, but increased 18-fluorodeoxyglucose uptake. These findings supported the diagnosis of cardiac sarcoidosis. High-dose steroids initially reduced frequency of PVCs but had to be withdrawn due to severe side effects. An ICD was implanted. Our case demonstrates the utility of multimodality imaging to diagnose and guide management of this entity.

BACKGROUND:During a healthy pregnancy women experience cardiovascular and hemodynamic changes and normal ranges of left ventricular (LV) function on two-dimensional speckle tracking echocardiography (STE) are not well defined. The aim of this study was to describe the cardiovascular changes that occur during the second and third trimesters of a healthy pregnancy using STE. METHODS:Pregnant subjects were enrolled retrospectively if they underwent a transthoracic echocardiography (TTE) between 2011-2014. Subjects with abnormal TTE findings, hypertension, diabetes, preeclampsia, prior cardiac surgery, poor imaging quality or in the 1st trimester were excluded. A total of 74 pregnant subjects were categorized into the 2nd or 3rd trimesters. Twenty-one healthy age-matched females were selected as a control group. RESULTS:The heart undergoes extensive remodeling during pregnancy with increased LV septal thickness, posterior wall thickness, cavity size and mass (p=0.045, p=0.002, p<0.001, p=0.018, respectively). However, myocardial mechanical function measured by: global longitudinal strain, radial strain, circumferential strain, systolic and diastolic global longitudinal strain rate (GLSR), global radial strain rate (GRSR) and global circumferential strain rate, remains preserved. Only time to peak strain rate corrected for heart rate for diastolic GRSR and diastolic GLSR were significantly increased in the third trimester (p=0.016 for both). CONCLUSION/CONCLUSIONS:Despite extensive heart remodeling, many STE derived parameters of LV function in healthy pregnant women remain unchanged and valid for women in the 2nd and 3rd trimester. Future studies investigating early detection of pregnancy related heart disease can refer to these parameters as reference ranges.