Background: Cardiac dysfunction and cardiovascular events are prevalent among patients with chronic kidney disease without overt obstructive coronary artery disease, but the mechanisms remain poorly understood. Coronary microvascular dysfunction has been proposed as a link between abnormal renal function and impairment of cardiac function and cardiovascular events. We aimed to investigate the relations between chronic kidney disease, coronary microvascular dysfunction, cardiac dysfunction, and adverse cardiovascular outcomes. Methods: Patients undergoing cardiac stress positron emission tomography, echocardiogram, and renal function ascertainment at Brigham and Women’s Hospital were studied longitudinally. Patients free of overt coronary (summed stress score <3 and without a history of ischemic heart disease), valvular, and end-organ disease were followed up for the adverse composite outcome of death or hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was determined from positron emission tomography. Echocardiograms were used to measure cardiac mechanics: diastolic (lateral and septal E/e’) and systolic (global longitudinal, radial, and circumferential strain). Image analyses and event adjudication were blinded. The associations between estimated glomerular filtration rate (eGFR), CFR, diastolic and systolic indices, and adverse cardiovascular outcomes were assessed in adjusted models and mediation analyses. Results: Of the 352 patients (median age, 65 years; 63% female; 22% black) studied, 35% had an eGFR <60 mL·min −1 ·1.73 m −2 , a median left ventricular ejection fraction of 62%, and a median CFR of 1.8. eGFR and CFR were associated with diastolic and systolic indices, as well as future cardiovascular events (all P <0.05). In multivariable models, CFR, but not eGFR, was independently associated with cardiac mechanics and cardiovascular events. The associations between eGFR, cardiac mechanics, and cardiovascular events were partly mediated via CFR. Conclusions: Coronary microvascular dysfunction, but not eGFR, was independently associated with abnormal cardiac mechanics and an increased risk of cardiovascular events. Coronary microvascular dysfunction may mediate the effect of chronic kidney disease on abnormal cardiac function and cardiovascular events in those without overt coronary artery disease.

Background: The diagnostic yield of cardiac sarcoidosis (CS) by endomyocardial biopsy is limited. Fluorodeoxyglucose (FDG) positron emission tomography (PET) and cardiac magnetic resonance imaging (MRI) may facilitate noninvasive diagnosis, but the accuracy of this approach is not well defined. We aimed to correlate findings from FDG PET and cardiac MRI with histologic findings from explanted hearts of patients who underwent cardiac transplantation. Methods: We analyzed the explanted heart histology for all patients who underwent cardiac transplant at our center from April 2008 to July 2018 and had pre-transplant FDG PET (n=18) or cardiac MRI (n=31). The likelihood of CS based on FDG PET or cardiac MRI was categorized in a blinded fashion using a previously published method. Results: Using a CS probable cutoff for FDG PET resulted in a sensitivity of 100.0% (95% CI: 54.1% to 100.0%) and a specificity of 33.3% (95% CI: 9.9%-65.1%). Three of the nine CS probable by FDG PET cases were found to be arrhythmogenic cardiomyopathy. The test

Background: Lipid-rich necrotic core (LRNC), a high-risk coronary plaque feature assessed by coronary computed tomography angiography, is associated with increased risk of future cardiovascular events in patients with subclinical, nonobstructive coronary artery disease. Psoriasis is a chronic inflammatory condition that is associated with increased prevalence of high-risk coronary plaque and risk of cardiovascular events. This study characterized LRNC in psoriasis and how LRNC modulates in response to biologic therapy. Methods: Consecutive biologic naïve psoriasis patients (n=209) underwent coronary computed tomography angiography at baseline and 1-year to assess changes in LRNC using a novel histopathologically validated software (vascuCAP Elucid Bioimaging, Boston, MA) before and after biologic therapy over 1 year. Results: Study participants were middle-aged, predominantly male with similar cardiometabolic and psoriasis status between treatment groups. In all participants at baseline, LRNC was associated with Framingham risk score (β [standardized β]=0.12 [95% CI, 0.00–0.15]; P =0.045), and psoriasis severity (β=0.13 [95% CI, 0.01–0.26]; P =0.029). At 1-year, participants receiving biologic therapy had a reduction in LRNC (mm 2 ; 3.12 [1.99–4.66] versus 2.97 [1.84–4.35]; P =0.028), while those who did not receive biologic therapy over 1 year demonstrated no significant change with nominally higher LRNC (3.12 [1.82–4.60] versus 3.34 [2.04–4.74]; P =0.06). The change in LRNC was significant compared with that of the nonbiologic treated group (ΔLRNC, −0.22 mm 2 versus 0.14 mm 2 , P =0.004) and remained significant after adjusting for cardiovascular risk factors and psoriasis severity (β=−0.09 [95% CI, −0.01 to −0.18]; P =0.033). Conclusions: LRNC was associated with psoriasis severity and cardiovascular risk factors in psoriasis. Additionally, there was favorable modification of LRNC in those on biologic therapy. This study provides evidence of potential reduction in LRNC with treatment of systemic inflammation. Larger, longer follow-up prospective studies should be conducted to understand how changes in LRNC may translate into a reduction in future cardiovascular events in psoriasis.