Sipuleucel-T associated inflammatory cardiomyopathy: a case report and observations from a large pharmacovigilance database.

AIMS: The major cardiovascular (CV) adverse effects observed with sipuleucel-T from large multi-institutional clinical trials included thromboembolic events, myocardial infarction, and congestive heart failure in up to 0.3% of patients with CV risk factors. The incidence, outcomes, and mechanisms in real-world clinical settings of these CV adverse effects to date have not been fully elucidated. Our study identified a patient with sipuleucel-T-induced inflammatory cardiomyopathy, which led to the identification of CV adverse effects associated with sipuleucel-T from a large pharmacovigilance database and elucidation of its potential mechanisms. METHODS AND RESULTS: Using the MedDRA term 'cardiac disorders' (System Organ Class level), CV adverse events associated with sipuleucel-T versus all other drugs were reviewed from VigiBase, a large pharmacovigilance database. Disproportionality analysis was calculated by the information component (IC), a Bayesian disproportionality indicator. A positive IC025 (IC 95% lower end credibility interval) value (>0) is the traditional threshold used in statistical signal detection at the Uppsala Monitoring Centre. From VigiBase, the total number of CV adverse drug reaction reported with sipuleucel-T was 306 out of a total of 22 980 104 adverse drug reactions in VigiBase on 10/25/2020. MedDRA preferred terms levels were grouped into major CV adverse drug reaction categories where we observed significant reports of myocardial ischaemia, supraventricular tachycardia (particularly atrial fibrillation/atrial flutter), congestive heart failure, and valvular disorders. Myocardial ischemia included acute myocardial infarction (IC025 2.3) with n = 4/26 (15%) of these individual case safety reports considered fatal. Among patients with 'cardiac failure congestive' (IC025 1.5), 11 of these 43 cases (26%) were fatal with 42 (98%) of these cases considered to be solely due to sipuleucel-T. CONCLUSIONS: Patients with CV risk factors who are receiving sipuleucel-T may be at higher risk for congestive heart failure, myocardial ischemia, and supraventricular tachycardia. Electrocardiograms during weekly sipuleucel-T infusions and left ventricular function monitoring with echocardiogram should be considered in these patients. Our findings are suggestive of another rare presentation of T-cell-mediated CV toxicity with cancer immunotherapy.

Additional value of transluminal attenuation gradient in CT angiography to predict hemodynamic significance of coronary artery stenosis.

OBJECTIVES: The current study evaluates the incremental value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (CCO), and TAG with exclusion of calcified coronary segments (ExC) over coronary computed tomography angiogram (CTA) alone using fractional flow reserve (FFR) as the gold standard. BACKGROUND: TAG is defined as the contrast opacification gradient along the length of a coronary artery on a coronary CTA. Preliminary data suggest that TAG provides additional functional information. Interpretation of TAG is hampered by multiple heartbeat acquisition algorithms and coronary calcifications. Two correction models have been proposed based on either dephasing of contrast delivery by relating coronary density to corresponding descending aortic opacification (TAG-CCO) or excluding calcified coronary segments (TAG-ExC). METHODS: Eighty-five patients with intermediate probability of coronary artery disease were prospectively included. All patients underwent step-and-shoot 256-slice coronary CTA. TAG, TAG-CCO, and TAG-ExC analyses were performed followed by invasive coronary angiography in conjunction with FFR measurements of all major coronary branches. RESULTS: Thirty-four patients (40%) were diagnosed with hemodynamically-significant coronary artery disease (i.e., FFR ≤0.80). On a per-vessel basis (n = 253), 59 lesions (23%) were graded as hemodynamically significant, and the diagnostic accuracy of coronary CTA (diameter stenosis ≥50%) was 95%, 75%, 98%, and 54% for sensitivity, specificity, negative predictive value, and positive predictive value, respectively. TAG and TAG-ExC did not discriminate between vessels with or without hemodynamically significant lesions (-13.5 ± 17.1 HU [Hounsfield units] × 10 mm(-1) vs. -11.6 ± 13.3 HU × 10 mm(-1), p = 0.36; and 13.1 ± 15.9 HU × 10 mm(-1) vs. -11.4 ± 11.7 HU × 10 mm(-1), p = 0.77, respectively). TAG-CCO was lower in vessels with a hemodynamically-significant lesion (-0.050 ± 0.051 10 mm(-1) vs. -0.036 ± 0.034 10 mm(-1), p = 0.03) and TAG-ExC resulted in a slight improvement of the net reclassification index (0.021, p < 0.05). CONCLUSIONS: TAG did not provide incremental diagnostic value over 256-slice coronary CTA alone in assessing the hemodynamic consequences of a coronary stenosis. Correction for temporal nonuniformity of contrast delivery or exclusion of calcified coronary segments slightly enhanced the results.

Magnetic resonance imaging-defined areas of microvascular obstruction after acute myocardial infarction represent microvascular destruction and haemorrhage.

AIMS: Lack of gadolinium-contrast wash-in on first-pass perfusion imaging, early gadolinium-enhanced imaging, or late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) imaging after revascularized ST-elevation myocardial infarction (STEMI) is commonly referred to as microvascular obstruction (MVO). Additionally, T2-weighted imaging allows for the visualization of infarct-related oedema and intramyocardial haemorrhage (IMH) within the infarction. However, the exact histopathological correlate of the contrast-devoid core and its relation to IMH is unknown. METHODS AND RESULTS: In eight Yorkshire swine, the circumflex coronary artery was occluded for 75 min by a balloon catheter. After 7 days, CMR with cine imaging, T2-weighted turbospinecho, and LGE was performed. Cardiovascular magnetic resonance images were compared with histological findings after phosphotungstic acid-haematoxylin and anti-CD31/haematoxylin staining. These findings were compared with CMR findings in 27 consecutive PCI-treated STEMI patients, using the same scanning protocol. In the porcine model, the infarct core contained extensive necrosis and erythrocyte extravasation, without intact vasculature and hence, no MVO. The surrounding-gadolinium-enhanced-area contained granulation tissue, leucocyte infiltration, and necrosis with morphological intact microvessels containing microthrombi, without erythrocyte extravasation. Areas with IMH (median size 1.92 [0.36-5.25] cm(3)) and MVO (median size 2.19 [0.40-4.58] cm(3)) showed close anatomic correlation [intraclass correlation coefficient (ICC) 0.85, r = 0.85, P = 0.03]. Of the 27 STEMI patients, 15 had IMH (median size 6.60 [2.49-9.79] cm(3)) and 16 had MVO (median size 4.31 [1.05-7.57] cm(3)). Again, IMH and MVO showed close anatomic correlation (ICC 0.87, r = 0.93, P < 0.001). CONCLUSION: The contrast-devoid core of revascularized STEMI contains extensive erythrocyte extravasation with microvascular damage. Attenuating the reperfusion-induced haemorrhage may be a novel target in future adjunctive STEMI treatment.

A rare cause of systolic murmur: unruptured right sinus of Valsalva aneurysm with right ventricular outflow tract obstruction and supracristal ventricular septal defect.

Dyspnea and heart murmur are common reasons for referrals in cardiology and both are associated with a broad differential diagnosis. Sinus of Valsalva aneurysms are rare abnormalities of the aortic root that should be considered in the differential diagnosis in young and middle aged patients. Sinus of Valsalva aneurysms are often associated with supracristal ventricular septal defects and can be identified on transthoracic echocardiography. Diagnosis of a SVA should trigger a careful search for ventricular septal defect, which may necessitate transesophageal echocardiography.

Patterns of anticoagulation in patients hospitalized with atrial fibrillation: warfarin is underused in paroxysmal atrial fibrillation.

Paroxysmal atrial fibrillation (PAF) has a similar stroke risk when compared with chronic atrial fibrillation (CAF). Our study sought to define the incidence of warfarin use at time of admission and discharge in patients hospitalized with PAF and CAF. Anticoagulation rates upon hospital admission were 89% in the patients with CAF and 38% in patients with PAF, and increased to 100% for patients with CAF and 81% for patients with PAF at the time of hospital discharge. Despite a similar risk of stroke, patients with paroxysmal atrial fibrillation were less likely to receive long-term oral anticoagulation (AC) compared to patients with chronic atrial fibrillation.