Search

The heart oxidizes fatty acids for its energy production. The physiological balance between fatty acid uptake and its oxidation prevents lipid accumulation in cardiac myocytes. However, accumulation of lipids due to various processes such as obesity, diabetes, heart failure, myocardial ischemia or infarction can result in damage to the heart tissue, also known as cardiolipotoxicity. We present a unique case of a 69-year-old gentleman with a history of heart failure and ventricular tachycardia. Endomyocardial biopsy to assess for restrictive cardiomyopathy/amyloid showed no evidence of amyloid, significant inflammation or fibrosis, but did show intracellular accumulation of significant amorphous material in most cardiac myocytes. We review the literature regarding the pathogenesis of cardiolipotoxicity, which has no definite cause or treatment yet identified.

Objectives The most common genetic alterations in prostate cancer are fusions of ERG and other members of the E26 transformation-specific (ETS) family of transcription factors, including ETV1, ETV4, and FLI1. Analyzing TCGA data, we found that similar to ERG fusion, FLI1 fusion-associated FLI1 mRNA level increases. ERG IHC stain has been a surrogate test for ERG fusion. Therefore, we hypothesize that FLI IHC stain could also be used to detect FLI1 fusion in prostate cancer. Methods In total, 111 primary prostate adenocarcinoma (>10% by volume) cases from our institute were selected for tissue microarray (TMA) construction. The regular full section slides and TMA slides were subject to IHC stain of ERG and FLI1 (Santa Cruz, SC-113). The criteria for positive FLI1 are (1) nuclear staining; (2) only in tumor cells, not in nontumor cells; and (3) FLI1-positive cells should be negative for ERG IHC staining. Results For prostate TMA slides, ~50% of cases were positive for ERG; ~30% of cases were weakly positive for FLI1. However, all of the FLI1 weakly positive cases were positive for ERG as well possibly due to cross-reactivity between ERG and FLI1, which was demonstrated in other studies. Conclusion Overall, we conclude that the cross-reactivity between FL1 and ERG precluded the detection of FLI1 fusion in prostatic adenocarcinoma under current conditions. We are in the process of selecting some cases to detect FLI1 fusion by next-generation sequencing (NGS) and FISH.

Introduction The heart oxidizes fatty acids for its energy production. However, excessive accumulation of lipids due to various processes such as obesity, diabetes, heart failure (HF), myocardial ischemia, or infarction can result in damage to the heart tissue, also known as cardiolipotoxicity. Case A 69-year-old gentleman with a history of non-ischemic cardiomyopathy, right ventricle failure, permanent atrial fibrillation, ventricular tachycardia and cardiac cirrhosis presented to the hospital with exertional dyspnea, orthopnea, and decreased functional capacity. Physical exam was pertinent for elevated jugular venous distension, bibasilar rales, and bilateral pitting pedal edema. Laboratory findings were significant for brain type natriuretic peptide 1641 pg/ml, hemoglobin A1c 6.1%, total cholesterol 79 mg/dl, triglyceride 84 mg/dl, low density lipoprotein (LDL) 53 mg/dl, and high density lipoprotein (HDL) 9 mg/dl. Chest x-ray demonstrated mild pulmonary vascular congestion. Electrocardiogram showed atrial fibrillation and right bundle branch block. Transthoracic echocardiogram showed normal left ventricular systolic function with ejection fraction of 55%, severely dilated right ventricle with severely reduced systolic function and markedly dilated right and left atrium. Right heart catheterization showed findings consistent with mild pulmonary hypertension from diastolic HF and severe tricuspid regurgitation. Endomyocardial biopsy showed intracellular accumulation of significant amorphous material in most cardiac myocytes. Electron microscopy revealed fat lobules and inclusion bodies within the myocytes, consistent with cardiolipotoxicity (figure 1). Guideline directed medical management of HF was initiated and patient was subsequently discharged home. Discussion Due to various stressors such as HF, myocardial ischemia, infarction or atrophy, there is increased expression of genes involved in glucose metabolism rather than fatty acid oxidation. This leads to increased accumulation of lipids in the failing myocardium, thereby leading to cardiolipotoxicity. Increased lipid accumulation causes cardiac steatosis thereby leading to ER dysfunction, contractile dysfunction, and cell death. Our case describes a distinct metabolic phenotype of myocardial dysfunction for which no definite cause or treatment has been identified. Further research is required to advance our knowledge on cardiac metabolism in normal myocardium as well as in patients with HF, which could result in development of novel therapeutic interventions and strategies in these patients.