Pathogenic BCS1L Mutation Resulting in Hypertrophic Cardiomyopathy: A Unique Presentation of Nuclear Mitochondrial Disease.

A 21-year-old man with sensorineural hearing loss and glaucoma presented with severely limited exercise capacity since childhood. He was found to have biventricular concentric hypertrophy with greatest wall thickening at the posterior and lateral walls of the left ventricle apex (1.7 cm) and the free wall of the right ventricle (1.1 cm). There was no inducible left ventricular outflow tract obstruction. Metabolic testing revealed marked lactic aciduria (1,650.1 µmol/mmol creatinine) and plasma lactate (3.9 mmol/L). A sarcomeric hypertrophic cardiomyopathy gene panel was unremarkable, but mitochondrial gene analysis revealed a homozygous c.385G>A (p.Gly129Arg) pathogenic mutation in the BCS1L gene. This gene is responsible for an assembly subunit of cytochrome complex III in the respiratory transport chain and is the rarest respiratory chain defect. This gene has not frequently been implicated in cardiomyopathy. Mitochondrial hypertrophic cardiomyopathy is more rare than hypertrophic cardiomyopathy resulting from sarcomeric mutations and is more likely to be symmetric, less frequently results in left ventricular outflow tract obstruction, and is more likely to progress to dilated cardiomyopathy. Evidence-based screening protocols have not been established; treatment follows guideline-directed medical therapy for congestive heart failure, including evaluation for heart transplantation. This report expands the phenotype of the BCS1L mutation and suggests that affected patients may need screening for underlying cardiomyopathy.

Large Left Ventricular Pseudoaneurysm Presenting as an Embolic Stroke After a "Silent" Myocardial Infarction.

A 72-year-old woman with no history of coronary artery disease presented with an acute left middle cerebral artery stroke and was found to have a large left ventricular pseudoaneurysm measuring 8.7 × 7.6 cm and 2 large left ventricular thrombi, the source of her systemic embolization. Despite initial medical management, she developed refractory New York Heart Association functional class III heart failure, uncontrolled atrial fibrillation, and further enlargement of her pseudoaneurysm to 5.5 × 10.6 × 9.2 cm. She underwent urgent aneurysmectomy. Left ventricular pseudoaneurysms are rare and most commonly occur following an acute myocardial infarction when a ventricular free-wall rupture is contained by pericardium or thrombi. Historically, left ventricular angiography displaying a lack of an overlying coronary artery was the gold standard for diagnosis. Now, noninvasive imaging such as computed tomography, magnetic resonance imaging, and echocardiogram with ultrasound-enhancing agent, are reliable diagnostic tools. They can distinguish a pseudoaneurysm from a true left ventricular aneurysm using characteristic findings such as a narrow aneurysm neck, bidirectional doppler flow between the pseudoaneurysm and the left ventricle, and abrupt changes in the cardiac wall structures. Progressive dilation, wall thinning, and dyskinesis can result in refractory heart failure, arrhythmias, and thrombi formation from venous stasis. Pseudoaneurysms have a 30% to 45% risk of rupture and can be treated with left ventricular aneurysmectomy.

Predictors and outcome of electrical storm-induced cardiogenic shock.

AIM: Limited information is available about the short- and long-term outcomes in electrical storm (ES)-induced cardiogenic shock (CS) and its predictors. METHODS AND RESULTS: This is a retrospective, single-centre cohort study of consecutive patients with ES admitted to the Cardiac Intensive Care Unit between 2015 and 2020. The proportion of ES patients who developed CS was adjudicated, and clinical predictors of in-hospital ventricular arrhythmia (VA)-related mortality and 1-year all-cause mortality were investigated. Of the 214 patients with ES, 33.6% developed CS. Left-ventricular ejection fraction, admission lactate, absence of an implantable cardioverter defibrillator, and admission central venous pressure were independently associated with development of CS (P < 0.03 for all). Based on these variables, a FLIC score was developed (https://riskcalc.org/FLICscore/) to predict ES-induced CS [area under the curve (AUC) = 0.949, with AUC = 0.954 in a validation cohort, both P < 0.001]. Patients who developed CS had a 11.3-fold [95% confidence interval (CI) 2.7-12.8] increased odds for in-hospital VA-related mortality and 9.4-fold (95% CI 4.0-22.4) increased odds for in-hospital all-cause mortality. A FLIC score above 0.62 was associated with a 6.2- and 5.8-fold increased odds for respectively similar endpoints. Patients with ES-induced CS received more treatment modalities to manage the ES (4.5 ± 1.8 vs. 2.3 ± 1.2, P < 0.001) and had longer length of stay [14 (8-27) vs. 8 (5-13), P < 0.001] than patients without CS. Interestingly, if patients with ES-induced CS survived to discharge, their outcomes were similar to those without CS at 1 year. CONCLUSION: Cardiogenic shock in ES is a frequent and potentially life-threatening complication with high short-term mortality. A novel risk score could identify patient at risk, generating a potential for early risk-based interventions.

Tumor Molecular Profiling for an Individualized Approach to the Treatment of Hepatocellular Carcinoma: A Patient Case Study.

Hepatocellular carcinoma (HCC) is increasing in incidence, and the associated mortality rate remains among the highest. For advanced HCC, sorafenib has been shown to slightly prolong survival, and regorafenib and nivolumab, both recently approved by the United States Food and Drug Administration (FDA), may produce clinical benefits to a limited extent. Systemic chemotherapy has been shown to produce a modest response, but there is no clinically valid biomarker that can be used to predict which patients may benefit. In this case study, we present two patients with metastatic HCC, they received systemic treatment using capecitabine, oxaliplatin, and either bevacizumab or sorafenib. The tumor response to treatment was determined by the progression-free survival (PFS). Molecular profiling of the tumors showed differential expression of biochemical markers and different mutational status of the TP53 and β-catenin (CTNNB1) genes. We hypothesize that the PFS correlates with the tumor molecular profiles, which may be predictive of the therapeutic response to systemic chemotherapy. Further investigation is indicated to correlate tumor biomarkers and treatment responses, with the objective of personalizing the therapies for patients with advanced HCC.

The impact of pregnancy on headache evaluation in the emergency department, a retrospective cohort study.

BACKGROUND: Headache is one of the most common emergency department complaints with three million visits annually in the USA. This is further complicated with 30% of those emergency visits being for a hypertensive disorder of pregnancy. There is no currently well-established guideline for diagnostic imaging with a common concern being ionizing radiation exposure in pregnancy. The purpose of this study was to assess the difference in imaging studies ordered for pregnant and non-pregnant patients who reported to a tertiary care emergency department with headache. OBJECTIVE: The purpose of this study was to assess the difference in imaging studies ordered for pregnant and non-pregnant patients who reported to a tertiary care emergency department with headache. STUDY DESIGN: This retrospective cohort study identified all reproductive age female patients who presented to the emergency department with a chief complaint of "headache." They were then divided into cohorts based on pregnancy status. Rates and types of imaging studies utilized in patient evaluation were then compared. RESULTS: Two thousand seven hundred ninety patients met our criteria for evaluation; 95 were found to be pregnant. Head CTs were ordered significantly less and MRIs were ordered significantly more in the pregnant cohort as compared to the non-pregnant cohort with a P value of <0.0001 and an odds ratio of 4.21 and a P value of 0.0127 and an odds ratio of 0.49, respectively. CONCLUSION: Our data shows a difference in evaluation for pregnant patients as compared to their non-pregnant cohort. CT should not be considered contraindicated in the pregnant population and the amount of ionizing radiation to the fetus is well within the maximum safe dose, particularly with appropriate shielding. The time difference, cost, fetal exposure risk, and availability of CT compared to MRI should be taken into account when establishing a criterion for diagnostic evaluation. This difference validates the need for further research into a well-established guideline for the emergent evaluation of headache in the ED without special bias placed on pregnancy status.