Genetic Modifiers of Hereditary Neuromuscular Disorders and Cardiomyopathy.

Novel genetic variants exist in patients with hereditary neuromuscular disorders (NMD), including muscular dystrophy. These patients also develop cardiac manifestations. However, the association between these gene variants and cardiac abnormalities is understudied. To determine genetic modifiers and features of cardiac disease in NMD patients, we have reviewed electronic medical records of 651 patients referred to the Muscular Dystrophy Association Care Center at the University of Cincinnati and characterized the clinical phenotype of 14 patients correlating with their next-generation sequencing data. The data were retrieved from the electronic medical records of the 14 patients included in the current study and comprised neurologic and cardiac phenotype and genetic reports which included comparative genomic hybridization array and NGS. Novel associations were uncovered in the following eight patients diagnosed with Limb-girdle Muscular Dystrophy, Bethlem Myopathy, Necrotizing Myopathy, Charcot-Marie-Tooth Disease, Peripheral Polyneuropathy, and Valosin-containing Protein-related Myopathy. Mutations in COL6A1, COL6A3, SGCA, SYNE1, FKTN, PLEKHG5, ANO5, and SMCHD1 genes were the most common, and the associated cardiac features included bundle branch blocks, ventricular chamber dilation, septal thickening, and increased outflow track gradients. Our observations suggest that features of cardiac disease and modifying gene mutations in patients with NMD require further investigation to better characterize genotype-phenotype relationships.

South Asian-Specific MYBPC3 Δ25bp Deletion Carriers Display Hypercontraction and Impaired Diastolic Function Under Exercise Stress.

Background: A 25-base pair (25bp) intronic deletion in the MYBPC3 gene enriched in South Asians (SAs) is a risk allele for late-onset left ventricular (LV) dysfunction, hypertrophy, and heart failure (HF) with several forms of cardiomyopathy. However, the effect of this variant on exercise parameters has not been evaluated. Methods: As a pilot study, 10 asymptomatic SA carriers of the MYBPC3 Δ25bp variant (52.9 ± 2.14 years) and 10 age- and gender-matched non-carriers (NCs) (50.1 ± 2.7 years) were evaluated at baseline and under exercise stress conditions using bicycle exercise echocardiography and continuous cardiac monitoring. Results: Baseline echocardiography parameters were not different between the two groups. However, in response to exercise stress, the carriers of Δ25bp had significantly higher LV ejection fraction (%) (CI: 4.57 ± 1.93; p < 0.0001), LV outflow tract peak velocity (m/s) (CI: 0.19 ± 0.07; p < 0.0001), and higher aortic valve (AV) peak velocity (m/s) (CI: 0.103 ± 0.08; p = 0.01) in comparison to NCs, and E/A ratio, a marker of diastolic compliance, was significantly lower in Δ25bp carriers (CI: 0.107 ± 0.102; p = 0.038). Interestingly, LV end-diastolic diameter (LVIDdia) was augmented in NCs in response to stress, while it did not increase in Δ25bp carriers (CI: 0.239 ± 0.125; p = 0.0002). Further, stress-induced right ventricular systolic excursion velocity s' (m/s), as a marker of right ventricle function, increased similarly in both groups, but tricuspid annular plane systolic excursion increased more in carriers (slope: 0.008; p = 0.0001), suggesting right ventricle functional differences between the two groups. Conclusions: These data support that MYBPC3 Δ25bp is associated with LV hypercontraction under stress conditions with evidence of diastolic impairment.

Stent placement for long-segment total occlusion of an aberrant right subclavian artery: A 7-year follow-up.

An aberrant origin of the right subclavian artery arising as the most distal vessel from the aortic arch is an uncommon but clinically important anomaly. Its abnormal course may result in esophageal compression with dysphagia, or tracheal compression resulting in asthma or stridor, and can greatly complicate radial artery access for coronary angiography. When an aberrant right subclavian artery is obstructed by atherosclerotic plaque, it may produce symptoms of arm ischemia such as pain and weakness. For the past 75 years, the standard treatment approach for symptomatic aberrant right subclavian artery has been surgical correction. There are only three case reports of percutaneous therapy, all for nonocclusive stenosis. There are no reported cases of percutaneous treatment of a completely occluded aberrant right subclavian artery. We report a patient with exertional right arm heaviness and weakness who was found to have a 60-mm long aberrant right subclavian artery occlusion. The blockage was successfully treated with angioplasty and placement of a single stent using percutaneous vascular access. Chest computerized tomography and duplex ultrasonography 5 years after treatment demonstrated a patent stent. At 7-year follow-up, she remained symptom-free and had a normal radial pulse. This case represents the first report of total occlusion of aberrant right subclavian artery treated percutaneously. Long-term durability supports this as a viable alternative to surgery in appropriately selected patients.

Reverse Takotsubo cardiomyopathy: a story of a critically ill man with transient cardiac dysfunction.

Reverse Takotsubo cardiomyopathy (TCM) is a recently described variant of classic TCM. In contrast to classic TCM, the regional wall motion abnormalities are localized in the basal segments. The condition can be triggered by acute stressful events, including acute medical illnesses. The wall motion abnormalities and left ventricular dysfunction are usually completely reversible. We present a case of an 84-year-old man with a complicated postoperative course after laparoscopic cholecystectomy with multiple laparotomies and recurrent sepsis. Echocardiographic evaluation demonstrated left ventricular dysfunction and wall motion abnormalities in a pattern resembling reverse TCM. He had no significant coronary disease on angiography and follow-up echocardiography showed complete resolution of left ventricular systolic dysfunction and regional wall motion abnormalities.