Anomalous Aortic Origin of a Coronary Artery in Adults.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is the second leading cause of sudden death in youth. However, its significance and optimal management in adults is poorly understood. Our objective is to characterize AAOCA in a large single-center adult cohort based on coronary anatomic variants and surgical management strategies. METHODS: We reviewed imaging, clinic, and operative reports for 645 adults with an encounter diagnosis code of congenital coronary anomaly from July 2015 to July 2017. After excluding other congenital heart defects, we characterized 167 patients with AAOCAs by anatomic variant, symptoms at diagnosis, indication for advanced imaging, and if performed, surgical repair. To describe the anatomic variant, we classified the origin and course by following the atomization scheme developed by the Congenital Heart Surgeon's Society's AAOCA registry. RESULTS: Among adults with AAOCA, the anomalous origin involved the right coronary artery in 57% (96 of 167), left main coronary artery in 23% (39 of 167), left anterior descending in 2% (4 of 167), circumflex in 16% (26 of 167), and multiple coronaries in 1% (2 of 167). Anomalous right coronary arteries were diagnosed at an older median age than anomalous left main coronary arteries (55 vs 51 years, respectively; P = .026). Surgical repair of AAOCA occurred in 22% (36 of 167) of patients. Concomitant cardiac surgical procedures accompanied 36% (13 of 36) of them. No deaths occurred over a median follow-up of 2.5 years. CONCLUSIONS: Most patients in our single-center AAOCA registry were diagnosed in the presence of cardiac symptoms. Concomitant aortic valve disease and coronary atherosclerotic burden complicate both the evaluation and surgical approach to adult AAOCA repair.

Mineralocorticoid receptor antagonism by finerenone is sufficient to improve function in preclinical muscular dystrophy.

AIMS: Duchenne muscular dystrophy (DMD) is an X-linked inherited disease due to dystrophin deficiency causing skeletal and cardiac muscle dysfunction. Affected patients lose ambulation by age 12 and usually die in the second to third decades of life from cardiac and respiratory failure. Symptomatic treatment includes the use of anti-inflammatory corticosteroids, which are associated with side effects including weight gain, osteoporosis, and increased risk of cardiovascular disease. Novel treatment options include blockade of the renin-angiotensin-aldosterone system, because angiotensin as well as aldosterone contribute to persistent inflammation and fibrosis, and aldosterone blockade represents an efficacious anti-fibrotic approach in cardiac failure. Recent preclinical findings enabled successful clinical testing of a combination of steroidal mineralocorticoid receptor antagonists (MRAs) and angiotensin converting enzyme inhibitors in DMD boys. The efficacy of MRAs alone on dystrophic skeletal muscle and heart has not been investigated. Here, we tested efficacy of the novel non-steroidal MRA finerenone as a monotherapy in a preclinical DMD model. METHODS AND RESULTS: The dystrophin-deficient, utrophin haploinsufficient mouse model of DMD was treated with finerenone and compared with untreated dystrophic and wild-type controls. Grip strength, electrocardiography, cardiac magnetic resonance imaging, muscle force measurements, histological quantification, and gene expression studies were performed. Finerenone treatment alone resulted in significant improvements in clinically relevant functional parameters in both skeletal muscle and heart. Normalized grip strength in rested dystrophic mice treated with finerenone (40.3 ± 1.0 mN/g) was significantly higher (P = 0.0182) compared with untreated dystrophic mice (35.2 ± 1.5 mN/g). Fatigued finerenone-treated dystrophic mice showed an even greater relative improvement (P = 0.0003) in normalized grip strength (37.5 ± 1.1 mN/g) compared with untreated mice (29.7 ± 1.1 mN/g). Finerenone treatment also led to significantly lower (P = 0.0075) susceptibility to limb muscle damage characteristic of DMD measured during a contraction-induced injury protocol. Normalized limb muscle force after five lengthening contractions resulted in retention of 71 ± 7% of baseline force in finerenone-treated compared with only 51 ± 4% in untreated dystrophic mice. Finerenone treatment also prevented significant reductions in myocardial strain rate (P = 0.0409), the earliest sign of DMD cardiomyopathy. Moreover, treatment with finerenone led to very specific cardiac gene expression changes in clock genes that might modify cardiac pathophysiology in this DMD model. CONCLUSIONS: Finerenone administered as a monotherapy is disease modifying for both skeletal muscle and heart in a preclinical DMD model. These findings support further evaluation of finerenone in DMD clinical trials.

Long-term Outcomes of Surgery for Invasive Valvular Endocarditis Involving the Aortomitral Fibrosa.

BACKGROUND: Reconstruction of the intervalvular fibrosa (IVF) for invasive double-valve infective endocarditis (IE) is a technically challenging operation. This study presents the long-term outcomes of two surgical techniques for IVF reconstruction. METHODS: From 1988 to 2017, 138 patients with invasive double-valve IE underwent surgical reconstruction of the IVF, along with double-valve replacement (Commando procedure, n = 86) or aortic valve replacement with mitral valve repair (hemi-Commando procedure, n = 52). Mean follow-up was 41 ± 5.9 months. RESULTS: Reoperation was required in 82% of patients, and 34% underwent emergency surgery. Pathologic features included positive blood cultures (90%), prosthetic valve IE (75%), aortic root abscess (78%), mitral annular abscess (24%), and intracardiac fistula (12%). There were 28 hospital deaths: 21 (24%) in the Commando group and 7 (14%) in the hemi-Commando group (P = .12). Overall survival at 1, 5, and 10 years was 67%, 48%, and 37%, respectively. Coronary artery disease, native valve IE, and causative organism (Staphylococcus aureus, coagulase-negative Staphylococcus, and viridans streptococci) were risk factors for late mortality. Freedom from reoperation at 1, 5, and 8 years was 87%, 74%, and 55%, respectively. Freedom from recurrent IE at 1, 5, and 8 years was 90%, 78%, and 67%, respectively. CONCLUSIONS: Although it is technically demanding, surgery for invasive IE involving IVF, which provides the only chance for cure, can be performed with reasonable clinical outcomes. In cases of IE invading the IVF and limited to the anterior mitral valve leaflet, a hemi-Commando procedure that includes mitral valve repair has improved early outcomes.