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Examines the genetic heterogeneity of familial atrial myxoma syndromes. Incidence; Transmission; Signs and symptoms; Isolation of genomic DNA; Importance of gene identification; Cause of familial atrial myxomas.

The likelihood of success of conservative management of obstructive hypertrophic cardiomyopathy (HC) and the predictors of failure of conservative therapy are not known. We therefore evaluated the efficacy of an algorithm for the management of symptoms and predictors of failed conservative therapy in 249 consecutive symptomatic patients with obstructive HC referred to a dedicated HC program for management in general or for septal reduction therapy (SRT) in particular. There was considerable practice variation in the extent to which conservative therapy was optimized before referral for SRT. Over 3.7 ± 2.9-year follow-up, symptoms resolved with addition of or increase in dosage of a β blocker, calcium channel blocker, or disopyramide in 16%, 10%, and 10% of patients, respectively. Pacing with short atrioventricular delay controlled symptoms in 4 of 9 patients. In 63% of patients, conservative measures failed to control symptoms. Multivariate predictors of failure of conservative therapy were presence of New York Heart Association class III or IV symptoms (hazard ratio 2.0, 95% confidence interval 1.4 to 2.9, p = 0.001) and greater septal wall thickness (hazard ratio 1.06, 95% confidence interval 1.02 to 1.10, p = 0.003) at presentation. At time of presentation, 93 patients (37%) were already on optimal therapy and were referred for SRT. Of the remaining 156 patients who did not require immediate SRT, 93 (60%) were free from a recommendation for SRT at the end of the follow-up period. In conclusion, in symptomatic patients with obstructive HC, conservative therapy is successful in >1/3 of referred patients at 3.7-year follow-up, obviating SRT in these patients. Clinicians in programs offering SRT should optimize conservative therapy before recommending SRT. [ABSTRACT FROM AUTHOR]

We report on the long QT syndrome occurring in conjunction with nontoxic multinodular goiter and sensorineural deafness in several siblings of a large family. Autosomal and X-linked recessive and dominant modes of inheritance are possible for the different phenotypes. The affected family members had various phenotype combinations, suggesting variable expressivity and incomplete penetrance. [Copyright &y& Elsevier]

An inflammatory cause of atrial fibrillation (AF) has been proposed on the basis of the presence of lymphocytic infiltrates in the biopsy results of patients with lone AF, alterations of C-reactive protein (CRP) and interleukin-6 levels in subjects with AF, and the time course of postoperative AF. Many previous studies exploring inflammatory factors in AF have been confounded by concomitant medical illnesses. Subjects with lone AF provide a unique opportunity to eliminate the effects of associated conditions. We therefore sought to determine CRP levels in homogenous cohorts of patients with lone AF or AF and hypertension. One hundred twenty-one subjects with lone AF, 52 subjects with AF and hypertension, and 75 control subjects were enrolled and studied. Plasma CRP levels were determined using a commercially available immunoassay. There was no significant difference in CRP levels between subjects with lone AF and controls (1.34 vs 1.21 mg/L, p = 0.18). CRP levels in subjects with AF and hypertension were elevated compared with those of controls and those of subjects with lone AF, although this difference was attributable to increased body mass indexes. CRP levels were not elevated in subjects with lone AF compared with controls. In conclusion, these findings clarify previous observations of elevations in CRP levels in subjects with AF and suggest that this marker of systemic inflammation is associated not with the arrhythmia per se, but rather with underlying cardiovascular disease. [Copyright &y& Elsevier]

Dilated cardiomyopathy associated with lamin A/C (LMNA) gene variants (LMNA-related dilated cardiomyopathy [DCM]) is a life-threatening condition with a high unmet need, accounting for approximately 6% of idiopathic DCM cases. Currently, no disease-specific treatments target the underlying disease mechanism. ARRY-371797 (PF-07265803), a potent, selective, oral, small-molecule inhibitor of the p38α mitogen-activated protein kinase pathway, improved 6-minute walk test (6MWT) distance in 12 patients with symptomatic LMNA-related DCM in a 48-week, open-label, phase 2 study. This long-term extension study examined the safety and efficacy of ARRY-371797 in patients from the phase 2 study. 6MWT, N-terminal pro-B-type natriuretic peptide concentration, and 12-item Kansas City Cardiomyopathy Questionnaire score were assessed at weeks 48, 72, 96, 120, and 144 from phase 2 study baseline. Eight patients enrolled (mean [SD] age, 51 [10] years, 4 male). Mean 6MWT increased by >30 m (>10%) from phase 2 study baseline up to week 120. The decrease in N-terminal pro-B-type natriuretic peptide observed in the phase 2 study was maintained throughout the present study. Twelve-item Kansas City Cardiomyopathy Questionnaire Physical Limitation increased from baseline at all visits except week 96 (range: -0.8 [week 96] to 13.8 [week 120]); results for other domains were variable. Treatment was generally well tolerated; 2 patients discontinued because of causes not considered treatment-related. There were no deaths. ARRY-371797 was generally well tolerated over median (range) 155.7 (61 to 327)-week exposure; evidence suggested preserved exercise capacity over the study period. The ongoing, pivotal, phase 3, randomized, placebo-controlled study REALM-DCM investigates the efficacy and safety of ARRY-371797 (PF-07265803) in LMNA-related DCM. (ClinicalTrials.gov Identifier: NCT02351856)., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)