This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM.

AimsTo assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ≤35%).Methods and resultsA 5‐day open‐label run‐in (sacubitril/valsartan 50 mg twice daily) preceded an 11‐week, double‐blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily (‘condensed’ regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily (‘conservative’ regimen)]. Patients were stratified by pre‐study dose of angiotensin‐converting enzyme inhibitor/angiotensin‐receptor blocker (ACEI/ARB; low‐dose stratum included ACEI/ARB‐naïve patients). Of 540 patients entering run‐in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre‐defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in (‘condensed’ vs. ‘conservative’) 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre‐defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down‐titration over 12 weeks (77.8% vs. 84.3% for ‘condensed’ vs. ‘conservative’; P = 0.078). Rates by ACEI/ARB pre‐study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high‐dose/‘condensed’ vs. high‐dose/‘conservative’ and 84.9% vs. 73.6% (P = 0.030) for low‐dose/‘conservative’ vs. low‐dose/‘condensed’.ConclusionsInitiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low‐dose ACEI/ARB group.

Intravenous amiodarone, at the doses used in this study, produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm.

We performed echocardiography prospectively 4.9 +/- 0.7 years apart (mean +/- SD), in 74 patients with systemic lupus erythematosus. On the basis of the first study, the patients were distributed in four groups according to the type of valvular involvement: 7 patients had vegetations (Libman-Sacks endocarditis; group 1); 6 patients had rigid and thickened valves with stenosis, regurgitation, or both (group 2); 5 patients had miscellaneous forms of valvular involvement without valvular dysfunction (group 3), as did the 60 controls; and 56 patients had no valvular disease (group 4). The overall prevalence of clinically important valvular disease (groups 1 and 2) was 18 percent. Patients in group 1 were younger than those in group 2 (33.5 +/- 16.7 vs. 47.8 +/- 17.6 years; P less than 0.05), had a shorter mean duration of lupus (4.8 +/- 2.2 vs. 10.7 +/- 6.4 years; P less than 0.001), and had received a smaller cumulative dose of steroids (21.5 +/- 13.1 vs. 79.5 +/- 63.4 g of methylprednisolone or its equivalent; P less than 0.05). During the five-year follow-up, one patient in group 1 and five in group 2 required valve surgery, no patient in group 3 had valvular dysfunction, and five patients in group 4 had mild valvular lesions. We conclude that clinically important valvular involvement in systemic lupus is relatively frequent and sometimes requires surgery. Echocardiography can identify a subset of lesions (valvular thickening and dysfunction), other than verrucous (Libman-Sacks) endocarditis, that are prone to hemodynamic deterioration.

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Survival after infective endocarditis is fair (81% probability of survival at 10 years), and the most common types of cardiac death are sudden and postoperative. Aortic valve involvement is an independent predictor of the need for late cardiac surgery. The rate of recurrences is not negligible (incidence density at 15 years, 0.0030 per patient-year).

Valvular involvement is frequently found in patients with the primary antiphospholipid syndrome. The lesions are left-sided, causing regurgitation that may be clinically important.

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