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Hypomagnesemia is commonly observed in heart transplant (HT) recipients receiving calcineurin inhibitors. Since low serum magnesium (s-Mg) has been implicated in the progression of atherosclerosis, potentially leading to worsening coronary heart disease, arrhythmias and sudden death, we investigated the association between s-Mg and HT outcomes. Between 2002 and 2017, 150 HT patients assessed for s-Mg were divided into high (≥1.7 mg/dL) and low s-Mg groups according to the median value of all s-Mg levels recorded during the first 3 months post-HT. Endpoints included survival, cardiac allograft vasculopathy (CAV), any-treated rejection (ATR) and NF-MACE. Kaplan-Meier analysis showed that at 15 years after HT, both survival (76 vs 33%, log-rank p = 0.007) and freedom from CAV (75 vs 48%, log-rank p = 0.01) were higher in the high versus low s-Mg group. There were no significant differences in freedom from NF-MACE or ATR. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant 2.6-fold increased risk of mortality and 4-fold increased risk of CAV (95%CI 1.06 to 6.4, p = 0.04; 95%CI 1.12 to 14.42, p = 0.01, respectively). In conclusion, low s-Mg is independently associated with increased mortality and CAV in HT patients. Larger multi-center prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Minimal attention has been paid to understanding the implications of the chronicity of heart failure (HF) diagnosis on prognosis of hospitalized patients with acute HF (AHF). We aimed to assess the differences in outcomes between hospitalized patients with AHF that are new-onset (de-novo) AHF and acutely decompensated chronic HF (ADCHF). We analyzed data of 2,328 patients with AHF, who were enrolled in the HF survey in Israel. Patients were classified into de-novo AHF and ADCHF. A total of 721 (31%) patients were classified as de-novo AHF and 1,607 (69%) patients were classified as ADCHF. Patients with de-novo AHF were more likely to be younger, with fewer co-morbidities represented by lower Charlson index, and less likely to have past myocardial infarction as well as coronary revascularization. At 30 days mortality rates were similar in both groups (9% vs 8% in de-novo AHF and ADCHF, respectively). Survival analysis showed that at 1 and 10 years the all-cause mortality rates were significantly higher in patients with ADCHF (33% vs 22% and 90% vs 72%, 1 and 10 years, log-rank p < 0.001, respectively). Consistently, multivariable analysis showed that patients with ADCHF had an independently 58% and 48%, higher mortality risk at 1 and 10 years, respectively, (1-year hazard ratio = 1.58; 95% confidence interval 1.05 to 2.38, p = 0.03; 10-year hazard ratio = 1.48; 95% confidence interval = 1.23 to 2.77; p < 0.001). In conclusion, previous history of HF is an independent predictor of 1-year and 10-year mortality after hospitalization for AHF. Distinction between de-novo AHF and ADCHF may improve our understanding and risk stratification of patients with AHF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Familial dilated cardiomyopathy is a major cause of advanced heart failure and heart transplantation. In most families, the disease-causing mutation is unknown, and relatives should therefore undergo periodic screening to facilitate early diagnosis and therapy. In the present study, we describe a novel titin truncation mutation causing adult-onset familial dilated cardiomyopathy in an Israeli Arab family. The family members underwent physical examination, electrocardiography, and Doppler echocardiography. Linkage to candidate loci was performed, followed by gene sequencing. We identified 13 clinically affected family members (8 men and 5 women, mean age 47 ± 12 years). Compared with their healthy first-degree relatives, the affected relatives had a larger end-diastolic left ventricular dimension (60 ± 10 vs 49 ± 4 mm, p <0.001), lower ejection fraction (43 ± 11% vs 60 ± 6%, p <0.001), and markedly higher end-systolic volume indexes but no difference in wall thickness or diastolic function. The linkage studies or direct sequencing excluded LMNA, MYH7, TNNT2, TNNI3, SCN5A, DES, SGCD, ACTC, PLN, and MYH6 but established linkage to the TTN locus at chromosome 2q31, yielding a maximum (2-point) LOD score of 3.44. Sequence analysis identified an insertion (c.58880insA), causing protein truncation after 19,628 amino acids (p.S19628IfsX1). No founder effect was found among the Israeli Arabs. In conclusion, titin is a giant protein with a key role in sarcomere assembly, force transmission, and maintenance of resting tension. Although some mutations result in skeletal myopathy, others cause isolated, maturity-onset cardiomyopathy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In obese patients with coronary artery disease (CAD), the vascular endothelium is usually impaired, and the modification or reversal of endothelial dysfunction may significantly enhance treatment. Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment, but its impact on endothelial function in obese patients with CAD has not yet been investigated. Eighty consecutive obese, nonhypertensive, stable patients with CAD (65 men; mean age 65 +/- 11 years, mean body mass index 32 +/- 3 kg/m2) were randomly assigned to either sibutramine 10 mg/day (n = 40) or routine treatment (n = 40; controls) for 4 months. The percentage improvement in endothelium-dependent brachial artery flow-mediated dilation (%FMD) and endothelium-independent nitroglycerin-mediated vasodilation were assessed at baseline and after 4 months using high-resolution ultrasound. At baseline, all patients had %FMD of 5.4 +/- 3.1% and percentage improvement in endothelium-independent nitroglycerin-mediated vasodilation of 9.2 +/- 2.9%, showing no significant differences. After 4 months, however, initial body weight was reduced by 11.4 +/- 1.2% in the sibutramine group compared with only 2.2 +/- 1.3% in controls (p <0.001), demonstrating a significant improvement in postintervention %FMD (8.9 +/- 2.4%, p = 0.01, compared with baseline) in the sibutramine group compared with controls (5.2 +/- 3.6%, p = 0.68, compared with baseline). No significant therapeutic effect on the percentage improvement in endothelium-independent nitroglycerin-mediated vasodilation was seen in either group (9.2 +/- 2.5% vs 9.1 +/- 3.0%, respectively, p = 0.792). In addition, sibutramine therapy was associated with significant C-reactive protein reduction compared with routine treatment (44% vs 9%, p = 0.035). Thus, short-term therapy with sibutramine, together with diet and lifestyle intervention, is associated with improved endothelial function assessed by brachial artery %FMD in nonhypertensive, stable patients with CAD.

This study examined left ventricular (LV) filling properties and exercise hemodynamics noninvasively before and after an exercise training program in patients with chronic heart failure (HF). Although exercise training did not improve LV filling properties in patients with advanced HF, LV filling properties determined the hemodynamic benefit attainable from exercise in this patient group.

Purpose: Recent reports suggest that decreased functional capacity in patients with heart failure may be associated with abnormalities in glucose metabolism. We followed patients with coronary artery disease who participated in the Bezafibrate Infarction Prevention study to determine the incidence of diabetes by baseline functional status during a 7.7-year follow-up., Methods: The sample comprised 2616 nondiabetic patients aged 45 to 74 years with a fasting blood glucose level <7 mmol/L (126 mg/dL). They were divided into three groups by New York Heart Association (NYHA) criteria: class I (n = 1986 patients), class II (n = 518), and class III (n = 112). The detection of a fasting blood glucose level > or =7 mmol/L during follow-up was defined as the criterion for the development of diabetes., Results: The study groups had similar demographic and clinical characteristics, except that patients with symptomatic heart failure (NYHA class II or III) were more likely to have angina. During follow-up, diabetes developed in 259 patients (13%) in NYHA class I, 76 (15%) in class II, and 22 (20%) in class III (P for trend = 0.05). At the last visit, patients in NYHA class III were twice as likely (17% [n = 19]) to have fasting blood glucose levels > or =7 mmol/L as those in NYHA class I (7.8% [n = 154]) or class II (8.7% [n = 45]) (P = 0.005). In a multivariate analysis, NYHA class III was associated with a 1.7-fold (95% confidence interval [CI]: 1.1 to 2.6) increase in the rate of development of diabetes, but NYHA class II was not (hazard ratio = 1.0; 95% CI: 0.8 to 1.3)., Conclusion: Among patients with coronary artery disease, advanced heart failure (NYHA class III) is associated with a significantly increased risk of developing diabetes during a 6- to 9-year follow-up.

Unlike thrombolytic agents, there are conflicting data regarding the time-dependent effect of aspirin treatment on outcome in acute myocardial infarction (AMI). We sought to evaluate the impact of timing of aspirin administration (before vs after thrombolysis) on mortality of patients with AMI. Our study included 1,200 patients with ST elevation AMI treated with thrombolysis. Early (n = 364) versus late (n = 836) users were defined as those receiving emergency aspirin before versus after initiation of thrombolysis, respectively. Time (median) from symptom onset to initiation of aspirin treatment was significantly shorter in early versus late users (1.6 vs 3.5 hours; p <0.001). There were no significant differences between the 2 groups with respect to baseline clinical characteristics. Early aspirin users were more likely to develop reischemia, to be treated with beta blockers, to be referred to coronary angiography, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery. Early users experienced lower mortality at 7 days (2.5% vs 6.0%, p = 0.01), 30 days (3.3% vs 7.3%, p = 0.008), and 1 year (5.0% vs 10.6%, p = 0.002) than late users. This survival benefit persisted for patients with and without previous aspirin therapy or revascularization and after adjustment for baseline characteristics and therapies at 7 days (odds ratio 0.36, 95% confidence interval 0.15 to 0.79), at 30 days (odds ratio 0.39, 95% confidence interval 0.17 to 0.82), and at 1 year (odds ratio 0.41, 95% confidence interval 0.21 to 0.74). Our study proposes a time-dependent benefit from aspirin in patients with AMI treated with thrombolysis.