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The aim of this study is to explore the impact of metabolic syndrome (MS) on the outcome of patients with non-clinically diagnosed diabetes with acute coronary syndrome (ACS) based on a comprehensive nationwide registry during a 1-year follow-up. In the ACS Israeli Survey, 1,060 consecutive patients with non-clinically diagnosed diabetes were admitted due to ACS; 359 patients with MS features on admission were compared with 701 subjects without MS. A modified National Cholesterol Education Program Adult Treatment Panel III definition of MS was used in patients who presented with ≥3 of the 5 components: (1) hyperglycemia, defined as occasional blood glucose on admission >140 mg/dl; (2) preexisting hypertension; (3) body mass index >28 kg/m2; (4) high-density lipoprotein cholesterol ≤40 mg/dl (men) or ≤50 mg/dl (women); and (5) triglycerides ≥150 mg/dl. Patients with MS were more frequently women (27% vs 12%, p = 0.001), were in Killip ≥II on admission (19% vs 14%, p = 0.03), and had higher 30-day (5.0% vs 1.7%, p = 0.002) and 1-year (8.9% vs 4.6%, p = 0.005) crude mortality rates. Patients with hyperglycemia (glucose >140 mg/dl) and MS had higher 30-day mortality rates compared with patients with hyperglycemia without MS (8.3% vs 2.5%, p <0.05). Multivariate analysis identified MS as a strong independent predictor of 30-day and 1-year mortality with hazard ratios of 2.54 (95% confidence interval 1.22 to 5.31) and 1.96 (95% confidence interval 1.18 to 3.24), respectively. In conclusion, MS defined early at admission is a strong independent predictor of mortality and morbidity in patients with non-clinically diagnosed diabetes with ACS. [Copyright &y& Elsevier]

Studies systolic septal thickening and motion in patients following coronary artery bypass grafting (CABG) and mitral valve replacement (MVR). Absence of significant difference between patients following CABG and MVR regarding the extent of systolic anterior motion at rest or during dobutamine infusion; Augmented anterioposterior cardiac motion after pericardiotomy.

Mitral regurgitation (MR) complicating acute myocardial infarction (AMI) is associated with increased mortality. The prognostic significance of only mild MR detected by echocardiography in patients with AMI is unknown. This study assessed the long-term risk associated with mild MR detected by color Doppler echocardiography within the first 48 hours of admission in 417 consecutive patients with AMI. No MR was detected in 271 patients (65%), mild MR was seen in 121 patients (29%), and moderate or severe MR was noted in 25 patients (6%). One-year mortality rates were 4.8%, 12.4%, and 24%, respectively (p<0.001). Multivariate analysis revealed that mild MR was independently associated with increased 1-year mortality (p<0.05) after adjustment for age, gender, previous myocardial infarction, diabetes mellitus, systemic hypertension, Killip grade > or =2 on admission, and left ventricular ejection fraction < or =40%. The hazard ratio for 1-year mortality was 2.31 (95% confidence interval 1.03 to 5.20) for mild MR and 2.85 (95% confidence interval 0.95 to 8.51) for moderate or severe MR. Thus, mild MR detected by color Doppler echocardiography within the first 2 days of admission in patients with AMI is a significant independent risk predictor for 1-year all-cause mortality. [ABSTRACT FROM AUTHOR]

Patients with primary growth hormone (GH) resistance-Laron Syndrome (LS)-have no GH signal transmission, and thus, no generation of circulating insulin-like growth factor-I (IGF-I), and should serve as a unique model to explore the controversies concerning the longterm effect of GH/IGF-I deficiency on cardiac dimension and function. We assessed 8 patients with LS (4 men, 4 women) with a mean (+/- SD) age of 38+/-7 years (range 22 to 45), and 8 aged-matched controls (4 men, 4 women) with a mean age of 38+/-9 years (range 18 to 47) by echocardiography at rest, following exercise, and during dobutamine administration. Left ventricular (LV) septum, posterior wall, and end-diastolic diameter were significantly reduced in untreated patients with LS compared with the control group (p<0.05 for all). Systolic Doppler-derived parameters, including LV stroke volume, stroke index, cardiac output, and cardiac index, were significantly lower (p<0.05 for all) than in the control subjects, whereas LV diastolic Doppler parameters, including mitral valve waves E, A, E/A ratio, and E deceleration time, were similar in both groups. LV ejection fraction at rest as well as the stress-induced increment of the LV ejection fraction were similar in both groups. Our results show that untreated patients with long-term IGF-I deficiency have reduced cardiac dimensions and output but normal LV ejection fraction at rest and LV contractile reserve following stress. [ABSTRACT FROM AUTHOR]

We investigated which physical parameter has the greatest impact on the perceived loudness of a systolic murmur in aortic stenosis. Loudness of murmur in aortic stenosis correlated best with peak momentum transfer—and thus with body size—so that loud murmurs predict severe disease less reliably in larger patients. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

The aim of the present study was to evaluate whether assessment of stroke volume index (SVI) can be used to improve risk stratification among patients with low-gradient severe aortic stenosis and preserved ejection fraction (EF). Study population comprised 409 patients with aortic valve area ≥1.00 cm², mean gradient <40 mm Hg, and a normal EF (≥50%) who were followed up in a tertiary referral center from 2004 to 2012. Echocardiographic parameters and clinical data were collected. Multivariate Cox proportional hazards regression modeling was used to evaluate the association between SVI and the risk of all-cause mortality. Mean age of study patients was 78 ± 11 years, and 42% were men. The mean SVI was 39 ± 7 ml/m² (tertile 1 = 32 ± 4 ml/m²; tertile 2 = 39 ± 1 ml/m²; tertile 3 = 47 ± 4 ml/m²). Multivariate analysis showed that the SVI was the most powerful echocardiographic parameter associated with long-term outcome: each 5 ml/m² reduction in SVI was associated with a 20% increase in adjusted mortality risk (p = 0.01). Consistently, Kaplan-Meier analysis showed that the cumulative probability of survival during 3 years of follow-up was 60%, 72%, and 73% among patients in the low-, intermediate-, and high-SVI groups, respectively (p = 0.012). Our findings suggest that in patients with low-gradient severe aortic stenosis and preserved EF, there is a graded inverse relation between SVI and the risk of long-term mortality. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. To determine the long-term association of brachial artery flow-mediated dilation (FMD) and adverse cardiovascular (CV) events in healthy subjects, we prospectively assessed brachial FMD in 618 consecutive healthy subjects with no apparent heart disease, 387 men (63%), and mean age 54 ± 11 years. After overnight fasting and discontinuation of all medications for ≥12 hours, FMD was assessed using high-resolution linear array ultrasound. Subjects were divided into 2 groups: FMD ≤11.3% (n = 309) and >11.3% (n = 309), where 11.3% is the median FMD, and were comparable regarding CV risk factors, lipoproteins, fasting glucose, C-reactive protein, concomitant medications, and Framingham 10-year risk score. In a mean clinical follow-up of 4.6 ± 1.8 years, the composite CV events (all-cause mortality, nonfatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting, and percutaneous coronary interventions) were significantly more common in subjects with FMD £11.3% rather than >11.3% (15.2% vs 1.2%, p = 0.0001, respectively). Univariate analysis demonstrated that the median FMD significantly predicted CV events (odds ratio 2.78, 95% CI 1.35 to 5.71, p <0.001). Multivariate analysis, controlling for traditional CV risk factors, demonstrated that median FMD was the best independent predictor of long-term CV adverse events (odds ratio 2.93, 95% CI 1.28 to 6.68, p <0.001). In conclusion, brachial artery median FMD independently predicts long-term adverse CV events in healthy subjects with no apparent heart disease in addition to those derived from traditional risk factor assessment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more oftein diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

One thousand fifty-one consecutive patients who had acute myocardial infarction were classified into 3 risk groups by 4 echocardiographic risk assessments: left ventricular ejection fraction, left ventricular filling pattern, estimated systolic pulmonary artery pressure, and mitral regurgitation, with 30-day mortality rates of 13.7%, 3.8%, and 1%, respectively (p &#60;0.001). Independent echocardiographic and clinical predictors of 30-day mortality included age (10 years, hazard ratio [HR] 1.30, 95% confidence interval [CI] 0.91 to 1.89), female gender (HR 2.12, 95% CI 0.94 to 4.74), Killip’s class ≥II on admission (HR 3.09, 95% CI 1.38 to 7.11), group 2 (moderate) risk (HR 2.89, 95% CI 1.07 to 8.56), and group 1 (high) risk (HR 8.16, 95% CI 2.95 to 25.23). [Copyright &y& Elsevier]

Among 90 consecutive patients with various degrees of left ventricular (LV) dysfunction (normal patients, LV hypertrophy, LV ejection fraction <50%, and <30%), the mitral valve pulse-wave E/A ratio showed a characteristic U-shaped curve with increasing severity of LV dysfunction. In contrast, there was a significant progressive decrease in flow propagation velocity of the E-wave (Vp) and a significant increase in E/Vp values with increasing severity of LV dysfunction. The E/Vp ratio was the best predictor of pulmonary congestion, and in a subgroup of patients who underwent cardiac catheterization, it was the only significant predictor of LV end-diastolic pressure. [Copyright &y& Elsevier]

There is limited organized "real life" data regarding the long-term structural and functional durability of transcatheter aortic valve implants, a topic of major importance. We assessed the 5-year structural and functional integrity outcomes following trans-catheter aortic valve implantation (TAVI) with both self-expandable and balloon-expandable prosthetic valve devices. This study included 450 consecutive patients who underwent TAVI for severe symptomatic aortic stenosis (AS) between September 2008 and December 2011. Data were acquired from a multicenter Israeli registry and the median follow up time was 5.6 years. In 184 patients (40.9%) who survived 5 years, prostheses displayed sustained hemodynamic performance, with average peak and mean aortic valve gradients of 16.2 ± 8.9 and 9.2 ± 6.6 mm Hg, respectively. Late structural valve deterioration was found in 22 (12.3%) patients. Of these, 16 (8.9%) experienced valve deterioration and 6 (3.3%) experienced valve failure. Among the 6 patients with bioprosthetic valve failure, only 3 underwent re-interventions. Bioprosthetic valve dysfunction occurred more frequently in patients with small valves (23 mm) and high peak and mean transvalvular gradients at baseline. In conclusion, a relatively low rate of valve deterioration or failure was noted in our long-term follow-up study after TAVI procedures with both the catheter-based self-expandable and balloon-expandable prosthetic valves., (Copyright © 2019 Elsevier Inc. All rights reserved.)