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Background: Aortic valve replacement, particularly in elderly patients with small aortic annulus, could lead to patient-prosthesis mismatch. Sutureless bioprosthesis could be an ideal solution for these patients. We compared results of aortic valve replacement with sutureless versus stented bioprosthetic valves., Methods: Of the 63 patients undergoing aortic valve replacement with sutureless bioprosthesis between 2011 and 2014 in our department, 22 (20 women, 77 ± 6 years) had a small annulus less than 21 mm (sutureless group). They were matched for sex, age, body surface area, and left ventricular ejection fraction with 22 patients (20 women, 79 ± 6 years) undergoing stented bioprosthesis valve replacement (stented group). Body mass index and body surface area were 28 ± 5 kg/m(2) and 28 ± 3 kg/m(2) (p = 0.9), 1.6 ± 0.2 m(2) and 1.6 ± 0.1 m(2) (p = 0.9), in the sutureless and stented groups, respectively. Logistic EuroSCOREs were similar between groups., Results: Postoperative peak transvalvular gradient was lower in the sutureless group (15 ± 7 mm Hg versus 20 ± 11 mm Hg; p = 0.02). The indexed effective orifice area was greater in the sutureless group (1.12 ± 0.2 cm(2)/m(2) versus 0.82 ± 0.1 cm(2)/m(2); p < 0.05). Aortic cross-clamp and cardiopulmonary bypass times were 47 ± 21 and 67 ± 15 minutes, respectively (p < 0.05) in the sutureless group versus 70 ± 22 and 85 ± 21 minutes, respectively (p = 0.02) in the stented group. Intensive care unit stay, hospitalization, and major complications were not significantly different between groups. At follow-up, regression of left ventricular hypertrophy was better in the sutureless group (93 ± 21 g/m(2) versus 106 ± 14 g/m(2); p = 0.02)., Conclusions: Sutureless bioprosthetic valves demonstrate improved hemodynamic performance compared with stented valves in elderly patients with small aortic annulus, providing better regression of left ventricular hypertrophy and decreased rates of patient-prosthesis mismatch. Aortic cross-clamp and cardiopulmonary bypass times are also decreased., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Inflammation has been implicated in the initiation, progression and manifestation of hypertensive heart disease. We sought to determine the role of monocytes/macrophages in hypertension and pressure overload induced left ventricular (LV) remodeling., Methods and Results: We used two models of LV hypertrophy (LVH). First, to induce hypertension and LVH, we fed Sabra salt-sensitive rats with a high-salt diet. The number of macrophages increased in the hypertensive hearts, peaking at 10 weeks after a high-salt diet. Surprisingly, macrophage depletion, by IV clodronate (CL) liposomes, inhibited the development of hypertension. Moreover, macrophage depletion reduced LVH by 17% (p<0.05), and reduced cardiac fibrosis by 75%, compared with controls (p=0.001). Second, to determine the role of macrophages in the development and progression of LVH, independent of high-salt diet, we depleted macrophages in mice subjected to transverse aortic constriction and pressure overload. Significantly, macrophage depletion, for 3 weeks, attenuated LVH: a 12% decrease in diastolic and 20% in systolic wall thickness (p<0.05), and a 13% in LV mass (p=0.04), compared with controls. Additionally, macrophage depletion reduced cardiac fibrosis by 80% (p=0.006). Finally, macrophage depletion down-regulated the expression of genes associated with cardiac remodeling and fibrosis: transforming growth factor beta-1 (by 80%) collagen type III alpha-1 (by 71%) and atrial natriuretic factor (by 86%)., Conclusions: Macrophages mediate the development of hypertension, LVH, adverse cardiac remodeling, and fibrosis. Macrophages, therefore, should be considered as a therapeutic target to reduce the adverse consequences of hypertensive heart disease., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Familial restrictive cardiomyopathy (RCM) caused by a single gene mutation is the least common of the inherited cardiomyopathies. Only a few RCM-causing mutations have been described. Most mutations causing RCM are located in sarcomere protein genes which also cause hypertrophic cardiomyopathy (HCM). Other genes associated with RCM include the desmin and familial amyloidosis genes. In the present study we describe familial RCM with severe heart failure triggered by a de novo mutation in TTN, encoding the huge muscle filament protein titin., Methods and Results: Family members underwent physical examination, ECG and Doppler echocardiogram studies. The family comprised 6 affected individuals aged 12-35 years. Linkage to candidate loci was performed, followed by gene sequencing. Candidate loci/gene analysis excluded 18 candidate genes but showed segregation with a common haplotype surrounding the TTN locus. Sequence analysis identified a de novo mutation within exon 266 of the TTN gene, resulting in the replacement of tyrosine by cysteine. p.Y7621C affects a highly conserved region in the protein within a fibronectin-3 domain, belonging to the A/I junction region of titin. No other disease-causing mutation was identified in cardiomyopathy genes by whole exome sequencing., Conclusions: Our study shows, for the first time, that mutations in TTN can cause restrictive cardiomyopathy. The giant filament titin is considered to be a determinant of a resting tension of the sarcomere and this report provides genetic evidence of its crucial role in diastolic function., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Adverse cardiovascular events (CVE) tend to peak during early morning post-waking hours. Our objective was to explore a possible correlation between early and late morning hours and flow-mediated dilation (FMD), and whether early morning FMD reduction contributes to a circadian pattern of cardiac and vascular vulnerability., Methods: Brachial FMD was prospectively assessed in 268 consecutive healthy subjects, 169 (63%) men, mean age 53 ± 11 years, without any concomitant medications. Following an overnight fast, FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high-resolution ultrasound. All subjects were followed up by phone every 6 months for combined CVE, which included all-cause mortality, myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions., Results: The cohort was divided into Group A with FMD performed immediately post-waking, between 6:00 and 10:00 am [n=151 (56%) subjects], and Group B after 10:00 am [n=117 (46%) subjects]. Although both groups were comparable regarding baseline brachial artery diameter and the prevalence of risk factors, FMD was significantly lower in Group A compared with Group B subjects (10.4 ± 3.4% vs. 13.5 ± 3.5%, p=0.007, respectively). In a mean follow-up of 45 ± 21 months, the composite CVEs were significantly more common in subjects with ≤(n=128) vs. >(n=140) the median FMD of 11.3% [18/128 (14.1%) vs. 1/140 (0.7%), p=0.007, respectively]. Furthermore, FMD independently predicted long-term adverse CVE., Conclusions: FMD is blunted in early compared to late morning post-waking hours, and independently predicts long-term adverse CVE in healthy subjects with no apparent heart disease., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: Untreated patients with congenital growth hormone deficiency (GHD) and IGF-I deficiency are characterized not only by dwarfism but also by acromicria and organomicria, such as the heart. We assessed cardiac dimensions and function in very young patients with Laron syndrome (LS) undergoing IGF-I replacement therapy., Design: Two to seven echocardiographic measurements were performed during IGF-I replacement therapy on male (n=4) and female (n=4) LS -patients, mean+/-SD age of 7.1+/-3.6 years (range 1.6-11.6 years), weight 16.1+/-9.7 kg, and height 89.9+/-18.5 cm. As aged- and gender-matched controls served 44 healthy children, age: 8.7+/-5.5 years, weight: 36.1+/-22.4 kg, and height: 129.7+/-33.1cm. Data of LS patients were normalized to body surface area and compared to the control group as well as nomograms of normal echocardiographic parameters for this age group., Results: Left ventricular diastolic and systolic dimensions (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls with IGF-I treated LS compared with controls while the shortening fraction (%) and intraventricular septum thickness (mm) were similar. When compared with standard values for this age group, all treated LS patients were within 1 standard deviation of the mean., Conclusion: IGF-I therapy of young patients with Laron syndrome maintain LV dimensions and function within the normal range of aged-matched controls.

Background: Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. The aim of this study was to detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects without apparent coronary artery disease (CAD)., Methods: We prospectively assessed brachial flow-mediated dilation (FMD) in 435 consecutive healthy subjects: 281 (65%) men, mean age 54+/-12 years and body mass index 28+/-4 kg/m(2). After overnight fasting and discontinuation of all medications for > or =12 h, FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high resolution linear array ultrasound., Results: Subjects were divided into 2 groups: below (n=221) and above (n=214) the median FMD of 10.7%, and were comparable regarding CAD risk factors, lipoproteins, fasting glucose, C-reactive protein, and concomitant medications, with a mean clinical follow-up of 32+/-2 months. Composite cardiovascular endpoints (all-cause mortality, non-fatal myocardial infarction, heart failure or angina pectoris hospitalization, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with below median FMD of 10.7%, than above (11.8% vs 4.7%, p=0.007, respectively). Univariate analysis demonstrated that median FMD significantly predicted cardiovascular events [odds ratio (OR) of 2.78 and 95% CI 1.35 to 5.71 (p=0.003)]. After multivariate analysis including conventional CAD risk factors, median FMD was the best independent predictor of long-term cardiovascular adverse events [OR of 2.70 and 95% CI 1.16 to 6.32 (p=0.011)]., Conclusions: Brachial artery median FMD independently predicts long-term adverse cardiovascular events in healthy subjects in addition to traditional risk factor assessment.

Background: Two distinct right coronary artery (RCA) morphologies have been previously described: sigma- and C-shaped RCAs. While the C-shaped RCA was significantly associated with atherosclerosis, the sigma-shaped was not. The association of RCA morphology and vascular endothelial function has not yet been assessed., Methods: To evaluate the association between the RCA's morphology and flow-mediated endothelium-dependent dilation (FMD) in patients without evidence of atherosclerotic lesions, we prospectively assessed FMD in 49 consecutive patients with non-specific chest pain, who were referred to our laboratory 30+/-10 days after corroboration of normal coronary arteries on coronary angiography. Endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin-mediated vasodilation (NTG) were assessed using high resolution (15 MHz) linear array ultrasound. The patients were divided into 2 groups according to their RCA morphology on coronary angiograms (sigma and C) which were analyzed by 2 independent readers who were blinded to the patients' FMD results., Results: The C-shaped group exhibited a significantly lower FMD compared to the sigma-shaped group (9.0+/-4.2% vs. 14.3+/-4.7%, p<0.04, respectively), while NTG was the same in both groups. There were no significant group differences in other variables., Conclusions: Endothelium-dependent FMD in the brachial artery is significantly greater in sigma- compared to C-shaped RCA in coronary arteries without overt atherosclerotic lesions, suggesting a potential mechanism whereby C-shaped RCA are predisposed to atherosclerosis.

Objectives: To describe the incidence of atrial fibrillation induced by dobutamine stress echocardiography and characterize patients at risk of developing atrial fibrillation, by constructing a simple validated risk score index., Design: An observational study using prospectively collected data., Methods: 3800 consecutive patients in sinus rhythm undergoing dobutamine stress echocardiography were randomly divided to a case (2/3) and test group (1/3). Associations of predetermined demographic, clinical, electrocardiographic and echocardiographic variables were calculated in patients with and without atrial fibrillation induced by dobutamine stress echocardiography in the case group. Logistic regression analysis determined significant independent risk predictors, a scoring index was constructed and validated on the test group., Results: There was a 2% incidence of dobutamine stress echocardiography-induced atrial fibrillation in the study population. Risk predictors of atrial fibrillation included: a history of atrial fibrillation (2 points), increased left atrial diameter, right bundle branch block, decreased rest heart rate and hypertension (1 point each). The case subgroup low-risk patients (score 0-2) had a 1% risk, moderate-risk patients (score 3) a 2.7% and high-risk patients (score 4-6) a 14.5% risk of developing atrial fibrillation during dobutamine stress echocardiography. The rates in the test subgroup were 1%, 3.8% and 15.3%, respectively., Conclusion: Atrial fibrillation during dobutamine stress echocardiography is not common, the risk of developing atrial fibrillation during dobutamine stress echocardiography can be predicted by using a simple risk score system comprised of clinical, electrocardiographic and rest echocardiographic variables, which may be of help when planning a dobutamine stress echocardiography test in selected cases.

Background: Freeze-tolerant fish survive sub-zero temperatures by non-colligatively lowering the freezing temperature of their body fluids using anti-freeze proteins (AFPs). We sought to evaluate and compare the effects of prolonged sub-zero cryopreservation of transplanted rat hearts using AFP I or AFP III., Methods: Two heterotopic rat heart transplantation protocols were used. In Protocol 1 (n = 104), hearts (n = 8/group) were preserved for 12, 18 and 24 hours in University of Wisconsin solution (UW) at 4 degrees C, UW at -1.3 degrees C, UW/AFP I at -1.3 degrees C and UW/AFP III at -1.3 degrees C, with and without nucleation. Post-operative evaluation consisted of visual viability scoring of the hearts after 60 minutes. Protocol 2 (n = 58) involved evaluation of 24-hour post-transplant viability, echocardiography (fractional shortening [FS], left ventricular end-systolic and -diastolic diameter [ESD, EDD] and anterior and posterior wall systolic and diastolic thickness [AWT-S, AWT-D, PWT-S, PWT-D]), TUNEL staining and electron microscopy (EM) findings for hearts preserved for 18, 21 and 24 hours in UW at 4 degrees C or UW/AFP III at -1.3 degrees C., Results: Hearts preserved in UW at -1.3 degrees C with nucleation froze and died. Three of 8 hearts preserved in UW at 4 degrees C for 24 hours died, whereas all hearts preserved at -1.3 degrees C survived. Hearts preserved in UW/AFP for 18 and 24 hours at -1.3 degrees C had superior viability scores compared with those in UW at 4 degrees C. Hearts in AFP III at -1.3 degrees C displayed greater AWT-S and AWT-D (3.5 +/- 0.2 vs 2.4 +/- 0.2, p < 0.05, and 3.5 +/- 0.2 vs 2.2 +/- 0.2, p < 0.05, respectively) after 18-hour preservation. In the 21-hour preservation group, AFP-treated hearts displayed improved echocardiographic systolic contraction indices, including: improved FS (27 +/- 3.7 vs 15 +/- 4, p = 0.04); diminished ESD (0.28 +/- 0.57 vs 0.47 +/- 0.6, p < 0.05); greater AWT-S (3.4 +/- 0.18 vs 2.8 +/- 0.2, p < 0.05); and fewer positively TUNEL-stained nuclei per specimen (35 +/- 14 vs 5.3 +/- 2.7, p = 0.04). Also, improved EM scores were noted compared with UW at 4 degrees C., Conclusions: In prolonged sub-zero cryopreservation, AFPs protect the heart from freezing, improve survival and hemodynamics, and reduce apoptotic cell death.

Background: Protruding aortic arch thrombus is associated clinically with life-threatening emboli. Definitive treatment for aortic arch thrombus removal has demanded complicated vascular surgical procedures, with high morbidity and mortality., Methods and Results: Transesophageal echocardiography (TEE) enabled diagnosis of a protruding thrombus at the aortic arch in 5 patients, and a simultaneous lesion in the descending aorta in 1 patient. Four patients had visceral emboli, coinciding with peripheral emboli in 2 patients, and the fifth patient had peripheral and cerebral emboli. One patient had had ischemic stroke and femoral emboli a few months previously. Mean patient age was 51 years. None had clinical evidence of coronary or peripheral atherosclerotic occlusive disease. Risk factors included hypertension (n = 2), smoking (n = 4), and preexisting thrombophilia (n = 4). Five patients underwent TEE-guided aortic balloon thrombectomy from the arch with a 34-mm occluding balloon catheter. One patient also underwent balloon thrombectomy from the descending aorta with a 14F Foley catheter. Access into the aorta was obtained through the iliac artery (n = 4) during laparotomy because of visceral ischemia or through the transfemoral approach (n = 2). Previous procedures included superior mesenteric embolectomy (n = 3), segmental bowel resection (n = 1), splenectomy (n = 1), and peripheral arterial embolectomy n = 3). Real-time intraoperative TEE enabled visualization of the protruding thrombus and assisted with maneuvering of the balloon catheter. At completion peripheral thrombectomy thrombus material was retrieved in 4 patients. Postoperatively there were no clinically proved new procedure-related visceral emboli, and all patients received anticoagulant therapy thereafter. Follow-up TEE within 2 weeks and up to 7 years revealed no recurrent aortic arch thrombus., Conclusions: TEE-guided aortic balloon thrombectomy used in 6 procedures was effectively completed without visceral or peripheral ischemic complications. It enabled removal of the life-threatening source of emboli from the proximal aorta, thereby averting the need of major aortic surgery.

Study Objectives: Assessment of global myocardial performance by a single index (ie, the myocardial performance index [MPI]) has been suggested as an appealing alternative to the individual assessment of systolic and diastolic left ventricular (LV) function We sought to test the prognostic value of MPI in comparison to clinical characteristics and echocardiographic parameters of LV filling and ejection in acute myocardial infarction (AMI)., Patients: Four hundred seventeen consecutive patients with AMI were examined within 24 h of hospital admission., Interventions: Doppler echocardiographic measures of systolic, diastolic, and global myocardial performance were assessed within 24 h of hospital admission. In addition to MPI (ie, the sum of the isovolumic time intervals divided by ejection time), we determined the isovolumic/heterovolumic time ratio, which expresses the time "wasted" by the myocardium to generate and decrease LV pressure without moving blood., Results: The end points of the study at 30 days were death (4.7%), congestive heart failure (23%), and recurrent infarction (4.8%), and occurred in 109 patients, who were compared as group B to 314 patients without an event (group A). Multivariate analysis identified only age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.07), LV ejection fraction (LVEF) < or = 40% (OR, 3.82; 95% CI, 2.15 to 6.87), and E-wave deceleration time (EDT) of < or = 130 ms (OR, 2.29; 95% CI, 1.0 to 5.21) as independent predictors of adverse events., Conclusion: LVEF and EDT are powerful and independent echocardiographic predictors of poor outcome following AMI, and are superior to indexes of global LV performance. Both parameters should be taken into consideration when deciding about the management of these patients.

Background: Evidence linking cardiovascular risk factors to aortic valve sclerosis (AVS) has led to the assumption that the latter is an atherosclerosis-like process. However, triglyceride (TG)-rich lipoproteins, an important risk factor for atherosclerosis, have been rarely investigated in connection with AVS., Methods: A cross-sectional study of 246 healthy individuals (mean age 59+/-6 years, 77% men) was conducted. Subjects underwent an echocardiographic assessment and extensive blood lipid measurements, including evaluation of TG-related indices, such as serum apolipoprotein (apo) C(II) and C(III) levels, apo C(III) levels in VLDL+LDL particles, and apo C(III) ratio (C(III) level in HDL/C(III) level in VLDL+LDL)., Results: Twenty-three patients (9.3%) were diagnosed as having AVS. On average, these patients were 5 years older and had higher levels of serum cholesterol, LDL-C and LP(a), compared with non-AVS subjects. In addition, the AVS patients exhibited higher concentrations of serum apo C(II), serum apo C(III) and apo C(III) in VLDL+LDL, and a lower apo C(III) ratio. Adjusting for age and gender, a 1 S.D. increment in apo C(III) in VLDL+LDL was associated with odds ratio (OR) of 1.76 (95% CI: 1.17-2.65) for AVS. Further adjustment for atherosclerotic risk factors did not alter the association appreciably (OR=1.65, 95% CI: 1.06-2.58)., Conclusion: TG-rich lipoproteins may be involved in the early development of AVS. Confirmation in prospective studies is required.