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During the period of 1986–1997 the first 4 publications on the mechanical and metabolic properties of heat acclimated rat's heart were published. The outcome of these studies implied that heat acclimation, sedentary as well as combined with exercise training, confers long lasting protection against ischemic/reperfusion insult. These results promoted a clinical study on patients with coronary artery disease scheduled for elective coronary artery bypass operations aiming to elucidate whether exploitation of environmental stress can be translated into human benefits by improving physiological recovery. During the 1998 study, immediate-post operative chamber stiffness was assessed in patients acclimatized to heat and low intensity training in the desert (spring in the Dead Sea, 17–33°C) vs. patients in colder weather (spring in non-desert areas, 6–19°C) via echocardiogram acquisition simultaneous with left atrial pressure measurement during fast intravascular fluid bolus administration. We showed that patients undergoing “heat acclimatization combined with exercise training” were less susceptible to ischemic injury, therefore expressing less diastolic dysfunction after cardiopulmonary bypass compared to non-acclimatized patients. This was the first clinical translational study on cardiac patients, while exploiting environmental harsh conditions for human benefits. The original experimental data are described and discussed in view of the past as well as the present knowledge of the protective mechanisms induced by Heat Acclimation Mediated Cross-tolerance.

Background Congestive heart failure (CHF) is a significant health care burden in developed countries. However, the molecular events leading from cardiac hypertrophy to CHF are unclear and preventive therapeutic approaches are limited. We have previously described that microphthalmia-associated transcription factor (MITF) is a key regulator of cardiac hypertrophy, but its cardiac targets are still uncharacterized. Methods and results Gene array analysis of hearts from MITF-mutated mice indicated that ErbB2 interacting protein (Erbin) is a candidate target gene for MITF. We have recently demonstrated that Erbin is decreased in human heart failure and plays a role as a negative modulator of pathological cardiac hypertrophy. Here we show that Erbin expression is regulated by MITF. Under basal conditions MITF activates Erbin expression by direct binding to its promoter. However, under β-adrenergic stimulation Erbin expression is decreased only in wild type mice, but not in MITF-mutated mice. Yeast two-hybrid screening, using MITF as bait, identified an interaction with the cardiac-predominant four-and-a-half LIM domain protein 2 (FHL2), which was confirmed by co-immunoprecipitation in both mouse and human hearts. Upon β-adrenergic stimulation, FHL2 and MITF bind Erbin promoter as a complex and repress MITF-directed Erbin expression. Overexpression of FHL2 alone had no effect on Erbin expression, but in the presence of MITF, Erbin expression was decreased. FHL2–MITF association was also increased in biopsies of heart failure patients. Conclusion MITF unexpectedly regulates both the activation and the repression of Erbin expression. This ligand mediated fine tuning of its gene expression could be an important mechanism in the process of cardiac hypertrophy and heart failure.

The management of acute Stanford Type A intramural hematoma (IMH) of the aorta remains controversial. Most surgeons advocate emergency surgery in a manner similar to frank acute Type A dissection. Others recommend a conservative approach to this distinct clinicopathological entity. We describe a case of acute aortic pathology initially diagnosed as Type A IMH with organ malperfusion, subsequently identified as acute Type B pathology with retrograde and antegrade extension. An endovascular approach was successfully used to exclude the site of origin.

BACKGROUND In vitro studies suggested that circulating inflammatory cytokines cause septic myocardial dysfunction. However, no in vivo clinical study has investigated whether serum inflammatory cytokine concentrations correlate with septic myocardial dysfunction. METHODS Repeated echocardiograms and concurrent serum inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α, and monocyte chemoattractant protein-1) and cardiac biomarkers (high-sensitivity [hs] troponin-T and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) were examined in 105 patients with severe sepsis and septic shock. Cytokines and biomarkers were tested for correlations with systolic and diastolic dysfunction, sepsis severity, and mortality. RESULTS Systolic dysfunction defined as reduced left ventricular ejection fraction (LVEF) P = .006 and U tests). In contrast, NT-proBNP strongly correlated with both reduced LVEF and reduced e′-wave velocity, and hs-troponin-T correlated mainly with reduced e′-wave. CONCLUSIONS Unlike cardiac biomarkers, none of the measured inflammatory cytokines correlates with systolic or diastolic myocardial dysfunction in severe sepsis or septic shock.

Background Presenting systolic blood pressure (SBP) is a powerful predictor of mortality in many cardiovascular settings, including acute coronary syndromes, cardiogenic shock, and acute heart failure. Objectives This study evaluated the association of presenting SBP with in-hospital outcomes, specifically all-cause mortality, in acute aortic dissection (AAD). Methods The study included 6,238 consecutive patients (4,167 with type A and 2,071 with type B AAD) enrolled in the International Registry of Acute Aortic Dissection. Patients were stratified in 4 groups according to presenting SBP: SBP >150, SBP 101 to 150, SBP 81 to 100, or SBP ≤80 mm Hg. Results The relationship between presenting SBP and in-hospital mortality displayed a J-curve association, with significantly higher mortality rates in patients with very high SBP (26.3% for SBP >180 mm Hg in type A AAD, 13.3% for SBP >200 mm Hg in type B AAD; p = 0.005 and p = 0.018, respectively) as well as in those with SBP ≤100 mm Hg (29.9% in type A, 22.4% in type B; p = 0.033 and p = 0.015, respectively). This relationship was mainly from increased rates of in-hospital complications (acute renal failure, coma, and mesenteric ischemia/infarction in patients with SBP >150 mm Hg; stroke, coma, cardiac tamponade, myocardial ischemia/infarction, and acute renal failure in patients with SBP ≤80 mm Hg). Notably, presenting SBP ≤80 mm Hg was independently associated with in-hospital mortality in both type A (p = 0.001) and type B AAD (p = 0.003). Conclusions Presenting SBP showed a clear J-curve relationship with in-hospital mortality in patients with AAD. Although this association was related to increased rates of comorbid conditions at the edges of the curve, SBP ≤80 mm Hg was an independent correlate of in-hospital mortality.

BACKGROUND: Previous studies demonstrated that left atrium (LA) size is associated with mortality in an elderly population. It remains unclear whether indices of LA function including reservoir, conduit, or booster elements of LA function provide incremental prognostic information. HYPOTHESIS: Echocardiographic measures of the various parameters of LA function would predict 5‐year mortality in a community‐dwelling population of 85 to 86 year olds independently of LA volume. METHODS: Subjects ages 85 to 86 years old underwent home echocardiography. LA volumes were assessed by the biplane Simpson's method from apical views using measurements of phasic volumes and functions of the LA, including LA expansion index. LA passive and active emptying fractions were assessed. Survival status at 5‐year follow‐up was assessed. RESULTS: Two hundred eighty‐two subjects were included, of whom 87 (31%) had died at follow‐up. Survival of the subjects in the lowest quartile of the LA expansion index as well as LA active filling index was significantly lower. When measurements of LA volume index were added to the model, the relationship between survival and indices of LA function remained significant. CONCLUSIONS: This study demonstrated that elderly subjects aged 85 to 86 years with significantly impaired LA function had increased 5‐year mortality independently of indices of LA volume.

OBJECTIVES To evaluate the role mitral regurgitation (MR) etiology and severity play in outcomes for patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND Multiple prior studies have investigated the influence of MR severity on outcomes for patients undergoing TAVR. Less has been published regarding the effects of MR etiology on outcomes, including its impact on heart failure hospitalization. METHODS Two hundred and seventy patients undergoing TAVR at 2 hospitals were enrolled. Each patient had a baseline and follow-up (within 30 days of TAVR) echocardiogram that was analyzed. MR was graded as none, mild, moderate, or severe, as well as functional or degenerative. We compared patient outcomes, including death and heart failure hospitalization, among none-mild MR, moderate-severe functional MR, and moderate-severe degenerative MR groups. RESULTS Two hundred and seventy patients underwent TAVR, reducing mean aortic valve gradients from 45 ± 15 mm Hg to 9 ± 4 mm Hg. On multivariable analysis, only patients with moderate-severe degenerative MR had decreased survival free of death or CHF hospitalization compared to those with none-mild MR (P = .011). Subanalysis showed patients with moderate-severe degenerative MR were more likely to be hospitalized for heart failure at 2 years compared to those with moderate-severe functional MR (P = .02). Patients with moderate-severe degenerative MR were also less likely to have improvement in MR severity at follow up (P = .01). CONCLUSIONS Special consideration should be given to patients with moderate-severe degenerative MR undergoing TAVR. As transcatheter approaches for mitral valve repair and replacement continue to evolve, moderate-severe degenerative MR patients may benefit from consideration of double valve intervention.

Background and Objectives Using non-invasive, high-frequency ultrasonography (HF-u/s), we showed that low-level laser phototherapy (LLL) inhibits de-novo formation of abdominal aortic aneurysms (AAA) in apolipoprotein-E-deficient (Apo-E-/-) mice. The current study tests the effect of LLL on the progression of pre-induced AAA. Study Design/Material and Methods AAA was induced in Apo-E-/- mice (age16–20 weeks) by subcutaneous infusion of angiotensin-II using osmotic minipumps (1000 ng/kg/minutes, 4 weeks). HF-u/s (40 MHz, 0.01 mm resolution, Vevo-770, VisualSonics) was used to measure the maximum cross-sectional-diameter (MCD) of the suprarenal abdominal aorta, the anterior wall displacement (AWD), and radial wall velocity (RWV). The aortas of mice that developed >35% dilatation at 2 weeks over baseline were exposed retroperitoneally and treated with LLL (780 nm, 2.2 J/cm2, 9 minutes) or sham-operated. HF-u/s was repeated at 4 weeks, the mice sacrificed by perfusion fixation, and the aortas excised for histopathology. Results Of all mice with >35% MCD expansion of the suprarenal aorta at 2 weeks, 7(58%) of 12 non-treated, but only 1(7%) of 14 LLL, had increased MCD(> 1 SD) at 4 weeks (P

Background Epidemiological features of infective endocarditis have changed during the last decades because of increases in the prevalence of health care exposure and of Staphylococcus aureus bloodstream infection. Consequently, the role of surgery is evolving. We aim to provide a contemporary profile of epidemiological, microbiological, and clinical features of infective endocarditis in a tertiary medical center, and identify predictors of mortality. Methods A prospective observational cohort study of consecutive adult patients with definite endocarditis according to the modified Duke criteria. Data were collected from January 1, 2009 through October 31, 2011 following a predefined case report form designed by the ICE-PCS. Results Among 70 endocarditis episodes, 25.7% involved prosthetic valves and 11.5% were device related. Forty-four percent of episodes were health-care associated. The predominant causative microorganism on native valve, prosthetic valve and device related endocarditis was Staphylococcus aureus (33.3%). Viridans group streptococci accounted for the majority of community-acquired endocarditis (36.1%). At least one complication occurred in 50% of the episodes. One third of the patients who had an indication for surgery were operated upon. Six month case fatality ratio was 40%. Sixty-five percent of patients with a contraindication to surgery died, compared with 9% and 28.5% who were treated surgically and medically, respectively. In multivariable analysis, age was a predictor of mortality. Conclusion Compared with other series, we observed more health-care associated endocarditis, and a higher mortality. Nearly half of all deaths were in patients who had a contraindication to surgery. Careful evaluation of contraindications to surgery is warranted.

Infusion of angiotensin-II (Ang-II) in apolipoprotein-E-deficient mice (Apo-E(-/-)) results in suprarenal abdominal aortic aneurysm (AAA) in 30-85% of cases. This study identifies the apparent mechanism by which some animals do, but others do not, develop AAA in this model.Male Apo-E(-/-) mice were infused with Ang-II (n=21) or saline (n=6) and sacrificed at 4 weeks. Aortas were excised, embedded in paraffin, sectioned (250 μm intervals), and stained. Sites of transmedial disruption (TMD) were identified and characterized, and their relationship to the 4 major aortic side branches (celiac, superior mesenteric, and renals) were determined.The frequency of TMDs in Ang-II-infused mice that formed AAA (n=9) was similar to those that did not (n=12) (AAA vs. no-AAA: 25 of 36[69%] vs. 28 of 48[58%] branches, P=.3 by chi-square). All TMDs were at branch points. However, in animals with AAA, the mean maximum length of the TMDs was significantly larger (1.94±1.6 vs. 0.65±0.5mm, P=.007 by Mann Whitney U test), the #mac-2(+) macrophages per 0.01mm(2) of defect area was greater (32±10 vs. 19±11, P.02 by Kruskal-Wallis with Conover-Inman post hoc), the % area of attempted repair occupied by collagen was less (17±13% vs. 44±15%, P=.0009 by Mann Whitney U test), and the density of collagen per unit length of media missing was also markedly less (0.13±0.2 vs. 1.14±1.0, P=.0001 by Mann Whitney U test).Reinforcement of transmedial defects at branch points by wall matrix is a key intrinsic player in limiting AAA formation in the Ang-II-infused, Apo E(-/-) mouse and a potentially important mechanism-based therapeutic target for management of small, slowly progressing aneurysms.

ErbB2 interacting protein (Erbin) is a widely expressed protein and participates in inhibition of several intracellular signaling pathways. Its mRNA has been found to be present in relatively high levels in the heart. However, its physiological role in the heart has not been explored. In the present work, we elucidated the role of Erbin in cardiac hypertrophy. Cardiac hypertrophy was induced in mice either by isoproterenol administration or by aortic constriction. The level of Erbin was significantly decreased in both models. Erbin(-/-) mice rapidly develop decompensated cardiac hypertrophy, and following severe pressure overload all Erbin(-/-) mice died from heart failure. Down-regulation of Erbin expression was also observed in biopsies derived from human failing hearts. It is known that Erbin inhibits Ras-mediated activation of the extracellular signal-regulated kinase (ERK) by binding to Soc-2 suppressor of clear homolog (Shoc2). Our data clearly show that ERK phosphorylation is enhanced in the heart tissues of Erbin(-/-) mice. Furthermore, we clearly demonstrate here that Erbin associates with Shoc2 in both whole hearts and in cardiomyocytes, and that in the absence of Erbin, Raf is phosphorylated and binds Shoc2, resulting in ERK phosphorylation. In conclusion, Erbin is an inhibitor of pathological cardiac hypertrophy, and this inhibition is mediated, at least in part, by modulating ERK signaling.

Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis.Prospective, analytic cohort study.Tertiary academic institute.A cohort of ICU patients with severe sepsis or septic shock.Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock.Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e'-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and -2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s'-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e'-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e'-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively).Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

A new murmur of aortic insufficiency is a classic physical examination sign of acute aortic dissection (AAD); we sought to further describe AAD patients presenting with aortic insufficiency murmur without a prior history of aortic valve disease or repair. Patients enrolled from January 1996- June

Objective: Bicuspid aortic valve (BAV) is the most common congenital heart malformation (>1%). Patients with BAV are at risk to develop complications, some are life threatening. Previous studies ha...

Although degenerative aortic valve disease is common with increasing age, limited data exist regarding prevalence and prognosis of aortic valve disease among the oldest old. Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed at home in 498 randomly selected subjects. Subjects were divided into 3 groups; normal subjects, subjects with valve calcium but without stenosis (AVC), and subjects with aortic stenosis (AS). Survival status at 5-year follow-up was assessed via the centralized population registry. AVC was noted in 55% of the study subjects and AS was seen in 8.2%. There were no significant differences between the 3 groups in any of the clinical parameters examined including risk factors for atherosclerotic heart disease. Of the 498 subjects, 107 (21%) had died at the time of 5-year follow-up. Five-year mortality was similar among the normal (17%) and AVC (20%) subjects but was significantly higher among the subjects with AS (46%; p0.0001). AS was associated with a nearly fourfold increased likelihood of mortality (hazard ratio 3.7, 95% confidence interval 1.4 to 9.3). In conclusion, among subjects ≥85 years of age, the prevalence of AS is higher than previously reported and not associated with traditional vascular risk factors. AS but not AVC alone was independently predictive of 5-year mortality.

Objectives This study sought to investigate the blood pressure (BP) response after transcatheter aortic valve implantation (TAVI) and its correlation with short- and mid-term clinical outcomes. Background TAVI is an emerging therapy for aortic stenosis patients at high surgical risk. The acute hemodynamic sequelae of this procedure and their clinical relevance are yet unclear. Methods Consecutive patients who underwent TAVI in a single center were prospectively monitored for BP response during 5 post-procedural days. Clinical parameters, adverse events, and medical treatment were recorded during hospitalization, at 30 days, and at 12 months after the procedure. Patients were divided according to their post-procedural BP response into 2 groups: increased BP and stable BP. Results One hundred and five patients were analyzed. Overall, systolic BP increased immediately after TAVI in the entire cohort by an average of 15 ± 31 mm Hg. This rise was sustained and led to intensification of antihypertensive treatment in 53 patients (51%); these patients were designated as the increased BP group. The increase in systolic BP after TAVI was associated with an increase in stroke volume and cardiac output and was not related to age, baseline cardiac function, or procedural outcomes. Patients with increased BP after TAVI had a significantly better prognosis with fewer adverse events in the hospital (21% vs. 62%, p Conclusions After TAVI, a substantial number of patients have a significant rise in systolic BP necessitating long-term treatment. This increase in BP is associated with an increase in cardiac output and predicts a better clinical outcome.

Objective: Limited data are available regarding the incidence and clinical impact of renal dysfunction following cardioversion of atrial fibrillation. The objective of this study was to assess the incidence and implications of renal dysfunction following cardioversion of atrial fibrillation. Methods: We conducted a nested case-control study to determine the incidence, timing, risk factors and outcome of atrial fibrillation cardioversion associated with renal dysfunction (AFCARD) in a tertiary medical center. Consecutive patients undergoing direct current cardioversion (DCCV) for atrial fibrillation in our institution during 2008-2009 with measurements of creatinine before and following cardioversion were included. AFCARD was defined as a rise in serum creatinine greater than 25% from baseline within a week following DCCV. Results: One hundred and twelve patients were included in the study, of whom 19 (17%) developed AFCARD. One patient required hemodialysis. Patients with AFCARD had a higher incidence of advanced heart failure, diabetes mellitus and were more frequently treated with digoxin and enoxaparin. Patients with AFCARD had a significantly decreased survival rate at 1 year (63 vs. 92%; p < 0.001). Conclusions: AFCARD is relatively common and is associated with increased mortality. These findings suggest a role for close surveillance of renal function following DCCV.

Conduction disorders requiring permanent pacemaker (PPM) implantation are a known complication of transcatheter aortic valve implantation (TAVI). Indications for permanent pacing in this setting are still controversial. The study aim was to characterize the natural history of conduction disorders related to TAVI, and to identify predictors for long-term pacing dependency.Consecutive patients who underwent TAVI were included in this prospective observational study. The conduction system was investigated by reviewing 12-lead ECGs during hospitalization and up to 1-year follow-up and by analyzing pacemaker interrogation data. Multivariate analysis was performed in order to identify independent predictors for pacemaker dependency.Of 110 patients included in the analysis, 38 (34.5%) underwent PPM implantation. Of those, 26 (68.4%) had a long-term pacing dependency (required PPM), while 12 (31.6%) did not (not-required PPM). Logistic regression revealed that baseline RBBB (P = 0.01, OR = 18.0), baseline PR interval (P = 0.019, OR = 1.14), post-TAVI PR interval and the change in PR interval from baseline (P0.001 for both, OR = 1.17 for each 10 milliseconds increment) were independent predictors for long-term pacing dependency. A PR interval increment of greater than 28 milliseconds had the best accuracy in predicting pacemaker dependency.Increased pre- and postprocedural PR intervals and pre-existing RBBB are reliable predictors for long-term PPM dependency, while left bundle branch block or QRS width are misleading factors. Our study suggests that the decision for implanting PPM after TAVI should be based mostly on the prolongation of the PR interval.

Background Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .

Frailty is a biologic syndrome reflecting a state of decreased physiological reserve of increasing importance in cardiovascular disease given the aging of the population. The relation between frailty and indexes of cardiac structure and function remains unclear, particularly in the "oldest old." The objective of this study was to examine the association between cardiac function and frailty in an age-homogenous, community-dwelling population of subjects aged 85 and 86 years. Subjects were recruited at ages 85 to 86 from the Jerusalem Longitudinal Cohort Study that has followed an age-homogenous cohort of Jerusalem residents. Subjects underwent echocardiography at their place of residence with standard assessment of cardiac structure and function. Frailty was defined according to the "phenotype of frailty" including at least 3 of the following: weakness, slowness, low physical activity level, exhaustion, and weight loss; 405 subjects (193 men and 212 women) were enrolled in the study. Subjects defined as frail had significantly lower ejection fraction compared with the non-frail group (53.7 ± 0.09% vs 56.4 ± 0.09%; p

Aims Shock is among the most dreaded and common complications of type A acute aortic dissection (TAAAD). However, clinical correlates, management, and short- and long-term outcomes of TAAAD patients presenting with shock in real-world clinical practice are not known. Methods and Results We evaluated 2,704 patients with TAAAD enrolled in the International Registry of Acute Aortic Dissection between January 1, 1996, and August 18, 2012. On admission, 407 (15.1%) TAAAD patients presented with shock. Most in-hospital complications (coma, myocardial or mesenteric ischemia or infarction, and cardiac tamponade) were more frequent in shock patients. In-hospital mortality was significantly higher in TAAAD patients with than without shock (30.2% vs 23.9%, P =.007), regardless of surgical or medical treatment. Most shock patients underwent surgical repair, with medically managed patients demonstrating older age and more complications at presentation. Estimates using Kaplan-Meier survival analysis indicated that most (89%) TAAAD patients with shock discharged alive from the hospital survived 5years, a rate similar to that of TAAAD patients without shock (82%, P =.609). Conclusions Shock occurred in 1 of 7 TAAAD patients and was associated with higher rates of in-hospital adverse events and mortality. However, TAAAD survivors with or without shock showed similar long-term mortality. Successful early and aggressive management of shock in TAAAD patients has the potential for improving long-term survival in this patient population.

Background and Objectives Recent in vitro studies by our group indicated that low level laser irradiation (LLLI) modifies cellular processes essential to the progression of abdominal aortic aneurysm (AAA). Using high-frequency ultrasonography (HF-u/s) in the angiotensin-II (Ang-II)-infused, apolipoprotein-E-deficient (Apo-E−/−) mouse model of AAA, we found that LLLI markedly inhibited aneurysm formation and preserved arterial wall elasticity. We now report, using quantitative histopathology, the likely mechanism underlying the preventative effect of LLLI on aneurysm formation in this model. Study Design/Materials and Methods This study was performed on 32 Apo-E−/− mice of which 10 were Ang-II-infused and LLL-irradiated (780 nm, 2 J/cm2, 9-minutes), 12 were Ang-II-infused but not irradiated, and 10 were saline infused. The aortas were excised at 28d, sectioned at 250 µm intervals, and stained with H + E, Movat-pentachrome and picrosirius-red for histomorphometry, and immunostained with Mac-2 and α-actin for detection of macrophages and SMCs, respectively. Results Transmural disruptions of the aorta occurred with distinct predilection for branch orifices. In the LLLI-treated animals, the frequency of these disruptions was lower (#branches with break points: 17 of 40 vs. 32 of 48, P = 0.023 by Chi-squared), their size smaller (length [mm]: 0.48 ± 0.26 vs. 0.98 ± 1.42, P = 0.044 by ANOVA with FPLSD), and the number of Mac-2-positive macrophages in the intramural areas of these disruptions lower than in the non-treated control (#Macrophages/0.01 mm2 at break points: 11.6 ± 7.2 vs. 26.0 ± 15.7, P = 0.016 by Kruskal–Wallis). The average size of the medial SMCs was larger reflecting a heightened synthetic state (SMC size [µm2]: 463.9 ± 61.4 vs. 354.9 ± 71.7, P = 0.001 by ANOVA with FPLSD). Furthermore, at sites of transmural disruption, the %area occupied by collagen of the overall area of attempted repair (%Col/WO) was significantly greater in the LLLI-treated animals versus control (%Col/WO: 41 ± 13 vs. 32 ± 16, P = 0.009 by ANOVA with FPLSD). Conclusion Enhanced matrix reinforcement and modification of the inflammatory response at sites of transmural injury are prominent mechanisms by which LLLI reduces AAA progression in this model. Lasers Surg. Med. 44: 664–674, 2012. © 2012 Wiley Periodicals, Inc.

Improved understanding of changes in cardiac structure and function related to the aging process is critical to design strategies to reduce the high mortality and morbidity related to cardiovascular disease in the growing elderly population. Echocardiography, as a noninvasive, easily portable imaging technique not requiring radiation or contrast media is an ideal method of imaging the aging heart. Echocardiography has provided important insights into changes in cardiac structure and function occurring with aging. These changes include increased wall thickness and LV mass, increased myocardial fibrosis with resulting changes in diastolic and longitudinal systolic function and degenerative calcification of the left-sided valves. In addition, echocardiography has shown the prognostic importance of elevated LV mass, elevated LA volume and decreases in systolic function in the elderly as well as changes in cardiac structure associated with diseases in the elderly such as dementia and functional disability.

Individuals aged85 years are the world's most rapidly growing age group and have a high incidence of cardiovascular mortality. The objective of this study was to prospectively determine the prognosis of abnormal cardiac structure and function in an age-homogenous, community-dwelling population of subjects born in 1920 and 1921. Subjects were recruited from the Jerusalem Longitudinal Cohort Study. Echocardiography was performed with a portable echocardiograph at the subjects' places of residence. Standard echocardiographic assessment of cardiac structure and function was performed. Five-year mortality was assessed through a centralized government database. Five hundred two subjects (235 men, 267 women) were enrolled in the study, of whom 107 (21%) had died at the time of 5-year follow-up. Subjects who died had significantly higher left atrial volume indexes (42.3 ± 16.5 vs 36.6 ± 12.5 ml/m2, p0.01) and left ventricular mass indexes (133.1 ± 47.6 vs 119.8 ± 30.6 g/m2, p0.05). Ejection fractions were significantly lower in subjects who died (52.5 ± 11.5% vs 56.4 ± 9.4%, p0.003), but indexes of left ventricular diastolic function were not significantly different between the 2 groups (E/e' ratio 13.0 ± 5.3 vs 12.2 ± 4.9, p = 0.18). In conclusion, elevated left atrial volume index and left ventricular mass index and decreased LV systolic function predicted 5-year mortality in a community-dwelling population of subjects aged 85 years, even after correction for possible confounders. Left ventricular diastolic dysfunction did not predict 5-year mortality in this cohort.

Combined heat acclimation (AC) and exercise training (EX) enhance exercise performance in the heat while meeting thermoregulatory demands. We tested the hypothesis that different stress-specific adaptations evoked by each stressor individually trigger similar cardiac alterations, but when combined, overriding/trade-off interactions take place. We used echocardiography, isolated cardiomyocyte imaging and cDNA microarray techniques to assay in situ cardiac performance, excitation-contraction (EC) coupling features, and transcriptional programs associated with cardiac contractility. Rat groups studied were controls (sedentary 24°C); AC (sedentary, 34°C, 1 mo); normothermic EX (treadmill at 24°C, 1 mo); and heat-acclimated, exercise-trained (EXAC; treadmill at 34°C, 1 mo). Prolonged heat exposure decreased heart rate and contractile velocity and increased end ventricular diastolic diameter. Compared with controls, AC/EXAC cardiomyocytes demonstrated lower l-type Ca2+current ( ICaL) amplitude, higher Ca2+transient (Ca2+T), and a greater Ca2+T-to- ICaLratio; EX alone enhanced ICaLand Ca2+T, whereas aerobic training in general induced cardiac hypertrophy and action potential elongation in EX/EXAC animals. At the genomic level, the transcriptome profile indicated that the interaction between AC and EX yields an EXAC-specific molecular program. Genes affected by chronic heat were linked with the EC coupling cascade, whereas aerobic training upregulated genes involved with Ca2+turnover via an adrenergic/metabolic-driven positive inotropic response. In the EXAC cardiac phenotype, the impact of chronic heat overrides that of EX on EC coupling components and heart rate, whereas EX regulates cardiac morphometry. We suggest that concerted adjustments induced by AC and EX lead to enhanced metabolic and mechanical performance of the EXAC heart.

Aims Assessing the quality of wall motion (WM) on echocardiograms remains a challenge. Previously, we validated an automated application used by experienced echocardiographers for WM classification based on longitudinal two-dimensional (2D) strain. The aim of this study was to show that the use of this automatic application was independent of the user's experience. Methods and results We compared the WM classifications obtained by the application when used by 12 highly experienced readers (Exp-R) vs. 11 inexperienced readers (InExp-R). Both classifications were compared with expert consensus classifications using the standard visual method. Digitized clips of cardiac cycles from three apical views in 105 patients were used for these analyses. Reproducibility of both groups was high (overall intra-class correlation coefficient: InExp-R = 0.89, Exp-R = 0.83); the lowest was noted for hypokinetic segments (InExp-R = 0.79, Exp-R = 0.72). InExp-R scores were concordant with Exp-R mode scores in 88.8% of segments; they were overestimated in 5.8% and underestimated in 3.2%. The sensitivity, specificity, and accuracy of InExp-R vs. Exp-R for classifying segments as normal/abnormal were identical (87, 85, and 86%, respectively). Conclusion Classification of WM from apical views with an automatic application based on longitudinal 2D strain by InExp-R vs. Exp-R was similar to visual classification by Exp-R. This application may be useful for inexperienced echocardiographers/technicians and may serve as an automated ‘second opinion’ for experienced echocardiographers.

OBJECTIVES: To examine the association between cardiac function and activities of daily living (ADLs) in an age-homogenous, community-dwelling population born in 1920 and 1921. DESIGN: Cross-sectional analysis of a prospective cohort study. SETTING: Community-dwelling elderly population. PARTICIPANTS: Participants were recruited from the Jerusalem Longitudinal Cohort Study, which has followed an age-homogenous cohort of Jerusalem residents born in 1920 and 1921. Four hundred eighty-nine of the participants (228 male, 261 female) from the most recent set of data collection in 2005 and 2006 underwent echocardiography at their place of residence in addition to structured interviews and physical examination. MEASUREMENTS: A home-based comprehensive assessment was performed to assess health and functional status, including performance of ADLs. Dependence was defined as needing assistance with one or more basic ADLs. Standard echocardiographic assessment of cardiac structure and function, including ejection fraction (EF) and diastolic function as assessed using early diastolic mitral annular tissue velocity measurements obtained using tissue Doppler, was performed. RESULTS: Of the participants with limitation in at least one ADL, significantly more had low EF (

A transgenic mouse model for conditional induction of long-term hibernation via myocardium-specific expression of a VEGF-sequestering soluble receptor allowed the dissection of the hibernation process into an initiation and a maintenance phase. The hypoxic initiation phase was characterized by peak levels of K(ATP) channel and glucose transporter 1 (GLUT1) expression. Glibenclamide, an inhibitor of K(ATP) channels, blocked GLUT1 induction. In the maintenance phase, tissue hypoxia and GLUT1 expression were reduced. Thus, we employed a combined “-omics” approach to resolve this cardioprotective adaptation process. Unguided bioinformatics analysis on the transcriptomic, proteomic and metabolomic datasets confirmed that anaerobic glycolysis was affected and that the observed enzymatic changes in cardiac metabolism were directly linked to hypoxia-inducible factor (HIF)-1 activation. Although metabolite concentrations were kept relatively constant, the combination of the proteomic and transcriptomic dataset improved the statistical confidence of the pathway analysis by 2 orders of magnitude. Importantly, proteomics revealed a reduced phosphorylation state of myosin light chain 2 and cardiac troponin I within the contractile apparatus of hibernating hearts in the absence of changes in protein abundance. Our study demonstrates how combining different “-omics” datasets aids in the identification of key biological pathways: chronic hypoxia resulted in a pronounced adaptive response at the transcript and the protein level to keep metabolite levels steady. This preservation of metabolic homeostasis is likely to contribute to the long-term survival of the hibernating myocardium., Graphical Abstract Research Highlights ► The hibernation process was dissected into an initiation and a maintenance phase. ► Glibenclamide, an inhibitor of K(ATP) channels, blocked GLUT1 induction. ► The maintenance phase was characterized by attenuated tissue hypoxia. ► Phosphorylation of myosin light chain 2 and cardiac troponin I was reduced. ► Combining of proteomics and transcriptomics improved the bioinformatic pathway analysis.

Echocardiography is a well-accepted tool for the diagnosis and quantification of pericardial effusion (PEff). Given the increasing use of computed tomographic (CT) scanning, more PEffs are being initially diagnosed by computed tomography. No study has compared quantification of PEff by computed tomography and echocardiography. The objective of this study was to assess the accuracy of quantification of PEff by 2-dimensional echocardiography and computed tomography compared to the amount of pericardial fluid drained at pericardiocentesis. We retrospectively reviewed an institutional database to identify patients who underwent chest computed tomography and echocardiography before percutaneous pericardiocentesis with documentation of the amount of fluid withdrawn. Digital 2-dimensional echocardiographic and CT images were retrieved and quantification of PEff volume was performed by applying the formula for the volume of a prolate ellipse, π × 4/3 × maximal long-axis dimension/2 × maximal transverse dimension/2 × maximal anteroposterior dimension/2, to the pericardial sac and to the heart. Nineteen patients meeting study qualifications were entered into the study. The amount of PEff drained was 200 to 1,700 ml (mean 674 ± 340). Echocardiographically calculated pericardial effusion volume correlated relatively well with PEff volume (r = 0.73, p0.001, mean difference -41 ± 225 ml). There was only moderate correlation between CT volume quantification and actual volume drained (r = 0.4, p = 0.004, mean difference 158 ± 379 ml). In conclusion, echocardiography appears a more accurate imaging technique than computed tomography in quantitative assessment of nonloculated PEffs and should continue to be the primary imaging in these patients.

Haptides are a family of short peptides homologous to C-termini sequences of fibrinogen chains β and γ (haptides Cβ and preCγ, respectively) which were previously shown to penetrate and bind cells.This work investigates the systemic effect of the haptides with possible clinical implications.Intra-arterial monitoring in rats recorded the haptides' effects on systemic blood pressure. In parallel, their effect was also tested in vitro on isolated rat peritoneal mast cells and on human mast cells.Intra-arterial monitoring in rats showed that intravenous administration of low haptides concentrations (35-560 μg/kg rat) caused a shocklike behavior with transient decrease in the systolic and diastolic blood pressure by up to 55% (P .05) in a dose-dependent manner and a minor increase in their heart rate. Randomly scrambled sequences of the haptides had no such effect, suggesting a specific interaction with receptors. Intravenous administration of blockers to histamine receptors H1 and H2 before haptides administration attenuated this effect. Furthermore, in vitro incubation of human LAD2 mast cell line or isolated rat peritoneal mast cells with the haptides caused degranulation of the mast cells. We found that the haptides Cβ and preCγ activated mast cells causing histamine release, resulting in a steep decrease in blood pressure, comparable to anaphylactic shock.In treating vascular occlusive diseases, massive fibrinolysis is induced, and haptide-containing sequences are released. We suggest that treatment with histamine receptor blockers or with mast cell stabilizing agents in such pathological conditions may overcome this effect.

A 2002 International Registry of Acute Aortic Dissection (IRAD) analysis determined the sensitivities for computed tomography (CT), transesophageal echocardiography (TEE), and magnetic resonance imaging in the diagnosis of acute aortic dissection (AAD) to be 93%, 88%, and 100%, respectively, with CT

By high frequency ultrasound, we showed that low level laser photobiomodulation (PBM), used widely for pain and wound healing, prevents de novo formation and progression of pre-existing abdominal aortic aneurysm (AAA) in angiotensin-II(Ang-II)-infused apolipoprotein e-deficient mice. We also showed

Haptides are a family of 19–21-mer cell-binding and permeating peptides homologous to sequences in the C termini on both fibrinogen β- and γ-chain (Cβ and preCγ, respectively). The effect of the Haptides on the cardiovascular system was studied by different assays, including the activity of isolated perfused rat heart and blood vessels in the organ bath. Haptides (50–80 µg/ml) decreased the hemodynamic functions of perfused rat hearts by up to 60% (p < 0.05) in a dose-dependent manner. Whole fibrinogen or a control nonrelated peptide (Cα) did not show such an effect. The NO donor, sodium nitroprusside, reversed the inhibitory effects of Haptides. L-NAME, an endothelial nitric oxide synthase (eNOS) inhibitor, did not further augment the effect of the Haptides. Perfused FITCHaptides were attached to the coronary endothelium. In myocardial homogenates and HUVEC, Haptides significantly decreased eNOS activity, but had no effect on the contraction of isolated cultured adult cardiomyocytes. Haptides also significantly enhanced the contraction of rings of rat aorta and human mammary artery vessels ex vivo only when the endothelium was intact. Haptides seem to affect the coronary endothelium, but not the cardiomyocytes, by inhibiting eNOS activity, causing vasoconstriction, temporary ischemia and impaired myocardial function that seem to be related to the amino acid composition of the Haptides.

Aims Increased early detection of abdominal aortic aneurysm (AAA) and the severe complications of its current treatment have emphasized the need for alternative therapeutic strategies that target pathogenetic mechanisms of progression and rupture. Recent in vitro studies from our laboratory have shown that low-level laser irradiation (LLLI) (780 nm) modifies cellular processes fundamental to aneurysm progression. The present study was designed to determine whether LLLI retards the progression of suprarenal AAA in vivo . Methods and results High-frequency ultrasonography (0.01 mm resolution) was used to quantify the effect of LLLI on aneurysmatic aortic dilatation from baseline to 4 weeks after subcutaneous infusion of angiotensin II by osmotic minipumps in the apolipoprotein E-deficient mouse. At 4 weeks, seven of 15 non-irradiated, but none of the 13 LLLI, mice had aneurysmal dilatation in the suprarenal aneurysm-prone segments that had progressed to ≥50% increase in maximal cross-sectional diameter (CSD) over baseline ( P = 0.005 by Fisher's exact test). The mean CSD of the suprarenal segments (normalized individually to inter-renal control segments) was also significantly lower in irradiated animals (LLLI vs. non-irradiated: 1.32 ± 0.14 vs. 1.82 ± 0.39, P = 0.0002 by unpaired, two-tailed t -test) with a 94% reduction in CSD at 4 weeks compared with baseline. M-mode ultrasound data showed that reduced radial wall velocity seen in non-treated was significantly attenuated in the LLLI mice, suggesting a substantial effect on arterial wall elasticity. Conclusion These in vivo studies, together with previous in vitro studies from this laboratory, appear to provide strong evidence in support of a role for LLLI in the attenuation of aneurysm progression. Further studies in large animals would appear to be the next step towards testing the applicability of this technology to the human interventional setting.

Octogenarian Israeli prime-minister Ariel Sharon recently sustained a mild, reversible stroke. A patent foramen ovale (PFO) was detected and anticoagulants were given pending PFO closure. A few days later, he sustained major intracerebral hemorrhage and has since remained in vegetative state. The events triggered serious criticism in the mass media, experts promoting one management option over others. Because knowledge of outcome and hindsight bias evaluation of appropriateness of care, we sought to systematically review the clinical case.We performed a formal decision analysis to identify the preferred management between anticoagulation, antiplatelets, PFO closure, or no treatment. Using the best evidence available, we built a decision tree.recurrent stroke and treatment complications within 1 year.Optimal decision was found to be critically sensitive to assumptions about etiology, efficacy and safety of treatments, recurrence risk, and to small changes in utilities. In multiway sensitivity analysis, when the risk of recurrent stroke was0.12 per year, no treatment was the best management. PFO closure is dominant only when the risk of recurrent stroke is0.12 per year closure effectiveness is assumed to be0.28. When closure effectiveness is0.6, it is inferior to anticoagulation and antiplatelet management.Uncertainties precluded a clear-cut answer and choice was found to be a "toss-up," often associated with much controversy. Use of novel therapies, such as PFO closure, outside clinical trials will not reduce uncertainty about efficacy.

A key energy-saving adaptation to chronic hypoxia that enables cardiomyocytes to withstand severe ischemic insults is hibernation, i.e., a reversible arrest of contractile function. Whereas hibernating cardiomyocytes represent the critical reserve of dysfunctional cells that can be potentially rescued, a lack of a suitable animal model has hampered insights on this medically important condition. We developed a transgenic mouse system for conditional induction of long-term hibernation and a system to rescue hibernating cardiomyocytes at will. Via myocardium-specific induction (and, in turn, deinduction) of a VEGF-sequestering soluble receptor, we show that VEGF is indispensable for adjusting the coronary vasculature to match increased oxygen consumption and exploit this finding to generate a hypoperfused heart. Importantly, ensuing ischemia is tunable to a level at which large cohorts of cardiomyocytes are driven to enter a hibernation mode, without cardiac cell death. Relieving the VEGF blockade even months later resulted in rapid revascularization and full recovery of contractile function. Furthermore, we show that left ventricular remodeling associated with hibernation is also fully reversible. The unique opportunity to uncouple hibernation from other ischemic heart phenotypes (e.g., infarction) was used to determine the genetic program of hibernation; uncovering hypoxia-inducible factor target genes associated with metabolic adjustments and induced expression of several cardioprotective genes. Autophagy, specifically self-digestion of mitochondria, was identified as a key prosurvival mechanism in hibernating cardiomyocytes. This system may lend itself for examining the potential utility of treatments to rescue dysfunctional cardiomyocytes and reverse maladaptive remodeling.

Objectives We examined whether mitral regurgitation (MR) augments post-myocardial infarction (MI) remodeling. Background MR doubles mortality after MI, but its additive contribution to left ventricular (LV) remodeling is debated and has not been addressed in a controlled fashion. Methods Apical MIs were created in 12 sheep, and 6 had an LV-to-left atrial shunt implanted, consistently producing regurgitant fractions of ∼30%. The groups were compared at baseline, 1, and 3 months. Results Left ventricular end-systolic volume progressively increased by 190% with MR versus 90% without MR (p Conclusions In this controlled model, moderate MR worsens post-MI remodeling, with reduced contractility. Pro-hypertrophic pathways are initially upregulated but subsequently fall below infarct-only levels and baseline; with sustained caspase 3 elevation, transformation to a failure phenotype occurs. Extracellular matrix turnover increases in MR animals. Therefore, MR can precipitate an earlier onset of dilated heart failure.

Background Acute type A aortic dissection (AAD) remains a highly lethal entity for which emergent surgical correction is standard care. Prior studies have identified specific clinical findings as being predictive of outcome. The prognostic significance of specific findings on imaging studies is less well described. We sought to identify the prognostic value of transesophageal echocardiography (TEE) in medically and surgically treated patients with AAD. Methods We studied 522 AAD patients enrolled over 6 years in the International Registry of Acute Aortic Dissection who underwent TEE. Multivariate analysis identified independent associations of inhospital mortality, first using clinical variables (model 1), after which TEE data were added to build a final model (model 2). Results Inhospital mortality was 28.7%. Transesophageal echocardiographic evidences of pericardial effusion ( P = .04), tamponade ( P P = .02), and patent false lumen ( P = .08) were more frequent in nonsurvivors. Dilated ascending aorta ( P = .03), dissection localized to the ascending aorta ( P = .02), and thrombosed false lumen ( P = .08) were less common in nonsurvivors. Model 1 identified age ≥70 years, any pulse deficit, renal failure, and hypotension/shock as independent predictors of death. Model 2 identified dissection flap confined to ascending aorta (odds ratio 0.2, 95% CI 0.1-0.6) and complete thrombosis of false lumen (odds ratio 0.15, 95% CI 0.03-0.86) as protective. In the medically treated group, mortality was 31% for subjects with a partially or completely thrombosed false lumen versus 66% in the presence of a patent false lumen. Conclusions Transesophageal echocardiography provides prognostic information in AAD beyond that provided by clinical risk variables.

In vitro studies suggested that circulating inflammatory cytokines cause septic myocardial dysfunction. However, no in vivo clinical study has investigated whether serum inflammatory cytokine concentrations correlate with septic myocardial dysfunction.Repeated echocardiograms and concurrent serum inflammatory cytokines (IL-1β, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α, and monocyte chemoattractant protein-1) and cardiac biomarkers (high-sensitivity [hs] troponin-T and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) were examined in 105 patients with severe sepsis and septic shock. Cytokines and biomarkers were tested for correlations with systolic and diastolic dysfunction, sepsis severity, and mortality.Systolic dysfunction defined as reduced left ventricular ejection fraction (LVEF)50% or55% and diastolic dysfunction defined as e'-wave8 cm/s on tissue-Doppler imaging (TDI) or E/e'-ratio were found in 13 (12%), 24 (23%), 53 (50%), and 26 (25%) patients, respectively. Forty-four patients (42%) died in-hospital. All cytokines, except IL-1, correlated with Sequential Organ Failure Assessment and APACHE (Acute Physiology and Chronic Health Evaluation) II scores, and all cytokines predicted mortality. IL-10 and IL-18 independently predicted mortality among cytokines (OR = 3.1 and 28.3, P = .006 and0.0001). However, none of the cytokines correlated with LVEF, end-diastolic volume index (EDVI), stroke-volume index (SVI), or s'-wave and e'-wave velocities on TDI (Pearson linear and Spearman rank [ρ] nonlinear correlations). Similarly, no differences were found in cytokine concentrations between patients dichotomized to high vs low LVEF, EDVI, SVI, s'-wave, or e'-wave (Mann-Whitney U tests). In contrast, NT-proBNP strongly correlated with both reduced LVEF and reduced e'-wave velocity, and hs-troponin-T correlated mainly with reduced e'-wave.Unlike cardiac biomarkers, none of the measured inflammatory cytokines correlates with systolic or diastolic myocardial dysfunction in severe sepsis or septic shock.

International audience; Background - The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods - Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results - EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions - In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

High levels of microphthalmia transcription factor (MITF) expression have been described in several cell types, including melanocytes, mast cells, and osteoclasts. MITF plays a pivotal role in the regulation of specific genes in these cells. Although its mRNA has been found to be present in relatively high levels in the heart, its cardiac role has never been explored. Here we show that a specific heart isoform of MITF is expressed in cardiomyocytes and can be induced by beta-adrenergic stimulation but not by paired box gene 3 (PAX3), the regulator of the melanocyte MITF isoform. In 2 mouse strains with different MITF mutations, heart weight/body weight ratio was decreased as was the hypertrophic response to beta-adrenergic stimulation. These mice also demonstrated a tendency to sudden death following beta-adrenergic stimulation. Most impressively, 15-month-old MITF-mutated mice had greatly decreased heart weight/body weight ratio, systolic function, and cardiac output. In contrast with normal mice, in the MITF-mutated mice, beta-adrenergic stimulation failed to induce B-type natriuretic peptide (BNP), an important modulator of cardiac hypertrophy, while atrial natriuretic peptide levels and phosphorylated Akt were increased, suggesting a cardiac stress response. In addition, cardiomyocytes cultured with siRNA against MITF showed a substantial decrease in BNP promoter activity. Thus, for what we believe is the first time, we have demonstrated that MITF plays an essential role in beta-adrenergic-induced cardiac hypertrophy.

Heparin is an important medication in the treatment of patients with unstable angina pectoris. We designed an observational study to compare the effects of standard heparin (SH) with low molecular weight heparin (LMWH) on vascular endothelial growth factor (VEGF) levels in patients undergoing coronary artery bypass grafting (CABG).Thirty-two patients with unstable angina pectoris undergoing CABG were prospectively categorized into two groups according to the type of heparin administration before surgery. VEGF levels determined by enzyme linked immunosorbent assay (ELISA) were compared between the two groups' blood samples obtained before the surgery and pericardial fluid after pericardial opening.There was no difference in preoperative characteristics between the two groups. Serum VEGF levels were similar (P=0.3) in patients treated by SH (85+/-55 pg/ml) compared to those treated with LMWH (105+/-64 pg/ml). VEGF levels in the pericardial fluid were significantly raised (P0.0001) in patients of LMWH group (36+/-13 pg/ml) compared to SH group (13+/-6 pg/ml). A good correlation was observed between VEGF in the serum and platelet count in both SH group (r=0.8) and LMWH group (r=0.7).Local response of the ischemic myocardium, as expressed by VEGF levels, differs in patients treated with SH compared to patients treated with LMWH. VEGF levels in pericardial fluid of patients receiving LMWH were 2-3-folds higher than patients in SH group.