Bicuspid aortic valve area in normal heart.

INTRODUCTION: Bicuspid aortic valve (BAV) is a common congenital valve abnormality. There are no data in the literature regarding the range of aortic valve area (AVA) in normal functioning BAV. We aimed to evaluate the normal range of BAV area and to compare it to subjects with tricuspid aortic valve (TAV). METHODS: Bicuspid aortic valve subjects were identified from Sheba medical center echocardiographic database and were compared with TAV subjects. Inclusion criteria were normal tissue leaflets appearance and normal functioning valve in the presence of normal echocardiogram. Echocardiographic data, patients hemodynamics, and size were collected. AVA was measured with both planimetry and the continuity equation. RESULTS: Fifty BAV and 50 control subjects were studied (37 men, age 40 ± 13 years). All studies were performed with normal hemodynamics. Fusion between the coronary leaflets was the most common morphology (82%), followed by fusion between the right coronary leaflet with the noncoronary leaflet (18%). The left ventricular outflow tract (LVOT) diameter in BAV group was significantly larger (2.3 ± 0.3 cm vs 2.1 ± 0.2; P < .001). The BAV group presented with a larger AVA planimetry (3.8 ± 0.9 vs 3.3 ± 0.6; P < .001). However, measuring AVA using continuity equation has shown no differences between groups. If using the principles of coefficient of contraction, it seems that measuring AVA by planimetry overestimates the real anatomic AVA. CONCLUSION: This data provide normal values for echocardiographically determined AVA in BAV subjects. This population was characterized by large LVOT diameter and large AVA. The larger AVA measured with the planimetry emphasizes the limitation of this method in BAV population.

Tricuspid Regurgitation following Lead Extraction: Risk Factors and Clinical Course.

BACKGROUND: Transvenous lead extraction can lead to tricuspid valve damage. OBJECTIVES: To assess the incidence, risk factors and clinical outcome of tricuspid regurgitation (TR) following lead extraction. METHODS: We prospectively collected data on patients who underwent lead extraction at the Sheba Medical Center prior to laser use (i.e., before 2012). Echocardiography results before and following the procedure were used to confirm TR worsening, defined as an echocardiographic increase of at least one TR grade. Various clinical and echocardiographic parameters were analyzed as risk factors for TR. Clinical and echocardiographic follow-up was conducted to assess the clinical significance outcome of extraction-induced TR. RESULTS: Of 152 patients who underwent lead extraction without laser before 2012, 86 (56%) (192 electrodes) had echocardiography results before and within one week following the procedure. New or worsening TR was discovered in 13 patients (15%). Use of mechanical tools and younger age at extraction were found on multivariate analysis to be factors for TR development (P = 0.04 and P = 0.03 respectively). Average follow-up was 22.25 ± 21.34 months (range 8-93). There were no significant differences in the incidence of right-sided heart failure (50% vs. 23%, P = 0.192) or hospitalizations due to heart failure exacerbations (37.5% vs. 11%, P = 0.110). No patient required tricuspid valve repair or replacement. Death rates were similar in the TR and non-TR groups (20% vs. 33%). CONCLUSIONS: TR following lead extraction is not uncommon but does not seem to affect survival or outcomes such as need for valve surgery. Its long-term effects remain to be determined.

Morphological features of the P-waves at surface electrocardiogram as surrogate to mechanical function of the left atrium following a successful modified maze procedure.

AIMS: Absent left atrium (LA) mechanical contraction may occur following the modified Cox-maze operation, and was found to impose a potential risk for the occurrence of thrombo-embolic stroke. It is unknown whether certain morphological P-wave characteristics can surrogate absent LA mechanical activity. The aim of this study was to evaluate the morphological features of the P-waves on the surface electrocardiogram (ECG) of patients who underwent the maze operation and to relate them to the contractile profile of the LA. METHODS AND RESULTS: Electrocardiogram tracings of 150 consecutive patients that were in sustained sinus rhythm following the maze operation were evaluated. P-waves were scrutinized for morphology, duration, axis, and amplitude. Clinical, surgery-related, and echocardiographic data were collected and analysed. Forty-seven patients (31%) had no evidence of LA contraction at 3 months after surgery (baseline assessment) and on follow-up echocardiography. Multivariate analysis showed that a positive-only P-wave deflection at lead V1 (P = 0.03), a negative-only deflection at aVL, and a P-wave amplitude of ≤ 0.05 mV at the septal-anterior leads (P < 0.001 for both) were associated with absent LA mechanical contraction. In a secondary analysis, a risk score involving the above three parameters was developed for the prediction of stroke occurrence. Patients at the high-risk score group had a 30% survival freedom of stroke compared with 70% for patients at intermediate risk (P < 0.001). CONCLUSION: Absent LA mechanical contraction following the modified maze operation may be accompanied by a distinguished pattern of the P-waves on the surface ECG.

Modulation of cardiac macrophages by phosphatidylserine-presenting liposomes improves infarct repair.

Herein we investigated a new strategy for the modulation of cardiac macrophages to a reparative state, at a predetermined time after myocardial infarction (MI), in aim to promote resolution of inflammation and elicit infarct repair. The strategy employed intravenous injections of phosphatidylserine (PS)-presenting liposomes, mimicking the anti-inflammatory effects of apoptotic cells. Following PS-liposome uptake by macrophages in vitro and in vivo, the cells secreted high levels of anti-inflammatory cytokines [transforming growth factor ß (TGFß) and interleukin 10 (IL-10)] and upregulated the expression of the mannose receptor--CD206, concomitant with downregulation of proinflammatory markers, such as tumor necrosis factor α (TNFα) and the surface marker CD86. In a rat model of acute MI, targeting of PS-presenting liposomes to infarct macrophages after injection via the femoral vein was demonstrated by magnetic resonance imaging (MRI). The treatment promoted angiogenesis, the preservation of small scars, and prevented ventricular dilatation and remodeling. This strategy represents a unique and accessible approach for myocardial infarct repair.

Prevalence and clinical predictors of reverse remodeling in patients with dilated cardiomyopathy.

BACKGROUND: Contemporary therapiesimprove prognosis and may restore left ventricular (LV) sizeand function. OBJECTIVES: To examine the prevalence, clinical features and therapies associated with reverse remodeling (RR) in dilated cardiomyopathy (DCM). METHODS: The study group comprised 188 DCM patients who had undergone two echo examinations at least 6 months apart. RR was defined as increased LV ejection fraction (LVEF) by > or = 10% concomitant with > or = 10% decreased LV end-diastolic dimension. RESULTS: RR occurred in 50 patients (26%) and was associated with significantly reduced end-systolic dimension, left atrial size, grade of mitral regurgitation, and pulmonary artery pressure. NYHA class improved in the SRR group. RR was less common in familial DCM and a long-standing disease and was more prevalent in patients with prior exposure to chemotherapy. Recent-onset disease, Iower initial LVEF and normal electrocardiogram were identified as independent predictors of RR. Beta-blocker dose wasrelated to improved LVEF but not to RR. Over a mean follow-up of 23 months, 16 patients (12%) from the 'no-RR' group died or underwent heart transplantation compared to none from the RR group (P < 0.01). CONCLUSIONS: Contemporary therapies led to an an improvement in the condition of a considerable number of DCM patients. A period of close observation while optimizing medical therapy should be considered before deciding on invasive procedures.

Effects of tricuspid valve regurgitation on clinical and echocardiographic outcome in patients with cardiac resynchronization therapy.

AIMS: The severity of tricuspid regurgitation (TR) is a predictor of outcome among heart failure patients. The interaction between cardiac resynchronization therapy (CRT) and TR has not been described. In this study, we examined the effect of pre-implant TR, and worsened TR post-implant, on response to CRT and overall survival. METHODS AND RESULTS: We included all patients with successfully implanted CRT systems between 2007 and 2010. Patients were divided into two groups pre-implant: (Gp 1) no-or-mild TR; and (Gp 2) moderate-or-severe TR. Post-implant, patients were divided into two groups: (Gp A) improved or stable TR; and (Gp B) worsened TR. The clinical and echocardiographic outcome of all patients was assessed. The study included 193 patients. Thirty-five subjects (18%) had moderate or severe TR pre-implant (Gp 2). Baseline echo parameters and 6 min walk distance were worse in Gp 2 compared with Gp 1 (mild or no TR). There was no significant difference in clinical response to CRT between the two groups. However, Gp 2 had a significantly lower echocardiographic response (35 vs. 60%, P = 0.01) and higher mortality over 3 years (OR = 6.70, 95% CI = 1.8-24.5, P = 0.004). Post-implant, 25 patients (13%) developed worsened TR (Gp B), not associated with deterioration in right ventricle function or elevation in pulmonary artery pressure. Worsened TR predicted a reduced clinical response to CRT (42 vs. 70%, P = 0.006), when compared with Gp A. CONCLUSIONS: The presence of baseline moderate or severe TR is associated with increased mortality but does not predict clinical or echocardiographic response to CRT. Patients with worsened TR following CRT are less likely to clinically respond to CRT. Pacing leads passing through the tricuspid valve may worsen TR. It is conceivable that avoidance of lead-induced TR by alternative implantation techniques could improve the response rate to CRT.

Mitral valve repair: isolated posterior compared to anterior or bileaflet pathology.

OBJECTIVES: The results of mitral valve (MV) repair for anterior leaflet pathology (ALP) are considered less favorable than those for posterior leaflet pathology (PLP). We compared clinical and echocardiography outcomes of PLP repair with ALP and/or bileaflet pathology (BLP) repair. METHODS: Between 2004 and 2011, 407 patients underwent MV repair due to degenerative MV: 276 patients (68%) had PLP and 131 (32%) had ALP/BLP. Mean age was 59 ± 12 and 56 ± 15 years in PLP and ALP/BLP groups, respectively (p = 0.03). Patient characteristics and co-morbidities were similar between groups. Valve repair techniques included leaflet resection (61% and 24%), annuloplasty (99% and 97%), and artificial chordea (46% and 67%), in the PLP and ALP/BLP groups, respectively. RESULTS: There was one (0.4%) in-hospital death in the PLP group, and none in the ALP/BLP group. Early complication rate was similar between groups. Completed clinical and late echocardiography follow-up was 95% (29 ± 22 months, 1 to 87). Freedom from reoperation was 98% (270/276) and 98% (129/131), and there were three (1%) and three (2%) late deaths, in the PLP and ALP/BLP groups, respectively (NS). Late echocardiography revealed that 89% and 94% of patients (PLP and ALP/BLP groups, respectively) were free from moderate or severe mitral regurgitation (MR) (p = 0.13). All other late valve-related complications were similar between groups. CONCLUSIONS: Anterior and bileaflet MV disease can be repaired with early and mid-term results similar to those of posterior MV disease. All patients with severe MR due to anterior or posterior pathology should be considered equally for early valve repair.

Pseudo-discordance mimicking low-flow low-gradient aortic stenosis in transcatheter aortic valve replacement patients with severe symptomatic aortic stenosis.

BACKGROUND: While the combination of a small aortic valve area (AVA) and low mean gradient is frequently labeled 'low-flow low-gradient aortic stenosis (AS)', there are two potential causes for this finding: underestimation of mean gradient and underestimation of AVA. METHODS: In order to investigate the prevalence and causes of discordant echocardiographic findings in symptomatic patients with AS and normal left ventricular (LV) function, we evaluated 72 symptomatic patients with AS and normal LV function by comparing Doppler, invasive, computed tomography (CT) LV outflow tract (LVOT) area, and calcium score (CaSc). RESULTS: Thirty-six patients had discordant echocardiographic findings (mean gradient < 40 mmHg, AVA ≤ 1 cm²). Of those, 19 had discordant invasive measurements (true discordant [TD]) and 17 concordant (false discordant [FD]): In 12 of the FD the mean gradient was > 30 mmHg; technical pitfalls were found in 10 patients (no reliable right parasternal Doppler in 6). LVOT area by echocardiography or CT could not differentiate between concordants and discordants nor between TD and FD (p = NS). CaSc was similar in concordants and FD (p = 0.3), and it was higher in true concordants than in TD (p = 0.005). CaSc positive predictive value for the correct diagnosis of severe AS was 95% for concordants and 93% for discordants. CONCLUSIONS: Discordant echocardiographic findings are commonly found in patients with symptomatic AS. Underestimation of the true mean gradient due to technical difficulties is an important cause of these discrepant findings. LVOT area by echocardiography or CT cannot differentiate between TD and FD. In the absence of a reliable and compete multi-window Doppler evaluation, patients should undergo CaSc assessment.

Brachial artery endothelial function predicts platelet function in control subjects and in patients with acute myocardial infarction.

Platelet activation occurs in an endothelium-dependent flow-mediated dilation (FMD) impairment environment. The aim of this study was to explore the association between platelet reactivity and brachial artery FMD in individuals without established cardiovascular disease (controls) and acute myocardial infarction (AMI) patients. We prospectively assessed brachial artery FMD in 151 consecutive subjects, 104 (69%) controls, and 47 (31%) AMI patients; 115 (76%) men, mean age 53 ± 11 years. Following overnight fasting and discontinuation of all medications for ≥ 12 h, percent change in brachial artery FMD (%FMD) and endothelium-independent, nitroglycerin-mediated vasodilation (%NTG) were assessed. Platelet aggregation was assessed by conventional aggregometry, and platelet adhesion and aggregation under flow conditions by cone-and-plate(let) technology (Impact-R). Smoking, diabetes, and hypertension were more common in AMI compared to control subjects (p < 0.01 for all). Furthermore, aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors, and statin administration were more common in AMI compared to controls (p < 0.01 for all). %FMD but not %NTG was significantly lower in AMI patients compared to controls (10.2 ± 4.2% vs. 15.4 ± 4.4%; p < 0.001 and 17.2 ± 3.9% vs. 18.0 ± 3.7%, p = 0.803, respectively). %FMD was significantly and inversely associated with all platelet functions tests (p < 0.001) in all study participants. In a multivariate logistic regression (unadjusted and adjusted for age, gender, smoking status, diabetes mellitus, hypertension, hypercholesterolemia, overweight, family history, and concomitant medications), %FMD remained the best predictor of platelet function, irrespective of group allocation (AMI patients or controls). In conclusion, FMD is inversely correlated to platelet reactivity in both controls and AMI patients.

Prevascularization of cardiac patch on the omentum improves its therapeutic outcome.

The recent progress made in the bioengineering of cardiac patches offers a new therapeutic modality for regenerating the myocardium after myocardial infarction (MI). We present here a strategy for the engineering of a cardiac patch with mature vasculature by heterotopic transplantation onto the omentum. The patch was constructed by seeding neonatal cardiac cells with a mixture of prosurvival and angiogenic factors into an alginate scaffold capable of factor binding and sustained release. After 48 h in culture, the patch was vascularized for 7 days on the omentum, then explanted and transplanted onto infarcted rat hearts, 7 days after MI induction. When evaluated 28 days later, the vascularized cardiac patch showed structural and electrical integration into host myocardium. Moreover, the vascularized patch induced thicker scars, prevented further dilatation of the chamber and ventricular dysfunction. Thus, our study provides evidence that grafting prevascularized cardiac patch into infarct can improve cardiac function after MI.

Influence of anesthesia on hemodynamic assessment of mitral stenosis severity.

BACKGROUND: The treatment of choice for severe rheumatic mitral stenosis (MS) is balloon mitral valvuloplasty (BMV). Assessment of MS severity is usually performed by echocardiography. Before performing BMV, invasive hemodynamic assessment is also performed. The effect of anesthesia on the invasive assessment of MS severity has not been studied. The purpose of the present study was to assess changes in invasive hemodynamic measurement of MS severity before and after induction of general anesthesia. METHODS: The medical files of 22 patients who underwent BMV between 2014 and 2020 were reviewed. Medical history, laboratory, echocardiographic and invasive measurements were collected. Anesthesia induction was performed with etomidate or propofol. Pre-procedural echocardiographic measurements of valve area using pressure half time, and continuity correlated well with invasive measurements using the Gorlin formula. RESULTS: After induction of anesthesia the mean mitral valve gradient dropped by 2.4 mmHg (p = 0.153) and calculated mitral valve area (MVA) increased by 0.2 cm2 (p = 0.011). A wide variability in individual response was observed. While a drop in gradient was noted in 14 patients, it increased in 7. Gorlin derived MVA rose in most patients but dropped in 4. Assuming a calculated MVA of 1.5 cm2 and below to define clinically significant MS, 4 patients with pre-induction MVA of 1.5 cm2 or below had calculated MVA above 1.5 cm2 after induction. CONCLUSIONS: The impact of general anesthesia on the hemodynamic assessment of MS is heterogeneous and may lead to misclassification of MS severity.

Pulse pressure is a predictor of vascular endothelial function in middle-aged subjects with no apparent heart disease.

Elevated pulse pressure (PP) is increasingly being recognized as a cardiovascular risk factor. To investigate whether PP is associated with endothelial function in subjects with no apparent heart disease we prospectively assessed brachial flow-mediated dilation (FMD) in 525 consecutive subjects with no apparent heart disease [323 (61%) men, mean age 52 +/- 11 years, mean body mass index (BMI) 26 +/- 4 kg/m(2)]. Following an overnight fast and discontinuation of all medications for >/= 12 hours, the FMD and endothelium-independent, nitroglycerin-mediated vasodilation (NTG) were assessed using high-resolution linear array ultrasound. Univariate linear analysis revealed a significant inverse association between FMD and PP (r = -0.65, p < 0.01), systolic blood pressure (r = -0.52, p < 0.01) and age (r = -0.21, p < 0.05). Multivariate analysis showed that PP was the strongest independent predictor of FMD. We therefore divided the study population into two groups: group A (n = 290) the median PP of 50 mmHg. Male sex, hypertension, diabetes, BMI, heart rate, and the use of aspirin, long-acting nitrates, calcium channel blockers, angiotensin-converting enzyme inhibitors and beta blockers were significantly more common in Group B compared with Group A. FMD but not NTG was significantly greater in patients with PP the median PP (14.9 +/- 7.9% vs 10.8 +/- 8.8%, p < 0.001 and 16.1 +/- 9.6% vs 14.8 +/- 8.4%, p = 0.38; respectively). Thus, PP is inversely associated with brachial FMD in middle-aged subjects with no apparent heart disease, suggesting a potential mechanism whereby elevated PP contributes to cardiovascular disease. Long-term follow-up is warranted to elucidate the incidence of coronary artery disease in both study groups.

Fast track evaluation of patients with acute chest pain: experience in a large-scale chest pain unit in Israel.

BACKGROUND: Many patients present to the emergency department with chest pain. While in most of them chest pain represents a benign complaint, in some patients it underlies a life-threatening illness. OBJECTIVES: To assess the routine evaluation of patients presenting to the ED with acute chest pain by means of a cardiologist-based chest pain unit using different noninvasive imaging modalities. METHODS: We evaluated the records of 1055 consecutive patients who presented to the ED with complaints of chest pain and were admitted to the CPU. After an observation period and according to the decision of the attending cardiologist, patients underwent myocardial perfusion scintigraphy, multidetector computed tomography, or stress echocardiography. RESULTS: The CPU attending cardiologist did not prescribe non-invasive evaluation for 108 of the 1055 patients, who were either admitted (58 patients) or discharged (50 patients) after an observation period. Of those remaining, 444 patients underwent MDCT, 445 MPS, and 58 stress echocardiography. Altogether, 907 patients (86%) were discharged from the CPU. During an average period of 236 +/- 223 days, 25 patients (3.1%) were readmitted due to chest pain of suspected cardiac origin, and only 8 patients (0.9%) suffered a major adverse cardiovascular event. CONCLUSIONS: Utilization of the CPU enabled a rapid and thorough evaluation of the patients' primary complaint, thereby reducing hospitalization costs and occupancy on the one hand and avoiding misdiagnosis in discharged patients on the other.

Do all intra-ventricular conduction defect ECG patterns respond equally to CRT?

PURPOSE: Response to cardiac resynchronization therapy (CRT) is well-established in patients with typical left bundle branch block (LBBB) but modest or even negative in those with intraventricular conduction delay (IVCD). However, IVCD pattern is heterogeneous, and it is possible that QRS patterns may also respond to CRT. METHODS: Consecutive baseline ECGs of 239 patients implanted between 2007 and 2010 with CRT were analyzed. ECGs were classified into the following three groups: (a) typical LBBB (TLBBB) according to accepted guidelines (n = 67); (b) IVCD with LBBB pattern criteria in V1, 1, and aVL but with QS or rS in V5-V6 which we defined as atypical LBBB (ALBBB) (n = 74); and (c) all other IVCD (OIVCD) patterns (n = 98). Endpoints were 2 years mortality and echocardiographic response, defined as a decrease of ≥ 10% in indexed LVESV or an increase of ≥ 5% in left ventricular ejection fraction at 1 year of follow-up. RESULTS: Baseline clinical characteristics were similar among all the three groups. Rates of echocardiographic response were lower among those with OIVCD compared to those with LBBB and ALBBB (50% vs. 75% and 72%, respectively, p = 0.01 for both comparisons). A multivariable model showed a lower likelihood of echocardiographic response in OIVCD [HR = 0.40; (0.16-0.98)] and a similar likelihood in ALBBBB [HR = 0.98; (0.40-2.40)] compared to TLBBB. Cumulative 2-year survival was 88% in ALBBB, 86% in TLBBB, and 76% in OIVCD (p value = 0.011). CONCLUSION: Patients with ALBBB may have a favorable echocardiographic response to CRT and display similar survival rates to typical LBBB. This subgroup of IVCD should be considered for CRT. Atypical left bundle branch morphology defined as QS or rS in lead V1, broad R waves in lead I, and aVL but with QS or rS in V5-V6 is associated with favorable echocardiographic response to CRT and displays similar survival rates to typical LBBB patients.

Effect of injectable alginate implant on cardiac remodeling and function after recent and old infarcts in rat.

BACKGROUND: Adverse cardiac remodeling and progression of heart failure after myocardial infarction are associated with excessive and continuous damage to the extracellular matrix. We hypothesized that injection of in situ-forming alginate hydrogel into recent and old infarcts would provide a temporary scaffold and attenuate adverse cardiac remodeling and dysfunction. METHODS AND RESULTS: We developed a novel absorbable biomaterial composed of calcium-crosslinked alginate solution, which displays low viscosity and, after injection into the infarct, undergoes phase transition into hydrogel. To determine the outcome of the biomaterial after injection, calcium-crosslinked biotin-labeled alginate was injected into the infarct 7 days after anterior myocardial infarction in rat. Serial histology studies showed in situ formation of alginate hydrogel implant, which occupied up to 50% of the scar area. The biomaterial was replaced by connective tissue within 6 weeks. Serial echocardiography studies before and 60 days after injection showed that injection of alginate biomaterial into recent (7 days) infarct increased scar thickness and attenuated left ventricular systolic and diastolic dilatation and dysfunction. These beneficial effects were comparable and sometimes superior to those achieved by neonatal cardiomyocyte transplantation. Moreover, injection of alginate biomaterial into old myocardial infarction (60 days) increased scar thickness and improved systolic and diastolic dysfunction. CONCLUSIONS: We show for the first time that injection of in situ-forming, bioabsorbable alginate hydrogel is an effective acellular strategy that prevents adverse cardiac remodeling and dysfunction in recent and old myocardial infarctions in rat.

Vascular endothelial function predicts mortality risk in patients with advanced ischaemic chronic heart failure.

AIMS: Endothelial function is impaired in advanced chronic heart failure (ACHF) patients. We explored a possible association between endothelial function and subsequent mortality risk in ACHF. METHODS AND RESULTS: We prospectively assessed brachial flow-mediated dilation (FMD) in 82 consecutive New York Heart Association class IV ischaemic ACHF patients with a mean left ventricular ejection fraction (LVEF) of 22 +/- 3%. Following overnight fasting and discontinuation of all medications for > or = 12 h, percent increase in FMD (%FMD) and nitroglycerin-mediated vasodilation were assessed using linear array ultrasound. All patients were followed for 14 +/- 2 months for adverse cardiovascular events, including death, hospitalization for CHF exacerbation, or myocardial infarction. Patients were divided into two groups: those with an FMD lesser than or equal to the median %FMD of 4.6% (n = 41) and those with an FMD above the median (n = 41). Both groups were comparable regarding cardiovascular risk factors, LVEF, and concomitant medications. During follow-up, 22 (53.6%) patients with FMD lesser than or equal to the median had composite adverse cardiovascular events compared with only eight patients (19.5%) with FMD above the median (P < 0.01). Furthermore, fiver deaths (12.1%) occurred in patients with FMD lesser than or equal to the median, compared with no deaths in patients with FMD above the median (P < 0.03). Cox regression analyses revealed that FMD was an independent predictor for these events. CONCLUSION: Flow-mediated dilation is associated with increased mortality risk in ischaemic ACHF patients.

Evaluation of a peritoneal-generated cardiac patch in a rat model of heterotopic heart transplantation.

Tissue engineering holds the promise of providing new solutions for heart transplant shortages and pediatric heart transplantation. The aim of this study was to evaluate the ability of a peritoneal-generated, tissue-engineered cardiac patch to replace damaged myocardium in a heterotopic heart transplant model. Fetal cardiac cells (1 x 10(6)/scaffold) from syngeneic Lewis rats were seeded into highly porous alginate scaffolds. The cell constructs were cultured in vitro for 4 days and then they were implanted into the rat peritoneal cavity for 1 week. During this time the peritoneal-implanted patches were vascularized and populated with myofibroblasts. They were harvested and their performance in an infrarenal heterotopic abdominal heart transplantation model was examined (n = 15). After transplantation and before reperfusion of the donor heart, a 5-mm left (n = 6) or right (n = 9) ventriculotomy was performed and the patch was sutured onto the donor heart to repair the defect. Echocardiographical studies carried out 1-2 weeks after transplantation showed normal LV function in seven of the eight hearts studied. After 1 month, visual examination of the grafted patch revealed no aneurysmal dilatation. Microscopic examination revealed, in most of the cardiac patches, a complete disappearance of the scaffold and its replacement by a consistent tissue composed of myofibroblasts embedded in collagen bundles. The cardiac patch was enriched with a relatively large number of infiltrating blood vessels. In conclusion, cardiac patches generated in the peritoneum were developed into consistent tissue patches with properties to seal and correct myocardial defects. Our study also offers a viable rat model for screening and evaluating new concepts in cardiac reconstruction and engineering.

Long-Term Functional and Structural Durability of Bioprosthetic Valves Placed in the Aortic Valve Position via Percutaneous Rout in Israel.

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.

Effect of image quality on accuracy of two-dimensional strain echocardiography for diagnosing ischemic chest pain: a 2DSPER multicenter trial substudy.

Few data exist regarding the effect of image quality on measurements of two-dimensional longitudinal strain (2DLS). In the 2DLS for Diagnosing Chest Pain in the Emergency Room (2DSPER) multicenter study, 2DLS was not useful for ruling out acute coronary syndromes (ACS) in the emergency department (ED). The aim of this substudy was to determine the effect of 2D image quality on the diagnostic accuracy of 2DLS for ACS. We reviewed apical views used for 2DLS analysis in all 605 patients included in the 2DSPER study. Studies with the best image quality (HighQ, n = 177), were compared to the lower quality group (LowQ, n = 428). Abnormal 2DLS was defined as PSS20% > - 17% (PSS20% being the peak left ventricular systolic strain value identifying the 20% worst strain values). Global longitudinal strain (GLS) and PSS20% were significantly worse in LowQ compared to HighQ patients. LowQ independently predicted abnormal 2DLS (OR 1.9, 95% CI 1.3-2.9, P = 0.003). The sensitivity of PSS20% > - 17% for ACS was 85% for LowQ vs. 73% for HighQ (P = 0.2), specificity 22% vs. 38% (P < 0.0001) and overall accuracy 29% vs. 44% (P = 0.0004). Despite better overall accuracy in the HighQ group there was no significant difference between the receiver operating characteristic curves of either GLS or PSS20% in the two groups and abnormal 2DLS did not predict ACS even in HighQ patients (OR 1.7, 95% CI 0.7-4.3, P = 0.3). LowQ echo is associated with worse 2DLS. Abnormal 2DLS was not clinically useful for excluding ACS in the ED even in patients with optimal 2D image quality.Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01163019.

Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium.

BACKGROUND: Cell labeling with superparamagnetic iron oxide (SPIO) nanoparticles enables noninvasive MRI and tracking of transplanted stem cells. We sought to determine whether mesenchymal stem cell (MSC) outcome is affected by SPIO labeling in a rat model of myocardial infarction. METHODS AND RESULTS: Rat MSCs were labeled with SPIO (ferumoxides; Endorem; Guerbet, Villepinte, France). By trypan-blue exclusion assay, almost 100% of the cells remained viable after labeling. Seven days after MI, rats were randomized to injections of 2x10(6) SPIO-labeled MSCs, 2x10(6) unlabeled MSCs, or saline. Labeled cells were visualized in the infarcted myocardium as large black spots by serial MRI studies throughout the 4-week follow-up. The presence of labeled cells was confirmed by iron staining and real-time polymerase chain reaction on postmortem specimens. At 4 weeks after transplantation, the site of cell injection was infiltrated by inflammatory cells. Costaining for iron and ED1 (resident macrophage marker) showed that the iron-positive cells were cardiac macrophages. By real-time polymerase chain reaction, the Y-chromosome-specific SRY DNA of MSCs from male donors was not detected in infarcted hearts of female recipients. Serial echocardiography studies at baseline and 4 weeks after cell transplantation showed that both unlabeled and labeled MSCs attenuated progressive left ventricular dilatation and dysfunction compared with controls. CONCLUSIONS: At 4 weeks after transplantation of SPIO-labeled MSCs, the transplanted cells are not present in the scar and the enhanced MRI signals arise from cardiac macrophages that engulfed the SPIO nanoparticles. However, both labeled and unlabeled cells attenuate left ventricular dilatation and dysfunction after myocardial infarction.