Assessment of severity in aortic stenosis-incremental value of endocardial function parameters compared with standard indexes.

Several studies have reported that patients (pts) with severe aortic stenosis and similar pressure gradients or even similar aortic valve areas may have quite different symptomatic status and clinical outcomes suggesting that other factors might have a significant impact on the pathophysiology of this disease. Our purpose was to assess the severity of subendocardial wall dysfunction in symptomatic and asymptomatic pts with aortic stenosis using tissue Doppler imaging (TDI), strain rate imaging (SRI) and cyclic variation of integrated backscatter (IB). We studied 68 pts with aortic valvar stenosis and 46 subjects with no signs of heart disease. SRI/IB indexes were calculated in the apical four chambers views at endocardial level. Early diastolic endocardial strain rate showed the best correlation with transvalvar pressure gradients and valve areas. Compared with controls, symptomatic pts showed a more marked decrease in endocardial strain, strain rate and cyclic variation of IB. Receiver operating characteristic (ROC) curves suggested that the thresholds offering an adequate compromise between sensitivity and specificity for the prediction of symptoms were >/=60 mm Hg for the pressure gradient, less than 0.60 cm(2)/m(2) for aortic valve area, less than 20% for strain, less than 2.0 s(-1) for strain rate and less than 3.0 dB for cyclic variation. The combination of pressure gradient, aortic valve area and SRI/IB parameters resulted in an improvement of the overall performance for predicting the symptomatic state. Thus, SRI/IB parameters have an incremental value in differentiating symptomatic and asymptomatic pts with aortic stenosis compared with conventional hemodynamic parameters.

Autologous myoblast transplantation for chronic ischemic mitral regurgitation.

OBJECTIVES: This study was designed to assess whether post-myocardial infarction (MI) in-scar transplantation of skeletal myoblasts (SM) could reduce chronic ischemic mitral regurgitation (MR) by decreasing left ventricular (LV) remodeling. BACKGROUND: Extensive work has confirmed the relationship between ischemic MR and post-myocardial infarction (MI) remodeling of the LV. METHODS: An infero-posterior MI was created in 13 sheep, thereby resulting in increasing MR. Two months post-MI, the animals were randomized and in-scar injected with expanded autologous SM (n = 6, mean: 251 x 10(6) cells) or culture medium only (n = 7). Three-dimensional echocardiography was performed at baseline, before transplantation, and for two months thereafter (sacrifice), with measurements of LV end-diastolic and end-systolic volumes (ESV), ejection fraction (EF), MR stroke volume, and leaflet tethering distance; wall motion score index (WMSi) was assessed by two-dimensional echo. RESULTS: Measurements were similar between groups at baseline and before transplantation. At sacrifice, transplantation was found to have reduced MR progression (regurgitant volume change: -1.83 +/- 0.32 ml vs. 5.9 +/- 0.7 ml in control group, p < 0.0001) and tethering distance (-0.41 +/- 0.09 cm vs. 0.44 +/- 0.12 cm in control group, p < 0.001), with significant improvement of EF (2.01 +/- 0.94% vs. -4.86 +/- 2.23%, p = 0.02), WMSi (-0.25 +/- 0.11 vs. 0.13 +/- 0.03 in controls, p < 0.01) and a trend to a lesser increase in ESV (23.3 +/- 3.5 ml vs. 35.4 +/- 4.2 ml in control group, p = 0.055). CONCLUSIONS: Autologous skeletal myoblast transplantation attenuates mild-to-moderate chronic ischemic MR, which otherwise is progressive, by decreasing tethering distance and improving EF and wall motion score, thereby enhancing valve coaptation. These data shed additional light on the mechanism by which skeletal myoblast transplantation may be cardioprotective.

Echocardiographic assessment of ventricular asynchrony in dilated cardiomyopathy and congenital heart disease: tools and hopes.

Ventricular dyssynchrony is a relatively common problem in patients with heart failure, in particular those with wide QRS complex, and appears to have a deleterious effect on the natural history of heart failure, as it has been associated with increased mortality. Mechanistic studies, observational evaluations, and randomized trials have consistently demonstrated the beneficial effects of cardiac resynchronization therapy (CRT) in patients with moderate-to-severe chronic systolic heart failure and ventricular dyssynchrony who have failed optimal medical treatment. However, despite the promising results, it is estimated that in approximately 30% of patients undergoing CRT, the symptoms of heart failure do not improve or become even worse. One of the most important reasons for this failure is probably the lack of distinct mechanical dyssynchrony before implantation. A number of echocardiographic tools have been developed during the past 3 years for quantitative measurement of the severity of dyssynchrony before and after CRT. This review discusses the actual and potential role of different echocardiographic techniques in selection of patients and optimization of CRT and the value of some new clinical applications such as in congenital heart disease.

Transplantation of cardiac-committed mouse embryonic stem cells to infarcted sheep myocardium: a preclinical study.

BACKGROUND: Heart failure develops after myocardial infarction and is a major cause of morbidity and mortality. The ability to direct differentiation of embryonic stem cells (ESC) towards a cardiomyogenic phenotype makes them an attractive therapeutic option for cardiac repair, but species-specific and individual-specific immunological imprinting remains a hurdle. Our aim was to ascertain whether the purported immune privilege of ESC allows for their cross-species engraftment in a clinically relevant large-animal model. METHODS: We studied engraftment and differentiation of cardiac-committed mouse ESC in 18 sheep in which a myocardial infarction had been induced; nine controls received medium and nine sheep (five of which were immunosuppressed) received ESC. The gain in myocardial function was measured by echocardiography 1 month after cell transplantation. FINDINGS: Cardiac-committed murine ESC engrafted in infarcted myocardium of immunosuppressed and immunocompetent sheep, and differentiated into mature cardiomyocytes that expressed connexins. Colonisation of the scar area by ESC was accompanied by a functional benefit of the damaged myocardium. Left-ventricular ejection fraction deteriorated in the control group by a median of 9.9% (range -20 to 0.3) relative to baseline (p=0.011) whereas in the treated group it improved by 6.6% (-5.7 to 50.8; comparison between groups p=0.002). INTERPRETATION: These findings obtained in a clinically relevant large-animal model of heart failure strengthen the potential therapeutic use of ESC to regenerate the severely dysfunctional myocardium and bring additional evidence for an immune privilege of these cells.

Skeletal myoblast transplantation through a catheter-based coronary sinus approach: an effective means of improving function of infarcted myocardium.

AIMS: This study was designed to assess the functional effects of a transvenous coronary sinus technique of skeletal myoblast delivery in infarcted myocardium. METHODS AND RESULTS: An anterior myocardial infarction was created percutaneously in 14 sheep. Simultaneously, a muscle biopsy was harvested and expanded. Two weeks later, sheep were instrumented percutaneously with a dedicated catheter incorporating an extendable needle for puncture of the venous wall and, under endovascular ultrasound guidance, a microcatheter was advanced through the needle into the target scar for cell delivery. Following the baseline echocardiographic assessment of left ventricular (LV) function, sheep were randomly allocated to receive four-staged in-scar injections of either autologous cells (n=7) or culture medium (n=7). Two months later, LV function was reassessed blindly and hearts were explanted for subsequent histological and immunohistochemical analysis. There were no acute procedural complications. Baseline LV ejection fraction (EF) was significantly lower in transplanted sheep than in controls [38% (35-48) vs. 51% (38-55), respectively, P=0.03; median (range)]. Two months later, LVEF was significantly higher in the transplanted group than in controls [50% (47-56) vs. 39% (36-47), respectively, P=0.002]. Clusters of myoblasts were identified by histology and immunohistochemistry in three of the seven transplanted sheep. CONCLUSION: These data suggest the functional efficacy of the transvenous coronary sinus technique as a less invasive means of cell delivery to infarcted myocardium.