Endoventricular patch reconstruction of ischemic failing ventricle. a single center with 20 years experience. advantages of magnetic resonance imaging assessment.

The left ventricular reconstruction (LVR) with endoventricular circular patch plasty (EVCPP) was reported in 1984 as a surgical method to rebuild left ventricular aneurysm or asynergy after myocardial infarction. Scarred LV wall can be dyskinetic or akinetic according to the type of infarction (transmural or not), and the progressive dilatation of LV (remodeling) depends on the size of the asynergic scar. Assessment of this extension and of LV volume and performances, is easy and reliable by magnetic resonance (CMR). The surgical technique is based on the insertion inside the ventricle on contractile myocardium, of a circular patch restoring curvature and physiological volume, and allowing exclusion of asynergic non resectable regions. The ventricular reconstruction method also has other components that include coronary revascularization (almost always), mitral repair (if needed) and endocardectomy when spontaneous or inducible ventricular tachycardia (VT) are present. The experience of the authors (> 1100 cases) and results obtained by other Centers, allows proposal of this technique as a way to treat the ischemic failing ventricle.

Ventricular arrhythmias after LV remodelling: surgical ventricular restoration or ICD?

UNLABELLED: Ventricular arrhythmias cause ~50% of deaths in remodeled ventricles after myocardial infarction, and the Multicenter Automatic Defibrillator Implantation Trial (MADIT II) showed that the Implantable Cardioverter Defibrillator (ICD) saved lives in high risk coronary patients with advanced left ventricular dysfunction. We studied 382 patients with remodeled hearts by preoperative Ventricular stimulation (PVS) to evaluate surgical ventricular restoration (SVR) that excludes scar and lower ventricular volume alters the early and late arrhythmia process without ICD utilization. METHODS: Clinical and hemodynamic results before and after SVR in post-infarction patients, are compared to contrast spontaneous and/or inducible ventricular tachycardia to patients without arrhythmias. Study arrhythmia groups included: Spontaneous in 87 patients with clinical documented ventricular arrhythmias and inducible or not inducible ventricular tachycardia: Inducible in 105 patients without clinical ventricular arrhythmias but PVS inducible ventricular tachycardia; and No arrhythmias in 190 patients without spontaneous or PVS inducible ventricular tachycardia. RESULTS: Preoperative LV end systolic volume index helped define preoperative arrythmia potential: Spontaneous > 120/m(2), inducible > 100 ml/m(2), and none < 100ml/m(2). Overall operative mortality rate was 7.6% (29/382). Sudden cardiac death rate was 2.5% causing 18.7% of all deaths. Surgical management reduced inducible ventricular tachycardia, from 41% preoperatively (144/352) to 8% (26/307) at early study, and 8% (14/177) one year later. Cardiac mortality was low at 5-years and not different between groups, despite use of only one late ICD device. CONCLUSIONS: Favorable electrical success rate and low mortality always included volume reduction to interrupt functional re-entry circuits, but also added endocardiectomy, cryoablation, CABG and mitral repair when needed. Overall SVR findings show volume and shape alteration limits ventricular arrhythmias that impair prognosis, and suggests ICD devices are not needed.

Mechanical synchrony: role of surgical ventricular restoration in correcting LV dyssynchrony during chamber rebuilding.

Cardiac failure is frequently complicated by intra and or interventricular conduction delay that results in dyssynchronized cardiac contraction and relaxation. In contrast to an electrical intervention by biventricular pacing, this study tests the capacity of geometric rebuilding by surgical ventricular restoration (SVR) to restore a more synchronous contractile pattern through mechanical reconstruction without exogenous pacing input. Thirty patients (58 +/- 8 years) undergoing SVR at the Cardiothoracic Center of Monaco were prospectively evaluated with a protocol which uses simultaneous measurements of ventricular volumes and pressure to construct pressure/volume (P/V) and pressure/length (P/L) loops. Mean QRS duration was within normal limits (100 +/- 17 ms) preoperatively. Preoperative LV contraction was highly asynchronous. Endocardial time motion was either early or delayed at the end-systolic phase, yielding P/L loops with abnormal in size, shape, and orientation. Postoperatively, SVR resulted in leftward shifting of P/V loops and increased area; endocardial time motion and P/L loops almost normalized. The hemodynamic consequences of SVR included improved ejection fraction; reduced end-diastolic and end-systolic volume index; more rapid peak filling rate; peak ejection rate and mechanical efficiency resulting in mechanical intraventricular resynchronization that improves LV performance.

Functional ischemic mitral regurgitation in anterior ventricular remodeling: results of surgical ventricular restoration with and without mitral repair.

Ischemic functional mitral regurgitation following ischemic cardiomyopathy is a secondary phenomenon to ventricular dilation, and therapeutic approaches to this complication are not uniform. Solutions to improve mitral function include either mitral repair or observing the effects of coronary revascularization and/or ventricular rebuilding during surgical ventricular restoration (SVR). The present study of 108 patients (comprising 18% of our 588 SVR population) reports the effects of mitral repair following SVR and CABG by comparing geometric, functional, hemodynamic and outcome changes to SVR patients without mitral repair. The degree of mitral regurgitation went from 2.9 +/- 1.2 before to 0.7 +/- 0.7 after SVR and mitral repair. SVR improved EF from 29 +/- 7% to 34 +/- 10% p 0.001; reduced end diastolic volume from 243 +/- 74 to 163 +/- 53 ml and end systolic volume from 170 +/- 63 to 107 +/- 41 ml, p 0.000. Ventricular size and shape geometric measurements improved in all patients, either with and without mitral repair. SVR improved tenting and papillary muscle width between muscle heads in all patients, but alterations in mitral annular size improved only following mitral repair. Preoperative mitral regurgitation occurred in patients with larger ventricular volume and lower ejection fraction and was an independent predictor of operative mortality risk.

Surgical anterior ventricular endocardial restoration (SAVER) in the dilated remodeled ventricle after anterior myocardial infarction. RESTORE group. Reconstructive Endoventricular Surgery, returning Torsion Original Radius Elliptical Shape to the LV.

OBJECTIVES: The goal of this study was to evaluate the safety and efficacy of surgical anterior ventricular endocardial restoration (SAVER). The procedure excludes noncontracting segments in the dilated remodeled ventricle after anterior myocardial infarction. BACKGROUND: Anterior infarction leads to change in ventricular shape and volume. In the absence of reperfusion, dyskinesia develops. Reperfusion by thrombolysis or angioplasty leads to akinesia. Both lead to congestive heart failure by dysfunction of the remote muscle. The akinetic heart rarely undergoes surgical repair. METHODS: A new international group of cardiologists and surgeons from 11 centers (RESTORE group) investigated the role of SAVER in patients after anterior myocardial infarction. From January 1998 to July 1999, 439 patients underwent operation and were followed for 18 months. Early outcomes of the procedure and risk factors were investigated. RESULTS: Concomitant procedure included coronary artery bypass grafting in 89%, mitral valve (MV) repair in 22% and MV replacement in 4%. Hospital mortality was 6.6%, and few patients required mechanical support devices such as intraaortic balloon counterpulsation (7.7%), left ventricular assist device (0.5%) or extracorporeal membrane oxygenation (1.3%). Postoperatively, ejection fraction increased from 29 +/- 10.4 to 39 +/- 12.4%, and left ventricular end systolic volume index decreased from 109 +/- 71 to 69 +/- 42 ml/m2 (p < 0.005). At 18 months, survival was 89.2%. Time related survival at 18 months was 84% in the overall group and 88% among the 421 patients who had coronary artery bypass grafting or MV repair. Freedom from readmission to hospital for congestive heart failure at 18 months was 85%. Risk factors for death at any time after the operation included older age, MV replacement and lower postoperative ejection fraction. CONCLUSIONS: Surgical anterior ventricular endocardial restoration is a safe and effective operation in the treatment of the remodeled dilated anterior ventricle after anterior myocardial infarction.

Copper-induced conformational changes in the N-terminal domain of the Wilson disease copper-transporting ATPase.

The Wilson disease copper-transporting ATPase plays a critical role in the intracellular trafficking of copper. Mutations in this protein lead to the accumulation of a toxic level of copper in the liver, kidney, and brain followed by extensive tissue damage and death. The ATPase has a novel amino-terminal domain ( approximately 70 kDa) which contains six repeats of the copper binding motif GMTCXXC. We have expressed and characterized this domain with respect to the copper binding sites and the conformational consequences of copper binding. A detailed analysis of this domain by X-ray absorption spectroscopy (XAS) has revealed that each binding site ligates copper in the +1 oxidation state using two cysteine side chains with distorted linear geometry. Analysis of copper-induced conformational changes in the amino-terminal domain indicates that both secondary and tertiary structure changes take place upon copper binding. These copper-induced conformational changes could play an important role in the function and regulation of the ATPase in vivo. In addition to providing important insights on copper binding to the protein, these results suggest a possible mechanism of copper trafficking by the Wilson disease ATPase.

Expression, purification, and metal binding properties of the N-terminal domain from the wilson disease putative copper-transporting ATPase (ATP7B).

The putative copper binding domain from the copper-transporting ATPase implicated in Wilson disease (ATP7B) has been expressed and purified as a fusion to glutathione S-transferase. Immobilized metal ion affinity chromatography revealed that the fusion protein is able to bind to columns charged with different transition metals with varying affinities as follows: Cu(II)>>Zn(II)>Ni(II)>Co(II). The fusion protein did not bind to columns charged with Fe(II) or Fe(III). 65Zinc(II) blotting analysis showed that the domain is able to bind Zn(II) over a range of pH values from 6.5 to 9.0. Competition 65Zn(II) blotting showed that Cd(II), Hg(II), Au(III), and Fe(III) can successfully compete with Zn(II), at comparable concentrations, for binding to the domain. In contrast, the domain had little or no affinity for Ca(II), Mg(II), Mn(II), and Ni(II) relative to copper. Neutron activation analysis of the copper bound to the domain showed a copper:protein ratio of 6.5-7.3:1. Both Cu(II) and Cu(I) were found to have a higher affinity for the domain relative to Zn(II). In addition, a sharp, reproducible transition was only observed in competition experiments with copper, which may suggest that copper binding has some degree of cooperativity.