Constantine L. Athanasuleas

Surgical anterior ventricular endocardial restoration (SAVER) in the dilated remodeled ventricle after anterior myocardial infarction

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.

Surgical Ventricular Restoration: The RESTORE Group Experience

Congestive heart failure may be caused by late left ventricular (LV) dilation following anterior infarction. Early reperfusion prevents transmural necrosis, and makes the infarcted segment akinetic rather than dyskinetic. Surgical ventricular restoration (SVR) reduces LV volume and creates a more elliptical chamber by excluding scar in either akinetic or dyskinetic segments.The international RESTORE group applied SVR in a registry of 1198 post-infarction patients between 1998 and 2003. Early and late outcomes were examined and risk factors identified.Concomitant procedures included coronary artery bypass grafting in 95%, mitral valve repair in 22%, and mitral valve replacement in 1%. Overall 30-day mortality after SVR was 5.3% (8.7% with mitral repair vs. 4.0% without repair, p < .001) Perioperative mechanical support was uncommon (< 9%).Global systolic function improved postoperatively, as ejection fraction increased from 29.6 ± 11.0% to 39.5 ± 12.3% (p < .001) and left ventricular end systolic volume index decreased from 80.4 ± 51.4 ml/m2 to 56.6 ± 34.3 ml/m2 (p < .001). Overall 5-year survival was 68.6 ± 2.8%, Logistic regression analysis identified EF ≤ 30%, LVESVI ≥ 80 ml/m2, advanced NYHA functional class, and age ≥75 years as risk factors for death. Five-year freedom from hospital readmission for CHF was 78%. Preoperatively, 67% of patients were class III or IV, and postoperatively 85% were class I or II.SVR improves ventricular function and is highly effective therapy in the treatment of ischemic cardiomyopathy with excellent 5-year outcome.

The STICH trial: misguided conclusions.

gestive heart failure (CHF) after ischemic dilated cardiomyopathy following myocardial infarction because the authors conclude that adding surgical ventricular reconstruction to reduce ventricular volume to coronary artery bypass grafting (CABG) does not improve symptoms or exercise tolerance and fails to lower death rate or cardiac rehospitalization. The original study examined the role of surgical ventricular reconstruction or ‘‘surgical ventricular restoration’’ (SVR) in the dilated ventricles of patients with CHF with regional scar after anterior myocardial infarction (Figure 1). The adverse effects of dilatation are codified by White and associates 2 (Figure 2,A), who showed that increased ventricular volume rather than altered ejection fraction became the principal surrogate for mortality. Dor 3 showed that the SVR procedure excludes the underlying culprit scar that causes stretch of compensating remote muscle, identified similar regional noncontraction from either aneurysm or akinetic segments that received thrombolysis or angioplasty, and demonstrated that rebuilding left ventricular (LV) size and shape toward normal improves cardiac efficiency by restoring remote muscle function. The keynote finding of similarly absent function in aneurysm without reperfusion (in which the thinned scar collapses during venting) and akinesia after reperfusion (in which the thick myocardium with inner shell scar is covered by normal anterior myocardium that does not collapse during venting) introduced a ‘‘new SVR target’’ and initiates ‘‘a learning curve’’ for procedure application. SVR after CABG is based on an international database registry of more than 5000 patients. 3-5 This database (Figure 3) demonstrates favorable survival compared with CHF natural history studies 6 and a CABG patient cohort whose abnormal ejection fraction and class III/IV New York Heart Association classification matched the RESTORE (Reconstructive Endoventricular Surgery, returning Torsion Original Radius Elliptical Shape) group registry cohort 4,7 in National Heart, Lung, and Blood Institute STICH grant application and the worldwide SVR registry. A prospective randomized trial was designed for ‘‘evidence based medicine’’ confirmation. The 490 STICH trial patients requiring SVR did not show survival or rehospitalization differences compared with the greater than 5000 patient registry SVR database, thereby raising this question: Is SVR an improper concept or did the STICH trial have improper execution? The solution to this question will determine whether STICH results provide credible data that guide the treatment of patients with CHF. We conclude that it did not, and this editorial supports this deduction with trial evidence, reports casualties of the STICH findings, poses new questions requiring answers, and outlines future STICH report meaningful data analysis that may properly respond to grant questions.

Surgical ventricular restoration for the treatment of heart failure

Heart failure (HF) is an emerging epidemic affecting 15 million people in the USA and Europe. HF-related mortality was unchanged between 1995 and 2009, despite a decrease in the incidence of cardiovascular disease. Conventional explanations include an aging population and improved treatment of acute myocardial infarction and HF. An adverse relationship between structure and function is the central theme in patients with systolic dysfunction. The normal elliptical ventricular shape becomes spherical in ischemic, valvular, and nonischemic dilated cardiomyopathy. Therapeutic decisions should be made on the basis of ventricular volume rather than ejection fraction. When left ventricular end-systolic volume index exceeds 60 ml/m2, medical therapy, CABG surgery, and mitral repair have limited benefit. This form–function relationship can be corrected by surgical ventricular restoration (SVR), which returns the ventricle to a normal volume and shape. Consistent early and late benefits in the treatment of ischemic dilated cardiomyopathy with SVR have been reported in >5,000 patients from various international centers. The prospective, randomized STICH trial did not confirm these findings and the reasons for this discrepancy are examined in detail. Future surgical options for SVR in nonischemic and valvular dilated cardiomyopathy, and its integration with left ventricular assist devices and cell therapy, are described.

The STICH trial unravelled

The STICH trial was designed to compare coronary bypass (CABG) alone vs. CABG plus surgical ventricular reconstruction (SVR) in patients with left ventricular (LV) dysfunction and akinetic or dyskinetic LV segments from prior anterior wall myocardial infarction (MI). It reported that adding SVR to coronary bypass CABG was not associated with a greater improvement in symptoms, exercise tolerance, or reduced intermediate mortality. This trial was federally funded to provide evidence-based methodology for this comparison, but its implementation was faulty in many ways. Surgical ventricular reconstruction treats congestive heart failure (CHF) by reducing LV volume, perhaps the most powerful predictor of mortality in dilated cardiomyopathy and more predictive than ejection fraction (EF) –4 (Figures 1 and 2). The 490 patients who underwent SVR in STICH was predicated on favourable reports of recovery in over 5000 patients worldwide and registry data from approximately 1200 patients that decreased LV endsystolic volume index (LVESVI) 40% (ranging 30–58%, Table 1), –8 but had different results. Is SVR an improper concept or was the STICH trial improperly executed? Eligibility for STICH required that ‘all patients will be evaluated further for appropriateness of SVR indicated by evidence of absent viability in the anterior ventricle by nuclear scan determination, LVESVI ≥60 ml/m, and akinesia ≥35% of the anterior wall’ (http://clinicaltrials.gov/archine/NTC00023595/2005_06_23). Echocardiography was specifically excluded for measuring LV volume because of its inaccuracy when regional asynergy is present. Selection of STICH centres was based on capability to measure volume by cardiac magnetic resonance (CMR) imaging (Excerpt 1). However, STICH enrolled a quite different group of patients, namely those with NYHA Class II– IV CHF (within 3 months of entry), coronary artery disease that was amenable to CABG, an EF ≤35% [defined by echocardiogram, left ventriculogram, CMR, or gated single photon (SPECT) studies], and ‘dominant anterior left ventricular dysfunction’. Accurate viability and LV volume were not done in all patients as planned. STICH required that all patients have dyskinesia or akinesia with evidence of non-viability in 35% of the anterior ventricular wall (Excerpt 2). Dyskinesia is caused by no reperfusion of the LV after infarction. Akinesia accompanies early thrombolysis or angioplasty and results in a dilated but thick LV. STICH, however, reports that only half of patients had akinesia or dyskinesia and 13% had no prior history of infarction. Surgical ventricular reconstruction has never been reported or recommended in patients with regional dysfunction alone and absent scar. The STICH surgical therapy committee specifically defined SVR as ‘any ventricular reconstruction method that consistently results in a low operative mortality, an average EF increase of ≥10%, and an average LVESVI decrease of ≥30% as assessed on the four-month post-operative CMR measurement’ (Excerpt 3). STICH, however, measured LVESVI in only 212 of 490 patients (43%) in the CABG-only group and in 161 of 490 patients (33%) in the CABG plus SVR group by echocardiography. The number of CMR measurements is not given. STICH reported that SVR lowered LVESVI an average of only 19%. Patients should be excluded from the analysis if the originally defined goals were not met. Patients in the SVR trial underwent SVR based on qualitative rather than quantitative assessment. Perhaps they had hibernation of ischaemic areas or post-infarction stunning, both of which are clearly not indications for SVR. Surgeons cannot know when SVR should be performed without accurate viability and volume information. The STICH patients cannot be compared with previously reported patients with SVR. Dor’s 1000 patients and the 1198 patients in the RESTORE group had prior history of MI, akinesia, or dyskinesia involving ≥35% of the LV, reduced EF, and LVESVI ≥60 mL/m. Furthermore, only 49% of patients in STICH had NYHA class III or IV CHF vs. .66% in the RESTORE registry. STICH trial original protocol deviations can be viewed in ‘history of changes’ on: http://clinicaltrials.gov/show/NCT00023595. Why was accurate LVESVI by CMR or nuclear study retracted? The principal investigator may change the protocol, but only with approval from the NIH grant administration officer. Though it does not require approval from other trial participants, the grant administrator must assume the responsibility for investigational review board (IRB) notification of changes for all trial participants. The STICH publication does not report changes during the trial.

Surgical ventricular reconstruction.

To the Editor: Jones et al. (April 23 issue)1 discount the possibility that the selection of patients was a factor in the negative outcome of the Surgical Treatment for Ischemic Heart Failure (STICH) trial (ClinicalTrials.gov number, NCT00023595). Their argument, however, would be much strengthened by providing information on the clinical profile and number of patients who were eligible for the trial but were not enrolled. Such information is sorely needed to determine the generalizability of the findings of a trial in which the yearly recruitment averaged only three patients per site.

Effects of antegrade versus integrated blood cardioplegia on left ventricular function evaluated by echocardiographic real-time 3-dimensional speckle tracking

OBJECTIVE The objective of this study was to evaluate left ventricular free wall and interventricular septal function by 2-dimensional transthoracic echocardiography and live/real-time 3-dimensional transthoracic speckle tracking echocardiography before and after on-pump cardiac surgery and to assess the effect of mode of cardioplegia delivery. METHODS A total of 22 patients were studied 1 day before and 4 to 5 days after surgery. Cold blood cardioplegia was delivered by intermittent antegrade infusion or by the integrated method. The latter includes a combination of intermittent antegrade and retrograde cardioplegia with a terminal warm amino acid-enriched reperfusion. RESULTS The overall group displayed significant deterioration of septal function after surgery by 2-dimensional transthoracic echocardiography, as assessed by wall motion score index, yet subgroup analysis by 3-dimensional transthoracic speckle tracking echocardiography permitted distinction of outcomes achieved by antegrade or integrated delivery methods. Analysis after surgery showed that only the antegrade group displayed statistically significant deterioration in the strain parameters of some of the segments of the septum and free wall when strain was measured in the free wall and septum in the longitudinal, circumferential, and radial modes of deformation (P < .05). In contrast, only the integrated group displayed significant improvement in global radial, circumferential, and longitudinal strain (P < .05). CONCLUSIONS These findings by 3-dimensional transthoracic speckle tracking echocardiography indicate that integrated cardioplegia offers superior myocardial protection of the left ventricular free wall and septum compared with the antegrade mode of cardioplegia delivery.

The effect of prophylactic nitroglycerin infusion on the incidence of regional wall-motion abnormalities and ST segment changes in patients undergoing coronary artery bypass surgery.

Abstract The effects of nitroglycerin (NTG) on regional wall‐motion abnormalities, ST segment changes, and the incidence of myocardial infarction (MI), cardiac failure, and mortality were studied in 30 patients undergoing coronary artery bypass. Patients received continuous infusions of either normal saline or NTG (1 μg/kg per min [low dose] or 2 μg/kg per min [high dose]) beginning at anesthesia and continuing for 4 hours postoperatively. The occurrence of wall‐motion abnormalities as detected by transesophageal echocardiography was 38 events in the normal saline group (N = 10). Significantly fewer events (p < 0.05) were recorded in the low dose and high dose NTG groups (20 events and 15 events, respectively) compared to controls. There were no significant differences between the control and NTG groups with regard to the incidence of Holter ST segment events or the incidence of MI, cardiac failure, or cardiac death. NTG reduced the incidence of echocardiographic wall‐motion abnormalities in a dose dependent manner while having no significant effect on other parameters examined.

Resuscitation in cardiac surgical patients: Symptoms versus cause

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Surgical Restoration of the Postinfarction Dilated Ventricle

Surgical restoration of the failing heart is related to rebuilding cardiac architecture and linked to: (a) understanding that the structure of the failing dilated heart involves changing the normal elliptic shape toward a dilated spherical form; (b) recognizing the anatomic fiber orientation framework and its functional implications; (c) establishing imaging measurement guidelines to determine indications for surgical intervention that focus upon volume and remote muscle evaluation rather than ejection fraction; and (d) summarizing left ventricular restoration results whereby rebuilding normal elliptic configuration improves function, reduces ventricular arrhythmias, alleviates mechanical dyssynchrony, and causes progressive improvement that extends long-term prognosis.