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.

Effects of the Dor procedure on left ventricular dimension and shape and geometric correlates of mitral regurgitation one year after surgery.

OBJECTIVES: In the present study we retrospectively analyzed ventriculographic data from symptomatic patients after myocardial infarction who underwent the Dor procedure (endoventricular circular patch plasty repair) to evaluate left ventricular shape 1 year after the operation and to analyze the geometric correlates of late mitral regurgitation. METHODS: Forty-four patients with previous transmural anterior myocardial infarction comprised the study group. Left ventricular volumes, global left ventricular systolic and diastolic sphericity, the extent of wall motion abnormalities, and the presence and degree of mitral regurgitation were analyzed before and 1 year after operation. RESULTS: Comparing preoperative diastole to systole within the cardiac cycle, left ventricular shape becomes more elliptical in systole than it was in diastole (eccentricity index closer to 1). The intervention leads to an increased diastolic sphericity, but for each cardiac cycle, the systolic shape is more elliptical relative to its diastolic counterpart in respect to basal conditions. Mitral regurgitation was detected after operations in 17 patients; 14 of them did not have mitral regurgitation before operations. Patients with late mitral regurgitation had greater preoperative volumes and more spherical chamber than did patients without late mitral regurgitation. CONCLUSIONS: Despite a more spherical postoperative left ventricular chamber, systolic pump function improves after the Dor procedure, mainly for the improvement in inferior wall shortening. The presence of late mitral regurgitation is relatively frequent in this series of patients, and this emphasizes the importance of a more accurate quantitative evaluation of preoperative functional mitral regurgitation to repair the valve when appropriate. Geometric correlates of late mitral regurgitation appeared to be greater chamber sphericity and larger ventricular volumes preoperatively.

Surgical anterior ventricular endocardial restoration (SAVER) for dilated ischemic cardiomyopathy.

Anterior infarction changes ventricular shape and volume. Akinesia is most commonly observed after early reperfusion. Dyskinesia develops in the absence of reperfusion. Both produce heart failure by dysfunction of the remote muscle. Traditional surgery deals with dyskinesia. This study evaluates surgical anterior ventricular endocardial restoration (SAVER), an operation that excludes the apical and septal scar in both akinesia and dyskinesia. A new international group of cardiologists and surgeons from 13 centers, the RESTORE Group) investigated SAVER in ischemic cardiomyopathy following anterior infarction. From January 1998 to July 2000, 662 patients underwent surgery. Early and 3-year outcomes were investigated. Concomitant procedures included coronary artery bypass grafting (CABG) in 92%, mitral repair in 22%, and mitral replacement in 3%. Hospital mortality was 7.7%. Mortality among 606 patients with SAVER and CABG alone was 4.9%. It was 8.1% among 147 patients who underwent concomitant mitral valve repair. Few patients required IABPs (8.4%), LVADs (0.4%), or ECMO (0.6%). Postoperatively, ejection fraction increased from 29.7% +/- 11.3% to 40.0% +/- 12.3% and left ventricular end systolic volume decreased from 96 +/- 63 to 62 +/- 39 mL/m(2) (P <. 05). At 3 years, the survival rate was 89.4% +/- 1.3%. Survival was lower among those with preoperative volume >80 mL/m(2) compared with volume < or = 80 mL/m(2) (83.5% +/- 3.3% v 94.5% +/- 2.0%). Freedom from readmission to hospital for heart failure was at 88.7% at 3 years and was not related to preoperative volume. SAVER is a safe and effective procedure for treating the remodeled dilated anterior ventricle following anterior myocardial infarction.

Intermediate survival and predictors of death after surgical ventricular restoration.

This study examined the effects of Dor procedure on long-term survival in patients with previous transmural anterior myocardial infarction who were referred to a single experienced center for left ventricular reconstruction by endoventricular patch-plasty repair. Our aim was to evaluate the impact of this procedure on long-term survival and to assess the ability of preoperative, perioperative, and postoperative variables to predict late survival. Major indications for surgery were left ventricular dysfunction, angina, ventricular arrhythmias, or a combination of the three; 20 patients underwent urgent cardiac surgery. The total group was 245 patients, with 8.1% hospital mortality, and 19 patients lost to follow-up [corrected]. The study group comprised 207 patients. Many pre- and postoperative clinical, hemodynamic, and functional variables, as well as operative parameters, were studied by univariate analysis. During a mean follow-up period of 39+/-19 months, 30 end points were observed, including 27 deaths and 3 heart transplants. Event-free survival was 98%+/-1% at 1 year, 95.8%+/-1.4% at 2 years, and 82.1%+/-3.3% at 5 years. Cox regression analysis showed preoperative New York Heart Association functional class, ejection fraction, end systolic volume index, and remote asynergy as independent predictors of mortality. The procedure has a favorable impact on 5-year survival. Independent predictors of late survival are the preoperative functional status and the left ventricular systolic function.

Left ventricular remodeling and functional mitral regurgitation: mechanisms and therapy.

Myocardial damage that results in dysfunction and remodeling changes left ventricular shape and size. Mitral competence requires the functional integrity of all components of the mitral apparatus. Progressive remodeling ultimately leads to geometric distortion of multiple elements of the mitral apparatus, resulting in functional mitral regurgitation (MR). In this article, we examine the mechanisms of functional MR in the remodeled ventricle. Surgical treatment should aim to correct all abnormalities of the mitral apparatus. These include (1) revascularization of viable myocardium, (2) reduction of ventricular volume and restoration of shape, (3) realignment of papillary muscles, and (4) reduction of annular orifice size.

Changes in left ventricular mass and volumes in patients receiving angiotensin-converting enzyme inhibitor therapy for left ventricular dysfunction after Q-wave myocardial infarction.

OBJECTIVES: We evaluated global and segmental left ventricular (LV) mass and LV mass/volume ratio in patients with LV dysfunction receiving angiotensin-converting enzyme (ACE) inhibitor therapy after acute myocardial infarction (MI). BACKGROUND: ACE inhibitors attenuate LV dilatation and compensatory hypertrophy after acute MI in animal models. However, LV remodeling in patients after acute MI has been largely defined on the basis of changes in chamber volume alone. METHODS AND RESULTS: Twenty-nine patients with LV ejection fraction <40% received the ACE inhibitor ramipril (range 2.5 to 20 mg/day) within 5 days of their first Q-wave MI. Magnetic resonance imaging was performed at baseline and at 3 months, providing global and regional LV volumes and mass from summated serial short-axis slices. Mean arterial blood pressure was unchanged from baseline to 3-month follow-up (89 +/- 10 to 92 +/- 17 mm Hg). LV mass decreased (90 +/- 25 to 77 +/- 21 gm/m2, p < 0.0005) as LV end-diastolic volumes increased (65 +/- 13 to 73 +/- 22 ml/m2, p < 0.01). Global LV mass to volume ratio decreased from 1.40 +/- 0.28 to 1.08 +/- 0.18 gm/ml (p < 0.0001), as did circumferential wall thickness to volume ratio of noninfarcted myocardium at the base of the LV (0.06 +/- 0.02 to 0.05 +/- 0.02 mm/ml, p < 0.001). LV ejection fraction increased from 35 +/- 6 to 40 +/- 9% (p < 0.001) in the presence of an increase in calculated end-systolic wall stress (185 +/- 57 to 227 +/- 54 gm/cm2, p < 0.01). CONCLUSIONS: ACE inhibitor therapy was associated with improved LV function in the face of a decrease in mass to volume ratio of the LV as well as a decrease in wall thickness to volume ratio of noninfarcted myocardium. Whether ACE inhibitor therapy had direct or indirect effects on these changes in LV mass and function are open questions that require further investigation.

Restoration of contractile function in the enlarged left ventricle by exclusion of remodeled akinetic anterior segment: surgical strategy, myocardial protection, and angiographic results.

A variant of the Dor cardioprotective approach for reducing ventricular volume was applied to 12 consecutive postinfarction patients with akinetic anterior segments. Cardioplegia was avoided for restoration, but used for revascularization and valve replacement. The continually perfused beating open heart was used for protection during surgical anterior ventricular restoration (SAVR). These ischemic cardiomyopathy patients (age 77 +/- 6 years) preoperatively had high LVEDVI (170 vs 75 mL/m2, normal) and LVESVI (132 vs 25 mL/m2, normal) and 20 +/- 8% ejection fraction (mean +/- S.D.). An oval patch with outer flange for hemostasis was used. Patients also underwent revascularization (10/12), reoperation (6/12), and valve procedures (6/12). Continuous perfusion of the beating open heart was used for cardiac protection during restoration. Blood cardioplegia was used for revascularization and valvular procedures. Transesophageal echocardiogram (TEE) estimated intraventricular contractility in all patients, and biplane ventriculograms were used in 8 patients to measure cardioreduction. Immediate hemodynamic performance was excellent in all patients, despite 178 +/- 34 minutes of bypass. Extracorporeal circulation was stopped 10 minutes after closing the ventriculotomy. No intraaortic balloon pump or LV assist devices were needed. Ejection fraction estimated by TEE increased from 20% to 45%; and biplane ventriculograms showed 28% reduction of LVEDVI, 39% reduction of LVESVI, and raised ejection fraction from 20% to 35%. The spherical ventricular shape after akinetic infarction was made into a more normal elliptical contour by this procedure. Subsequently, restoration may become as important as revascularization in treating akinetic segments after anterior infarction.

Angiotensin-converting enzyme inhibitor therapy affects left ventricular mass in patients with ejection fraction > 40% after acute myocardial infarction.

OBJECTIVES: We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy decreases left ventricular (LV) mass in patients with a left ventricular ejection fraction (LVEF) > 40% and no evidence of heart failure after their first acute Q wave myocardial infarction (MI). BACKGROUND: Recently, ACE inhibitor therapy has been shown to have an early mortality benefit in unselected patients with acute MI, including patients without heart failure and a LVEF > 35%. However, the effects on LV mass and volume in this patient population have not been studied. METHODS: Thirty-five patients with a LVEF > 40% after their first acute Q wave MI were randomized to titrated oral ramipril (n = 20) or conventional therapy (control, n = 15). Magnetic resonance imaging (MRI) performed an average of 7 days and 3 months after MI provided LV volumes and mass from summated serial short-axis slices. RESULTS: Left ventricular end-diastolic volume index did not change in ramipril-treated patients (62 +/- 16 [SD] to 66 +/- 17 ml/m2) or in control patients (62 +/- 16 to 68 +/- 17 ml/m2), and stroke volume index increased significantly in both groups. However, LV mass index decreased in ramipril-treated patients (82 +/- 18 to 73 +/- 19 g/m2, p = 0.0002) but not in the control patients (77 +/- 15 to 79 +/- 23 g/m2). Systolic arterial pressure did not change in either group at 3-month follow-up. CONCLUSIONS: In patients with a LVEF > 40% after acute MI, ramipril decreased LV mass, and blood pressure and LV function were unchanged after 3 months of therapy. Whether the decrease in mass represents a sustained effect that is associated with a decrease in morbid events requires further investigation.

Hyperbaric oxygen limits infarct size in ischemic rabbit myocardium in vivo.

BACKGROUND: We explored the ability of increased oxygen pressure to modify necrosis in an open-chest rabbit model of myocardial ischemia and reperfusion. METHODS AND RESULTS: A branch of the left coronary artery was occluded for 30 minutes followed by 3 hours of reperfusion. Infarction was measured by triphenyl tetrazolium staining and expressed as a percentage of the ischemic zone. Untreated rabbits were ventilated with 100% oxygen at 1 atm absolute. Treatment animals were exposed to hyperbaric oxygen at 2.5 atm absolute. The 1.0-atm control hearts developed 41.5 +/- 4.6% infarction of the ischemic zone. Animals exposed to hyperbaric oxygen during ischemia only, reperfusion only, or ischemia and reperfusion had significantly smaller infarcts with respect to control animals (16.2 +/- 2.9%, 14.5 +/- 3.7%, and 9.8 +/- 2.7%, respectively; P < or = .01), indicating that they had been protected by the procedure. When hyperbaric oxygen was begun 30 minutes after the onset of reperfusion, no protection was seen (35.8 +/- 3.8%). CONCLUSIONS: We conclude that hyperbaric oxygen limits infarct size in the reperfused rabbit heart and that the effect can be achieved when hyperbaric oxygen is begun at reperfusion.

Ischaemic preconditioning is not dependent on neutrophils or glycolytic substrate at reperfusion in rabbit heart.

OBJECTIVE: The aim was to determine whether reperfusion with either neutrophil free reperfusate or perfusate containing only pyruvate as the metabolic substrate would alter the protection against infarction afforded by preconditioning. METHODS: Rabbit hearts (n = 4-14 per group) underwent 30 minutes of regional ischaemia followed by 120 minutes of reperfusion. Blood reperfused groups experienced both ischaemia and reperfusion in situ while Krebs reperfused groups experienced regional ischaemia in situ but were reperfused with Krebs buffer in vitro. In another group, glucose in Krebs buffer was replaced by pyruvate. RESULTS: Preconditioning with 5 minutes regional ischaemia caused smaller infarct size in the blood reperfused hearts: 43.0(SEM 5.4)% v 8.8(4.2)%. In Krebs reperfused hearts, preconditioning caused a similar reduction of infarct size [49.9(2.5)% v 22.9(4.3)%] which was not different from that seen in the blood reperfused hearts. Replacing the glucose in the Krebs buffer by pyruvate also had no effect on infarct size in either the control or the preconditioned hearts [40.9(6.1)% v 11.8(5.2)%]. Histology of the ischaemic zones revealed 59.6(15.0) neutrophils per 10 high power fields in hearts reperfused in situ but only 2.6(0.6) in Krebs reperfused hearts, equal to the numbers in nonischemic blood perfused myocardium [2.8(0.9)]. CONCLUSIONS: The mechanism of preconditioning is not due to attenuation of neutrophil function during reperfusion. Furthermore, substituting pyruvate for glucose in the reperfusate did not prevent the protection against infarction afforded by ischaemic preconditioning.

Cyclooxygenase products are not involved in the protection against myocardial infarction afforded by preconditioning in rabbit. Cyclooxygenase pathway's involvement in preconditioning.

The mechanism whereby preconditioning with a transient period of ischemia renders the heart resistant to infarction from a subsequent ischemic insult is unknown. The purpose of this study was to determine whether cyclooxygenase pathways are involved in preconditioning's protection. Two inhibitors of that pathway, meclofenamate (MEC) and aspirin (ASP), were test in an in situ and a blood perfused isolated heart model, respectively. Preconditioning was achieved with 5 minute ischemia and 10 minutes reperfusion. All in situ hearts underwent 30 minute ischemia followed by 180 minute reperfusion, while the isolated hearts experienced 45 minute ischemia plus 120 minute reperfusion. Infarct size was measured with TTC stain. In the in situ model, 39.9% +/- 4.2% of the ischemic zone was infarcted in control hearts but only 8.8% +/- 2.2% in preconditioning hearts. Pretreatment with MEC (5 mg/Kg) caused no alteration of infarct size in either non preconditioned (34.3% +/- 8.3%) or preconditioned hearts (6.7% +/- 3.3%). In isolated hearts, 45 minute ischemia caused 31.0% +/- 5.9% of the ischemic zone to be infarcted in control hearts and only 5.4% +/- 2.2% in preconditioned hearts. Pretreatment with ASP (1 mg/Kg) failed to affect infarct size in either non preconditioned (35.7% +/- 3.7%) or preconditioned hearts (10.2% +/- 1.9%). The data indicate that cyclooxygenase pathways are not involved in the preconditioning's protection.

Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart.

BACKGROUND: Preconditioning (5 minutes of ischemia followed by 10 minutes of recovery) renders the heart very resistant to infarction from subsequent ischemia. This study tests whether adenosine receptors might mediate preconditioning protection. METHODS AND RESULTS: We examined the effect on infarct size of pretreatment with either of two adenosine receptor antagonists in both control and preconditioned in situ rabbit hearts. Hearts underwent 30 minutes of regional ischemia plus 3 hours of reperfusion, and infarct size was measured with tetrazolium. Infarct size averaged 39% of the zone at risk in controls but only 8% in preconditioned hearts. Preconditioned and nonpreconditioned hearts receiving either blocker had infarcts not different in size from the controls. A 5-minute intracoronary infusion of adenosine was as effective as 5 minutes of ischemia in protecting parabiotically perfused isolated hearts against infarction from a 45-minute ischemic insult. Similarly, intracoronary infusion of N6-1-(phenyl-2R-isopropyl)adenosine, an A1-selective adenosine receptor agonist, at a dose that delayed conduction but did not dilate the coronary vessels, also limited infarct size. The protection disappeared when we reduced the coronary concentration of drug by intravenous infusion of adenosine, indicating that cardiac rather than peripheral receptors were involved in the protection. CONCLUSIONS: We conclude that adenosine released during the preconditioning occlusion stimulates cardiac A1 receptors, which leaves the heart protected against infarction even after the adenosine has been withdrawn.

Examination of two small-molecule antiperoxidative agents in a rabbit model of postischemic myocardial infarction.

Peroxidation of membrane phospholipid may be a causal contributor to the development of irreversible postischemic myocardial injury. In this study, two small-molecule antiperoxidative agents were tested for their ability to salvage reperfused rabbit myocardium and reduce infarct size as assessed by direct histological evaluation of hearts following a 30-min occlusion of a coronary arterial branch and a 72-h reperfusion period. The compounds tested are novel analogs of alpha-tocopherol (vitamin E), and share with the parent compound an ability to scavenge the peroxyl radicals that propagate and amplify lipid peroxidation initiated by partially reduced oxygen; however, the new analogs are significantly more potent peroxyl-radical scavengers that alpha-tocopherol. Each antiperoxidant (3 mg/kg) was administered by intravenous bolus injection in two stages: 20% of the total dose was given 15 min before occlusion, and the remaining 80% was given 5 min before reperfusion. The results revealed that neither antiperoxidant offered a sustained reduction in infarct size (expressed as a percentage of the region at risk) as compared to a nontreated vehicle control. The implications of the present study with respect to the purported cardioprotective effects of antiperoxidants in the setting of ischemia reperfusion and the pathogenic role of lipid peroxidation in the postischemic heart are discussed.

Inhibition of protein synthesis does not block myocardial protection afforded by preconditioning.

It is currently unknown how preconditioning the heart with brief periods of ischemia makes it resistant to infarction from a subsequent ischemic insult. The protein synthesis inhibitors, cycloheximide and actinomycin D, were used to determine whether preconditioning involves synthesis of a protective protein. Ischemia was produced by occlusion of a branch of the left coronary artery in open-chest anesthetized rabbits. All groups were subjected to 30 min of ischemia followed by 3 h of reperfusion. The first two groups served as noninhibited controls. Group 1 was subjected to ischemia with no preconditioning. Group 2 was preconditioned with two 5-min ischemic periods each followed by 10 min of reperfusion, before the 30-min ischemic period. Groups 3 and 4 were the same as groups 1 and 2, respectively, except that cycloheximide was administered before coronary occlusion. Groups 5 and 6 were also the same as groups 1 and 2 except that actinomycin D was administered before coronary occlusion. After 3 h of reperfusion all hearts were removed and the size of the ischemic zone and infarct were determined. The percent of the ischemic zone infarcted was small and similar in all preconditioned groups (3.3 +/- 1.1% for group 2, 7.4 +/- 3.3% for group 4, and 0.5 +/- 0.7% for group 6). All nonpreconditioned groups had large infarcts with no differences between groups (39.0 +/- 8.5% for group 1, 31.6 +/- 6.3% for group 3, 30.8 +/- 5.9% for group 5). Because neither cycloheximide nor actinomycin D could block protection afforded by preconditioning, it seems unlikely that synthesis of a protective protein is the mechanism of protection.

A reappraisal of surgical intervention for acute myocardial infarction.

Eighty-three patients underwent coronary artery bypass during acute evolving myocardial infarction 6.8 +/- 2.8 hours after the onset of symptoms. Linear discriminant analysis of preoperative variables identified predictors of mortality with an accuracy of 84%. Significant predictors in decreasing order of importance were cardiogenic shock, age over 65 years, left ventricular ejection fraction less than or equal to 0.30, cardiac index less than or equal to 2.0 L/min/m2, and absent collateral flow. Time to reperfusion did not influence outcome nor did the infarct-related artery. Hospital mortality was 15.6% (13/83). Among 51 low-risk patients under 65 years of age without cardiogenic shock, there were three deaths (5.9%). Follow-up angiography was performed in 21 patients. The graft patency rate was 94%. Left ventricular ejection fraction improved from 0.39 +/- 0.10 to 0.49 +/- 0.11 (p less than 0.05). Left ventricular end-systolic volume decreased from 53.2 +/- 19.3 ml/m2 to 41.4 +/- 16.8 ml/m2 (p less than 0.05), and end-diastolic volume remained unchanged: 86.2 +/- 21.2 ml/m2 before operation and 78.7 +/- 24.0 ml/m2 after operation (no significant difference). Regional ejection fraction of the infarct area, determined by the centerline method, increased 0.23 +/- 0.15. In contrast, among 215 patients treated by nonsurgical reperfusion (intracoronary thrombolysis or angioplasty, or both), mortality was 13.5%. In this group, reperfusion was successful in 144 patients (67%) and 89 underwent follow-up angiography. Persistent patency of the infarct artery was demonstrated in 73 (82%). Ejection fraction increased from 0.45 +/- 0.10 to 0.50 +/- 0.15 (p less than 0.05). We conclude that preoperative variables enable identification of patients with evolving acute myocardial infarction in whom coronary artery bypass is associated with low operative mortality and improved ventricular performance.