Coronary-artery bypass surgery in patients with ischemic cardiomyopathy

BACKGROUND The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to guideline-directed medical therapy, as compared with medical therapy alone, in patients with coronary artery disease, heart failure, and severe left ventricular systolic dysfunction remains unclear. METHODS From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35% or less and coronary artery disease amenable to CABG were randomly assigned to undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy alone (medical-therapy group, 602 patients). The primary outcome was death from any cause. Major secondary outcomes included death from cardiovascular causes and death from any cause or hospitalization for cardiovascular causes. The median duration of follow-up, including the current extended-follow-up study, was 9.8 years. RESULTS A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in 398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524 patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82; P<0.001 by log-rank test). CONCLUSIONS In a cohort of patients with ischemic cardiomyopathy, the rates of death from any cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were significantly lower over 10 years among patients who underwent CABG in addition to receiving medical therapy than among those who received medical therapy alone. (Funded by the National Institutes of Health; STICH [and STICHES] ClinicalTrials.gov number, NCT00023595.

Coronary bypass surgery with or without surgical ventricular reconstruction

Coronary bypass surgery with or without surgical ventricular reconstruction. Jones RH, Velazquez EJ, Michler RE, Sopko G, Oh JK, O'Connor CM, Hill JA, Menicanti L, Sadowski Z, Desvigne-Nickens P, Rouleau JL, Lee KL; STICH Hypothesis 2 Investigators. Collaborators (379)Bochenek A, Krejca M, Trusz-Gluza M, Wita K, Zembala M, Przybylski R, Kukulski T, Cherniavsky A, Marchenko A, Romanov A, Wos S, Deja M, Golba K, Kot J, Rao V, Iwanochko M, Renton J, Hemeon S, Rogowski J, Rynkiewicz A, Betlejewski P, Sun B, Crestanello J, Binkley P, Chang J, Ferrazzi P, Gavazzi A, Senni M, Sadowski J, Kapelak B, Sobczyk D, Wrobel K, Pirk J, Jandova R, Velazquez E, Smith P, Milano C, Adams P, Menicanti L, Di Donato M, Castelvecchio S, Dagenais F, Dussault G, Dupree C, Sheridan B, Schuler C, Yii M, Prior D, Mack J, Racine N, Bouchard D, Ducharme A, Lavoignat J, Maurer G, Grimm M, Lang I, Adlbrecht C, Religa Z, Biederman A, Szwed H, Sadowski Z, Rajda M, Ali I, Howlett J, MacFarlane M, Siepe M, Beyersdorf F, Cuerten C, Wiechowski S, Mokrzycki K, Hill J, Beaver T, Olitsky D, Bernstein V, Janusz M, O'Neill V, Grayburn P, Hebeler R, Hamman B, Aston S, Gradinac S, Vukovic M, Djokovic L, Benetis R, Jankauskiene L, Friedrich I, Buerke M, Paraforos A, Quaini E, Cirillo M, Chua L, Lim C, Kwok B, Kong S, Stefanelli G, Labia C, Bergh C, Gustafsson C, Daly R, Rodeheffer R, Nelson S, Maitland A, Isaac D, Holland M, Di Benedetto G, Attisano T, Sievers H, Schunkert H, Stierle U, Haddad H, Hendry P, Donaldson J, Birjiniuk V, Harrington M, Nawarawong W, Woragidpunpol S, Kuanprasert S, Mekara W, Konda S, Neva C, Hathaway W, Groh M, Blakely J, Lamy A, Demers C, Rizzo T, Drazner M, DiMaio J, Joy J, Benedik J, Marketa K, Beghi C, De Blasi M, Helou J, Dallaire S, Kron I, Kern J, Bergin J, Phillips J, Aldea G, Verrier E, Harrison L, Piegas L, Paulista P, Farsky P, Veiga-Kantorowitz C, Philippides G, Shemin R, Thompson J, White H, Alison P, Stewart R, Clapham T, Rich J, Herre J, Pine L, Kalil R, Nesralla I, Santos M, Pereira de Moraes M, Michler R, Swayze R, Arnold M, McKenzie N, Smith J, Nicolau J, Oliveira S, Stolf N, Ferraz M, Filgueira J, Batlle C, Rocha A, Gurgel Camara A, Huynh T, Cecere R, Finkenbine S, St-Jacques B, Ilton M, Wittstein I, Conte J, Breton E, Panza J, Boyce S, McNulty M, Starnes V, Lopez B, Biederman R, Magovern J, Dean D, Grant S, Hammon J, Wells G, De Pasquale C, Knight J, Healy H, Maia L, Souza A, McRae R, Pierson M, Gullestad L, Sorensen G, Murphy E, Ravichandran P, Avalos K, Horowitz J, Owen E, Ascheim D, Naka Y, Yushak M, Gerometta P, Arena V, Borghini E, Johnsson P, Ekmehag B, Engels K, Rosenblum W, Swayze R, Amanullah A, Krzeminska-Pakula M, Drozdz J, Larbalestier R, Wang X, Busmann C, Horkay F, Szekely L, Keltai M, Hetzer R, Knosalla C, Nienkarken T, Chiariello L, Nardi P, Arom K, Ruengsakulrach P, Hayward C, Jansz P, Stuart S, Oto O, Sariomanoglu O, Dignan R, French J, Gonzalez M, Edes I, Szathmarine V, Yakub M, Sarip S, Alotti N, Lupkovics G, Smedira N, Pryce J, Cokkinos D, Palatianos G, Kremastinos D, Stewart R, Rinkes L, Esrig B, Baptiste M, Booth D, Ramaiah C, Ferraris V, Menon S, Martin L, Couper G, Rosborough D, Vanhaecke J, Strijckmans A, Carson P, Dupree C, Miller A, Pina I, Selzman C, Wertheimer J, Goldstein S, Cohn F, Hlatky M, Kennedy K, Rankin S, Robbins R, Zaret B, Rouleau J, Desvigne-Nickens P, Jones R, Lee K, Michler R, O'Connor C, Oh J, Rankin G, Velazquez E, Hill J, Beyersdorf F, Bonow R, Desvigne-Nickens P, Jones R, Lee K, Oh J, Panza J, Rouleau J, Sadowski Z, Velazquez E, White H, Jones R, Velazquez E, O'Connor C, Rankin G, Sellers M, Sparrow-Parker B, McCormick A, Albright J, Dandridge R, Rittenhouse L, Wagstaff D, Wakeley N, Burns S, Williams M, Bailey D, Parrish L, Daniels H, Grissom G, Medlin K, Lee K, She L, McDaniel A, Lokhnygina Y, Greene D, Moore V, Pohost G, Agarwal S, Apte P, Bahukha P, Chow M, Chu X, Doyle M, Forder J, Ocon M, Reddy V, Santos N, Tripathi R, Varadarajan P, Oh J, Blahnik F, Bruce C, Lin G, Manahan B, Miller D, Miller F, Pellikka P, Springer R, Welper J, Wiste H, Mark D, Anstrom K, Baloch K, Burnette A, Clapp-Channing N, Cowper P, Davidson-Ray N, Drew L, Harding T, Hunt V, Knight D, Patterson A, Redick T, Sanderford B, Feldman A, Bristow M, Chan T, Diamond M, Maisel A, Mann D, McNamara D, Bonow R, Berman D, Helmer D, Holly T, Leonard S, Woods M, Panza J, McNulty M, Grayburn P, Aston S. SourceDuke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA. [email protected] Abstract BACKGROUND: Surgical ventricular reconstruction is a specific procedure designed to reduce left ventricular volume in patients with heart failure caused by coronary artery disease. We conducted a trial to address the question of whether surgical ventricular reconstruction added to coronary-artery bypass grafting (CABG) would decrease the rate of death or hospitalization for cardiac causes, as compared with CABG alone. METHODS: Between September 2002 and January 2006, a total of 1000 patients with an ejection fraction of 35% or less, coronary artery disease that was amenable to CABG, and dominant anterior left ventricular dysfunction that was amenable to surgical ventricular reconstruction were randomly assigned to undergo either CABG alone (499 patients) or CABG with surgical ventricular reconstruction (501 patients). The primary outcome was a composite of death from any cause and hospitalization for cardiac causes. The median follow-up was 48 months. RESULTS: Surgical ventricular reconstruction reduced the end-systolic volume index by 19%, as compared with a reduction of 6% with CABG alone. Cardiac symptoms and exercise tolerance improved from baseline to a similar degree in the two study groups. However, no significant difference was observed in the primary outcome, which occurred in 292 patients (59%) who were assigned to undergo CABG alone and in 289 patients (58%) who were assigned to undergo CABG with surgical ventricular reconstruction (hazard ratio for the combined approach, 0.99; 95% confidence interval, 0.84 to 1.17; P=0.90). CONCLUSIONS: Adding surgical ventricular reconstruction to CABG reduced the left ventricular volume, as compared with CABG alone. However, this anatomical change was not associated with a greater improvement in symptoms or exercise tolerance or with a reduction in the rate of death or hospitalization for cardiac causes. (ClinicalTrials.gov number, NCT00023595.

Retrograde cardioplegia preserves myocardial function after induced coronary air embolism

AbstractCoronary air embolism is a potential complication of cardiopulmonary bypass. We compared left ventricular function before and after the administration of antegrade or retrograde cardioplegic solution in a porcine model of coronary air embolism. Nineteen pigs were placed on cardiopulmonary bypass support and cooled to 32° C. The heart was initially arrested with antegrade cold blood cardioplegic solution. The aortic crossclamp was released at 30 minutes and 0.02 cc/kg body weight of air was injected into the left anterior descending artery distal to the first diagonal branch. After 5 minutes the aorta was reclamped and the animals treated with 15 ml/kg body weight of 1:4 blood cardioplegic solution delivered by the antegrade (n = 6) or retrograde (n = 7) method. Control animals (n = 6) were not treated. Changes in regional preload recruitable stroke work were used to assess left ventricular performance before and after cardiopulmonary bypass. Two control animals could not be weaned from cardiopulmonary bypass. Left ventricular function was best preserved after treatment of induced coronary air embolism with retrograde cardioplegia (90% of baseline). Coronary air embolism treatment with antegrade cardioplegia resulted in diminished left ventricular performance (68% of baseline). In control animals left ventricular contractility was significantly impaired (39% of baseline). We conclude that administration of retrograde cardioplegic solution may be an effective method of treating coronary air embolism. The favorable outcome seen with cardioplegia may be in part because of its ability to protect the ischemic myocardium while the solution mechanically dislodges air from the vascular bed. (J Thorac Cardiovasc Surg 1997;113:917-22

Severity of Remodeling, Myocardial Viability, and Survival in Ischemic LV Dysfunction After Surgical Revascularization

AbstractObjectivesThis study sought to test the hypothesis that end-systolic volume (ESV), as a marker of severity of left ventricular (LV) remodeling, influences the relationship between myocardial viability and survival in patients with coronary artery disease and LV systolic dysfunction.BackgroundRetrospective studies of ischemic LV dysfunction suggest that the severity of LV remodeling determines whether myocardial viability predicts improved survival with surgical compared with medical therapy, with coronary artery bypass grafting (CABG) only benefitting patients with viable myocardium who have smaller ESV. However, this has not been tested prospectively.MethodsInteractions of end-systolic volume index (ESVI), myocardial viability, and treatment with respect to survival were assessed in patients in the prospective randomized STICH (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease) trial of CABG versus medical therapy who underwent viability assessment (n = 601; age 61 ± 9 years; ejection fraction ≤35%), with a median follow-up of 5.1 years. Median ESVI was 84 ml/m2. Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria.ResultsMortality was highest among patients with larger ESVI and nonviability (p < 0.001), but no interaction was observed between ESVI, viability status, and treatment assignment (p = 0.491). Specifically, the effect of CABG versus medical therapy in patients with viable myocardium and ESVI ≤84 ml/m2 (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.56 to 1.29) was no different than in patients with viability and ESVI >84 ml/m2 (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m2 (HR: 0.87; 95% CI: 0.44 to 1.74). ESVI and viability assessed as continuous rather than dichotomous variables yielded similar results (p = 0.562).ConclusionsAmong patients with ischemic cardiomyopathy, those with greater LV ESVI and no substantial viability had worse prognosis. However, the effect of CABG relative to medical therapy was not differentially influenced by the combination of these 2 factors. Lower ESVI did not identify patients in whom myocardial viability predicted better outcome with CABG relative to medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595

Does prior coronary angioplasty affect outcomes of surgical coronary revascularization? Insights from the STICH trial

Background: The STICH trial showed superiority of coronary artery bypass plus medical treatment (CABG) over medical treatment alone (MED) in patients with left ventricular ejection fraction (LVEF) ≤35%. In previous publications, percutaneous coronary intervention (PCI) prior to CABG was associated with worse prognosis. Objectives: The main purpose of this study was to analyse if prior PCI influenced outcomes in STICH. Methods and results: Patients in the STICH trial (n = 1212), followed for a median time of 9.8 years, were included in the present analyses. In the total population, 156 had a prior PCI (74 and 82, respectively, in the MED and CABG groups). In those with vs. without prior PCI, the adjusted hazard-ratios (aHRs) were 0.92 (95% CI = 0.74–1.15) for all-cause mortality, 0.85 (95% CI = 0.64–1.11) for CV mortality, and 1.43 (95% CI = 1.15–1.77) for CV hospitalization. In the group randomized to CABG without prior PCI, the aHRs were 0.82 (95% CI = 0.70–0.95) for all-cause mortality, 0.75 (95% CI = 0.62–0.90) for CV mortality and 0.67 (95% CI = 0.56–0.80) for CV hospitalization. In the group randomized to CABG with prior PCI, the aHRs were 0.76 (95% CI = 0.50–1.15) for all-cause mortality, 0.81 (95% CI = 0.49–1.36) for CV mortality and 0.61 (95% CI = 0.41–0.90) for CV hospitalization. There was no evidence of interaction between randomized treatment and prior PCI for any endpoint (all adjusted p &gt; 0.05). Conclusion: In the STICH trial, prior PCI did not affect the outcomes of patients whether they were treated medically or surgically, and the superiority of CABG over MED remained unchanged regardless of prior PCI. Clinical trial registration: Clinicaltrials.gov; Identifier: NCT0002359

Heart transplantation in children with congenital heart disease

ObjectivesThe aim of this study was to describe heart transplantation in children with congenital heart disease and to compare the results with those in children undergoing transplantation for other cardiac diseases.BackgroundReports describe decreased survival after heart transplantation in children with congenital heart disease compared with those with cardiomyopathy. However, transplantation is increasingly being considered in the surgical management of children with complex congenital heart disease. Present-day results from this group require reassessment.MethodsThe diagnoses, previous operations and indications for transplantation were characterized in children with congenital heart disease. Pretransplant course, graft ischemia time, posttransplant survival and outcome (rejection frequency, infection rate, length of hospital stay) were compared with those in children undergoing transplantation for other reasons (n = 47).ResultsThirty-seven children (mean [±SD] age 9 ± 6 years) with congenital heart disease underwent transplantation; 86% had undergone one or more previous operations. Repair of extracardiac defects at transplantation was necessary in 23 patients. Causes of death after transplantation were donor failure in two patients, surgical bleeding in two, pulmonary hemorrhage in one, infection in four, rejection in three and graft atherosclerosis in one. No difference in 1- and 5-year survival rates (70% vs. 77% and 64% vs. 65%, respectively), rejection frequency or length of hospital stay was seen between children with and without congenital heart disease. Cardiopulmonary bypass and donor ischemia time were significantly longer in patients with congenital heart disease. Serious infections were more common in children with than without congenital heart disease (13 of 37 vs. 6 of 47, respectively, p = 0.01).ConclusionsDespite the more complex cardiac surgery required at implantation and longer donor ischemic time, heart transplantation can be performed in children with complex congenital heart disease with success similar to that in patients with other cardiac diseases

Myocardial viability and survival in ischemic left ventricular dysfunction

BACKGROUND The assessment of myocardial viability has been used to identify patients with coronary artery disease and left ventricular dysfunction in whom coronary-artery bypass grafting (CABG) will provide a survival benefit. However, the efficacy of this approach is uncertain. METHODS In a substudy of patients with coronary artery disease and left ventricular dysfunction who were enrolled in a randomized trial of medical therapy with or without CABG, we used single-photon-emission computed tomography (SPECT), dobutamine echocardiography, or both to assess myocardial viability on the basis of pre-specified thresholds. RESULTS Among the 1212 patients enrolled in the randomized trial, 601 underwent assessment of myocardial viability. Of these patients, we randomly assigned 298 to receive medical therapy plus CABG and 303 to receive medical therapy alone. A total of 178 of 487 patients with viable myocardium (37%) and 58 of 114 patients without viable myocardium (51%) died (hazard ratio for death among patients with viable myocardium, 0.64; 95% confidence interval [CI], 0.48 to 0.86; P = 0.003). However, after adjustment for other baseline variables, this association with mortality was not significant (P = 0.21). There was no significant interaction between viability status and treatment assignment with respect to mortality (P = 0.53). CONCLUSIONS The presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and left ventricular dysfunction, but this relationship was not significant after adjustment for other baseline variables. The assessment of myocardial viability did not identify patients with a differential survival benefit from CABG, as compared with medical therapy alone.National Heart, Lung, and Blood Institute (NHLBI/NIH)[U01-HL-069009]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069010]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069011]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069012]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069012-03]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069013]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-069015]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-070011]National Heart, Lung, and Blood Institute (NHLBI/NIH)[HL-072683]SorinAstellas HealthcareBraccoLantheus Medical ImagingMitralignRegeneRxNovartisGileadBoehringer Ingelheim Pharmaceutical

Influence of Baseline Characteristics, Operative Conduct, and Postoperative Course on 30-Day Outcomes of Coronary Artery Bypass Grafting Among Patients With Left Ventricular Dysfunction Results From the Surgical Treatment for Ischemic Heart Failure (STICH) Trial

Background Patients with severe left ventricular dysfunction, ischemic heart failure, and coronary artery disease suitable for coronary artery bypass grafting (CABG) are at higher risk for surgical morbidity and mortality. Paradoxically, those patients with the most severe coronary artery disease and ventricular dysfunction who derive the greatest clinical benefit from CABG are also at the greatest operative risk, which makes decision making regarding whether to proceed to surgery difficult in such patients. To better inform such decision making, we analyzed the Surgical Treatment for Ischemic Heart Failure (STICH) CABG population for detailed information on perioperative risk and outcomes. Methods and Results In both STICH trials (hypotheses), 2136 patients with a left ventricular ejection fraction of 35% and coronary artery disease were allocated to medical therapy, CABG plus medical therapy, or CABG with surgical ventricular reconstruction. Relationships of baseline characteristics and operative conduct with morbidity and mortality at 30 days were evaluated. There were a total of 1460 patients randomized to and receiving surgery, and 346 (approximate to 25%) of these high-risk patients developed a severe complication within 30 days. Worsening renal insufficiency, cardiac arrest with cardiopulmonary resuscitation, and ventricular arrhythmias were the most frequent complications and those most commonly associated with death. Mortality at 30 days was 5.1% and was generally preceded by a serious complication (65 of 74 deaths). Left ventricular size, renal dysfunction, advanced age, and atrial fibrillation/flutter were significant preoperative predictors of mortality within 30 days. Cardiopulmonary bypass time was the only independent surgical variable predictive of 30-day mortality. Conclusions CABG can be performed with relatively low 30-day mortality in patients with left ventricular dysfunction. Serious postoperative complications occurred in nearly 1 in 4 patients and were associated with mortality. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595

Synaptic Reorganization in the Adult Rat's Ventral Cochlear Nucleus following Its Total Sensory Deafferentation

Ablation of a cochlea causes total sensory deafferentation of the cochlear nucleus in the brainstem, providing a model to investigate nervous degeneration and formation of new synaptic contacts in the adult brain. In a quantitative electron microscopical study on the plasticity of the central auditory system of the Wistar rat, we first determined what fraction of the total number of synaptic contact zones (SCZs) in the anteroventral cochlear nucleus (AVCN) is attributable to primary sensory innervation and how many synapses remain after total unilateral cochlear ablation. Second, we attempted to identify the potential for a deafferentation-dependent synaptogenesis. SCZs were ultrastructurally identified before and after deafferentation in tissue treated for ethanolic phosphotungstic acid (EPTA) staining. This was combined with pre-embedding immunocytochemistry for gephyrin identifying inhibitory SCZs, the growth-associated protein GAP-43, glutamate, and choline acetyltransferase. A stereological analysis of EPTA stained sections revealed 1.11±0.09 (S.E.M.)×109 SCZs per mm3 of AVCN tissue. Within 7 days of deafferentation, this number was down by 46%. Excitatory and inhibitory synapses were differentially affected on the side of deafferentation. Excitatory synapses were quickly reduced and then began to increase in number again, necessarily being complemented from sources other than cochlear neurons, while inhibitory synapses were reduced more slowly and continuously. The result was a transient rise of the relative fraction of inhibitory synapses with a decline below original levels thereafter. Synaptogenesis was inferred by the emergence of morphologically immature SCZs that were consistently associated with GAP-43 immunoreactivity. SCZs of this type were estimated to make up a fraction of close to 30% of the total synaptic population present by ten weeks after sensory deafferentation. In conclusion, there appears to be a substantial potential for network reorganization and synaptogenesis in the auditory brainstem after loss of hearing, even in the adult brain

Laboratory Evaluation of a Low Prime ClosedCircuit Cardiopulmonary Bypass System

We have explored the potential advantages of a low prime closed-circuit cardiopulmonary bypass (CPB) system using a non-human primate model. Although manufacturers have reduced priming volumes in individual CPB components, the standard circuit volume remains high because of the tubing diameter and length necessary for gravity drainage. By replacing gravity drainage with the negative pressure generated by a centrifugal pump, we can realize significant tubing volume reduction. Closed-circuit bypass was conducted on 13 baboons ranging from 5-15 kg. The circuit consisted of a centrifugal pump, a hollow fiber oxygenator, and l/4" arterial and venous tubing. The design of the circuit included the capacity to remove a limited amount of venous air. Circulatory arrest during deep hypothermia with volume displacement into a reservoir was also accomplished with this circuit. The potential benefits of this low prime closed-circuit bypass system include blood conservation and reduction in blood surface area contact. The future safe clinical use of this type of closed-circuit bypass for routine open heart surgery will depend upon the incorporation of a device in the venous line to remove air. This is the greatest threat to patient safety in a closed circuit system and its use for open chest surgery must wait until an efficient venous air elimination device is available