Myocardial Viability and Long-Term Outcomes in Ischemic Cardiomyopathy.

BACKGROUND: The role of assessment of myocardial viability in identifying patients with ischemic cardiomyopathy who might benefit from surgical revascularization remains controversial. Furthermore, although improvement in left ventricular function is one of the goals of revascularization, its relationship to subsequent outcomes is unclear. METHODS: Among 601 patients who had coronary artery disease that was amenable to coronary-artery bypass grafting (CABG) and who had a left ventricular ejection fraction of 35% or lower, we prospectively assessed myocardial viability using single-photon-emission computed tomography, dobutamine echocardiography, or both. Patients were randomly assigned to undergo CABG and receive medical therapy or to receive medical therapy alone. Left ventricular ejection fraction was measured at baseline and after 4 months of follow-up in 318 patients. The primary end point was death from any cause. The median duration of follow-up was 10.4 years. RESULTS: CABG plus medical therapy was associated with a lower incidence of death from any cause than medical therapy alone (182 deaths among 298 patients in the CABG group vs. 209 deaths among 303 patients in the medical-therapy group; adjusted hazard ratio, 0.73; 95% confidence interval, 0.60 to 0.90). However, no significant interaction was observed between the presence or absence of myocardial viability and the beneficial effect of CABG plus medical therapy over medical therapy alone (P = 0.34 for interaction). An increase in left ventricular ejection fraction was observed only among patients with myocardial viability, irrespective of treatment assignment. There was no association between changes in left ventricular ejection fraction and subsequent death. CONCLUSIONS: The findings of this study do not support the concept that myocardial viability is associated with a long-term benefit of CABG in patients with ischemic cardiomyopathy. The presence of viable myocardium was associated with improvement in left ventricular systolic function, irrespective of treatment, but such improvement was not related to long-term survival. (Funded by the National Institutes of Health; STICH ClinicalTrials.gov number, NCT00023595.).

Initial Invasive Versus Conservative Management of Stable Ischemic Heart Disease in Patients With a History of Heart Failure or Left Ventricular Dysfunction: Insights From the ISCHEMIA Trial.

BACKGROUND: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but <45% is unknown. METHODS: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years. RESULTS: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF >45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, -12.1% [95% CI, -22.6 to -1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, -1.6% [95% CI, -3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy-associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF. CONCLUSIONS: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure).

BACKGROUND: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study). METHODS: The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. RESULTS: At baseline, women were older (63.4 versus 59.3 years; P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48-0.89; P=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.

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 prespecified 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. (Funded by the National Heart, Lung, and Blood Institute; STICH ClinicalTrials.gov number, NCT00023595.).

Renal function and coronary bypass surgery in patients with ischemic heart failure.

OBJECTIVE: Chronic kidney disease is a known risk factor in cardiovascular disease, but its influence on treatment effect of bypass surgery remains unclear. We assessed the influence of chronic kidney disease on 10-year mortality and cardiovascular outcomes in patients with ischemic heart failure treated with medical therapy (medical treatment) with or without coronary artery bypass grafting. METHODS: We calculated the baseline estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula, chronic kidney disease stages 1-5) from 1209 patients randomized to medical treatment or coronary artery bypass grafting in the Surgical Treatment for IsChemic Heart failure trial and assessed its effect on outcome. RESULTS: In the overall Surgical Treatment for IsChemic Heart failure cohort, patients with chronic kidney disease stages 3 to 5 were older than those with stages 1 and 2 (66-71 years vs 54-59 years) and had more comorbidities. Multivariable modeling revealed an inverse association between estimated glomerular filtration rate and risk of death, cardiovascular death, or cardiovascular rehospitalization (all P < .001, but not for stroke, P = .697). Baseline characteristics of the 2 treatment arms were equal for each chronic kidney disease stage. There were significant improvements in death or cardiovascular rehospitalization with coronary artery bypass grafting (stage 1: hazard ratio, 0.71; confidence interval, 0.53-0.96, P = .02; stage 2: hazard ratio, 0.71; confidence interval, 0.59-0.84, P < .0001; stage 3: hazard ratio, 0.76; confidence interval, 0.53-0.96, P = .03). These data were inconclusive in stages 4 and 5 for insufficient patient numbers (N = 28). There was no significant interaction of estimated glomerular filtration rate with the treatment effect of coronary artery bypass grafting (P = .25 for death and P = .54 for death or cardiovascular rehospitalization). CONCLUSIONS: Chronic kidney disease is an independent risk factor for mortality in patients with ischemic heart failure with or without coronary artery bypass grafting. However, mild to moderate chronic kidney disease does not appear to influence long-term treatment effects of coronary artery bypass grafting.

Optimal medical therapy with or without surgical revascularization and long-term outcomes in ischemic cardiomyopathy.

OBJECTIVES: Optimal medical therapy in patients with heart failure and coronary artery disease is associated with improved outcomes. However, whether this association is influenced by the performance of coronary artery bypass grafting is less well established. Thus, the aim of this study was to determine the possible relationship between coronary artery bypass grafting and optimal medical therapy and its effect on the outcomes of patients with ischemic cardiomyopathy. METHODS: The Surgical Treatment for Ischemic Heart Failure trial randomized 1212 patients with coronary artery disease and left ventricular ejection fraction 35% or less to coronary artery bypass grafting with medical therapy or medical therapy alone with a median follow-up over 9.8 years. For the purpose of this study, optimal medical therapy was collected at baseline and 4 months, and defined as the combination of 4 drugs: angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, statin, and 1 antiplatelet drug. RESULTS: At baseline and 4 months, 58.7% and 73.3% of patients were receiving optimal medical therapy, respectively. These patients had no differences in important parameters such as left ventricular ejection fraction and left ventricular volumes. In a multivariable Cox model, optimal medical therapy at baseline was associated with a lower all-cause mortality (hazard ratio, 0.78; 95% confidence interval, 0.66-0.91; P = .001). When landmarked at 4 months, optimal medical therapy was also associated with a lower all-cause mortality (hazard ratio, 0.82; 95% confidence interval, 0.62-0.99; P = .04). There was no interaction between the benefit of optimal medical therapy and treatment allocation. CONCLUSIONS: Optimal medical therapy was associated with improved long-term survival and lower cardiovascular mortality in patients with ischemic cardiomyopathy and should be strongly recommended.

Blood Transfusion and Increased Perioperative Risk in Coronary Artery Bypass Grafts.

OBJECTIVE: To correlate blood transfusions and clinical outcomes during hospitalization in coronary artery bypass grafting surgery (CABG). METHODS: Transfusion, clinical and hematological data were collected for 1,378 patients undergoing isolated or combined CABG between January 2011 and December 2012. The effect of blood transfusions was evaluated through multivariate analysis to predict three co-primary outcomes: composite ischemic events, composite infectious complications and hospital mortality. Because higher risk patients receive more transfusions, the hospital mortality outcome was also tested on a stratum of low-risk patients to isolate the effect of preoperative risk on the results. RESULTS: The transfusion rate was 63.9%. The use of blood products was associated with a higher incidence of the three coprimary outcomes: composite infectious complications (OR 2.67, 95% CI 1.70 to 4.19; P<0.001), composite ischemic events (OR 2.42, 95% CI 1.70 to 3.46; P<0.001) and hospital mortality (OR 3.07, 95% CI 1.53 to 6.13; P<0.001). When only patients with logistic EuroSCORE ≤ 2% were evaluated, i.e., low-risk individuals, the mortality rate and the incidence of ischemic events and infectious complications composites remained higher among the transfused patients [6% vs. 0.4% (P<0.001), 11.7% vs. 24,3% (P<0.001) and 6.5% vs. 12.7% (P=0.002), respectively]. CONCLUSION: The use of blood components in patients undergoing CABG was associated with ischemic events, infectious complications and hospital mortality, even in low-risk patients.

Consequences of the prolonged waiting time for patient candidates for heart surgery.

OBJECTIVE: To assess mortality and the psychological repercussions of the prolonged waiting time for candidates for heart surgery. METHODS: From July 1999 to May 2000, using a standardized questionnaire, we carried out standardized interviews and semi-structured psychological interviews with 484 patients with coronary heart disease, 121 patients with valvular heart diseases, and 100 patients with congenital heart diseases. RESULTS: The coefficients of mortality (deaths per 100 patients/year) were as follows: patients with coronary heart disease, 5.6; patients with valvular heart diseases, 12.8; and patients with congenital heart diseases, 3.1 (p<0.0001). The survival curve was lower in patients with valvular heart diseases than in patients with coronary heart disease and congenital heart diseases (p<0.001). The accumulated probability of not undergoing surgery was higher in patients with valvular heart diseases than in the other patients (p<0.001), and, among the patients with valvular heart diseases, this probability was higher in females than in males (p<0.01). Several patients experienced intense anxiety and attributed their adaptive problems in the scope of love, professional, and social lives, to not undergoing surgery. CONCLUSION: Mortality was high, and even higher among the patients with valvular heart diseases, with negative psychological and social repercussions.

Inducible myocardial ischemia and outcomes in patients with coronary artery disease and left ventricular dysfunction.

OBJECTIVES: The study objectives were to test the hypotheses that ischemia during stress testing has prognostic value and identifies those patients with coronary artery disease (CAD) with left ventricular (LV) dysfunction who derive the greatest benefit from coronary artery bypass grafting (CABG) compared with medical therapy. BACKGROUND: The clinical significance of stress-induced ischemia in patients with CAD and moderately to severely reduced LV ejection fraction (EF) is largely unknown. METHODS: The STICH (Surgical Treatment for IsChemic Heart Failure) trial randomized patients with CAD and EF ≤35% to CABG or medical therapy. In the current study, we assessed the outcomes of those STICH patients who underwent a radionuclide (RN) stress test or a dobutamine stress echocardiogram (DSE). A test was considered positive for ischemia by RN testing if the summed difference score (difference in tracer activity between stress and rest) was ≥4 or if ≥2 of 16 segments were ischemic during DSE. Clinical endpoints were assessed by intention to treat during a median follow-up of 56 months. RESULTS: Of the 399 study patients (51 women, mean EF 26 ± 8%), 197 were randomized to CABG and 202 were randomized to medical therapy. Myocardial ischemia was induced during stress testing in 256 patients (64% of the study population). Patients with and without ischemia were similar in age, multivessel CAD, previous myocardial infarction, LV EF, LV volumes, and treatment allocation (all p = NS). There was no difference between patients with and without ischemia in all-cause mortality (hazard ratio: 1.08; 95% confidence interval: 0.77 to 1.50; p = 0.66), cardiovascular mortality, or all-cause mortality plus cardiovascular hospitalization. There was no interaction between ischemia and treatment for any clinical endpoint. CONCLUSIONS: In CAD with severe LV dysfunction, inducible myocardial ischemia does not identify patients with worse prognosis or those with greater benefit from CABG over optimal medical therapy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Blood transfusion and increased perioperative risk in coronary artery bypass grafts

Abstract Objective: To correlate blood transfusions and clinical outcomes during hospitalization in coronary artery bypass grafting surgery (CABG). Methods: Transfusion, clinical and hematological data were collected for 1,378 patients undergoing isolated or combined CABG between January 2011 and December 2012. The effect of blood transfusions was evaluated through multivariate analysis to predict three co-primary outcomes: composite ischemic events, composite infectious complications and hospital mortality. Because higher risk patients receive more transfusions, the hospital mortality outcome was also tested on a stratum of low-risk patients to isolate the effect of preoperative risk on the results. Results: The transfusion rate was 63.9%. The use of blood products was associated with a higher incidence of the three coprimary outcomes: composite infectious complications (OR 2.67, 95% CI 1.70 to 4.19; P<0.001), composite ischemic events (OR 2.42, 95% CI 1.70 to 3.46; P<0.001) and hospital mortality (OR 3.07, 95% CI 1.53 to 6.13; P<0.001). When only patients with logistic EuroSCORE ≤ 2% were evaluated, i.e., low-risk individuals, the mortality rate and the incidence of ischemic events and infectious complications composites remained higher among the transfused patients [6% vs. 0.4% (P<0.001), 11.7% vs. 24,3% (P<0.001) and 6.5% vs. 12.7% (P=0.002), respectively]. Conclusion: The use of blood components in patients undergoing CABG was associated with ischemic events, infectious complications and hospital mortality, even in low-risk patients.

Conseqüências do prolongamento do tempo de espera em pacientes candidatos à cirurgia cardiáca / Consequences of the prolonged waiting Time for patients candidates for heart surgery

OBJECTIVE - To assess mortality and the psychological repercussions of the prolonged waiting time for candidates for heart surgery. METHODS - From July 1999 to May 2000, using a standardized questionnaire, we carried out standardized interviews and semi-structured psychological interviews with 484 patients with coronary heart disease, 121 patients with valvular heart diseases, and 100 patients with congenital heart diseases. RESULTS - The coefficients of mortality (deaths per 100 patients/year) were as follows: patients with coronary heart disease, 5.6; patients with valvular heart diseases, 12.8; and patients with congenital heart diseases, 3.1 (p<0.0001). The survival curve was lower in patients with valvular heart diseases than in patients with coronary heart disease and congenital heart diseases (p<0.001). The accumulated probability of not undergoing surgery was higher in patients with valvular heart diseases than in the other patients (p<0.001), and, among the patients with valvular heart diseases, this probability was higher in females than in males (p<0.01). Several patients experienced intense anxiety and attributed their adaptive problems in the scope of love, professional, and social lives, to not undergoing surgery. CONCLUSION - Mortality was high, and even higher among the patients with valvular heart diseases, with negative psychological and social repercussions

Resultados imediatos da cirurgia de revascularização miocárdica: comparação entre homens e mulheres / Immediate results of myocardial revascularization: comparison between men and women

OBJETIVO: Avaliar a morbimortalidade de homens e mulheres submetidos à cirurgia de revascularização miocárdica isolada e os fatores relacionados às diferenças eventualmente encontradas. MÉTODOS: Análise comparativa de 2032 pacientes, 1402 (69 por cento) homens e 630 (31 por cento) mulheres submetidos consecutivamente à cirurgia, de janeiro 1999 a dezembro 2002. RESULTADOS: As mulheres apresentaram idade média mais elevada, maior número de fatores de risco e taxas de angina instável. Enxertos com artéria torácica interna foram mais freqüentemente usados nos homens, 85,6 por cento vs. 78,3 por cento, p<0,001. Não houve diferenças nas taxas de complicações pós operatórias, exceto as infecções, mais freqüentes nas mulheres. A mortalidade hospitalar foi de 4,1 por cento e 6,3 por cento, para homens e mulheres respectivamente, p=0,026. Na análise multivariada o sexo feminino não foi identificado como fator prognóstico independente para óbito, assim como o uso de enxertos com artéria torácica não foi também isoladamente identificado como fator protetor, porém a interação sexo-artéria torácica interna foi significativa; foram ainda selecionados, idade (OR 1,03; [IC] 95 por cento 1,01 a 1,06; p=0,004), insuficiência renal no pré-operatório (OR 1.82; [IC] 95 por cento 1,07 a 3,11; p=0,028) e cirurgia de urgência/emergência (OR 2,85; [IC] 95 por cento 1,32 a 6,14; p=0,008). CONCLUSÃO: O sexo feminino apresentou maior mortalidade operatória porém não se mostrou fator prognóstico independente para óbito; o uso de enxertos com artéria torácica mostrou-se protetor; pacientes mais idosos, com insuficiência renal e em situação emergencial apresentaram maiores índices de óbito hospitalar.