Marek A. Deja

Coronary-Artery Bypass Surgery in Patients with Left Ventricular Dysfunction

BACKGROUND The role of coronary-artery bypass grafting (CABG) in the treatment of patients with coronary artery disease and heart failure has not been clearly established. METHODS Between July 2002 and 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 medical therapy alone (602 patients) or medical therapy plus CABG (610 patients). The primary outcome was the rate of death from any cause. Major secondary outcomes included the rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. RESULTS The primary outcome occurred in 244 patients (41%) in the medical-therapy group and 218 (36%) in the CABG group (hazard ratio with CABG, 0.86; 95% confidence interval [CI], 0.72 to 1.04; P=0.12). A total of 201 patients (33%) in the medical-therapy group and 168 (28%) in the CABG group died from an adjudicated cardiovascular cause (hazard ratio with CABG, 0.81; 95% CI, 0.66 to 1.00; P=0.05). Death from any cause or hospitalization for cardiovascular causes occurred in 411 patients (68%) in the medical-therapy group and 351 (58%) in the CABG group (hazard ratio with CABG, 0.74; 95% CI, 0.64 to 0.85; P<0.001). By the end of the follow-up period (median, 56 months), 100 patients in the medical-therapy group (17%) underwent CABG, and 555 patients in the CABG group (91%) underwent CABG. CONCLUSIONS In this randomized trial, there was no significant difference between medical therapy alone and medical therapy plus CABG with respect to the primary end point of death from any cause. Patients assigned to CABG, as compared with those assigned to medical therapy alone, had lower rates of death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes. (Funded by the National Heart, Lung, and Blood Institute and Abbott Laboratories; STICH ClinicalTrials.gov number, NCT00023595.).

Influence of mitral regurgitation repair on survival in the surgical treatment for ischemic heart failure trial.

Background— Whether mitral valve repair during coronary artery bypass grafting (CABG) improves survival in patients with ischemic mitral regurgitation (MR) remains unknown. Methods and Results— Patients with ejection fraction ⩽35% and coronary artery disease amenable to CABG were randomized at 99 sites worldwide to medical therapy with or without CABG. The decision to treat the mitral valve during CABG was left to the surgeon. The primary end point was mortality. Of 1212 randomized patients, 435 (36%) had none/trace MR, 554 (46%) had mild MR, 181 (15%) had moderate MR, and 39 (3%) had severe MR. In the medical arm, 70 deaths (32%) occurred in patients with none/trace MR, 114 (44%) in those with mild MR, and 58 (50%) in those with moderate to severe MR. In patients with moderate to severe MR, there were 29 deaths (53%) among 55 patients randomized to CABG who did not receive mitral surgery (hazard ratio versus medical therapy, 1.20; 95% confidence interval, 0.77–1.87) and 21 deaths (43%) among 49 patients who received mitral surgery (hazard ratio versus medical therapy, 0.62; 95% confidence interval, 0.35–1.08). After adjustment for baseline prognostic variables, the hazard ratio for CABG with mitral surgery versus CABG alone was 0.41 (95% confidence interval, 0.22–0.77; P=0.006). Conclusion— Although these observational data suggest that adding mitral valve repair to CABG in patients with left ventricular dysfunction and moderate to severe MR may improve survival compared with CABG alone or medical therapy alone, a prospective randomized trial is necessary to confirm the validity of these observations. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Effects of preoperative aspirin in coronary artery bypass grafting: a double-blind, placebo-controlled, randomized trial.

OBJECTIVE This trial was undertaken to determine the safety and efficacy of preoperative aspirin administration in a contemporary cardiac surgical practice setting. METHODS This randomized, double-blind, parallel-group, single-center trial involved patients with stable coronary artery disease who were assigned to receive either 300 mg of aspirin or placebo the night before coronary bypass surgery. Using a random digit table, patients were allocated to receive the tablet from 1 of the 40 coded bottles containing either aspirin or placebo. Patients, surgeons, anesthetists, and investigators were all masked to treatment allocation. The primary safety end points were as follows: more than 750 mL of bleeding during the first postoperative 12 hours and more than 1000 mL of total discharge from the chest drains. The secondary efficacy end point was a composite of cardiovascular death, myocardial infarction, or repeat revascularization. RESULTS A total of 390 patients were allocated to aspirin (387 analyzed) and 399 to placebo (396 analyzed). The follow-up median was 53 months. Fifty-four placebo recipients and 86 aspirin recipients bled more than 750 mL in the first 12 hours (odds ratio [OR], 1.81; 95% confidence interval [CI], 1.25-2.63), while total chest drain discharge was above 1000 mL in 96 placebo and 131 aspirin recipients (OR, 1.60; 95% CI, 1.17-2.18). Preoperative aspirin decreased the long-term hazard of nonfatal coronary event (infarction or repeat revascularization)-hazard ratio (HR), 0.58 (95% CI, 0.33-0.99)--and tended to decrease the hazard of a major cardiac event (cardiovascular death, infarction, or repeat revascularization--HR, 0.65 [95% CI, 0.41-1.03]). CONCLUSIONS Performing coronary grafts on aspirin is associated with increased postoperative bleeding but may decrease the long-term hazard of coronary events.

Diazoxide protects myocardial mitochondria, metabolism, and function during cardiac surgery: A double-blind randomized feasibility study of diazoxide-supplemented cardioplegia

OBJECTIVES The study was designed to assess whether diazoxide-mediated cardioprotection might be used in human subjects during cardiac surgery. METHODS Forty patients undergoing coronary artery bypass grafting were randomized to receive intermittent warm blood antegrade cardioplegia supplemented with either diazoxide (100 micromol/L) or placebo (n = 20 in each group). Mitochondria were assessed before and after ischemia and reperfusion in myocardial biopsy specimens. Myocardial oxygen and glucose and lactic acid extraction ratios were measured before ischemia and in the first 20 minutes of reperfusion. Hemodynamic data were collected, and troponin I, creatine kinase-MB, and N-terminal prohormone brain natriuretic peptide levels were measured. All outcomes were analyzed by using mixed-effects modeling for repeated measures. RESULTS No deaths, strokes, or infarcts were observed. Patients received, on average, 36.2 +/- 1.2 mg of diazoxide and 37.3 +/- 1.9 mg of placebo (P = .6). Diazoxide added to cardioplegia prevented mitochondrial swelling (8899 +/- 474 vs 9273 +/- 688 pixels before and after the procedure, respectively; P = .6) compared with that seen in the placebo group (8474 +/- 163 vs 11,357 +/- 759 pixels, P = .004). No oxygen debt was observed in the diazoxide group. Glucose consumption and lactic acid production returned to preischemic values faster in the diazoxide group. The following hemodynamic parameters differed between the diazoxide and placebo groups, respectively, in the postoperative period: cardiac index, 3.0 +/- 0.09 versus 2.6 +/- 0.09 L . min(-1) . m(-2) (P = .002); left cardiac work index, 2.81 +/- 0.07 versus 2.31 +/- 0.07 kg/m(2) (P < .001); oxygen delivery index, 420 +/- 14 versus 377 +/- 13 mL . min(-1) . m(-2) (P = .03); and oxygen extraction ratio, 29.3% +/- 1.1% versus 32.6% +/- 1.1% (P = .02). Postoperative myocardial enzyme levels did not differ, but N-terminal prohormone brain natriuretic peptide levels were lower in the diazoxide group (120 +/- 27 vs 192 +/- 29 pg/mL, P = .04). CONCLUSIONS Supplementing blood cardioplegia with diazoxide is safe and improves myocardial protection during cardiac surgery, possibly through its influence on the mitochondria.

Severity of remodeling, myocardial viability, and survival in ischemic LV dysfunction after surgical revascularization

OBJECTIVES This 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. BACKGROUND Retrospective 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. METHODS Interactions 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/m(2). Viability was assessed by single-photon emission computed tomography or dobutamine echocardiography using pre-specified criteria. RESULTS Mortality 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/m(2) (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/m(2) (HR: 0.87; 95% CI: 0.57 to 1.31). Other ESVI thresholds yielded similar results, including ESVI ≤60 ml/m(2) (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). CONCLUSIONS Among 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).

Diazoxide provides protection to human myocardium in vitro that is concentration dependent

BACKGROUND Diazoxide has been shown to confer significant myocardial protection in many experiments. This study was designed to assess its influence on the structural injury and functional recovery of human myocardium subjected to hypoxia/reoxygenation in vitro. METHODS The isolated electrically driven human right atrial trabeculae, obtained during cardiac surgery, were studied. The tissue bath was oxygenated with 95% oxygen and 5% carbon dioxide, hypoxia being obtained by replacing oxygen with argon. The influence of diazoxide on atrial contractility was studied first. Next, the two trabeculae from one atrial appendage were studied simultaneously, adding diazoxide to the tissue bath 10 minutes before hypoxia in one, with another serving as a control. We tested 10(-4.5) mol/L and 10(-4) mol/L diazoxide in three sets of experiments testing 30, 60, and 90 minutes of hypoxia. We continued reoxygenation for 120 minutes (in 60-minute and 90-minute hypoxia experiments) and subsequently tested reaction to 10(-4) mol/L norepinephrine. Apart from continuous recording of the contraction force, we measured the troponin I release into the tissue bath after ischemia and reoxygenation. RESULTS Diazoxide exerted a negative inotropic effect in human atrial muscle (pD(2)=3.96 +/- 0.18). Both concentrations of diazoxide studied resulted in better functional recovery of atrial trabeculae subjected to 30 minutes of hypoxia. With longer hypoxia, only the higher diazoxide concentration provided significant protection as assessed by contractility. After 120 minutes of reoxygenation, only diazoxide-treated muscle was viable enough to respond to norepinephrine. Only 10(-4) mol/L diazoxide resulted in lower troponin I release during hypoxia and reoxygenation. CONCLUSIONS This study shows that diazoxide provides significant concentration-dependent protection against hypoxia/reoxygenation injury to human myocardium in vitro.

Statistical agreement of left ventricle measurements using cardiac magnetic resonance and 2D echocardiography in ischemic heart failure

Summary Background The aim of this study was to compare cardiac magnetic resonance imaging (CMR) with 2-dimensional echocardiography (2D echo) in the assessment of left ventricle (LV) function parameters and mass in patients with ischemic heart disease and severely depressed LV function. Although 2D echo is commonly used to assess LV indices, CMR is the state-of-the-art technique. Agreement between these 2 methods in these patients has not been well established. Material/Methods LV indexed end systolic and diastolic volumes (EDVi and ESVi), indexed mass (LVMi) and ejection fraction (EF) were assessed in 67 patients (12 women), using 2D echo and CMR. Results According to statistical analysis (Bland-Altman), 2D echo underestimated LV EDV and ESV and overestimated EF and LVMi compared to CMR. The highest correlation between 2D echo and CMR was found for EDVi (R2=0.73, p<0.0001) and ESVi (R2=0.69, p<0.0001) and the lowest for EF (R2=0.21, p=0.001) and LVMi (R2=0.20, p=0.002). The maximal differences between 2D echo and CMR were found for highest mesurements of LV volumes and mass, and for lowest EF values. Conclusions There is moderate to strong correlation between CMR and 2D echo in the assessment of LV function parameters and mass in patients with ischemic heart failure. Between-method agreement depends on the degree of LV dysfunction. The results of assessment of the severely damaged LV obtained by the use of 2D echo should be interpreted with caution.

Gastric tonometry as a method of visceral oxygenation monitoring in patients undergoing coronary revascularisation.

OBJECTIVE The aim of the study was to assess gastric mucosal pH during certain parts of a major cardiac procedure (hypo- and normothermic), and then throughout the first postoperative day. METHODS Gastric mucosal pH was measured using a tonometer, in 15 patients subjected to elective CABG procedures. The patients were also assessed haemodynamically and serum lactate concentrations were measured. RESULTS It was found that cardiopulmonary bypass did not suppress visceral perfusion. The most critical was the period between 4th and 12th postbypass hour when a tendency towards decreased cardiac output and oxygen delivery was noted. At the same time oxygen consumption was increasing which resulted in triggering of anaerobic metabolic pathways, that was mirrored by significant rise in serum lactate levels. During this period of time the lowest, although not critical levels of gastric mucosal pH were recorded, suggesting a relative decrease in splanchnic perfusion. CONCLUSION Extracorporeal circulation does not significantly compromise splanchnic perfusion. Tonometry is a valuable, non-invasive method of visceral oxygenation monitoring. The first postoperative day is an especially critical time for a cardiac patient--a frequent control of haemodynamic and acid-base balance parameters is absolutely mandatory.

Open aortic arch surgery in chronic dissection with visceral arteries originating from different lumens.

OBJECTIVES Surgical management of chronic aortic dissection is controversial, especially when the dissection extends into the abdominal aorta in which the visceral arteries originate from different lumens and is combined with aortic arch pathology necessitating surgery. The aim of the study was to evaluate the results of open surgery in this complex aortic pathology. METHODS Between June 2002 and 2015, a total of 17 patients (median age 57, range 32-76 years) necessitating complete arch replacement presented complex chronic dissection of the thoraco-abdominal aorta with the visceral arteries originating from different lumens. Fourteen patients (82%) had had previous cardiac surgery, which was performed on the proximal aorta in all but one because of acute type A dissection. Nine patients without considerable dilatation of the descending aorta received aortic arch replacement with distal resection of the dissection membrane, and 8 patients with progressive dilatation of the thoracic aorta underwent aortic arch and descending aorta replacement via clamshell approach. RESULTS No early (defined as 30-day, 90-day and in-hospital period) deaths, strokes or spinal cord injuries occurred. Only 1 patient (6%) presented temporary neurological dysfunctions (delirium, agitation), which resolved completely before discharge, and an injury of the recurrent laryngeal nerve was documented in 2 patients (12%). Temporary dialysis was necessary in 1 case. The follow-up was complete for all patients. All but one patient, who died due to leukaemia 23 months after surgery, were alive at the last follow-up (median duration 33 months, range 2-118 months). No patient needed a reoperation or an intervention on the thoracic and/or abdominal aorta. Moreover, no noticeable progression of the chronic dissection in the downstream aorta was documented in any patient. CONCLUSIONS The results after conventional aortic arch repair with distal resection of the dissection membrane and, if necessary, with replacement of the progressively dilated chronic dissected thoracic aorta can offer excellent results in experienced hands and, therefore, this technique may be considered as a preferable option for surgical treatment of chronic aortic dissection with involvement of the aortic arch and the visceral arteries originating from different lumens.

Left internal mammary artery improves 5-year survival in patients under 40 subjected to surgical revascularization.

BACKGROUND The population of young patients under 40 requiring coronary bypass surgery is characterized by an extremely and unusually rapid progression of coronary heart disease. The aim of the present study was to assess the clinical status and quality of life in these patients after surgery in relation to the type of conduit used to revascularize the left anterior descending artery (LAD). METHODS One hundred seventeen patients under 40 (range, 30-40 years) underwent coronary artery bypass grafting (CABG) at our institution between 1991 and 1999. Ninety-one patients received LIMA to LAD graft (group A), and in 26 patients the saphenous vein was used to graft this vessel (group B). Seventy-eight patients (63 in group A and 15 in group B) were assessed after a mean time of 71 +/- 26 months. They were asked to fill out a questionnaire aimed at their subjective assessment of their quality of life as compared with their preoperative status. RESULTS Five-year actuarial survival was higher in patients with LIMA to LAD graft (log rank test: P < .004). The functional status of patients in group B was significantly worse in comparison to group A: respectively, CCS 2.2 +/- 1.1 versus 1.5 +/- 0.7; (P = .02), NYHA 2.2 +/- 1.1 versus 1.3 +/- 0.5; (P = .002). Patients in group B more frequently required reinstitution of nitroglycerine treatment (93% versus 56%; P = .025). We failed to show differences between the 2 groups as far as subjective quality of life is concerned. In summary, 63% of patients perceived it to be worse, 29% to be better, and 8% felt it had not changed. CONCLUSION The use of LIMA is crucial in patients undergoing CABG under the age of 40 in order to achieve the best possible surgical results. Quicker recurrence of coronary disease symptoms is observed when a vein is used to graft the LAD. It may reflect an earlier progress of atherosclerosis in venous grafts.