Myocardial protection with phosphocreatine in high-risk cardiac surgery patients: a randomized trial.

BACKGROUND: This study was conducted to test the hypothesis that phosphocreatine (PCr), administered intravenously and as cardioplegia adjuvant in patients undergoing cardiac surgery with prolonged aortic cross clamping and cardiopulmonary bypass (CPB) time, would decrease troponin I concentration after surgery. METHODS: In this randomized, double-blind, placebo-controlled pilot study we included 120 patients undergoing double/triple valve repair/replacement under cardiopulmonary bypass in the cardiac surgery department of a tertiary hospital. The treatment group received: intravenous administration of 2 g of PCr after anesthesia induction; 2.5 g of PCr in every 1 L of cardioplegic solution (concentration = 10 mmol/L); intravenous administration of 2 g of PCr immediately after heart recovery following aorta declamping; 4 g of PCr at intensive care unit admission. The control group received an equivolume dose of normosaline. RESULTS: The primary endpoint was peak concentration of troponin I after surgery. Secondary endpoints included peak concentration of serum creatinine, need for, and dosage of inotropic support, number of defibrillations after aortic declamping, incidence of arrhythmias, duration of Intensive Care Unit (ICU) stay, length of hospitalization. There was no difference in peak troponin I concentration after surgery (PCr, 10,508 pg/ml [IQR 6,838-19,034]; placebo, 11,328 pg/ml [IQR 7.660-22.894]; p = 0.24). There were also no differences in median peak serum creatinine (PCr, 100 µmol/L [IQR 85.0-117.0]; placebo, 99.5 µmol/L [IQR 90.0-117.0]; p = 0.87), the number of patients on vasopressor/inotropic agents (PCr, 49 [88%]; placebo, 57 [91%]; p = 0.60), the inotropic score on postoperative day 1 (PCr, 4.0 (0-7); placebo, 4.0 (0-10); p = 0.47), mean SOFA score on postoperative day 1 (PCr, 5.25 ± 2.33; placebo, 5,45 ± 2,65; p = 0.83), need for defibrillation after declamping of aorta (PCr, 22 [39%]; placebo, 25 [40%]; p = 0.9),, duration of ICU stay and length of hospitalization as well as 30-day mortality (PCr, 0 (0%); placebo,1 (4.3%); p = 0.4). CONCLUSION: PCr administration to patients undergoing double/triple valve surgery under cardiopulmonary bypass is safe but is not associated with a decrease in troponin I concentration. Phosphocreatine had no beneficial effect on clinical outcomes after surgery. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov with the Identifier: NCT02757443. First posted (published): 02/05/2016.

CABG Improves Outcomes in Patients With Ischemic Cardiomyopathy: 10-Year Follow-Up of the STICH Trial.

OBJECTIVES: The authors investigated the impact of coronary artery bypass grafting (CABG) on first and recurrent hospitalization in this population. BACKGROUND: In the STICH (Surgical Treatment for Ischemic Heart Failure) trial, CABG reduced all-cause death and hospitalization in patients with and ischemic cardiomyopathy and left ventricular ejection fraction <35%. METHODS: A total of 1,212 patients were randomized (610 to CABG + optimal medical therapy [CABG] and 602 to optimal medical therapy alone [MED] alone) and followed for a median of 9.8 years. All-cause and cause-specific hospitalizations were analyzed as time-to-first-event and as recurrent event analysis. RESULTS: Of the 1,212 patients, 757 died (62.4%) and 732 (60.4%) were hospitalized at least once, for a total of 2,549 total all-cause hospitalizations. Most hospitalizations (66.2%) were for cardiovascular causes, of which approximately one-half (907 or 52.9%) were for heart failure. More than 70% of all hospitalizations (1,817 or 71.3%) were recurrent events. The CABG group experienced fewer all-cause hospitalizations in the time-to-first-event (349 CABG vs. 383 MED, adjusted hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.03) and in recurrent event analyses (1,199 CABG vs. 1,350 MED, HR: 0.78, 95% CI: 0.65 to 0.94; p < 0.001). This was driven by fewer total cardiovascular (CV) hospitalizations (744 vs. 968; p < 0.001, adjusted HR: 0.66, 95% CI: 0.55 to 0.81; p = 0.001), the majority of which were due to HF (395 vs. 512; p < 0.001, adjusted HR: 0.68, 95% CI: 0.52-0.89; p = 0.005). We did not observe a difference in non-CV events. CONCLUSIONS: CABG reduces all-cause, CV, and HF hospitalizations in time-to-first-event and recurrent event analyses. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Society of Thoracic Surgeons Risk Score and EuroSCORE-2 Appropriately Assess 30-Day Postoperative Mortality in the STICH Trial and a Contemporary Cohort of Patients With Left Ventricular Dysfunction Undergoing Surgical Revascularization.

BACKGROUND: The STICH trial (Surgical Treatment for Ischemic Heart Failure) demonstrated a survival benefit of coronary artery bypass grafting in patients with ischemic cardiomyopathy and left ventricular dysfunction. The Society of Thoracic Surgeons (STS) risk score and the EuroSCORE-2 (ES2) are used for risk assessment in cardiac surgery, with little information available about their accuracy in patients with left ventricular dysfunction. We assessed the ability of the STS score and ES2 to evaluate 30-day postoperative mortality risk in STICH and a contemporary cohort (CC) of patients with a left ventricle ejection fraction ≤35% undergoing coronary artery bypass grafting outside of a trial setting. METHODS AND RESULTS: The STS and ES2 scores were calculated for 814 STICH patients and 1246 consecutive patients in a CC. There were marked variations in 30-day postoperative mortality risk from 1 patient to another. The STS scores consistently calculated lower risk scores than ES2 (1.5 versus 2.9 for the CC and 0.9 versus 2.4 for the STICH cohort), and underestimated postoperative mortality risk. The STS and ES2 scores had moderately good C statistics: CC (0.727, 95% CI: 0.650-0.803 for STS, and 0.707, 95% CI: 0.620-0.795 for ES2); STICH (0.744, 95% CI: 0.677-0.812, for STS and 0.736, 95% CI: 0.665-0.808 for ES2). Despite the CC patients having higher STS and ES2 scores than STICH patients, mortality (3.5%) was lower than that of STICH (4.8%), suggesting a possible decrease in postoperative mortality over the past decade. CONCLUSIONS: The 30-day postoperative mortality risk of coronary artery bypass grafting in patients with left ventricular dysfunction varies markedly. Both the STS and ES2 score are effective in evaluating risk, although the STS score tend to underestimate risk. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Efficiency of Various Cerebral Protection Techniques Used during the Surgical Treatment of Chronic Pulmonary Thromboembolism.

Circulatory arrest during pulmonary thromboendarterectomy (PTE) for chronic pulmonary embolism leads to an increased risk of cerebral ischemia and neurological complications. This study aimed to assess the efficacy of various cerebral protection techniques used during the surgical treatment of chronic pulmonary thromboembolism. We prospectively studied 61 patients with chronic pulmonary thromboembolism who underwent PTE. We compared the dynamics of cerebral oxygen saturation (rSO2, %) during the surgical treatment and analyzed neurological complications during the early postoperative period in two groups of patients: 30 patients who underwent surgery under conditions of moderate hypothermia (23°C-24°C) combined with antegrade unilateral cerebral perfusion (ACP group) and 31 patients who underwent thromboendarterectomy under deep hypothermic circulatory arrest (18°C, DHCA group) combined with craniocerebral hypothermia. In the ACP group, regional rSO2 decreased by less than 20% from baseline during the course of PTE. In the DHCA group, a more profound reduction of cerebral oxygen supply (by >30% from baseline) was recorded compared with the ACP group (p < .05). During the early postoperative period, 29% of patients in the DHCA group exhibited neurological complications, compared with only 7% of patients from the ACP group. The results of logistic regression analysis indicated that the risk of progressive neurological deficit depended on the duration of the intraoperative period when the absolute values of regional rSO2 were <40%. The method with the best adjustment to human physiology in patients with chronic pulmonary thromboembolism was antegrade cerebral perfusion. This method provides a smaller decrease in cerebral oxygen supply during thromboendarterectomy and significantly reduces the risk of ischemia and neurological complications in the early postoperative period.

Comparison of Transesophageal and Transthoracic Echocardiographic Measurements of Mechanism and Severity of Mitral Regurgitation in Ischemic Cardiomyopathy (from the Surgical Treatment of Ischemic Heart Failure Trial).

Mitral regurgitation (MR) is common in ischemic heart disease and contributes to symptoms and mortality. This report compares the results of baseline transesophageal echocardiography (TEE) and transthoracic echocardiography (TTE) imaging of the mechanism and severity of functional MR in patients with ischemic cardiomyopathy in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Independent core laboratories measured both TTE and TEE images on 196 STICH participants. Common measurements to both models included MR grade, mitral valve tenting height and tenting area, and mitral annular diameter. For each parameter, correlations were assessed using Spearman rank correlation coefficients. A modest correlation was present between TEE and TTE for overall MR grade (n = 176, r = 0.52). For mechanism of MR, modest correlations were present for long-axis tenting height (n = 152, r = 0.35), tenting area (n = 128, r = 0.27), and long-axis mitral annulus diameter (n = 123, r = 0.41). For each measurement, there was significant scatter. Potential explanations for the scatter include different orientation of the imaging planes between TEE and TTE, a mean temporal delay of 6 days between TEE and TTE, and statistically significant differences in heart rate and blood pressure and weight between studies. In conclusion, TEE and TTE measurements of MR mechanism and severity correlate only modestly with enough scatter in the data that they are not interchangeable.

Randomized trial of fish oil infusion to prevent atrial fibrillation after cardiac surgery: data from an implantable continuous cardiac monitor.

OBJECTIVE: To test the hypothesis that perioperative OMEGA-3 polyunsaturated fatty acid infusion would reduce the incidence of postoperative atrial fibrillation in patients after coronary artery bypass grafting as assessed by an implantable continuous cardiac monitor. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Tertiary cardiothoracic referral center. PARTICIPANTS: Thirty-nine patients with coronary artery disease who underwent surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were assigned randomly to receive either OMEGA-3 polyunsaturated fatty acids (200 mg/kg/day starting before anesthesia induction for 24 hours followed by 100 mg/kg/day for 7 days) or placebo. The primary outcome was freedom from atrial fibrillation at 2-year follow-up. Reveal(®) cardiac monitor was implanted subcutaneously in all patients. Data from the cardiac monitor were collected on the 10th day and 3, 6, 12, and 24 months postoperatively. MEASUREMENT AND MAIN RESULTS: Postoperative atrial fibrillation developed in 4 (19%) patients in the control group and in 5 (27.8%) patients in the study group at 10-day follow-up (p = 0.88). At 2-year follow-up, 5 (27.8%) patients in the control group and 6 (35.3%) patients in the study group had atrial fibrillation (p = 0.9). Atrial fibrillation duration predicted risk of cardiovascular hospitalization at the 2-year follow-up (regression coefficient estimate = 0.24, standard error 0.02, p<0.0001; R(2) = 0.74). CONCLUSIONS: Infusion of OMEGA-3 polyunsaturated fatty acids failed to prevent the occurrence of atrial fibrillation in 2 years after coronary artery bypass grafting surgery. The cumulative atrial fibrillation duration registered by the continuous cardiac monitor at the 2-year follow-up was a significant predictor of an adverse outcome.

Assessment of results of surgical treatment for persistent atrial fibrillation during coronary artery bypass grafting using implantable loop recorders.

OBJECTIVES: We report our experience with a modified mini-maze procedure and pulmonary vein isolation using radiofrequency energy for treating persistent atrial fibrillation during coronary artery bypass grafting (CABG). METHODS: Ninety-five patients with persistent atrial fibrillation and coronary heart disease underwent open heart surgery combined with intraoperative irrigated radiofrequency ablation. Patients were randomized into the following three groups: CABG and irrigated radiofrequency pulmonary vein isolation (CABG+PVI, n = 31); CABG and an irrigated radiofrequency modified mini-maze procedure (CABG+MM, n = 30); and isolated CABG (CABG alone, n = 34). All patients received implantable loop recorders. RESULTS: No reoperation and no hospital mortality were recorded. Mean follow-up was 14.4 ± 9.7 months. The implantable loop recorder-determined freedom from atrial fibrillation was 80% in the CABG+PVI group, 86.2% in the CABG+MM group and 44.1% in the CABG alone group. CONCLUSIONS: Patients with concomitant atrial fibrillation and coronary heart disease may benefit from intraoperative ablation to prevent relapse of arrhythmia.

Mechanisms of functional mitral regurgitation in ischemic cardiomyopathy determined by transesophageal echocardiography (from the Surgical Treatment for Ischemic Heart Failure Trial).

The mechanisms underlying functional mitral regurgitation (MR) and the relation between mechanism and severity of MR have not been evaluated in a large, multicenter, randomized controlled trial. Transesophageal echocardiography (TEE) was performed in 215 patients at 17 centers in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Both 2-dimensional (n = 215) and 3-dimensional (n = 81) TEEs were used to assess multiple quantitative measurements of the mechanism and severity of MR. By 2-dimensional TEE, leaflet tenting area, anterior and posterior leaflet angles, mitral annulus diameter, left ventricular (LV) end-systolic volume index, LV ejection fraction (LVEF), and sphericity index (p <0.05 for all) were significantly different across MR grades. By 3-dimensional TEE, mitral annulus area, leaflet tenting area, LV end-systolic volume index, LVEF, and sphericity index (p <0.05 for all) were significantly different across MR grades. A multivariate analysis showed a trend for annulus area (p = 0.069) and LV end-systolic volume index (p = 0.071) to predict effective regurgitant orifice area and for annulus area (p = 0.018) and LV end-systolic volume index (p = 0.073) to predict vena contracta area. In the STICH trial, multiple quantitative parameters of the mechanism of functional MR are related to MR severity. The mechanism of functional MR in ischemic cardiomyopathy is heterogeneous, but no single variable stands out as a strong predictor of quantitative severity of MR.

Influence of baseline left ventricular function on the clinical outcome of surgical ventricular reconstruction in patients with ischaemic cardiomyopathy.

AIMS: The Surgical Treatment for Ischemic Heart Failure (STICH) trial demonstrated no overall benefit when surgical ventricular reconstruction (SVR) was added to coronary artery bypass grafting (CABG) in patients with ischaemic cardiomyopathy. The present analysis was to determine whether, based on baseline left ventricular (LV) function parameters, any subgroups could be identified that benefited from SVR. METHODS AND RESULTS: Among the 1000 patients enrolled, Core Lab measures of baseline LV function with adequate quality were obtained in 710 patients using echocardiography, in 352 using cardiovascular magnetic resonance, and in 344 using radionuclide imaging. The relationship between LV end-systolic volume index (ESVI), end-diastolic volume index, ejection fraction (EF), regional wall motion abnormalities, and outcome were first assessed only by echocardiographic measures, and then by 13 algorithms using a different hierarchy of imaging modalities and their quality. The median ESVI and EF were 78.0 (range: 22.8-283.8) mL/m2 and 28.0%, respectively. Hazard ratios comparing the randomized arms by subgroups of LVESVI and LVEF measured by echocardiography found that patients with smaller ventricles (LVESVI <60 mL/m2) and better LVEF (≥33%) may have benefitted by SVR, while those with larger ventricles (LVESVI >90 mL/m(2)) and lower LVEF (≤25%) did worse with SVR. Algorithms using all three imaging modalities found a weaker relationship between LV global function and the effects of SVR. The extent of regional wall motion abnormality did not influence the effects of SVR. CONCLUSIONS: Subgroup analyses of the STICH trial suggest that patients with less dilated LV and better LVEF may benefit from SVR, while those with larger LV and poorer LVEF may do worse. Clinical Trial Registration #: NCT00023595.

Benefit of ablation of first diagnosed paroxysmal atrial fibrillation during coronary artery bypass grafting: a pilot study.

OBJECTIVES: Whether patients with recent onset of paroxysmal atrial fibrillation (PAF) might benefit of epicardial atrial fibrillation (AF) ablation concomitant to coronary artery bypass graft (CABG) is not known. The aim of this prospective, randomized, single-centre pilot study is the comparison of patients with first diagnosed AF submitted to CABG and treated with and without epicardial pulmonary vein isolation (PVI). METHODS: Patients with first diagnosed PAF and indication for CABG were enrolled in this prospective randomized pilot study. The primary endpoint was AF-free survival (AF burden <0.5%) between the two groups at 18-month follow-up. The secondary endpoints were the percentage of AF burden defined through continuous monitoring using an implantable loop recorder, thromboembolic events and procedural complications. All patients were implanted with a subcutaneous cardiac monitor to track the cardiac rhythm and measure the AF burden. RESULTS: This study enrolled 35 patients (mean age 59 ± 7 years, 74% males), followed up for 18 months after CABG. The patients were randomly allocated to two groups, CABG alone (n = 17) and CABG with concomitant PVI (n = 18). At 18-month follow-up after surgery, 16 (89%) patients in the CABG + PVI group were AF-free (i.e. AF% < 0.5%) vs 8 (47%) in the CABG only group (log-rank test, P = 0.007). At the end of follow-up, the mean AF burden in the CABG and the CABG + PVI group was 7.8 ± 5.1 and 1.6 ± 1.8%, respectively (P < 0.001). Two (18.2%) of the 11 patients with AF recurrences were completely asymptomatic. CONCLUSIONS: Patients with recent-onset AF submitted to CABG may benefit of concomitant ablation of the arrhythmia for preventing recurrences.

Ablation of paroxysmal atrial fibrillation during coronary artery bypass grafting: 12 months' follow-up through implantable loop recorder.

OBJECTIVES: The study aimed to identify responders to atrial fibrillation (AF) ablation, through continuous subcutaneous monitoring in patients with paroxysmal atrial fibrillation (PAF), who underwent epicardial pulmonary vein isolation (PVI) concomitantly with coronary artery bypass grafting (CABG). METHODS: Seventy-two patients aged 61.6±4.7 years with PAF underwent epicardial PVI with bipolar radiofrequency during CABG. Conduction block was confirmed by pacing. At the end of the procedure, the implantable loop recorder (ILR) for continuous monitoring was implanted in all patients. Follow-up data were collected through the ILR telemetry. Patients with an AF burden (AF%)<0.5% were considered AF free (responders). Patients with AF%>0.5% were classified as non-responders. The AF episodes stored by the implanted device were visually inspected by the investigators to confirm the arrhythmia. The data were collected each month during 1-year follow-up. RESULTS: No procedure-related complications occurred either for ablation or for the monitoring device. At the first post-ablation follow-up (1 month) during the blanking period, 37 patients (51%) were AF free, that is, with AF%<0.5%. At the end of the blanking period (3rd follow-up), 44 (61%) patients were AF free. At 12 months' follow-up, 52 (72%) patients were AF free. Among 20 (28%) patients with AF recurrence, six (30%) patients were completely asymptomatic. There were no ischaemic strokes during the 1-year follow-up. CONCLUSION: Concomitant AF ablation during CABG is effective in the treatment of AF, as assessed through 1 year of continuous monitoring. Use of subcutaneous monitors is safe and accurate for AF detection, clinically relevant in identifying responders and non-responders and managing the medical therapies accordingly.

Coronary artery bypass grafting with and without concomitant epicardial cardiac resynchronization therapy in patients with ischemic cardiomyopathy: a randomized study.

BACKGROUND: Epicardial implantation of a cardiac resynchronization therapy (CRT) system during coronary artery bypass grafting (CABG) may be an additional treatment method for improving left ventricle (LV) systolic function and dyssynchrony in patients with ischemic heart failure. OBJECTIVE: The objective was to compare the long-term results in patients with severe ischemic heart failure who underwent CABG alone or CABG combined with concomitant epicardial implantation of a CRT system. METHODS: One hundred sixty-four consecutive patients with severe ischemic heart failure and LV dyssynchrony were enrolled into 2 groups: CABG alone (n = 80) and epicardial CRT implantation during CABG (CABG + CRT) (n = 84). This prospective, randomized, and single-blind study was designed to compare clinical and echocardiography data after 6, 12, and 18 months of follow-up. RESULTS: In the CABG group, LV systolic function, dyssynchrony signs, and quality of life did not change postoperatively, compared with preoperative data. In contrast, these parameters significantly improved in the CABG + CRT group. The 2 treatment groups did not differ with respect to postoperative improvement in Canadian Cardiovascular Society class (P = .68). The improvement in the New York Heart Association functional class was much more pronounced in the CABG + CRT group than in the CABG group (P = .029). In the CABG group, 21 patients (26.2%) had died by the 18-month follow-up, compared with 9 patients (10.7%) in the CABG + CRT group (P = .012, log-rank test). CONCLUSION: Epicardial implantation of a CRT system concomitantly with CABG facilitates the early postoperative period, improves LV systolic function, improves the quality of life, and decreases LV dyssynchrony. Moreover, mortality in the CABG + CRT group was significantly lower than in the CABG group.

Coronary artery bypass grafting with concomitant cardiac resynchronisation therapy in patients with ischaemic heart failure and left ventricular dyssynchrony.

OBJECTIVE: We have tested the hypothesis that epicardial implantation of cardiac resynchronisation therapy (CRT) system during coronary artery bypass grafting (CABG) may be an additional treatment method, which can decrease the mortality and improve left ventricle (LV) systolic function in patients with ischaemic heart failure (HF) and LV dyssynchrony. METHODS: One hundred and seventy-eight consecutive patients with severe ischaemic HF and LV dyssynchrony were enrolled in two groups: CABG alone (n=87) and epicardial CRT implantation during CABG (n=91). The primary end point of the study was the comparison of mortality between two groups at 18 months of follow-up. RESULTS: Twenty-three patients (26.1%) in the CABG group died at 18 months of follow-up compared with nine (10%) in CABG+CRT group (log-rank test, p=0.006). The Cox regression analysis revealed that LV dyssynchrony (hazard ratio (HR) 2.634 (1.206-5.751), p=0.015) was the independent predictor of all-cause death and HF hospitalisation. LV systolic function, dyssynchrony signs and quality of life did not change significantly post-CABG compared to pre-CABG data in CABG group patients. On the contrary, echocardiography revealed an improved LV ejection fraction (42±1.9 vs 28±2.7; p<0.001), smaller LV end-systolic volume (120±57.5 vs 164±61.4; p=0.04) and improved LV synchrony in the CABG+CRT group compared with the CABG group. In the CABG+CRT group, more patients improved by two NYHA classes (NYHA, New York Heart Association; 49 vs 0; p=0.028), had a longer 6-min-walk test distance (452±65 vs 289±72; p<0.001) and a better quality of life (22.9±5 vs 46.4±11; p<0.001) compared with the CABG group. CONCLUSION: For majority of the patients with ischaemic HF and evidence of LV dyssynchrony, CABG neither eliminates dyssynchrony nor improves systolic function. Epicardial implantation of a CRT system concomitant with CABG facilitates patient management in the early postoperative period, improves LV systolic function and quality of life and is associated with low mortality at 18 months of follow-up.