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ORIGINAL ARTICLE |
Modarres Cardiovascular Research Center and Department of Cardiovascular Surgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mahnoosh Foroughi, MD, Tel: +9821 22083106, Fax: +9821 22083106, Email: mahnoosh.foroughi{at}gmail.com, Department of Cardiovascular Surgery, Shahid Modarres Medical Center, Saadat-Abad, Tehran, 1998734383, Iran.
ABSTRACT
QT-interval prolongation has been shown to predict mortality in coronary artery disease and heart failure. To assess the prognostic value of QT interval for death due to low cardiac output after coronary artery bypass grafting, the QT interval was measured in 3 consecutive beats on the preoperative electrocardiogram (leads II and V4) in 30 patients who died perioperatively due to heart failure and a control group of 168 randomly matched hospital survivors during the same 3-year period. Mean corrected QT interval was significantly longer in the patients who died compared to the control group (480.7 ± 96.2 vs. 425.4 ± 21 ms). Among the variables evaluated, QT prolongation was the only independent predictor of perioperative death. In patients admitted for coronary artery bypass grafting, QT interval measurement is a simple clinical tool that may identify patients with a greater probability of a troublesome operative course.
Key Words: Low Cardiac Output • Coronary Artery Bypass • Electrocardiography • Hospital Mortality
INTRODUCTION
The QT interval of the surface electrocardiogram (ECG) includes the electrical activation of the ventricles and represents the time from onset of ventricular depolarization to complete repolarization. Prolongation of this interval has been associated with ventricular arrhythmias that may trigger ventricular fibrillation and sudden cardiac death. Preclinical evaluation of delayed ventricular repolarization, manifested as prolonged QT interval, is routinely used as an indicator of potential risk of pro-arrhythmia, such as impending torsades de pointes. The cardiovascular complication rate is increased in high-risk patients with prolonged QT intervals. The corrected QT (QTc) prolongation is especially associated with an increased mortality rate (predominantly due to arrhythmias) in patients with advanced heart failure.1–3 Only a few studies have specifically addressed sudden cardiac death. Prolongation of the QT interval increases the risk of coronary heart disease, ventricular arrhythmias, and sudden death in diabetic or elderly patients and after myocardial infarction (MI).4–11 An association between QT prolongation and cardiovascular risk factors has been demonstrated in middle-aged and elderly subjects. Furthermore, to our knowledge, no study so far has evaluated the effect of QT prolongation on other possible etiologies of death in patients undergoing cardiac surgery. Other possibly harmful consequences of prolonged QT interval have not been evaluated in the medical literature. The aim of this study was to assess the effect of prolonged QT interval in patients with coronary artery disease undergoing coronary artery bypass grafting (CABG) as a predictor of low cardiac output leading to operative death.
PATIENTS AND METHODS
A retrospective study was conducted at Modarres Hospital, a University-affiliated tertiary medical center in Tehran, from April 2005 to March 2008. There were 43 deaths in patients undergoing CABG during this period. Six patients whose deaths were unrelated to cardiac etiology (uncontrollable bleeding or cerebrovascular accident) were excluded. A further 7 patients who died due to cardiac pathology were also excluded: 2 had left bundle branch block and were excluded because of related extended QRS duration, and 5 had refractory ventricular tachycardia. The remaining 30 patients who died perioperatively solely due to pump failure formed the study group. All of these patients manifested cardiovascular shock despite pharmacological and circulatory support. Of the patients with a normal convalescence who were discharged from the hospital in an acceptable condition during the same 3-year period, 168 were randomly selected as a control group. They were matched for sex, diabetes, hypertension, use of drugs such as angiotensin converting enzyme inhibitors and diuretics, left ventricular (LV) ejection fraction, and history of MI. Hypertension was defined as use of antihypertensive medication for high blood pressure, or systolic blood pressure 
140 mm Hg and/or diastolic blood pressure 90 mm Hg. Diabetes was defined as use of blood glucose-lowering medication, insulin use, and/or non-fasting or post-loaded glucose level >10 mmol·L–1. History of MI was assessed by ECG evidence or proven history of MI. Exclusion criteria included left bundle branch block, atrial fibrillation, preoperatively implanted pacemakers, emergency CABG, CABG concomitant with other cardiac operations, and use of class III antiarrhythmic drugs.
Anesthesia in our institution was provided according to a fixed protocol. Premedication consisted of oral diazepam 10–15 mg 2 h before the operation. After insertion of peripheral venous and radial arterial cannulae under local anesthesia, general anesthesia was induced with sufentanil 2.5 µg·kg–1 and midazolam 0.1 mg·kg–1. Anesthesia was maintained with sufentanil, midazolam, and pancuronium. Cefuroxime 1.5 g was administered after induction. Lactated Ringer’s solution was used to obtain a mean arterial pressure>60 mm Hg to maintain filling pressures and cardiac output. Transfusions of packed cells were given if the hemoglobin fell below 6.0 g·dL–1. In the intensive care unit, inotropic support with dopamine was started at a cardiac index <2.2 L·min–1 ·m–2. Patient characteristics and perioperative variables were recorded. Nonpulsatile cardiopulmonary bypass (CPB) was initiated using a roller pump and membrane oxygenator. The extracorporeal circuit was primed with 1,500 mL lactated Ringer’s solution. Flow during CPB was maintained at 2.2 L·min–1 ·m–2 with moderate hypothermia (32°C) and alpha-stat regulation of blood pH. Heparin 3 mg·kg–1 was given directly into the right atrium before cannulation of the aorta. During CPB, the mean arterial pressure was allowed to vary between 60 and 90 mm Hg. Deviations beyond this range were corrected with phenylephrine or nitroglycerine. On termination of CPB, heparin was neutralized with protamine sulfate. Cold blood cardioplegic solution was infused into the aortic root to maintain cardiac arrest during aortic crossclamping. Parallel retrograde blood cardioplegia was also administrated for maintenance. In all patients, CABG was performed through a median sternotomy, and the left anterior descending artery was always grafted using the left internal mammary. Patients with low cardiac output in the operating room were routinely reevaluated for graft patency to rule out inadequate revascularization and exclude the possibility of graft closure. On both occasions when low output was detected, all grafts were found to be patent.
A standard 12-lead ECG tracing at 25 mm·s–1 paper speed and 10 mm/mV amplitude, which is generally adequate for accurate measurements, was used to determine QT-interval duration. The ECG recorded at the first visit was used for this study. Mean QT-interval duration for 3 consecutive beats in leads II and V4 was calculated. Each QT interval was measured from the beginning of the QRS complex to visual return of the T wave to the isoelectric line. When the T wave was interrupted by the U wave, the end of the T wave was defined as the nadir between the T and U waves. The most common calculation method in current use is Bazett’s formula; thus heart rate was corrected using the Bazett formula, and QTc interval duration was defined as the mean duration of all QTc intervals measured. Prolonged QTc was defined as a QTc interval>440 ms. The measurements of every ECG were made by 2 cardiologists blinded to the hospital course of the patients. The average of the 2 readings was used.
Statistical analysis was performed using SPSS 11.5 for Windows (SPSS Inc., Chicago, IL, USA). Normal and continuous variables are described by mean and standard deviation, whereas categorical variables are summarized by number of patients and percentage. Comparisons of categorical variables were carried out using the chi-squared test or Fisher’s exact test if n <5. Comparison of 2 normal (determined by the Kolmogorov-Smirnov test) and continuous variables was accomplished with Student’s t test. Multivariate analysis was undertaken with step-wise logistic regression, including the variables with statistical significance in univariate analysis and those with known clinical impact. A p value <0.05 was considered to represent a significant difference.
RESULTS
During the study period, 2,834 patients underwent CABG, of whom 43 (1.52%) died in the perioperative period. Death was due to pump failure 30 cases: 15 in operating room and 15 postoperatively, mainly in the intensive care unit. Baseline patient characteristics are summarized in Table 1
. An acceptable match was observed between the study and control groups regarding the previously defined variables. The QTc data are also presented in Table 1. The mean QTc interval was considerably longer in the study group compared to controls. Demographic (age, hypertension, diabetes, QTc) and clinical (MI, LV ejection fraction) variables that might influence perioperative events were entered for logistic regression analysis (Table 2). Only QTc prolongation (QTc >440 ms) was found to be an independent predictor of perioperative death (p =0.003); the effects of age, LV function, and drug usage were not significant.
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Failure to achieve adequate cardiac output and end-organ oxygen delivery can be caused by many, often codependent, factors. The factor contributing most to depressed postoperative cardiac function is the same pathology that existed immediately prior to the operation. Even after successful surgery, it is unusual to see an immediate improvement in contractile function. Preoperative cardiac abnormalities are not limited to systolic function and may involve diastolic, valvular, vascular, and of course electrophysiological function. All of these aspects are crucial determinants of outcome.
Most physicians think of ECG interpretation as primarily based on pattern recognition. Possible etiologic factors of QT prolongation include demographic variations (advanced age, female sex), congenital (various genetic disorders), heart-related (low LV ejection fraction, LV hypertrophy, ischemia, slow heart rate), metabolic disorders (hypokalemia, hypomagnesemia), endocrine diseases (diabetes), and drug use (class IA or III antiarrhythmics, antibiotics, antihistaminics, anti-depressants, methadone). However, the ECG contains highly refined quantitative data reflecting a number of abnormalities of cardiac electrophysiology and structure. Some epidemiological studies have shown that prolongation of QTc constitutes a risk factor for cardiovascular death because it may be a marker of myocardial ischemia, LV dysfunction, or LV hypertrophy. Acute ischemia can prolong the QT interval by several physiological mechanisms: impaired myocardial response to catecholamines, abnormal flux of calcium ions during the cardiac action potential, change in intracellular hydrogen, and perturbation of potassium currents.12 All of these pathological conditions may contribute to a higher incidence of low cardiac output syndrome in patients undergoing CABG, who already have reduced myocardial perfusion.
Predictors of poor survival after CABG have been determined in the general population; however, the relationship between mortality after CABG and QT interval has not been fully investigated. The present study revealed that QTc interval was more prolonged in patients who died due to low cardiac output following CABG. Kramer and colleagues13 assessed the relationship between the degree of coronary artery disease, LV function, and the duration of the QT interval. In patients with 1-, 2-, and 3-vessel disease, significant changes in QTc were observed only when LV function was impaired (LV ejection fraction <60%); in such patients, QTc interval increased significantly from 1- to 3-vessel coronary disease. Vrtovec and colleagues2 investigated the predictive value of prolonged QTc interval for mortality in patients with heart failure undergoing CABG. Mortality was 6-times higher (9.1% vs. 1.5%) in patients who exhibited prolonged QTc interval, and it was the only independent predictor of postoperative mortality on multivariate analysis. Their study population was not similar to ours, being selected from patients with heart failure. The study design was also different from the present study. Algra and colleagues12 conducted a study on patients who had an ambulatory ECG and were followed up for 2 years. Some of these patients suffered sudden death during follow-up; in those without intraventricular conduction defects and cardiac dysfunction, QT prolongation was a risk factor for sudden death independent of age, history of MI, heart rate, and drug use. In patients with cardiac dysfunction, QTc prolongation did not predict an increased risk of sudden death. These findings contrast with those of the present study, although the study populations differed.
Our study design might have caused some selection bias that prevents extrapolation of the results to all patients undergoing CABG. Three of these issues are stated here. First, QT measurement was performed conventionally using a 12-lead ECG without computerized techniques; however, we are not sure whether this would significantly alter our results. Second, Bazett’s correction formula is not optimal in the case of extreme heart rates. Typically, our patients had normal mean heart rates on the hospital admission ECG, so this would not have had a significant impact on our study. Third, the limited sample size may reduce the statistical power of our analysis. Another matched prospective cohort study is recommended to assess more precisely the effect of prolonged QTc on perioperative heart failure and consequent mortality in patients undergoing CABG surgery. This may be quite difficult because we only had 30 patients to evaluate out of 2,834 CABG operations.
Efforts have been focused on earlier and better identification of high-risk patients who need more aggressive medical and interventional treatment. Our data show one important finding: that the QTc interval was longer in patients who died perioperatively due to low cardiac output. In patients admitted for CABG, the QTc is a simple and useful clinical tool to identify those with a greater probability of having an abnormal operative course. Patients with a prolonged QTc should be managed cautiously. This might include correction of etiologic factors of prolonged QT, such as rectifying electrolyte imbalance or causative drug discontinuation. Further studies involving a larger number of patients are required to elucidate the clinical value of our finding.
Presented at the 17th Annual Meeting of Asian Society for Cardiovascular and Thoracic Surgery, Taipei, Taiwan, March 5–8, 2009.
REFERENCES
Asian Cardiovasc Thorac Ann 2009;
17:604-607
© 2009 by SAGE Publications
DOI: 10.1177/0218492309349068
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