Giora Landesberg

Perioperative Myocardial Infarction

More than 230 million major surgeries are performed annually worldwide,1 and this number grows continuously. The 30-day mortality associated with moderate- to high-risk noncardiac surgery in recent large cohorts and population-based studies exceeds 2%2–4 and surpasses 5% in patients at high cardiac risk.5 Cardiac complications constitute the most common cause of postoperative morbidity and mortality,4,6 having considerable impact on the length and cost of hospitalization.7 As our population ages, more high-risk cardiac patients will undergo surgery, and perioperative myocardial infarction (PMI) can be an increasing problem. Traditionally, MI was defined by the World Health Organization criteria, ECG criteria, and cardiac enzymes. Defining PMI, however, is often difficult because most PMIs occur without symptoms in anesthetized or sedated patients, ECG changes are subtle and/or transient, and the creatine kinase-MB isoenzyme has limited sensitivity and specificity because of coexisting skeletal muscle injury.8 Consequently, PMI was often recognized late (postoperative day 3 to 5), resulting in high (30% to 70%9) mortality. Cardiac troponin assays have changed this definition.10 The recent universal definition of MI11 is based on a rise and/or fall of cardiac biomarkers (preferably troponin) in the setting of myocardial ischemia: cardiac symptoms, ECG changes, or imaging findings. Studies using serial troponin measurements demonstrate that most PMIs start within 24 to 48 hours of surgery during the greatest postoperative stress.12–15 Le Manach et al15 observed early ( 24 hours) peaks in troponin in 1136 patients after abdominal aortic aneurysmectomy. Yet, 90% of troponin elevations began within <24 hours. Two distinct mechanisms may lead to PMI: acute coronary syndrome and prolonged myocardial oxygen supply-demand imbalance in the presence of stable coronary artery disease (CAD), designated type 1 and type 2 by the universal definition of MI.11 This distinction …

Myocardial infarction after vascular surgery: the role of prolonged stress-induced, ST depression-type ischemia.

OBJECTIVES The goal of this study was to investigate the nature of the association between silent ischemia and postoperative myocardial infarction (PMI). BACKGROUND Silent ischemia predicts cardiac morbidity and mortality in both ambulatory and postoperative patients. Whether silent stress-induced ischemia is merely a marker of extensive coronary artery disease or has a closer association with infarction has not been determined. METHODS In 185 consecutive patients undergoing vascular surgery, we correlated ischemia duration, as detected on a continuous 12-lead ST-trend monitoring during the period 48 h to 72 h after surgery, with cardiac troponin-I (cTn-I) measured in the first three postoperative days and with postoperative cardiac outcome. Postoperative myocardial infarction was defined as cTn-I >3.1 ng/ml accompanied by either typical symptoms or new ischemic electrocardiogram (ECG) findings. RESULTS During 11,132 patient-hours of monitoring, 38 patients (20.5%) had 66 transient ischemic events, all but one denoted by ST-segment depression. Twelve patients (6.5%) sustained PMI; one of those patients died. All infarctions were non-Q-wave and were detected by a rise in cTn-I during or immediately after prolonged, ST depression-type ischemia. The average duration ofischemia in patients with PMI was 226+/-164 min (range: 29 to 625), compared with 38+/-26 min (p = 0.0000) in 26 patients with ischemia but not infarction. Peak cTn-I strongly correlated with the longest, as well as cumulative, ischemia duration (r = 0.83 and r = 0.78, respectively). Ischemic ECG changes were completely reversible in all but one patient who had persistent new T wave inversion. All ischemic events culminating in PMI were preceded by an increase in heart rate (delta heart rate = 32+/-15 beats/min), and most (67%) of them began at the end of surgery and emergence from anesthesia. CONCLUSIONS Prolonged, ST depression-type ischemia progresses to MI and is strongly associated with the majority of cardiac complications after vascular surgery.

Prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurement after noncardiac surgery: a systematic review and meta-analysis.

Background:There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. Methods:The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessing whether a postoperative troponin or creatine kinase muscle and brain isoenzyme measurement was an independent predictor of mortality or a major cardiovascular event. Independent investigators determined study eligibility and abstracted data in duplicate. Results:Fourteen studies, enrolling 3,318 patients and 459 deaths, demonstrated that an increased troponin measurement after surgery was an independent predictor of mortality (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.2–5.2), but there was substantial heterogeneity (I2 = 56%). The independent prognostic capabilities of an increased troponin value after surgery in the 10 studies that assessed intermediate-term (≤ 12 months) mortality was an OR = 6.7 (95% CI 4.1–10.9, I2 = 0%) and in the 4 studies that assessed long-term (more than 12 months) mortality was an OR = 1.8 (95% CI 1.4–2.3, I2 = 0%; P < 0.001 for test of interaction). Four studies, including 1,165 patients and 202 deaths, demonstrated an independent association between an increased creatine kinase muscle and brain isoenzyme measurement after surgery and mortality (OR 2.5, 95% CI 1.5–4.0, I2 = 4%). Conclusions:An increased troponin measurement after surgery is an independent predictor of mortality, particularly within the first year; limited data suggest an increased creatine kinase muscle and brain isoenzyme measurement also predicts subsequent mortality. Monitoring troponin measurements after noncardiac surgery may allow physicians to better risk stratify and manage their patients.

Perioperative myocardial ischemia and infarction: identification by continuous 12-lead electrocardiogram with online ST-segment monitoring.

Background Perioperative myocardial ischemia is conventionally monitored using five electrocardiographic leads, with only one precordial lead placed at V5. This is based on studies from more than a decade ago. The authors reassessed this convention by analyzing data obtained from continuous on-line 12-lead electrocardiographic monitoring. Methods One hundred eighty-five consecutive patients undergoing vascular surgery were monitored by continuous 12-lead ST-trend analysis during and for 48–72 h after surgery. Cardiac troponin I was measured in the first 3 postoperative days, and cardiac outcome was prospectively recorded. Ischemia was defined as ST deviation, relative to the reference preanesthesia electrocardiogram, of 0.2 mV or more in one lead or 0.1 mV or more in two contiguous leads, lasting more than 10 min. Results During 11,132 patient-hours of monitoring, 38 patients (20.5%) had 66 transient ischemic events, with all but one denoted by ST-segment depression. Twelve patients (6.5%) sustained postoperative infarction (cardiac troponin I > 3.1 ng/ml). Among the 38 patients with ischemia, lead V3 most frequently (86.8%) demonstrated ischemia, followed by V4 (78.9%) and V5 (65.8%). Among the 12 patients with infarction, V4 was most sensitive to ischemia (83.3%), followed by V3 and V5 (75% each). Combining two precordial leads increased the sensitivity for detecting ischemia (97.4% for V3 + V5 and 92.1% for either V4 + V5 or V3 + V4) and infarction (100% for V4 + V5 or V3 + V5 and 83.3% for V3 + V4). On average, baseline preanesthesia ST was above isoelectric in V1 through V3 and below isoelectric in V5 through V6. Lead V4 was closest to the isoelectric level on the baseline electrocardiogram, rendering it most suitable for ischemia monitoring. Conclusions As a single lead, V4 is more sensitive and appropriate than V5 for detecting prolonged postoperative ischemia and infarction. Two precordial leads or more are necessary so as to approach a sensitivity of greater than 95% for detection of perioperative ischemia and infarction.

Troponin elevation in severe sepsis and septic shock: The role of left ventricular diastolic dysfunction and right ventricular dilatation

Objective:Serum troponin concentrations predict mortality in almost every clinical setting they have been examined, including sepsis. However, the causes for troponin elevations in sepsis are poorly understood. We hypothesized that detailed investigation of myocardial dysfunction by echocardiography can provide insight into the possible causes of troponin elevation and its association with mortality in sepsis. Design:Prospective, analytic cohort study. Setting:Tertiary academic institute. Patients:A cohort of ICU patients with severe sepsis or septic shock. Interventions:Advanced echocardiography using global strain, strain-rate imaging and 3D left and right ventricular volume analyses in addition to the standard echocardiography, and concomitant high-sensitivity troponin-T measurement in patients with severe sepsis or septic shock. Measurements and Main Results:Two hundred twenty-five echocardiograms and concomitant high-sensitivity troponin-T measurements were performed in a cohort of 106 patients within the first days of severe sepsis or septic shock (2.1 ± 1.4 measurements/patient). Combining echocardiographic and clinical variables, left ventricular diastolic dysfunction defined as increased mitral E-to-strain-rate e′-wave ratio, right ventricular dilatation (increased right ventricular end-systolic volume index), high Acute Physiology and Chronic Health Evaluation-II score, and low glomerular filtration rate best correlated with elevated log-transformed concomitant high-sensitivity troponin-T concentrations (mixed linear model: t = 3.8, 3.3, 2.8, and –2.1 and p = 0.001, 0.0002, 0.006, and 0.007, respectively). Left ventricular systolic dysfunction determined by reduced strain-rate s′-wave or low ejection fraction did not significantly correlate with log(concomitant high-sensitivity troponin-T). Forty-one patients (39%) died in-hospital. Right ventricular end-systolic volume index and left ventricular strain-rate e′-wave predicted in-hospital mortality, independent of Acute Physiology and Chronic Health Evaluation-II score (logistic regression: Wald = 8.4, 6.6, and 9.8 and p = 0.004, 0.010, and 0.001, respectively). Concomitant high-sensitivity troponin-T predicted mortality in univariate analysis (Wald = 8.4; p = 0.004), but not when combined with right ventricular end-systolic volume index and strain-rate e′-wave in the multivariate analysis (Wald = 2.3, 4.6, and 6.2 and p = 0.13, 0.032, and 0.012, respectively). Conclusions:Left ventricular diastolic dysfunction and right ventricular dilatation are the echocardiographic variables correlating best with concomitant high-sensitivity troponin-T concentrations. Left ventricular diastolic and right ventricular systolic dysfunction seem to explain the association of troponin with mortality in severe sepsis and septic shock.

Perioperative Myocardial Ischemia in Carotid Endarterectomy Under Cervical Plexus Block and Prophylactic Nitroglycerin Infusion

Perioperative myocardial ischemia was evaluated in 36 consecutive carotid endarterectomy procedures carried out on patients with a high (72.2%) prevalence of ischemic heart disease. The procedures were performed under cervical plexus block plus a prophylactic intravenous nitroglycerin infusion. Findings of myocardial ischemia on perioperative (48 hours) continuous electrocardiogram recordings were correlated with preoperative cardiac status, perioperative continuous intra-arterial blood pressure measurements, and postoperative cardiac outcome. In two patients, ST segment analysis was un-interpretable because of bundle-branch blocks. Altogether, 64 episodes of significant ST segment depression were detected in 18 (52.9%) of the remaining procedures. In 8 (23.5%) procedures, ST segment depressions occurred either during carotid artery clamping at the time of the largest rise in blood pressure or within 2 hours of declamping, when blood pressure tended to decline. There were four (11.7%) postoperative cardiac events: three myocardial infarctions (one Q wave and two non-Q wave) and one episode of unstable angina pectoris. All four patients with cardiac events had early signs of myocardial ischemia either at the time of cross-clamping, or soon after declamping of the carotid artery. All myocardial infarctions developed following prolonged (> 10 hours) myocardial ischemia, starting with the first 20 hours after surgery. Thus, ST segment depression occurring during clamping or soon after carotid declamping was associated with cardiac complications (sensitivity 100% and specificity 86.6%) and suggests the possible usefulness of on-line ST segment trend monitoring.

Step baroreflex response in awake patients undergoing carotid surgery: time- and frequency-domain analysis

Step baroreceptor stimulation can provide an insight into the baroreflex control mechanism, yet this has never been done in humans. During carotid surgery under regional anesthesia, a step increase in baroreceptor stimulation occurs at carotid declamping immediately after removal of the intra-arterial atheromatous plaque. In 10 patients, the R-R interval and systolic and diastolic blood pressures (BP) were continuously recorded, and signals obtained within the time window from 10 min before until 10 min after carotid declamping were analyzed. Mean +/- SD time signals, power spectra, and transfer and coherence functions before and after declamping were calculated. Immediately after carotid declamping, both heart rate (HR) and BP declined in an exponential-like manner lasting 10.3 +/- 5.9 min, and their power spectra increased in the entire frequency range. Transfer function magnitude and coherence functions between BP and HR increased predominantly in the midfrequency region (approximately 0.1 Hz), with no change in phase function. Thus, in carotid endarterectomy patients, step increase in baroreceptor gain elicits a prolonged decline in HR and BP. Frequency analyses support the notion that the baroreflex control mechanism generates the midfrequency HR and BP variability, although other frequency regions are also affected.Step baroreceptor stimulation can provide an insight into the baroreflex control mechanism, yet this has never been done in humans. During carotid surgery under regional anesthesia, a step increase in baroreceptor stimulation occurs at carotid declamping immediately after removal of the intra-arterial atheromatous plaque. In 10 patients, the R-R interval and systolic and diastolic blood pressures (BP) were continuously recorded, and signals obtained within the time window from 10 min before until 10 min after carotid declamping were analyzed. Mean ± SD time signals, power spectra, and transfer and coherence functions before and after declamping were calculated. Immediately after carotid declamping, both heart rate (HR) and BP declined in an exponential-like manner lasting 10.3 ± 5.9 min, and their power spectra increased in the entire frequency range. Transfer function magnitude and coherence functions between BP and HR increased predominantly in the midfrequency region (∼0.1 Hz), with no change in phase function. Thus, in carotid endarterectomy patients, step increase in baroreceptor gain elicits a prolonged decline in HR and BP. Frequency analyses support the notion that the baroreflex control mechanism generates the midfrequency HR and BP variability, although other frequency regions are also affected.

Carotid-Cardiac Interaction: Heart Rate Variability During the Unblocking of the Carotid Artery

Multiresolution representations of the heart rate variability (HRV) using the wavelet transforms are proposed to characterize the autonomic nervous system regulation of cardio-vascular activity during carotid surgery. Results suggest that the power in all frequency bands was low during the surgery and increased after the declamping of the carotid artery.

PRO: Preoperative Coronary Revascularization in High-Risk Patients Undergoing Vascular Surgery

Morris Mosseri, MD** Dr. Kertai has done an excellent job in the core review in distilling the essence from the complex and multifaceted literature on preoperative coronary revascularization. However, under the surface, a titanic debate takes place on some major issues: Does any randomized controlled trial (RCT) always provide better evidence than any observational study? Can two recent RCTs completely overturn the data accumulated by a number of previous observational studies? Was the methodology used to generate the data adequately convincing? First some basic facts that must be acknowledged in the discussion:

The Enigma of Postoperative Troponin Elevation.

July 2016 • Volume 123 • Number 1 www.anesthesia-analgesia.org 5 Copyright