Cardiology Consultation and Assessment of Cardiac Risk 1

Sources of Perioperative Myocardial Injury in Cardiac Surgery

Myocardial injury manifested as transient cardiac contractile dysfunction or acute myocardial infarction (AMI) remains an important source of postoperative complication and death in patients undergoing cardiac surgery. Patients who experience a perioperative myocardial infarction (MI) have a poor long-term prognosis; only 51% of such patients remain free from adverse cardiac events after 2 years, compared with 96% of patients without perioperative MI.

It is important to understand how perioperative myocardial injury results in morbidity and mortality to clarify the determinants of perioperative risk. This is particularly important with respect to cardiac outcomes because the definition of cardiac morbidity represents a continuum rather than a discrete event.

Myocardial necrosis is the result of progressive pathologic ischemic changes that start to occur in the myocardium within minutes after interruption of its blood flow (eg during cardiac surgery) ( Box 1.1 ). The duration of the interruption of blood flow, either partial or complete, determines the extent of myocardial necrosis, and both the duration of the period of aortic cross-clamping (AXC) and the duration of cardiopulmonary bypass (CPB) are known to be the main determinants of postoperative outcomes. In a study with an average follow-up of 10 years after complex cardiac surgery, Khuri observed a direct relation between the lowest mean myocardial pH recorded during or after the period of AXC and long-term patient survival. Patients who experienced acidosis (pH <6.5) had decreased survival compared with those who did not. Because myocardial acidosis reflects both myocardial ischemia and poor myocardial protection during CPB, this study demonstrated the relation of the adequacy of intraoperative myocardial protection to long-term outcome.

BOX 1.1

Determinations of Perioperative Myocardial Injury

• Disruption of blood flow

• Reperfusion of ischemic myocardium

• Adverse systemic effects of cardiopulmonary bypass

Surgical Reperfusion of Ischemic Myocardium

Interventions requiring interruption of blood flow to the heart must be followed by restoration of perfusion. Numerous experimental studies have provided compelling evidence that reperfusion, although essential for tissue and organ survival, is not without risk because of the potential extension of cell damage as a result of reperfusion itself. Myocardial ischemia of limited duration (<20 min) that is followed by reperfusion leads to functional recovery without evidence of structural injury or biochemical evidence of tissue injury. ^, However, reperfusion of cardiac tissue that has been subjected to an extended period of ischemia results in a phenomenon known as myocardial reperfusion injury. Thus, a paradox exists in that tissue viability can be maintained only if reperfusion is instituted within a reasonable period, but doing so risks extending the injury beyond that caused by the ischemic insult itself.

Myocardial reperfusion injury is defined as the death of myocytes, which were alive at the time of reperfusion, as a direct result of one or more events initiated by reperfusion. The cellular damage that results from reperfusion can be reversible or irreversible, depending on the duration of the ischemic insult. If reperfusion is initiated within 20 minutes after the onset of ischemia, the resulting myocardial injury is reversible and is characterized functionally by depressed myocardial contractility, which eventually recovers completely. Myocardial tissue necrosis is not detectable in the previously ischemic region, although functional impairment of contractility may persist for a variable period, a phenomenon known as myocardial stunning. Initiation of reperfusion after longer than 20 minutes, however, results in escalating degrees of irreversible myocardial injury or cellular necrosis. The extent of tissue necrosis that develops during reperfusion is directly related to the duration of the ischemic event. Tissue necrosis originates in the subendocardial region of the ischemic myocardium and extends to the subepicardial region of the area at risk; this is often referred to as the wavefront phenomenon. The cell death that occurs during reperfusion can be characterized microscopically by explosive swelling, which includes disruption of the tissue lattice, contraction bands, mitochondrial swelling, and calcium phosphate deposition within mitochondria.

The magnitude of reperfusion injury is directly related to the magnitude of the ischemic injury that precedes it. In its most severe form, it manifests as a “no-reflow” phenomenon. In cardiac surgery, prevention of myocardial injury after release of the AXC, including prevention of no-reflow, is directly dependent on the adequacy of myocardial protection during the period of AXC. The combination of ischemic and reperfusion injury is probably the most frequent and most serious type of injury leading to poor outcomes in cardiac surgery today.

Adverse Systemic Effects of Cardiopulmonary Bypass

In addition to the effects of disruption and restoration of myocardial blood flow, cardiac morbidity may result from systemic insults due to CPB circuit-induced contact activation. Inflammation in cardiac surgical patients is produced by complex humoral and cellular interactions, including activation, generation, or expression of thrombin, complement, cytokines, neutrophils, adhesion molecules, mast cells, and multiple inflammatory mediators. Because of the redundancy of the inflammatory cascades, profound amplification occurs to produce multiorgan system dysfunction that can manifest as coagulopathy, respiratory failure, myocardial dysfunction, renal insufficiency, and neurocognitive defects. Coagulation and inflammation also are linked closely through networks of both humoral and cellular components, including tissue factor and proteases of the clotting and fibrinolytic cascades (see Chapter 28 ). Vascular endothelial cells mediate inflammation and the crosstalk between coagulation and inflammation. Surgery alone activates specific hemostatic responses, immune mechanisms, and inflammatory responses mediated by the release of various cytokines and chemokines. This complex inflammatory reaction can lead to death from nonischemic causes and suggests that preoperative risk factors may not adequately predict morbidity. The ability to risk-adjust populations is critical for the study of interventions that may influence these responses to CPB.

Echocardiography

Cardiac contractile dysfunction is the most prominent feature of myocardial injury, even though there are no perfect measures of postoperative cardiac function. The need for inotropic support, low cardiac output (CO) diagnosed with the use of CO measurement technologies, and assessment of abnormal ventricular function by transesophageal echocardiography (TEE) are practical intraoperative options for evaluation of cardiac contractility. Use of inotropic support and CO measurements are not entirely reliable measures, however, because they depend on loading conditions and interpractitioner variability. Failure to wean from CPB, in the absence of systemic factors such as hyperkalemia and acidosis, is the best evidence of intraoperative myocardial injury or cardiac dysfunction, but it also may be multifactorial and, therefore, is a less robust outcome measure.

Because RWMAs on TEE follow the onset of ischemia within 10 to 15 seconds, echocardiography can be a sensitive and rapid monitor for cardiac ischemia/injury. The importance of echocardiographic assessment of cardiac function is further enhanced by its value as a predictor of long-term survival. For patients undergoing CABG, a postoperative decrease in left ventricular ejection fraction (LVEF) compared with the preoperative baseline predicts decreased long-term survival.

Nevertheless, the use of echocardiography for detecting postoperative left ventricular (LV) systolic dysfunction has some challenges. Echocardiographic and Doppler systems have the limitation of being sensitive to alterations in loading conditions, similar need for inotropic support and CO determinations, and the interpretation of TEE images is operator dependent. Additionally, myocardial stunning (postischemic transient ventricular dysfunction) is a common cause of new postoperative RWMAs, and the resulting wall motion abnormalities and LV systolic dysfunction are often transient.

Electrocardiography

The presence of new persistent Q waves of at least 0.03 seconds duration, broadening of preexisting Q waves, or new QS deflections on the postoperative ECG have been considered evidence of perioperative AMI. However, new Q waves also may be caused by unmasking of an old MI and, therefore, are not indicative of a new AMI. Crescenzi and colleagues demonstrated that the presence of a new Q wave together with high levels of biomarkers was strongly associated with postoperative cardiac events, whereas the isolated appearance of a new Q wave had no impact on postoperative cardiac outcome. Additionally, new Q waves may disappear over time. Signs of non–Q-wave MI, such as ST-T wave changes, are even less reliable signs of AMI after cardiac surgery in the absence of biochemical evidence. ST-segment changes are less specific for perioperative MI because they can also be caused by changes in body position, hypothermia, transient conduction abnormalities, pericarditis, and electrolyte imbalances.

Biomarkers

Numerous studies have demonstrated the value of cardiac biomarkers in predicting short- and long-term outcomes in patients undergoing cardiac surgery. For example, Klatte and coworkers reported on the implications of CK-MB level in high-risk CABG patients. They reported that unadjusted 6-month mortality rates were 3.4%, 5.8%, 7.8%, and 20.2% for patients with CK-MB ratios (peak CK-MB value divided by the upper limit of normal for the laboratory test) of <5, between 5 and 10, between 10 and 20, and >20, respectively. The relation remained statistically significant after adjustment for LVEF, congestive heart failure (CHF), cerebrovascular disease, peripheral vascular disease, cardiac arrhythmias, and the method of cardioplegia delivery. In the Arterial Revascularization Therapies Study (ARTS), 496 patients with multivessel coronary artery disease undergoing CABG were evaluated by CK-MB testing after surgery and at 30 days and 1 year of follow-up. Patients with increased cardiac enzyme levels after CABG were at increased risk for both death and repeat AMI within the first 30 days. CK-MB increase also was independently related to late adverse outcome. Other studies have similarly documented the prognostic value of cTn I. Increased cTn I or T after CABG has been associated with a cardiac cause of death and with major postoperative complications within 2 years after CABG. ^,

Brain natriuretic peptide (BNP) can be detected in the early stages of ischemia and decreases shortly after ischemic insult, allowing better detection of reinjury. BNP concentrations after CABG in patients who experienced cardiac events within 2 years after surgery were significantly greater than those in patients free of cardiac events. Soluble CD40 ligand (sCD40L) is another early biomarker of myocardial ischemia, and CPB causes an increase in the concentration of plasma sCD40L. A corresponding decrease in platelet CD40L suggests that this prothrombotic and proinflammatory protein is derived primarily from platelets and may contribute to the thrombotic and inflammatory complications associated with CPB. Future research will be required to determine how these biomarkers may be used to assess outcome after cardiac surgery.

Predictors of Perioperative and Postoperative Morbidity and Mortality

Clinical and angiographic predictors of operative mortality were initially defined from the results of the Coronary Artery Surgery Study (CASS). ^, A total of 6630 patients underwent isolated CABG between 1975 and 1978. Women had a significantly greater mortality rate than men; mortality increased with advancing age in men, but this was not a significant factor in women. Increasing severity of angina, manifestations of HF, and number and extent of coronary artery stenoses all correlated with greater mortality, whereas LVEF was not a predictor. Urgency of surgery was a strong predictor of outcome.

A risk-scoring scheme for cardiac surgery (CABG and valve) was introduced by Paiement and associates at the Montreal Heart Institute in 1983. Eight risk factors were identified: (1) poor LV function, (2) HF, (3) unstable angina or recent MI (within 6 weeks), (4) age greater than 65 years, (5) severe obesity (body mass index >30 kg/m ² ), (6) reoperation, (7) emergency surgery, and (8) other significant or uncontrolled systemic disturbances. The investigators identified three classes of patients: those with none of the listed risk factors (normal), those presenting with one risk factor (increased risk), and those with more than one factor (high risk). In a study of 500 consecutive patients undergoing cardiac surgery, it was found that operative mortality increased with increasing risk score (confirming the scoring system).

One of the most used scoring systems for CABG was developed by Parsonnet and colleagues ( Table 1.1 ). Fourteen risk factors were identified for in-hospital or 30-day mortality after univariate regression analysis of 3500 consecutive operations. An additive model was constructed and prospectively evaluated in 1332 cardiac procedures. Five categories of risk were identified with increasing mortality rates, complication rates, and length of stay at the Newark Beth Israel Medical Center. The Parsonnet Index is used frequently as a benchmark for comparisons among institutions. However, it was created earlier than the other models and may not be representative of the current practice of CABG. Since publication of the Parsonnet model, numerous technical advances now in routine use have diminished CABG mortality rates. Bernstein and Parsonnet simplified the risk-adjusted scoring system in to provide a handy tool in preoperative discussions with patients and their families and for preoperative risk calculation and stratification. The authors developed a logistic regression model, in which 47 potential risk factors were considered, and a method requiring only simple addition and graphic interpretation was designed for relatively easy approximation of the estimated risk. The final estimates provided by the simplified model correlated well with the observed mortality ( Fig. 1.1 ).

The Society of Thoracic Surgeons (STS) National Adult Cardiac Surgery Database represents the most robust source of data for calculating risk-adjusted scoring systems. Established in 1989, the database included 892 participating hospitals in 2008 and has continued to grow. This provider-supported database, one of the largest in the world, allows participants to benchmark their risk-adjusted results against regional and national standards. New patient data are brought into the STS database on a semiannual basis. These new data are analyzed, modeled, and tested using a variety of statistical algorithms. Since 1990, when more complete data collection was achieved, risk stratification models have been developed for both CABG and valve replacement surgery. Models developed in 1995 and 1996 were shown to have good predictive value. ^, In 1999, the STS analyzed the database for valve replacement with and without CABG to determine trends in risk stratification. Between 1986 and 1995, 86,580 patients were analyzed. After the significant risk factors were determined by univariate analysis, a standard logistic regression analysis was performed using the training-set population to develop a formal model. The preoperative risk factors associated with greatest operative mortality rates were salvage status, renal failure (dialysis dependent and nondialysis dependent), emergent status, multiple reoperations, and New York Heart Association class IV status. The addition of CABG increased the mortality rate significantly for all age groups and for all subset models.

There are currently three general STS risk models: CABG, valve (aortic or mitral), and valve plus CABG. These three models comprise seven specific, precisely defined procedures: the CABG model refers to an isolated CABG; the valve model includes isolated aortic or MV replacement and MV repair; and the valve plus CABG model includes AV replacement with CABG, MV replacement with CABG, and MV repair with CABG. Besides operative mortality, these models were developed for eight additional end points: reoperation, permanent stroke, renal failure, deep sternal wound infection, prolonged (>24 h) ventilation, composite major morbidity or mortality, prolonged length of stay (>14 days), and short length of stay (<6 days and alive). These models are updated every few years and are calibrated annually to provide an immediate and accurate tool for regional and national benchmarking, and they have been proposed for public reporting. The calibration of the risk factors is based on the ratio between observed and expected results (O/E ratio), and calibration factors are updated quarterly. The expected mortality (E) is calibrated to obtain a national O/E ratio. The models are available as a simple online calculator ( https://riskcalc.sts.org/stswebriskcalc/calculate ).

The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is another widely used model for cardiac operative risk evaluation. It was constructed from an analysis of 19,030 patients undergoing a diverse group of cardiac surgical procedures from 128 centers across Europe ( Tables 1.2 and 1.3 ). ^, The following risk factors were associated with increased mortality: age, female sex, elevated serum creatinine level, extracardiac arteriopathy, chronic airway disease, severe neurologic dysfunction, previous cardiac surgery, recent MI, reduced LVEF, chronic HF, pulmonary hypertension, active endocarditis, unstable angina, procedure urgency, critical preoperative condition, ventricular septal rupture, noncoronary surgery, and thoracic aortic surgery. For a given individual, each of these risk factors is assigned a score, and the sum of these is used to predict surgical risk. In 2003, a more sophisticated, logistic version of EuroSCORE was released to permit more accurate risk assessment in individuals deemed to be at very high risk.

The additive EuroSCORE has been used widely and validated across various centers in Europe and around the world, making it a primary tool for risk stratification in cardiac surgery. Although its accuracy has been well established for CABG and isolated valve procedures, its predictive ability in combined CABG and valve procedures has been less well studied. Karthik and associates showed that, in patients undergoing combined procedures, the additive EuroSCORE significantly underpredicted the risk when compared with the observed mortality. The logistic EuroSCORE performed better in this setting.

In 2011, the EuroSCORE was recalibrated to keep up with new evidence. The revised EuroSCORE, known as EuroSCORE II, permits more accurate risk estimation yet preserves the powerful discrimination of the original model. The EuroSCORE II is currently the recommended model for assessment of cardiac surgical risk. It can be accessed online www.euroscore.org/calc.html or downloaded as a smartphone application.

Many other investigators have developed risk assessment models using data representing different populations and different surgical practices. Hannan and colleagues evaluated predictors of mortality after valve surgery using data from 14,190 patients in New York state. A total of 18 independent risk factors were identified in the 6 models of differing combinations of valve surgery and CABG. Shock and dialysis-dependent renal failure were among the most significant risk factors for in-hospital mortality in all models.

Dupuis and associates attempted to simplify the approach to evaluating the risk of cardiac surgical procedures in a manner similar to the original American Society of Anesthesiologists (ASA) physical status classification. They developed a score that uses a simple categorization of five classes plus an emergency status ( Box 1.3 ). The Cardiac Anesthesia Risk Evaluation (CARE) score model collected data from 1996 to 1999 and included 3548 patients to predict both in-hospital mortality and a diverse group of major morbidities. It combined clinical judgment and the recognition of three risk factors previously identified by multifactorial risk indices: comorbid conditions categorized as controlled or uncontrolled, the complexity of the surgery, and the urgency of the procedure. The CARE score demonstrated predictive characteristics similar or superior to those of the more complex indices. The development of these risk models for cardiac surgery provides a powerful new tool to improve patient care, select procedures, counsel patients, and compare outcomes.

BOX 1.3

Cardiac Anesthesia Risk Evaluation (CARE) Score

From Dupuis JY, Wang F, Nathan H, Lam M, Grimes S, Bourke M. The Cardiac Anesthesia Risk Evaluation Score: a clinically useful predictor of mortality and morbidity after cardiac surgery. Anesthesiology. 2001;94:194-204 with permission.

• 1 = Patient with stable cardiac disease and no other medical problem (a noncomplex surgery is undertaken)

• 2 = Patient with stable cardiac disease and one or more controlled medical problems ^a

  a Examples: controlled hypertension, diabetes mellitus, peripheral vascular disease, chronic obstructive pulmonary disease, controlled systemic diseases, others as judged by clinicians.

  (a noncomplex surgery is undertaken)

• 3 = Patient with any uncontrolled medical problem ^b

  b Examples: unstable angina treated with intravenous heparin or nitroglycerin, preoperative intraaortic balloon pump, heart failure with pulmonary or peripheral edema, uncontrolled hypertension, renal insufficiency (creatinine level >140 μmol/L), debilitating systemic diseases, others as judged by clinicians.

  or any patient in whom a complex surgery is undertaken ^c

  c Examples: reoperation, combined valve and coronary artery surgery, multiple valve surgery, left ventricular aneurysmectomy, repair of ventricular septal defect after myocardial infarction, coronary artery bypass of diffuse or heavily calcified vessels, others as judged by clinicians.

• 4 = Patient with any uncontrolled medical problem and in whom a complex surgery is undertaken

• 5 = Patient with chronic or advanced cardiac disease for whom cardiac surgery is undertaken as a last hope to save or improve life

• E = Emergency: surgery as soon as diagnosis is made and operating room is available