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External Validation of the Recalibrated ThoracicRevised Cardiac Risk Index for Predicting the Riskof Major Cardiac Complications After LungResectionAlessandro Brunelli, MD, Stephen D. Cassivi, MD, MS, Juan Fibla, MD, PhD,Lisa A. Halgren, Dennis A. Wigle, MD, PhD, Mark S. Allen, MD,Francis C. Nichols, MD, K. Robert Shen, MD, and Claude Deschamps, MD

Division of General Thoracic Surgery, Mayo Clinic, Rochester, Minnesota

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Background. The recalibrated thoracic revised cardiacrisk index (ThRCRI) has been recently proposed as aspecific tool for cardiac risk stratification before lungresection. However, the ThRCRI has never been exter-nally validated in a population other than the one fromwhich it was derived. The objective of this study was tovalidate the ThRCRI in an external population of candi-dates having undergone major lung resections to assessits reliability for cardiac risk stratification across differentsamples.

Methods. We analyzed 2,621 patients undergoing lo-ectomy (2,431) or pneumonectomy (190) in a singleenter from 2000 to 2009. Patients were grouped into fourlasses of risk (A, B, C, and D) according to the recali-rated ThRCRI. The outcome variable measured was theccurrence of major cardiac complications (cardiac arrest,

omplete heart block, acute myocardial infarction, pul-

Ospedali Riuniti Ancona, Via Conca 1, Ancona 60020, Italy; e-mail:brunellialex@gmail.com.

© 2011 by The Society of Thoracic SurgeonsPublished by Elsevier Inc

onary edema, cardiac death during admission). Inci-ence of major cardiac events was assessed in the fourisk class groupings to assess the discriminative abilityf the index score.

Results. The incidence of major cardiac morbidity was.2% (59 cases). Patients were grouped into four risklasses according to their recalibrated ThRCRI. Incidencef major cardiac morbidity in risk classes A, B, C, and Dere 0.9%, 4.2%, 8%, and 18%, respectively (p < 0.0001).Conclusions. The recalibrated ThRCRI is a reliable

nstrument that can be used during preoperative workupo differentiate patients needing further cardiologic test-ng from those who can proceed without any furtherardiac testing.

(Ann Thorac Surg 2011;92:445–8)

© 2011 by The Society of Thoracic Surgeons

Recent guidelines have recommended the use of car-diac risk scores as a screening tool to select patients

needing preoperative specialized cardiologic testing be-fore proceeding to their surgical procedure. The recentlypublished American Heart Association/American Col-lege of Cardiology [1] and European Society of Cardiol-ogy/European Society of Anesthesiology guidelines [2]have recommended the Revised Cardiac Risk Index(RCRI) [3] as the preferred risk scoring tool to assesscardiac risk in patients undergoing noncardiac surgicalprocedures. Similarly, the joint European RespiratorySociety/European Society of Thoracic Surgeons (ERS-ESTS) task force on fitness for radical treatment of lungcancer patients endorsed these recommendations andproposed a cardiologic algorithm incorporating this scor-ing system as a preliminary screening instrument [4].

Accepted for publication March 22, 2011.

Presented at the Poster Session of the Forty-seventh Annual Meeting ofThe Society of Thoracic Surgeons, San Diego, CA, Jan 31–Feb 2, 2011.

Address correspondence to Dr Brunelli, Division of Thoracic Surgery,

However, the RCRI was originally developed from amixed surgical population, including only a small groupof patients specifically undergoing general thoracic sur-gery procedures. This characteristic of the RCRI hasprompted its recalibration in a population of patientsundergoing a major lung resection [5]. The resultantrecalibrated Thoracic Revised Cardiac Risk Index (ThRCRI),however, has never been validated in an external sampleof patients to test its reliability. Therefore, the objective ofthis study was to test the ThRCRI in a large independentpopulation of patients undergoing major lung resectionsto assess its reliability in predicting major cardiaccomplications.

Patients and Methods

We performed an observational study using prospec-tively collected data. The study was reviewed and ap-proved by the Mayo Clinic Institutional Review Board.

Our review included all 2,621 major lung resections(2,431 pulmonary lobectomy or bilobectomy and 190pneumonectomy) performed in our single-institution se-

ries from January 2000 through December 2009. The

0003-4975/$36.00doi:10.1016/j.athoracsur.2011.03.095

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446 BRUNELLI ET AL Ann Thorac SurgEXTERNAL VALIDATION OF THRCRI 2011;92:445–8

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indication for resection was for nonneoplastic disease(161 cases), primary lung cancer (2,288 cases), or meta-static disease (172 cases).

In general, exclusion criteria for operability were inaccordance with recently published guidelines [6]. Allpatients with a history of cardiac disease or significantcardiac risk factors underwent a preoperative cardiacevaluation by a qualified cardiologist, including history,physical evaluation, resting electrocardiogram (ECG),and if indicated, additional specialized tests, such asechocardiography, stress testing, or other more invasivetests.

All patients who were analyzed for this study andunderwent lung resection were deemed in stable cardiaccondition with optimized medical therapy. If a patientwas deemed to have a prohibitive cardiac risk withunstable hemodynamic conditions, the appropriate treat-ment was instituted as per ACC/AHA guidelines [1], andthe patient was subsequently reevaluated for surgicalresection.

As a rule, all the operations were performed through astandard serratus-anterior muscle-sparing thoracotomyor video-assisted thoracoscopic approach by board-certified thoracic surgeons. Patients were usually extu-bated in the operating room and transferred to a dedi-cated intermediate care thoracic surgery unit withcardiac telemetry monitoring. Patients were admitted tothe intensive care unit only in rare cases of majorcardiopulmonary complications requiring assisted me-chanical ventilation, multiple inotropic support, or inva-sive cardiologic monitoring such as a pulmonary arterycatheter.

Postoperative treatment focused on a strategy of earlyambulation, physical and respiratory rehabilitation, anti-biotic and antithrombotic prophylaxis, and incisionalpain control using a combination of intravenous patient-controlled analgesia and oral analgesics, with epiduralanalgesia being added for patients with planned thora-cotomies. Chest pain was assessed at least twice daily,and treatment was titrated to achieve a pain score lowerthan 4 (on a scale from 0 to 10) in the first postoperative72 hours [7].

The recalibrated ThRCRI is a four-class risk scorecomprising four weighted factors [5] (Table 1): (1) isch-

mic heart disease (defined as the presence of any of theollowing: history of myocardial infarction, history of aositive exercise test, current complaint of chest painonsidered to be due to myocardial ischemia, use ofitrate therapy, or ECG with pathologic Q waves), score �.5 points; (2) history of cerebrovascular disease (transient

able 1. The Four Class Groupings of the Recalibratedhoracic Revised Cardiac Risk Index

Class Score

A 0B 1–1.5C 2–2.5

(D �2.5

schemic attack or stroke), score � 1.5 points; (3) serumreatinine level greater than 2 mg/dL, score � 1 point; and4) planned performance of pneumonectomy, score � 1.5oints. According to the individual weighted scores as-igned to each factor, an aggregate score was calculated forach patient. Patients were then grouped into the fourifferent classes of risk according to their scores, and inci-ence of major cardiac events was assessed in each class.ajor cardiac complications were considered as those oc-

urring during the surgical admission or within 30 daysfter the pulmonary resection and included acute myocar-ial infarction (diagnosed by ECG changes and increasederum troponin level), pulmonary edema (confirmed byonsistent findings at chest radiography), ventricular fibril-ation or primary cardiac arrest, complete heart block, andny cardiac-related death. Finally, the bootstrap resamplingechnique was applied to assess the incidence of majorardiac morbidity in 1,000 samples (of the same number ofatients as the original dataset) of each class of risk. For

nstance, 1,000 random samples of 1,909 cases each wereenerated for class A and the incidence of cardiac morbidityas assessed in each of these samples [8–10].All statistical tests were performed on the statistical

oftware Stata 9.0 (Stata Corp, College Station, TX).

Results

The characteristics of the patients in this study aredisplayed in Table 2. There were 77 major cardiac com-plications in 59 patients (cumulative incidence 2.2%): 19cases of pulmonary edema, 16 acute myocardial infarc-tions, 18 cardiac arrests, 4 cases of complete heart block,and 20 cardiac-related deaths (of 49 total deaths; 40.8%).

Patients were grouped into four risk classes (A, B, C,and D) according to their ThRCRI, predicting an incre-mental risk of cardiac morbidity (p � 0.0001; Table 3).

atients in class D had a 18-fold higher risk of majorardiac complications compared with patients in class A

Table 2. Characteristics of Patients in the Study (n � 2,621)

Variables Value

Age, years 65.6 (12)Male, n 1,420 (54%)Diagnosis, n

Nonneoplastic 161 (6%)Malignant primary 2,288 (87%)Malignant secondary 172 (7%)

FEV1% 80.3% (18%)Dlco% 77.9% (19%)Coronary artery disease, n 442 (17%)Cerebrovascular disease, n 120 (5%)Serum creatinine �2 mg/dL, n 63 (2.5%)Pneumonectomy, n 190 (7.2%)

Results are expressed as means (SD) unless otherwise specified.

FEV1 � forced expiratory volume of air in 1 second; Dlco � diffusionapacity of lung for carbon monoxide.

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The receiver operating characteristic area under thecurve of the ThRCRI in this population was 0.75 forpredicting major cardiac events, indicating moderatediscrimination of the risk index. Bootstrap analysisshowed that the risk of major cardiac complications inclass A was less than 1.5% in 99% of samples, whereas inclass B, the cardiac risk was lower than 5% in 80% butgreater than 2% in 99% of bootstrapped samples. Class Chad a risk of cardiac complications greater than 5% in60% of samples, and class D had a risk greater than 15%in 77% of samples.

Comment

Cardiac morbidity remains a major contributor to com-plications after thoracic surgical procedures. Recentlypublished guidelines from international medical andsurgical societies have recommended the use of cardiacrisk scores as screening tools for stratifying the cardiacrisk of patients undergoing noncardiac surgery. TheERS-ESTS task force for evaluating fitness of lung resec-tion candidates with lung cancer recommended the ap-plication of the Revised Cardiac Risk Index [4] in thisetting. An RCRI lower than 2 has been reported to bessociated with a low risk of cardiac complications, andypically, patients in this risk category do not needdditional cardiac evaluation. However, an RCRI greaterhan 2 has been associated with an increased cardiac risk,nd the task force recommendation is to obtain a cardi-logy consultation with noninvasive testing as per AHA/CC guidelines [1]. However, this initial RCRI score wasriginally developed in a varied surgical population in-luding only a limited number of thoracic surgery pa-ients. Of the 2,893 patients making up the derivation set,nly 346 (12%) underwent intrathoracic procedures [3].For this reason, the RCRI was recently recalibrated in a

specific population of patients undergoing a major pul-monary resection and showed a higher discrimination forthoracic surgery patients than did the traditional score[5]. Only four of the original six factors demonstrated areliable association with major cardiac morbidity. Incontrast to the original paper by Lee and colleagues [3],the ThRCRI also weighted the four factors separately toachieve a more discriminating predictive model of risk ofcardiac complications. Although Brunelli and coworkersused a bootstrap technique [8-10] for its internal valida-

Table 3. Distribution of Patients in Each Class of theRecalibrated Revised Cardiac Risk Index (ThRCRI)

ThRCRI Score Risk Class No. of CasesMajor CardiacComplications

A 1,909 18 (0.9%)–1.5 B 616 26 (4.2%)–2.5 C 25 2 (8%)

�2.5 D 71 13 (18%)

p � 0.0001.

ion, the ThRCRI has never been validated in another

arge population of thoracic surgery patients other thanhe one from which it was derived.

Thus, the objective of this investigation was to exter-ally test the ThRCRI in a larger sample of patientsndergoing a major pulmonary resection to assess itseliability to stratify the risk of major cardiac morbiditynd demonstrate its utility as a cardiac screening tooleneralizable across different thoracic surgery centers. Inhis series, the ThRCRI showed a better discrimination intratifying the risk of cardiac complications, comparedith the original recalibration paper (0.75 versus 0.72) [5].

Class A had a minimal risk. Clearly these patients do notneed further cardiac evaluation before proceeding totheir surgical resection. Classes C and D had a greaterrisk. More in-depth assessment and optimization of ther-apy may be indicated in these groups. Contrary to therecalibration paper of Brunelli and colleagues [3], weound a significant difference between risk classes C and, which is more in keeping with the original four-class

tructure of the RCRI proposed by its originator [3]. Thisiscrepancy may be in part explained by a different caseix or different operability selection criteria.The ThRCRI is the only specific cardiac risk score in

horacic surgery. Several other scores have been devel-ped and tested in this setting, but they incorporatedardiac as well as pulmonary morbidity, including alsoinor cardiac complications such as atrial fibrillation

11–14].Although this analysis was performed in a homoge-

eous, sizable group of patients undergoing major pul-onary resections, it may have potential limitations. The

etrospective nature of the study may permit inherentroblems of selection bias. Variation in definition ofariables and outcomes may occur and are difficult tossess retrospectively. A prospective study would beesirable to confirm these results. The validation of thecore was performed on patients undergoing major pul-onary resections (lobectomy or pneumonectomy). The

ssumption that the ThRCRI is reliable to stratify theardiac risk also after other thoracic procedures includ-ng minor lung resections, esophageal procedures, or

ediastinal surgery may require separate validation. Theecalibrated score aimed at stratifying the risk of majorardiac events. Its use for predicting the occurrence ofther frequent cardiac complications such as atrial fibril-

Fig 1. Rates of cardiac complications according to the Thoracic Re-

vised Cardiac Risk Index classes, A, B, D, and D.

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lation is not directly applicable and would require furtherspecific evaluation.

In conclusion, we were able to validate the recalibratedThRCRI in an external independent large series of majorpulmonary resections. Although the generalizability ofthe present findings would benefit from confirmation in aprospective, multicenter study, we believe they nonethe-less support the use of this score as a screening instru-ment during cardiac risk stratification for selecting pa-tients needing further cardiologic testing beforepulmonary resection.

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2. Poldermans D, Bax JJ, Boersma E, et al. Guidelines forpre-operative cardiac risk assessment and perioperativecardiac management in non-cardiac surgery: the task forcefor preoperative cardiac risk assessment and perioperativecardiac management in non-cardiac surgery of the EuropeanSociety of Cardiology (ESC) and endorsed by the EuropeanSociety of Anaesthesiology (ESA). Eur Heart J 2009;30:2769–812.

3. Lee TH, Marcantonio ER, Mangione CM, et al. Derivationand prospective validation of a simple index for prediction ofcardiac risk of major noncardiac surgery. Circulation 1999;100:1043–1049.

4. Brunelli A, Charloux A, Bolliger CT, et al, for the EuropeanRespiratory Society and European Society of Thoracic Sur-

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5. Brunelli A, Varela G, Salati M, et al. Recalibration of therevised cardiac risk index in lung resection candidates. AnnThorac Surg 2010;90:199–203.

6. Colice GL, Shafazand S, Griffin JP, Keenan R, Bolliger CT, forthe American College of Chest Physicians. Physiologic eval-uation of the patient with lung cancer being considered forresectional surgery: ACCP evidence-based clinical practiceguidelines (2nd edition). Chest 2007;132(Suppl):161–77.

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