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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 12  |  Issue : 1  |  Page : 22-26
Role of cardiac biomarkers (troponin I and CK-MB) as predictors of quality of life and long-term outcome after cardiac surgery


1 Department of Cardiothoracic Anesthesia and Intensive Care, Università Vita-Salute San Raffaele, Milano, Italia e Istituto Scientifico San Raffaele, Milano, Italy
2 Department of Cardiac Surgery, Università Vita-Salute San Raffaele, Milano, Italia e Istituto Scientifico San Raffaele, Milano, Italy

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Date of Submission26-Sep-2008
Date of Acceptance28-Nov-2008
 

   Abstract 

Perioperative and postoperative morbidity and mortality associated with cardiac surgery affect both the outcome and quality of life. Markers such as troponin effectively predict short-term outcome. In a prospective cohort study in a University Hospital we assessed the role of cardiac biomarkers, also as predictors of long-term outcome and life quality after cardiac surgery with a three-year follow-up after conventional heart surgery. Patients were interviewed via phone calls with a structured questionnaire examining general health, functional status, activities of daily living, perception of life quality and need for hospital readmission. Descriptive statistics and multivariate analysis were performed. Out of 252 consecutive patients, 8 (3.2%) died at the three years follow up: 7 for cardiac complications and 1 for cancer. Thirty-six patients (13.5%) had hospital readmission for cardiac causes (mostly for atrial fibrillation or other arrhythmias (9.3%), but none needed cardiac surgical reintervention; 21 patients (7.9%) were hospitalised for non-cardiac causes. No limitation in function activities of daily living was reported by most patients (94%), 92% perceived their general health as excellent, very good or good and none considered it insufficient; 80% were NYHA I, 17% NYHA II, 3% NYHA III and none NYHA IV. Multivariate analysis indicated preoperative treatment with digitalis or nitrates, and postoperative cardiac biomarkers release was independently associated to death. Elevated cardiac biomarker release and length of hospital stay were the only postoperative independent predictors of death in this study.

Keywords: Cardiac biomarkers, outcome, mortality, quality of life, troponin

How to cite this article:
Bignami E, Landoni G, Crescenzi G, Gonfalini M, Bruno G, Pappalardo F, Marino G, Zangrillo A, Alfieri O. Role of cardiac biomarkers (troponin I and CK-MB) as predictors of quality of life and long-term outcome after cardiac surgery. Ann Card Anaesth 2009;12:22-6

How to cite this URL:
Bignami E, Landoni G, Crescenzi G, Gonfalini M, Bruno G, Pappalardo F, Marino G, Zangrillo A, Alfieri O. Role of cardiac biomarkers (troponin I and CK-MB) as predictors of quality of life and long-term outcome after cardiac surgery. Ann Card Anaesth [serial online] 2009 [cited 2019 Jan 17];12:22-6. Available from: http://www.annals.in/text.asp?2009/12/1/22/45009



   Introduction Top


Cardiac surgery is associated with perioperative and postoperative morbidity and mortality, which in turn affect both the outcome and quality of life. Identification of higher-risk patients may allow for better targeting of investigation, monitoring, and treatment, ultimately leading to an improvement in their outcome. [1],[2],[3]

In this, cardiac markers play a major role: postprocedural elevation of cardiac troponin (CTN) in the setting of percutaneous [4] and surgical [5],[6] revascularisation relates to new irreversible myocardial injury on delayed-enhancement magnetic resonance imaging. creatine kinase (CK)-MB is also suitable for this purpose. [7],[8]

In the present study, we evaluated the significance of elevations in CTN I and CK-MB in a large cohort of consecutive patients undergoing cardiac surgery in relation to short- and long-term outcomes and perceived quality of life in survivors. [9],[10],[11] Adjustment for potential confounding factors inherent to patient cohort was applied.


   Materials and Methods Top


A cohort of 267 adult consecutive cardiac surgical patients operated upon over 2-months period at a University Hospital were analysed in order to study the long-term survival and quality of life of patients and to identify the in-hospital predictors of long-term outcome. Patients who were lost at follow-up ( n = 15) were excluded from the analysis. The study cohort consisted of the remaining 252 patients.

The study was carried out according to the principles of the Declaration of Helsinki. The ethical committee approved the study protocol. Patients provided written informed consent.

All patients received a standard premedication (morphine 0.1 mg/kg i.m.; scopolamine 0.25 mg i.m.; diazepam os prn) administered 1 h before surgery, had one large-bore iv catheter and a radial artery cannulated before induction of anaesthesia; pulse oximetry, 5 leads ECG with automated ST-segment analysis, central venous pressure, capnometry and urine output were monitored as well. Temperature was monitored with a bladder or rectal probe with the aim of maintaining 36.5°C throughout the non-cardiopulmonary bypass (CPB) period. Induction of anaesthesia was performed with fentanyl-propofol and orotracheal intubation facilitated by pancuronium. Anaesthesia was maintained with propofol (2-4 mg/kg/h) and isoflurane (end-tidal concentration < 1 MAC) and top-up doses of fentanyl up to a total of 20 mcg/kg (BH) or 25 mcg/kg (CPB). No aprotinin was used.

CPB was conducted with an institutional custom pack including a coated membrane oxygenator, in mild hypothermia (32-33°C). Pump flow was set at 2.4 l/min/m 2 . Myocardial protection was ensured by means of anterograde and retrograde cold blood cardioplegia according to Buckeberg protocol.

Blood samples were drawn at arrival in intensive care unit, 4 and 18 h postoperatively to assay levels of CTN I and CK-MB. CTN I and mass CK-MB were analyzed with Dimension X Pand (Dade-Bohering diagnostics).

Follow-up

After discharge, patients were interviewed by phone calls in order to assess their survival and quality of life. [12],[13] Time from surgery to interview was 39 ± 11 months.

Statistical analysis

Descriptive statistics such as proportions, means (standard deviations) medians (interquartile range) were used to summarise the results. Data were stored electronically and analysed by use of Epi Info 2002 software (CDC, Atlanta, GA) and SAS software, version 8 (SAS Institute, Cary, NC). Data on patients who withdrew from follow-up were censored at the time of withdrawal. Statistical comparison between groups was performed through a two-tailed Chi-square test or through a students' t -test when appropriate. Data are presented as mean ± SD; non-normally distributed variables are expressed as median (25 th -75 th percentile).

We used forward logistic regression to assess the independent correlates of death among the overall cardiac surgery population. Variables with univariate significance ( p < 0.05) were entered into the multivariate regression. For this analysis, we present the odds ratio and 95% CI for each significant perioperative variable. This multivariate analysis was performed including troponin I first and then CK-MB


   Results Top


Among a total of 252 patients included in the study, coronary patients were 107 (84 CABG and 23 combined procedures); the remaining 145 underwent a valve operation (94 mitral repair or replacement, 59 aortic valve replacement, 22 tricuspid repair or replacement with 30 patients undergoing combined procedures)

The demographic, clinical, and biochemical characteristics of the study cohort are shown in [Table 1] with related data comparing those who had died with survivors at 3 years.

Two patients (0.8%) died in hospital, and this number increased to 8 (3.2%) at 3-years follow-up with one death due to cancer. These patients were likely to have preoperative lower ejection fraction and to be on digitalis or nitrates [Table 1].

Postoperatively they were likely to have higher serum CTN I and CK-MB levels, to have cardiac complications requiring intra-aortic ballon pump, and to have acute renal failure, leading to a prolonged ICU stay and hospital stay [Table 1],[Table 2],[Table 3].

Multivariate analysis

The analysis was performed through logistic regression with forward stepwise selection that incorporated all study variables and either CTN I or CK-MB (strongly correlated between themselves: r 2 = 0.96). CTN I was the strongest independent predictor of term mortality ( p = 0.002 with a 15% increased mortality risk for every ng/ml increase in the serum postoperative concentration OR = 1.15, 95%; CI 1.05-1.26) and was the only preoperative postoperative factor that entered into the analysis together with preoperative treatment with digitalis ( p = 0.002) and nitrates ( p = 0.003). When the analysis was repeated adding CK-MB and removing cardiac troponin I, CK-MB confirmed cardiac biomarkers to be an independent predictors of mortality ( p = 0.009) together with digitalis ( p = 0.001) and nitrates ( p = 0.002).

Outcome and quality of life

8 patients died (3.0%), 7 of them for cardiac complications and 1 for cancer.

Thirty-six patients (13.5%) needed hospital readmission because of cardiac causes: atrial fibrillation or other arrhythmias (9.3%), myocardial infarction (0.3%), hearth failure (1.9%), percutaneous stenting (2.2%); and other causes (1.9%). None needed cardiac surgical reintervention, and 21 patients (7.9%) were recovered for non-cardiac causes.

The questions contained in the MOS Short-form General Health Survey (MOS S-F 20), showed no limitation in functional activities of day-to-day life by most patients (94%). Moreover, 92% perceived their general health as excellent, very good or good; none considered it insufficient. In addition, 80% were New York Heart Association (NYHA) I, 17% NYHA II, 3% NYHA III and none NYHA IV.

It should be noted that 74% of the interviewed patients declared they were feeling better after cardiac surgery, and 98% of them did not feel any thoracic pain.


   Discussion Top


Elevated cardiac biomarker release and length of hospital stay were the only postoperative independent predictors of death in this study. Our study also confirms that survivors can enjoy a clinical improvement and a good quality of life without severe limitations at long-term follow-up.

CTN isoforms are proteins belonging to the thin filament regulatory system of the contractile complex. They are specific for the heart and never expressed in skeletal muscle. Because of their high sensitivity and specificity for the heart, troponins are appropriate markers for the diagnosis of perioperative myocardial infarction. [14] At present, the most popular biomarker for myocardial damage is cardiac troponin I (cTnI), with nearly total myocardial tissue specificity and extreme sensitivity, reflecting even a very small amount of myocardial necrosis. Postoperative serum cardiac troponin concentration (cTnI) is increased in all patients undergoing different types of cardiac surgery, an observation that highlights the essential sensitivity of the biochemical marker and a constant level of perioperative myocardial injury. [15],[16],[17]

Causes of cardiac biomarkers elevation may include direct, surgery-related tissue damage, ischemia/reperfusion injury, suboptimal cardiac protection, perioperative myocardial infarction, and preoperative factors such as the extent of underlying coronary artery disease and the presence of left ventricular hypertrophy. The prognostic significance of elevated postprocedural CTN I release has been established by numerous clinical investigation following cardiac surgery; however, such studies have been performed with a shorter follow-up.

Bashour CA et al. [18] considered a follow-up of 24 or 30 months, which has been studied in connection with prolonged intensive care.

Fellahi JL et al. [19] focused on patients who underwent coronary artery bypass grafting (CABG) with a follow-up of 2 years after surgery.

Other authors showed a poor long-term outcome in high-risk subgroups such as patients requiring renal replacement [20] and those with a complicated post-operative course after cardiac surgery requiring prolonged (>7 days) mechanical ventilation. [21],[22]

Lasocki S et al. [23] appeared closer to our results showing that high values of cTn I concentration at one time point, 20 h after the end of surgery, was associated with major postoperative complications after adult cardiac surgery. Concentration of cTn I 20 h after the surgery is an independent predictor of in-hospital mortality, and elevated concentrations of cTn I are associated with death from cardiac causes.

Data presented in this study suggest that elevated cardiac biomarkers after cardiac surgery are associated to poor outcome after cardiac surgery. Identifying patients who are at considerably increased risk may allow for a more intensive monitoring and intervention and facilitate the efficient use of clinical resources. If increased-risk patients could be identified at an early postoperative stage, measures could be instituted to improve their outcome. These might include interventions proven to increase survival in other settings, such as treatment with b-blockers and agents that influence the renin-angiotensin-aldosterone system.

The following limitations to the present study are acknowledged. The study design was observational and no randomisation was introduced; however, the data analysed in our study were all prospectively collected and entered into a database as part of routine patient management at our institution. CTN I levels were available to the clinicians attending the patients and may have prompted interventions that could have influenced the outcome. We did not collect data about temperature after CPB; this issue is of great importance since it has been shown [6] that hypothermia causes alternations in biomarkers. Failing to preserve normothermia during the non-cooling phases of the operation may result in higher levels of Troponin. Furthermore, no data on statin use was collected in this cohort of patients; statins have recently been indicated as prime modulators of the inflammatory response. We also did not perform a power analysis. Cardiac troponin T is being lately referred to as a more specific isoform as its assay has a sole manufacturer: we chose cTn I because it allows for comparison with an amount of literature.


   Conclusions Top


Our 3-year follow-up study shows a low (3.2%) long-term mortality with excellent quality of life in patients undergoing cardiac surgery. Elevated cardiac biomarkers release, preoperative digitalis and nitrates were the only independent predictors of death.

 
   References Top

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5.Selvanayagam JB, Pigott D, Balacumaraswami L, Petersen SE, Neubauer S, Taggart DP. Relationship of irreversible myocardial injury to troponin I and creatine kinase-MB elevation after coronary artery bypass surgery: Insights from cardiovascular magnetic resonance imaging. J Am Coll Cardiol 2005;45:629-31.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
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12.Stewart AL, Greenfield S, Hays RD, Wells K, Rogers WH, Berry SD, et al . Functional status and well-being of patients with chronic conditions: Results from the Medical Outcomes Study. JAMA 1989;262:907-13.  Back to cited text no. 12  [PUBMED]  
13.Stewart AL, Hays RD, Ware JE Jr. The MOS short-form general health survey: Reliability and validity in a patient population. Med Care 1988;26:724-35.  Back to cited text no. 13  [PUBMED]  
14.Adams JE 3rd, Sicard GA, Allen BT, Bridwell KH, Lenke LG, Dαvila-Romαn VG, et al . Diagnosis of perioperative myocardial infarction with measurement of cardiac troponin I. N Engl J Med 1994;330:670-4.  Back to cited text no. 14    
15.Dehoux M, Provenchθre S, Benessiano J, Lasocki S, Lecharny JB, Bronchard R, et al . Utility of cardiac troponin measurement after cardiac surgery. Clin Chim Acta 2001;311:41-4.  Back to cited text no. 15    
16.Antman EM, Tanasijevic MJ, Thompson B, Schactman M, McCabe CH, Cannon CP, et al . cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. N Engl J Med 1996;335:1342-9.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Lindahl B, Toss H, Siegbahn A, Venge P. Marker of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. Circulation 1997;95:2053-9.  Back to cited text no. 17    
18.Bashour CA, Yared JP, Ryan TA, Rady MY, Mascha E, Leventhal MJ, et al . Long-term survival and functional capacity in cardiac surgery patients after prolonged intensive care. Crit Care Med 2000;28:3847-53.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Fellahi JL, Guι X, Richomme X, Monier E, Guillou L, Riou B. Short and long-term prognostic value of postoperative cardiac troponin I concentration in patients undergoing coronary artery bypass grafting. Anesthesiology 2003;99 :270-4.  Back to cited text no. 19    
20.Zangrillo A, Landoni G, Franco A, Aletti G, Roberti A, Calabrò MG, et al . Long-term outcome of patients who require renal replacement therapy after cardiac surgery. EJA 2005;22:1-6.  Back to cited text no. 20    
21.Engoren M, Burder NF, Zacharias A. Long-term survival and health status after prolonged mechanical ventilation after cardiac surgery. Crit Care Med 2000;28:2742-9.  Back to cited text no. 21    
22.Pappalardo F, Franco A, Landoni G, Cardano P, Zangrillo A, Alfieri O. Long-term outcome and quality of life of patients requiring prolonged mechanical ventilation after cardiac surgery. Eur J Cardiothorac Surg 2004;25:548-52.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]
23.Lasocki S, Provenchθre S, Bιnessiano J, Vicaut E, Lecharny JB, Desmonts JM, et al . Cardiac troponin I an independent predictor of in-hospital death after adult cardiac surgery. Anesthesiology 2002;97:405-11.  Back to cited text no. 23    

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Correspondence Address:
Giovanni Landoni
Department of Cardiothoracic and Vascular Anesthesia, Istituto Scientifico San Raffaele, Milano
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.45009

Clinical trial registration None

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    Tables

  [Table 1], [Table 2], [Table 3]

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