- Email: [email protected]
Prognostic models for cardiovascular events after successful primary percutaneous coronary intervention
168
Letters to the Editor
Treated hyperthyroid patients without cardiac symptoms were not included. d) Only short-term follow-up was available. In conclusion, in successfully treated hyperthyroidism, autoimmune myocarditis can be identified and CMR is of diagnostic value even in the absence of other clinical and/or laboratory findings. However, further studies are needed to assess the clinical implications of these results. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [10]. There is no conflict of interest related to this work. References [1] Anakwue RC, Onwubere BJ, Anisiuba BC, Ikeh VO, Mbah A, Ike SO. Congestive heart failure in subjects with thyrotoxicosis in a black community. Vasc Health Risk Manag 2010;6:473–7. [2] Fatourechi V, Edwards WD. Graves' disease and low-output cardiac dysfunction: implications for autoimmune disease in endomyocardial biopsy tissue from eleven patients. Thyroid 2000;10(7):601–5.
[3] Mavrogeni S, Spargias K, Markussis V, et al. Myocardial inflammation in autoimmune diseases: investigation by cardiovascular magnetic resonance and endomyocardial biopsy. Inflamm Allergy Drug Targets 2009;8:390–7. [4] Mavrogeni S, Spargias C, Bratis C, et al. Myocarditis as a precipitating factor for heart failure: evaluation and 1-year follow-up using cardiovascular magnetic resonance and endomyocardial biopsy. Eur J Heart Fail 2011;13:830–7. [5] Friedrich M, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: a JACC White Paper. J Am Coll Cardiol 2009;53:1475–87. [6] Chen YT, Yang GG, Hsu YH. Thyroid storm and lymphocytic myocarditis. Intern Med 2010;49:593–6. [7] Lorin De La Grandmaison G, Izembart M, Fornes P, et al. Myocarditis associated with Hashimoto's disease: a case report. Int J Legal Med 2003;117:361–4. [8] Umpierrez GE, Challapalli S, Patterson C. Congestive heart failure due to reversible cardiomyopathy in patients with hyperthyroidism. Am J Med Sci 1995;310:99–102. [9] Abdel-Aty H, Boye P, Zagrosek A, et al. Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches. J Am Coll Cardiol 2005;45:1815–22. [10] Coats AJS, Shewan LG. Statement on Authorship and Publishing Ethics in the International Journal of Cardiology. Int J Cardiol 2011;153:257–8.
0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.04.089
Prognostic models for cardiovascular events after successful primary percutaneous coronary intervention Konstantinos Toutouzas a,⁎,1, Andreas Synetos a,1, Antonios Karanasos a, Charalampia Nikolaou a, Archontoula Michelongona a, Demosthenes Panagiotakos b, Eleftherios Tsiamis a, Costas Tsioufis a, Dimitris Tousoulis a, Christodoulos Stefanadis a a b
First Department of Cardiology, Hippokration Hospital, University of Athens, Athens, Greece Department of Nutrition-Dietetics, Harokopio University, Athens, Greece
a r t i c l e
i n f o
Article history: Received 9 February 2012 Received in revised form 10 April 2012 Accepted 14 April 2012 Available online 9 May 2012 Keywords: Angioplasty Coronary interventions Prognosis Coronary artery disease
Several prognostic models have been proposed for the prediction of the outcome of patients with chronic stable angina or acute coronary syndromes undergoing revascularization. The introduction of the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score (SXscore), has shifted the attention toward stratifying the individual risk according to lesion complexity, and to the extent and distribution of coronary atheromatosis [1,2]. However, the absence of clinical factors has led to the creation of a pure clinical model (Age, Creatinine, and Ejection Fraction; ACEF) and of two combined risk models, the Global Risk Classification (GRS) and the Clinical SYNTAX score (CSS) [3,4] that have incorporated clinical variables into the SXscore.
⁎ Corresponding author at: 26 Karaoli and Dimitriou str., Holargos, 15562, Athens, Greece. Tel.: + 30 210 6510860; fax: +30 210 7250153. E-mail address: [email protected] (K. Toutouzas). 1 These authors contributed equally to this article.
There are several prognostic models for the outcome after primary PCI. However, there are no studies including only patients with successful primary PCI. The aim of this study was 1) to validate and compare the performance of the GRS and the CSS in patients undergoing successful primary PCI, and 2) to evaluate whether the combined risk models provide additive prognostic information to the ACEF score, the EuroSCORE, and the SXscore. Three hundred and forty five consecutive patients that underwent successful primary PCI due to STEMI in our hospital were recruited out of 361 primary PCIs. Successful primary PCI was defined as the presence of TIMI flow 3 after the procedure [5,6]. The SXscore for each patient was calculated by a team of 2 experienced interventional cardiologists. All coronary lesions with a diameter stenosis ≥ 50% in vessels ≥ 1.5 mm were scored using the SXscore algorithm, which is available on the website (www.syntaxscore.com). EuroSCORE was calculated based on the original methodology [7]. The ACEF score was calculated based on the modified formula proposed by Ranucci et al. [8], (i.e., ACEF= [age / left ventricular ejection fraction (LVEF)] + 1 if serum creatinine N2 mg/dl). The GRS and the CSS were derived as previously described [4,9]. Renal dysfunction was defined as serum creatinine N2 mg/dl [8]. The investigated outcomes included: adverse events that were assessed during hospitalization, as well as at 1, 6, 12 and 24 months after hospital discharge. The follow-up was performed in our outpatient department or by telephone. The primary endpoint was the 2-year incidence of fatal cardiac events (cardiovascular death; CVD), consisting of sudden death, myocardial infarction, or death secondary to heart failure. Deaths were considered cardiac following the ICD-10 definitions.
Letters to the Editor
169
Table 1 Baseline demographic and angiographic characteristics of the participants. Sex (male) Age (years) Number of diseased vessels LM 1VD 2VD 3VD Culprit vessel LAD LCX RCA Type of stent EES ZES SES PES BMS POBA Vessel diameter (mm) Total stent length (mm) Medication after PCI Aspirin Clopidogrel Prasugrel Beta blockers ACE inhibitors Statins
295 (85.5%) 63 ± 12
191 (55.3%) 34 (9.8%) 120 (34.7%) 157 (45.6%) 77 (22.3%) 34 (9.9%) 22 (6.3%) 47 (13.7%) 7 (2.0%) 3.05 ± 0.45 29.56 ± 14.79 345 (100%) 336 (97.3%) 9 (2.6%) 341 (99.1%) 335 (97.1%) 342 (99.1%)
ROC curve
CVD
SxScore ACEF CSS Reference Line
Sensitivity
0,8
0,6
0,4
SCORE SxSCORE Euroscore GRS ACEF CSS
0,2
Area ,665 ,635 ,658 ,783 ,781
0,0 0,2
0,4
0,6
0,8
1.0
1 - Specificity Diagonal segments are produced by ties. Fig. 1. ROC curves for cardiovascular death at 2-year follow-up.
Sensitivity
13 (3.7%) 197 (57.1%) 80 (23.1%) 69 (20%)
Secondary end points were: target lesion failure (TLF), repeat revascularization (RR), stent thrombosis (ST) and major adverse cardiac event (MACE). Specifically, target lesion failure (TLF) was defined as heart attack attributed to the target vessel (target vessel myocardial infarction), and ischemia-driven target lesion revascularization [10]. Repeat revascularization (RR) was considered as any kind or revascularization in any coronary artery. Stent thrombosis (ST) was defined according to the ARC definitions [11]. Major adverse cardiovascular events (MACE) were defined as the composite of death from all causes, nonfatal myocardial infarction, or target vessel revascularization. Data are presented as mean ± SD or absolute and relative frequencies. The Kolmogorov–Smirnov test was used to assess normal-
0,0
MACE
SxScore ACEF CSS Reference Line
0,8
Data are presented as mean ± SD or absolute and relative frequencies. LM: Left main coronary artery; VD: Vessel Disease; LAD: Left Anterior Descending Artery; LCX: Left Circumflex Artery; RCA: Right Coronary Artery; ACE: Angiotensin converting enzyme; EES: Everolimus Eluting Stent; ZES: Zotarolimus Eluting Stent; SES: Sirolimus Eluting Stent; PES: Paclitaxel eluting Stent; BMS: Bare metal Stent; POBA: Plain old Balloon Angioplasty.
1.0
ROC Curve
1,0
0,6
0,4
SCORE SxSCORE Euroscore GRS ACEF CSS
0,2
0,0
0,0
0,2
0,4
0,6
Area ,638 ,673 ,646 ,639 ,703
0,8
1,0
1 - Specificity Diagonal segments are produced by ties. Fig. 2. ROC curves for major adverse cardiac events at 2-year follow-up.
ity. Receiver Operating Characteristic (ROC) curves were plotted and the corresponding C-statistics were calculated in order to evaluate scores’ performance in predicting the outcomes. Comparisons between Cstatistic values were performed using the Z-test. Unadjusted predictors of MACE and CVD during follow-up were assessed by Cox proportional hazard models. Predictors with p-value b0.10 were included in a multiadjusted analysis with backward elimination, after excluding multicollinearity by analysis of variance inflation factor, in order to identify independent predictors of events at follow-up. Data analyses were performed using the SPSS 19 software (SPSS Inc., Chicago IL, USA). Baseline clinical and procedural characteristics of the population are shown in Table 1. The median follow-up period was 476 days (mean 496 ± 5 days). GRS was higher in patients with CVD, TLF, ST, RR and MACE as compared with patients with no event. CSS score was higher in patients with CVD, TLF RR, MACE, as well as in those who died, as compared with those who did not experience an event. The ROC curves for CVD and MACE at 2-year follow-up are presented in Figs. 1 and 2 respectively. The corresponding C-statistics for the CSS, GRS, SxScore, ACEF, and EUROscore for 2-year CVD mortality were 0.781, 0.658, 0.665, 0.783, and 0.635 and for 2-year MACE were 0.703, 0.646, 0.638, 0.639 and 0.673 respectively. Pairwise comparisons between Cstatistics revealed that the CSS score better classified event from eventfree patients, as compared with all other scores (Bonferroni corrected ps b 0.05), with the exception of 2-year CVD where there was no significant difference between the CSS and the ACEF scores. The results of the unadjusted and the multi-adjusted analysis are shown in Table 2. Because CSS was non-normally distributed and the assumption of linearity was not achieved, log transformation was performed resulting to normal distribution of the new variable (logCSS). Despite the fact that renal dysfunction and LVEF were included in the definition of CSS, collinearity was low (All variance inflation factors b1.25). Unadjusted analysis showed that log-CSS, renal dysfunction, and LVEF were predictors of MACE and CVD; whereas, multi-adjusted analysis, controlling for renal dysfunction and LVEF, revealed that logCSS was an independent predictor of MACE and CVD during follow-up. A separate multi-adjusted analysis was performed for the GRS, because there was high collinearity with the CSS. GRS was also found to be a predictor of MACE and CVD during follow-up, even after adjustment for LVEF and renal dysfunction. The main findings of the current study are: 1) CSS predicts better compared to GRS, SxScore, ACEF and EuroSCORE the incidence of cardiovascular death and/or MACE, and 2) CSS is an independent
170
Letters to the Editor
Table 2 Unadjusted and multi-adjusted predictors of MACE and CVD at 2-year follow-up. Multi-adjusteda analysis for MACE
Unadjusted analysis for MACE LVEF CSS-log Renal dysfunction
b
95% CI
P value
b
95% CI
P value
− 0.16 2.69 2.51
0.83–0.89 3.88–57.03 4.39–38.11
b0.0001 b0.0001 b0.0001
− 0.13 1.78
0.82–0.92 1.73–20.41
b 0.0001 b 0.0001
Multi-adjusteda analysis for CVD
Unadjusted analysis for CVD LVEF CSS-log Renal dysfunction
− 0.22 4.36 3.08
0.74–0.85 13.71–454.74 7.03–68.48
b0.0001 b0.0001 b0.0001
−0.17 2.62
0.77–0.90 2.70–70.81
b 0.0001 0.002
CI: confidence interval; LVEF: Left Ventricular Ejection Fraction.; CSS: Clinical Syntax Score. a Variables entered in the models were: LVEF, CSS-log, and renal dysfunction.
predictor of cardiovascular death and/or MACE after successful primary PCI for the treatment of STEMI. The clinical characteristics of the studied population and primary outcomes of the present study were similar to studies previously published. The data provided in other studies are not comparable to our population, as we included only patients with successful primary PCI. However, the inclusion criteria of the current study justify the better results regarding the outcome of MACE and of stent thrombosis. In other studies the range for cardiovascular mortality and MACE was 13– 36% and 8.9–11.9%, respectively, versus 5.5 and 8.9% of the studied population [12–17]. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1–2). No conflicts of interest.
References [1] Sianos G, Morel MA, Kappetein AP, et al. The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention Aug 2005;1(2):219–27. [2] Dawkins KD, Morel MA, Serruys PW. Counting the score: the SYNTAX score and coronary risk. EuroIntervention May 2009;5(1):33–5. [3] Capodanno D, Miano M, Cincotta G, et al. EuroSCORE refines the predictive ability of SYNTAX score in patients undergoing left main percutaneous coronary intervention. Am Heart J Jan 2010;159(1):103–9. [4] Garg S, Sarno G, Garcia-Garcia HM, et al. A new tool for the risk stratification of patients with complex coronary artery disease: the clinical SYNTAX score. Circ Cardiovasc Interv Aug 2010;3(4):317–26. [5] Smith Jr SC, Dove JT, Jacobs AK, et al. ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines)—executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) endorsed by the Society for Cardiac Angiography and Interventions. Circulation Jun 19 2001;103(24):3019–41. [6] Hamada S, Nishiue T, Nakamura S, et al. TIMI frame count immediately after primary coronary angioplasty as a predictor of functional recovery in patients with TIMI 3 reperfused acute myocardial infarction. J Am Coll Cardiol Sep 2001;38(3):666–71.
0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.04.088
[7] Singh M, Rihal CS, Lennon RJ, Garratt KN, Holmes Jr DR. A critical appraisal of current models of risk stratification for percutaneous coronary interventions. Am Heart J May 2005;149(5):753–60. [8] Ranucci M, Castelvecchio S, Menicanti L, Frigiola A, Pelissero G. Risk of assessing mortality risk in elective cardiac operations: age, creatinine, ejection fraction, and the law of parsimony. Circulation Jun 23 2009;119(24):3053–61. [9] Capodanno D, Caggegi A, Miano M, et al. Global risk classification and clinical SYNTAX (synergy between percutaneous coronary intervention with TAXUS and cardiac surgery) score in patients undergoing percutaneous or surgical left main revascularization. JACC Cardiovasc Interv Mar 2011;4(3):287–97. [10] Nikolsky E, Lansky AJ, Sudhir K, et al. SPIRIT IV trial design: a large-scale randomized comparison of everolimus-eluting stents and paclitaxel-eluting stents in patients with coronary artery disease. Am Heart J Oct 2009;158(4):520–6 [e2]. [11] Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation May 1 2007;115(17):2344–51. [12] Garg S, Sarno G, Serruys PW, et al. Prediction of 1-year clinical outcomes using the SYNTAX score in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a substudy of the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials. JACC Cardiovasc Interv Jan 2011;4(1):66–75. [13] Magro M, Nauta S, Simsek C, et al. Value of the SYNTAX score in patients treated by primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: The MI SYNTAXscore study. Am Heart J Apr 2011;161(4):771–81. [14] Pedersen S, Galatius S, Mogelvang R, et al. Long-term clinical outcome in STEMI patients treated with primary PCI and drug-eluting or bare-metal stents: insights from a high-volume single-center registry. J Invasive Cardiol Aug 2011;23(8):328–33. [15] Simsek C, Magro M, Boersma E, et al. Comparison of six-year clinical outcome of sirolimus- and paclitaxel-eluting stents to bare-metal stents in patients with STsegment elevation myocardial infarction: an analysis of the RESEARCH (rapamycineluting stent evaluated at Rotterdam cardiology hospital) and T-SEARCH (taxus stent evaluated at Rotterdam cardiology hospital) registries. J Invasive Cardiol Aug 2011;23(8):336–41. [16] Dirksen MT, Vink MA, Suttorp MJ, et al. Two year follow-up after primary PCI with a paclitaxel-eluting stent versus a bare-metal stent for acute ST-elevation myocardial infarction (the PASSION trial): a follow-up study. EuroIntervention May 2008;4(1):64–70. [17] Vink MA, Dirksen MT, Suttorp MJ, et al. 5-year follow-up after primary percutaneous coronary intervention with a paclitaxel-eluting stent versus a bare-metal stent in acute ST-segment elevation myocardial infarction: a follow-up study of the PASSION (Paclitaxel-Eluting Versus Conventional Stent in Myocardial Infarction with STSegment Elevation) trial. JACC Cardiovasc Interv Jan 2011;4(1):24–9.
Letters to the Editor
Treated hyperthyroid patients without cardiac symptoms were not included. d) Only short-term follow-up was available. In conclusion, in successfully treated hyperthyroidism, autoimmune myocarditis can be identified and CMR is of diagnostic value even in the absence of other clinical and/or laboratory findings. However, further studies are needed to assess the clinical implications of these results. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [10]. There is no conflict of interest related to this work. References [1] Anakwue RC, Onwubere BJ, Anisiuba BC, Ikeh VO, Mbah A, Ike SO. Congestive heart failure in subjects with thyrotoxicosis in a black community. Vasc Health Risk Manag 2010;6:473–7. [2] Fatourechi V, Edwards WD. Graves' disease and low-output cardiac dysfunction: implications for autoimmune disease in endomyocardial biopsy tissue from eleven patients. Thyroid 2000;10(7):601–5.
[3] Mavrogeni S, Spargias K, Markussis V, et al. Myocardial inflammation in autoimmune diseases: investigation by cardiovascular magnetic resonance and endomyocardial biopsy. Inflamm Allergy Drug Targets 2009;8:390–7. [4] Mavrogeni S, Spargias C, Bratis C, et al. Myocarditis as a precipitating factor for heart failure: evaluation and 1-year follow-up using cardiovascular magnetic resonance and endomyocardial biopsy. Eur J Heart Fail 2011;13:830–7. [5] Friedrich M, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: a JACC White Paper. J Am Coll Cardiol 2009;53:1475–87. [6] Chen YT, Yang GG, Hsu YH. Thyroid storm and lymphocytic myocarditis. Intern Med 2010;49:593–6. [7] Lorin De La Grandmaison G, Izembart M, Fornes P, et al. Myocarditis associated with Hashimoto's disease: a case report. Int J Legal Med 2003;117:361–4. [8] Umpierrez GE, Challapalli S, Patterson C. Congestive heart failure due to reversible cardiomyopathy in patients with hyperthyroidism. Am J Med Sci 1995;310:99–102. [9] Abdel-Aty H, Boye P, Zagrosek A, et al. Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches. J Am Coll Cardiol 2005;45:1815–22. [10] Coats AJS, Shewan LG. Statement on Authorship and Publishing Ethics in the International Journal of Cardiology. Int J Cardiol 2011;153:257–8.
0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.04.089
Prognostic models for cardiovascular events after successful primary percutaneous coronary intervention Konstantinos Toutouzas a,⁎,1, Andreas Synetos a,1, Antonios Karanasos a, Charalampia Nikolaou a, Archontoula Michelongona a, Demosthenes Panagiotakos b, Eleftherios Tsiamis a, Costas Tsioufis a, Dimitris Tousoulis a, Christodoulos Stefanadis a a b
First Department of Cardiology, Hippokration Hospital, University of Athens, Athens, Greece Department of Nutrition-Dietetics, Harokopio University, Athens, Greece
a r t i c l e
i n f o
Article history: Received 9 February 2012 Received in revised form 10 April 2012 Accepted 14 April 2012 Available online 9 May 2012 Keywords: Angioplasty Coronary interventions Prognosis Coronary artery disease
Several prognostic models have been proposed for the prediction of the outcome of patients with chronic stable angina or acute coronary syndromes undergoing revascularization. The introduction of the SYNTAX (Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery) score (SXscore), has shifted the attention toward stratifying the individual risk according to lesion complexity, and to the extent and distribution of coronary atheromatosis [1,2]. However, the absence of clinical factors has led to the creation of a pure clinical model (Age, Creatinine, and Ejection Fraction; ACEF) and of two combined risk models, the Global Risk Classification (GRS) and the Clinical SYNTAX score (CSS) [3,4] that have incorporated clinical variables into the SXscore.
⁎ Corresponding author at: 26 Karaoli and Dimitriou str., Holargos, 15562, Athens, Greece. Tel.: + 30 210 6510860; fax: +30 210 7250153. E-mail address: [email protected] (K. Toutouzas). 1 These authors contributed equally to this article.
There are several prognostic models for the outcome after primary PCI. However, there are no studies including only patients with successful primary PCI. The aim of this study was 1) to validate and compare the performance of the GRS and the CSS in patients undergoing successful primary PCI, and 2) to evaluate whether the combined risk models provide additive prognostic information to the ACEF score, the EuroSCORE, and the SXscore. Three hundred and forty five consecutive patients that underwent successful primary PCI due to STEMI in our hospital were recruited out of 361 primary PCIs. Successful primary PCI was defined as the presence of TIMI flow 3 after the procedure [5,6]. The SXscore for each patient was calculated by a team of 2 experienced interventional cardiologists. All coronary lesions with a diameter stenosis ≥ 50% in vessels ≥ 1.5 mm were scored using the SXscore algorithm, which is available on the website (www.syntaxscore.com). EuroSCORE was calculated based on the original methodology [7]. The ACEF score was calculated based on the modified formula proposed by Ranucci et al. [8], (i.e., ACEF= [age / left ventricular ejection fraction (LVEF)] + 1 if serum creatinine N2 mg/dl). The GRS and the CSS were derived as previously described [4,9]. Renal dysfunction was defined as serum creatinine N2 mg/dl [8]. The investigated outcomes included: adverse events that were assessed during hospitalization, as well as at 1, 6, 12 and 24 months after hospital discharge. The follow-up was performed in our outpatient department or by telephone. The primary endpoint was the 2-year incidence of fatal cardiac events (cardiovascular death; CVD), consisting of sudden death, myocardial infarction, or death secondary to heart failure. Deaths were considered cardiac following the ICD-10 definitions.
Letters to the Editor
169
Table 1 Baseline demographic and angiographic characteristics of the participants. Sex (male) Age (years) Number of diseased vessels LM 1VD 2VD 3VD Culprit vessel LAD LCX RCA Type of stent EES ZES SES PES BMS POBA Vessel diameter (mm) Total stent length (mm) Medication after PCI Aspirin Clopidogrel Prasugrel Beta blockers ACE inhibitors Statins
295 (85.5%) 63 ± 12
191 (55.3%) 34 (9.8%) 120 (34.7%) 157 (45.6%) 77 (22.3%) 34 (9.9%) 22 (6.3%) 47 (13.7%) 7 (2.0%) 3.05 ± 0.45 29.56 ± 14.79 345 (100%) 336 (97.3%) 9 (2.6%) 341 (99.1%) 335 (97.1%) 342 (99.1%)
ROC curve
CVD
SxScore ACEF CSS Reference Line
Sensitivity
0,8
0,6
0,4
SCORE SxSCORE Euroscore GRS ACEF CSS
0,2
Area ,665 ,635 ,658 ,783 ,781
0,0 0,2
0,4
0,6
0,8
1.0
1 - Specificity Diagonal segments are produced by ties. Fig. 1. ROC curves for cardiovascular death at 2-year follow-up.
Sensitivity
13 (3.7%) 197 (57.1%) 80 (23.1%) 69 (20%)
Secondary end points were: target lesion failure (TLF), repeat revascularization (RR), stent thrombosis (ST) and major adverse cardiac event (MACE). Specifically, target lesion failure (TLF) was defined as heart attack attributed to the target vessel (target vessel myocardial infarction), and ischemia-driven target lesion revascularization [10]. Repeat revascularization (RR) was considered as any kind or revascularization in any coronary artery. Stent thrombosis (ST) was defined according to the ARC definitions [11]. Major adverse cardiovascular events (MACE) were defined as the composite of death from all causes, nonfatal myocardial infarction, or target vessel revascularization. Data are presented as mean ± SD or absolute and relative frequencies. The Kolmogorov–Smirnov test was used to assess normal-
0,0
MACE
SxScore ACEF CSS Reference Line
0,8
Data are presented as mean ± SD or absolute and relative frequencies. LM: Left main coronary artery; VD: Vessel Disease; LAD: Left Anterior Descending Artery; LCX: Left Circumflex Artery; RCA: Right Coronary Artery; ACE: Angiotensin converting enzyme; EES: Everolimus Eluting Stent; ZES: Zotarolimus Eluting Stent; SES: Sirolimus Eluting Stent; PES: Paclitaxel eluting Stent; BMS: Bare metal Stent; POBA: Plain old Balloon Angioplasty.
1.0
ROC Curve
1,0
0,6
0,4
SCORE SxSCORE Euroscore GRS ACEF CSS
0,2
0,0
0,0
0,2
0,4
0,6
Area ,638 ,673 ,646 ,639 ,703
0,8
1,0
1 - Specificity Diagonal segments are produced by ties. Fig. 2. ROC curves for major adverse cardiac events at 2-year follow-up.
ity. Receiver Operating Characteristic (ROC) curves were plotted and the corresponding C-statistics were calculated in order to evaluate scores’ performance in predicting the outcomes. Comparisons between Cstatistic values were performed using the Z-test. Unadjusted predictors of MACE and CVD during follow-up were assessed by Cox proportional hazard models. Predictors with p-value b0.10 were included in a multiadjusted analysis with backward elimination, after excluding multicollinearity by analysis of variance inflation factor, in order to identify independent predictors of events at follow-up. Data analyses were performed using the SPSS 19 software (SPSS Inc., Chicago IL, USA). Baseline clinical and procedural characteristics of the population are shown in Table 1. The median follow-up period was 476 days (mean 496 ± 5 days). GRS was higher in patients with CVD, TLF, ST, RR and MACE as compared with patients with no event. CSS score was higher in patients with CVD, TLF RR, MACE, as well as in those who died, as compared with those who did not experience an event. The ROC curves for CVD and MACE at 2-year follow-up are presented in Figs. 1 and 2 respectively. The corresponding C-statistics for the CSS, GRS, SxScore, ACEF, and EUROscore for 2-year CVD mortality were 0.781, 0.658, 0.665, 0.783, and 0.635 and for 2-year MACE were 0.703, 0.646, 0.638, 0.639 and 0.673 respectively. Pairwise comparisons between Cstatistics revealed that the CSS score better classified event from eventfree patients, as compared with all other scores (Bonferroni corrected ps b 0.05), with the exception of 2-year CVD where there was no significant difference between the CSS and the ACEF scores. The results of the unadjusted and the multi-adjusted analysis are shown in Table 2. Because CSS was non-normally distributed and the assumption of linearity was not achieved, log transformation was performed resulting to normal distribution of the new variable (logCSS). Despite the fact that renal dysfunction and LVEF were included in the definition of CSS, collinearity was low (All variance inflation factors b1.25). Unadjusted analysis showed that log-CSS, renal dysfunction, and LVEF were predictors of MACE and CVD; whereas, multi-adjusted analysis, controlling for renal dysfunction and LVEF, revealed that logCSS was an independent predictor of MACE and CVD during follow-up. A separate multi-adjusted analysis was performed for the GRS, because there was high collinearity with the CSS. GRS was also found to be a predictor of MACE and CVD during follow-up, even after adjustment for LVEF and renal dysfunction. The main findings of the current study are: 1) CSS predicts better compared to GRS, SxScore, ACEF and EuroSCORE the incidence of cardiovascular death and/or MACE, and 2) CSS is an independent
170
Letters to the Editor
Table 2 Unadjusted and multi-adjusted predictors of MACE and CVD at 2-year follow-up. Multi-adjusteda analysis for MACE
Unadjusted analysis for MACE LVEF CSS-log Renal dysfunction
b
95% CI
P value
b
95% CI
P value
− 0.16 2.69 2.51
0.83–0.89 3.88–57.03 4.39–38.11
b0.0001 b0.0001 b0.0001
− 0.13 1.78
0.82–0.92 1.73–20.41
b 0.0001 b 0.0001
Multi-adjusteda analysis for CVD
Unadjusted analysis for CVD LVEF CSS-log Renal dysfunction
− 0.22 4.36 3.08
0.74–0.85 13.71–454.74 7.03–68.48
b0.0001 b0.0001 b0.0001
−0.17 2.62
0.77–0.90 2.70–70.81
b 0.0001 0.002
CI: confidence interval; LVEF: Left Ventricular Ejection Fraction.; CSS: Clinical Syntax Score. a Variables entered in the models were: LVEF, CSS-log, and renal dysfunction.
predictor of cardiovascular death and/or MACE after successful primary PCI for the treatment of STEMI. The clinical characteristics of the studied population and primary outcomes of the present study were similar to studies previously published. The data provided in other studies are not comparable to our population, as we included only patients with successful primary PCI. However, the inclusion criteria of the current study justify the better results regarding the outcome of MACE and of stent thrombosis. In other studies the range for cardiovascular mortality and MACE was 13– 36% and 8.9–11.9%, respectively, versus 5.5 and 8.9% of the studied population [12–17]. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010;144:1–2). No conflicts of interest.
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0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2012.04.088
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