Prognostic Significance of the Occurrence of Acute Heart Failure After Successful Primary Percutaneous Coronary Intervention

ABSTRACT: Background. Acute heart failure (AHF) has an adverse impact on short- and long-term outcomes in patients with acute ST-elevation myocardial infarction (STEMI). The aims of the present study were to determine independent predictors for the occurrence of AHF during hospitalization and to assess the impact of AHF on 30-day and 1-year outcomes in patients with STEMI who were successfully treated with primary percutaneous coronary intervention (pPCI). Methods and Results. The study included 1,074 consecutive patients with STEMI who had no signs of heart failure (HF) at admission (Killip class I) and were treated with successful pPCI. Successful PPCI was defined as postprocedural TIMI 3 grade flow. Acute HF developed in 11.1% patients during hospitalization, which was predominantly mild to moderate (Killip classes II and III). Independent predictors for the occurrence of AHF were: anterior infarction, peak creatinine-kinase (CK) > 2,000 U/L and 3-vessel coronary disease. 30-day and 1-year mortality rates were significantly higher in patients with AHF compared to patients without AHF. AHF during hospitalization was an independent predictor of 30-day mortality (hazard ratio [HR] 10.5) and 1-year mortality (HR 4.4). Conclusion. Even after successful pPCI, the occurrence of AHF during hospitalization remains an independent predictor of 30-day and 1-year mortality. J INVASIVE CARDIOL 2010;22:307–311 Key words: heart failure, acute ST-elevation myocardial infarction, primary percutaneous coronary intervention    Development of acute heart failure (AHF) has an adverse impact on short- and long- term outcomes in patients with acute ST-elevation myocardial infarction (STEMI).^1–4 Acute HF complicates STEMI due to a complex interaction of structural, hemodynamic, neurohormonal and genetic maladaptations.⁴ Abrupt myocyte loss due to necrosis is an obvious mechanism that leads to left ventricular (LV) systolic and/or diastolic dysfunction and AHF.⁴ Other causes that may lead to AHF are myocardial stunning and/or hibernation (in patients undergoing reperfusion therapy), and arrhythmias and mechanical complications (acute mitral regurgitation).^1,4,5 Primary percutaneous coronary intervention (pPCI) is indicated as the reperfusion therapy of choice because it reduces myocardial damage and improves short- and long-term outcomes in patients with STEMI compared to fibrinolytic therapy.^1,2 But even in the pPCI era, the problem of heart failure (HF) still exists, because in some patients, even timely and successful pPCI cannot prevent extensive myocardial damage, and sometimes the restoration of coronary blood flow may lead to reperfusion in jury. Both situations result in the development of AHF, which seriously influences the patient’s outcome. Previous studies have reported that the short- and long-term outcomes are worse in patients with STEMI who develop AHF during hospitalization compared to patients who present with HF at admission.^1,3,6 Limited data exist on the incidence and prognostic significance of AHF during hospitalization in patients undergoing pPCI.¹ The majority of data on the occurrence of AHF originates from randomized clinical trials.⁷ To the best of our knowledge, there are no data on the prognostic significance of AHF on the short- and long-term outcomes after successful pPCI.    The goals of this study were: 1) to evaluate the incidence of and identify independent predictors of the occurrence of AHF during hospitalization; and 2) to evaluate the impact of AHF on 30-day and 1-year outcomes in patients with STEMI after successful pPCI. Methods    Study population, data collection and definitions. Our study included data from the RISK-PCI trial electronic database for a subgroup of 1,074 consecutive STEMI patients enrolled in the RISK-PCI trial who met the following criteria: 1) no signs of HF at admission (according to the Killip classification); and 2) successful pPCI. The design and methods of the RISK-PCI trial were published elsewhere.⁸    In brief, our RISK-PCI trial was an observational, longitudinal, cohort, large-volume (about 600 pPCIs per year) single-center trial which was planned to include 1,750 consecutive patients ≥ 18 years of age presenting with STEMI and treated with pPCI. The patients could not be in cardiogenic shock at admission nor display any contraindication to dual antiplatelet therapy or contrast agents. Successful pPCI is defined as thrombolysis in myocardial infarction (TIMI) flow grade 3 and/or stenosis 2 All patients received unfractionated heparin (UFH) during the first 2–3 days or longer if clinically indicated. Patients showing clinical signs of HF were treated with diuretics, inotropic agents or digitalis (in patients with supraventricular tachyarrhythmias to slow a rapid ventricular rate) at the discretion of the investigators.    Demographic, clinical, angiographic and procedural data were collected and analyzed. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault formula, and the value of CrCl 2,9 Patients who developed HF during hospitalization were identified when the symptoms and clinical signs of HF appeared for the first time after clinical evaluation. The degree of HF was categorized according to the Killip classification: Class II included pulmonary congestion with rales up to 50% of the lung fields or only the third heart sound; Class III included pulmonary edema with rales over 50% of the lung fields; Class IV included cardiogenic shock.² Patients were followed up at 30 days and at 1 year after enrollment. Follow-up data were obtained by telephone interviews. No patients were lost during follow up.    Statistical analysis. Continuous variables were expressed as the mean ± standard deviation (SD), whereas categorical variables were expressed as frequency and percentage. Analysis for data normality was performed using the Kolmogorov-Smirnov test. Baseline differences between groups were analyzed using the Student’s t-test for continuous variables and the Pearson chi-squared test for categorical variables. Multivariable backward stepwise logistic regression models (backward method, with p Results    Patients’ baseline characteristics and independent predictors of acute HF development. During hospitalization, AHF developed in 120 (11.1%) patients of which 117 (97.5%) were Killip class II AHF, and only 3 patients (2.5%) developed pulmonary edema. Among the patients with Killip class II, 53 (45.2%) had the third heart sound, without bibasilar pulmonary rales. There were no patients with cardiogenic shock.    In comparison to patients without HF, patients with in-hospital AHF were older and more frequently had a history of previous MI and aortocoronary bypass grafting. They also suffered from hypertension, diabetes and renal dysfunction more than patients without HF, and presented more often with anterior MI. Baseline angiography showed that patients with AHF more frequently presented with 3-vessel coronary disease and thrombotic occlusion (TIMI flow 0) of the IRA than patients without HF. A higher peak CK and a lower ejection fraction were observed in patients with AHF. Patients with the occurrence of AHF received beta-blockers less often and ACE-inhibitors more often, during hospitalization compared to the group without AHF.    There was no difference in the long-term medications and planned revascularization (in patients with multivessel coronary disease) between the two analyzed groups following discharge up to 1 year.    In the multivariable logistic regression model, independent predictors of the occurrence of AHF were: anterior infarction, peak CK and 3-vessel coronary disease. The ROC analysis was used for identifying the cut-off value for a peak CK of 2,000 U/L because peak CK as a continuous variable (first entered in the model) was an independent predictor for the occurrence of AHF (OR 1.02; 95CI 1.00–1.003; p = 0.001). This is presented in Figure 1.    Mortality. Patients with the occurrence of AHF had higher 30-day and 1-year mortality rates compared to patients without AHF. The occurrence of AHF was an independent predictor for 30-day and 1-year mortality (Table 4).    The causes of 30-day morality were: ischemic stroke (3 patients), reinfarction (5 patients) and sudden cardiac death (6 patients). The causes of 1-year mortality were: ischemic stroke (3 patients), reinfarction (15 patients), sudden cardiac death (6 patients) and carcinoma (1 patient). The highest mortality rate was observed in the first 30 days after enrollment: 56% of all deaths and 81.8% of patients with AHF died in the first 30 days. The mortality rate between 30 days and 1 year was low.    The 30-day survival curves, estimated according to the Kaplan-Meier method and stratified according to AHF during hospitalization, are presented in Figure 2. The cumulative 1-year survival curves, estimated according to the Kaplan-Meier method and stratified according to AHF during hospitalization, are presented in Figure 3. Discussion    AHF during hospitalization occurred in 11.1% of our patients. The incidence of HF during hospitalization was higher in our patients compared to those from a previous study analyzing patients undergoing pPCI (1.6%), 1 probably because we also included the group with the third heart sound.² On the other hand, the incidence of AHF in our study was lower compared to studies from the fibrinolytic era, or studies that included patients with acute coronary syndrome.^3,6,10,11    The baseline characteristics of our patients are in agreement with previous studies.^1,4,6,12,13 There was no significant difference between groups regarding the duration of symptoms or door-to-needle time, which is in agreement with a previously published study that analyzed the incidence of AHF in patients undergoing pPCI.¹ Just like in the previous study,³ we also showed that patients with AHF were less likely to receive beta-blockers, but more likely to receive ACE-inhibitors in the acute course of the infarction.    The independent predictors of the occurrence of AHF in our study were in agreement with the results from previous studies which analyzed the problem of AHF and/or LV systolic dysfunction in patients undergoing pPCI.^1,12,14 These studies included pPCI patients regardless of the post-procedural TIMI flow. In our patients undergoing pPCI, independent predictors of AHF were age and peak CK.¹ In another study, independent predictors for LV systolic dysfunction in patients undergoing pPCI were peak CK and door-to-balloon time.¹² In a trial analyzing the composite endpoint, comprising a Killip score ≥ 3, HF functional class ≥ 3 and 30-day mortality following pPCI, the independent predictors were: ejection fraction, diabetes, multivessel coronary disease, unsuccessful reperfusion and age, and an elevated level of N-terminal pro-brain natriuretic peptide.¹⁴ In our study, age was not an independent predictor of the occurrence of AHF, although patients with AHF were older than those without AHF. The peak CK correlates with the extent of myocardial necrosis, which remains the most important cause of AHF after acute MI, even in the pPCI era.^1,4,12 The next independent predictor for AHF in our study was anterior MI, which generally correlates with more extensive myocardial necrosis.¹⁵ We also identified 3-vessel coronary disease as an independent predictor of AHF development, indicating that angiographic variables may influence the occurrence of AHF.    Although our patients had predominantly mild or moderate AHF, they had higher 30-day and cumulative 1-year mortality rates compared to the group without HF. Moreover, AHF during hospitalization was an independent predictor of both 30-day and cumulative 1-year mortality. The highest mortality rate in our study in the first 30 days is in agreement with the results from the previous trial.¹ Although the inclusion criteria in our study differed from other studies and limited the validity of the comparison (we included only patients with successful pPCI), it is noteworthy that our patients with AHF had lower short-term and long-term mortality during hospitalization compared with previous studies which included all patients undergoing pPCI and with studies from the fibrinolytic era.^1,12,16–18 AHF occurrence during hospitalization and LV systolic dysfunction in patients undergoing pPCI were confirmed as independent predictors for both short- and long-term mortality.^1,12 In the study analyzing LV systolic dysfunction after pPCI, 1-month mortality was higher in patients with a LV ejection fraction (LVEF) 40% (35% vs. 5.8%; p 12    AHF during hospitalization in patients undergoing pPCI was confirmed as an independent predictor of in-hospital and 6-month mortality. In comparison to patients who presented with HF, those who developed AHF during hospitalization had a substantially higher risk of death — HR 2.44 and HR 5.19, respectively.¹ In comparison to the results from the fibrinolytic trial,18 the 1-year mortality rate in our study was much lower. In this study 1-year mortality was 25.2% in patients with HF versus 5.3% in patients without HF. From the *Clinical Centre of Serbia-Emergency Hospital, Coronary Care Unit, §Cardiology Clinic, £University of Belgrade, School of Medicine, and the ∞Institute for Medical Statistics and Informatics, Belgrade, Serbia. The authors report no conflicts of interest regarding the content herein. Manuscript submitted January 4, 2010, provisional acceptance given Janu- ary 11, 2010, final version accepted February 12, 2010. Address for correspondence: Lidija Savic, MD, Brace Jerkovic 51/6, 11000 Belgrade, Serbia. E- mail: lidijasavic@ptt.rs References

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