In-Hospital Percutaneous Coronary Intervention Improves In-Hospital Survival in Patients with Acute Inferior MI

From the ^*Regional Medical Cardiology Centre, Royal Victoria Hospital, Belfast, Northern Ireland, the ^§Department of Cardiology, Craigavon Area Hospital, Craigavon, N. Ireland, and the ^£Department of Medical Statistics, School of Medicine, Queens University Belfast, N. Ireland. Disclosures: Drs. McClelland and Walsh received research grants from the Research and Development office, Belfast, Northern Ireland. Dr. Owens received funding from the Frances and Augustus Newman Foundation, England. Manuscript submitted August 20, 2008, provisional acceptance given September 24, 2008, manuscript accepted November 24, 2008. Address for correspondence: Colum Owens, Regional Medical Cardiology Centre, Royal Victoria Hospital, Grosvenor Road, Belfast, Northern Ireland BT12 6BA. E-mail: columowens@yahoo.co.uk

ABSTRACT: Objective. Assess the interaction between fibrinolysis and in-hospital percutaneous coronary intervention (PCI) in patients with inferior myocardial infarction (MI), particularly those with electrocardiographic evidence of right ventricular infarction (RVI). Design. Retrospective observational study. Patients. Consecutive patients with inferior MI identified from an MI registry between January 1998 and January 2004. Interventions. Propensity analyses and multiple regression analysis were used to determine the mortality benefit of PCI. Main outcome measures. In-hospital morbidity and mortality. Results. In total, 465 patients with inferior MI received fibrinolytic therapy (median pain-to-needle time of 167 minutes; IQR 100–311 minutes). The main predictors of PCI were recurrent chest pain, peak creatine kinase, age, reinfarction, presence of heart failure and male gender. Significant independent predictors of in-hospital mortality were age ≥ 75 years, RVI, initial systolic blood pressure ≤ 80 mmHg, female gender and no in-hospital PCI. In-hospital PCI was performed in 184/465 (40%) patients; 55 (30%) had rescue PCI performed ≤ 6 hours post fibrinolysis, 45 (24%) within 6–24 hours and 84 (46%) ≥ 24 hours. In-hospital PCI was associated with reduced in-hospital mortality (PCI: 9 [5%] vs. no PCI: 40 [14 %]; p Conclusion. A strategy of timely fibrinolysis combined with in-hospital PCI including rescue PCI may result in a significant reduction in in-hospital mortality and morbidity in patients with inferior MI, particularly those with RVI.

J INVASIVE CARDIOL 2009;21:40–44

Key Words: inferior MI, percutaneous coronary intervention, right ventricular infarction

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At present, there is much debate regarding the optimal method of reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI). Fibrinolytic therapy has been shown to confer survival benefit in over 100,000 patients, particularly when administered within 2–3 hours post-symptom onset.¹ Proponents of pharmacological therapy point to its widespread availability, rapid administration and lack of dependence on operator experience or institutional resources, though dissatisfaction with this strategy relates to suboptimal reperfusion, reinfarction and bleeding complications.2 Primary PCI, if delivered in a timely manner, confers survival benefit, driven mainly by reduction in reinfarction.^2,3 Although the ASSENT-4 (Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction) trial demonstrated that a strategy of immediate PCI (1–3 hours) after TNK-tenecteplase administration was associated with higher in-hospital mortality, cardiac ischemic complications and stroke compared with those who received direct PCI alone, other trials where PCI was delayed for a mean of 17 hours after fibrinolysis did not show an increase in mortality.^2,4 Furthermore, the recent WEST (Which Early ST-elevation myocardial infarction therapy) study found that 30-day mortality was 4% with tenecteplase and usual care versus 1% with tenecteplase and an invasive approach within 24 hours of enrollment.² The choice of reperfusion strategies is particularly relevant to patients with acute inferior STEMI where the absolute mortality benefit of reperfusion therapy is less than for those with anterior myocardial infarction (MI) or MI with left bundle-branch block.⁵ Nevertheless, patients with right ventricular infarction (RVI) complicating inferior MI have an increased in-hospital mortality of up to 22%,⁶ and successful reperfusion by PCI can result in improved survival rates and shorter in-hospital stays.^7,8 In this retrospective study, we looked at data from our acute MI registry and assessed the interaction between patients with inferior STEMI receiving fibrinolytic therapy and in-hospital PCI. We also assessed the influence of electrocardiographic (ECG) evidence of RVI on morbidity and mortality.

Methods

Study group. All patients admitted to the cardiology department at the Royal Victoria Hospital, Belfast are entered prospectively into an MI registry. Their demographics, clinical characteristics and blood results are collected and stored. From this registry, all patients with inferior STEMI between January 1998 and January 2004 were selected. ECG evidence of inferior STEMI was defined as ≥ 1 mm ST elevation in ≥ 2 inferior leads (II, III, aVF). MI was confirmed by elevation of cardiac enzymes (creatine kinase [CK] increased to at least twice the normal laboratory upper range with CK-MB at least 7% of the total CK) or elevation of cardiac troponin-I ≥ 1 ng/mL (January 2000–January 2004). All patients who received fibrinolytic therapy within 12 hours of symptom onset (either pre-hospital or in-hospital) were included in the analysis. Angiographic and interventional treatment were directed and individualized by the attending physician and recorded for each patient. In-hospital morbidity and mortality. In-hospital morbidity included ventricular fibrillation, nonsustained ventricular tachycardia (NSVT), second-/third-degree AV block, need for temporary or permanent pacemaker, congestive cardiac failure (CCF) (≥ 2 episodes requiring diuretic therapy), cardiogenic shock (systolic blood pressure [SBP] 30 minutes and requiring inotropic support), further ischemic chest pain (defined by post-infarct pain ≥ 15 minutes requiring analgesia, nitrates or new STT changes), reinfarction (chest pain with new or further ST-segment elevation), new-onset atrial fibrillation and hemorrhagic/ischemic stroke. In-hospital death was defined as death within the index MI admission. Electrocardiographic criteria. All patients had an initial 12-lead ECG and an 80-lead body surface map performed at initial presentation. From the acute inferior STEMIs, RVI was defined as ST elevation ≥ 1mm in 2 right ventricular leads on the 80-lead body surface map, 1 lead of which had to include the standard lead V4R. We used the 80-lead body surface map in this study to detect RVI, as it has been shown to increase the diagnostic yield of RVI compared with the 12-lead ECG with right ventricular leads V2R and V4R by a factor of 1.38.⁵

Statistical Methods

Categorical variables were compared with Pearson’s chi-squared test and continuous variables with the independent samples t-test. Multivariable analysis was performed using forward, stepwise binary logistic regression to determine independent predictors of in-hospital mortality. Inclusion in the final model was determined by the Wald chi-squared test. The selected clinical variables included age (categorical variable 75 years), gender, hypertension, hypercholesterolemia, family history of ischemic heart disease, diabetes mellitus, past history of MI, smoking history, initial systolic blood pressure, heart rate, Killip Class, creatinine clearance, admission via the mobile coronary care unit (MCCU), in-hospital PCI, and ECG evidence of RVI. All tests were two-sided and in all cases, a p-value 9 The propensity variables that correlated with PCI are shown in Table 1. The score was used to divide the population according to deciles of propensity score and was used as a single covariate to predict in-hospital mortality.¹⁰ All calculations were carried out using SPSS software, version 14.0 (SPSS, Inc., Chicago, Illinois). The study complies with the Declaration of Helsinki and was approved by the Queen’s University of Belfast Research Ethics Committee. All patients gave informed consent.

Results

Baseline characteristics, morbidity and mortality. There were 3,951 patients admitted with symptoms consistent with acute coronary syndrome in the study period and 465 patients met the entry criteria for inferior STEMI treated with fibrinolytic therapy. Admission via the MCCU was the case for 240 (52%) patients. The fibrinolytic agent used was tenecteplase/reteplase/alteplase in 380 (82%) and streptokinase in 85 (18%) patients. The median pain-to-needle time was 167 minutes (interquartile range 100–311 minutes). The initial SBP was ≤ 80 mmHg in 94 (20%) patients. Killip Class was assessed in 464 patients as one patient was in cardiac arrest when first seen. Twenty-five (5%) had a Killip Class ≥ 3. Ventricular fibrillation occurred in 34 (7%) patients. Further ischemic pain occurred in 137 (29%) patients, with 42 (9%) having reinfarction. CCF and cardiogenic shock occurred in 117 (25%) and 43 (9%) patients, respectively. Although 50 patients (11%) had second-/third-degree AV block during their hospital stay, only 12 (3%) required pacemaker therapy. Forty-nine patients (11%) died in-hospital. Percutaneous coronary intervention vs. no percutaneous coronary intervention. Of the 465 patients, 270 (58%) proceeded to cardiac catheterization and 219 (81%) had a significant residual stenosis in the right coronary artery (RCA) post fibrinolysis (stenosis ≥ 70% at angiography). PCI was undertaken in 184 (40%) patients (Figure 1). Patients undergoing PCI compared with no PCI were younger (61 [± 12.0] vs. 66 [± 12.0]; p Propensity analyses. The most important predictors for in-hospital PCI included recurrent ischemic chest pain, peak CK, age, reinfarction, heart failure along with male gender (Table 1). The in-hospital mortality rate across the cohort deciles is shown in Table 2. As can be seen, the relative risk for death ranges from 11.8 to 1.0, favoring PCI, and the mortality rate clearly decreases as the likelihood of PCI increases. Right ventricular infarction vs. no right ventricular infarction. RVI occurred in 240 (52%) patients (Figure 2). Patients with RVI were older (66 ± 12.5 years vs. 63 ± 12.0 years; p = 0.005), but were comparable with respect to gender, hypertension, hypercholesterolemia, family history of ischemic heart disease (IHD) and past history of IHD/MI. Patients with RVI were higher-risk (mean TIMI risk score 4.1 [± 2.6] vs. 3.3 [± 2.4]; p 55%: 85 [35%] vs. 107 [48%]; p = 0.037). There were no differences in the number of patients referred for cardiac catheterization (RVI: 142 [59%] vs. no RVI: 128 [57%]; p = 0.6) and percutaneous intervention (RVI: 98 [41%] vs. no RVI: 86 [38%]; p = 0.5). In-hospital morbidity was significantly higher in patients with RVI with respect to ventricular fibrillation, NSVT, second-/third-degree AV block, further ischemic pain and cardiogenic shock. In-hospital mortality was significantly higher for RVI (41 [17%] vs. 8 [4%]; p Predictors of in-hospital mortality. Age ≥ 75 years, female gender, non-smoking, not admitted by MCCU, no PCI in-hospital, RVI, weight Discussion This retrospective study demonstrates that timely fibrinolysis (median pain-to-needle time 6 hours post index admission. This is comparable to the Mayo Clinic STEMI protocol, where approximately 36% of patients underwent rescue PCI for suspected failed reperfusion.¹ The propensity analysis shows that the factors determining patient selection for PCI was largely based on clinical factors such as post-infarction angina, peak CK, age, reinfarction, presence of heart failure and male gender (Table 1). The physician operator was not an independent variable in the propensity analysis. This reflects “real-world” practice where the need for PCI is based on the patients’ ongoing clinical status and factors other than ECG indicators for lytic failure. The propensity analysis also demonstrates that those patients with the lowest probability of proceeding to PCI had the highest mortality with a relative risk of 11.8 (Table 2). This is further confirmed in that no in-hospital PCI was an independent predictor of death (OR, 2.8 [1.2–6.4]; p = 0.019) (Table 5). The mortality benefit seen in this study, though at odds with the recent meta-analysis for “facilitated angioplasty”,¹¹ is in keeping with data published previously from our MI registry and trial evidence from the recent WEST study and GRACIA-1 (Grupo de Análisis de la Cardiopatiá Isquémica Aguda) study.^2,12,13 The WEST study showed that a contemporary pharmacologic regimen, rapidly delivered, coupled with a strategy of regimented rescue and routine coronary intervention within 24 hours of initial treatment was associated with a low 30-day mortality.^1,2 In the GRACIA-1 study, patients randomized six hours after fibrinolysis to angiography and intervention within 24 hours versus an ischemia-guided conservative approach tended to have a reduced rate of death or reinfarction.^2,13 The timing of PCI in the GRACIA-1 study is in contrast to the ASSENT-4 PCI strategy of early PCI (1–3 hours post fibrinolysis) and demonstrates that the optimal timing of cointervention in patients receiving fibrinolysis still remains uncertain.² Our data are also in line with the recent REACT (Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis) study which showed that PCI employed early after failed fibrinolysis in STEMI patients results in a lower composite outcome of death, re-MI, cerebrovascular accident, and severe heart failure compared with those receiving repeat fibrinolysis or conservative therapy.^2,14 It is interesting to note the interaction of benefit of PCI with RVI. As Table 3 demonstrates, the mortality benefit of PCI was seen mainly in those with electrocardiographic evidence of RVI, reflecting the high mortality of RVI complicating inferior STEMI. To date, there are limited data on the role of PCI in patients with inferior MI and RVI. In a small study on the effect of primary angioplasty in acute RVI, failure to restore flow to the RCA and its right ventricular branches was associated with impaired recovery of right ventricular function, persistent hemodynamic compromise and a high in-hospital mortality rate.⁷ In contrast, complete reperfusion of the RCA resulted in dramatic recovery of right ventricular performance, a shorter in-hospital stay and an excellent clinical outcome.⁷ It is likely that in our study, the improved in-hospital morbidity and mortality (Table 3) were due to the successful restoration of RCA flow compared to the no-PCI patients. Study limitations. This study is retrospective and observational in design and thus the conclusions reached are hypothesis-generating. However, we believe the numbers included in this study do suggest a benefit. The propensity analyses are inherently limited by the number and accuracy of the variables evaluated.¹⁰ Although we have adjusted for all accepted confounding variables, in a retrospective study, it is impossible to adjust for all possible confounders. It is also difficult to account for the changes in practice, both pharmacological and in the use of stents, over the study period.

Conclusion

Although driven mainly by patient clinical characteristics, a strategy of timely fibrinolysis combined with in-hospital PCI including rescue PCI may result in a significant reduction in in-hospital mortality and morbidity in patients with inferior STEMI, particularly those with ECG evidence of RVI.

References

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