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(Circulation. 1997;96:436-441.)
© 1997 American Heart Association, Inc.

Articles

In-Hospital Outcome of Elderly Patients With Acute Inferior Myocardial Infarction and Right Ventricular Involvement

Héctor Bueno, MD; Ramón López-Palop, MD; Javier Bermejo, MD; José L. López-Sendón, MD; ; Juan L. Delcán, MD

From the Department of Cardiology, Hospital General Universitario "Gregorio Marañón," Madrid, Spain.

Correspondence to Héctor Bueno, Department of Cardiology, Hospital General Universitario "Gregorio Marañón," Dr Esquerdo, 46, 28007 Madrid, Spain.

	Abstract

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Background There are some specific high-risk subgroups of patients with acute inferior myocardial infarction, such as older patients and those with right ventricular involvement. However, the clinical implications of right ventricular infarction in elderly subjects have not been studied previously.

Methods and Results To determine the clinical impact of right ventricular involvement in elderly patients with inferior myocardial infarction, we studied the in-hospital outcome of 198 consecutive patients 75 years of age with a first acute inferior myocardial infarction according to the presence of ECG or echocardiographic criteria of right ventricular infarction. In patients with right ventricular involvement (41%), in-hospital case fatality rate was 47% (mainly because of nonreversible low cardiac output cardiogenic shock) compared with 10% in patients without right ventricular involvement (P<.001). Patients with right ventricular involvement also had a significantly higher incidence of cardiogenic shock (32% versus 5%), which was independent of left ventricular ejection fraction, complete AV block (33% versus 9%), and interventricular septal rupture (9% versus 0%). After adjustment for age, sex, diabetes, shock on admission, left ventricular systolic dysfunction, and complete AV block, right ventricular infarction remained a powerful independent predictor of in-hospital death (adjusted odds ratio, 4.0; 95% confidence interval, 1.3 to 14.2).

Conclusions Elderly patients with acute inferior myocardial infarction have a substantially increased risk of death during hospitalization when right ventricular involvement is present. The poorer outcome is due mainly to the high incidence of cardiogenic shock and its infrequent reversibility.

Key Words: myocardial infarction • aging • mortality • prognosis • shock

	Introduction

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Certain subgroups of high-risk patients with acute inferior myocardial infarction have been defined previously.¹ Some clinical studies have shown that patients with acute inferior myocardial infarction and right ventricular involvement (RVI) have a worse short-term prognosis than patients without RVI in the general population.^{2 3} The cause of the poorer outcome is related primarily to the development of low cardiac output shock.^{4 5 6 7 8} Although it is also known that old patients with acute myocardial infarction fare worse than young patients,^{9 10} the clinical implications of RVI in elderly patients with inferior myocardial infarctions have not been previously investigated. This study was designed to assess the clinical relevance of RVI in acute inferior myocardial infarction in this specific subgroup of patients.

	Methods

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Patients
One hundred ninety-eight patients 75 years admitted from January 1989 through December 1995 to the coronary care unit (CCU) of our institution with a first Q-wave acute myocardial infarction of inferior (Q waves 0.04 second wide in two or more of the II, III, and aVF leads) and/or posterior location (R wave in V₁ or V₂ 0.04 second with an R/S voltage ratio >1) were screened by surface ECGs that included V_3R and V_4R leads that searched for the presence of RVI.

Definitions
RVI was diagnosed by the presence of an ST-segment elevation 0.1 mV in the V_3R or V_4R lead^{2 11 12 13 14} in the ECG performed immediately after CCU admission and/or by the presence of right ventricular free wall motion abnormalities or right ventricular dilatation detected in an acute-phase (48 hours) two-dimensional transthoracic echocardiographic study.^{15 16 17 18 19}

Exclusions
Seven patients were excluded because the time from symptom onset to CCU admission was >48 hours; after that time interval, usually only patients with a complicated evolution are admitted to the CCU. The presence of repolarization abnormalities in V_3R and V_4R was the cause of exclusion in five other patients (owing to complete right bundle-branch block in three and pacemaker rhythm in two) in whom an echocardiographic study was not available or was considered to be of inadequate quality to assess the right ventricular size and function.

Variables
Data were retrospectively obtained from a database prospectively designed to assess the prognostic determinants of the outcome of first acute myocardial infarctions in elderly (75 years old) patients. The clinical history, physical examination, and 16-lead (12 standard leads plus V_3R, V_4R, V₇, and V₈) ECG were obtained immediately after CCU admission. Serial laboratory studies, chest radiographs, and echocardiographic, isotopic, and hemodynamic studies obtained during hospitalization for clinical purposes were analyzed. Pulmonary edema, cardiogenic shock, mechanical complications, ventricular fibrillation, ventricular tachycardia, complete AV block, reinfarction, and life-threatening noncardiac complications were grouped as major complications. Shock was defined as the concurrence of persistent hypotension and clinical signs of low cardiac output²⁰ and was considered cardiogenic after the exclusion of hypovolemia, arrhythmias, and mechanical complications. The remaining variables analyzed have been previously defined.²¹

Statistical Analysis
Continuous variables are expressed as median (25th to 75th percentiles). The ² test was used to assess the significance of the differences between proportions, and the rank sum Wilcoxon U test was used for comparisons between means. Ordinal variables such as Killip class and categorized left ventricular ejection fraction (LVEF) were compared with the Mantel-Haenszel test for linear association. To estimate the influence of LVEF on the effect of RVI on mortality, a stratified analysis was performed. Finally, to assess the independent weight of the presence of RVI on mortality, we performed two multiple logistic regression analyses, one including all variables with known prognostic impact available at the time of admission and one also incorporating variables obtained during hospitalization. All analyses were performed with a JMP statistical program (version 3.0.1, SAS Institute Inc, 1994), except the Mantel-Haenszel tests for linear association, which were performed with SPSS (version 4.0, SPSS Inc, 1990). All probability values were two-tailed, and a value of P.05 was considered significant.

	Results

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Baseline and Infarct Characteristics
There was evidence of RVI in 77 of 186 patients with inferior acute myocardial infarction (41%). Compared with patients without evidence of RVI, no differences were observed between groups in the clinical and demographic baseline characteristics except for a tendency for patients with RVI to be older (Table 1). The clinical presentation and the time from symptom onset to CCU admission were similar in both groups. Patients with RVI developed greater peak levels of creatine kinase and creatine kinase–MB. At the time of CCU admission, 12 patients with RVI (16%) were in shock compared with 1% of patients without RVI (P=.0001). Two-dimensional echocardiography was performed in 67 of 77 patients with RVI (87%) and in 97 of 109 of those without RVI (89%). The RVI group had a larger proportion of patients with an LVEF 0.30 (16% versus 6%, P=.059). Left ventricular hypertrophy was observed less frequently patients with RVI (28% versus 14%, P=.04). Postinfarction mitral regurgitation was as frequent in patients with RVI (55%) as in patients without RVI (52%, P=NS), but the incidence of moderate to severe (grades III and IV/IV) mitral regurgitation was higher in patients with RVI (11% versus 2%, P=.033).

View this table: [in this window] [in a new window]   Table 1. Baseline and Infarct Characteristics

Therapeutic Management
Acute reperfusion therapy, either with thrombolytic agents or with primary PTCA, was used in a similar proportion of patients from each group (25% and 26%; Table 2). No significant correlation between the use of thrombolytic therapy or primary angioplasty and mortality was found in either group. Patients with RVI were more frequently treated with inotropic agents, digoxin, and diuretics and less often with intravenous nitroglycerin, oral ß-blockers, calcium channel entry blockers, and nitrates. Temporary pacing was used four times more in patients with RVI. All patients with RVI and marked hypotension or low cardiac output signs received volume loading within a few minutes of admission or after the beginning of hemodynamic deterioration when it happened in hospital. Patients received volume replacement to obtain a minimum pulmonary capillary wedge pressure of 16 mm Hg if they had hemodynamic monitoring or as needed to overcome signs of low cardiac output unless clinical signs of pulmonary congestion appeared. Of these 25 patients, 17 (68%) were also treated with dobutamine.

View this table: [in this window] [in a new window]   Table 2. Differences in Therapeutic Management

Clinical Course
Most patients with RVI suffered a complicated in-hospital course (Table 3). The incidence of shock was seven times higher in patients with RVI. Cardiogenic shock was observed in 25 patients with RVI (32%) and in 5 patients without RVI (5%). Patients with RVI also had higher incidences of complete AV block, ventricular tachycardia, and mechanical complications, particularly rupture of the interventricular septum. On the other hand, they had a lower incidence of postinfarction angina. The in-hospital case fatality rate was 47% in patients with RVI and 10% in patients without RVI (unadjusted odds ratio, 7.8; 95% confidence interval, 3.7 to 17.5). Among patients with RVI, 84% of those (21 of 25) who developed cardiogenic shock and 90% of those (9 of 10) who had mechanical complications died. In patients without RVI, these figures were 80% (4 of 5) and 80% (4 of 5), respectively. As the table in the Figure shows, the odds ratios of in-hospital death for patients with RVI compared with those without RVI were much higher in patients with normal or near-normal LVEF than in those with a significant systolic dysfunction. Moreover, a linear association between LVEF and in-hospital death was evident only in patients without RVI (the Figure).

View this table: [in this window] [in a new window]   Table 3. Hospital Course

View larger version (32K): [in this window] [in a new window]   Figure 1. In-hospital death rates of patients with and without right ventricular involvement (RVI) according to the left ventricular ejection fraction (LVEF). A significant linear association between LVEF and in-hospital death rate was found only in patients without RVI (probability values in the Mantel-Haenszel test for linear association). Also shown are the crude, LVEF-stratified, and LVEF-adjusted odds ratios (ORs) of dying according to the presence or absence of RVI.

Prognosis
Patients with RVI accounted for 77% of all deaths. In the group as a whole, nonsurvivors were older (82 versus 79 years, P<.0001), were more frequently women (60% versus 49%, P=.063) or diabetic (39% versus 26%, P=.087), had greater mean peaks of creatine kinase (2304 versus 1432 IU/L, P=.0001) and creatine kinase– MB (299 versus 203 IU/L, P=.005), and more frequently had an LVEF 0.40 (39% versus 17%, P=.007) and complete AV block development (43% versus 11%, P<.0001). The independent prognostic value of RVI was assessed by a multiple logistic regression analysis in which we included all the other significant prognostic factors available at the time of admission at CCU (age, sex, antecedent of diabetes, and shock at time of admission). After this adjustment (Table 4), RVI was selected as one of the most powerful independent predictors of in-hospital death in older patients with a first acute inferior myocardial infarction. A second analysis, which also incorporated prognostic information obtained during hospitalization (Table 4), confirmed that RVI remains a strong determinant of short-term mortality after adjustment for left ventricular systolic dysfunction and complete AV block development.

View this table: [in this window] [in a new window]   Table 4. Predictors of In-Hospital Death in Elderly Patients With Acute Inferior Myocardial Infarction

	Discussion

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In the present study, elderly patients with acute inferior myocardial infarction and RVI had a much poorer short-term prognosis compared with those without RVI. The presence of RVI is a strong independent predictor of in-hospital death and is associated with a higher incidence of major complications, particularly cardiogenic shock, mechanical complications (especially rupture of the interventricular septum), and complete AV block.

Using simple criteria available at the time of admission at the CCU, we found that patients with RVI had an adjusted odds of in-hospital death 5.6 times higher than those without RVI, corroborating in an older population what Zehender et al² showed in a nonselected group. The other variables independently associated with higher in-hospital mortality in our population (age and the presence of shock at the time of admission) are also similar to those found in the above-mentioned study, with the exception of LVEF.

The occurrence of in-hospital death in patients with RVI was essentially related to the high incidence of two events: cardiogenic shock (32%) and mechanical complications (13%) and to their extremely high case fatality rates (84% and 90%, respectively). Thirty-one of 36 deaths (86%) occurring in patients with RVI were due to one of these two causes. These findings differ somewhat from previous studies. It has been reported that the characteristic clinical presentation of RVI is usually much less frequent than the actual presence of RVI.^{3 7 22 23} The incidence of cardiogenic shock in these studies ranges from 8% to 49%, depending on the criteria used to diagnose RVI.^{2 3 24 25 26} However, there is neither information about the influence of age nor reference to older age in these studies. Zehender et al² found an incidence of 27% based on electrocardiographic criteria. In our population, the incidence was slightly higher (32%), but the most striking finding was that while RVI has been described as a reversible cause of cardiogenic shock,^{3 4 5 6 7} most of the elderly patients who developed cardiogenic shock as a result of RVI died as a consequence.

The main cause of death in older patients with acute myocardial infarction at any location is cardiogenic shock, but the causes for the higher incidence of this complication in the elderly are not fully understood.¹⁰ The observational character of this study limits the possibility to explain the reasons why elderly patients have such a high susceptibility to right ventricular infarction and such a low tolerance for low cardiac output cardiogenic shock. Inferior infarcts with right ventricular involvement have been described as larger^{27 28} ; therefore, the cause of the worse prognosis might be related to a more pronounced left ventricular systolic dysfunction. In fact, contrary to the results of the study conducted at Freiburg in patients with acute inferior myocardial infarction in a younger population,² a depressed LVEF was an independent predictor of in-hospital death in our group as a whole. However, we have shown that the association between LVEF and in-hospital case fatality rate is very weak in patients with RVI (the Figure). Moreover, after adjustment for LVEF, RVI remains an independent predictor of in-hospital death. All these findings suggest that in the elderly right ventricular dysfunction plays an important role in the development of cardiogenic shock and its progression to death. This clinical behavior may be caused by a higher pulmonary vascular resistance or by particularities in the pathophysiology of cardiac function during acute myocardial infarction in the elderly. The main difference in the physiologies of the aged and young hearts is the progressive difficulty in aged hearts in left ventricular filling, characterized by a reduced early filling and an increased atrial contribution,^{29 30 31 32 33 34 35} and an increase in the end-diastolic pressure for a given volume.³² Nevertheless, the functional importance of this alteration under normal conditions is not great and probably becomes evident only in situations that impair diastolic filling,³⁶ such as RVI. A second major difference in the cardiac performance in the elderly is the distinct mechanism by which the left ventricle adapts to stress. In young subjects, the need for an increase in cardiac output, such as during exercise, is obtained basically through an increase in heart rate and ejection fraction, whereas in elderly subjects, the cardiac output is increased with small changes in LVEF, modest increases in heart rate, and marked increases in end-systolic volume and, particularly, end-diastolic volume. In other words, cardiac output during stress is essentially maintained through the Frank-Starling mechanism.³⁷ The catastrophic outcome of RVI in elderly patients may be the consequence of two mechanisms that, combined with left ventricular damage, cause an impairment of the left ventricular function that may be difficult to reverse. The right ventricular systolic dysfunction can cause a severe reduction in left ventricular preload,^{8 38} which is essential for the aged left ventricular performance, that may fail to improve after volume loading (as happened in our population) because of a marked limitation of the left ventricle to dilate, which is caused by right ventricular dilatation⁸ and perhaps aggravated by an age-related increase in pericardial stiffness.³⁶

The other relevant finding concerning the poor prognosis of elderly patients with RVI is the high incidence of mechanical complications, particularly rupture of the interventricular septum. In our group, the seven patients with rupture of the interventricular septum had RVI. Six of them died during hospitalization. Surgical correction was attempted in three patients, but only one survived surgery and was discharged alive. Autopsy and surgical series have outlined a strong relation between RVI and interventricular septal rupture.^{24 27 39 40 41} Our study suggests that this complication is fairly frequent in elderly patients, with an incidence two to three times higher than in previous reports.^{2 3 26} The cause of the high incidence of cardiac rupture in the elderly remains undefined and may be due to age-related structural changes of the ventricular myocardium, a reduced coronary collateral circulation, or different hemodynamic conditions during acute myocardial infarction.

Clinical Implications
Elderly patients with acute inferior myocardial infarction and RVI should be considered a subgroup of patients at high risk of death during hospitalization, prone to develop shock early during the clinical course. Prompt clinical, echocardiographic, and hemodynamic investigations must be performed to define the mechanism of shock (caused most frequently by low cardiac output and less often is secondary to rupture of the interventricular septum) and to facilitate the therapeutic strategy. The optimal treatment of RVI-related cardiogenic shock in older patients remains to be defined, but volume loading alone (and probably in combination with dobutamine) seems to be an insufficient approach.

Study Limitations
Our present study is observational in nature and lacks some potentially relevant clinical (eg, preinfarct daily life performance ability or pulmonary disease antecedents) and functional (eg, right ventricular ejection fraction and more precise data of the hemodynamic status) information. Therefore, further studies to understand the pathophysiological mechanisms of RVI-associated cardiogenic shock in the elderly are needed. Patients were treated on an individual, nonprotocolized basis; hence, conclusions about the optimal treatment of these cases can only be suggested from our study, and prospective studies addressing this question are warranted.

In conclusion, our observations suggest that (1) RVI is a strong independent predictor of in-hospital death in older patients with acute inferior myocardial infarction, (2) these patients have a very high hemodynamic susceptibility that frequently leads to low cardiac output cardiogenic shock, (3) RVI-associated cardiogenic shock in the elderly is often not dependent on left ventricular systolic dysfunction and is rarely reversible, (4) there is a relatively high incidence of rupture of the interventricular septum in these patients, and (5) the in-hospital case fatality rates of RVI-associated cardiogenic shock and mechanical complications are extremely high in the elderly.

	Footnotes

 
Presented in part at the XVIIth Congress of the European Society of Cardiology, Amsterdam, Netherlands, August 20-24, 1995, and at the 45th Annual Scientific Session, American College of Cardiology, Orlando, Fla, March 24-27, 1996.

Received December 19, 1996; revision received February 6, 1997; accepted February 10, 1997.

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