Acute coronary syndromes in patients with pre-existing moderate to severe valvular disease of the heart: lessons from the Euro-Heart Survey of acute coronary syndromes
David Hasdaia,
Eli I Leva,
Solomon Beharb,
Valentina Boykob,
Nicholas Danchinc,
Alec Vahaniand and
Alexander Battlera,*
a Department of Cardiology, Rabin Medical Center, 39 Jabotinsky Street, Petah Tikva 49100, Israel
b Neufeld Cardiac Research Institute, Tel Hashomer, Israel
c Hôpital Européen Georges Pompidou, Paris, France
d Hopital Bichat, Paris, France
* Corresponding author. Tel.: +972-3-9377107; fax: +972-3-9249850
E-mail address: abattler{at}clalit.org.il
Received 16 September 2002;
revised 8 October 2002;
accepted 9 October 2002
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Abstract
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Aim To determine the frequency of pre-existing valvular disease (VD) among patients with acute coronary syndromes (ACS) and to compare the clinical characteristics, clinical course, treatment, and outcomes of ACS patients with and without pre-existing VD.
Methods and results The Euro Heart Survey ACS prospectively enrolled 10,484 ACS patients in 103 hospitals in 25 countries across Europe and the Mediterranean basin. Of the 10,207 patients with data on VD status, 489 (4.8%) had a diagnosis of pre-existing VD: 3.7% of 4339 ST-segment-elevation-ACS patients, 5.2% of 5210 non-ST-segment-elevation-ACS patients, and 10.8% of 658 undetermined-electrocardiogram-ACSpatients. Moderate/severe mitral regurgitation had been diagnosed in 54.0% (48.7% without and 5.3% with concomitant mitral stenosis), and moderate/severe aortic stenosis occurred in 31.7% (26.4% without and 5.3% with concomitant aortic regurgitation). Patients with pre-existing VD had worse baseline clinical and demographic characteristics, were more likely to present with heart failure and less likely to have typical angina, and had a more complicated in-hospital course (heart failure, atrial arrhythmias, and renal failure). They were more likely to receive inotropic agents, diuretics, amiodarone, and warfarin, and less likely to receive antiplatelet agentsand beta-adrenergic blockers. As compared to patients without VD, the adjustedrisk (95% confidence interval) of in-hospital death for VD patients was 1.55 (0.85, 2.80), 1.92 (1.03, 3.59), and 1.77 (0.75, 4.17) for ST-segment-elevation-ACS, non-ST-segment-elevation-ACS, and undetermined-electrocardiogram-ACS, respectively.
Conclusions Patients with ACS and pre-existing VD constitute about 5% of all ACS patients; they have high-risk features and poor prognosis. There is a need to better define their optimal treatment, in order to improve their prognosis.
Key Words: Acute coronary syndrome Acute myocardial infarction Mitral regurgitation Aortic stenosis Valves Prognosis
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1. Introduction
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Valvular disorders often complicate the acute coronary syndromes (ACS).1 There are, however, very little recent data regarding the frequency of pre-existing significant valvular disease (VD) of the heart among patients admitted due to an ACS, the clinical characteristics of these patients, their clinical course while in-hospital, their treatment both in-hospital and at discharge, and their outcomes. This is most likely because patients with moderate to severe disease of the heart valves have been almost universally excluded from clinical studies of ACS.
The Euro Heart Survey of Acute CoronarySyndromes (Euro Heart Survey ACS) was a prospective survey of patients admitted due to an ACS in 103 hospitals across 25 countries in Europe andthe Mediterranean basin.2 Because patients with pre-existing moderate to severe VD of the heart were a pre-defined subgroup of patients in this survey that were planned for analysis, this cohort offers a unique opportunity to elucidate theircharacteristics, treatments, and outcomes.
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2. Methods
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2.1. Euro heart survey ACS
The details of the Euro Heart Survey ACS have been previously described in detail. The survey wasperformed in clusters composed of academicand non-academic hospitals and hospitals with and without cardiac catheterisation laboratories and cardiac surgery facilities. The enrolment period was planned from September 4 to December 31, 2000. Due to technical delays (primarily delays in approval by ethic committees in several countries), the Expert Committee decided to extend theduration of the survey to May 15, 2001.
All patients with suspected ACS, screened at the emergency room, chest pain units, catheterisation laboratory, or otherwise were registered on a screening log (after acquisition of written informed consent if required), but they were not enrolled until the diagnosis of ACS was confirmed. Patients who had been in another hospital for a short (<12h) observation period and were transferred for diagnosis and management were also registered, and information from the referring hospital was sought. However, patients who were referred only for a specific treatment (i.e. cardiac catheterisation or coronary bypass surgery) were not included. For all logged patients, we recorded the tentative initial diagnosis made by the attending physicians based on the initial electrocardiographic pattern: ACS with ST elevation, ACS without ST elevation, and ACS with an undetermined electrocardiographic pattern. The full case report form was filled outfor patients with a discharge diagnosis of unstable angina or myocardial infarction.
The case report form included details regarding the demographic, clinical, and electrocardiographic characteristics of the patient, the diagnostic and treatment modalities, the in-hospital complications, and the discharge status.
2.2. Pre-existing VD
Patients with significant VD, defined as having moderate to severe stenosis and/or regurgitation of the mitral and/or aortic valves, were a pre-defined subgroup for subsequent analysis. The information regarding pre-existing VD was extracted from prior medical charts and documents, as well as from information supplied by the patient. Confirmation of the valvular diagnosis by echocardiography or other imaging modalities was not required. Based on the derived data, the valvular pathology was categorised based on the valves involved and the presence of stenosis or regurgitation (Table 1).
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Table 1 Characterisation of the pre-existing valvular pathology based on the initial electrocardiographic type of ACS
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2.3. Analysis
For each group of ACS patients divided based on their initial electrocardiographic pattern (withST elevation, without ST elevation, and withan undetermined electrocardiographic pattern),patients were divided into subgroups of patients with and without significant VD. Within each group of ACS patients, the clinical characteristics ofpatients with significant VD, their clinical course while in-hospital, their treatment both in-hospital and at discharge, and their in-hospital and 30-day outcomes were compared to the subgroup ofpatients without significant pre-existing VD.
To determine whether the differences in mortality in hospital between subgroups were due to differences in baseline clinical and demographic characteristics, logistic regression models wereformulated for each group of ACS patients.
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3. Results
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Of the 10,484 patients enrolled in Euro HeartSurvey ACS, information regarding prior moderate to severe VD of the heart was missing for 277 patients (92 with ACS with ST-segment elevation, 157 with ST-segment elevation, and 28 with an undetermined electrocardiogram upon admission). Of the remaining 10,207 patients, 489 (4.8%)patients had a diagnosis of a significant VD of the heart (Table 1): 3.7% of patients with ST-segment elevation, 5.2% of patients without ST-segmentelevation, and 10.8% of patients with an undetermined electrocardiogram upon admission. The predominant valvular pathology was moderate to severe mitral regurgitation, occurring in 54.0% of the patients with significant valvular heart disease (48.7% without concomitant mitral stenosis and 5.3% with moderate to severe mitral stenosis).Moderate to severe aortic stenosis was also frequent, occurring in 31.7% of patients with significant VD of the heart (26.4% without concomitant aortic regurgitation and 5.3% of patients withmoderate to severe aortic regurgitation). Anadditional 6.7% had significant disease of both the mitral and aortic valves. In eight patients (1.6%), the specific VD was unknown to the patient or not recorded in the chart, although the patient was known to have significant VD.
For all groups of ACS patients, the subgroups of patients with significant VD of the heart were older, more likely to be of female gender, lighter in weight, more often had diabetes mellitus and chronic renal failure, and more likely to have had a prior cardiac ischaemic event, heart failure, or a revascularisation intervention (Table 2). Patients with significant VD were less likely to be current smokers.
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Table 2 Baseline demographic and clinical characteristics of patients with V(+) and without V() pre-existing VD based on the initial electrocardiographic type of ACS
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Patients with significant pre-existing VD were less likely to have typical angina upon presentation (Table 3). In addition, these patients were more likely to present with heart failure, lower systolic blood pressure, and a faster heart rate.
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Table 3 Clinical characteristics and physical findings upon admission of patients with V(+) and without V() pre-existing VD based on the initial electrocardiographic type of ACS
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While in hospital, patients with significant pre-existing VD were less likely to receive antiplatelet agents, but much more likely to receive treatment with warfarin (Table 4). Patients with VD were much more likely to receive digoxin, diuretics, intravenous inotropic agents, and amiodarone. Treatment with angiotensin converting enzymeinhibitors was slightly more common amongpatients with VD, whereas treatment with beta-adrenergic blockers was slightly less common. Among patients with ST-segment elevation ACS, 55 patients (37%) with significant VD received reperfusion treatment, as compared with 2413 patients (58%) without significant VD. Of these patients who received reperfusion treatment, 34 (62%) and 1291 (54%) patients, respectively, received thrombolytic therapy.
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Table 4 In-hospital medical treatment of patients with V(+) and without V() pre-existing VD based on the initial electrocardiographic type of ACS
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In-hospital complications were more common among patients with VD, especially the occurrence of heart failure of all severities ranging from mild heart failure to cardiogenic shock (Table 5). Atrial fibrillation or flutter and renal failure also more frequently occurred among patients with VD.Accordingly, patients with heart failure morecommonly underwent mechanical ventilation and intra-aortic balloon counter pulsation (Table 6). Despite their worse in-hospital course, patients with significant VD underwent coronary angiography and percutaneous coronary revascularisation less often than patients without significant VD. Differences in the rates of coronary artery bypass grafting surgery between patients with and without significant VD were observed only in the subgroup of patients with an undetermined electrocardiographic pattern; surgery was performed two-fold more commonly in patients with VD in this electrocardiographic subgroup. We have no data regarding the frequency of valvular repair or replacement during bypass surgery.
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Table 5 In-hospital complications of patients with V(+) and without V() pre-existing VD based on the initial electrocardiographic type of ACS
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Table 6 In-hospital invasive procedures of patients with V(+) and without V() pre-existing VD based on the initial electrocardiographic type of ACS
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Among the patients in this cohort who underwent an evaluation of left ventricular systolic function
, a greater proportion of patients with pre-existing significant VD had left ventricular dysfunction, defined as a left ventricular ejection fraction of 0.4 or lower: 24% of ST-segment-elevation patients without VD versus 48% of those with VD; 13% of non-ST-segment-elevation patients without VD versus 26% of those with VD; 38% of undetermined-electrocardiogram patients without VD versus 53% of those with VD.
Among the surviving patients, patients withpre-existing VD were less likely to be discharged with antiplatelet agents, beta-adrenergic blockers, and statins, but more likely to receive warfarin, digoxin, diuretics, and amiodarone (Table 7).
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Table 7 Medical treatment at discharge from hospital of surviving patients with V(+) and without V() pre-existing VD based on the initial electrocardiographic type of ACS
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The unadjusted in-hospital and 30-day mortality rates were significantly worse for patients with pre-existing significant VD for all groups of ACS patients (Table 8). The adjusted risk of in-hospital death for patients with pre-existing VD was 1.55 (0.85, 2.80), 1.92 (1.03, 3.59), and 1.77 (0.75, 4.17) for ST-segment-elevation ACS, non-ST-segment-elevation ACS, and undetermined-electrocardiogram ACS, respectively.
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Table 8 In-hospital and 30-day mortality status of patients with and without pre-existing VD based on the initial electrocardiographic type of ACS
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4. Discussion
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There is significant overlap between the pathogenesis of atherosclerotic disease of the coronary arteries and VD of the heart, in particular aortic stenosis and mitral annulus calcification.3,4 Anunderlying VD may also cause an ACS, for example a coronary thromboembolism in a patient with mitral stenosis.5 Other pre-existing valvular pathologies, such as aortic stenosis, may precipitate myocardial ischaemia through a mechanism unrelated tocoronary artery disease, with symptoms and signs that accurately mimic those of ACS. Lastly, valvular pathologies of the heart, in particular mitralregurgitation, may be the result of complicationsof ACS.1 Thus, VD of the heart and ACS may be concomitant cardiac conditions.
Most of the recent literature has focused on the valvular complications of ACS.1 However, there is a paucity of data regarding pre-existing VD of the heart and ACS. The major findings of the current analysis were that pre-existing significant VD of the heart occurred in approximately 5% of patients with ACS. The unadjusted in-hospital and 30-day mortality rates were at least two-fold higher forpatients with pre-existing VD of the heart, irrespective of the initial pattern of the electrocardiogram upon presentation. After adjusting for some of the demographic and clinical differences betweenpatients with and without pre-existing VD, the risk of dying decreased, but there was still a strong trend for increased mortality in patients with pre-existing VD. Thus, the subgroup of patients with ACS and pre-existing significant VD of the heart should be regarded as high-risk.
4.1. Clinical implications
Left-ventricular systolic dysfunction has been considered one of the most important predictors of outcome after ACS.6,7 More recently, this paradigm has been expanded with focus also placed onleft ventricular diastolic function. Indeed, restrictive left-ventricular diastolic filling patterns, as depicted by echocardiography, have been reported to be of even greater prognostic significance among patients with ACS than left-ventricular ejection fraction.8,9 The current study further expands this paradigm, underscoring the significance of co-existing VD on outcomes of ACS patients. Thus, a thorough assessment of all components of cardiac function is needed in order to better predict outcomes of ACS patients. More specifically, an echocardiographic examination should be encouraged as part of the routine assessment of ACS patients.
4.2. Limitations
The shortcomings of the Euro Heart Survey ACS have been previously discussed in detail.2 Nonetheless, this survey is the largest, most recent, and most extensive of its kind among ACS patients in this broad region of the world. The diagnosis of significant pre-existing VD was not confirmed in a uniform manner and with strict criteria (especially echocardiographic criteria), but rather relied on diagnoses extracted from the patients' medical records or information provided by the patient. However, given that a large proportion of patients that were considered to have significant pre-existing VD had also previously experienced other cardiac complications (such as myocardial infarction) and had undergone cardiac interventions (revascularisation procedures and pacemakerimplantation), it is likely that the diagnosis was reliably made during their prior workup. Moreover, an echocardiographic examination at the time of presentation with ACS may be misleading regarding the severity of valvular pathology (although it is essential for the diagnosis of VD); for example, reduced left ventricular function during acutecardiac ischaemia may be associated with anattenuated gradient across the aortic valve.Acute cardiac ischaemia in itself may also cause certain valvular pathologies.1 Thus, the accurate diagnosis of pre-existing VD, especially its severity, must rely on information obtained prior to the acute event. Finally, our analysis did not determine the optimal treatment of ACS patients with pre-existing VD, especially the necessity and timingof valvular repair or replacement. This should be the focus of specifically designed studies in the future.
4.3. Conclusions
The patients with ACS and pre-existing significant VD of the heart constitute a small, yet sick groupof patients with a worse prognosis. There is a genuine need to vigilantly identify these patients, especially because they often have undetermined electrocardiographic patterns, and to better define their optimal treatment, in order to improve their prognosis.
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References
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