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Glucose Metabolism and Left Ventricular Function after Acute Myocardial Infarction

Dan Eik Høfsten

Summary

This PhD thesis is based on three original manuscripts from a single clinical study. The study wasconducted at the Department of Medical Research and the Department of Medicine at FunenHospital Svendborg.

Background

Patients with diabetes are at increased risk of an adverse outcome after acute myocardialinfarction. Recent data suggests that this is also true for patients with abnormal glucosemetabolism below the diagnostic threshold for diabetes. The excess mortality among patients withdiabetes is largely attributable to an increased incidence of post‐infarction congestive heartfailure, suggesting that left ventricular function plays an important role in the causal pathway ofthis association. It is however presently unknown whether dysglycemia affects the extent of acuteischemic damage, or how it affects the risk of subsequent progressive left ventricular dysfunctionthat may ultimately result in congestive heart failure and death.

Methods

During a 22 month period, we consecutively included 213 patients with a validated diagnosis ofacute myocardial infarction, admitted to the coronary care unit at Funen Hospital, Svendborg.Patients without a pre‐study diagnosis of diabetes were screened for dysglycemia using astandardized oral glucose tolerance test before discharge. Left ventricular function was assessedby means of transthoracic echocardiography, using established markers of left ventricular systolic(wall motion index score, left ventricular ejection fraction, and peak longitudinal systolic tissuevelocity) and diastolic (deceleration time of early transmitral diastolic flow, peak early trans‐mitraldiastolic flow‐velocity to peak early diastolic mitral annular‐velocity index, and left atrial volumeindex) function. To estimate left ventricular functional reserve, echocardiography was repeatedduring low‐dose dobutamine infusion (at 10 μg/kg/minute). Furthermore, plasma levels of Nterminalpro‐B‐type natriuretic peptide (NT‐proBNP) were measured as an indicator ofneurohormonal activation due to left ventricular dysfunction. Echocardiography was repeatedafter 1, 3 and 6 months. After the end of this follow‐up, patients were followed prospectively forclinical events until 12 months after inclusion of the last patient.

Results

In accordance with previous studies in patients with acute myocardial infarction, a high prevalenceof abnormal glucose metabolism was observed. A previous diagnosis of diabetes was present in15% of all patients, and in the remaining patients, abnormal glucose metabolism was present in58% (26% of which fulfilled the criteria for newly detected diabetes). On the initialechocardiographic examination, an approximately linear increase in all markers of left ventriculardysfunction was observed with increasing degree of dysglycemia. The same was true for NTproBNPlevels. There was also a strikingly linear increase in the risk of death or admission for heartfailure during follow‐up with increasing degree of dysglycemia, even after adjustment fordifferences in left ventricular function, as well as age, gender, and other relevant risk factions.Analysis of echocardiograms obtained during dobutamine infusion showed the same linear trendwith increasing degree of dysglycemia, and furthermore indicated, that markers of left ventricularfunction obtained under these conditions were more closely related to NT‐proBNP leves (as asurrogate of increased left ventricular filling pressure) than values measured at rest.Analysis of the serial echocardiographic examinations showed, that the deleterious effect ofdysglycemia on left ventricular function was sustained throughout the first six monts postinfarction,as the relative differences between the four glucometabolic groups were virtuallyunchanged at the end of clinical follow‐up.

Conclusions

Patients with abnormal glucose metabolism have more pronounced impairment of left ventricularsystolic and diastolic function as well as impaired functional reserve in the acute phase ofmyocardial infarction, and this difference is maintained for at least six months after the initialischemic event. However, this relationship does not alone explain the excess mortality in patientswith dysglycemia. A multidisciplinary approach to the individual patient, including assessment ofboth left ventricular function and glucose metabolism, could therefore potentially improve riskstratification as well as outcome after acute myocardial infarction.