Beneficial effect of ischemic preconditioning on post-infarction left ventricular remodeling and global left ventricular function

Abstract

Background

Preinfarction angina (PA) is a clinical analogue of ischemic preconditioning that improves postinfarct prognosis. Data concerning the association of PA with post infarction left ventricular (LV) remodeling and LV diastolic function are limited. We aimed to evaluate this association in patients with acute myocardial infarction (AMI) in the modern clinical era of widespread use of revascularization and antiremodeling medical treatment.

Methods

We studied 53 patients with anterior AMI who underwent complete reperfusion and received up to date antiremodeling medical treatment. LV remodeling, systolic and diastolic function were assessed using 2D echocardiography at baseline and 6 at months follow-up. Patients were divided into two groups regarding the presence or absence of PA.

Results

LV remodeling at follow-up was less frequent in the PA group (25 vs. 55 %, P <.05). Patients with PA had lower end-systolic volume index at baseline and follow up (24.1±6 vs. 30.1±14 ml/m ², P <.001 and 25.3±8 vs. 35.6±2 ml/m ², P =.001 respectively). Additionally at 6 months, they had better LV ejection fraction (52.1±9 vs. 42.9±10 %, P =.002) and exhibited improved diastolic filling as reflected by mitral E/e′ (14.6±5 vs. 18.8±8, P =.05).

Conclusions

Ischemic preconditioning in the form of PA promotes better LV systolic and diastolic function in the mid-term and is associated with less postinfarct LV remodeling in this specific study population. The results of the study underline the possible need for further risk stratification of AMI patients regarding the absence of PA.

1 Summary

We aimed to investigate the possible association of preinfarction angina (PA) and left ventricular (LV) remodeling and LV performance 6 months following an acute anterior wall myocardial infarction. Patients with PA experienced less severe LV remodeling while they exhibited better LV systolic function and improved LV diastolic filling properties.

Ischemic preconditioning, first described 2 decades ago , has been considered as the most efficient intervention to reduce infarct size other than reperfusion . Today there is clear evidence that this phenomenon occurs in humans and one of the most relevant clinical counterparts include preinfarction angina (PA) Numerous studies have shown that the presence of angina in a variable time period before the acute presentation of myocardial infarction (AMI) may offer significant protection by limiting infarct size and by preserving left ventricular systolic (LV) function, thus improving short- and long-term prognosis .

Postinfarction LV remodeling and the type of LV diastolic filling, are associated with significant morbidity and mortality . Especially LV remodeling is still a common sequelae in patients with AMI, despite the generalized implementation of revascularization policy and broad antiremodeling drug administration . However, there are only sparse data regarding their association with preinfarction angina in today’s clinical milieu . Until recently, most of the studies that have evaluated the effect of PA on AMI patients were performed before the widespread use of percutaneous coronary intervention (PCI). We hypothesized that patients with AMI and effective revascularization with a history of PA will exhibit reduced LV remodeling and improved diastolic filling properties compared to patients with no clinical evidence of ischemic preconditioning. If this hypothesis would prove true it would probably influence risk stratification of these patients and possibly prognosis in the long term.

2 Methods

The study was conducted at the Cardiology department of AHEPA University Hospital and its protocol was approved by the Institutional Committee on human research. The study complied with the Declaration of Helsinki, and all patients gave written inform consent before enrolment.

Sixty two consecutive patients were first enrolled in the study. Patients were considered eligible if they presented with an acute anterior wall ST-elevation AMI with a angiographically documented left anterior descending coronary artery stenosis (as the culprit lesion) and no history of cardiovascular disease. AMI was defined according to ACC guidelines . All patients received successful reperfusion with thrombolysis, PCI, or coronary artery bypass grafting (CABG). The initial therapeutic approach was either with thrombolysis or primary PCI. If thrombolysis failed rescue angioplasty was performed. All patients underwent coronary angiography during their hospitalization. In patients with residual stenosis on left anterior descending artery >70% or TIMI flow <III elective angioplasty was performed. In the case where angioplasty was not feasible, CABG was performed. All patients were also treated with an antiremodeling regimen including antiplatelets, angiotensin-converting enzyme inhibitors, β-blockers and statins where ever possible.

Patients were excluded from the study if they had a poor echocardiographic image, any history of coronary heart disease, any history of terminal or systematic disease, any severe valve disease or cardiomyopathy, collateral circulation graded >1 according to Rentrop classification , and finally, if they were diabetics on glibenclamide treatment (preconditioning inhibitor) .

On hospital admission, all patients were interviewed regarding the time of their most recent chest pain or discomfort, if any. PA was defined as typical chest pain episodes at rest or stress lasting less than 20 min and having the same character with the final admission episode, as previously described . All patients with PA included in the study had angina episodes within 48 hours before admission, thus, were possibly protected by ischemic preconditioning through the first or second window of protection . A standard 12-lead discharge electrocardiogram (ECG) was interpreted on every patient, and the number of leads with abnormal Q waves and negative T waves were recorded. ECG was reassessed at discharge. Blood samples for measuring creatine phosphokinase MB fraction (CPK MB) levels were taken on admission, then every 8 h for the first day, and subsequently every morning till discharge. In addition B-type natriuretic peptide (BNP) levels at discharge were assessed using a commercially available immunofluoresence assay (BNP Triage, Biosite, San Diego, CA, USA).

All patients underwent a complete echocardiographic study, including 2D, color flow, spectral Doppler, as well as tissue Doppler imaging (TDI) using a GE Vingmed Vivid 7 system (GE Vingmed Ultrasound AS, Horten, Norway), at the day of discharge. The echocardiographic study was repeated at the end of follow-up in order to estimate LV remodeling. LV (end-systolic and end-diastolic) volumes and ejection fraction were estimated using Simpson’s modified biplane method and were further corrected for body surface area (end-systolic and end-diastolic volume index) . An increase of end-diastolic volume >20% at follow-up was used as the index of LV remodeling, as previously described .

The wall motion score index (WMSi) was obtained semiquantitatively using a 16-segment division of the LV . Pulsed Doppler echocardiography in order to assess standard LV diastolic filling velocities was performed using the apical four-chamber view. Peak early filling velocity (E wave) and E-wave deceleration time (DT) were recorded Using conventional color TDI, we assessed longitudinal strain (LS) of the basal (LS basal) and mid (LS mid) segment of anterior wall, using the two-chamber view . Apical anterior segment was not estimated because TDI is angle dependent and LV apex is not an ideal target for quantifying LS . LS was calculated as ( L − L _o)/ L _o, where L _ois the original length at end-diastole and L is the length at end-systole. Color TDI was used to assess mitral annulus velocities. A 5-mm sample volume was placed at the apical four-chamber view on the septal and lateral corner of the mitral annulus and the early diastolic velocity (e′) was recorded. The velocities obtained by the two different points of the mitral annulus were averaged . Furthermore, the ratio of early transmitral filling velocity (E wave) to early diastolic mitral annulus velocity (LV E/e′ index) was calculated .

All echocardiographic measurements were obtained by a single experienced operator (C.E.P.) from three different cardiac cycles and were further averaged.

The follow-up was undertaken at 6 months when a complete echocardiographic study was repeated in order to assess LV remodeling and LV systolic and diastolic function. Major cardiovascular events including myocardial infarction, stroke and heart failure decompensation were recorded, as well as hospitalizations during this period.

Data are expressed as mean±S.D. Frequencies were expressed as a percentage. Differences between groups were assessed by Student’s unpaired t test and Mann-Whitney test, as appropriate. Categorical variables were compared using chi-square or Fisher’s Exact test, as appropriate. P <.05 was considered significant. SPSS statistical software (SPSS 12.0, Chicago, IL, USA) was used for all the analyses.