Assessment of Right Ventricle Function and Myocardial Fibrosis by Cardiovascular Magnetic Resonance in Patients with Inferior Wall Myocardial Infarction

Mailing Address: Priscila Neri Lacerda Rua Reitor Miguel Calmon, s/n. Postal Code: 40110-100. Vale do Canela, Salvador, BA – Brazil E-mail: priscilanlacerda@hotmail.com Assessment of Right Ventricle Function and Myocardial Fibrosis by Cardiovascular Magnetic Resonance in Patients with Inferior Wall Myocardial Infarction Priscila Neri Lacerda,1 Rafael Fernandes Almeida,2 Fernanda Gabriella Figueiredo Pinto,2 Adilson Machado Gomes Júnior,1 Jéssica Mendes Santos,1 Cristiano Ricardo Bastos de Macêdo,2 André Maurício Souza Fernandes,2 Roque Aras Júnior2 Universidade Federal da Bahia (UFBA);1 Hospital Ana Neri,2 Salvador, BA – Brazil


Introduction
Right ventricular dysfunction (RVD) can be observed in 30% to 50% of patients with inferior wall myocardial infarction (I-MI) and it might be associated with atrioventricular block, hemodynamic instability and in-hospital mortality. 1,2[3] The assessment of right ventricle (RV) by echocardiography is technically difficult due to the lack of an adequate acoustic window and its peculiar anatomical conformation. 3,4The capability to precisely visualize the RV makes cardiac magnetic resonance (CMR) the method of choice for estimating the extent of myocardial damage and the functional impairment by means of highly accurate and reproducible measures of RV. [3][4][5][6] Following myocardial infarction, cardiac remodeling involves an inflammatory reaction followed by scar

Right ventricle function and myocardial fibrosis
Int J Cardiovasc Sci.2017;30 (2): 109-116   Original Article formation at the site of infarction. 7However, sustained fibrotic activity results in stiffening of the myocardium and is associated with progressive ventricular dysfunction and severe prognosis. 7,8][11][12] This study aimed to evaluate the association between myocardial fibrosis and RVD in patients with I-MI, using CMR.

Study population
A total of fifty-seven patients with acute ST segment elevation myocardial infarction with inferior wall involvement (ST segment elevation in D2, D3 and aVF derivations on the electrocardiography) were prospectively recruited at Ana Neri Hospital, Brazil, between January and December 2014.Patients were excluded if they had metallic implants incompatible with CMR, glomerular filtration rate (GFR) < 30 ml/min, severe claustrophobia or gadolinium hypersensitivity.
Clinical data including age, sex, family history, comorbidities and cardiovascular risk factors were retrospectively collected from patients' medical records.CMR was performed during hospitalization to estimate parameters of RV function and to quantify myocardial fibrosis.Right ventricular ejection fraction (RVEF), end-systolic volume and end-diastolic volume were measured to estimate ventricular function.LGE-CMR technique was used to measure myocardial fibrosis in the inferior wall.Patients were stratified by ventricular function, considering RVD if RVEF < 40%.
The study was approved by the ethical, institutional review board (Ana Nery Hospital Ethics Committee) and the National Ethics Committee and all patients provided written informed consent.

CMR acquisition
Patients were scanned in the supine position and CMR studies were performed using a 1.5 T whole-body scanner (Avanto, Siemens Medical Solutions, Germany).An 8 channel cardiac coil was used for signal reception.Scout images were obtained to plan the four-chamber, three-chamber and two-chamber views, as well as short axis cine imaging.ECG-gated steady-state free precession (SSFP) short-axis images of the ventricles were acquired during breath holds with 20 image frames per cardiac cycle.Acquisition parameters were: 8-mm slice thickness, FOV 300, matrix 128 x 128.
A stack of images, using a minimum of 8 and a maximum of 12 slices in short-axis plane (slice thickness 8-mm; gap 2-mm) was acquired, allowing coverage of the entire cardiac volume.Every effort was made to obtain adequate images with a satisfactory right ventricle depiction.
LGE-CMR enabled the assessment of myocardial fibrosis, as presented in Figure 1.After a bolus of 0.2 mmol/kg of contrast agent (Gadodiamide, Omniscan™, GE Healthcare), images were acquired using a T1-weighted segmented inversion-recovery turbo fast low-angle shot sequence (echo time 4.8 ms; voxel size 1.4×2.4×7mm; flip angle, 20°).The inversion time was meticulously adjusted for optimal nulling of normal myocardium.A non-viable segment was one in which delayed enhancement comprised more than 50% of wall thickness.

CMR analysis
Ventricular mass, volume, and systolic function, including RVEF, were analyzed using the cine MR images and ARGUS 4D VF software.End-systolic and end-diastolic frames were identified by the smallest and largest cavity area, respectively.Ventricular contours were manually traced in both systolic and diastolic frames, for at least 8 slices from base to apex.
The regions of interest were manually traced along the areas of fibrosis (Figure 2).Fibrosis mass was obtained by multiplying this area by the slice thickness and by myocardium density (1.05 g/ml).

Statistical analysis
Continuous variables were expressed as mean ± SD if normally distributed and otherwise as median and range.The Kolmogorov-Smirnov test was used to test variable normality.Categorical variables were given as counts and percentages of total.Continuous variables were compared by Student's t-test for independent samples and comparisons of categorical variables

Results
Fifty-seven patients were selected between January and December 2014 according to our inclusion criteria.CMR imaging exam was performed in forty individuals, and seventeen participants were excluded due to impossibility of performing the exam or technical issues on their CMR (Figure 3).
Patients were stratified by RV function and both study groups had similar clinical characteristics (Table 4).Student's t-test showed that mean fibrosis area and mean fibrosis mass were higher in the group of patients with RVD (p = 0.092, p = 0.051 respectively).There were no statistically significant differences in the number of non-viable segments between groups.

Discussion
Recent studies have been focused in the negative impact of RVD in patients with I-MI, as it is considered an important independent predictor of mortality in these patients. 13The assessment of RV function and its predictors enables early identification of individuals who tend to have worse outcomes and poor prognosis.The present study, in agreement with previous reports, [14][15][16][17] confirms the ability of CMR to precisely evaluate RV function and quantify myocardial fibrosis.
In our study group, composed mostly of male and elderly patients, hypertension was the most prevalent cardiovascular risk factor (55%) followed by smoking (40%), diabetes mellitus (25%) and heart failure (25%).Smarz et al. 18 have reported a similar prevalence of these cardiovascular risk factors in 90 patients with I-MI, except for the prevalence of dyslipidemia of 70%, which was different from that found in our study (20%).
In the present study, RVD was evident in 33% of cases with I-MI, which was similar to the prevalence of 32% reported in previous studies on 50 patients with I-MI. 19,20onsidering that similar clinical features were observed between patients with RVD and patients with preserved ventricular function, our study could investigate, with relative precision, the association between RV function and myocardial fibrosis.
Our study revealed a negative correlation between RVEF and variables such as smoking, dyslipidemia, diabetes and fibrosis mass.The analysis showed a strong trend towards the association between RVEF and fibrosis mass (p = 0.05), indicating that grater mass of fibrosis is related to lower RVEF.This finding suggests that fibrosis is a possible predictor of RVD.
Furthermore, the current study showed an important trend towards higher mean fibrosis mass in patients with RVD compared to patients with preserved ventricular function (22 ± 12g vs 15 ± 8 g, p = 0.051).This result indicates a possible association between RVD and myocardial fibrosis within inferior wall, with clinical and prognostic significance in patients with I-MI.A similar association has been reported in a study by Kaandorp et al., 21 which results showed higher values of RV end-diastolic volume in the group of patients with higher mean fibrosis mass. 3e small sample size of our study population is the main limitation to the present findings.Moreover, the amount of patients excluded (30%) due to the lack of CMR imaging data is an important limitation of the present study.Therefore, further studies with larger series are needed to confirm our findings.

Conclusions
The CMR seems to be an adequate method for risk stratification of patients with I-MI and RV dysfunction.The findings of our study indicate a possible association between myocardial fibrosis in the left ventricular inferior wall and RVD in patients with I-MI.Nevertheless, further studies with larger series are needed to confirm our findings.

Figure 2 -
Figure 2 -Measurement of fibrosis by late gadolinium enhancement (1 represents the area of fibrosis).

Figure 1 -Figure 3 -
Figure 1 -Late gadolinium enhancement-cardiac magnetic resonance images from patients with inferior wall myocardial infarction (white arrows show myocardial fibrosis in the inferior wall).

Table 2
Prevalence of cardiovascular risk factors.