Does quantitative left ventricular regional wall motion change after fibrous tissue resection in endomyocardial fibrosis?

OBJECTIVES: We compared left ventricular regional wall motion, the global left ventricular ejection fraction, and the New York Heart Association functional class pre- and postoperatively.
INTRODUCTION: Endomyocardial fibrosis is characterized by fibrous tissue deposition in the endomyocardium of the apex and/or inflow tract of one or both ventricles. Although left ventricular global systolic function is preserved, patients exhibit wall motion abnormalities in the apical and inferoapical regions. Fibrous tissue resection in New York Heart Association FC III and IV endomyocardial fibrosis patients has been shown to decrease morbidity and mortality.
METHODS: We prospectively studied 30 patients (20 female, 30+/-10 years) before and 5+/-8 months after surgery. The left ventricular ejection fraction was determined using the area-length method. Regional left ventricular motion was measured by the centerline method. Five left ventricular segments were analyzed pre- and postoperatively. Abnormality was expressed in units of standard deviation from the mean motion in a normal reference population.
RESULTS: Left ventricular wall motion in the five regions did not differ between pre- and postoperative measurements. Additionally, the left ventricular ejection fraction did not change after surgery (0.45+/-0.13% x 0.43+/-0.12% pre- and postoperatively, respectively). The New York Heart Association functional class improved to class I in 40% and class II in 43% of patients postoperatively (p<0.05).
CONCLUSIONS: Although endomyocardial fibrosis patients have improved clinical symptoms after surgery, the global left ventricular ejection fraction and regional wall motion in these patients do not change. This finding suggests that other explanations, such as improvements in diastolic function, may be operational.

INTRODUÇÃO

The clinical and pathological features of endomyocardial fibrosis (EMF) were first described by Jack N. P. Davies in 1948.1 EMF is a restrictive cardiomyopathy characterized by fibrous tissue (FT) deposition in the endomyocardium of the apex and/or inflow tract of one or both ventricles.2 The involvement of the subvalvar apparatus by FT may cause atrioventricular regurgitation. Ventricular volumes are usually normal or decreased by FT deposition, whereas atrial volumes are enlarged and reflect diastolic dysfunction.3 Clinical manifestation occurs as right or left cardiac failure, depending on the degree of bilateral ventricle involvement.4 Diagnosis may be performed noninvasively by echocardiography3 or magnetic resonance imaging5 via recognition of apical obliteration, atrioventricular valve regurgitation, and diastolic dysfunction or, more rarely, by invasive contrast ventriculography.6 Although the global LV ejection fraction (EF) is preserved in these patients, a previous study by our group showed that patients exhibit wall motion abnormalities in the apical and inferoapical regions that are unrelated to the amount of FT deposition.6 Treatment for patients in the New York Heart Association (NYHA) functional classes (FC) III and IV who are unresponsive to clinical treatment involves surgery.7 The surgical treatment consists of FT resection and repair or replacement of atrioventricular valves. This has been shown to decrease both morbidity and mortality.8 It has been previously reported that surgical treatment improves contractile myocardial function,9 although quantitative assessment of both global and regional myocardial function before and after FT resection has not been performed. Therefore, the objective of our study was to quantitatively compare LV regional wall motion, the global LVEF, and the NYHA FC pre- and postoperatively in EMF patients.

METHODS

We prospectively studied 30 patients (20 female, 30±10 years) with LV EMF before and 5±8 months after surgery. Seventeen patients (57%) had moderate to severe RV EMF associated with LV EMF. Thirteen (43%) patients were classified in NYHA FC IV and 17 (57%) patients in NYHA FC III. The diagnosis of EMF was based on clinical presentation as well as electrocardiographic and echocardiographic data. The typical echocardiographic examination showed apical obliteration, atrial dilation, and variable degrees of atrioventricular valve regurgitation.3 Fourteen (47%) patients underwent LV FT resection, and 16 (53%) underwent biventricular FT resection. Additionally, three patients (10%) underwent mitral valve replacement, one (3%) tricuspid replacement, five (17%) mitral valve repair, seven (23%) tricuspid valve repair, and 12 (40%) mitral and tricuspid repairs. The angiographic images of the LV were performed using a pigtail catheter in the anterior right oblique projection at 30º, and these images confirmed the EMF diagnosis.10 The LVEF was determined by the area-length method,11,12 and the regional LV wall motion was quantified using the centerline method.13,14 Contrast images representing the LV in maximum systole and diastole were selected, and their contours were traced onto paper by hand for later calculations. The images were analyzed by two independent observers who were blinded to identity of the patients, as previously described.6 Using a specific program,15 the ventricular images were recorded in a microcomputer with the aid of a digitalizing table (CURTA/model IS/ONE). The centerline was constructed in the computer between the end-diastolic and end-systolic contours. Motion was measured in 100 equidistant chords perpendicular to the centerline. The length of each chord indicated the motion of the corresponding point in the LV contour. The chords were normalized to cardiac size by dividing each length by the final diastolic margin, and a unit without dimensions was obtained. Abnormality was expressed as units of standard deviation from the mean motion of the normal reference population comprised of 103 individuals (52 men, 52±10 years) with normal LV according to clinical, electrocardiographic, and angiographic data. Positive values indicated hyperkinesia, and negative values indicated hypokinesia. Chord measurement was initiated at the level of the aortic valve, and the chords were successively numbered in a clockwise direction from the aortic valvular plane to the mitral plane.16 The regions from 1 to 10 demarcated by the chords were excluded because their analysis revealed great variation in length. Chords 81 to 100 were also excluded since they represented the mitral valve.16 The LV was divided into five regions: anterobasal (AB, chords 10 to 23), anterolateral (AL, chords 24 to 37), apical (A, chords 38 to 52), inferoapical (IA, chords 53 to 66), and inferobasal (IB, chords 67 to 80) (Figure 1).

Figure 1-

The left ventricle was divided into five regions: anterobasal: chords 10 to 23, anterolateral: chords 24 to 37, apical: chords 38 to 52, inferoapical: chords 53 to 66, and inferobasal: chords 67 to 80. Chords 1 to 10 were excluded due to their high variability in length, and chords 81 to 100 were excluded since they represent the mitral valve

Our Institutional Review Board approved this study, and informed consent was obtained from all patients.

Statistical analyses

Paired t-tests were used to compare regional LV wall motion and the LV ejection fraction before and after surgery. The Mann-Whitney test was used to compare the NHYA functional class pre- and postoperatively. A probability (P) value less than 0.05 was considered statistically significant. Statistical analyses were performed using SPSS v 15 (SPSS Inc. Chicago, IL, USA).

RESULTS

Quantitatively, LV wall motion in the five regions did not differ between the pre- and postoperative time points (AB: pre −0.78 ± 0.25 x post −0.96 ± 0.24, p= 0.559; AL: pre −0.90 ± 0.33 x post −1.26 ± 0.26, p= 0.275 ; A: pre −1.84 ± 0.31 x post −1.94± 0.34, p= 0.732; IA: pre −1.69 ± 0.29 x post −2.23 ± 0.39, p= 0.158, IB: pre −0.92 ± 0.21x post −1.24 ± 0.30, p= 0.347; Figure 2). Similarly, the LVEF did not change after surgery (0.45±0.13% x 0.43±0.12 pre- and postoperatively, respectively). However, the NYHA FC was classified as III in 17 patients (57%) and IV in 13 patients (43%), and it improved to I in 40% and II in 43% of the patients postoperatively (p<0.05, Figure 3). Seventeen percent of the postoperative patients remained in NYHA FC III and IV.

Figure 2-

Quantitatively, LV wall motion in the five regions did not differ pre- and postoperatively in EMF patients; AB – anterobasal; AL - anterolateral; A - apical; IA - inferoapical; IB – inferobasal

Figure 3-

The NYHA functional class improved to I in 40% and II in 43% of the patients postoperatively

DISCUSSION

This report demonstrates that LVEF and quantitative regional wall motion do not change even though EMF patients show improvements in their clinical symptoms after surgery. Regional wall motion has been shown to be present in EMF patients in A and IA regions,6 and we demonstrate herein that the wall motion abnormalities do not change after FT resection. In histopathological specimens obtained from surgical resection, the FT extends irregularly into the underlying myocardium17 and separates groups of myocardial fibers. Additionally, FT is composed of a superficial compact layer of collagen and a deeper layer of loose FT, and the myocardial fibers commonly show degenerative changes. The apical and inferoapical wall motion abnormalities are maintained as the FT is resected, likely by FT that penetrates into the myocardium and/or myocytes that have degenerated. Our findings are reinforced by the mildly depressed LVEF that does not change after resection. In contrast to previous studies affirming that surgery improves contractile function by releasing the myocardium,9,18 no changes in global or regional functions were observed in our study. In contrast to previous work, we used a quantitative technique to compare regional wall motion in EMF patients before and after surgical resection.

However, the high rates of symptom improvement require an explanation. It is likely that FT resection causes an increase in LV volumes, which may improve ventricular filling, produce a less steep pressure-volume relationship, and improve diastolic function. We have previously shown that EMF patients exhibit delayed myocardial relaxation, increased ventricular stiffness, and enlarged left atrium volumes.3 Potential changes in diastolic function after FT resection were not assessed, although the present study suggests that further evaluation of such changes would be valuable.

In our study, surgery resulted in an impressive response, as measured by the NYHA FC. We have previously shown that the NYHA FC is strongly related to maximum oxygen consumption in EMF patients19,20 and is a major factor in the decision for surgical indication.10 Early surgery is the only intervention that may reduce morbidity and improve survival in patients presenting NYHA FC III and IV.10 Medically treated symptomatic patients have a mortality rate of 50% over 2 years,21 whereas the operative mortality rate is about 15% to 20%. Furthermore, the actuarial probability of survival at 17 years post-treatment is 55% when operative mortality is considered.22

The improvements in morbidity and mortality observed with surgical treatment are only achieved in symptomatic patients. Clinical treatment of EMF patients as well as patients with other restrictive cardiomyopathies is complex, because hypovolemia or hypervolemia can lead to hypotension or pulmonary congestion, respectively.23 Additionally, medical treatments must be used with caution because vasodilators may cause hypotension and medications that decrease heart rate in an attempt to improve ventricular filling have not proved beneficial.23

EMF is a “neglected” disease in cardiology because it almost exclusively affects the poorest people in developed countries.24 EMF is still prevalent in tropical areas of South America, Africa, and Asia, and over 12 million people are currently estimated to have EMF.25 Endomyocardial fibrosis is found in 9% of the general population in affected regions of Mozambique,9 accounting for 15% to 25% of all cardiac deaths in equatorial Africa. Unfortunately, EMF most severely affects those regions least equipped for cardiovascular surgery.25

The cause and pathogenesis of EMF remain unknown. The unifying explanation considers EMF and Loeffler’s syndrome to be extremes of the same disease due to the similarity between the heart lesions in both disorders.26 Several variables, including environmental (geography, nutritional deficiency, high cerium intake, and parasitic infectious) and host (genetic predisposition, ethnicity, hypereosinophilia, autoimmunity, and inflammatory processes) factors, are involved in the pathogenesis of EMF.25–27 Of note, eosinophils remain a major risk factor for EMF in Uganda and Nigeria, but their role in the pathogenesis of this disease is still not understood.28

The age and sex predominance of EMF vary depending on the region considered. As observed in our study, EMF mainly affects young female adults in Brazil. Male predominance occurs in Kerala and Nigeria, whereas the disease strikes primarily female patients in Uganda.25 The incidence in Africa peaks in people between the ages of 11 and 15 years.9 In Uganda, bimodal peaks occur at age 10 and age 30.26 In contrast, heart failure in developed countries is a disease of the elderly.29

Ventricular involvement depends on the geographic area. In our hospital, 52.4% of the patients had biventricular involvement, 27.9% RV involvement, and 30.7% LV involvement.30 RV and biventricular involvement are more common in Africa.9, 31

CONCLUSION

Even though EMF patients show improvements in clinical symptoms after surgery, the LVEF and quantitative regional wall motion do not change. These results suggest that the improvements in symptoms are due to improvements in diastolic function.