Pediatr Cardiol 22:499±502, 2001 DOI: 10.1007/s002460010283

Left Ventricular Functions in Children with Chronic Pulmonary Diseases S. El-Saiedi, S. Samouel Cairo University Children's Hospital, Cairo, Egypt

Abstract. We evaluated left ventricular (LV) functions in 32 patients with chronic pulmonary diseases (CPDs) and compared them to 16 healthy controls. Echocardiographic assessment of both systolic and diastolic parameters of LV was performed for all patients and controls. LV systolic functions were found to be preserved in mild states, but with evident hypoxia the aortic acceleration and deceleration times decreased. LV diastolic functions were impaired in cases with pulmonary hypertension as re¯ected by a decreased ratio of peak ¯ow velocity of early ®lling to peak ¯ow velocity of late ®lling. Key words: Chronic pulmonary diseases ±± Echocardiography Hypertrophy and functional abnormalities of the right ventricle (RV) resulting from long-standing pulmonary diseases have been well documented [15, 17, 20, 21]. The heart is composed of two muscular pumps, right and left, that are connected in series to one another by the pulmonary and systemic circulations. The ventricular septum is the key structure of interacting pumping cardiac function. Thus, the left ventricle (LV) is a€ected by factors in¯uencing the right ventricle [9]. We planned this work to study the e€ect of pulmonary hypertension secondary to chronic lung diseases in children on the systolic and diastolic functions of the left ventricle. Research Design and Methods Study Population Thirty-two patients with chronic pulmonary disease (CPD) attending a chest clinic at Cairo University Children's Hospital volCorrespondence to: S. El-Saiedi, Osman Ahmad Osman Towers, Cournish EL Maadi, Tower 12, App. 61, Cairo, Egypt; email: [email protected]

unteered to participate in this study. We included patients aged 1 year to 15 years. Duration of CPD illness was more than 1 year. CPD included interstitial pulmonary ®brosis, cystic ®brosis, primary ciliary dyskinesia, congenital and acquired bronchiectasis, a1-antitrypsin de®ciency, and immunode®ciency disorder causing chronic chest infection. We excluded patients less than 1 year old, patients during acute infectious exacerbation's, patients su€ering from cardiac disease (e.g., congenital heart or rheumatic heart disease), and patients with systemic hypertension. Sixteen healthy normal children were included as controls.

Procedures A detailed history was taken and full clinical examination was done.All patients were subjected to a tuberculin test, chest x-ray, throacic computed tomography (when indicated), lung biopsy (when indicated), immunoglobulins analysis (when indicated), arterial blood gases analysis, and 12-lead electrocardiograph (ECG). Echocardiographic examination was performed using a Toshiba Sonolayer SSA-270 A, with 3.75- and 5-MHz transducers. Mmode, two-dimensional, pulsed, and continuous-wave Doppler examination with simultaneous ECG recording were used. In the presence of tricuspid regurgitation, the pressure gradient between the right ventricle and right atrium was estimated. Then we used the Bernoulli equation to estimate the pulmonary artery systolic pressure (PASP) [3]. Pulsed Doppler was placed carefully just above the aortic valve and at the tip of the mitral valve lea¯ets to obtain the aortic and mitral ¯ow parameters [7].

Results The age of patients ranged from 1.5 to 14 years with a mean of 7.1 ‹ 3.8 years. There were 16 males and 16 females. The duration of illness ranged from 1 to 12 years with a mean duration of 5.41 ‹ 3.51 years. The mean age for controls was 6.28 ‹ 3.67 years with a range from 1.5 to 15 years. The control group included 11 males and 5 females. The oxygen saturation of blood ranged from 74 to 98.8 with a mean of 91.72 ‹ 7.81. The heart rate was higher in CPD patients (105 ‹ 21.5 beat/min) in contrast to controls (89.8 ‹ 14.6 beat/min). Left ventricular (LV) measurements including LV end systolic and end diastolic dimensions together

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Table 1. Systolic functions of LV in controls and CPD patients Controls (n = 16) SV FS EF AoF Ao Acc Ao Dec LVET PEP PEP/LVET

37.75 39.44 70.63 97.19 84.88 204.75 289.63 62.13 0.22

‹ ‹ ‹ ‹ ‹ ‹ ‹ ‹ ‹

11.17 4.77 6.32 12.98 8.29 13.16 16.38 11.01 0.04

CPD (n = 32)

p value

35.02 ‹ 14.83 38.25 ‹ 5.12 69.78 ‹ 7.11 98.09 ‹ 11.38 76.41 ‹ 14.71 178.5 ‹ 23.47 254.91 ‹ 30.52 60.59 ‹ 13.64 0.24 ‹ 0.06

NS NS NS NS <0.05 <0.01 <0.01 NS NS

SV, stroke volume; FS, fractional shortening; EF, ejection fraction; AoF, peak aortic ¯ow velocity; Ao Acc, aortic acceleration time; Ao Dec, aortic deceleration time; LVET, left ventricular ejection time; PEP, preejection period.

with posterior wall thickness did not show any signi®cant di€erence between patients and controls. There was a signi®cant positive correlation between pulmonary artery systolic pressure and interventricular wall thickness (r = )0.612, p < 0.01). Table 1 shows that the acceleration and deceleration phase of aortic ¯ow and LV ejection time are signi®cantly shorter in CPD patients compared to controls. The more commonly assessed systolic functions of LV (i.e., stroke volume, fractional shortening, and ejection fraction) did not show statistically signi®cant di€erences in patients in relation to controls. Table 2 shows a signi®cantly lower peak ¯ow velocity of early ®lling (E) and a signi®cantly short duration of deceleration and total time of early ®lling. Lower atrial contribution (A) to total ®lling time was noted in CPD patients when compared to controls. Figure 1 shows that PASP is negatively correlated to mitral E/A ratio (r = )0.38, p < 0.01). It was also noted that PASP is negatively correlated to both acceleration time (r = )0.425, p < 0.01) and deceleration time (r = )0.0496, p < 0.01) of early ®lling through the mitral valve.

Table 2. Diastolic functions of LV in controls and CPD patients Controls (n ˆ 16) ME MEt Acc MEt Dec MEt MA MAt ME/A MEt/At MAt/Et + At IVRT

94.06 67.76 118 185.75 47.88 113.25 1.98 1.69 412.25 66.19

‹ ‹ ‹ ‹ ‹ ‹ ‹ ‹ ‹ ‹

CPD (n ˆ 32) 9.13 9.41 27.25 30.48 6.56 27.89 0.16 0.29 79.22 4.68

83.53 66.72 89.91 154.63 48.91 98.13 1.79 1.64 350.88 62.28

‹ ‹ ‹ ‹ ‹ ‹ ‹ ‹ ‹ ‹

p value 12.26 13.44 22.22 30.65 10.94 23.63 0.48 0.43 63.64 12.54

<0.01 NS <0.01 <0.01 NS NS NS NS <0.01 NS

ME, mitral peak early ¯ow velocity; MEt Acc, acceleration time of early ¯ow; MEt Dec, deceleration time of early ¯ow; MEt, total time of early ¯ow; MA, mitral peak late ¯ow velocity; MAt, time of atrial contribution to mitral ¯ow; ME/A, ratio of early to late peak ¯ow velocities; MEt/MAt, ratio of time of early to late ¯ows; MAt/ MEt+MAt, ratio of atrial contribution to total mitral ¯ow time; IVRT, iso-volumic relaxation time.

Fig. 1. Correlation of PASP vs M E/A: r =

0.38, p < 0.01.

ure has long been recognized. Only recently have abnormalities in diastolic function been appreciated [11]. Left Ventricular Systolic Function

Discussion Clinical studies have suggested that LV hypertrophy may occur in patients with cor pulmonale by means of bio-chemical and anatomic changes, including decreased concentration of norepinephrine abnormal histochemical appearance of the adrenergic nerve ®bers, a depressed myo®brillar adenosine triphosphate activity, and an increased amount of collagen ®bers [16]. The importance of ventricular systolic abnormalities in the development of congestive heart fail-

The aortic acceleration and deceleration times measured by pulsed Doppler echocardiography may be useful as an index of LV systolic function and for detecting cardiomyopathy [6]. Our results show no signi®cant di€erences in the routine echocardiographic parameters of systolic function. The acceleration and deceleration phases of aortic blood ¯ow were lower in CPD patients compared to the control group. Cargill et al. [4] found that aortic peak and mean acceleration and acceleration time were not a€ected by moderate or severe hypoxemia. Although the ejection time measured was

El-Saiedi et al.: LV Functions in CPD

shortened signi®cantly during severe hypoxemia, these variables were no longer signi®cant when appropriate corrections were made for heart rate. Cargill et al. reported that hypoxemia did not signi®cantly alter LV systolic performance. In agreement with our work, Louie et al. [12] reported that despite relative under®lling of the LV in RV pressure overload (RVPO), resting LV ejection fraction is preserved, whereas ejection fraction is depressed for the volumes replete with LV of patients with RV volume overload (RVVO). Iwanaga et al. [8] studied patients su€ering from pulmonary hypertension and found that the septal side of the LV does not act as a part of the global LV. The systolic function of the septal side of the LV is disturbed due to distortion of the ventricular septum, but systolic function of the free wall side is maintained within the normal range when the LV myocardium is kept normal. A study conducted by Jessup and colleagues [10] to investigate the e€ect of RV pressure overload secondary to chronic PHT on LV size, function, and IVS motion in 13 patients mentioned that as a result of abnormal septal position, the septal-free wall dimensions of the LV were reduced, but there was no evidence of depressed LV performance in their patients. They concluded that resting LV function is well preserved in patients with PHT, despite signi®cant alterations in septal position and LV size. Similarly, Badke [2] concluded that RV pressure overload displaces the septum toward the LV free wall; acutely this displacement is primarily at the end of diastole, but chronically it occurs at the end of systole as well, maintaining the septal contribution to LV ejection. Thus, chronic RVPO is associated with signi®cant changes in LV diastolic shape but maintenance of normal LV function. Accordingly, the LV function is usually preserved in RVPO states, but with RVPO the earliest parameter to be a€ected is aortic acceleration and deceleration time.

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®ndings showed severe LV diastolic impairment, directly related to the progressive increase in pulmonary pressure, as expressed by linear regression analysis between PASP and transmitral E/A ratio. They concluded that chronic RV pressure overload induces LV ®lling impairment despite a normal systolic phase due to a septal leftward shift which distorts early diastolic LV geometry, delaying LV ®lling phase, and the functional diastolic impairment of the LV is closely correlated to PHT levels. In contrast to our results, Nakamura et al. [14], who studied 25 adult CPD patients, detected prolongation of the deceleration phase of early ®lling of LV in CPD patients, especially in those with PHT. They reported that the LV hypertrophies in a situation of typical pressure overload. Because of LV wall hypertrophy the LV compliance decreased, leading to prolongation of the deceleration phase of early ®lling of LV. Stojnic et al. [18] detected impairment of LV diastolic function in patients with PHT in the form of reduced peak E and increased peak A velocities. They concluded that disturbed LV diastolic function in patients with PHT could not be attributed to reduced RV diastolic compliance, pericardial interaction, LV compression, or any other direct results of RV dilatation but seemed to be much more closely related to the presence of PHT. Similarly, Mizushige et al. [13] studied 36 adult patients with CPD and reported a decreased peak E/A ratio and an adequate correlation of PASP with peak E/A ratio. In contrast to our results, the deceleration phase of early ®lling of LV was prolonged in CPD patients compared to controls. Tutar et al. [19] showed that LV diastolic impairement in chronic cor pulmonale is directly related to a progressive increase in pulmonary hypertension as expressed by correlation analysis of PASP vs E/A ratio and isovolumic relaxation time. From the presented data, it was observed that LV diastolic functions were similarly impaired in children with pulmonary hypertension.

Left Ventricular Diastolic Function Diastolic dysfunction has been described in pediatric and adult patients with LV hypertrophy, systemic hypertension, hypertrophic cardiomyopathy, and coronary artery disease and may precede abnormalities of systolic function [1,5]. The diastolic abnormalities reported in this study are in agreement with the results of Schena et al. [16], who studied 30 patients with CCP and PHT secondary to COPD and detected a decreased peak E ¯ow velocity and increased peak A ¯ow velocity with inversion of A/E peak ¯ows. At the same time, their

Conclusions Pulmonary hypertension a€ects LV systolic and diastolic functions in childhood and echocardiography can disclose these abnormalities. Chronic RV pressure over loads induce LV impairment despite normal systolic phase due to septal leftward shift. In fact, chronic RV pressure overload distorts early diastolic LV geometry and the functional diastolic impairment of the LV is closely correlated to pulmonary hypertension levels.

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