Amit Sharma^1*, Pallavi Sharma², Rashmi Sharma³

¹CMO, IIIM Jammu, Jammu and Kashmir, INDIA.

{²Senior Resident, Department of Ophthalmology} {³Senior Resident, Department of Pharmacology} Government Medical College, Jammu, Jammu and Kashmir, INDIA.

Email: amitmedicinerrl@gmail.com

DISCUSSION

The present Doppler-Echocardiographic study was conducted to examine the left ventricular systolic and diastolic functions in patients with pulmonary arterial hypertension due to chronic obstructive pulmonary disease. A total of 70 subjects (35 patients with chronic obstructive airway disease and 35 apparently healthy persons) were studied by detailed two-dimensional and Doppler examination. Left ventricular dimensions were determined as per the standard protocol and left ventricular systolic functions were recorded. Mitral inflow Doppler was used for the assessment of left ventricular filling patterns and relaxation. The pulmonary venous flow patterns were studied by pulsed Doppler method. In the present study, the aortic and left atrial dimensions in patients with pulmonary arterial hypertension were comparable to the average control values (2.87±0.53 cm versus 2.97±0.43 cm, p=0.370 and 3.13±0.67cm versus 3.08±0.75 cm, p=0.800, respectively). The mean diastolic left ventricular internal diameter (LVIDd) and especially left ventricular end-diastolic volume (LVEDV) were reduced in patients with pulmonary hypertension as compared to the control values (3.85±1.04 cm versus 4.14±0.78 cm, p=0.187 and 75.03±43.89 mL versus 94.99±25.75 mL, p=0.024, respectively). These observations are largely in agreement with the published data. Krayenbuehl HP, et al (1978) found that the average transverse LVIDd on transthoracic echocardiography in patients with pulmonary hypertension of different etiologies was significantly lower than that of healthy controls¹⁴. Lazar JM, et al (1993) found that LVEDV in patients with pulmonary arterial hypertension was significantly reduced as compared to that of healthy volunteers¹⁵. In a recent study by Marcus JT, et al (2001), LVEDV in patients with primary pulmonary hypertension, as determined by magnetic resonance imaging, was significantly reduced compared to healthy population¹⁶. The reduced LVIDd and LVEDV in patients with pulmonary arterial hypertension can be explained by the bulging of interventricular septum towards left in these patients which decreases the left ventricular cavity size. In our study, LVEDV showed a significant positive correlation with left atrial size (r=0.293, p=0.014) and a significant inverse correlation with pulmonary artery systolic pressure (r= -0.265, p=0.027) and PaC0₂ (r= -0.328, p=0.006) From these observations, it follows and seems likely that a higher PaC0₂ reflecting a more advanced form of pulmonary disease with more severe cor pulmonale causes a greater degree of shift of the interventricular septum towards left causing thereby a severe compromise of left ventricular cavity size. The latter likely causes left atrial distension and a greater degree of left ventricular diastolic dysfunction. The systolic left ventricular internal diameter (LVIDs) and left ventricular end-systolic volume (LVESV) in our patients with pulmonary hypertension were also significantly lower than the corresponding values in the control subjects (2.30±0.76 cm versus 2.73±0.53 cm, p=0.008 and 20.61±20.89 cm versus 33.36±11.75 cm, p-0.003, respectively). The other parameters of left ventricular systolic performance, like left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were significantly higher in the group of subjects with pulmonary arterial hypertension. Previous studies in this regard are scarce and, occasionally, conflicting. In an angiographic study of left ventricular functions, Krayenbuehl HP, et al (1978) tailed to demonstrate any difference in the LVESV and LVEF between patients of pulmonary hypertension and healthy controls¹⁴. Steele P, et al¹⁷ measured LVEF in 28 patients with stable chronic obstructive pulmonary disease (COPD) and 92 patients with acutely decompensated COPD by bedside radionuclide ventriculography. They found that LVEF was normal in patients with severe lung disease irrespective of clinical stability in these patients. In the few patients of COPD who had reduced LVEF, the abnormal left ventricular functions were attributable to the associated coronary artery disease. Tutor E, et al¹⁸ observed that left ventricular systolic functions were well preserved in patients with chronic cor pulmonale, as evidenced by normal LVFS on echocardiography. On the contrary, in the magnetic resonance imaging study by Marcus JT, et al¹⁶, LVESV was found to be normal while LVEF was reduced in patients with chronic right ventricular pressure overload due to primary pulmonary hypertension. The reduced LVEDV in patients with pulmonary hypertension can theoretically reduce left ventricular systolic performance through Frank Starling mechanism. However, the actual importance of such a mechanism in affecting the left ventricular systolic functions of patients with pulmonary hypertension is not clear as of now and seems to be negligible under ordinary circumstances. In fact, in a recent study by Moustapha A, et al¹⁹, LVEF was found to be preserved in patients with pulmonary hypertension of different etiologies irrespective of the severity of pulmonary hypertension. In our study, LVEF in patients with pulmonary hypertension was higher than that in the controls. Further, LVEF showed a significant positive correlation with PaC0₂ (r=0.286, p=0.016) and pulmonary artery systolic pressure (r=0.316, p=0.008).The reasons for these observations are not clear. An effect of higher heart rate increasing the left ventricular pumping ability in our patients through Bowdich phenomenon seems unlikely since the two groups of subjects in our study had identical heart rates. It is possible that future studies on larger number of subjects might make the issue more clear since the previous studies including the present one had included only small numbers of patients. Left ventricular stroke volume was normal in our subjects with Pulmonary hypertension. Likewise, the diastolic and systolic thickness of interventricular septum and left ventricular posterior wall were comparable between the two groups. Similar observations have been made by some previous observers as well. On the other hand, interventricular septal motion was found to be paradoxical in 15 (43%) of our patients with pulmonary hypertension as compared to none in the control group. Moustapha A, et al¹⁹ found paradoxical interventricular septal motion in 70% of patients with pulmonary hypertension. The paradoxical septal motion in patients with pulmonary hypertension is likely due to the right ventricular pressure overload causing leftward displacement of interventricular septum with flattening or reversal of the septal curvature and subsequent compression of the left ventricular cavity, which is maximal at end-systole and early diastole. Patients with severe pulmonary hypertension are more likely to exhibit paradoxical motion of interventricular septum. The flat right ventricular diameter in patients with pulmonary hypertension was significantly higher than that of controls (3.05±0.81cm versus 2.17±0.36 cm; p=0.000). RV flat dimension had a highly significant inverse relation with FEV1/FVC (r= -0.362, p=0.002) and a highly significant positive correlation with the degree of C0₂ retention (r=0.352, p=0.003) and mean pulmonary artery pressure (r=.459, p=0.000). These observations are theoretically plausible and also consistent with some previous observations. The elevated right ventricular dimension in patients with cor pulmonale seems to be due to chronic pressure overload affecting contractile performance of right ventricle, thereby decreasing its pumping ability and increasing the right ventricular end-diastolic volume. Further, the greater the degree of respiratory compromise, the higher the deleterious effects on the performance of right ventricle and the greater the degree of right ventricular enlargement. The mean velocity of early left ventricular filling (E velocity) in patients with pulmonary arterial hypertension was 0.53±0.23 m/s while the mean velocity of late left ventricular filling (E velocity) in such patients was 0.64±0.16m/s, against 0.65±0.20m/s (p=0.031) and 0.50±0.18m/s (p=0.003), respectively, in healthy subjects. The ratio of early to late mitral filling velocity (E/A ratio) was 0.86±0.35 against the value of 1.34±0.30 in normal controls (p=0.000). Johnson GL, et al (1991) found that E/A ratio were lower in patients with pulmonary arterial hypertension due to cystic fibrosis than normal controls²⁰. Stojnic L, et al (1992) found that patients with pulmonary hypertension had a dominant "A" wave on transmitral Doppler, as compared to control who had a dominant "E" wave¹⁴. Schema M, et al (1996) found that patients with pulmonary hypertension had reversed E/A ratio²¹. Tutor, et al¹⁸ also reported the E/A ratio in patients with pulmonary arterial hypertension to be on lower side than in healthy population. Moustapha A, et al¹⁹ in their study found a reduced E/A ratio in patients with chronic pulmonary hypertension. Importantly, we found the mitral E/A ratio having a positive correlation with FEV1/FVC (r=0.544, p=0.000) and inverse relationship with PaC0₂ (r=-0.399, p=0.001), RV flat dimension (r= -0.461, p=0.000), and mean pulmonary artery pressure (r= -0.470, p=0.000). These findings again point towards the strong association between the severity of respiratory impairment in COPD and the degree of left ventricular diastolic dysfunction. With progressively more advanced lung dysfunction and the consequent worsening compromise of left ventricular cavity size, the filling pattern of left ventricle becomes more and more abnormal with late atrial phase of left ventricular filling assuming even greater physiological importance. On pulmonary venous Doppler interrogation, the systolic, diastolic and atrial reversal flow velocities were all found to be normal in patients with pulmonary arterial hypertension, with systolic flow velocity being the most prominent pulmonary venous flow signal. Further, the pulmonary venous Doppler velocities did not show any significant relationship except for an inverse relation of PVd velocity with LVEF (r= -0.257, p=0.032) and a similar relationship of PVar velocity with LVEDV (r= -0.303, p=0.011). Also PVd velocity was significantly related to PVar velocity and vice versa (r=0.606, p=0.000). In the absence of detailed studies about the pulmonary venous Doppler patterns in patients with pulmonary arterial hypertension, especially that due to chronic obstructive pulmonary disease, the significance of our observations in this regard remains elusive. Further studies might be needed for a better understanding of pulmonary venous flow patterns in such patients.              In conclusion our study demonstrated that left ventricular diastolic functions are impaired in patients with pulmonary hypertension due to COPD, as compared to normal sex- and age-matched controls. This is confirmed by higher mean velocity of early left ventricular filling (E) than mean velocity of late left ventricular filling (A) and a higher ratio of early left ventricular filling (E) to late left ventricular filling (A) - the E/A ratio. The deceleration time and isovolumic relaxation time are also prolonged in these patients. These results are consistent with literature available on this topic. On the other hand, the pulmonary venous flow velocities are largely normal in patients with pulmonary hypertension.

CONCLUSION

Thus we conclude that patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease have reduced left ventricular internal dimension and that this reduction bears a relation with the level of respiratory compromise and with the severity of pulmonary hypertension. However, left ventricular systolic function is well preserved in these patients irrespective of the severity of lung disease. On the other hand, left ventricular diastolic function is abnormal in patients with pulmonary hypertension as compared to normal age- and sex-matched control population. This is reflected by a higher ratio of late to early left ventricular filling velocities, a prolonged deceleration time of the early left ventricular filling velocity, and increased isovolumic relaxation time of left ventricle in patients with pulmonary arterial hypertension than the control population. Further, the degree of filling abnormalities bears a direct relation with the degree of pulmonary disorder and with severity of pulmonary hypertension.

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