Cardiovascular Diseases Poster Session



Materials & Methods


Discussion & Conclusion



INABIS '98 Home Page Your Session Symposia & Poster Sessions Plenary Sessions Exhibitors' Foyer Personal Itinerary New Search

Effects Of Additional Vasodilator Therapy In Patients With Chronic Heart Failure And Restrictive Left Ventricular Filling

Contact Person: Nikolay P Nikitin (nimed@silk.org)

Discussion and Conclusion

The results of the present study confirm the earlier data that a pattern of transmitral flow may change with the time. If a restrictive pattern develops in a patient who had a nonrestrictive pattern at baseline, it indicates more severe heart failure and poorer prognosis (8-10,12-14). On the contrary, transition of restrictive pattern into a nonrestrictive pattern is associated with an improvement in functional class, exercise capacity and prognosis (14,17).

However, data are limited on the effects of pharmacological treatment on restrictive filling. Several investigators explored effects of acute interventions. Makhoul et al. (16) studied the effect of high dose intravenous isosorbide dinitrate on LV diastolic filling in patients with severe CHF. The study showed that the PE/PA ratio decreased with a reduction in pulmonary capillary wedge pressure and right atrial pressures, indicating preload dependence of transmitral flow velocity. Pozzoli et al. (15) demonstrated that nitroprusside infusion may lead to reverting of restrictive transmitral flow. It was found that changes in LV filling patterns induced by loading manipulations provide additional prognostic information. Patients with irreversible restrictive filling had a higher event rate (51%) than patients with reversible restrictive filling (19%).

Two recent studies were reported to investigate effects of long-term pharmacological therapy. Traversi et al. (14) showed that chronic optimized medical therapy (including captopril, diuretics, oral nitrates or hydralazine, digitalis in various combinations) caused reversion of a restrictive LV filling pattern into a nonrestrictive pattern in 19 patients from 68 patients studied. Changes in transmitral flow patterns after chronic optimized therapy were correlated with changes in pulmonary wedge pressure, and accompanied by changes in functional capacity and better prognosis. Seventeen of the 21 events occurred in the 49 patients (event rate 35%) with a persistent restrictive pattern, whereas the event rate was much lower in the 19 patients with a reversible restrictive pattern (5%). Temporelli et al. (17) have recently reported that the prolongation of an initially short deceleration time obtained with long-term optimal oral therapy predicts a more favorable outcome in clinically stable patients with CHF.

Our study has demonstrated that more intensive vasodilator therapy (with use of oral nitrates) in addition to standard therapy is superior to standard treatment alone (angiotensin-converting enzyme inhibitors, diuretics and digitalis) in reverting the restrictive pattern of LV diastolic filling. A possible mechanism involved is a decline in LV filling pressure. Direct hemodynamic measurements were not performed in this study. However, several previous studies showed that restrictive LV filling is associated with high LV filling pressure (6,7), and that reversion of restrictive LV filling is caused by a decrease in LV filling pressure (15). Stevenson et al. (18), who used hemodynamic monitoring, demonstrated that aggressive nitrate therapy effectively reduces left ventricular filling pressures. Another potential mechanism is an unloading of the right ventricle leading to less ventricular interaction (19).

In this study, the reversion of restrictive LV filling on nitrate therapy was accompanied by an improvement in clinical status and exercise capacity in patients with CHF. These favorable changes were present despite no significant changes in LV ejection fraction. The improvement in functional parameters may be explained by less pulmonary congestion and by an increase in stroke volume as a result of less ventricular interaction. These findings also support the conception that diastolic properties are more closely related to exercise capacity than systolic function in CHF.

Angiotensin-converting enzyme inhibitors and beta-blockers are known to improve survival in patients with CHF. We now suggest that an additional improvement in clinical and functional status can be achieved in patients with restrictive patterns of LV filling as a result of more intensive vasodilator therapy. Serial Doppler studies of LV transmitral filling may bring additional information regarding the efficacy of such therapy.

Limitations of the study. Coronary angiography was not performed in this study, so the etiology of CHF in the study population could not be confirmed with certainty.

Data were obtained in those patients with CHF, who had a restrictive pattern of LV diastolic filling. This characteristic hampers the application of the results to patients with other transmitral flow patterns.

Mortality was not an end-point in this study. The power of the study was limited by the relatively small number of patients because of the restriction to patients with predominant early (restrictive) pattern of LV filling. The prognostic role of additional vasodilator therapy in CHF should be addressed in more powerful studies.

Nitrate tolerance is a well-known factor limiting efficacy of these agents. However, we believe that eccentric scheme of nitrate administration and concomitant use of ACE inhibitors allowed to avoid nitrate tolerance in the majority of patients in this study.

Conclusions. More intensive chronic vasodilator therapy (with use of nitrates in addition to standard therapy) is superior to standard pharmacological therapy alone in reverting restrictive left ventricular filling in patients with congestive heart failure. This effect of vasodilator therapy is accompanied by an improvement in clinical status and exercise tolerance but not in left ventricular systolic function. Serial Doppler studies of transmitral filling pattern may bring additional information regarding the efficacy of pharmacological treatment. Further studies are required to elucidate the prognostic role of more intensive vasodilator therapy in chronic heart failure.

Back to the top.

<= Results DISCUSSION & CONCLUSSIONS References =>

| Discussion Board | Next Page | Your Poster Session |
Nikitin, NP.; Alyavi, AL.; Goloskokova, VY.; (1998). Effects Of Additional Vasodilator Therapy In Patients With Chronic Heart Failure And Restrictive Left Ventricular Filling. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/cvdisease/nikitin0543/index.html
© 1998 Author(s) Hold Copyright