|Year : 2002 | Volume
| Issue : 1 | Page : 5
End-diastolic left ventricular pressure reduction in ischemic heart failure induced by Ramipril alone and Ramipril + Carvedilol: a Doppler-Echocardiographic study
Federico Cacciapuoti, Antonietta Buonomo, Fulvio Cacciapuoti, Rodolfo Grella, Diana Lama, Maria D'Avino, Paola Bolognino
Department of Internal Medicine, Second University of Naples, Naples, Italy
|Date of Web Publication||22-Jun-2010|
Cattedra di Medicina Interna, Facoltą di Medicina e Chirurgia, Seconda Universitą di Napoli (S.U.N.), Piazza L. Miraglia, 280138-Napoli
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Thirty-four patients affected by Ischemic Heart Failure (IHF) were evaluated by Echocardiography (E).
They had reduced Ejection Fraction % (EF%) evaluated by the cube volume-formula and evident from a decrease of V.max. of E wave and an increase of V. max. of A wave of mitral doppler inflow pattern, with reversal of E/A wave ratio. In addition, an increase of Iso-Volumic Relaxation Time (IVRT) and E wave Deceleration Time (DT) were present, while the pulmonary veins flow-pattern reflected increased End Diastolic Left Ventricular Pressure (EDLVP). Patients were treated with Ramipril (Group I) or Ramipril and Carvedilol (Group II). These drugs were given concommitant with other drugs (Digitalis, Diuretics, Antiplatelets and Nitrates). M-Mode and 2D-Echo were performed one week after the end of therapy.
The echocardiographic parameters were evaluated in all patients at baseline and compared with those obtained respectively after Ramipril (Group I) and Ramipril + Carvedilol (Group II). Results showed a rise of LVESV and a decrease of LVEDV with progressive increase of EF% (from 30 to 40%). This change was also displayed by an increase of V. max. of E and a little decrease of A waves V. max. of mitral pattern (without inversion of their ratio in the Group I) and a similar but more evident change of V. max. of both waves, with reversal of E/A ratio in Group II. Conclusion: Ramipril, given with conventional drugs, resulted in poor reduction of EDLVP whereas the combination of Ramipril + Carvedilol added to conventional therapy, induced a more evident functional reduction of this hemodynamic parameter.
Keywords: Ischemic Heart Failure, End Diastolic Left Ventricular Pressure, Echocardiography Ramipril, Carverdilol
|How to cite this article:|
Cacciapuoti F, Buonomo A, Cacciapuoti F, Grella R, Lama D, D'Avino M, Bolognino P. End-diastolic left ventricular pressure reduction in ischemic heart failure induced by Ramipril alone and Ramipril + Carvedilol: a Doppler-Echocardiographic study. Heart Views 2002;3:5
|How to cite this URL:|
Cacciapuoti F, Buonomo A, Cacciapuoti F, Grella R, Lama D, D'Avino M, Bolognino P. End-diastolic left ventricular pressure reduction in ischemic heart failure induced by Ramipril alone and Ramipril + Carvedilol: a Doppler-Echocardiographic study. Heart Views [serial online] 2002 [cited 2020 Feb 27];3:5. Available from: http://www.heartviews.org/text.asp?2002/3/1/5/64423
| Introduction|| |
Ischemic Heart Failure (IHF) induces an abnormal elevation of End Diastolic Left Ventricular Pressure (EDLVP) dependent both on the reduced left ventricular diastolic relaxation (with reduced filling) and the increase in peripheral vascular resistance.
This last is due to activation of the neuro-endocrine system, a mechanism counterbalancing the reduced stroke volume ,, . Activation of the renin-angiotensin system and the sympathetic nervous system results in an increase in preload and afterload, which at least initially increases cardiac contractility.
However, persistent activation of the neuroendocrine system is deleterious and leads to ventricular remodelling.
Therefore, it is necessary to minimize or block this neurohormonal activation and/or its peripheral effects with pharmacologic therapy.
Interventions which inhibit, antagonize, or otherwise favorably modulate neurohormonal activation such as ACE inhibition and beta-blockade produce improved outcomes in heart failure patients ,, . Among several b-blockers, Carvedilol seems to be the more useful because it blocks α1 and β2-receptors , , inducing vasodilatation, increase in ejection fraction (EF), and decrease in EDLVP , . Among ACE-inhibitors, Ramipril is one of the most useful in reducing or minimizing the Renin-Angiotensin-Aldosterone-System (RAAS.) secretion , . The objective of this study was to verify if, in patients with IHF and already treated with conventional therapy, the addition of Ramipril and/or Carvedilol, is able to reduce EDLVP and if this change is evident using Doppler Echocardiography (2DEcho) parameters.
| Materials|| |
end-systolic-diameter (LVESD). Left ventricular volumes (LVEDV, LVESV) using the cube-formula were obtained. The ejection fraction % (EF%) was evaluated according to the following formula:
Mitral inflow parameters recorded by two-dimensional Doppler echocardiography (2D-Echo) were: maximum Velocity (V. max.) of E and A waves and E/A ratio  . The isovolumic relaxation time (IVRT) and the deceleration time (DT) of E wave were also evaluated.
The pattern of pulmonic vein flow was recorded in all patients  . At the time of the study, all patients were already receiving Digitalis (0.125 or 0.25 mg. per os/day), Furosemide (12.5 or 25 mg per os/day), an antiplatelet drug, and nitrates.
The ACE inhibitor Ramipril, (2.5 mg. per os/day) was given to 16 patients at random and constituted Group I.
In the remaining 18 patients, combined Ramipril + Carvedilol were added and constituted Group II. Carvedilol, under guidance of arterial pressure and heart rate, was added incrementally from 3.125 mg b.i.d to 25 mg b.i.d over a period of 40 days. One week after the initiation of therapy, M-mode and 2D-Echo parameters were repeated and recorded.
| Statistical analysis|| |
The values of LVEDV, LVESV and EF% obtained in basal conditions in all patients and those recorded in each group were compared with those obtained in groups I and II. V. max. of E and A waves, their ratio (E/A), and the values of IVRT and DT were recorded at baseline and were compared with groups I and II.
Finally, the systolic-diastolic pattern of pulmonary venous flow was measured basally in all patients and compared with that recorded after Ramipril (Group I) and Ramipril + Carvedilol (Group II). For all parameters evaluated, the Student t-test for unpaired data was used.
A p<0.05 value was considered significant.
| Results|| |
In two patients in Group II, it was impossible to give Carvedilol because it induced an excessive reduction of the arterial pressure (in one) and bronchospasm (in the other).
In addition, in one patient in Group II, the maximum dose of 25 mg. b.i.d was not achieved because the maximum dose tolerated was 25 mg. in the morning and 6.25 mg in the afternoon. Therefore, the number of patients was 16 in Group 1 and 16 in Group II.
[Table 1] shows the baseline value ±1SD of LVEDV and the mean values achieved in Groups I and II. This parameter increased from baseline 289.4±17 ml to 293.4±18 ml in Group I and to 314.5±19 ml in Group II, with a p <0.05 and p <0.01 respectively. On the contrary, the mean value of LVESV decreased from basal conditions (201.3±18 ml) in patients treated with Ramipril alone (189.8±19 ml) and in those who received Ramipril + Carvedilol (186.3±17 ml). Differences were significant, with a p <0.05 (in Group I) and p <0.01 (in group II). EF% under basal conditions was 30.0±1.4% and increased to 35.3±1.3% in Group I, p <0.05. Group II patients (Ramipril + Carvedilol), EF% reached 40.6±1.8%, p <0.01). In basal conditions, the value of V. max. of E wave was 0.82±0.12 m/sec.; the mean of V. max. of A wave was 0.91±0.15 m/sec.; E/A ratio was 0.91±0.14. [Figure 1]. After treatment with Ramipril alone (Group I) , V. max. of E wave was 0.83±0.13 m/sec.; V. max. of A wave was 0.90±0.5 m/sec and E/A wave ratio was 0.94±0.7.
In Group 1 "mitral" parameter differences with respect to the baseline values were not significant (N.S.).
After Ramipril + Carvedilol (Group II) the mean of E wave was 0.87±0.12 m/sec; V. max. of A wave was 0.81±0.6 cm/sec; the mean value of E/A wave ratio was1.07±0.4. [Figure 2]. As opposed to Group I patients, the difference in values in mitral parameters in Group II patients was statistically significant (p <0.05 for V.max. of E wave; p <0.01 for V. max. of A wave and p <0.01 for E/A wave ratio).
The mean of IVRT was 65±0.8 msec. and the mean value of E wave DT was 165±1.4 msec in basal conditions. After Ramipril (Group I) IVRT resulted of 72±1.4 msec and DT of E wave was 174±2 msec. Differences in respect to the basal values were significant (p <0.05). In Group II patients the mean was 84±1.4 msec and 186±1 msec respectively, with a p <0.01.
The basal mean value of the pulmonary venous pattern and those recorded after Ramipril (Group I) and Ramipril + Carvedilol (Group II) is shown in [Table 2]. In basal conditions, the mean of systolic pulmonary vein flow (S) was 0.76±0.13 msec. A mean value of 0.44±0.14 msec was achieved for the diastolic wave (D) and 0.25±0.10 msec was measured for the diastolic reverse flow (A wave) [Figure 3]. In Group I, the systolic wave (S) was 0.67±0.10 msec (p <0.05); the diastolic wave (D) was 0.53±0.13 msec (p <0.05); the reverse diastolic wave (A) was 0.18±0.11 msec. (p <0.01). Finally, in Group II, the pulmonary venous flow showed a systolic wave (S) equal to 0.68±0.7 msec.; a diastolic wave (D)= to 0.57±0.8 msec. and a reverse diastolic wave (A) of 0.23±0.8 msec [Figure 4].
| Discussion|| |
It is common knowledge that the pattern and V max of E and A waves of diastolic mitral flow and their ratio depends on a lot of factors that make difficult their comparison in different subjects affected by the same disease. These difficulties depend on: the position of the sample volume between the mitral leaflets  , on the cardiac rhythm  , on the P-R interval  and on the age  . In addition, it seems dependent also on the heart rate. Decubitus can also influence the E/A ratio  . Finally, the changes of V. max. of E or A waves can be a consequence of variable loads on the left ventricle, rather than on its diastolic function.
IVRT, E wave DT and the values of pulmonary venous flow are less dependent on these factors.
In order to minimize these difficulties, we have enrolled the patients affected by IHF only, within a certain age limit (41 to 55 years), and all patients were in sinus rhythm with a P-R interval between 0.16 and 0.20 sec. The ultrasonographic evaluation was standardized and performed in the left lateral decubitus of 20, placing the sample volume between the mitral leaflets.
The increased EF% obtained after both treatments (Ramipril or Ramipril + Carvedilol) is likely due to the reduction of LVESV (with the rise of V. max. of E wave) and to the increase in LVEDV (with reduction of V. max. of A wave) .
But, this last effect was greater than the first and, consequently the EF% increased.
The rise of V. max. of E wave (due to the passive emptying of left atrium into left ventricle) depends on the highest pressure difference between the left atrium and the left ventricle at early diastole; the decrease of V. max. of A wave (due to the active emptyng of left atrium into left ventricle) is due to the reduced pressure difference between left atrium and the left ventricle at end diastole.
In addition, the decrease in vascular resistance (induced by Ramipril and/or Carvedilol) also facilitates the emptying of left ventricle during systole ,.
After Ramipril alone, there were no significant changes in V. max. of E and A waves and E/A ratio, but these were more evident (with reversal of E/A ratio) in patients receiving Ramipril and Carvedilol (group II). Ramipril:
ACE-inhibitors decreases serum-concentration of Angiotensin II and reduces afterload with consequent reduction of EDLVP. In the AIRE study, Ramipril given to patients with clinical evidence of heart failure due to ischemia reduced mortality, stroke or reinfarction, and delayed progression to more severe heart failure. These results were recently confirmed by the extension of the study, which also showed prolongation of survival  . Carvedilol: There are various classes of b-blockers with varying activity. First class b-blockers (i.e. Propranolol) are absolutely not used because of its negative inotropic effect that is superimposed to the peripheral vasoconstriction, which is a consequence of a2-receptor blockade. Second class b-blockers (i.e. Metoprolol or Bisoprolol) are well-tolerated because they do not act on peripheral resistance.
Finally, third class b-blocker (i.e., Carvedilol) achieves excellent results, especially in patients with hypokinesia and dilatation of the left ventricle, because they block both cardiac (blocks b1-receptors) and peripheral actions  . Its simultaneous effect on b1-b2 and a1-receptors results in positive inotropic action and peripheral vasodilatation. The adrenergic effect of this drug is of type b1>a1>b2  . Its cardiac action has been reported to be due to blockade of b-receptors, whereas the peripheral vasodilation is due to a1-receptor blockade ,,,.
The administration of Carvedilol in increasing doses induces a progressive increase in ventricular performance and a progressive reduction of heart failure symptoms, both at rest and after effort , . Finally, the pulmonary venous pattern of the impaired relaxation recorded in our patients in basal conditions showed a significant lowering of V. max. of S wave and an increase of D and A waves after the addition of two drugs ( to traditional therapy. These changes depend on the true decrease of EDLVP but not on the pseudo-normalization of the Doppler mitral patterns.
| Conclusion|| |
Some drugs such as Ramipril and/or Carvedilol, added to conventional therapy for IHF in NYHA II-III class, seem to reduce EDLVP and increaseEF% in these patients.
These effects seem mainly due to the reduction of peripheral resistance with consequent increase of the left ventricular cavity during systole.
These changes are responsible for the reduction of EDLVP evident by Mono 2D and Doppler echocardiography.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]