Severe Right Heart Failure Research Articles

Predicting Post LVAD Acute Severe Right Heart Failure Using Bayesian Analysis

Purpose Right heart failure (RHF) continues to be a major adverse event post LVAD implantation. The risk of developing RHF post implant is multifactorial and difficult to predict. We have previously published Bayesian models to predict early and late RHF. In this analysis, we focused on pre-operative variables that predicted severe acute RHF as defined in INTERMACS as 'need for RVAD following LVAD or death during the VAD implants hospitalization with RHF as the primary cause'. Methods We used INTERMACS data from continuous flow LVADs from 2012-2016 (n=2,661). The model using pre-implant variables was made using Tree Augmented Naïve Bayes Analysis (GeNie) and predictors ranked by their diagnostic value. The impact of these variables on each other as well as the final outcome (RHF) were noted. Results Post LVAD implantation, severe acute RHF was noted in 126 patients (4.7%). Vast majority of patients in INTERMACS were males (80%) with over 50% patients implanted as destination therapy. 34 pre-implant variables, including both modifiable and non-modifiable, were found to impact the risk of post-implant acute severe RHF. (Figure 1) Key factors included INTERMACS Profile, major clinical event pre-implant (ECMO, IABP, mechanical ventilation), inotropes, platelets, albumin and AST. The performance assessment using areas under the curve ROC was 0.79 for the derived model. Conclusion By using a Bayesian approach, we explored pre-implant factors that were predictive of post-operative acute severe RHF. This would allow further risk stratification for patients undergoing LVAD implantation. Right heart failure (RHF) continues to be a major adverse event post LVAD implantation. The risk of developing RHF post implant is multifactorial and difficult to predict. We have previously published Bayesian models to predict early and late RHF. In this analysis, we focused on pre-operative variables that predicted severe acute RHF as defined in INTERMACS as 'need for RVAD following LVAD or death during the VAD implants hospitalization with RHF as the primary cause'. We used INTERMACS data from continuous flow LVADs from 2012-2016 (n=2,661). The model using pre-implant variables was made using Tree Augmented Naïve Bayes Analysis (GeNie) and predictors ranked by their diagnostic value. The impact of these variables on each other as well as the final outcome (RHF) were noted. Post LVAD implantation, severe acute RHF was noted in 126 patients (4.7%). Vast majority of patients in INTERMACS were males (80%) with over 50% patients implanted as destination therapy. 34 pre-implant variables, including both modifiable and non-modifiable, were found to impact the risk of post-implant acute severe RHF. (Figure 1) Key factors included INTERMACS Profile, major clinical event pre-implant (ECMO, IABP, mechanical ventilation), inotropes, platelets, albumin and AST. The performance assessment using areas under the curve ROC was 0.79 for the derived model. By using a Bayesian approach, we explored pre-implant factors that were predictive of post-operative acute severe RHF. This would allow further risk stratification for patients undergoing LVAD implantation.

Right Heart Failure during Support with a Left Ventricular Assist Device is Associated with Primary Graft Dysfunction after Heart Transplantation

Introduction Primary graft dysfunction (PGD) is a devastating complication of heart transplantation that is associated with high rates of morbidity and mortality. Right heart failure (RHF) while on LVAD support may identify patients at higher risk for post-transplant complications. This study investigated the relationship between RHF while on LVAD support and post-transplant outcomes. Methods Patients with durable, continuous-flow LVADs who were transplantated between 2010 and 2016 at Barnes-Jewish Hospital were included. Data collection was performed through retrospective chart review. RHF was defined as the need for right ventricular assist device, the extended use of inotropes for more than 14 consecutive days post-LVAD implant, the need to reinitiate inotropes after 14 days but before 30 days after LVAD, or heart failure requiring medical intervention >30 days after discharge from LVAD implantation. The primary outcome was the incidence of PGD after transplant compared between patients with and without RHF. Secondary outcomes included 30-day and 1-year survival, incidence of vasoplegia, severity of PGD, and outcomes stratified by type of RHF. A multivariate logistic regression model was created and included baseline characteristics differing between groups using a p-value of Results Among the 141 patients included in the study, 41 developed RHF while supported with an LVAD. The cohort had a median age of 58, was mostly male (78.7%), and mostly white (74.5%). Most patients had a non-ischemic cardiomyopathy (57%) and were implanted with a HeartMate II LVAD (84.4%). The RHF group had a higher incidence of donor-recipient weight mismatch (3.0% vs. 14.6%, p=0.018) and lower donor EF (55% vs 60%, p=0.018), with no other significant differences in baseline characteristics. In the RHF cohort, 18 patients developed PGD as compared to 14 patients in the group without RHF (43.9% vs. 14.0%, p Conclusions The results of this study show that patients supported with LVADs who develop early severe or late RHF are at increased risk of PGD and death following cardiac transplantation. Donor factors may further increase the risk of these outcomes and should be carefully assessed in this high-risk group. Given the striking increase in PGD, increased vigilance for PGD and aggressive early hemodynamic support should be anticipated for these patients.

Timing Of RVAD Insertion and The Associated Outcomes in CF-LVAD Patients

Study Right ventricular assist devices (RVAD) are commonly used for severe right heart failure (RHF) after continuous flow left ventricular assist device (CF-LVAD) insertion. However, the timing of RVAD insertion and the associated outcomes in CF-LVAD patients remains unclear. This study evaluates the effect of timing of RVAD insertion on long-term outcomes of CF-LVAD patients. Methods We performed a retrospective review CF-LVAD implantations from Jan 2001 through Mar 2017 at our center. From this, we culled out patients who received an RVAD and divided this cohort into early insertion (≤24 hours after CF-LVAD placement) and delayed insertion (>24 hours and ≤30days after CF-LVAD placement) groups. We compared early and late outcomes in the two groups. Results Within the CF-LVAD placement cohort (n=692), 61 (8.82%) patients required RVAD for severe RHF, with 35 (57.4%) patients in the early insertion group and 26 (42.6%) in the delayed insertion group. The majority of patients received temporary-type RVADs (CentriMag=42, TandemHeart=3) while some received durable-type RVADs (HeartWare=5, HeartMateII=1, Abiomed5000=4, Jarvik2000=1, Thoratec PVAD=3, Biomedicus=1). The mean duration of RVAD support was 48.8 days. In the early group, 17 (48.6%) patients were successfully weaned vs. 10 (38.5%) in the delayed group (p=NS). Overall differences between the early and late group have been summarized in Table 1 . Thirty-day mortality was similar for early 19 (54.3%) vs. delayed group 15 (57.7%) (p=NS) (Figure 1). There was no significant difference between the two groups in successfully bridging to transplantation. The 12-month overall survival rate in early placement patients was 16.7% and 26.9% in the delayed placement patients (p=NS) (Figure 1). Conclusions In this cohort of patients, no significant differences were found between the early and delayed groups in length of stay or 30-day readmission rates. There is no effect of timing of RVAD insertion on long-term outcomes of CF-LVAD patients. Prospective randomized trials can be designed to answer this equipoise effectively.

Percutaneous Mechanical Circulation Support Combined with Extracorporeal Membrane Oxygenation (oxyRVAD) in Secondary Right Heart Failure.

Right heart failure (RHF) because of pulmonary hypertension (PH) is a frequently encountered clinical problem with high mortality. The last resort, if pharmacological therapy fails, is mechanical circulatory support. There is a lack of percutaneous systems to support the right ventricle (RV). Venoarterial extracorporeal membrane oxygenation is widely used as a bailout in acute RHF in non-left ventricular assist device patients. Venoarterial extracorporeal membrane oxygenation does not unload the left ventricle and may cause failure of the left ventricle if used for a longer period of time. We report the long-term use of an ECMO-based percutaneous right ventricular assist system (oxyRVAD) capable to deliver up to 6 L/min of blood flow with a returning cannula placed in the main pulmonary artery used in RHF originating from PH with poor oxygenation. We present a series of four patients on oxyRVAD (mean treatment duration 15 ± 7.6 days). Patients benefited from the system clinically; however, two patients eventually died while on oxyRVAD. Nevertheless, we provide a proof-of-concept of this system in PH patients, which is feasible and might provide a useful "bridge-to-recovery" or "bridge-to-transplant" option in the management of patients with severe RHF because of PH.

Efficacy and safety of a calcium sensitizer, levosimendan, in patients with right heart failure due to pulmonary hypertension.

Despite using vasoactive and pulmonary hypertension (PH) specific therapies, the in-hospital mortality of severe PH with right heart failure (RHF) is high. We conducted a prospective analysis evaluating the efficacy and safety of levosimendan in PH patients with severe acute RHF. Forty-five PH patients hospitalized between January 2016 and November 2016 were recruited into a single arm, prospective, open-label study. Levosimendan was administered at the rate of .05-0.1 μg/kg/min, up to a total dose of 12.5 mg. The primary endpoints were changes of World Health Organization Function Class (WHO-FC) and Borg dyspnoea scores. Secondary endpoints included changes in 6-min walk distance (6-MWD), biochemical markers and right heart structure and function together with adverse events on day 7 and incidence of major cardiovascular events (death or readmission due to RHF) on day 30. Forty-five PH patients were enrolled. On the 7th day after levosimendan infusion, seven out of 13 PH patients with WHO-FC IV improved by one class (P = .008). Borg dyspnoea scores, 6-MWD and NT-proBNP improved significantly (P < .001). Compared with baseline, the right atrial transverse dimension, end-systolic eccentricity index and tricuspid annular plane systolic excursion improved significantly (58.8 ± 13.1 mm vs 53.7 ± 12.4 mm; 1.50 ± 0.27 vs 1.38 ± 0.23; 15.0 (13.0, 16.0) mm vs 15.8 (14.0, 17.4) mm, P < .005, respectively). One patient occurred sudden death after discharge during follow-up. Intravenous levosimendan can effectively improve severe RHF of PH patients in hospital and well tolerated.

154 - Hemodynamics Predictors of INTERMACS Defined Early Right Ventricular Failure after Left Ventricular Assist Devices

Introduction: Right heart failure (RHF) is a frequent complication following left ventricular assist device (LVAD) implantation and is a major factor of postoperative morbidity and mortality. However, identifying LVAD patients at risk for RHF postoperatively still remains an unsolved problem. The objective of our study is to identify preoperative hemodynamics predictors of RVF during LVAD support. Methods: Patients who underwent implantation of Heartmate II or Heartware LVADs at our center between December 2011 and December 2016 were identified. Early RVF was defined according to the latest INTERMACS definition based upon both documentation of elevated central venous pressure (CVP) and manifestations of elevated CVP before discharge. Severity was further stratified according to duration of inotrope/IV vasodilator/iNO therapy as mild (≤7 days), moderate (8–14 days), and severe (>14 days or need from mechanical RV support). Results: Among 111 patients (98 male, median 64.6 years old) who underwent LVAD implantation with 88 HeartMate II (74.6%) and 28 Heartware (23%), 75 (66.4%) experienced early RV failure. Of the 75 patients who met the INTERMACS RHF definition, 32 had mild RHF (42.7%), 27 had moderate RHF (36%), and 16 had severe RHF (21.3%). Population was stratified according to moderate-severe RVF vs mild RVF. Pre-LVAD hemodynamics demonstrated significant differences in patients who experienced moderate-severe acute RHF: right atrial pressure (RAP) (14.5 Vs. 9.00 P < .002), mean pulmonary pressure (MPAP) (40.5 Vs. 35.0 P < .025) and central venous pressure (CVP)/pulmonary capillary wedge pressure (PCWP) (0.55 Vs. 0.41 P < .034). By univariate analysis RAP, MPAP and RAP/PCWP were significantly associated with risk of moderate/severe RHF. In a multivariable model only MPAP and CVP/PCWP were significantly predictive of RHF. Area under the curve analysis demonstrated MPAP (0.684) and CVP/PCWP (0.724). Conclusions: Pre-LVAD hemodynamic data can be used to stratify patients post-LVAD implantation at risk for moderate-severe RHF. This is first study to investigate the importance of pre-LVAD hemodynamics predicting early moderate or severe RHF defined using the new INTERMACS definition.

Contemporary outcome of unplanned right ventricular assist device for severe right heart failure after continuous-flow left ventricular assist device insertion.

The timely use of a right ventricular assist device (RVAD) becomes necessary for severe right heart failure (RHF) after left ventricular assist device (LVAD) insertion. This study evaluates outcomes in patients who required unplanned RVAD support early after continuous-flow (CF) LVAD insertion. We retrospectively reviewed 305 patients who underwent HeartMate II/HeartWare CF-LVAD insertion between 2009 and 2014. Twenty-seven (9%) patients required unplanned RVAD for severe RHF early after LVAD insertion. We compared early and late outcomes in patients with and without RVAD. The median time to RVAD implantation after primary CF-LVAD implantation was 1.0 (0-3) day. Seventeen (63%) patients could be weaned from RVAD after median of 14 (10-18) days. In 278 patients in the isolated LVAD group, overall survival at 3 and 12 months was 95% and 86%, whereas 59% and 54% in the unplanned RVAD group, respectively ( P < 0.001). The 12-month overall survival rate in patients who were weaned from RVAD was 75% ( P = 0.189 vs isolated LVAD group), whereas in patients who could not be weaned from RVAD, the overall survival was 20% ( P < 0.001 vs RVAD weaning group and isolated LVAD group). Readmission free rate for RHF at 1 year was 53% in the unplanned RVAD group and 90% in the isolated LVAD group ( P = 0.002). Among patients who required unplanned RVAD after CF-LVAD implantation, above 60% of the patients could be weaned from RVAD. However, careful attention should be paid to the recurrent or sustained RHF.

Protein-losing Enteropathy in Association with Right Heart Failure

A 65-year-old woman, with past history of mitral valve replacement, developed severe right heart failure. In addition to elevated right heart pressure, she had significant hypoalbuminemia as the important cause of refractory edema. Technetium-99m-labelled human serum albumin scintigraphy showed leak of protein from the transverse colon and the excretion of alpha 1 antitrypsin in the stool was markedly increased. Diagnosis of protein losing enteropathy was established. The etiology was increased lymphatic pressure secondary to right heart failure of multifactorial cause, including elevated left side filling pressures and out of proportion pulmonary hypertension due to old tuberculosis, resulting in significant tricuspid regurgitation. The patient was managed conservatively with increased dose of furosemide from 10-20mg every other day up to 40-60mg/day, and maximum dose of tolvaptan (a vasopressin 2 receptor blocker) of 15mg/ day, in addition to high protein diet.

In-Series Versus In-Parallel Mechanical Circulatory Support for the Right Heart: A Simulation Study.

Right heart failure (RHF) is a serious health issue with increasing incidence and high mortality. Right ventricular assist devices (RVADs) have been used to support the end-stage failing right ventricle (RV). Current RVADs operate in parallel with native RV, which alter blood flow pattern and increase RV afterload, associated with high tension in cardiac muscles and long-term valve complications. We are developing an in-series RVAD for better RV unloading. This article presents a mathematical model to compare the effects of RV unloading and hemodynamic restoration on an overloaded or failing RV. The model was used to simulate both in-series (sRVAD) and in-parallel (pRVAD) (right atrium-pulmonary artery cannulation) support for severe RHF. The results demonstrated that sRVAD more effectively unloads the RV and restores the balance between RV oxygen supply and demand in RHF patients. In comparison to simulated pRVAD and published clinical and in silico studies, the sRVAD was able to provide comparable restoration of key hemodynamic parameters and demonstrated superior afterload and volume reduction. This study concluded that in-series support was able to produce effective afterload reduction and preserve the valve functionality and native blood flow pattern, eliminating complications associated with in-parallel support.

Efficacy of inhaled iloprost on top of other targeted therapies for patients with pulmonary hypertension and severe right heart failure

To investigate the efficacy and safety of inhaled iloprost on top of other pulmonary hypertension (PH) specific therapies for patients with PH and severe right heart failure. We consecutively enrolled WHO functional class IV patients with PH and chronic thromboembolic pulmonary hypertension (CTEPH) in Shanghai Pulmonary Hospital from January 2011 to January 2013. Inhaled iloprost was administrated to all enrolled patients, oral endothelin antagonist receptors (ERAs) and/or type 5 phosphodiasterase inhibitors (PDE5-I) were also used as basis therapies. The in-hospital outcomes and the changes of right heart functional parameters were observed. Twenty-four patients with PH and 5 patients with CTEPH were enrolled. After a mean treatment duration of (23 ± 13) days, 3 patients dead and significant improvement was observed in the remaining 26 patients. Compared with the baseline, heart rate decreased from (99 ± 14) to (91 ± 12) bpm (P = 0.001), plasma NT-proBNP level decreased from 5 823 (3 029-13 248) to 3 220 (1 678-6 720) ng/L (P < 0.001), tricuspid annular plane systolic excursion (TAPSE) increased from (1.3 ± 0.4) to (1.4 ± 0.3) cm (P = 0.018), right ventricular diameter decreased (left-to-right diameter from (57 ± 11) to (53 ± 10) mm, P = 0.040, and superoinferior diameter from (69 ± 11) to (64 ± 16) mm, P = 0.027), Tbil also decreased from (41 ± 34) to (26 ± 17) µmol/L (P < 0.001). No severe side effects were observed. The strategy of inhaled iloprost on top of other PAH-specific target therapy medications is effective and safe for PH patients with severe right heart failure.

Late Right Heart Failure after Left Ventricular Assist Device Implantation: Clinical Predictors and Outcomes

Purpose Early Right heart failure (RHF) after left ventricular assist device (LVAD) implantation has been well studied. However, the significance of late RHF (LRHF) remains unclear. This study aimed to assess the predictors and outcomes of LRHF after LVAD implantation. Methods and Materials A retrospective analysis of 73 consecutive patients implanted with HeartMate II LVAD was conducted. 23 (32%) patients presenting with New York Heart Association (NYHA) Class III symptoms, systemic congestion, and severe RHF on echocardiogram 1 month after LVAD implantation comprised the LRHF group. 50 (68%) patients had no signs of RHF (NRHF group). The Model for End-Stage Liver Disease (MELD) XI scores was calculated for all patients. Results The LRHF group patients were more often assigned for destination therapy (56% vs. 27%, p=0.01), had higher pre-operative MELD XI score (16.2±4.4 vs. 13.8±3.2, p=0.03), lower serum albumin level (3.1±0.7 vs. 3.4±0.5 g/dl), tendency to higher central venous pressure (CVP, 15±5 vs. 13±6 mm Hg, p=0.06) and higher ratio of right ventricle to left ventricle diastolic dimension (RVDD/LVDD: 0.7±0.2 vs. 0.6±0.1, p=0.07) on pre-operative echocardiogram compared to the NRHF group. Preoperative MELD XI score ≥ 17 was identified in 54% of the LRHF group patients and 10% of the NRHF group patients (p=0.001) and was the only independent predictor of LRHF (odds ratio 6.8, confidence interval 1.6 - 23.1, p=0.009) by multivariate analysis. At 6 months the LRHF patients had higher serum creatinine (1.4±1.1 mg/dl vs. 1.1±0.2, p=0.03), higher CVP (14.5±5.7 vs. 6.3±2.9 mm Hg) and RVDD/LVDD (0.8±0.2 vs. 0.7±0.2, p=0.05) compared to NRHF group. In addition, 7 (29%) patients of the LRHF group versus 5 (10%) patients of the NRHF group died over 9.5±6.3 months follow up period (p=0.04). Conclusions LRHF may be predicted by pre-operative MELD XI score ≥ 17. LRHF persisted up to 6 months after LVAD implantation, and was associated with a higher mortality.

Aortic arch operation under deep hypothermic circulatory arrest

To summarize the surgical experience of aortic arch operation under deep hypothermic circulatory arrest. 22 patients suffering from aortic dissection or descending aorta aneurysm with the involvement of aortic arch received operation under deep hypothermic circulatory arrest. Eight patients underwent ascending aorta and partial aortic arch replacement, one patient received aortic root, ascending aorta, and partial aortic arch replacement, 2 patients received ascending aorta and total arch replacement, 2 patients received aortic valve replacement plus ascending aorta and partial aortic arch replacement, 8 patients underwent ascending aorta and total arch replacement plus elephant trunk technique (stunted elephant trunk used in 6 cases), and 1 patient received left partial aortic arch and descending aorta replacement. Coronary artery bypass grafting was performed concomitantly in 4 cases. Three patients died peri-operatively with a mortality rate of 13.6%. One patient had aortic dissection rupture before operation leading to cardiac tamponade, acute inferior myocardial infarction, and cardiac arrest. This patient received operation while resuscitation. After operation, the patient had severe right heart failure and died 16 hours later. One patient had bleeding and multi-organ failure, and died 3 days later. The third patient, with acute aortic dissection did not awake after operation, had pulmonary infection and multi-organ failure, and died 39 days later. Re-thoracotomy for bleeding was required in 3 cases; delayed awareness occurred in 3 cases; and 2 cases had renal failure after operation. Aortic arch operation includes partial aortic arch replacement, total arch replacement, and total arch replacement with elephant trunk technique. The operation procedure is selected according to the primary lesion and how aortic arch has been affected. Deep hypothermic circulatory arrest with selective cerebral perfusion facilitates complicated aortic arch operation, resulting in a reduction of mortality and morbidity for arch aneurysms or dissection.

Severe right heart failure after heart transplantation. A single-center experience

We reviewed our heart transplantation recipient population, using hard criteria defining severe right heart failure (RHF), and analyzed possible risk factors for outcome after RHF. Between 1983 and 1998 621 cardiac transplantations were performed at our institution. RHF was defined by the necessity to implant an assist device or echocardiographically confirmed right ventricular ballooning with concomitant end organ failure. RHF patients were compared with a matched control group. Thirty-five patients (5.9%) with severe RHF after transplantation fulfilled inclusion criteria. Of these, 32 patients died, while none of the control patients died (P < 0.001). Increased preoperative pulmonary capillary wedge (P = 0.005) and mean pulmonary artery pressure (P = 0.006) were identified as significant risk factors for severe RHF. Severe RHF as defined in our study is irreversible in almost every case without differences among therapeutical concepts. Hence, improvement of postoperative outcome necessitates avoidance or aggressive therapy of possible risk factors.

Importance of angiotensin-converting enzyme in pulmonary hypertension.

Angiotensin II causes pulmonary vasoconstriction in man and in animals, and angiotensin-converting enzyme (ACE) inhibitors have prevented the development of chronic pulmonary hypertension in animals models. Angiotensin II may contribute to lung vascular remodeling in pulmonary hypertensive disease, since cilazapril, an inhibitor of ACE, reduces pulmonary vascular medical thickening in chronically hypoxic rats with established pulmonary hypertension. Furthermore, the ACE DD genotype, which has been associated with increased circulating and tissue ACE activity, has been associated with left ventricular hypertrophy in human hypertensive disorders. The ACE DD genotype may also 'permit' a greater hypertrophic adaptation of the pressure-over-loaded right ventricle. In fact, we have shown that pulmonary hypertension patients with maintained cardiac output and less right-heart failure fall into the group with the DD genotype and that patients with a low cardiac output and more severe right-heart failure fall into the group with the non-DD genotype, supporting the hypothesis. We assessed cardiopulmonary hemodynamics in patients with primary (unexplained) pulmonary hypertension and segregated the patients based on their ACE genotype. For similar mean pulmonary artery pressures in the DD and non-DD groups, the cardiac output was substantially lower in the patients with the non-DD genotype, whereas the values for mean right atrial pressure and pulmonary vascular resistance were double when compared with the DD group. Our data show that the ACE DD genotype is prevalent in patients with severe pulmonary hypertension and is a marker of maintained right ventricular function.

Effect of tricuspid annuloplasty in mitral/aortic valve replacement on the clinical aspects and global function of the right heart chamber

The clinical improvement after mitral or aortic valve surgery is primarily due to the correction of the aortic/mitral valve function and the subsequent decrease of pulmonary artery pressure. The hemodynamic effect of an additional tricuspid annuloplasty, however, is still unclear. To assess the influence of a tricuspid annuloplasty using DeVega- or Carpentier-technique on the clinical outcome, hemodynamics, and right ventricular function in patients with moderate to severe tricuspid insufficiency, 38 patients were studied pre- and 11 +/- 4 months postoperatively. The clinical degree of left heart failure was graded according to the criteria of the NYHA. The extent of right heart failure (RHF) was determined using a clinical score from 0 (no signs) to 3 (severe RHF with pleural effusion/ascites). Mean pulmonary artery pressure (PAPm), end-diastolic volume index (RVEDVI), and ejection fraction (RVEF) of the right ventricle using biplane cineventriculography, as well as the angiographic and dopplerechocardiographic degree of tricuspid insufficiency were determined. The patients were assigned to three groups: gr.I (n = 12): preoperatively no tricuspid insufficiency (TI), gr. II (n = 12): with preop. TI and without tricuspid annuloplasty (TA), gr. III (n = 14): with preop. TI and TA. The patients of all three groups improved postoperatively from NYHA functional class III to class II (p less than 0.001). The clinical score of RHF decreased from 0.8 +/- 0.5 to 0.3 +/- 0.5 in gr. I, from 1.4 +/- 1.1 to 0.6 +/- 0.7 in gr. II, and from 1.7 +/- 1.0 to 0.8 +/- 0.8 in gr. III (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)