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Introduction: Recently, a stratification of the heart failure (HF) phenotypes, which classifies HF into 3 subtypes based on ejection fraction, has been introduced. Before that, clinical trials and registries have been mainly devoted to HF with reduced ejection fraction (HFrEF). As a result, data on long‑term survival trends for individual HF phenotypes are scarce., Objectives: The study aimed to evaluate survival according to the HF phenotype and to identify predictors of mortality., Patients and Methods: Patients hospitalized for HF in our referral center between January 2014 and May 2019 were included in the analysis. HF phenotyping was based on EF: reduced (HFrEF with EF <40%), mildly reduced (HFmrEF with EF = 40%-49%), and preserved (HFpEF with EF ≥50%)., Results: Of 2601 patients included in the study, 1608 individuals (62%) presented with HFrEF, 331 patients with HFmrEF (13%), and 662 patients with HFpEF (25%). The median follow‑up was 2.43 years (interquartile range, 1.56-3.49). The risk of death was 61% higher in HFrEF than in HFpEF (P <0.001), while in HFmrEF and HFpEF it was similar. Survival rates at 1 and 5 years in HFrEF, HFmrEF, and HFpEF were 81%, 84%, 84%, and 47%, 61%, and 59%, respectively. The HF phenotypes differed in most of the parameters that affect prognosis. Only the use of inotropes, which was linked to an increased risk of death, and the use of angiotensin‑converting enzyme inhibitors, which reduced this risk, were independent of the HF phenotype., Conclusions: Survival in HFrEF is worse as compared with HFmrEF and HFpEF, where it is similar. The HF phenotypes differ in most of the parameters that affect survival.

Methylated arginine metabolites interrupt nitric oxide synthesis, which can result in endothelium dysfunction and inadequate vasodilation. Since little is known about the dynamics of arginine derivatives in patients with heart failure (HF) during physical exercise, we aimed to determine this as well as its impact on the patient outcomes. Fifty-one patients with HF (left ventricle ejection fraction-LVEF ≤ 35%, mean 21.7 ± 5.4%) underwent the cardiopulmonary exercise test (CPET). Plasma concentrations of L-arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were measured before and directly after CPET. All patients were followed for a mean of 23.5 ± 12.6 months. The combined endpoint was: any death, urgent heart transplantation, or urgent LVAD implantation. L-arginine concentrations increased significantly after CPET ( p = 0.02), when ADMA ( p = 0.01) and SDMA ( p = 0.0005) decreased. The parameters of better exercise capacity were positively correlated with post-CPET concentration of L-arginine and inversely with post-CPET changes in ADMA, SDMA, and baseline and post-CPET SDMA concentrations. Baseline and post-CPET SDMA concentrations increased the risk of endpoint occurrence (HR 1.02, 95% CI 1.009-1.03, p = 0.04 and HR 1.02, 95% CI 1.01-1.03, p = 0.02, respectively). In conclusion, in patients with HF, extensive exercise is accompanied by changes in arginine derivatives that can reflect endothelium function. These observations may contribute to the explanation of the pathophysiology of exercise intolerance in HF.

Introduction: There is still little information regarding a detailed description and predictors of different subtypes of heart failure (HF) in the Polish population., Objectives: This study sought to characterize the differences between hospitalized patients with HF divided into HF with preserved ejection fraction (HFpEF; EF ≥50%), mildly reduced EF (HFmrEF; EF 40%-49%), and reduced EF (HFrEF; EF <40%), and to identify factors related to each HF subtype., Patients and Methods: Patients from the hospital database whose hospitalization was coded as HF‑related between 2014 and 2019 were included in the analysis., Results: A total of 2601 patients were included, of whom 62% had HFrEF, 13% had HFmrEF, and 25% had HFpEF. The patients with HFpEF, as compared with those with HFrEF and HFmrEF, were older (70.5 vs 61.6 vs 66.5 years, P <0.001), less often male (44% vs 68.3% vs 81.3%, P <0.001), and less likely to have an ischemic etiology of HF (19.3% vs 49.8% vs 34.4%, P <0.001) but they were more likely to have hypertension (87.3% vs 78.2% vs 78.2%, P <0.001), atrial fibrillation (64.5% vs 55.6% vs 59.5%, P <0.001), cancer (32.2% vs 19.6% vs 28.7%; P <0.001), and anemia (25.5% vs 15.9% vs 20.5%, P <0.001). Of 3 multivariable models, the one predicting HFpEF was the strongest (P <0.001, area under the curve, 0.79), and included age, sex, aortic stenosis, hypertension, anemia, cancer, thyroid abnormality, atrial fibrillation, longer history of HF, ischemic etiology, coronary artery disease, diabetes mellitus, and liver failure., Conclusions: HFrEF and HFpEF differed significantly in terms of baseline characteristics, while HFmrEF was in the middle of the HF spectrum, tending to be a mixture of HFpEF and HFrEF characteristics.

Objectives: The present study was a prospective, single-center, single-arm study to investigate the efficacy of transcatheter pulmonary artery denervation (TPADN) in patients with combined postcapillary and precapillary PH (Cpc-PH) associated with left heart failure with reduced ejection fraction (HF-rEF)., Background: Pulmonary hypertension (PH) in patients with left ventricular systolic dysfunction has a negative impact on outcome., Methods: The combination of pulmonary artery systolic pressure (PAPs) ≥60 mmHg, transpulmonary pressure gradient (TPG) ≥12 mmHg, nonreversible mean PAP, and pulmonary vascular resistance (PVR) ≥3.5 Wood Units was considered as too high risk for heart transplantation (HTx). The clinical efficacy endpoint was an improvement in 6-min walking test and the hemodynamic endpoints were changes in PAPs, PVR, and TPG between baseline and 6 months. Circumferential radiofrequency applications were delivered around distal main, left and right pulmonary arteries. At each ablation point temperature was 45°C and energy 10 W., Results: TPADN was performed in 10 patients. At 6-month in 5 patients we observed reduction in PAP, PVR, TPG, and DPG and then 1 had successful HTx, 2 are on HTx waiting list, 2 received LVADs, 2 patients did not improve, and 3 patients died., Conclusions: TPADN may be beneficial in selected patients with HF-rEF and Cpc-PH., (© 2021 Wiley Periodicals LLC.)

Aims: This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS-986231, a novel second-generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF)., Methods and Results: Forty-six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose-escalation cohorts in this double-blind, randomized, placebo-controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m 2 received one 6-h i.v. infusion of BMS-986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS-986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time-averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS-986231 increased non-invasively measured time-averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug-related arrhythmia or symptomatic hypotension with BMS-986231. Analyses of adverse events throughout the 30-day follow-up did not identify any toxicities specific to BMS-986231, with the potential exception of infrequent mild-to-moderate headaches during infusion. There were no treatment-related serious adverse events., Conclusions: BMS-986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS-986231 should be further assessed in patients with heart failure., (© 2017 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Pulmonary hypertension (PH) is recognised in about 60% of patients referred for heart transplantation (HTx), and it influences the patient's prognosis., Aim: To assess the prognostic value of reactive PH in patients listed for elective HTx., Methods: A total of 522 patients were enlisted from the Polish National Registry (POLKARD), listed for HTx, in whom complete haemodynamic data were reported. The endpoint was all-cause death before HTx. Heart transplantation, elective or urgent, was considered as an end of the follow-up (mean follow-up 1.47 ± 1.26 years). Patients were divided into three subgroups: no PH, passive PH, reactive PH taking into account mean pulmonary artery pressure (PAP) of 25 mm Hg, pulmonary capillary wedge pressure (PCWP) 15 mm Hg, and pulmonary vascular resistance (PVR) 3.0 Wood units. Haemodynamic, clinical, echocardiographic, and biochemical assessments (including NT-proBNP, hs-CRP) were performed. The Heart Failure Survival Score (HFSS) was calculated., Results: Estimated death rate was comparable between patients with no PH, passive PH, and reactive PH, despite the fact that the patients with reactive PH had the worst pulmonary haemodynamic scores (mean PAP 38.4 ± 7.8, PCWP 27 ± 7.4 mm Hg and PVR 4.8 ± 1.7 Wood units). In patients with reactive PH, in multifactor Cox analysis only the serum Na level influenced survival. According to the Kaplan-Meier method, patients with reactive PH, with mean PAP ≥ 41.4 mm Hg had the worst prognosis, estimated survival was: one year - 83%, two years - 65%., Conclusions: Reactive PH is common among patients with chronic HF listed to HTx (28%). It has no further influence on short-term prognosis as compared with patients with no PH and passive PH. Serum Na concentration and mean PAP ≥ 41.4 mm Hg influence the prognosis of patients with reactive PH.

Background: The benefits of rehabilitation in heart failure (HF) patients are well established. Little is known about Nordic walking (NW) training in HF patients especially in those with cardiovascular implantable electronic devices (CIEDs)., Purpose: The purpose of this study was to assess safety, effectiveness, adherence to and acceptance of home-based telemonitored NW in HF patients, including those with CIEDs (i.e. cardiac resynchronisation therapy, implantable cardioverter-defibrillator)., Methods: The study design was a single-centre, prospective, parallel-group, randomised (2:1), controlled trial among 111 HF patients, New York Heart Association (NYHA) II-III; left ventricular ejection fraction (EF) ≤ 40%. The intervention was a home-based telemonitored eight-week NW (training group (TG) n = 77) five times weekly vs usual care alone (control group (CG) n = 34). Outcome measures included a primary end point of functional capacity assessed by peak oxygen consumption (VO2peak). Secondary end points included: workload duration (t) in cardiopulmonary exercise test (CPET), six-minute walking test (6-MWT) distance and quality of life (QoL), Medical Outcome Survey Short Form 36 (SF-36); safety; adherence to and acceptance of NW. Measurements were made before and after intervention., Results: NW resulted in significant improvement in: VO2peak (16.1 ± 4.0 vs 18.4 ± 4.1(ml/kg/min), p = 0.0001), t (471 ± 141 vs 577 ± 158 (s), p = 0.0001), 6-MWT(428 ± 93 vs 480 ± 87 (m), p = 0.0001) and QoL (79.0 ± 31.3 vs 70.8 ± 30.3 (score), p = 0.0001). We did not observe favourable results in the CG. The differences between the TG and CG were significant in: ΔVO2peak (Δ2.0 ± 2.4 vs Δ-0.2 ± 2.1, p = 0.0004); Δt (Δ108 ± 108 vs Δ0.94 ± 109, p = 0.0031); Δ6-MWT (Δ53.8 ± 63.9 vs Δ22.0 ± 68.7, p = 0.0483). In neither group were there deaths nor necessity for hospitalisation. We did not observe any intervention from CIEDs during NW. All patients in the TG completed rehabilitation and accepted it well., Conclusion: In HF patients, including those with CIEDs, home-based telemonitored NW is safe and effective. NW was well accepted by patients and adherence was high and promising., (© The European Society of Cardiology 2014.)

Introduction: The assessment of prognosis is crucial for the clinical management of patients with heart failure (HF)., Objectives: The aim of the study was to evaluate the usefulness of novel biomarkers for the assessment of prognosis in patients with HF, compared with a detailed assessment based on routine laboratory tests., Patients and Methods: The study included 179 patients with HF. In all patients, routine laboratory tests were performed and selected biomarkers were measured (N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, growth hormone, myeloperoxidase, metaloproteinase 9, procollagen type III, soluble toll like receptor 2, insulin growth factor, and neutrophil gelatinase-associated lipocain). The primary endpoint was death or urgent heart transplantation, while the secondary endpoints encompassed primary endpoints plus cardioverter intervention or hospitalization for HF., Results: The mean age of the study group was 52.5 years (91% were men). Most patients had advanced HF. During a 6-month follow-up, 21 primary endpoints and 63 secondary endpoints were recorded. A multiple regression analysis showed that of all laboratory variables and biomarkers, only uric acid and sodium were independent predictors of primary endpoints, and only estimated glomerular filtration rate had a predictive value for secondary endpoints. None of the biomarkers were a significant prognostic factor in the study population., Conclusions: Biomarkers do not outweigh the value of standard laboratory tests. Routine laboratory workup allows to assess multiorgan damage and provides the most significant prognostic data. Biochemical tests should remain the gold standard for the assessment of prognosis in patients with HF.

Background: Pulmonary hypertension is a contradiction for heart transplantation (HTx). The aim of the study was to examine prognostic significance of pulmonary hemodynamic variables in patients with severe chronic heart failure (HF) considered for HTx., Methods: Patients with HF were qualified to HTx in Poland. We measured pulmonary artery systolic pressure (PASP), pulmonary capillary wedge pressure (PCWP), transpulmonary gradient (TPG), cardiac output (CO), pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR). We performed biochemical evaluation, 6-min walking test, VO2max. Death or emergency HTx were assumed as the endpoints in the follow-up. Death or any kind of HTx were considered an end of observation. Survival analysis was conducted using Kaplan-Meier curves (long rank test with strait defined by terciles of analyzed hemodynamic parameters)., Results: Six hundred and fifty-eight patients were qualified to HTx between 2003 and 2007. The mean follow-up: 601 days. 87.8% male. Mean age was under 50, III and IV NYHA class. Mean PASP was 44.3 ± 16.9 mm Hg, TPG 10.0 ± 6.6 mm Hg and PVR 2.9 mm Hg, PCWP20.9 ± 9.3 mm Hg. PASP and PCWP had influence on survival or emergency HTx. There was a significant difference in survival between patients with PCWP > 25 mm Hg and PCWP < 25 mm Hg. The worst prognosis was with PASP higher than 50 mm Hg. One-, two-, and three-year survival was 75%, 58% and 48% compared to patients with PASP < 35 mm Hg (80%, 70%, and 68%, respectively)., Conclusions: In patients qualified to HTx, pathological values of pulmonary hemodynamic parameters have a significant influence on survival. The worst prognosis have patients with PASP > 50 mm Hg, and PCWP > 25 mm Hg. Pulmonary hemodynamic parameters are important during allocation process to HTx.

Introduction:  Data regarding standardized trends in mortality from heart failure (HF) in the general population are limited., Objectives:  The aim of the study was to evaluate trends in HF mortality in Poland in the years 1980-2010., Patients and Methods:  An analysis of a database of mortality records from 1980-2010 based on National Statistics was performed. Mortality trends for HF by age and sex were analyzed by polynomial or linear regression., Results:  Total crude numbers of HF deaths in 1980 were 21,519 and 23,008 for women and men, respectively, whereas, in 2010, there were 23,304 and 19,558. There was a significant change in mortality trends for HF, from a decline during the first phase of the study to an increase during the most recent years, 2005-2010 (P <0.005 for changes of trends for both sexes). The lowest value reached in 2005 constituted 47% and 41% of the baseline for women and men, respectively. These ratios increased to 59% and 52% in 2010. Stratification by age and sex brought similar results, with the exception of the youngest groups, which showed initial increases in the rates for the years 1980-1985., Conclusions:  There was a significant decline in the rates of HF mortality in the Polish population for both men and women, showing a maximal reduction of about 50% around 2005. However, between 2005 and 2010, a significant increase in the rates of HF mortality was observed (crude difference equaled 12% for women and 11% for men). It is unknown whether this is a temporary or permanent trend, and the issue requires further investigation.

Background: Based on the results of clinical trials, the prognosis for patients with severe heart failure (HF) has improved over the last 20 years. However, clinical trials do not reflect 'real life' due to patient selection. Thus, the aim of the POLKARD-HF registry was the analysis of survival of patients with refractory HF referred for orthotopic heart transplantation (OHT)., Methods: Between 1 November 2003 and 31 October 2007, 983 patients with severe HF, referred for OHT in Poland, were included into the registry. All patients underwent routine clinical and hemodynamic evaluation, with NT-proBNP and hsCRP assessment. Death or an emergency OHT were assumed as the endpoints. The average observation period was 601 days. Kaplan-Meier curves with log-rank and univariate together with multifactor Cox regression model the stepwise variable selection method were used to determine the predictive value of analyzed variables., Results: Among the 983 patients, the probability of surviving for one year was approximately 80%, for two years 70%, and for three years 67%. Etiology of the HF did not significantly influence the prognosis. The patients in NYHA class IV had a three-fold higher risk of death or emergency OHT. The univariate/multifactor Cox regression analysis revealed that NYHA IV class (HR 2.578, p < 0.0001), HFSS score (HR 2.572, p < 0.0001) and NT-proBNP plasma level (HR 1.600, p = 0.0200), proved to influence survival without death or emergency OHT., Conclusions: Despite optimal treatment, the prognosis for patients with refractory HF is still not good. NYHA class IV, NT-proBNP and HFSS score can help define the highest risk group. The results are consistent with the prognosis of patients enrolled into the randomized trials.

Background: Atrial fibrillation (AF) is the most common arrhythmia among patients (pts) with heart failure and has significant influence on survival., Aim of the Study: to assess prognosis of pts with refractory heart failure (HF) qualified for heart transplantation (HTX)., Material/methods: 872 pts (107 W and 765 M) were qualified for HTX between Dec 2003 and Oct 2007. Patient's death or super urgent heart transplantation were considered the end point in Kaplan-Meier survival curves., Results: 680 pts were on sinus rhythm (SR) and 192(22.0%) had atrial fibrillation (AF). During follow-up (1-1464 days, mean 550 days) 155 pts (17.7%) died, 17.65% with SR and 18.23% with AF (ns). EF - mean 21,6 (SR) and 21,8 (FA), NYHA 3,1 (SR), NTproBNP- mean 3635, 4 (SR) and 4349,4 (FA), Arronson - mean 7,8 (SR) and 7,7 (FA). There were no significant differences between groups. We analyzed influence of heart rate (Kaplan-Maier method) on survival. The pts were divided according to HR: gr.I <70/min, gr II 71-89/min, gr III >90/min. The shortest survival rate was noticed in group III. There was no difference in survival between group I and II., Conclusions: The prognosis for patients qualified for heart transplant does not depend on the type of the dominant cardiac rhythm (atrial fibrillation or sinus rhythm). The prognosis is significantly better for those patients whose basic, resting heart rate does not exceed 90 bpm regardless of the rhythm type.

Introduction: The aim of the study was to analyze the influence of body weight of the adult heart recipient on the chance to obtain a transplant., Methods: We analyzed the data from all 658 patients listed for heart transplantation., Results: During the follow-up period, 325 (49%) of listed patients underwent transplantation with 102 (15%) succumbing before heart transplantation. The mean weight of transplanted patients was 73.7 +/- 13.7 kg and 81.2 +/- 15.4 kg for those not transplanted (P < .00001). Patients were divided according to body weight in two groups: light = below 80 kg (n = 360) or heavy > or = 80 kg or above (n = 297). On the transplant list, 111 heavy patients (37%) versus 213 light patients (59%) underwent the procedure, a significant difference. The waiting time among light patients was 255 versus heavy patients of 395 days (P < .005). There was a similar number of deaths before transplantation among the light (n = 56 360 patients; 15.5%) versus the heavy group (49/297; 16%). Upon multivariate Cox mode analysis independent factors related to not receiving a heart transplant were greater weight, systolic blood pressure, pulmonary vascular resistance, Heart Failure Survival Score (HFSS) score and lower N-terminal pro-brain natriuretic peptide (NTproBNP) levels., Conclusions: Among adult heart transplant candidates, the chance to receive a heart transplant significantly decreased when the recipient's weight exceeded 80 kg. Patients with a body weight more than 110 kg had a poor chance to receive a heart transplantation.

Unlabelled: Most methods used in the risk assessment of heart transplant candidates do not include new biomarkers., Aims: The aim of the study was to examine the value of NTproBNP and hsCRP and their combined use together with HFSS score in the risk assessment of patients with heart failure enlisted for heart transplantation., Methods: Data of 658 patients enlisted for heart transplantation in all active transplantation centers were stored in a prospective registry. The composite end point-death or urgent transplantation was recorded during the follow-up., Results: Death or urgent transplantation was recorded in 161 (24%) of pts. 102 (15%) patients died and 59 (9%) were transplanted urgently. Kaplan-Meier curves for risk of death or urgent transplantation where highly significant when pts were stratified by the quartiles of NT proBNP (P < .000001) or quartiles according to the hsCRP level on admission (P < .002). In the multivariate Cox proportional hazard model, the significance was observed for NTproBNP (P < .01) and HFSS (P < .02), and borderline significance for hsCRP (P = .057). When ROC analyses of the area under the curve (AUC) values were considered, AUC area was for HFSS - 0.645, for NTproBNP - 0.653 and for hsCRP - 0.566. When all those variables were included together in the model, the AUC value rose to 0.6943. Based on those results a weighted risk model with all three parameters was proposed., Conclusion: HFSS, NTproBNP and hsCRP levels are independent stratification variables of survival or need for urgent heart transplantation. Their predictive value is moderately increased when they are analyzed together.

Background: Heart rate variability (HRV), heart rate turbulence (HRT), and heart rate recovery (HRR), indices that reflect autonomic nervous system (ANS) activity, are outcome predictors in patients with chronic heart failure (CHF). It is not clear, however, whether they reflect the same components of ANS activity. No study has examined the effects of physical training (PT) training on HRV, HRT, and HRR in CHF., Study Objective: To examine the responses of HRV, HRT, and HRR to a PT program in patients presenting with CHF., Methods: In 41 patients (mean age = 58.7 +/- 10.2 years) in New York Heart Association CHF functional classes II or III, and with a left ventricular ejection fraction <40%, HRV, HRT, and HRR were measured before and after 8 weeks of PT., Results: The training was clinically effective in all patients. Before versus after PT, standard deviation of all normal RR intervals increased from 107 +/- 30 to 114 +/- 32 ms (P = 0.047), high frequency increased from 210 +/- 227 to 414 +/- 586 ms(2)/Hz (P = 0.02), and the low/high frequency ratio decreased from 1.8 +/- 1.55 to 1.1 +/- 1.2 (P = 0.002). HRT and HRR did not change significantly after PT., Conclusions: In patients with CHF, the positive effects of PT were limited to HRV indices, which reflect parasympathetic activity, without significantly changing HRR and HRT. These observations indicate that different mechanisms modulate HRV, HRR, and HRT, which provide complementary information regarding ANS activity. The 8-week PT program failed to completely normalize ANS function.

Background: Despite physicians' increasing knowledge regarding heart failure (HF), a significant percentage of patients still do not receive adequate treatment. The aim of this multicentre, retrospective descriptive study was to reveal the pharmacotherapy patterns in HF patients hospitalized in cardiology (CARD) and internal medicine (INT) wards in Poland., Methods: Included into the study were 800 consecutive patients who were admitted to the hospitals: 350 patients from 7 CARD wards and 450 patients from 9 INT wards., Results: The average age in the study group was about 70 years (youngest participant under 40 and oldest at 95 years of age). Decompensation of HF or acute HF were the most frequent causes of hospitalization (in both groups > 50%). The main etiology was coronary artery disease, either alone or together with hypertension (from about 60% in INT patients to about 78% in CARD patients, p = NS). With regard to pharmacotherapy, angiotensin converting enzyme inhibitors were used in 81% of cases (77% CARD and 83% INT; p = 0.05); out of this group, doses were at optimal or larger in 39.3% of patients (38% CARD patients and 39.4% INT patients). Beta-blockers were administered in 31.4% and 19.1% of patients from the CARD and INT groups respectively (p < 0.0001), but optimal dosing was negligible., Conclusions: Compared with an assessment conducted several years ago, the past education initiatives have significantly improved the quality of standard-based HF treatment. However, suboptimal dosing and the use of drugs that do not improve prognosis remain an unresolved issue in this population.

Background: The short- and long-term effects of levodopa (L-dopa), an oral dopaminergic prodrug, were assessed in patients with severe left ventricular dysfunction., Methods and Results: Initially, 26 patients were included in the study group. After clinical, radiographic, and radionuclide examination, each patient underwent right heart catheterization (Swan-Ganz thermodilution catheter). Plasma noradrenaline levels were measured. In two patients, a favorable hemodynamic response to L-dopa was not observed, another two required permanent pacemaker implantation. These four patients were excluded from the study. Two patients required permanent pacemaker implantation. The remaining 22 patients with favorable hemodynamic response to L-dopa (increase in cardiac index, stroke volume index, reduction in total systemic resistance) were randomized in a nonblinded fashion to the conventional (11 patients) or conventional plus L-dopa (11 patients) treatment groups. During the study period, two patients, one from each group, died. They were excluded from the analysis. The final analyzed study group consisted of 20 men, aged 33-69, in New York Heart Association functional class IV (9 patients) and III (11 patients). The cause of congestive heart failure was primary dilated cardiomyopathy in 11 patients and ischemic heart disease in 9 patients. After 3 months' treatment, all patients were crossed over. Clinical, radiographic, radionuclide, and hemodynamic evaluation was repeated at the end of the 3-month treatment period. After 3 months of therapy with L-dopa in each group (covariance analysis), there was improvement in clinical, radiographic (relative heart volume, -128 mL/m2), radionuclide (left ventricular ejection fraction, +4.6; right ventricular ejection fraction, +4.8%), hemodynamic (mean pulmonary wedge pressure, -8 mmHg; total systemic resistance, -1.8 Wu; total pulmonary resistance, -3.5 Wu), and neurohumoral (noradrenaline, -218 pg/mL) measures., Conclusions: The addition of L-dopa to conventional therapy has beneficial short- and long-term effects in patients with severe left ventricular dysfunction.

The study group consisted of 8 men with congestive heart failure. They ranged in age from 33 do 63 years (mean 48). Three patients were in class III NYHA, five in class IV. Idiopathic cardiomyopathy was diagnosed in 6 patients, one individual displayed ischemic heart disease and one patient was after mitral and aortic-valve replacement despite a normally functioning prosthetic valve. L-dopa was given orally beginning with 250 mg every six hours until a total daily dose of 4.0 g was achieved with no side effects (patients additionally received 50 mg of pyridoxine hydrochloride). Afterwards L-dopa was withheld for 24-36 hours. Having completed this washout period, patients underwent right heart catheterization, with placement of a balloon-tipped thermodilution catheter in a pulmonary artery, so that balloon inflation allowed recording of the pulmonary capillary wedge pressure. Right atrial and pulmonary arterial pressures were monitored continuously. Systemic arterial pressure was measured by mercury manometer. Cardiac output was determined by the thermodilution technique. Rest and effort hemodynamic measurements were repeated before and one, three hours after administration of 1-dopa. The base-line hemodynamic values were consistent with the clinical presentation of severe congestive heart failure. The average cardiac index (CI-1/min/m2--rest--1.93; 25 Watt-3.1) and stroke volume index (SVI-m1/m2--rest--22.2; 25 Watt-32.0) were markedly lowered. Left ventricular filling pressure and pulmonary artery pressure were elevated. The systemic vascular resistance was significantly increased (SVR -j.W.--rest--22.7; 25 Watt-14.2). Administration of 1-dopa resulted in the increase in cardiac index and stroke volume index accompanied by a substantial reduction in systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)