Different Degrees Of Heart Failure Research Articles

#2970 Heart failure with preserved ejection fraction on chronic kidney patients: innocent bystander? A cohort study in Portuguese population

Abstract Background and Aims Heart failure (HF) consists in a significant public health challenge, with high prevalence worldwide and a substantial impact on morbidity and mortality. In chronic kidney disease (CKD), HF can act both as a risk factor and a complication, exacerbating the overall outcomes for affected individuals. This study aims to elucidate the prevalence of distinct types of heart failure, encompassing preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmrEF), and reduced ejection fraction (HFrEF) in CKD patients. Moreover, we purpose to identify the potential of these subtypes to influence the outcomes of mortality and start of kidney replacement therapy (KRT), as a different therapeutic approach is suitable for each. Method Observational retrospective cohort study of 3008 CKD patients, with follow-up in Nephrology out-patient clinic in a Portuguese hospital, from February, 2012 to October, 2019. Ejection fraction was accessed by echocardiogram and information was collected from health records. To access mortality, patients who started KRT along the study were excluded. Results A total of 3008 patients, of which 91.7% Caucasians and 54.5% males, with an average age of 68.2 (±15.9) years was enrolled in the study. The mean follow-up time was 3.21 (±1.97) years and the mean estimated glomerular filtration rate at baseline was 47.63 ± 33.1 ml/min/1.73 m2. Among the participants, 769 individuals (25.5%) were diagnosed with HF. Specifically, 319 patients (41.5%) exhibited HFpEF; 85 patients (11%) had HFmrEF, and 117 patients (15.2%) had HFrEF, while the ejection fraction (EF) was unknown in 32.2% of cases. In the HF group, the incidence of diabetes was 55.6%, compared to 37.5% in the non-HF group. As for hypertension, the prevalence of was 91.8% in the HF group and 78.6% in the non-HF group. When assessing all-cause mortality during the follow-up, the hazard ratio (HR) for the HF group was 3.54 (95% CI, 2.94-4.26) compared to the non-HF group. Furthermore, for the initiation of KRT, the HR was 1.57 (95% CI, 1.19-2.06), favoring patients without heart failure. Across different types of HF, in comparison to the group without HF, the hazard ratio during follow up were notably different. Specifically, the HR was 5.39 (95% CI, 3.66-7.94) for patients with HFrEF, 3.43 (95% CI, 2.18-5.40) for patients with HFmrEF and 2.99 (95% CI, 2.32-3.87) for the HFpEF. When assessing the initiation of kidney replacement therapy (KRT), HFrEF and HFpEF also exhibited statistically different data comparing to those without HF. Specifically, HFrEF showed a HR of 2.14 (95%, 1.27-3.63), while HFpEF had a HR of 1.79 (95%, 1.25-2.56). The Kaplan-Meier analysis demonstrated a steeper descent curve for both survival and start of KRT for the HF group compared to the non-HF group (log-rank p < 0.0001) over the study period. Within the HF group, the worst survival outcomes were observed in the HFrEF subgroup, followed by HFmrEF and HFpEF (log-rank p < 0.0001). Conclusion Heart failure is a prevalent condition in CKD patients and worsens outcomes. Our analysis of real-world data suggests a threefold higher risk of mortality among for patients with HF, and a fivefold increase in the subgroup of HFrEF, comparing to patients without HF. Notably, preserved EF yielded a HR of 3.3 for mortality when compared to those without heart failure, underscoring the importance of clinical accurate assessment, since both entities may present with preserved ejection fraction in echocardiogram. Despite the study's sample limitations and the fact that it is unicentric, we believe this work holds significance as it highlights the importance of the establishment of different degrees of HF as it can change the prognosis in terms of mortality and progression to kidney replacement therapy in CKD patients. In addition to the established association between reduced EF and mortality, the HFpEF showed to exert a notable influence on outcomes comparing to patients without HF. This emphasizes the importance of not neglecting this entity, as it should treated appropriately.

Cardiac workload study in patients with hypertrophic cardiomyopathy

The relevance of studying the heart load is determined by the need to assess its reserves at different degrees of heart failure for further selection of treatment tactics. The aim of the work is to evaluate the influence of pressure and cardiac output changes on the left and right ventricular workload in patients with hypertrophic obstructive cardiomyopathy. The haemodynamic data of 69 patients divided into two subgroups according to the value of cardiac index greater and less than the mean value were considered. It was found that the change in the left ventricular power of the heart of patients with hypertrophic obstructive cardiomyopathy is determined by the change in both cardiac index and blood pressure. In better-off patients with high cardiac index, the effect of blood pressure is higher and cardiac output is lower. In severe patients with a low cardiac index, the influence of blood pressure is reduced and cardiac index is increased. The formation of right ventricular power, both in patients with high cardiac index and low, is not affected by changes in cardiac output. Changes in the right ventricular power index are determined by variations in pulmonary artery pressure to a greater extent in well patients and to a lesser extent in severe patients. Since there are 23.1% variations in cardiac index and 60% variations in pulmonary arterial pressure, it is assumed that there is a regulatory mechanism that changes cardiac output opposite to pulmonary artery pressure fluctuations. Comparison of left and right ventricular power indices with the data given in the literature showed that both for all examined patients with hypertrophic obstructive cardiomyopathy and divided into groups, the average values of left and right ventricular power indices correspond to the range of power fluctuations in healthy people at rest. The range of left ventricular power index variation by 3.5 times, and right ventricular power index variation by 10 times in patients with hypertrophic obstructive cardiomyopathy is determined by multifunctional relationships of cardiovascular system function indices (pressures and cardiac output), which determines the necessity of personalised therapy selection, taking into account the mechanisms of their formation. The results obtained during the study of the effect of changes in pressure and cardiac index on the power developed by the left and right parts of the heart must be taken into account when choosing therapy in patients with hypertrophic obstructive cardiomyopathy. Practical significance. The results will be used in the choice of treatment in order to optimize the load on the heart in patients with hypertrophic obstructive cardiomyopathy.

Diagnosis and treatment of arrhythmogenic cardiomyopathy in children

Objective: To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children. Methods: A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022. Results: A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable. Conclusions: ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.

ARTERYAL HIPERTENSION AND VERY ELDERLY PATIENTS. THE EXPERIENCE OF AN INTERNAL MEDICINE DEPARTMENT

Objective: The purpose of this study is to highlight the clinical and paraclinical characteristics of fragile hypertensive patients, over 85 years old, admitted to a mixed internal medicine department (Covid and non-Covid) between January 2022 and October 2022. Design and method: Between January 2022 and October 2022, 80 patients with a primary or secondary diagnosis of arterial hypertension were admitted, of which only 23 (28.75%) were over 85 years old. Of the 23 patients, 13 (56.52%) were hospitalized with a diagnosis of Sars Cov 2 infection. Regarding the gender distribution, 12 are women (52.17%) and 11 are men (47.82%). Patients comorbidities: 14 patients (60.86%) with different degrees of heart failure, atrial fibrillation (39.13%) - 8 patients and one patient was diagnosed with atrial fibrillation during hospitalization, cognitive disorders and dementia in a proportion of 47.82 % (11 patients) and a significant number of patients were admitted with moderate-severe anemia (13 patients, 56.52%). Of the 9 patients with atrial fibrillation, 5 are male (55%) and 4 (45%) female, cardiac enzymes (troponin and CK MB) are within normal limits in 8 patients. During the medical tests, 3 patients (13.04%) were diagnosed withdifferent of neoplasia. Only 2 patients (8.69%) presented slight dyselectrolytemia (hyponatremia and hypokalemia). Results: Pathologies are treated with: angiotensin converting enzyme inhibitors (17.39% - 4 patients), calcium channel blockers (39.13% - 9), anticoagulants (39.13% - 9 patients), diuretics (26.08 %-6 patients) and beta blockers (11 pac-47.82%). 13 patients (56.52%) died and 43.47% were discharged with an improved condition. 9 patients died as a result of Covid multiple organ system failure, 1 death was of cardiovascular cause and 3 non-Covid pulmonary failure deaths. Conclusions: Frail patients, older than 85 years, with multiple comorbidities, require detailed investigations and adjustments of medication doses according to their status in order to maintain the discreet balance in which they are.

Postoperative complications in pediatric cardiac surgery patients done in a tertiary hospital

Introduction Postoperative complications can involve several organs and have a major effect on in-hospital stay length and quality of life of the children after discharge from the hospital. Although the complications are strictly related to the surgical procedure, postoperative pulmonary complications represent an important and probably underestimated cause of morbidity and mortality in postoperative pediatric heart surgery. Aim The aim of this study was to evaluate the relation between complication and the overall outcome. Patients and methods This retrospective descriptive study included 100 children (ages from 0 to 18 years old, excluding preterm babies) who underwent open heart surgery in Cardiothoracic Surgery Department of Assiut University in a 1-year period. The preoperative and intraoperative parameters included technique of operation, cardiopulmonary bypass time, and aortic cross-clamp time. The postoperative parameters included occurrence of postoperative complications, such as arrhythmias, heart failure, pulmonary congestion with chest infection, wound infection, and bleeding, and hospital stay of the patients. Results The occurrence of complications after congenital heart surgeries using cardiopulmonary bypass has significant relation with the cardiopulmonary bypass time; therefore, the longer the cardiopulmonary bypass time, the more the probability of cardiac and extracardiac complications. This study shows the same result as studies in adult surgery, demonstrating that complications after heart surgery significantly are associated with increased hospital stay time. Conclusion Surgery is the optimal and the final treatment for congenital heart diseases; nearly a quarter of the patients who undergo congenital heart surgery experience postoperative complications, complex congenital heart diseases with different degrees of heart failure, or respiratory failure, and carry more risk for complications. So close monitoring and timely intervention and treatment are very critical to avoid occurrence of multiple complications as reported in our study.

The influence of metformin and the presence of type 2 diabetes mellitus on mortality and hospitalisation in patients with heart failure.

Metformin is one of the antihyperglycaemic drugs, reducing the risk of major cardiovascular events, including fatal ones. Although it is formally contraindicated in moderate and severe functional stages of heart failure (HF), it is commonly used in patients with concomitant type 2 diabetes mellitus (T2DM). We sought to evaluate the effect of metformin and T2DM on total mortality and hospitalisation rates in patients with HF. This retrospective analysis included 1030 adult patients (> 18 years) with HF from the Polish section of the HF Long-Term Registry (enrolled between 2011 and 2014). Patients with T2DM (n = 350) were identified and divided into two groups: those receiving metformin and those not. Both groups were subjected to one-year follow-up. Mean patient age was 65.3 ± 13.5 years, with the predominance of male sex (n = 726) and obesity (mean body mass index 30.3 ± 5.5 kg/m2) and mean left ventricular ejection fraction was 34.3% ± 14.1%. Among patients with T2DM (n = 350) only 135 (38.6%) were treated with metformin. During one-year follow-up, 128 patients with HF died, of whom 53 had T2DM (15.1% vs. 10.9%, hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.87-0.91, p = 0.045). Metformin was associated with a lower mortality rate compared to other antihyperglycaemic agents (9.6% vs. 18.6%, HR 0.85; 95% CI 0.81-0.89, p = 0.023). There were no significant differences in the hospitalisation rate, including that due to HF decompensation, among patients treated with metformin and the remainder (53.5% vs. 40.0%, respectively HR 0.93, 95% CI 0.82-1.04, p = 0.433). Metformin treatment in patients with different degrees of HF and T2DM is associated with a reduction in mortality and does not affect the hospitalisation rate.

Replication of pressure-volume loop with controllable ESPVR and EDPVR curves on a personalized mock circulatory loop based on elastance function.

In the development of a left ventricular assist device (LVAD), it is important to evaluate the LVAD's hemodynamic effect on the compromised left ventricle (LV) before surgical implantation. The mock circulatory loop (MCL) is widely accepted as an in vitro test platform to evaluate LVADs across a wide range of operational conditions as a way to examine how the device and the cardiovascular system interact. Unfortunately, most MCLs represent an oversimplified model of cardiac function, with disease states simulated through generalized changes in heart rate and stroke volume. Because heart failure (HF) severity varies substantially among patients, an MCL is needed that can mimic the pressure-volume loop of an individual patient. In this work, two numerical elastance models, derived from a specific pressure volume loop template, were used to control the LV simulator of the MCL to simulate different degrees of HF. The numerical elastance model was then scaled to change the slopes of the end-systolic (ESPVR) and end-diastolic (EDPVR) pressure volume relationship curves to simulate systolic and diastolic dysfunction. The resulting experimental pressure volume loops are consistent with theoretical loops, demonstrating the feasibility of creating an MCL that can be customized for the patient.

Evaluation of Energy Loss in Left Ventricle Obtained by Vector Flow Mapping in Patients with Different Degrees of Heart Failure

Evaluation of Energy Loss in Left Ventricle Obtained by Vector Flow Mapping in Patients with Different Degrees of Heart Failure

Reseachthevalueof the Type B Natriuretic Peptide (Nt-Probnp) In the Treatment of Heart Failure in Children

Measurement of the type B Natriuretic peptide(NT-ProBNP) has become a potent diagnostic aid as a means of identifying patients with heart failure.Thefore, we conducted a study assess the effects of NT-proBNP- guided therapy of children with heart failure. Objective: To study the value of the type B Natriuretic peptide (NT-proBNP) in treatment of heart failure in children. Study method: A prospectivecase-control study was carried out. Study patients: 100 children were diagnosed with heart failure and they were also classified into different degrees of heart failure according to modified Ross Heart Failure Classification. The control group had 100 patients without cardiovascular disease. Quantitative serum NT-proBNP concentrations and cardiac ultrasound data were analyzedbefore and after treatment and compared between the treatment group and the control group. Results: NT-proBNP concentration in a disease group (HF) was 1125.26 ± 1823.40 pg/ml. The concentration level in the control group was 26.74 ± 38.79 pg / ml. The difference between the two groups is statistically significant (p <0.01). NT- ProBNP concentrations decrease with the state to improve the level of heart failure after treatmnet. Conclusion: NT-proBNP is valuable to assess the outcomes oftreatmentfor children with heart failure. Keyword: NT-ProBNP, heart failure, children

Alteration of Notch signaling and functionality of adipose tissue derived mesenchymal stem cells in heart failure

AimCirculating mesenchymal cells increase in heart failure (HF) patients and could be used therapeutically. Our aim was to investigate whether HF affects adipose tissue derived mesenchymal cell (adMSC) isolation, functional characteristics and Notch pathway. Methods and resultsWe compared 25 patients with different degrees of HF (11 NYHA classes I and II and 14 NYHA III and IV) with 10 age and gender matched controls. 100% adMSC cultures were obtained from controls, while only 72.7% and 35.7% from patients with mild or severe HF (p<0.0001). adMSC from HF patients showed higher markers of senescence (p16 positive cells: 14±2.3% in controls and 35.6±5.6% (p<0.05) and 69±14.7% (p<0.01) in mild or severe HF; γ-H2AX positive cells: 3.7±1.2%, 19.4±4.1% (p<0.05) and 23.7±3.4% (p<0.05) respectively), lower proliferation index (Ki67 positive cells: 21.5±4.9%, 13.2±2.8% and 13.7±3.2%, respectively), reduced pluripotency-associated genes (Oct4 positive cells: 86.7±4.9%, 55±12% (p<0.05) and 43.3±8.7% (p<0.05), respectively; NANOG positive cells: 89.8±3.7%, 39.6±14.4% (p<0.01) and 47±8.1%, respectively), and decreased differentiation markers (α-sarcomeric actin positive cells: 79.8±4.6%, 49±18.1% and 47±12.1% (p<0.05) and CD31-positive endothelial cells: 24.5±2.9%, 0.5±0.5% (p<0.001) and 2.3±2.3% (p<0.001), respectively).AdMSC from HF patients also showed reduced Notch transcriptional activity (lowered expression of Hey 1 and Hey 2 mRNAs). Stimulation with TNF-α of adMSC isolated from controls affected the transcription of several components of the Notch pathway (reduction of Notch 4 and Hes 1 mRNAs and increase of Notch 2 and Hey 1 mRNAs). ConclusionsIn HF yield and functionality of adMSC are impaired and their Notch signaling is downregulated.

Changes and significance of plasma cardiotrophin-1 in children with heart failure

Objective To explore the changes and significance of plasma cardiotrophin-1(CT-1) in children with heart failure. Methods Forty children with heart failure(NYHA II, n=14; NYHA Ⅲ, n=16; NYHA Ⅳ, n=10) were chosen as observation group, and 20 healthy children without heart failure were taken as healthy control group.Plasma CT-1 was measured by a double antibody sandwich enzyme-linked immunosorbent assay(ELISA). N terminal probrain natriuretic peptide(NT-pro BNP) concentration was tested by Pu Rui fluorescent dry quantitative analyzer.Left ventricular ejection fraction(LVEF) was evaluated by GE Vivid 7 doppler echocardiography and cardiac function assessed by modified ROSS score.Plasma CT-1 level, NT-pro BNP and LVEF were compared between the 2 groups.The correlation of plasma CT-1 level with NT-pro BNP and LVEF were analyzed in patients with different degrees of heart failure. Results Plasma levels of CT-1 and NT-pro BNP were significantly higher in children with heart failure than those in healthy control group(P<0.01), and with progression of heart failure, the levels of CT-1 and NT-pro BNP progressively increased in heart failure children.Plasma CT-1 level in different NYHA had statistical significance(F=55.5, P<0.01). Plasma CT-1 level was positive correlated with NT-pro BNP and modified ROSS score(r=0.787, 0.848, all P<0.01), and negative associated with LVEF(r=-0.66, P<0.01), respectively, in heart failure children. Conclusions Plasma CT-1 level is significantly elevated in heart failure children.There are good correlation among CT-1, NT-pro BNP and LVEF.Plasma CT-1 is a reliable marker of reflecting the severity of heart failure, combined with NT-pro BNP detection helps to improve the diagnostic accuracy of heart failure in children. Key words: Cardiotrophin-1; N terminal probrain natriuretic peptide; Heart failure; Child

Pharmacokinetics of Pentoxifylline and Its Main Metabolites in Patients With Different Degrees of Heart Failure Following a Single Dose of a Modified‐Release Formulation

Pentoxifylline (PTX) is extensively metabolized in the body, and all its 3 plasma metabolites (M1, M4, M5) are pharmacologically active. The authors evaluated the pharmacokinetics of PTX and its metabolites in 20 patients with chronic heart failure (CHF). Eleven had moderate and 9 severe CHF. The time courses of PTX, M1, M4, and M5 plasma levels were determined after oral administration of a sustained-release 600-mg tablet of PTX, and for each compound, AUC, maximal plasma concentration (C(max)), and time to C(max) (T(peak)) were calculated. Compared with patients with moderate CHF, those with severe CHF showed a significant delay in T(peak) of PTX (3.9 vs 1.6 hours) and M5 (5.6 vs 3.6 hours), a 59% significant increase in M5 AUC, and a 56% nonsignificant increase in PTX AUC. In the whole population, the AUCs of PTX, M4, and M5 were inversely correlated with markers of liver function, whereas the AUCs of M4 and M5 were inversely correlated with the creatinine clearance. In view of the kinetic features of slow-release formulations (flip-flop phenomenon), the delay in T(peak) of PTX in patients with severe CHF compared with moderate CHF should be ascribed to a reduced elimination rate.

Effect of spironolactone on C-reactive protein levels in patients with heart disease

Animal evidence shows that aldosterone is pro-inflammatory and that aldosterone blockade is anti-inflammatory. Therefore part of the beneficial effect of aldosterone blockade that might contribute to it reducing mortality could be an anti-inflammatory effect. However, there are no previous data on whether aldosterone blockade is anti-inflammatory in man. We performed 4 separate studies to investigate whether spironolactone treatment would reduce levels of C-reactive protein (CRP), a marker of inflammation, in serum samples taken from patients suffering from different degrees of heart failure. We found in all 4 studies that spironolactone had no significant effect compared with placebo, on CRP levels in these patients. These studies provide evidence against the hypothesis that the clinical benefits produced by aldosterone blockade are due to it having anti-inflammatory effects.

Radionuclide monitoring of left ventricular function after sublingual nifedipine administration at rest and during moderate physical activity

Background. This study investigates the acute effects of nifedipine administration on left ventricular (LV) function in patients with different degrees of heart failure at a fixed heart rate under resting conditions and during moderate physical activity. Methods and Results. Eleven patients with non-rate-responsive DDD pacemakers were studied. According to baseline LV ejection fraction, patients were divided into 2 groups: 6 patients with an ejection fraction of less than 50% (group 1) and 5 patients with an ejection fraction of 50% or more (group 2). LV function was monitored by a radionuclide system (Vest) at rest and during moderate physical activity (10-minute walk test) before and after sublingual nifedipine administration (10 mg). In all patients, both the systolic blood pressure and diastolic blood pressure were significantly reduced (P < .05) 6 minutes after nifedipine administration. In group 1, end-diastolic volume and ejection fraction decreased after 3 minutes and remained significantly lower (P < .05) than resting values until 10 minutes after drug administration, whereas end-systolic volume was unchanged. In group 2, nifedipine induced a minor decrease in end-diastolic volume and a slight but not significant decrease in ejection fraction and end-systolic volume. During the walk test, nifedipine induced similar changes in all parameters of cardiac performance in both groups. Conclusions. In patients with impaired LV function, acute nifedipine administration has a negative effect on cardiac performance, which occurs before blood pressure reduction. On the other hand, during moderate physical activity, nifedipine does not affect the improvement in LV function. (J Nucl Cardiol 2001;8:669-76.)

Hypotension after first-dose ACE inhibitor administration in heart failure--should doctors stop worrying?

Heart failure therapy has dramatically changed in the last two decades. Whereas before, the focus was on symptomatic treatment of heart failure with diuretics and digitalis glycosides, the advent of ACE inhibitors, beta-blocking drugs and aldosterone receptor antagonists has drastically changed our insight in how to approach the heart failure patient. A number of large, controlled clinical trials have clearly indicated that these agents may impact on the natural history of the syndrome and not only improve symptoms, but, in addition, reduce morbidity and mortality. The first drug developed in this context, the ACE inhibitor, has been evaluated against placebo in patients with mild, moderate and severe heart failure, improving survival in each category; its reductions in mortality ranging from 16% in mild to moderate heart failure to 31% in patients with severe heart failure [1,2]. Furthermore, ACE inhibitors decrease hospitalisations for heart failure by approximately 15%. Importantly, in patients who have a reduced systolic left ventricular function, but are still asymptomatic, ACE inhibition prevents or retards the development of heart failure in 37% [3]. When then a beta-blocker is added to the ACE inhibitor, a further 30–35% reduction in mortality is achieved as well as an additional 30% reduction in hospitalisations in both mild, moderate as well as severe heart failure [4–7]. Similar figures are obtained when in advanced heart failure an aldosterone antagonist is added. In the only study investigating this, the RALES study, a 30% reduction in mortality and in cardiovascular hospitalisations was observed over and above those achieved by ACE inhibitors alone [8]. Thus, accumulating evidence from various controlled studies disprove the old notion of heart failure being a terminal disorder requiring symptomatic rather than preventive treatment. As a consequence the focus has shifted towards treatment in the early stages of the disease and to prevention. One might expect that, against this background of a sizeable improvement of survival and significant reductions in both heart failure and all-cause hospitalisations, patient management would have changed significantly over the past years. Indeed, patient management guidelines specify the need for early treatment with ACE inhibitors and beta-blockers, in the later stages followed by aldosterone antagonist being mandatory in the treatment of heart failure [9]. Nevertheless, despite the available evidence-based treatment strategies and clear and precise patient management guidelines, few patients actually receive optimal medical treatment. Somehow evidence-based medicine and strategies have not translated to clinical practice. Patients either do not receive the therapy they need or receive it in insufficient dosages. In the case of ACE inhibition this is particularly true. Nearly 15 years after the first large study demonstrating a beneficial effect of ACE inhibition on mortality in severe heart failure [1], later followed by other studies providing the same evidence in different degrees of heart failure [2,10], at present only 20–40% of patients with heart failure receive an ACE inhibitor, usually in dosages that do not conform to those used in the large studies, which, at least in that context, had shown their beneficial effect. Why is this? Quite a few possibilities may apply. Heart failure patients or patients at risk of heart failure are often not detected, as the required diagnostic tools are not or insufficiently available for the health care provider, who, in most instances, is the general practitioner. The patient or his relatives may to some extent be unknowingly at fault and be unaware of the disease, not perceiving its seriousness, and also be unaware of the therapeutic possibilities and not demand them. It is also likely that the health care provider may be at fault, again without realizing this. Health care providers of different backgrounds, e.g. general practitioners, internists or geriatricians, may not be aware of the results of the large, controlled studies showing the benefits of the ACE inhibitor. Doctors, including specialists, may not be convinced that the results of large, controlled studies on the effect of these medications

Prognostic value of baroreflex sensitivity assessed by phase IV of Valsalva manoeuvre in patients with mild-to-moderate heart failure.

In patients with heart failure, impairment of baroreflex function occurs early and contributes to sympathetic activation, however, at present its prognostic role has not been definitively established. To evaluate the prognostic significance of baroceptor impairment in patients with different degrees of heart failure. We enrolled 52 consecutive patients with heart failure, referred to our institution for functional evaluation. Twenty-eight suffered from ischemic cardiomyopathy and 26 from dilated cardiomyopathy. Thirteen patients were in NYHA class I, 20 in NYHA class II and 19 in class III. All patients underwent baroreflex assessment by phase IV Valsalva manoeuvre using Finapres finger monitoring of arterial blood pressure, echocardiography [with evaluation of left ventricular ejection fraction (LVEF), fractional shortening (LVFS), left ventricular end diastolic diameter (LVEDD) and mean pulmonary artery pressure] and functional evaluation by cardiopulmonary exercise test and 6-min walk corridor test within 2 days of hospital admission. Mean duration of follow-up was 26 months (range 6-35 months). At baseline, evaluation in 13 patients BRS was normal (>5 ms/mmHg), in 17 moderately impaired (1.5-5 ms/mmHg) and in 22 severely depressed (<1.5 ms/mmHg). Baroreflex function was relatively preserved in patients in NYHA class I (5.1+/-2.5) in comparison to patients in NYHA class II and III (2.1+/-2.3 and 2.08+/-1.9 ms/mmHg, respectively). Of the 52 patients who entered the study at the end of follow-up 15 died of cardiac cause and 5 underwent heart transplantation. Survival free from heart transplantation was 62% in patients with normal baroreflex function, 62% in patients with moderate impairment of baroreflex and 66% in patients with major derangement. NYHA class, LVEF, LVFS and LVEDD were significantly associated with event free survival while baroreflex function was not. Our results suggest that evaluation of BRS impairment by phase IV Valsalva manoeuvre has limited prognostic value in patients with heart failure.

Trasplante cardíaco en el ventrículo único

Univentricular heart is an uncommon congenital heart disease. A select group of these patients (those with severe pulmonary stenosis or atresia) can reach adult age with different degrees of heart failure and severe chronic hypoxemia. Patients with adequate pulmonary tree development are likely to undergo heart transplantation when usual palliative techniques are contraindicated. Three cases of univentricular heart with pulmonary stenosis in which heart transplantation was the optimal choice are reported. Different techniques used to assess pulmonary tree development are analysed.

Changes in cardiac β-Adrenoceptors in human heart diseases: Relationship to the degree of heart failure and further evidence for etiology-related regulation of β1 and β2 subtypes

Radioligand binding studies were performed to investigate total β-adrenoceptor density (Bmax) and β 1 and β 2 subtype distribution in left ventricular biopsies obtained from 8 prospective transplant donors serving as controls and from 143 patients with different degrees of heart failure (NYHA class II to IV) undergoing aortic or mitral valve surgery due to aortic or mitral stenosis, aortic or mitral regurgitation, as well as combined aortic or mitral valve lesions (stenosis and regurgitation). In 13 other patients, heart failure was due to hypertrophic obstructive cardiomyopathy ( N = 6, NYHA III), tetralogy of Fallot ( N = 4, NYHA III), or Becker's muscular dystrophy ( N = 3, NYHA IV). Bmax was assessed by (−)-(1251)-iodocyanopindolol used as radioligand. Competition experiments with the highly selective β 1-adrenoceptor antagonist CGP 20712A were performed for determination of β 1- and β 2-adrenoceptor subtypes. In biopsies taken from transplant donors, the Bmax was found to be 70.1 ± 5.8 fmol/mg protein. In all groups investigated the extent of total β-adrenoceptor downregulation was related to the degree of heart failure. The decrease in Bmax was found to be about 20% (NYHA II), 45% (NYHA III), and 60% (NYHA IV) when compared with controls. There was no significant difference in the reduction of total β-adrenoceptor density between isolated aortic or mitral valve diseases and combined valve lesions. Independent of the degree of heart failure, selective downregulation of the β 1 subtype was found in patients with isolated or combined aortic valve diseases, hypertrophic obstructive cardiomyopathy, and Becker s muscular dystrophy. A reduction of both β 1 and β 2 adrenoceptors was found in patients with heart failure due to isolated and combined mitral valve diseases and tetralogy of Fallot. It is concluded that not only the degree of heart failure, but the etiology of the underlying heart disease may influence the β 1- and β 2-adrenoceptor subtype regulation.