Stages Of Congestive Heart Failure Research Articles

Novel nonsurgical left ventricular assist device and system

Treatment options for advanced stages of congestive heart failure remain limited. Left ventricular assist devices (LVADs) have emerged as a means to support failing circulation. However, these devices are not without significant risk such as major open chest surgery. We utilized a novel approach for device placement at the aorto-left atria continuity as a site to create a conduit capable of accommodating a percutaneous LVAD system. We designed and developed an expandable nitinol based device for placement at this site to create a shunt between the LA and aorta. Our experiments support this anatomic location as an accessible and feasible site for accommodation of an entirely percutaneous LVAD. The novelty of this approach would bypass the left ventricle, and thereby minimize complications and morbidities associated with current LVAD placement.

903NT-proBNP as a marker of effectiveness of cardiac rehabilitation after myocardial infarction

The need to assess the level of brain natriuretic peptide (N-terminal pro b-type peptide) in patients with congestive heart failure (CHF) is caused by diagnostic accuracy of the given marker. A research method: determination of the level NT-proBNP in the blood plasma in the late stages of the hospital and sanatorium treatment, and its dynamics (NT-proBNP1 – NT-proBNP2) (ΔNT-proBNP), as a criterion for the effectiveness of the carried therapy. The received results: As a result of examination and treatment of 52 persons with acute myocardial infarction, and send to the sanatorium stage of rehabilitation weak negative correlations between the taking of medicines (nitrates, inhibitors angiotensin converting enzyme, beta-blockers) and dynamics NT-proBNP (Δ) were not found (p>0,05). Only for medicines from the group of calcium antagonists (AC) and an indicator ΔNT-proBNP the correlation at the level of r=+0.39 (p<0,05) was significant. Thus it is impossible to exclude the influence AC on the functional state of the cardiovascular system (a myocardium relaxation, change the blood pressure and heart rate). For the indicator ΔNT-proBNP an average degree of correlation dependence with carried «magnetotherapy» (in addition to the basic treatment) (r=0.61), and less dependent – for iodobromine baths (r=0.35; p>0,05) was established. In this case, you should explain the positive impact of additional modern methods of treatment and rehabilitation by decrease in peripheral vascular resistance in patients with atherosclerotic defeat of vessels, improvement of the rheological structure of blood and lymphatic drainage condition at a reduced ejection fraction (EF) 50,5±8,1% (M±m), and Class I of CHF, both before and after treatment. ΔNT-roBNP is most preferable in an estimation of dynamics of a condition of patients with coronary artery disease (CAD) (-198,8±486,5 -459,5±644,2 ng/ml; p<0.05), rather than an indicator LVFV (left ventricular ejection fraction) (+2,4±30,9%) or functional class CHF (1,22±0,098 vs 1,28±0,11; p>0.05). ΔNT-roBNP minimum depending on quality of visualization of heart and subjectivity of an estimation of a clinical condition of patients. The sanatorium stage of rehabilitation of patients with CAD is characterized increase of tolerance to physical activity (increase of the maximum level METs +26,4+66%, the executed loading in Vt +20.9+80.1%) with decrease in level NTproBNP. High values of NT-proBNP at patients with CAD and CHF in the course of rehabilitation allow to assume presence of significant defeat of coronary arteries in pool right coronary artery and diagonal branches, taking into account the data coronary angiography, whereas considerable dynamics of the ΔNT-proBNP in a greater degree is characteristic for defeat left circumflex artery. Conclusions: The determination of the level NT-proBNP is an important tool in the development of proper patient treatment with CHF, including situations where the stage CHF in the course of treatment does not change at all.

Radial and Longitudinal Strain and Strain Rate Assessed by Speckle‐Tracking Echocardiography in Dogs with Myxomatous Mitral Valve Disease

Assessment of left ventricular (LV) function using conventional echocardiographic methods is difficult in mitral regurgitation (MR) owing to altered hemodynamic loading conditions. Newer methods such as speckle-tracking echocardiography (STE) provide assessment of LV strain (St) and strain rates (SR). Global St and SR are 1) decreased in dogs with clinical signs of congestive heart failure (CHF) due to myxomatous mitral valve disease (MMVD) compared with clinically healthy dogs, and are 2) associated with conventional echocardiographic indices of MMVD severity. The study subjects were 93 privately owned dogs with different MMVD severities. Prospectively recruited dogs were grouped according to MMVD severity based on echocardiographic evaluation of MR and presence of clinical signs. Global radial and longitudinal St, SR, and indices of LV dyssynchrony were assessed. On group-wise comparisons, dogs with CHF had increased global longitudinal St, global longitudinal and radial SR in systole (SRs), and early diastole (SRe) compared with dogs with no or minimal MR (all P < .04). On multiple regression analyses, these global STE variables increased with degree of MR, but associations with left atrial-to-aortic root ratio (LA/Ao) were best described by second-order polynomial equations. Thus, curvilinear relationships were found for LA/Ao and longitudinal St, SRs, and SRe (all P < .002) and radial St and SRe (all P < .001). Assessed by STE, LV function appeared to be augmented in moderate-to-severe disease. However, at CHF stages with greatly enlarged atria, a decrease to levels comparable to dogs with no or minimal MR was observed.

CorBene

Congestive heart failure (CHF) is one of the most common medical disorders. The prognosis tends to be unfavorable and the quality of care needs further improvement. The aim of the CorBene project is to improve the health-related quality of life and the prognosis in patients in all stages of CHF and to reduce the hospitalization rate. For this purpose a modern collaborative treatment program involving all relevant health care professionals was developed. The key feature is the close collaboration between family physicians, practicing cardiologists, hospitals and rehabilitation facilities. The CorBene model was launched in Cologne and then spread to North-Rhine/Westphalia and to Saarland. Currently, there is the possibility to offer it in all German states. Preliminary analyses confirm an optimal, guideline-based therapy of CHF.

Partial external mitral annuloplasty in dogs with myxomatous mitral valve degeneration and congestive heart failure: Outcome in 9 cases

Objective To report the outcome of partial external mitral annuloplasty in dogs with congestive heart failure (CHF) due to mitral regurgitation caused by myxomatous mitral valve degeneration (MMVD). Animals, materials and methods Nine client-owned dogs with CHF due to mitral regurgitation caused by MMVD. Surgery consisted of a double row of pledget-butressed continuous suture lines placed into the left ventricle parallel and just ventral to the atrioventricular groove between the subsinuosal branch of the left circumflex coronary artery and the paraconal branch of the left coronary artery. Results Two dogs died during surgery because of severe hemorrhage. Two dogs died 12 and 36 h after surgery because of acute myocardial infarction. Three dogs were euthanized 2 and 4 weeks after surgery because of progression of CHF, 1 was euthanized 30 days after surgery for non-cardiac disease, and 1 survived for 48 months. In the 5 dogs that survived to discharge there was no significant change in the left atrium to aortic ratio with surgery (3.6 ± 0.56 before surgery; 3.1 ± 0.4 after surgery; p = 0.182), and no significant change in mitral regurgitant fraction in 4 dogs in which this measurement was made (78.7 ± 2.0% before surgery; 68.7 ± 7.5% after surgery; p = 0.09). Conclusions Partial external mitral annuloplasty in dogs with CHF due to MMVD was associated with high perioperative mortality and most dogs that survived to discharge failed to show clinically relevant palliation from this procedure. Consequently, partial external mitral annuloplasty is not a viable option for dogs with mitral regurgitation due to MMVD that has progressed to the stage of CHF.

The bone marrow–cardiac axis: role of endothelial progenitor cells in heart failure☆

Congestive heart failure (CHF) remains a leading cause of mortality in the developed world. The complex mechanisms involved in the pathophysiology of heart failure (HF) explain some of the limited impact of current recognised therapeutic strategies. There is, therefore, a definite need for new alternative molecular and biological pathways to address the treatment of this condition. Over the past decade, much research has focussed upon identifying the ideal cell type to promote myocardial regeneration. Recently, striking reports suggested the concept that bone-marrow (BM)-derived endothelial progenitor cells (EPCs) participate in cardiac regeneration and function recovery in the setting of progressive HF. The modulation of this complex interaction between the BM and the circulating EPCs could be at the crossroad of multiple therapeutic strategies aimed to protect or restore the myocardium in the setting of the CHF. However, there are uncertainties and unresolved issues regarding the mechanisms possibly responsible for the functional benefits observed in chronic experimental and pre-clinical studies. Hence, the BM-cardiac axis concept has created overwhelming enthusiasm and subsequent scepticism in the field of cardiac repair and regeneration. Further intensive research in basic science and clinical arenas are needed to elucidate the potential association between BM and heart function recovery, particularly in the progression towards advance stages of CHF. In this review, we focus on the importance of the BM-cardiac axis and BM-derived EPCs in the pathophysiology, clinical progression and potential treatment of CHF.

Crataegus extract WS®1442 in patients with congestive heart failure class NYHA II-III: The SPICE trial

WS®1442 is registered for treatment of early stages of congestive heart failure (CHF) in several countries, e.g. Germany. As there was no study available regarding efficacy and safety of WS®1442 in more severely impaired patients already treated with optimal therapy, SPICE (Survival and Prognosis: Investigation on Crataegus Extract WS®1442) was performed. SPICE is a double-blind mortality trial conducted in 156 centres in 13 European countries. Patients were eligible if their left ventricular function was markedly impaired (WMI≤1.2). These patients already receiving optimal pharmacological therapy (83% ACE-inhibitors, 64% β-blockers, 56% glycosides, 39% spironolactone, 85% diuretics) were randomised to WS®1442 or placebo. Treatment duration was 2 years; primary endpoint was the time until first cardiac event (sudden cardiac death (SCD), death due to progressive heart failure, myocardial infarction, hospitalization; FCE). 2681 patients (mean age 60yrs, 84% males, 44% NYHAIII, mean LVEF 24%) were randomised and evaluated. At all times, WS®1442 was superior to placebo regarding FCE, but without reaching statistical significance. For the first 18 months of WS®1442 treatment, deaths due to cardiac cause were reduced significantly (–20%; p=0.046) and WS®1442 postponed cardiac deaths by four months. This effect was even more pronounced in patients with LVEF≥25% (–33% reduction; p=0.044) and also holds true for total mortality and SCD up to 24 months. In conclusion, the study confirms the safety of WS®1442 in CHF patients with a mean LVEF of 24% and being treated with optimal pharmacological therapy. More important, WS®1442 may postpone deaths due to cardiac cause in this patient population.

The ZDSD, a New Rat Model of Metabolic Syndrome: Evidence of Cardiovascular Disease

A new rat model, the ZDSD, has an intact leptin system while having typical metabolic syndrome biomarkers. The goal was to determine if ZDSD also suffer from cardiovascular disease typical of metabolic syndrome. ZDSD and control SD blood pressures (BP) were monitored for several weeks. Right ventricular to left ventricular plus septum weight ratios, RV/(LV+S), were measured. None of the 6 ZDSD had high systemic BP. Two ZDSD developed systemic hypotension that correlated with severe diabetes and weight loss. ZDSD RV/(LV+S) tended to be higher than SD RV/(LV+S) indicative of RV hypertrophy and pulmonary hypertension. Results suggest that the severely diabetic ZDSD were in end stage congestive heart failure (CHF) resulting from a particularly malignant form of metabolic syndrome. A younger cohort of less severely diabetic ZDSD need to be studied in order to know if systemic hypertension plays a role in development of CHF in this model of metabolic syndrome.Supported by PreClinOmics. L Meulen and A Boice were 2009 Indy Project SEED Scholars supported by American Chemical Society (ACS), Lilly, DowAgroSciences, IUPUI Indiana Clinical and Translational Sciences Institute (CTSI)

Analysis of Metabolic Remodeling in Compensated Left Ventricular Hypertrophy and Heart Failure

Congestive heart failure (CHF) is associated with a change in cardiac energy metabolism. However, the mechanism by which this change is induced and causes the progression of CHF is unclear. We analyzed the cardiac energy metabolism of Dahl salt-sensitive rats fed a high-salt diet, which showed a distinct transition from compensated left ventricular hypertrophy to CHF. Glucose uptake increased at the left ventricular hypertrophy stage, and glucose uptake further increased and fatty acid uptake decreased at the CHF stage. The gene expression related to glycolysis, fatty acid oxidation, and mitochondrial function was preserved at the left ventricular hypertrophy stage but decreased at the CHF stage and was associated with decreases in levels of transcriptional regulators. In a comprehensive metabolome analysis, the pentose phosphate pathway that regulates the cellular redox state was found to be activated at the CHF stage. Dichloroacetate (DCA), a compound known to enhance glucose oxidation, increased energy reserves and glucose uptake. DCA improved cardiac function and the survival of the animals. DCA activated the pentose phosphate pathway in the rat heart. DCA activated the pentose phosphate pathway, decreased oxidative stress, and prevented cell death of cultured cardiomyocytes. Left ventricular hypertrophy or CHF is associated with a distinct change in the metabolic profile of the heart. DCA attenuated the transition associated with increased energy reserves, activation of the pentose phosphate pathway, and reduced oxidative stress.

Tissue Doppler and Strain Imaging in Dogs with Myxomatous Mitral Valve Disease in Different Stages of Congestive Heart Failure

Tissue Doppler imaging (TDI) including strain and strain rate (SR) assess systolic and diastolic myocardial function. TDI, strain, and SR variables of the left ventricle (LV) and the interventricular septum (IVS) differ significantly between dogs with myxomatous mitral valve disease (MMVD) with and without congestive heart failure (CHF). Sixty-one dogs with MMVD with and without CHF. Ten healthy control dogs. Prospective observational study. Radial motion: None of the systolic variables were altered and 3 of the diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Longitudinal motion: 2 systolic velocities and 3 diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Difference in systolic velocity time-to-peak between LV and IVS was significantly increased in dogs with MMVD with and without CHF compared with control dogs. In total, 11 (23%) of 48 TDI and strain variables differed significantly between groups. Left atrial to aortic ratio was positively correlated to early diastolic velocities, percentage increase in left ventricular internal diameter in systole was positively correlated to systolic and diastolic velocities, and mitral E wave to peak early diastolic velocity in the LV basal segment (E/Em) was positively correlated to radial strain and SR. Few TDI and strain variables were changed in dogs with MMVD with and without CHF. Intraventricular dyssynchrony may be an early sign of MMVD or may be an age-related finding.

MicroRNA-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiac myocytes

GLUT4 shows decreased levels in failing human adult hearts. We speculated that GLUT4 expression in cardiac muscle may be fine-tuned by microRNAs. Forced expression of miR-133 decreased GLUT4 expression and reduced insulin-mediated glucose uptake in cardiomyocytes. A computational miRNA target prediction algorithm showed that KLF15 is one of the targets of miR-133. It was confirmed that over-expression of miR-133 reduced the protein level of KLF15, which reduced the level of the downstream target GLUT4. Cardiac myocytes infected with lenti-decoy, in which the 3′UTR with tandem sequences complementary to miR-133 was linked to the luciferase reporter gene, had decreased miR-133 levels and increased levels of GLUT4. The expression levels of KLF15 and GLUT4 were decreased at the left ventricular hypertrophy and congestive heart failure stage in a rat model. The present results indicated that miR-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiomyocytes.

The role of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) as a prognostic marker in older people: the impact of reduced renal function

SummaryThe N-terminal pro-brain natriuretic peptide (NT-pro-BNP) is released in response to volume expansion and/or increased tension on left ventricular myocytes. NT-pro-BNP is a useful diagnostic and prognostic biomarker both in patients with dyspnoea of unknown aetiology, and for risk assessment of patients with established heart failure. However, impaired kidney function – a common condition in older people as well as a strong risk factor for cardiovascular disease is associated with elevated circulating levels of NT-pro-BNP. Therefore, it is important to know the kidney function when interpreting an elevated NT-pro-BNP measurement obtained in older people in order to diagnose or stage congestive heart failure.

A clinical score to predict 6-month prognosis in elderly patients starting dialysis for end-stage renal disease.

The aim of this study was to develop and validate a prognostic score for 6-month mortality in elderly patients starting dialysis for end-stage renal disease. Using data from the French Rein registry, we developed a prognostic score in a training sample of 2500 patients aged 75 years or older who started dialysis between 2002 and 2006, which we validated in a similar sample of 1642 patients. Multivariate logistic regression with 500 bootstrap samples allowed us to select risk factors from 19 demographic and baseline clinical variables. The overall 6-month mortality was 19%. Age was not associated with early mortality. Nine risk factors were selected and points assigned for the score were as follows: body mass index <18.5 kg/m2 (2 points), diabetes (1), congestive heart failure stages III to IV (2), peripheral vascular disease stages III to IV (2), dysrhythmia (1), active malignancy (1), severe behavioural disorder (2), total dependency for transfers (3) and unplanned dialysis (2). The median score was 2. Mortality rates ranged from 8% in the lowest risk group (0 point) to 70% in the highest risk group (> or =9 points) and 17% in the median group (2 points). Seventeen percent of all deaths occurred after withdrawal from dialysis, ranging from 0% for a score of 0-1 to 15% for a score of 7 or higher. This simple clinical score effectively predicts short-term prognosis among elderly patients starting dialysis. It should help to illuminate clinical decision making, but cannot be used to withhold dialysis. It ought to only be used by nephrologists to facilitate the discussion with the patients and their families.

Abstract 833: MicroRNA-206 Controls Cardiac Myosin Heavy Chain Gene Expression By Targeting RXR-α

MicroRNA (miRNA) is a small noncoding RNA that modulates posttranscriptional translation. Growing evidence indicates that miRNA is involved in basic cell functions and oncogenesis. In order to find a possible functional role of miRNA in the heart, we first suppressed the expression of Dicer and Ago2, which are required for miRNA biogenesis and function, by lenti-virus-mediated siRNA in neonatal rat cardiomyocytes. Knockdown of Dicer and Ago2 expression significantly increased their beating rate; therefore, we hypothesized that miRNA may regulate the expression of cardiomyocyte contractile protein since cardiac contractility depends on the expression of two myosin heavy chain (MHC) genes, α and β, which are regulated in an antithetical manner by developmental, physiological, and pathological signals. As siRNA against Dicer, which results in the loss of all miRNA function, upregulated α-MHC and downregulated β-MHC mRNA expression, we tried to identify functional miRNAs which have an opposite effect against Dicer siRNA on α/β-MHC expression in the heart. We first performed miRNA microarray analysis in the heart of Dahl salt-sensitive rats in which systemic hypertension caused compensated concentric left ventricular hypertrophy (LVH) at the age of 11 weeks, followed by congestive heart failure (CHF) at the age of 17 weeks. In this model, decreased α/β-MHC ratio is observed at LVH and CHF stages. Next we overexpressed miRNAs which are upregulated in LVH and CHF stages in neonatal rat cardiomyocytes by lenti-virus. After screening these miRNAs, miR-206 was found to decrease the α/β-MHC mRNA expression ratio. The computational miRNA target prediction algorithm showed one of the targets of miR-206 is RXR-α, which regulates α/β-MHC transcription. Forced expression of miR-206 reduced the translation of RXR-α. Moreover, when the expression of RXR-α was downregulated by siRNA, the α/β-MHC mRNA expression ratio decreased in the same manner as miR-206. In conclusion, miR-206 controls the gene expression of MHC isoforms by targeting RXR-α, and these results suggest that miR-206 regulates cardiac contractility.

Outcomes Following Surgical Ventricular Restoration for Patients With Clinically Advanced Congestive Heart Failure (New York Heart Association Class IV)

Background It has been well documented that survival in patients with advanced congestive heart failure (CHF) receiving medical therapy is worse with advancing stages of disease (New York Heart Association [NYHA] IV versus NYHA III). However, such comparisons are rare in the surgical treatments for CHF. Surgical ventricular restoration (SVR) is an accepted therapy for patients with ischemic cardiomyopathy after anterior wall myocardial infarction. We evaluated the impact of advanced stage of CHF (NYHA IV) on survival after SVR. Methods and Results A retrospective review was conducted of SVR patients at our institution between January 2002 and December 2005. Seventy-eight patients underwent SVR during the study period; 34 patients were NYHA IV and 44 patients were NYHA II/III before surgery. NYHA IV patients had significantly worse preoperative ejection fraction (EF), left ventricular end systolic volume index (LVESVI), and stroke volume index (SVI). Both groups demonstrated significant improvement in EF and LVESVI after SVR, and there were no differences between the groups with regard to postoperative EF, LVESVI, or SVI. There were 3 operative deaths in each group ( P = 1.00). Sixty-five percent ( P < .0001) of NYHA IV patients and 82% ( P < .0001) of NYHA II/III patients improved to NYHA class I or II at follow-up. NYHA IV patients trended toward reduced Kaplan-Meier survival at 32 months (68% versus 88%, P = .08), although NYHA IV was not a significant predictor of mortality. Conclusions NYHA IV patients demonstrate similar improvements in cardiac function with acceptable, although decreased, survival after SVR when compared with those with less severe clinical disease. These outcomes are superior to those reported for medical management, indicating that patients with clinically advanced CHF who are appropriate candidates should be considered for SVR irrespective of preoperative NYHA class.

Contractile three‐dimensional bioengineered heart muscle for myocardial regeneration

Tissue engineered heart muscle may be able to provide a treatment modality for early stage congestive heart failure. In this study, we describe a new method to engineer functional 3-dimensional heart muscle utilizing a biodegradable fibrin gel. Primary cardiac myocytes were isolated from hearts of 2- to 3-day-old rats and processed in one of the two ways. For the first method (layering approach), the cells were plated directly on the surface of a fibrin gel-coated on polydimethylsiloxane (PDMS) surfaces. The cells were cultured in growth media and the contractile performance evaluated after formation of 3-dimensional tissue constructs. For the second method (embedding approach), the cells were suspended with thrombin and plated on 35 mm tissue culture surfaces coated with PDMS. Fibrinogen was then added to the surface. Within 7 days after initial cell plating, a 3-dimensional tissue construct of cells derived from primary heart tissue (termed bioengineered heart muscle, BEHM) resulted for both approaches. Histological evaluation showed the presence of uniformly distributed cardiac cells throughout the BEHM, both in longitudinal and cross sections. The stimulated active force of BEHMs formed using the layering approach was 835.5 +/- 57.2 muN (N = 6) and 145.3 +/- 44.9 muN (N = 6) using the embedding approach. The stimulated active force was dependent on the initial plating density. It was possible to maintain the contractile function of BEHM in culture for up to 2 months with daily medium changes. The BEHMs exhibited inotropy in response to external calcium and isoproterenol and could be electrically paced at frequencies of 1-7 Hz. We describe a novel method to engineer contractile 3-dimensional cardiac tissue construct with a fourfold increase specific force compared to our previous model.

Evaluation of Right Ventricular Function in Patients With Congestive Left Heart Failure by the Doppler Derived Total Cardiac Performance Index (TEI index)

Background. This study aimed to assess the serial changes of right ventricular (RV) function in patients with congestive heart failure (CHF) from the acute to the convalescent stage using the Doppler derived total cardiac performance index (TEI index).Methods. Sixteen patients (11 men; mean age, 67 years) with acute left heart failure and sinus rhythm were studied by two-dimensional and Doppler echocardiography during the acute and convalescent stages of CHF. The ratio of early to late diastolic filling velocity (E/A) of both ventricles and the volume and ejection fraction of the left ventricle (LV) were measured. The isovolumic contraction (RVICT), relaxation times (RVIRT), and the ejection time (RVET) were measured from the recordings of the RV inflow or outflow velocities and the electrocardiogram. The RV TEI index was calculated as (RVICT + RVIRT) / RVET.Results. During the acute stage, the RVICT and RVIRT were prolonged, the RVET was shortened, and subsequently the RV TEI index was increased. As the condition improved, the RVICT and RVIRT were shortened, the RVET was prolonged, and the RV TEI index was significantly decreased along with a decrease in the LV volume and an increase in the LV ejection fraction.Conclusions. The RV TEI index seems to be useful for evaluating global RV function in patients with congestive left heart failure.

Surgical aspects of congestive heart failure

Despite tremendous advances in the medical management of congestive heart failure the gold standard for the treatment of end stage congestive heart failure remains cardiac transplantation. The acknowledged critical limitation of sufficient suitable organ donors has resulted in the refinement and development of novel surgical alternatives for the treatment of congestive heart failure. These approaches include the extension of current conventional cardiac operations such as mitral valve repair to the failing ventricle, surgically reconstructing the size and shape of the failing left ventricle in order to optimize geometry and render it a more efficient pump, and partial or complete replacement of the ventricle with a mechanical device. The continued evolution of such therapies is likely to one day have a significant epidemiologic impact on patients suffering from end stage heart failure.

Anemia, chronic renal disease and congestive heart failure—the cardio renal anemia syndrome: the need for cooperation between cardiologists and nephrologists

Many patients with congestive heart failure (CHF) fail to respond to maximal CHF therapy and progress to end stage CHF with many hospitalizations, poor quality of life (QoL), progressive chronic kidney disease (CKD) which can lead to end stage kidney disease (ESKD), or die of cardiovascular complications within a short time. One factor that has generally been ignored in many of these people is the fact that they are often anemic. The anemia in CHF is due mainly to the frequently-associated CKD but also to the inhibitory effects of cytokines on erythropoietin production and on bone marrow activity, as well as to their interference with iron absorption from the gut and their inhibiting effect on the release of iron from iron stores. Anemia itself may further worsen cardiac and renal function and make the patients resistant to standard CHF therapy. Indeed anemia in CHF has been associated with increased severity of CHF, increased hospitalization, worse cardiac function and functional class, the need for higher doses of diuretics, progressive worsening of renal function and reduced QoL. In both controlled and uncontrolled studies of CHF, the correction of the anemia with erythropoietin (EPO) and oral or intravenous (IV) iron has been associated with improvement in many cardiac and renal parameters and an increased QoL. EPO itself may also play a direct role in improving the heart unrelated to the improvement of the anemia--by reducing apoptosis of cardiac and endothelial cells, increasing the number of endothelial progenitor cells, and improving endothelial cell function and neovascularization of the heart. Anemia may also play a role in the worsening of acute myocardial infarction and chronic coronary heart disease (CHD) and in the cardiovascular complications of renal transplantation. Anemia, CHF and CKD interact as a vicious circle so as to cause or worsen each other- the so-called cardio renal anemia syndrome. Only adequate treatment of all three conditions can prevent the CHF and CKD from progressing.

The long-term survival benefit conferred by intermittent dobutamine infusions and oral amiodarone is greater in patients with idiopathic dilated cardiomyopathy than with ischemic heart disease

Background Intermittent dobutamine infusions (IDI) combined with oral amiodarone improve the survival of patients with end-stage congestive heart failure (CHF). The purpose of the present study was to evaluate whether the response to long-term treatment with IDI + amiodarone is different in patients with ischemic heart disease (IHD) versus idiopathic dilated cardiomyopathy (IDC). Methods The prospective study population consisted of 21 patients with IHD (the IHD Group) and 16 patients with IDC (the IDC Group) who presented with decompensated CHF despite optimal medical therapy, and were successfully weaned from an initial 72-h infusion of dobutamine. They were placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 μg/kg/min, for 8 h. Results There were no differences in baseline clinical and hemodynamic characteristics between the 2 groups . The probability of 2-year survival was 44% in the IDC Group versus 5% in the IHD Group (long-rank, P = 0.004). Patients with IDC had a 77% relative risk reduction in death from all causes compared to patients with IHD (odd ratio 0.27, 95% confidence interval 0.13 to 0.70, P = 0.007). In contrast, no underlying disease-related difference in outcomes was observed in a retrospectively analyzed historical Comparison Group of 29 patients with end stage CHF treated by standard methods. Conclusions Patients with end stage CHF due to IDC derived a greater survival benefit from IDI and oral amiodarone than patients with IHD.