Symptomatic Dilated Cardiomyopathy Research Articles

Quality of life and societal costs in patients with dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a major cause of heart failure impairing patient wellbeing and imposing a substantial economic burden on society, but respective data are missing. This study aims to measure the quality of life (QoL) and societal costs of DCM patients. A cross-sectional evaluation of QoL and societal costs of DCM patients was performed through the 5-level EuroQol and the Medical Consumption Questionnaire and Productivity Cost Questionnaire, respectively. QoL was translated into numerical values (i.e. utilities). Costs were measured from a Dutch societal perspective. Final costs were extrapolated to 1 year, reported in 2022 Euros, and compared between DCM severity according to NYHA classes. A total of 550 DCM patients from the Maastricht cardiomyopathy registry were included. Mean age was 61 years, and 34% were women. Overall utility was slightly lower for DCM patients than the population mean (0.840vs. 0.869, P=0.225). Among EQ-5D dimensions, DCM patients scored lowest in 'usual activities'. Total societal DCM costs were €14 843 per patient per year. Cost drivers were productivity losses (€7037) and medical costs (€4621). Patients with more symptomatic DCM (i.e. NYHA class III or IV) had significantly higher average DCM costs per year compared to less symptomatic DCM (€31 099vs. €11 446, P< 0.001) and significantly lower utilities (0.631vs. 0.883, P< 0.001). DCM is associated with high societal costs and reduced QoL, in particular with high DCM severity.

DCM Support: cell therapy and circulatory support for dilated cardiomyopathy patients with severe ventricular impairment.

The DCM Support trial (NCT03572660) uses a percutaneous circulatory support device (Impella CP, Abiomed, Danvers, MA, USA) to improve the safety of an intracoronary cell infusion procedure in patients with dilated cardiomyopathy (DCM) and a severely reduced left ventricular ejection fraction (LVEF). DCM Support is a single-site, single-arm Phase II trial enrolling 20 symptomatic DCM patients with an LVEF≤35% despite optimal medical and device therapy. After 5days of granulocyte colony-stimulating factor therapy and a subsequent bone marrow aspiration, patients undergo an intracoronary infusion of autologous bone-marrow-derived mononuclear cells. The Impella CP device is used to provide haemodynamic support during the infusion procedure. The trial's primary endpoint is change in LVEF from baseline at 3months. Secondary efficacy endpoints are change in LVEF from baseline at 12months, and change in exercise capacity, New York Heart Association class, quality of life, and N-terminal pro-B-type natriuretic peptide levels from baseline at 3 and 12months. Safety endpoints include procedural safety and major adverse cardiac events at 3 and 12months. This is the first trial to assess the safety and efficacy of cytokine and autologous intracoronary cell therapy with a procedural circulatory support device for patients with severe left ventricular impairment. This novel combination may allow us to target a patient population most at need of this therapy.

954 DILATED CARDIOMYOPATHY AND ATRIOVENTRICULAR BLOCK RELATED TO THE MUTATION IN THE LMNE GENE: DESCRIPTION OF A FAMILY

Abstract The proband was patient A2, suffering by severe left ventricular dysfunction (EF 20%) and II degree Mobitz type 1 atrioventricular block, requiring dual chamber ICD implantation, and retinitis pigmentosa. He had three brothers A1, A4, A5 suffering also by dilated cardiomyopathy and ICD/CRTD recipients. His sister A3, his daughter B1 and the firstborn brother A1 were also affected by retinitis pigmentosa. Genetic analysis was performed in A2 by NGS of a panel of genes related to heart disease and retinitis pigmentosa. It documented the presence of a missense pathogenetic variant (class 4) of the LMNA gene in heterozygosis (c.949G&amp;gt;A). This variant has been described in several scientific papers as associated with cardiac impairment in patients suffering from atrioventricular block and dilated cardiomyopathy. Laminin A/C is a fundamental protein of the nuclear envelope of the cell. Germline mutations in the LMNA gene, present on chromosome 22 (1q22), encoding the A/C lamina, have been causally linked to four different diseases with 42 reported mutations: Dilated cardiomyopathy (DCM) with disease of the conduction system; Limb girdle muscular dystrophy (LGMD); Autosomal dominant variant of Emery-Dreifuss muscular dystrophy (EDMD); Autosomal dominant partial lipodystrophy. LMNA-related dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and/or reduced systolic function frequently preceded or accompanied by significant conduction system disease. Family studies suggest that conduction system disease commonly precedes the development of DCM by a few years to a decade or more. Conduction system involvement usually starts with disease of the sinus node and/or atrioventricular node that can manifest as sinus bradycardia, sinus node arrest with junctional rhythms, or heart block (commonly first-degree heart block that progresses to second- and third-degree block). The following are also common: symptomatic bradyarrhythmias requiring cardiac pacemakers, supraventricular arrhythmias including atrial flutter, atrial fibrillation, supraventricular tachycardia, and the sick sinus syndrome (i.e., tachycardia-bradycardia syndrome), ventricular arrhythmias including frequent premature ventricular contractions and ventricular tachycardia Sudden cardiac death may occur with progressive disease. Although more malignant, life-threatening arrhythmias may occur with longstanding and usually previously symptomatic DCM, sudden cardiac death can also be the presenting manifestation of LMNA-related DCM, with minimal or no left ventricular dysfunction. In the cardiological setting, the AVB associated with DCM is a reliable marker for LMNA gene molecular screening. Regarding retinitis pigmentosa, the variant in heterozygosis c538C&amp;gt;G was found in the RHO gene in the proband, classifiable as pathogenetic. This gene encodes a protein necessary for the function of retinal photoreceptors and pathogenic mutations have been found in 30-40% of hereditary forms of retinitis pigmentosa. In conclusion, we believe that the tests carried out confirmed the hypothesis of a hereditary form of cardiomyopathy and retinitis pigmentosa, which seem to segregate independently in the family. Both mutations can be transmitted in 50% of cases, regardless of sex. For this reason we recommended to extend genetic analysis to all the first-degree relatives (siblings and children).

Autoinflammation leading to autoimmunity in adult-onset Still\u2019s disease: more than simple coincidence?

BackgroundAdult-onset Still’s disease (AOSD) should be considered in the differential diagnosis of patients with endocarditis, with or without a cardiac decompensation.Case presentationWe report the case of a 68-year-old Caucasian male diagnosed with AOSD after an initial acute manifestation of endocarditis with severe aortic acute manifestation of endocarditis with severe aortic insufficiency. The histological findings revealed Libman–Sacks endocarditis. He was treated with the IL-1 receptor inhibitor anakinra. Two years later the patient developed a symptomatic dilated cardiomyopathy with reduced ejection fraction (23.5%) and functional anti-beta-1-adrenergic receptor antibodies, which was initially treated with plasmapheresis; anakinra was maintained. While his AOSD symptoms responded well, our patient presented with recurrent arthritis in multiple joints, dual-energy CT showed urate deposition compatible with a gouty arthropathy. Over 7 years, he presented with recurrent episodes of arthritis and the adjustment of dosages of colchicine and febuxostat was needed. In 2018, our patient died due to a deterioration of his underlying cardiac disease.ConclusionsOnly two cases with initial endocarditis prior to AOSD diagnosis have been published, and we are not aware of any other cases reporting -β1AR-Ab development with DCM and gout in the setting of AOSD treated with anakinra.

Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy

BackgroundMetabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in patients with nonischemic dilated cardiomyopathy (DCM) and compared its incremental value on top of N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Methods and ResultsA total of 149 metabolites were measured in plasma and urine samples of 273 patients with DCM and with varying stages of disease (patients with DCM and normal left ventricular reverse remodeling, n = 70; asymptomatic DCM, n = 72; and symptomatic DCM, n = 131). Acylcarnitines, sialic acid and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by unibiomarker linear regression, sparse partial least squares discriminant analysis, random forest, and conditional random forest analyses. However, the absolute difference in the metabolic profile among groups was marginal. A decision-tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish patients with DCM and left ventricular reverse remodeling from symptomatic DCM (area under the curve 0.813 ± 0.138 vs 0.739 ± 0.114; P = 0.02). ConclusionFunctional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in nonischemic DCM.

Torsion Mechanics as an Indicator of More Advanced Left Ventricular Systolic Dysfunction in Secondary Mitral Regurgitation in Patients with Dilated Cardiomyopathy: A 2D Speckle-Tracking Analysis

Left ventricular (LV) twist serves as a compensatory mechanism in systolic dysfunction and its degree of reduction may reflect a more advanced stage of disease. Aim: The aim was to investigate twist alterations depending on the degree of functional mitral regurgitation (MR) by speckle-tracking echocardiography. Methods: Sixty-three patients with symptomatic dilated cardiomyopathy (DCM) were included. Patients were divided according to MR vena contracta width (VCW): group 1 with VCW <7 mm (mild/moderate MR) and group 2 with VCW ≥7 mm (severe MR). Results: There were no differences in LV geometry and function between groups. Group 2 showed lower endocardial basal rotation (BR) (–2.04° ± 1.83° vs. –3.23° ± 1.83°, p = 0.012); epicardial BR (–1.54° ± 1.18° vs. –2.31° ± 1.22°, p = 0.015); endocardial torsion (0.41°/cm ± 0.36°/cm vs. 0.63°/cm ± 0.44°/cm, p = 0.033) and mid-level circumferential strain (CSmid) (–6.12% ± 2.64% vs. –7.75% ± 2.90%, p = 0.028), when compared with group 1. Multivariable linear regression analysis identified endocardial BR, torsion and CSmid, as the best predictors of larger VCW. In the ROC curve analysis, endocardial BR and CSmid values greater than or equal to –3.63° and –9.35%, respectively, can differentiate patients with severe MR. Conclusions: In DCM patients, torsional profile was more altered in severe MR. Endocardial BR, endocardial torsion, and CSmid, can be used as indicators of advanced structural wall architecture damage.

60. Mid-term outcome of cardiac resynchronization therapy in pediatrics: single institution experience

Cardiac resynchronization therapy (CRT) has become an increasingly important therapeutic option for patients (pts) to treat dyssynchrony associated moderate and severe heart failure. Few reports however, determined the beneficial effects of CRT in pediatrics and midterm outcome following this therapy. Our aim is to assess the mid-term outcomes of CRT in children with evidence of dyssynchrony associated heart failure. Cardiac resynchronization therapy is beneficial in treating congenital heart disease patients who have evidence of dyssynchrony associated heart failure. Retrospective review of 18 consecutive pediatric patients who underwent CRT at our institution between January 2002 and August 2011 Cardiac resynchronization pacemaker was implanted in 18 pts the majority of pts (14) with congenital heart disease. Fourteen pts had preexisting complete heart block and chronic right ventricular pacing. Epicardial left ventricular leads were implanted in all pts while the atrial and right ventricular leads approach varied according to the pt size and anatomy. Indication for CRT was symptomatic dilated cardiomyopathy with evidence of electrical and/or mechanical dyssynchrony demonstrated by M-mode, 3-D echo, or tissue Doppler. The median age of this cohort was 14 years (range 6 months–16 years), the median follow-up time was 7.2 years (range 1–10 years). Subjectively, 16 out of 18 pts reported symptomatic improvement with decreased hospitalizations. The left ventricular ejection fraction improved from mean of 27% (SD 13%) to mean of 50% (SD 13%) ( P value P value P value = 0.1) suggesting that electrical resynchronization is not a prerequisite for clinical improvement in this cohort. Children including those with congenital heart disease patients who have evidence of dyssynchrony associated heart failure appear to benefit from cardiac resynchronization therapy on the mid-term. Selection criteria should include the use of new technologies to demonstrate mechanical dyssynchrony beside other conventional indications of CRT. Further studies looking at long-term benefits of CRT in pediatric and CHD patients are needed.

Decrease in dendritic cells in endomyocardial biopsies of human dilated cardiomyopathy

Dendritic cells (DCs) are sentinels of the immune system-their role in myocardial disease is unknown as yet. We investigated their myocardial presence in human dilated cardiomyopathy (DCM). Endomyocardial biopsies from 72 patients with DCM (EF ∼30%), as well as myocardial specimens from 18 suicide or accident victims were immunohistochemically analysed for myeloid and plasmacytoid DCs, antigen-presenting cells (APCs), and other leucocytes; also tissue fibrosis and apoptosis were histologically quantified. The myocardial viral genome was identified through polymerase chain reaction, and patients underwent clinical follow-up in 3-6 months. We found myocardial DCs of all examined subtypes and maturation stages (fascin, CD11c, CD209, CD83, and CD304), as well as markers for APCs (HLA-DR and CD40) and T-cell activation (CD69) to be significantly decreased in DCM compared with controls. In contrast, regulatory T cells (the GITR epitope), apoptosis (by TUNEL reaction and immunostaining with BCL-2), and a DC chemokine receptor (CCR7) were overexpressed, while no significant differences were observed for macrophages (CD68). Immature myeloid and plasmacytoid DCs strongly correlated with endothelial progenitor cells (CD34), which were similarly reduced in DCM, and inversely correlated with fibrosis. Myeloid DCs were especially reduced in virus-positive biopsies, and their numbers correlated with positive change in EF (ΔEF) at follow-up. Myocardial DCs are reduced in heart biopsies of symptomatic DCM patients. Such a reduction correlates with an unfavourable short-term outcome in terms of EF, and could result from myocardial tissue damage, cellular death, and insufficient vascularization in chronic heart failure.

Beta-adrenergic adaptation in idiopathic dilated cardiomyopathy: differences between children and adults

This editorial refers to ‘Beta-adrenergic adaptation in paediatric idiopathic dilated cardiomyopathy’, by S.D. Miyamoto et al. , doi:10.1093/eurheartj/ehs229 The study of Miyamoto et al .1 found differences in beta-adrenergic adaptation to heart failure (HF) in explanted heart tissue between children and adults with symptomatic dilated cardiomyopathy (DCM). Differences included: (i) down-regulation of beta-1- and beta-2-adrenergic receptors in children but maintained beta-2-adrenergic receptor expression in adults; and (ii), in children, uncoupling of the beta-1-adrenergic receptors and stimulatory G-proteins, among others.1 An important family of cell surface protein receptors, the G-protein-coupled receptors (GPCRs), enable cells to sense and respond to outside signals. For children with cardiomyopathy and heart failure, we need a better understanding of the structure–function relationships and the detailed regulation of GCPRs, as well as the drugs that stimulate or inhibit these relationships. Understanding beta-adrenergic adaptation in children with HF should indicate how cardiomyocytes interact with their extracellular environment and adapt to new situations, such as when epinephrine acts on cells to increase blood pressure and heart rate. Miyamoto and colleagues observed that the GCPR signalling system has become the target of prescription drugs, including beta-blockers, to relieve HF.1 In fact, about half of all medications act on these receptors, so learning about them is key to developing better drugs. The GPCR initiates a cascade of signals into the cell, prompting it to respond appropriately, as well as a secondary cascade in which a feedback signal leads to desensitization. A molecule called beta-arrestin binds to the GPCR and reduces or temporarily stops GPCR's sensitivity. Beta-arrestin, in addition to receptor desensitization, is involved in receptor endocytosis and activating extracellular signal-regulated kinase (ERK) and other …

What a nice 'scoobie'!!

A 69-year-old obese and depressive female patient with symptomatic dilated cardiomyopathy was implanted with cardiac resynchronization therapy in combination with …

Assessment of mechanical ventricular synchrony in Doberman Pinschers with dilated cardiomyopathy

Objectives Loss of temporal synchrony of myocardial contraction has been shown to reduce systolic function and be responsible for disease progression in people. The objective of this study is the assessment of inter- and intra ventricular synchrony in healthy Doberman Pinschers and those with dilated cardiomyopathy (DCM) by use of conventional Doppler and tissue velocity imaging. Animals A total of 60 scans from 35 client-owned Doberman Pinschers presented for cardiac evaluation were analysed. Methods Retrospective analysis of data. Using the European Society of Veterinary Cardiology DCM taskforce scoring system, Doberman Pinschers were classified into 4 groups: Control (Group 1; n = 12), depressed systolic function other than DCM (Group 2; n = 9), preclinical DCM (Group 3; n = 8) and symptomatic DCM (Group 4; n = 6). The time intervals between the beginning of the QRS complex and the peak velocity of pulmonic flow (Q-P) and the peak aortic flow (Q-Ao) were used to assess global synchrony between both ventricles. The time intervals between the beginning of the QRS complex and the peak myocardial systolic velocity (Q-peak S) and the onset of myocardial systolic velocity (Q-start S) were measured at the base of the right and left ventricular free wall (RVFW and LVFW) and interventricular septum (IVS), and used to determine segmental longitudinal inter- and intra ventricular synchrony. Results No significant loss of global or segmental longitudinal inter- or intra ventricular synchrony was identified between the groups. Conclusion Impairment of longitudinal fibre synchrony does not appear to be significantly associated with clinical status of DCM in Doberman Pinschers, although it was identified in certain individuals.

Intramyocardial administration of autologous bone marrow mononuclear cells in a critically ill child with dilated cardiomyopathy

Almost half of the children with symptomatic dilated cardiomyopathy receive a transplant or die within 2 years; however, cardiac stem cell transplantation has become a promising therapeutic option. The present case demonstrates for the first time, to our knowledge, the intramyocardial administration of autologous bone marrow mononuclear cells in a critically ill 4-month-old child with severe dilated cardiomyopathy. Left ventricular ejection fraction increased from 20% before stem cell transplantation to 41% at 4 months of follow-up.

Symptomatic Calcific Constrictive Pericarditis Presenting Years After Presumed Resolved Inflammatory Heart Disease

Inflammatory heart diseases are characterized as a focal, diffuse, or sparse inflammatory process of the myocardium and its adjacent structures. In adults, inflammatory heart disease often progresses to symptomatic dilated cardiomyopathy and heart failure. We report the case of a 42-year-old woman who was diagnosed with right-sided heart failure, presumably secondary to inflammatory heart disease, after the acute onset of exercise intolerance. Nine years after the initial diagnosis, she developed clinical symptoms of calcified constrictive pericarditis. Pericardiectomy was performed and the patient resumed normal functional capacity. In conclusion, close monitoring and careful evaluation of patients with presumed inflammatory heart disease is warranted because of the potential for late-occurring chronic constrictive sequelae.

Prevalence of erythrovirus genotypes in the myocardium of patients with dilated cardiomyopathy

Parvovirus B19 (PVB19) is a member of the human erythrovirus family detected frequently in endomyocardial biopsies from patients with dilated cardiomyopathy. Human erythroviruses cluster into three genotypes 1-3 which share a high degree of homology between major structural proteins and may cause indistinguishable infections clinically and serologically. In human cardiac tissue erythrovirus genotypes other than PVB19 have not yet been reported. Three hundred seventeen consecutive patients with symptomatic dilated cardiomyopathy (median left ventricular ejection fraction: 28.6%, range 5-45%) who underwent endomyocardial biopsy for the elucidation of the etiology, were analyzed using a new consensus PCR assay designed for the detection of the three erythrovirus genotype sequences. Endomyocardial biopsies of 151 (47.6%) patients were erythrovirus-positive. Genotype 1 specific sequences were detected in 43/151 (28.5%) of positive biopsy samples, whereas genotype 2-specific sequences so far considered rare in human disease and not yet been described in human heart tissue was identified in 108/151 (71.5%) of virus-positive endomyocardial biopsies with a preference in patients above 50 years of age. In spite of younger age, systolic left ventricular dysfunction of genotype 1-positive patients was significantly reduced as compared to genotype 2-positive patients (24.4+/-10.4% vs. 31.0+/-9.5%, P=0.0001) at the initial presentation. The data show that two genetically distinct erythrovirus variants with a different age distribution are detectable in endomyocardial biopsies of patients with dilated cardiomyopathy. The erythrovirus genotype 2, not described previously in human heart tissue, is highly prevalent in the heart but the less prevalent genotype 1 is associated with more severe disturbed cardiac function.

Mechanical dyssynchrony by 3D echo correlates with acute haemodynamic response to biventricular pacing in heart failure patients

One-third of dilated cardiomyopathy patients receiving a biventricular pacing-device do not respond to this form of therapy. Therefore, the utility of mechanical dyssynchrony by real-time 3D echocardiography (RT3DE) for predicting systolic response to biventricular pacing, of which maximal rate of pressure rise (dP/dt(max)) served as the gold-standard, was evaluated. Seventeen consecutive heart failure patients (aged 64 +/- 10 years, 8 male, 6 ischaemic cardiomyopathy, mean QRS duration 136 +/- 32 ms) underwent RT3DE and biventricular pacing. Post-processing software provided data of global left ventricular (LV) function and the systolic dyssynchrony index of 17 LV segments (SDI(17), %) for mechanical dyssynchrony. During biventricular pacing, percentual change in dP/dt(max) compared to the non-pacing mode, DeltadP/dt(max) was measured invasively with conductance catheters. LV ejection fraction was 31 +/- 10%, SDI(17) was 10.2 +/- 4.2% and percentual DeltadP/dt(max) during biventricular pacing was 14.5 +/- 12.4. A significant correlation (r = 0.729, P = 0.001) was found between SDI(17) and percentual DeltadP/dt(max), and between QRS duration and percentual DeltadP/dt(max) (r = 0.721, P = 0.001). The present study suggests that mechanical dyssynchrony measured by RT3DE shows a good correlation with invasively determined acute haemodynamic response to biventricular pacing in patients with symptomatic dilated cardiomyopathy. Future studies are needed to further define the clinical utility of RT3DE in identifying patients who are most likely to respond to cardiac resynchronization therapy.

Heart failure complicated by atrial fibrillation: mechanistic, prognostic, and therapeutic implications.

Atrial fibrillation and congestive heart failure are two distinct clinical entities that are responsible for significant morbidity and mortality in the Western world. Hypertension, coronary artery disease, and nonischemic cardiomyopathy represent the most prevalent underlying pathologies of both diseases, implying a coincidence of both in many patients. The prevalence of atrial fibrillation with a progressive degree of congestive heart failure is increasing, as judged by New York Heart Association functional class. Moreover, the presence of congestive heart failure has been identified as one of the most powerful independent predictors of atrial fibrillation, with a sixfold increase in relative risk of its development. On the other hand, atrial fibrillation can cause or significantly aggravate symptoms of congestive heart failure in previously asymptomatic or well-compensated patients. In some patients, symptomatic dilated cardiomyopathy may develop over time entirely due to atrial fibrillation with rapid ventricular rates. Upon restoration of sinus rhythm, this type of "tachymyopathy" has been shown to be often reversible. Recent investigations of the physiologic and structural changes of the atrial myocardium ("electrical and structural remodeling") have shown that neurohumoral activation, fibrosis, and apoptosis are demonstrable with both diseases. On the other hand, experimental data suggest that the substrates of atrial fibrillation in congestive heart failure are different from those of pure atrial tachycardia-related forms of atrial fibrillation. This review highlights the clinical and pathophysiologic similarities and differences of atrial fibrillation and congestive heart failure relevant to the understanding, treatment, and prevention of these diseases in the population at risk.

Immunohistologic evidence of myocardial disease in apparently healthy relatives of patients with dilated cardiomyopathy

ObjectivesThis study investigated whether apparently healthy relatives of patients with idiopathic dilated cardiomyopathy (DCM) who have left ventricular enlargement (LVE) have biopsy evidence of underlying myocardial disease. BackgroundLeft ventricular enlargement with normal systolic function is common among asymptomatic relatives of patients with DCM. Although there is circumstantial evidence to suggest that LVE may be a marker of early DCM, its pathophysiologic significance remains uncertain. MethodsOver six years, 767 asymptomatic relatives of 183 consecutive patients with DCM were evaluated: 37 (5%) had DCM and 104 (14%) had LVE (left ventricular end-diastolic dimension >112% predicted) with normal systolic function. Right ventricular biopsy was performed in 32 relatives with LVE, 14 patients with symptomatic DCM and 6 control subjects with normal ventricular function undergoing elective coronary artery bypass graft surgery. Histologic and immunohistochemical analyses, including quantitative double immunofluorescence, were performed for leukocyte markers (CD3 and CD68), intercellular adhesion molecule-1 (ICAM-1) and human leukocyte antigen class II antigens (DR and DQ). ResultsHistologic findings consistent with DCM were present in 50% of the patients with DCM, 25% of the relatives with LVE and 0% of the control subjects. The median CD3 count was 2.4/mm2in patients with DCM, 4/mm2in relatives with LVE and 0 in control subjects (p = 0.04). Using a threshold of >7 cells/mm2, 21% of patients with DCM and 25% of relatives with LVE were CD3-positive (p = 0.01). Quantitative analysis demonstrated DR expression on 55.8 ± 22.8%, 63.5 ± 18.8% and 30.9 ± 15.7% of the endothelial surface in patients with DCM, relatives and control subjects, respectively (p = 0.003). Corresponding values for ICAM expression were 35.6 ± 15.1%, 36.7 ± 14.5% and 17.3 ± 7.9% (p = 0.013). When combining inflammatory and histologic changes, 28 (86%) of LVE, 14 (100%) of DCM and no control biopsies were abnormal (p < 0.001). ConclusionsMost asymptomatic relatives of patients with DCM with LVE have histopathologic and immunopathologic findings similar to those of patients with established disease. Clinical identification and follow-up of such individuals are warranted to prevent presentation with advanced DCM and to enable assessment of interventions aimed at attenuating disease progression.

Dilated cardiomyopathy

The management of patients with dilated cardiomyopathy (DCM) heart failure starts with the determination of the underlying diagnosis, definition of the hemodynamic character (eg, systolic, diastolic, valvular, right- and left-sided heart dysfunction), recognition of complicating factors (eg, atrial fibrillation, renal dysfunction), and consideration for any surgically remedial lesions (eg, severe valvular regurgitation, high-grade coronary artery occlusive disease). Angiotensin-converting enzyme inhibitors, beta-blocking agents, digoxin, and judicious diuretic administration make up the therapeutic plan for patients with symptomatic DCM heart failure. Angiotensin-converting enzymes are indicated for patients with DCM who have mild or no detectable symptoms; whether this subgroup would benefit from long-term beta-blockade remains to be established. Spirolactone also has been shown to be effective in patients with more advanced stages of heart failure. Biventricular pacing (cardiac resynchronization therapy) recently has been approved for use in patients with DCM and a left ventricular or intraventricular conduction defect and a QRS duration of longer than 140 msec. More intense pharmacotherapy, mechanical devices, and transplantation are directed at patients with severely symptomatic end-stage DCM. The effectiveness of any heart failure treatment plan is very much dependent on nonpharmacologic approaches, including dietary measures, exercise conditioning, and similar considerations, all of which are best delivered by dedicated heart failure programs.

Beta‐blockers treatment of patients with symptomatic dilated cardiomyopathy – Five year follow‐up

European Journal of Heart FailureVolume 2, Issue S1 p. 59-59 AbstractsFree Access Beta-blockers treatment of patients with symptomatic dilated cardiomyopathy – Five year follow-up R. Roszczyk, R. Roszczyk Cardiology, CSK WAM, Warsaw, PolandSearch for more papers by this authorJ. Adamus, J. Adamus Cardiology, CSK WAM, Warsaw, PolandSearch for more papers by this authorE. Sztwiertnia-Roszczyk, E. Sztwiertnia-Roszczyk Cardiology, CSK WAM, Warsaw, PolandSearch for more papers by this authorP. Œnigurowicz, P. Œnigurowicz Cardiology, CSK WAM, Warsaw, PolandSearch for more papers by this author R. Roszczyk, R. Roszczyk Cardiology, CSK WAM, Warsaw, PolandSearch for more papers by this authorJ. Adamus, J. Adamus Cardiology, CSK WAM, Warsaw, PolandSearch for more papers by this authorE. Sztwiertnia-Roszczyk, E. Sztwiertnia-Roszczyk Cardiology, CSK WAM, Warsaw, PolandSearch for more papers by this authorP. Œnigurowicz, P. Œnigurowicz Cardiology, CSK WAM, Warsaw, PolandSearch for more papers by this author First published: 19 May 2004 https://doi.org/10.1016/S1388-9842(00)80210-XAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume2, IssueS1June 2000Pages 59-59 RelatedInformation

Lymphocyte β -adrenoceptor Downregulation in Great Danes with Occult Dilated Cardiomyopathy (DCM) and with DCM and Heart Failure

The importance of the adrenergic nervous system in supporting the failing heart has long been known. The adrenergic drive on cardiac structure and function has however some adverse effects, which include myocardial β -adrenoceptor (β -AR) downregulation and decreased β -adrenergic responsiveness to cathecolamines. In dog lymphocytes, β1-AR and β2-AR populations are almost equally represented (with a slight prevalence of β2) and a significant correlation between cardiac and lymphocytic adrenoceptors has been found. The aim of the present study was to investigate possible differences between the concentration of lymphocyticβ -AR in healthy dogs, dogs with dilated cardiomyopathy (DCM) and dogs with occult DCM. Three groups of great danes were considered: a control group (n =10), dogs with DCM (n =9) and dogs with occult DCM (n =4). Lymphocytic β -AR populations were determined in all dogs. A substantial and significant decrease (P<0.05) in total-AR, β1-AR and β2-AR concentrations in the lymphocytes of dogs with symptomatic DCM and occult DCM compared to the control group was found. Although the mean value of the lymphocyteβ1 -AR number in the asymptomatic group was double compared to the DCM group, this difference was not statistically significant. We conclude that in dogs β -AR downregulation occurs early in the course of dilated cardiomyopathy. This finding may suggest the value of early use of a β -blocker in the therapeutic regimen. Moreover, the continuous monitoring of lymphocytic β -AR may represent a useful tool for the development of a more effective individual therapy.