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Echocardiographic findings in myocarditis.

This study analyzes morphologic and functional alterations detected by M-mode and 2-dimensional echocardiography in 41 patients with histologically proven myocarditis and different clinical presentations: congestive heart failure (63%), atrioventricular block (17%), chest pain (15%) and supraventricular arrhythmias (5%). Left ventricular dysfunction was common (69%), particularly in patients with congestive heart failure (88%), often without or with minor cavity dilatation. Patients with atrioventricular block or chest pain had usually preserved ventricular function. Right ventricular dysfunction was present in 23%. Additional findings included asynergic ventricular areas (64%), left ventricular "hypertrophy" sometimes reversible (20%), hyperrefractile myocardial areas (23%), ventricular thrombi (15%) and "restrictive" ventricular filling (7%). It is concluded that echocardiographic features of myocarditis are polymorphous and nonspecific. The echocardiographic pattern can simulate alternatively dilated, hypertrophic, restrictive or "right" ventricular cardiomyopathy, as well as coronary artery disease. In an appropriate clinical context, echocardiography can be helpful in the diagnosis of myocarditis and in the selection of patients for endomyocardial biopsy.

Adult↗

Bioepidemiology of cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, primarily due to immunoglobulin light chain (AL) or transthyretin (ATTR) amyloid, is an increasingly recognized cause of heart failure. Modern diagnostic advances suggest that ATTR, particularly in older adults, may be more prevalent than historically reported. METHODS: All Olmsted County decedents aged &#x2265;40 years from 1970 to 1976 were identified. Available ventricular myocardium from retained paraffin blocks was screened histologically for amyloid using sulfated Alcian blue staining; positive cases underwent grading and proteomic typing by laser microdissection coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Beyond prevalence estimation, this analysis characterizes amyloid type, deposition grade and distribution, associated comorbidities, and cause-of-death patterns, comparing amyloid-positive decedents with age- and sex-matched controls. RESULTS: Of 2,566 eligible deaths, 1,028 autopsy cases with evaluable myocardium formed the study cohort (mean age 70.5 years; 61.1% male; 97% White). Cardiac amyloid was present in 52 cases giving an overall prevalence of 5.1% (95% CI: 3.8-6.6, which rose from 0% under age 60 to 37.5% (95% CI: 21.1-56.3) in those &#x2265;90 years (p < 0.001). While prevalence estimates were higher in men above age 80 compared to women, there was no evidence of an interaction of age and sex (p = 0.90). The quantity of amyloid was sufficient for typing in 38 cases: ATTR (84.2%), AL (7.9%), serum amyloid A (5.3%), and apolipoprotein A-IV (2.6%). Adjusted estimates assuming untyped mild cases were ATTR-type increased ATTR prevalence to 4.5% (95% CI: 3.3-5.9) overall. Comorbidity profiles were similar between amyloid-positive and negative groups, though syncope and leg weakness were more common in amyloid-positive decedents. CONCLUSIONS: In an unselected autopsy cohort, cardiac amyloid was common, particularly ATTR in older adults. Prevalence increased steeply after age 80. These findings suggest that ATTR amyloidosis is not rare and is likely underdiagnosed and has similar prevalence in women and men, despite the male predominance reported in the literature.

Humans↗

Alterations in hypertrophic gene expression by dietary copper restriction in mouse heart.

Dietary copper (Cu) restriction causes a hypertrophic cardiomyopathy similar to that induced by work overload in rodent models. However, a possible change in the program of hypertrophic gene expression has not been studied in the Cu-deficient heart. This study was undertaken to fill that gap. Dams of mouse pups were fed a Cu-deficient diet (0.35 mg/kg diet) or a Cu-adequate control diet (6.10 mg/kg) on the fourth day after birth, and weanling mice continued on the dams' diet until they were sacrificed. After 5 weeks of feeding, Cu concentrations were dramatically decreased in the heart and the liver of the mice fed the Cu-deficient diet. Corresponding to these changes, serum ceruloplasmin concentrations and hepatic Cu,Zn-superoxide dismutase activities were significantly (P<0.05) depressed. The size of the Cu-deficient hearts was greatly enlarged as estimated from the absolute heart weight and the ratio of heart weight to body weight. The abundances of mRNAs for atrial natriuretic factor, beta-myosin heavy chain, and alpha-skeletal actin in left ventricles were all significantly increased in the Cu- deficient hearts. Furthermore, Cu deficiency activated the expression of the c-myc oncogene in the left ventricle. This study thus demonstrated that a molecular program of alterations in embryonic genes, similar to that shown in the work-overloaded heart, was activated in the hypertrophied heart induced by Cu deficiency.

Animals↗

Outpatients on biventricular assist devices.

As waiting times for transplants have lengthened, long-term mechanical circulatory support (MCS) has become more common in patients who present with severe cardiogenic shock leading to multiorgan failure. With these patients, we used the biventricular assist device (BVAD, Berlin Heart). In this report, we will describe our 4 years of experience with 11 patients on a BVAD who were discharged home while awaiting transplantation. The 11 patients underwent BVAD implantation from 1997 to 2000. These were 2 women and 9 men. The mean support time was 382 days (range: 156 - 567). The indication for BVAD was cardiomyopathy--six dilated, one restrictive and four ischemic. These patients were monitored for infections, thromboembolic events, bleeding complications, and psychological effects during the time they spent at home. Our experience shows that all of the patients could leave hospital following sufficient training for dressings and anticoagulation after recovering completely from secondary organ dysfunction. The mean time period the patients spent at home was 48 days (range: 3 - 182) days. Seven patients (63 %) had to be readmitted to the hospital--due to transitory ischemic attacks in two cases, hemorrhoidal bleeding in one and wound infections in four cases. One patient died of a traumatic accident during sexual activity. The use of a BVAD is feasible for outpatient use as a bridge to transplantation. It ensures the survival of the patient, enables recovery from multiorgan failure and offers an acceptable quality of life.

Adult↗

Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid.

The spontaneously hypertensive rat (SHR) is a model of cardiomyopathy characterized by a restricted use of exogenous long-chain fatty acid (LCFA) for energy production. The aims of the present study were to document the functional and metabolic response of the SHR heart under conditions of increased energy demand and the effects of a medium-chain fatty acid (MCFA; octanoate) supplementation in this situation. Hearts were perfused ex vivo in a working mode with physiological concentrations of substrates and hormones and subjected to an adrenergic stimulation (epinephrine, 10 microM). (13)C-labeled substrates were used to assess substrate selection for energy production. Compared with control Wistar rat hearts, SHR hearts showed an impaired response to the adrenergic stimulation as reflected by 1) a smaller increase in contractility and developed pressure, 2) a faster decline in the aortic flow, and 3) greater cardiac tissue damage (lactate dehydrogenase release: 1,577 +/- 118 vs. 825 +/- 44 mU/min, P < 0.01). At the metabolic level, SHR hearts presented 1) a reduced exogenous LCFA contribution to the citric acid cycle flux (16 +/- 1 vs. 44 +/- 4%, P < 0.001) and an enhanced contribution of endogenous substrates (20 +/- 4 vs. 1 +/- 4%, P < 0.01); and 2) an increased lactate production from glycolysis, with a greater lactate-to-pyruvate production ratio. Addition of 0.2 mM octanoate reduced lactate dehydrogenase release (1,145 +/- 155 vs. 1,890 +/- 89 mU/min, P < 0.001) and increased exogenous fatty acid contribution to energy metabolism (23.7 +/- 1.3 vs. 15.8 +/- 0.8%, P < 0.01), which was accompanied by an equivalent decrease in unlabeled endogenous substrate contribution, possibly triglycerides (11.6 +/- 1.5 vs. 19.0 +/- 1.2%, P < 0.01). Taken altogether, these results demonstrate that the SHR heart shows an impaired capacity to withstand an acute adrenergic stress, which can be improved by increasing the contribution of exogenous fatty acid oxidation to energy production by MCFA supplementation.

Acute Disease↗

Cardiomyopathies: diagnosis of types and stages.

Primary cardiomyopathies have as dominant feature the involvement of heart muscle itself. They are not the result of other diseases and should be defined as diseases of heart muscle not consequent to disorders of other parts of the cardiovascular apparatus. Most of them are consequent to genetic defects and can be subdivided into three major groups: isolated, associated with skeletal muscle diseases, associated with neurological disorders. Primary cardiomyopathies show an evolution from mild to more severe stages. Four types of cardiomyopathies are classically described: dilated, hypertrophic, restrictive and arrhythmogenic. However, from a clinical point of view, it is possible to distinguish seven stages: pre-clinical, prevalently arrhythmogenic, prevalently pseudo-hypertrophic, spotty fibrotic, restrictive, dilated and refractory heart failure. In the course of their evolution, cardiomyopathies can shift from a clinical picture to another, consequently requiring frequent examinations of patients in order to adjust their treatment.

Cardiomyopathies↗

Effect of food restriction on the phosphocreatine energy shuttle components in rat heart.

Malnutrition has been associated with changes in cardiac metabolism and performance. We have previously reported a diabetic-type cardiomyopathy associated with chronic food restriction and weight loss. Because the creatine-phosphocreatine-creatine kinase system is important in the contractile process, we studied the components of this system in rats fed a food-restricted diet (33% of control animal intake). After 4 weeks of food restriction, total creatine kinase (CK) activities were reduced by 28% in ventricles and by 38% in atria. The CK isoenzymes in the heart were not equally affected. The BB isoenzyme was decreased by 77% and 78%, the MB isoenzyme by 45% and 43%, the MM isoenzyme by 22% and 19% and CKmito by 16% and 15% in ventricles and atria, respectively. In contrast, brain CK activity which is predominantly the BB isoenzyme, was slightly higher in the food-restricted than in control rats. Further studies on ventricular tissue from food-restricted rats revealed a 27% decline in myofibrillar CR activity and a 58% decline in myofibrillar ATPase activity. Phosphocreatine and creatine concentrations were not changed by food restriction, however, ATP was decreased by 23% in ventricles from rats on the restricted diet. Cardiac mitochondrial oxidative phosphorylation was also impaired. State 3 respiration with alpha-ketoglutarate was reduced 20% in the food-restricted heart. These changes are compared to those which we previously observed in the diabetic rat heart and the significance of these findings is discussed.

Adenosine Triphosphatases↗

Dilated cardiomyopathies as a cause of congestive heart failure.

DEFINITION AND CLASSIFICATION: Cardiomyopathies are disorders affecting the heart muscle that frequently result in congestive heart failure. Five major forms are recognized: dilated, hypertrophic, restrictive, right ventricular, and nonclassifiable cardiomyopathies with distinct hemodynamic properties. Furthermore, the new WHO/WHF definition also comprises inflammatory cardiomyopathy, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy is defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm2), the term viral cardiomyopathy or viral persistence in dilated cardiomyopathy should be applied. DIAGNOSIS AND TREATMENT: In recent years, there have been breakthroughs in understanding the molecular and genetic mechanisms involved in this group of conditions, enabling improvement of diagnostic strategies and introduction of new therapies. Ongoing evaluation of antiviral, immunoglobulin, and immunosuppressive therapies including the European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID), removal of antibodies by immunoadsorption, anticytokine and gene therapy, as well as the mechanical support devices may provide new treatment options.

Cardiomyopathy, Dilated↗

Severe cardiac involvement in children with systemic sclerosis and myositis.

OBJECTIVE: To assess the outcome of children with systemic sclerosis (SSc) and features of polymyositis. METHODS: The charts of 4 children who met the American College of Rheumatology criteria for SSc and had features of polymyositis, as defined by the presence of proximal muscle weakness and elevated serum creatine phosphokinase or aldolase level, were retrospectively reviewed. RESULTS: All children had multivisceral involvement including (1) myocardial perfusion defects in all cases, with mild to severe dilated cardiomyopathy in 3; (2) lung restrictive syndrome in 3; (3) mild to severe esophageal involvement in all cases; and (4) severe intestinal dysfunction in one child. Combination therapy of corticosteroids, methotrexate (MTX), and cyclosporine resulted in improved skin thickness and muscle strength scores in all cases, as well as in lung restrictive syndrome in 2, but was not effective regarding the progression of intestinal malabsorption in one patient, esophageal dysmotility in 3 patients, and dilated cardiomyopathy in 3. Endstage cardiac failure caused 2 deaths. In one child, heart transplantation was performed for the first time in this indication. CONCLUSION: Children with diffuse cutaneous SSc and features of polymyositis are prone to develop severe cardiomyopathy. Combination therapy of corticosteroids, MTX, and cyclosporine seems to be active on muscle, skin, and lung involvement but does not impair progression of esophageal or myocardial dysfunction. Heart transplantation might be considered, as an experimental treatment, in young patients with severe cardiomyopathy and no other irreversible organ damage.

Adolescent↗

Health related quality of life and psychological wellbeing in patients with hypertrophic cardiomyopathy.

OBJECTIVE: To assess the health related quality of life and psychological wellbeing of patients with hypertrophic cardiomyopathy, to correlate these with symptoms, clinical, and psychosocial factors. DESIGN: Questionnaire distributed to 171 hypertrophic cardiomyopathy patients aged at least 14 years, selected at random from a dataset of 480 patients. Assessments included the Short Form 36 (SF-36) Health Survey, the Hospital Anxiety and Depression questionnaire, and measures of adjustment, worry, and patient satisfaction. RESULTS: There was an 80.1% response rate to the questionnaire. Patients had severe limitations in all eight dimensions of quality of life assessed by the SF-36: physical functioning, role limitations owing to physical problems, role limitations owing to emotional problems, social functioning, mental health, general health perceptions, vitality, and bodily pain. Levels of anxiety and depression were also high compared with population norms. Quality of life was particularly impaired in patients with chest pain and dyspnoea, but was less consistently related to clinical cardiological measures. Adjustment to the condition and patient satisfaction were generally good. In multivariate analysis, quality of life was associated with a combination of symptom patterns and psychosocial factors. No differences in quality of life, anxiety or depression were observed between patients with no known family history, those with familial cardiomyopathy, and patients with a family history of premature sudden death. CONCLUSIONS: Hypertrophic cardiomyopathy is associated with substantial restrictions in health related quality of life. Symptoms, adjustment, and quality of interactions with clinical staff contribute to these limitations. Recognition of the problems confronted by patients with hypertrophic cardiomyopathy requires continued efforts at education both of the public and health professionals.

Adaptation, Psychological↗

Restrictive-type hemodynamics following valve surgery for rheumatic heart disease.

Over a six-year period three patients with rheumatic valvular disease presented with congestive heart failure due to abnormalities in myocardial diastolic function. Each patient previously had been operated for mitral stenosis; one patient had additional aortic valve replacement for aortic insufficiency. The mean time for the development of symptoms following surgery was 4.7 years. In all patients, left ventricular systolic function was normal (radionuclide or angiographic ejection fraction greater than 0.50). Abnormalities in diastolic function involved the left ventricle in all patients. Biopsy material from right (one patient) and left (one patient) ventricles was nonspecific in its histologic appearance. Other disease processes, such as constrictive pericarditis and diabetic cardiomyopathy were considered to be clinically unimportant in these patients. Restrictive-type hemodynamics in patients with postoperative rheumatic heart disease may comprise a newly recognized entity.

Aortic Valve Stenosis↗

Changes in left ventricular filling during follow-up study in survivors and nonsurvivors of idiopathic dilated cardiomyopathy.

The assessment of left ventricular diastolic function by Doppler echocardiography shows both a nonrestrictive and restrictive type of filling in idiopathic dilated cardiomyopathy. These different filling patterns are related to the symptoms of cardiac failure and the prognosis. It remains to be established whether changes of Doppler parameters during follow-up procedures were of clinical relevance. Doppler echocardiography of left ventricular filling was done in 45 patients with idiopathic dilated cardiomyopathy at the time of their diagnosis and repeatedly during a follow-up study of 38 +/- 19 months. The deceleration time of early filling, the maximum early and atrial Doppler velocities and their ratios, as well as echocardiographic parameters of cardiac dimensions and systolic function, were measured. During the follow-up period, seven patients died and four patients underwent heart transplantation because of progressive heart failure. The deceleration time was shorter in patients who died or had to undergo heart transplantation as compared with survivors (119 +/- 43 ms vs 188 +/- 63 ms; P < .005). There was no difference in changes of clinical symptoms in survivors and nonsurvivors. The systolic function improved only in survivors. The difference in deceleration time remained significant between both groups, and it also remained a prognostic discriminator. Peak early velocity increased in nonsurvivors (from 0.66 +/- 0.20 m/s to 0.95 +/- 0.21 m/s; P < .01), while it remained constant in survivors (0.65 +/- 0.17 m/s and 0.67 +/- 0.25 m/s). The peak early/atrial velocity ratio varied widely in either group during the follow-up study, its changes were closely related to the concomitant changes of clinical symptoms (r = .59; P < .005) with a decrease of the peak early/atrial velocity ratio in patients with clinical improvement and an increase of the peak early/atrial velocity ratio in those without clinical improvement. The Doppler echocardiographic deceleration time discriminated between survivors and nonsurvivors in idiopathic dilated cardiomyopathy at the time of the initial diagnostic procedure, and this difference was persistent during the follow-up study. The serial evaluation of patients with idiopathic dilated cardiomyopathy showed a close association of changes in diastolic filling with changes in clinical symptoms.

Blood Flow Velocity↗

[Classification of cardiomyopathies according to the WHO/ISFC Task Force--more questions than answers?].

The most recent WHO/ISFC classification of cardiomyopathies (1995) describes as cardiomyopathies all heart muscle diseases, which demonstrate a disturbance of cardiac function. It distinguishes primarily according to hemodynamic criteria the following 5 forms: 1. dilated (DCM), 2. hypertrophic (HCM), 3. restrictive (RCM) from 4. arrhythmogenic right ventricular (ARVCM) and assembles in 5. non-classified cardiomyopathies (NKCM) the non-classifiable forms. When compared to the 18-year-old former classification several points have been altered: 1. ARVCM has been introduced as a new entity. 2. The new term ischemic cardiomyopathy has been reserved for the remodeling process of the non-infarcted myocardium and does not mean hemodynamic alterations of an infarcted area (aneurysm), of stunned or hibernating myocardium. Hypertensive cardiomyopathy corresponds to left ventricular hypertrophy in hypertensive patients, valvular cardiomyopathy identifies cardiomegaly, which cannot sufficiently be explained by the valvular dysfunction (stenoses or insufficiency) alone. For the first time the term inflammatory cardiomyopathy has been used and defined as acute or chronic myocarditis associated with cardiac dysfunction, for which etiological and pathogenetic factors, e.g. viral or microbial infection or autoimmune processes have been made responsible. Two ISFC task forces have just recently clarified in consensus conferences the immunohistopathological criteria for chronic myocarditis or dilated cardiomyopathy with inflammation (DCMi: > 14 lymphocytes or macrophages/mm3) and set standards for molecular and virological diagnoses in endomyocardial biopsies.

Cardiomyopathies↗

[AL amyloidosis--a hematologic disease with initial cardiac manifestation. 2 case reports].

Cardiac involvement in AL-amyloidosis due to a multiple myeloma is present in up to 90% of cases. We present two patients with cardiac symptoms in whom a hematologic disease could be diagnosed because of suspicious cardiac finding. The leading symptom was dyspnea. The routinely performed laboratory tests, especially the erythrocyte sedimentation rate and the electrophoresis, were normal. After exclusion of coronary artery disease an infiltrative cardiomyopathy was suspected because of the echocardiographic examination with marked left ventricular hypertrophy, the restrictive flow pattern at the mitral valve and the electrocardiogram with a low voltage in limb leads and absent R waves in left precordial leads. Further, hematologic workup confirmed the production of light chains due to a myeloma. If the echocardiographic examination and the electrocardiogram raises the suspicion of an infiltrative cardiomyopathy as the cause of dyspnea, an immunofixation should be done in spite of normal laboratory tests to confirm or rule out the presence of a light chain disease due to a myeloma.

Amyloid↗

[Negativity of myocardial scintigraphy with technetium-pyrophosphate in a case of primary cardiac amyloidosis].

We describe herein the case of a 62-year-old man affected by congestive heart failure of obscure origin, in which the clinical history, the electrocardiographic and echocardiographic findings were compatible with the diagnosis of amyloid cardiomyopathy. Cardiac catheterization disclosed a restrictive physiology. Tc-99m-pyrophosphate myocardial scintiscan was negative despite the markedly increased left ventricular wall thickness on echocardiographic examination. A definite diagnosis was obtained by means of endomyocardial biopsy.

Amyloidosis↗

Multicenter study on hepatitis C virus infection in patients with dilated cardiomyopathy. North Italy Transplant Program (NITP).

Preliminary epidemiological and histological studies from Japan suggested that hepatitis C virus (HCV) infection has a role in the development of dilated cardiomyopathy (DCM). This multicenter study was conducted to verify this hypothesis on a large cohort of Italian patients with end-stage heart failure. Antibodies to HCV were determined in the 752 consecutive patients (608 males and 144 females; age, 53 +/- 13 years) who entered the waiting list for cardiac transplantation from 1995 to 1997 at the six cardiac surgery centers participating in the North Italy Transplant program. Three hundred and nine patients (41%) had dilated, 9 (1%) restrictive, and 4 (0.5%) hypertrophic cardiomyopathy; 284 patients (38%) had ischemic, 65 (9%) valvular, and 22 (3%) congenital heart disease; 5 patients (0.5%) had primary pulmonary hypertension; 54 patients (7%) had other or nonspecified heart disease. Overall, 41 of 752 patients (5.4%) resulted anti-HCV-reactive. Serological evidence of HCV infection was found in 12 of 309 patients with DCM (3.9%; 95% CI, 1.7-6.0), and in 29 of 443 without DCM (6.5%; 95% CI, 4.2-8.8), without statistical difference (difference of prevalence rate: 2.6%; 95% CI, -4.9 to 5.8). In conclusion, HCV does not seem to have a primary role in the pathogenesis of DCM. However, since our findings are in disagreement with those obtained in smaller series of patients of other ethnicity, large studies from different countries should be conducted.

Aged↗

Doppler estimation of filling pressures in a patient with hypertrophic cardiomyopathy.

A case of hypertrophic cardiomyopathy is presented with a restrictive mitral filling pattern but predominant systolic pulmonary vein flow velocities. A stepwise Doppler work-up including color M-mode, Doppler tissue imaging of the mitral annulus velocity and loading manipulations could clarify the underlying hemodynamic mechanisms. The Doppler data were correlated with invasive measurements.

Adult↗

The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus.

Recent evidence has defined an important role for PPARalpha in the transcriptional control of cardiac energy metabolism. To investigate the role of PPARalpha in the genesis of the metabolic and functional derangements of diabetic cardiomyopathy, mice with cardiac-restricted overexpression of PPARalpha (MHC-PPAR) were produced and characterized. The expression of PPARalpha target genes involved in cardiac fatty acid uptake and oxidation pathways was increased in MHC-PPAR mice. Surprisingly, the expression of genes involved in glucose transport and utilization was reciprocally repressed in MHC-PPAR hearts. Consistent with the gene expression profile, myocardial fatty acid oxidation rates were increased and glucose uptake and oxidation decreased in MHC-PPAR mice, a metabolic phenotype strikingly similar to that of the diabetic heart. MHC-PPAR hearts exhibited signatures of diabetic cardiomyopathy including ventricular hypertrophy, activation of gene markers of pathologic hypertrophic growth, and transgene expression-dependent alteration in systolic ventricular dysfunction. These results demonstrate that (a) PPARalpha is a critical regulator of myocardial fatty acid uptake and utilization, (b) activation of cardiac PPARalpha regulatory pathways results in a reciprocal repression of glucose uptake and utilization pathways, and (c) derangements in myocardial energy metabolism typical of the diabetic heart can become maladaptive, leading to cardiomyopathy.

Animals↗