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Myocarditis, simply defined as inflammation of the heart muscle, is a commonly encountered cardiac disease in primary and secondary care, both in the UK and on Operational deployments. In the UK Armed Forces, myocarditis results in deaths as well as the premature termination of military careers on medical grounds. The aetiology is usually the result of a number of infectious aetiologies with viruses being the most common pathogens in the vast majority of cases. However, it may also be the result of autoimmune activation, chemical or pharmacological toxins, environmental insult or hypersensitivity reactions. Particular aetiologies that are more likely to be seen in a military population are discussed and include certain infections, smallpox vaccine, and hyperthermia and hypothermia. The clinical features can be highly variable ranging from an asymptomatic infection to fulminant heart failure. Features pertinent to the military doctor, including the natural history, investigative modalities and management strategies, with a particular emphasis on the occupational impact of myocarditis in the UK Armed Forces are reviewed.

Objective A predictable relation between genotype and disease expression is needed in order to use genetic testing for clinical decision-making in hypertrophic cardiomyopathy (HCM). The primary aims of this study were to examine the phenotypes associated with sarcomere protein (SP) gene mutations and test the hypothesis that variation in non-sarcomere genes modifies the phenotype. Methods Unrelated and consecutive patients were clinically evaluated and prospectively followed in a specialist clinic. High-throughput sequencing was used to analyse 41 genes implicated in inherited cardiac conditions. Variants in SP and non-SP genes were tested for associations with phenotype and survival. Results 874 patients (49.6±15.4 years, 67.8% men) were studied; likely disease-causing SP gene variants were detected in 383 (43.8%). Patients with SP variants were characterised by younger age and higher prevalence of family history of HCM, family history of sudden cardiac death, asymmetric septal hypertrophy, greater maximum LV wall thickness (all p values

The role of copy-number variants (CNV) as a cause of hypertrophic cardiomyopathy (HCM) is poorly studied. The aim of this study was to use high-throughput sequence (HTS) data combined with a read-depth strategy, to screen for CNV in cardiomyopathy-associated genes in a large consecutive cohort of HCM patients.Five-hundred-and-five unrelated HCM patients were genotyped using a HTS approach for 41 cardiovascular genes. We used a previously validated read-depth strategy (ExomeDepth) to call CNVs from the short-read sequence data. Detected CNVs in 19 cardiomyopathy-associated genes were then validated by comparative genomic hybridization array.Twelve CNVs were identified. Four CNVs in 4 patients (0.8% of the cohort) were validated: one large deletion in MYBPC3, one large deletion in PDLIM3, one duplication of the entire TNNT2 gene and one large duplication in LMNA.Our data suggest that the proportion of HCM cases with pathogenic CNVs is small (1%). For the small subset of patients with clearly interpretable CNVs, our findings have direct clinical implications. Short read sequence data can be used for CNV calling, but the high false positive rate requires a validation step. The two-step strategy described here is effective at identifying novel genetic causes of HCM and similar techniques should be applied whenever possible.

Aims Surgical myectomy has been successfully used to treat patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). More recently, alcohol septal ablation has been advocated as a less invasive, but equally effective alternative therapy. The aim of this non-randomized cohort study was to compare subjective and objective outcomes in patients undergoing these therapies. Methods Forty-four patients (25 male; age 41±15 years) with symptomatic drug-refractory obstructive HCM were studied. Twenty-four patients underwent surgical myectomy and 20 alcohol septal ablation. All patients underwent clinical evaluation, echocardiography and upright maximal cardiopulmonary exercise testing using a cycle ergometer before and following their intervention. Results Peak gradient was reduced to a similar extent by both modalities (myectomy: 83±23 to 15±10mmHg ( P

To determine the effect of multisite pacing on left ventricular function.Prospective observational study.18 patients with heart failure with a dilated poorly functioning left ventricle (LV) and left bundle branch block.Pacing for 5 minutes in random order at the right ventricle (RV) apex, RV outflow tract, mid posterolateral LV, RV apex and LV simultaneously, and RV outflow tract and LV simultaneously. The best achieved measurements with RV, LV, and biventricular pacing were compared.LV dimension, filling characteristics, and long axis indices were measured on echocardiography simultaneously with LV pressure. Cycle efficiency (%)--that is, the ratio of the area of the acquired pressure dimension loop to that of the ideal loop for that segment--quantified coordination.The pacing site that gave the best achieved cycle efficiency differed between patients (biventricular in five, LV in two, RV in seven, and no site in four). In patients with baseline incoordination (cycle efficiencyor = 72%, n = 12) cycle efficiency improved significantly with RV pacing (cycle efficiency 76%, p = 0.01) but not with LV (65%) or biventricular (67%) pacing. LV based pacing induced premature short axis contraction in a subset of patients (n = 4), which was associated with a prolonged time from the Q wave on the ECG to the onset of inward movement of the long axis (from apex to mitral ring): biventricular 145 ms, LV 105 ms, RV 85 ms (biventricular v RV, p0.05). Excluding patients with baseline incoordination in whom premature activation occurred, pacing at all sites led to a similar increase in cycle efficiency (RV 78%, LV 72%, biventricular 73%).Ventricular coordination can be improved with pacing in patients with baseline incoordination. Short and long axis fibres may be asynchronised in a subset of patients with LV or biventricular pacing, which may worsen coordination. The clinical significance of these findings remains to be defined.

Background — Although studies have suggested that “late-onset” hypertrophic cardiomyopathy (HCM) may be caused by sarcomeric protein gene mutations, the cause of HCM in the majority of patients is unknown. This study determined the prevalence of a potentially treatable cause of hypertrophy, Anderson-Fabry disease, in a HCM referral population. Methods and Results — Plasma α-galactosidase A (α-Gal) was measured in 79 men with HCM who were diagnosed at ≥40 years of age (52.9±7.7 years; range, 40–71 years) and in 74 men who were diagnosed at Conclusion — Anderson-Fabry disease should be considered in all cases of unexplained hypertrophy. Its recognition is important given the advent of specific replacement enzyme therapy.

Conventional Doppler indices of left ventricular diastolic function do not correlate with symptoms or exercise capacity in patients with hypertrophic cardiomyopathy, because of their dependence on loading conditions. Diastolic mitral annular velocity measured using Doppler tissue imaging has been reported to be a preload independent index of left ventricular diastolic function.To determine the relation between diastolic annular velocities combined with conventional Doppler indices and symptoms or exercise capacity in hypertrophic cardiomyopathy.85 patients with hypertrophic cardiomyopathy and 60 normal controls were studied. Diastolic mitral annular velocities, transmitral left ventricular filling, and pulmonary venous velocities were measured.Early diastolic velocities at lateral and septal annulus were lower in patients with hypertrophic cardiomyopathy than in controls (lateral Ea: 10 (3) v 18 (4) cm/s, p0.0001; septal Ea: 7 (2) v 12 (3) cm/s, p0.0001). Unlike conventional Doppler indices alone, transmitral early left ventricular filling velocity (E) to lateral Ea ratio correlated inversely with peak oxygen consumption (r = -0.42, p0.0001). Patients in New York Heart Association (NYHA) class III had a higher transmitral E to lateral Ea ratio (12.0 (4.6)) than those in NYHA class II (7.6 (3.1), p0.005) or class I (6.6 (2.6), p0.0001).Early diastolic mitral annular velocities are reduced in patients with hypertrophic cardiomyopathy. Unlike conventional Doppler indices alone, the transmitral E to lateral Ea ratio correlates with NYHA functional class and exercise capacity.

The European Society of Cardiology has convened a Task Force on Sudden Cardiac Death in order to provide a comprehensive, educational document on this important topic. The main document has been published in the European Heart Journal in August 2001[1]. The Task Force has now summarized the most important clinical issues on sudden cardiac death and provided tables with recommendations for risk stratification and for prophylaxis of sudden cardiac death. The present recommendations are specifically intended to encourage the development and revision of national guidelines on prevention of sudden cardiac death. The common challenge for cardiologists, physicians of other medical specialties and health professionals throughout Europe is to realize the potential for sudden cardiac death prevention and to contribute to public health efforts to reduce its burden.

BACKGROUND—Two common mutations of the haemochromatosis associated gene (HFE) (cys282tyr (C282Y) and his63asp (H63D)) have been implicated in haemochromatosis and as modulators in cardiovascular disease. OBJECTIVE—To investigate the role of these mutations in the pathogenesis of idiopathic dilated cardiomyopathy. DESIGN AND SETTING—Case-control and prospective cohort study of patients attending a cardiomyopathy unit in a tertiary referral cardiac centre. METHODS—207 unrelated white patients with dilated cardiomyopathy, followed up for 259 patient years, and 200 controls were tested for HFE C282Y and H63D mutations by polymerase chain reaction and restriction digestion. RESULTS—31/207 patients (15%) v 24/200 controls (12%) carried C282Y (adjusted odds ratio (OR) 1.2 (95% confidence interval 0.7 to 2.2)), 74/207 (36%) v 53/200 (27%) carried H63D (OR 1.6 (1.1 to 2.5)), and 10/207 (4.8%) v 4/200 (2%) were compound heterozygotes (OR 2.6 (0.8 to 8.5)). Four patients and six controls were H63D homozygous and one was C282Y homozygous. There was a progressive increase in mean serum iron ([Fe]) and transferrin saturations from patients with no mutation ([Fe] = 16.3 µmol/l, transferrin saturation = 23.7%) through H63D heterozygotes (17.5 µmol/l, 25.8%), C282Y heterozygotes (17.1 µmol/l, 26.6%), H63D homozygotes (20.0 µmol/l, 33.5%), compound heterozygotes (26.8 µmol/l, 41.7%), and C282Y homozygotes (34 µmol/l, 71%). At follow up (median 90 months) the rate of death or cardiac transplantation was 52/207 (25%). C282Y heterozygotes had less ventricular dilatation (mean (SD): 59.9 (1.7) mm v 64.9 (0.9) mm, p

BACKGROUND—Left ventricular enlargement with normal systolic function is common in asymptomatic relatives of patients with familial dilated cardiomyopathy, many of whom progress to overt dilated cardiomyopathy at follow up. OBJECTIVE—To examine maximal and submaximal gas exchange variables of cardiopulmonary exercise testing in asymptomatic relatives with left ventricular enlargement. DESIGN AND SETTING—Controlled evaluation of metabolic exercise performance of patients with dilated cardiomyopathy and asymptomatic relatives with left ventricular enlargement identified through prospective family screening in a cardiomyopathy outpatient clinic. METHODS—23 relatives with left ventricular enlargement, 33 normal controls, 29 patients with dilated cardiomyopathy, and 10 elite athletes with echocardiographic criteria of left ventricular enlargement ("physiological" enlargement) underwent symptom limited upright cycle ergometry using a ramp protocol. RESULTS—Peak oxygen consumption (pVO2; mean (SD)) was significantly reduced in relatives with left ventricular enlargement (78 (16.3)%) v normal controls (96%, p VO2 was less than 80% of predicted in 75% of patients, 58% of relatives, 22% of controls, and none of the athletes. Oxygen pulse (pVO2/heart rate) was less than 80% of predicted in 69% of patients, 35% of relatives, 6% of controls, and none of the athletes. The slope of minute ventilation v CO2 production (ΔVE/ΔVCO2) was > 30 in 68% of patients, 50% of relatives, and in none of the controls or athletes. Anaerobic threshold, occurring in relatives at 37 (14)% of the predicted VO2, was higher than in the patients (32%, p

AIM—To screen for a mutation of the cardiac troponin T gene in two families where there had been sudden deaths without an increase in left ventricular mass but with myocardial disarray suggesting hypertrophic cardiomyopathy. METHODS—DNA from affected individuals from both families was used to screen the cardiac troponin T gene on an exon by exon basis. Mutation screening was achieved by polymerase chain reaction and direct sequencing. Where appropriate, a mutation was confirmed by restriction digest. RESULTS—A novel missense mutation of exon 9 was found in the affected individuals of one of the families. This mutation at amino acid 94 resulted in the substitution of arginine for leucine and was not found in 100 normal control samples. A mutation of the cardiac troponin T gene was excluded in the second family. CONCLUSIONS—A mutation of the gene for the sarcomeric protein cardiac troponin T can cause familial hypertrophic cardiomyopathy with marked myocyte disarray and frequent premature sudden death in the absence of myocardial hypertrophy at clinical or macroscopic level. Keywords: hypertrophic cardiomyopathy; troponin T

OBJECTIVES This study was performed to evaluate the characteristics, mode of inheritance and etiology of familial dilated cardiomyopathy (FDC). BACKGROUND A genetic form of disease transmission has been identified in a relevant proportion of patients with dilated cardiomyopathy (DCM). Variable clinical characteristics and patterns of inheritance, and an increased frequency of cardiac antibodies have been reported. An analysis of FDC may improve the understanding of the disease and the management of patients. METHODS Of 350 consecutive patients with idiopathic DCM, 281 relatives from 60 families were examined. Family studies included clinical examination, electrocardiography, echocardiography and blood sampling. Of the 60 DCM index patients examined, 39 were attributable to FDC and 21 were due to sporadic DCM. Clinical features, histology, mode of inheritance and autoimmune serology were examined, molecular genetic studies were undertaken and the difference between familial and sporadic forms was analyzed. RESULTS Only a younger age (p = 0.0005) and a higher ejection fraction (p = 0.03) could clinically distinguish FDC patients from those with sporadic DCM. However, a number of distinct subtypes of FDC were identified: 1) autosomal dominant, the most frequent form (56%); 2) autosomal recessive (16%), characterized by worse prognosis; 3) X-linked FDC (10%), with different mutations of the dystrophin gene; 4) a novel form of autosomal dominant DCM with subclinical skeletal muscle disease (7.7%); 5) FDC with conduction defects (2.6%), and 6) rare unclassifiable forms (7.7%). The forms with skeletal muscle involvement were characterized by a restrictive filling pattern; the forms with isolated cardiomyopathy had an increased frequency of organ-specific cardiac autoantibodies. Histologic signs of myocarditis were frequent and nonspecific. CONCLUSIONS Familial dilated cardiomyopathy is frequent, cannot be predicted on a clinical or morphologic basis and requires family screening for identification. The phenotypic heterogeneity, different patterns of transmission, different frequencies of cardiac autoantibodies and the initial molecular genetic data indicate that multiple genes and pathogenetic mechanisms can lead to FDC.

Aims Atrioventricular synchronous pacing exerts beneficial effects, including reduction of left ventricular outflow tract gradients, in patients with hypertrophic obstructive cardiomyopathy. The Pacing in Cardiomyopathy study was initiated to explore the effects of pacing in a double-blind randomized crossover fashion. The aims were to ascertain the beneficial effects of pacing in a controlled study and to rule out a placebo effect by pacing. This paper deals with the outcome of pacing on quality of life during 1 year of follow-up. Methods Quality of life was evaluated with the Karolinska questionnaire, validated for patients paced for bradyarrhythmias and ischaemic heart disease. Drug-refractory patients with hypertrophic obstructive cardiomyopathy were recruited for the study and after a temporary pacing procedure implanted with permanent pacemakers. Patients were randomized to two study arms defining the sequence of pacemaker programming. In one arm the pacemaker was inactive, in the other active. After 3 months the pacemaker was reprogrammed to the alternate mode and a further 3 months followed. After this period subsequent pacemaker programming corresponded to the mode preferred by the patient. A last assessment was made 1 year after baseline examinations. Results Eighty patients completed the first crossover period and 75 completed the full 1 year of follow-up. Active pacing induced significant quality of life improvements, in the order of 9–44%, regardless of programming sequence. Discontinuation of pacing after a first active period resulted in the return of symptoms. Fourteen patients requested early reprogramming after having been programmed to inactive pacing after a first period of active pacing. Seventy-six patients preferred active pacing after the crossover period. A further 6 months of pacing induced progressive improvement in symptoms already favourably influenced. Conclusion Atrioventricular synchronous pacing has a profound beneficial effect on most domains of quality of life in patients with hypertrophic obstructive cardiomyopathy refractory to drug treatment.

Background The therapeutic options for hypertrophic obstructive cardiomyopathy (HOCM) classically include medical treatment with beta-blockers and calcium antag-onists or myectomy–myotomy as a surgical possibility for refractory cases. The observation that pacemaker activation of the heart in HOCM reduces the subaortic gradient is well known but less well investigated. Methods Eighty-three patients (33 female and 50 male) mean age 53 (18–82) years, with symptoms refractory to drug treatment and a resting gradient above 30 mmHg, who responded favourably to temporary pacing, were included in this prospective study and had a pacemaker (DDD) implanted. After an initial double-blind crossover phase of 6 months, patients were reinvestigated at 12 months and followed for a mean of 36 months. Results As observed during a screening investigation, the obstruction was significantly reduced from 72±35 mmHg to 29±24 mmHg ( P

Verapamil alleviates symptoms in patients with hypertrophic cardiomyopathy (HCM), but the underlying mechanism of improvement remains speculative. Baseline and dipyridamole myocardial blood flow (MBF) were measured in 15 HCM patients (14 men, 42 +/- 10 years), before and after 4 weeks of verapamil SR 480 mg daily, using O-15 labelled water and positron emission tomography (PET). Subendocardial (endo) and subepicardial (epi) MBF was measured in the septum (thickness 25.4 +/- 5.8 mm). Pre-treatment baseline whole heart MBF was 1.02 +/- 0.28 ml/min/g and 1.01 +/- 0.30 ml/min/g on treatment (p = ns). Dipyridamole MBF was 1.39 +/- 0.31 ml/min/g off treatment and 1.23 +/- 0.34 ml/min/g on treatment (p = ns). Coronary flow reserve (dipyridamole/resting MBF) was 1.45 +/- 0.52 and 1.30 +/- 0.51, respectively (p = ns). At baseline, the septal endo/epi MBF ratio was uniform off and on treatment (1.13 +/- 0.18 vs 1.18 +/- 0.21, p = ns). Before treatment, the endo/epi ratio following dipyridamole decreased to 0.93 +/- 0.24 (p < 0.01 vs baseline) and 5/15 (33%) patients had a ratio < 0.8 which would suggest subendocardial underperfusion. During treatment, the endo/epi ratio following dipyridamole was no more different from baseline (1.06 +/- 0.24, p = ns vs baseline) and 2/14 (14%) patients had an endo/epi < 0.8. PET can be successfully used to determine transmural MBF in vivo in patients with hypertrophied ventricles. Despite symptomatic improvement, high dose verpamil therapy does not increase total MBF in patients with HCM but may improve septal transmural MBF distribution during dipyridamole in some patients.

Objective—To assess the frequency of circulating cardiac specific autoantibodies in HIV positive patients with and without echocardiographic evidence of left ventricular dysfunction. Subjects—74 HIV positive patients including 28 with echocardiographic evidence of heart muscle disease, 52 HIV negative people at low risk of HIV infection, and 14 HIV negative drug users who had all undergone non-invasive cardiac assessment were studied along with a group of 200 healthy blood donors. Results—Cardiac autoantibodies detected by indirect immunofluorescence (serum dilution 1/10) were more common in the HIV positive patients (15%), particularly the HIV heart muscle disease group (21%), than in HIV negative controls (3.5%) (both p

Thallium-201 perfusion abnormalities are common in patients with hypertrophic cardiomyopathy and may be associated with an adverse prognosis in the young. The aim of this study was to prospectively determine the relationship between thallium-201 defects during dipyridamole stress to clinical presentation and outcome in a large consecutive series of patients with hypertrophic cardiomyopathy.Thallium-201 single photon computed tomography was performed in 216 patients with hypertrophic cardiomyopathy during dipyridamole stress (0.5 mg. kg-1). Fixed perfusion defects occurred in 25%, and reversible defects in 22%. A combination of defects was present in 7%. Fixed defects were associated with: a history of syncope (17 of 46 with, vs 36 of 170 without syncope, P = 0.03); larger left ventricular end-diastolic (46.9 +/- 7.4 mm vs 43.3 +/- 6.4 mm; P = 0.001) and end-systolic dimension (30.2 +/- 8.4 mm vs 24.5 +/- 5.9 mm, P0.0001); increased left atrial diameter (46.1 +/- 8.1 mm vs 40.5 +/- 7.7 mm, P0.0001); lower fractional shortening (35.9 +/- 10.4% vs 43.8 +/- 8.6%, P0.0001): and lower maximal exercise oxygen consumption (24.2 +/- 8.1 ml. min-1. kg-1 vs 29.4 +/- 8.8 ml. min-1. kg-1, P0.0003). Reversible defects did not correlate with symptomatic status, but were associated with: larger left atrial dimensions (44.5 +/- 8.1 mm vs 41.0 +/- 8.0 mm; P = 0.009) and greater maximal left ventricular wall thickness (24.0 +/- 7.0 mm vs 20.6 +/- 7.0 mm, P = 0.003). The mean follow up time was 41 +/- 21 months, range 0.6-124. There was no association between any thallium-201 abnormality and disease related death in young or adult patients.The present study shows that fixed thallium-201 perfusion defects detected during dipyridamole stress in patients with hypertrophic cardiomyopathy are associated with syncope, larger left ventricular cavity dimensions and reduced exercise capacity. Although the event rate was relatively small, there was no evidence for an association between thallium-201 defects and survival.

Non-sustained ventricular tachycardia on Holter and syncope have been considered risk factors for sudden death in hypertrophic cardiomyopathy. Aims In these patients the coronary vasodilator reserve is impaired despite normal coronaries, so we evaluated the correlation between the severity of coronary vasodilator reserve impairment and the occurrence of syncope and non-sustained ventricular tachycardia. Methods and Results Eighty-four patients with hypertrophic cardiomyopathy (62 males, age 43 +/- 12 years) had a two-dimensional echocardiographic study and a 48-h Holter. Myocardial blood flow was measured by positron emission tomography, at baseline and after dipyridamole, and the coronary vasodilator reserve was computed as dipyridamole myocardial blood flow/baseline myocardial blood flow. In 27 patients, subendocardial and subepicardial myocardial blood flow was measured in the septum and the subendocardial/subepicardial ratio was computed. Twenty of 84 patients had at least one syncopal episode, and 26 had at least one run of non-sustained ventricular tachycardia on Holter. Baseline and dipyridamole myocardial blood flow, coronary vasodilator reserve, and baseline and dipyridamole subendocardial/subepicardial myocardial blood flow ratio were similar in patients with and without syncope and with and without non-sustained ventricular tachycardia on Holter. However, patients with nonsustained- ventricular tachycardia had larger left ventricular end-diastolic (47+/-6 vs 44+/-5 mm, P

Sudden cardiac death continues to be the leading cause of mortality in developed countries. Electrical alternans of the ST segment and the T wave on the surface ECG as a noninvasive marker of patients at risk is a phenomenon that was initially observed early in this century and was seen then to be associated with cardiac rhythm disturbances. Substantial evidence indicates that T wave alternans (TWA) is related to myocardial ischemic as a harbinger of malignant ventricular arrhythmias because it reflects dispersion and heterogeneity of repolarization. Recent data have demonstrated a significant correlation between TWA and vulnerability to ventricular arrhythmias in individuals with or without organic heart disease, it also predicts the results of electrophysiological testing and arrhythmia-free survival in patients with a variety of cardiac diseases. This article reviews the historical background of TWA and discusses the early experimental and recent clinical evidence implying an integral link between TWA and ischemia-induced cardiac vulnerability.

Background: There is great disparity in the literature as to the presence and relevance of enterovirus in heart tissue from patients with dilated cardiomyopathy (DCM). Published estimates of enteroviral positive tissue in DCM range from 0 to 50%. Very little sequence information is so far available on those samples which are positive. Hypothesis: Re-examination of fresh biopsy material from patients previously tested, plus 13 new cases of DCM, and sequencing the products would yield information on the validity of the technique and on the type of virus being detected. Methods: RNA from biopsy or explant tissue was tested for the presence of enterovirus using reverse transcriptase polymerase chain reaction (PCR). The nucleotide sequences of all positive PCR products were determined by direct sequencing. Results: Positive PCR signals were found in 10% of samples from patients with DCM and in 16% of control tissues. Two DCM and 12 control samples gave the same nucleotide sequence, which was different from the CB3 used as a positive control. The other 4 DCM samples all produced multiple bands on sequencing. Conclusion: The results do not support a major role for enterovirus in DCM. There is need for some caution, however, as a review of the literature shows that studies using single biopsies, such as this one, produce consistently lower estimates for enterovirus than do those wherein multiple biopsies are examined.

Idiopathic dilated cardiomyopathy (IDCM) is the main cause of cardiac transplantation in young adults in the 20-40 years age group in the Western world. Recent evidence supports a possible role for autoimmune pathogenesis in IDCM and it has been suggested that T cells could mediate the disease. Cardiac myosin is one of the putative autoantigens recognized by antibodies from patients with IDCM, but T cell responses to cardiac myosin have not previously been assessed. Proliferation to cardiac myosin by peripheral blood mononuclear cells (PBMC) from patients, their relatives and controls was assessed in a lymphoproliferation assay specifically designed to measure low frequency T cell precursor responses. The study group consisted of 23 patients with IDCM and 29 relatives. The control groups consisted of 10 patients with heart failure secondary to ischaemic heart disease (IHD) and 22 healthy laboratory controls. A response to myosin was observed in 16.7% of the subjects studied. However, these responses were all of low precursor frequency and no dose response for antigen-specific proliferation could be observed. More importantly, there was no correlation between myosin-specific T cell responses and IDCM, as only one IDCM patient and four IDCM relatives (three out of the four with left ventricular enlargement (LVE)) were among the 14 subjects whose PBMC exhibited a proliferative response. However, proliferation of PBMC to purified protein derivative of Mycobacterium bovis (PPD) was significantly suppressed in IDCM patients when compared with the laboratory control group (P

AIM: Myocarditis and dilated cardiomyopathy may be phases of an organ-specific autoimmune disease of the myocardium. To provide evidence for autoimmune involvement in myocarditis, cardiac autoantibodies were detected in patient sera from the Myocarditis Treatment Trial. METHODS AND RESULTS: Cardiac antibody status was assessed by indirect immunofluorescence and by anti-alpha-myosin enzyme-linked immunosorbent assay in 53 patients from the Myocarditis Treatment Trial (35 males, aged 42 +/- 15 years); all had clinical myocarditis, but only 24 were classified as having histological myocarditis (Dallas criteria). By immunofluorescence, cardiac antibodies were more common in myocarditis (13/53) than in ischaemic (11/186, P = 0.0001) or in normal controls (24/270, P = 0.001). Abnormally raised anti-alpha-myosin antibodies were also more frequent in myocarditis (9/53) than in ischaemic (4/92, P = 0.01) or normal controls (4/203, P = 0.001); 34% of myocarditis patients were positive with one or both tests. Similar proportions of patients with and without histological myocarditis had antibodies by immunofluorescence (8/24 vs 5/29, P = ns) and by enzyme-linked immunosorbent assay (4/24 vs 5/29, P = ns). CONCLUSION: The detection of disease-specific cardiac autoantibodies supports autoimmune involvement in a subset of patients with clinical myocarditis. The lack of correlation of antibody with biopsy features suggests that diagnosis of myocarditis should not be made on histology alone. Autoimmune markers may provide adjunct diagnostic tools and identify patients in whom immunosuppression is of potential benefit.

OBJECTIVE: To determine the relation of cardiac autoantibody and disease status in a consecutive series of patients with dilated cardiomyopathy by prospective antibody testing at diagnosis and at follow up. METHODS: Antibody status was assessed by indirect immunofluorescence in 110 patients with dilated cardiomyopathy (85 male, mean (SD) age 44 (13) years) at diagnosis and at follow up (mean (SD) 14 (12) months); in 57 of them cardiac specific anti-alpha myosin antibody titres were also measured by an enzyme-linked immunosorbent assay (ELISA). Patients underwent complete evaluation at diagnosis and clinical and non-invasive assessment at follow up, including exercise testing with maximal oxygen consumption measurements. RESULTS: The frequency of cardiac specific antibodies by immunofluorescence was lower at follow up than at diagnosis (28 (25%) v 11 (10%), P = 0.002). Mean (SEM) anti-alpha myosin antibody titres at follow up were also lower than at diagnosis (0.24 (0.02) v 0.30 (0.02), P = 0.038); 24% of patients at diagnosis and 14% at follow up had an abnormal ELISA result. None of the patients who were negative by immunofluorescence or ELISA at diagnosis became positive at follow up. Presence of antibody at diagnosis was associated with milder symptoms and greater exercise capacity at follow up and persistence of antibody at follow up was associated with stable disease and milder symptoms at diagnosis. CONCLUSIONS: Cardiac specific autoantibodies in dilated cardiomyopathy become undetectable with disease progression; this is a recognised feature of other autoimmune conditions, such as type 1 diabetes. Detection of these antibodies at diagnosis and at follow up may provide a non-invasive marker of early dilated cardiomyopathy.

Background: A proportion of patients with dilated cardiomyopathy (DCM) may have ongoing myocardial damage secondary to viral or immune mediated myocardial inflammation. Hypothesis: The prognostic determinants identify patients with decreased survival but do not provide a measure of myocardial damage. To obtain an objective assessment of myocardial damage in DCM, we measured plasma levels of creatine kinase (CK), its isoenzymes (CK-MM and CK-MB), and separated the isoforms of CK-MM and CK-MB. Methods: The cohort consisted of 77 consecutive patients (61 men, 16 women) with DCM (World Health Organization criteria), aged 49 ± 14 years (range 19–60). Patients had been symptomatic for 29 ± 38 months (range 0.5–200 months) with 48 in New York Heart Association class I/II and 29 in class III/IV at the time of diagnosis. During median follow-up of 27 months from diagnosis (range 0.6–165), 50 patients remained clinically stable and 27 had deteriorated. Results: A significantly higher proportion of patients with DCM had abnormal MB2/MB1 ratio compared with normal volunteers (11,14% vs. 1, 1%, p = 0.003). Patients who deteriorated had higher MB2/MB1 ratio, (1.22 ± 0.62 vs. 0.85 ± 0.56;p = 0.01), and more frequently had abnormal MB2/ MB1 ratio (8,30% vs. 3,6%;p=0.004) and CK and CK-MM activities (5, 19% vs. 2, 4%;p = 0.03) than those who remained stable. Patients with DCM with high CK-MB activity had 3.13-fold increased odds of sudden death or need for cardiac transplantation (95% confidence interval 1.53–6.40, p = 0.008). Thus, CK measurements, in particular CK-MB isoforms, are markers of myocardial damage in a subset of patients with DCM and could be useful in investigating the possibility of persistent myocardial damage in these patients.

Retrospective and prospective analyses of heart transplant recipients showed no significant association between acute rejection and the detection of cytomegalovirus (CMV) infection by culture or the polymerase chain reaction (PCR) for viral DNA, neither on grounds of the incidence of both conditions nor in relation to which was diagnosed first in the patient. Semiquantitative PCR of serial blood and endomyocardial biopsy specimens from individual patients revealed different patterns in the development of the viral DNA in the blood and the heart, also clear episodes of CMV infection in CMV antibody-negative recipients of hearts from CMV antibody-negative donors, none of whom went on to develop a CMV-specific antibody response. None of these findings was associated with the development of rejection in the patient. On the other hand, in those patients who did experience rejection, peak levels of CMV DNA in the blood and the heart were usually not reached until 6 weeks or more after transplantation, whereas in those in whom rejection was not detected at all during the period of observation, peak levels of CMV DNA were detected earlier, mainly with in the first 6 weeks after transplantation. In several cases, the delayed increase in CMV DNA in those with rejection, albeit not the delay itself, was linked to treatment with steroids. These findings support the view that CMV infection and rejection are independent events, but that the timing of the infection, and whether or not rejection is detected, are indicative of the general status of the immune response in individual patients.

Patients with hypertrophic cardiomyopathy frequently complain of chest pain during daily activities. ST-segment depression is described in association with sudden death and pacing, but its prevalence during ambulatory electrocardiographic monitoring is unknown. The aim of this study was to determine the relation of ambulatory ST-segment depression to clinical characteristics, risk factors for sudden death and thallium-201 perfusion in patients with hypertrophic cardiomyopathy. Continuous 48 h ambulatory electrocardiographic monitoring was performed in 113 patients (age 38 +/- 14 years) with hypertrophic cardiomyopathy. Ninety-four (83%) recordings were suitable for ST-segment analysis. A total of 109 episodes of ST-segment depression (or = 1 mm from baseline) were recorded in 25 (27%) patients (mean 4 +/- 5). In patientsor = 30 years of age (but not30) there was an association between ST-segment depression and a history of exertional chest pain (seven of 12 vs one of 20; P = 0.001), and dyspnoea NYHA class II/III (seven of 15 vs one of 17; P = 0.008). There was no association between ST-segment depression and risk markers for sudden death, i.e. family history of sudden death, syncope and non-sustained ventricular tachycardia, in any group. Reversible thallium-201 defects occurred in 27 (29%) of the 94 patients with analysed recordings but were not associated with symptoms, risk factors for sudden death or ambulatory ST-segment depression. In young patients with hypertrophic cardiomyopathy, ischaemia-like ST-segment depression is common and is associated with a history of typical angina and dyspnoea. Reversible thallium-201 perfusion defects are associated with neither symptomatic status nor ambulatory ST-segment depression.

Increased QT dispersion, which has been proposed as a marker of ventricular repolarization inhomogeneity, may predispose to ventricular arrhythmias. Data on QT dispersion in patients with congestive heart failure are scarce. In this study, conventional 12-lead ECGs were recorded in 135 consecutive patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy. Seventy-five patients were excluded from QT interval assessments due to one or more of the following reasons: (1) low amplitude of the T wave (n = 3), (2) atrial fibrillation (n = 26) and (3) bundle branch block (n = 46). QT dispersion was calculated as (1) QT-range: the difference between the maximum and minimum QT intervals on any of the 12 leads and (2) QT-SD: the standard deviation of the QT interval in all the 12 leads. RR intervals were measured in leads II, aVL, V2 and V5. QT-SD (20.85 +/- 5.00 ms) was significantly (r = 0.8997, P0.001) related to QT-range (65.65 +/- 15.77 ms), but not to the QT interval. Neither QT-range nor QT-SD was significantly related to age, left ventricular dimensions, left ventricular end diastolic pressure, left ventricular ejection fraction or left ventricular wall thickness. There was no significant difference in QT dispersion between survivors and those who died (n = 8) or were transplanted (n = 9) during 34 +/- 23 month follow-up. No significant difference in QT dispersion was observed between patients with and without ventricular tachycardia (or = three consecutive beats) detected on 24-h Holter ECGs. RR interval variation was significantly lower in patients who died compared with survivors (standard deviation: 10.37 +/- 3.61 vs 36.02 +/- 35.03 ms, P0.001; coefficient of variance: 1.87 +/- 0.7% vs 4.50 +/- 4.9%, P = 0.001). This was also true in patients with bundle branch block. These observations suggest that QT dispersion in idiopathic dilated cardiomyopathy is not significantly related to either QT interval or cardiac size and function and does not predict death. The application of QT dispersion assessment is limited by the commonly encountered atrial fibrillation and bundle branch block in this patient population. However, reduced RR variation on standard 12-lead ECGs has important prognostic implications in these patients.

A male freestyle skier was found to have atrial fibrillation during a routine physiological assessment. This was found to be associated with the consumption of an unusually large amount of alcohol. Athletes should be counselled about the potential dangers of alcohol consumption before exhaustive exercise.

Organ- and disease-specific cardiac autoantibodies are found in a third of dilated cardiomyopathy patients from the U.K. and Italy and represent markers of autoimmune involvement. The role of autoimmunity may vary in dilated cardiomyopathy patients from different countries due to differences in genetic susceptibility to autoimmune diseases. The aim of this study was to assess the frequency of organ-specific cardiac autoantibodies detected by immunofluorescence in a consecutive series of patients with dilated cardiomyopathy and in disease and normal control subjects from Poland. The study groups included 79 patients with idiopathic (WHO criteria) dilated cardiomyopathy, 55 patients with other cardiac disease and 60 normal subjects. Cardiac antibody tests were performed by indirect immunofluorescence on human heart; skeletal muscle was used to identify cross-reacting antibodies. The frequency of organ-specific cardiac autoantibodies was higher in patients with dilated cardiomyopathy (21/79, 27%) than in controls with other cardiac disease (1/55, 2% P < 0.001) or in normal subjects (7/60, 12% P < 0.02). Conversely, cross-reactive antibodies were detected in similar proportions in patients with dilated cardiomyopathy (5/79, 6%), disease controls (7/55, 13%) and normal subjects (6/60, 10%, P = ns). The organ-specific antibody was more common in patients with dilated cardiomyopathy with insidious onset of disease (17/34, 50%) compared to those who did not exhibit this feature (4/45, 9%, P < 0.0001). Organ- and disease-specific cardiac autoantibodies were found in 27% of Polish patients with dilated cardiomyopathy at diagnosis; this is evidence for autoimmune involvement in a subset of patients from our country, as seen in a previously reported series of Western European origin. The association of antibody status with insidious onset of symptoms is in keeping with the long latency period observed in other autoimmune disorders.

OBJECTIVE--To use an enzyme linked immunoassay (ELISA) technique to assess frequency and disease specificity of anti-alpha-myosin antibodies in patients with dilated cardiomyopathy and their relatives. METHODS--Evaluation was performed on sera (dilution 1/320) from 123 consecutive patients with dilated cardiomyopathy (WHO criteria) (age 42 (SD 14) years), 252 of their relatives (35 (17) years), 203 healthy controls (45 (16) years), and 92 patients with ischaemic heart disease (63 (11) years). RESULTS--Abnormal antibody levels were commoner in patients with dilated cardiomyopathy (25, 20%) than in ischaemic heart disease (4, 4%), or normal controls (4, 2%, P = 0.001). Forty one (16%) of the relatives had abnormal results compared to the controls (4, 2%, P < 0.001) and antibodies were detected in 20 (38%) of pedigrees. Relatives from non-familial kindreds had higher antibody levels than those with familial disease (P << 0.001), and higher antibody levels were identified in 53 relatives of probands who had abnormal results compared to 116 relatives for whom the proband had a normal result (0.37 (SEM 0.02) v 0.22 (0.01); P < 0.001). CONCLUSIONS--The finding of anti-alpha-myosin antibodies in 20% of patients with dilated cardiomyopathy, in 16% of their asymptomatic relatives, and in 38% of families (particularly those with non-familial disease and where proband also had an abnormal result) provides additional evidence for autoimmunity against alpha myosin in a subset of patients.

This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon deflation (13.4 +/- 2.8; p0.01) compared with baseline levels (8.8 +/- 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/- 3.1; p0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7; p0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND--It has been shown that heart rate variability is decreased in patients with congestive heart failure and that depressed heart rate variability is associated with a propensity to ventricular arrhythmias. Little is known, however, about heart rate variability in patients with both congestive heart failure and ventricular arrhythmias. METHODS--Spectral heart rate variability was analysed from 24 hour ambulatory electrocardiograms in 15 controls, 15 patients with non-sustained ventricular tachycardia associated with clinically normal hearts (NHVT group), and 40 patients with congestive heart failure (CHF group) secondary to either ischaemic heart disease (n = 15) or idiopathic dilated cardiomyopathy (n = 25). Of the 40 patients with congestive heart failure 15 had no appreciable ventricular arrhythmias (ventricular extrasystoles < 10 beats/h and no salvos) and formed the CHF-VA- group. Another 15 patients with congestive heart failure and non-sustained ventricular tachycardia formed the CHF-NSVT group. RESULTS--Heart rate variability was significantly lower in the CHF group than in controls (mean (SD) total frequency 23 (12) v 43 (13) ms; low frequency 12 (8) v 28 (9) ms; high frequency 8 (5) v 14 (7) ms; p < 0.001). The differences in heart rate variability between controls and the NHVT group, between ischaemic heart disease and dilated cardiomyopathy, and between the CHF-VA- and CHF-NSVT groups were not significant. In the CHF group heart rate variability was significantly related to left ventricular ejection fraction but not associated with ventricular arrhythmias. The frequency of ventricular extrasystoles was significantly related to the high frequency component of heart rate variability (r = 0.54, p < 0.05) in the NHVT group. Stepwise multiple regression analysis showed that in the CHF group, heart rate variability was predominantly related to left ventricular ejection fraction (p < 0.05). There was no significant difference in heart rate variability between survivors (n = 34) and those who died suddenly (n = 6) at one year of follow up in the CHF group. CONCLUSION--In patients with congestive heart failure, heart rate variability is significantly decreased. The depressed heart rate variability is principally related to the degree of left ventricular impairment and is independent of aetiology and the presence of ventricular arrhythmias. The data suggest that analysis of heart rate variability does not help the identification of patients with congestive heart failure at increased risk of sudden death.

OBJECTIVE--To test the hypothesis that the loss of the inhibitory effect of the cardiac ventricular afferent fibres on the vasomotor centre would result in increased vasoconstrictor drive to the forearm and renal vascular beds during supine exercise in heart transplant recipients. DESIGN--Comparison of regional haemodynamic response to exercise in heart transplant recipients and two age matched control groups. SETTING--Regional heart transplant unit. PATIENTS AND METHODS--Orthotopic heart transplant recipients (n = 10), patients with NYHA class II heart failure (n = 10), and normal controls (n = 10) underwent short duration maximal supine bicycle exercise. MAIN OUTCOME MEASURES--Simultaneous measurements were made of heart rate, systemic blood pressure, oxygen consumption (VO2), forearm blood flow, and renal blood flow. Forearm blood flow was measured by forearm plethysmography and renal blood flow by continuous renal vein thermodilution. RESULTS--The peak forearm vascular resistance was significantly greater in the transplant group than in the controls (mean (SEM) 75 (18) v 40 (7) resistance units, p < 0.05). The percentage fall in renal blood flow at peak exercise was significantly greater in heart transplant recipients than in the controls (44% (4%) v 32% (4%), p < 0.05) as was the percentage increase in renal vascular resistance (transplants: 116% (19%) v controls: 78% (17%), p < 0.05). Regional haemodynamics during exercise in the heart failure group were not significantly different from those in the controls. CONCLUSIONS--These findings suggest that surgical division of the cardiac ventricular afferent fibres results in increased vasoconstrictor drive to the kidneys and non-exercising muscle during exercise. This mechanism may contribute to persistent exercise limitation and renal impairment after heart transplantation.

Late potentials detected by the signal-averaged ECG (SAECG) identify post-infarction patients at risk from sustained ventricular tachycardia (VT) and sudden death. Hypertrophic cardiomyopathy (HCM) is also associated with increased risk of sudden death. In adults, episodes of non-sustained VT on ambulatory ECG monitoring are a marker of high risk patients. In children and adolescents, however, there is no reliable ECG marker, and clinical features have low predictive accuracy. The prognostic value of the SAECG in HCM has not been systematically evaluated. We examined the relation of detailed time domain, frequency domain, and spectral temporal mapping analysis of the SAECG and clinical and echocardiographic features, and the results of 48 h ambulatory ECG monitoring in 121 consecutive patients with HCM. Non-sustained VT on Holter monitoring was recorded in 27 (23%) patients. An abnormal time domain SAECG was present in three (11%) patients with VT vs three (3%) without VT (ns). Of the SAECG variables, reduced (below 150 microV) voltage of the initial 40 ms of the signal-averaged QRS complex was the best predictor for non-sustained VT (sensitivity: 95%; specificity: 74%: positive predictive accuracy: 64%; negative predictive accuracy: 97%). Nine patients (of whom eight wereor = 30 years of age) experienced catastrophic events: three died suddenly and six had been resuscitated from out-of-hospital ventricular fibrillation. None of them had an abnormal time domain SAECG. The frequency domain analysis and spectral temporal mapping of the SAECG did not improve the identification of patients with VT or patients with catastrophic events. In conclusion, alterations of the initial portion of the signal-averaged QRS complex identified patients with HCM and non-sustained VT, but the SAECG was not useful in identifying young patients who suffered cardiac arrest.

BACKGROUND Elevation of pulmonary vascular resistance is an important determinant of right ventricular function in patients with end-stage biventricular heart failure. Vasodilator drug therapy directed at the pulmonary vasculature is used in the hemodynamic assessment of patients for orthotopic heart transplantation, and therapy aimed at decreasing pulmonary vascular resistance and transpulmonary pressure gradient has been advocated in patients awaiting heart transplantation. Adenosine infusion has been shown to cause selective pulmonary vasodilatation in normal subjects and in patients with primary pulmonary hypertension but has not been assessed in patients with biventricular heart failure. METHODS AND RESULTS Using two infusion doses, we studied the pulmonary and renal hemodynamic effects of adenosine on patients referred for heart transplantation (n = 21) and compared it with sodium nitroprusside (n = 18). Patients received 30% oxygen via face mask throughout the study. Adenosine at 100 micrograms/kg min achieved the same percentage fall in pulmonary vascular resistance as nitroprusside (41 +/- 6% versus 42 +/- 4%) and a greater and more consistent fall in transpulmonary pressure gradient (35 +/- 6% versus 9 +/- 30%, p less than 0.02). The mean arterial blood pressure fell by 16 mm Hg with nitroprusside but was unchanged by adenosine, indicating that in contrast to nitroprusside, adenosine acted as a selective pulmonary vasodilator. Despite this, cardiac index showed only a modest increase with adenosine (1.73 +/- 0.09 to 1.89 +/- 0.16 l.m-2, p less than 0.05), and there was a rise in pulmonary capillary wedge pressure from baseline at the higher dose (29.7 +/- 2.5 to 33.4 +/- 3.4 mm Hg, p less than 0.05). Renal blood flow was unchanged during adenosine infusion. CONCLUSIONS Adenosine is a potent selective pulmonary vasodilator in patients with biventricular heart failure and is preferable to sodium nitroprusside as a test for the reversibility of pulmonary vasoconstriction. However, its deleterious effects on left atrial pressure make it unsuitable as a therapeutic agent in patients awaiting heart transplantation.

Two families are described in which individuals showed widespread myocardial disarray at histological examination, in the absence of macroscopic cardiac hypertrophy. In one family the clinical presentation was that of sudden unexpected cardiac death in four family members; members of the other family presented with electrocardiographic repolarisation changes and abnormalities of left ventricular diastolic function. The finding of myocardial disarray, the characteristic histological abnormality of hypertrophic cardiomyopathy, in the absence of increased cardiac mass suggests a wider range of abnormality in hypertrophic cardiomyopathy than is currently recognised.

Objective: To describe the characteristics of sudden arrhythmic death syndrome (SADS) and compare its incidence with official national mortality statistics for unascertained deaths. Design and setting: Sudden unexplained deaths were prospectively surveyed through 117 coroners’ jurisdictions in England. Consecutive cases meeting the following criteria were included: white Caucasian, aged 4–64 years, no history of cardiac disease, last seen alive within 12 h of death, normal coroner’s autopsy, cardiac pathologist’s confirmation of a normal heart and negative toxicology. Main outcome measures: The estimated mortality from SADS was calculated and the official mortality statistics for unascertained causes of deaths in 4–64-year-olds was identified for the same time period. Results: 115 coroner’s cases were reported and 56 (49%) SADS victims were identified: mean age 32 years, range 7–64 years and 35 (63%) male. 7 of 39 cases (18%) had a family history of other premature sudden deaths (

Dilated cardiomyopathy (DCM) has been recognised as a familial condition in a proportion of cases.1 Left ventricular enlargement (LVE) with normal systolic function is common in asymptomatic relatives of patients with familial DCM; these relatives do not fulfil the diagnostic criteria for DCM. Many such relatives go on to develop overt DCM.1 Although LV fractional shortening is by definition normal in relatives with LVE, the implication that these relatives have underlying myocardial pathology2 would suggest that subtle LV systolic and diastolic abnormalities are detectable with appropriate techniques. We hypothesised that Doppler tissue imaging (DTI),3,4 might reveal subtle abnormalities of systolic and diastolic function that may help to predict asymptomatic relatives with LVE that will go on to develop DCM. The aim of this study was to characterise LV systolic and diastolic function in asymptomatic relatives with LVE, using DTI and conventional echocardiographic techniques. Sixteen asymptomatic relatives with LVE (mean (SD) age 37 (13) years), from 15 families attending a referral centre between 1998 and 1999, underwent echocardiography and were compared with 22 patients with DCM (mean age 43 (9) years) undergoing follow up evaluation during the same time period. The majority of patients with DCM were in New York …

The diagnosis of hypertrophic cardiomyopathy has relied on echocardiographic demonstration of unexplained left ventricular hypertrophy. The prevalence of hypertrophic cardiomyopathy defined in this way has been estimated to be 1:500 and experience indicates that these criteria are relatively specific when other causes of left ventricular hypertrophy are absent. In recent years, however, the systematic evaluation of pedigrees performed in the context of molecular genetic studies revealed that in some families with hypertrophic cardiomyopathy up to 20% of adults who carry a disease causing gene defect do not fulfil conventional echocardiographic criteria. None the less, most of these individuals show symptoms, electrocardiographic alterations, and/or minor echocardiographic abnormalities. Revised diagnostic criteria in members of families with hypertrophic cardiomyopathy are proposed, including major and minor criteria based on symptoms, and electrocardiographic and echocardiographic abnormalities. Given that the chance of inheriting the gene defect is 1:2, the likelihood that symptoms plus electrocardiographic or echocardiographic abnormalities are the expression of a disease causing gene is high.

To determine the range of survival rates of patients with hypertrophic cardiomyopathy (HCM) by comparing and contrasting the natural history of a cohort of patients seen between 1988 and 2002 with that of other published series.956 adult (or = 16 years old) patients with HCM (572 men, mean (SD) age 42 (15) years, range 16-88) were evaluated by ECG, Holter, exercise testing, and echocardiography. Patient characteristics and survival data were compared with those in natural history studies from referral and non-referral centres published between 1960 and January 2003.The duration of follow up was 69 (45) months. 120 (12.6%) patients died or underwent cardiac transplantation. Sudden cardiac death (n = 48) was the most common mode of death. The annual rate of sudden death or implantable cardioverter-defibrillator discharge was 1.02 (95% confidence interval (CI) 0.76 to 1.26). Annual rates for heart failure death or transplantation and stroke related death were 0.55% (95% CI 0.37% to 0.78%) and 0.07% (95% CI 0.02% to 0.19%), respectively. When studies published within the last 10 years of the study period were compared with earlier reports, the size of individual study cohorts was larger (309 (240.6) v 136.5 (98.8), p = 0.058) and the proportion with severe functional limitation NYHA class III/IV lower (12.4% v 24.8%, p0.0001), and fewer patients underwent septal myotomy-myectomy (5.2% v 18.7%, p0.0001). Published sudden death rates over the last 10 years were lower than previously published figures (median 1.0% (range 0.1-1.7) v 2.0% (0-3.5)).Published survival rates in HCM cohorts have improved progressively over the past 40 years. In the modern era the prevalence of disease related complications is similar in all reporting centres.

To determine the frequency of systolic impairment (SI) and its impact on the natural history of hypertrophic cardiomyopathy (HCM).1080 patients (mean (SD) age 43 (15) years, 660 men) with HCM were evaluated. Initial assessment included history, examination, 48 hour Holter monitoring, cardiopulmonary exercise testing, and echocardiography; SI was defined as a fractional shortening (FS)or = 25%. Survival data were collected at clinic visits or by direct communication with patients and their general practitioners. The results of serial echocardiography in 462 patients with normal FS at presentation are also reported.26 (2.4%) patients (49 (14) years, 18 men) had SI at the initial visit. During follow up (58 (49) months), nine (34.6%) died or underwent cardiac transplantation compared with 108 (10.2%) patients with normal FS (p = 0.01). Five year survival from death (any cause) or transplantation was 90.1% (95% confidence interval (CI) 87.8 to 92.4) in patients with normal systolic function versus 52.4% (95% CI 25.2 to 79.6, p0.0001) in patients with SI. In patients who underwent serial echocardiography, 22 (4.8%, aged 41 (15) years) developed SI over 66 (40) months; the annual incidence of SI was 0.87% (95% CI 0.54 to 1.31). On initial evaluation patients who developed SI had a higher frequency of syncope (67 (15.2%) v 10 (45.5%) of those who did not develop SI, p = 0.001), non-sustained ventricular tachycardia (91 (20.6%) v 11 (50%), p = 0.002), and an abnormal blood pressure response on exercise (131 (29.7%) v 15 (68.2%), p = 0.001). Patients with SI had greater wall thinning (p = 0.001), left ventricular cavity enlargement (p0.0005), and deterioration in New York Heart Association functional class (p = 0.001) during follow up. Thirteen (59.1%) patients who progressed to SI died or underwent transplantation compared with 38 (8.6%) patients who maintained normal systolic function.SI is an infrequent complication of HCM but, when present, is associated with a poor prognosis.

In March 2002, a 25 year old white woman presented to the British Olympic Medical Centre after bouts of syncope and pre-syncope. The athlete was an international rower, competing in the single sculls event, and was training an average of 10 sessions/week. Training sessions included rowing and weight training, with training across the full range of intensities. The presenting symptoms included two episodes of syncope after 2000 m maximal tests on a rowing ergometer, together with episodes of pre-syncope on water that had not resulted in syncope. All episodes of pre-syncope/syncope occurred immediately after exercise in a seated position. The duration of syncope was not formally documented but was described as lasting one or two minutes, with periods of malaise lasting for considerable periods (more than one hour) after syncope. There had been no previous examination of heart rate and/or blood pressure response during these episodes. Separately the patient noted a tendency for pre-syncope and syncope during medical procedures. There was no family history of heart disease including sudden “unexplained” death. On examination, the athlete was in sinus rhythm with bradycardia (about 40 beats/min) and sinus arrhythmia. All other measures, including PR and QT interval, were within normal limits. Resting blood pressure was 110/70 mm Hg. Echocardiography showed normal intracardiac dimensions (maximum left ventricular wall thickness; 10 mm) with normal systolic function of both left and right ventricles. Origins of left and right coronary arteries were normal. Mild pulmonary valve regurgitation was noted (inaudible clinically). During integrated cardiopulmonary exercise stress testing, the athlete completed level 5 of a BRUCE protocol stopping because of maximal exercise capacity. …