Sudden death as a presenting symptom of hypertrophic cardiomyopathy: treatment with an implantable cardioverter defibrillator

Aborted sudden death as the presenting manifestation of hypertrophic cardiomyopathy in a 14-year-old child is reported. Documented ventricular fibrillation was the cause of cardiac arrest. No ventricular arrhythmia was induced during programmed electrical stimulation. An implantable cardioverter-defibrillator was indicated. As the patient had a family history of myocardial disease, he had undergone a cardiovascular evaluation 4 years before the major event, and was found normal. It is suggested that normal physical examination, ECG, echocardiogram should not rule out the diagnosis of hypertrophic cardiomyopathy when a family history is present. Left ventricular hypertrophy may develop during childhood in patients with hypertrophic cardiomyopathy.     

Detection of hepatitis C virus RNA from the heart of patients with hypertrophic cardiomyopathy

We investigated hepatitis C virus (HCV) infection in 35 patients with hypertrophic cardiomyopathy and 40 patients with ischemic heart disease who were consecutively admitted to our hospital. Frequency of positive anti-HCV antibody was significantly higher in patients with hypertrophic cardiomyopathy (6 of 35 patients, 17.1%) than that in patients with ischemic heart disease (1 of 40 patients, 2.5%, p = 0.036). In three of these six patients with hypertrophic cardiomyopathy, HCV RNA was detected in myocardial tissue. In two of these three patients, HCV RNA was detected from biopsy and autopsy specimens of the ventricles, but not in the serum, suggesting that HCV may replicate in myocardial tissue and may be relevant to ventricular hypertrophy. Thus, HCV infection may play a role in the development of hypertrophic cardiomyopathy.     

Diastolic dysfunction in hypertrophic myocardiopathy: evaluation with radioisotopic ventriculography

Diastolic function was evaluated in 13 patients with hypertrophic cardiomyopathy and 10 normal subjects of comparable age. Time-activity curves were used to derive peak filling rate, time to peak filling rate and average filling velocity during the first third of diastole. Left ventricular ejection fraction was significantly higher in patients with hypertrophic cardiomyopathy. Time to peak filling rate and filling velocity during the first third of diastole were significantly lower in patients compared to controls. Thus, radionuclide techniques can be used to evaluate diastolic filling in clinical practice.     

Roentgenologic symptomatology of cardiomyopathies (author's transl)

In a material of 162 patients with different types of cardiomyopathy it was found that the standard chest radiograms could give important contributions to the diagnosis of the disease. The two main groups hypertrophic and other cardiomyopathy could in most instances be separated from each other. Nearly all patients had an abnormal chest radiogram when first studied. A positive roentgen diagnosis no standard chest examination supports a clinically suspected diagnosis of cardiomyopathy and should be possible in at least 80% of the patients. Angiocardiography can always provide the diagnosis in unclear cases and gives details of anatamy and function of the left and right ventricles in patients where surgical intervention of an intraventricular obstruction is contemplated.     

Clinical course of hypertrophic cardiomyopathy in a non selected population. The Experience of the Italian Multicenter Cardiomyopathy Study

BACKGROUND: Most of the information available on the clinical course and prognosis of hypertrophic cardiomyopathy (HCM) is based on data generated from international referral centres and as a result, it constitutes a potentially biased perspective of the disease process in this complex and diverse condition. A multicentric study was therefore set up with the aim of providing information on unselected patient populations with HCM. METHODS: The study group comprised 330 patients from 5 non-referral hospitals (mean age 42 +/- 16 years, M/F 226/104, 74-22%-obstructive, 299-91%-in NYHA class I-II) who were followed up regularly for 9.5 +/- 5.6 years. RESULTS: The vast majority of patients (n = 272, 82%) remained asymptomatic or mildly symptomatic during the follow-up period, whereas the remaining patients (n = 58, 18%) experienced clinical deterioration or died. Of the 18 patients (5%) who died of cardiovascular causes related to hypertrophic cardiomyopathy, 14 had progressive congestive heart failure and only 4 died suddenly. The annual mortality rate for cardiovascular disease was 0.57%, while the mortality rate due to sudden cardiac death was only 0.1%. The cumulative survival rate was 98, 95 and 93%, at 5, 10 and 15 years of follow-up respectively. Atrial fibrillation proved to be a relatively common (n = 81, 24%) and particularly unfavourable clinical feature, with higher mortality rate for cardiovascular causes related to hypertrophic cardiomyopathy. Syncope occurred in 47 patients (14%) but did not appear to have prognostic significance. CONCLUSIONS: In an unselected population, hypertrophic cardiomyopathy had a relatively benign prognosis that was inconsistent with its prior characterization as a generally progressive disorder, based primarily on the experience of selected referral institutions. Sudden unexpected cardiac death was distinctly uncommon, although a sizable proportion of patients, particularly the subset prone to atrial fibrillation, did experience clinical deterioration.     

Nonmetastatic accumulations in bone radionuclide scans in a patient with breast neoplasm

Left ventricular dilation and systolic dysfunction develop in 14-16% of patients with hypertrophic cardiomyopathy. Such findings may easily be misdiagnosed as dilated cardiomyopathy. It is unknown whether left ventricular dilatation and systolic dysfunction in patients with hypertrophic cardiomyopathy are reversible. A 35-year-old man had been a heavy drinker for 13 years and was abstinent for 1 year. Five years previously he suffered cardiac arrest and, based on echocardiographic, radionuclide, and cardiac catheterization findings, the diagnosis of alcohol-induced dilated cardiomyopathy was established. At presentation the heart was of normal size, with concentric left ventricular hypertrophy and only slightly reduced systolic function. Hypertrophic cardiomyopathy was diagnosed since no other cause for left ventricular hypertrophy could be detected. In hypertrophic cardiomyopathy, alcohol may induce reversible systolic dysfunction and left ventricular dilatation.     

'Isolated' pulmonary valve stenosis as part of more widespread cardiovascular disease

In 25 patients aged 6 days to 9 years presenting as 'isolated' pulmonary valve stenosis, histology of the myocardium of right and left ventricles, coronary arteries, and ascending aorta has shown abnormality in one or all these areas. Myocardial necrosis, old and recent, unrelated to coronary occlusion was frequent. Myocardial 'dysplasia' involving both ventricles, and resembling hypertrophic cardiomyopathy (HOCM, ASH) was found in 10 and a relation of this to myocardial injury in the fetus is postulated. Varying degrees of coronary occlusion were frequently seen in both right and left coronary arteries. The histology of the ascending aorta was abnormal showing 'higgledy-piggledy' disorder of smooth muscle components in 12 (48%). In a different series of 53 patients who had pulmonary valvotomy for apparent 'isolated' pulmonary valve stenosis there were 14 with clinical evidence of left ventricular abnormality consistent with the pathological changes described, 2 with the same aortic histological changes, and 2 with macroscopical left ventricular hypertrophy. Two of them developed classical hypertrophic cardiomyopathy years later. It is suggested that when pulmonary valve stenosis presents with a thick tricuspid poorly mobile valve, particularly in infants or in patients with evidence of other congenital stigmata, it may be part of a more widespread cardiovascular abnormality. This should be recognized and considered in the evaluation of surgical patients and late survivors who may show unexpected clinical features.     

Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy

BACKGROUND: Mutations in the gene for cardiac myosin-binding protein C account for approximately 15 percent of cases of familial hypertrophic cardiomyopathy. The spectrum of disease-causing mutations and the associated clinical features of these gene defects are unknown. METHODS: DNA sequences encoding cardiac myosin-binding protein C were determined in unrelated patients with familial hypertrophic cardiomyopathy. Mutations were found in 16 probands, who had 574 family members at risk of inheriting these defects. The genotypes of these family members were determined, and the clinical status of 212 family members with mutations in the gene for cardiac myosin-binding protein C was assessed. RESULTS: Twelve novel mutations were identified in probands from 16 families. Four were missense mutations; eight defects (insertions, deletions, and splice mutations) were predicted to truncate cardiac myosin-binding protein C. The clinical expression of either missense or truncation mutations was similar to that observed for other genetic causes of hypertrophic cardiomyopathy, but the age at onset of the disease differed markedly. Only 58 percent of adults under the age of 50 years who had a mutation in the cardiac myosin-binding protein C gene (68 of 117 patients) had cardiac hypertrophy; disease penetrance remained incomplete through the age of 60 years. Survival was generally better than that observed among patients with hypertrophic cardiomyopathy caused by other mutations in the genes for sarcomere proteins. Most deaths due to cardiac causes in these families occurred suddenly. CONCLUSIONS: The clinical expression of mutations in the gene for cardiac myosin-binding protein C is often delayed until middle age or old age. Delayed expression of cardiac hypertrophy and a favorable clinical course may hinder recognition of the heritable nature of mutations in the cardiac myosin-binding protein C gene. Clinical screening in adult life may be warranted for members of families characterized by hypertrophic cardiomyopathy.     

Hypertrophic obstructive cardiomyopathy in pediatric patients: results of surgical treatment

Between April 1975 and May 1995, 25 pediatric patients on one hospital service underwent extended left ventricular septal myectomy because of hypertrophic obstructive cardiomyopathy. Ages ranged from 2 months to 20 years (mean, 11.2 years). Seventeen patients had moderate to severe mitral valve insufficiency. Medical therapy had failed in all patients and one patient had undergone dual-chamber pacemaker implantation without improvement. Left ventricular outflow tract gradients ranged from 50 to 154 mm Hg (mean, 99.9 +/- 25.2). Concomitant cardiac procedures included mitral valve repair (n = 2), automatic implantable cardioverter defibrillator implantation (n = 1), and closure of atrial septal defect (n = 1). Intraoperative premyectomy left ventricular outflow tract gradients ranged from 20 to 117 mm Hg (mean, 60.4 + 26.2) and postmyectomy gradients ranged from 0 to 20 mm Hg (mean, 6.6 +/- 5.9). Postmyectomy mitral insufficiency was reduced to a regurgitant fraction of 0% to 12%, and no patient required mitral valve replacement. One patient required a pacemaker because of complete heart block; on subsequent follow-up, normal sinus rhythm had returned. There was no early mortality and no instance of aortic or mitral valve injury or ventricular septal defect. Follow-up ranged from 10 months to 20 years (mean, 6.4 years). There were no late deaths. Left ventricular outflow tract gradients by echocardiography were a mean of 14.2 mm Hg with a median of 5.0 mm Hg. All patients had normal sinus rhythm. Reoperation because of recurrent left ventricular outflow tract obstruction was necessary in two patients at 3.2 years and 12.4 years after initial myectomy, respectively. All patients but one have New York Heart Association class I or II function. We conclude that extended septal myectomy is a safe and effective means of relieving cardiac symptoms and left ventricular outflow tract obstruction in pediatric patients with severe hypertrophic obstructive cardiomyopathy unresponsive to medical management, and late survivorship compares favorably with the natural history of the disease.     

Mid-ventricular obstruction: a variant of obstructive cardiomyopathy

In two patients with clinical and catheterization findings of hypertrophic obstructive cardiomyopathy, the level of intraventricular obstruction was found to be in the mid-ventricular area rather than at the junction of the inflow and outflow tracts. One patient died suddenly shortly after unsuccessful outflow tract myectomy. In vivo recognition of this probably rare variant form of obstructive cardiomyopathy rests mainly on the angiograhic appearance of the left ventricle and on the recording of pressures in multiple sites of the left ventricular cavity. Surgical relief of the obstruction in these patients is not likely to be obtained by a transaortic left ventricular outflow myectomy but may require either papillary muscle resection by the transatrial or transventricular approach or mid-ventricular septectomy, or both.     

Report from the XVII Congress of the European Society of Cardiology, Stockholm, Sweden, August 1997

Cardiac dysrhythmias in septic patients often reflect hypovolaemia, hypokalaemia or endocarditis as cardiac manifestation of the infection, but may be indicative for underlying cardiac pathology previously undiagnosed. We report on the case of a patient with severe peritonitis, on whom transoesophageal echocardiography (TEE) had been performed intraoperatively due to progressive circulatory instability. TEE revealed first diagnosis of asymmetric hypertrophic cardiomyopathy, which complicated the features of septic syndrome. Further perioperative treatment to support the circulation was successfully adjusted on the grounds of this diagnosis.     

Acute myocardial infarction due to vasospasm in a 13-year-old-boy

We describe an unusual case of acute myocardial infarction due to vasospasm in a 13-year-old boy. He was admitted to our hospital with severe congestive heart failure and shock. He had experienced a feeling of chest oppression with dyspnea while running, which grew worse. He then lost consciousness and was brought by ambulance to our intensive care unit. He had had similar but milder episodes of chest oppression months earlier. The family history revealed that his father had died suddenly from hypertrophic cardiomyopathy and that his grandmother also had hypertrophic cardiomyopathy. On admission, the patient was bathed in a cold sweat, his pulse was weak, and his blood pressure was too low to measure. Coarse crackling and wheezing were audible in both lung fields. Administration of catecholamine and intra-aortic balloon pumping failed to stabilize the hemodynamic variables, but percutaneous cardiopulmonary support proved to be lifesaving. Coronary arteriography performed during his convalescence showed on evidence of atherosclerosis. The acetylcholine provocation test ultimately revealed a diagnosis of acute myocardial infarction due to vasospasm.     

Imaging strategies for brain tumours

Growth factors have been shown to be associated with primary hypertrophic cardiomyopathy. Octreotide, a long acting somatostatin analogue, can prevent the stimulating effect of growth factors and decrease the left ventricular mass in patients with acromegaly. In the light of these results, three patients with primary hypertrophic cardiomyopathy were treated with subcutaneous octreotide (50 micrograms three times a day during the first week and 100 micrograms twice a day for the following three weeks). Initially, two patients were in New York Heart Association class II in and one was in class III. At the end of a four week treatment session all were in class I. There were significant decreases in left ventricular posterior wall thickness, interventricular septum thickness, and left ventricular mass in all three patients. Both left ventricular end diastolic and end systolic diameters had increased in all of the patients at the end of the fourth week. Two of three patients showed improved diastolic filling: their hyperdynamic systolic performance returned to normal. No side effects were observed during octreotide treatment. The considerable improvement obtained with the short term octreotide treatment in patients with primary hypertrophic cardiomyopathy seems promising.     

Voluntary muscle involvement in hypertrophic cardiomyopathy. A study of eleven patients

Hypertrophic cardiomyopathy is generally considered to be a primary disease of cardiac muscle, although several clinical observations suggest that the pathologic process might be more diffuse. To further examine this possibility, electromyography and voluntary muscle biopsies were done on 11 patients with hypertrophic cardiomyopathy. In 10 of 10 patients electromyography showed reductions in mean potential amplitude and duration, with an increased incidence of short-duration polyphasic deflections (findings traditionally accepted as indicative of a myopathic process). Light and electron microscopic studies of the biopsy material showed abnormalities in eight of 11 patients: four had central core or target fibers, or both, and two of these, plus four others, had subsarcolemmal mitochondrial proliferation with or without abnormal ultrastructure. These findings indicate that hypertrophic cardiomyopathy is only one aspect of a larger disease spectrum, with abnormalities in both voluntary and cardiac muscle.     

Chronic coronary pseudoaneurysm after stent implantation

A 14-year-old boy presented with anorexia and weakness whereon the diagnosis of dimorphic anaemia was made. An excellent response to iron and vitamin B12 was observed. In addition, the patient had non-obstructive hypertrophic cardiomyopathy. At endoscopy 2.5 years later, an adenocarcinoma was diagnosed and the patient underwent a high subtotal gastrectomy. To the best of our knowledge, this rare association has never been reported in children. CONCLUSION: We report a youngster with pernicious anaemia, associated with nonobstructive hypertrophic cardiomyopathy in whom gastric adenocarcinoma was found. Patients with pernicious anaemia are at greater risk of developing gastric carcinoma than the general population, therefore we recommend routine periodic gastroscopic surveillance in the paediatric population with pernicious anaemia.     

Syncope and ventricular arrhythmias in hypertrophic cardiomyopathy are not related to the derangement of coronary microvascular function

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 non-sustained ventricular tachycardia had larger left ventricular end-diastolic (47 +/- 6 vs 44 +/- 5 mm, P < 0.05) and end-systolic diameters (30 +/- 6 vs 27 +/- 4 mm, P < 0.05). CONCLUSIONS: (1) Coronary vasodilation is not more severely impaired in patients with hypertrophic cardiomyopathy and syncope or non-sustained ventricular tachycardia. (2) The left ventricle is more dilated in hypertrophic cardiomyopathy with non-sustained ventricular tachycardia.     

Is there increased sympathetic activity in patients with hypertrophic cardiomyopathy?

OBJECTIVES: This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy. BACKGROUND: Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking. METHODS: Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis. RESULTS: There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean +/- SD 7.24 +/- 0.88 versus 7.59 +/- 0.57 ln[ms2], p = 0.072). Although there was no significant difference in the high frequency component (5.31 +/- 1.14 versus 5.40 +/- 0.91 ln[ms2], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 +/- 1.00 versus 6.72 +/- 0.61 ln[ms2], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 +/- 8% versus 43 +/- 8%, p = 0.018) and the high frequency component significantly increased (16 +/- 6% versus 12 +/- 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 +/- 0.64 versus 1.33 +/- 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients. CONCLUSIONS: Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone.     

Comparison of coronary vasodilator reserve in elite rowing athletes versus hypertrophic cardiomyopathy

Compared to normal volunteers, coronary vasodilation reserve is reduced in patients with hypertrophic cardiomyopathy but not in rowing athletes with left ventricular hypertrophy. Positron emission tomography can provide complementary information to distinguish between the athlete's heart and hypertrophic cardiomyopathy.     

Identification of two novel mutations in the ventricular regulatory myosin light chain gene (MYL2) associated with familial and classical forms of hypertrophic cardiomyopathy

Five disease genes encoding sarcomeric proteins and associated with familial and classical forms of hypertrophic cardiomyopathy have been determined since 1989. In 1996 two other genes encoding ventricular regulatory and essential myosin light chains were shown to be associated with a particular phenotype of the disease characterized by mid left ventricular obstruction. The aim of the present study was to search for mutations in the ventricular regulatory myosin light chain gene (MYL2), located on chromosome 12q23q24.3, in a panel of 42 probands presenting a classical phenotype of familial hypertrophic cardiomyopathy. Single-strand conformation polymorphism analysis was used to search for mutations in the coding segments of the MYL2 gene, and the abnormal products were sequenced. Two novel missense mutations, Phe18Leu in exon 2 and Arg58Gln in exon 4 were identified in three unrelated families. None of the affected patients had hypertrophy localized only at the level of the papillary muscle with mid left ventricular obstruction. By analysis of genetic recombinations, one of these mutations identified in a large family allowed us to refine the localization of the MYL2 gene on the genetic map, in an interval of 6 cM containing six informative microsatellite markers. In conclusion, we show that mutations in the MYL2 gene may be involved in familial and classical forms of hypertrophic cardiomyopathy, and we provide new tools for the genetic analysis of patients with familial hypertrophic cardiomyopathy.     

Cerebral cysticercosis in Campina Grande, Paraíba--northern Brazil. Computerized tomography diagnosis importance

A woman with Noonan syndrome had clinical and haemodynamic features of restrictive cardiomyopathy. There was no ventricular hypertrophy on echocardiography but myocardial biopsies showed myocyte hypertrophy without pathological disarray. This case illustrates the overlap of the cardiac phenotypes of Noonan syndrome, restrictive cardiomyopathy, and hypertrophic cardiomyopathy.