Counselling issues in familial hypertrophic cardiomyopathy.

To illustrate the variable clinical presentations and rates of progression in familial hypertrophic cardiomyopathy (FHC), phenotypes and genotypes were compared in three FHC families with different genetic defects. In the first family, the FHC abnormality was a protein truncating mutation (Gln969X) in the cardiac myosin binding protein C gene. The second family had a missense change (Asn755Lys) in the same gene. A missense mutation (Arg453Cys) in the cardiac beta myosin heavy chain gene was present in the third family. Penetrance associated with the Gln969X defect was 27% in the age range 0 to 40 years. This was considerably less than the 93% penetrance (0 to 40 years) observed in the two families with missense mutations. The variable penetrance in FHC, as well as the unpredictability of sudden cardiac death, complicates clinical diagnosis and management, including genetic counselling. Although a genetic disease with a predominantly adult onset, there are counselling issues in FHC which set it aside from other adult onset disorders.

Molecular pathology of familial hypertrophic cardiomyopathy caused by mutations in the cardiac myosin binding protein C gene.

DNA studies in familial hypertrophic cardiomyopathy (FHC) have shown that it is caused by mutations in genes coding for proteins which make up the muscle sarcomere. The majority of mutations in the FHC genes result from missense changes, although one of the most recent genes to be identified (cardiac myosin binding protein C gene, MYBPC3) has predominantly DNA mutations which produce truncated proteins. Both dominant negative and haploinsufficiency models have been proposed to explain the molecular changes in FHC. This study describes two Australian families with FHC caused by different mutations in MYBPC3. The first produces a de novo Asn755Lys change in a cardiac specific domain of MYBPC3. The second is a Gln969X nonsense mutation which results in a truncated protein. Neither mutation has previously been found in the MYBPC3 gene. The consequences of DNA changes on the function of cardiac myosin binding protein C are discussed in relation to current molecular models for this disorder.

Value of hepatic computerized tomographic scanning during amiodarone therapy.

Amiodarone therapy is difficult to monitor because of the poor correlation between plasma amiodarone levels and clinical efficacy or toxicity. Monitoring tissue levels may give a better measure of effectiveness, but tissue levels cannot be easily measured. The iodine-containing amiodarone and its major metabolite, desethylamiodarone (DA), are highly tissue-bound, and it has been shown that computerized tomographic (CT) scanning of the abdomen will detect drug deposition in the liver. Ten patients receiving chronic amiodarone therapy were studied by abdominal CT scanning. Liver CT density was increased in 6; 68 to 94 CT units (normal 50 to 65) and liver/spleen relative CT density increased in 5; 1.4 to 2.0 (normal 1.0 to 1.3). Estimates of liver drug levels (based on a calibration curve with inorganic iodide) gave values of up to 3 g of amiodarone and DA per kilogram weight of liver. Absolute and relative liver CT density correlated significantly with plasma levels of DA (r = 0.65, p less than 0.05), but not with amiodarone (r = 0.55, p less than 0.1). No significant correlation was found with QTc intervals. This indirect estimate of liver deposition of amiodarone and DA may prove useful in guiding antiarrhythmic therapy.

Echocardiographic features of a mediastinal pancreatic pseudocyst.

Cross sectional echocardiography detected a mediastinal pancreatic pseudocyst which caused extracardiac compression in a 49 year old man. Computed tomography confirmed the presence of a cystic lesion lying behind the heart and extending from the pancreas to above the carina. Surgical decompression resulted in resolution of the clinical and echocardiographic findings.

Intra-aortic balloon ECG artefact.

Patients undergoing intra-aortic balloon counter pulsation (IABP) for acute life threatening cardiac disease usually have abnormal electrocardiograms (ECGs) and are prone to arrhythmias and conduction disturbances. We report a patient in whom movement of the electrocardiographic lead to the left leg by the balloon catheter caused artefact simulating a conduction disturbance and arrhythmia.

Prognosis after an initial non-Q-wave myocardial infarction related to coronary arterial anatomy.

Eighty-six consecutive hospital survivors (aged less than or equal to 60 years) of a first non-Q-wave acute myocardial infarction (MI) were followed up prospectively. Coronary arteriography was performed a median of 2 weeks after MI. The size of the MI was small (as judged by a mean peak creatine kinase level of 906 IU/liter); 90% were in Killip class I, and the mean left ventricular ejection fraction was 60 +/- 11% (+/- standard deviation). Forty-nine patients had 1 vessel significantly narrowed by disease (greater than or equal to 70% luminal diameter reduction), 19 had 2-vessel, 2 had 3-vessel, 3 had left main (greater than or equal to 50% luminal diameter reduction), and 13 minimal or no coronary artery disease (CAD). Complete occlusion of the MI-related vessel was present in 33 patients. All 33 and an additional 5 patients had collateral vessels to the MI area. During a mean follow-up of 25 months, 1 cardiac death and 4 recurrent infarcts (3 with non-Q-wave MI) occurred. Angina occurred in 53 patients (62%) and responded medically in all but 7 who underwent coronary artery surgery. Angina after MI occurred frequently in patients with severe proximal left anterior descending CAD (greater than or equal to 90%), and in those with CAD (greater than or equal to 50%) in a vessel supplying collaterals to the infarct area. Because angina can be managed medically in most patients and the outcome is good, routine coronary angiography is not indicated in asymptomatic survivors less than or equal to 60 years of a first non-Q-wave MI.

Results after repair of coarctation of the aorta beyond infancy: a 10 to 28 year follow-up with particular reference to late systemic hypertension.

The late outcome in 160 patients aged 1 to 54 years who had surgical repair of coarctation of the aorta was examined 10 to 28 years postoperatively. Twenty years postoperatively the probability of survival of patients discharged from the hospital aged 1 to 19 years at operation was a little less than that of the general population (95% versus 97%). The discrepancy between patients and the general population was more marked in those aged 20 to 39 years and was grossly different when surgical repair was undertaken beyond age 40. There were 19 late deaths (12%), 79% due to cardiovascular disease. Thirteen patients had a poor result because of recoarctation (11 patients) or the development of complications at the site of repair (2 patients). Most patients were hypertensive before operation. The frequency of hypertension decreased markedly in the first few postoperative years. Blood pressure was normal in most patients 5 to 10 years after operation, but when followed up for longer periods the proportion of patients with hypertension increased. Hypertension was more common in patients operated on after 20 years of age than in those aged 5 to 19 years at operation (p = 0.007). The likelihood of being alive without complications and with a normal blood pressure was 69% at 10 years, 55% at 15 years, and 20% at 25 years postoperatively.

Fatal atheromatous embolization during coronary angiography.

Multiple fatal embolism following left heart catheterization is described in two patients. Postmortem examination showed friable atheromatous aortic plaques as the likely source of emboli that clinically involved the heart, peripheral blood vessels, brain, gastrointestinal system and solid organs. Histologic examination showed widespread arterial embolism by atheromatous material.

Mitral valve vegetations in bacterial endocarditis resembling left atrial myxoma.

A patient with Staphylococcus aureus endocarditis is reported whose echocardiogram closely resembled that found in left atrial myxoma. Because of severe mitral incompetence, the valve was replaced using cardiopulmonary bypass and at operation a large 3 cm friable vegetation was found attached to the posterior leaflet of the mitral valve. Histological examination showed changes typical of bacterial endocarditis with no evidence of myxoma.

Sociomedical study of patients over 75 in general practice.

In a survey of people of 75 years and over in a general practice situated in the north-west of England a total of 297 patients was examined. Among the many previously unreported medical conditions and social needs were seven unknown malignant conditions, 28 patients with heart failure, five with diabetes, and one with myxoedema. A high incidence of nutritional anaemia was also found. It is concluded that such a survey can detect much hidden illness and disability and that general practice is the right setting for it.