John F. Goodwin

Amiodarone for long-term management of patients with hypertrophic cardiomyopathy.

Fifty-three patients with hypertrophic cardiomyopathy who had serious arrhythmias (45 patients), refractory chest pain (5 patients) or a high risk of sudden death (3 patients) received amiodarone for 6 to 96 months (median 18) after completion of a loading and an initial maintenance period. The dose of amiodarone was altered by 50 to 200 mg/day at 3- to 6-month intervals, guided by electrocardiographic monitoring, plasma drug level measurements and side-effect questionnaires. Ventricular tachycardia was suppressed in 24 patients (92%) with doses of 100 to 400 mg/day (median 300); none died suddenly during a mean follow-up of 27 months. Although symptomatic episodes of frequent or prolonged supraventricular tachycardia or paroxysmal atrial fibrillation/flutter were abolished in 8 of 9 patients on 100 to 600 mg/day (median 300), in 1 patient incessant atrial flutter developed that was relatively refractory to direct-current cardioversion. In 11 patients with atrial fibrillation, sinus rhythm was restored in 7 (after direct-current cardioversion in 3) with doses of 100 to 600 mg/day (median 300) and has been maintained in 5 with associated improvement in symptoms. Despite discontinuation of beta-blocker therapy, chest pain was unchanged in 17 patients, was impaired in 11 and was worse in only 2. Amiodarone was discontinued in 3 patients; in 1 because of hair loss, in 1 because of neurologic symptoms and in 1 because of facial discoloration; in the latter 2 patients, amiodarone was restarted after 1 and 14 months, and was tolerated and effective at the lower dosage.(ABSTRACT TRUNCATED AT 250 WORDS)

Sudden death in hypertrophic cardiomyopathy: associated accessory atrioventricular pathways.

Sudden death is a known but unpredictable complication of hypertrophic cardiomyopathy. We describe two patients who both had a strong family history of the disorder complicated by sudden death. Necropsy disclosed accessory bypass tracts, concealed in one and previously suspected in the other. One died from ventricular fibrillation and the other, who died outside hospital, had previously complained of palpitation. Arrhythmia complicating pre-excitation appears to be one of the factors responsible for sudden death in hypertrophic cardiomyopathy.

Hydralazine in the management of left ventricular failure

This study was designed to compare the short and long-term effects of hydralazine when used as a vasodilator in the treatment of left ventricular failure. The hemodynamic changes after the acute intravenous and long-term oral administration of hydralazine were compared in a group of 16 patients with left ventricular failure (14 patients with congestive cardiomyopathy and two with hypertensive heart failure). After 20 mg of hydralazine, administered intravenously there was a 56 percent increase in stroke volume (P < 0.001) and a 27 percent decrease in left ventricular filling pressure (P < 0.001) but no significant change in heart rate despite a 16 percent decrease in mean arterial pressure (P < 0.001). Seven of the patients then took hydralazine, 200 to 300 orally/day for 4 to 6 weeks. They were restudied during therapy with the drug and again 48 to 72 hours after stopping it. After the period of oral treatment there was a 71 percent increase in stroke volume (P < 0.001) and a 25 percent decrease in left ventricular filling pressure (P < 0.05). Forty-eight to 72 hours after discontinuation of drug administration, left ventricular filling pressure had returned to the control value (−3 percent, P < 0.05), but the stroke volume was still slightly elevated (14 percent, P < 0.05). The results show that oral administration of hydralazine can produce sustained benefit with changes similar to those induced by intravenous administration. The second control study after discontinuation of hydralazine therapy confirmed that these changes had been induced by and were dependent on the drug.

M mode echocardiography in hypertrophic cardiomyopathy: Diagnostic criteria and prediction of obstruction

Abstract To assess the reliability of the classic echocardiographic features in the heart with hypertrophic cardiomyopathy as criteria that differentiate it from normal heart and as predictors of outflow tract obstruction versus nonobstruction, 70 patients with clinical and angiographic evidence of hypertrophic cardiomyopathy were studied with M mode echocardiography. The diagnostic sensitivity and specificity of the classic features were assessed: ventricular septal thickness, 83 and 94 percent (sensitivity and specificity, respectively); ventricular septal amplitude of movement, 71 and 89 percent; ventricular septal thickness to left ventricular posterior wall ratio, 79 and 94 percent; left ventricular end-systolic dimension, 54 and 86 percent; septal-mitral valve distance at the onset of systole, 29 and 100 percent; systolic anterior motion of the mitral valve, 61 and 100 percent; and mid systolic closure of the aortic valve, 61 and 100 percent. No single M mode echocardiographic feature was consistently abnormal in hypertrophic cardiomyopathy. In nonobstructive hypertrophic cardiomyopathy, ventricular septal thickness greater than or equal to 13 mm (sensitivity 68 percent and specificity 94 percent) and ventricular septal thickness to posterior wall ratio greater than or equal to 1.5 (sensitivity 82 percent and specificity 94 percent) were the individual features with the greatest diagnostic value from the norm. Patients with obstruction at rest and labile obstruction (gradient only on provocation) had echocardiographically identical features. Ventricular septal thickness greater than or equal to 13 mm plus systolic anterior motion of the mitral valve or mid systolic closure of the aortic valve were the features that in combination best differentiated obstructive (resting and labile) from nonobstructive hypertrophic cardiomyopathy (sensitivity 82 percent and specificity 68 percent) and the heart with obstructive hypertrophic cardiomyopathy from the normal heart (sensitivity 82 percent and specificity 100 percent).

Hypertrophic Cardiomyopathy: A Disease in Search of Its Own Identity"

The search for the identity of hypertrophic cardiomyopathy continues. The paper by Yamaguchi et al.’ in a recent issue of this Journal draws attention to another variation in the spectrum. These workers describe 30 patients in a series of 1,002 consecutive patients investigated with left ventricular angiography and coronary arteriography whose electrocardiograms showed giant inverted T waves with high QRS voltage in the absence of systemic hypertension or occIusive coronary artery disease. In all 30 patients the ventriculogram in the right anterior oblique projection revealed a characteristic spade-like configuration due to concentric apical hypertrophy of the left ventricle and associated with obliteration or elimination of the cavity of the apical portion of the left ventricle at end-systole. Two dimensional echocardiography revealed a similar configuration. No systolic pressure gradient was found even on provocation. The upper half of the septum remained thin instead of bulging into the left ventricle, and systolic anterior motion of the mitral valve was not seen. Many of the cases with apical hypertrophy did not have asymmetric hypertrophy of the septum. The angiographic appearance was contrasted with the “banana” shape observed in hypertrophic obstructive cardiomyopathy in which the authors claim the free wall thickness is increased in all segments. It was not associated with obliteration of the cavity at the apex and the septum was rhomboid in shape in systole in the left anterior oblique projection. All patients showed electrocardiographic abnormalities between the 2nd and 6th decade of life. In four patients, there was a striking progression of electrocardiographic changes over a period of only a few years.

Massive Thrombotic Occlusion of the Large Pulmonary Arteries

In 23 cases of massive thrombotic occlusion of the large pulmonary arteries thrombosis secondary to pulmonary embolism was the major cause, but a proportion (30 per cent) was considered to have primary thrombosis in situ. The pathologic criteria, symptoms, signs, and results of special investigations are given in detail, and the diagnosis, etiology, and precipitating factors are discussed.

Effects of surgical closure of ventricular septal defects upon pulmonary vascular disease.

poor (Bloomfield, 1964). There is less agreement as to the criteria for selection of patients with ventricular septal defects and pulmonary vascular disease for operation, partly because of the constantly improving techniques of operation and postoperative care, and partly because the long-term results of the closure of such defects are known in only a comparatively small number of patients followed over a relatively short period. Additional confusion has been caused by the differing interpretations of the definition of pulmonary hypertension in relation to ventricular septal defect, and by increased awareness of the difficulties in interpreting haemodynamic data, in view of the lability of the pulmonary vascular bed in children. We are therefore presenting our experience of 42 patients with ventricular septal defect and pulmonary vascular disease, describing the patients selected and setting out our follow-up studies on 25 of these patients, who have been followed for up to 8 years after operation. We have concentrated upon the importance of the clinical signs of pulmonary vascular disease in determining the indications for operation.

Relation of left ventricular function and prognosis in hypertrophic cardiomyopathy: An angiographic study

Left ventricular cineangiograms performed at the time of diagnosis in 88 patients with hypertrophic cardiomyopathy were digitized to evaluate the relation of left ventricular function and prognosis in hypertrophic cardiomyopathy. Eleven patients died suddenly after a mean follow-up period of 7.5 +/- 7 years, 10 patients died of congestive heart failure or after cardiac surgery and 67 were alive after a mean follow-up period of 8.6 +/- 4 years. Measurements of left ventricular volume, ejection fraction, peak rate of ejection and filling and time to peak rate of ejection and filling were derived from curves of ventricular volume and its rate of change during the cardiac cycle. Patients who died suddenly had a lower peak rate of ventricular ejection (stroke volume-normalized peak ejection rate 5.41 +/- 0.69 versus 6.24 +/- 1.33 s-1; p = 0.006) and lower peak rate of ventricular filling (end-diastolic volume-normalized peak filling rate 4.02 +/- 0.94 versus 4.88 +/- 1.53 s-1; p = 0.02) and stroke volume-normalized peak filling rate (4.75 +/- 1.08 versus 5.82 +/- 1.70 s-1; p = 0.01) compared with survivors. Stepwise regression analysis revealed that sudden death was best predicted by the combination of increased end-diastolic volume, small end-systolic volume and low peak filling rate (predictive accuracy 32%, false negative 18% and false positive 28%). The addition of clinical features and hemodynamic measurements to the analysis improved predictive accuracy to 43% (false negative 18% and false positive 18%). Ambulatory electrocardiographic monitoring performed in 57 of the 88 patients 1 month to 17 years (median 8 years) after diagnosis revealed ventricular tachycardia in 14 (25%). Of these, 10 who survived had hyperkinetic systolic function at diagnosis, whereas the 4 who died suddenly had impaired systolic function (end-diastolic volume-normalized peak ejection rate 5.93 +/- 1.2 versus 4.01 +/- 1.2 s-1, respectively; p = 0.04). In hypertrophic cardiomyopathy, ventricular tachycardia is a sensitive but nonspecific marker of adults who are at risk of sudden death. Impaired systolic function may be an important determinant of which patients with ventricular tachycardia die suddenly. This study shows that indexes of ventricular function contribute to the identification of patients at particular risk of sudden death. However, the predictive power of the clinical features and hemodynamic and angiographic measurements that could be assessed was poor.(ABSTRACT TRUNCATED AT 400 WORDS)

The natural history of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is estimated to affect 1:500 individuals. It may develop at any age but typically develops during adolescence or early adulthood. Mortality rates in HCM are lower than initially suspected, especially in treated patients, but remain higher than those in the general population. Although the majority of HCM patients develop few or no symptoms, a significant minority will develop advanced heart failure, atrial fibrillation, or stroke. The presence of left ventricular outflow tract obstruction, development of systolic dysfunction (i.e., end-stage HCM), and possibly apical aneurysms has been associated with worse outcomes.

The natural history of left ventricular hypertrophy in hypertrophic cardiomyopathy: an electrocardiographic study.

The natural history of electrocardiographic left ventricular hypertrophy was assessed in relation to clinical features, treatment with propranolol and prognosis in 100 patients with hypertrophic cardiomyopathy who were followed 5‐20 years (mean 8 years). Seventy‐one patients received propranolol, 120‐800 mg/day (mean 240 mg). At diagnosis, the voltage measurement from SV1 ± RV5 was 37 ± 20 mm, the R wave in aVL was 12 ± 6 mm and the mean frontal plane voltage was 15 10 mm. After 5 years, these values were increased to 43 ± 22 mm (p < 0.0002), 14 ± 6 mm (p < 0.003) and 17 ± 10 mm (p < 0.01), respectively. Neither a left ventricular outflow tract gradient nor propranolol treatment influenced these voltage changes. Twenty patients had an increase of more than 10 mm in SV1 ± RV5, which was associated with exertional chest pain (p < 0.006) and death (p < 0.02). Four patients had a decrease of more than 10 mm in SV1 ± RV5. Two of these received high-dose propranolol, one 720 mg/day for 12 years and another 800 mg/day for 12 years. No other patient received more than 480 mg of propranolol daily. In hypertrophic cardiomyopathy there is electrocardiographic evidence of progressive hypertrophy, which is associated with poor prognosis and is not influenced by treatment with propranolol in moderate dosage. Regression of hypertrophy is rare and may be related to long-term treatment with high‐dose propranolol.