Cardiac histologic findings in patients with life-threatening ventricular arrhythmias of unknown origin.

Percutaneous endomyocardial biopsy (right ventricle in 10, left ventricle in 2) was performed in 12 patients, aged 9 to 57 years, with serious ventricular arrhythmias occurring in the setting of normal cardiac anatomy and mechanical function. Light microscopic examination of tissue revealed histologic abnormalities in 11 patients, including myocardial cellular hypertrophy in 7, interstitial fibrosis in 5, endocardial fibrosis in 2, myocardial degenerative changes in 1 and increased interstitial cellularity in 1. One patient had histologic evidence of acute lymphocytic myocarditis. Thus, a majority of patients with serious ventricular arrhythmias and normal cardiac anatomy had histologic abnormalities, bringing into question the concept of primary electrical heart disease or idiopathic ventricular tachycardia.

Electrophysiologic testing in the upright position: improved evaluation of patients with rhythm disturbances using a tilt table.

Patients are traditionally evaluated in the supine position in the electrophysiology laboratory, although symptoms due to a cardiac rhythm disturbance are often maximal clinically during standing. The assumption of the upright position results in dependent displacement of blood, followed by prompt vasoconstriction to maintain arterial pressure. This normal response may aggravate tachyarrhythmias by increasing catecholamine levels or may precipitate vasodepressor syncope if the vasoconstrictor response is absent. The use of a tilt table during electrophysiologic testing was evaluated over a 12 month period in 104 patients having a mean age of 60 years (range 37 to 81): 59 with supraventricular tachycardia, 6 with vasovagal syncope and 39 with carotid sinus hypersensitivity. Twenty-three patients (22%) had significant abnormalities when upright that were not present when supine: eight patients with supraventricular tachycardia who had their clinical syndromes of palpitation and syncope reproduced when upright, but only minimal symptoms when supine; two patients with supraventricular tachycardia who had sustained atrioventricular reentry when upright, but only two to eight beats of tachycardia when supine; six patients with syncope and a normal cardiac evaluation before electrophysiologic testing who had their typical spells only after being placed upright during a vasovagal event and seven patients with carotid sinus hypersensitivity who had their clinical syndromes reproduced with carotid sinus massage only when upright, developing hypotension despite maintaining their heart rate with sinus rhythm or pacing (vasodepressor response). In 22% of patients, electrophysiologic testing in the upright position provided clinically important information that was not evident during standard testing in the supine position.

Symptomatic "isolated" carotid sinus hypersensitivity: natural history and results of treatment with anticholinergic drugs or pacemaker.

Because syncope may occur intermittently in patients with carotid sinus hypersensitivity, a knowledge of its natural history is needed as a basis for interpreting the usefulness of therapy. Fifty-six consecutive patients are described (47 men and 9 women; mean age 61 years) with carotid sinus hypersensitivity and syncope in whom 24 hour ambulatory monitoring and intracardiac electrophysiologic study revealed no other cause for the syncope. The mean duration of symptoms was 44 months (range 1 to 480) and the mean number of episodes was 4.0 (range 1 to 20). During a follow-up period of 6 to 120 months (median 40), syncope recurred in 3 of 13 patients who received no treatment, in 2 of 23 patients who received a pacemaker and in 4 of 20 patients who received anticholinergic drugs (incidences corrected for totals available at follow-up: 27, 9 and 22%, respectively). Two-thirds of the patients receiving no treatment were asymptomatic compared with all nine of the patients with syncope and a pure cardioinhibitory response to carotid sinus massage who received an atrioventricular (AV) sequential pacemaker. Although pacing was effective in abolishing syncope, its use should be reserved for recurrent episodes because of the high rate of spontaneous remission of symptoms.

Effect of amiodarone on left ventricular ejection and filling in hypertrophic cardiomyopathy as assessed by radionuclide angiography.

Left ventricular (LV) function at rest was assessed by radionuclide angiography in 30 patients with hypertrophic cardiomyopathy (HC) before and during treatment with amiodarone (600 to 800 mg for 1 week, 200 to 400 mg/day thereafter) for an initial maintenance period of 1 month in 30 patients and 6 months in 12 patients. The reproduciblity of the measurements was assessed by performing control studies within 24 hours in 13 patients and at 1 to 6 months in 6 patients, and 95% confidence limits for spontaneous change were determined. There was a significant decrease in heart rate at 1 month (from 67 +/- 9 vs 61 +/- 9 beats/min, p less than 0.004) with no further decrease at 6 months. Systemic blood pressure did not change. After amiodarone therapy, for each of the measurements of LV function except peak ejection rate, there was no mean change and the number of patients in whom the values increased and decreased by more than the 95% confidence limits were approximately equal. Peak ejection rate showed a significant decrease at 1 month, but this effect was not maintained at 6 months; 4 of 6 patients who showed a significant decrease at 1 month were reevaluated at 6 months, and in all 4 the values had returned to control levels. These findings suggest that the 95% confidence limits for spontaneous change were not wide enough and that chronic oral amiodarone therapy does not alter radionuclide indexes of LV function at rest in patients with hypertrophic cardiomyopathy.

Role of invasive electrophysiologic testing in patients with symptomatic bundle branch block.

Electrophysiologic testing was performed in 112 symptomatic patients with bundle branch block. Abnormalities included HV interval 70 ms or longer (35 patients), infra-Hisian block with atrial pacing (6 patients) and sinus node dysfunction (23 patients). Inducible ventricular tachycardia occurred in 47 patients (42%). Therapy was based on the electrophysiologic test result: group I--16 patients with no therapy (normal study results); group II--34 patients with permanent pacing alone; group III--39 patients with antiarrhythmic therapy alone; and group IV--21 patients with both antiarrhythmic therapy and permanent pacing. Cumulative 4-year survival rates were 83% in group I, 84% in group II, 63% in group III and 84% in group IV (mean follow-up 2.5 years). Recurrent syncope occurred in 19% of group I, 6% of group II, 33% of group III and 19% of group IV. In symptomatic patients with bundle branch block and normal electrophysiologic test results, prognosis is good without treatment. In patients undergoing permanent pacing based on electrophysiologic testing, survival is good and rate of symptom recurrence is low. Electrophysiologic testing identifies patients with inducible ventricular tachycardia for whom antiarrhythmic therapy is indicated but who nevertheless have a poor prognosis.

Results of percutaneous transluminal coronary angioplasty for unstable angina pectoris in patients 70 years of age and older.

Between November 1980 and November 1985, 54 patients ages greater than or equal to 70 years underwent percutaneous transluminal coronary angioplasty for unstable angina, defined as recent-onset (less than 1 month) angina, new onset of rest angina (greater than or equal to 2 episodes) or accelerating class III or IV angina. In these 20 men and 34 women, disease was 1-vessel in 34 (63%) and multivessel in 20 (37%). The mean (+/- standard deviation) ejection fraction was 0.62 +/- 0.12. Angioplasty was successful in 43 patients (80%). In the 11 unsuccessful cases, emergency coronary artery bypass grafting for acute occlusion was performed in 3 and elective coronary artery bypass surgery in 8. There were no deaths. Two patients (4%) sustained Q-wave myocardial infarctions. The mean duration of follow-up for the total group was 37 months (6 to 73 months). Of the 43 patients with successful dilation, 4 died, 1 had an non-Q-wave myocardial infarction and 8 had symptomatic restenosis (4 underwent successful repeat angioplasty, 1 had repeat percutaneous transluminal coronary angioplasty and then bypass surgery, 1 had repeat bypass surgery alone and 2 had medical therapy). At last follow-up, 3 patients had stable class III or IV angina and 31 patients (72%) were angina-free.

Gender differences in the management and outcome of acute myocardial infarction in unselected patients in the thrombolytic era.

This study compares the clinical features, management, and outcome in men and women from a consecutive, unselected series of patients with acute myocardial infarction (AMI) who were admitted to a university cardiac center over a 3-year period. It is a retrospective observational study of 1,059 admissions with AMI identified through the Hospital In-Patient Enquiry (HIPE) registry, validated according to Minnesota Manual criteria, and followed for a period of up to 5 years (median 36 months). Women comprised 40% of all admissions, had a higher hospital mortality (24% vs. 16%, p<0.001), and were less likely to receive thrombolysis (23% vs. 33%, p<0.01), admission to coronary care (65% vs. 77%, p<0.001), or subsequent invasive or noninvasive investigations (55% vs. 63%, p<0.01). However, women with AMI were older than men with AMI (71 vs. 65 years, p<0.001). After adjusting for age, differences that remained significant were prevalence of hypertension (odds ratio [OR] 2.12, 95% confidence intervals [CI] 1.56 to 2.88) and cigarette smoking (OR 0.47, 95% CI 0.35 to 0.65), management in coronary care (OR 0.66, 95% CI 0.49 to 0.88), and hospital mortality (OR 1.48, 95% CI 1.07 to 2.04). Excess mortality occurred predominantly in women <65 years old (18% vs. 8%, OR [multivariate] 2.35, 95% CI 1.19 to 4.56), among whom multivariate analysis demonstrated a significantly lower thrombolysis rate (OR 0.48, 95% CI 0.27 to 0.86). In this group, lack of thrombolysis independently predicted hospital mortality (OR 5.37, 95% CI 1.45 to 19.82). Female gender was not an independent predictor of mortality following AMI (OR 1.42, 95% CI 0.90 to 2.26). Thus, among unselected patients, female gender is associated with, but not an independent predictor of, reduced survival after AMI. Gender differences in mortality are greatest in younger patients, who are less likely to receive thrombolysis and in whom lack of thrombolysis is independently associated with mortality after AMI.

Surgical treatment of accessory atrioventricular pathways and symptomatic tachycardia in children and young adults.

Twenty-seven patients aged 21 years or younger (mean 15) with symptomatic tachycardia underwent operation for ablation of an accessory atrioventricular pathway. Six patients had associated Ebstein's malformation of the tricuspid valve. Supraventricular tachycardia had been present for a mean of 5 years. At electrophysiologic study, 4 patients were found to have 2 accessory pathways. Left ventricular free wall pathways were found in 14 patients, right ventricular free wall pathways in 10 and septal pathways in 6. Successful initial ablation of all the pathways was achieved in 26 of the 27 patients. No patient died perioperatively and none had persistent complete heart block. During a mean follow-up of 11 months, no patient had recurrence of an arrhythmia related to the accessory pathway. Thus, the surgical treatment of children and young adults with accessory atrioventricular pathways and symptomatic supraventricular tachycardia is safe and effective. For these patients, unless the tachycardia can be easily controlled with a minimal number of drugs and adverse effects, surgical ablation should be considered early in the clinical course.

Histopathologic changes in asymptomatic relatives of patients with idiopathic dilated cardiomyopathy.

Echocardiographic screening of asymptomatic relatives of patients with idiopathic dilated cardiomyopathy identifies a subset with left ventricular enlargement who are assumed to have early familial idiopathic dilated cardiomyopathy. This study shows for the first time that the myocardium in such relatives demonstrates abnormal cellularity.

Carotid sinus hypersensitivity and syncope.

The patient with a hypersensitive carotid sinus reflex and syncope may pose special challenges in evaluation and treatment. Specifically, although the finding of carotid sinus hypersensitivity may indeed indicate an exaggerated vagal tone that causes syncope, it may also be a chance association in a patient with syncope due to another cause. Careful clinical and electrophysiologic testing may be needed to distinguish these two possibilities. Furthermore, the need for drug therapy or cardiac pacing (or both) must be determined on an individual basis, depending on the relative contributions of cardioinhibitory and vasodepressor components to the patient's symptoms and also on the degree of patient limitation.

Clinical intracardiac electrophysiologic testing: technique, diagnostic indications, and therapeutic uses.

Clinical cardiac electrophysiologic testing has evolved rapidly since 1968, when the technique was first described. In an electrophysiologic study, electrode catheters are positioned within the heart to record electrical activity from the atrium, atrioventricular conduction tissue, and ventricle. Programmed stimulation is then performed, which involves pacing of the atrium or ventricle and introducing critically timed premature stimuli during sinus rhythm or paced rhythm. The use of programmed stimulation in conjunction with intracardiac recordings in electrophysiologic studies has facilitated the diagnosis of mechanisms of arrhythmias and the assessment of therapy. Electrophysiologic testing is useful in selected patients with sinus node dysfunction, conduction system disorders, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation and in survivors of out-of-hospital cardiac arrest and patients with symptomatic but unsubstantiated rhythm disturbances. Therapeutic approaches that can be assessed by electrophysiologic testing include serial drug testing to determine the effectiveness of antiarrhythmic agents, antitachycardia pacing, the implantable defibrillator, transcatheter ablation, and electrophysiologically guided surgical procedures. In this review, we discuss the methods of electrophysiologic testing, its clinical applications in diagnosing the various cardiac rhythm disturbances, and its use in assessing various therapeutic modalities.

Refractory supraventricular tachycardia in the neonate: treatment with temporary antitachycardial pacing.

Although intracardiac antitachycardial pacing techniques are frequently used to terminate reentrant supraventricular tachycardia in adults, this approach has rarely been used in neonates. We describe two neonates, both of whom were in circulatory shock due to recurrent paroxysmal supraventricular tachycardia, who were treated with temporary antiatachycardial pacing. This approach allows repeated termination of the tachycardia at the bedside until an adequate therapeutic concentration of an effective drug regimen is achieved and obviates repeated direct-current cardioversion.

Propafenone for the treatment of refractory complex ventricular ectopic activity.

The results of therapy with propafenone were evaluated in 45 patients with complex ventricular ectopic activity that had been refractory to a mean of 3.8 antiarrhythmic drugs. The cardiac diagnoses were ischemic heart disease (in 16 patients), cardiomyopathy (in 7), mitral valve prolapse (in 7), mitral valve prolapse (in 7), idiopathic ventricular ectopic beats (in 6), valvular heart disease (in 5), and hypertension (in 4). The frequency of ventricular ectopic beats was established after therapy with antiarrhythmic agents had been discontinued. Patients then received propafenone during a dose-ranging protocol. An effective response was defined as a reduction in total ventricular ectopic beats of 80% or more. During dose ranging, therapy failed in four patients because of side effects, in eight because of a reduction in ventricular ectopic beats of less than 80%, and in three because of an aggravation of the arrhythmia. Thirty patients had a reduction in total ventricular ectopic beats of 80% or more. During a mean follow-up of 12.4 months, therapy failed in 1 patient because of sustained ventricular tachycardia and in 7 because of intolerable side effects; 22 patients continued to receive propafenone. PR and QRS intervals were significantly prolonged (P = 0.001), but the corrected QT interval and the heart rate were unchanged. The mean trough plasma level of propafenone associated with an effective response was 756 ng/ml, and that associated with intolerable side effects was 920 ng/ml. Thus, in patients with refractory complex ventricular ectopic beats, propafenone was effective and well tolerated initially in 67% of patients and during long-term administration in 49%, and toxicity was minor in most patients.

Impact of intracardiac electrophysiologic testing on the management of elderly patients with recurrent syncope or near syncope.

Seventy-five patients, 75 years of age and over, experienced recurrent syncope, with the etiology remaining unclear but presumably cardiogenic, after cardiac and neurologic examinations and noninvasive laboratory testing (including an electrocardiogram and ambulatory electrocardiographic monitoring). The mean number of previous syncopal spells was 14 (range, 1 to 64) over a mean of 36 months (range, 1 to 480 months). These patients underwent invasive electrophysiologic testing and a potential cause for syncope was identified in 68%. Abnormal findings at electrophysiologic testing included: sinus node dysfunction (55%); abnormal His-bundle conduction (39%); and ventricular tachycardia (14%), with some patients having more than one abnormality. No major complications were associated with the electrophysiologic testing. Patients were subsequently treated with permanent cardiac pacing or antiarrhythmic drugs or both, depending upon results of the electrophysiologic study. Follow-up examinations (mean of 26 months; range, 1 to 70) were possible in 90% of patients. No further syncope occurred in 84% of patients with an abnormal electrophysiologic study who received subsequent therapy to prevent the identified abnormality. Thus, in this difficult group of patients with recurrent syncope of uncertain etiology, electrophysiologic testing was safe and indicated abnormalities of conduction or rhythm in 68% of patients; treatment to correct these abnormalities prevented recurrent syncope in 84%.

Management and outcome of acute myocardial infarction in older patients in the thrombolytic era.

OBJECTIVE: Acute myocardial infarction (AMI) is an important cause of mortality and morbidity in older patients. The aim of this study was to determine the proportion of unselected admissions with AMI that is older than 75 years and to examine management and outcomes in this group. DESIGN: An historical cohort study of consecutive unselected admissions with AMI identified using the Hospital In Patient Enquiry (HIPE) database and validated according to MONICA criteria for definite or probable AMI. SETTING: An acute cardiac unit in a university teaching hospital/cardiac tertiary referral center. RESULTS: Of 1059 patients, 606 (57%) were older than 65 years and 309 (29.2%) were older than 75 years. Mean age in this group was 80.5 years. Hospital mortality was almost twice as high as in patients younger than 75 years (28% vs 15%, P < .001), and age was an independent predictor of short- and long-term mortality following AMI. Women constituted a significantly higher proportion of older patients. Family history of AMI and cigarette smoking were less prevalent in older patients. Mean cholesterol was lower and comorbidities were higher. Other baseline characteristics, including previous AMI, did not differ. However older patients were less likely to receive thrombolysis (13% vs 36%, P < .001), aspirin (76% vs 86%, P < .01), or beta-blockers (25% vs 51%, P < .001) and were less likely to undergo cardiac catheterization or revascularization. Only 53% were admitted to coronary care. CONCLUSION: Patients more than age 75 comprise almost one-third of patients with AMI and have a poor prognosis. Although age is an independent predictor of mortality following AMI, suboptimal management may contribute to the high mortality in these patients.

Idiopathic dilated cardiomyopathy: familial prevalence and HLA distribution.

OBJECTIVES: To compare HLA distribution in familial and non-familial dilated cardiomyopathy, because a serum marker that could identify families at risk of developing dilated cardiomyopathy should be of use in screening for the disease. PATIENTS: 100 patients with dilated cardiomyopathy. METHODS: 200 first degree relatives from 56 of the proband families were screened for dilated cardiomyopathy by echocardiography. The HLA profile of the patients with dilated cardiomyopathy, as well as of the familial and non-familial subgroups, was compared with that of 9000 normal controls. RESULTS: The familial prevalence of dilated cardiomyopathy in this patient group was "definite" in 14 of 56 (25%) and "possible" in 25 of 56 (45%). The HLA-DR4 frequency in the 100 patients with dilated cardiomyopathy was similar to that in the 9000 controls (39% v 32%). However, the DR4 subtype was significantly more common in the 25 probands with a familial tendency to dilated cardiomyopathy than in the 31 probands with non-familial dilated cardiomyopathy (68% v 32%; P < 0.05). CONCLUSIONS: The present finding supports an HLA linked predisposition to familial dilated cardiomyopathy. The HLA type DR4 was significantly more common in familial than in non-familial cases. The DR4 halotype was associated with two thirds of the families at risk for dilated cardiomyopathy.

Hospital mortality of acute myocardial infarction in the thrombolytic era.

OBJECTIVE: To examine the management and outcome of an unselected consecutive series of patients admitted with acute myocardial infarction to a tertiary referral centre. DESIGN: A historical cohort study over a three year period (1992-94) of consecutive unselected admissions with acute myocardial infarction identified using the HIPE (hospital inpatient enquiry) database and validated according to MONICA criteria for definite or probable acute myocardial infarction. SETTING: University teaching hospital and cardiac tertiary referral centre. RESULTS: 1059 patients were included. Mean age was 67 years; 60% were male and 40% female. Rates of coronary care unit (CCU) admission, thrombolysis, and predischarge angiography were 70%, 28%, and 32%, respectively. Overall in-hospital mortality was 18%. Independent predictors of hospital mortality by multivariate analysis were age, left ventricular failure, ventricular arrhythmias, cardiogenic shock, management outside CCU, and reinfarction. Hospital mortality in a small cohort from a non-tertiary referral centre was 14%, a difference largely explained by the lower mean age of these patients (64 years). Five year survival in the cohort was 50%. Only age and left ventricular failure were independent predictors of mortality at follow up. CONCLUSIONS: In unselected consecutive patients the hospital mortality of acute myocardial infarction remains high (18%). Age and the occurrence of left ventricular failure are major determinants of short and long term mortality after acute myocardial infarction.

Safety of dobutamine stress echocardiography in 474 consecutive studies.

BACKGROUND: With expanding applications and increasingly aggressive stress protocols, concerns about the safety of dobutamine stress echocardiography (DSE) have arisen. The purpose of this study was to analyse prospectively the safety, adverse event profile and complication rate of DSE. METHODS: Prospective data were recorded in a consecutive series of 474 patients undergoing DSE. Dobutamine was administered intravenously in graded infusion, each stage over 3 min, at 10, 20, 40 and, if required, 50 micrograms/kg/min. Atropine (1 mg) was administered thereafter if the response remained suboptimal. RESULTS: The mean dose of dobutamine was 42 micrograms/kg/min, with 111 patients (23%) receiving 50 micrograms/kg/min. Atropine was required for 27 patients (6%). No patient died or suffered a myocardial infarction. Sustained ventricular tachycardia occurred in one patient, angina pectoris in 127 (27%), non-sustained ventricular tachycardia in eight (2%) and supraventricular tachycardia in 19 (4%). Profound bradycardia requiring cessation of the test occurred in one patient. Pulmonary oedema developed in one patient. A hypotensive response requiring cessation of the test was seen in one patient. Test termination because the patient complained of nausea, tremor or headache was not required. CONCLUSION: DSE is safe. Side effects are rare and when they occur, are usually minor. Ischaemic pain is effectively treated by termination of the test and sublingual administration of nitrates.

Evaluation of patients with diabetes mellitus for coronary artery disease using dobutamine stress echocardiography.

BACKGROUND: There is a high prevalence of coronary artery disease (CAD) in patients with diabetes mellitus. Detection of inducible ischaemia using treadmill exercise testing may be limited by the relatively poor inherent predictive accuracy of the test. The purpose of this study was to determine the value of dobutamine stress echocardiography (DSE) for the detection of CAD in patients with diabetes mellitus. METHODS: Patients with diabetes mellitus referred for cardiac assessment were considered eligible for study. DSE was performed in a standard fashion. Significant CAD was defined as a > 50% luminal diameter stenosis on coronary angiography. RESULTS: A total of 52 patients (mean age 59 years) with diabetes mellitus were studied prospectively using DSE. Risk factors for CAD included hypertension in 19, family history in 21, hypercholesterolaemia in 14, history of smoking in 38. The sensitivity, specificity, positive and negative predictive values of DSE for detection of CAD were 82, 54, 84 and 50% respectively. CONCLUSION: The specificity of DSE for CAD in patients with diabetes mellitus is low. Whether this reflects an underdetection of small vessel disease by contrast coronary angiography or whether it relates to test performance is unclear.

Comparison of dobutamine stress echocardiography and treadmill exercise electrocardiography for detection of coronary artery disease.

BACKGROUND: Critical analysis of treadmill exercise testing (TMET) for the detection of coronary artery disease has revealed many shortcomings. Excellent diagnostic accuracy has been reported for dobutamine stress echocardiography (DSE). METHODS: A prospective comparison of DSE and TMET for the detection of coronary artery disease in routine clinical practice was performed using contrast cineangiography (significant stenosis > or = 50%) as a gold standard. RESULTS: A total of 116 patients (82 men, 34 women) were studied. Significant stenosis was detected by coronary angiography in 92 patients (79%). Single vessel disease occurred in 28, double-vessel disease in 32, and multivessel disease in 32 patients. Although sensitivity of DSE was better than that of TMET (82 versus 40%), specificity was worse (63 versus 79%). Positive predictive values for both DSE and TMET were good at 89 and 87%, respectively, whereas negative predictive values were poor for both (47% for DSE, 26% for TMET). CONCLUSIONS: Overall, DSE performs better than TMET in terms of sensitivity and positive and negative predictive value. Its lower specificity than that of TMET may lead to more patients being referred for diagnostic coronary angiography. The poor negative predictive value of DSE and TMET means that one should not be falsely reassured by normal results.