A syndrome of congenital cardiomyopathy with mitral regurgitation, complete heart block and atrial arrhythmia

A distinctive syndrome of cardiomyopathy with mitral regurgitation, complete heart block and atrial arrhythmia was noted in four male patients aged 19 to 49 years. Each presented with cardiac enlargement and varying degrees of left ventricular failure. One patient was known to have had complete heart block from infancy and another patient from 13 years of age. Each had chronic atrial fibrillation or flutter, with a regular ventricular rhythm at 35 to 45/min. Hemodynamic studies showed dilatation and poor contractility of the left ventricle, considerable mitral regurgitation, reduced resting cardiac output and elevated left ventricular end-diastolic pressures. The clinical course in follow-up periods of up to 5 years has been one of relatively mild, slowly progressive congestive heart failure. Mitral valve replacement and permanent pacemaker installation in one patient had no effect on the clinical course. The mitral valve showed redundant leaflet tissue with mucoid degenerative changes. This syndrome appears to represent a form of congenital cardiomyopathy which involves degeneration or fibrotic changes in both the myocardium and the conduction system. Familial occurrence has not been recognized.     

Treatment of acute inflammatory myocarditis assisted by endomyocardial biopsy

Right ventricular endomyocardial biopsy was performed to make a diagnosis of inflammatory myocarditis in 10 patients with congestive heart failure. All 10 patients were treated with immunosuppressive agents (either prednisone alone or prednisone in combination with azathioprine) and were followed up prospectively. Each patient had serial invasive and noninvasive assessments of cardiac performance, and 9 of 10 had one or more follow-up endomyocardial biopsies. The course of four patients who showed dramatic improvement in association with immunosuppressive therapy is described in detail. In addition to these four patients, one other had definite improvement and four subjects had stabilization of previously progressive heart failure; the condition of one patient worsened, and he died despite immunosuppression. In the seven patients who had cell inflammation, six underwent a second biopsy after a period of immunosuppressive therapy, and in each case, the inflammatory infiltrate had been eliminated. In two of these patients, signs and symptoms of myocarditis recurred after discontinuation of therapy, and myocardial biopsy confirmed the recrudescence of cell inflammation. Reinstitution of therapy improved symptoms and histologic findings.It is concluded that endomyocardial biopsy can be used to diagnose inflammatory myocarditis and to monitor the histologic results of therapy. Our findings constitute circumstantial evidence that immunosuppressive therapy is effective in eliminating myocardial cell inflammation and thereby improving myocardial performance.     

Early anthracycline cardiotoxicity

Eight patients in whom cardiac dysfunction developed within four weeks of receiving their first or second course of daunorubicin or doxorubicin are described. Four patients presented with pericarditis; three of these four had evidence of myocardial dysfunction. Histopathologic analysis of these patients was consistent with an acute myocyte damage and secondary inflammatory process. An additional group of four patients presented with symptoms and signs of heart failure. These patients were either elderly or had evidence of previous cardiac disease. One of these patients suffered a myocardial infarction 24 hours after receiving 60 mg/m² of daunorubicin; earlier doses in the same course had been associated with evidence of myocardial ischemia. We conclude that anthracycline antibiotics may manifest clinically significant cardiotoxicity at total cumulative doses much less than have been associated with chronic cardiomyopathy.     

Diagnostic accuracy of an ultrasonic multiple transducer cardiac imaging system.

Eighty patients with various forms of heart disease were studied with the use of a newly developed ultrasonic system having 20 transducers arranged in a linear array. This system allows visualization of the heart in two dimensions in real time. All 15 patients with the mitral valve prolapse syndrome, 13 patients with mitral stenosis, five patients with pericardial effusion, four patients with atrial septal defect, and one patient with left ventricular dyssynergy were properly recognized with this system. One of five patients with hypertrophic myopathy and one of four patients with congestive myopathy were not recognized with this system. Criteria for the recognition of these system. Criteria for the recognition of these conditions are presented as well as the probable cause for false-positive and false-negative diagnoses in this series. Since only qualitative criteria were used, it was not possible to differentiate patients with coronary artery disease or patients with left ventricular volume overload from patients without cardiac pathology. The accuracy of this new system was judged against the clinical examination, conventional echocardiography, cardiac catheterization, and left ventricular angiography. It is assumed that the criteria for diagnosis developed during this study will be supplemented and the equipment improved in the future; however, the ease of operation of this system and the relative accuracy of diagnosis at this stage of its development are extremely interesting. It presents an excellent opportunity to obtain additional information about the cardiac patient without using invasive procedures and without risk.     

Echocardiography: Pericardial thickening and constrictive pericarditis

A total of 167 patients with pericardial thickening noted on M mode echocardiography were studied retrospectively. After the echocardiogram, 72 patients underwent cardiac surgery, cardiac catheterization or autopsy for various heart diseases; 96 patients had none of these procedures. In 49 patients the pericardium was directly visualized at surgery or autopsy; 76 percent of these had pericardial thickening or adhesions. In another 8 percent, pericardial adhesions were absent, but no comment had been made about the appearance of the pericardium itself. In the remaining 16 percent, no comment had been made about the pericardium or pericardial space. Cardiac catheterization in 64 patients revealed 24 with hemodynamic findings of constrictive pericarditis or effusive constrictive disease.Seven echocardiographic patterns consistent with pericardial adhesions or pericardial thickening are described and related when possible to the subsequent findings at heart surgery or autopsy. The clinical diagnoses of 167 patients with pericardial thickening are presented. The hemodynamic diagnosis of constrictive pericardial disease was associated with the echocardiographic finding of pericardial thickening, but there were no consistent echocardiographic patterns of pericardial thickening diagnostic of constriction. However, certain other echocardiographic abnormalities of left ventricular posterior wall motion and interventricular septal motion and a high E-F_o slope were suggestive of constriction.     

Bundle branch block and sudden death

It is clear from the available data that the prognosis for patients with chronic BBB depends to a large extent on the presence and etiology, as well as the severity, of the associated heart disease. In most patients, the terminal event is usually one of heart failure or the complication of coronary artery disease. In the absence of clinically detectable heart disease, the long-term prognosis for this group of patients is good.Patients with chronic bundle branch block Have been shown to have an incidence of ventricular arrhythmias greater than that found in a normal population. The mechanism of sudden death in any single unmonitored patient is speculative. Most patients dying suddenly, especially those with coronary artery disease, probably do so from ventricular fibrillation. Patients with documented transient high-degree AV block are at a substantial risk of sudden death.No clinical variable (such as age, syncope, angina, shortness of breath), or physical finding (such as S₃ gallop, cardiomegaly, heart failure), or electrocardiographic finding (such as RBBB with LAD, RBBB with RAD, P-R interval prolongation), or electrophysiologic variable (such as A-H or H-V interval prolongation) is useful in predicting progression to complete heart block. All the above variables occur frequently in patients with BBB and yet the progression to CHB is relatively infrequent. One might single out His-Purkinje block with normal AV nodal conduction during atrial pacing as a possible marker for development of complete heart block. However, the opposite, namely a normal H-V interval, does not rule out progression to complete heart block.The data available on the use of pacing in patients with unexplained recurrent syncope or dizziness suggests that this approach is reasonable provided an effort has been made to exclude noncardiac cause for the symptoms. Some suggest that documentation of bradyarrhythmia or measurement of H-V interval is essential prior to institution of pacing. Further studies are needed to clarify this point.BBB complicating acute myocardial infarction places the individual at significant risk of developing congestive heart failure, with mortality usually secondary to myocardial failure or refractory ventricular arrhythmias. The pressence of high-degree AV block per se does appear to increase the mortality in patients without pump failure. Recent data suggest that immediate survival may be enhanced by prophylactic pacing in patients at high risk for abrupt complete heart block complicating acute myocardial infarction, but who do not manifest evidence of heart failure. The assumption that prophylactic pacing will improve survival of patients with bundle branch block and significant heart failure complicating acute myocardial infarction is purely speculative.Insufficient and conflicting data prevent a definitive statement regarding the usefulness of the P-R and H-V intervals as guidelines for the management of patients with recent-onset bundle branch block and acute myocardial infarction.Permanent pacing appears to benefit survivors of acute myocardial infarction complicated by BBB and transient high-degree AV block. However, the evidence is far from convincing.Little information is available on the influence of antiarrhythmic therapy on sudden death in patients with BBB. All currently used antiarrhythmic agents have a potentially high risk when administered to patients with BBB. Since there is no convincing prospective study as to the efficacy of drugs in preventing sudden death in patients with BBB, drug selection and its use in this group of patients remains at the discretion of the individual physician. It is based on the individual physician's experience with the drug in question and his perception of the benefit-to-risk ratio of the agent to be used.     

Effect of lithium on cardiovascular performance: Report on extended ambulatory monitoring and exercise testing before and during lithium therapy

To assess the effect of long-term lithium therapy on cardiac arrhythmias and cardiovascular performance, extended ambulatory electrocardiographic monitoring was performed in 12 patients, and rest and exercise electrocardiograms in 10 of 12, before and during lithium therapy. Lithium increased the frequency of premature ventricular contractions in three patients, decreased it in one, and produced no change in eight. Three of four patients with atrial arrhythmias showed improvement during lithium therapy. Exercise performance was unchanged. Although 7 of the 12 patients manifested T wave flattening in the resting electrocardiogram, none had S-T segment displacement at rest or on treadmill exercise. Before lithium therapy, arrhythmias on exercise included premature atrial contractions in four patients, ventricular arrhythmias in four (premature ventricular contractions in four, with couplets in two and with ventricular tachycardia in one). During lithium therapy, exercise did not provoke premature atrial contractions or ventricular tachycardia in any of the patients, but three patients had premature ventricular contractions (with couplets in one case).We conclude that lithium at therapeutic levels may precipitate or aggravate ventricular arrhythmias. When administered to patients with heart disease, factors that interfere with renal clearance of lithium (heart failure, salt restriction, long-term diuretic therapy) must be recognized and doses must be adjusted accordingly. Careful follow-up and electrocardiographic monitoring are advisable if lithium is to be used in the presence of ventricular arrhythmias. Cardiovascular performance as assessed by treadmill exercise testing was not affected by long-term lithium therapy.     

Joint manifestations of Lyme borreliosis in Czechoslovakian patients

Involvement of the musculoskeletal system in 50 Lyme borreliosis patients seen in Czechoslovakia is described. Thirty-three patients reported tick bites or that they had removed a tick, four patients had been bitten by some other insect. Skin reaction following tick bite were found in 29 patients. Neurologic involvements have been described in 40 subjects. In one patient complete heart block developed after ECM, so that a permanent pacemaker was necessary for two weeks. Mainly three types of involvement of the musculoskeletal system were observed, mostly as intermittent episodes of arthralgia or migratory musculoskeletal pain. In 37 patients brief attacks of monoarthritis or asymmetrical oligoarthritis were seen, chiefly of intermittent subacute course. Chronic arthritis was diagnosed in seven cases, sacroiliitis in four patients. The authors discuss differential diagnosis, especially in patients with chronic joint involvement.     

New instrument for transvenous cardiac biopsy

A new forceps is described for obtaining serial endomyocardial biopsy specimens from the human heart. The instrument is introduced percutaneously into the right internal jugular vein and used to obtain tissue from the apex of the right ventricle. Eighty-five biopsy procedures have been performed in 19 patients after cardiac transplantation. The tchnique used was 100 percent successful in obtaining endomyocardial biopsy specimens, and there were no significant complications. A biopsy procedure may be performed within 5 minutes. Serial percutneous transvenous endomyocardial biopsies are now routinely performed with this instrument in new heart transplant recipients and in patients with primary cardiomyopathy.     

Detection of ventricular arrhythmias in real-time with a portable analog computer

Recent studies on the occurrence of sudden death emphasize that many patients have ventricular premature contractions as prodromes of lethal arrhyhmlas. A portable, 6 ounce analog computer has been developed to detect tachycardias (heart rate 150 to 190 beats/min), bradycardias (heart rate less than 50 beats/min) and ventricular premature contractions. When preset limits are exceeded, acoustic warnings are sounded, and the patient may transmit his electrocardiogram by telephone, without additional equipment, to a receiving device that graphically reproduces the electrocardiogram in real-time. Hospital studies in 26 ambulatory patients with a variety of arrhythmias have been completed. Tachycardias and bradycardias were detected in every instance during 30 observation periods in six patients. Reproducible warnings were triggered in 19 of the 20 patients with ventricular premature contractions of various configurations during each of 5 observation periods (100 observations). In one patient, the electrical vector of the ventricular premature contraction closely resembled the normal QRS vector and was not detected. Appropriate electrode placement is essential to avoid initial Q waves and to maximize the difference between the vector of ventricular premature contraction and that of the normal QRS complex. No false positive acoustic alarms were sounded. Our results demonstrate that it is possible to detect ventricular premature contractions readily and reproducibly in ambulatory patients. Use of this detector may permit large scale monitoring of patients with a high risk of sudden death.     

Cardiac calcification in uremia A clinical, biochemical and pathologic study

Clinical, electrocardiographic and biochemical data are correlated with pathologic findings in six patients receiving chronic dialysis who demonstrated moderate to severe metastatic calcification of the myocardium at postmortem. Electrocardiographic changes or congestive heart failure were the only clue to metastatic calcification since x-ray signs of osteitis fibrosa or soft tissue metastatic calcification were absent. First degree heart block, the initial electrocardiographic finding in five cases, occurred within thirteen months of death and was subsequently associated with intraventricular conduction defect in four patients. This progressed to complete heart block in two patients. Sudden death occurred in two patients and intractable congestive heart failure was observed in two patients. Calcium deposition and fibrosis of the atrioventricular (A-V) node were seen in four patients with partial or complete heart block. Marked calcium deposition in the interventricular septum was noted in four patients with intraventricular conduction defect. Two patients with congestive heart failure showed moderate to severe metastatic calcification of the ventricular myocardium. One patient who died suddenly showed nearly complete calcific obliteration of the sino-atrial node. Calcium deposition with luminal narrowing of small myocardial vessels was found in all cases. The artery to the A-V node was narrowed in four patients and to the sino-atrial node in one patient. Parathyroid hyperplasia was noted in all patients.     

Cardiac arrest recorded on ambulatory electrocardiograms

To characterize the events that precede and precipitate sudden cardiac death (SCD), the long-term electrocardiograms of 27 patients who had SCD while being monitored were analyzed. In 20 patients, SCD was associated with ventricular tachyarrhythmias (ventricular tachyardia [VT]/ventricular fibrillation [VF]) and in 7 it was associated with bradyarrhythmias. Seventeen of the patients were men and 10 were women. Twenty-one patients had coronary artery disease, 2 had idiopathic dilated cardiomyopathy, 2 had mitral stenosis and 1 patient had mitral valve prolapse. Four patients with VT/VF had a previous nonfatal cardiac arrest. In the 20 patients with tachyarrhythmia-related SCD, 3 or more VT beats always preceded degeneration to VF. In 5 patients, the frequency or complexity of ventricular arrhythmias increased in the hour before SCD. In 11 of 20, there was a 20% or greater increase in underlying heart rate in the hour before SCD. The R-on-T phenomenon was observed in 4 patients. The long-short phenomenon initiated VT/VF in 2 patients. Only 2 patients with VT/VF were resuscitated. No patient with bradyarrhythmia-related SCD had manifest atrioventricular block or bundle branch block. Two of 7 patients had an episode of nonsustained bradycardia in the hour before arrest. No patient was resuscitated. In conclusion, VT that degenerates into VF is the most common arrhythmia associated with SCD. VT/VF is frequently preceded by an increase in heart rate and complex ectopy. VT is most often initiated by late ventricular premature complexes. Twenty-five percent of patients who have SCD have associated bradyarrhythmias that may occur without premonitory events.     

Repetitive beating after single ventricular extrastimuli: Incidence and prognostic significance in patients with recurrent ventricular tachycardia

The incidence of repetitive ventricular beating in response to programmed single ventricular extrastimuli delivered during spontaneous rhythm was tabulated in 59 patients with recurrent ventricular tachycardia. Repetitive beating occurred in only nine patients (15 percent). The repetitive response seemed to be a result of bundle branch reentry in four subjects and possibly a result of other mechanisms in five. There was no difference in the incidence of repetitive beating or type of repetitive response in patients with and without ischemic heart disease. During an average patient follow-up period of 13.6 months, there were eight sudden and six nonsudden deaths. Life table analysis revealed a significantly greater incidence of sudden death in patients with ischemic than in patients with nonischemic heart disease. There was no significant difference in the incidence of sudden death in patients with and without repetitive beating. It is concluded that the repetitive response to single ventricular extrastimulation is infrequent in patients with recurrent ventricular tachycardia, and that repetitive beating is not a prognostic indicator or an indicator of vulnerability to ventricular tachycardia.     

Hemodynamic observations in patients with unstable angina pectoris

Brachial and pulmonary arterial pressures were monitored for 48 hours in 26 patients with unstable angina pectoris and documented occlusive coronary artery disease. The circulatory response during 56 episodes of spontaneous anginal pain permitted the division of responses into three distinctive hemodynamic subsets. Patients in group I had an increased heart rate only with the spontaneous attack of angina; patients in group II had associated increases in brachial arterial pressure and slight increases in heart rate during the episodes of pain; patients in group III demonstrated increases in both brachial and pulmonary arterial diastolic pressures with minimal changes in heart rate. Resting hemodynamic data during pain-free periods were normal in 25 of 26 patients. Patients in all groups who had more than one episode of pain had similar hemodynamic responses to the first and later episodes. Although myocardial hypoxemia appears to be responsible for the spontaneous attack of angina, the hemodynamic responses to the attack varied but were highly specific for any one patient.Our observations suggest that there may be various pathogenic mechanisms for “spontaneous” or resting angina in patients with occlusive coronary artery disease but that the mechanism and associated hemodynamic changes may be specific for individual patients.     

Wenckebach atrioventricular block (Mobitz type I) in children and adolescents

Mobitz type I atrioventricular block in children, adolescents and young adults without overt heart disease or drug intoxication has been considered less significant than Mobitz type II block. In highly trained athletes and some nonathletes it has been presumed to be a benign manifestation of heightened vagal tone. Experience with 16 young patients, 6 female and 10 male, tends to alter the concept of benignity. Known onset of Wenckebach and varying first degree block was between 6 months and 17 years of age. Of eight patients followed up for 5 to 18 years, five have fixed complete heart block and three first degree block. Of eight followed up for 1 to 4 years, two have fixed complete heart block and the others varying first, second and third degree block. Two have required a pacemaker implant. On intracardiac electrography performed in seven patients, four manifested during sinus rhythm a Wenckebach response to atrial pacing at abnormally slow rates; in addition, the His bundle electrograms showed A-H delay in one patient, H-V delay in two patients and delay in both intervals in one patient. Of three patients studied during complete heart block all manifested A-H block and one also H-V prolongation. The occurrence of Wenckebach block in 7 of 16 children and adolescents before the development of fixed complete heart block suggests that such block is probably more common than heretofore recognized and may be a phase in the natural history of the development of idiopathic heart block. It often represents significant disease of the cardiac conduction system, which may be progressive, and it has a guarded prognosis.     

Familial occurrence of sinus bradycardia, short PR interval, intraventricular conduction defects, recurrent supraventricular tachycardia, and cardiomegaly.

Four members of a family presenting with sinus bradycardia, a short P-R interval, intraventricular conduction defects, recurrent supraventricular tachycardia (SVT), syncope, and cardiomegaly had His bundle studies and were found to have markedly shortened A-H intervals (30 to 55 msec.) with normal H-V times (35 to 50 msec.). Right atrial pacing at rates as high as 170 to 215 per minute failed to increase the A-H or H-V intervals significantly. The data are compatible with the presence of an A-V nodal bypass tract (James bundle) or even complete absence of an A-V node. Ventricular pacing and spontaneous ventricular premature beats resulted in a short ventriculoatrial conduction time (110 msec.) suggesting that if A-V nodal bypass tracts exist, they are utilized in an antegrade and retrograde fashion. None of the features of WPW syndrome was present. The mechanism of syncope in the mother and daughter was intermittent third-degree heart block. Both went on to develop permanent complete heart block despite electrophysiologic studies demonstrating 1:1 A-V conduction at extremely rapid atrial pacing rates and both required implantation of permanent pacemakers. The mechanism of syncope in the two brothers was possibly marked sinus bradycardia, but transient complete heart block has not been ruled out. Permanent pacemaker therapy was recommended for both. The nature of the cardiomegaly, which was mild in three patients, is not known. Although not well documented, several maternal relatives have had enlarged hearts, SVT, complete heart block, and syncope.     

Stokes-Adams attacks due to acute nonspecific myocarditis.

Ten patients, all below 30 years of age (8 females and 2 males) developed Stokes-Adams attacks from complete heart block due to acute nonspecific myocarditis. Coexisting thyrotoxicosis was present in two patients and cardiogenic shock was seen in four. Temporary transvenous pacing was instituted in all but one patient. Except for two patients who developed permanent complete heart block, normal A-V conduction returned in between 1 to 12 hours after ventricular pacing in seven patients and after 12 hours of isoprenaline therapy in the final patient. The ECG returned to normal in six patients and all 10 patients survived their acute illness.     

Unexpected myocardial disease in patients with life threatening arrhythmias

It is not unusual for an individual without recognisable clinical heart disease to have a life threatening arrhythmia. This report describes the results of endomyocardial biopsy in twelve patients who presented with life threatening arrhythmias and normal or near normal cardiac function. The eight men and four women (mean age 35) presented with ventricular tachycardia or fibrillation (nine cases), high grade heart block with inadequate ventricular escape (two cases), and dangerous ventricular extrasystoles (Lown grade 4, one case). In ten of the twelve patients symptoms had been present for less than or equal to 6 months at presentation. No patient had a normal electrocardiogram. Electrophysiological testing confirmed the clinical arrhythmia in all but three patients. Endomyocardial biopsy demonstrated lymphocytic myocarditis in two patients, granulomatous myocarditis in two patients, small vessel vasculitis in one patient, and cardiomyopathic changes in six patients. In one patient the biopsy specimen was normal. Endomyocardial biopsy is a valuable diagnostic tool in patients with unexplained life threatening arrhythmias. In this study half the patients had a treatable form of heart muscle disease.     

Sequential chemotherapy and late intensification for malignant lymphomas of aggressive histologic type

Fifty-six patients with malignant lymphoma of aggressive histologic type (51 large cell, three diffuse undifferentiated, and two nodular mixed) were treated with three non-cross-resistant combination chemotherapy regimens that were introduced sequentially according to the response to therapy. The objective was to increase the complete remission rate by changing the chemotherapy regimen early if the patient did not attain a complete remission after three courses of treatment. Late intensification was also used with the aim of prolonging the duration of complete remission. The overall complete remission rate obtained with this approach was 82 percent (100 percent in stages I to III and 66 percent in stage IV). The projected survival at four years is 71 percent (93 percent for stages I to III and 55 percent for stage IV). Eighty percent of patients with complete remission are projected to have continued remission at four years. Compared with previous experience with Adriamycin-based combination regimens, these results represent an improvement in remission and survival parameters. The most significant gains occurred in the prolongation of survival of patients with stages I to III disease and in the improved duration of complete remission of patients with stage IV disease. Toxicity included 15 documented infections among 320 courses of therapy, four cases of congestive heart failure, one case of bleomycin lung toxicity, and two cases of liver dysfunction. This multiple combination regimen represents an improvement over previous results utilizing Adriamycin-based combination chemotherapy.     

Spontaneous echocardiographic contrast in the descending aorta

The visualization of echocardiographic spontaneous contrast is a common phenomenon in patients undergoing transesophageal echocardiographic studies. Its pathophysiology is not well understood, but it has been related to the presence of a low flow state in the cardiac chambers. We report the presence of spontaneous contrast in the descending aorta of four patients, a location not previously described in the absence of aortic dissection. In two patients, spontaneous contrast was noted in both the left atrium and the descending aorta. In one patient with moderate left ventricular dysfunction, spontaneous contrast was noted in the descending aorta and in the left ventricle. In the remaining case, no cardiac or aortic abnormalities were observed and this represents the first time that spontaneous contrast has been identified in a patient with an echocardiographically normal heart. The occurrence of spontaneous contrast has been considered an abnormal echocardiographic finding, since it has always been described in patients with clinical symptoms and cardiac abnormalities. The fact that spontaneous contrast can be visualized in patients with very mild structural cardiac abnormalities or none at all, warrants further investigation, especially when therapeutic or prognostic implications are considered.