Digoxin biotransformation.

Serum digoxin and metabolites were assayed in plasma and urine by HPLC in 10 dialysis-dependent patients with end-stage renal failure (group I) and in five patients with comparatively normal renal function (group II) after ingestion of 150 muCi 3H-digoxin-12 alpha. Thirteen patients were on maintenance digoxin therapy and were at steady state. Metabolites found regularly but usually in small amounts, were 3 beta-digoxigenin and its mono- and bis-digitoxosides, and 3-keto and 3 alpha(epi)-digoxigenin. Quantitatively the most abundant metabolites were polar and averaged 26% (7 to 76) of the radioactivity in plasma 6 hr after drug, and 60% (11 to 88) for digoxin for all 15 patients. Neither values between group I and II for the polar metabolites nor digoxin differed significantly. The metabolites reacted with antibody to digoxin to varying degrees and may make up an important component of the serum digoxin concentration when determined by standard radioimmunoassay. In some patients, digoxin undergoes extensive biotransformation, mainly, we suggest by hydrolysis, oxidation, epimerization, and conjugation to polar end-metabolites.

Value and limitations of clinical electrophysiologic study in assessment of patients with unexplained syncope.

We assessed the value of clinical electrophysiologic study using intracardiac recording and programed electrical stimulation in 34 patients who had unexplained syncope and/or presyncope. All patients had normal electrocardiograms, and no abnormality was detected by clinical examination, ambulatory electrocardiographic recording, or treadmill testing. The electrophysiologic results were diagnostic in four patients (11.8 percent) and led to appropriate therapy that totally relieved symptoms. The results were abnormal but not diagnostic in two patients (5.8 percent) and normal in the remaining 28 patients (82.4 percent). The patients were followed for a mean period of 15 months (range two to 44) after electrophysiologic testing. Sixteen patients (47 percent) had no further episodes in the absence of any intervention. In four patients (11.8 percent), a definitive diagnosis was made during follow-up. In seven patients, permanent pacing was instituted empirically with relief of syncope. Two patients continued to have syncopal spells. We conclude that the diagnostic yield of electrophysiologic testing is low in a patient population that has no electrocardiographic abnormality or clinical evidence of cardiac disease. Empirical permanent pacing in patients with symptoms continuing after our study appeared to be beneficial, but this result is difficult to evaluate because of the high incidence of spontaneous remission in this group. Persistent attempts to document electrocardiographic abnormalities during a typical episode of symptoms appears to be the only definitive way to confirm or exclude an arrhythmic cause of the symptoms.

Comparison of the electrophysiologic effects of intravenous and oral verapamil in patients with paroxysmal supraventricular tachycardia.

The electrophysiologic effects of intravenous verapamil (a bolus dose of 0.15 mg/kg body weight followed by infusion of 0.005 mg/kg per min) were compared with those of oral verapamil (80 mg every 6 hours for 48 hours) in eight patients who had paroxysmal supraventricular tachycardia. The mechanism of tachycardia was atrioventricular (A-V) nodal reentry in four patients and A-V reentry utilizing an accessory pathway for retrograde conduction in the remaining four. The electrophysiologic effects of oral and intravenous verapamil were similar. Both preparations significantly prolonged anterograde effective and functional refractory periods of the A-V node (p less than 0.001). Both significantly increased the shortest pacing cycle length maintaining 1:1 anterograde conduction over the A-V node (p less than 0.001). Retrograde conduction over the A-V node was greatly prolonged with verapamil in one patient but was unaffected in the others. There was no significant effect on sinoatrial conduction time, sinus nodal recovery time or atrial or ventricular refractoriness. Both preparations prevented induction of tachycardia in six patients none of whom had recurrence of sustained tachycardia while receiving long-term oral therapy (5 to 10 months). Neither preparation had a significant effect in two patients and this predicted failure of long-term oral therapy in one of these patients. The results of acute drug testing with intravenous verapamil can be extrapolated to predict the electrophysiologic results and response to long-term therapy with oral verapamil.

Two years experience with the Palmaz-Schatz coronary stent in a heterogeneous patient population.

Between January 1991 and December 1992, 136 Palmaz-Schatz coronary stents were implanted in 113 native coronary arteries in 106 patients. Forty-seven patients presented with stable angina, 50 with unstable angina, 7 with congestive cardiac failure and unstable angina and 2 were asymptomatic. Stenting was carried out in 15 patients for restenosis after coronary angioplasty (PTCA), 32 for significant dissection during PTCA (with 19 acute and 13 threatened closure), 10 for suboptimal PTCA results and 56 for de novo lesions, 52 (92.9%) of which were either ACC/AHA type B or C. Successful delivery was achieved in 97.2% (103/106) of patients or 97.3% (110/113) of vessels. Percent diameter stenosis was reduced from 78 +/- 13% to 4 +/- 11%. There were two subacute stent thromboses (1.9%), resulting in Q-Wave myocardial infarction. Three deaths (2.9%) occurred, all from the group with congestive cardiac failure and unstable angina. Major bleeding/vascular complications occurred in 4 patients (3.9%). All patients were followed up for a mean of 18 months (6 months to 30 months). Eighty-five patients were asymptomatic. Three patients were angina-free but continued to have, albeit improved, congestive cardiac failure. Ten patients had recurrence of angina, all within 6 months of the stenting procedure. Four were treated medically and 4 had PTCA of whom one eventually had coronary bypass surgery. Two patients had new lesions, successfully treated by PTCA or stenting. In conclusion, a high rate of successful delivery of the Palmaz-Schatz coronary stent can be achieved in a wide spectrum of patients with few complications which are mostly related to anticoagulation. It offers very effective bailout for acute closure during PTCA. Despite the presence of unfavorable pre-procedure patient and lesion characteristics, the acute and long term clinical results are encouraging.

Carotid floating plaques associated with multiple cerebral embolic strokes. Case reports.

The authors describe 2 patients with multiple cerebral infarcts and hemorrhagic transformation caused by artery-to-artery emboli. Ulcerated plaques with free-floating thrombus adherent to the plaque were detected at the carotid bifurcation by duplex sonography. No other embolic source could be found. One patient developed an occipital infarction due to carotid emboli passing through a fetal-type posterior communicating artery. Both patients recovered well without recurrence of stroke or transient ischemic attack with antiplatelet treatment only. Follow-up carotid duplex sonography showed disappearance of floating thrombus in 1 patient and consolidation of the lesion in the other.

Myasthenia gravis with giant lymph node hyperplasia: report of a case.

A 17-year-old female developed myasthenia gravis (MG) and retroperitoneal giant lymph node hyperplasia (GLNH). Her myasthenic symptoms improved after the removal of the retroperitoneal tumor. Moreover, she has done well in daily activities without medication for one year. To our knowledge, the coexistence of MG and GLNH has been reported in only one case. We encountered this second case with this association and believe it has some relationship with the first. Further research on this patient is warranted to elucidate the problem.

Clinical application of a new Palmaz-Schatz coronary stent delivery system with a short (8 mm) nonarticulated stent.

The standard Palmaz-Schatz coronary stent delivery system (SDS), with a 15 mm articulated stent and a 5F protective sheath, is relatively rigid and high in profile. Its use is contraindicated in vessels where there is severe tortuosity proximal to or in the lesion itself. Recently a new SDS, with a short (8 mm) nonarticulated stent, has become available. We present three patients with complex coronary anatomy solved with this new SDS. The first patient had a distal stenosis in an extremely tortuous and diffusely diseased right coronary artery (RCA). The second patient had a severe proximal RCA stenosis occurring at a bend of more than 90 degrees. The third patient had a very long stenosis of the left anterior descending coronary artery involving the ostium, requiring multiple tandem stenting. The availability of this short stent will greatly expand the clinical application of intracoronary stenting to patients with complex coronary anatomy.

Electrocardiographic criteria for differentiating aberrancy and ventricular extrasystole in chronic atrial fibrillation: validation by intracardiac recordings.

Many electrocardiographic criteria have been proposed for the differentiation of ventricular extrasystole and supraventricular conduction with aberrancy in atrial fibrillation but the validity of these have not been confirmed by intracardiac studies. We recorded His bundle electrograms in nineteen patients (eleven men, eight women) referred for diagnosis of abnormal QRS complexes in the context of chronic atrial fibrillation. Of 1,068 wide QRS complexes analyzed, 91% proved to be of ventricular origin. Electrocardiographic criteria which were specific for ventricular extrasystole included: left bundle branch block morphology, right bundle branch block morphology with a monophasic R in lead V1 or an RS or QS pattern in lead V6, presence of a "compensatory pause", i.e., compensatory cycle (V2-V3) longer than the average cycle length of ten normally conducted beats preceding the abnormal complex (927 +/- 317 vs 780 +/- 199, mean +/- SD in msec. p less than 0.005), frontal QRS axis of the abnormal complex directed superiorly or to the right and the presence of a "short-long" cycle sequence. Right bundle branch morphology with a triphasic R in lead V1 or QRS pattern in V6 and concordant initial vector in lead V1 or in more than one ECG leads were very specific for supraventricular conduction with aberrancy. Analysis of coupling interval and Ashman's phenomenon, i.e., the long-short cycle sequence, were not specific for supraventricular conduction with aberrancy. We conclude that in digitalis-treated patients with chronic atrial fibrillation the majority of abnormal QRS complexes are of ventricular origin. The diagnosis of ventricular extrasystole or aberrancy can be made using a single ECG lead (V1) and applying a combination of easily applied criteria.

Torsades de pointes, a common arrhythmia, induced by medication.

Between May 1980 and April 1981 four patients were referred to one hospital with syncope or recurrent ventricular fibrillation while taking antiarrhythmic or phenothiazine drugs. In all the patients ventricular tachyarrhythmias with the characteristics of torsades de pointes were documented in association with prolonged QT intervals. With removal of the offending agent (in all the patients) supplemented by temporary overdrive pacing (in two patients) the tachyarrhythmias subsided. This study suggests that drug-induced torsades de pointes is an important clinical entity that occurs more frequently than has been suspected.

False left ventricular aneurysm as a complication of open heart surgery.

A false aneurysm developed at the site of left ventricular venting in an 8-year-old boy who had undergone aortic valve commissurotomy under cardiopulmonary bypass. The diagnosis was made by clinical examination and chest radiography and confirmed by left ventricular cineangiography. The aneurysm was successfully resected.

Atrioventricular dissociation during paroxysmal junctional tachycardia.

We describe the rare occurrence of atrioventricular dissociation in three patients during paroxysmal junctional tachycardia. The mechanism of tachycardia was atrioventricular nodal reentry in to patients. The third patient had reentrant tachycardia that utilized the AV node for at least part of the reentrant circuit. This patient also had a nodoventricular pathway that may have participated in the reentrant circuit. In two patients, ventricular tachycardia was diagnosed prior to electrophysiologic assessment and medication to prevent tachycardia was not successful. After electrophysiological studies, treatment directed at suppressing AV nodal reentry prevented recurrent tachycardia. These case studies demonstrate the importance of detailed electrophysiological assessment of tachycardia in patients whose arrhythmia does not respond to empirical antiarrhythmic therapy.

Comparative functional effects of chronic ventricular demand and atrial synchronous ventricular inhibited pacing.

We compared the effects of chronic ventricular inhibited (VVI) and atrial synchronous ventricular inhibited (VDD) pacing on functional capacity in 8 patients with complete atrioventricular heart block. Permanent VDD (Medtronic #2409, ASVIP) pacemakers were implanted in four men and four women (age range 27-76 years, mean 58.9 +/- 18.4 years), and randomly assigned to a three-month period of VDD or VVI pacing in this single blinded, crossover study. Functional capacity was assessed by questionnaire, graded treadmill exercise testing and radionuclide angiocardiography prior to pacemaker implant and following each pacing period. Following 3 months of pacing in each of VVI and VDD pacing modes, maximum heart rate (83.4 +/- 14 vs 134.9 +/- 16.4 beats/min, p less than 0.001) and double product (147.5 +/- 58.3 vs 218.9 +/- 52.7, p less than .001) were greater with VDD pacing. Although exercise duration on treadmill exercise testing (5.3 +/- 2.9 vs 6.9 +/- 3.1 minutes, p less than 0.1) was greater in the VDD mode, the difference was not significant. Similarly, there was no significant difference in functional capacity as measured by questionnaire scores (50.1 +/- 8.4 vs 46.9 +/- 8.9, p less than 0.1) or in left ventricular ejection fraction for the two pacing modes (.54 vs .55, p less than .5). Only one patient reported a subjective improvement with physiologic (VDD) pacing, whereas the remaining patients stated no preference. We conclude that VDD pacing offers improved maximal cardiac work during exercise compared to VVI pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiography, cardioenzymes and myocardial imaging to detect perioperative myocardial infarction.

Serial electrocardiography, technetium-99m pyrophosphate scintigraphy and measurement of myocardial creatine kinase (CK2) and lactic dehydrogenase isoenzyme activity (specifically the LD1 to LD2 ratio) were evaluated prospectively in 26 patients who underwent aortocoronary bypass grafting and 11 patients who underwent valvular or other thoracic surgery, as methods of diagnosing perioperative myocardial infarction. Of the 26 patients who had aorto coronary bypass grafting, 7 (group 1) had myocardial infarction perioperatively; of these, only 2 had positive results from all four diagnostic tests. The other 19 patients (group 2) had no perioperative myocardial infarction and the only diagnostic method yielding positive results was the LD1 to LD2 ratio, in 7 of the 19. In the 11 patients who did not undergo aortocoronary bypass grafting (group 3), only 1 patient had myocardial infarction perioperatively; results from the measurement of CK2 isoenzyme activity and LD1 to LD2 ratio were positive while electrocardiography and 99mTc pyrophosphate scintigraphy yielded negative results. The respective sensitivity (%) and specificity (%) of the four diagnostic methods were as follows: electrocardiography: 38, 100; 99mTc pyrophosphate scintigraphy: 88, 100; LD1 to LD2 ratio: 100, 68; CK2: 38, 100. When the CK2 criterion was redefined, using patients in group 2 as controls, the sensitivity and specificity of this method became 100 and 90 respectively. The authors conclude that 99MTc pyrophosphate scintigraphy and measurement of myocardial creatine kinase isoenzyme are of comparable value and are the most reliable indicators of perioperative myocardial infarction.

Total disconnection of the right ventricular free wall: surgical treatment of right ventricular tachycardia associated with right ventricular dysplasia.

Arrhythmogenic right ventricular dysplasia is a myopathy that affects the right ventricular free wall (RVFW) and gives rise to recurrent reentrant ventricular tachycardia (VT). Because the entire right ventricle is potentially arrhythmogenic, ablating a single site of VT may not eliminate the arrhythmia. We developed an operation to confine any arrhythmic activity arising from the right ventricle to that chamber: total disconnection of the RVFW from the left ventricle. We performed RVFW disconnection in two patients with refractory VT associated with arrhythmogenic right ventricular dysplasia. At least two sites or origin of morphologically distinct VT were identified in the RVFW in each patient. RVFW disconnection was carried out under normothermic cardiopulmonary bypass. An encircling incision was made along the attachment of the RVFW to the aortoventricular unit and the tricuspid annulus; the right coronary artery and its RVFW branches were left intact. Electrical activity of the two chambers became dissociated, and VT arising from the RVFW was confined to that chamber. Postoperatively, there was no clinical evidence of hemodynamic impairment (follow-up 4 months and 3 months). Left ventricular function was unchanged and right ventricular flow was maintained by atrial contraction and motion of the septum toward the RVFW during left ventricular systole. One patient had incessant right ventricular tachycardia confined to the RVFW for 3 weeks. We conclude that RVFW disconnection is feasible and applicable to patients with refractory VT originating in the diffusely diseased RVFW.