Torsade de pointes: an unusual manifestation of chloral hydrate poisoning.
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Biomedical subjects
Publications and source records attributed to C M Pratt.
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On the basis of epidemiologic studies, more than 10 million Americans have echocardiographic evidence of mitral valve prolapse. Although ventricular arrhythmias occur frequently (over 50 percent of patients with mitral valve prolapse), they rarely result in sustained ventricular tachycardia or sudden cardiac death. However, a common problem in clinical practice is a patient with mitral valve prolapse and symptomatic complex ventricular arrhythmias refractory or intolerant to both beta blockers and conventional type I antiarrhythmics. These drugs are known to have frequent side effects, toxicity, and proarrhythmic effects. In 17 patients with mitral valve prolapse who presented with symptomatic complex ventricular arrhythmias and who were unresponsive to an average of the three conventional agents, moricizine (Ethmozine) was effective in suppressing 90 percent of ventricular premature depolarizations, 99 percent of nonsustained runs of ventricular tachycardia, as well as all sustained runs of ventricular tachycardia, resulting in abolition of palpitations, dizziness, and syncopal episodes. Its efficacy as well as its low frequency of minor side effects makes it ideal for future consideration in the population with mitral valve prolapse, who are frequently young and may therefore require therapy for many years.
This was a prospective, placebo-controlled, single-blind trial of moricizine (ethmozine) in a dose averaging 10 mg/kg/day in 50 patients, the single entrance criterion being the presence of 10 or more runs of nonsustained ventricular tachycardia (VT) on a screening 24 hr ambulatory electrocardiographic (ECG) recording. Electrophysiologic study was not included as part of this trial design. The placebo frequency of VT (average 3 days of recording) was 1036 +/- 479 runs of VT per day. Most patients (31/50) had coronary artery disease. The study population had a mean left ventricular ejection fraction (LVEF) of 36 +/- 16%; 20 patients also had a history of sustained VT. Protocol failure was defined as failure to achieve a 75% or greater reduction in runs of VT (as judged by ambulatory ECG recording) and/or recurrence of sustained VT while on moricizine. Among the 48 patients treated with moricizine, the drug was initially efficacious in 35 (73%), with two-thirds having total abolition of nonsustained VT. Although it was effective in reducing runs of nonsustained VT, moricizine was ineffective in preventing the recurrence of sustained VT (63% failure rate). Side effects were uncommon and the drug was well tolerated in most patients with LVEFs of 30% or less.
Initial base-line electrocardiograms are used to assess the efficacy of treatment for ventricular arrhythmias. This approach assumes that in the absence of treatment the frequency of arrhythmia would remain constant. To test the validity of this assumption, we studied 26 clinically stable patients with symptomatic but not life-threatening ventricular arrhythmias, during two periods of placebo treatment separated by a mean of 17 months. As compared with the initial placebo period, there were significant reductions in ventricular premature depolarizations (50 per cent), pairs (65 per cent), and ventricular tachycardia (83 per cent) during the second period of placebo administration (P less than or equal to 0.05 for all comparisons). Over one third of the patients gave the appearance of receiving successful therapy during the second placebo period, even when the reported spontaneous variability of ventricular arrhythmia was taken into consideration. If unrecognized, these long-term spontaneous changes in the frequency of arrhythmia could result in continuation of unnecessary and potentially toxic therapy and lead to incorrect conclusions regarding the efficacy of antiarrhythmic drugs in clinical trials. We therefore recommend that the frequency of arrhythmia be reassessed annually in the absence of treatment in patients similar to those in our study. These recommendations should not be applied to patients with life-threatening ventricular arrhythmias.
Results are reported of analysis of the variability of complex ventricular arrhythmias in a cohort of 110 patients selected for the presence of ventricular tachycardia (VT). All patients were enrolled in investigational antiarrhythmic drug trials and had an average of 4 consecutive days of placebo ambulatory electrocardiographic recording to serve as the database for this study. Using a statistical approach incorporating analysis of variance, the minimum percent reductions of ventricular premature complexes, couplets and VT were calculated to establish "drug effect" rather than variability at a significance level of 0.05. The relative variability of ventricular arrhythmias in prognostically important groups was also analyzed: (1) coronary artery disease (CAD) (n = 57) vs no CAD (n = 53); (2) patients with a left ventricular ejection fraction of 40% or less (n = 52) vs those with an ejection fraction greater than 40% (n = 58); and (3) patients with frequent runs of VT (10 or more runs/day, n = 63) vs infrequent VT (n = 47). Multiple regression analysis revealed that patients with CAD have significantly greater premature ventricular complex variability than patients without CAD (p less than 0.01). Also, patients with frequent VT runs have greater VT variability than that previously reported in smaller studies, thus requiring greater VT reductions to establish drug effect. Whether the variability of ventricular arrhythmia is itself an independent risk factor for sudden cardiac death is unknown.
A prospective, randomized trial was designed to assess the efficacy of intracoronary thrombolytic therapy with streptokinase (STK) in acute myocardial infarction. Sixty-four patients with acute myocardial infarction were randomized within 6 hours of onset of symptoms to 1 of 3 groups. Sixteen patients were treated by conventional means (control group). Nineteen patients underwent coronary arteriography and received corticosteroids and intracoronary and intravenous nitroglycerin (NTG group). Twenty-nine patients received management identical to that of the NTG group, with the addition of intracoronary STK therapy (STK group). Recanalization was demonstrated in 21 of 29 patients (72%) in the STK group. Global and regional ejection fraction (EF) was determined by radionuclide ventriculography before any intervention and 7 to 10 days later. No significant improvement in global EF was achieved in the control and NTG groups. In STK patients as a group, global EF did not increase significantly; however, in patients recanalized with STK, EF improved from 42 +/- 17% to 49 +/- 16% (p = 0.023). All groups showed wide variability of response. Improvement in global EF of more than 5% was noted in 44% of patients recanalized with STK. When subgrouped on the basis of initial global EF of 45% or less or more than 45%, only patients recanalized with STK with an initial EF of 45% or less had an improved global EF (from 30 +/- 10% to 42 +/- 10%, p = 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)
Dopamine receptor stimulation causes vascular and neurohumoral responses that may be beneficial in patients with heart failure. Oral inactivity, emesis and adrenergic-induced arrhythmias have limited the use of currently available compounds. Fenoldopam (SKF-82526-J) is a new, orally available, selective, dopamine-receptor agonist with potent renal vasodilating properties (six times that of dopamine) without positive inotropic or adrenergic activity. Drug efficacy was clinically evaluated in 10 patients with heart failure after single oral doses of placebo and 50, 100 and 200 mg of medication. Placebo produced no changes. Peak efficacy was noted 30 minutes to 1 hour after the 200 mg dose with mean blood pressure decreasing from 96 +/- 15 (mean +/- SD) to 83 +/- 8 mm Hg (p less than 0.05), pulmonary capillary wedge pressure decreasing from 23 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05) and mean pulmonary artery pressure decreasing from 32 +/- 9 to 29 +/- 8 mm Hg (p less than 0.05). Systemic vascular resistance decreased from 1,987 +/- 887 to 1,191 +/- 559 dynes.s.cm-5 (p less than 0.05) with a subsequent 55% increase in cardiac index from 2.2 +/- 1.1 to 3.1 +/- 1.3 liters/min per m2 (p less than 0.05). Heart rate and right atrial pressure did not change (p greater than 0.05). No emesis or new tachycardia was noted at any dose. Baseline hemodynamics generally returned within 3 to 4 hours. Fenoldopam, therefore, is a short-acting, orally effective drug that decreases systemic vascular resistance and increases cardiac index in patients with heart failure and represents a new class of oral compounds that may be useful in treating such patients.
Nitroglycerin is absorbed in vitro into polyvinyl chloride tubing, and it has been recommended that nitroglycerin be administered intravenously through specialized polyethylene infusion sets. To determine if tubing type is essential to achieve physiologic effectiveness, we studied dose responses to intravenous nitroglycerin in 15 patients with heart failure using standard polyvinyl chloride tubing in seven (group 2) and special polyethylene infusion sets in seven (group 1) (one patient was excluded from analysis because of technical difficulties). We monitored heart rate, blood pressure, right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output. Cardiac index, systemic and pulmonary vascular resistance, triple index, rate pressure product, stroke volume, stroke volume index, and stroke work index were calculated. Baseline and treatment measurements were obtained from five to 15 minutes after the infusion of 10, 20, 40, and 80 micrograms of nitroglycerin per minute. Over-all, systolic blood pressure decreased (p less than 0.05) about 8 percent and mean blood pressure approximately 12 percent, mean pulmonary artery pressure and mean pulmonary capillary wedge pressure decreased 30 to 40 percent, and the decline in mean right atrial pressure was 35 percent of baseline (all p less than 0.05). Heart rate and cardiac index did not change (p greater than 0.05). Pulmonary vascular resistance decreased slightly (p = 0.07) and systemic vascular resistance significantly (p less than 0.05). When the two groups were compared physiologic changes were virtually identical (p less than 0.05). Two-way analysis of variance for baseline corrected data proved no differences between tubing sets (p less than 0.05), but the infusion concentration rate was highly related to response (p = 0.0001). A significant (p less than 0.05) decrease in mean blood pressure and mean right atrial pressure was noted at lower dose rates (20 micrograms per minute and 40 micrograms per minute, respectively) in group 1. Beneficial hemodynamic effects in heart failure patients can, then, be predicted to occur at 80 micrograms per minute infusion rates; these responses seem independent of the type of infusion tubing system employed. Additionally, when patients given intravenous nitroglycerin for various reasons were followed for 48 hours, the majority receiving infusions via polyvinyl chloride tubing (group 2) did not require dosage adjustments. Also, at lower flow rates, more solution than calculated may be delivered when polyethylene tubing infusion sets are employed with volumetric infusion pumps.
Ten patients with recurrent episodes of ventricular tachycardia (VT) had electrophysiologic studies in the basal state and on chronic oral ethmozin (12.1 +/- 0.6 SE mg/kg/day). Ethmozin significantly prolonged the AH interval (basal: 75 +/- 8 SE msec; ethmozin: 91 +/- 10 msec, p less than 0.05), the HV interval (51 +/- 3; 66 +/- 5 msec, p less than 0.01), and the QRS duration (101 +/- 4; 118 +/- 4 msec, p less than 0.001). Atrial and ventricular refractory periods and the corrected QT interval were not significantly affected by ethmozin. VT was induced in 7 of 10 patients in the basal state by means of programmed right ventricular extrastimulation or rapid burst ventricular pacing. On oral ethmozin nine patients had inducible VT. VT cycle length was consistently prolonged on ethmozin (250 +/- 13; 326 +/- 14 msec, p less than 0.001). Four of the seven patients with VT on basal ambulatory monitoring had total abolition of spontaneous VT on ethmozin. Ethmozin failed to prevent induction of VT in most patients despite significant reductions in ventricular arrhythmia on ambulatory monitoring. Further studies comparing VT induction with ambulatory monitoring in patients on ethmozin are needed to confirm these findings and to define the clinical significance of this dissociation.
The ECG detection of ST segment depression during maximal treadmill exercise has diagnostic and prognostic significance in coronary artery disease. This study of 200 consecutive patients undergoing Bruce exercise testing for chest pain documents the ability of a transtelephonic ECG system, capable of storing segments of ECG memory during exercise, to reliably record ST segment depression detected during simultaneous exercise testing (sensitivity 79%; specificity 99.6%). Of the three transtelephonic ECG systems tested, the modified precordial V5 snap-on lead most accurately reflected ST segment amplitude and morphology with no "false positives" (specificity 100%) and few "false negatives" (sensitivity 78%). Therefore, this system is a potentially important clinical tool for accurately and conveniently monitoring coronary patients during exercise outside the hospital (e.g., following myocardial infarction) as well as for providing useful clinical information for ambulatory patients with undiagnosed sporadic chest pain.
Gonococcal endocarditis appeared with striking frequency in the preantibiotic era compared with its surprising rarity today. We present a series of four episodes of gonococcal endocarditis, which presented to our institution in the last 2 years, after no cases in the previous decade. Three episodes involved the aortic valve and required emergency aortic valve replacement. One episode involved the tricuspid valve and was successfully cured with antibiotic infusion alone. Combining our four patients with the available 25 well-documented gonococcal endocarditis cases reported in the English medical literature during the antibiotic era, we demonstrated that the disease incidence may be increasing, that infections more often involve left-sided cardiac structures (particularly the aortic valve), and that the association with a quotidian fever curve, rash and arthritis, and overt gonococcal infection is less common than previously reported. These patients frequently present with fulminant and dramatic valvular insufficiency without immediately positive blood cultures and complete echocardiographic evaluation seems to provide a valuable aid in making a presumptive diagnosis of endocarditis and directing appropriate clinical management.
A 37-year-old woman took 2.5 g of amantadine hydrochloride in a suicide attempt. Subsequently, cardiopulmonary arrest developed and was treated successfully. During the arrest and over the subsequent 48 hours, malignant tachyarrhythmias were manifested by torsade de pointe and repeated episodes of ventricular fibrillation. Therapy with adrenergic agents such as isoproterenol and particularly dopamine seemed to exacerbate the ventricular tachyarrhythmias. The patient subsequently died of aspiration pneumonia and respiratory distress, and postmortem examination revealed a normal cardiovascular system. It appears that the dopaminergic activity of amantadine has potential for induction of malignant arrhythmias, particularly in the face of adrenergic agents such as dopamine and isoproterenol. This previously unreported observation needs to be considered in critically ill patients with amantadine toxicity.
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Two-dimensional echocardiography and gated radionuclide ventriculography were performed in 93 patients (66 men, 27 women; mean age 61 years) with 95 episodes of acute myocardial infarction within 48 hours and at 10 days after infarction. Electrocardiographic sites of infarction were: 35 anterior, 49 inferoposterior and 11 nonlocalized. Abnormal motion of the anterior wall, septum or apex was seen in 97 and 100% of anterior infarctions by radionuclide ventriculography and echocardiography, respectively. Abnormal motion of an inferior or posterior wall segment was seen in 91% of inferoposterior infarctions by echocardiography versus 61% seen by radionuclide ventriculography. Ejection fractions determined by echocardiography and radionuclide ventriculography correlated well (r = 0.82) and did not change from the first 48 hours to 10 days after infarction (0.48 +/- 0.14). Similarly, wall motion score showed minimal change from the first 48 hours to 10 days. In-hospital mortality was 37 and 42% in patients with an ejection fraction of 0.35 or less by echocardiography and radionuclide ventriculography, respectively. No mortality was seen in patients with an ejection fraction above 0.40 by either test. The echocardiographic wall motion score was also predictive of mortality (40 versus 2%; score less than or equal to 0.50 versus greater than 0.50). The 1 year mortality rate in the 81 short-term survivors was 17%. Mortality was lowest in patients with an ejection fraction above 0.49 or wall motion score above (0.79 (2 to 5%) and worse in those with an ejection fraction below 0.36 or wall motion score below 0.51 (36 to 63%) by either technique. Thus in acute myocardial infarction, echocardiography and radionuclide ventriculography provide a comparable assessment of left ventricular function and wall motion in anterior infarction. Echocardiography appears more sensitive in detecting inferoposterior wall motion abnormalities. Both techniques are capable of identifying subgroups of patients with a high risk of death during the acute event and with an equally high mortality rate over a 1 year follow-up period.
This placebo-controlled, double-blind, longitudinal crossover study compares the efficacy of disopyramide and ethmozine, a new investigational drug, in suppressing frequent (40 or more per hour) ventricular premature depolarizations (VPDs) in 27 patients completing a 37 day protocol. Although both drugs significantly reduced VPDs relative to placebo, ethmozine was a superior antiarrhythmic drug in ach9eving near-total abolition of VPDs (30% of patients), which was never observed during disopyramide dosing (p less than .05). At the 80% VPD reduction level, ethmozine was effective in 56% of all patients compared with an effectiveness in only 22% of patients during disopyramide therapy (p less than .05). The mean peak plasma level of ethmozine was 0.66 +/- 0.8 micrograms/ml, which significantly fell to a trough level of 0.1 +/- 0.08 micrograms/ml (p less than .001). Mean peak and trough plasma levels of disopyramide exhibited less fluctuation (2.6 +/- 0.9 micrograms/ml vs 2.2 +/- 0.9 micrograms/ml). Ethmozine had no effect on the QT interval, whereas disopyramide prolonged it significantly. Importantly, while disopyramide produced serious side effects in 30% of patients, ethmozine was well tolerated with no statistically significant side effects compared with placebo.
Several large, prospective, randomized, clinical trials involving more than 11,500 patients testing five beta-blockers with respect to efficacy in reducing mortality after myocardial infarction as well as in preventing recurrent infarctions have been completed. The majority of the studies demonstrated significant mortality reduction when patients were begun on oral beta-blocker therapy prior to discharge from the hospital and maintained on the drug for at least 1 year. Similar benefit has not yet been demonstrated when beta-blockers are instituted parenterally during the early hours of infarction. Most patients should receive, routinely, a beta-blocker at the time of discharge from the hospital after infarction.
The overall management and prognosis of patients with acute myocardial infarction must take into account not only infarct size but also the site and locus of involvement as determined by electrocardiography. Transmural versus nontransmural infarction is discussed in relation to therapy and prognosis.
Based on a sound foundation of data in thousands of patients who underwent ambulatory ECG recording after myocardial infarction, it is clear tht ventricular arrhythmias are harbingers of sudden cardiac death. Ambulatory electrocardiography, usually performed for 24 hours, continues to be the standard by which clinicians can identify patients at risk for sudden cardiac death after acute myocardial infarction. Ideally, this test should be performed in the late hospitalization phase of acute myocardial infarction, usually 1 to 2 days prior to discharge from the hospital, and the results made known to the clinician prior to the patient's departure from the hospital. Although performed less frequently, low-level exercise testing prior to discharge from the hospital has been shown in some studies to be of prognostic value in defining a group at high risk for sudden cardiac death. This test offers the additional benefit of allowing the clinician to more knowledgeably prescribe an exercise regimen after hospitalization. The specific role of electrophysiologic testing is presently under clinical investigation. At present, only patients with documented spontaneous sustained ventricular tachycardia or sudden cardiac death after myocardial infarction should be candidates for this study. Although it may be possible in the future that electrophysiologic testing will also be used in patients with high-risk arrhythmia detected on ambulatory electrocardiography, at present this is the subject of clinical investigation in academic medical centers and is not recommended as part of standard therapy.