Myopotential interference with DDD pacemakers: endocardial electrographic telemetry in the diagnosis of pacemaker-related arrhythmias

Skeletal myopotentials may inhibit the output of unipolar demand ventricular pacemakers, resulting in protracted episodes of asystole in susceptible patients. The new DDD-mode pacemakers have, in addition to a unipolar ventricular lead, a unipolar atrial lead to enable atrioventricular sequential or atrial synchronous function. During clinical investigation of a new dual-unipolar cardiac pacing system programmed to operate in the DDD mode (Pacesetter AFP models 281 and 283), 6 patients were noted (5 men and 1 woman, aged 22 to 68 years) who manifested paroxysmal acceleration of ventricular pacing rate approaching the maximal tracking rate. Two patients also had abrupt slowing or cessation of ventricular output. With the use of atrial electrographic recordings (obtained with telemetry), the following mechanisms of rate change were found: myopotential tracking, myopotential inhibition, interference-mode asynchronous operation, sudden increases in sinus rate, and pacemaker-mediated reentrant tachycardia. In all patients, reprogramming of the implanted devices, based on telemetered atrial electrography, resulted in disappearance of the arrhythmias and loss of symptoms while maintaining the DDD pacing mode. Thus, several mechanisms of rhythm disturbances are peculiar to dual-chamber cardiac pacing systems that use unipolar electrodes. Endocardial telemetry combined with extensive programming capability offers the best opportunity for proper diagnosis and management of these problems.     

Quantitative differences in the hemodynamic effects of captopril and nitroprusside in severe chronic heart failure

The hemodynamic effects of oral captopril and intravenous nitroprusside were compared in 15 patients with severe chronic congestive heart failure. At doses of both drugs titrated so as to produce similar decreases in systemic vascular resistance in each patient, nitroprusside produced substantially greater increases in cardiac index (+0.67 versus +0.31 liters/min/m2, p less than 0.01) but smaller decreases in mean arterial pressure (-18.4 versus -11.0 mm Hg, p less than 0.01) than did captopril. This finding was due to a significant decrease in heart rate with captopril (-7 beats/min, p less than 0.01) which was not seen with nitroprusside, since changes in stroke volume index with both drugs were similar. Nitroprusside produced a decrease in pulmonary arteriolar resistance quantitatively similar to the decrease in systemic vascular resistance, but the decrease in pulmonary arteriolar resistance with captopril was not significant. Despite similar decreases in systemic resistance, captopril produced a greater decrease in left ventricular filling pressure (-10.2 versus -6.9 mm Hg, p less than 0.01) but a smaller decrease in mean right atrial pressure (-3.1 versus -5.3 mm Hg, p less than 0.01) than did nitroprusside. Thus, captopril has actions independent of its systemic vasodilator effects which account for the quantitative differences observed in its hemodynamic responses compared with those of nitroprusside in patients with severe chronic heart failure. These differences support experimental evidence that angiotensin, in addition to its direct systemic arterial vasoconstrictor actions, exerts positive chronotropic effects and alters ventricular compliance but has minimal direct effects on the limb venous circulation and on the pulmonary vasculature.     

Relation between serum sodium concentration and the hemodynamic and clinical responses to converting enzyme inhibition with captopril in severe heart failure

The relation between pretreatment serum sodium concentration and the early and late effects of captopril was examined in 77 consecutive patients with severe chronic heart failure, in whom cardiac catheterization was performed during initiation of treatment and after 2 to 8 weeks. Two groups of patients were defined: 37 patients had hyponatremia (serum sodium less than 135 mEq/liter, group A) and 40 patients had a normal serum sodium concentration (greater than or equal to 135 mEq/liter, group B). With first doses of captopril, patients in group A showed more marked hemodynamic responses than did patients in group B (p less than 0.02). The changes in mean arterial pressure and left ventricular filling pressure seen with first doses of the drug varied linearly and inversely with the pretreatment serum sodium concentration (r = -0.58 and r = -0.53, respectively); this was likely related to the finding that, before administration of captopril, the serum sodium concentration varied linearly and inversely with the logarithm of the plasma renin activity (r = -0.78). However, the pretreatment serum sodium concentration did not predict the long-term hemodynamic or clinical responses to converting enzyme inhibition. Symptomatic hypotension occurred early in the course of therapy (within 24 hours of initiating captopril therapy) in 9 (12%) of the 77 patients; 8 of these 9 had severe hyponatremia (serum sodium less than 130 mEq/liter) and comprised 53% of the 15 patients in our study with such low serum sodium concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Failure of low doses of amrinone to produce sustained hemodynamic improvement in patients with severe chronic congestive heart failure

Although amrinone produces acute hemodynamic improvement in patients with severe chronic congestive heart failure (CHF), it has not produced clinical benefits in long-term controlled trials. To determined if the administration of subtherapeutic doses of amrinone may account for its lack of efficacy in these studies, the dose requirements of the drug were investigated in 30 patients with severe CHF. Doses of 100 mg of oral amrinone produced moderate increases in cardiac index (0.35 liters/min/m2) and decreases in pulmonary capillary wedge pressure (6.8 mm Hg) and systemic vascular resistance (16%) (all p less than 0.01); these effects, however, were short-lived (less than 2.5 hours). Doses of 200 mg of oral amrinone produced marked increases in cardiac index (0.56 liters/min/m2) and substantial decreases in left ventricular filling pressure (9.9 mm Hg) and systemic vascular resistance (30%) (all p less than 0.01), and these effects persisted for longer than 4 hours. Only 4 patients showed hemodynamic responses with 100 mg of the drug that were sufficiently marked and long-lasting to merit chronic therapy, whereas 28 patients had such a response with the 200-mg dose. When 200 mg of amrinone was administered orally every 8 hours, sustained hemodynamic benefits were seen for 48 hours. However, 16 of 22 patients who received 600 mg of the drug daily for more than 1 week had intolerable adverse reactions that required drug withdrawal. In conclusion, hemodynamically effective doses of amrinone (600 mg/day) cannot be tolerated for long periods by most patients with severe chronic CHF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy of captopril in low-renin congestive heart failure: importance of sustained reactive hyperreninemia in distinguishing responders from nonresponders

To determine the efficacy of converting-enzyme inhibition in patients with low-renin congestive heart failure (CHF), the long-term hemodynamic and clinical responses to captopril were evaluated in 26 consecutive patients with severe, chronic CHF whose pretreatment plasma renin activity (PRA) was less than 2 ng/ml/hour. After 2 to 8 weeks of continuous treatment with captopril, 14 patients (54%) showed long-term hemodynamic benefits, of whom 13 (50%) improved clinically by at least 1 New York Heart Association functional class. To distinguish responders from nonresponders, patients were grouped based on the presence or absence of sustained reactive hyperreninemia (PRA during chronic therapy greater than 4 ng/ml/hour). After 2 to 8 weeks of therapy with captopril, 14 patients had sustained reactive hyperreninemia. Their cardiac index increased by 0.33 liters/min/m2 (p less than 0.01), left ventricular filling pressure decreased by 12.6 mm Hg (p less than 0.001), mean right atrial pressure decreased by 4.9 mm Hg (p less than 0.001) and systemic vascular resistance decreased by 529 dyne s cm-5 (p less than 0.001). Twelve of these 14 patients improved clinically. Twelve other patients had no reactive increase in PRA, and these patients showed no significant improvement in any hemodynamic variable after 2 to 8 weeks of treatment with captopril; only 1 of the 12 patients improved clinically (p less than 0.001 between groups). The 2 groups were otherwise similar with regard to pretreatment demographic, hemodynamic and hormonal variables.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences in hemodynamic effects of nitroprusside and prazosin in severe chronic congestive heart failure: evidence for a direct negative chronotropic effect of prazosin.

To compare the hemodynamic effects of prazosin and nitroprusside in patients with severe congestive heart failure, nine patients with heart failure refractory to conventional therapy received oral prazosin and intravenous nitroprusside administered so as to produce a similar decrease in left ventricular filling pressure in each patient. By this comparison, both drugs produced similar decreases in mean right atrial pressure, mean pulmonary arterial pressure and systemic and pulmonary vascular resistance. However, with nitroprusside, cardiac index increased more (+0.97 versus +0.73 liters/min per m2, P less than 0.01) and mean arterial pressure decreased less (-13.7 versus -18.3 mm Hg, P less than 0.05) than with prazosin. Both drugs produced similar changes in stroke volume index (+11.7 cc/beat per m2 with nitroprusside and +12.5 with prazosin) and stroke work index (+8.1 g-m/m2 with nitroprusside and +6.6 with prazosin). Therefore, the differences in the hemodynamic responses observed with the two agents were due to the significantly greater decrease in heart rate with prazosin (-8 beats/min) than with nitroprusside (-2 beats/min, P less than 0.05). These clinical data support experimental evidence suggesting that there is a significant negative chronotropic action of prazosin independent of its peripheral vascular effects.     

Hemodynamic and clinical significance of the pulmonary vascular response to long-term captopril therapy in patients with severe chronic heart failure

Exercise capacity in patients with left heart failure is closely related to the performance of the right ventricle and the pulmonary circulation. To determine the significance of changes in pulmonary resistance during long-term vasodilator therapy, hemodynamic studies were performed before and after 1 to 3 months of treatment with captopril in 75 patients with severe chronic left heart failure. Patients were grouped according to the relative changes in pulmonary and systemic resistances during long-term therapy: patients in Group I (n = 24) showed greater decreases in pulmonary arteriolar resistance (PAR) than in systemic vascular resistance (SVR) (% delta PAR/% delta SVR greater than 1.0), whereas patients in Group II showed predominant systemic vasodilation (% delta PAR/% delta SVR less than 1.0). Despite similar changes in systemic resistance, patients in Group I showed greater increases in cardiac index, stroke volume index and left ventricular stroke work index (p less than 0.01 to 0.001) but less dramatic decreases in mean systemic arterial pressure (p less than 0.02) than did patients in Group II. Despite similar changes in left ventricular filling pressure, patients in Group I showed greater decreases in mean pulmonary artery and mean right atrial pressures (p less than 0.02 to 0.01) than did patients in Group II. Pretreatment variables in Groups I and II were similar, except that plasma renin activity was higher (8.7 +/- 2.1 versus 3.0 +/- 0.6 ng/ml per h) and serum sodium concentration was lower (133.1 +/- 0.9 versus 137.1 +/- 0.6 mEq/liter) in Group II than in Group I (both p less than 0.05). Both groups improved clinically after 1 to 3 months, but symptomatic hypotension occurred more frequently in Group II than in Group I (36 versus 8%) (p less than 0.005). These findings indicate that changes in the pulmonary circulation modulate alterations in both right and left ventricular performance during the treatment of patients with left heart failure. Hyponatremic patients are likely to experience symptomatic hypotension with captopril because they are limited in their ability to increase cardiac output as a result of an inadequate pulmonary vasodilator response to the drug.     

Shunt flow and pulmonary hemodynamics during labor and delivery in the Eisenmenger syndrome.

The Eisenmenger syndrome carries a high mortality rate in a women during delivery and the immediate postpartum period. It has been suggested that marked changes in shunt flow and pulmonary hemodynamics may be responsible. These functions were studied under various physiologic and pharmacologic conditions during labor and delivery in a patient with the Eisenmenger syndrome. Uterine contractions were associated with a decrease in the ratio of pulmonary to systemic blood flow (Qp/Qs) from 1.58 to 1.05. The Qp/Qs ratio also decreased (to 0.83) when forceps were applied during uterine contractions. Epidural anesthesia, oxytocin and the supine position did not adversely affect pulmonary hemodynamics or shunt flow. On the basis of these results, if pregnancy cannot be terminated in a patient with the Eisenmenger syndrome, it is recommended that the patient be given high concentration of oxygen and epidural anesthesia and that serial arterial blood gas determinations be performed to detect changes in shunt flow.     

Provocation of myocardial ischemic events during initiation of vasodilator therapy for severe chronic heart failure: Clinical and hemodynamic evaluation of 52 consecutive patients with ischemie cardiomyopathy

Although hydralazine provokes myocardial ischemie events in hypertensive patients not in heart failure by producing reflex tachycardia, the frequency of and mechanisms underlying ischemie events when this drug is administered as a vasodilator agent to patients with heart failure is unknown. The responses to hydralazine in 52 consecutive patients with severe chronic heart failure secondary to coronary artery disease were reviewed. Twelve patients (23 percent) had 16 ischemie events during the initial administration of hydralazine (angina at rest in 12 and myocardial infarction in 4); these generally occurred in the absence of significant tachycardia and hypotension. Thirty-five of the 52 patients received nitroprusside (8 of whom had ischemie events with hydralazine), but this drug provoked ischemia in only 1 of the 35 although it resulted in greater decreases in systemic arterial pressure than occurred with hydralazine. In patients with an ischemie event only with hydralazine, left ventricular filling pressure decreased 14.6 mm Hg with nitroprusside but only 3.9 mm Hg with hydralazine (probability [p] < 0.01). Provocation of ischemia with hydralazine may therefore be due to the relative preservation of elevated left ventricular preload with this drug, since ischemie events are not common with nitroprusside despite greater decreases in systemic pressures.     

Pharmacologic and behavioral effects on arrhythmias that immediately follow abrupt coronary occlusion: a canine model of sudden coronary death

We have developed and studied a chronically instrumented canine model in which occlusion of a major coronary artery by an implanted balloon occluder promptly leads to arrhythmias that are reasonably reproducible on successive occlusions. Dogs were studied while conscious, and the electrocardiogram and electrograms from ischemic and nonischemic ventricular epicardium were recorded. Either the left anterior descending or circumflex coronary artery was occluded for up to 5.5 minutes. Experiments were performed in a carefully controlled environment at intervals sufficient for full recovery between occlusions. The arrhythmias that occurred were single or multiple premature ventricular depolarizations, runs of ventricular premature depolarizations or ventricular fibrillation. We measured the time from the onset of occlusion to the onset of arrhythmia (latency) and the severity of the arrhythmia (grade). Latency increased with successive occlusions in the same environment until no arrhythmia occurred during an occlusion of 5.5 minutes. In this state, addition of behavioral stress usually led to recurrence of arrhythmia. Stress decreased latency (P < 0.02) and increased grade. We also studied the effects of tolamolol (a beta blocking agent), UM-272 (an analog of propranolol) and diazepam. Tolamolol increased latency (P < 0.02) and tended to decrease grade. UM-272 had variable effects, but it clearly did not exert a protective action. The severity of arrhythmia was inversely related to latency, and latency decreased with increases in heart rate. The results obtained indicate that the model is useful for studies on arrhythmias that follow soon after the onset of ventricular ischemia, and they emphasize the relation between stress, enhanced sympathetic activity and ventricular arrhythmias.     

Vasodilator and inotropic therapy for severe chronic heart failure: passion and skepticism

Although substantial progress has been made in the last 5 years in the development of vasodilator and inotropic drugs for the management of patients with severe chronic heart failure, much of the enthusiasm that surrounded the introduction of many of these agents has subsequently been tempered by reports of drug failure or adverse reactions. In this review and analysis, currently available vasodilator and inotropic agents are critically and comparatively evaluated to assess their respective advantages and limitations. It is apparent that the ability of most of these drugs to produce substantial clinical benefits in patients with severe heart failure has probably been overstated. Therapy fails to achieve the desired clinical results all too frequently, possibly as the result of: the choice of an ineffective drug; the administration of an effective drug in subtherapeutic doses; the administration of an effective drug to improperly selected patients; the failure of initial hemodynamic benefits to be sustained; the occurrence of severe or serious adverse reactions; and the failure to alter concomitant therapy appropriately. The present analysis indicates that there is no uniformly effective or safe vasodilator or inotropic drug for patients with severe heart failure; all agents have important limitations. Of the available therapeutic choices, however, long-term converting enzyme inhibition appears to produce more consistent hemodynamic and clinical benefits with an acceptable degree of adverse reactions than other pharmacologic approaches for the management of these severely ill patients.     

Electrophysiologic effects of acute myocardial infarction in man.

Six patients undergoing surgery for ischemic heart disease were studied by means of epicardial electrodes affixed to the left ventricle. One patient who underwent triple coronary arterial bypass and plication of a left ventricular aneurysm had evidence of an acute myocardial infarction 1 day after operation. A surface electrocardiogram and a bipolar electrogram from the left ventricle were recorded before and after development of the infarction. The bipolar electrogram showed a marked loss of voltage and delay of conduction that were not present in the patients who underwent surgery but did not sustain an acute myocardial infarction. Thus, any acute myocardial infarction in conscious persons appears to be associated with areas of delayed epicardial action and diminution of local voltage. This observation suggests that the electrophysiologic mechanisms of infarction in man are similar to those of infarction in the dog.     

Spectrum of exercise thallium-201 myocardial perfusion imaging in patients with chest pain and normal coronary angiograms.

Twenty-seven consecutive patients with chest pain and no significant obstructive coronary lesions on arteriography were studied with thallium-201 myocardial imaging during exercise and at rest. Fifteen of the patients had typical and 12 atypical angina pectoris. All underwent treadmill exercise electrocardiographic testing; the results were abnormal in 10 patients (37 percent), normal in 14 (52 percent) and uninterpretable in 3 (11 percent). The exercise and resting thallium-201 myocardial images were normal in 23 patients (85 percent); the results of exercise testing were normal in 12 of these patients, abnormal in 8 and uninterpretable in 3. Four patients had a perfusion defect on exercise thallium-201 myocardial imaging; the defect filled in by 4 hours in two patients but persisted in the other two. In contrast, when thallium-201 myocardial imaging was performed in 28 consecutive patients with angiographic coronary artery disease, only 5 patients (16 percent) had normal exercise and resting thallium-201 myocardial images. Therefore, thallium-201 myocardial imaging offers a more effective means of identifying patients with chest pain and no obstructive coronary artery disease than the clinical history or the exercise electrocardiographic test, or both. However, 15 percent of these patients will have abnormal exercise thallium-201 myocardial images because of factors that have not yet been identified.     

Coronary flow studies in patients with left ventricular hypertrophy of the hypertensive type. Evidence for an impaired coronary vascular reserve

Increased myocardial blood flow occurs in ventricular hypertrophy, but flow per 100 grams of myocardium remains normal. The increase in flow may be obtained at the expense of the existing coronary vascular reserve or by an increase in the vascular bed. The coronary vascular reserve was studied by analyzing the hyperemic reaction to selective injection of contrast agent into the coronary arteries in 25 patients: a control group (9 patients) with chest pain syndrome, normal coronary arteries and a normal left ventricle (Group I) and 16 patients with aortic stenosis, left ventricular hypertrophy and normal coronary arteries (Group II). The hyperemic response in Groups I and II was 73.3 +/- 2.2 and 65.8 +/- 9.1 percent, respectively (difference not significant). Group II was subdivided into two groups: Group IIA had five patients with a left ventricular mass of less than 200 g (mean 158.8 +/- 25.9); this group had a hyperemic response of 102.3 +/- 9.9 percent. Group IIB had 11 patients with a left ventricular mass of more than 200 g (mean 308.9 +/- 22.5) and a hyperemic response of 49.27 +/- 10.42 percent. The hyperemic response was correlated with the diastolic left ventricular-aortic gradient (r = +0.64, p less than 0.001), left ventricular mass (r = -0.51, p less than 0.01) and aortic diastolic pressure (r = +0.636, p less than 0.001). Group I had a left ventricular mass similar to that of Group IIA (124.9 +/- 9 and 158.8 +/- 26 g, respectively) but a lower hyperemic response (73.3 +/- 2 and 102.3 +/- 10 percent, respectively). These data suggest that severe left ventricular hypertrophy is associated with a reduction in coronary vascular reserve; it is speculated that this decrease in the vascular reserve capacity may be related to the ischemic component of hypertrophic heart disease.     

Coronary angiographic morphology in myocardial infarction: a link between the pathogenesis of unstable angina and myocardial infarction

It has previously been shown that analysis of coronary morphology can separate unstable from stable angina. An eccentric stenosis with a narrow neck or irregular borders, or both, is very common in patients who present with acute unstable angina, whereas it is rare in patients with stable angina. To extend these observations to myocardial infarction, the coronary morphology of 41 patients with acute or recent infarction and nontotally occluded infarct vessels was studied. For all patients, 27 (66%) of 41 infarct vessels contained this eccentric narrowing, whereas only 2 (11%) of 18 noninfarct vessels with narrowing of 50 to less than 100% had this lesion (p less than 0.001). In addition, a separate group of patients with acute myocardial infarction who underwent intracoronary streptokinase infusion were also analyzed in similar fashion. Fourteen (61%) of 23 infarct vessels contained this lesion after streptokinase infusion compared with 1 (9%) of 11 noninfarct vessels with narrowing of 50 to less than 100% (p less than 0.01). Therefore, an eccentric coronary stenosis with a narrow neck or irregular borders, or both, is the most common morphologic feature on angiography in both acute and recent infarction as well as unstable angina. This lesion probably represents either a disrupted atherosclerotic plaque or a partially occlusive or lysed thrombus, or both. The predominance of this morphology in both unstable angina and acute infarction suggests a possible link between these two conditions. Unstable angina and myocardial infarction may form a continuous spectrum with the clinical outcome dependent on the subsequent change in coronary supply relative to myocardial demand.