Felix Burkart

Atrial Natriuretic Peptide and Atrial Pressure in Patients with Congestive Heart Failure

To define the relation between atrial pressures and the release of atrial natriuretic peptide, we measured plasma concentrations of the peptide in 26 patients with cardiac disease--11 with normal atrial pressures and 15 with elevated atrial pressures (11 of these 15 had elevated pressures in both atria). Mean peptide levels (+/- SEM) in the peripheral venous blood were increased in the 11 patients with cardiac disease and normal atrial pressures, as compared with 60 healthy controls (48 +/- 14 vs. 17 +/- 2 pmol per liter). In the patients with elevated atrial pressures, peptide concentrations were increased twofold in peripheral venous, right atrial, pulmonary arterial, and systemic arterial plasma, as compared with the concentrations in the patients with normal atrial pressures. A step-up in peptide concentration was seen between the venous and right atrial plasma (P less than 0.002) and between the pulmonary and systemic arterial plasma (P less than 0.01), suggesting release of the peptide from the atria. A linear relation was found between right atrial pressure and right atrial peptide concentration (r = 0.835, P less than 0.001) and between pulmonary wedge pressure and the systemic arterial peptide concentration (r = 0.866, P less than 0.001). Right atrial pressure and the peptide concentration both increased with exercise testing in the nine patients evaluated. We conclude that the release of atrial natriuretic peptide is at least partly regulated by right and left atrial pressures. Distinguishing the relative contributions of the two atria and defining the role of peptide release in the pathogenesis of heart failure will require further investigation.

Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel antiarrhythmic study of infarct survival (BASIS)

In view of the high risk of sudden cardiac death and the prognostic importance of complex ventricular ectopic activity, the effects of prophylactic antiarrhythmic treatment were investigated prospectively in patients with persisting asymptomatic complex arrhythmias after myocardial infarction. End points were total mortality and arrhythmic events (sudden death, sustained ventricular tachycardia and ventricular fibrillation). Of 1,220 consecutively screened survivors of myocardial infarction, 312 had Lown class 3 or 4b arrhythmia on 24 h electrocardiographic recordings before hospital discharge and consented to the study. They were randomized to individualized antiarrhythmic treatment (Group 1, n = 100), treatment with low dose amiodarone, 200 mg/day (Group 2, n = 98) or no antiarrhythmic therapy (Group 3 [control group], n = 114). During the 1 year follow-up period, 10 patients in Group 1 died, as did 5 in Group 2 and 15 in Group 3. On the basis of an intention to treat analysis, the probability of survival of patients given amiodarone was significantly greater than that of control patients (p less than 0.05). In addition, arrhythmic events were significantly reduced by amiodarone (p less than 0.01). These effects were less marked and not significant for individually treated patients (Group 1). These findings suggest that low dose amiodarone decreases mortality in the 1st year after myocardial infarction in patients at high risk of sudden death.

Antihypertensive beta blocking action as related to renin and age: A pharmacologic tool to identify pathogenetic mechanisms in essential hypertension

Three hundred fifteen patients with essential hypertension were classified according to low (18 percent), normal (59 percent) or high (23 percent) renin-sodium index. The proportion of patients with low renin hypertension progressively increased with increasing age and blood pressure, there being no difference between the sexes. Two high renin groups emerged: a younger group with early moderate hypertension, and an older group with severe hypertension consequent to possibly ischemic renal disease. Long-term beta blocking monotherapy in 137 patients resulted in a reduction of idastolic pressure to 95 mm Hg or less in 65 percent: 85 percent in those with high and 73 percent in those with normal renin activity; pressure was reduced to this level in only 1 of 24 patients (4 percent) with a low renin index. Antihypertensive efficacy was also related to age, since diastolic pressure was normalized in 80 percent of patients under age 40 years, in 50 percent of those aged 40 to 60 years, but in only 20 percent of those over age 60 years. Age may heolp in patient selection but is no substitute for the more reliable renin index, especially in patients over age 40 years, or with high pressure. Using studiew with propranolol as a standard, similar renin responses were obtained with two cardioselective beta1 type blocking drugs, atenolol and metoprolol, as well as with two nonselective beta2+1 receptor antagonists, LL21945 exhibiting prolonged receptor affinity and oxprenolol in slow release form. These long-acting drugs, which proved effective in single daily doses, could be of value in improving patient compliance...

Intermittent pacemaker dysfunction caused by digital mobile telephones

OBJECTIVES This study was designed to evaluate possible interactions between digital mobile telephones and implanted pacemakers. BACKGROUND Electromagnetic fields may interfere with normal pacemaker function. Development of bipolar sensing leads and modern noise filtering techniques have lessened this problem. However, it remains unclear whether these features also protect from high frequency noise arising from digital cellular phones. METHODS In 39 patients with an implanted pacemaker (14 dual-chamber [DDD], 8 atrial-synchronized ventricular-inhibited [VDD(R)] and 17 ventricular-inhibited [VVI(R)] pacemakers), four mobile phones with different levels of power output (2 and 8 W) were tested in the standby, dialing and operating mode. During continuous electrocardiographic monitoring, 672 tests were performed in each mode with the phones positioned over the pulse generator, the atrial and the ventricular electrode tip. The tests were carried out at different sensitivity settings and, where possible, in the unipolar and bipolar pacing modes as well. RESULTS In 7 (18%) of 39 patients, a reproducible interference was induced during 26 (3.9%) of 672 tests with the operating phones in close proximity (<10 cm) to the pacemaker. In 22 dual-chamber (14 DDD, 8 VDD) pacemakers, atrial triggering occurred in 7 (2.8%) of 248 and ventricular inhibition in 5 (2.8%) of 176 tests. In 17 VVI(R) systems, pacemaker inhibition was induced in 14 (5.6%) of 248 tests. Interference was more likely to occur at higher power output of the phone and at maximal sensitivity of the pacemakers (maximal vs. nominal sensitivity, 6% vs. 1.8% positive test results, p = 0.009). When the bipolar and unipolar pacing modes were compared in the same patients, ventricular inhibition was induced only in the unipolar mode (12.5% positive test results, p = 0.0003). CONCLUSION Digital mobile phones in close proximity to implanted pacemakers may cause intermittent pacemaker dysfunction with inappropriate ventricular tracking and potentially dangerous pacemaker inhibition.

Beneficial effect of amiodarone on cardiac mortality in patients with asymptomatic complex ventricular arrhythmias after acute myocardial infarction and preserved but not impaired left ventricular function.

To determine whether the beneficial effect of low-dose amiodarone on survival in patients with complex ventricular arrhythmias after myocardial infarction was dependent on left ventricular (LV) function, results of the Basel Antiarrhythmic Study of Infarct Survival were analyzed. Two hundred twelve patients after acute myocardial infarction with asymptomatic complex arrhythmias were randomly assigned to receive amiodarone 200 mg/day or to a control group and followed up for 1 year. Results of mortality and arrhythmic events were related to baseline radionuclide LV ejection fraction. With preserved (greater than or equal to 40%) LV ejection fraction, there was a significantly lower 1-year cardiac mortality in patients treated with amiodarone (1 of 68 or 1.5%) versus control subjects (5 of 56 or 8.9%; p less than 0.03). This was not the case for patients with LV ejection fraction less than 40%. Similarly, arrhythmic events were significantly reduced only in patients with preserved LV function. These results suggest an interaction between the effects of amiodarone on survival and LV dysfunction in patients after acute myocardial infarction. Because of 2 other small studies with similar results, this finding may be of clinical relevance and should be addressed in ongoing and future research with this drug.

Plasma Adrenaline and Noradrenaline in Patients with Acute Myocardial Infarction: Relationship to Ventricular Arrhythmias of Varying Severity

Plasma adrenaline (A) and noradrenaline concentrations (NA) were determined in 41 patients admitted to the coronary care unit (CCU). Eleven with suspected acute myocardial infarction (AMI), subsequently excluded as a diagnosis, had significantly elevated A and NA compared with 20 normal resting subjects. Patients with proven infarcts but no ventricular fibrillation had even higher levels of A and NA. Nine patients with ventricular fibrillation as a complication of AMI showed the highest plasma catecholamine values on admission. Patients with AMI and congestive heart failure exhibited substantially increased A, while NA was only slightly elevated compared with that of AMI patients without congestive heart failure. High plasma catecholamines and the relationship between adrenaline and the severity of ventricular arrhythmias suggest that the sympathetic nervous system plays an important role in sustaining a vicious circle of increased myocardial damage and increased irritability during the acute phase of AMI.

Silent ischemia after percutaneous transluminal coronary angioplasty: Incidence and prognostic significance

OBJECTIVES The objective of this observational study was to assess the incidence and prognostic significance of silent ischemia after percutaneous transluminal coronary angioplasty. BACKGROUND Apart from coronary angioplasty, prognosis of patients with silent ischemia is similar to that of patients with angina pectoris. However, similar data concerning silent ischemia associated with restenosis after coronary angioplasty are missing. METHODS A consecutive series of 490 patients was investigated for asymptomatic ischemia on thallium-201 scintigraphy 6 months after successful coronary angioplasty. Repeat angiography was performed in a subgroup of patients with ischemia and repeat angioplasty was performed when clinically indicated. Patients were followed up for 2.2 +/- 0.8 years for cardiac events. RESULTS Six months after coronary angioplasty, ischemia was present in 112 (28%) of 405 patients, and 60% of these 112 were asymptomatic. Ischemia was associated with significant stenosis in 97%; in contrast, results of exercise electrocardiography were negative in 74% of patients with scintigraphic ischemia and angiographic restenosis. The degree of restenosis was similar in patients with symptomatic or silent ischemia (80 +/- 16% vs. 81 +/- 21%). The long-term prognosis of patients with silent ischemia was remarkably similar to that of symptomatic patients. A worse outcome of symptomatic patients was found only if repeat coronary angioplasty for restenosis was considered a separate event (p < 0.01). Silent and symptomatic ischemia predicted an increased risk for recurrent ischemic events but not for death. CONCLUSIONS Thus, absence of symptoms and negative findings on an exercise electrocardiogram may not reflect a good angioplasty result. In addition, silent ischemia due to restenosis after coronary angioplasty has a significant prognostic importance for recurrent symptomatic ischemic events that may be reduced by repeat angioplasty.

Important differences between short- and long-term hemodynamic effects of amiodarone in patients with chronic ischemic heart disease at rest and during ischemia-induced left ventricular dysfunction

To assess and compare the hemodynamic profile of short-and long-term amiodarone administration in the same set of patients and to investigate hemodynamic mechanisms responsible for the antianginal effect of this drug, 10 patients with documented coronary artery disease and stable angina pectoris were studied. Simultaneous right heart catheterization and equilibrium radionuclide angiocardiography were performed at rest and during exercise before therapy (control), after a 5 minute intravenous infusion of 7.5 mg/kg of amiodarone and after 21.0 +/- 4.3 days of peroral therapy (10 days 800 mg/day, 7 days 400 mg/day and then 200 mg/day). After acute drug administration, ejection fraction, stroke index and systolic blood pressure decreased, whereas heart rate, left and right ventricular filling pressures and systemic vascular resistance increased. These effects were reversed after long-term therapy; all measured values returned to control levels except for heart rate, which decreased below the control value, and right atrial pressure, which remained slightly elevated. Amiodarone drug levels decreased from 4.8 +/- 1.8 after intravenous infusion to 1.2 +/- 0.6 mg/liter after long-term therapy. After adjustment for hemodynamic changes at rest, there were still significant reductions in heart rate, mean arterial pressure and rate-pressure product during exercise. It is concluded that the marked negative inotropic effect of amiodarone administered acutely in the dose applied calls for cautious use of this drug when administered intravenously. In contrast, long-term oral amiodarone therapy seems hemodynamically safe, even in patients with moderately depressed left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Acebutolol/Nifedipine Therapy in Patients With Chronic Coronary Artery Disease: Additional Improvement of Ischemia-Induced Left Ventricular Dysfunction

To assess acute hemodynamic effects of combined oral nifedipine (10 mg) and acebutolol (100 mg), 21 patients with angiographically documented coronary artery disease and stable angina pectoris were studied (three groups of seven randomized patients). Simultaneous hemodynamic and equilibrium radionuclide ejection fraction measurements were performed at rest and during exercise before treatment, 1 hour after administration of nifedipine, acebutolol or a combination of the two and again 1 hour after combined nifedipine and acebutolol. At the same exercise level achieved without drugs, angina, subjectively scored by the patients, decreased significantly after nifedipine, acebutolol and a combination of the two in association with a significant improvement in left ventricular ejection fraction (p less than 0.01). There was an additive effect of both drugs on heart rate, systolic blood pressure and therefore the double product (p less than 0.01 each). The negative effects of acute beta receptor blockade on cardiac index, resting ejection fraction and total peripheral resistance were balanced by the vasodilatory action of nifedipine. In patients with borderline heart failure no untoward effects were seen after combined therapy. Thus, acute combined acebutolol/nifedipine therapy in patients with stable angina proved to be hemodynamically superior to therapy with either drug alone and safe even in patients with moderately depressed left ventricular function. This finding provides a basis for appropriately designed long-term studies.

VDD(R) pacing: short- and long-term stability of atrial sensing with a single lead system.

Background: Recent studies have shown that the atrial signal can reliably be sensed for VDD(R) pacing via atrial floating electrodes incorporated in a single‐pass lead. However, there remains concern about the long‐term stability of atrial sensing and proper VDD function under real‐life conditions. This study investigated the long‐term reliability of atrial sensing and atrioventricular synchronous pacing using a new single lead VDD(R) pacing system. Methods and Results: In 20 consecutive patients (ages 71 ± 14 years) with normal sinus node function and high‐degree heart block, a single lead VDD(R) pacemaker (Unity(tm), Intermedics) was implanted, Atrial sensing was studied at implantation, at discharge, and at 1, 3, 6, 12, and 18 months of follow‐up. At implant, the measured P wave amplitude was 2.3 ± 1.2 mV. By telemetry, the atrial sensing threshold was 0.79 ± 0.41 mV at discharge, 0.75 ± 0.43 mV at 1 month, 0.73 ± 0.43 mV at 3 months, 0.76 ± 0.41 mV at 6 months, 0.79 ± 0.41 mV at 12 months, and 0.77 ± 0.35 mV at 18 months of follow‐up (P = NS). Appropriate VDD pacing was assessed by the percentage of correct atrial synchronization (PAS = atrial triggered ventricular paced complexes ± total number of ventricular paced complexes) during repeated Holters. PAS was 99.99%± 0.01 % at 1 month, 99.99%± 0.02% at 3 months, and 99.98%± 0.05% at 12 months of follow‐up (P = NS). No atrial oversensing with inappropriate ventricular pacing was observed, neither during isometric arm exercise testing nor spontaneously during Holier monitoring. Conclusion: The long‐term stability of atrial sensing with almost 100% correct atrial synchronous tracking and the lack of inappropriate pacing due to atrial oversensing make the new Unity VDD(R) system a highly reliable single lead pacing system. In view of the lower costs and the ease of single lead implantation, this system may offer an interesting alternative to DDD pacemakers in patients with normal sinus node function.