Large clinical trials in the management of ventricular arrhythmias. Applying group results to individual cases.

Applying the results of clinical trials to everyday practice in an appropriate manner can be difficult. Earlier clinical trials focused on the secondary prevention of ventricular arrhythmias. Studying patients at high risk of recurrent ventricular arrhythmias is important, but the overall impact on arrhythmic death is low. Recent arrhythmia trials have studied specific patient populations for the primary prevention of ventricular arrhythmias. New trials will expand the investigation to other populations. This article summarizes the results of large clinical trials in the management of ventricular arrhythmias and attempts to provide guidelines for applying their results to everyday clinical practice.

Programming of sensor driven pacemakers.

The chronotropic response is the most important means by which cardiac output is increased and oxygen delivery is maintained in response to increased oxygen consumption during exercise or stress. When the chronotropic response is suboptimal or absent, exercise intolerance results. This condition, called chronotropic incompetence can be treated effectively with a sensor-driven rate-responsive pacemaker. The effectiveness of this therapy assumes that the pacemaker is programmed appropriately. This article focuses on the programming of sensor-driven pacemakers and provides additional suggestions for follow-up testing to ensure maximal benefit from these devices.

Syncope and inducible ventricular fibrillation in a woman with hemochromatosis.

BACKGROUND: Hemochromatosis has been associated with atrial tachyarrhythmias and congestive heart failure as a consequence of dilated or restrictive cardiomyopathy. Inducible ventricular fibrillation has not been previously described. METHODS AND RESULTS: An electrophysiologic study was conducted in a woman after two episodes of syncope. Polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) were induced with ventricular programmed stimulation. Magnetic resonance imaging demonstrated signal loss in the liver consistent with hemochromatosis, but normal cardiac size and function. Hematologic studies supported a diagnosis of hemochromatosis. CONCLUSION: Cardiac hemochromatosis may be associated with serious ventricular arrhythmias.

Nonpharmacologic validation of the intrinsic heart rate in cardiac transplant recipients.

BACKGROUND: The maximum sinus rate during exertion in humans is inversely related to age. However, the sinus rate at rest is quite variable. The intrinsic heart (IHR) following pharmacologic blockade of autonomic tone with propranolol and atropine has been proposed as a test of sinus node function and is related to age by the linear regression equation: IHR = 118.1 - (0.57 x age). Whether this relationship exists for transplanted hearts for which the donor sinus node is denervated has not been determined. METHODS: The relationship between the resting heart rate and the age of the donor heart was examined in 103 patients 1 year following orthotopic cardiac transplantation in the absence of rejection or intercurrent illness. Patients receiving beta-blockers, calcium blockers, antiarrhythmic drugs, digitalis, theophylline, or with biopsy evidence of rejection or abnormal coronary arteriograms were excluded from analysis. RESULTS: The recipient age, left ventricular ejection fraction, pulmonary capillary pressure, cardiac index, donor heart ischemic time and cardiopulmonary bypass time did not correlate with the rate of the resting donor sinus node. The resting heart rate was inversely related to age of the donor heart by the linear regression equation: HR = 112.0 - (046 x age). CONCLUSION: The resting rate of the denervated sinus node is related to donor age with a regression equation that is similar, though slightly slower, than that predicted after pharmacologic autonomic blockade.

The effects of ventricular fibrillation duration and site of initiation on the defibrillation threshold during early ventricular fibrillation.

OBJECTIVES: The purpose of this study was to determine if the defibrillation threshold (DFT) is lower during the first few cycles of ventricular fibrillation (VF) than after 10 s of VF and, if so, if the effect is caused by local or global factors. BACKGROUND: The DFT may be low very early during VF because: (1) for the first few cycles VF arises from a localized region close to a defibrillation electrode where the shock field is strong (local factors), or (2) during early VF the effects of ischemia and sympathetic discharge have not yet fully developed and the heart has not yet completely dilated (global factors). METHODS: Protocol 1 included seven pigs in which a defibrillation electrode and a pacing catheter were both placed in the right ventricular apex. VF was induced by delivering a high current premature stimulus from the pacing catheter that should have caused reentry confined to the right ventricular apex for the first few cycles of VF. A bipolar electrogram was recorded from the tip of the defibrillation catheter. Using a three reversal up-down protocol, the DFT was determined for biphasic shocks delivered after 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 activations in this electrogram and after 10 s (control). Protocol 2 included seven pigs undergoing the same procedure as in protocol 1 except that an additional pacing catheter was placed in the left ventricle. Defibrillation thresholds were determined after 1, 2, 3, 4 and 5 VF activations following VF induction from the right ventricle (RV) or the left ventricle (LV) and after 10 s (control). RESULTS: In protocol 1, the mean +/- SD DFrs were lower during the first three cycles than after 10 s of VF (3.0 +/- 4.1 J for the first VF cycle vs 15.8 +/- 6.6 J after 10 s of VF, p < 0.05). In protocol 2, the DFF for the first few cycles of VF induced away from the defibrillation electrode in the LV (6.9 +/- 1.4 J for the first VF cycle) was significantly lower than that after 10 s of VF (16.0 +/- 2.2 J), whereas the DFF for the first few cycles induced near the defibrillation electrode in the right ventricular apex was significantly lower (2.3 +/- 2.7 J for the first VF cycle) than that induced from the LV. CONCLUSIONS: This study demonstrates that the DFT is significantly lower during the first few VF cycles of VF than after 10 s of VF and that this decrease may be caused by both local factors and global factors. These results provide an impetus for exploring earlier shock delivery in implantable devices.

Defibrillation efficacy with endocardial electrodes is influenced by reductions in cardiac preload.

Little is known about the effects of cardiac preload and cardiac geometry on defibrillation efficacy with endocardial electrodes. We studied nine pigs implanted with an endocardial lead system in the normal and reduced preload state. In the reduced preload state, a balloon catheter was inflated in the inferior vena cava (IVC) for 20 seconds prior to the induction of ventricular fibrillation (VF). Complete occlusion of the IVC and reductions in preload were confirmed by observing deformation of the contrast-filled balloon, a reduction in cardiac size by fluoroscopy, and reductions in ventricular pressures. Biphasic shocks were delivered after 10 seconds of VF using a recursive up-down protocol. VF was induced 20 times for each preload state, and the 50% effective doses (ED50) for energy, current, and voltage were estimated by averaging all shocks for that state. At reduced preloads, energy decreased from 12.1 +/- 3.0 J (+/- SD) to 10.5 +/- 2.9 J (p < 0.01), voltage decreased from 415 +/- 51 V to 390 +/- 51 V (p < 0.05), and current decreased from 8.6 +/- 1.5 A to 7.6 +/- 1.5 A (p < 0.01), while impedance rose from 49.2 +/- 3.8 omega to 52.8 +/- 4.4 omega (p < 0.001). We conclude that reducing cardiac preload and cardiac size significantly lowers ED50 defibrillation energy, current, and voltage. This outcome may be caused directly by the decrease in blood volume as evidenced by increased impedance and/or may be due to changes in heart geometry and stretch.