Biomedical subjects

R B Kleiman

Publications and source records attributed to R B Kleiman.

13 recordsLinked to original sources

PubMed1994

Comparison of simultaneous versus sequential defibrillation pulsing techniques using a nonthoracotomy system.

The defibrillation threshold (DFT) using simultaneous (SIML) versus sequential (SEQ) pathways for shock delivery was compared in 16 patients with an implanted cardioverter defibrillator. All patients had three-lead nonthoracotomy systems (NTL) using a left chest subcutaneous patch, a right ventricular endocardial lead, and a lead in the coronary sinus (n = 5) or superior vena cava (n = 11). The DFT were determined 2-44 days (17 +/- 17 days) after implantation. The DFT was defined as the lowest energy shock that resulted in successful defibrillation. The first pathway tested was SIML in 12 and SEQ in 4 patients with output beginning at or above the intraoperative DFT, routinely 18 J. The second pathway was tested beginning 2-4 J above the DFT of the first tested pathway. All shocks were delivered in 2-4 J decrement or increment steps. The SEQ pathway shocks resulted in a significantly lower DFT than SIML pathway shocks (14 +/- 6 vs 18 +/- 6 J; P < 0.01). There was no difference in the time delay after ventricular fibrillation initiation before shock delivery for the successful defibrillation between SIML versus SEQ pathways (7 +/- 2 secs for both pathways). In 7 of 16 patients, defibrillation using SEQ pathway resulted in a > 5 J lowering of DFT, while only one patient had > 5 J lowering of DFT using SIML shocks (P < 0.05). These results have important implications for selecting the optimal pathway for implantable cardioverter defibrillator therapy with a multilead NTL system.

Adult↗

PubMed1994

Effectiveness of noninvasive programmed stimulation for initiating ventricular tachyarrhythmias in patients with third-generation implantable cardioverter defibrillators.

Previous generations of implantable cardioverter defibrillators (ICDs) required invasive electrophysiological testing to assess defibrillator function. Newer third-generation ICDs include the capability for performing noninvasive programmed stimulation (NIPS) and may reduce the need for invasive studies to assess tachycardia recognition and antitachycardia therapy algorithms. The effectiveness of ICD-based NIPS for the induction of ventricular arrhythmias has not, however, been formally assessed. Third-generation ICDs were implanted in 79 patients, who underwent a total of 166 postoperative defibrillator tests. NIPS with rapid ventricular pacing was performed in all patients in an attempt to induce ventricular fibrillation. In patients with prior sustained uniform ventricular tachycardia, programmed stimulation with up to three extrastimuli was performed in order to attempt to initiate the clinical ventricular tachcardia. Ventricular fibrillation was induced with NIPS in 146 of 166 studies (88%). Ventricular tachycardia was initiated with NIPS in 104 of 123 studies (85%). The type of defibrillator and the use of endocardial or epicardial rate sensing/pacing leads did not influence the efficacy of NIPS. NIPS with third-generation ICDs is generally effective at inducing ventricular fibrillation and clinically relevant ventricular tachycardias, and reduces the need to perform invasive electrophysiological testing following device implantation. In a minority of patients temporary transvenous pacing catheters must still be used to facilitate arrhythmia induction.

Adult↗

PubMed1993

Endocardial mapping during sinus rhythm in patients with coronary artery disease and nonsustained ventricular tachycardia.

Programmed stimulation in patients with nonsustained ventricular tachycardia (VT) and coronary artery disease (CAD) induces sustained VT in 30 to 50% of patients. The presence of inducible, sustained VT identifies patients at high risk for sudden death. This study sought to determine whether patients with nonsustained VT who have inducible, sustained VT would have differences of left ventricular endocardial activation and conduction compared with those of patients without inducible, sustained VT. Thirty-six patients with CAD referred for evaluation of nonsustained VT underwent programmed ventricular stimulation and catheter mapping of left ventricular endocardial activation. Using previously validated methods, electrograms were classified as normal, abnormal or fractionated based on measurement of local electrogram duration and amplitude. Programmed stimulation induced sustained, uniform VT in 16 of 36 patients (44%). Patients with inducible, sustained, uniform VT had significantly more sites with abnormal (48%) and fractionated (5.5%) electrograms than did those without inducible VT (35% abnormal and 0.4% fractionated; p = 0.05 and 0.01, respectively). Patients with inducible VT had a mean of 15% of mapped sites displaying late electrograms versus only 3% in those without inducible VT (p < 0.01). The duration of the longest local electrogram in patients with inducible, sustained, uniform VT was 128 ms compared with 100 ms in those without inducible VT (p < 0.001). Thus, patients with CAD presenting with nonsustained VT who have inducible, sustained, uniform VT have significantly greater degrees of local conduction slowing and delayed activation than do those without inducible, sustained, uniform VT. These observations support reentry as the mechanism of the induced arrhythmias in these patients.

Cardiac Pacing, Artificial↗

PubMed1993

Unique sensing errors in third-generation implantable cardioverter-defibrillators.

OBJECTIVES: Third-generation cardioverter-defibrillators appear to be susceptible to unique sensing errors. This study was performed to determine the incidence and types of sensing errors in combination therapy implantable devices. BACKGROUND: One of the advantages offered by third-generation implantable cardioverter-defibrillators is the combination of bradycardia and antitachycardia pacing and cardioversion-defibrillation capabilities in a single device. The potential for unique sensing errors, those caused by the conflicts presented by combining bradycardia and tachycardia sensing and therapy algorithms in the same device, has not been previously addressed. METHODS: To determine the incidence of important sensing errors, 61 patients with a combination therapy device (Cadence [Ventritex] and PCD [Medtronic]) were studied for a 25-month period. In addition to surface electrocardiographic recordings during implantation and routine device testing, real-time and stored electrograms recorded from the rate-sensing leads (Cadence) and real-time marker channel recordings (PCD) were reviewed to diagnose sensing errors that resulted in symptoms, device inefficacy or delivery of inappropriate therapy. After recognition, specific reprogramming steps were performed in an attempt to avoid recurrent sensing errors. RESULTS: A total of 13 sensing errors were diagnosed in 12 patients (19.7%); the incidence was similar in both devices. Five distinct categories of sensing errors were identified. After device reprogramming, only one recurrent error occurred in 98 patient-months of follow-up. CONCLUSIONS: Important sensing errors occur in approximately 20% of patients with third-generation combination therapy cardioverter-defibrillators. Prompt diagnosis of sensing errors can lead to specific reprogramming steps to avoid recurrent errors.

Algorithms↗

PubMed1993

Implantable cardioverter-defibrillator therapy in the absence of significant symptoms. Rhythm diagnosis and management aided by stored electrogram analysis.

BACKGROUND: This report describes the value of stored ventricular electrogram analysis in the diagnosis and management of patients experiencing minimal or no symptoms before implantable cardioverter-defibrillator (ICD) therapy. METHODS AND RESULTS: The study population included 48 patients who received the Cadence Tiered Therapy Defibrillator System, an investigational third-generation ICD with ventricular electrogram storage capabilities. Criteria for arrhythmia diagnosis were based on analysis of the electrogram rate, RR interval variability, and morphology. Twenty-nine of the 48 patients (60%) experienced at least one episode of antitachycardia pacing or shock (one shock or more in 25 of 29 patients) that was preceded by minimal or no symptoms during a mean follow-up of 15.1 +/- 7.8 months. There were 194 tachycardia episodes registered by the device, including 101 for which ventricular electrograms were stored and available for analysis. Of the 101 stored electrograms, 74 were classified as ventricular tachycardia (VT), 24 as non-VT rhythms (atrial fibrillation, 13; supraventricular tachycardia, six; rate-sensing lead disruption, four; T wave oversensing, one), and only three as indeterminate rhythms. Based on the electrogram analysis, changes in tachycardia detection criteria and/or antiarrhythmic drug regimens were implemented and were associated with a reduction in the number of device responses for non-VT rhythms from 24 during the initial study period to three during 11.0 +/- 7.2 months of additional follow-up. CONCLUSIONS: ICD responses in the absence of symptoms are relatively common in third-generation devices with antitachycardia pacing capabilities. Despite potential limitations such as the effect of bundle branch block on the electrogram morphology during supraventricular tachycardia, the availability of electrogram storage capabilities allowed a presumptive diagnosis of the events precipitating asymptomatic device responses. Device reprogramming based on analysis of stored electrograms was associated with a dramatic reduction in the incidence of ICD responses for non-VT rhythms.

Atrial Fibrillation↗

PubMed1992

Acute and chronic cycle length dependent increase in ventricular pacing threshold.

Several factors have been shown to influence ventricular pacing threshold in humans, including pacing lead location (endocardial vs epicardial), lead maturation, and antiarrhythmic agents. To determine whether ventricular pacing rate has a significant influence on acute and chronic pacing thresholds, we measured pacing thresholds in 16 patients receiving an implantable antitachycardia pacemaker cardioverter defibrillator (Cadence). Ventricular pacing thresholds were determined using the device programmer at cycle lengths of 600, 400 and 300 msec at the time of implantation; prior to hospital discharge at 3-14 days; and during follow-up outpatient visits at 6-8 weeks, 3 months, and 6 months to 1 year. Eleven patients had an epicardial lead system and five an endocardial lead system. Eleven patients were being treated with antiarrhythmic drug therapy. Device output ranged from 1-10 V and was adjustable in 1-V increments (pulse width was held constant at 1 msec). A cycle length dependent increase in pacing threshold (defined as a > or = 1-V increase in threshold at 400 or 300 msec relative to 600 msec) was observed in 10/16 patients during 12/72 pacing trials at 400 msec, and in 15/16 patients during 31/67 trials at 300 msec. In trials in which an increase in pacing threshold occurred, the magnitude of the increase at 400 msec relative to 600 msec was only 1 V in all 12 trials, but at 300 msec the increase ranged from 4-9 V in 7/31 (23%) trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Arrhythmia Agents↗

PubMed1992

Failure of defibrillator paddle as mimic for subcutaneous patch lead during nonthoracotomy implantable cardioverter defibrillator lead configuration assessment.

It is a common, although virtually unsubstantiated, practice to assess the efficacy of nonthoracotomy lead systems for implantable cardioverter defibrillators using a defibrillator paddle as mimic for the subcutaneous patch lead. We report a case in which an adequate defibrillation threshold was documented with the nonthoracotomy lead system using a defibrillator paddle but not following implantation of the true subcutaneous patch lead. This case suggests that the substitution of a defibrillator paddle for the subcutaneous patch lead during nonthoracotomy lead system evaluation may have significant limitations in assessing lead configuration efficacy.

Adult↗

PubMed1990

Outward currents in hypertrophied feline ventricular myocytes.

In the present study we have characterized the inward rectifying K current, I(K1), and the delayed rectifying outward current, I(X1), in single feline ventricular myocytes isolated from normal cats and animals with experimentally induced RVH. The ionic currents described in this study share many characteristics with the ionic currents first observed in multicellular preparations, but differ from them in several important respects, most notably the presence of a negative slope region in the background (IK1) current: voltage relationship and the relative insensitivity of I(X1) to block by traditional K channel blockers. These findings are similar to those reported for these currents in other preparations of single ventricular or Purkinje myocytes. The present study also demonstrates that there are several abnormalities of I(K1) and I(X1) in hypertrophied myocardium. The magnitude of I(K1) is larger in hypertrophy myocytes, while the magnitude of I(X1) is reduced. I(X1) showed steeper rectification, slower activation, and more rapid deactivation in hypertrophy myocytes, abnormalities which may contribute to the prolonged AP duration of hypertrophied myocardium. These findings, in addition to our previous report on alterations of the slow inward Ca current in hypertrophied myocardium, add to our understanding of the electrophysiologic derangements induced by pressure overload cardiac hypertrophy.

Action Potentials↗

PubMed1989

Outward currents in normal and hypertrophied feline ventricular myocytes.

The properties of the inward rectifier K current (IK1) and the delayed rectifier K current (IK) were studied in single feline myocytes isolated from the right ventricle of normal cats and cats with experimentally induced right ventricular hypertrophy (RVH). IK1 demonstrated time-dependent decay during hyperpolarizations and showed inward rectification with a prominent negative-slope region between -30 and -10 mV. Both IK1 and IK was carried primarily by K ions. The activation of IK during depolarizations followed a monoexponential time course, whereas the deactivation of IK tail currents was either mono- or biexponential depending on the repolarization potential. IK showed marked rectification at positive potentials. A comparison of these currents in normal and hypertrophy myocytes revealed that in RVH the magnitude of IK1 is increased, whereas the magnitude of IK is decreased. IK showed steeper rectification, had slower activation, and had more rapid deactivation in RVH. These abnormalities of the IK may contribute to the prolongation of action potential duration, which characterizes pressure-overload cardiac hypertrophy.

Animals↗

PubMed1988

Prognosis following sustained ventricular tachycardia occurring early after myocardial infarction.

Eighty-seven patients with sustained ventricular tachycardia (VT) between 3 and 90 days after acute myocardial infarction (AMI) were evaluated to define factors associated with a high risk of arrhythmia recurrence or death. Most patients had poor left ventricular function (mean ejection fraction 29 +/- 12%), multivessel coronary artery disease (71%) and inducible sustained VT with programmed stimulation (87%). During a mean follow-up of 26 months, 36 patients (41%) died and 21 patients had arrhythmia recurrence (with 19 sudden deaths). Factors independently associated with mortality included: (1) treatment before 1981 (p less than 0.01); (2) anterior AMI (p less than 0.05); (3) short time from AMI to first episode of VT (p less than 0.06); and (4) multivessel coronary artery disease (p less than 0.07). Factors independently associated with arrhythmia recurrence were: (1) medical treatment (as opposed to surgical) (p less than 0.01); (2) greater than or equal to 3 episodes of spontaneous VT (p = 0.01); (3) multivessel coronary disease (p less than 0.05); and (4) anterior AMI (p less than 0.07). Medically and surgically treated patients did not differ significantly in overall survival (49 vs 61%, respectively), although short-term (6 month) surgical survival improved from 31% during the first half of the study to 96% in the latter half (p less than 0.01). For patients with sustained VT early after AMI the risk of death and arrhythmia recurrence can be assessed based on clinical and angiographic characteristics; in addition, surgical treatment is associated with a lower incidence of arrhythmia recurrence than medical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Electrophysiologic and mechanical properties of single feline RV and LV myocytes.

With the advent of techniques to isolate large numbers of single adult mammalian ventricular myocytes, it has become possible to determine whether, as a result of the different pressure loading of the right and left ventricles (RV and LV), RV and LV myocytes differ in electromechanical properties. We studied the morphology, contraction and electrophysiology of the L-type slow inward calcium current (Isi) in isolated adult feline RV and LV myocytes. The maximum width of LV myocytes was slightly greater than for RV myocytes (25.9 +/- 7.0 microns vs. 25.1 +/- 7.9 microns, P = 0.05), but RV and LV myocytes did not differ significantly in maximum length or two-dimensional surface area. RV and LV myocytes did not differ significantly in the extent of shortening or rates of shortening and relaxation. The voltage dependence of activation and inactivation and the time course of activation and recovery from inactivation of Isi also did not differ significantly between RV and LV myocytes. We conclude that despite the different pressure loads on the RV and LV, single myocytes from either ventricle have similar physiologic properties.

Action Potentials↗

PubMed1988

Effects of phenylephrine on calcium current and contractility of feline ventricular myocytes.

Previous studies on numerous cardiac preparations have shown that stimulation of alpha 1-receptors produces a positive inotropic effect. The cellular basis for this effect is not well understood. Isolated feline ventricular myocytes were used in the present study to examine the idea that the increase in contractility induced by stimulation of alpha 1-receptors is produced by an increase in inward Ca2+ current and that this event is caused by the stimulation of protein kinase C (PKC). These experiments showed that phenylephrine (10(-4) M) increased Ca2+ current from 0.56 +/- 0.02 (control) to 1.12 +/- 0.25 nA and increased contractile magnitude by 201 +/- 28%. The effect on Ca2+ current was completely blocked by propranolol (10(-7)M), whereas after beta-receptor blockade, contractile state was still 130 +/- 8% of control levels. alpha 1-Receptor blockade by prazosin eliminated this residual inotropic component of phenylephrine. Lower concentrations of phenylephrine (10(-7)M) were without effect on Ca2+ current and contractility as was stimulation of PCK with 150 nM of a phorbol ester. These results suggest that the positive inotropic effect of alpha 1-receptor stimulation in adult feline ventricular myocytes is not produced by increasing inward Ca2+ current and that this response is also not associated with stimulation of PKC.

Animals↗

PubMed1988

Calcium currents in normal and hypertrophied isolated feline ventricular myocytes.

The magnitude and kinetics of the slow inward calcium current (Isi) were compared in single right ventricular myocytes that were isolated from normal cats and cats with right ventricular hypertrophy. Peak inward current density was greater in hypertrophy than normal myocytes (-20.4 +/- 15.3 vs. -10.4 +/- 8.8 microA/cm2, P less than 0.05). When we blocked early outward currents with intracellular CsCl, however, the peak magnitude of Isi was shown to be similar in hypertrophy and normal myocytes (-16.4 +/- 11.2 vs. -12.7 +/- 3.0 microA/cm2, P = NS). The increased net inward current in hypertrophy was thus due to a decrease in Cs-sensitive early outward current rather than an increase in the magnitude of Isi. The fast component of inactivation of Isi was similar in hypertrophy and normal myocytes, but the slow component was delayed in hypertrophy (slow time constant; tau slow = 75.9 +/- 14.7 ms vs. tau slow = 60.6 +/- 4.9 ms, P less than 0.05). These abnormalities of Isi may contribute to the prolonged duration of the action potential and of contraction in hypertrophied myocardium, but a defect in excitation-contraction coupling distal to Isi appears to produce the diminished magnitude of contraction.

Action Potentials↗