Search PubMed⌕ Search

Biomedical subjects

Steven M Markowitz

Publications and source records attributed to Steven M Markowitz.

At least 19 recordsLinked to original sources
PubMed2006

Newly detected atrial fibrillation following dual chamber pacemaker implantation.

INTRODUCTION: Pacemaker (PPM)-detected atrial high-rate episodes (AHREs) of even 5-minute duration may identify patients at increased risk for stroke and death. In this study, we sought to determine the incidence of newly detected atrial fibrillation (AF defined as an AHRE > or = 5 minutes) in patients following dual-chamber PPM implantation and to define the clinical predictors of developing AF. METHODS AND RESULTS: We evaluated 262 patients (142 male; age 74 +/- 12 years) without documented AF who underwent PPM implantation for sinus node dysfunction (n = 122) or atrioventricular block (n = 140). Information regarding patient demographics, cardiovascular diseases, and medication history was obtained. The cumulative percentages of ventricular pacing as well as the frequency, duration, and time to first episode of an AHRE were also determined. During follow-up of 596 +/- 344 days, an AHRE > or = 5 minutes was detected in 77 (29%) patients. Of these, 47 (61%) patients had an AHRE > or = 1 hour, 22 (29%) patients had an AHRE > or = 1 day, and 12 (16%) patients had an AHRE > or = 1 week. An AHRE > or = 5 minutes was seen in 24% and 34% of patients at 1 year and 2 years, respectively. Among patients with sinus node dysfunction, > or = 50% cumulative ventricular pacing was the only significant predictor of an AHRE > or = 5 minutes (HR 2.2; CI 1.0-4.7; P = 0.04). CONCLUSIONS: Within 1 year of PPM implantation, AF is detected in 24% of patients without history of AF. In patients with sinus node dysfunction, > or = 50% cumulative right ventricular pacing is associated with a 2-fold increase in risk of developing AF.

Aged↗
PubMed2006

Right and left ventricular outflow tract tachycardias: evidence for a common electrophysiologic mechanism.

INTRODUCTION: "Idiopathic" ventricular arrhythmias most often arise from the right ventricular outflow tract (RVOT), although arrhythmias from the left ventricular outflow tract (LVOT) are also observed. While previous work has elucidated the mechanism and electropharmacologic profile of RVOT arrhythmias, it is unclear whether those from the LVOT share these properties. The purpose of this study was to characterize the electropharmacologic properties of RVOT and LVOT arrhythmias. METHODS AND RESULTS: One hundred twenty-two consecutive patients (61 male; 50.9 +/- 15.2 years) with outflow tract arrhythmias comprise this series, 100 (82%) with an RVOT origin, and 22 (18%) with an LVOT origin. The index arrhythmia was similar: sustained ventricular tachycardia (VT) (RVOT = 28%, LVOT = 36%), nonsustained VT (RVOT = 40%, LVOT = 23%), and premature ventricular complexes (RVOT = 32%, LVOT = 41%) (P = 0.32). Cardiac magnetic resonance imaging and microvolt T-wave alternans results (normal/indeterminate) were also comparable. In addition, 41% with RVOT foci and 50% with LVOT foci were inducible for sustained VT (P = 0.48), and induction of VT was catecholamine dependent in a majority of patients in both groups (66% and 73%; RVOT and LVOT, respectively; P = 1.0). VT was sensitive to adenosine (88% and 78% in the RVOT and LVOT groups, respectively, P = 0.59) as well as blockade of the slow-inward calcium current (RVOT = 70%, LVOT = 80%; P = 1.00) in both groups. CONCLUSIONS: Electrophysiologic and pharmacologic properties, including sensitivity to adenosine, are similar for RVOT and LVOT arrhythmias. Despite disparate sites of origin, these data suggest a common arrhythmogenic mechanism, consistent with cyclic AMP-mediated triggered activity. Based on these similarities, these arrhythmias should be considered as a single entity, and classified together as "outflow tract arrhythmias."

Action Potentials↗
PubMed2006

Cardiac arrhythmias.

Explore the source record for details and available documents.

Arrhythmias, Cardiac↗
PubMed2005

Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract.

BACKGROUND: Tachycardia-induced cardiomyopathy caused by ventricular tachycardia is a well-defined clinical entity. Less well appreciated is whether simple ventricular ectopy can result in cardiomyopathy. We sought to examine a potential causal relationship between repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract and cardiomyopathy and the role of ablation in reversing this process. METHODS AND RESULTS: The study consisted of 27 patients (11 men; age, 47+/-15 years) with repetitive monomorphic ventricular ectopy, including 8 patients (30%) with depressed ventricular function (ejection fraction < or =45%). All patients underwent assessment of cardiac structure and function. The burden of ectopy was quantified through 24-hour Holter monitoring. Patients then underwent ablation guided by 3D mapping. After ablation, patients underwent repeated Holter monitoring and reassessment of cardiac function. Patients with depressed ventricular function were more likely to be older than patients with normal function (58+/-14 versus 42+/-18 years; P=0.013). However, the burden of ventricular ectopy was similar in patients with (17,859+/-13,488 ectopic beats per 24 hours) and without (17,541+/-11,479 ectopic beats per 24 hours; P=0.800) preserved ventricular function. Successful ablation was performed in 23 patients (85%), including 7 of 8 patients with depressed ventricular function. In this latter group, ventricular function improved in all patients (from 39+/-6% to 62+/-6%; P=0.017). CONCLUSIONS: Repetitive monomorphic ventricular ectopy (in the absence of sustained ventricular tachycardia) originating from the right ventricular outflow tract is an underappreciated cause of unexplained cardiomyopathy. Successful ablation of the focal source of ventricular ectopy results in normalization of left ventricular function. Patients with ectopy-induced cardiomyopathy are significantly older than patients with preserved ventricular function, which suggests either that older patients are more susceptible to the development of a cardiomyopathy or that the cardiomyopathy has had a longer period of time in which to evolve.

Adult↗
PubMed2005

Usefulness of prolonged QRS duration to identify high-risk ischemic cardiomyopathy patients with syncope and inducible ventricular tachycardia.

We evaluated 61 consecutive patients who had coronary artery disease, decreased left ventricular function, and syncope and underwent implantation of a cardioverter-defibrillator because sustained ventricular tachycardia was inducible at electrophysiologic testing. During a follow-up of 3.0 +/- 1.8 years, 23 patients (38%) developed ventricular tachycardia. Prolonged QRS duration (>/=120 ms) was the only significant predictor of arrhythmia. The 1- and 2-year rates without ventricular arrhythmia were 82% and 77%, respectively, in patients whose QRS duration was <120 ms. In contrast, 1- and 2-year rates without ventricular arrhythmia were only 64% and 51%, respectively, in patients whose QRS duration was >/=120 ms (risk ratio 3.7, 95% confidence interval 1.4 to 9.8, p = 0.0092).

Aged↗
PubMed2005

Effect of transthoracic shocks on left ventricular function.

Although defibrillating shocks are thought to depress ventricular function transiently, the independent effects of high strength shocks (without the metabolic sequelae of pre-shock fibrillation) have not been assessed systematically in humans. Therefore, we delivered three consecutive synchronized monophasic transthoracic shocks (200, 200 and 360 J) at 60s intervals during sinus rhythm and evaluated the effect on left ventricular chamber size and function as determined by transesophageal echocardiography in 11 patients (mean age 67+/-8 years, 9M/2F) with depressed left ventricular function (left ventricular ejection fraction: 14-37%). The shocks did not alter hemodynamics consistently. On average, the shocks did not alter stroke volume, cardiac output, left ventricular ejection fraction or regional wall thickening (all p>0.05 versus baseline). This effect was highly variable and 36% of patients experienced a >25% reduction in cardiac output by the final shock. There was a tendency for regional wall thickening to worsen in the best baseline sextant with an offsetting significant increase in thickening in the worst baseline sextant (p=0.05). Thus, repetitive defibrillation strength transthoracic shocks do not impair left ventricular function consistently in patients with cardiomyopathy. However, the effect is widely variable and potentially important depression of left ventricular function does occur in some patients.

Aged↗
PubMed2004

Effect of beta-adrenergic blockade on dynamic electrical restitution in vivo.

The slope of the action potential duration (APD) restitution curve may be a significant determinant of the propensity to develop ventricular fibrillation, with steeper slopes associated with a more arrhythmogenic substrate. We hypothesized that one mechanism by which beta-blockers reduce sudden cardiac death is by flattening the APD restitution curve. Therefore, we investigated whether infusion of esmolol modulates the APD restitution curve in vivo. In 10 Yorkshire pigs, dynamic APD restitution curves were determined from measurements of APD at 90% repolarization with a monophasic action potential catheter positioned against the right ventricular septum during right ventricular apical pacing in the basal state and during infusion of esmolol. APD restitution curves were fitted to the three-parameter (a, b, c) exponential equation, APD = a.[1 - e((-b.DI))] + c, where DI is the diastolic interval. Esmolol decreased the maximal APD slope, 0.68 +/- 0.14 vs. 0.94 +/- 0.24 (baseline), P = 0.002, and flattened the APD restitution curve at shorter DIs, 75 and 100 ms (P < 0.05). To compare the slopes of the APD restitution curves at similar steady states, slopes were also computed at points of intersection between the restitution curve and the lines representing pacing at a fixed cycle length (CL) of 200, 225, 250, 275, and 300 ms using the relationship CL = APD + DI. Esmolol decreased APD restitution slopes at CLs 200-275 ms (P < 0.05). Esmolol flattens the cardiac APD restitution curve in vivo, particularly at shorter CLs and DIs. This may represent a novel mechanism by which beta-blockers prevent sudden cardiac death.

Action Potentials↗
PubMed2004

Significance of adenosine-induced atrioventricular block in patients with unexplained syncope.

OBJECTIVES: The purpose of this study was to test whether a prolonged (>/=6 seconds) period of AV block in response to adenosine triphosphate (ATP) identifies additional patients at risk for bradycardia who may benefit from pacemaker implantation. BACKGROUND: Bradycardia is a common etiology for syncope in patients without underlying structural heart disease. Conventional testing using electrophysiologic and tilt table studies often fail to identify patients prone to episodes of symptomatic bradycardia. METHODS: Adenosine testing was performed in 92 consecutive patients (64 women, age 55 +/- 21 years) with syncope of uncertain origin referred for tilt table testing. The adenosine test measured the maximal R-R interval after bolus administration of intravenous adenosine 150 mug/kg to upright patients. A positive adenosine AV block response was defined as a maximal R-R interval > or =6 seconds. RESULTS: A total of 21 patients (23%) had a positive response. During mean follow-up of 14.3 +/- 5.9 months, 14 patients (16%) had recurrent syncope. Among patients with a positive adenosine response, 3 patients (14%) had recurrent syncope. In comparison, 11 of 69 patients (16%) without adenosine-induced AV block had recurrent syncope (P = 1.00). CONCLUSIONS: Prolonged adenosine-induced AV block in patients with unexplained syncope failed to predict recurrent syncopal episodes. These data do not support therapeutic interventions (e.g., pacemaker implantation) based on a positive adenosine AV block response alone.

Adenosine Triphosphate↗
PubMed2004

Single-stage adenosine tilt testing in patients with unexplained syncope.

INTRODUCTION: We previously have shown that a 3-minute single-stage adenosine tilt test has a diagnostic yield comparable to a two-stage protocol consisting of a 30-minute drug-free tilt followed by a 15-minute isoproterenol tilt. In this study, we sought to further define the clinical utility of adenosine tilt testing in patients with unexplained syncope by prospectively evaluating test specificity and determining predictors of a positive test response. METHODS AND RESULTS: The specificity of single-stage adenosine tilt testing was determined using 30 control subjects. To determine the diagnostic yield of this protocol, adenosine tilts were performed in 129 patients with unexplained syncope. The adenosine tilt test protocol had high specificity (100%) but a low overall diagnostic yield (18%). However, the yield was affected significantly by age. In patients </=40 years of age, the tilt test was positive in 15 (41%) of 37 patients, which was significantly greater than the yield in patients between the ages of 41 and 64 years (6/41 patients [15%], P = 0.012) and those >/=65 years of age (2/41 patients [5%], P < 0.0001). CONCLUSION: These data support single-stage adenosine tilt testing in patients </=40 years of age because the diagnostic yield of the test is maximal in this group and the test can be completed in </=3 minutes. Conversely, the diagnostic yield of adenosine tilt testing in patients >40 years of age is low, suggesting that the clinical utility of this protocol is limited in these patients.

Adenosine↗
PubMed2004

Time course and predictors of autonomic dysfunction after ablation of the slow atrioventricular nodal pathway.

Withdrawal of parasympathetic tone has been reported after ablation in the posteroseptal right atrium and has been attributed to injury of vagal efferent fibers. The purpose of this study was to assess the time course and predictors of autonomic dysfunction after slow pathway ablation. In 30 patients with AV nodal reentrant tachycardia, time- and frequency-domain measures of heart rate variability (HRV) were measured before, 30 minutes after, and 1 day after slow pathway ablation. There were significant reductions in mean RR interval (724 +/- 163 vs 836 +/- 164 ms, P < 0.05), SD of RR intervals (29 +/- 17 vs 40 +/- 18 ms, P < 0.05), root mean squared difference (15 +/- 8 vs 29 +/- 17 ms, P < 0.05), and high frequency power (4.1 +/- 0.4 vs 4.5 +/- 0.6 log10ms2, P < 0.05) 30 minutes after ablation. However, these parameters returned to baseline 1 day after ablation. Multivariate regression identified isoproterenol dose during the diagnostic study (P = 0.02) and radiofrequency duration (P = 0.02) as statistically significant predictors of heart rate change (R2= 0.45). These findings suggest that changes in autonomic tone after ablation in the posteroseptal right atrium are transitory and resolve within 1 day of the procedure. These short-term changes may be related to procedural variables rather than direct injury to vagal efferent fibers.

Adult↗
PubMed2003

Pharmacogenetic considerations in diseases of cardiac ion channels.

Phenotypic variation within a species arises from differences in genetic makeup between individuals. This inherent diversity empowers the species as a whole to explore and expand into new environmental niches and also to survive new stressors within an ever-changing environment. Paradoxically, one class of stressors currently challenging the human population is therapeutic drugs: medications designed to combat disease are often associated with a host of nonspecific side effects. Following earlier studies of the involvement of some cardiac ion currents in unwanted drug interactions, recent reports have identified not only the ion channel subunits involved but also a range of mutations and single nucleotide polymorphisms in ion channel genes that predispose to both drug-induced and familial cardiac arrhythmia. The tendency for individuals harboring specific, often common, gene variants to succumb to life-threatening cardiac arrhythmia, and the contribution of other factors such as drug interaction to disease etiology in these cases, are discussed here together with potential pharmacogenetic strategies for arrhythmia circumvention and therapy.

Animals↗
PubMed2003

An update on electrical cardioversion of atrial fibrillation.

Atrial fibrillation is the most frequently encountered sustained arrhythmia in clinical practice. Electrical cardioversion of atrial fibrillation using damped sine wave shocks has been a mainstay of therapy for nearly 4 decades; its limitation remains a failure rate that approaches 20%. Although several alternatives have been proposed, including delivering 720 J shocks using dual monophasic defibrillators, ibutilide pretreatment and internal cardioversion, each of these approaches has significant limitations, which preclude its routine use. Recent data demonstrate that routine use of biphasic shocks for cardioversion of atrial fibrillation is associated with a marked improvement in cardioversion efficacy and suggest that biphasic shocks may be the preferred method for the transthoracic electrical cardioversion of atrial fibrillation.

Anti-Arrhythmia Agents↗
PubMed2003

Endocardial detection of repolarization alternans.

Repolarization alternans (RPA) is prognostic of sudden cardiac death and is thought to be mechanistically linked to the initiation of ventricular tachyarrhythmias. Thus, implantable cardiac device detection of RPA may be therapeutically valuable. Because alternans detection is currently limited to surface electrocardiograms, we investigated whether RPA could be measured using a single right-ventricular endocardial lead in humans. Such a location was chosen because it is consistent with the requirements for long-term implantable-device implementation. During diagnostic electrophysiological testing, 28 patients (23 male, 5 female; 61 +/- 15 years) were evaluated for surface T-wave alternans (TWA; the current "gold standard" for RPA detection) and endocardial RPA during 5 min of 550-ms right-atrial pacing. Power spectral analysis indicated that 11/28 patients had both surface TWA and endocardial RPA, 9/28 patients had neither, and 8/28 patients had discordant results (71% concordance; p = 0.02). Importantly, unlike surface TWA, endocardial RPA was detectable on a beat-to-beat basis. Given the putative mechanistic link between RPA and ventricular arrhythmias, beat-to-beat endocardial RPA detection might be of diagnostic or therapeutic utility.

Algorithms↗
PubMed2002

Response to adenosine differentiates focal from macroreentrant atrial tachycardia: validation using three-dimensional electroanatomic mapping.

BACKGROUND: We previously proposed that adenosine has mechanism-specific effects on atrial tachycardia (AT), such that adenosine terminates AT attributable to triggered activity, transiently suppresses automatic rhythms, and has no effect on macroreentrant AT. This, however, remains controversial, because other studies have reported that adenosine terminates reentrant AT. To clarify this issue, we used 3D electroanatomic mapping to delineate the tachycardia circuit and thereby determine whether the response to adenosine differentiates focal from macroreentrant AT. METHODS AND RESULTS: We examined the effect of adenosine on 43 ATs in 42 consecutive patients (59+/-15 years of age; 26 female) who received adenosine during tachycardia and whose mechanism of AT was characterized by pharmacological perturbation, entrainment, 3D electroanatomic mapping, and results of radiofrequency ablation. Eight tachycardias were macroreentrant (noncavotricuspid isthmus-dependent), and 35 ATs were focal (either triggered or automatic). Adenosine administered during AT (at doses sufficient to result in AV block) terminated or transiently suppressed focal AT in 33 of 35 cases, whereas 8 of 8 macroreentrant ATs were adenosine insensitive (P<0.001). Twenty-eight of 35 focal ATs were located along the crista terminalis or tricuspid annulus. CONCLUSIONS: The response of AT to adenosine can immediately differentiate atrial tachycardia arising from a focal source from that attributable to macroreentry. This finding can be exploited to facilitate developing a focused, strategic ablative approach at the onset of a procedure.

Adenosine↗