Abstract: The proarrhythmic effects of cocaine may be mediated in part by its effects on cardiac repolarization properties. This study evaluated the acute effects of smoking cocaine 25 mg on the electrocardiograms of 14 habitual cocaine users during a 12-minute observation period. After cocaine administration, heart rate increased by a mean of 22 beats/min (p <0.0001). One patient developed accelerated junctional rhythm, and 5 had nonspecific ST-T-wave abnormalities. The electrocardiograms revealed significant prolongation of the QTc interval (p <0.001) after cocaine administration. In addition, T-wave amplitude decreased and U-wave amplitude increased in response to cocaine use (p <0.05). QRS duration was unchanged by cocaine, whereas the PR interval shortened slightly. The repolarization changes observed after cocaine use were similar to those reported for other sympathomimetic agents and may be a contributing factor in the association between cocaine use and ventricular arrhythmias.
Abstract: BACKGROUND: Mechanical unloading during left ventricular assist device (LVAD) support may lead to cardiac recovery. Predictors of recovery, however, have not been identified. We aimed to evaluate the time course and durability of echocardiographic, electrocardiographic (ECG), histologic, and neurohormonal changes that occur with LVAD support and to screen for non-invasive markers of cardiac recovery. METHODS: LVAD patients underwent monthly testing, including echocardiographic, ECG, and serum B-type natriuretic peptide (BNP) measurement. Paired myocardial tissue samples from implant and explant were also analyzed. RESULTS: Thirty-six LVAD patients were prospectively followed for an average of 101 +/- 99 days. Left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD) significantly improved at 30 days compared with pre-LVAD (19% +/- 6.6% vs 33% +/- 8.1%, 7.1 +/- 1.2 cm vs 4.9 +/- 1.0 cm, respectively; both p < 0.001), with no improvement thereafter. At 30 days, QRS duration and QTc interval were significantly decreased from pre-LVAD (both p < 0.05). There was a marked reduction in BNP, myocyte size, and collagen deposition with LVAD support (all p < 0.01). In screening for markers of recovery, the decrease in QTc was inversely related to LVEDD at 60 days. Changes in QRS and myocyte diameter also correlated with the improvement in LVEF at 30 days. No patients had sufficient recovery for device explantation. CONCLUSIONS: We demonstrate echocardiographic, ECG, histologic, and neurohormonal improvement during LVAD support. Cardiac recovery peaked by 60 days, and there was a trend toward progressive improvement in QRS duration with ongoing support. We report the association of ECG changes with echocardiographic and histologic improvements. Future prospective studies may yield important markers of recovery.
Abstract: INTRODUCTION: Catecholamines are known to affect cardiac repolarization, and provocation with either isoproterenol or epinephrine has been proposed as a tool for uncovering latent repolarization abnormalities. This study systematically compares the effects of isoproterenol and epinephrine infusions on QT interval (QT), T waves and U waves in normal subjects. METHODS AND RESULTS: Twenty-four normal subjects (29 +/- 8 years) were evaluated during graded infusions of up to 0.30 microg/kg/minute epinephrine and 5.0 microg/minute isoproterenol. Heart rates at peak doses were 81 +/- 13 bpm at 0.28 +/- 0.04 microg/kg/minute epinephrine and 104 +/- 5 bpm at 2.4 microg/minute isoproterenol. The longest absolute QT increase was 4 +/- 5 msec above baseline during isoproterenol (P < 0.001) and 12 +/- 23 msec during epinephrine (P = 0.07), while the longest corrected QT interval (QTc) increase was 67 +/- 28 msec (P < 0.0001) and 79 +/- 40 msec (P < 0.0001) above baseline during isoproterenol and epinephrine, respectively (P = 0.12 for difference). There was a 2-fold increase in U-wave amplitude during each intervention (P < 0.001). The specificity of paradoxical QT prolongation (>or=30 msec at 0.05 microg/kg/minute or >or=35 msec at 0.10 microg/kg/minute epinephrine) and an increase in QTc >or=600 msec at any dose epinephrine were 100%. However, the specificity of other proposed criteria that utilized QTc measurement (>or=30 msec at 0.10 microg/kg/minute or >or=65 msec at any dose) was poor whether all leads or only lead II were assessed. CONCLUSION: Both epinephrine and isoproterenol are associated with QTc prolongation and amplification of the U wave in normal subjects. The specificity of proposed criteria for epinephrine provocation in diagnosis of the long-QT syndrome is variable; however, paradoxical QT prolongation at low-dose epinephrine or a QTc >or=600 msec is highly specific.
Abstract: INTRODUCTION: Typical and atypical atrial flutters (AFLs) and atrial tachycardias (ATs) have been reported in patients with prior surgical atrial fibrillation ablation. The underlying mechanisms for this group of atrial tachyarrhythmias have not been well characterized and the efficacy of catheter ablation in their treatment is unknown. METHODS AND RESULTS: Twenty patients (6 females) with a surface ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation underwent 26 electrophysiology studies. Patients manifesting sustained, organized, and beat-by-beat reproducible atrial electrical activity underwent complete right and left atrial catheter mapping and catheter ablation. One patient had no inducible tachyarrhythmia, while 5 patients had nonmappable arrhythmias. Nineteen of the 31 potentially mappable atrial tachyarrhythmias were completely characterized in 14 patients. The underlying mechanisms were macro-reentrant left AFL (n = 9), focal left AT (n = 3), typical right AFL (n = 6), and atypical right AFL (n = 1). Of the 19 completely characterized atrial arrhythmias, catheter ablation was performed for 18, and the procedure was successful for 13 of these. After a mean follow-up of 15 +/- 10 months, 15 of 20 patients (75%) were in sinus rhythm including 10 of 13 patients (77%) with AT/flutter ablation. Ten patients, including 6 following ablation, were maintaining sinus rhythm without antiarrhythmic medications. CONCLUSIONS: Patients with an ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation may have multiple tachycardia mechanisms with the right or left atrium as the site of origin. Many of these rhythms may resolve with further maturation of surgical atrial fibrillation ablation (SAFA) lesions or be treatable with antiarrhythmic medication. However, persistent tachyarrhythmias can often be treated successfully with catheter mapping and ablation.
Abstract: Maintenance of a reduced body weight is accompanied by decreased energy expenditure that is due largely to increased skeletal muscle work efficiency. In addition, decreased sympathetic nervous system tone and circulating concentrations of leptin, thyroxine, and triiodothyronine act coordinately to favor weight regain. These "weight-reduced" phenotypes are similar to those of leptin-deficient humans and rodents. We examined metabolic, autonomic, and neuroendocrine phenotypes in 10 inpatient subjects (5 males, 5 females [3 never-obese, 7 obese]) under 3 sets of experimental conditions: (a) maintaining usual weight by ingesting a liquid formula diet; (b) maintaining a 10% reduced weight by ingesting a liquid formula diet; and (c) receiving twice-daily subcutaneous doses of leptin sufficient to restore 8 am circulating leptin concentrations to pre-weight-loss levels and remaining on the same liquid formula diet required to maintain a 10% reduced weight. During leptin administration, energy expenditure, skeletal muscle work efficiency, sympathetic nervous system tone, and circulating concentrations of thyroxine and triiodothyronine returned to pre-weight-loss levels. These responses suggest that the weight-reduced state may be regarded as a condition of relative leptin insufficiency. Prevention of weight regain might be achievable by strategies relevant to reversing this leptin-insufficient state.
Abstract: Methods to correct the QT interval for heart rate are often in disagreement and may be further confounded by changes in autonomic state. This can be problematic when trying to distinguish the changes in QT interval by either drug-induced delayed repolarization or from autonomic-mediated physiological responses. Assessment of the canine dynamic QT-RR interval relationship was visualized by novel programming of the dynamic beat-to-beat confluence of data or "clouds". To represent the nonuniformity of the clouds, a bootstrap sampling method that computes the mathematical center of the uncorrected beat-to-beat QT value (QTbtb) with upper 95% confidence bounds was adopted and compared with corrected QT (QTc) using standard correction factors. Nitroprusside-induced reflex tachycardia reduced QTbtb by 43 ms, whereas an increase of 55 and 16 ms was obtained using the Bazett (QTcB) and Fridericia (QTcF) formulae, respectively. Phenylephrine-induced reflex bradycardia increased QTbtb by 3 ms but decreased QTcB by 20 ms and QTcF by 12 ms. Delayed repolarization with E-4031 (1-[2-(6-methyl-2-pyridyl)ethyl]-4-methylsulfonylaminobenzoyl)-piperidine), an inhibitor of rectifier potassium current, increased QTbtb by 26 ms but QT prolongation calculations using QTcF and QTcB were between 12 and 52% less, respectively, when small decreases in heart rate (5-8 beats per minute) were apparent. Dynamic assessment of beat-to-beat data, using the bootstrap method, allows quantification of QT interval changes under varying conditions of heart rate, autonomic tone, and direct repolarization that may not be distinguishable with use of standard correction factors.
Abstract: The etiology of U waves on the electrocardiogram is uncertain. We previously found that U waves could be amplified by isoproterenol infusion. Whether other autonomic interventions modify U-wave amplitude is unknown. Twenty-five healthy subjects underwent graded infusions of esmolol and phenylephrine. Heart rate, T-wave amplitude, U-wave amplitude, and QT and QU intervals were measured using interactive computerized electrocardiogram software. Heart rate decreased with both interventions ( P < .001), though to a greater degree with phenylephrine. U-wave amplitude increased by 16.3% during phenylephrine ( P < .001) but decreased by 14.5% during esmolol ( P < .001). The change in U-wave amplitude was strongly dose-dependent for both phenylephrine ( P < .001) and esmolol ( P < .001). T-wave amplitude increased with phenylephrine (597-692 microV, P < .001) but decreased with esmolol (632-568 microV, P < .001). QT and QU intervals increased with both interventions ( P < .001). We conclude that sympathetic and parasympathetic activities are important determinants of U-wave timing and amplitude.
Abstract: OBJECTIVES: In a retrospective study, we sought to evaluate the effect of left ventricular assist device (LVAD) therapy on ventricular tachyarrhythmias in patients with advanced congestive heart failure. BACKGROUND: Despite the increasing use of LVAD as a bridge to cardiac transplantation, our knowledge regarding its effect on ventricular arrhythmias is currently limited to small series. Little is known about the prevalence, predictors, and clinical consequences of ventricular arrhythmias in LVAD recipients. METHODS: We reviewed the pre- and post-LVAD course of the last 100 consecutive adult patients to receive a HeartMate LVAD (Thoratec Laboratories Corp., Pleasanton, California) at our institution. All ventricular arrhythmias sustained for at least 30 s or requiring defibrillation were analyzed. All documented pre- and post-LVAD sustained ventricular arrhythmias were classified either as monomorphic ventricular tachycardia (MVT) or polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF). RESULTS: Our population had an average age of 51 years, had predominately ischemic cardiomyopathy (63%), and a mean left ventricular ejection fraction of 20 +/- 10%. New-onset MVT was observed in 18 patients who did not have MVT before LVAD placement. After LVAD, new-onset MVT was 4.5 times more likely than elimination of previously present MVT (p = 0.001), whereas the effect of LVAD on incidence of PVT/VF was not significant. In a multivariate Cox proportional hazards regression analysis, serum electrolyte abnormality was an independent predictor of post-LVAD ventricular arrhythmias. Preoperative MVT did not predict postoperative MVT. CONCLUSIONS: After LVAD placement, there is a significant rise in the incidence of de novo MVT. By contrast, the incidence of PVT/VF was unaffected by LVAD placement.
Abstract: Prolonged repolarization time, an important contributor to the pathogenesis of ventricular arrhythmias, is usually identified by a long QT interval (QT) on the ECG but is frequently confounded by the presence of a U wave. The physiological basis and clinical relevance of the U wave is unresolved. To better understand the relationship between the T and U waves, this study examined their behavior during nonresting autonomic conditions. Twenty-five healthy subjects were evaluated during sympathomimetic infusion with isoproterenol and vagal inhibition with atropine. As heart rate (HR) increased in response to isoproterenol, the QU interval (QU) decreased by an eightfold greater extent than QT. Furthermore, a marked increase in U wave amplitude and decrease in T wave amplitude were observed with T and U wave fusion at higher HRs. During atropine, QU decreased by only a threefold greater extent than QT, T and U wave amplitudes were affected only minimally, and T-U wave fusion was not observed. These results demonstrate that sympathomimetic stimulation causes striking alterations in the timing and amplitude of U waves that differ from effects on the T wave. These effects are not observed during vagal inhibition. Thus, the U wave represents a component of cardiac repolarization that is electrocardiographically and physiologically distinct from the T wave with a unique response to sympathomimetic stimulation.
Abstract: In light of the significant morbidity and mortality from atrial fibrillation (AF), there has been significant interest in the development of percutaneous catheter ablation procedures for the suppression of AF. Given the success of the surgical Maze procedure, initial catheter-based approaches involved creation of linear atrial lesions. Success rates were low and utility was limited by a high complication rate and long procedural times. The recent discovery that AF is often initiated by atrial ectopic beats has resulted in therapies designed to target the ectopic sources, particularly those within the pulmonary veins. Experience and technological advances have improved the efficacy and safety of such procedures. This article will review catheter ablation procedures for the maintenance of sinus rhythm in patients with AF.
Abstract: Although the incidence of typhoid fever in the United States has been low since the 1940s, Salmonella Typhi continues to cause outbreaks. We reviewed reported outbreaks of typhoid fever from 1960 to 1999. There were 60 outbreaks; in 54, exposure occurred within the United States. These 54 outbreaks accounted for 957 total cases (median 10) and 4 deaths. In 36 (67%) outbreaks the route of transmission was identified, and in 16 (62%) of the 26 foodborne outbreaks an asymptomatic carrier was identified by culture or serology. The median incubation period was 2 weeks. Isolates from 10 (40%) of 25 outbreaks were phage type E1. The average frequency of outbreaks decreased from 1.85/year during 1960-79 to 0.85/year during 1980-99 (P=0.0001). S. Typhi outbreaks in the United States are generally small in size but can cause significant morbidity, and are often foodborne, warranting thorough investigation.
Abstract: Clinically important supraventricular arrhythmias are occasionally encountered in patients following cardiac transplantation and the use of catheter ablation as a treatment has been reported. The following three cases are described: (1) atrial flutter, including electroanatomic mapping of the donor and recipient components of the right atrium, (2) a mid-septal accessory pathway, and (3) atrioventricular nodal reentrant tachycardia (AVNRT). A Medline database search was performed and articles addressing catheter ablation following cardiac transplantation were reviewed. The efficacy of RFA for treating various arrhythmia mechanisms was evaluated based on a summary of published case reports.
Abstract: OBJECTIVES: We sought to determine whether the relationship between heart rate (HR) and QT interval (QT) differs as HR increases in response to exercise, atropine and isoproterenol. BACKGROUND: Autonomic nervous system influences on repolarization are poorly understood and may complicate the interpretation of QT measurements. METHODS: Twenty-five normal subjects sequentially underwent graded-intensity bicycle exercise, atropine injection and isoproterenol infusion. Serial 12-lead electrocardiograms were recorded at steady state during each condition and analyzed using interactive computer software. The HR-QT data were modeled linearly and the slopes (quantifying QT adaptation to HR) as well as the QT intervals at 100 beats/min for each intervention were compared by repeated-measures analysis of variance. RESULTS: As HR increased, QT was longer for isoproterenol in comparison to exercise or atropine, which were similar. The HR-QT slope (ms/beats/min) was less steep for isoproterenol (-0.83 +/- 0.53) than for atropine (-1.45 +/- 0.21) or exercise (-1.37 +/- 0.23) (p < 0.0001). In comparison to men, women had more negative HR-QT slopes during all interventions. At 100 beats/min, the QT was 364 ms during isoproterenol, which was significantly longer than that during exercise (330 ms) or atropine (339 ms) (p < 0.0001). Isoproterenol produced a dose-dependent increase in U-wave amplitude that was not observed during exercise or atropine. CONCLUSIONS: In comparison to exercise and atropine, isoproterenol is associated with much less QT shortening for a given increase in HR and, therefore, greater absolute QT intervals. Our findings demonstrate that autonomic conditions directly affect the ventricular myocardium of healthy subjects, causing differences in QT that are independent of HR.
Abstract: R-R interval variability (RR variability) is increasingly being used as an index of autonomic activity. High-frequency (HF) power reflects vagal modulation of the sinus node. Since vagal modulation occurs at the respiratory frequency, some investigators have suggested that HF power cannot be interpreted unless the breathing rate is controlled. We hypothesized that HF power during spontaneous breathing would not differ significantly from HF power during metronome-guided breathing. We measured HF power during spontaneous breathing in 20 healthy subjects and 19 patients with heart disease. Each subject's spontaneous breathing rate was determined, and the calculation of HF power was repeated with a metronome set to his or her average spontaneous breathing rate. There was no significant difference between the logarithm of HF power measured during spontaneous and metronome-guided breathing [4.88 +/- 0.29 vs. 5.29 +/- 0.30 ln(ms(2)), P = 0.32] in the group as a whole and when patients and healthy subjects were examined separately. We did observe a small (9.9%) decrease in HF power with increasing metronome-guided breathing rates (from 9 to 20 breaths/min). These data indicate that HF power during spontaneous and metronome-guided breathing differs at most by very small amounts. This variability is several logarithmic units less than the wide discrepancies observed between healthy subjects and cardiac patients with a heterogeneous group of cardiovascular disorders. In addition, HF power is relatively constant across the range of typical breathing rates. These data indicate that there is no need to control breathing rate to interpret HF power when RR variability (and specifically HF power) is used to identify high-risk cardiac patients.
Abstract: Neurogenic stunned myocardium (NSM), a syndrome of reversible left ventricular dysfunction best described after subarachnoid hemorrhage, has not been associated with peripheral neuropathy. We describe a woman with Guillain-Barre syndrome in whom a syndrome compatible with NSM developed in the setting of a physiologically documented increase in sympathetic cardiovascular tone. This case supports the presumed unifying role of excessive sympathetic nervous system activation in the pathogenesis of NSM.
Abstract: Between 23 June and 15 July 1994, 21 cases (19 primary and 2 secondary) of Escherichia coli O157:H7 infection were identified in the Bethel, Connecticut, area. Three pulsed-field gel electrophoresis (PFGE) patterns from 15 isolates (I, n = 13; II, n = 2; and III, n = 1) were observed. A case-control study that excluded secondary cases and patients with PFGE II and III patterns (n = 16) demonstrated that consumption of food from one supermarket was associated with illness (15/16 cases vs. 31/47 geographically matched controls, odds ratio [OR] undefined, lower 95% confidence interval OR = 1.45, P = .018). No one food was associated with illness. Inspection of the supermarket revealed deficiencies in hygiene and meat handling practices. The 2 cases with PFGE II ate raw beef and raw lamb from a second supermarket. These outbreaks demonstrate the value of PFGE in supporting epidemiologic investigations and the potential for outbreaks arising from retail outlets.
