Evidence of specialized conduction cells in human pulmonary veins of patients with atrial fibrillation

Specialized Conducting Cells in Human PV. Introduction: Depolarizations similar to those from the sinus node have been documented from the pulmonary veins after isolation procedures. We assessed the hypothesis that sinus node-like tissue is present in the pulmonary veins of humans. Methods and Results: Pulmonary vein tissue was obtained from five autopsies (four individuals with a history of atrial fibrillation and one without a history of atrial arrhythmias) and five transplant heart donors. Autopsy veins were fixed in formaldehyde and processed for light microscopy to identify areas having possible conductive-like tissue. Areas requiring additional study were extracted from paraffin blocks and reprocessed for electron microscopy. Donor specimens were fixed in formaldehyde for histologic sections and glutaraldehyde for electron microscopy. Myocardial cells with pale cytoplasm were identified by light microscopy in 4 of the 5 autopsy subjects. Electron microscopy confirmed the presence of P cells, transitional cells, and Purkinje cells in the pulmonary veins of these cases. Conclusion: Our report is the first to show the presence of P cells, transitional cells, and Purkinje cells in human pulmonary veins. Whether these cells are relevant in the genesis of atrial fibrillation requires further study.     

New approach to biphasic waveforms for internal defibrillation: fully discharging capacitors

INTRODUCTION: The use of two independent, fully discharging capacitors for each phase of a biphasic defibrillation waveform may lead to the design of a simpler, smaller, internal defibrillator. The goal of this study was to determine the optimal combination of capacitor sizes for such a waveform. METHODS AND RESULTS: Eight full-discharge (95/95% tilt), biphasic waveforms produced by several combinations of phase-1 capacitors (30, 60, and 90 microF) and phase-2 capacitors (1/3, 2/3, and 1.0 times the phase-1 capacitor) were tested and compared to a single-capacitor waveform (120 microF, 65/65% tilt) in a pig ventricular fibrillation model (n = 12, 23+/-2 kg). In the full-discharge waveforms, phase-2 peak voltage was equal to phase-1 peak voltage. Shocks were delivered between a right ventricular lead and a left pectoral can electrode. E50s and V50s were determined using a ten-step Bayesian process. Full-discharge waveforms with phase-2 capacitors of < or =40 microF had the same E50 (6.7+/-1.7 J to 7.3+/-3.9 J) as the single-capacitor truncated waveform (7.3+/-3.7 J), whereas waveforms with phase-2 capacitors of > or =60 microF had an extremely high E50 (14.5+/-10.8 J or greater, P < 0.05). Moreover, of the former set of energy-efficient waveforms, those with phase-1 capacitors of > or =60 microF additionally exhibited V50s that were equivalent to the V50 of the single-capacitor waveform (344+/-65 V to 407+/-50 V vs 339+/-83 V). CONCLUSION: Defibrillation efficacy can be maintained in a full-discharge, two-capacitor waveform with the proper choice of capacitors.     

Vagal responses induced by endocardial left atrial autonomic ganglion stimulation before and after pulmonary vein antrum isolation for atrial fibrillation

BACKGROUND: Elimination of vagal inputs into the left atrium (LA) may be necessary for successful catheter ablation of atrial fibrillation (AF). These vagal inputs are clustered in autonomic ganglia (AG) that are close to the pulmonary vein antrum (PVA) borders, but whether standard intracardiac echocardiography (ICE)-guided PVA isolation (PVAI) affects these inputs is unknown. OBJECTIVE: The purpose of this study was to assess whether standard ICE-guided PVAI affects vagal responses induced by endocardial AG stimulation in the LA. METHODS: Twenty consecutive patients undergoing first-time PVAI (group 1) and 20 consecutive patients undergoing repeat PVAI for AF recurrence (group 2) were enrolled in the study. Before ablation, electrical stimulation (20 Hz, pulse duration 10 ms, voltage range 12-20 V) was performed through an 8-mm-tip ablation catheter. Based on prior data, regions around all four PVA borders were carefully mapped and stimulated to localize AG inputs. A positive stimulated vagal response was defined as atrioventricular (AV) block, asystole, or increase in mean RR interval by >50%. Locations of positive vagal responses were recorded wth biplane fluoroscopy and CARTO. All patients then underwent standard ICE-guided PVAI by an operator blinded to the locations of vagal responses. Stimulation of the AG locations was then repeated postablation. RESULTS: Patients (age 54 +/- 11 years, 30% female, ejection fraction 54% +/- 7%) had a history of paroxysmal (75%) and persistent (25%) AF. In group 1, vagal responses were induced in all 20 patients around a mean of 3.8 +/- 0.4 PVAs per patient. The most common response was asystole (53%), mean RR slowing >50% (28%), and AV block (20%). Postablation, vagal responses could no longer be induced in all 20 patients. A diminished response was induced (RR slowing <50%) in 2/20 patients around one PVA each. In group 2, vagal responses were not induced in any of the 20 repeat patients. Stimulation capture postablation was confirmed because transient, nonsustained (<30 seconds) AF or atrial flutter was induced in all 40 patients with stimulation, whether vagal responses were induced or not. CONCLUSIONS: Standard ICE-guided PVAI eliminates vagal responses induced by AG stimulation. Responses are not seen in patients presenting for repeat PVAI, despite clinical recurrence of AF.     

Nonexcitatory stimulus delivery improves left ventricular function in hearts with left bundle branch block

INTRODUCTION: Preliminary data in a heart failure animal model and isolated muscle preparation have suggested that nonexcitatory stimulation (NES) improves left ventricular (LV) function. METHODS AND RESULTS: We compared biventricular (BV) pacing with NES in an animal model with left bundle branch block (LBBB). The left bundle branch (LBB) was ablated in eight normal heart pigs and led to >50% increase in QRS duration (mean 100 +/- 15 msec). End-diastolic LV pressure, end-systolic LV pressure, LV pressure (LV dP/dtmax), aortic pulse pressure, and LV ejection fraction were measured before pre-LBB ablation and compared with post-LBB ablation (AAI pacing), BV pacing, NES delivery, and BV+NES. Moreover, to evaluate LV diastolic function, we measured the early (E wave) and late flows (A wave) through the mitral valve using spectral Doppler. Compared with post-LBB ablation, NES led to a significant increase in LV dP/dtmax (1,047 +/- 224 mmHg/sec vs 897 +/- 116 mmHg/sec; P < 0.05), LV ejection fraction (64% +/- 18% vs 49% +/- 17%; P < 0.05), and aortic pulse pressure (18 +/- 3.6 mmHg vs 16 +/- 2.8 mmHg; P < 0.05). Moreover, improvement in LV hemodynamic parameters was significantly higher during NES delivery when compared with BV pacing. No significant changes in E wave, A wave, and E/A were recorded during NES, NES+BV, and BV pacing. CONCLUSION: Our preliminary data demonstrate that NES is superior to BV pacing in improving LV function in an animal model with LBBB. Moreover, we demonstrated that NES does not affect transmitral valve flow and subsequently LV diastolic function.     

Electrical storm in patients with an implantable defibrillator: incidence, features, and preventive therapy: insights from a randomized trial.

AIMS: The purpose of this study was to assess the incidence, features, and clinical sequelae of 'electrical storm' (ES). METHODS AND RESULTS: This study is a prospectively designed secondary analysis of SHIELD; a randomized trial of azimilide for suppression of ventricular tachycardia/fibrillation (VT/VF) leading to implanted cardioverter defibrillator (ICD) therapies. Systematic and rigorous follow-up and blinded adjudication of ICD therapy allowed identification of all ESs (>/=3 separate VT/VF episodes leading to ICD therapies within 24 h). Of 633 ICD recipients, 148 (23%) experienced at least one ES over 1-year follow-up. No clinical predictors of ES were identified. Frequent VT episodes accounted for 91% of all ESs, with the remaining being VF alone or both VT plus VF. ES led to a 3.1-fold increase in arrhythmia-related hospitalization (95% CI 2.3-4.3; P<0.0001) compared with patients with isolated VT/VF, and to a 10.2-fold increase (95% CI 6.4-16.3; P<0.0001) compared with patients without VT/VF. Compared with placebo, azimilide (75 and 125 mg/day) reduced the risk of recurrent ES by 37% (HR=0.63, 95% CI 0.35-1.11, P=0.11) and 55% (HR=0.45, 95% CI 0.23-0.87, P=0.018), respectively. However, the reduction in time-to-first ES did not reach statistical significance by both doses (75 and 125 mg) of azimilide (HR=0.82, 95% CI 0.56-1.19, P=0.29 and HR=0.69, 95% CI 0.46-1.04, P=0.07), respectively. CONCLUSION: ES is common and unpredictable in ICD recipients and it is a strong predictor of hospitalization.     

Treatment of atrioventricular node reentrant tachycardia with encainide: reversal of drug effect with isoproterenol

To determine the efficacy of encainide in the treatment of atrioventricular (AV) node reentrant tachycardia, Holter electrocardiographic (ECG) monitoring, exercise treadmill testing and programmed electrical stimulation were performed in 16 patients while they were taking no medication and after steady state levels were reached during treatment with encainide (75 to 200 mg/day; mean 117 +/- 47). In addition, to study the possible reversal of drug effects by sympathetic stimulation, AV node conduction and tachycardia induction were reassessed during isoproterenol infusion (1 to 3 micrograms/min), a dose calculated to increase the rest heart rate by 25 +/- 10%. Sustained AV node reentrant tachycardia could be initiated in all 16 patients in the control state, in 2 patients after encainide and in 10 patients during isoproterenol infusion. The shortest mean atrial paced cycle length sustaining 1:1 AV conduction was 358 +/- 57 ms during the control study, which increased to 409 +/- 59 ms with encainide (p less than 0.01 versus control) and decreased to 313 +/- 31 ms during isoproterenol infusion (p less than 0.01 versus control and encainide). The shortest mean ventricular paced cycle length with 1:1 ventriculoatrial conduction was 337 +/- 56 ms in the control study, 551 + 124 ms with encainide infusion (p less than 0.01 versus control) and 354 +/- 72 ms during isoproterenol infusion in the encainide-loaded state (p less than 0.01 versus both control and encainide). During a mean follow-up period of 19 +/- 10 months, significant clinical recurrences occurred in 4 of the 10 patients in whom tachycardia could still be initiated with encainide (with or without isoproterenol).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction

Aging increases and caloric restriction (CR) decreases morbidity and mortality associated with the cardiovascular system. Using Affymetrix microarrays, we identified changes in heart gene expression induced by aging and CR in male mice. Eight weeks of CR (CR8) reproduced 19% of the long-term CR (LTCR)-related expression changes. Because CR8 begins to extend the life span of these mice, these genes may be keys to its cardioprotective effects. CR8 and LTCR changed gene expression in a manner consistent with reduced remodeling and fibrosis, and enhanced contractility and energy production via lipid beta-oxidation. Molecular and histochemical studies indicated that CR reduced natriuretic peptide precursor type B and collagen expression, and reduced perivascular collagen deposition. We found smaller cardiomyocytes in the left ventricle of old-LTCR mice, suggesting reduced age-related cell death. Eight weeks of control feeding returned 97% of the LTCR-responsive genes to control expression levels. Thus, key CR-induced effects are rapidly responsive to diet, suggesting reduced caloric intake has rapid, positive effects on the heart.     

Detecting cardiac involvement in sarcoidosis: a call for prospective studies of newer imaging techniques.

Diagnosis of cardiac involvement in sarcoidosis is challenging and usually relies on a combination of clinical findings and imaging abnormalities. The case of a 53-yr-old female is described who presented with ventricular tachycardia and suspected angiosarcoma involving the right atrium and superior vena cava. A combination of magnetic resonance imaging and (18)F-2-fluoro-2-deoxyglucose-positron emission tomography were essential to the diagnosis of cardiac sarcoidosis. Reversibility of the disease was predicted more clearly by (18)F-2-fluoro-2-deoxyglucose-positron emission tomography than by magnetic resonance imaging, and clinical activity was predicted by persistent hypermetabolism on serial (18)F-2-fluoro-2-deoxyglucose-positron emission tomography.     

Acceptance of tamoxifen chemoprevention by physicians and women at risk

BACKGROUND: In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial, tamoxifen was shown to reduce breast carcinoma risk by 49% in high-risk women. The purpose of the current study was to identify factors associated with being offered, and accepting, tamoxifen chemoprevention. METHODS: The records of 219 women who sought risk evaluation after the publication of the NSABP P-1 trial between September 1998 and October 2002 were reviewed. Risk was calculated using the model of either Gail et al. or Claus et al. The impact of individual risk factors on the offering and acceptance of tamoxifen was compared using the Fisher exact test and logistic regression analysis. RESULTS: Tamoxifen was offered to 137 women (63%) in the current study. The magnitude of Gail risk, age, menopausal status, hysterectomy, and history of lobular carcinoma in situ (LCIS) or atypical hyperplasia (AH) were all found to be significant predictors of a patient being offered tamoxifen. On multivariate analysis, only a history of AH or LCIS and hysterectomy were found to be significant, with odds ratios of 20.3 and 3.4, respectively. Fifty-seven of the women who were offered tamoxifen (42%) took the drug. Only a history of LCIS or AH and older age were found to be predictive of tamoxifen acceptance. CONCLUSIONS: In the current study, risk due to AH or LCIS was found to be the main predictor of being offered and accepting tamoxifen chemoprevention.