Pramesh Kovoor

Evaluation of the role of IKAChin atrial fibrillation using a mouse knockout model

OBJECTIVES We sought to study the role of I(KACh) in atrial fibrillation (AF) and the potential electrophysiologic effects of a specific I(KACh) antagonist. BACKGROUND I(KACh) mediates much of the cardiac responses to vagal stimulation. Vagal stimulation predisposes to AF, but the specific role of I(KACh) in the generation of AF and the electrophysiologic effects of specific I(KACh) blockade have not been studied. METHODS Adult wild-type (WT) and I(KACh)-deficient knockout (KO) mice were studied in the absence and presence of the muscarinic receptor agonist carbachol. The electrophysiologic features of KO mice were compared with those of WT mice to assess the potential effects of a specific I(KACh) antagonist. RESULTS Atrial fibrillation lasting for a mean of 5.7+/-11 min was initiated in 10 of 14 WT mice in the presence of carbachol, but not in the absence of carbachol. Atrial arrhythmia could not be induced in KO mice. Ventricular tachyarrhythmia could not be induced in either type of mouse. Sinus node recovery times after carbachol and sinus cycle lengths were shorter and ventricular effective refractory periods were greater in KO mice than in WT mice. There was no significant difference between KO and WT mice in AV node function. CONCLUSIONS Activation of I(KACh) predisposed to AF and lack of I(KACh) prevented AF. It is likely that I(KACh) plays a crucial role in the generation of AF in mice. Specific I(KACh) blockers might be useful for the treatment of AF without significant adverse effects on the atrioventricular node or the ventricles.

Risk to Patients From Radiation Associated With Radiofrequency Ablation for Supraventricular Tachycardia

BACKGROUND Radiofrequency ablation may be associated with prolonged fluoroscopy times. Previous studies have calculated radiation risks by measuring the radiation dose at a limited number (6) of body sites. This is an inherently inaccurate measure. Our study aimed to quantify more precisely patient-related radiation risks associated with radiofrequency ablation for supraventricular tachycardia. METHODS AND RESULTS Nine female patients having radiofrequency ablation for supraventricular tachycardia were studied. The radiation dose was determined at 41 body sites in each patient with the use of thermoluminescent dosimeters and was correlated with that measured simultaneously with a Diamentor dose-area product meter. The estimated mean organ doses (mGy) per 60 minutes of fluoroscopy were: lungs 30.8; bone marrow 4.3; left breast 5.1; right breast 3. 5; and thyroid 2.4. From the average organ doses, the estimated mean total lifetime excess risk of a fatal malignancy was 294 per million cases (0.03%) per 60 minutes of fluoroscopy. The risk calculation from the Diamentor dose-area product and thermoluminescent dosimeters were similar, suggesting that radiation dose was measured accurately. The estimated risk of radiation-induced malignancy increased with increasing body mass index (P=0.03). CONCLUSIONS Prolonged fluoroscopy during radiofrequency ablation may potentially cause a small increase in the lifetime risk of fatal malignancy, with lung malignancy being most likely. This risk is small only with the use of techniques and x-ray equipment optimized to keep radiation as low as possible. The risk is increased in obese patients.

Organization of Myocardial Activation During Ventricular Fibrillation After Myocardial Infarction Evidence for Sustained High-Frequency Sources

Background—Studies of ventricular fibrillation (VF) in small mammals have revealed localized sustained stationary reentry. However, studies in large mammals with surface mapping techniques have demonstrated only relatively short-lived rotors. The purpose of this study was to identify whether sustained high-frequency activation with low beat-to-beat variability was present at intramural sites in a postinfarct ovine model of VF. Methods and Results—VF was induced in 12 sheep 77±40 days after anterior myocardial infarction. Electrical activation was recorded with 20 multielectrode transmural plunge needles. Unipolar electrogram frequency content and local cycle duration variability were studied in 30-second recordings beginning 5 seconds after the onset of VF. Higher mean beat frequency was associated with lower SD of the cycle duration intervals (r=−0.91, P<0.001). The mean beat frequency and the SD of cycle duration intervals of the highest-frequency electrode were 8.8±2.0 Hz and 17±11 ms. In 3 cases, a region with regular activation throughout the recording was identified (SD of the cycle duration interval, 6.0±0.7 ms). Two of these sites and 67% of all sites with low local cycle duration variability were intramural. They occurred within regions with a high dominant frequency as determined by fast Fourier transform of the unipolar electrogram. Conclusions—Regions with the highest frequency of activation during VF were always associated with a low local cycle duration variability and usually intramural in this chronic infarct model. In a minority of cases, a region of stable, rapid, and very regular activation could be identified. These findings support the hypothesis that relatively stable periodic sources form a component of the mechanism of VF in this model.

Outcomes of Early Risk Stratification and Targeted Implantable Cardioverter-Defibrillator Implantation After ST-Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

BACKGROUND Methods to identify high-risk patients and timing of implantable cardioverter-defibrillator (ICD) therapy after ST-elevation myocardial infarction need further optimization. METHODS AND RESULTS We evaluated outcomes of early ICD implantation in patients with inducible ventricular tachycardia. Consecutive patients treated with primary percutaneous coronary intervention for acute ST-elevation myocardial infarction underwent early left ventricular ejection fraction (LVEF) assessment. Patients with LVEF >40% were discharged (group 1); patients with LVEF < or =40% underwent risk stratification with electrophysiological study. If no ventricular tachycardia was induced, patients were discharged without an ICD (group 2). If sustained monomorphic ventricular tachycardia (> or =200-ms cycle length) was induced, an ICD was implanted before discharge (group 3). Follow-up was obtained up to 30 months in all patients and up to 48 months in a subgroup of patients with LVEF < or =30% without an ICD. The primary end point was total mortality. Group 1 (n=574) had a mean LVEF of 54+/-8%; group 2 (n=83), 32+/-6%; and group 3 (n=32), 29+/-7%. At a median follow-up of 12 months, there was no significant difference in survival between the 3 groups (P=0.879), with mortality rates of 3%, 3%, and 6% for groups 1 through 3, respectively. In the subgroup of group 2 patients with LVEF < or =30% and no ICD (n=25), there was 9% mortality at a median follow-up of 25 months. In group 3, 19% had spontaneous ICD activation resulting from ventricular tachycardia. CONCLUSIONS Early ICD implantation limited to patients with inducible ventricular tachycardia enables a low overall mortality in patients with impaired LVEF after primary percutaneous coronary intervention for ST-elevation myocardial infarction.

Noncontact mapping of the left ventricle: insights from validation with transmural contact mapping.

It is not clear whether the noncontact electrograms obtained using the EnSite system in the left ventricle resemble most closely endocardial, intramural, or epicardial contact electrograms or a summation of transmural electrograms. This study compared unipolar virtual electrograms from the EnSite system with unipolar contact electrograms from transmural plunge needle electrodes using a 256‐channel mapping system. The study also evaluated the effects of differing activation sites (endocardial, intramural, or epicardial). A grid of 50–60 plunge needles was positioned in the left ventricles of eight male sheep. Each needle had four electrodes to record from the endocardium, two intramural sites, and the epicardium. Correlations between contact and noncontact electrograms were calculated on 32,242 electrograms. Noncontact electrograms correlated equally well in morphology and accuracy of timing with endocardial (0.88 ± 0.15), intramural (0.87 ± 0.15), epicardial (0.88 ± 0.15), and transmural summation contact electrograms (0.89 ± 0.14) during sinus rhythm, endocardial pacing, and epicardial pacing. There was a nonlinear relationship between noncontact electrogram accuracy as measured by correlation with the contact electrogram and distance from the multielectrode array (MEA): beyond 40 mm accuracy decreased rapidly. The accuracy of noncontact electrograms also decreased with increasing distance from the equator of the MEA. Virtual electrograms from noncontact mapping of normal left ventricles probably represent a summation of transmural activation. Noncontact mapping has similar accuracy with either endocardial or epicardial sites of origin of electrical activity provided the MEA is within 40 mm of the recording site. (PACE 2004; 27:570–578)

Effect of prehospital triage on revascularization times, left ventricular function, and survival in patients with ST-elevation myocardial infarction.

Shorter reperfusion times lead to better outcomes in patients with ST-elevation myocardial infarction (STEMI). We assessed the efficacy of prehospital triage with bypass of community hospitals and early activation of the cardiac catheterization team on revascularization times, left ventricular (LV) ejection fraction, and survival. Patients with STEMI (624) were divided into 3 groups determined by site of triage: ambulance field triage (163), interventional center emergency department (202), and 3 community hospital emergency departments (259). Compared with community hospital and interventional center triages, ambulance field triage resulted in a significant median decrease in door-to-balloon times of 68 and 27 minutes, respectively (p <0.001). LV ejection fraction was highest in the field triage group (52 +/- 13%) compared with the interventional center (49 +/- 12%) and community hospital (48 +/- 12%, p = 0.017) groups. Thirty-day mortality was lowest in the ambulance field group (3%) compared with the interventional facility (11%) and community hospital (4%, p = 0.007) groups. There was a significant difference in long-term survival with up to 30-month follow-up among the 3 triage groups (p = 0.041). With time-dependent Cox regression modeling the difference in survival was significant only during the first week after STEMI (p = 0.020). Every extra minute of symptom onset to reperfusion time was associated with a relative risk of long-term mortality of 1.003 (95% confidence interval 1.000 to 1.006, p = 0.027). In conclusion, field triage of patient with STEMI decreased revascularization times, which preserved LV function, and improved early survival.

Electrophysiology-guided defibrillator implantation early after ST-elevation myocardial infarction.

BACKGROUND Sudden death risk is highest early after myocardial infarction (MI). Inducible ventricular tachycardia (VT) confers increased risk of spontaneous ventricular arrhythmias. OBJECTIVE The purpose of this study was to evaluate outcomes of electrophysiology (EP)-guided defibrillator implantation early after ST-elevation MI in patients with ejection fraction ≤40%. METHODS EP study was performed 9 days after MI (n = 360). Predischarge defibrillator was recommended if VT with cycle length ≥200 ms was induced with ≤4 extrastimuli (EP-positive [EP(pos)], n = 142). EP-negative (EP(neg)) patients were discharged without a defibrillator (n = 218). Primary endpoint was either sudden death or spontaneous ventricular arrhythmia. RESULTS Defibrillator was implanted in 71% of EP(pos) patients (median 21 days post-MI) and withheld in 94% of EP(neg) patients. At 2 years, primary endpoint was 4.3% in the EP(neg) group and 22% in the EP(pos) group (adjusted hazard ratio 0.46, P = .035, EP(neg) vs EP(pos)). Lack of a defibrillator in EP(pos) patients conferred a fourfold increased risk of sudden death (P = .014). EP(neg) patients without a defibrillator were at significantly lower risk for the primary endpoint than were EP(pos) patients without a defibrillator (adjusted HR 0.34, P = .011). Short inducible VT cycle length (200-230 ms) and use of the fourth extrastimulus identified patients at significant arrhythmic risk. CONCLUSION EP study performed early after MI identified patients at significant long-term arrhythmic risk at a critical time after MI in whom defibrillator implantation was protective. A large majority of patients (EP(neg); two thirds) were at significantly lower risk of arrhythmic events without a defibrillator in the long term.

Cooled Needle Catheter Ablation Creates Deeper and Wider Lesions Than Irrigated Tip Catheter Ablation

Objectives: To design and test a catheter that could create deeper ablation lesions.

Long-Term Arrhythmia-Free Survival in Patients With Severe Left Ventricular Dysfunction and No Inducible Ventricular Tachycardia After Myocardial Infarction

Background— A negative electrophysiology study (EPS) may delineate a subgroup of patients with severely impaired left ventricular ejection fraction (LVEF) whose care can be safely managed long-term without an implantable cardioverter-defibrillator. Methods and Results— Consecutive patients treated with primary percutaneous coronary intervention for ST-segment–elevation myocardial infarction underwent early (median 4 days) LVEF assessment. Patients with LVEF ⩽40% underwent EPS. A prophylactic implantable cardioverter-defibrillator was implanted for a positive (inducible monomorphic ventricular tachycardia) but not a negative (no inducible ventricular tachycardia or inducible ventricular fibrillation/flutter) EPS result. Patients who would have become eligible for a late primary prevention implantable cardioverter-defibrillator with LVEF ⩽30% or ⩽35% with New York Heart Association class II/III heart failure were included and analyzed according to EPS result. Patients with LVEF >40%, ineligible for EPS, were followed up as control subjects (n=1286). The primary end point was survival free of death or arrhythmia (resuscitated cardiac arrest or sustained ventricular tachycardia/ventricular fibrillation). EPS performed in 128 patients with LVEF ⩽30% or with LVEF ⩽35% and heart failure was negative in 63% (n=80) and positive in 37% (n=48). Implantable-cardioverter defibrillators were implanted in <0.1%, 4%, and 90% of control, EPS-negative, and EPS-positive patients, respectively. The distribution of time to death or arrhythmia was comparable in control patients and EPS-negative patients with LVEF ⩽30% or with LVEF ⩽35% and heart failure (P=0.738), who both differed significantly from EPS-positive patients (P<0.001). At 3 years, 91.8±3.2%, 93.4±1.0%, and 62.7±7.5% of control, EPS-negative, and EPS-positive patients were free of death or arrhythmia, respectively. Conclusions— Revascularized patients with ST-segment–elevation myocardial infarction with severely impaired left ventricular function but no inducible ventricular tachycardia have a favorable long-term prognosis without the protection of an implantable cardioverter-defibrillator.

Clinical and Electrocardiographic Correlates of Normal Coronary Angiography in Patients Referred for Primary Percutaneous Coronary Intervention

This study sought to determine the prevalence as well as clinical and electrocardiographic correlates of patients referred for primary percutaneous coronary intervention (PCI) who had angiographically normal coronary arteries. Data for 690 consecutive patients with ST-elevation myocardial infarction (STEMI) referred for primary PCI within a metropolitan area health service were reviewed. Characteristics of patients with angiographically normal coronary arteries (n = 87; 13%) were compared with patients with angiographically shown culprit lesions (control group; n = 594). Nine patients with significant coronary disease, but no identifiable culprit lesion, were excluded. Electrocardiograms (ECGs) from both groups were reviewed by 2 cardiologists blinded to angiographic findings. Patients in the normal coronaries group were younger and had fewer risk factors. On expert review of ECGs, 55% of patients in the normal coronaries group had ST-elevation criteria for STEMI (vs 93% in the control group; p <0.001), but the ECG was considered consistent with a diagnosis of STEMI by both observers in only 33% (vs 92% in the control group; p <0.001). Left branch bundle block independently correlated with normal coronary arteries on multivariate analysis (odds ratio for STEMI 0.016, 95% confidence interval 0.004 to 0.064, p <0.001). The discharge diagnosis in the normal coronaries group was predominantly pericarditis (n = 72; 83%). In conclusion, the prevalence of angiographically normal coronary arteries in patients referred for primary PCI was 13%. Electrocardiographic correlation suggested that this can be reduced by adherence to conventional electrocardiographic criteria for STEMI diagnosis and review of ECGs by experienced clinicians.