Michael E. Cain

American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Scientific Statement on Noninvasive Risk Stratification Techniques for Identifying Patients at Risk for Sudden Cardiac Death A Scientific Statement From the American Heart Association Council on Clinical Cardiology Committee on Electrocardiography and Arrhythmias and Council on Epidemiology and Prevention

The International Classification of Diseases, Tenth Revision, defines sudden cardiac death (SCD) as death due to any cardiac disease that occurs out of hospital, in an emergency department, or in an individual reported dead on arrival at a hospital. In addition, death must have occurred within 1

Standards for analysis of ventricular late potentials using high-resolution or signal-averaged electrocardiography. A statement by a Task Force Committee of the European Society of Cardiology, the American Heart Association, and the American College of Cardiology.

Sufficient data are available to recommend the use of the high-resolution or signal-averaged electrocardiogram in patients recovering from myocardial infarction without bundle branch block to help determine their risk for developing sustained ventricular tachyarrhythmias. However, no data are available about the extent to which pharmacological or nonpharmacological interventions in patients with late potentials have an impact on the incidence of sudden cardiac death. Therefore, controlled, prospective studies are required before this issue can be resolved. As refinements in techniques evolve, it is anticipated that the clinical value of high-resolution or signal-averaged electrocardiography will continue to increase.

Demonstration of a widely distributed atrial pacemaker complex in the human heart.

Atrial depolarization was analyzed in 14 patients with the Wolff-Parkinson-White syndrome undergoing surgery to ablate accessory atrioventricular pathways associated with tachyarrhythmias. Bipolar potentials were recorded simultaneously from 156 atrial epicardial electrodes arranged in three templates to fit the anterior and posterior aspects of both atria. Spontaneous or sinus rhythms were recorded, as were atrial escape rhythms after overdrive pacing at rates of 150 and 200 beats/min. Atrial activation maps revealed different patterns of impulse initiation varying from typical unifocal sinus node impulse origin, unifocal extranodal impulse origin, and multicentric impulse origin from two to four widely distributed atrial pacemaker sites. In subjects demonstrating only unifocal impulse origin during control or sinus rhythm, other widely divergent pacemaker sites were recorded in other maps during subsequent rhythms. In addition to sites located at the upper superior vena cava-right atrium junction, pacemakers also dominated at sites anterior and inferior to the sinus node region during both control and escape depolarizations. Most of the subjects were found to have two or more pacemaker sites when maps of all control and postpacing conditions were analyzed. The right atrial pacemaker region encompassed a zone of 7.5 X 1.5 cm centered about the long axis of the sulcus terminalis posteriorly and the precaval band anteriorly. An unexpected finding was the participation of left atrial escape pacemakers. The functional behavior of both the control and escape pacemakers, as assessed by sinus node recovery time, was normal, indicating physiologic operation of the extranodal sites as part of an overall system of distributed pacemakers involved in the control of rate. Although functional assessment was limited in these initial patient studies, correspondence with similar observations in extensive previous canine studies supports the concept of a widely distributed atrial pacemaker complex in man.

Fast-Fourier transform analysis of signal-averaged electrocardiograms for identification of patients prone to sustained ventricular tachycardia.

Electrocardiograms obtained from patients during arrhythmia-free intervals do not identify those prone to sustained ventricular tachycardia (VT) despite the occult delayed activation that is presumably present. To determine whether frequency-domain analysis facilitates detection of this hallmark of predisposition to VT, fast-Fourier transform analysis (FFTA) procedures were developed and tested with a computer-generated mathematical model. The FFTA approach developed allows inherent limitations of high-gain amplification and a priori filtering used commonly for time-domain analysis to be avoided. After demonstrating that FFTA detected low-amplitude oscillatory waveforms in signal-averaged recordings in the frequency domain, the procedure was applied to signal-averaged X, Y, and Z lead recordings from the following three groups of patients: group I, patients with prior myocardial infarction and episodic sustained VT (n = 16); group II, patients with prior myocardial infarction without overt sustained VT (n = 35); and group III, normal control subjects (n = 10). Results of FFTA demonstrated significant (p less than .0001) differences in the decibel drop at 40 Hz and the area under the curve from the fundamental frequency to the frequency at which the spectral amplitude was decreased by 60 dB for both the terminal 40 msec of the QRS and ST segment in patients in group I compared with those in groups II and III, in whom results were similar. Results were independent of QRS duration (r = .2), left ventricular ejection fraction (r = .19), and complexity of spontaneous ventricular ectopy. Thus, patients known to manifest sustained VT also exhibited relatively greater high-frequency content in arrhythmia-free intervals in the terminal QRS and ST segment than those without VT (88%, 15%, and 0% in groups I through III, respectively). FFTA offers promise for the noninvasive detection of patients at risk for the development of sustained VT.

Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart.

BackgroundTo determine the mechanisms of ventricular tachycardia (VT) in humans, three-dimensional intraoperative mapping of up to 156 intramural sites was performed in 13 patients with healed myocardial infarction and refractory VT. Methods and ResultsMapping was of sufficient density to define the mechanism of 10 VTs in eight patients. In five of 10 cases, sustained VT was initiated in the subendocardium or epicardium by intramural reentry with marked conduction delay as well as functional and anatomic block most prominent in the subendocardium and midmyocardium. The initiating beats of reentrant VT induced by programmed electrical stimulation arose in the endocardium or midmyocardium by progressive slowing of conduction leading to unidirectional block. Multiple simultaneous reentrant circuits can be present. In contrast, five of the 10 sustained VTs were initiated by a focal mechanism as defined by the absence of electrical activity between the termination of one beat and the initiation of the next despite the presence of multiple intervening intramural electrode recording sites. Comparisons of the mapping data with results of histopathological analysis of tissue demonstrated that the location of infarction as well as that of adjacent fibrotic muscle determined sites of both fixed and functional conduction block during macroreentrant VT and that slowing of conduction occurred in a direction transverse rather than longitudinal to fiber orientation. ConclusionsBoth intramural reentry and a focal mechanism underlie sustained VT in patients with healed myocardial infarction.

Ventricular activation during ventricular endocardial pacing. II. Role of pace-mapping to localize origin of ventricular tachycardia

Intraoperative pace-mapping has been proposed as a method of identifying the origin of ventricular tachycardia; however, both epicardial activation and electrocardiographic configuration have limitations in localizing the origin of ventricular tachycardia. Because most ventricular tachycardias associated with ischemic heart disease appear to arise near the endocardium, this study evaluated the ability of bipolar catheter endocardial pacing at or near the endocardial site of origin of spontaneous ventricular tachycardia to mimic the QRS configuration of the spontaneous tachycardia. Twelve patients were studied who had ventricular tachycardia whose origin was determined with catheter endocardial mapping. Three patients had ventricular tachycardia with two distinct configurations. The electrocardiogram of ventricular tachycardia was compared with the electrocardiogram produced by pacing at the site of origin (10 patients) and at multiple (two to nine) additional sites in 8 patients. It was observed that (1) pacing at the known site of origin of ventricular tachycardia produced an electrocardiogram and activation sequence similar to those produced by the ventricular tachycardia; (2) pacing at sites in close proximity to the site of origin of ventricular tachycardia produced either a similar or a grossly different electrocardiographic pattern from that during ventricular tachycardia. It is concluded that catheter endocardial pace-mapping (1) is a corroborative method of identifying the origin of ventricular tachycardia; (2) may be useful in patients with noninducible ventricular tachycardia or rapid ventricular tachycardia who cannot undergo catheter or intraoperative mapping; and (3) is neither easier, more accurate nor quicker than direct localization by mapping during ventricular tachycardia.

Cryosurgical treatment of atrioventricular node reentrant tachycardia.

Paroxysmal supraventricular tachycardia most commonly arises from reentry within the atrioventricular (AV) node. Although ablation of the His bundle has gained popularity for treating patients with AV node reentrant tachycardia refractory to medical therapy, undesirable sequelae include complete heart block and the necessity for a permanent pacemaker. To obviate this limitation, we have developed a discrete cryosurgical procedure that interrupts the reentrant circuit responsible for AV node reentrant tachycardia without blocking AV conduction. After first characterizing the salutary effects of this approach in experimental animals, we performed this procedure in eight patients with AV node reentrant tachycardia. Preoperative, intraoperative, and postoperative electrophysiologic studies were performed in each patient. Under conditions of normothermic cardiopulmonary bypass and during atrial pacing at a constant rate with continuous monitoring of AV conduction, nine separate 3 mm cryolesions (-60 degrees C for 2 min) were placed at predetermined sites around the triangle of Koch in the lower right atrial septum. Postoperatively, each patient had a single AV node conduction curve. No patient had AV node reentrant tachycardia induced or has experienced AV node reentrant tachycardia clinically during a follow-up of up to 5 years. The cryosurgical procedure had no detrimental effects on the AH or HV interval or on the paced cycle length at which AV node Wenckebach occurred. Based on these results, this curative operation offers promise for patients with AV node reentrant tachycardia that is refractory to medical treatment.

Regional Myocardial Sympathetic Denervation Predicts the Risk of Sudden Cardiac Arrest in Ischemic Cardiomyopathy

OBJECTIVES The PAREPET (Prediction of ARrhythmic Events with Positron Emission Tomography) study sought to test the hypothesis that quantifying inhomogeneity in myocardial sympathetic innervation could identify patients at highest risk for sudden cardiac arrest (SCA). BACKGROUND Left ventricular ejection fraction (LVEF) is the only parameter identifying patients at risk of SCA who benefit from an implantable cardiac defibrillator (ICD). METHODS We prospectively enrolled 204 subjects with ischemic cardiomyopathy (LVEF ≤35%) eligible for primary prevention ICDs. Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia) and viability (insulin-stimulated (18)F-2-deoxyglucose). The primary endpoint was SCA defined as arrhythmic death or ICD discharge for ventricular fibrillation or ventricular tachycardia >240 beats/min. RESULTS After 4.1 years follow-up, cause-specific SCA was 16.2%. Infarct volume (22 ± 7% vs. 19 ± 9% of left ventricle [LV]) and LVEF (24 ± 8% vs. 28 ± 9%) were not predictors of SCA. In contrast, patients developing SCA had greater amounts of sympathetic denervation (33 ± 10% vs. 26 ± 11% of LV; p = 0.001) reflecting viable, denervated myocardium. The lower tertiles of sympathetic denervation had SCA rates of 1.2%/year and 2.2%/year, whereas the highest tertile had a rate of 6.7%/year. Multivariate predictors of SCA were PET sympathetic denervation, left ventricular end-diastolic volume index, creatinine, and no angiotensin inhibition. With optimized cut-points, the absence of all 4 risk factors identified low risk (44% of cohort; SCA <1%/year); whereas ≥2 factors identified high risk (20% of cohort; SCA ∼12%/year). CONCLUSIONS In ischemic cardiomyopathy, sympathetic denervation assessed using (11)C-HED PET predicts cause-specific mortality from SCA independently of LVEF and infarct volume. This may provide an improved approach for the identification of patients most likely to benefit from an ICD. (Prediction of ARrhythmic Events With Positron Emission Tomography [PAREPET]; NCT01400334).

Radiation Exposure to Patients and Medical Personnel During Radiofrequency Catheter Ablation for Supraventricular Tachycardia

Radiofrequency catheter ablation is an effective alternative to medical therapy for patients with supraventricular arrhythmias. The purpose of this study was to determine the risks to the patient and to medical personnel due to radiation exposure from fluoroscopy during radiofrequency ablation of supraventricular tachycardia. One hundred eight consecutive patients with Wolff-Parkinson-White syndrome or atrioventricular nodal reentry who underwent the ablation procedure were studied. The ablation procedure was successful in 95% of the patients studied. Preexcitation or supraventricular tachycardia recurred in 5% of the patients during a mean follow-up of 9 +/- 4 months. The mean fluoroscopy time was 50 +/- 31 minutes. An anthropomorphic radiologic phantom was used to determine organ exposure and the effective dose equivalents for the patient and medical personnel. The patients effective dose equivalent during a representative ablation procedure was 1.7 rems, which is comparable to other invasive cardiovascular procedures. The risk of inducing a fatal cancer from this exposure is 1 chance in 745, which is 1% of the spontaneous risk. The risk of a serious birth defect is 1 chance in 80,000, which is 0.1% of the current incidence of serious birth defects in the United States. The cardiologist who receives the highest exposure among medical personnel, would incur 1.8 mrems per case or 450 mrems per year if 250 procedures were performed. This exposure is 9% of the recommended annual limit. These results demonstrate the efficacy of radiofrequency energy ablation of supraventricular tachycardia and confirm that radiation exposure to patients and medical personnel is within established guidelines.

Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides.

We have recently detected accumulation of lysophosphoglycerides, catabolites of phospholipids, in ischemic myocardium early after coronary occlusion. In the present study we delineated effects of selected concentrations of albumin-bound lysophosphatidyl choline (LPC) comparable to those accompanying ischemia in vivo on action potentials of isolated canine Purkinje fibers. Lysophosphoglycerides induced concentration-dependent (0.75-3.0 HIM) decreases in resting membrane potential, overshoot of phase 0, maximal velocity of upstroke (V) of phase 0, and action potential duration. The highest concentrations (2.0-3.0 mM) induced fractionation of the action potential into several components, unresponsiveness to external stimulation, and enhanced automaticity at normal and reduced membrane potentials. LPC induced a rightward shift in the membrane response curve, a 40-fold prolongation of conduction time, and an increase in the ratio of effective refractory period to action potential duration such that the effective refractory period persisted beyond action potential duration, resulting in postrepolarixation refractoriness. These electrophysiological alterations were entirely reversible after 70 minutes of perfuslon without LPC, with the exception of a persistent depression in the Vmal of phase 0. Lysophosphatidyl ethanolamine (LPE) elicited alterations in action potentials identical to those elicited by LPC. Furthermore, LPC (3.0 mM) induced comparable alterations in action potentials recorded from isolated rabbit papillary muscles. Since lysophospholipids accumulate early after myocardial ischemia, and since concentrations equivalent to those occurring in vivo induce electrophysiological alterations resembling those seen in ischemic myocardium in vivo, lysophosphoglycerides may be of major importance as biochemical mediators of malignant dysrhythmia induced by ischemia. Ore Res 44: 822-832, 1979