William J. Mandel

Evaluation of Sino-atrial Node Function in Man by Overdrive Suppression

Sino-atrial node (SAN) function was evaluated in 46 patients, three of whom had the sick sinus syndrome. Patients were paced from the right atrium for 15 to 180 sec at rates of 90, 110, 130, and 150 beats/min. The rapid cessation of pacing was associated with suppression of the SAN at all paced rates and at all durations of pacing. The observed pause was terminated by a sinus beat in all instances. The duration of pacing had little influence on the duration of the observed pause. The pause increased as the pacing rate was increased until, at a rate of 150 beats/min, a marked decrease in the pause was noted. Atropine (1.5-3.0 mg iv) diminished but did not eliminate the SAN suppression. Subthreshold pacing did not suppress SAN function. Three patients with sick sinus syndrome had a greater degree of SAN suppression than normal patients (4732 ± 415 msec [SSS] M ± SEM; 1041 ± 56 msec for normal patients).The determination of the duration of the pause following cessation of atrial pacing provides a technique for recognition of abnormalities of SAN function.

Studies on the mechanism of sinus node dysfunction in the sick sinus syndrome.

The intrinsic heart rate (IHR) was determined in 17 patients with symptomatic sinus bradycardia by administering atropine 0.04 mg/kg and propranolol 0.2 mg/kg, i.v. In this way, sick sinus (SSS) patients with intrinsic sinus node (SN) dysfunction could be distinguished from those patients with disturbed autonomic regulation of SN function. Sick sinus syndrome patients with normal corrected sinus node recovery time (SNRTC), adjusted for the magnitude and direction of autonomic chronotrophy, consistently had normal IHRs and therefore abnormalities of autonomic regulation. Sick sinus syndrome patients with abnormal adjusted SNRTC consistently had abnormal IHRs and therefore abnormalities of intrinsic SN function. We conclude that more than one pathophysiologic mechanism can produce the clinical manifestations of sick sinus syndrome and that abnormal prolongation of SNRTC is dependent upon the underlying mechanism of sinus node dysfunctio

Assessment of Sinus Node Function in Patients with the Sick Sinus Syndrome

Thirty-one patients with symptomatic sinus node dysfunction were evaluated with electrocardiograms, Holter monitor recordings, exercise, isoproterenol infusions, atropine administration, Valsalva maneuvers, carotid sinus massage, and overdrive pacing. Four basic clinical subsets were recognized: (1) carotid sinus hypersensitivity (2) bradycardia-tachycardia syndrome, (3) episodic sinus arrest, and (4) persistent symptomatic sinus bradycardia. The study group demonstrated a normal heart rate response to exercise and isoproterenol infusion (%&Dgr; = +95 exercise, +144 isoproterenol) in the face of diminished responsiveness to atropine administration (%&Dgr; = +23). Marked carotid sinus hypersensitivity was demonstrated in eight patients, and four patients demonstrated slight abnormalities during performance of Valsalva maneuvers. Significant suppression of sinus node dysfunction was observed following atrial overdrive in the study group (postpacing pause = 3087 ± 464 msec) as compared to patients without significant sinus node function (postpacing pause = 1073 ± 63 msec) (P < 0.001). In patients with intact V-A conduction, ventricular overdrive also resulted in sinus node suppression (postpacing pause = 1901 ± 357 msec). There was a marked decrease in the degree of sinus node depression following atropine administration. Ten of 31 patients demonstrated various degrees of A-V block following atrial pacing at rates less than 100 beats/min.It is concluded that the present methods of evaluation of sinus function, especially sinus node recovery time following overdrive pacing, may prove of value in the investigation of patients with syncope of unknown etiology.

Characteristics of wave fronts during ventricular fibrillation in human hearts with dilated cardiomyopathy : Role of increased fibrosis in the generation of reentry

OBJECTIVES We sought to evaluate the characteristics of wave fronts during ventricular fibrillation (VF) in human hearts with dilated cardiomyopathy (DCM) and to determine the role of increased fibrosis in the generation of reentry during VF. BACKGROUND The role of increased fibrosis in reentry formation during human VF is unclear. METHODS Five hearts from transplant recipients with DCM were supported by Langendorff perfusion and were mapped during VF. A plaque electrode array with 477 bipolar electrodes (1.6-mm resolution) was used for epicardial mapping. In heart no. 5, we also used 440 transmural bipolar recordings. Each mapped area was analyzed histologically. RESULTS Fifteen runs of VF (8 s/run) recorded from the epicardium were analyzed, and 55 episodes of reentry were observed. The life span of reentry was short (one to four cycles), and the mean cycle length was 172 +/- 24 ms. In heart no. 5, transmural scroll waves were demonstrated. The most common mode of initiation of reentry was epicardial breakthrough, followed by a line of conduction block parallel to the epicardial fiber orientation (34 [62%] of 55 episodes). In the areas with lines of block, histologic examination showed significant fibrosis separating the epicardial muscle fibers and bundles along the longitudinal axis of fiber orientation. The mean percent fibrous tissue in these areas (n = 20) was significantly higher than that in the areas without block (n = 28) (24 +/- 7.5% vs. 10 +/- 3.8%, p < 0.0001). CONCLUSIONS In human hearts with DCM, epicardial reentrant wave fronts and transmural scroll waves were present during VF. Increased fibrosis provides a site for conduction block, leading to the continuous generation of reentry.

Task force I: Standardization of terminology and interpretation

The development of a soundly based, widely acceptable uniform terminology for electrocardiographic interpretation is difficult. Physicians frequently disagree about the classification of features in an individual record, and similar disagreements occur in reports generated by different computer programs.‘-1s Some disagreement results from technical error, but the remainder arises from differences in measurement technique, terminology and criteria. Standard rules for measurement, classification and description of electrocardiographic features appear desirable to improve patient care by improving the consistency and quality of the report as well as communication between the interpreter and the user. The standards should be flexible enough to provide for continuing incorporation of improvements in electrocardiographic diagnoses, for classification of features from different populations and for different categories of users. Standards for medical procedures are more readily accepted if they are logical, easily understandable and auth0ritative.l’ However, significant variability in electrocardiographic classification persists even when physicians agree to use identical criteria.44 Imprecise identification of the onset and offset of electrocardiographic deflections is one source of variability in classification procedure, but this type of error can be minimized by proper selection of criteria.lzJs There is no comprehensive list of definitions and criteria designed for the use of electrocardiographic interpreters. The New York Heart Association monograph on nomenclature14 focuses on comprehensive cardiac diagnosis rather than the electrocardiographic report. One of the best known digital coding systems, the Minnesota Code, has precisely defined criteria for classifying electrocardiographic features but is more useful in large scale clinical studies than in the interpretation of routine clinical reports.15J6 Types of interpretive statements: Selecting criteria for each electrocardiographic interpretive statement may be more difficult than selecting terminology. Statements can be divided arbitrarily into three types: (1) Type A refers to an anatomic lesion or pathophysiologic state that can be verified by nonelectrocardiographic evidence; this includes hypertrophy, infarction, ischemia, pulmonary disease and drug and metabolic effects. Selection of optimal criteria for type A statements depends on confirmatory nonelectrocardiographic information, which is limited in many instances at present. (2) Type B refers to an anatomic or functional disturbance that is detectable by the electrocardiogram itself (including special intracardiac leads). Criteria for these statements are based on characteristic features, and pertain mostly to arrhythmias and conduction disturbances. (3) Type C refers to electrocardiographic features that do not fit into type A and B categories. These include electrical axis, nonspecific T wave abnormalities, “premature repolarization,” and unusual voltage. It appears reasonable to define interim standards for types B and C statements at this time, with the understanding that they may be modified by additional information. Selection of criteria: For any type of electrocardiographic statement criteria should be selected with regard to sources of uncertainty that determine the accuracy of the statement; this principle is common to all medical diagnoses. 11~17-21 With respect to electrocardiographic diagnosis, numerous sources of uncertainty include physiologic variations from complex to complex or from day to day, variations in recording equipment or technique, recognition and measurement of the recorded wave forms, morphologic and etiologic classification of electrocardiographic features, and inadequate communication between the interpreter and user of the report.2,22*23 Criteria for classification into different categories should not depend on a difference between measurements resulting from chance variations.zJ4 Borderline regions should be defined on the basis of total precision for both the measurement and the criteria. The definition of pathologic states responsible for the electrocardiographic changes is not necessarily precise. This may complicate establishment of valid criteria. The problem of classifying “microinfarcts” in a correlative study of electrocardiographic criteria is one example of this situation.25 Variations in electrocardiographic measurements associated with age and other constitutional factors make it imperative that all comparisons be made between similar population samples. Collection of data from large samples of healthy and diseased populations

Disparity between the clinical and electrophysiologic effects of amiodarone in the treatment of recurrent ventricular tachyarrhythmias

Nine patients with life-threatening ventricular arrhythmias were administered oral amiodarone over a period of months. Sustained ventricular tachycardia (VT) was induced during programmed stimulation in seven of the nine patients prior to their receiving amiodarone therapy. Despite an excellent clinical response to the drug over a period of 10 to 24 months (median 15 months), sustained VT was still able to be initiated in seven patients after 7 to 20 weeks of therapy, with multiform VT induced in several patients both before and after amiodarone. Some effects of the drug were noted, however, in that the induced VT was often slower with an increased QRS width, and right ventricular refractory periods were prolonged. Repeated ambulatory ECG monitoring in six patients showed a reduction in the frequency and complexity of spontaneous ventricular arrhythmias, but there was no consistent effect on the prematurity of the ventricular complexes. The reason for the disparity in some patients between the effects of amiodarone on the electrical initiation of VT and its clinical recurrence is unclear, but the findings suggest that the clinical efficacy of amiodarone in patients with ventricular arrhythmias may not be reliably predicted by electrophysiologic studies (EPS).

Aging-related increase to inducible atrial fibrillation in the rat model.

Aging and Atrial Fibrillation. Introduction: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging‐related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging‐related AF.

The signal-averaged electrocardiogram as a screening test for inducibility of sustained ventricular tachycardia in high risk patients: A prospective study

The role of the signal-averaged electrocardiogram in predicting the induction of sustained monomorphic ventricular tachycardia in high risk patients was assessed prospectively in 100 consecutive patients. Presenting diagnoses were syncope (38 patients), nonsustained ventricular tachycardia (24 patients), sustained ventricular tachycardia (25 patients) and sudden cardiac arrest (13 patients). Using programmed ventricular stimulation, 71 patients (group I) did not have and 29 patients (group II) did have inducible sustained monomorphic ventricular tachycardia. Using the signal-averaged electrocardiogram with filtering (6 dB/octave) at high pass corner frequencies of 67 and 100 Hz, the two groups were compared. The signal-averaged electrocardiogram was considered abnormal if all of the following criteria were satisfied: 1) the total filtered QRS complex duration was greater than 120 ms, 2) the duration of the terminal QRS complex of less than or equal to 20 microV was greater than or equal to 30 ms, and 3) at least one deflection (late potential) was present in this region. Differences between groups I and II in these three measures were highly significant (p less than or equal to 0.001). The sensitivity and specificity of signal averaging for predicting the induction of sustained ventricular tachycardia were 93 and 94%, respectively. Stepwise logistic regression analysis identified the signal-averaged electrocardiogram as the best predictor of induction of sustained monomorphic ventricular tachycardia, independent of left ventricular ejection fraction, presence of ventricular aneurysm, myocardial infarction and other clinical variables (chi-square = 93.2, p less than 0.0001). The signal-averaged electrocardiogram is a sensitive and specific test for the induction of sustained monomorphic ventricular tachycardia, having independent predictive value.

Altered Atrial Electrical Restitution and Heterogeneous Sympathetic Hyperinnervation in Hearts With Chronic Left Ventricular Myocardial Infarction Implications for Atrial Fibrillation

Background The substrates for the increased incidence of atrial fibrillation (AF) in hearts with chronic left ventricular myocardial infarction (MI) remain poorly defined. We hypothesized that chronic MI is associated with atrial electrical and neural remodeling that enhances AF vulnerability. Methods and Results We created MI in 8 dogs by permanent occlusion of the left anterior descending (LAD) coronary artery. Seven dogs (3 with thoracotomy) that had no LAD occlusion served as controls. Eight weeks after surgery, the incidence and duration of pacing‐induced AF in the open chest anesthetized state were significantly (P<0.05) higher in the MI than in control dogs. Multisite biatrial monophasic action potential (MAP) recordings showed increased heterogeneity of MAP duration (MAPD) and MAPD restitution slope. AF in the MI groups was preceded by significantly higher MAPD (P<0.01) and MAP amplitude (P<0.05) alternans in both atria compared with controls. Epicardial mapping using 1792 bipolar electrodes (1‐mm spatial resolution) showed multisite wavebreaks of the paced wavefronts leading to AF in MI but not in control dogs. Multiple wavelets in MI dogs were associated with significantly higher incidence and longer duration of AF compared with control. The density of biatrial tyrosine hydroxylase (TH) and growth‐associated protein43 (GAP43) nerves were 5‐ to 8‐fold higher and were more heterogeneous in MI compared with control dogs. Conclusions Chronic ventricular MI with no atrial involvement causes heterogeneous alteration of atrial electrical restitution and atrial sympathetic hyperinnervation that might provide important substrates for the observed increased AF vulnerability. (Circulation. 2003;108:360‐366.)

Underdetection of ventricular tachycardia by algorithms to enhance specificity in a tiered-therapy cardioverter-defibrillator

OBJECTIVES The goal of this study was to determine the incidence and clinical significance of underdetection in 125 patients treated with a tiered-therapy cardioverter-defibrillator, the Medtronic PCD. BACKGROUND Underdetection, distinct from undersensing, is a unique, potential complication of new algorithms that enhance specificity in tiered-therapy cardioverter-defibrillators. These algorithms may delay or prevent recognition of ventricular tachycardia even though electrograms are sensed accurately and RR intervals meet the programmed interval criterion. METHODS Underdetection was defined as delay in detection > 5 s at electrophysiologic study or symptomatic delay or detection failure at follow-up of 15 +/- 8 months. RESULTS We identified six specific mechanisms of underdetection caused by algorithms to discriminate sustained ventricular tachycardia from sinus tachycardia, atrial fibrillation, ventricular fibrillation and nonsustained ventricular tachycardia. Underdetection caused detection delays in 13 (1.9%) of 677 induced ventricular tachyarrhythmia episodes in 12 patients (9.6%). During follow-up, underdetection occurred in 7 (9.9%) of 71 patients in whom ventricular tachycardia therapies were programmed. Failure to detect ventricular tachycardia occurred in 6 (0.6%) of 988 spontaneous ventricular tachycardia episodes in four patients (5.6%); 2 episodes required external cardioversion. After defibrillator reprogramming, underdetection did not occur. CONCLUSIONS Algorithms to enhance specificity cause underdetection of ventricular tachycardia in a significant minority of patients with tiered-therapy cardioverter-defibrillators. Optimal programming can minimize underdetection.