Scott Sakaguchi

Arrhythmogenic right ventricular cardiomyopathy/dysplasia clinical presentation and diagnostic evaluation: Results from the North American Multidisciplinary Study

BACKGROUND Prior reports on patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) focused on individuals with advanced forms of the disease. Data on the diagnostic performance of various testing modalities in newly identified individuals suspected of having ARVC/D are limited. OBJECTIVE The purpose of the Multidisciplinary Study of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia was to study the clinical characteristics and diagnostic evaluation of a large group of patients newly identified with ARVC/D. METHODS A total of 108 newly diagnosed patients with suspected ARVC/D were prospectively enrolled in the United States and Canada. The patients underwent noninvasive and invasive tests using standardized protocols that initially were interpreted by the enrolling center and adjudicated by blind analysis in six core laboratories. Patients were followed for a mean of 27 +/- 16 months (range 0.2-63 months). RESULTS The clinical profile of these newly diagnosed patients differs from the profile of reported patients with more advanced disease. There was considerable difference in the initial and final classification of the presence of ARVC/D after the diagnostic tests were evaluated by the core laboratories. Final clinical diagnosis was 73 affected, 28 borderline, and 7 unaffected. Individual tests agreed with the final diagnosis in 50% to 70% of the 73 patients with a final classification of affected. CONCLUSION The clinical profile of 108 newly diagnosed probands with suspected ARVC/D indicates that a combination of diagnostic tests is needed to evaluate the presence of right ventricular structural, functional, and electrical abnormalities. Echocardiography, right ventricular angiography, signal-averaged ECG, and Holter monitoring provide optimal clinical evaluation of patients suspected of ARVC/D.

Pharmacotherapy of Neurally Mediated Syncope

A wide variety of pharmacological agents are currently used for prevention of recurrent neurally mediated syncope, especially the vasovagal faint. None, however, have unequivocally proven long-term effectiveness based on adequate randomized clinical trials. At the present time, beta-adrenergic receptor blockade, along with agents that increase central volume (eg, fludrocortisone, electrolyte-containing beverages), appear to be favored treatment options. The antiarrhythmic agent disopyramide and various serotonin reuptake blockers have also been reported to be beneficial. Finally, vasoconstrictor agents such as midodrine offer promise and remain the subject of clinical study. Ultimately, though, detailed study of the pathophysiology of these syncopal disorders and more aggressive pursuit of carefully designed placebo-controlled treatment studies are essential if pharmacological prevention of recurrent neurally mediated syncope is to be placed on a firm foundation.

Syncope Associated With Exercise, a Manifestation of Neurally Mediated Syncope

A retrospective review of patients evaluated at a university-based referral hospital was performed to assess the basis for syncope associated with exercise in young patients. Over an 8-year period, 54 consecutive young patients (aged 12 to 30 years) were referred for evaluation of frank syncope. Twelve patients had syncope associated with exercise (group I) and 42 patients had syncope not associated with exercise (group II). Patients underwent physical examination, chest x-ray, 2-dimensional echocardiography, and in selected cases, cardiac catheterization. Head-up tilt-table testing was performed in 11 of 12 group I patients. Ten group I patients had no evidence of structural heart disease: 9 of these 10 (90%) developed syncope with tilt-table testing. Head-up tilt-table testing was performed in 41 of 42 group II patients: 34 (83%) developed syncope with tilt-table testing. Standard cardiac electrophysiologic study was performed in 9 of 12 group I and in 30 of 42 group II patients, and identified a basis for syncope in only 2 group I and 1 group II patients. Among 9 group I patients with a positive result on head-up tilt-table testing and no evidence of structural heart disease (mean follow-up 4.3 years), 7 are without further episodes of syncope; 3 have discontinued medication and 5 have resumed at least limited exercise. In conclusion, susceptibility to tilt-induced syncope was the most frequent finding in young patients without structural heart disease referred for evaluation of exercise-associated syncope. Tilt-table testing may be an important diagnostic tool for the evaluation of these patients.

Comparison of automatic and patient-activated arrhythmia recordings by implantable loop recorders in the evaluation of syncope

The implantable loop recorder (ILR) has become an important tool for evaluating patients with recurrent syncope. Second generation ILRs have the ability to record events either automatically (auto activated) or by manual activation (patient activated). In an attempt to evaluate the relative utility of the auto-activation feature, this study stratified ILR events based on a grading system designed to classify detected arrhythmias in terms of the likelihood that they provide a diagnostic basis for syncope. Data from 50 patients (27 men, mean age 64 ± 22 years) who underwent ILR implantation for investigation of recurrent syncope were assessed. The arrhythmia syncope grading system used 5 levels, ranging from grade 0 (rhythm recorded during syncope) to grade IV (rhythm unlikely to provide a diagnostic basis for syncope). Thirty-six patients (72%) demonstrated ≥1 auto-activated or patient-activated recording during a follow-up of 14.3 ± 7.9 months. Of the total of 529 recordings, 223 (194 after auto activation [86.9%]) from 30 patients showed a rhythm abnormality. Auto activation was more effective for documenting arrhythmias that were recorded during syncope or those with highest probability of providing a syncope diagnosis (grade 0 or I arrhythmias: auto activated, 19 patients, patient activated, 3 patients). Times from ILR implantation to first grade 0 and grade I arrhythmias were 13.4 and 7.8 months, respectively. The ILR auto-activation feature proved effective in providing a high probability basis for syncope (196 arrhythmia recordings [87.1%] in 27 patients) and enhanced the diagnostic effectiveness of the device compared with patient activation alone (29 arrhythmia recordings [12.9%] in 6 patients).

Biventricular implantable cardioverter defibrillators improve survival compared with biventricular pacing alone in patients with severe left ventricular dysfunction.

Introduction: Biventricular cardiac pacemakers provide important hemodynamic benefit in selected patients with heart failure and severe left ventricular (LV) dysfunction. Nevertheless, these patients remain at high mortality risk. To address this issue, we examined mortality outcome in patients with heart failure treated with biventricular pacemakers alone and those treated with biventricular implantable cardioverter defibrillators (ICDs).

Relationship of paroxysmal atrial tachyarrhythmias to volume overload: assessment by implanted transpulmonary impedance monitoring.

Background— Clinical experience suggests that atrial tachyarrhythmias (ATs) are a frequent comorbidity in heart failure patients with left ventricular systolic dysfunction and that volume overload may increase AT susceptibility. However, substantiating this apparent relationship in free-living patients is difficult. Recently, certain implantable cardioverter-defibrillators provide, by measuring transpulmonary electric bioimpedance, an index of intrathoracic fluid status (OptiVol index [OI]). The goal of this study was to determine whether periods of greater intrathoracic fluid congestion (as detected by OI) correspond with increased AT event frequency. Methods and Results— This analysis retrospectively assessed the relation between AT events and OI estimate of volume overload in patients with left ventricular systolic dysfunction and OI-capable implantable cardioverter-defibrillators. OI values were stratified into 3 levels: group 1, 60. An OI threshold-crossing event was defined as OI≥60, a value previously associated with clinically significant volume overload. Findings in 59 patients (mean left ventricular ejection fraction, 24%) with 225 follow-up visits (mean, 3.8 visits per patient) were evaluated. AT prevalence was 73%. AT frequency (percent of patients visits with at least 1 episode of AT since previous device interrogation) was greater in group 3 versus group 1 ( P =0.0342). Finally, in terms of temporal sequence, AT episodes preceded OI threshold-crossing event in 43% of incidences, followed threshold-crossing event in 29%, and was simultaneous or indeterminate in the remainder. Conclusions— These findings not only support the view that worsening pulmonary congestion is associated with increased AT frequency in patients with left ventricular dysfunction but also suggest that AT events may be responsible for triggering episodic pulmonary congestion more often than previously suspected. Received February 24, 2009; accepted August 24, 2009. # CLINICAL PERSPECTIVE {#article-title-2}Background—Clinical experience suggests that atrial tachyarrhythmias (ATs) are a frequent comorbidity in heart failure patients with left ventricular systolic dysfunction and that volume overload may increase AT susceptibility. However, substantiating this apparent relationship in free-living patients is difficult. Recently, certain implantable cardioverter-defibrillators provide, by measuring transpulmonary electric bioimpedance, an index of intrathoracic fluid status (OptiVol index [OI]). The goal of this study was to determine whether periods of greater intrathoracic fluid congestion (as detected by OI) correspond with increased AT event frequency. Methods and Results—This analysis retrospectively assessed the relation between AT events and OI estimate of volume overload in patients with left ventricular systolic dysfunction and OI-capable implantable cardioverter-defibrillators. OI values were stratified into 3 levels: group 1, <40; group 2, 40 to 60; and group 3, >60. An OI threshold-crossing event was defined as OI≥60, a value previously associated with clinically significant volume overload. Findings in 59 patients (mean left ventricular ejection fraction, 24%) with 225 follow-up visits (mean, 3.8 visits per patient) were evaluated. AT prevalence was 73%. AT frequency (percent of patients visits with at least 1 episode of AT since previous device interrogation) was greater in group 3 versus group 1 (P=0.0342). Finally, in terms of temporal sequence, AT episodes preceded OI threshold-crossing event in 43% of incidences, followed threshold-crossing event in 29%, and was simultaneous or indeterminate in the remainder. Conclusions—These findings not only support the view that worsening pulmonary congestion is associated with increased AT frequency in patients with left ventricular dysfunction but also suggest that AT events may be responsible for triggering episodic pulmonary congestion more often than previously suspected.

Efficacy of biphasic waveform cardioversion for atrial fibrillation and atrial flutter compared with conventional monophasic waveforms

B on extensive experience with implantable cardioverter-defibrillators and automatic external defibrillators, the utility of biphasic transthoracic shock has been demonstrated in the setting of lifethreatening ventricular tachyarrhythmias. These observations have led to the application of biphasic waveforms during elective transthoracic cardioversion for atrial fibrillation (AF). The present report compares cardioversion outcomes in 2 sequential groups of patients with AF undergoing transthoracic cardioversion. It was undertaken in an attempt to ascertain the extent to which biphasic waveform technique enhances transthoracic AF cardioversion success rates. • • • Records of 145 patients were reviewed. The patients were referred to our center for elective transthoracic cardioversion between January 1999 and September 2001, and had undergone this procedure in the electrophysiologic laboratory. Patients with atrial flutter (20 patients, 14%) were also included because of the similarity of the arrhythmia and the treatment required. Demographic and clinical data—including arrhythmia type and duration, underlying disease, and concomitant medications—were documented, along with echocardiographic data including left atrial diameter and left ventricular ejection fraction. Procedural data—including the number of cardioversion attempts made, energy levels used, and anesthetic employed— were documented. Similarly, complications were recorded, particularly skin irritation. A successful cardioversion procedure was defined as restoration of sinus rhythm for 1 cycle after energy application. Recurrence of the arrhythmia 2 hours after a successful cardioversion (i.e., before the patient left the observation unit) was deemed an “early recurrence.” The statistical significance of the efficacy of biphasic waveform cardioversion compared with monophasic waveform shock cardioversion was evaluated using chi-square and Fisher’s exact tests. A p value of 0.05 was considered statistically significant. Data were obtained in 145 sequential patients who underwent elective electrical cardioversion for AF or atrial flutter. Eighty-two patients (mean age 67 15 years) received biphasic waveform cardioversion, and the remaining 63 patients (mean age 66 14 years) underwent cardioversion with a monophasic waveform device. The ratio of men to women was 1.8:1 and 2:1 for the biphasic and monophasic waveform cardioversion study groups, respectively. The presenting arrhythmia was AF in 70 patients (85%) in the biphasic group and in 55 patients (87%) in the monophasic group. Atrial flutter was present in 12 patients (15%) in the biphasic group and in 8 patients (13%) in the monophasic group. The mean duration of patients’ treatment for the arrhythmia event was 36 56 and 60 106 days (p NS) for the biphasic and monophasic groups, respectively. Baseline clinical characteristics for patients in each treatment group are listed in Table 1. Underlying disease processes (i.e., cardiomyopathy, coronary artery disease, valvular heart disease, lung disease, and other structural heart disease) were found to be similarly prevalent in both treatment groups. Patients in the monophasic waveform group tended to use more digoxin, amiodarone, and other antiarrhythmic medications compared with biphasic group patients. The frequencies of usage of blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors were similar in both groups. The mean left atrial diameter was 46 10 mm in the biphasic group and 45 12 mm in the monophasic waveform group. Mean left ventricular ejection fraction was similar for the biphasic and monophasic groups (49 13% and 49 15%, respectively). Procedure success rate was 99% (81 patients) in the biphasic waveform cardioversion group compared with 81% (51 patients) in the group treated with monophasic waveform (p 0.001). The mean energy required for procedural success was 126 46 J and 228 83 J for the biphasic and monophasic waveform groups, respectively (p 0.001). The mean number of attempts before achieving procedural success was 1.3 0.8 for the biphasic cardioversion group and 1.2 0.4 for the monophasic cardioversion group. The treated arrhythmia recurred in 10 biphasic group patients (12%) and in 6 monophasic group patients (12%). All recurrences were in patients with AF. Skin irritation was not observed in any of the patients who received biphasic waveform shock, whereas 2 patients (3%) who received monophasic waveform shock required topical treatment for irritation at patch sites. • • • From the Cardiac Arrhythmia Center, Cardiovascular Division, Department of Medicine, Minneapolis, Minnesota. Dr. Ermis is supported in part by a grant from the Midwest Arrhythmia Research Foundation, Minneapolis, Minnesota. Dr. Benditt’s address is: Cardiac Arrhythmia Center, MMC 508, 420 Delaware Street, Minneapolis, Minnesota 55455. Manuscript received April 9, 2002; revised manuscript received and accepted June 7, 2002.

Comparison of Tilt Angles and Provocative Agents (Edrophonium and Isoproterenol) to Improve Head-Upright Tilt-Table Testing

Patients with syncope underwent head-up tilt testing at 60 degrees and 80 degrees followed by edrophonium or isoproterenol challenge when indicated. The 80 degrees tilt protocol and edrophonium provocation were found to be as effective or more effective in eliciting neurally mediated syncope in susceptible patients.

Improved survival of cardiac transplantation candidates with implantable cardioverter defibrillator therapy: role of beta-blocker or amiodarone treatment.

Introduction: Survival in patients awaiting cardiac transplantation is poor due to the severity of left ventricular dysfunction and the susceptibility to ventricular arrhythmia. The potential role of implantable cardioverter defibrillators (ICDs) in this group of patients has been the subject of increasing interest. The aims of this study were to ascertain whether ICDs improve the survival rate of patients on the waiting list for cardiac transplantation and whether any improvement is independent of concomitant beta‐blocker or amiodarone therapy.

Multiple-Sensor Systems for Physiologic Cardiac Pacing

The first implantable cardiac pacemakers were designed to pace at a fixed rate, with no attempt to reproduce normal heart rate changes. However, technologically advanced pacemakers were introduced that adjusted the pacing rate by sensing the patients native atrial activity and adjusting the ventricular pacing rate accordingly. By the mid-1980s, artificial sensors were introduced into pacing systems and provided another means for pacemakers to adjust their rates appropriately. Incorporation of artificial sensors in implantable pacing systems revolutionized the technology of cardiac pacing and its clinical practice [1-6]. Initially, artificial sensors were viewed exclusively as a means to modify the pacing rate in response to changing levels of physical exertion. In that rate-adaptive role, sensor-based pacemakers have been well received by physicians and patients Figure 1, Table 1. More recently, the role of artificial sensors expanded to include automatic adjustment of certain programmable pacemaker settings, such as the interval between atrial and ventricular pacing stimuli (that is, the atrioventricular interval). In addition, sensors are also being used to inform the pacing system of the development of certain arrhythmias, particularly atrial flutter or fibrillation. This latter capability permits those pacemakers that use the patients atrium to set the pacing rate (atrial tracking) to change their mode of operation to one in which the pacing rate is determined by the sensor. This mode-switching feature prevents the undesirable high-rate pacing that can occur if the pacemaker continues to track the atrial rate during a pathologic atrial tachycardia. Soon, sensors will allow pacemakers to adjust many other operating characteristics automatically (such as the level of energy output, electrical polarity of the intracardiac electrodes, pacing mode, and so on) [7], thereby optimizing efficiency of operation while minimizing the need for specialized medical follow-up. Table 1. International Generic Pacemaker Code* Figure 1. Changes in pacing mode use in North America in the past decade (see ). In the past decade, physicians have gained considerable clinical experience with rate-adaptive pacing systems that incorporate a single artificial sensor [8-16]. Although this experience has been largely favorable, no single artificial sensor is suitable for all potential pacing system applications [6, 17]. Consequently, pacemakers using combinations of artificial sensors that can operate in a complementary manner are being developed and clinically evaluated (Table 2). This review surveys the role of artificial sensors in cardiac pacing systems and examines the rationale for and the clinical status of pacemakers that use multiple artificial sensors. Table 2. Current Multiple Artificial Sensor Pacing Systems* Role of Sensors in Cardiac Pacing Systems Rationale for Using Sensors To Adjust Pacing Rate Although prevention of symptoms such as syncope or dizziness resulting from severe bradycardia is the primary goal of pacemaker therapy, careful selection of the pacing system and its mode operation also provide the opportunity to improve exercise tolerance [8-13, 18], to diminish the risk for development of atrial fibrillation [19-24], and to decrease overall mortality rates [18, 21-26]. In terms of exercise tolerance, appropriate heart rate responsiveness contributes the most to increased cardiac output during exertion. This applies to healthy persons and to most patients with pacemakers, whether they are vigorously active or must simply manage the physical demands associated with activities of daily living (such as climbing stairs, walking, carrying groceries, and doing the laundry) [1, 4, 8-18]. For example, studies by Karlof [27], Fananapazir and coworkers [28], Ausubel and colleagues [29], and Ryden and associates [30] clearly show that exercise capacity, stroke volume changes with exercise, and maximum oxygen consumption (a measure of the bodys ability to provide essential fuel for vigorous exertion) depend primarily on heart rate change in most patients. In addition, Ryden and associates [30] also showed that over a wide range of atrioventricular intervals, there was no difference between maximum oxygen uptake in patients with pacemakers during rate-adaptive, single- and dual-chamber pacing. Furthermore, in terms of the hearts own energy requirements during exercise, Nordlander and colleagues [31] found that increasing heart rate, such as occurs with rate-adaptive pacing, does not necessarily adversely affect myocardial oxygen consumption compared with fixed-rate pacing. In fact, provision of an appropriate heart rate change during exercise may prevent ventricular dilation and reduce the need for premature encroachment on cardiac compensatory responses. In principle, providing heart rate responsiveness in many patients with pacemakers can be accomplished using the patients own native atrial or sinus node rate to determine the appropriate moment-to-moment ventricular paced rate (that is, atrial tracking, such as in the VD or DDD pacing modes shown in Table 1. Indeed, if a healthy sinus node is present, such an approach not only provides the most physiologic heart rate response but also maintains a relatively normal relation between atrial and ventricular contractions. However, symptomatic disturbances of sinoatrial function [that is, the sick sinus syndrome] are common in patients with pacemakers [1, 19-24]. In fact, they are the primary indication for a pacemaker in more than 50% of patients who have them in Western countries [18]. Consequently, tracking the native atrial rate often does not provide the optimal physiologic heart rate response. Consequently, other techniques, such as the incorporation of artificial sensors into implantable pacing systems, are essential in many patients with pacemakers to ensure reliable heart rate responsiveness [1-6, 18]. Current Sensor Systems The sensing of atrial electrical potentials by an intra-atrial electrode with subsequent adjustment of ventricular pacing rate (that is, atrial tracking) was the first attempt to develop a sensor-triggered rate-adaptive pacemaker [32, 33]. In that case, the sensor is the patients own atrial rate. However, for the reasons previously noted, tracking to adjust the pacing rate may not be suitable in many patients. The earliest efforts to develop artificial sensors to adjust the rate of implantable cardiac pacemakers were reported in the mid-1960s [34]. However, not until the mid-1970s did Cammilli and coworkers [35], using central venous pH sensing, provide the first implantable device. Theoretically, reduced central venous pH associated with exercise would signal the pacemaker to increase its rate. The resulting additional cardiac output would then not only tend to normalize the pH but ultimately would also cause the pacemaker to slow down again (a closed-loop sensor system). Unfortunately, the pH sensor was not particularly stable in the long term, and the relation between pH and heart rate was complex. For the most part, researchers have abandoned the pH sensor concept. The first commercially successful sensor-based pacing system used a specialized ceramic element with piezoelectric characteristics (that is, they produce an electrical potential when physically deformed, such as by vibration) bonded to the inside surface of the pacemaker shield (Activitrax; Medtronic Inc., Minneapolis, Minnesota) [3, 4, 10-12, 36-39]. With this device and its more recent derivatives, the metal of the pacemaker shield may be thought of as a drum head. The ceramic activity sensor emits electrical signals (the piezoelectric effect) approximately in proportion to the vibrations transmitted through the pacemaker from the patients working muscle and skeleton. These piezoelectric signals are an indirect but useful reflection of the patients physical activity (thus, the widely used term activity sensor) and can be used to change the pacing rate appropriately [11, 12, 36-41]. The rapid clinical acceptance of the first activity-based, rate-adaptive pacing system encouraged development of similar pacemakers. Some manufacturers adopted the activity detection concept, either by using the drum head design described previously (such as Synchrony devices, Siemens-Pacesetter Systems, Sylmar, California) or an accelerometer modification (such as Relay; Intermedics Inc., Freeport, Texas). Other manufacturers devised unique rate-adaptive sensor solutions [42-52]. For example, measurement of the interval from the pacing stimulus to the peak of the T wave (the so-called stim-T interval, an estimate of the QT interval for paced heart beats), has proved effective (for example, Rhythmyx; Vitatron Medical b.v., Dieren, the Netherlands) [43]. This concept is based on the fact that the stim-T interval (like the QT interval on the standard electrocardiogram) is modified by changes in circulating or locally released catecholamines. Thus, for a given heart rate, a change in myocardial catecholamine exposure (for example, in association with physical exertion) will modify the stim-T interval and provide a marker for altered levels of physical activity. Similarly, estimation of exercise-induced change in minute ventilation by transthoracic plethysmography (such as Meta; Telectronics Inc., Sydney, Australia), or in central venous temperature using a thermistor on the pacing lead (such as Kelvin; Cook Pacemakers Inc., Leechburg, Pennsylvania) have yielded useful rate-adaptive pacing techniques [14, 44-47]. Additional promising concepts for rate-adaptive sensors include monitoring exercise-induced changes in central venous oxygen saturation using an intravascular oxygen sensor, and measuring exercise-related changes in right ventricular pressure characteristics (using a small pressure sensor built into the ventricular pacing lead) [50-52]. Conversely, some other interesting sensor proposals, s