Serial Holter Monitoring Research Articles

PO-695-08 PULMONARY VEIN ISOLATION (PVI) AND POSTERIOR WALL ISOLATION (PWI) FOR ATRIAL FIBRILLATION USING POINT-BY-POINT PULSED ELECTRIC FIELDS: SPACE AF ACUTE RESULTS

Pulsed electrical field (PEF) has been used for pulmonary vein isolation (PVI). The CENTAURI System enables PEF ablation via standard contact force ablation catheters. The point-by-point clinical workflow may enable treatment beyond PVI, including posterior wall isolation (PWI). SPACE AF study is evaluating feasibility and safety of PVI with PWI using PEF in patients with high burden paroxysmal and persistent AF. CENTUARI PEF System (Galaxy Medical) and a focal contact force sensing catheter (ThermoCool ST, Biosense Webster) were used for PEF ablation for wide antral PVI with PWI. Operators chose one of three doses (19A, 22A, 25A) with contact force of >5g. Primary efficacy outcome was entrance/exit block of all pulmonary veins (PVs) after a 20-minute wait. Composite safety endpoint comprised of pre-specified adverse events including microbubble formation on intracardiac echo (ICE), ST-segment changes, phrenic nerve palsy, esophageal temperature rises, NIH stroke scale (NIHSS) changes, PV stenosis, and silent cerebral lesions after PEF ablation. CT of the PVs will be done at 3 months. Cranial MRI was done at 24 hours in a subset of patients. Secondary endpoint includes recurrence of AF post-ablation at 6 and 12 months with serial Holter monitoring. SPACE AF will report on 30 patients. Thus far, 12 patients (58% Male, age 55.8±10.5 years) have been treated. Acute PVI and PWI was achieved in all 12 patients (100%). An average of 113.8±12.1 applications were delivered per patient. Energy settings were 32% at 22A and 68% at 25A. There were no ST-segment changes, microbubble formations, phrenic nerve injuries, or esophageal temperature rises during PEF ablation. There were no changes to NIHSS pre- vs. post-procedure. Three (3) patients have participated in the cranial MRI sub-study, and all had negative DWI and FLAIR post-procedure. No patients experienced procedure- or device-related AEs at 30 days. PV anatomy will be assessed at 90 days. Long-term AF recurrence outcomes will be assessed at 6-month and 12-month follow-up via 48-hour Holter. Cardiac ablation using PEF delivered through standard focal catheters is safe and acutely successful when performing PWI after PVI. Further results on additional patients and AF recurrence will be presented.

Association of Premature Ventricular Contraction Burden on Serial Holter Monitoring With Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

A high burden of premature ventricular contractions (PVCs) at disease diagnosis has been associated with an overall higher risk of ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC). Data regarding dynamic modification of PVC burden at follow-up with Holter monitoring and its impact on arrhythmic risk in ARVC are scarce. To describe changes in the PVC burden and to assess whether serial Holter monitoring is dynamically associated with sustained ventricular arrhythmias during follow-up in patients with ARVC. In this cohort study, patients with a definite ARVC diagnosis, available Holter monitoring results at disease diagnosis, and at least 2 additional results of Holter monitoring during follow-up were enrolled from 6 ARVC registries in North America and Europe. Data were collected from June 1 to September 15, 2021. The association between prespecified variables retrieved at each Holter monitoring follow-up (ie, overall PVC burden; presence of sudden PVC spikes, defined as absolute increase in PVC burden ≥5000 per 24 hours or a relative ≥75% increase, with an absolute increase of ≥1000 PVCs; presence of nonsustained ventricular tachycardia [NSVT]; and use of β-blockers and class III antiarrhythmic drugs) and sustained ventricular arrhythmias occurring within 12 months after that Holter examination was assessed using a mixed logistical model. In 169 enrolled patients with ARVC (mean [SD] age, 36.3 [15.0] years; 95 men [56.2%]), a total of 723 Holter examinations (median, 4 [IQR, 4-5] per patient) were performed during a median follow-up of 54 (IQR, 42-63) months and detected 75 PVC spikes and 67 sustained ventricular arrhythmias. The PVC burden decreased significantly from the first to the second Holter examination (mean, 2906 [95% CI, 1581-4231] PVCs per 24 hours; P < .001). A model including 24-hour PVC burden (odds ratio [OR] 1.50 [95% CI, 1.10-2.03]; P = .01), PVC spikes (OR, 6.20 [95 CI, 2.74-13.99]; P < .001), and NSVT (OR, 2.29 [95% CI, 1.10-4.51]; P = .03) at each follow-up Holter examination was associated with sustained ventricular arrhythmia occurrence in the following 12 months. These findings suggest that in patients with ARVC, changes in parameters derived from each Holter examination performed during follow-up are associated with the risk of sustained ventricular arrhythmias within 12 months of disease diagnosis.

Cardioneuroablation for Treatment of Atrioventricular Block.

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563 Effect of PHOX2B Genotype and Age on Heart Rate Variability in Pediatric Patients with Congenital Central Hypoventilation Syndrome

Abstract Introduction Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy causing a wide array of cardiac autonomic nervous system (ANS) abnormalities (abnormal heart rate (HR) regulation, decreased HR variability (HRV), prolonged sinus pauses). CCHS is caused by mutations throughout the PHOX2B gene. Different types and locations of PHOX2B mutations have been associated with different levels of CCHS cardiac phenotype severity. We hypothesized that HRV in CCHS will be influenced by age and PHOX2B genotype. Methods PHOX2B mutation-confirmed CCHS patients in our cohort followed longitudinally with serial Holter monitoring were included. HRV measures were extracted from Holter monitoring reports and analyzed using linear mixed-effect models. Additional analyses explored which variables predicted sinus pauses and cardiac pacemaker implantation using linear and logistic regression. Only data preceding implantation of a cardiac pacemaker were included in analysis. Results 97 patients (0–18 years old) were enrolled in the study: 21 with the 20/25 genotype, 21 with the 20/26 genotype, 26 with the 20/27 genotype, 7 with genotypes ranging from 20/28-20/33, and 22 with non-polyalanine repeat expansion mutations (NPARMs). There were 965 total observations (Holters). The following HRV metrics were analyzed: min- and max-HR, longest-RR, SDNN, ASDNN5, SDANN5, and RMSDD. Statistically significant differences were observed between PHOX2B genotypes for min-HR and longest-RR (ps&amp;lt;0.05). Age by genotype interactions emerged such that certain metrics in HRV had different developmental trajectories by genotype (ps&amp;lt;0.05). Min-HR and longest-RR predicted eventual cardiac pacemaker implantation (AUCs&amp;gt;0.78). As for predictors of sinus pauses, different HRV metrics emerged as predictors across PHOX2B genotypes suggesting their utility in predicting cardiac pacemaker implantation dependent on genotype. Conclusion HRV in patients with CCHS is dependent on age and PHOX2B genotype, with significant differences in HRV metrics between patients with PHOX2B genotypes 20/25, 20/26, and 20/27 and the patients with 20/28-20/33 genotypes as well as those with NPARMs. Consistent with treatment guidelines, min-HR and longest-RR were predictive of eventual cardiac pacemaker implantation. Differences in the HRV metrics which predict sinus pauses as well as the overall group differences observed and trajectory-based differences may improve anticipatory management by earlier risk identification for prolonged sinus pauses in CCHS. Support (if any) None

P2834Diagnostic yield of holter recording after atrial fibrillation ablation - detection of asymptomatic recurrences during a one-year follow-up period

Abstract Background Strategies to detect recurrences after atrial fibrillation (AF) catheter ablation vary widely. Whereas a symptom-based approach may overestimate procedural success due to asymptomatic recurrences, continuous invasive monitoring with implantable devices may be refused by patients and is not routinely recommended. In trial settings, Holter monitoring is recommended at one year after ablation, though more frequent and intensive follow-up is encouraged for more accurate detection of arrhythmia recurrences. Purpose To study the diagnostic yield of Holter monitoring in the detection of asymptomatic recurrent arrhythmias after cryoballoon catheter ablation for AF. Methods Prospective registry on AF patients who underwent cryoballoon ablation with subsequent follow-up in our centre. Follow-up comprised routine (i.e. at 3, 6, and 12 months) and symptom-driven electrocardiographic (ECG) registrations after a three-month blanking period. In addition, patients were scheduled for six-day Holter monitoring shortly after the blanking period, at six months and at the end of the one-year follow-up period. For the current analysis, we studied the Holter recordings of the patients without previously detected arrhythmia recurrence and determined the proportion of asymptomatic recurrences at each respective monitoring period. Results We studied 364 patients with a median age of 60 years (IQR 54–66) and a median CHA2DS2-VASc score of 1 (IQR 1–2). One-year recurrences were documented in 119 (32.7%) patients, of which 90 were initially detected on Holter recording and 39 on ECG registrations (Table). A total of 34 patients did not report symptoms during the documentation of recurrent arrhythmia and comprised 28.6% (34/119) of all recurrences and 37.8% (34/90) of the Holter-detected recurrences. At the three-month Holter registration, 33.3% of the patients with recurrences did not report symptoms, which was 29.4% and 62.5% at the six- and twelve-month registrations, respectively (Figure). Timing and detection of recurrences Time after ablation 3 months 3–6 months 6 months 6–12 months 12 months Patients with Holter-detected recurrences 57/119 (47.9%) 17/119 (14.3%) 16/119 (13.4%) Patients with ECG-documented recurrences 18/119 (15.1%) 11/119 (9.2%) Proportions of asymptomatic recurrences Conclusions In this cohort of AF patients with serial six-day Holter monitoring after cryoballoon ablation, up to one-third of the patients had asymptomatic recurrences. Whereas Holter monitoring shortly after the blanking period detected nearly half of all one-year recurrences, the proportion of asymptomatic detected recurrences was higher in recordings at one year and seems therefore important in the detection of asymptomatic recurrences after catheter ablation.

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study

BackgroundAtrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy. ObjectivesThe goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF. MethodsThis multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months. ResultsA total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093). ConclusionsAF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741)

Abstract 79: 30-Day Cardiac Monitoring is Feasible and Effective in a Community Setting

Prolonged cardiac rhythm monitoring reveals atrial fibrillation (AF) in 16-42% of patients who undergo monitoring for up to 6 months after a cryptogenic stroke. The feasibility of prolonged cardiac monitoring, AF detection rates and the impact of earlier screening after suspected cardioembolic infarct in a community setting is unknown. Methods: This prospective study examined patient compliance and AF detection rates with prolonged cardiac monitoring started within 30 days of a stroke/TIA. 181 patients ≥ 55 years old with a suspected cardioembolic stroke/TIA that occurred in the preceding 30 days were referred for 30-day cardiac monitoring. Patients were educated about reasons for monitoring and test procedures for 15-20 minutes. A Spiderflash-t or Northeast DR 200 monitor, programmed for detecting AF, was used. Auto-triggered and patient-activated recordings obtained during two consecutive 15-day monitoring periods were assessed. Either 3-day serial ECG or ≥24h Holter monitor was also completed in 119/181 patients. The primary outcome was patient compliance with 30 days of monitoring. Secondary outcomes included detection of any duration of AF within the two monitoring periods. Results: The compliance rate for the full 30-day monitoring period was 98.9% (179/181). AF was detected on 30-day monitor in 11.6% (21/181) of patients. Of the patients who received both 3-day serial ECG or ≥24h Holter and 30-day monitoring, AF was only detected in 0.84% (1/119) with 3-day serial ECG and/or Holter monitoring vs. 14.3% (17/119) with 30-day monitoring. AF was detected in 76.2% (16/21) of patients in the first 15 day period. 14 patients had AF lasting longer than 6 minutes, 5 had AF lasting between 30 secs - 6 min and 2 had AF &lt; 30 secs. Of patients who completed the 30-day monitoring, 38.8% had AF recurring through the 30 days. 85.7% (18/21) of patients were switched to a novel oral anticoagulant (NOAC), while 3 patients died and thus could not be switched to a NOAC. In conclusion, 30-day cardiac monitoring is feasible in a community setting with high compliance rates, yields similar AF detection rates as seen in clinical trials and positively impacts patient management. There are missed opportunities for secondary stroke prevention in the community without 30-day monitoring.

Abstract 12250: Prediction of Patients With Chronic Heart Failure at Risk for Sudden Cardiac Death by Combination of Cardiac I-123 Metaiodobenzylguanidine Imaging and Long Runs of Non-Sustained Ventricular Tachycardia:a Serial Evaluation Study

Background: Identification of patients (pts) with chronic heart failure (CHF) at risk for sudden cardiac death (SCD) is an important objective. Cardiac I-123 metaiodobenzylguanidine (MIBG) imaging provides prognostic information in pts with CHF. On the other hand, long runs of non-sustained ventricular tachycardia (high-grade NSVT) has been associated with an increased risk of SCD in pts with coronary artery disease. However, there is little information available on the comparison of the prognostic significance for SCD between MIBG and high grade-NSVT in patients with CHF. Methods and Results: We studied 105 consecutive outpatients (NYHA class: 2.1±0.6), with LVEF 27%.High-grade NSVT was defined as consecutive 6 or more beats and more than 100 bpm. All pts underwent 24-hour ECG Holter monitoring and MIBG at the entry and every year after entry for three years. In the serial Holter monitoring, 32 pts had high-grade NSVT. At the last evaluation of MIBG study, 51 pts had abnormal WR. During the mean follow-up period of 5.1±3.5 years, 22 pts had SCD. A multivariate Cox analysis revealed that both abnormal WR and high-grade NSVT were significantly and independently associated with SCD (abnormal WR; hazard ratio 3.4 [95%CI 1.2-10.0], p = 0.025, high-grade NSVT; hazard ratio 3.3[95%Cl 1.3-8.2], p = 0.012). Pts with both abnormal WR and high-grade NSVT and those with either abnormal WR or high-grade NSVT had a significantly higher SCD risk than those with none of these parameters (47 [9/47] % vs 29 [13/45] % vs 0 [0/41] %, p&lt;0.0001). Conclusion: The combination of abnormal WR and high-grade NSVT would be more strongly associated with an increased risk of SCD in CHF pts.

Randomized controlled trial of vagal modulation by sham feeding in elective non-gastrointestinal (orthopaedic) surgery

Enhanced recovery, in part, aims to reduce postoperative gastrointestinal dysfunction (PGID). Acquired - or established- vagal dysfunction may contribute to PGID, even for surgery not involving the gastrointestinal tract. However, direct evidence for this is lacking. We hypothesized that chewing gum reduces morbidity (including PGID) by preserving efferent vagal neural activity postoperatively after elective orthopaedic surgery. In a two-centre randomized controlled trial (n=106), we explored whether patients randomized to prescribed chewing gum for five days postoperatively sustained less morbidity (primary outcome, defined by the Postoperative Morbidity Survey), PGID and faster time to become morbidity free (secondary outcomes). In a subset of patients (n=38), cardiac parasympathetic activity was measured by serial Holter monitoring and assessed using time and frequency domain analyses. Between September 2011 and April 2014, 106 patients were randomized to chewing gum or control. The primary clinical outcome did not differ between groups, with similar morbidity occurring between patients randomized to control (26/30) and chewing gum (21/28; absolute risk reduction (ARR):13% (95%C I:- 6-32); P=0.26). However, chewing gum reduced PGID (ARR:20% (95% CI: 1-38); P=0.049). Chewing gum reduced time to become morbidity-free (relative risk (RR): 1.62 (95% CI: 1.02-2.58); P=0.04) and was associated with a higher proportion of parasympathetic activity contributing to heart rate variability (11% (95% CI: 1-20); P=0.03). Chewing gum did not alter overall morbidity, but reduced PGID. These data show for the first time that prescription of sham feeding preserves vagal activity in surgery not directly involving the gastrointestinal tract. ISRCTN20301599.

Long-Term Effect of Continuing Sports Activity in Competitive Athletes With Frequent Ventricular Premature Complexes and Apparently Normal Heart

The long-term outcome of athletes with frequent ventricular premature complexes (VPCs) and apparently normal heart has not been fully clarified. To evaluate the clinical and prognostic significance of VPCs and the influence of continuing sports activity during follow-up, we studied 120 healthy athletes (96 men; median age 16 years) in whom frequent VPCs (>100 VPCs/24 hours) were discovered by chance during preparticipation screening. All athletes were followed up for a median of 84 months. During follow-up, 96 underwent serial 24-hour Holter recording and 62 underwent serial echocardiography. The median number of VPCs/24 hours on basal Holter was 3,760. During follow-up, 81 athletes continued sports activity, whereas 39 did not. No athlete died or developed overt heart disease. The median number of VPCs/24 hours decreased in both athletes who continued sports activity and those who did not (from 3,805 to 1,124, p <0.0001 and from 5,787 to 1,298, p <0.0001, respectively). During follow-up, left ventricular ejection fraction slightly decreased to <55% in 9 of 62 athletes who, in respect to the remaining 53, had more VPCs/24 hours both in the basal state (12,000 vs 3,880) and during follow-up (10,702 vs 1,368), and a longer follow-up (95 vs 36 months). In conclusion, (1) frequent VPCs in athletes without heart disease have a long-term benign prognostic significance, (2) sporting activity does not modify this benign outcome, (3) during follow-up, the burden of VPCs decreases whether or not subjects continue sports activity, and (4) in 14.5% of athletes, ejection fraction slightly decreases over time.

Wireless remote monitoring of reconstructed 12-lead ECGs after ablation for atrial fibrillation using a hand-held device

ObjectiveAtrial fibrillation (AF) surveillance using a wireless handheld monitor capable of 12-lead electrocardiogram reconstruction was performed, and arrhythmia detection rate was compared with serial Holter monitoring. MethodsTwenty-five patients were monitored after an AF ablation procedure using the hand-held monitor for 2 months immediately after and then for 1 month approximately 6 months postablation. All patients underwent 12-lead 24-hour Holter monitoring at 1, 2, and 6 months postablation. ResultsDuring months 1-2, 425 of 2942 hand-held monitor transmissions from 21 of 25 patients showed AF/atrial flutter (Afl). The frequency of detected arrhythmias decreased by month 6 to 85/1128 (P < .01) in 15 of 23 patients. Holter monitoring diagnosed AF/Afl in 8 of 25 and 7 of 23 patients at months 1-2 and month 6, respectively (P < .01 compared with wireless hand-held monitor). Af/Afl diagnosis by wireless monitoring preceded Holter detection by an average of 24 days. ConclusionsWireless monitoring with 12-lead electrocardiogram reconstruction demonstrated reliable AF/Afl detection that was more sensitive than serial 12-lead 24-hour Holter monitoring.

Serial Holter ST-Segment Monitoring after First Acute Myocardial Infarction

Based on serial Holter monitoring performed 7 times within 3 years after a first acute myocardial infarction, we assessed the prevalence, variability and long-term clinical importance of transient myocardial ischemia (TMI) defined as episodes of ambulatory ST-segment depression. In all, 121 consecutive male patients <70 years old were studied. The prevalence of TMI on different Holter recordings varied around 20% ranging between 18 and 27%. Fifty-five of the patients (46%) had TMI on at least 1 of the 7 Holter recordings. Considerable variability was found within and between patients for the presence of TMI. No high-risk group for cardiac death, nonfatal reinfarction or coronary revascularization during up to 10 years of follow-up could be identified by the detection of TMI. From these results we conclude that a routine search for TMI on serial Holter monitoring cannot be recommended in male survivors of an uncomplicated first acute myocardial infarction.

Lack of proarrhythmia as assessed by Holter monitor after atrial radiofrequency ablation of supraventricular tachycardia in children

The purpose of this study was to assess the short-term arrhythmogenicity of atrial radiofrequency (RF) ablation lesions in children. Patients with the greatest exposure to RF energy comprised the study group. Holter data on 35 RF ablation procedures in 31 patients with a median age of 13.2 years (range 3 months to 20 years) was retrospectively analyzed. Patients received an average of 19.9 (SD = 13.6) RF lesions, all delivered by an atrial approach. Supraventricular ectopy and ventricular ectopy were compared immediately before and after and 4 to 9 weeks after RF ablation by serial Holter monitoring. Factors thought to possibly predispose patients to a proarrhythmic effect were used to define subgroups for separate analysis. No increase in ambient supraventricular ectopy or ventricular ectopy was observed either immediately after or 4 to 9 weeks after RF ablation compared with the baseline Holter recordings. Children exposed to relatively large doses of RF energy may demonstrate transient and asymptomatic nonsustained tachycardias in the short term. However, no new sustained tachycardias and no increase in supraventricular or ventricular ambient ectopy are detected by short-term Holter monitoring.

Nonreentrant Mechanisms Underlying Spontaneous Ventricular Arrhythmias in a Model of Nonischemic Heart Failure in Rabbits

The goal of this study was to define the mechanisms of spontaneously occurring ventricular arrhythmias in the setting of nonischemic heart failure. Three-dimensional cardiac mapping from 232 intramural sites was performed in four rabbits with heart failure induced by combined aortic regurgitation and aortic stenosis and in four control rabbits. During the development of heart failure, serial echocardiographic examination demonstrated a progressive increase in left ventricular (LV) chamber dimensions and a decrease in LV systolic function over 19 +/- 2 months. Serial Holter monitoring demonstrated spontaneously occurring premature ventricular complexes (PVCs) (up to 13,000 per day) and couplets in all four rabbits with heart failure, and runs of nonsustained ventricular tachycardia (VT) up to 26 beats long in three. Mapping of spontaneous rhythm was performed for up to 60 minutes. None of the control rabbits demonstrated spontaneous arrhythmias during mapping. Three rabbits with heart failure demonstrated isolated PVCs, and two demonstrated couplets and runs of nonsustained VT up to 4 beats long. The three-dimensional activation sequence of 50 sinus beats (42 from rabbits with heart failure; 8 from control rabbits), 19 PVCs, and 37 beats of couplets and nonsustained VT was determined and the mechanism of arrhythmia defined for all ventricular ectopic beats analyzed. Normal sinus beats from the failing rabbits activated rapidly, with a total activation time of 28 +/- 1 ms (P = .18 versus sinus beats from control hearts, 26 +/- 1 ms). Sinus beats preceding PVCs in the rabbits with heart failure activated in a similar fashion, with a total activation time of 26 +/- 1 ms. In each case, these PVCs initiated in the subendocardium by a nonreentrant mechanism based on the absence of intervening electrical activity between the termination of the preceding beat and the initiation of the next (225 +/- 7 ms), despite the presence of multiple intervening electrode recording sites. Couplets and monomorphic and polymorphic VTs were due to repetitive nonreentrant activation at the same or different subendocardial sites. Total activation time of beats of VT averaged 44 +/- 1 ms and did not differ from that of isolated PVCs (43 +/- 2 ms, P = .65). Pathological analysis of tissue demonstrated myocardial fiber hypertrophy, degenerative changes, and interstitial fibrosis throughout the failing hearts. Spontaneously occurring PVCs, couplets, and VT in a model of nonischemic heart failure are due to nonreentrant mechanisms such as triggered activity or abnormal automaticity. Approaches to the treatment of spontaneously occurring ventricular arrhythmias in patients with nonischemic heart failure should be directed at nonreentrant mechanisms.

ESVEM and the Hazards of Clinical Trials

During the past 15 years, our approach to patients with cardiovascular disease has undergone significant and often dramatic changes. These changes have primarily occurred as a result of large-scale multicenter clinical trials involving many patients and extending over several years. One such trial is the ESVEM study,1 which was initiated in 1985, involved 14 centers, screened more than 2000 patients, and ultimately enrolled 486 patients with life-threatening ventricular arrhythmias. The trial had two major purposes: (1) to determine whether serial electrophysiological testing or serial Holter monitoring provided the better method of predicting the long-term therapeutic efficacy of antiarrhythmic drugs and (2) to determine which of the six antiarrhythmic drugs tested was most effective. In this issue of Circulation , Reiter and coworkers2 report on results obtained in a subgroup of 146 patients who were among the 242 patients comprising the electrophysiological arm of the ESVEM trial. In this subgroup of 146, Holter monitoring was also performed. The authors report that the therapeutic efficacy of the various drugs was no greater when predicted by both tests (concordant results) than when predicted by only one of the two tests (discordant results). Although not specifically stated, the hypothesis being tested was that the ability of a drug to suppress the arrhythmia trigger (as reflected by the suppression of the ventricular premature beats recorded by Holter monitoring) and to alter the arrhythmia substrate (as reflected by the inability to induce ventricular tachycardia by electrophysiological testing) should predict better long-term efficacy than the ability to accomplish either alone. This hypothesis makes intuitive sense if we assume that both the trigger and the substrate remain unchanged for the duration of the …

Angiotensin-Converting Enzyme Inhibition During Thrombolytic Therapy in Acute Myocardial Infarction

The adjunctive use of angiotensin-converting enzyme (ACE) inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation, and increase prostacyclin and bradykinin levels. In the chronic phase, remodeling may be attenuated. At present, a large number of controlled clinical trials mainly focusing on the effects of ACE inhibition in the chronic phase is underway. Only a few studies concentrate on the effect of acute intervention with ACE inhibitors in ischemia-reperfusion, i.e., thrombolysis in myocardial infarction. In the Captopril and Thrombolysis pilot Study (CAT pilot study), 3 and 6.25 mg of captopril was well tolerated as adjunctive therapy to intravenous streptokinase. The decrease in mean arterial blood pressure (36 +/- 11%) after 6.25 mg was comparable to the control group (30 +/- 7%). Furthermore, norepinephrine levels decreased dose dependently to 47 +/- 6 and 38 +/- 7% from baseline, respectively. These results prompted a large nationwide acute intervention trial with captopril in 300 patients receiving thrombolytic therapy: the Captopril and Thrombolysis Study (CATS). The primary hypothesis of CATS supposes a very early effect of converting enzyme inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion. This will be evaluated by serial echocardiography, Holter monitoring, and neurohumoral measurements immediately upon thrombolysis and during the first year after myocardial infarction. Blinded data show a favorable blood pressure response, with systolic hypotension <100 mm Hg occurring in only 0.8% of patients.

The use of ambulatory monitoring in the prognostic evaluation of patients with sustained ventricular tachycardia treated with amiodarone.

We recently reported a retrospective experience with serial Holter monitoring as a guide to therapy in patients with sustained ventricular tachycardia treated with amiodarone. To confirm and substantiate these findings, a prospective study was designed that included baseline 24 hr Holter monitoring and serial Holter monitoring after 1 week of therapy with amiodarone. Fifty-two patients with documented sustained ventricular tachycardia who manifest nonsustained ventricular tachycardia on baseline Holter monitoring were treated with amiodarone. Thirty-four patients (group I) had nonsustained ventricular tachycardia completely suppressed and 18 patients (group II) had continued nonsustained ventricular tachycardia on serial Holter monitoring performed on days 8, 9, and 10 of therapy. At 11.6 +/- 1.0 (mean +/- SE) months follow-up, three (9%) group I patients and 12 (67%) group II patients had recurrent sustained ventricular tachycardia or sudden cardiac death (p less than .01). The sensitivity, specificity, positive and negative predictive value, and predictive accuracy of ventricular tachycardia on 24, 48, and 72 hr Holter monitoring over days 8, 9, and 10 for predicting recurrent sustained ventricular tachycardia or sudden cardiac death were analyzed. The positive and negative predictive values were 89% and 84%, 69% and 89%, and 67% and 91% for 24, 48, and 72 hr Holter monitoring, respectively. Overall predictive accuracy was 85%, 83%, and 83%, respectively. We conclude that early Holter monitoring is useful in assessing the clinical efficacy of amiodarone in patients with sustained ventricular tachycardia who manifest nonsustained ventricular tachycardia on baseline Holter monitoring.

Antitachycardia Strategies

The development of an antitachycardia strategy requires a cascade of assessments and decisions. The patient's problem and level of risk must be assessed in order to determine the goals of therapy. Empirical therapy is appropriate in low-risk situations, and during that ultimate emergency, the treatment of cardiac arrest. Quantitative objective assessment of therapeutic efficacy is indicated in most other situations. Such assessments may be primarily passive, such as recording of drug blood levels or serial Holter monitoring; or provocative, as in serial electrophysiologic, exercise, or psychological stress testing. Selection of an antiarrhythmic modality requires a balance between the risk of therapy and the risks related to the arrhythmia. Any antitachycardia strategy must also consider relative costs, and regulatory and reimbursement policies.

Sudden sinus slowing with junctional escape: a common mode of initiation of juvenile supraventricular tachycardia.

After noting bradycardia-induced supraventricular tachycardia (SVT) in two successive children with SVT, we analyzed Holter monitor recordings done on 66 children with suspected or proved SVT. Ten children had apparent reentry SVT. The most common mode of initiation (eight of 10 patients) was not premature atrial beats, but sudden sinus pause with a junctional escape beat (JEB), usually fused with the delayed sinus P wave, initiating the tachycardia. Electrophysiologic studies in five children who had this mode of initiation showed evidence of reentry in four, possibly by dual atrioventricular nodal (AVN) pathways. Since sudden sinus pause and JEB are relatively uncommon in adults, the disappearance of this phenomenon with age may be the most significant reason why children often have less tachyarrhythmia as they get older. Both propranolol and digoxin significantly increased the numbers of episodes of SVT in the three patients tested with serial Holter monitoring.