Purpose: Endomyocardial biopsy is invasive and has low sensitivity to detect Antibody-Mediated Rejection (AMR) and Acute Cellular Rejection (ACR). Plasma donor-derived cell-free DNA (ddcfDNA) measured by shotgun sequencing and SNP analysis is a non-invasive assay, with excellent sensitivity but poor specificity. AMR and ACR affect different allograft compartments via distinct molecular pathogenesis, suggesting distinct cfDNA sources and thus epigenomics. Here, we combine SNP analysis and cell-free chromatin immunoprecipitation sequencing (cfChIP-Seq) to improve cfDNA diagnostic performance.

BACKGROUND Little is known of the variations of the heart rate during spontaneous cardioinhibitory neurally-mediated syncope. Their knowledge has both academic and practical implications for the optimization of rate drop response (RDR) pacing mode. METHODS AND RESULTS We describe variations of the rhythm occurring during 48 syncopal episodes documented by implantable loop recorder. The presyncopal phase of 18 s (interquartile range 9-65) was characterized by a fall in heart rate from 83 +/- 20 bpm to maximal bradycardia or (multiple) asystolic pauses which lasted a median of 19 s (10-30). The recovery phase lasted 22 s (7-52). The total duration of the cardioinhibitory reflex was 85 s (47-116). We then calculated the potential increase in benefit that an optimally programmed drop rate detection could provide compared with a reference Lower Rate detection. Compared with Lower Rate detection (defined as two consecutive beats at 40 bpm), drop rate detection (assumed to be drop size = 20 bpm, detection window = 1 min, and drop rate = 50 bpm) would have been able to introduce intervention pacing, a median of 5.7 s (interquartile range -5.1- -10.4) earlier in 28 cases (58%). CONCLUSION Cardioinhibitory neurally-mediated reflex varies widely from a few seconds to some minutes. In our data the total duration was <2 min. Optimal RDR programming, being potentially able to anticipate the detection of the cardioinhibitory reflex by a few seconds, could provide an increase in benefit for cardiac pacing therapy in prevention of syncope.

Einleitung: Das Schlafapnoe-Syndrom (SAS) ist durch ein erhöhtes kardiovaskuläres Risiko charakterisiert. Garrigue, et al. 2002 berichten erstmalig über den Effekt einer nächtlichen Überstimulierung (Nocturnal Overdrive Pacing, NOP) auf den Apnoe-Hypopnoe-Index (AHI) bei Patienten mit einem DDD Schrittmacher. Ziel unserer Studie war die Analyse von Anzahl und Dauer der Apnoen/Hypopnoen bei SAS Patienten während Zweikammer oder atrialem Overdrive Pacing im Vergleich zum normalen Schrittmachermodus bei Spontanrhythmus.

Dual chamber pacing has proven beneficial in patients with sudden drops in heart rate as seen in vasovagal syncope and carotid sinus syndrome. Newer algorithms for faster detection of an insidious drop in heart rate and short lasting intervention pacing at a high rate, as in the rate drop response algorithm in the Medtronic Kappa series of pacemakers, might improve the effect of pacing. Two case reports, that demonstrate the use of these rate drop response algorithms, are presented. A 24-year-old woman with recurrent episodes of syncope and repeated tilt-table tests with vasovagal cardioinhibitory outcomes had a Medtronic Kappa 400 pacemaker implanted. Syncope was abolished during repeat tilt-table testing following pacemaker implantation and proper functioning of the rate drop response algorithm. The patient has been free of syncope during follow-up apart from a single episode that occurred due to neglect of vasovagal warning symptoms. A 52-year-old man with coronary artery disease developed recurrent blackouts. Carotid sinus massage resulted in 5.5 s of asystole and presyncope. A Medtronic Kappa 700 pacemaker with a rate drop response algorithm was implanted and the patient became asymptomatic. The rate drop response algorithm is discussed in detail based upon the case reports, and recommendations are given for the use of this algorithm in patients with vasovagal syncope and carotid sinus syndrome.

We have developed an algorithmic method for automatic determination of stimulation thresholds in both cardiac chambers in patients with intact atrioventricular (AV) conduction. The algorithm utilizes ventricular sensing, may be used with any type of pacing leads, and may be downloaded via telemetry links into already implanted dual‐chamber Thera® pacemakers. Thresholds are determined with 0.5 V amplitude and 0.06 ms pulse‐width resolution in unipolar, bipolar, or both lead configurations, with a programmable sampling interval from 2 minutes to 48 hours. Measured values are stored in the pacemaker memory for later retrieval and do not influence permanent output settings. The algorithm was intended to gather information on continuous behavior of stimulation thresholds, which is important in the formation of strategies for programming pacemaker outputs. Clinical performance of the algorithm was evaluated in eight patients who received bipolar tined steroid‐eluting leads and were observed for a mean of 5.1 months. Patient safety was not compromised by the algorithm, except for the possibility of pacing during the physiologic refractory period. Methods for discrimination of incorrect data points were developed and incorrect values were discarded. Fine resolution threshold measurements collected during this study indicated that: (1) there were great differences in magnitude of threshold peaking in different patients; (2) the initial intensive threshold peaking was usually followed by another less intensive but longer‐lasting wave of threshold peaking; (3) the pattern of tissue reaction in the atrium appeared different from that in the ventricle; and (4) threshold peaking in the bipolar lead configuration was greater than in the unipolar configuration. The algorithm proved to be useful in studying ambulatory thresholds.

Pacing and Clinical ElectrophysiologyVolume 20, Issue 3 p. 751-752 Opening Remarks: Neurocardiogenic Syncope, an International Symposium, September 1996 DAVID G. BENDITT, Corresponding Author DAVID G. BENDITTAddress for reprints: David G. Benditt, M.D., Cardiac Arrhythmia Center, University of Minnesota Medical School, Box 508 UMHC, Minneapolis, MN 55455. Fax: (612) 624-4937.Search for more papers by this authorMARK ERICKSON, MARK ERICKSONSearch for more papers by this authorMICHAEL D. GAMMAGE, MICHAEL D. GAMMAGESearch for more papers by this authorTOBY MARKOWITZ, TOBY MARKOWITZSearch for more papers by this authorRICHARD SUTTON, RICHARD SUTTONSearch for more papers by this author DAVID G. BENDITT, Corresponding Author DAVID G. BENDITTAddress for reprints: David G. Benditt, M.D., Cardiac Arrhythmia Center, University of Minnesota Medical School, Box 508 UMHC, Minneapolis, MN 55455. Fax: (612) 624-4937.Search for more papers by this authorMARK ERICKSON, MARK ERICKSONSearch for more papers by this authorMICHAEL D. GAMMAGE, MICHAEL D. GAMMAGESearch for more papers by this authorTOBY MARKOWITZ, TOBY MARKOWITZSearch for more papers by this authorRICHARD SUTTON, RICHARD SUTTONSearch for more papers by this author First published: 30 June 2006 https://doi.org/10.1111/j.1540-8159.1997.tb03900.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume20, Issue3March 1997Pages 751-752 RelatedInformation

This study examined the effectiveness of cardiac pacing using the Thera DR rate‐drop response algorithm for prevention of recurrent symptoms in patients with carotid sinus syndrome (CSS) or vasovagal syncope. The algorithm comprises both diagnostic and treatment elements. The diagnostic element consists of a programmable “window” used to identify heart rate changes compatible with an evolving neurally mediated syncopal episode. The treatment arm consists of pacing at a selectable rate and for a programmable duration. Forty‐three patients (mean age 53 ± 20.4 years) with CSS alone (n = 8), CSS in conjunction with vasovagal syncope (n = 4), or vasovagal syncope alone (n = 31) were included. Thirty‐nine had recurrent syncope, while the remaining four reported multiple presyncopal events. Prior to pacing, 40 ± 152 syncopal episodes (range from 1 to approximately 1,000 syncopal events) over the preceding 56 ± 84.5 months. Postpacing follow‐up duration was 204 ± 172 days. Three patients have been lost to follow‐up and in one patient the algorithm was disabled. Among the remaining 39 individuals, 31 (80%) indicated absence or diminished frequency of symptoms, or less severe symptoms. Twenty‐three patients (23/29, or 59%) were asymptomatic with respect to syncope or presyncope. Sixteen patients had symptom recurrences. Of these, seven experienced syncope (7/39, or 18%) and 9 (29%) had presyncope: the majority of patients with recurrences (6/7 syncope and 7/9 presyncope) were individuals with a history of vasovagal syncope. Consequently, although symptoms were observed during postpacing follow‐up, they appeared to be of reduced frequency and severity. Thus, our findings suggest that a transient period of high rate pacing triggered by the Thera DR rate‐drop response algorithm was beneficial in a large proportion of highly symptomatic patients with CSS or vasovagal syncope.

Activity-triggered, rate-variable pacing systems offer a wide range of pacemaker patients the benefits of an appropriate paced chronotropic response. However, optimizing settings for these devices often entails treadmill exercise testing. To assess simpler procedures for predicting appropriate settings, pacing rates of "strapped-on" and implanted Activitrax pacemakers were evaluated during arm exercise, walk-in-place exercise and treadmill exercise (0% slope at 1.5, 2.0 and 3.0 mph). For exercise of similar duration, steady-state pacing rates of implanted devices during arm and walk-in-place exercise were lower than those achieved during treadmill exercise. Linear regression analysis resulted in the slope of these relations most closely approaching 1.0 for arm exercise at "low" activity threshold, while walk-in-place tended to result in slopes approaching 1.0 at all activity thresholds. Similarly, although strapped-on devices underestimated rates obtained with implanted devices, differences fell within a narrow range (-6 to -14%). Thus, in patients with implanted or strapped-on Activitrax pacemakers, relatively simple exercise procedures suitable for office or clinic environment may be useful to provide an estimate of pacing rates during physical activity, and may thereby facilitate selection of appropriate programmable settings.

In the present study a multiprogrammable, atrial synchronous, ventricular inhibited pacemaker (Enertrax) was used in six patients. This pacer makes it possible to evaluate pacemaker performance non-invasively and facilitates the correct interpretation of the difficult ECGs produced by these complex pacemakers.