Normal Atrioventricular Conduction Research Articles

Pacing mode survival in patients with single chamber atrial pacemaker for sinus node dysfunction

BackgroundSingle chamber atrial pacemaker should be sufficient for patients with sinus node dysfunction (SND) with normal atrioventricular (AV) conduction. However, most patients undergo dual chamber pacemaker implantation because of concern of new onset AV block. The annual incidence of new AV block has been reported from 0.6 to 4.4 % in various studies. ObjectivesOur aim is to assess mode survival in sinus node dysfunction with normal AV conduction patients implanted with AAIR. MethodsPatients who underwent single chamber atrial pacemaker implantation for SND with normal AV conduction between January 2014 and December 2021 were followed up for pacemaker device change, new onset AV block, bundle branch block, atrial fibrillation (AF), lead complications, reoperation and mortality rate. ResultsA total of 113 patients underwent single chamber atrial pacemaker implantation for SND during the study period. Mean age was 55.6 ± 12.7 years. During a mean follow up of 48.7 ± 24.9 months, none of the patients required pacemaker device change to VVIR/DDDR. Nine patients underwent reoperation, 5 for lead dislodgment, 1 for high threshold, 1 for pocket site erosion and 3 for pulse generator change. None developed AV block or AF with slow ventricular rate. Only 4 patients developed AF (3 paroxysmal,1 permanent). There were 3 deaths during follow up and none were sudden deaths. ConclusionSingle chamber atrial pacing is an acceptable mode of pacing in patients with SND in developing countries. Development of AV conduction abnormalities is rare in this relatively younger population.

Adaptive versus conventional cardiac resynchronisation therapy in patients with heart failure (AdaptResponse): a global, prospective, randomised controlled trial

Continuous automatic optimisation of cardiac resynchronisation therapy (CRT), stimulating only the left ventricle to fuse with intrinsic right bundle conduction (synchronised left ventricular stimulation), might offer better outcomes than conventional CRT in patients with heart failure, left bundle branch block, and normal atrioventricular conduction. This study aimed to compare clinical outcomes of adaptive CRT versus conventional CRT in patients with heart failure with intact atrioventricular conduction and left bundle branch block. This global, prospective, randomised controlled trial was done in 227 hospitals in 27 countries across Asia, Australia, Europe, and North America. Eligible patients were aged 18 years or older with class 2-4 heart failure, an ejection fraction of 35% or less, left bundle branch block with QRS duration of 140 ms or more (male patients) or 130 ms or more (female patients), and a baseline PR interval 200 ms or less. Patients were randomly assigned (1:1) via block permutation to adaptive CRT (an algorithm providing synchronised left ventricular stimulation) or conventional biventricular CRT using a device programmer. All patients received device programming but were masked until procedures were completed. Site staff were not masked to group assignment. The primary outcome was a composite of all-cause death or intervention for heart failure decompensation and was assessed in the intention-to-treat population. Safety events were collected and reported in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02205359, and is closed to accrual. Between Aug 5, 2014, and Jan 31, 2019, of 3797 patients enrolled, 3617 (95·3%) were randomly assigned (1810 to adaptive CRT and 1807 to conventional CRT). The futility boundary was crossed at the third interim analysis on June 23, 2022, when the decision was made to stop the trial early. 1568 (43·4%) of 3617 patients were female and 2049 (56·6%) were male. Median follow-up was 59·0 months (IQR 45-72). A primary outcome event occurred in 430 of 1810 patients (Kaplan-Meier occurrence rate 23·5% [95% CI 21·3-25·5] at 60 months) in the adaptive CRT group and in 470 of 1807 patients (25·7% [23·5-27·8] at 60 months) in the conventional CRT group (hazard ratio 0·89, 95% CI 0·78-1·01; p=0·077). System-related adverse events were reported in 452 (25·0%) of 1810 patients in the adaptive CRT group and 440 (24·3%) of 1807 patients in the conventional CRT group. Compared with conventional CRT, adaptive CRT did not significantly reduce the incidence of all-cause death or intervention for heart failure decompensation in the included population of patients with heart failure, left bundle branch block, and intact AV conduction. Death and heart failure decompensation rates were low with both CRT therapies, suggesting a greater response to CRT occurred in this population than in patients in previous trials. Medtronic.

Pseudo-pacemaker syndrome with prolonged PR interval: A narrative review.

Pseudo-pacemaker syndrome (PPMS) is a rare complication of first-degree atrio-ventricular (AV) block in which a very prolonged PR interval causes AV dyssynchrony and subsequent symptoms of hemodynamic instability in the absence of an implanted pacemaker. The aim of this manuscript was to describe a unique case of PPMS and to provide a comprehensive review of the topic to help clinicians in the diagnosis and management of this condition. Through systematic research on PubMed, Google Scholar, EBSCO, and Ovid MEDLINE and using the search strings "pseudo-pacemaker syndrome" and "symptomatic first-degree AV block," we identified 14 articles accounting for 17 cases of PPMS, including our case report. The most common age group for PPMS was middle-aged and young adults, with an average age of 47 years. Palpitations were the most common presenting symptom and four main etiologies of PPMS were identified, as follows: (1) Idiopathic PPMS with evidence of impaired conduction over the AV node (20% of cases), (2) PPMS associated with reversable inflammatory causes (13%) or (3) associated with iatrogenic surgical or interventional procedures leading to the permanent damage of the normal AV conduction system (20%), and, finally, (4) PPM related to dual AV nodal physiology (DAVNP) as a primary finding (27%) or occurring after fast or slow pathway ablation for treatment of AV nodal re-entrant tachycardia (AVNRT) (20%). Treatment should be patient-tailored and based on the specific etiology once identified. However, the treatment of PPMS due to DAVNP without AVNRT presentation is yet to be clarified.

Doppler-derived cardiac performance and evaluation of alternative measures of AV conduction to predict unvfavuorable haemodynamics in patients with long PR (DEEPER PR Study)

Abstract Funding Acknowledgements Type of funding sources: None. Background Prolonged atrio-ventricular (AV) conduction has been shown to compromise cardiac performance. Long PR relates to unfavorable clinical outcome and even increased mortality. The PR interval is traditionally used to describe AV conduction, but this parameter comprises inter-atrial and AV conduction delays and may therefore not optimally reflect hemodynamic consequences of prolonged AV conduction. Ventricular conduction delay also impacts ventricular filling and cardiac performance, while delayed inter-atrial activation may alleviate LV hemodynamic compromise. It is unknown, which parameter of AV conduction relates closest to cardiac performance. The objective of this study is to characterize segments of the PR interval in patients with long PR vs. matched controls with normal PR and to investigate the association of various measures of AV conduction to Doppler-derived cardiac performance. Methods 52 hospitalized pts with AVB I° (group A), and 52 controls (matched according to age, gender, LVEF, group B) were studied in detail by digitalized 12 lead ECG and 2-D, Doppler, and tissue Doppler echocardiography. Segments of PR were compared between matched groups. Seven measures of AV conduction were correlated to LV and RV filling fraction, total isovolumic times, and Tei indices and ranked by logistic regression and ROC-AUC in the combined patient cohort. Results PR was 227.5 (212;251)ms (A) vs. 182 (164;190)ms (B); p<0.001). P wave duration was 127(114;136)ms (A) vs. 113(102.5;126.8)ms (B); p<0.001 with longer RA and LA activation in group A. Reduced LV filling fraction (PQ Δ0.045, PePV6 Δ0.050, AUC 0.681 vs. 0.719), prolonged combined LV isovolumic times (PR: Δ19ms, 15.8%, PePV6: Δ31ms, 26.9%, AUC 0.619 vs 0.698), and higher LV Tei indices (PR: Δ0.045, 10.3%, PePV6: Δ0.083, 19.8%, AUC 0.566 vs 0.626) were best predicted by the variable PePV6 (interval between the end of P in V1 and Rpeak in V6) according to bivariate correlations, logistic regression analyses, and ROC-AUC. Applying PePV6 instead of PR re-categorized 20% of pts as having prolonged vs normal AV conduction. Prolonged PePV6 was also best suited to predict worse RV hemodynamics. Although significant linear correlations were demonstrated, a non-linear component of the association between AV timing and LV filling appeard to be present with pronounced impairment of cardiac performance beyond the 3rd quartile of PePV6 (148ms), respectively. Conclusion Prolonged PR comprises prolonged atrial activation (30%) and delayed AV conduction (70%). In this study, PePV6, a novel parameter eliminating P wave duration and accounting for initial LV activation, was best suited to identify compromise of Doppler-derived LV and RV hemodynamics by delayed AV conduction. PePV6 prolongation beyond the 3rd quartile may particularly affect cardiac performance. These findings inform future clinical studies and should give rise to investigation of PePV6 in larger patient populations.

P221 ASSOCIATION BETWEEN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE AND A SEVERE DILATED CARDIOMYOPATHY: A CASE REPORT

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 and PKD2 genes, encoding polycystin 1 and 2. We report the case of a 51–year–old woman with arterial hypertension and stage V chronic kidney disease from polycystic kidney disease, without a significant family health history. She was admitted to our Cardiology Ward for worsening dyspnea, dependent oedemas and a 3/6 systolic heart murmur detected. Blood tests showed mild anemia and hyperkalemia, severe renal failure (creatinine 6 mg/dl) and normal both liver and thyroid function. The ECG showed sinus rhythm with normal atrioventricular conduction, low voltage in precordial leads and non–specific repolarization disturbances. Hemodialysis and intravenous decongestion therapy were started. A transthoracic two–dimensional echocardiography was performed and a dilated left ventricle with severe global systolic dysfunction (EF 25%) was documented, with severe secondary mitral regurgitation (MR) with a central jet (EROA 0,5 cm2). A possible bicuspid aortic valve was suggested with moderate aortic regurgitation. CT scans showed small pleural and pericardial effusions, polycystosis affecting both kidneys and liver. Coronary CT showed a subcritical interventricular artery stenosis and confirmed a bicuspid aortic valve. Magnetic resonance angiography was negative for intracranial aneurysms. Finally, genetic testing revealed a heterozygous pathogenic mutation of PKD1 gene (c.9622del G p.Ala3208Hisfs*108 exone 28). Maximum tolerated heart failure therapy was prescribed after discharge, resulting in symptoms reduction but only mild echocardiographic improvement (EF 30% with severe MR). An edge–to–edge transcatheter mitral valve repair was proposed. In literature we learn that PKD1 mutations are linked to various cardiomyopathies: hypertrophic, dilated, left ventricular non compaction. We report the association of ADPKD with a complex dilated cardiomyopathy with severe secondary MR, an aortic congenital defect and an associated subcritical coronary artery stenosis. Further investigations are needed to study the genetic aspect of the ADPKD when associated with different cardiac anomalies.

P349 EARLY DIAGNOSIS OF HEREDITARY CARDIAC AMYLOIDOSIS(ATTRV) IN A CARRIER: WHEN IS ENDOMYOCARDIAL BIOPSY INDICATED?

Abstract Background Hereditary transthyretin amyloidosis (ATTRv) is a rare, adult–onset, autosomal dominant genetic disorder caused by mutations in the TTR gene. The growing availability of effective therapies determining a greater benefit the earlier they start, highlights the importance of identifying cardiac involvement even in the absence of left ventricular hypertrophy. Clinical Case A 58–year–old man came to our observation for exertional dyspnea and received a diagnosis of hereditary transthyretin amyloidosis (Val142Leu). Family screening led to the identification of the 56–year–old brother who was carrier of the same mutation. This patient was symptomatic for palpitations. Blood tests, including cardiac Troponin and NTproBNP, were normal. The ECG showed sinus rhythm, with normal atrioventricular and intraventricular conduction but frequent premature ventricular contractions. Transthoracic echocardiogram was normal, including strain rate evaluation. In order to identify early cardiac involvement, the patient underwent cardiac magnetic resonance imaging and biphosphonate scintigraphy that were negative for cardiac involvement. Neurological examination showed initial bilateral carpal tunnel syndrome. Due to the presence of premature ventricular contractions, the patient underwent to an endomyocardial biopsy which unpredictably showed a slight focal positivity to Congo Red staining, and immunohistochemistry confirmed a slight focal positivity for transthyretin. Therefore, the patient started therapy with Tafamidis. At 12–month follow up cardiac scintigraphy was still negative as well as ventricular thickness resulted within normal limits. Conclusion This case shows that in ATTR mutation carriers, an initial cardiac involvement can be present even in the absence of left ventricular hypertrophy and positive bisphosphonate scintigraphy. In the presence of clinical symptoms and/or suspicious signs of disease, such as arrhythmias, an endomyocardial biopsy may be indicated in order to start disease modifying therapy earlier.

Clinical, electrocardiographic, and echocardiographic parameters associated with the development of pacing and implantable cardioverter-defibrillator indication in patients with transthyretin amyloid cardiomyopathy.

This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients. This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16-32. According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.

Update in LV Only Fusion CRT Pacing: Annals and Future Perspectives.

Triple-chamber cardiac devices are utilized for cardiac resynchronization therapy (CRT) and is the standard-of-care therapy for heart failure (HF) patients in the current guidelines. In the setting of biventricular (BIV) pacing it involves a mandatory implantation of right ventricular (RV) lead that allows simultaneous BIV pacing with 0 ms VV (ventricular to ventricular) interval. Nevertheless, it seems that response to CRT is not related to RV lead position. RV pacing is known for deleterious effects on RV/Left Ventricle (LV) function and should not be used in persons with normal atrioventricular conduction (AV) and sinus rhythm. As it compensates for the additional asynchrony induced by unnecessary stimulation of RV pacing, only pacing the left ventricle (LV) may result in improved cardiac resynchronization therapy (CRT) outcomes and a decrease in the number of individuals who do not respond to the procedure. Furthermore, leadless LV fusion CRT pacing without RV lead could be a potential CRT therapy alternative to BIV pacing in nonischemic heart failure patients with preserved AV conduction. The aim of our study is to made an update in cardiac resynchronization therapy with LV only fusion pacing.

Feasibility of clinical and electrocardiographic follow-up of prinzmetal angina using the metaverse

Abstract Background The recent pandemic triggered an acceleration in adopting innovative technologies and telemedicine novelties. The metaverse, representing a merge of digital worlds using augmented reality (AR) and virtual reality (VR), promises disruptive transformation in healthcare. The feasibility of combining the metaverse with cardiovascular telemedicine services empowering remote consultation as well as assisting heart disease prevention and diagnosis, has not been investigated yet in cardiology. Purpose We evaluated the feasibility of combined clinical and electrocardiographic follow-up inside the metaverse on top of standard of care for a patient who presented with prinzmetal angina. Methods A digital consultation room combining AR/VR was created in a metaverse platform (GDPR compliant, CE marked class I medical device). Patient and cardiologist were given a personal and secured login account. Interactions and connections were made via virtual avatars. Patient was instructed to ask for a consultation in case of any cardiac related symptom occurred. The patient was equipped with a previously validated portable hospital-grade 12-lead smartphone-based electrocardiograph device which was directly integrated to the metaverse platform. Results A 30 years old obese active smoker patient presented for recurrent episodes of typical cardiac chest pain at rest. ECG showed sinus rhythm, normal atrioventricular and intraventricular conduction and no repolarization abnormalities. Laboratory test were normal, echocardiography showed a normal biventricular function with no focal abnormalities or valvular disease. Coronary angiogram excluded the presence of coronary artery disease, and the most possible diagnostic scenario was prinzmetal angina from coronary artery spasm. The patient was therefore discharged under treatment with diltiazem 120 mg twice daily, a multiple lead smartphone ECG device as well as the access to metaverse via his avatar, since no ECG were available during the episodes. Ten days later, the patient experienced an episode of palpitation accompanied with general discomfort. He subsequently logged into the metaverse where the cardiologist was available. The anamnesis of the episode was collected as well as the auto-recorded ECG by the patient. Although the clinical and electrocardiographic data were reassuring, the physician proposed to seek for medical attention. Hospital work up was consistent with the diagnosis provided in the virtual consultation. Conclusions To our knowledge, we conducted the first medical act in cardiology inside the metaverse combining VR environment with existing cardiovascular technological innovations as support information to the standard of care. Exploiting the full potential of the metaverse could serve as an unparalleled leap in the way cardiovascular medicine is delivered and could introduce new dimensions to cardiology in terms of health education, disease prevention and diagnosis. Funding Acknowledgement Type of funding sources: None.

277 THE OLDEST CLINICAL SIGN IN ONE OF THE MOST RECENTLY DISCOVERED SYNDROMES: A CASE REPORT ON DIGITAL CLUBBING AND BRUGADA SYNDROME IN A YOUNG MALE

Abstract A 21-year-old male arrived by ambulance in the Emergency Department following a syncopal episode with head trauma to the ground. The patient denied similar episodes in the past. He only reported a history of myoclonus and tics in childhood, limited to involuntary eye movements, treated in the past with valproic acid. In the last period, he was not taking any drugs at home. Physical examination revealed no heart, lung, or abdominal alterations, but the presence of bilateral hand fingers clubbing. The electrocardiogram showed: sinus tachycardia (107 bpm), normal atrioventricular conduction, incomplete right bundle branch block, and ST-T segment elevation in the right precordial derivations. Routine blood samples showed mild neutrophilic leukocytosis, while the high sensitivity troponin was normal. Neurological examination revealed repetitive, stereotyped ocular movements indicative of tics without other alterations responsible for the syncopal episode. Subsequently, the patient underwent a brain CT scan with a contrast medium, which excluded acute brain hemorrhages. Therefore, a cardiological consultation was requested. The trans-thoracic echocardiogram showed regular chamber dimensions and preserved biventricular functions. Also, no valve alterations or pericardial effusion were present. Considering EKG alterations and no neurological disease explaining the actual clinical picture, the cardiologists decided to hospitalize the patient to the Cardiology ward for further assessments. Because of digital clubbing, a chest-X ray and global spirometry were performed to exclude a respiratory disease but resulted in the normal range. In addition, in the suspicion of Brugada syndrome, the patient underwent a test with the infusion of Ajmaline, a sodium-channel blocking, class-1A antiarrhythmic agent. The drug was infused into a vein in about 5 minutes, observing the EKG trace constantly up to 10 minutes after administration to highlight possible changes. Within a few minutes, a type-1 Brugada syndrome pattern appeared, characterized by the morphological alterations of the QRS in V1-V2, with an elevation of the J point and an ST-segment elevation with a negative T wave. According to the ESC Guidelines, in consideration of the syncopal episode and the type-1 induced Brugada pattern, the implantation of a subcutaneous implantable defibrillator for the primary prevention of arrhythmias was performed. Lastly, a genetic evaluation was performed before hospital discharge, to identify which genetic alteration was responsible for Brugada syndrome and obtain more information regarding the possible link with digital clubbing, still not available. In the patient described in the present case report, no cause of classical disease associated with digital clubbing was present. To the best of our knowledge, the present is the first case report describing the association between digital clubbing and Brugada syndrome. It is possible that signaling pathways, such as PDGF, VEGF and HPGD, often involved in the release of fibrogenic and growth cytokines in the pathogenesis of digital clubbing may be also present in Brugada syndrome. However, further observations are needed to understand better the possible association between these two conditions. In particular, it should be clarified if patients with digital clubbing need a proper screening for Brugada Syndrome and if the presence of digital clubbing in a patient with a diagnosis of Brugada syndrome represents a marker of a more severe disease.

968 LYME CARDITIS: COMPLETE AV DISSOCIATION PRESENTING AS DYSPNEA IN THE EMERGENCY DEPARTMENT

Abstract Background Lyme carditis (LC), an early disseminated manifestation of Lyme disease, has important clinical implications for patients. High-degree atrioventricular block is the most common presentation of LC, and usually resolves with antibiotic therapy. Clinical case A 31 years-old man without remote pathological history and cardiovascular risk factors presents for resting dyspnea. In the EKG, findings of paroxysms third-degree atrioventricular block with a junctional escape rhythm were found. No abnormalities found on the transthoracic echocardiogram. After the tick bite reported about 1-2 months earlier, given the suspicion of Lyme carditis, serology for Borrelia Burgdoferi was tested, which was then positive, and empirical antibiotic therapy has been initiated. During the EKG monitoring, paroxysms of second-degree type I atrioventricular block and first-degree AVB were relevated. In few days, we assisted to a complete retrieval of normal atrioventricular conduction. Therefore, a loop recorder was implanted, cardiac resonance was performed and then discharged. About 4 weeks later the patient performed a stress test on the cycloergometer to identify frequency-dependent atrioventricular blocks, which was then negative. Rationale The suspicion and the early diagnosis of Lyme carditis is fundamental to identify this unusual transient condition, thus preventing unnecessary PM implantation in otherwise healthy young individuals.

550 FINGOLIMOD IN MULTIPLE SCLEROSIS: BRADYCARDIA, ATRIOVENTRICULAR BLOCKS AND EFFECT ON THE QT-INTERVAL. A PROSPECTIVE STUDY.

Abstract Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) that is mainly characterized by inflammatory demyelination, leading to severe neurological disability. MS typically affects young adults and usually arise with acute relapses, followed by partial or complete remission period. Currently, there is no definite treatment for MS. However Sphingosine-1-phosphate receptor modulators (S1PRMs), a class of disease-modifying treatments (DMTs), have shown a positive effect of the S1P pathway and S1PRMs on immune cell trafficking and neuroprotection, leading to the approval of 3 drugs (Fingolimod (Gilenya®), Siponimod (Mayzent®), and Ozanimod (Zeposia®)) for MS treatment [1]. Since S1PR have extensive expression on cardiomyocytes and vascular endothelial cells, cardiovascular effect, such as atrioventricular block (AVB), sinus bradycardia, orthostatic hypotension or hypertension, are expected [2]. At present, the approved S1PRMs require 6-h continuous cardiac monitoring after first dose and after every up titration. Nevertheless, so far no study has investigated the risk of cardiovascular adverse events in MS patients treated with S1PRMs. The aim of the present study was to define the incidence of cardiovascular adverse events (AEs) in relapsing-MS patients, without cardiac pre-existing conditions, treated with Fingolimod 0.5 mg/die. We enrolled 9 consecutive patients (mean age 34 years) admitted to the Neurology Department at University of Bari, between February and May 2022. All patients underwent 12 lead ECG, trans-thoracic Echocardiogram and BP evaluation. A six hours continuous monitoring of heart rate and blood pressure by telemetry started immediately after Fingolimod administration. A 12 lead ECG was obtained at the 5th and 6th hour of monitoring. During six hours monitoring blood pressure did not change significantly. As regards the entity of the HR changes, we found a decrease of 12 ± 8 bpm especially between the 2nd and the 3rd hour of monitoring; at the 3rd hour of monitoring, two of our youngest patients experienced a second degree type 1 AVB but normal atrio-ventricular conduction restored during the 5th hour of monitoring. All patients remained asymptomatic and were discharged in good clinical conditions after the end of six hour monitoring. Given the higher incidence of cardiovascular AEs in patients with MS receiving S1PRMs, a comprehensive assessment of patient conditions is recommended. During Fingolimod treatment, heart rate, brady-arrhythmias, and blood pressure should be monitored via active electrocardiography recording for at least 6 h after the first dose; monitoring could be potentially prolonged according to patient situation, although in our cohort the maximal conduction delay occurred within 3 hours. Our perspective is to obtain a long-term follow-up (1–3 years) focusing on heart rate and blood pressure variations, in order to elaborate a prediction model of cardiovascular risk in patients receiving S1PRMs. [1] Zhao Z, et al. Front Immunol. 2021 Dec 7;12:795574. [2] Paolicelli D et al. J Clin Pharmacol. 2015 Oct;55(10):1131-6.

Abstract 11446: Impact of Higher Synchronized Left Ventricular Pacing Rate for Prognosis on Cardiac Resynchronization Therapy

Background: The adaptive cardiac resynchronization therapy (aCRT) algorithm provides synchronized left ventricular pacing (sLVP) to produce fusion with the intrinsic right ventricular activation in normal atrioventricular (AV) conduction. Although sLVP has benefits over biventricular pacing (BiV), the adequate sLVP rate for better clinical outcome is still unclear. Purpose: The aim of this study was to assess the association between sLVP rate and clinical outcome. Methods: Among our cohort of 271 consecutive patients who had CRT implantation between April 2016 and August 2021, we evaluated 63 CRT patients without considerably prolonged AV conduction to whom we applied the aCRT algorithm (48 males, mean age: 64±14 years old, and the median follow up period: 316 days [interquartile range: 212-809days]). Results: At follow-up 6 months after CRT implantation, the frequency of CRT responder was 71% (n=45). The sLVP rate was significantly higher in responder compared to non-responder (75±30 vs 47±40 %, p=0.003). Receiving operating characteristics (ROC) curve analysis revealed that optimal cut-off value during sLVP rate was 59.4% for prediction of CRT responder (an area under the curve: 0.70, sensitivity: 80%, specificity: 61%, positive predictive value: 84%, and negative predictive value: 55%). Kaplan-Meier analysis demonstrated that higher sLVP group (sLVP≥59.4%, n=43) had better prognosis (cardiac death and heart failure hospitalization) compared to lower sLVP group (sLVP<59.4%, n=20) (log-rank p<0.001) (Figure) and multivariate Cox hazard analysis revealed that higher rate was associated with good prognosis (p<0.001). Conclusion: sLVP was associated with CRT response and higher sLVP rate (≥59.4%) may be important for good prognosis in patient with aCRT.

Evaluation of left atrial and left ventricular functions in patients with Wolff-Parkinson-White syndrome before and after radiofrequency catheter ablation using three-dimensional speckle tracking echocardiography.

Wolff-Parkinson-White (WPW) syndrome is one of the most common congenital cardiac abnormalities among ventricular pre-excitation syndromes. Radiofrequency catheter ablation (RFCA) treatment of accessory pathways (APs) in WPW patients is an established curative therapy restoring normal atrioventricular conduction. We have not encountered any studies evaluating both the LA and LV functions of these patients before and after RFCA with three dimensional-speckle tracking echocardiography (3D-speckle tracking echocardiography (STE)). The purpose of the current study was to assess the LA and LV functions in patients with WPW syndrome before and after RFCA using 3D-STE. A total of 21 patients with WPW syndrome who had been scheduled for RFCA were prospectively recruited for this study. 3D-STE examinations of the patients were performed 12-24h before ablation and 1 month after ablation. The LV-global longitudinal strain (LV-GLS) and LV-global circumferential strain (LV-GCS) were significantly depressed in the pre-RFCA WPW group than in the control group (-14.3±2.1vs. -21.5±2.2, p<.001; -12.6±1.8vs. -20.4±1.8, p<.001, respectively). The left atrial strain-reservoir (LAS-r) and LAS-active were significantly decreased in the pre-RFCA WPW group than in the control group (31.9±2.4vs. 48.8±2.6, p<.001; 11.7±2vs. 26.5±2.1, p<.001, respectively). The LV-GLS, LV-GCS, LAS-r, and LAS-active values improved after RFCA compared to before. The results of our study indicated that there are subclinical impairments in LV and LA myocardial dynamics in the apparently healthy WPW patients, and these deteriorations improve after RFCA of AP.

A puzzling overnight change in the QRS morphology

Pacemakers set in a bipolar pacing mode often result in no discernible spikes on surface 12‑lead ECG registrations. In this situation, left axis deviation combined with wide QRS can help to identify the paced ECG morphology. We present a case of a non-pacemaker dependent patient whose normal atrioventricular conduction also appeared as atypical left axis deviation with wide QRS on the ECG. These two depolarization-repolarization morphologies, and the switch between the two raised differential diagnostic questions. The case also illustrates a paced ECG demonstrating the concept of Littmann: a close relationship between leads V2 and aVL.

Feasibility of clinical and electrocardiographic follow-up of prinzmetal angina using the metaverse

Abstract Background The recent pandemic triggered an acceleration in adopting innovative technologies and telemedicine novelties. The metaverse, representing a merge of digital worlds using augmented reality (AR) and virtual reality (VR), promises disruptive transformation in healthcare. The feasibility of combining the metaverse with cardiovascular telemedicine services empowering remote consultation as well as assisting heart disease prevention and diagnosis, has not been investigated yet in cardiology. Purpose We evaluated the feasibility of combined clinical and electrocardiographic follow-up inside the metaverse on top of standard of care for a patient who presented with prinzmetal angina. Methods A digital consultation room combining AR/VR was created in a metaverse platform (GDPR compliant, CE marked class I medical device). Patient and cardiologist were given a personal and secured login account. Interactions and connections were made via virtual avatars. Patient was instructed to ask for a consultation in case of any cardiac related symptom occurred. The patient was equipped with a previously validated portable hospital-grade 12-lead smartphone-based electrocardiograph device which was directly integrated to the metaverse platform. Results A 30 years old obese active smoker patient presented for recurrent episodes of typical cardiac chest pain at rest. ECG showed sinus rhythm, normal atrioventricular and intraventricular conduction and no repolarization abnormalities. Laboratory test were normal, echocardiography showed a normal biventricular function with no focal abnormalities or valvular disease. Coronary angiogram excluded the presence of coronary artery disease, and the most possible diagnostic scenario was prinzmetal angina from coronary artery spasm. The patient was therefore discharged under treatment with diltiazem 120 mg twice daily, a multiple lead smartphone ECG device as well as the access to metaverse via his avatar, since no ECG were available during the episodes. Ten days later, the patient experienced an episode of palpitation accompanied with general discomfort. He subsequently logged into the metaverse where the cardiologist was available. The anamnesis of the episode was collected as well as the auto-recorded ECG by the patient. Although the clinical and electrocardiographic data were reassuring, the physician proposed to seek for medical attention. Hospital work up was consistent with the diagnosis provided in the virtual consultation. Conclusions To our knowledge, we conducted the first medical act in cardiology inside the metaverse combining VR environment with existing cardiovascular technological innovations as support information to the standard of care. Exploiting the full potential of the metaverse could serve as an unparalleled leap in the way cardiovascular medicine is delivered and could introduce new dimensions to cardiology in terms of health education, disease prevention and diagnosis. Funding Acknowledgement Type of funding sources: None.

Outcomes in patients with electrocardiographic left ventricular dyssynchrony following transcatheter aortic valve replacement

Left bundle branch block (LBBB) and atrioventricular (AV) conduction abnormalities requiring permanent pacemaker (PPM) implantation occur frequently following transcatheter aortic valve replacement (TAVR). The resultant left ventricular (LV) dyssynchrony may be associated with adverse clinical events. The purpose of this study was to assess the adverse outcomes associated with LV dyssynchrony due to high-burden right ventricular (RV) pacing or permanent LBBB following TAVR in patients with preserved left ventricular ejection fraction (LVEF). Consecutive TAVR patients at the University of Michigan from January 2012 to June 2017 were included. Pre-existing cardiac implantable electronic device, previous LBBB, LVEF <50%, or follow-up period <1 year were excluded. The primary outcome was all-cause mortality. Secondary outcomes included cardiomyopathy (defined as LVEF ≤45%), a composite endpoint of cardiomyopathy or all-cause mortality, and the change in LVEF at 1-year follow-up. A total of 362 patients were analyzed (mean age 77 years). LV dyssynchrony group (n = 91 [25.1%]) included 56 permanent LBBB patients, 12 permanent LBBB patients with PPM, and 23 non-LBBB patients with PPM and high-burden RV pacing. Remaining patients served as control (n = 271 [74.9%]). After adjusted analysis, LV dyssynchrony had significantly higher all-cause mortality (adjusted hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.07-4.37) and cardiomyopathy (adjusted HR 14.80; 95% CI 6.31-14.69). The LV dyssynchrony group had mean LVEF decline of 10.5% ± 10.2% compared to a small increase (0.5% ± 7.7%) in control. Among TAVR patients with preserved LVEF and normal AV conduction, development of postprocedural LV dyssynchrony secondary to high-burden RV pacing or permanent LBBB was associated with significantly higher risk of death and cardiomyopathy at 1-year follow-up.

Design of Mid-Q Response: A prospective, randomized trial of adaptive cardiac resynchronization therapy in Asian patients.

AimsThe aim of the Mid‐Q Response study is to test the hypothesis that adaptive preferential left ventricular‐only pacing with the AdaptivCRT algorithm has superior clinical outcomes compared to conventional cardiac resynchronization therapy (CRT) in heart failure (HF) patients with moderately wide QRS duration (≥120 ms and <150 ms), left bundle branch block (LBBB), and normal atrioventricular (AV) conduction (PR interval ≤200 ms).MethodsThis prospective, multi‐center, randomized, controlled, clinical study is being conducted at approximately 60 centers in Asia. Following enrollment and baseline assessment, eligible patients are implanted with a CRT system equipped with the AdaptivCRT algorithm and are randomly assigned in a 1:1 ratio to have AdaptivCRT ON (Adaptive Bi‐V and LV pacing) or AdaptivCRT OFF (Nonadaptive CRT). A minimum of 220 randomized patients are required for analysis of the primary endpoint, clinical composite score (CCS) at 6 months post‐implant. The secondary and ancillary endpoints are all‐cause and cardiovascular death, hospitalizations for worsening HF, New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ), atrial fibrillation (AF), and cardiovascular adverse events at 6 or 12 months.ConclusionThe Mid‐Q Response study is expected to provide additional evidence on the incremental benefit of the AdaptivCRT algorithm among Asian HF patients with normal AV conduction, moderately wide QRS, and LBBB undergoing CRT implant.

A case of myopericarditis recurrence after third dose of BNT162b2 vaccine against SARS-CoV-2 in a young subject: link or causality?

The rate of post-vaccine myocarditis is being studied from the beginning of the massive vaccination campaign against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a direct cause–effect relationship has been described, in most cases, the vaccine pathophysiological role is doubtful. Moreover, it is not quite as clear as having had a previous myocarditis could be a risk factor for a post-vaccine disease relapse. A 27-year-old man presented to the emergency department for palpitations and pericardial chest pain radiated to the upper left limb, on the 4th day after the third dose of BNT162b2 vaccine. He experienced a previous myocarditis 3 years before, with full recovery and no other comorbidities. Electrocardiogram showed normal atrioventricular conduction, incomplete right bundle branch block, and diffuse ST-segment elevation. A cardiac echo showed lateral wall hypokinesis with preserved ejection fraction. Troponin-T was elevated (160 ng/L), chest X-ray was normal, and the SARS-CoV-2 molecular buffer was negative. High-dose anti-inflammatory therapy with ibuprofen and colchicine was started; in the 3rd day high-sensitivity Troponin I reached a peak of 23000 ng/L. No heart failure or arrhythmias were observed. A cardiac magnetic resonance was performed showing normal biventricular systolic function and abnormal tissue characterization suggestive for acute non-ischaemic myocardial injury (increased native T1 and T2 values, increased signal intensity at T2-weighted images and late gadolinium enhancement, all findings with matched subepicardial distribution) at the level of mid to apical septal, anterior, and anterolateral walls. A left ventricular electroanatomic voltage mapping was negative (both unipolar and bipolar), while the endomyocardial biopsy showed a picture consistent with active myocarditis. The patient was discharged in good clinical condition, on bisoprolol 1.25 mg, ramipril 2.5 mg, ibuprofen 600 mg three times a day, colchicine 0.5 mg twice a day. We presented the case of a young man with history of previous myocarditis, admitted with a non-complicated acute myopericarditis relapse occurred 4 days after SARS-CoV-2 vaccination (3rd dose). Despite the observed very low incidence of cardiac complications following BNT162b2 administration, and the lack of a clear proof of a direct cause–effect relationship, we think that in our patient this link can be more than likely. In the probable need for additional SARS-CoV-2 vaccine doses in the next future, studies addressing the risk-benefit balance of this subset of patient are warranted. We described a multidisciplinary management of a case of myocarditis recurrence after the third dose of SARS-CoV-2 BNT162b2 vaccine.

Impact of pre-existing right or left bundle branch block on patients undergoing surgical aortic valve replacement.

Contemporary data on the prognostic impact of pre-existing left or right bundle branch block on clinical outcomes after aortic valve (AV) replacement are limited. The aim of this study was to evaluate the impact of pre-existing bundle branch block on clinical outcomes in patients undergoing AV replacement. Data from patients who underwent AV replacement surgery between 2004 and 2020 were obtained from our departmental database. Of the 2704 study patients, 203 (7.5%) had pre-existing bundle branch block and 2501 (92.5%) had normal atrioventricular conduction. The mean age was 68 (13) years, 1697 (63%) were male and 683 (25%) had a unicuspid or bicuspid AV. The in-hospital mortality rate was higher in patients with pre-existing bundle branch block compared to those without on admission (5.9% vs 2.9%, P = 0.032), and more frequent in patients with left compared with right bundle branch block (11.9% vs 4.3%, P = 0.003). New pacemaker implantation was most frequent in those patients with pre-existing left bundle branch block, followed by right and no bundle branch block on admission (28.6% vs 7.5% vs 2.8% respectively, P < 0.001; odds ratio 4.96 95% confidence interval 2.96-8.08, P < 0.001). The 10-year cumulative survival rate was lower in patients with bundle branch block compared with patients with no bundle branch block (76.8% vs 82.8%, log-rank P < 0.001; hazard ratio 0.73, confidence interval 0.54-0.99, P = 0.042). This study indicates that patients with pre-existing bundle branch block have a higher incidence of pacemaker implantation and all-cause mortality after AV replacement compared with patients without a conduction disturbance.