Atrioventricular Conduction Disturbances Research Articles

Transient Atrioventricular Conduction Disturbance During Vein of Marshall Alcohol Ablation

Transient Atrioventricular Conduction Disturbance During Vein of Marshall Alcohol Ablation

ALSTER-TAVR 2024: clinical results at one year following optimized self-expanding, transcatheter aortic valve peplacement employing the cusp-overlay technique.

Atrioventricular (AV) conduction disturbances are still common following transcatheter aortic valve replacement (TAVR). The study evaluates the feasibility and clinical effect of self-expanding (SE)-TAVR employing an optimized cusp-overlay technique (COT) at 1 year in a German all-comers population. We analyzed 1-year clinical outcomes in patients who received a SE valve employing the optimized COT. Consecutive patients who underwent SE-TAVR (EvolutR, EvolutPRO) after introduction of the COT as the default implantation technique in 2020 were included (n = 101). Consecutive TAVR patients from the same operators using the conventional implantation technique (CIT) served as the control group (n = 116). The COT was successfully performed in more than 80% of the patients in the COT group. (81.2%, n = 82/101). At discharge, no difference regarding AV block of at least II (CIT 19.47% vs COT 21%; P = .86) and permanent pacemaker (PPM) implantation (CIT 17.5% vs COT 19%; P = .73) was observed between the cohorts. New left bundle branch block (LBBB) was significantly less frequent in the COT group (CIT 40.71% vs COT 26%; P = .029). Paravalvular leakage (PVL) greater than I° was reduced in the COT cohort (CIT 8.62% vs COT 0.99%; P = .012). There was no significant difference in mortality (CIT 18.27% vs COT 13.83%; P = .44), stroke (CIT 9.62% vs COT 15.96%; P = .16) or cardiovascular rehospitalization after 1 year (CIT 25.96% vs 24.47%; P = .92) between the groups. Implementation of COT-TAVR was feasible and safe, and it resulted in an improvement of TAVR outcomes regarding PVL greater than I° and new onset LBBB. However, with respect to PPM, no difference was observed 1-year post-TAVR.

His bundle pacing in a patient with atrioventricular conduction abnormalities, persistent atrial flutter at high thromboembolic and bleeding risk after hybrid coronary revascularization and left atrial appendage closure - case report

We present a case of a 78-year-old patient with persistent atrial fl utter, history of atrial fi brillation and atrioventricular conduction disturbances, including fi rst-degree atrioventricular block (AVB) and paroxysmal complete AVB. Echocardiography revealed mildly reduced left ventricular ejection fraction (LVEF, 44%). The patient had high thromboembolic risk, had previous ischemic stroke, suffered from chronic coronary artery disease treated with hybrid coronary revascularization (minimally invasive direct coronary artery bypass grafting and subsequent percutaneous coronary intervention) as well as left atrial appendage closure. Because of high bleeding risk, double antiplatelet therapy (acetylsalicylic acid and clopidogrel) combined with low dose of low-molecular-weight heparin after cardiac surgery were introduced. Due to persistent atrial fl utter, complete AVB, lack of intraventricular conduction abnormalities, mildly reduced LVEF and expected high right ventricle pacing burden, the patient was referred for dual-chamber pacemaker implantation using conduction system pacing (CSP), preferentially His bundle pacing (HBP). The procedure was performed with good outcome and CSP was utilized via HBP. After reassessment of thromboembolic and bleeding risk, the patient was discharged home on reduced dose of dabigatran. Short-term follow-up showed stable HBP parameters along with no additional symptoms. Despite good short-term outcomes and no complications in studied patient, large randomized controlled trials are needed to verify long-term safety and effi cacy of HBP to optimize clinical care of patients with atrioventricular conduction abnormalities using a personalized approach. 

Abstract 17229: Atrioventricular Conduction System Changes During Transcatheter Aortic Valve Replacement (TAVR)

Introduction: Transcatheter aortic valve replacement (TAVR) is complicated by atrioventricular (AV) conduction disturbance in 8-15% of cases. Prior studies have not utilized complete electrophysiology studies (EPS) with continuous recording during TAVR. We sought to better understand the potential utility of intraprocedural electrophysiologic study to identify patients at risk for developing high-grade AV conduction disturbances after TAVR. Hypothesis: Intraprocedural EPS has the potential to identify patients at risk of developing AV conduction block after TAVR. Methods: We conducted a prospective study of TAVR patients at BIDMC between 5/2021-3/2023, excluding those with pre-existing pacemakers/defibrillators. We performed EPS in the cath lab prior to and after valve replacement: atrial pacing to AV block, recording His bundle electrogram (HBE) and RV pacing to assess VA conduction. When possible we recorded the HBE continuously during valve implant. Results: We studied 400 consecutive patients. Forty-three patients (10.8%) received permanent pacemakers (PPMs). Patients receiving PPM had significantly longer post-HV intervals, greater change in HV interval as well as longer AV Wenckebach cycle length after valve replacement. There were no differences in pre-TAVR AV Wenckebach cycle length or VA conduction. Twenty patients (46.5% of all PPMs) were implanted for AV block post discharge, and after adjustment for age, gender, and baseline HV interval, the only predictor of need for post-discharge PPM was peri-TAVR change in HV interval with an adjusted OR of 1.19 per each 10 ms increase. Conclusions: In contrast to prior studies, we have found that EPS at the time of TAVR may have utility in predicting AV conduction disturbances. Larger increases in HV interval and AV block CL were associated with need for PPM. Measuring the peri-TAVR change in HV interval may be useful in predicting late AV block.

Diagnostics of cardiac amyloidosis

The early diagnosis of cardiac amyloidosis is decisive for the success of treatment of affected persons. The thorough clinical investigation of the patient should be followed by appropriate diagnostics using modern procedures. The main symptoms are dyspnea, loss of performance and edema and in later stages cardiac arrhythmias in the form of atrioventricular conduction disturbances and atrial fibrillation but ventricular arrhythmias occur more rarely. During heart failure due to cardiac amyloidosis an increase of cardiac enzymes frequently occurs (e.g., creatine kinase, troponin, N‑terminal pro-brain natriuretic peptide), which can be included in the risk stratification and treatment monitoring, taking certain limitations into consideration. The investigation of light chains in serum and/or urine should be carried out immediately, as soon as there is a clinical and echocardiographic suspicion of cardiac amyloidosis. Subsequently, either cardiac magnetic resonance imaging (MRI) or bone scintigraphy should be carried out, depending on the locally available options. Depending on the results of these two imaging procedures, a decision must be made as to whether further diagnostic steps (e.g., endomyocardial biopsy) are necessary. In the last decade bone scintigraphy has proven to be a blessing for the diagnostics of cardiac amyloidosis but many partial aspects and limitations necessitate special and careful consideration. A Perugini score of 2 or 3 is initially "indicative" of cardiac amyloidosis but not yet "confirmative" for a specific subtype. Only after an additional negative result of the light chain determination, can the diagnosis of ATTR amyloidosis be noninvasively made. Cardiac amyloidosis shows a particularly characteristic contrast enhancement in cardiac MRI, which mostly begins in the inner (subendocardial) layers of the basal left ventricular (LV) wall and frequently appears to be circular in the cross-sectional view of the left ventricle. Supplementary T1 and extracellular volume fraction mapping results, which are shown as color-coded maps, enable the rapid and elegant assessment of the myocardial structure and the extent of amyloid deposition. An additional investigation of the TTR gene is recommended in the case of ATTR amyloidosis for a differentiation between hereditary and acquired ATTR, as from this, further therapeutic consequences can be derived.

Ventricular pacing dependency after transcatheter aortic valve replacement: a prospective cohort.

Atrioventricular conduction disturbance occurs in a significant number of patients undergoing transcatheter aortic valve replacement (TAVR). However, not all cases are ventricular pacing-dependent. Thus, we aimed to study the incidence, predictors, and outcomes of new ventricular pacing dependency (VpDep) after TAVR. We prospectively analyzed 130 consecutive transfemoral TAVR cases performed in Ramathibodi Hospital between 2015 and 2020. Three patients with prior ventricular pacing-dependent on cardiac implantable electronic devices (CIEDs) were excluded. The endpoints were VpDep at 1 month and all-cause mortality at the follow-up period end in 2021. The effects of variables on VpDep and all-cause mortality were evaluated using multivariate binary logistic regression and Cox regression analyses, respectively. First-degree atrioventricular block (AVB) was considered severe when the PR interval was >300 ms. Of the 127 patients [mean age, 81.8 years; 62.2% females; 67.7% balloon-expandable (BE) device], 7 patients (5.5%) had CIEDs implanted before TAVR that were not ventricular pacing-dependent. TAVR was successfully performed in 126 (99.2%) patients. Periprocedural stroke, cardiac tamponade, and major bleeding occurred in 2 (1.6%), 4 (3.1%), and 4 (3.1%) patients, respectively. The VpDep incidence at 1 month was 7.9% (n=10) among all patients and 34.5% among those with CIEDs (n=29). VpDep was more likely to occur in patients with pre-existing right bundle branch block (RBBB) [odds ratio (OR), 21.38; 95% confidence interval (CI): 3.28-139.33; P=0.001] and severe 1st degree or Mobitz I AVB (OR, 14.79; 95% CI: 1.65-132.74; P=0.016). After a mean follow-up of 25.8 months [standard deviation (SD), 21.2 months], death from any cause occurred in 18 patients (14.2%). However, VpDep was not associated with an increased mortality. In this real-world cohort, pre-existing conduction abnormalities were significantly associated with a higher risk of VpDep. Mortality was similar between patients with and without VpDep.

New-onset atrial high-rate episodes between his bundle pacing and conventional right ventricular septum pacing in patients with atrioventricular conduction disturbance.

The effect of His bundle pacing (HBP) on the incidence of new-onset atrial fibrillation (AF) after pacemaker implantation (PMI) for atrioventricular conduction disturbance (AVCD) remains unknown. We compared the incidence of new-onset atrial high-rate episode (AHRE) in conventional right ventricular (RV) septum pacing (RVSP) and His bundle pacing (HBP) after PMI for AVCD. One hundred and four consecutive patients who underwent dual chamber PMI for AVCD in our hospital were screened. Thirty-five patients with mitral or aortic valve disease, history of open-heart surgery, prior AF, subclinical AF, cumulative ventricular pacing percentage < 90%, and RV lead revision were excluded, and 69 patients were effectively enrolled in this study. The primary endpoint was new-onset AHRE within the follow-up period. New-onset AHRE was defined as an atrial high-rate episode that occurred 3months after PMI and lasted for > 6min at an atrial heart rate > 190bpm. RV leads were placed in the His bundle region and RV septum region in 22 and 47 patients, respectively. The mean follow-up period was 539 ± 218days. The follow-up period was 2years after PMI or until the new-onset AHRE occurred. The incidence of new-onset AHRE was lower in the HBP group than in the RVSP group (11% vs. 43%, p = 0.01). Multivariate analysis in the Cox regression hazard model showed that HBP had a significantly lower risk of new-onset AHRE compared with RVSP (HR = 0.21; 95% confidence interval 0.04-0.78, p = 0.02). The incidence of new-onset AHRE was significantly less in HBP compared to RVSP during the 2-year follow-up period after pacemaker implantation in AVCD patients with RV pacing dependence.

Prediction of atrioventricular conduction disturbance after ablation of persistent atrial fibrillation.

The prevalence of atrioventricular conduction disturbance (AVCD) in patients with persistent atrial fibrillation (AF) has not yet been fully investigated. We sought to identify the predictors of AVCD in patients with AF by analyzing the relationship between pre-ablation heart rate during AF and the PR interval in sinus rhythm after ablation. We analyzed pre-ablation 24-h Holter electrocardiogram (ECG) and 12 lead ECG 12months after ablation of 121 consecutive patients with persistent AF who underwent their first ablation procedure and maintained sinus rhythm at 12months. AVCD was defined as a first-degree atrioventricular block (AVB), second-degree AVB, high-degree AVB, or third-degree AVB observed on ECG at 12months after ablation. Seventeen out of 121 patients (14.0%) had AVCD at 12months. In the group with AVCD, total heartbeat (THB) and maximum heart rate (Max HR) were significantly lower, and the prevalence of concomitant Cavo-tricuspid isthmus-dependent atrial flutter before ablation and the appearance of macro reentrant atrial tachycardia (AT) during the procedure were significantly higher than those in the group without AVCD. Multiple regression analysis revealed that maximum HR and macro reentrant AT were significant predictors of AVCD. Receiver operating characteristic curve analysis revealed that Max HR of <165.0bpm predicts AVCD with a sensitivity of 76.47% and a specificity of 74.00%. In patients with persistent AF, low Max HR and the presence of macro reentrant AT during the ablation procedure were predictors of AVCD.

New insights into the correlation between genotype and cardiac phenotype in laminopathies

Abstract Funding Acknowledgements Type of funding sources: None. Background Genotype-phenotype correlation and risk stratification for heart failure progression in patients with cardiolaminopathies are poorly defined. Purpose The primary aim of the present study is to characterize and correlate phenotype with genotype and sex. The secondary aim is to test the two main existing prognostic scores (the Arbustini and the Whabi score), both developed to predict ventricular arrhythmic events in cardiolaminopathies, for both major ventricular arrhythmias (MVA) and end-stage heart failure (ESHF). Methods This is a retrospective, single-center study, including patients with lamin (LMNA) and/or emerin (EMD) genetic variants. Data were collected from the first medical contact (FMC) to the last follow-up (FU). Results 28 patients (57% male, 82% probands, 68% with a family history of sudden death) were included: 96% harbored LMNA heterozygous variants, 15% had non-missense variants, 11% had variant previously never described. Functionally, 50% were variant of undetermined significance (VUS, C3), the rest were either pathogenetic or likely pathogenic (C4/C5) variants. Median age at FMC was 41 years (IQR 30-55 years), median FU was 11 years (IQR 8-18 years). At FMC, all patients had cardiac involvement, 54% had muscle involvement. By the last FU, 54% developed atrial fibrillation, 43% atrioventricular block (AVB) &amp;gt; I degree, 50% carried an implantable cardioverter defibrillator (21% with resynchronization), 50% had suffered at least one episode of MVA, 25% developed ESHF: 11% died due to refractory HF, 14% underwent heart transplantation (mean age 43.5 ± 9 years). The age of onset of the different types of cardiac phenotype was not influenced by sex. The penetrance of atrioventricular (AV) conduction defects (Figure 1 Panel A) and of atrial tachyarrhythmias (Figure 1 Panel B) was higher and earlier in subjects with non-missense variants. Subjects with VUS, compared to those with pathogenetic/likely pathogenetic variants, showed a significantly lower and later penetrance of MVA (Figure 2 Panel A) and a later penetrance of non- sustained ventricular tachycardia (NSVT, Figure 2, Panel B), but not of AV conduction disturbances, atrial arrhythmias, or contractile dysfunction. Arbustini score at FMC proved to be a predictor of both MVA and ESHF, while Whabi score only predicted MVA. Conclusions In our series, the prevalence and the age of appearance of the different cardiac phenotypes of cardiolaminopathies were not influenced by sex, while the presence of VUS correlated with a lower risk of ventricular arrhythmias, but not of the other cardiac manifestations including contractile disfunction and heart failure. Our data suggest the importance of a close cardiac monitoring and of larger prospective studies even in patients with VUS. All patients developed a sever cardiac phenotype by the age of 60.

P325 CARDIAC SARCOIDOSIS PRESENTING WITH ATRIOVENTRICULAR BLOCK AND SUBSEQUENT CARDIAC ARREST: A CASE REPORT

Abstract A 53–year–old male patient with no significant past medical history and no familiar history for cardiac diseases presented to the emergency department for asymptomatic bradycardia. The ECG showed complete atrioventricular block in the absence of pathological findings on the echocardiogram and no coronary lesions were found on coronary angiography. The patient underwent pacemaker (PM) implantation. A few months later the patient suffered from cardiac arrest in sustained ventricular tachycardia, effectively treated with DC shock. The echocardiogram showed mild right ventricular dilation and dysfunction with regional wall motion abnormalities, especially in the subtricuspid site. Cardiac magnetic resonance imaging (MRI) showed focal areas of delayed enhancement with a non–ischaemic pattern and distribution with a hook sign, highly suggestive of cardiac sarcoidosis. FDG PET showed cardiac, hepatic, splenic, and lymph nodal uptake. In the suspicion of systemic sarcoidosis, an hepatic biopsy was performed, being the liver the most accessible site. The histological examination showed the presence of non–caseating granulomas. Therefore, a diagnosis of Systemic Sarcoidosis (SS) with Cardiac involvement was made and the PM was upgraded to CRT–D in secondary prevention. The patient was discharged with cortisone therapy. Three months after discharge, a new total body PET–CT scan was performed and showed, in comparison to the previous one, the absence of areas of significant hypermetabolism in the cardiac, hepatic and bone fields. Cardiac sarcoidosis (CS) is a rare inflammatory granulomatous myocardial disease of unknown etiology that should be suspected in young patients with atrioventricular conduction disturbances and complex ventricular arrhythmias. The diagnostic approach is challenging: imaging techniques (MRI, PET) can be suggestive of CS but biopsy with histological demonstration of the non–caseous granuloma is mandatory. Endomyocardial biopsy (which has suboptimal sensitivity due to focal lesion) could be avoided if there is a more accessible and less invasive extracardiac site for biopsy. Early diagnosis relies on multidisciplinary collaboration and is essential for staging and long–term management of the disease and prevention of sudden cardiac death. Cortisone therapy remains the mainstay of treatment.

Incidence and management of atrioventricular conduction disorders in new-onset left bundle branch block after TAVI: A prospective multicenter study

New-onset left bundle branch block (LBBB) is one of the most frequent complications after transcatheter aortic valve implantation (TAVI) and is associated with delayed high degree atrioventricular (AV) block. The objectives of this study were to determine the incidence of AV block in such a population and to assess the performance and safety of a risk stratification algorithm on the basis of electrophysiology study (EPS) followed by implantation of a pacemaker or implantable loop recorder (ILR). This was a prospective open-label study with 12-month follow-up. From June 8, 2015, to November 8, 2018, 183 TAVI recipients (mean age 82.3 ± 5.9 years) were included at 10 centers. New-onset LBBB after TAVI persisting for >24 hours was assessed by electrophysiology study during initial hospitalization. High-risk patients (His-ventricle interval ≥70 ms) were implanted with a dual-chamber pacemaker recording AV conduction disturbance episodes. Patients at lower risk were implanted with an ILR with automatic remote monitoring. A high-grade AV conduction disorder was identified in 56 patients (30.6%) at 12 months. Four subjects were symptomatic, all in the ILR group. No complications were associated with the stratification procedure. Patients with His-ventricle interval ≥70 ms displayed more high-grade AV conduction disorders (53.2% [25 of 47] vs 22.8% [31 of 136]; P < .001). In a multivariate analysis, His-ventricle interval ≥70 ms was independently associated with the occurrence of a high-grade conduction disorder (subdistribution hazard ratio 2.4; 95% confidence interval 1.2-4.8; P = .010). New-onset LBBB after TAVI was associated with high rates of high-grade AV conduction disturbances. The stratification algorithm provided safe and valuable aid to management decisions and reliable guidance on pacemaker implantation.

An overview of brady dysrhythmias in the emergency department

Bradyarrhythmias, which include physiological and pathological disorders such as sinus node dysfunction and atrioventricular conduction disturbances are frequent clinical findings in the emergency department. Although some benign bradyarrhythmias do not need treatment, acute unstable bradycardia can lead to cardiac arrest. A thorough history and physical examination should cover potential causes of sinoatrial node dysfunction or atrioventricular block in patients with confirmed or suspected bradycardia. Based on the severity of the symptoms, the underlying causes, the presence of possibly reversible causes, the presence of negative indications, and the danger of asystole progression, bradyarrhythmias are managed. Bradyarrhythmias that are unstable or symptomatic are treated with medication and/or pacing. Bradycardia is described as an adult heart rate of less than 60 beats per minute. Syncope, presyncope, momentary light-headedness or dizziness, exhaustion, dyspnea with exertion, heart failure symptoms, or disorientation brought on by cerebral hypoperfusion are typical signs of bradycardia. Atropine plays a significant role in the management of bradyarrhythmias because it counteracts the impact of the parasympathetic vagus nerve system, which can cause an increase in heart rate. Atropine administration is indicated in cases with vagus-mediated asystole, obstructions in the atrioventricular node, and sinus bradycardia. Installation of temporary pacemaker, permanent pacemaker is also among the effective management strategies of the bradyarrythmias. Diagnosis and management of bradyarrythmias in emergency department is of utmost importance since it can prevent morbidity and mortality. The purpose of this research is to review the available information about an overview of bradydysrhythmias in the emergency department.

Inflammation begets isolated atrioventricular conduction disturbances in young an observation from indian registry data

Abstract Background High grade AV block is less commonly encountered in patients &amp;lt;60 years. The aetiological role of inflammatory conditions is not well studied in this group of patients. Purpose To determine the prevalence of myocardial inflammation in young patients presenting with High grade AV block and assess its response to immunosuppression. Methodology This is a prospective, registry based, observational study conducted at two centers from Jan 2020 to Dec 2021. Myocardial inflammation was detected using Cardiac PET, and/or histopathological examination. Those with evidence of inflammation were started on graded immunosuppression. Results 318 patients were enrolled. Mean EF was 55.2±7.0%. Cardiac PET was performed in 87/318 (27.3%). Myocardial inflammation was seen in 57/87 (65%). LV basal septum was most commonly involved. 44/57 (77%) were started on immunosuppressive therapy after excluding indolent tuberculosis.8 patients died during follow-up with all deaths being sudden in nature. 5/44 (11.3%) had reversal of CHB with resolution of cPET findings. Conclusion Significant proportion of young patients with High grade AV block have segmental myocardial inflammation. Immunosuppression helps restore AV conduction in some of these patients. Long-term studies are required to assess adverse impact of inflammation on cardiac contractile function. Funding Acknowledgement Type of funding sources: None.

Impact of common rhythm disturbances on echocardiographic measurements and interpretation.

Transthoracic echocardiography (TTE) remains the workhorse of noninvasive cardiac imaging, allowing to easily obtain precise information on cardiac structure and function. Over time, Doppler interrogation of blood flow velocities, direction, and timing in several locations within the heart became the primary method for haemodynamic assessment, replacing cardiac catheterization in most clinical settings and providing valuable diagnostic and prognostic information on a wide spectrum of cardiac pathological processes. Abnormalities in heart rate, rhythm, and intracardiac electrical conduction are commonly encountered during the performance of echocardiographic studies. Up to now, only a modest attention has been given to the impact of these abnormalities on the reading and interpretation of echocardiographic examination and this assessment has not yet been carried out in a global and systematic way. Tachyarrhythmias, bradyarrhythmias and atrioventricular conduction disturbances influence cardiac structure and mechanics as well as Doppler flow patterns. For this reason, and to be able to avoid misinterpretation, echocardiographers must be aware of the consequences of these common rhythm disturbances on echocardiographic findings. This narrative review aims to describe the current knowledge on this topic, focusing on the expected mechanical effects and Doppler patterns observed on transthoracic echocardiography in patients with common rhythm (tachycardia and bradycardia, atrial flutter and fibrillation and ectopic beats) and conduction disturbances (namely, atrioventricular block).

The usefulness of His bundle pacing in a heterogeneous population of patients with impaired left ventricular systolic function.

His bundle pacing (HBP) maintains a physiological activation pattern of ventricular activation, and in patients with intraventricular conduction delay (IVCD) it can normalize wide QRS duration. A total of 181 patients from the HBP registry were enrolled into a the study, which was conducted at the Department of Electrocardiology in Katowice, Poland. The patients had left ventricular ejection fraction (LVEF) < 50% and were implanted between November 2015 and April 2019. The HBP indications were as follows: 1) bradycardia and atrioventricular conduction disturbances with expected high pacing burden, 2) IVCD, LVEF ≤ 35%, with an indication for resynchronization therapy, 3) the need to upgrade to resynchronization therapy due to pacing-induced cardiomyopathy. Pacing parameters and echocardiographic and clinical data were assessed for up to 2 years of follow-up (FU). His bundle pacing was successful in 154 (85.1%) patients. Eighty-two patients completed a 6-month FU. The mean age was 70.6 ± 9.23 years, and 79% were males. At 6 months FU LVEF improved from 35.3 ± 8.22% to 43.1 ± 10.14% (p < 0.0001), and indexed left ventricular end-systolic volume (LVESVi) decreased from 63.1 ± 25.21 mL/m² to 51.9 ± 22.79 mL/m² (p < 0.0001). In 53.1%, the LVESVi reduction was greater than 15%. The improvement in LVEF and LVESVi was also observed after 24 months of FU. His bundle pacing in permanently paced patients when LVEF is reduced below 50% is associated with improvement in LVEF and reverse left ventricle remodeling.

P426 TELEMONITORING FOR THE SAFE MANAGEMENT OF NEW THERAPIES IN PATIENTS WITH MULTIPLE SCLEROSIS: THE RITMO PROJECT

Abstract Back in 2012 AIFA authorized the use of Fingolimod in patients with multiple sclerosis; due to possible adverse effects, continuous ECGraphic monitoring is mandatory during the first 6 hours after the administration of the first dose of the drug. Health Telematic Network, in collaboration with the Department of Cardiology of the University of Brescia, has provided a remote telemonitoring system based on the TelMed Telemedicine platform accessible from the computers of the departments, currently in use in 42 hospital departments participating in the project “Nuove Reti Sanitarie” of the General Directorate of Health of the Lombardy Region for the monitoring of patients with chronic heart failure and COPD; the patients were subjected to continuous ECG monitoring through a system consisting of the central unit IntelliVue M130, monitor IntelliVue MP2 and the traces were managed through the application WEBACCESS of the central unit M3150; the monitoring allowed the continuous recording of the ECG, the detection of arrhythmias in real time and the storage of any alarm detected; the WEBACCESS application allowed the cardiologist (local and remote HTN) to view in real time the traces and any alarm detected and stored; in case of detection of arrhythmias, the cardiologist liaised with the Neurology department to discuss the specific case and the necessary measures. Results 21258 ECGraphic monitors were analyzed, in a total of 6865 patients (2282 males – mean age 44 years, 4583 females – mean age 45 years); drug–related side effects occurred in 30% of cases as sinus bradycardia, atrioventricular conduction disturbances in 3% of cases (first degree atrioventricular block 1.6%, transient episodes of second and third degree atrioventricular block in 1.4% of cases) and. QT interval prolongation in 9.8% of cases. Adverse events, transient and reversible, were immediately recognized and treated according to the AIFA recommendations for the use of the drug, allowing treatment for all patients monitored. Conclusions The use of Fingolimod has provided satisfactory clinical results with a high safety profile; the use of continuous telemonitoring has allowed to extend the number of subjects treated and to manage effectively and in real time the few side effects encountered.

Development of atrioventricular and intraventricular conduction disturbances in patients undergoing transcatheter aortic valve replacement with new generation self-expanding valves: A real world multicenter analysis

BackgroundHigh degree cardiac conduction disturbances (HDCD) remain a major complication after transcatheter aortic valve replacement (TAVR), especially with self-expandable valves (SEV). Our aim was to investigate peri-procedural and in-hospital modification of atrioventricular and intracardiac conduction associated to new generation SEV implantation, and the development of new HDCD resulting in permanent pacemaker implantation (PPM) in patients undergoing TAVR. Methods and resultsThree-hundred forty-four consecutive patients with severe aortic stenosis who underwent TAVR with a new generation SEV [Evolut-R/Pro (n = 130), Acurate-neo (n = 79), Portico (n = 75) and Allegra (n = 60)] were included. An analysis of baseline, post-TAVR and pre-discharge ECG and procedural aspects were centrally performed. A significant increase in baseline PR interval (169.6 ± 28.2 ms) and QRS complex width (101.7 ± 25.9 ms) was noted immediately post-TAVR (188.04 ± 34.49; 129.55 ± 30.02 ms), with a partial in-hospital reversal (179.4 ± 30.1; 123.06 ± 30.94 ms), resulting in a net increase at hospital discharge of 12.6 ± 38.8 ms and 21.4 ± 31.6 ms (p < 0.001), respectively. The global incidence of new onset persistent HDCD at hospital discharge was 46.3%, with 17.7% of patients requiring PPM. Independent predictors of new onset HCDC at hospital discharge were valve recapture (OR: 2.8; 95% IC: 1.1–7.2, p = 0.033) and implantation depth ≥ 6 mm (OR: 1.9 05% IC 1.1–3.3, p = 0.015), while higher implantation (<3 mm (OR: 0.3, 95% IC 0.1–0.7, p = 0.014) and use of Acurate-Neo valve (OR: 0.4; 95% IC 0.2–0.8, p = 0.009) were protective factor. ConclusionsNew generation self-expanding aortic valves were associated with a significant increase in PR and QRS interval at hospital discharge leading to a very high rate of HDCD. While valve recapture and implantation depth were independent predictors for the occurrence of HDCD, use of Accurate-Neo valve was a protective factor.

EP News: Basic and Translational

van Ouwerkerk et al (Circulation February 3, 2022; https://doi.org/10.1161/CIRCULATIONAHA.121.054347, PMID 35113653) investigated the pathogenic missense variant p.G125R in the TBX5 transcription factor that causes Holt-Oram syndrome (HOS; hand-heart syndrome) and early onset of atrial fibrillation (AF). The TBX5-p.G125R variant was introduced in the mouse genome (Tbx5G125R). The authors observed a high incidence of atrial extrasystoles and atrioventricular conduction disturbances in patients with HOS.

Patient-Specific TBX5-G125R Variant Induces Profound Transcriptional Deregulation and Atrial Dysfunction.

The pathogenic missense variant p.G125R in TBX5 (T-box transcription factor 5) causes Holt-Oram syndrome (also known as hand-heart syndrome) and early onset of atrial fibrillation. Revealing how an altered key developmental transcription factor modulates cardiac physiology in vivo will provide unique insights into the mechanisms underlying atrial fibrillation in these patients. We analyzed ECGs of an extended family pedigree of Holt-Oram syndrome patients. Next, we introduced the TBX5-p.G125R variant in the mouse genome (Tbx5G125R) and performed electrophysiologic analyses (ECG, optical mapping, patch clamp, intracellular calcium measurements), transcriptomics (single-nuclei and tissue RNA sequencing), and epigenetic profiling (assay for transposase-accessible chromatin using sequencing, H3K27ac [histone H3 lysine 27 acetylation] CUT&RUN [cleavage under targets and release under nuclease sequencing]). We discovered high incidence of atrial extra systoles and atrioventricular conduction disturbances in Holt-Oram syndrome patients. Tbx5G125R/+ mice were morphologically unaffected and displayed variable RR intervals, atrial extra systoles, and susceptibility to atrial fibrillation, reminiscent of TBX5-p.G125R patients. Atrial conduction velocity was not affected but systolic and diastolic intracellular calcium concentrations were decreased and action potentials were prolonged in isolated cardiomyocytes of Tbx5G125R/+ mice compared with controls. Transcriptional profiling of atria revealed the most profound transcriptional changes in cardiomyocytes versus other cell types, and identified over a thousand coding and noncoding transcripts that were differentially expressed. Epigenetic profiling uncovered thousands of TBX5-p.G125R-sensitive, putative regulatory elements (including enhancers) that gained accessibility in atrial cardiomyocytes. The majority of sites with increased accessibility were occupied by Tbx5. The small group of sites with reduced accessibility was enriched for DNA-binding motifs of members of the SP (specificity protein) and KLF (Krüppel-like factor) families of transcription factors. These data show that Tbx5-p.G125R induces changes in regulatory element activity, alters transcriptional regulation, and changes cardiomyocyte behavior, possibly caused by altered DNA binding and cooperativity properties. Our data reveal that a disease-causing missense variant in TBX5 induces profound changes in the atrial transcriptional regulatory network and epigenetic state in vivo, leading to arrhythmia reminiscent of those seen in human TBX5-p.G125R variant carriers.

Incidence and Predictors of Permanent Pacemaker Implantation after Transcatheter Aortic Valve Procedures: Data of The Netherlands Heart Registration (NHR).

Atrioventricular conduction disturbance leading to permanent pacemaker (PM) implantation is a frequent and relevant complication after transcatheter aortic valve implantation (TAVI). We aimed to evaluate the rate of post-TAVI permanent PM implantation over time and to identify the predictive factors for post-TAVI PM. The data were retrospectively collected by the Netherlands Heart Registration (NHR). In total, 7489 isolated TAVI patients between 2013 and 2019 were included in the final analysis. The primary endpoint was a permanent PM implantation within 30 days following TAVI. The incidence of the primary endpoint was 12%. Post-TAVI PM showed a stable rate over time. Using multivariable logistic regression analysis, age (OR 1.01, 95% CI 1.00–1.02), weight (OR 1.00, 95% CI 1.00–1.01), creatinine serum level (OR 1.15, 95% CI 1.01–1.31), transfemoral TAVI approach (OR 1.34, 95% CI 1.11–1.61), and TAVI post-dilatation (OR 1.58, 95% CI 1.33–1.89) were shown to be independent predictors of PM. Male sex (OR 0.80, 95% CI 0.68–0.93) and previous aortic valve surgery (OR 0.42, 95% CI 0.26–0.69) had a protective effect on post-TAVI PM. From a large national TAVI registry, some clinical and procedural factors have been identified as promoting or preventing post-TAVI PM. Further efforts are required to identify high-risk patients for post-TAVI PM and to reduce the incidence of this important issue.