Intracardiac Conduction Research Articles

Prediction of CRT response using a novel CRT responder score in an Asian patient population

Abstract Introduction Cardiac Resynchronization Therapy (CRT) guidelines, derived from trials among U.S. and European patients, assign weaker recommendations to those with midrange QRS duration (<150ms). Patient height and body size may modulate CRT efficacy. Moreover, these factors may affect CRT utilization and efficacy in Asia. Aim The purpose of this analysis was to determine the prediction scoring system model for CRT responders in a Japanese patient population. Methods We analyzed the database of the Multicenter Prospective Pilot Study to Test LV Intracardiac Conduction Time as a Predictor of CRT Response (BIO|SELECT) which was a single-arm study conducted at 28 hospitals in Japan. This study enrolled patients eligible for a de-novo CRT-defibrillator (CRT-D) based on current guideline indications, who had no recent or planned cardiac surgery and were planned to receive a Sentus ProMRI OTW quadripolar LV lead and a BIOTRONIK CRT-D with multipole pacing feature. Patients were followed for 7 months after implantation. Four accepted parameters to define CRT response [LVESV (cut-off -15%), LVEF (+5%), BNP (-25%), and NYHA class (one class improvement)] were combined into a composite benefit index (CBI) by forming the normalized sum, with CBI = 4.0 meaning response. The CBI was found to be more robust than the individual 4 parameters due to the reduced influence of noise and measurement errors in single parameters. Several factors were studied to create the scoring tool. The CRT responder score was the sum of these individual scores (range 0-100). To construct a predictive scoring system, logistic regression analysis was performed with a backward selection procedure. In addition, the Akaike information criterion (AIC) was applied to determine the best model among those tested. The score was then assigned employing the β coefficient of each variable divided by the reference value. The model's calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. Results A total of 196 patients were enrolled in this study (mean age 69 years, mean LVEF 30%, left bundle-branch block [LBBB] 58%). The Ooccurrence of CRT response during the 7-month follow-up was 54%. Future CRT responders were significantly predicted by low age (< 70 years)(18 points), female (19 points), prior heart failure hospitalization (16 points), body mass index (<20) (17 points), QRS/height (<0.858)(30 points). This score predicted CRT response well (area under curve 0.72; 95% CI 0.643-0.798). When the cut-off of 63 points or more was applied the sensitivity was 0.56, the specificity was 0.72, and the negative predictive value was 0.58. Conclusions The CRT responder score is a novel approach for the prediction of CRT response, but should be validated and further improved to increase its predictive value. This approach highlights the role of preventing the development of severe heart failure and could help to identify individuals who might benefit from CRT.

The positive F wave in lead V1 of typical atrial flutter is caused by activation of the right atrial appendage: Insight from mapping during entrainment from the right atrial appendage.

Typical atrial flutter (AFL) is a macroreentrant tachycardia in which intracardiac conduction rotates counterclockwise around the tricuspid annulus. Typical AFL has specific electrocardiographic characteristics, including a negative sawtooth-like wave in the inferior lead and a positive F wave in lead V1. This study aimed to analyze the origin of the positive F wave in lead V1, which has not been completely understood. This study enrolled 10 patients who underwent radiofrequency catheter ablation for a typical AFL. Electroanatomical mapping was performed both during typical AFL and entrainment from the right atrial appendage (RAA). The 12-lead electrocardiogram (ECG) and three-dimensional (3D) electroanatomical maps were analyzed. The positive F wave in lead V1 changed during entrainment from the RAA in all the cases. The 3D map during entrainment from the RAA revealed an area of antidromic capture around the RAA, which collided with the orthodromic wave in the anterior right atrium. This area of antidromic capture around the RAA was the only difference from the 3D electroanatomical map of AFL and is considered the cause of the change in the F wave in lead V1 during entrainment. The analysis of the differences in the 12-lead ECG and 3D maps between tachycardia and entrainment from the RAA clearly demonstrated that activation around the RAA is responsible for the generation of the positive F wave in lead V1 of typical AFL.

Тиамин-зависимая мегалобластная анемия (синдром Роджерса) у ребенка трех лет

Thiamine responsive megaloblastic anemia (TRMA), or Rogers syndrome, is a rare autosomal recessive disease characterized by the development of megaloblastic anemia, diabetes mellitus, and progressive sensorineural hearing loss. In some cases, the syndrome causes ophthalmological disorders (retinitis pigmentosa, optic nerve atrophy, maculopathy, nystagmus), heart diseases (paroxysmal atrial fibrillation, supraventricular tachycardia, congenital heart defects, intracardiac conduction disorders) and neurological disorders (epilepsy, cerebrovascular accidents). TRMA develops due to a mutation in the SLC19A2 gene, which encodes ThTr-1 (thiamine transporter protein) expressed in hematopoietic stem cells, pancreatic beta cells, and inner ear cells. The article presents a clinical case of TRMA in a three-year-old child, with the onset in the first year of life, manifesting as anemia and diabetes mellitus. Thiamine therapy ensured a pronounced positive dynamics: the patient's peripheral blood parameters normalized. The clinical description and the literature review herein aim to raise awareness of doctors of all specialties about this syndrome. An atypical clinical picture and lack of knowledge about TRMA often delay the diagnosis and start of therapy.

Study of the course of recurrent myocardial infarction in the acute stage within the framework the hospital register

Aim. To study the features of the course of primary and recurrent myocardial infarction and compare their prognosis in the acute stage of the disease within the framework of the hospital register of the vascular center.Material and methods. The data from the acute coronary syndrome register of N. V. Sklifosovsky Research Institute for Emergency Medicine were used. The inclusion criteria were: transmural acute myocardial infarction (AMI) with ST-segment elevation (codes I21.0-I21.3 according to the International Classification of Diseases); permanent residence in Moscow and the Moscow region. The described part of the study included all patients with transmural myocardial infarction (codes I21.0-I.21.3) admitted from January 1, 2017 to December 31, 2017. Of the AMI patients admitted during this period (n=329), 214 met the inclusion criteria, with primary AMI in 153 and recurrent AMI in 61.Results. Patients with recurrent AMI were significantly older, more often had a disability group. Smoking and arterial hypertension were more frequent risk factors among patients with recurrent AMI than in primary AMI. All indices reflecting the severity of coronary artery disease and its complications were also significantly more common in the group with recurrent AMI. Diabetes mellitus was more common in these patients. Taking medications before hospitalization, as well as the regularity of this intake, were significantly more common in patients who had repeated AMI. The mortality rate of patients with recurrent AMI was 4.6 times higher than that of patients with primary AMI. Such complications as atrial fibrillation and flutter, intracardiac conduction disturbance requiring temporary endocardial stimulator placement, acute heart failure requiring intra-aortic balloon counterpulsation, respiratory failure requiring artificial ventilation, cardiogenic shock were significantly more common in patients with recurrent AMI. Kaplan-Meyer curves clearly demonstrate the differences in hospital mortality among the two groups of patients. These curves also clearly show that patients with primary AMI died mostly in the first days of the disease, but patients with recurrent AMI could die at a much later date, up to 12 days after admission. Analysis of factors determining the mortality risk during hospitalization showed that recurrent AMI is an independent predictor of death.Conclusion. The results of our work indicate the need for prompt identification of patients who had previously undergone AMI upon their admission to the vascular center, as well as the development of more active prevention tactics for such patients.

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial

BackgroundStereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75–85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation.ObjectiveA single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk.MethodsPatients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D.DiscussionDEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure.Trial registrationNCT05594368.

Prolonged PR intervals are associated with epicardial adipose tissue and recurrence after catheter ablation in persistent atrial fibrillation.

Epicardial adipose tissue (EAT) has been reported to promote myocardial fibrosis and to affect intracardiac conduction. The PR interval reflects the conduction from the atria to the Purkinje fibers and may be associated with the EAT volume, especially in persistent atrial fibrillation (AF) patients. We aimed to investigate the relationship between the EAT and PR interval in patients with persistent AF. We enrolled 268 persistent AF patients who underwent catheter ablation (CA) and divided the patients into two groups: the normal PR interval group (PR interval less than 200ms: Group N) and long PR interval group (PR interval 200ms or more: Group L). We then analyzed the association between the total EAT volume around the heart and PR interval and calculated the ratio of the duration of the P wave (PWD) to the PR interval (PWD/PR interval). Moreover, we investigated whether a long PR interval was associated with the outcomes after ablation. The total EAT volume was significantly larger in Group L than Group N (Group N: 131.4 ± 51.8ml vs. Group L: 151.3 ± 63.3ml, p = 0.039). A positive correlation was also observed between the PWD/PR interval and EAT volume in Group L (r = 0.345, p = 0.039). A multivariate analysis also revealed that a long PR interval was independently associated with AF recurrence after CA (hazard ratio [HR] 2.071, p = 0.032). The total EAT volume was associated with a long PR interval, and a long PR interval was a significant risk factor for recurrence after ablation in persistent AF patients.

How to ablate the septo-pulmonary bundle: a case-based review of percutaneous ablation strategies to achieve roof line block.

Electrical conduction through cardiac muscle fibres separated from the main myocardial wall by layers of interposed adipose tissue are notoriously difficult to target by endocardial ablation alone. They are a recognised important cause for procedural failure due to the difficulties of delivering sufficient energy via the endocardial radiofrequency catheter to reach the outer epicardial layer without risking adverse events of the otherwise thin walled atria. Left atrial ablations for atrial fibrillation (AF) and tachycardia are commonly affected by the presence of several epicardial structures, with the septo-pulmonary bundle (SPB), Bachmann's bundle, and the ligament of Marshall all posing substantial challenges for endocardial procedures. Delivery of a transmural lesion set is essential for sustained pulmonary vein isolation and for conduction block across linear atrial lines which in turn has been described to translate into a reduced AF/atrial tachycardia recurrence rate. To overcome the limitations of endocardial-only approaches, surgical ablation techniques for epicardial or combined hybrid endo-epicardial ablations have been described to successfully target these connections. Yet, these techniques confer an increase in procedure complexity, duration, cost, and morbidity. Alternatively, coronary venous system ethanol ablation has been successfully employed by sub-selecting the vein of Marshall to facilitate mitral isthmus line block, although this approach is naturally limited to this area by the coronary venous anatomy. Increased awareness of the pathophysiological relevance of these epicardial structures and their intracardiac conduction patterns in the era of high-resolution 3D electro-anatomical mapping technology has allowed greater understanding of their contribution to the persistence of AF as well as failure to achieve transmural block by traditional ablation approaches. This might translate into novel catheter ablation strategies with procedural success rates comparable to surgical 'cut-and-sew' techniques. This review aims to give an overview of percutaneous catheter ablation strategies to target the SPB, an important cause of failed block across the roof line and isolation of the left atrial posterior wall and/or the pulmonary veins. Existing and investigational technologies will be discussed and an outlook of future approaches provided.

Incidence of cardiac events in on-pump elective surgical interventions on the aorta and heart valves

Aim. To determine the incidence and predictors of cardiovascular events in onpump cardiac operations in modern practice.Material and methods. The study included 200 patients who underwent various elective cardiac surgical interventions. Cardiovascular events (CVEs) were determined within 30 days from the operation, according to medical records and autopsy protocols. We identified major CVEs (cardiovascular death, stroke, myocardial infarction) and minor CVEs (angina pectoris, significant ventricular arrhythmias, atrial fibrillation or flutter episodes, AV conduction disorders, etc.). A comprehensive preoperative examination was performed, including an extended echocardiography protocol and coronary angiography.Results. In 101 patients (50,05%), various CVEs were identified: 4,0% had major CVEs and 46,05% had minor CVEs and various non-cardiac complications, while perioperative mortality was 2,0%. Most ischemic CVEs, as well as most intracardiac conduction disorders, were registered during the first 3 days after surgery. In contrast, episodes of atrial fibrillation/flutter occurred 2-7 days after the intervention. There were following preoperative examination parameters with the highest prognostic value: history of heart failure, age >65 years, history of myocardial infarction, occlusion of at least one coronary artery, and diabetes.Conclusion. The data obtained indicate the high efficiency of current surgical and anesthetic technologies, which lead to relatively low risk of severe and fatal events. The parameters of the preoperative examination, which determine the increased risk of intervention, are highlighted.

Influence of cardiovascular risk factors on the cognitive functions of schizophrenia patients

Cardiovascular risk factors (CVRF) are quite often observed in the group of patients with schizophrenia, contributing to a deterioration in their standard of living. In addition, CVRF can cause death of such patients. However, the influence of these factors on many spheres of schizophrenia patients, in particular cognitive functions, remain understudied. The objective of the research was to study the effect of CVRF (hypertension (HT), cardiac disorders (ischemic heart disease), intracardiac conduction disturbance), diabetes mellitus (DM), and myocardial infarction (MI) on cognitive functions of schizophrenia patients. The study involved 102 patients diagnosed with paranoid schizophrenia who were hospitalized in psychiatric departments № 1 and № 5 of the State Institution «Lugansk Republican Clinical Psychoneurological Hospital», Lugansk People»s Republic. All study participants were divided into two study groups: 1st — the control group (n = 52), 2nd — the group of patients with CVFR (n = 50). The mean age of the patients was 47.7±5.6 years; there were 40 males (39.2 %) and 62 females (60.8 %). Clinical, psychopathological, catamnestic, psychometric, and statistical research methods were used. As a result of the study, it was found that the patients with CVFR had poorer cognitive test scores for almost all of the presented parameters. Regression analysis in relation to the effect of CVFR on the general state of cognitive functions showed that all these factors considerably affected the cognitive status, with HT being the most statistically significant. CVFR can have a negative impact on the state of cognitive functions in schizophrenia patients.

Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography.

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the allocation of a growing number of donor hearts with extended criteria. These marginal grafts are associated with a high risk of primary graft failure and may benefit from ex situ perfusion before transplant. This technology allows for extended organ preservation using warm oxygenated blood perfusion with continuous metabolic monitoring. The only NESP device currently available for clinical practice perfuses the organ in an unloaded non-working state, which does not allow for functional assessment of the beating heart. We therefore developed an original platform of NESP in working mode conditions with adjustment of left ventricular preload and afterload. This protocol was applied in porcine hearts. Ex situ functional assessment of the heart was achieved with intracardiac conductance catheterization and surface echocardiography. Along with a description of the experimental protocol, we herein report the main results, as well as pearls and pitfalls associated with the acquisition of pressure-volume loops and myocardial power during NESP. Correlations between hemodynamic findings and ultrasound variables are of major interest, especially for further rehabilitation of donor hearts before transplantation. This protocol aims to improve the assessment of donor hearts to both increase the donor pool and reduce the incidence of primary graft failure.

Functional Assessment of the Donor Heart During <em>Ex Situ</em> Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography

Heart transplantation remains the gold standard treatment for advanced heart failure. However, the current critical organ shortage has resulted in the allocation of a growing number of donor hearts with extended criteria. These marginal grafts are associated with a high risk of primary graft failure and may benefit from ex situ perfusion before transplant. This technology allows for extended organ preservation using warm oxygenated blood perfusion with continuous metabolic monitoring. The only NESP device currently available for clinical practice perfuses the organ in an unloaded non-working state, which does not allow for functional assessment of the beating heart. We therefore developed an original platform of NESP in working mode conditions with adjustment of left ventricular preload and afterload. This protocol was applied in porcine hearts. Ex situ functional assessment of the heart was achieved with intracardiac conductance catheterization and surface echocardiography. Along with a description of the experimental protocol, we herein report the main results, as well as pearls and pitfalls associated with the acquisition of pressure-volume loops and myocardial power during NESP. Correlations between hemodynamic findings and ultrasound variables are of major interest, especially for further rehabilitation of donor hearts before transplantation. This protocol aims to improve the assessment of donor hearts to both increase the donor pool and reduce the incidence of primary graft failure.

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).

Value of Periprocedural Electrophysiology Testing During Transcatheter Aortic Valve Replacement for Risk Stratification ofPatients With New-Onset Left Bundle-Branch Block.

BackgroundDespite being the most frequent complication following transcatheter aortic valve replacement (TAVR), optimal management of left bundle‐branch block (LBBB) remains unknown. Electrophysiology study has been proposed for risk stratification. However, the optimal timing of electrophysiology study remains unknown. We aimed to investigate the temporal dynamics of atrioventricular conduction in patients with new‐onset LBBB after TAVR by performing serial electrophysiology study and to deduce a treatment strategy.Methods and ResultsWe assessed consecutive patients undergoing TAVR via His‐ventricular interval measurement prevalve and postvalve deployment and the day after TAVR. Infranodal conduction delay was defined as a His‐ventricular interval >55 milliseconds. Among 107 patients undergoing TAVR, 53 patients (50%) experienced new‐onset LBBB postvalve deployment and infranodal conduction delay was noted in 24 of 53 patients intraprocedurally (45%). LBBB resolved the day after TAVR in 35 patients (66%). In patients with new‐onset LBBB postvalve deployment and no infrahisian conduction delay intraprocedurally, the His‐ventricular interval did not prolong in any patient to >55 milliseconds the following day. Overall, 4 patients (7.5%) with new‐onset LBBB after TAVR were found to have persistent infrahisian conduction delay 24 hours after TAVR. During 30‐day follow‐up, 1 patient (1.1%) with new LBBB and a normal His‐ventricular interval after TAVR developed new high‐grade atrioventricular block.ConclusionsAmong patients with new‐onset LBBB postvalve deployment, infrahisian conduction delay can safely be excluded intraprocedurally, suggesting that early intracardiac intraprocedural conduction studies may be of value in these patients.

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.

The Bradycardic Agent Ivabradine Acts as an Atypical Inhibitor of Voltage-Gated Sodium Channels.

Background and purpose: Ivabradine is clinically administered to lower the heart rate, proposedly by inhibiting hyperpolarization-activated cyclic nucleotide-gated cation channels in the sinoatrial node. Recent evidence suggests that voltage-gated sodium channels (VGSC) are inhibited within the same concentration range. VGSCs are expressed within the sinoatrial node and throughout the conduction system of the heart. A block of these channels thus likely contributes to the established and newly raised clinical indications of ivabradine. We, therefore, investigated the pharmacological action of ivabradine on VGSCs in sufficient detail in order to gain a better understanding of the pro- and anti-arrhythmic effects associated with the administration of this drug. Experimental Approach: Ivabradine was tested on VGSCs in native cardiomyocytes isolated from mouse ventricles and the His-Purkinje system and on human Nav1.5 in a heterologous expression system. We investigated the mechanism of channel inhibition by determining its voltage-, frequency-, state-, and temperature-dependence, complemented by a molecular drug docking to the recent Nav1.5 cryoEM structure. Automated patch-clamp experiments were used to investigate ivabradine-mediated changes in Nav1.5 inactivation parameters and inhibition of different VGSC isoforms. Key results: Ivabradine inhibited VGSCs in a voltage- and frequency-dependent manner, but did not alter voltage-dependence of activation and fast inactivation, nor recovery from fast inactivation. Cardiac (Nav1.5), neuronal (Nav1.2), and skeletal muscle (Nav1.4) VGSC isoforms were inhibited by ivabradine within the same concentration range, as were sodium currents in native cardiomyocytes isolated from the ventricles and the His-Purkinje system. Molecular drug docking suggested an interaction of ivabradine with the classical local anesthetic binding site. Conclusion and Implications: Ivabradine acts as an atypical inhibitor of VGSCs. Inhibition of VGSCs likely contributes to the heart rate lowering effect of ivabradine, in particular at higher stimulation frequencies and depolarized membrane potentials, and to the observed slowing of intra-cardiac conduction. Inhibition of VGSCs in native cardiomyocytes and across channel isoforms may provide a potential basis for the anti-arrhythmic potential as observed upon administration of ivabradine.

Rhythm disturbances following rapid-deployment aortic valve replacement.

ObjectivesThere have been reports of postoperative conduction disturbances after rapid-deployment aortic valve replacement. Our objective was to assess electrocardiogram changes in patients undergoing this procedure and review the literature on this topic.MethodsIn this retrospective case series, clinical data were extracted from patient records at St Vincent's Hospital Melbourne and the Australia New Zealand Society of Cardiac and Thoracic Surgeons database. Electrocardiogram data were obtained at baseline and postoperatively on day 5 and at week 6 and reviewed for rhythm disturbances and intracardiac conduction problems. Pacemaker status was also recorded.ResultsFrom 2013 to 2017, 100 consecutive patients underwent rapid-deployment aortic valve replacement with 1 valve type at our institution. Three patients were excluded because of paced rhythm preoperatively, leaving 97 patients (mean age 74.7 ± 8.12 years; 56.7% male) for analysis. Some 18.6% of patients developed new left bundle branch block at 5 days postoperatively and only 4.1% of patients found with persistent left bundle branch block at 6-week follow-up compared with preoperatively. No significant changes were observed in the frequencies of atrial fibrillation, first-degree heart block, and right bundle branch block. However, there was evidence of increases in paced rhythm and subsequent need for a permanent pacemaker. A total of 14 patients (14.4%) had a permanent pacemaker implanted at an average of 11.1 ± 2.9 days postoperatively.ConclusionsRhythm disturbances and conduction abnormalities are noted with the rapid-deployment aortic valves used at our institution, but appear comparable to other rapid-deployment aortic valve replacement bioprostheses. These abnormalities may be related to the effect of the sub-annular stent frame of the valve system and implantation technique.

Intracardiac conduction time as a predictor of cardiac resynchronization therapy response: Results of the BIO|SELECT pilot study.

BackgroundQuadripolar left ventricular (LV) leads are capable of sensing and pacing the left ventricle from 4 different electrodes, which may potentially improve patient response to cardiac resynchronization therapy (CRT).ObjectiveWe measured 3 different time intervals: right ventricular (RV)-sensed to LV-sensed during intrinsic rhythm (RVs-LVs), RV-paced to LV-sensed (RVp-LVs), and LV-paced to LV-sensed (LVp-LVs, between distal [LV1] and proximal pole on a quadripolar LV lead), and assessed their association with CRT response in terms of LV end-systolic volume (LVESV) and a composite benefit index (CBI) comprising LVESV, LV ejection fraction (LVEF), brain natriuretic peptide level, and NYHA class.MethodsA CRT-defibrillator system with quadripolar LV lead was implanted in 196 patients (mean age 69 years, mean LVEF 30%, left bundle-branch block [LBBB] 58%). Conduction intervals were measured before hospital discharge. At baseline and 7-month follow-up, echocardiographic and other components of CBI were determined.ResultsThe mean RVs-LV1s, RVp-LV1s, and LVp-LVs delays were 68 ± 38 ms, 132 ± 34 ms, and 99 ± 31 ms, respectively. From baseline to 7 months, LVESV decreased by 17.3% ± 28.6%. The RVs-LV1s interval correlated stronger with CBI (R2 = 0.12, P < .00001) than with LVESV change (R2 = 0.05, P = .006). In contrast, RVp-LV1s did not correlate and LVp-LVs correlated only weakly with CRT response. The subgroup of patients (44%) with LBBB and RVs-LV1s above the lower quartile (≥34 ms) showed the greatest response to CRT.ConclusionThe RVs-LVs interval during intrinsic rhythm is relevant for CRT success, whereas RVp-LVs and LVp-LVs intervals did not predict CRT response.

Acute effects of inhaled iloprost on intracardiac conduction in patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is asevere, life-threatening disorder despite the availability of specific drug therapy. Alack of endogenous prostacyclin secondary to downregulation of prostacyclin synthase in PAH may contribute to vascular pathologies. Therefore, prostacyclin and its analogs including inhaled iloprost may decrease pulmonary arterial pressure and ventricular pressure. Here, we studied that acute effects of iloprost used in pulmonary vasoreactivity testing on the intracardiac conduction system in patients with PAH. Atotal of35 (15idiopathic PAH, 20congenital heart disease) patients with PAH were included in this prospective study. Patients were divided into two groups: 22patients with negative pulmonary vasoreactivity in group1 and 13with positive pulmonary vasoreactivity in group2. Electrophysiological parameters including basic cycle length, atrium-His (AH) interval, His-ventricle (HV) interval, PR interval, QT interval, QRS duration, Wenckebach period, and sinus node recovery time (SNRT) were evaluated before and after pulmonary vasoreactivity testing in both groups. The AH interval (81 [74-93]; 80 [65.5-88], p = 0.019) and SNRT (907.7 ± 263.4; 854.0 ± 288.04, p = 0.027) was significantly decreased after pulmonary vasoreactivity testing. Mean right atrium pressure was found to be correlated with baseline AH (r = 0.371, p = 0.031) and SNRT (r = 0.353, p = 0.037). Inhaled iloprost can improve cardiovascular performance in the presence of PAH, primarily through areduction in right ventricular afterload and interventricular pressure. Decreased pressure on the interventricular septum and ventricles leads to conduction system normalization including of the AH interval and SNRT due to resolution of inflammation and edema.

Early Changes in Rat Heart After High-Dose Irradiation: Implications for Antiarrhythmic Effects of Cardiac Radioablation.

BackgroundNoninvasive cardiac radioablation is employed to treat ventricular arrhythmia. However, myocardial changes leading to early‐period antiarrhythmic effects induced by high‐dose irradiation are unknown. This study investigated dose‐responsive histologic, ultrastructural, and functional changes within 1 month after irradiation in rat heart.Methods and ResultsWhole hearts of wild‐type Lewis rats (N=95) were irradiated with single fraction 20, 25, 30, 40, or 50 Gy and explanted at 1 day or 1, 2, 3, or 4 weeks’ postirradiation. Microscopic pathologic changes of cardiac structures by light microscope with immunohistopathologic staining, ultrastructure by electron microscopy, and functional evaluation by ECG and echocardiography were studied. Despite high‐dose irradiation, no myocardial necrosis and apoptosis were observed. Intercalated discs were widened and disrupted, forming uneven and twisted junctions between adjacent myocytes. Diffuse vacuolization peaked at 3 weeks, suggesting irradiation dose‐responsiveness, which was correlated with interstitial and intracellular edema. CD68 immunostaining accompanying vacuolization suggested mononuclear cell infiltration. These changes were prominent in working myocardium but not cardiac conduction tissue. Intracardiac conduction represented by PR and QTc intervals on ECG was delayed compared with baseline measurements. ST segment was initially depressed and gradually elevated. Ventricular chamber dimensions and function remained intact without pericardial effusion.ConclusionsMononuclear cell–related intracellular and extracellular edema with diffuse vacuolization and intercalated disc widening were observed within 1 month after high‐dose irradiation. ECG indicated intracardiac conduction delay with prominent ST‐segment changes. These observations suggest that early antiarrhythmic effects after cardiac radioablation result from conduction disturbances and membrane potential alterations without necrosis.

Influence of cardiovascular risk factors on pre-mild cognitive decline at middle and old age

Much attention is currently paid to non-dementia cognitive impairment, such as mild cognitive impairment and pre-mild cognitive decline (PMCD), since their timely detection and optimal correction increase the possibility of preventing dementia.Objective: to analyze the neuropsychological characteristics of patients with PMCD depending on the presence or absence of cardiovascular risk factors (CVRFs): hypertension, cardiac disorders (ischemic heart disease, intracardiac conduction disturbance), and prior stroke and myocardial infarction, as well as diabetes mellitus.Patients and methods. Examinations were made in 182 patients (132 women, 50 men; mean age, 59.32±5.41 years) with PMCD and CVFRs, 101 patients (77 women, 24 men; mean age, 59.45±7.04 years) with PMCD without CVRFs, and 77 control persons (55 women, 22 men; mean age, 60.55±5.65 years). All underwent general clinical, neurological, and clinical psychological studies using rating scales and tests.Results and discussion. The patients with PMCD and CVRFs had lower scores on all neuropsychological tests than the control group and on most tests than the patients with PMCD without CVRFs. In addition to some deterioration in memory indicators, the patients with CVRFs performed worse executive function tests. Cluster analysis showed that in the patients with PMCD, the severity of cognitive decline was considerably affected by hypertension, cardiac disorders, and diabetes mellitus; among them, hypertension was of the most significance.Conclusion. The association of cognitive decline with the burden of CVRFs indicates their important role in the deterioration of cognitive functions in PMCD.