Next-generation pacemakers: from electrical devices to biological pacemakers

The invention of an electric pacemaker in the middle of the 20th century led to a revolution in the treatment of cardiac conduction system diseases. The improvement of pacemakers continued. In 1962, the first small series of external pacemakers for percutaneous and direct stimulation was produced in Kaunas. After a while, electric pacemakers became more reliable, smaller and lighter in weight, but the problem of foreign body associated infection and limited service life remained unresolved. Modern high-tech medicine strives to create less invasive electric pacemakers, but nevertheless, biological pacemakers can expand the therapeutic arsenal for the treatment of cardiac patients, being the most physiological for humans. The concept of an artificial biological pacemaker consists of the creation of an organic structure that generates a spontaneous rhythm from the implantation site in the myocardium. Various gene and cellular approaches were used to create biological pacemakers: a functional reorganization approach (use of adenovirus vectors for hyperexpression of genes encoding ion channels in cardiomyocytes); hybrid approach (use of fibroblasts to deliver genes of ion channels that provide heart automation); somatic reprogramming approach (overexpression of the transcription factor TBX18 using adenoviral vectors, which reprograms cardiomyocytes into induced sinoatrial node cells, creating cardiac stimulatory activity); cellular approach (transplantation of stem cells to a specific place in the heart, thereby creating biological stimulation). Modern methods of electrical cardiac stimulation and the developed concepts of the biological pacemaker clearly show the possibility of eliminating current problems associated with the use of an artificial pacemaker by replacing it with a biological one. Each of the approaches (gene, cellular, hybrid-cellular, somatic reprogramming) has its own advantages and disadvantages, which predisposes to further study and improvement in order to introduce a biological pacemaker into clinical practice.

MRI safety wih abandoned or functional epicardial pacing leads

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): HUS Medical Imaging Center research grant Background The Heart and Rhythm Society’s consensus statement 2017 approves magnetic resonance imaging (MRI) with cardiac implantable electronic devices (CIED), but excludes patients with epicardial and abandoned leads. Potential safety hazards of an MRI with epicardial pacing leads include heating of the tip of the lead and induction of current in the pacing lead resulting in inappropriate cardiac stimulation. Only a few small studies of MRI safety with epicardial pacing leads have been published and adverse events have been rare. The clinical dilemma remains, whether performing an MRI on a patient with CIED and epicardial pacing leads is safe. We have performed MRIs on patients with CIED and epicardial pacing leads when benefits have been considered to outweigh the risks after careful case-by-case evaluation following our institutional MRI with CIED safety protocol. Purpose The aim of this study was to evaluate the safety of performing an MRI scan on patients with CIED and abandoned or functional epicardial pacing leads. Methods All the clinically indicated MRI examinations conducted on adult patients with CIED and functional or abandoned epicardial leads (n = 24) performed in our hospital between November 2011 and October 2019 were included in this observational retrospective study. The data were retrospectively collected from electronic medical records. Results Altogether 24 MRIs were performed to 16 patients with functional or abandoned epicardial pacing leads (Table). 93.8% (15/16) patients had congenital heart disease. Cardiac MRI was the most frequent examination (21/24, 91.7%). 66.7% of the MRI scans (16/24) were conducted on patients with functional epicardial pacing leads. In 5/24 (20.8%) MRIs, the patient was pacemaker-dependent. A clinically significant event occurred in one MRI scan. This was transient elevation of the pacing lead threshold in a patient with functional epicardial ventricular pacing lead, that was implanted 29 years prior to the MRI. In another patient with 30-year-old functional epicardial pacing leads, clinically significant irreversible elevation in atrial pacing lead impedance was detected 6 months after the MRI and unlikely related to previous MRI examination. None of the patients experienced sensations leading to cessation of the MRI scans. No clinically significant pacing lead parameter changes were detected after MRIs performed on patients with modern (implanted year 2000 or later) functional epicardial pacing leads or functional endocardial leads and abandoned epicardial leads. Conclusions MRI examinations in patients with CIED and modern functional epicardial pacing leads were performed without detectable adverse events. Performing an MRI with old functional epicardial pacing leads may involve more risks.

Technical and electrophysiological aspects of multisite cardiac stimulation through the access of the middle cardiac vein

Funding Acknowledgements Type of funding sources: None. Main funding source(s): Alfredo Aurélio Marinho Rosa and Alfredo Aurélio Marinho Rosa Filho Background Heart failure (HF) is a serious, progressive disease, caused by ventricular dysfunction, leading to a worsening in quality and a reduction in life expectancy. Cardiac resynchronization therapy through multisite stimulation has become an important tool in the treatment of advanced HF, however, due to anatomical variations and even the absence of appropriate veins for the insertion of the left ventricular electrode, the access of the middle cardiac vein can be an option for biventricular cardiac stimulation. Objective: To present the technique used to access the middle cardiac vein (MCV) for the implantation of the left ventricular electrode and the results of this multisite stimulation. Material and Method: Between March 2006 and May 2016, 388 patients (PT) underwent biventricular stimulation (BIV) at our service. 276 PT (71.1%), were associated with the cardioverter-defibrillator (ICD), 226 PT (58.2%) were male and their age ranged from 28 to 84 years with an average of 64 years. In this group, in 63 PT (16.2%) the left ventricular electrode was implanted through CMV. The technique initially consists of introducing a deflectable catheter for marking the coronary sinus (SC) via the femoral approach, then the SC approach is performed by puncturing the left subclavian vein, introducing an 8F sheath up to the proximal 1/3, where the VCM venogram is performed by introducing a 0.014 "guide wire and the 5 F bipolar or quadripolar electrode, then defining the best electrode position from the smallest stimulated QRS. Results: In this group of 63 PT, 52 PT (82.5%) responded to cardiac resynchronization therapy. The most frequent cardiopathies involved were ischemic (38%), chagasic (25%), hypertensive (12%) and others (25%). The thresholds varied from 3.5 to 0.5 V, impedance from 600 to 1200 ohms and sensitivity between 10 and 20 mV. There were no complications in the trans or post implant and in 5 PT (7.9%), there was phrenic stimulation. The procedure time varied from 50 to 180 minutes. Conclusion: Multisite stimulation through the access of the middle cardiac vein proved to be a possible alternative, easy to perform and with a high PT index responsive to cardiac resynchronization therapy.

Age independently predicts hemodynamic, but not arrhythmic STEMI-related complications. Data from a cohort study on 848 STEMI patients

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Romanian Ministry of Education and Research, CNCS-UEFISCDI BACKGROUND Age is one of the most relevant prognostic factors in patients presenting with ST-segment elevation myocardial infarction (STEMI). However, it remains unknown whether this impaired prognosis is due to the occurrence of hemodynamic and/or arrhythmic STEMI-related complications. Understanding the mechanisms involved in STEMI-related complications with advancing age could significantly improve outcomes in this high-risk population. PURPOSE We aimed to investigate the contribution of advanced age to the occurrence of hemodynamic and arrhythmic complications in STEMI patients. METHODS A total of 848 consecutive patients treated by primary percutaneous coronary intervention for STEMI were evaluated. Heart failure, cardiogenic shock, asystole, inotropic and diuretic use, and kidney dysfunction were used as in-hospital markers of hemodynamic complications. Ventricular fibrillation, conduction disorders, cardiac stimulation, and antiarrhythmic drugs use were used as markers of arrhythmic complications. The relationship between age and the occurrence of hemodynamic and arrhythmic complications was evaluated. The contribution of age to in-hospital death was also assessed. RESULTS In-hospital death occurred in 50 (5.8%) patients; patients who deceased were significantly older than their non-deceased counterparts (70.9 ± 10.9 vs. 61.2 ± 11.8 years; p< 0.0001). There was no association between age and the occurrence of any of the evaluated arrhythmic complications (all p >0.05). However, patients who presented hemodynamic complications were significantly older than those who did not (all p< 0.05). Age >60 years was a significant predictor of hemodynamic complications (p< 0.0001) with 61.7% sensitivity and 60.4% specificity. The association between age and hemodynamic complications remained significant after correction for additional risk factors (i.e., hypertension, diabetes mellitus, pre-existing heart failure, Killip class on admission, symptom onset-to-cardiac catheterization laboratory time interval). CONCLUSIONS In the present study, age was identified as an independent predictor of STEMI-related hemodynamic, but not arrhythmic complications. These data indicate that whereas age does not seem to affect the occurrence of STEMI-related rhythm disorders, patients above the age of 60 should particularly benefit from closer follow-up and more intensive strategies to prevent life-threating hemodynamic complications.

Patient with an implantable cardiac electrical stimulation device. What should the anesthesiologist know?

Patients with implantable electric stimulation devices are challenging to the anesthesiologist since these cases demand a comprehensive knowledge about how the device operates, the indications for the implant and the implications that must be addressed during the perioperative period . This article is intended to provide the reader with clear and structured information so that the anesthesiologist will be able to safely deal with the situation of a patient with an implantable cardiac stimulation device, who has been programmed for emergent surgery. A search for the scientific evidence available was conducted in Pubmed / Medline, ScienceDirect, OVID, SciELO), for a non-systematic review. The incidence of the use of cardiac electric stimulation devices has been growing. Their operation is increasingly complex, and demands being constantly updated on the knowledge in the area.

Advances in Physiological Cardiac Stimulation

Advances in cardiac stimulation demonstrate that bradyarrhythmia treatments go beyond heart rate control. The concern with the ventricular stimulation site and, consequently, with the maintenance of intraventricular synchrony has become routine in most services. Techniques of physiological cardiac stimulation, such as stimulation of the bundle of His and the left branch, have been improved. Despite the indisputable benefits of these therapeutic modalities, there are technical difficulties that limit systematic use. In this sense, to make physiological cardiac stimulation more practical and reproducible, the concept of parahissian stimulation was expanded and studied. The technique, simpler and reproducible, contemplates a conventional approach of the right ventricle. The big difference is the use of QRS spatial variance analysis technology (Synchromax®, Exo S.A., Argentina) to confirm the maintenance of ventricular synchrony according to the implanted site.

Cardiac Stimulation in the Third Millennium: Where Do We Head from Here?

Over the years, pacemakers have evolved from a life-saving tool to prevent asystole to a device to treat heart rhythm disorders and heart failure, aiming at improving both cardiac function and clinical outcomes. Cardiac stimulation nowadays aims to correct the electrophysiologic roots of mechanical inefficiency in different structural heart diseases. This has led to awareness of the concealed risks of customary cardiac pacing that can inadvertently cause atrioventricular and inter-/intra-ventricular dyssynchrony, and has promoted the development of new pacing modalities and the use of stimulation sites different from the right atrial appendage and the right ventricular apex. The perspective of truly physiologic pacing is the leading concept of the continued research in the past 30 years, which has made cardiac stimulation procedure more sophisticated and challenging. In this article, we analyze the emerging evidence in favor of the available strategies to achieve an individualized physiologic setting in bradycardia pacing.

TRICUSPID VALVE REGURGITATION IN PATIENTS UNDERGOING ENDOCARDIAL LEADS PLACEMENT

Objective: To assess prospectively the presence and degree of tricuspid regurgitation (TR) after right ventricular (RV) lead placement utilizing 2-dimensional and doppler echocardiography in a group of patients implanted with Permanent pace-maker or implantable cardioverter defibrillator (ICD). Study Design: Descriptive cross sectional study. Place and Duration of Study: Study was conducted at OPD of AFIC/NIHD Rawalpindi from Jan to Jun 2019. Methodology: One hundred patients after cardiac stimulation system implantation were included in this study. Patients with severe valve disease, heart failure, congenital heart disease, pre-existing pulmonary hypertension and presence of moderate or severe tricuspid regurgitation were excluded. M-mode, 2 –dimensional and doppler echocardiographic studies were performed. Continuous-wave doppler measurements were made from apical four-chamber view in order to obtain maximum tricuspid flow velocities. A complete echocardiographic study was performed following device implantation. Echocardiographic measurements were repeated at 6-months of follow-up period. Those patients who developed tricuspid regurgitation were further assessed by color doppler, taking into account density and contour of the jet on continuous-wave doppler. Tricuspid regurgitation severity was classified into three groups: mild, moderate and severe according to the recommendations for non-invasive evaluation of native valvular regurgitation by the American Society of Echocardiography. The collected data was analysed by using SPSS-23. Results: Out of 100 patients, 67 (67%) were males and 33(33%) were females with the mean age of 65.29 ± 12.02 years. All the patients had normal chambers dimensions before the procedure. 65 (65%) had leads screwed to RV apex while 35 (35%) had through RV septum. 83 (83%) patients received a dual chamber device, while 17 (17%) patients got single chamber (ventricular) device implanted. Following device implantation after 6 months mild TR was noted in 4 (4%), moderate TR in 4 (4%) and severe TR 2 (2%) in cases. Conclusion: Tricuspid incompetence following endocardial leads implantation is not rare and occurred in approximately 10% of our patients. This complication may be preventable, because it is likely due to the interference of the endocardial lead with the TV.

Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome

BackgroundPathogenic variants of GNB5 encoding the β5 subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia.MethodsWe used echocardiography and telemetric ECG recordings to investigate consequences of Gnb5 loss in mouse.ResultsWe delineated a key role of Gnb5 in heart sinus conduction and showed that Gnb5-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance. Gnb5−/− mice were smaller and had a smaller heart than Gnb5+/+ and Gnb5+/−, but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR in Gnb5−/− mice. In contrast, Gnb5−/− mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. Homozygous Gnb5 loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the IDDCA cohort to 44 patients.ConclusionsOur data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations in Gnb5−/− mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism of Gnb5 signalling in the autonomic control of the heart will pave the way for future drug screening.