Modulation Scheme Analysis for Low-Power Leadless Pacemaker Synchronization Based on Conductive Intracardiac Communication

Conductive intracardiac communication (CIC) has been demonstrated as a promising concept for the synchronization of multi-chamber leadless cardiac pacemakers (LLPMs). To meet the 2–5 μ W power budget of a LLPM, highly specialized CIC-transceivers, which make optimal use of the cardiac communication channel, need to be developed. However, a detailed investigation of the optimal communication parameters for CIC-based LLPM synchronization is missing so far. This work analyzes the intracardiac communication performance of two low-power modulation techniques, namely On-Off-Keying (OOK) and Manchester-encoded baseband transmission (BB-MAN), as a function of the transmitted bit-energy. The bit error rate (BER) of a prototype dual-chamber LLPM was determined both in simulation and in-vitro experiments on porcine hearts. A BER of 1e − 4 was achieved with a median bit-energy in the range of 3-16 pJ (interquartile range: 4-15 pJ) for data rates from 75-500 kbps and a receiver input noise density of 7 nV/ √Hz . Both modulation schemes showed comparable performance, with BB-MAN having a slight bit-energy advantage (1-2 dB at 150-500 kbps) under equalized transceiver characteristics. This study demonstrates that reliable CIC-based LLPM synchronization is feasible at transmitted power levels < 10 nW under realistic channel conditions and receiver noise performance. Therefore, modulation techniques such, as BB-MAN or OOK, are preferable over recently proposed alternatives, such as pulse position modulation or conductive impulse signaling, since they can be realized with fewer hardware resources and smaller bandwidth requirements. Ultimately, a baseband communication approach might be favored over OOK, due to the more efficient cardiac signal transmission and reduced transceiver complexity

High-sensitive troponin T measurements: what do we gain and what are the challenges?

Cardiac troponin (cTn) I and T are structural proteins unique to the heart. Detection of cTn in peripheral blood indicates cardiomyocyte damage. As acute myocardial infarction (AMI) is the most important cause of cardiomyocyte damage, cTns have become an integral part in the diagnosis of AMI. For this indication, cTns are superior to all other biomarkers and therefore are the preferred marker for the diagnosis of AMI. However, cTn indicates and provides an estimate of cardiomyocyte damage irrespective of its cause. The major limitation of contemporary cTn assays is that they are often not elevated during the initial hours of AMI. Recent advances in assay technology have led to more sensitive and precise cTn assays that will have a profound impact on clinical practice. High-sensitive cTn (hs-cTn) assays have two differentiating features from contemporary cTn assays: (i) detection of cTn in a majority of healthy persons and (ii) precise definition of what is ‘normal' (=the 99th percentile). Recent multicentre studies have shown that hs-cTn assays improve the early diagnosis of patients with suspected AMI, particularly the early rule-out. To achieve best clinical use, cTn has to be interpreted as a quantitative variable. Rising and/or falling levels differentiate acute from chronic cardiomyocyte damage. The terms ‘troponin-positive' and ‘troponin negative' should therefore be avoided. ‘Detectable' levels will become the norm and will have to be differentiated from ‘elevated' levels. The differential diagnosis of a small amount of cardiomyocyte damage and therefore minor elevations of cTn is broad and includes acute and chronic cardiac disorders. The differential diagnosis of larger amount of injury and therefore more substantial elevations of cTn is largely restricted to AMI, myocarditis, and a rare patient with tako-tsubo cardiomyopath

A Robot Mimicking Heart Motions: An Ex-Vivo Test Approach for Cardiac Devices

PURPOSE: The pre-clinical testing of cardiovascular implants gains increasing attention due to the complexity of novel implants and new medical device regulations. It often relies on large animal experiments that are afflicted with ethical and methodical challenges. Thus, a method for simulating physiological heart motions is desired but lacking so far. METHODS: We developed a robotic platform that allows simulating the trajectory of any point of the heart (one at a time) in six degrees of freedom. It uses heart motion trajectories acquired from cardiac magnetic resonance imaging or accelero-meter data. The rotations of the six motors are calculated based on the input trajectory. A closed-loop controller drives the platform and a graphical user interface monitors the functioning and accuracy of the robot using encoder data. RESULTS: The robotic platform can mimic physiological heart motions from large animals and humans. It offers a spherical work envelope with a radius of 29 mm, maximum acceleration of 20 m/s(2) and maximum deflection of ±19° along all axes. The absolute mean positioning error in x-, y- and z-direction is 0.21 ±0.06, 0.31 ±0.11 and 0.17 ±0.12 mm, respectively. The absolute mean orientation error around x-, y- and z-axis (roll, pitch and yaw) is 0.24 ±0.18°, 0.23 ±0.13° and 0.18 ±0.18°, respectively. CONCLUSION: The novel robotic approach allows reproducing heart motions with high accuracy and repeatability. This may benefit the device development process and allows re-using previously acquired heart motion data repeatedly, thus avoiding animal trials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13239-021-00566-3

Predictors for early mortality and arrhythmic events in patients with cardiac resynchronization therapy with defibrillator: A two center cohort study

Background: Guidelines of heart failure therapy include cardiac resynchronization as standard ofcare in patients with severely depressed left ventricular function and wide QRS complex. It has beenshown that patients benefit regarding mortality and morbidity. However, early mortality precludes longtermbenefits from the device. The aim of the study was to identify predictors for early occurrence ofboth death and first-ever implantable cardioverter-defibrillator (ICD) therapy using a large combineddatabase of patients with cardiac resynchronization therapy with defibrillator (CRT-D).Methods: From two registries (tertiary care centers) 904 patients were identified, no single patient wasexcluded. Early death was defined as death occurring within the 3 years after implantation whereasearly ICD therapy as such occurring within the first year. 33 baseline parameters were compared usinguni- and multivariate analysis with the Cox model and binary logistic regression.Results: The population was predominantly male (77%), with mean age of 63 ± 11 years and primaryprevention indication in 80%. Mean follow-up was 55 ± 38 months. 256 (28%) patients hadICD therapies whereof the first-ever event occurred early in 52%. 270 (30%) patients died after 41 ±± 31 months, mostly from advancing heart failure (41%), 141 (52%) patients of them early. Independentpredictors for early ICD therapy were secondary prevention and renal failure. Independent predictors forearly mortality were a history of percutaneous coronary intervention and of peripheral vascular disease.Conclusions: Predictors for early mortality after CRT-D implantation were a history of percutaneouscoronary intervention and peripheral vascular disease, present in only a minority of patients, thus limitingtheir use in clinical practice

Sense-B-noise: an enigmatic cause for inappropriate shocks in subcutaneous implantable cardioverter defibrillators.

AIMS Subcutaneous implantable cardioverter defibrillators (S-ICDs) are well established. However, inappropriate shocks (IAS) remain a source of concern since S-ICDs offer very limited troubleshooting options. In our multicentre case series, we describe several patients who experienced IAS due to a previously unknown S-ICD system issue. METHODS AND RESULTS We observed six patients suffering from this novel IAS entity. The IAS occurred exclusively in primary or alternate S-ICD sensing vector configuration (therefore called 'Sense-B-noise'). IAS were caused by non-physiologic oversensing episodes characterized by intermittent signal saturation, diminished QRS amplitudes, and disappearance of the artefacts after the IAS. Noise/oversensing could not be provoked by manipulation, X-ray did not show evidence for lead/header issues and impedance measurements were within normal limits. The pooled experience of our centres implies that up to ∼5% of S-ICDs may be affected. The underlying root cause was discussed extensively with the manufacturer but remains unknown and is under further investigation. CONCLUSION Sense-B-noise is a novel cause for IAS due to non-physiologic signal oversensing, arising from a previously unknown S-ICD system issue. Sense-B-noise may be suspected if episodes of signal saturation in primary or alternate vector configuration are present, oversensing cannot be provoked, and X-ray and electrical measurements appear normal. The issue can be resolved by reprogramming the device to secondary sensing vector

Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction

Aims Angiogenic factors play an important role in the development of atherosclerosis and show pronounced changes during acute myocardial infarction (AMI). We analysed the impact of placental growth factor (PlGF) and its endogen opponent, soluble fms-like tyrosine kinase-1 (sFlt-1), on clinical outcome and the early diagnosis of AMI. Methods and results This multicentre study enrolled patients presenting with symptoms suggestive of AMI. The final diagnosis was adjudicated by two independent physicians. Levels of sFlt-1 and PlGF were compared with results of a standard troponin T and a novel high-sensitive troponin (hsTnT) assay. Of the 763 patients enrolled, 132 were diagnosed with AMI. Multivariable Cox regression analysis demonstrated sFlt-1 >84 ng/L [hazard ratios (HR) 2.6, 95% confidence intervals (CI) 1.2-5.4, P=0.01] and PlGF >20 ng/L (HR 3.6, 95% CI 1.3-10.4, P=0.02) as predictors for mortality during 1-year follow-up, independent from information provided by troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP). However, only sFlt-1 persisted as independent predictor for mortality when analysed together with hsTnT and NT-proBNP, and after adjusting for significant clinical parameters. For the diagnosis of AMI, the combination of troponin T and sFlt-1 improved the performance of troponin T alone and led to a negative predictive value of 98.3% already at time of presentation. However, sFlt-1 and PlGF added only limited diagnostic information when used together with hsTnT. Conclusion Only sFlt-1 but not PlGF provides overall independent prognostic information in patients presenting with symptoms suggestive of AMI. After the introduction of hsTnT in clinical routine, sFlt-1 and PlGF can only add limited diagnostic information for the detection or exclusion of AMI. Clinical Trial Registration Information: ClinicalTrials.gov, NCT0047058

High-sensitivity cardiac Troponin T delta concentration after repeat pulmonary vein isolation

Introduction: Difference between high-sensitivity cardiac troponin T concentrations (hs-cTnT) before and after ablation procedure (delta concentration) reflects the amount of myocardial injury. The aim of the study was to investigate hs-cTnT prognostic power for predicting atrial fibrillation (AF) recurrence after repeat pulmonary vein isolation (PVI) procedure. Materials and methods: Consecutive patients with paroxysmal AF undergoing repeat PVI using a focal radiofrequency catheter were included in the study. Hs-cTnT was measured before and 18-24 hours after the procedure. Standardized 3, 6 and 12-month follow-up was performed. Cox-regression analysis was used to identify predictors of AF recurrence. Results: A total of 105 patients undergoing repeat PVI were analysed (24% female, median age 61 years). Median (interquartile range) hs-cTnT delta after repeat PVI was 283 (127 - 489) ng/L. After a median follow-up of 12 months, AF recurred in 24 (23%) patients. A weak linear relationship between the total radiofrequency energy delivery time and delta hs-cTnT was observed (Pearson R2 = 0.31, P = 0.030). Delta Hs-cTnT was not identified as a significant long-term predictor of AF recurrence after repeated PVI (P = 0.920). Conclusion: This was the first study evaluating the prognostic power of delta hs-cTnT in predicting AF recurrence after repeat PVI. Delta hs-cTnT does not predict AF recurrence after repeat PVI procedures. Systematic measurement of hs-cTnT after repeat PVI does not add information relevant to outcome