Search

Background: Cardiac autonomic dysfunction after myocardial infarction identifies patients at high risk despite only moderately reduced left ventricular ejection fraction. We aimed to show that telemedical monitoring with implantable cardiac monitors in these patients can improve early detection of subclinical but prognostically relevant arrhythmic events., Methods: We did a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial at 33 centres in Germany and Austria. Survivors of acute myocardial infarction with left ventricular ejection fraction of 36-50% had biosignal analysis for assessment of cardiac autonomic function. Patients with abnormal periodic repolarisation dynamics (≥5·75 deg 2 ) or abnormal deceleration capacity (≤2·5 ms) were randomly assigned (1:1) to telemedical monitoring with implantable cardiac monitors or conventional follow-up. Primary endpoint was time to detection of serious arrhythmic events defined by atrial fibrillation 6 min or longer, atrioventricular block class IIb or higher and fast non-sustained (>187 beats per min; ≥40 beats) or sustained ventricular tachycardia or fibrillation. This study is registered with ClinicalTrials.gov, NCT02594488., Findings: Between May 12, 2016, and July 20, 2020, 1305 individuals were screened and 400 patients at high risk were randomly assigned (median age 64 years [IQR 57-73]); left ventricular ejection fraction 45% [40-48]) to telemedical monitoring with implantable cardiac monitors (implantable cardiac monitor group; n=201) or conventional follow-up (control group; n=199). During median follow-up of 21 months, serious arrhythmic events were detected in 60 (30%) patients of the implantable cardiac monitor group and 12 (6%) patients of the control group (hazard ratio 6·33 [IQR 3·40-11·78]; p<0·001). An improved detection rate by implantable cardiac monitors was observed for all types of serious arrhythmic events: atrial fibrillation 6 min or longer (47 [23%] patients vs 11 [6%] patients; p<0·001), atrioventricular block class IIb or higher (14 [7%] vs 0; p<0·001) and ventricular tachycardia or ventricular fibrillation (nine [4%] patients vs two [1%] patients; p=0·054)., Interpretation: In patients at high risk after myocardial infarction and cardiac autonomic dysfunction but only moderately reduced left ventricular ejection fraction, telemedical monitoring with implantable cardiac monitors was highly effective in early detection of subclinical, prognostically relevant serious arrhythmic events., Funding: German Centre for Cardiovascular Research (DZHK) and Medtronic Bakken Research Center., Competing Interests: Declaration of interests AB received funding from Medtronic Bakken Research Center as co-funding for the SMART-MI trial (providing implantable cardiac monitors and staff cost for implantable cardiac monitors core lab); and speaker honoraria from Bayer, Boerhinger Ingelheim, Edwards, Medtronic, and Novartis. MSt received consulting fees, speaker honoraria, and travel expenses from Medtronic. RW received grants from German Centre for Cardiovascular Research, Bristol Myers Squibb–Pfizer, and Grant Boston Scientific; speaker honoraria from Biotronik, Boston Scientific, Medtronic, Abiomed, Bristol Myers Squibb–Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Bayer, and Novartis; and travel expenses from Boston Scientific, Bristol Myers Squibb–Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Bayer. RW participated on advisory boards for Biotronik, Philips, Boehringer Ingelheim, and Daiichi Sankyo. ALu received grants and consulting fees from Boston Scientific and Biosense Webster; speaker honoraria from Boston Scientific, Biosense Webster, and Medtronic; travel expenses from Boston Scientific; and participated on data safety monitoring boards and societies for Boston Scientific. NG received grants from Boston Scientific and Medtronic and travel expenses from Bayer Vital. PC received research grants from Philips. LSM received grants from the German Research Foundation and the EU; speaker honoraria from Bayer, Astra Zeneca, Pfizer, Bristol Myers Squibb, Daiichi Sankyo, and Boehringer Ingelheim; travel expenses from Servier, Boehringer Ingelheim, and Vifor; and participated on data safety monitoring boards for Else Kröner-Fresenius-Stiftung. LSM is stock holder of Bayer and Fresenius Medical Care. MCB received consulting fees from Medtronic and Boston Scientific; speaker honoraria from Medtronic, Boston Scientific, and St Jude Medical; travel expenses from Medtronic, Jonhson & Johnson, Boston Scientific, and St Jude Medical; and participated on advisory boards for Medtronic. CL is member of the Expert Panel for medical devices for the European Commission. CU received consulting fees and speaker honoraria from Medtronic. JRE received consulting fees and speaker honoraria from Medtronic, Abbott, and Boston Scientific. UM received grants from German Centre for Cardiovascular Research (DZHK). All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Intraoperative testing of implantable cardioverter-defibrillators (ICDs) is time consuming and associated with risks. In the present study, we elucidated whether the initial implantation of an ICD with high energy output makes intraoperative defibrillation threshold testing (DFTT) unnecessary even though antiarrhythmic (AA) therapy is needed in the future., Methods: A total of 111 patients (94 men, 17 women) receiving an ICD with subsequent AA therapy (mexiletine, amiodarone, sotalol, flecainide) were analyzed retrospectively. DFT was performed during ICD implantation and after AA drug therapy. In a second step, DFT results from the study cohort were analyzed for implantation of virtual ICDs with either low (≤ 30 J, LOD), intermediate (34 J, IOD), or high energy output (36 J, HOD)., Results: In the study cohort, all patients reached the safety margin (SM) of 10 J between DFT and maximal shock energy of the ICD. After loading of AA agents, 6 patients (12%) with a LOD, 3 patients (11%) with an IOD, and 3 (13%) patients with a HOD failed the 10 J SM. Using virtual ICDs, 6 (5.5%) patients with a LOD, 1 patient (1%) with an IOD, and no patients with a HOD would have failed the 10 J SM. After loading of AA agents, 18 patients (16%) with a virtual LOD, 12 patients (10.8%) with an IOD, and still 9 patients (8%) with a HOD would have failed the 10 J SM., Conclusion: Our results demonstrate that the 10 J SM would have been achieved intraoperatively in all patients with virtual HOD ICDs. Thus, determination of the DFT during implantation does not seem to be obligatory. However, in patients receiving AA agents, DFT testing is still required.

Hereditary long QT syndrome (LQTS) is a cardiovascular disorder characterized by prolongation of the QT interval on the surface ECG and a high risk for arrhythmia-related sudden death. Mutations in a cardiac voltage-gated potassium channel, KCNQ1, account for the most common form of LQTS, LQTS1. The objective of this study was the characterization of a novel KCNQ1 mutation linked to LQTS. Electrophysiological properties and clinical features were determined and compared to characteristics of a different mutation at the same position. Single-strand conformation polymorphism analysis followed by direct sequencing was performed to screen LQTS genes for mutations. A novel missense mutation in the KCNQ1 gene, KCNQ1 P320H, was identified in the index patient presenting with recurrent syncope and aborted sudden death triggered by physical stress and swimming. Electrophysiological analyses of KCNQ1 P320H and the previously reported KCNQ1 P320A mutation indicate that both channels are non-functional and suppress wild type I(Ks) in a dominant-negative fashion. Based on homology modeling of the KCNQ1 channel pore region, we speculate that the proline residue at position 320 limits flexibility of the outer pore and is required to maintain the functional architecture of the selectivity filter/pore helix arrangement. Our observations on the KCNQ1 P320H mutation are consistent with previous studies indicating that pore mutations in potassium channel alpha-subunits are associated with more severe electrophysiological and clinical phenotypes than mutations in other regions of these proteins. This study emphasizes the significance of mutation screening for diagnosis, risk-assessment, and mutation-site specific management in LQTS patients., (Copyright 2009 Elsevier Inc. All rights reserved.)

We examined the costs and safety of follow-up of patients with an implantable cardioverter defibrillator (ICD). In a prospective study, a remote monitoring system was used to interrogate ICD devices via telephone. Twenty patients with an ICD were followed up conventionally (clinic visits) or remotely at 1, 3 and 6 months after implantation of the ICD. A total of 30 transmissions of ICD data were made via the remote monitoring system. Five transmissions (17%) were interrupted, mainly due to a loss of telemetry, but no data were lost. The duration of the remote follow-up was 12.7 min less than follow-up in clinic (25.8 min, P < 0.05). Five of the remote follow-up transmissions concerned arrhythmia episodes. These lasted significantly longer than those without arrhythmia (16.6 vs. 4.9 min, P < 0.05). In three patients an unscheduled visit to the outpatient clinic was necessary. The cost of remote follow-up for 100 ICD patients/year was calculated to be €44,267, or about 16% of the cost of conventional in-clinic follow-up.

Background: Patients with nonischemic cardiomyopathy (DCM) are at high risk for sudden cardiac death (SCD). However, the predictive value of prophylactic implantation of implantable cardioverter defibrillators (ICD) in this patient cohort is yet unclear., Methods and Results: Whether NT pro BNP levels and/or reproducible non sustained ventricular tachycardias (NSVTs) are predictive for SCD was prospectively tested in 30 patients with DCM and LVEF

Objective: Hereditary long QT syndrome (LQTS) is a genetically heterogeneous disease characterized by prolonged QT intervals and an increased risk for ventricular arrhythmias and sudden cardiac death. Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of LQTS. KCNQ1 is associated with two different entities of LQTS, the autosomal-dominant Romano-Ward syndrome (RWS), and the autosomal-recessive Jervell and Lange-Nielsen syndrome (JLNS) characterized by bilateral deafness in addition to cardiac arrhythmias. In this study, we investigate and discuss dominant-negative I(Ks) current reduction by a KCNQ1 deletion mutation identified in a RWS family., Methods: Single-strand conformation polymorphism analysis and direct sequencing were used to screen LQTS genes for mutations. Mutant KCNQ1 channels were heterologously expressed in Xenopus oocytes, and potassium currents were recorded using the two-microelectrode voltage clamp technique., Results: A heterozygous deletion of three nucleotides (CTT) identified in the KCNQ1 gene caused the loss of a single phenylalanine residue at position 339 (KCNQ1-deltaF339). Electrophysiological measurements in the presence and absence of the regulatory beta-subunit KCNE1 revealed that mutant and wild type forms of an N-terminal truncated KCNQ1 subunit (isoform 2) caused much stronger dominant-negative current reduction than the mutant form of the full-length KCNQ1 subunit (isoform 1)., Conclusion: This study highlights the functional relevance of the truncated KCNQ1 splice variant (isoform 2) in establishment and mode of inheritance in long QT syndrome. In the RWS family presented here, the autosomal-dominant trait is caused by multiple dominant-negative effects provoked by heteromultimeric channels formed by wild type and mutant KCNQ1-isoforms in combination with KCNE1.

Romano-Ward syndrome (RWS), the autosomal dominant form of the congenital long QT syndrome, is characterised by prolongation of the cardiac repolarisation process associated with ventricular tachyarrhythmias of the torsades de pointes type. Genetic studies have identified mutations in six ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1 and KCNE2 and the accessory protein Ankyrin-B gene, to be responsible for this disorder. Single-strand conformation polymorphism (SSCP) analysis and subsequent DNA sequence analysis have identified a KCNQ1 mutation in a family that were clinically conspicuous due to several syncopes and prolonged QTc intervals in the ECG. The mutant subunit was expressed and functionally characterised in the Xenopus oocyte expression system. A novel heterozygous missense mutation with a C to T transition at the first position of codon 343 (CCA) of the KCNQ1 gene was identified in three concerned family members (QTc intervals: 500, 510 and 530 ms, respectively). As a result, proline 343 localised within the highly conserved transmembrane segment S6 of the KCNQ1 channel is replaced by a serine. Co-expression of mutant (KCNQ1-P343S) and wild-type (KCNQ1) cRNA in Xenopus oocytes produced potassium currents reduced by approximately 92%, while IKs reconstitution experiments with a combination of KCNQ1 mutant, wild-type and KCNE1 subunits yielded currents reduced by approximately 60%. A novel mutation (P343S) identified in the KCNQ1 subunit gene of three members of a RWS family showed a dominant-negative effect on native IKs currents leading to prolongation of the heart repolarisation and possibly increases the risk of malign arrhythmias with sudden cardiac death.

Background: After acute myocardial infarction, the structural protein T is released considerably longer than cytosolic creatine kinase (CK), CK MB isoenzyme (CK-MB), or lactate dehydrogenase (LDH) and late troponin T release (> 48 hours after onset of chest pain) appears to be less affected by early coronary reperfusion., Objective: To investigate the precision of a single measurement of circulating troponin T concentrations 72 hours after onset of chest pain compared with standard scintigraphic and enzymatic estimates of myocardial infarct size., Methods: Quantitative single photon emission computed tomography thallium-201 scintigraphy at rest was performed in 37 patients 2-3 weeks after myocardial infarction (group 1: 14 patients without early coronary reperfusion; group 2: 23 patients with early reperfusion achieved by thrombolytic therapy, by percutaneous transluminal coronary angioplasty, or by both)., Results: In both groups, the number of myocardial segments with abnormal thallium-201 uptake indicating the individual extent of irreversible myocardial damage correlated significantly with the troponin T concentrations 72 hours after infarction as well as with peak concentrations of CK, CK-MB, and LDH., Conclusion: The data show that a single measurement of circulating troponin T 72 hours after onset of chest pain--independent of reperfusion--is superior for the estimation of myocardial infarct size to measurement of peak CK, CK-MB, or LDH, which require serial determinations and depend on coronary reperfusion.

Background: Structural complexities of the intact ventricular wall cause a very complex spread of activation. The effects of regional tissue damage and of antiarrhythmic drugs on directional differences in activation should help to further elucidate intramural conduction patterns., Methods and Results: In 10 healthy dogs and in 5 dogs with subacute anterior wall infarction, 6 parallel rows of 6 needle electrodes with 4 bipolar electrode pairs per needle were inserted into the left anterior ventricular wall. Using a computerized multiplexer-mapping system, the spread of activation in epi-, endo- and midmyocardial muscle layers and in the surviving epicardium, respectively, was reconstructed. Marked differences in conduction velocities relative to fiber orientation were evident in the surviving epicardium of infarcted hearts. Directional differences in conduction velocities, although less pronounced, were still preserved throughout the intact ventricular wall. Epicardial transverse conduction in intact hearts was significantly faster than transverse conduction in infarcted hearts (0.87 +/- 0.11 m/s vs 0.68 +/- 0.1 m/s). In normal hearts, propafenone (2 mg/kg) decreased conduction velocities primarily in longitudinal directions (-27 +/- 10%), but also moderately in transverse directions (-13 +/- 7 %) of all muscle layers, with no significant effect on straight (-4 +/- 8 %), but on oblique transmural conduction (-33 +/- 18 %). In infarcted hearts propafenone decreased conduction particularly in longitudinal direction (-23 +/- 14 %) without affecting conduction transverse to the fiber orientation (+3 +/- 6%)., Conclusions: Longitudinal intramural shortcircuits reduce directional differences in activation. Transmural infarction results in a loss of alternative intramural pathways, unmasking marked anisotropy in the surviving epicardium. Conduction delay in intramural pathways explains the effects of propafenone on transverse and oblique transmural conduction. Primarily longitudinal conduction delay results in reduced tissue anisotropy.