Acute human defibrillation performance of a subcutaneous implantable cardioverter-defibrillator with an additional coil electrode.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) delivers 80 J shocks from an 8 cm left-parasternal coil to a 59 cm3 left lateral pulse generator (PG). A system that defibrillates with lower energy could significantly reduce PG size. Computer modeling and animal studies suggested that a second shock coil either parallel to the left-parasternal coil or transverse from the xiphoid to the PG pocket would significantly reduce the defibrillation threshold. OBJECTIVE: The purpose of this study was to acutely assess the defibrillation efficacy of parallel and transverse configurations in patients receiving an S-ICD. METHODS: Testing was performed in patients receiving a conventional S-ICD system. Success at 65 J was required before investigational testing. A second electrode was temporarily inserted from the xiphoid incision connected to the PG with an investigational Y-adapter. Phase 1 (n = 11) tested the parallel configuration. Phase 2 (n = 21) tested both parallel and transverse configurations in random order. RESULTS: This study enrolled 35 patients (28 males (80%); mean age 51 ± 17 years; left ventricular ejection fraction 40% ± 15%; body mass index 26 ± 4 kg/m2; prior myocardial infarction 46%; congestive heart failure 49%; cardiomyopathy 63%). Compared to the conventional S-ICD system, mean shock impedance decreased for both parallel (69 ± 15 Ω vs 86 ± 20 Ω; n = 33; P < .001) and transverse (56 ± 14 Ω vs 81 ± 21 Ω; n = 20; P < .001) configurations. Shock success rates at 20, 30, and 40 J were 55%, 79%, 97%, and 25%, 70%, 90% for parallel and transverse configurations, respectively. Defibrillation threshold testing was well tolerated with no serious adverse events. CONCLUSION: Adding a second shock coil, particularly in the parallel configuration, significantly reduced the impedance and had a high likelihood of defibrillation success at energies ≤40 J. This may enable the development of a smaller S-ICD.

Five-year safety and efficacy of leadless pacemakers in a Dutch cohort.

BACKGROUND: Adequate real-world safety and efficacy of leadless pacemakers (LPs) have been demonstrated up to 3 years after implantation. Longer-term data are warranted to assess the net clinical benefit of leadless pacing. OBJECTIVE: The purpose of this study was to evaluate the long-term safety and efficacy of LP therapy in a real-world cohort. METHODS: In this retrospective cohort study, all consecutive patients with a first LP implantation from December 21, 2012, to December 13, 2016, in 6 Dutch high-volume centers were included. The primary safety endpoint was the rate of major procedure- or device-related complications (ie, requiring surgery) at 5-year follow-up. Analyses were performed with and without Nanostim battery advisory-related complications. The primary efficacy endpoint was the percentage of patients with a pacing capture threshold ≤2.0 V at implantation and without ≥1.5-V increase at the last follow-up visit. RESULTS: A total of 179 patients were included (mean age 79 ± 9 years), 93 (52%) with a Nanostim and 86 (48%) with a Micra VR LP. Mean follow-up duration was 44 ± 26 months. Forty-one major complications occurred, of which 7 were not advisory related. The 5-year major complication rate was 4% without advisory-related complications and 27% including advisory-related complications. No advisory-related major complications occurred a median 10 days (range 0-88 days) postimplantation. The pacing capture threshold was low in 163 of 167 patients (98%) and stable in 157 of 160 (98%). CONCLUSION: The long-term major complication rate without advisory-related complications was low with LPs. No complications occurred after the acute phase and no infections occurred, which may be a specific benefit of LPs. The performance was adequate with a stable pacing capture threshold.

Experience with malfunctioning leadless pacemakers: Troubleshooting and management during medium-term follow-up.

BACKGROUND: The Nanostim leadless pacemaker (LP) was launched in 2012. However, the use of Nanostim LP was suspended because of safety concerns. OBJECTIVE: The aim of this study was to report our experience with the management of malfunctioning Nanostim LPs, including premature battery depletion. METHODS: Fifty-one consecutive patients (mean age 83 ± 10 years; 65% male) who underwent Nanostim LP implantation between 2014 and 2016 at Isala Clinics were identified. Two patients were excluded from the analysis because of incomplete follow-up. The mean follow-up duration was 1114 ± 560 days. RESULTS: Nanostim LP malfunction occurred in 20 of 49 patients (40.8%). Premature LP battery failure was observed in 18 of 20 affected patients (90%). Furthermore, malpacing/malsensing was observed in 1 patient and mechanical dislocation of the Nanostim LP occurred in 1 patient. Of note, 17 of 18 Nanostim LPs with premature battery depletion (94%) showed normal device parameters 3 months before the diagnosis of (impending) premature battery failure. In 12 patients, Nanostim LPs with a mean device age at the time of extraction of 1040 ± 467 days was successfully extracted without complications. Implantation of another LP or a transvenous device was successfully performed in all 20 patients with Nanostim LP malfunction. All known cases of early-life battery failure were identified during the 3-monthly follow-up consultations. CONCLUSION: The incidence of Nanostim LP early-life battery failure was higher than previously reported. Nanostim LP extraction in an older population seems to be safe and effective. Three-monthly follow-up seems to be effective at preventing in-between Nanostim LP-related hospitalization.

Significantly less inappropriate shocks in ischemic patients compared to non-ischemic patients: The S-ICD experience of a high volume single-center.

BACKGROUND: The subcutaneous cardioverter-defibrillator (S-ICD) continues to be preferentially used in relatively young patients, with less advanced heart disease. OBJECTIVE: We, therefore, studied the short and long-term efficacy and safety of the S-ICD in subgroups of patients, which are underreported at present. METHODS: A total of 218 patients between November 2010 and February 2019 undergoing S-ICD with a follow up of at least 6 months implantation were included in a prospective registry. Mean follow up was 38 months. RESULTS: The most common indication for S-ICD implantation was ischemic cardiomyopathy (n = 106, 49%). Complication rate needing invasive intervention was 9% (n = 21). Appropriate shock rate in patients with an S-ICD was 3.5%/year. A total of 30 inappropriate shocks (IAS) occurred in 19 patients (8.7%; 2.7%/year). The proportion of appropriate and inappropriate shock rates in patients with different cardiomyopathies shows remarkable variances. There were significant more IAS (3.6%/year vs. 1.7%/year, p = .048) in patients with non-ischemic cardiomyopathy versus patients with ischemic cardiomyopathy. Multivariate analysis identified, besides type of cardiomyopathy, atrial fibrillation (AF) as predictor for IAS. CONCLUSION: In this real-world prospective registry we analyzed S-ICD performance in the more traditional ICD patient. Patients with ischemic cardiomyopathy had significantly less inappropriate therapy compared to patients with non-ischemic cardiomyopathy and appear to be appropriate patients for this type of device.

An immediate or early invasive strategy in non-ST-elevation acute coronary syndrome: The OPTIMA-2 randomized controlled trial.

BACKGROUND: In intermediate- and high-risk non-ST elevated acute coronary syndrome (NSTE-ACS) patients, a routine invasive approach is recommended. The timing of coronary angiography remains controversial. To assess whether an immediate (<3 hours) invasive treatment strategy would reduce infarct size and is safe, compared with an early strategy (12-24 hours), for patients admitted with NSTE-ACS while preferably treated with ticagrelor. METHODS: In this single-center, prospective, randomized trial an immediate or early invasive strategy was randomly assigned to patients with NSTE-ACS. At admission, the patients were preferably treated with a combination of aspirin, ticagrelor and fondaparinux. The primary endpoint was the infarct size as measured by area under the curve (AUC) of CK-MB in 48 hours. Secondary endpoints were bleeding outcomes and major adverse cardiac events (MACE): composite of all-cause death, MI and unplanned revascularization. Interim analysis showed futility regarding the primary endpoint and trial inclusion was terminated. RESULTS: In total 249 patients (71% of planned) were included. The primary endpoint of in-hospital infarct size was a median AUC of CK-MB 186.2 ng/mL in the immediate group (IQR 112-618) and 201.3 ng/mL in the early group (IQR 119-479). Clinical follow-up was 1-year. The MACE-rate was 10% in the immediate and 10% in the early group (hazard ratio [HR] 1.13, 95% CI: 0.52-2.49). CONCLUSIONS: In NSTE-ACS patients randomized to either an immediate or an early-invasive strategy the observed median difference in the primary endpoint was about half the magnitude of the expected difference. The trial was terminated early for futility after 71% of the projected enrollment had been randomized into the trial.

Direct Reprograming to Regenerate Myocardium and Repair Its Pacemaker and Conduction System.

The regenerative medicine field has been revolutionized by the direct conversion of one cell type to another by ectopic expression of lineage-specific transcription factors. The direct reprogramming of fibroblasts to induced cardiac myocytes (iCMs) by core cardiac transcription factors (Gata4, Mef2c, Tbx5) both in vitro and in vivo has paved the way in cardiac regeneration and repair. Several independent research groups have successfully reported the direct reprogramming of fibroblasts in injured myocardium to cardiac myocytes employing a variety of approaches that rely on transcription factors, small molecules, and micro RNAs (miRNAs). Recently, this technology has been considered for local repair of the pacemaker and the cardiac conduction system. To address this, we will first discuss the direct reprograming advancements in the setting of working myocardium regeneration, and then elaborate on how this technology can be applied to repair the cardiac pacemaker and the conduction system.

Disappearance of Idiopathic Outflow Tract Premature Ventricular Contractions After Catheter Ablation of Overt Accessory Pathways.

BACKGROUND: Multiple mechanisms have been proposed for idiopathic premature ventricular contractions (PVCs) originating from the outflow tracts (OTs). Recent observations such as the coexistence of these arrhythmias with atrioventricular nodal reentrant tachycardias and the association between discrete prepotentials and successful ablation sites of ventricular arrhythmias (VAs) from the OTs suggest a common link. OBJECTIVE: In this case series we draw attention to a unique association between accessory pathways (APs) and idiopathic PVCs from the OTs, disappearing after AP ablation. METHODS: We identified 6 cases in collaboration with several international electrophysiology centers, which presented with pre-excitation in association with OT, and in 1 case inflow tract (IT), PVCs on 12-lead surface ECG. RESULTS: Six cases displayed pre-excitation and PVCs, in 5 cases originating from the right ventricular outflow tract (RVOT) and in 1 case from the right ventricular inflow tract (RVIT). In all patients, PVCs were monomorphic and had fixed coupling intervals, in 3 cases presenting in bigeminy. Catheter ablation of the AP led to the simultaneous disappearance of PVCs in 5 of 6 cases. The sites of ablation were remote from the OTs in all these cases. In most cases, the occurrence of OT PVCs was closely associated with the presence of pre-excitation. CONCLUSION: The coexistence of pre-excitation and PVCs from the OTs and the fact that in 5 of 6 cases PVCs disappeared after AP ablation suggests a common mechanism for arrhythmia genesis.

Impact of percutaneous coronary intervention timing on 5-year outcome in patients with non-ST-segment elevation acute coronary syndromes. The 'wait a day' approach might be safer.

BACKGROUND: The OPTIMA trial was a randomised multicentre trial exploring the influence of the timing of percutaneous coronary intervention (PCI) on patient outcomes in an intermediate to high risk non-ST-elevation acute coronary syndrome (NSTE-ACS) population. In order to decide the best treatment strategy for patients presenting with NSTE-ACS, long-term outcomes are essential. METHODS: Five-year follow-up data from 133 of the 142 patients could be retrieved (94 %). The primary endpoint was a composite of death and spontaneous myocardial infarction (MI). Spontaneous MI was defined as MI occurring more than 30 days after randomisation. Secondary endpoints were the individual outcomes of death, spontaneous MI or re-PCI. RESULTS: No significant difference with respect to the primary endpoint was observed (17.8 vs. 10.1 %; HR 1.55, 95 % CI: 0.73-4.22, p = 0.21). There was no significant difference in mortality rate. However, spontaneous MI was significantly more common in the group receiving immediate PCI (11.0 vs. 1.4 %; HR 4.46, 95 % CI: 1.21-16.50, p = 0.02). We did not find a significant difference between the groups with respect to re-PCI rate. CONCLUSION: There was no difference in the composite of death and spontaneous MI. The trial suggests an increased long-term risk of spontaneous MI for patients treated with immediate PCI.

Pulmonary hypertension in a pregnant patient with thyrotoxicosis due to Graves' disease: considerations with respect to treatment.

A 13 weeks pregnant 24-year-old patient with a history of Graves' disease presented with progressive dyspnoea existing for 4-6 weeks. Blood tests showed severe thyrotoxicosis and transthoracic echocardiography suggested severe pulmonary hypertension (PH) which was thought to be secondary to thyrotoxicosis. PH secondary to thyrotoxicosis is often reversible and may occur 3-14 months after normalisation of free T4 and T3 levels. The maternal mortality risk of PH in pregnancy is high despite modern treatment strategies (17-33%). In this case, PH was carefully monitored for 1 month. No changes in pulmonary artery pressure were found despite immediate treatment with propylthiouracil and ß-blockade. We anticipated that the normalisation of pulmonary artery pressure would not occur during this pregnancy and that the risk of complications would remain high. In the interest of the mother an abortion was suggested. Termination of pregnancy took place at the gestational age of 16 weeks.

Whipple's disease presenting with neurological symptoms in an immunosuppressed patient.

We report an unusual case of Whipple's disease, which remained undiagnosed for several years in a patient being treated with immunosuppressive therapy for many years. The patient presented with a purpuric rash, neurological symptoms, lymphadenopathy and gastrointestinal symptoms. The diagnosis was made by endoscopic biopsy of the duodenum with periodic acid Schiff staining, as well as PCR testing on blood and cerebrospinal fluid. The patient was successfully treated with intravenous ceftriaxone, followed by oral co-trimoxazole for 1 year.