Clinical consequences of antibody formation, serum concentrations, and HLA-Cw6 status in psoriasis patients on Ustekinumab

Background: Ustekinumab for the treatment of psoriasis is currently administered in a standard dosing regimen. However, some patients tend to benefit from alternative dosing regimens, a step toward personalized medicine. Methods: To investigate the role of ustekinumab serum concentrations, anti-ustekinumab antibodies [AUA] and HLA-Cw6 status as tools for optimizing ustekinumab treatment, a multicenter prospective cohort study was conducted at an academic hospital with affiliated nonacademic hospitals in Belgium (cohort 1) and 2 academic hospitals in the Netherlands (cohort 2 and 3). Patients with plaque-type psoriasis were eligible if treated with ustekinumab for >16 weeks. Serum samples and Psoriasis Area and Severity Index scores were obtained at baseline, week 16, 28, 40, 52, and/or >64 of ustekinumab treatment. Results: A total of 137 patients with 229 observations for serum concentrations and AUA and 61 observations for HLA-Cw6 status were included. Presence of AUA (prevalence of 8.7%) was significantly associated with a diminished clinical response (P = 0.032). The median ustekinumab trough concentration was 0.3 mcg/mL (<0.02-3.80). No differences in serum concentrations were observed between moderate to good responders and nonresponders (P = 0.948). Serum trough concentrations were not affected by methotrexate comedication. Prevalence of HLA-Cw6 positivity was 41% with no statistically significant difference in clinical response between HLA-Cw6-positive and HLA-Cw6-negative patients (P = 0.164). Conclusions: The presence of AUA was associated with treatment failure in this patient population; measurement of AUA may therefore be a candidate marker for personalized pharmacotherapy. The clinical utility of ustekinumab serum trough concentrations or HLA-Cw6 status determination remains less clear. Further exploration on the potential of measuring ustekinumab serum concentrations and other biomarkers in predicting therapy outcomes should be encouraged

Swiss National Registry on Catheter Ablation Procedures: Changing Trends over the Last 20 Years

The Swiss Ablation Registry provides a national database for electrophysiologic studies and catheter ablations. We analyzed the database to provide an in-depth look at changing trends over the last 20 years. During the study period a total of 78622 catheter ablations (age 61.0 ± 1.2 years; 63.7% male) were performed in 29 centers. The number of ablations increased by approximately ten-fold in 20 years. Ablation for atrial fibrillation (AF) was the main driver behind this increase, with more than hundred-fold (39.7% of all ablations in 2019). Atrioventricular-nodal-reentrant-tachycardia (AVNRT) and accessory pathways, being the main indications for ablation in 2000 (44.1%/25.1%, respectively), made up of only a small proportion (15.2%/3.5%,) respectively in 2019. Fluoroscopy, ablation, and procedure durations were reduced for all ablations over time. The highest repeat ablations were performed for ventricular tachycardia and AF (24.4%/24.3%). The majority of ablations (63.0%) are currently performed in private hospitals and non-university public hospitals whereas university hospitals had dominated (82.4%) at the turn of the century. A pronounced increase in the number of catheter ablations in Switzerland was accompanied by a marked decrease in fluoroscopy, ablation, and procedure durations. We observed a shift toward more complex procedures in older patients with comorbidities

Wearable cardioverter defibrillator: A life vest till the life boat (ICD) arrives

It is well established that implantable cardioverter defibrillator (ICD) is a life saving device ensuring protection against life threatening ventricular arrhythmias. But there are certain situations like a recent myocardial infarction where the standard guidelines do not recommend the implantation of an ICD while the patient can still be at a risk of demise due to a life threatening ventricular arrhythmia. There could also be a temporary indication for protection while explanting an infected ICD system. The wearable cardioverter defibrillator (WCD) is a device which comes to the rescue in such situations. In this brief review, we discuss the historical aspects of the development of a WCD, technical aspects as well as the clinical trial data and real world scenario of its use

Extended Use of the Wearable Cardioverter-Defibrillator: Which Patients Are Most Likely to Benefit?

Background: Wearable cardioverter-defibrillators (WCD, LifeVest, ZOLL) can protect from sudden cardiac death bridging a vulnerable period until a decision on implantable cardioverter-defibrillator (ICD) implantation can be reached. WCD is commonly used for 3 months or less. It is unknown, which patients use WCD longer and which patients are most likely to benefit from it. Hypothesis: Extended use of WCD is reasonable in selected cases based on underlying heart disease and overall patient risk profile. Methods: We conducted a systematic and comprehensive research of all published clinical studies on PubMed reporting on the use of the WCD. Only original articles reporting on wear times and time to appropriate shocks were included in our analysis. Results: The search resulted in 127 publications. 14 parameters were reported necessary for inclusion in our analysis. Median wear times ranged from 16 to 394 days. The median wear time was especially long for patients suffering from nonischemic cardiomyopathy (NICM) (range: 50-71 days) and specifically peripartum cardiomyopathy (PPCM) (120 days) and for heart transplant candidates. There was a large variation of appropriate shocks according to indication for WCD use. In contrast to NICM in general, the number of appropriate shocks was particularly high in patients with PPCM (0 in 254 patients and 5 in 49 patients, respectively). The median and maximal time periods to the first appropriate shock were longest in patients with PPCM (median time to the first appropriate shock: 68 days). Conclusions: Prolonged use of WCD is not uncommon in available literature. Patients suffering from NICM and specifically PPCM seem most likely to have longer therapy duration with WCD with success. Careful patient selection for prolonged use may decrease the need for ICD implantation in the future; however, prospective data are needed to confirm this hypothesis

Outcomes during and after the use of the wearable cardioverter-defibrillator in a tertiary-care and a regional hospital in Switzerland

INTRODUCTION The wearable cardioverter-defibrillator (WCD) has established itself in treatment of potentially life-threatening ventricular arrhythmias, when implantation of an implantable cardioverter-defibrillator (ICD) is not warranted. Careful patient selection for this therapy is crucial, but unfortunately very little information from randomised controlled trials is available to guide clinical decision-making. Consequently, data from real-world patient registries play a more important role in this context. MATERIALS AND METHODS A retrospective observational study was conducted at the University Hospital of Zurich and the GZO Regional Healthcare Centre in Wetzikon. Clinical databases were screened for patients with a history of WCD use from the time of its approval in Switzerland in July 2014 until February 2018. Baseline characteristics, WCD data and outcome data, with an emphasis on ICD implantation and ICD therapies, were collected and analysed. RESULTS Two-hundred and seven patients were included in the primary analysis. Eighty-six percent were male and the mean age was 58 &plusmn; 13 years. The underlying heart disease was ischaemic cardiomyopathy (ICM), non-ischaemic cardiomyopathy (NICM) and congenital/inherited heart diseases in 60, 35 and 5%, respectively. The most common indication for WCD use was heart failure with an ejection fraction (EF) &lt;35% due to ICM or NICM (43 and 27%, respectively). Three of the 207 patients received an appropriate shock over a median WCD wear-time of 62 days (interquartile range [IQR] 35&ndash;95). No inappropriate shocks were registered. Median average daily wear-time was 22.6 hours (IQR 19.9&ndash;23.2) and was significantly shorter for patients for whom WCD discontinuation was due to comfort issues (17 patients, p = 0.003). After the end of WCD therapy, 48% were implanted with an ICD. In those receiving an ICD, the rate of appropriate ICD therapies (either shock or antitachycardia pacing) was 8% during a median follow-up of 110 days (IQR 23&ndash;421). CONCLUSION The WCD is safe and effective in terminating malignant ventricular arrhythmias. A substantial subgroup of patients, however, discontinued WCD use prematurely because of comfort issues. This subset of patients deserves further attention in clinical practice to ensure therapy adherence. &nbsp

Extended Use of the Wearable Cardioverter-Defibrillator: Which Patients Are Most Likely to Benefit?

Background. Wearable cardioverter-defibrillators (WCD, LifeVest, ZOLL) can protect from sudden cardiac death bridging a vulnerable period until a decision on implantable cardioverter-defibrillator (ICD) implantation can be reached. WCD is commonly used for 3 months or less. It is unknown, which patients use WCD longer and which patients are most likely to benefit from it. Hypothesis. Extended use of WCD is reasonable in selected cases based on underlying heart disease and overall patient risk profile. Methods. We conducted a systematic and comprehensive research of all published clinical studies on PubMed reporting on the use of the WCD. Only original articles reporting on wear times and time to appropriate shocks were included in our analysis. Results. The search resulted in 127 publications. 14 parameters were reported necessary for inclusion in our analysis. Median wear times ranged from 16 to 394 days. The median wear time was especially long for patients suffering from nonischemic cardiomyopathy (NICM) (range: 50–71 days) and specifically peripartum cardiomyopathy (PPCM) (120 days) and for heart transplant candidates. There was a large variation of appropriate shocks according to indication for WCD use. In contrast to NICM in general, the number of appropriate shocks was particularly high in patients with PPCM (0 in 254 patients and 5 in 49 patients, respectively). The median and maximal time periods to the first appropriate shock were longest in patients with PPCM (median time to the first appropriate shock: 68 days). Conclusions. Prolonged use of WCD is not uncommon in available literature. Patients suffering from NICM and specifically PPCM seem most likely to have longer therapy duration with WCD with success. Careful patient selection for prolonged use may decrease the need for ICD implantation in the future; however, prospective data are needed to confirm this hypothesis