Long-Term Clinical Results of Percutaneous Cervical Nucleoplasty for Cervical Radicular Pain:A Retrospective Cohort Study

PURPOSE: Percutaneous cervical nucleoplasty (PCN) is a minimally invasive treatment for cervical radicular pain due to a disc herniation. Preliminary results show equivalent patient-reported outcomes of PCN as compared to conventional anterior cervical discectomy. However, there is a paucity of long-term outcome data. Therefore, the primary objective of this study is to investigate the long-term clinical results of PCN. PATIENTS AND METHODS: A retrospective analysis was conducted on patients who underwent PCN at a secondary referral center between 2010 and 2014. Before surgery and five days after surgery, numeric rating scales (NRS) for arm pain and neck pain and data on complications were collected. To determine long-term follow-up outcomes, patients were sent a questionnaire booklet containing the Core Outcome Measures Index-Neck (COMI-Neck), NRS for arm pain and neck pain, Likert-scales on patient satisfaction and questions regarding the incidence of reoperations and complications. RESULTS: The baseline characteristics were collected for 158 patients. At a median follow-up of 41.5 months (interquartile range (IQR) 27.0 to 57.5), data were available for 118 patients (74.7%). At short-term follow-up, patients that underwent PCN had a mean decrease of 3.0 on the NRS for arm pain (95% CI 2.5 to 3.6) compared to baseline, while at long-term follow-up, a mean decrease of 2.8 (95% CI 1.0 to 3.6) was observed. At the long-term follow-up, 67.8% of the patients were fully recovered from all symptoms and 93.3% remained satisfied with the PCN treatment results. The reoperation rate for recurrent disc herniation was 21.4% at long-term follow-up. CONCLUSION: PCN appears to be a safe and effective treatment at short-term and long-term follow-up of a specific selection of cervical herniated discs, with an acceptable long-term reoperation rate. These study results suggest a potential role of PCN as a less invasive treatment option for cervical radicular pain due to a soft disc herniation, before anterior cervical discectomy should be considered

Phenotypic and Genetic Factors Associated with Absence of Cardiomyopathy Symptoms in PLN:c.40_42delAGA Carriers

The c.40_42delAGA variant in the phospholamban gene (PLN) has been associated with dilated and arrhythmogenic cardiomyopathy, with up to 70% of carriers experiencing a major cardiac event by age 70. However, there are carriers who remain asymptomatic at older ages. To understand the mechanisms behind this incomplete penetrance, we evaluated potential phenotypic and genetic modifiers in 74 PLN:c.40_42delAGA carriers identified in 36,339 participants of the Lifelines population cohort. Asymptomatic carriers (N = 48) showed shorter QRS duration (− 5.73 ms, q value = 0.001) compared to asymptomatic non-carriers, an effect we could replicate in two different independent cohorts. Furthermore, symptomatic carriers showed a higher correlation (rPearson = 0.17) between polygenic predisposition to higher QRS (PGSQRS) and QRS (p value = 1.98 × 10–8), suggesting that the effect of the genetic variation on cardiac rhythm might be increased in symptomatic carriers. Our results allow for improved clinical interpretation for asymptomatic carriers, while our approach could guide future studies on genetic diseases with incomplete penetrance.</p

Phenotypic and Genetic Factors Associated with Absence of Cardiomyopathy Symptoms in PLN:c.40_42delAGA Carriers

The c.40_42delAGA variant in the phospholamban gene (PLN) has been associated with dilated and arrhythmogenic cardiomyopathy, with up to 70% of carriers experiencing a major cardiac event by age 70. However, there are carriers who remain asymptomatic at older ages. To understand the mechanisms behind this incomplete penetrance, we evaluated potential phenotypic and genetic modifiers in 74 PLN:c.40_42delAGA carriers identified in 36,339 participants of the Lifelines population cohort. Asymptomatic carriers (N = 48) showed shorter QRS duration (− 5.73 ms, q value = 0.001) compared to asymptomatic non-carriers, an effect we could replicate in two different independent cohorts. Furthermore, symptomatic carriers showed a higher correlation (r Pearson = 0.17) between polygenic predisposition to higher QRS (PGSQRS) and QRS (p value = 1.98 × 10–8), suggesting that the effect of the genetic variation on cardiac rhythm might be increased in symptomatic carriers. Our results allow for improved clinical interpretation for asymptomatic carriers, while our approach could guide future studies on genetic diseases with incomplete penetrance. Graphical abstract: [Figure not available: see fulltext.].</p

PROGNOSTIC IMPLICATION OF THE MITRAL VALVE TENTING GEOMETRY IN PATIENTS WITH DILATED CARDIOMYOPATHY: TRANSTHORACIC REAL-TIME 3D ECHOCARDIOGRAPHIC STUDY

BACKGROUND: The pathogenic phospholamban R14del mutation causes dilated and arrhythmogenic right ventricular cardiomyopathies and is associated with an increased risk of malignant ventricular arrhythmias and end-stage heart failure. We performed a multicentre study to evaluate mortality, cardiac disease outcome, and risk factors for malignant ventricular arrhythmias in a cohort of phospholamban R14del mutation carriers. METHODS AND RESULTS: Using the family tree mortality ratio method in a cohort of 403 phospholamban R14del mutation carriers, we found a standardized mortality ratio of 1.7 (95% confidence interval, 1.4-2.0) with significant excess mortality starting from the age of 25 years. Cardiological data were available for 295 carriers. In a median follow-up period of 42 months, 55 (19%) individuals had a first episode of malignant ventricular arrhythmias and 33 (11%) had an end-stage heart failure event. The youngest age at which a malignant ventricular arrhythmia occurred was 20 years, whereas for an end-stage heart failure event this was 31 years. Independent risk factors for malignant ventricular arrhythmias were left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia with hazard ratios of 4.0 (95% confidence interval, 1.9-8.1) and 2.6 (95% confidence interval, 1.5-4.5), respectively. CONCLUSIONS: Phospholamban R14del mutation carriers are at high risk for malignant ventricular arrhythmias and end-stage heart failure, with left ventricular ejection fraction <45% and sustained or nonsustained ventricular tachycardia as independent risk factors. High mortality and a poor prognosis are present from late adolescence. Genetic and cardiac screening is, therefore, advised from adolescence onwards

The Netherlands Arrhythmogenic Cardiomyopathy Registry:design and status update

BACKGROUND: Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. AIM: To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. METHODS: This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. DISCUSSION: The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website ( www.acmregistry.nl ) and patient conferences

No major role for rare plectin variants in arrhythmogenic right ventricular cardiomyopathy

Aims Likely pathogenic/pathogenic variants in genes encoding desmosomal proteins play an important role in the pathophysiology of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, for a substantial proportion of ARVC patients, the genetic substrate remains unknown. We hypothesized that plectin, a cytolinker protein encoded by the PLEC gene, could play a role in ARVC because it has been proposed to link the desmosomal protein desmoplakin to the cytoskeleton and therefore has a potential function in the desmosomal structure. Methods We screened PLEC in 359 ARVC patients and compared the frequency of rare coding PLEC variants (minor allele frequency [MAF] <0.001) between patients and controls. To assess the frequency of rare variants in the control population, we evaluated the rare coding variants (MAF <0.001) found in the European cohort of the Exome Aggregation Database. We further evaluated plectin localization by immunofluorescence in a subset of patients with and without a PLEC variant. Results Forty ARVC patients carried one or more rare PLEC variants (11%, 40/359). However, rare variants also seem to occur frequently in the control population (18%, 4754/26197 individuals). Nor did we find a difference in the prevalence of rare PLEC variants in ARVC patients with or without a desmosomal likely pathogenic/pathogenic variant (14% versus 8%, respectively). However, immunofluorescence analysis did show decreased plectin junctional localization in myocardial tissue from 5 ARVC patients with PLEC variants. Conclusions Although PLEC has been hypothesized as a promising candidate gene for ARVC, our current study did not show an enrichment of rare PLEC variants in ARVC patients compared to controls and therefore does not support a major role for PLEC in this disorder. Although rare PLEC variants were associated with abnormal localization in cardiac tissue, the confluence of data does not support a role for plectin abnormalities in ARVC development