A long-term cost-effectiveness analysis of cardiac resynchronisation therapy with or without defibrillator based on health claims data.

BACKGROUND: In Germany, CRT devices with defibrillator capability (CRT-D) have become the predominant treatment strategy for patients with heart failure and cardiac dyssynchrony. However, according to current guidelines, most patients would also be eligible for the less expensive CRT pacemaker (CRT-P). We conducted a cost-effectiveness analysis for CRT-P devices compared to CRT-D devices from a German payer's perspective. METHODS: Longitudinal health claims data from 3569 patients with de novo CRT implantation from 2014 to 2019 were used to parametrise a cohort Markov model. Model outcomes were costs and effectiveness measured in terms of life years. Transition probabilities were derived from multivariable parametric survival regression that controlled for baseline differences of CRT-D and CRT-P patients. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The Markov model predicted a median survival of 84 months for CRT-P patients and 92 months for CRT-D patients. In the base case, CRT-P devices incurred incremental costs of € - 13,093 per patient and 0.30 incremental life years were lost. The ICER was € 43,965 saved per life year lost. In the probabilistic sensitivity analysis, uncertainty regarding the effectiveness was observed but not regarding costs. CONCLUSION: This modelling study illustrates the uncertainty of the higher effectiveness of CRT-D devices compared to CRT-P devices. Given the difference in incremental costs between CRT-P and CRT-D treatment, there would be significant potential cost savings to the healthcare system if CRT-D devices were restricted to patients likely to benefit from the additional defibrillator.

Survival of patients undergoing cardiac resynchronization therapy with or without defibrillator: the RESET-CRT project.

AIMS: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure. There is contradictory evidence whether defibrillator capability improves prognosis in patients receiving CRT. We compared the survival of patients undergoing de novo implantation of a CRT with defibrillator (CRT-D) option and CRT with pacemaker (CRT-P) in a large health claims database. METHODS AND RESULTS: Using health claims data of a major German statutory health insurance, we analysed patients with de novo CRT implantation from 2014 to 2019 without indication for defibrillator implantation for secondary prevention of sudden cardiac death. We performed age-adjusted Cox proportional hazard regression and entropy balancing to calculate weights to control for baseline imbalances. The analysis comprised 847 CRT-P and 2722 CRT-D patients. Overall, 714 deaths were recorded during a median follow-up of 2.35 years. A higher cumulative incidence of all-cause death was observed in the initial unadjusted Kaplan-Meier time-to-event analysis [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.38-1.92]. After adjustment for age, HR was 1.13 (95% CI: 0.95-1.35) and after entropy balancing 0.99 (95% CI: 0.81-1.20). No survival differences were found in different age groups. The results were robust in sensitivity analyses. CONCLUSION: In a large health claims database of CRT implantations performed in a contemporary setting, CRT-P treatment was not associated with inferior survival compared with CRT-D. Age differences accounted for the greatest part of the survival difference that was observed in the initial unadjusted analysis.

A Novel Locus and Candidate Gene for Familial Developmental Dyslexia on Chromosome 4q.

Objective: Developmental dyslexia is a highly heritable specific reading and writing disability. To identify a possible new locus and candidate gene for this disability, we investigated a four-generation pedigree where transmission of dyslexia is consistent with an autosomal dominant inheritance pattern. Methods: We performed genome wide array-based SNP genotyping and parametric linkage analysis and sequencing analysis of protein-coding exons, exon-intron boundaries and conserved extragenic regions within the haplotype cosegregating with dyslexia in DNA from one affected and one unaffected family member. Cosegregation was confirmed by sequencing all available family members. Additionally, we analyzed 96 dyslexic individuals who had previously shown positive LOD scores on chromosome 4q28 as well as an even larger sample (n = 2591). Results: We found a single prominent linkage interval on chromosome 4q, where sequence analysis revealed a nucleotide variant in the 3' UTR of brain expressed SPRY1 in the dyslexic family member that cosegregated with dyslexia. This sequence alteration might affect the binding efficiency of the IGF2BP1 RNA-binding protein and thus influence the expression level of the SPRY1 gene product. An analysis of 96 individuals from a cohort of dyslexic individuals revealed a second heterozygous variant in this gene, which was absent in the unaffected sister of the proband. An investigation of the region in a much larger sample further found a nominal p-value of 0.0016 for verbal short-term memory (digit span) in 2,591 individuals for a neighboring SNV. After correcting for the local number of analyzed SNVs, and after taking into account linkage disequilibrium, we found this corresponds to a p-value of 0.0678 for this phenotype. Conclusions: We describe a new locus for familial dyslexia and discuss the possibility that SPRY1 might play a role in the etiology of a monogenic form of dyslexia.