Influence of Remote Monitoring on Long-Term Cardiovascular Outcomes after Cardioverter-Defibrillator Implantation

AIMS: Device-based remote monitoring (RM) has been linked to improved clinical outcomes at short to medium-term follow-up. Whether this benefit extends to long-term follow-up is unknown. We sought to assess the effect of device-based RM on long-term clinical outcomes in recipients of implantable cardioverter-defibrillators (ICD). METHODS: We performed a retrospective cohort study of consecutive patients who underwent ICD implantation for primary prevention. RM was initiated with patient consent according to availability of RM hardware at implantation. Patients with concomitant cardiac resynchronization therapy were excluded. Data on hospitalizations, mortality and cause of death were systematically assessed using a nationwide healthcare platform. A Cox proportional hazards model was employed to estimate the effect of RM on mortality and a composite endpoint of cardiovascular mortality and hospital admission due to heart failure (HF). RESULTS: 312 patients were included with a median follow-up of 37.7months (range 1 to 146). 121 patients (38.2%) were under RM since the first outpatient visit post-ICD and 191 were in conventional follow-up. No differences were found regarding age, left ventricular ejection fraction, heart failure etiology or NYHA class at implantation. Patients under RM had higher long-term survival (hazard ratio [HR] 0.50, CI 0.27-0.93, p=0.029) and lower incidence of the composite outcome (HR 0.47, CI 0.27-0.82, p=0.008). After multivariate survival analysis, overall survival was independently associated with younger age, higher LVEF, NYHA class lower than 3 and RM. CONCLUSION: RM was independently associated with increased long-term survival and a lower incidence of a composite endpoint of hospitalization for HF or cardiovascular mortality.

Effect of C282Y Genotype on Self-Reported Musculoskeletal Complications in Hereditary Hemochromatosis

OBJECTIVE: Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype. METHODS: A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status. RESULTS: In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2-5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1-12.1]). CONCLUSION: Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.

Iron Overload in a Murine Model of Hereditary Hemochromatosis Is Associated with Accelerated Progression of Osteoarthritis Under Mechanical Stress

OBJECTIVE: Hereditary hemochromatosis (HH) is a disease caused by mutations in the Hfe gene characterised by systemic iron overload and associated with an increased prevalence of osteoarthritis (OA) but the role of iron overload in the development of OA is still undefined. To further understand the molecular mechanisms involved we have used a murine model of HH and studied the progression of experimental OA under mechanical stress. DESIGN: OA was surgically induced in the knee joints of 10-week-old C57BL6 (wild-type) mice and Hfe-KO mice. OA progression was assessed using histology, micro CT, gene expression and immunohistochemistry at 8 weeks after surgery. RESULTS: Hfe-KO mice showed a systemic iron overload and an increased iron accumulation in the knee synovial membrane following surgery. The histological OA score was significantly higher in the Hfe-KO mice at 8 weeks after surgery. Micro CT study of the proximal tibia revealed increased subchondral bone volume and increased trabecular thickness. Gene expression and immunohistochemical analysis showed a significant increase in the expression of matrix metallopeptidase 3 (MMP-3) in the joints of Hfe-KO mice compared with control mice at 8 weeks after surgery. CONCLUSIONS: HH was associated with an accelerated development of OA in mice. Our findings suggest that synovial iron overload has a definite role in the progression of HH-related OA