Five-year trends in cause-specific readmissions and cost burden of mitral transcatheter edge-to-edge repair.

OBJECTIVES: The study aimed to evaluate cost trends associated with mitral valve transcatheter edge-to-edge repair (TEER). BACKGROUND: TEER is a treatment option for patients at prohibitive surgical risk with moderate to severe mitral valve regurgitation and NYHA class III or IV symptoms. The 30-day costs and causes of readmission following TEER have not been well studied. METHODS: Patients undergoing mitral TEER in the United States from 2014 to 2018 were identified in the Nationwide Readmission Database. Patient characteristics, cause-specific readmission, and costs of the index hospitalization and readmissions were analyzed. Costs were trended over years using general linear regression. RESULTS: A total of 10,196 patients underwent mitral TEER during the study period. Thirty-day readmissions were stable over time at around 16%. The mean length of stay following TEER decreased from 7 days in 2014 to 5 days in 2018. There was a significant decline in the cost of the index hospitalization of $1311 per year, and a significant decline in the total 30-day cost of $1588 per year (p < 0.001). This was strictly due to a reduction in the cost of the index hospitalization without a change in readmission costs over time (p = 0.23). Infectious causes of readmissions significantly decreased while total cardiovascular readmissions, including heart failure, remained constant. CONCLUSION: The decreasing 30-day cost burden of TEER is primarily driven by the shorter index length of stay, as experience in TEER has grown and, length of stay has declined. However, cardiovascular readmissions, and consequently readmission costs, have remained steady.

KCNJ2 mutation causes an adrenergic-dependent rectification abnormality with calcium sensitivity and ventricular arrhythmia.

BACKGROUND: KCNJ2 mutations are associated with a variety of inherited arrhythmia syndromes including catecholaminergic polymorphic ventricular tachycardia 3. OBJECTIVE: To characterize the detailed cellular mechanisms of the clinically recognized KCNJ2 mutation R67Q. METHODS: Kir2.1 current density was measured from COS-1 cells transiently transfected with wild-type human Kir-2.1 (WT-Kir2.1) and/or a heterozygous missense mutation in KCNJ2 (R67Q-Kir2.1) by using the whole-cell voltage clamp technique. Catecholamine activity was simulated with protein kinase A-stimulating cocktail exposure. Phosphorylation-deficient mutants, S425N-Kir2.1 and S425N-Kir2.1/R67Q-S425N-Kir2.1, were used in a separate set of experiments. HA- or Myc-Tag-WT-Kir2.1 and HA-Tag-R67Q-Kir2.1 were used for confocal imaging. RESULTS: A 33-year-old woman presented with a catecholaminergic polymorphic ventricular tachycardia-like clinical phenotype and was found to have KCNJ2 missense mutation R67Q. Treatment with nadolol and flecainide resulted in the complete suppression of arrhythmias and symptom resolution. Under baseline conditions, R67Q-Kir2.1 expressed alone did not produce inward rectifier current while cells coexpressing WT-Kir2.1 and R67Q-Kir2.1 demonstrated the rectification index (RI) similar to that of WT-Kir2.1. After PKA stimulation, R67Q-Kir2.1/WT-Kir2.1 failed to increase peak outward current density; WT-Kir2.1 increased by 46% (n = 5), while R67Q-Kir2.1/WT-Kir2.1 decreased by 6% (n = 6) (P = .002). Rectification properties in R67Q-Kir2.1/WT-Kir2.1 demonstrated sensitivity to calcium with a decreased RI in the high-calcium pipette solution (RI 20.3% ± 4.1%) than in the low-calcium pipette solution (RI 36.5% ± 5.7%) (P < .05). Immunostaining of WT-Kir2.1 and R67Q-Kir2.1 individually and together showed a normal membrane expression pattern and colocalization by using the Pearson correlation coefficient. CONCLUSIONS: R67Q-Kir2.1 is associated with an adrenergic-dependent clinical and cellular phenotype with rectification abnormality enhanced by increased calcium. These findings are a significant advancement of our knowledge and understanding of the phenotype-genotype relationship of arrhythmia syndromes related to KCNJ2 mutations.