Indications and predictors for pacemaker implantation after isolated aortic valve replacement with bioprostheses : the CAREAVR study

OBJECTIVES: We sought to study the indications, long-term occurrence, and predictors of permanent pacemaker implantation (PPI) after isolated surgical aortic valve replacement with bioprostheses. METHODS: The CAREAVR study included 704 patients (385 females, 54.7%) without a preoperative PPI (mean +/- standard deviation age 75 +/- 7years) undergoing isolated surgical aortic valve replacement at 4 Finnish hospitals between 2002 and 2014. Data were extracted from electronic patient records. RESULTS: The follow-up was median 4.7years (range 1day to 12.3years). Altogether 56 patients received PPI postoperatively, with the median 507days from the operation (range 6days to 10.0years). The PPI indications were atrioventricular block (31 patients, 55%) and sick sinus syndrome (21 patients, 37.5%). For 4 patients, the PPI indication remained unknown. A competing risks regression analysis (Fine-Gray method), adjusted with age, sex, diabetes, coronary artery disease, preoperative atrial fibrillation (AF), left ventricular ejection fraction, New York Heart Association class, AF at discharge and urgency of operation, was used to assess risk factors for PPI. Only AF at discharge (subdistribution hazard ratio 4.34, 95% confidence interval 2.34-8.03) was a predictor for a PPI. CONCLUSIONS: Though atrioventricular block is the major indication for PPI after surgical aortic valve replacement, >30% of PPIs are implanted due to sick sinus syndrome during both short-term follow-up and long-term follow-up. Postoperative AF versus sinus rhythm conveys >4-fold risk of PPI.Peer reviewe

Validation and optimization of adiabatic T1ρ and T2ρ for quantitative imaging of articular cartilage at 3 T

Abstract Purpose: The aim of the present work was to validate and optimize adiabatic T1ρ and T2ρ mapping for in vivo measurements of articular cartilage at 3 Tesla (T). Methods: Phantom and in vivo experiments were systematically performed on a 3T clinical system to evaluate the sequences using hyperbolic secant HS1 and HS4 pulses. R1ρ and R2ρ relaxation rates were studied as a function of agarose and chondroitin sulfate concentration and pulse duration. Optimal in vivo protocol was determined by imaging the articular cartilage of two volunteers and varying the sequence parameters, and successively applied in eight additional subjects. Reproducibility was assessed in phantoms and in vivo. Results: Relaxation rates depended on agarose and chondroitin sulfate concentration. The sequences were able to generate relaxation time maps with pulse lengths of 8 and 6 ms for HS1 and HS4, respectively. In vivo findings were in good agreement with the phantoms. The implemented adiabatic T1ρ and T2ρ sequences demonstrated regional variation in relaxation time maps of femorotibial cartilage. Reproducibility in phantoms and in vivo was good to excellent for both adiabatic T1ρ and T2ρ. Conclusions: The findings indicate that sequences are suitable for quantitative in vivo assessment of articular cartilage at 3 T

Injury-related cell death and proteoglycan loss in articular cartilage : Numerical model combining necrosis, reactive oxygen species, and inflammatory cytokines

Osteoarthritis (OA) is a common musculoskeletal disease that leads to deterioration of articular cartilage, joint pain, and decreased quality of life. When OA develops after a joint injury, it is designated as post-traumatic OA (PTOA). The etiology of PTOA remains poorly understood, but it is known that proteoglycan (PG) loss, cell dysfunction, and cell death in cartilage are among the first signs of the disease. These processes, influenced by biomechanical and inflammatory stimuli, disturb the normal cell-regulated balance between tissue synthesis and degeneration. Previous computational mechanobiological models have not explicitly incorporated the cell-mediated degradation mechanisms triggered by an injury that eventually can lead to tissue-level compositional changes. Here, we developed a 2-D mechanobiological finite element model to predict necrosis, apoptosis following excessive production of reactive oxygen species (ROS), and inflammatory cytokine (interleukin-1)-driven apoptosis in cartilage explant. The resulting PG loss over 30 days was simulated. Biomechanically triggered PG degeneration, associated with cell necrosis, excessive ROS production, and cell apoptosis, was predicted to be localized near a lesion, while interleukin-1 diffusion-driven PG degeneration was manifested more globally. Interestingly, the model also showed proteolytic activity and PG biosynthesis closer to the levels of healthy tissue when pro-inflammatory cytokines were rapidly inhibited or cleared from the culture medium, leading to partial recovery of PG content. The numerical predictions of cell death and PG loss were supported by previous experimental findings. Furthermore, the simulated ROS and inflammation mechanisms had longer-lasting effects (over 3 days) on the PG content than localized necrosis. The mechanobiological model presented here may serve as a numerical tool for assessing early cartilage degeneration mechanisms and the efficacy of interventions to mitigate PTOA progression

Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype

Genetic factors play a role in periodontitis. Here we examined whether the risk haplotype of MHC class III region BAT1-NFKBIL1-LTA and lymphotoxin- polymorphisms associate with salivary biomarkers of periodontal disease. A total of 455 individuals with detailed clinical and radiographic periodontal health data were included in the study. A 610K genotyping chip and a Sequenom platform were used in genotyping analyses. Phospholipid transfer protein activity, concentrations of lymphotoxin-, IL-8 and myeloperoxidase, and a cumulative risk score (combining Porphyromonas gingivalis, IL-1 and matrix metalloproteinase-8) were examined in saliva samples. Elevated IL-8 and myeloperoxidase concentrations and cumulative risk scores associated with advanced tooth loss, deepened periodontal pockets and signs of periodontal inflammation. In multiple logistic regression models adjusted for periodontal parameters and risk factors, myeloperoxidase concentration (odds ratio (OR); 1.37, P=0.007) associated with increased odds for having the risk haplotype and lymphotoxin- concentration with its genetic variants rs2857708, rs2009658 and rs2844482. In conclusion, salivary levels of IL-8, myeloperoxidase and cumulative risk scores associate with periodontal inflammation and tissue destruction, while those of myeloperoxidase and lymphotoxin- associate with genetic factors as well.Peer reviewe

Thromboembolisms related to post-operative electrical cardioversions for atrial fibrillation in patients with surgical aortic valve replacement

Abstract Aims: Post-operative atrial fibrillation (POAF) is a frequent complication after open-heart surgery, and cardioversions (CV) are commonly performed to restore sinus rhythm. However, little data exists on thrombo-embolic risk related to early post-operative CV and on the recurrence of POAF after CV. CAREAVR study sought to assess the rate of strokes, transient ischaemic attacks (TIA), and mortality shortly after POAF-triggered CV in patients who underwent isolated surgical aortic valve replacement (SAVR) with a bioprosthesis. Methods and results: Altogether 721 patients underwent isolated SAVR with a bioprosthesis at four Finnish university hospitals. During post-operative hospitalization, after patients with prior chronic AF were excluded, 309/634 (48.7%) of patients had at least one episode of POAF [median time (interquartile range) 3 (3) days], and an electrical CV was performed in 113/309 (36.6%) of them. The length of hospital stay was not affected by CV. At 30 days follow-up, the rate of stroke, TIA or mortality was higher in those AF patients who underwent CV vs. those who did not (9.7% vs. 3.6%, P = 0.04, respectively; adjusted hazard ratio 2.63, 95% confidence interval 1.00–6.92, P = 0.05). Similar proportion of patients in both groups were in AF rhythm at discharge (32.7% vs. 35.7%, P = 0.18); and at 3 months (25.0% vs. 23.6%, P = 0.40), respectively. Conclusion: In this real-world population of patients undergoing isolated SAVR, the rate of POAF was nearly 50%. One-third of these patients underwent an electrical CV, and they exhibited over two-fold risk for thromboembolisms and mortality. Cardioversion did not affect the short-term prevalence of AF

Occurrence and classification of cerebrovascular events after isolated bioprosthetic surgical aortic valve replacement:a competing risk analysis of the CAREAVR study

Abstract Background: The long-term incidence of stroke and the proportion of cardioembolic events after bioprosthetic surgical aortic valve replacement (SAVR) remain largely unknown. Methods: The CAREAVR study sought to assess the rate of stroke and transient ischemic attack (TIA) in patients who underwent isolated surgical aortic valve replacement with a bioprosthesis at four Finnish university hospitals between 2002 and 2014. Data was collected retrospectively and included 721 patients. Median follow-up time was 4.8 [3.0–7.0] years. Results: At 5 years, freedom from stroke was 89.0%, from TIA 94.1%, and from stroke and TIA 83.7%. The median time between index procedure and stroke or TIA was 1.7 years [29 days–3.9 years]. Stroke was of cardioembolic origin in 44.4% of patients. In multivariable competing risk analysis, increased age (HR 1.03, 95%CI 1.00–1.06, p = 0.022), previous stroke or TIA (HR 1.75, 95%CI 1.14–2.70, p = 0.010), New York Heart Association (NYHA) class III or more (HR 1.51, 95%CI 1.01–2.24, p = 0.044) and insulin treatment at discharge (HR 1.20, 95%CI 1.09–3.64, p = 0.024) were independent predictors of stroke or TIA. Cerebrovascular events occurred in 47.2% of patients with ongoing anticoagulation therapy. Conclusion: In this study, the incidence of stroke in the early postoperative period after bioprosthetic SAVR was higher than previously documented. Almost half of strokes were of cardioembolic etiology. These findings highlight the need for the better prevention strategies for cardioembolic events after bioprosthetic SAVR

Performance of CHA2DS2-VASc score for stroke prediction after surgical aortic valve replacement

Abstract Objective: Stroke is a frequent complication occurring early and late after surgical aortic valve replacement. There is an unmet clinical need for simple tools to assess postoperative stroke risk. We sought to assess the predictive performance of Congestive heart failure; Hypertension; Age ≥75 (doubled); Diabetes mellitus; prior Stroke, transient ischemic attack or thromboembolism (doubled); Vascular disease; Age 65 to 74; Sex category (female) (CHA₂DS₂-VASc) score in patients undergoing surgical aortic valve replacement with a bioprosthesis. Methods: Seven hundred fourteen patients undergoing isolated surgical aortic valve replacement with a bioprosthesis at 4 university hospitals were included. Data were collected retrospectively from patient records and monitored by an independent party. Results: Median follow-up time was 4.8 years. Mean CHA₂DS₂-VASc score was 4.1 ± 1.6. Low (scores, 0–1), high (scores, 2–4), and very high (scores, 5–9) CHA₂DS₂-VASc scores were observed in 39 (5.5%), 400 (56.0%), and 262 (38.5%) patients, respectively. Incidences of stroke or transient ischemic attack at 1 year were 2.6%, 4.8%, and 10.7%; at 5 years incidences were 5.2%, 14.0%, and 21.9%; and at 10 years incidence were 5.2%, 20.7%, and 37.9% for patients in low, high, and very high scores, respectively. Incidences of major bleeds at 1 year were 0%, 1.8%, and 2.7%; at 5 years incidences were 0%, 5.4%, and 8.7%; and at 10 years incidences were 0%, 9.0%, and 27.1%, respectively. Competing risk analysis showed that patients with CHA₂DS₂-VASc score of 5 through 9 had a significantly increased risk of stroke or transient ischemic attack (hazard ratio, 4.75; 95% confidence interval, 1.09–20.6; P = .037) irrespective of preoperative or new-onset in-hospital atrial fibrillation compared with low-risk patients. Conclusions: CHA₂DS₂-VASc is a valuable tool to identify patients with increased risk of stroke and major bleeding, and for whom alternative strategies for prevention of late neurologic complications should be adopted