Long-term cardiovascular outcomes among immigrants and non-immigrants in cardiac resynchronization therapy: a nationwide study.

AIMS: To date, potential differences in outcomes for immigrants and non-immigrants with a cardiac resynchronization therapy (CRT), in a European setting, remain underutilized and unknown. Hence, we examined the efficacy of CRT measured by heart failure (HF)-related hospitalizations and all-cause mortality among immigrants and non-immigrants. METHODS AND RESULTS: All immigrants and non-immigrants who underwent first-time CRT implantation in Denmark (2000-2017) were identified from nationwide registries and followed for up to 5 years. Differences in HF related hospitalizations and all-cause mortality were evaluated by Cox regression analyses. From 2000 to 2017, 369 of 10 741 (3.4%) immigrants compared with 7855 of 223 509 (3.5%) non-immigrants with a HF diagnosis underwent CRT implantation. The origins of the immigrants were Europe (61.2%), Middle East (20.1%), Asia-Pacific (11.9%), Africa (3.5%), and America (3.3%). We found similar high uptake of HF guideline-directed pharmacotherapy before and after CRT and a consistent reduction in HF-related hospitalizations the year before vs. the year after CRT (61% vs. 39% for immigrants and 57% vs. 35% for non-immigrants). No overall difference in 5-year mortality among immigrants and non-immigrants was seen after CRT [24.1% and 25.8%, respectively, P-value = 0.50, hazard ratio (HR) = 1.2, 95% confidence interval (CI): 0.8-1.7]. However, immigrants of Middle Eastern origin had a higher mortality rate (HR = 2.2, 95% CI: 1.2-4.1) compared with non-immigrants. Cardiovascular causes were responsible for the majority of deaths irrespective of immigration status (56.7% and 63.9%, respectively). CONCLUSION: No overall differences in efficacy of CRT in improving outcomes between immigrants and non-immigrants were identified. Although numbers were low, a higher mortality rate among immigrants of Middle Eastern origin was identified compared with non-immigrants.

Efficacy of a web-based healthcare innovation to advance the quality of life and care of patients with an implantable cardioverter defibrillator (ACQUIRE-ICD): a randomized controlled trial.

AIMS: Modern clinical management of patients with an implantable cardioverter defibrillator (ICD) largely consists of remote device monitoring, although a subset is at risk of mental health issues post-implantation. We compared a 12-month web-based intervention consisting of goal setting, monitoring of patients' mental health-with a psychological intervention if needed-psychoeducational support from a nurse, and an online patient forum, with usual care on participants' device acceptance 12 months after implantation. METHODS AND RESULTS: This national, multi-site, two-arm, non-blinded, randomized, controlled, superiority trial enrolled 478 first-time ICD recipients from all 6 implantation centres in Denmark. The primary endpoint was patient device acceptance measured by the Florida Patient Acceptance Survey (FPAS; general score range = 0-100, with higher scores indicating higher device acceptance) 12 months after implantation. Secondary endpoints included symptoms of depression and anxiety. The primary endpoint of device acceptance was not different between groups at 12 months [B = -2.67, 95% confidence interval (CI) (-5.62, 0.29), P = 0.08]. Furthermore, the secondary endpoint analyses showed no significant treatment effect on either depressive [B = -0.49, 95% CI (-1.19; 0.21), P = 0.17] or anxiety symptoms [B = -0.39, 95% CI (-0.96; 0.18), P = 0.18]. CONCLUSION: The web-based intervention as supplement to usual care did not improve patient device acceptance nor symptoms of anxiety and depression compared with usual care. This specific web-based intervention thus cannot be recommended as a standardized intervention in ICD patients.

A large inherent delay between the ECG and EGM signals in the pacing system analyzer from Medtronic makes it unsuitable to estimate timing events during CRT implantation.

BACKGROUND: Following an observation of pacing markers being placed after the beginning of the paced QRS complex when using the analyzer module 2290 of the Medtronic 2090 programmer, we decided to determine the delay between the EGM and the ECG channels and comparing it to the St Jude Merlin® programmer. METHODS: We obtained ECG lead I simultaneously from both the ECG cable and by attaching the atrial clamps of the EGM cable on the left and right shoulder. We were then able to directly measure any delay. Then we compared measurements of start QRS to LV sense (qLV) in patients implanted with CRT in the last year where we had data on qLV at implant and at 6-month follow-up. At implant qLV was measured by the analyzer modules and at 6-month follow-up, it was measured in the pacing devices. RESULTS: We found that the delay between the EGM and ECG channels was 59 ±â€¯4 ms in the Medtronic analyzer (ECG first) and 4 ±â€¯3 ms in the St Jude analyzer (EGM first). In 16 CRT patients where the Medtronic analyzer had been used, the difference between qLV at implant and qLV at 6 months was 60 ±â€¯27 ms whereas this difference was 2 ±â€¯28 ms in 34 CRT patients where the St Jude analyzer had been used (p < 10-7). CONCLUSION: There is a delay of about 60 ms between the EGM and ECG channels of 2290 analyzer module of the Medtronic 2090 programmer making it unsuitable for determining timing measurements between QRS and EGM.

Left axis deviation in patients with left bundle branch block is a marker of myocardial disease associated with poor response to cardiac resynchronization therapy.

AIMS: Patients with left axis deviation (LAD) and left bundle branch block (LBBB) show less benefit from cardiac resynchronization therapy (CRT) compared to other LBBB-patients. This study investigates the reasons for this. METHODS: Sixty-eight patients eligible for CRT were included. Patients were divided into groups according to QRS-axis; normal axis (NA), left axis deviation (LAD) and right axis deviation (RAD). Before CRT implantation CMR imaging was performed to evaluate scar tissue. Echocardiography was performed before and after implantation. The electrical substrate was assessed by measuring interlead electrical delays. Response was evaluated after 8 months by left ventricular (LV) remodelling and clinical response. RESULTS: Forty-four (65%) patients were responders in terms of LV remodelling. The presence of LAD was found to be independently associated with a poor LV remodelling non-response OR 0.21 [95% CI 0.06-0.77] (p = 0.02). Patients with axis deviation had more myocardial scar tissue (1.3 ±â€¯0.6 vs. 0.9 ±â€¯0.6, P = 0.04), more severe LV hypertrophy (14 (64%) and 6 (60%) vs. 7 (29%), P = 0.05) and tended to have a shorter interlead electrical delay than patients with NA (79 ±â€¯40 ms vs. 92 ±â€¯48 ms, P = 0.07). A high scar tissue burden was more pronounced in non-responders (1.4 ±â€¯0.6 vs. 1.0 ±â€¯0.5, P = 0.01). CONCLUSIONS: LAD in the presence of LBBB is a predictor of poor outcome after CRT. Patients with LBBB and LAD have more scar tissue, hypertrophy and less activation delay.

Incidence of appropriate implantable cardioverter-defibrillator therapy and mortality after implantable cardioverter-defibrillator generator replacement: results from a real-world nationwide cohort.

AIMS: The safety of omitting implantable cardioverter-defibrillator (ICD) generator replacement in patients with no prior appropriate therapy, comorbid conditions, and advanced age is unclear. The aim was to investigate incidence of appropriate ICD therapy after generator replacement. METHODS AND RESULTS: We identified patients implanted with a primary prevention ICD (n = 4630) from 2007 to 2016, who subsequently underwent an elective ICD generator replacement (n = 670) from the Danish Pacemaker and ICD Register. The data were linked to other databases and evaluated the outcomes of appropriate therapy and death. Predictors of ICD therapy were identified using multivariate Cox regression analyses. A total of 670 patients underwent elective ICD generator replacement. Of these, 197 (29.4%) patients had experienced appropriate therapy in their 1st generator period. During follow-up of 2.0 ± 1.6 years, 95 (14.2%) patients experienced appropriate therapy. Predictors of appropriate therapy in 2nd generator period was low initial left ventricular ejection fraction (≤25%) [hazard ratio (HR) 1.87, confidence interval (CI) 1.13-1.95] and appropriate therapy in 1st generator period (HR 3.95, CI 2.57-6.06). For patients with appropriate therapy in 1st generator period, 4-year incidence of appropriate therapy was 50.6% vs. 16.4% in those without (P < 0.001). Among patients >80 years with no prior appropriate therapy 8.8% of patients experienced appropriate therapy after replacement. Comorbidity burden and advanced age were associated with reduced device utilization after replacement and a high competing risk of death without preceding appropriate therapy. CONCLUSION: A significant residual risk of appropriate therapy in the 2nd generator was present even among patients with advanced age and with a full prior generator period without any appropriate ICD events.

Clinical outcome in patients with implantable cardioverter-defibrillator and cancer: a nationwide study.

AIMS: Patients with cancer are insufficiently represented in randomized clinical trials investigating efficacy of implantable cardioverter-defibrillators (ICDs). We aimed to describe outcomes in patients with a pre-existing diagnosis of cancer at time of ICD implantation. METHODS AND RESULTS: We utilized Danish nationwide registries to identify primary and secondary prevention ICD implantations from 2007 to 2012. Multivariable Cox models were used to assess the risk of appropriate ICD therapy and mortality in patients with and without cancer at time of implantation. During a median follow-up of 2.1 years, 2935 primary prevention ICD and 2730 secondary prevention ICD implantations were identified. Out of these [289 (5.1%)] had pre-existing cancer [primary 140 (4.8%), secondary 149 (5.5%)]. No differential risk for appropriate ICD therapy was found between patients with or without cancer, [primary cancer: 19/140, no cancer: 380/2795, hazard ratio (HR) = 1.07 (0.67-1.69)] and [secondary cancer: 42/149, no cancer: 699/2581, HR = 1.28 (0.93-1.75)]. In primary patients, cancer was not associated with higher risk of 1-year [cancer: 10/140, no cancer: 133/2795, HR = 1.20 (0.84-2.28)] or all-time mortality [cancer: 22/140, no cancer: 339/2795, HR = 1.13 (0.74-1.75)]. In secondary patients, cancer was associated with a higher 1-year [cancer: 19/149, no cancer: 108/2581, HR = 2.62 (1.60-4.29)] and all-time mortality [cancer: 44/149, no cancer: 315/2581, HR = 2.36 (1.71-3.24)]. CONCLUSION: Implantable cardioverter-defibrillators were implanted in a minority of cancer patients. No difference in risk of appropriate therapy was observed between cancer and non-cancer patients, regardless of implant indication. Cancer was associated with increased mortality in secondary prevention ICD patients, but not in primary prevention ICD patients. In secondary prevention ICD patients, the majority of deaths were attributable to cancer.

The use of guideline recommended beta-blocker therapy in primary prevention implantable cardioverter defibrillator patients: insight from Danish nationwide registers.

Aims: We aimed to examine the use of guideline recommended beta-blocker therapy prior to and after primary prevention implantable cardioverter defibrillator (ICD) implantation in a 'real-life' setting. Methods and results: From the Danish Pacemaker and ICD Registry we identified all 1st-time primary prevention ICD and cardiac resynchronization therapy defibrillator (CRT-D) implantations in Denmark from 2007-12 (n = 2935). Use of beta-blocker, type and dose was acquired through the Danish Prescription Registry. According to guideline recommendations, we defined target daily doses as ≥50 mg carvedilol and ≥200 mg metoprolol. Prior to implantation 2427 of 2935 (83%) patients received beta-blocker therapy, with 2166 patients (89%) having initiated treatment 3 months or more prior to implantation. The majority of patients was prescribed carvedilol (52%) or metoprolol (41%). Patients on carvedilol reached target dosages more frequently than patients on metoprolol, with 39% of patients on carvedilol and 26% of patients on metoprolol at the time of implantation (P < 0.001 for all time-points). Increase in proportion of patients reaching target daily doses was observed for both carvedilol and metoprolol after ICD implantation. Carvedilol treatment was a strong predictor for being on target dose of BB at time of implant, as was treatment with angiotensin-converting enzyme inhibitors and/or spironolactone, no history of myocardial infarction, younger age and less pronounced heart failure symptoms. Conclusion: In a real-life setting of primary prevention ICD patients, 39% and 26% of patients were titrated to optimal target dose of carvedilol or metoprolol prior to implantation. A higher proportion of patients on carvedilol reached target dose, as compared with metoprolol.

Effectiveness of a comprehensive interactive eHealth intervention on patient-reported and clinical outcomes in patients with an implantable cardioverter defibrillator [ACQUIRE-ICD trial]: study protocol of a national Danish randomised controlled trial.

BACKGROUND: In Denmark and other countries, there has been a shift in the management of patients with an implantable cardioverter defibrillator (ICD) with remote device monitoring largely replacing in-hospital visits. Less patient-nurse and patient-physician interaction may lead to gaps in patients' quality of care and impede patients' adaptation to living successfully with the ICD. A comprehensive eHealth intervention that include goal-setting, monitoring of symptoms of depression, anxiety, and quality of life, psychological treatment, information provision, supportive tools, online dialogues with nursing staff and access to an online community network, may help fill these gaps and be particularly beneficial to patients who suffer from anxiety and depression. This study will evaluate the effectiveness of the ACQUIRE-ICD care innovation, a comprehensive and interactive eHealth intervention, on patient-reported and clinical outcomes. METHODS: The ACQUIRE-ICD study is a multicenter, prospective, two-arm, unblinded randomised controlled superiority trial that will enroll 478 patients implanted with a first-time ICD or ICD with cardiac synchronisation therapy (CRT-D) from the six implanting centers in Denmark. The trial will evaluate the clinical effectiveness and cost-effectiveness of the ACQUIRE-ICD care innovation, as add-on to usual care compared with usual care alone. The primary endpoint, device acceptance, assessed with the Florida Patient Acceptance Survey, is evaluated at 12 months' post implant. Secondary endpoints, evaluated at 12 and 24 months' post implant, include patient-reported outcomes, return to work, time to first ICD therapy and first hospitalisation, mortality and cost-effectiveness. DISCUSSION: The effectiveness of a comprehensive and interactive eHealth intervention that relies on patient-centred and personalised tools offered via a web-based platform targeted to patients with an ICD has not been assessed so far. The ACQUIRE-ICD care innovation promotes and facilitates that patients become active participants in the management of their disease, and as such addresses the need for a more patient-centered disease-management approach. If the care innovation proves to be beneficial to patients, it may not only increase patient empowerment and quality of life but also free up time for clinicians to care for more patients. TRIAL REGISTRATION: The trial has been registered on https://clinicaltrials.gov/ct2/show/NCT02976961 on November 30, 2016 with registration number [ NCT02976961 ].

Shortening of paced QRS duration after electrocardiographic optimization of left ventricular pacing vector in patients treated with Cardiac Resynchronization Therapy.

Background: Choice of left ventricular pacing vector (LVPV) affects the QRS-duration (QRSd) in patients with Cardiac Resynchronization Therapy (CRT). It is not known whether testing all LVPVs reduces QRSd compared to device-based "standard-programming". Methods: In patients implanted with CRT several ECGs were recorded for each usable LVPV (no phrenic nerve stimulation and threshold <3.5 V) and during "standard-programming" after device-based optimization of AV/VV delays. Results: 22 consecutive patients were included. Average QRSd reduction after CRT + "standard-programming" was 27.3 ±â€¯22 ms. Additional QRSd-reduction was possible in 4 patients by changing the LVPV, and in 5 other patients after optimization of AV- and VV delays without changing LVPV. Conclusions: Shortening of QRSd compared to "standard-programming" was possible approximately 40% of these patients treated with CRT by testing all LVPVs and re-optimizing AV/VV delays during follow-up. Studies of clinical effects are needed.

Accuracy of the ICD-10 discharge diagnosis for syncope.

AIMS: Administrative discharge codes are widely used in epidemiology, but the specificity and sensitivity of this coding is unknown and must be validated. We assessed the validity of the discharge diagnosis of syncope in administrative registers and reviewed the etiology of syncope after workup. METHODS AND RESULTS: Two samples were investigated. One sample consisted of 5262 randomly selected medical patients. The other sample consisted of 750 patients admitted or seen in the emergency department (ED) for syncope (ICD-10: R55.9) in three hospitals in Denmark. All charts were reviewed for baseline characteristics and to confirm the presence/absence of syncope and to compare with the administrative coding. In a sample of 600 admitted patients 570 (95%) and of 150 patients from ED 140 (93%) had syncope representing the positive predictive values. Median age of the population was 69 years (IQR: ± 14). In the second sample of 5262 randomly selected medical patients, 75 (1.4%) had syncope, of which 47 were coded as R55.9 yielding a sensitivity of 62.7%, a negative predictive value of 99.5%, and a specificity of 99.9%. CONCLUSION: ED and hospital discharge diagnostic coding for syncope has a positive predictive value of 95% and a sensitivity of 63%.

Increased post-operative ischemia in the femoral head found by microdialysis by the posterior surgical approach: a randomized clinical trial comparing surgical approaches in hip resurfacing arthroplasty.

BACKGROUND: Hip resurfacing arthroplasty (HRA) is associated with osteonecrosis of the femoral head and femoral neck fracture, which may be caused by a decrease in the perfusion of the bone initiated at surgery. Several studies have demonstrated a decreased blood flow during surgery depending on the choice of surgical approach. We investigated the effect of the surgical approach on the blood flow and metabolism in the femoral head and neck in HRA by Laser Doppler flowmetry (LDF) and microdialysis. MATERIALS AND METHODS: We conducted a randomized clinical trial on 38 patients, allocated to HRA by either the posterior (Post) or the antero-lateral (AntLat) surgical approach. LDF was performed during surgery and microdialysis after surgery to assess the concentration of the following metabolic markers: glucose, lactate, pyruvate and glycerol. RESULTS: At 44-50 h after surgery, the mean lactate/pyruvate (L/P) and lactate/glucose (L/G) ratio was higher in the Post group compared to the AntLat group; L/P 195.3 (SEM 123) in Post and 128.5 (108.0) in AntLat; L/G 16.9 (6.5) in Post and 8.9 (3.7) in AntLat (p L/P = 0.02 and p L/G = 0.03). There was no difference in the LDF measurements (p = 0.74). INTERPRETATION: HRA in the posterior approach results in increased post-operative ischemia in the femoral head and neck although during surgery, no difference in the blood flow was found. Still, the antero-lateral approach also causes considerable ischemia and other possible explanations, such as damage to the retinacular vessels during surgery or altered microcirculation because of heating from the cementation process, needs to be investigated.

The effect of increased plasma potassium on myocardial function; a randomized POTCAST substudy.

Plasma potassium (p-K) in the high-normal range has been suggested to reduce risk of cardiovascular arrythmias and mortality through electrophysiological and mechanical effects on the myocardium. In this study, it was to investigated if increasing p-K to high-normal levels improves systolic- and diastolic myocardial function in patients with low-normal to moderately reduced left ventricular ejection fraction (LVEF). The study included 50 patients (mean age 58 years (SD 14), 81% men), with a mean p-K 3.95 mmol/l (SD 0.19), mean LVEF 48% (SD 7), and mean Global Longitudinal Strain (GLS) -14.6% (SD 3.1) patients with LVEF 35-55% from "Targeted potassium levels to decrease arrhythmia burden in high-risk patients with cardiovascular diseases trial" (POTCAST). Patients were given standard therapy and randomized (1:1) to an intervention that included guidance on potassium-rich diets, potassium supplements, and mineralocorticoid receptor antagonists targeting high-normal p-K levels (4.5-5.0 mmol/l). Echocardiography was done at baseline and after a mean follow-up of 44 days (SD 18) and the echocardiograms were analyzed for changes in GLS, mechanical dispersion, E/A, e', and E/e'. At follow-up, mean difference in changes in p-K was 0.52 mmol/l (95%CI 0.35;0.69), P<0.001 in the intervention group compared to controls. GLS was improved with a mean difference in changes of -1.0% (-2;-0.02), P<0.05 and e' and E/e' were improved with a mean difference in changes of 0.9 cm/s (0.02;1.7), P = 0.04 and ? 1.5 (-2.9;-0.14), P = 0.03, respectively. Thus, induced increase in p-K to the high-normal range improved indices of systolic and diastolic function in patients with low-normal to moderately reduced LVEF.

Global constructive work is associated with ventricular arrhythmias after cardiac resynchronization therapy.

AIMS: Non-invasive left ventricular (LV) pressure-strain loops provide a novel method for quantifying myocardial work by incorporating LV pressure in measurements of myocardial deformation. Early studies suggest that myocardial work parameters such as global constructive work (GCW) could be useful and reliable in arrhythmia prediction, particularly in patients undergoing cardiac resynchronization therapy (CRT). The aim of this study was to evaluate whether the magnitude of GCW was associated with the occurrence of ventricular arrhythmias in patients after CRT. METHODS AND RESULTS: Patients on guideline-recommended treatment with a CRT defibrillator (CRT-D) were evaluated by 2D speckle-tracking echocardiography including measurements of GCW at least 6 months after implantation. The primary outcome was a composite of appropriate defibrillator therapy and sustained ventricular arrhythmia under the monitor zone. A total of 162 patients [mean age 66 years (±10), 122 males (75%)] were included. Sixteen (10%) patients experienced the primary outcome during a median follow-up of 18 months (interquartile range: 12-25) after the performance of index echocardiography. Patients with a below-median GCW (<1473 mmHg%) had a hazard ratio (HR) for the outcome of 8.14 [95% confidence interval (CI): 1.83-36.08], P = 0.006 compared with patients above the median in a univariate model and remained an independent predictor after multivariate adjustment for the estimated glomerular filtration rate and QRS duration [HR 4.75 (95% CI: 1.01-22.28), P < 0.05]. CONCLUSION: In patients treated with CRT-D, a GCW below median level was associated with a five-fold increase in the risk of ventricular arrhythmias.

Treatment-induced increase in total body potassium in patients at high risk of ventricular arrhythmias; a randomized POTCAST substudy.

OBJECTIVE: Hypokalemia is associated with increased risk of arrhythmias and it is recommended to monitor plasma potassium (p-K) regularly in at-risk patients with cardiovascular diseases. It is poorly understood if administration of potassium supplements and mineralocorticoid receptor antagonists (MRA) aimed at increasing p-K also increases intracellular potassium. METHODS: Adults aged≥18 years with an implantable cardioverter defibrillator (ICD) were randomized (1:1) to a control group or to an intervention that included guidance on potassium rich diets, potassium supplements, and MRA to increase p-K to target levels of 4.5-5.0 mmol/l for six months. Total-body-potassium (TBK) was measured by a Whole-Body-Counter along with p-K at baseline, after six weeks, and after six months. RESULTS: Fourteen patients (mean age: 59 years (standard deviation 14), 79% men) were included. Mean p-K was 3.8 mmol/l (0.2), and mean TBK was 1.50 g/kg (0.20) at baseline. After six-weeks, p-K had increased by 0.47 mmol/l (95%CI:0.14;0.81), p = 0.008 in the intervention group compared to controls, whereas no significant difference was found in TBK (44 mg/kg (-20;108), p = 0.17). After six-months, no significant difference was found in p-K as compared to baseline (0.16 mmol/l (-0.18;0.51), p = 0.36), but a significant increase in TBK of 82 mg/kg (16;148), p = 0.017 was found in the intervention group compared to controls. CONCLUSIONS: Increased potassium intake and MRAs increased TBK gradually and a significant increase was seen after six months. The differentially regulated p-K and TBK challenges current knowledge on potassium homeostasis and the time required before the full potential of p-K increasing treatment can be anticipated. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT03833089).

Dermatan sulphate in methoxy polyethylene glycol-polylactide-co-glycolic acid scaffolds upregulates fibronectin gene expression but has no effect on in vivo osteochondral repair.

PURPOSE: The purpose of the study was to investigate the effect of dermatan sulphate (DS) addition to biodegradable methoxy polyethylene glycol (MPEG) substituted polylactide-co-glycolic acid (PLGA) scaffolds for cartilage repair in vitro and in vivo. METHODS: Human chondrocytes from eight patients undergoing anterior cruciate ligament reconstruction were isolated and cultured in 5% oxygen on MPEG-PLGA scaffolds±DS for one, three, seven and 14 days. Analyses were performed using quantitative gene expression analysis for chondrogenic and cell attachment markers. An osteochondral drill hole defect was created in the intertrochlear groove of the distal femur in 20 New Zealand white rabbits (defects n=20). When bleeding was observed, the defects were treated with MPEG-PLGA scaffolds±DS. Twelve weeks after surgery the rabbits were sacrificed and the defects were analysed using histological grading with O'Driscoll scoring. RESULTS: DS addition to MPEG-PLGA scaffolds resulted in a significant upregulation of fibronectin gene expression on day 1. No differences were observed in chondrogenic gene expression. There were no differences between the two groups in histological grading (+DS 10.3 and -DS 9.6). CONCLUSIONS: Upregulation of fibronectin in vitro indicating early cell-scaffold interaction and attachment did not result in improved cartilage repair in an osteochondral defect model in rabbits.

Carpal Tunnel Syndrome in Patients Who Underwent Pacemaker Implantation and Relation to Amyloidosis, Heart Failure, and Mortality.

Advances in treatment warrant earlier diagnosis of cardiac amyloidosis (CA). Common cardiac and extracardiac manifestations of CA, such as pacemaker implantation and carpal tunnel syndrome (CTS), might provide screening opportunities for CA. However the association between CTS and CA in patients undergoing pacemaker implantation has not been well studied. This study examined the association between previous CTS surgery and adverse cardiovascular outcomes in patients who underwent pacemaker implantation. Using Danish nationwide registries, we identified all patients ≥50 years who underwent first-time pacemaker implantation during 2000 to 2018, examining the association between previous CTS surgery and adverse cardiovascular outcomes 5 years after pacemaker implantation. Cumulative incidence functions and Cox proportional hazard models were used to assess the differences. Among 57,315 patients who underwent pacemaker implantation, 2.2% (n = 1,266) had previous CTS surgery. Patients in the CTS cohort were older, more often female, and had more co-morbidities than patients without CTS. The cumulative 5-year mortality was higher among patients with CTS (44.6% [41.1% to 47.9%] versus 40.2% [39.7% to 40.6%], p = 0.04). In the adjusted models, previous CTS surgery was not associated with increased 5-year mortality, but it was associated with an increased rate of hospitalization for new-onset heart failure, (hazard ratio 1.32 [1.11 to 1.57], p = 0.002) and a higher risk of amyloidosis diagnosis after pacemaker implantation (hazard ratio 7.72 [2.96 to 20.10], p <0.0001), compared with no previous CTS surgery. In patients who underwent pacemaker implantation, adjusted models showed that previous CTS surgery was associated with a higher incidence of hospitalization for new-onset heart failure and amyloidosis diagnosis after pacemaker implantation. Screening for CA may be considered in patients undergoing pacemaker implantation.

Cause-specific death and risk factors of 1-year mortality after implantable cardioverter-defibrillator implantation: a nationwide study.

AIMS: Current treatment guidelines recommend implantable cardioverter-defibrillators (ICDs) in eligible patients with an estimated survival beyond 1 year. There is still an unmet need to identify patients who are unlikely to benefit from an ICD. We determined cause-specific 1-year mortality after ICD implantation and identified associated risk factors. METHODS AND RESULTS: Using Danish nationwide registries (2000-2017), we identified 14 516 patients undergoing first-time ICD implantation for primary or secondary prevention. Risk factors associated with 1-year mortality were evaluated using multivariable logistic regression. The median age was 66 years, 81.3% were male, and 50.3% received an ICD for secondary prevention. The 1-year mortality rate was 4.8% (694/14 516). ICD recipients who died within 1 year were older and more comorbid compared to those who survived (72 vs. 66 years, P < 0.001). Risk factors associated with increased 1-year mortality included dialysis [odds ratio (OR): 3.26, confidence interval (CI): 2.37-4.49], chronic renal disease (OR: 2.14, CI: 1.66-2.76), cancer (OR: 1.51, CI: 1.15-1.99), age 70-79 years (OR: 1.65, CI: 1.36-2.01), and age ≥80 years (OR: 2.84, CI: 2.15-3.77). The 1-year mortality rates for the specific risk factors were: dialysis (13.8%), chronic renal disease (13.1%), cancer (8.5%), age 70-79 years (6.9%), and age ≥80 years (11.0%). Overall, the most common causes of mortality were related to cardiovascular diseases (62.5%), cancer (10.1%), and endocrine disorders (5.0%). However, the most common cause of death among patients with cancer was cancer-related (45.7%). CONCLUSION: Among ICD recipients, mortality rates were low and could be indicative of relevant patient selection. Important risk factors of increased 1-year mortality included dialysis, chronic renal disease, cancer, and advanced age.

Combined 3D and hypoxic culture improves cartilage-specific gene expression in human chondrocytes.

BACKGROUND AND PURPOSE: In vitro expansion of autologous chondrocytes is an essential part of many clinically used cartilage repair treatments. Native chondrocytes reside in a 3-dimensional (3D) network and are exposed to low levels of oxygen. We compared monolayer culture to combined 3D and hypoxic culture using quantitative gene expression analysis. METHODS: Cartilage biopsies were collected from the intercondylar groove in the distal femur from 12 patients with healthy cartilage. Cells were used for either monolayer or scaffold culture. The scaffolds were clinically available MPEG-PLGA scaffolds (ASEED). After harvesting of cells for baseline investigation, the remainder was divided into 3 groups for incubation in conditions of normoxia (21% oxygen), hypoxia (5% oxygen), or severe hypoxia (1% oxygen). RNA extractions were performed 1, 2, and 6 days after the baseline time point, respectively. Quantitative RT-PCR was performed using assays for RNA encoding collagen types 1 and 2, aggrecan, sox9, ankyrin repeat domain-37, and glyceraldehyde-3-phosphate dehydrogenase relative to 2 hypoxia-stable housekeeping genes. RESULTS: Sox9, aggrecan, and collagen type 2 RNA expression increased with reduced oxygen. On day 6, the expression of collagen type 2 and aggrecan RNA was higher in 3D culture than in monolayer culture. INTERPRETATION: Our findings suggest that there was a combined positive effect of 3D culture and hypoxia on cartilage-specific gene expression. The positive effects of 3D culture alone were not detected until day 6, suggesting that seeding of chondrocytes onto a scaffold for matrix-assisted chondrocyte implantation should be performed earlier than 2 days before implantation.

A Randomized Trial of His Pacing Versus Biventricular Pacing in Symptomatic HF Patients With Left Bundle Branch Block (His-Alternative).

OBJECTIVES: This study sought to compare 2 ways of achieving cardiac resynchronization. BACKGROUND: Cardiac resynchronization therapy (CRT) in patients with symptomatic heart failure and left bundle branch block (LBBB) can be achieved with His-bundle pacing correcting the bundle branch block (His-CRT). The present study is the largest randomized study comparing His-CRT and biventricular pacing (BiV-CRT) to date. METHODS: Fifty patients with symptomatic heart failure, left ventricular ejection fraction (LVEF) ≤35% and LBBB according to electrocardiography were randomized 1:1 to His-CRT or BiV-CRT and followed for 6 months. At implantation, 7 patients crossed over from His-pacing to LV-pacing in the His-CRT group and 1 patient crossed over from LV-pacing to His-pacing in the BiV-CRT group. RESULTS: His-corrective pacing was achieved in 72% of the patients in the His-CRT group. Intention-to-treat 6-month follow-up LVEF increased by 16 ± 7% in the His-CRT group compared with 13 ± 6% in the BiV-CRT group (nonsignificant) and improvements were seen in clinical and physical parameters in both treatment arms with no significant differences between the groups. Pacing thresholds were higher for His-CRT compared with BiV-CRT both at implantation (1.8 ± 1.2 V vs. 1.2 ± 0.8 V; p < 0.01) and at 6-month follow-up (2.3 ± 1.4 V vs. 1.4 ± 0.5 V; p < 0.01). The per-protocol LVEF was significantly higher at 6 months (48 ± 8% vs. 42 ± 8%; p < 0.05) and the end-systolic volume was lower (65 ± 22 ml vs. 83 ± 27 ml; p < 0.05) in His-CRT patients compared with BiV-CRT. CONCLUSIONS: In heart failure patients with LBBB, His-CRT provided similar clinical and physical improvement compared with BiV-CRT at the expense of higher pacing thresholds.