Age-stratified comparison of prognosis in cardiac resynchronization therapy with or without prophylactic defibrillator for nonischemic cardiomyopathy-a nationwide cohort study.

AIMS: Prior studies have suggested that the benefit from primary preventive defibrillator treatment for patients with nonischemic cardiomyopathyy, treated with cardiac resynchronization therapy, may be age-dependent. We aimed to compare age-stratified mortality rates and mode of death in patients with nonischemic cardiomyopathy who are treated with either primary preventive cardiac resynchronization therapy with defibrillator (CRT-D) or CRT with pacemaker (CRT-P). METHODS AND RESULTS: All patients with nonischemic cardiomyopathy and CRT-P or primary preventive CRT-D who were implanted in Sweden during the period 2005-2020 were included. Propensity scoring was used to create a matched cohort. Primary outcome was all-cause mortality within 5 years. In all, 4027 patients were included: 2334 with CRT-P and 1693 with CRT-D. Crude 5-year mortality was 635 (27%) vs. 246 (15%), P < 0.001. In Cox regression analysis, adjusted for clinically relevant covariables, CRT-D was independently associated with higher 5-year survival [0.72 (0.61-0.85), P < 0.001]. Cardiovascular mortality was similar between groups (62 vs. 64%, P = 0.64), but death from heart failure was more common in the CRT-D group (46 vs. 36%, P = 0.007). In the matched cohort (n = 2414), 5-year mortality was 21% (24 vs. 16%, P < 0.001). In age-stratified analyses, CRT-P was associated with higher mortality in age groups <60 years and 70-79 years, but there was no difference in age groups 60-69 years or 80-89 years. CONCLUSION: In this nationwide registry-based study, patients with CRT-D had better 5-year survival compared to patients with CRT-P. The interaction between age and mortality reduction was not consistent, but patients with CRT-D aged <60 years had the largest absolute mortality reduction.

Sex-based differences in cardiac resynchronization therapy upgrade and outcome for patients with pacemaker and new-onset heart failure.

BACKGROUND: Patients with chronic right ventricular (RV) pacing are at an increased risk of heart failure. Previous studies have indicated that cardiac resynchronization therapy (CRT) is underused in this setting, and that there may be sex-based differences in both CRT use and clinical outcome. OBJECTIVE: To evaluate sex-based differences in CRT use and clinical outcome for patients with new-onset heart failure post RV pacing. METHODS: Data from the Swedish pacemaker registry was matched with data from the national death and disease registries. Patients with de novo pacemaker implant due to AV block during the period 2005-2020 were included. New-onset heart-failure within two years post-implant was evaluated, primary outcome was all-cause mortality. RESULTS: In all, 30183 patients (37% female) were included. Women were on average 3 years older, but had less comorbidities than men. Median follow-up time was 4.5 [2.0-8.0] years. Women had better age- and comorbidity-adjusted survival (HR 0.78 [0.73-0.84], p < .001). For the 3560 patients (12.4% men and 10.7% women, p < .001) who were diagnosed with new-onset heart failure, 5-year mortality was similar for men and women (50% vs. 48%, p = .29). However, women were less likely to receive CRT-upgrade (3.8% vs. 9.1%, p < .001), and those who did were almost ten years younger than the men. CONCLUSION: Women with pacemaker due to AV block are older but have less comorbidities than men. They are less likely to develop new-onset heart failure, but also less likely to receive a CRT upgrade if they do develop heart failure. Increased awareness of the positive effects of CRT upgrade and potential sex- and age-based discrimination is warranted.

Association between left ventricular lead position and intrinsic QRS morphology with regard to clinical outcome in cardiac resynchronization therapy for heart failure.

BACKGROUND: Left ventricular (LV) lead position may be an important factor for delivering effective cardiac resynchronization therapy (CRT). We therefore aimed to evaluate the effects of LV lead position, stratified by native QRS morphology, regarding the clinical outcome. METHODS: A total of 1295 CRT-implanted patients were retrospectively evaluated. LV lead position was classified as lateral, anterior, inferior, or apical, and was determined using the left and right anterior oblique X-ray views. Kaplan Meier and Cox regression were performed to evaluate the effects on all-cause mortality and heart failure hospitalization, and the potential interaction between LV lead position and native ECG morphologies. RESULTS: A total of 1295 patients were included. Patients were aged 69 ± 7 years, 20% were female, 46% received a CRT-Pacemaker (vs. CRT-Defibrillator), mean LVEF was 25% ± 7%, and median follow-up was 3.3 years [IQR 1.6-5-7 years]. Eight hundred and eighty-two patients (68%) had a lateral LV lead location, 207 (16%) anterior, 155 (12%) apical, and 51 (4%) inferior. Patients with lateral LV lead position had larger QRS reduction (-13 ± 27 ms vs. -3 ± 24 ms, p < .001). Non-lateral lead location was associated with a higher risk for all-cause mortality (HR 1.34 [1.09-1.67], p = .007) and heart failure hospitalization (HR 1.25 [1.03-1.52], p = .03). This association was strongest for patients with native left or right bundle branch block, and not significant for patients with prior paced QRS or nonspecific intraventricular conduction delay. CONCLUSIONS: In patients treated with CRT, non-lateral LV lead positions (including apical, anterior, and inferior positions) were associated with worse clinical outcome and less reduction of QRS duration. This association was strongest for patients with native LBBB or RBBB.

Efficacy of the antibacterial envelope to prevent cardiac implantable electronic device infection in a high-risk population.

AIMS: Infection is a serious complication of cardiac implantable electronic device (CIED) therapy. An antibiotic-eluting absorbable envelope has been developed to reduce the infection rate, but studies investigating the efficacy and a reasonable number needed to treat in high-risk populations for infections are limited. METHODS AND RESULTS: One hundred and forty-four patients undergoing CIED implantation who received the antibacterial envelope were compared with a matched cohort of 382 CIED patients from our institution. The primary outcome was the occurrence of local infection, and secondary outcomes were any CIED-related local or systemic infections, including endocarditis, and all-cause mortality. The results were stratified by a risk score for CIED infection, PADIT. The envelope group had a higher PADIT score, 5.9 ± 3.1 vs. 3.9 ± 3.0 (P < 0.0001). For the primary endpoint, no local infections occurred in the envelope group, compared with 2.6% in the control group (P = 0.04), with a more pronounced difference in the stratum with a high (>7 points) PADIT score, 0 vs. 9.9% (P = 0.01). The total CIED-related infections were similar between groups, 6.3% compared with 5.0% (P = 0.567). Mortality after 1600 days of follow-up did not differ between groups, 22.9 vs. 26.4%, P = 0.475. CONCLUSION: Our study confirms the clinical efficacy of an antibacterial envelope in the prevention of local CIED infection in patients with a higher risk according to the PADIT score. In an effort to improve cost-benefit ratios, ration of use guided by the PADIT score is advocated. Further prospective randomized studies in high-risk populations are called for.

Diagnosis and treatment of the rare procedural complication of malpositioned pacing leads in the left heart: a single center experience.

Objectives. This study assessed the management approach and outcome of the pacemaker or implantable cardioverter-defibrillator (ICD) leads malpositioned in the left heart. Malpositioned leads (MPLs) may have deleterious consequences, and appropriate management remains uncertain. Methods. The study population included all patients referred to a single institution for MPL in the left side of the heart after pacemaker or ICD implantation during the period from 2015 to 2021. The approach and outcome of lead management were retrospectively assessed. Results. During the study period, 6887 patients underwent device implantation. MPL was diagnosed in five patients (0.07%). In four cases, the pacing lead was placed in a coronary sinus (CS) branch, while the pacing lead was inside the left ventricle (LV) in one case. Symptoms suggestive of lead malposition were reported by 2 patients (40%). One of the patients presented with recurrent TIAs. Another presented with inappropriate ICD shocks. In one asymptomatic case, an ICD lead changed position from the right ventricle to the CS, suggesting idiopathic lead migration. In 4/5 patients, the leads were removed or repositioned by percutaneous approach, with no major periprocedural complications. Conclusions. In this series of MPL in the left heart, two patients presented with thromboembolic events or inappropriate ICD shocks. These serious complications highlight the critical need for early correct diagnosis and proper management of MPL.

Vectorcardiography Findings Are Associated with Recurrent Ventricular Arrhythmias and Mortality in Patients with Heart Failure Treated with Implantable Cardioverter-Defibrillator Device.

BACKGROUND: There is a need for refined risk stratification of sudden cardiac death and prediction of ventricular arrhythmias to correctly identify patients who are expected to benefit the most from implantable cardioverter-defibrillator (ICD) therapy. METHODS: We conducted a registry-based retrospective observational study on patients with either ischemic (ICMP) or nonischemic dilated cardiomyopathy (NICMP) treated with ICD between 2002 and 2013 at a tertiary referral center. We evaluated 3 vectorcardiography (VCG) indices; spatial QRS-T angle, QRS vector magnitude (QRSvm), and T-wave vector magnitude (Twvm), and their association with all-cause mortality and ventricular arrhythmias. The VCG indices were automatically computed from resting 12-lead electrocardiograms before ICD implantation. RESULTS: 178 patients were included in the study; 53.4% had ICMP, 79.2% were male, and mean ejection fraction was 27.4%. During the follow-up (median 89 months), 40 patients (23%) died; 31% had appropriate ICD therapy. In multivariate analysis with dichotomized variables, QRS-T angle >152° and Twvm <0.38 mV were significantly associated with increased mortality: HR 2.64 (95% CI 1.14-6.12, p = 0.02) and HR 5.30 (95% CI 2.31-12.11, p < 0.001), respectively. QRSvm <1.54 mV was borderline significant with mortality outcome (p = 0.10). The composite score of all 3 VCG indices, a score of 3, conferred an increased risk of mortality (including heart failure mortality) in multivariate analysis: HR 13.80 (95% CI 3.44-55.39, p < 0.001). CONCLUSION: The spatial QRS-T angle and Twvm are emerging VCG indices which are independently associated with mortality in patients with reduced left ventricular ejection fraction due to ICMP or NICMP. Using a composite score of all 3 vector indices, a maximum score was associated with poor long-term survival.

The ability of the electrocardiogram in left bundle branch block to detect myocardial scar determined by cardiovascular magnetic resonance.

AIMS: We aimed to improve the electrocardiographic 2009 left bundle branch block (LBBB) Selvester QRS score (2009 LBSS) for scar assessment. METHODS: We retrospectively identified 325 LBBB patients with available ECG and cardiovascular magnetic resonance imaging (CMR) with late gadolinium enhancement from four centers (142 [44%] with CMR scar). Forty-four semi-automatically measured ECG variables pre-selected based on the 2009 LBSS yielded one multivariable model for scar detection and another for scar quantification. RESULTS: The 2009 LBSS achieved an area under the curve (AUC) of 0.60 (95% confidence interval 0.54-0.66) for scar detection, and R2 = 0.04, p < 0.001, for scar quantification. Multivariable modeling improved scar detection to AUC 0.72 (0.66-0.77) and scar quantification to R2 = 0.21, p < 0.001. CONCLUSIONS: The 2009 LBSS detects and quantifies myocardial scar with poor accuracy. Improved models with extensive comparison of ECG and CMR had modest performance, indicating limited room for improvement of the 2009 LBSS.

Ejection fraction in left bundle branch block is disproportionately reduced in relation to amount of myocardial scar.

INTRODUCTION: The relationship between left ventricular (LV) ejection fraction (EF) and LV myocardial scar can identify potentially reversible causes of LV dysfunction. Left bundle branch block (LBBB) alters the electrical and mechanical activation of the LV. We hypothesized that the relationship between LVEF and scar extent is different in LBBB compared to controls. METHODS: We compared the relationship between LVEF and scar burden between patients with LBBB and scar (n = 83), and patients with chronic ischemic heart disease and scar but no electrocardiographic conduction abnormality (controls, n = 90), who had undergone cardiovascular magnetic resonance (CMR) imaging at one of three centers. LVEF (%) was measured in CMR cine images. Scar burden was quantified by CMR late gadolinium enhancement (LGE) and expressed as % of LV mass (%LVM). Maximum possible LVEF (LVEFmax) was defined as the function describing the hypotenuse in the LVEF versus myocardial scar extent scatter plot. Dysfunction index was defined as LVEFmax derived from the control cohort minus the measured LVEF. RESULTS: Compared to controls with scar, LBBB with scar had a lower LVEF (median [interquartile range] 27 [19-38] vs 36 [25-50] %, p < 0.001), smaller scar (4 [1-9] vs 11 [6-20] %LVM, p < 0.001), and greater dysfunction index (39 [30-52] vs 21 [12-35] % points, p < 0.001). CONCLUSIONS: Among LBBB patients referred for CMR, LVEF is disproportionately reduced in relation to the amount of scar. Dyssynchrony in LBBB may thus impair compensation for loss of contractile myocardium.

Evaluation of the ECG based Selvester scoring method to estimate myocardial scar burden and predict clinical outcome in patients with left bundle branch block, with comparison to late gadolinium enhancement CMR imaging.

BACKGROUND: Myocardial scar burden quantification is an emerging clinical parameter for risk stratification of sudden cardiac death and prediction of ventricular arrhythmias in patients with left ventricular dysfunction. We investigated the relationships among semiautomated Selvester score burden and late gadolinium enhancement-cardiovascular magnetic resonance (LGE-CMR) assessed scar burden and clinical outcome in patients with underlying heart failure, left bundle branch block (LBBB) and implantable cardioverter-defibrillator (ICD) treatment. METHODS: Selvester QRS scoring was performed on all subjects with ischemic and nonischemic dilated cardiomyopathy at Skåne University Hospital Lund (2002-2013) who had undergone LGE-CMR and 12-lead ECG with strict LBBB pre-ICD implantation. RESULTS: Sixty patients were included; 57% nonischemic dilated cardiomyopathy and 43% ischemic cardiomyopathy with mean left ventricular ejection fraction of 27.6% ± 11.7. All patients had scar by Selvester scoring. Sixty-two percent had scar by LGE-CMR (n = 37). The Spearman correlation coefficient for LGE-CMR and Selvester score derived scar was r = .35 (p = .007). In scar negative LGE-CMR, there was evidence of scar by Selvester scoring in all patients (range 3%-33%, median 15%). Fourteen patients (23%) had an event during the follow-up period; 11 (18%) deaths and six adequate therapies (10%). There was a moderate trend indicating that presence of scar increased the risk of clinical endpoints in the LGE-CMR analysis (p = .045). CONCLUSION: There is a modest correlation between LGE-CMR and Selvester scoring verified myocardial scar. CMR based scar burden is correlated to clinical outcome, but Selvester scoring is not. The Selvester scoring algorithm needs to be further refined in order to be clinically relevant and reliable for detailed scar evaluation in patients with LBBB.

Long-Term Results of Cardiac Resynchronization Therapy: A Comparison between CRT-Pacemakers versus Primary Prophylactic CRT-Defibrillators.

BACKGROUND: Cardiac resynchronization therapy (CRT) with or without a defibrillator has a positive effect on mortality and morbidity for patients with heart failure. However, comparisons between CRT-defibrillators (CRT-D) and CRT-pacemakers (CRT-P) are relatively scarce outside the clinical trial setting. This study aimed to assess baseline characteristics in relation to long-term prognosis in patients treated with CRT, and to investigate the potential benefit of CRT-D versus CRT-P. METHODS: Data were retrospectively collected from the medical records of all consecutive patients treated with CRT-P or primary prophylactic CRT-D at a large tertiary care center between 1999 and 2012. Predictors of mortality were investigated, and time-dependent analysis was performed with all-cause mortality as the primary end point. RESULTS: A total of 705 patients were included (69.6 ± 10 years, 78% New York Heart Association classes III-IV, left ventricular ejection fraction median 25%, 16% female, 36% CRT-D). The patients were followed for a median of 59 months. Annual mortality differed between CRT-D primary prophylactic and CRT-P groups (5.3% and 11.8%, respectively), but when adjusted for covariates, CRT-D treatment (compared to CRT-P) was not associated with better long-term survival. Independent predictors of survival were: age, use of loop diuretics, hemoglobin levels, and use of renin angiotensin aldosterone system blockers. CONCLUSIONS: In CRT treatment outside of the clinical trial setting, CRT-D treatment was not an independent predictor of long-term survival. Future research should focus on correct selection of the patients who receive enough benefit of an added defibrillator to justify CRT-D implantation instead of CRT-P treatment only.

Selvester scoring in patients with strict LBBB using the QUARESS software.

BACKGROUND: Estimation of the infarct size from body-surface ECGs in post-myocardial infarction patients has become possible using the Selvester scoring method. Automation of this scoring has been proposed in order to speed-up the measurement of the score and improving the inter-observer variability in computing a score that requires strong expertise in electrocardiography. In this work, we evaluated the quality of the QuAReSS software for delivering correct Selvester scoring in a set of standard 12-lead ECGs. METHOD: Standard 12-lead ECGs were recorded in 105 post-MI patients prescribed implantation of an implantable cardiodefibrillator (ICD). Amongst the 105 patients with standard clinical left bundle branch block (LBBB) patterns, 67 had a LBBB pattern meeting the strict criteria. The QuAReSS software was applied to these 67 tracings by two independent groups of cardiologists (from a clinical group and an ECG core laboratory) to measure the Selvester score semi-automatically. Using various level of agreement metrics, we compared the scores between groups and when automatically measured by the software. RESULTS: The average of the absolute difference in Selvester scores measured by the two independent groups was 1.4±1.5 score points, whereas the difference between automatic method and the two manual adjudications were 1.2±1.2 and 1.3±1.2 points. Eighty-two percent score agreement was observed between the two independent measurements when the difference of score was within two point ranges, while 90% and 84% score agreements were reached using the automatic method compared to the two manual adjudications. CONCLUSION: The study confirms that the QuAReSS software provides valid measurements of the Selvester score in patients with strict LBBB with minimal correction from cardiologists.

Maximizing QRS duration reduction in contemporary cardiac resynchronization therapy is feasible and shorter QRS duration is associated with better clinical outcome.

BACKGROUND: We aimed to evaluate if optimization by maximizing QRS duration (QRSd) reduction is feasible in an all-comer cardiac resynchronization therapy (CRT) population, and if reduced, QRSd is associated with a better clinical outcome. METHODS: Patients with LBBB receiving CRT implants during the period 2015-2020 were retrospectively evaluated. Implants from 2015-2017 were designated as controls. Starting from 2018, an active 12-lead electrogram-based optimization of QRSd reduction was implemented (intervention group). QRSd reduction was evaluated in a structured way at various device AV and VV settings, aiming to maximize the reduction. The primary endpoint was a composite of heart failure hospitalization or death from any cause. RESULTS: A total of 254 patients were followed for up to 6 years (median 2.9 [1.8-4.1]), during which 82 patients (32%) reached the primary endpoint; 53 deaths (21%) and 58 (23%) heart failure hospitalizations. Median QRS duration pre-implant was 162 ms [150-174] and post-implant 146ms [132-160]. Mean reduction in QRS duration was progressively larger for each year during the intervention period, ranging from - 9.5ms in the control group to - 24 in the year 2020 (p = 0.005). QRS reduction > 14 ms (median value) was associated with a lower risk of death or heart failure hospitalization (adjusted HR 0.54 [0.29-0.98] (p = 0.04). CONCLUSIONS: Implementing a general strategy of CRT device optimization by aiming for shorter QRS duration is feasible in a structured clinical setting and results in larger reductions in QRS duration post-implant. In patients with a larger QRS reduction, compared to those with a smaller QRS reduction, there is an association with a better clinical outcome.

Repositioning and optimization of left ventricular lead position in nonresponders to cardiac resynchronization therapy is associated with improved ejection fraction, lower NT-proBNP values, and fewer heart failure symptoms.

Background: Observational data suggest that an anterior or apical left ventricular (LV) position in cardiac resynchronization therapy (CRT) is associated with worse outcome and higher likelihood of "nonresponse." It is not known whether the benefits of optimizing LV lead position in a second procedure outweighs the procedural risks. Objective: To evaluate the clinical effects of LV lead repositioning. Methods: During the period 2015-2020, we identified all patients in whom the indication for the procedure was LV lead repositioning owing to "nonresponse" in combination with suboptimal LV lead position. All patients were followed with a structured visit 6 months post LV lead revision. Heart failure hospitalization and mortality data were gathered from the medical records and cross-checked with the population registry. Results: A total of 25 patients were identified who fulfilled the inclusion criteria. All procedures were successful in establishing LV lead pacing in a lateral mid or basal location. Median follow-up was 2.5 years [1.1-3.7]. There were improvements in NYHA class (mean -0.5 ± 0.5 class, P < .001), LV ejection fraction (+5 [interquartile range 2-11] absolute %, P = .01), QRS duration (-36 [-44 to -8], P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) (-615 [-2837 to +121] ng/L, P = .03). Clinical outcome was similar to a reference population with CRT (P = ns). Conclusion: In nonresponders to CRT with either an anterior or inferior LV lead position, it was feasible to perform LV lead repositioning in all cases, with a low complication rate. Changing the LV lead position was associated with improved LV ejection fraction, larger QRS reduction, and larger NT-proBNP reduction.

Cytosolic prostaglandin E synthase: expression patterns in control and Alzheimer's disease brains.

Anti-inflammatory drugs reduce the risk of Alzheimer's disease but fail to slow its progression. Studying the expression of prostaglandin E(2) synthases downstream of cyclooxygenase-2 is important. Here, the expression patterns of cytosolic prostaglandin E( 2) synthases, an immediate prostaglandin E(2) source was investigated. Sections taken from the middle frontal gyrus of brains of 10 patients with Alzheimer's and 5 age-matched controls were examined by immunostaining for the presence of the synthases. Immunofluorescence analysis of control brains showed that cytosolic prostaglandin E(2) synthases co-localize with microglia, neurons, and endothelium markers, but not with astrocytes or smooth muscle cells. Immunohistochemical staining for the synthases was positive in the pyramidal neurons of controls but barely detectable in the brain of Alzheimer's patients. These findings revealed that cytosolic prostaglandin E(2) synthases is found in microglia, neurons, and endothelium of control human middle frontal gyrus and that its levels decrease in pyramidal cells of Alzheimer's disease brains.

Cardiac magnetic resonance imaging in a patient with temporary external pacemaker: a case report.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly becoming the imaging modality of choice for many clinical disorders due to superior image quality and absence of radiation. However, access to MRI remains limited for most patients with cardiac implantable electronic devices due to potential safety concerns. In line with guidelines, there is no absolute contraindication to perform MRI, but warrants careful risk-benefit assessment. CASE SUMMARY: A 59-year-old man was admitted with a 5-day history of central chest pain and few week's history of general malaise, dry cough, and breathlessness. Electrocardiogram confirmed complete atrioventricular block (CAVB). A slight increase in cardiac enzyme was noted. Coronary angiogram revealed atheromatous changes, but no obstructive coronary lesion. A temporary transvenous pacemaker was inserted. Transthoracic echocardiogram confirmed a dilated left ventricle with severely reduced left ventricular function. To facilitate diagnosis (hence prognosis), management and mobilization, investigation with cardiovascular magnetic resonance (CMR) was warranted but contraindicated by the temporary transvenous pacemaker. An active fixation pacemaker lead was therefore placed in the right ventricle via percutaneous puncture of the right subclavian vein and connected to a pulse generator, both secured to the skin with sutures and adhesive medical dressing. Appropriate device programming and close patient monitoring ensured that CMR could be performed without any adverse effects. A diagnosis of acute myocarditis was confirmed. Regular device interrogation during an extended 3-week period with temporary pacing ruled out any device failure. As there was no resolution of CAVB, the patient received a dual-chamber pacemaker. DISCUSSION: Cardiovascular magnetic resonance was feasible and safely performed on a patient with a temporary permanent external pacemaker system using a standard screw-in pacing lead and a regular pulse generator fixed to the skin. Although more studies are needed for generalizability, CMR may be used in highly selected patients with a temporary pacemaker.

Elevated microsomal prostaglandin-E synthase-1 in Alzheimer's disease.

BACKGROUND: The proinflammatory prostaglandin E(2) (PGE(2)) fluctuates over time in the cerebrospinal fluid of patients with Alzheimer's disease (AD), but the cerebral distribution and expression patterns of microsomal prostaglandin-E synthase (mPGES)-1 have not been compared with those of normal human brains. METHODS: Middle frontal gyrus tissue from AD and age-matched control brains was analyzed by Western blot, immunofluorescence, and immunohistochemistry with mPGES-1-specific antibodies. RESULTS: Western blotting revealed that mPGES-1 expression was significantly elevated in AD tissue. Furthermore, immunofluorescence of mPGES-1 was observed in neurons, microglia, and endothelial cells of control and AD tissue. Although mPGES-1 was consistently present in astrocytes of control tissue, it was present in only some astrocytes of AD tissue. Immunohistochemical staining suggested that mPGES-1 was elevated in pyramidal neurons of AD tissue when compared with controls. CONCLUSIONS: The results suggest that mPGES-1 is normally expressed constitutively in human neurons, microglia, astrocytes, and endothelial cells but is up-regulated in AD.

Cardiovascular Magnetic Resonance to Predict Appropriate Implantable Cardioverter Defibrillator Therapy in Ischemic and Nonischemic Cardiomyopathy Patients Using Late Gadolinium Enhancement Border Zone: Comparison of Four Analysis Methods.

BACKGROUND: Late gadolinium enhancement (LGE) border zone on cardiac magnetic resonance imaging has been proposed as an independent predictor of ventricular arrhythmias. The purpose was to determine whether size and heterogeneity of LGE predict appropriate implantable cardioverter defibrillator (ICD) therapy in ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) patients and to evaluate 4 LGE border-zone algorithms. METHODS AND RESULTS: ICM and NICM patients who underwent LGE cardiac magnetic resonance imaging prior to ICD implantation were retrospectively included. Two semiautomatic algorithms, expectation maximization, weighted intensity, a priori information and a weighted border zone algorithm, were compared with a modified full-width half-maximum and a 2-3SD threshold-based algorithm (2-3SD). Hazard ratios were calculated per 1% increase in LGE. A total of 74 ICM and 34 NICM were followed for 63 months (1-140) and 52 months (0-133), respectively. ICM patients had 27 appropriate ICD events, and NICM patients had 7 ICD events. In ICM patients with primary prophylactic ICD, LGE border zone predicted ICD therapy in univariable and multivariable analysis measured by the expectation maximization, weighted intensity, a priori information, weighted border zone, and modified full-width half-maximum algorithms (hazard ratios 1.23, 1.22, and 1.05, respectively; P<0.05; negative predictive value 92%). For NICM, total LGE by all 4 methods was the strongest predictor (hazard ratios, 1.03-1.04; P<0.05), though the number of events was small. CONCLUSIONS: Appropriate ICD therapy can be predicted in ICM patients with primary prevention ICD by quantifying the LGE border zone. In NICM patients, total LGE but not LGE border zone had predictive value for ICD therapy. However, the algorithms used affects the predictive value of these measures.

Development of immunoassays for serum tartrate-resistant acid phosphatase isoform 5a.

BACKGROUND: Serum tartrate-resistant acid phosphatase (TRACP) consists of 2 structurally related isoforms, TRACP 5a and 5b. TRACP 5b is from bone-resorbing osteoclasts. TRACP 5a may be a macrophage product of inflammation. We used a novel antibody to TRACP 5a to standardize immunoassays for serum TRACP 5a activity and protein. METHODS: Biotinylated anti-TRACP antibodies were used to immobilize serum TRACP isoforms. TRACP activity was measured using 4-nitrophenyl phosphate as substrate. TRACP 5a protein was measured with an independent peroxidase-conjugated anti-TRACP antibody. Immunoassays were standardized for linearity of serum dose response, sensitivity and precision. Reference ranges for TRACP 5a were established from serum of 50 healthy males and 50 healthy age-matched females. Serum TRACP 5a activity and protein were determined in 29 cases of rheumatoid arthritis. RESULTS: Serum matrix interference in both TRACP 5a assays required dilution to 10% serum to approach linearity. Intra-assay and inter-assay CV% were <10%. Mean serum TRACP 5a activity and protein were significantly higher in healthy men than women. There was a slight, but significant age related increase in both serum TRACP 5a and 5b among females, but not males, from age 20 to 70 years. TRACP 5a activity was positively correlated to TRACP 5a protein in healthy sera. Neither TRACP 5a activity nor protein was correlated strongly to TRACP-5b activity. TRACP 5a protein was significantly increased in 8/29 RA sera, whereas TRACP 5a and 5b activities were not. TRACP 5a activity and protein were not significantly correlated in RA sera. CONCLUSIONS: Although TRACP 5a and 5b are related biosynthetically, their circulating levels in healthy humans were independent, suggesting differential regulation of expression. In chronic diseases, increased TRACP 5a may represent pathological processes of inflammation unrelated to bone metabolism.

Concomitant use of warfarin and ticagrelor as an alternative to triple antithrombotic therapy after an acute coronary syndrome.

INTRODUCTION: Treatment with warfarin in combination with clopidogrel has been shown to reduce the incidence of major bleeding as compared to triple antithrombotic therapy (TT; warfarin, clopidogrel and aspirin). However, there are uncertainties regarding the risk for thrombosis since poor-responsiveness to clopidogrel is common. Ticagrelor is a more potent platelet inhibitor, but data supporting concurrent use of ticagrelor and warfarin (dual antithrombotic therapy, DT) is limited. This study therefore sought to evaluate the risk of bleeding and thrombosis associated with DT after an acute coronary syndrome (ACS). MATERIALS AND METHODS: We identified all ACS patients on DT upon discharge from Helsingborg Hospital and Skåne University Hospital in Malmö and Lund, Sweden, during 2013. Patients on DT were compared with historical controls discharged with TT. Major bleeding was defined in accordance with the HAS-BLED derivation study. Patients were retrospectively followed for three months. RESULTS: In total, 107 DT patients were identified and compared with 159 controls on TT. Mean HAS-BLED bleeding risk score and duration of treatment were similar between the groups (HAS-BLED 2.2+/-0.8 vs 2.2+/-1.0 units, p=NS; duration 2.7+/-0.8 vs 2.5+/-0.9months, p=NS; DT vs TT). The incidence of spontaneous major bleeding was similar between the groups, as was a composite of all thrombotic events, i.e. peripheral embolism, stroke/TIA and acute coronary syndrome (bleeding 8/106 (7.5%) vs 11/157 (7.0%), p=NS; thrombosis 5/106 (4.7%) vs 5/157 (3.2%), p=NS; DT vs TT). CONCLUSIONS: Rates of thrombotic and bleeding events were similar in patients with TT and patients with ticagrelor and warfarin.