Vertebral fractures assessed by dual-energy X-ray absorptiometry and all-cause mortality. The Tromsø Study 2007-2020

Vertebral fractures have been associated with increased mortality, but findings are inconclusive, and many vertebral fractures avoid clinical attention. We investigated this association in a general population of 2,476 older adults aged ≥55 years from Tromsø, Norway, who were followed over 2007–2020, using dual-energy x-ray absorptiometry (DXA) at baseline to evaluate vertebral fractures (mild, moderate, or severe). We used multiple Cox regression models to estimate hazard ratios (HRs) for all-cause mortality, adjusted for age, sex, body mass index, education, smoking, alcohol intake, cardiovascular disease, and respiratory disease. Mean follow-up in the cohort was 11.2 (standard deviation, 2.7) years; 341 participants (13.8%) had ≥1 vertebral fracture at baseline, and 636 participants (25.7%) died between baseline and follow-up. Full-adjustment models showed a nonsignificant association between vertebral fracture status (yes/no) and mortality. Participants with ≥3 vertebral fractures (HR = 2.43, 95% confidence interval: 1.57, 3.78) or ≥1 severe vertebral fracture (HR = 1.65, 95% confidence interval: 1.26, 2.15) had increased mortality compared with those with no vertebral fractures. Dual-energy x-ray absorptiometry–based screening could be a potent and feasible tool in detecting vertebral fractures that are often clinically silent yet independently associated with premature death. Our data indicated that detailed vertebral assessment could be warranted for a more accurate survival estimation

Resting membrane potential is less negative in trabeculae from right atrial appendages of women, but action potential duration does not shorten with age

Aims: The incidence of atrial fibrillation (AF) increases with age. Women have a lower risk. Little is known on the impact of age, sex and clinical variables on action potentials (AP) recorded in right atrial tissue obtained during open heart surgery from patients in sinus rhythm (SR) and in longstanding AF. We here investigated whether age or sex have an impact on the shape of AP recorded in vitro from right atrial tissue. Methods: We performed multivariable analysis of individual AP data from trabeculae obtained during heart surgery of patients in SR (n = 320) or in longstanding AF (n = 201). AP were recorded by sharp microelectrodes at 37 °C at 1 Hz. Impact of clinical variables were modeled using a multivariable mixed model regression. Results: In SR, AP duration at 90% repolarization (APD90) increased with age. Lower ejection fraction and higher body mass index were associated with smaller action potential amplitude (APA) and maximum upstroke velocity (Vmax). The use of beta-blockers was associated with larger APD90. In tissues from women, resting membrane potential was less negative and APA as well as Vmax were smaller. Besides shorter APD20 in elderly patients, effects of age and sex on atrial AP were lost in AF. Conclusion: The higher probability to develop AF at advanced age cannot be explained by a shortening in APD90. Less negative RMP and lower upstroke velocity might contribute to lower incidence of AF in women, which may be of clinical relevance.</p

Validating risk models versus age alone for atrial fibrillation in a young Dutch population cohort:should atrial fibrillation risk prediction be expanded to younger community members?

BACKGROUND: Advancing age is the primary selection criterion for community screening for atrial fibrillation (AF), with selection often restricted to those aged ≥65 years. If multivariable models were shown to have considerable additional value over age alone in predicting AF risk among younger individuals, AF screening could be expanded to patients with lower age, but with high AF risk as per a validated risk model. METHODS: We validated risk models CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology model for AF) and FHS-AF (Framingham Heart Study model for AF), and risk scores CHA(2)DS(2)-VASc and CHA(2)DS(2)-VA, and presented their predictive abilities for 5-year and 10-year AF risk versus that of age alone in a young Dutch population cohort (PREVEND) free from AF at baseline. We assessed discrimination by the C-statistic and calibration by the calibration plot and stratified Kaplan-Meier plot using survey-weighted Cox models. RESULTS: During 5-year and 10-year follow-up there were n=98 (2.46/1000 person-years) and n=249 (3.29/1000 person-years) new AF cases, respectively, among 8265 participants with mean age 49±13 years. CHARGE-AF and FHS-AF both showed good discrimination for 5-year and 10-year AF (C-statistic range 0.83–0.86) with accurate calibration for 5-year AF, but overestimation of 10-year AF risk in highest-risk individuals. CHA(2)DS(2)-VASc and CHA(2)DS(2)-VA relatively underperformed. Age alone showed similar discrimination to that of CHARGE-AF and FHS-AF both in the overall, young PREVEND cohort and in subgroups for lower age and lower stroke risk. CONCLUSION: Multivariable models accurately discriminate for 5-year and 10-year AF risk among young European community-dwelling individuals. However, their additional discriminatory value over age alone was limited. Selection strategies for primary AF screening using multivariable models should not be expanded to younger individuals

Atrial fibrillation detected at screening is not a benign condition:Outcomes in screen-detected versus clinically detected atrial fibrillation. Results from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study

AIMS: It is unknown whether screen-detected atrial fibrillation (AF) carries cardiovascular risks similar to clinically detected AF. We aimed to compare clinical outcomes between individuals with screen-detected and clinically detected incident AF. METHODS: We studied 8265 participants (age 49 ± 13 years, 50% women) without prevalent AF from the community-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study. By design of the PREVEND study, 70% of participants had a urinary albumin concentration >10 mg/L. Participants underwent 12-lead ECG screening at baseline and every 3 years. AF was considered screen-detected when first diagnosed during a study visit and clinically detected when first diagnosed during a hospital visit. We analysed data from the baseline visit (1997–1998) up to the third follow-up visit (2008). We used Cox regression with screen-detected and clinically detected AF as time-varying covariates to study the association of screen-detected and clinically detected AF with all-cause mortality, incident heart failure (HF) and vascular events. RESULTS: During a follow-up of 9.8 ± 2.3 years, 265 participants (3.2%) developed incident AF, of whom 60 (23%) had screen-detected AF. The majority of baseline characteristics were comparable between individuals with screen-detected and clinically detected AF. Unadjusted, both screen-detected and clinically detected AF were strongly associated with mortality, incident HF, and vascular events. After multivariable adjustment, screen-detected and clinically detected AF remained significantly associated with mortality (HR 2.21 (95% CI 1.09 to 4.47) vs 2.95 (2.18 to 4.00), p for difference=0.447) and incident HF (4.90 (2.28 to 10.57) vs 3.98 (2.49 to 6.34), p for difference=0.635). After adjustment, screen-detected AF was not significantly associated with vascular events, whereas clinically detected AF was (1.12 (0.46 to 2.71) vs 1.92 (1.21 to 3.06), p for difference=0.283). CONCLUSION: Screen-detected incident AF was associated with an increased risk of adverse outcomes, especially all-cause mortality and incident HF. The risk of outcomes was not significantly different between screen-detected AF and clinically detected AF

The value of echocardiographic measurement of epicardial adipose tissue in heart failure patients

AIMS: Epicardial adipose tissue (EAT) is increasingly recognized as an important factor in the pathophysiology of heart failure (HF). Cardiac magnetic resonance (CMR) imaging is the gold‐standard imaging modality to evaluate EAT size, but in contrast to echocardiography, CMR is costly and not widely available. We investigated EAT thickness on echocardiography in relation to EAT volume on CMR, and we assessed the agreement between observers for measuring echocardiographic EAT. METHODS AND RESULTS: Patients with HF and left ventricular ejection fraction >40% were enrolled. All patients underwent CMR imaging and transthoracic‐echocardiography. EAT volume was quantified on CMR short‐axis cine‐stacks. Echocardiographic EAT thickness was measured on parasternal long‐axis and short‐axis views. Linear regression analyses were used to assess the association between EAT volume on CMR and EAT thickness on echocardiography. Intraclass correlation coefficient (ICC) was used to assess the interobserver agreement as well as the intraobserver agreement. EAT on CMR and echocardiography was evaluated in 117 patients (mean age 71 ± 10 years, 49% women and mean left ventricular ejection fraction 54 ± 7%). Mean EAT volume on CMR was 202 ± 64 mL and ranged from 80 to 373 mL. Mean EAT thickness on echocardiography was 3.8 ± 1.5 mm and ranged from 1.7 to 10.2 mm. EAT volume on CMR and EAT thickness on echocardiography were significantly correlated (junior‐observer: r = 0.62, P < 0.001, senior‐observer: r = 0.33, P < 0.001), and up to one‐third of the variance in EAT volume was explained by EAT thickness (R (2) = 0.38, P < 0.001). The interobserver agreement between junior and senior observers for measuring echocardiographic EAT was modest [ICC, 0.65 (95% confidence interval (CI) 0.47–0.77], whereas the intraobserver agreement was good (ICC 0.98, 95% CI 0.84–0.99). CONCLUSIONS: There was a modest correlation between EAT volume on CMR and EAT thickness on echocardiography. Limited agreement between junior and senior observers for measuring echocardiographic EAT was observed. EAT thickness on echocardiography is limited in estimating EAT volume

Assessment of causality of natriuretic peptides and atrial fibrillation and heart failure : a Mendelian randomization study in the FINRISK cohort

Aims Natriuretic peptides are extensively studied biomarkers for atrial fibrillation (AF) and heart failure (HF). Their role in the pathogenesis of both diseases is not entirely understood and previous studies several single-nucleotide poly-morphisms (SNPs) at the NPPA-NPPB locus associated with natriuretic peptides have been identified. We investigated the causal relationship between natriuretic peptides and AF as well as HF using a Mendelian randomization approach. Methods and results N-terminal pro B-type natriuretic peptide (NT-proBNP) (N= 6669), B-type natriuretic peptide (BNP) (N= 6674), and mid-regional pro atrial natriuretic peptide (MR-proANP) (N= 6813) were measured in the FINRISK 1997 cohort. N=30 common SNPs related to NT-proBNP, BNP, and MR-proANP were selected from studies. We performed six Mendelian randomizations for all three natriuretic peptide biomarkers and for both outcomes, AF and HF, separately. Polygenic risk scores (PRSs) based on multiple SNPs were used as genetic instrumental variable in Mendelian randomizations. Polygenic risk scores were significantly associated with the three natriuretic peptides. Polygenic risk scores were not significantly associated with incident AF nor HF. Most cardiovascular risk factors showed significant confounding percentages, but no association with PRS. A causal relation except for small causal betas is unlikely. Conclusion In our Mendelian randomization approach, we confirmed an association between common genetic variation at the NPPA-NPPB locus and natriuretic peptides. A strong causal relationship between natriuretic peptides and incidence of AF as well as HF at the community-level was ruled out. Therapeutic approaches targeting natriuretic peptides will therefore very likely work through indirect mechanisms.Peer reviewe

Reduction of blood culture contamination rate by an educational intervention

Background: Although mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown. Methods: In the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics. Results: Two-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61-73), 67% male, QRS-duration 177ms (IQR: 160-192), LV ejection fraction: 26 +/- 7%. Philips-cohort (n = 88): age 67 years (IQR: 59-74), 60% male, QRS-duration: 179 ms (IQR: 166-193), LV ejection fraction: 27 +/- 8. LV derived peak strain was comparable in the GE-(GE: -7.3 +/- 3.1%, TomTec: -6.4 +/- 2.8%, ICC: 0.723) and Philips-cohort (Philips: -7.7 +/- 2.7%, TomTec: -7.7 +/- 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC's of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen's kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530-0.705) and different cut-off values between vendors. Conclusions: Although global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted

Targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent atrial fibrillation:Results of the RACE 3 trial

Aims: Atrial fibrillation (AF) is a progressive disease. Targeted therapy of underlying conditions refers to interventions aiming to modify risk factors in order to prevent AF. We hypothesised that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF. Methods and results: We randomized patients with early persistent AF and mild-to-moderate heart failure (HF) to targeted therapy of underlying conditions or conventional therapy. Both groups received causal treatment of AF and HF, and rhythm control therapy. In the intervention group, on top of that, four therapies were started: (i) mineralocorticoid receptor antagonists (MRAs), (ii) statins, (iii) angiotensin converting enzyme inhibitors and/or receptor blockers, and (iv) cardiac rehabilitation including physical activity, dietary restrictions, and counselling. The primary endpoint was sinus rhythm at 1 year during 7 days of Holter monitoring. Of 245 patients, 119 were randomized to targeted and 126 to conventional therapy. The intervention led to a contrast in MRA (101 [85%] vs. 5 [4%] patients, P < 0.001) and statin use (111 [93%] vs. 61 [48%], P < 0.001). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers were not different. Cardiac rehabilitation was completed in 109 (92%) patients. Underlying conditions were more successfully treated in the intervention group. At 1 year, sinus rhythm was present in 89 (75%) patients in the intervention vs. 79 (63%) in the conventional group (odds ratio 1.765, lower limit of 95% confidence interval 1.021, P = 0.042). Conclusions: RACE 3 confirms that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF. Trial Registration number: Clinicaltrials.gov NCT00877643