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Background The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. Methods In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. Results We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. Conclusions Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration., Background: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. Methods: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. Results: We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. Conclusions: Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.

BACKGROUND: Left atrial (LA) speckle tracking provides detailed information on atrial function. Its utility for predicting subclinical atrial fibrillation (SCAF) is unclear. Therefore, we sought to investigate whether LA strain measures could predict SCAF detected by long-term continuous rhythm monitoring. METHODS: This was an echocardiographic substudy of the LOOP study, where elderly at risk of stroke were randomized to receive a loop recorder (Reveal LINQ) or control. Participants who received a loop recorder were included in this analysis. Echocardiography included LA reservoir, conduit, and contraction strain. Participants were followed with continuous rhythm monitoring for SCAF (≥6 minutes). Cox proportional hazards regression was applied to adjust for atrial fibrillation risk factors. RESULTS: In total, 956 participants were eligible for analysis. Median continuous rhythm monitoring was 35 months (IQR, 20–40 months), during which 278 (29%) were diagnosed with SCAF. The mean age was 74 years, 56% were male, median CHA2DS2-VASc-score was 4. LA reservoir strain was an independent predictor of SCAF after multivariable adjustments (HR, 1.04 [1.02–1.05], per 1% decrease) and so was contraction strain. The findings were unchanged in competing risk analyses and in participants with normal LA size and diastolic function. Participants with low reservoir strain (<33%) had a significantly higher risk of SCAF compared with those with high reservoir strain (incidence rate, 14.5 [12.4–16.9] versus 9.8 [8.2–11.8] events/100 person-years). The same was noted for low versus high contraction strain. CONCLUSIONS: LA reservoir and contraction strain are independent predictors of SCAF in elderly at risk of stroke. This also applies to individuals with normal LA size and diastolic function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450., BACKGROUND: Left atrial (LA) speckle tracking provides detailed information on atrial function. Its utility for predicting subclinical atrial fibrillation (SCAF) is unclear. Therefore, we sought to investigate whether LA strain measures could predict SCAF detected by long-term continuous rhythm monitoring. METHODS: This was an echocardiographic substudy of the LOOP study, where elderly at risk of stroke were randomized to receive a loop recorder (Reveal LINQ) or control. Participants who received a loop recorder were included in this analysis. Echocardiography included LA reservoir, conduit, and contraction strain. Participants were followed with continuous rhythm monitoring for SCAF (≥6 minutes). Cox proportional hazards regression was applied to adjust for atrial fibrillation risk factors. RESULTS: In total, 956 participants were eligible for analysis. Median continuous rhythm monitoring was 35 months (IQR, 20-40 months), during which 278 (29%) were diagnosed with SCAF. The mean age was 74 years, 56% were male, median CHA2DS2-VASc-score was 4. LA reservoir strain was an independent predictor of SCAF after multivariable adjustments (HR, 1.04 [1.02-1.05], per 1% decrease) and so was contraction strain. The findings were unchanged in competing risk analyses and in participants with normal LA size and diastolic function. Participants with low reservoir strain (<33%) had a significantly higher risk of SCAF compared with those with high reservoir strain (incidence rate, 14.5 [12.4-16.9] versus 9.8 [8.2-11.8] events/100 person-years). The same was noted for low versus high contraction strain. CONCLUSIONS: LA reservoir and contraction strain are independent predictors of SCAF in elderly at risk of stroke. This also applies to individuals with normal LA size and diastolic function. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Aims Mitral regurgitation (MR) can be difficult to quantify. We sought to investigate whether the MR jet area to left atrial (LA) area ratio (MR/LA ratio) method for quantifying MRs can be used to predict incident atrial fibrillation (AF) in the general population. Methods and results The study included 4466 participants from the 5th Copenhagen City Heart Study, a prospective general population study, who underwent transthoracic echocardiography. MR jet area was measured and indexed to LA area. The endpoint was incident AF. MR was quantified in 4042 participants (mean age: 57 years, 43% men). Of these, 198 (4.9%) developed AF during a median follow-up period of 5.3 years (interquartile range: 4.4–6.1 years). MR was present in 1938 participants (48%) including 1593 (39%) trace/mild MRs (MR/LA ratio ≤ 20% and ≤4 cm2). In unadjusted analysis, MR/LA ratio was associated with incident AF [HR: 1.06 (1.00–1.13), P = 0.042 per 5% increase] but not after adjusting for CHARGE-AF score. However, the association was modified by age (P for interaction = 0.034), such that MR/LA ratio was associated with AF only in participants ≤ 73 years. In these participants, MR/LA ratio ‘was’ independently associated with AF after adjusting for CHARGE-AF score [HR: 1.14 (1.06–1.24), P = 0.001, per 5% increase]. This finding persisted when restricting the analysis to participants without moderate or severe MR and normal LA size [HR: 1.35 (1.09–1.68), P = 0.005, per 5% increase]. Conclusion MR, including even trace regurgitations quantified by MR/LA ratio, is independently associated with incident AF in individuals ≤ 73 years of age., Aims Mitral regurgitation (MR) can be difficult to quantify. We sought to investigate whether the MR jet area to left atrial (LA) area ratio (MR/LA ratio) method for quantifying MRs can be used to predict incident atrial fibrillation (AF) in the general population. Methods and results The study included 4466 participants from the 5th Copenhagen City Heart Study, a prospective general population study, who underwent transthoracic echocardiography. MR jet area was measured and indexed to LA area. The endpoint was incident AF. MR was quantified in 4042 participants (mean age: 57 years, 43% men). Of these, 198 (4.9%) developed AF during a median follow-up period of 5.3 years (interquartile range: 4.4–6.1 years). MR was present in 1938 participants (48%) including 1593 (39%) trace/mild MRs (MR/LA ratio ≤ 20% and ≤4 cm2). In unadjusted analysis, MR/LA ratio was associated with incident AF [HR: 1.06 (1.00–1.13), P = 0.042 per 5% increase] but not after adjusting for CHARGE-AF score. However, the association was modified by age (P for interaction = 0.034), such that MR/LA ratio was associated with AF only in participants ≤ 73 years. In these participants, MR/LA ratio ‘was’ independently associated with AF after adjusting for CHARGE-AF score [HR: 1.14 (1.06–1.24), P = 0.001, per 5% increase]. This finding persisted when restricting the analysis to participants without moderate or severe MR and normal LA size [HR: 1.35 (1.09–1.68), P = 0.005, per 5% increase]. Conclusion MR, including even trace regurgitations quantified by MR/LA ratio, is independently associated with incident AF in individuals ≤ 73 years of ag

Background Impaired diastolic function is a hallmark of diabetic cardiomyopathy and a common feature in type 1 diabetes mellitus (T1DM). The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has in recent studies proved to have strong prognostic value. This study aimed to investigate the prognostic value of E/e'sr compared to E/e’ in T1DM without known heart disease. Methods In this prospective cohort of T1DM patients, echocardiography was performed including two-dimensional speckle tracking. Follow-up was performed using nationwide registries. Outcomes were all-cause mortality and major cardiovascular events (MACE). Results In total 1079 patients (age: 49.6 ± 14.5 years, 52.5% male, duration of diabetes 25.8 ± 14.6 years) were included in the study. During follow-up (median 6.3 years, IQR:5.7–6.9) 13.2% experienced MACE and 5.8% died. Following multivariable adjustment, both E/e'sr and E/e’ was significantly associated with both MACE (E/e'sr: HR 1.16 CI95%:[1.05–1.29], p = 0.005, per 10 cm increase) vs. (E/e’: HR 1.09 CI95%:[1.03–1.15], p = 0.001, per 1 unit increase) and all-cause mortality (E/e'sr: HR 1.20 [1.03–1.40], p = 0.016) vs. (E/e’: HR: 1.11 [1.02–1.20], p = 0.016). Sex modified the association between E/e'sr and MACE (p for interaction = 0.008) such that E/e'sr after multivariable adjustment only remained significantly associated with MACE in females (HR: 1.41 [1.19–1.67], p < 0.001) but not in males (HR: 1.06 [0.93–1.20], p = 0.42). In females, E/e'sr provided incremental information beyond the Steno T1 Risk Engine (Harrell's C-statistic: 0.78 (0.72–0.83) vs. 0.81 (0.75–0.86), p = 0.007). Conclusion In patients with T1DM, both E/e'sr and E/e’ provides independent prognostic information regarding prognosis. E/e'sr seems to have stronger prognostic value in females with T1DM., Background: Impaired diastolic function is a hallmark of diabetic cardiomyopathy and a common feature in type 1 diabetes mellitus (T1DM). The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has in recent studies proved to have strong prognostic value. This study aimed to investigate the prognostic value of E/e'sr compared to E/e’ in T1DM without known heart disease. Methods: In this prospective cohort of T1DM patients, echocardiography was performed including two-dimensional speckle tracking. Follow-up was performed using nationwide registries. Outcomes were all-cause mortality and major cardiovascular events (MACE). Results: In total 1079 patients (age: 49.6 ± 14.5 years, 52.5% male, duration of diabetes 25.8 ± 14.6 years) were included in the study. During follow-up (median 6.3 years, IQR:5.7–6.9) 13.2% experienced MACE and 5.8% died. Following multivariable adjustment, both E/e'sr and E/e’ was significantly associated with both MACE (E/e'sr: HR 1.16 CI95%:[1.05–1.29], p = 0.005, per 10 cm increase) vs. (E/e’: HR 1.09 CI95%:[1.03–1.15], p = 0.001, per 1 unit increase) and all-cause mortality (E/e'sr: HR 1.20 [1.03–1.40], p = 0.016) vs. (E/e’: HR: 1.11 [1.02–1.20], p = 0.016). Sex modified the association between E/e'sr and MACE (p for interaction = 0.008) such that E/e'sr after multivariable adjustment only remained significantly associated with MACE in females (HR: 1.41 [1.19–1.67], p < 0.001) but not in males (HR: 1.06 [0.93–1.20], p = 0.42). In females, E/e'sr provided incremental information beyond the Steno T1 Risk Engine (Harrell's C-statistic: 0.78 (0.72–0.83) vs. 0.81 (0.75–0.86), p = 0.007). Conclusion: In patients with T1DM, both E/e'sr and E/e’ provides independent prognostic information regarding prognosis. E/e'sr seems to have stronger prognostic value in females with T1DM.

Background: Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe. Methods: This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome. Results: 6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58–1.89] and 2.12 [1.91–2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75–16.41] for women with T1DM vs. 5.80 [2.72–12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93–2.54] vs. 1.99 [1.67–2.38] respectively, p for interaction 0.80). Conclusion: Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.

Background: Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe. Methods: This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome. Results: 6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58–1.89] and 2.12 [1.91–2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75–16.41] for women with T1DM vs. 5.80 [2.72–12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93–2.54] vs. 1.99 [1.67–2.38] respectively, p for interaction 0.80). Conclusion: Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.

AIMS: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite diabetes affects the myocardium, risk prediction models do not include myocardial function parameters. Myocardial performance index (MPI) reflects left ventricular function. The prognostic value of MPI has not been evaluated in large-scale diabetes populations.METHODS AND RESULTS: We evaluated two prospective cohort studies: Thousand&1 (1093 individuals with T1D) and Thousand&2 (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as incident events of hospital admission for acute coronary syndrome, heart failure, stroke, or all-cause mortality. For included individuals (56% male, 54 ± 15 years, MPI 0.51 ± 0.1, 63% T1D), follow-up was 100% after median of 5.3 years (range: 4.8-6.3). MPI was associated with MACE (HR 1.2, 95%CI 1.0-1.3, P = 0.012, per 0.10-unit increase) and heart failure (HR 1.3, 95%CI 1.1-1.6, P = 0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE and heart failure better in T1D than T2D (P = 0.031 for interaction). MPI added discriminatory power to the Steno T1 Risk Engine, based on clinical characteristics, in predicting MACE [area under the curve (AUC) from 0.77 to 0.79, P = 0.030] and heart failure (AUC from 0.77 to 0.83, P = 0.009) in T1D.CONCLUSION: MPI is independently associated with MACE and heart failure in T1D but not T2D and improves prediction in T1D. Echocardiographic assessment in T1D may enhance risk prediction.

Objective: To test the hypothesis that the increased risk of atrial fibrillation (AF) in men compared with women is explained by height. Methods: From the Copenhagen General Population Study, we included 106,207 individuals (47,153 men and 59,054 women) from 20 to 100 years of age, without a prior diagnosis of AF, examined between November 25, 2003, and April 28, 2015. The main outcome was AF incidence from national hospital registers until April 2018. The association of risk factors with AF incidence was assessed by cause-specific Cox proportional hazards regression and Fine-Gray subdistribution hazards regression analysis. Results: During a maximum of 14.4 years of follow-up (median, 8.9 years), incident AF was observed in 3449 men and 2772 women with 845 (95% CI, 815 to 875) and 514 (95% CI, 494 to 535) events per 100,000 person-years, respectively. The age-adjusted hazard of incident AF was 63% (95% CI, 55% to 72%) higher in men compared with women. Risk factors for AF were generally similar in men and women, except men were taller than women (179 cm vs 166 cm, respectively; P<.001). When controlling for height, the difference in hazard of incident AF between sexes disappeared. For population attributable risk of AF, height was the most important risk factor investigated and explained 21% and 19% of the risk of incident AF in men and women, respectively. Conclusion: A 63% higher risk of incident AF in men compared with women is explained by differences in height.

Aims . The European Society of Cardiology guidelines on diabetes and cardiovascular disease (CVD) recommend an electrocardiogram (ECG) in patients with diabetes and hypertension or with suspected CVD. We investigated whether ECG abnormalities can be used as a diagnostic and prognostic marker of heart failure (HF) in patients with type-2 diabetes (T2D) in secondary care diabetes-clinics. Methods . We included 722 patients with T2D in sinus rhythm. HF with preserved ejection fraction (HFpEF) was defined according to the European Society of Cardiology guidelines. Heart failure with mid-range ejection fraction (HFmrEF) was patients with dyspnoea and an LVEF 41-49%. Heart failure with reduced ejection fraction (HFrEF) or asymptomatic left ventricular systolic dysfunction (ALVSD) was defined as a LVEF ≤40%. Results . Overall, 24% patients had ECG abnormalities. A total of 15% had HF whereof 48% had ECG abnormalities. A normal ECG had a 99.3% negative predictive value (NPV) of ruling out HFrEF/ALVSD. In a sub-group with 0-1 simple clinical risk markers, the ECG ruled out both HFrEF/ALVSD, HFmrEF, and HFpEF with an NPV of 96.6%. The hazard-ratio (HR) of incident CVD or death in patients with HF and a normal ECG compared with patients without HF was 1.85 [95%CI 1.01-3.39], p = .05, while an abnormal ECG increased the HR to 3.84 [2.33-6.33], p < .001. Conclusion . HFrEF/ALVSD and HFmrEF were rare and HFpEF was frequent in this T2D population. A normal ECG ruled out HFrEF/ALVSD and in a sub-population with 0-1 simple clinical risk markers also both HFrEF/ALVSD, HFmrEF, and HFpEF.Key messages What is already known about this subject?In early studies of unselected patients from primary care with suspected chronic heart failure, the presence of a normal ECG was found be useful to rule out heart failure with reduced ejection fraction. What does this study add?This study confirms that a standard electrocardiogram when normal in 722 stable outpatients with type 2 diabetes c

Background Elderly individuals occupy an increasing part of the general population. Conventional and speckle-tracking transthoracic echocardiography may help guide risk stratification in these individuals. The purpose of this study was to evaluate the potential utility of conventional and speckle-tracking echocardiography in the screening of cardiac abnormalities in the elderly population. Methods Two cohorts of elderly individuals (sample size: 1441 and 944) were analyzed, who were part of a randomized controlled clinical trial (LOOP study) and of an observational study (Copenhagen City Heart Study), recruiting participants from the general population >70 years of age with cardiovascular risk factors (arterial hypertension, diabetes mellitus, heart failure, or prior stroke) and sinus rhythm. Participants underwent a comprehensive transthoracic echocardiographic examination, including myocardial speckle tracking. Cardiac abnormalities were defined according to the ASE/EACVI guidelines. Results Structural cardiac abnormalities such as left ventricular (LV) remodeling, mitral annular calcification (MAC), and aortic valve sclerosis (with or without stenosis) were highly prevalent in the LOOP study (40%, 39%, and 27%, respectively). Moreover, a high prevalence of functional cardiac alterations such as LV diastolic dysfunction (LVDD), abnormal LV longitudinal systolic strain (GLS), and abnormal left atrial (LA) reservoir strain was present in the LOOP study (27%, 18%, and 9%, respectively). Likewise, the rate of LVDD, abnormal GLS, and abnormal LA reservoir strain was comparable in the validation sample from the Copenhagen City Heart Study. In line with these findings, subjects with LV remodeling, MAC, and aortic valve changes had a higher prevalence of LVDD, abnormal GLS, and abnormal LA reservoir strain than those without structural cardiac alterations. Conclusion The findings of this study highlight the potential clinical utility of conventional and speckle-trac

Four-dimensional (4D) echocardiography may provide more accurate estimations of left atrial (LA) volumes than 2-dimensional (2D) measures. We sought to compare the concordance of a novel 4D LA quantification software versus 2D echocardiography against cardiac magnetic resonance (CMR). This was a multimodality imaging substudy of a randomized clinical trial (the LOOP study). Elderly participants with stroke risk factors were included. A subgroup of this study population underwent transthoracic echocardiography (n = 1441) and a subset underwent CMR within two weeks (n = 73). The mean age of the echocardiographic study population was 74 years and 54% were men. The maximal LA volume (LAVmax) was 47 mL by 2D, 52 mL by 4D, and 104 mL by CMR. While 2D echocardiography showed a moderate correlation with 4D (R2 = 0.51) it yielded significantly lower values for LAVmax with a mean difference of 4.5 ± 11.9 mL, p < 0.001. 4D echocardiography correlated strongly with CMR measurements (R2 = 0.70), whereas 2D echocardiography showed a moderate correlation (R2 = 0.53). However, both modalities systematically underestimated LAVmax largely compared to CMR (2D vs. CMR: − 54.9 ± 21.3 mL; 4D vs. CMR: − 49.7 ± 18.6 mL). Similar observations were made for minimal LA volume and LA volume before atrial contraction. Analyses time by 4D was shorter than for 2D (90 ± 11 vs. 118 ± 16 s, p < 0.001). Intra- and interobserver variability was lower for 4D than 2D. Four-dimensional echocardiography is faster, more reproducible, and correlates more closely to CMR than 2D echocardiography. Both 4D and 2D echocardiography systematically underestimates LA volumes compared to CMR, emphasizing that values of LA volumes are not interchangeable between echocardiography and CMR.

Frailty is a health condition leading to many adverse clinical outcomes. The relationship between frailty and advanced age, multimorbidity and disability has a significant impact on healthcare systems. Frailty increases cardiovascular (CV) morbidity and mortality both in patients with or without known CV disease. Though the recognition of this additional risk factor has become increasingly clinically relevant in CV diseases, uncertainty remains about operative definitions, screening, assessment, and management of frailty. Since the burdens of frailty components and domains may vary in the various CV diseases and clinical settings, the relevance of specific frailty-related aspects may be different. Understanding these issues may allow general cardiologists a clearer focus on frailty in CV diseases and thereby make more tailored clinical decisions and therapeutic choices in outpatients. Guidance on identification and management of frailty are sparse and an international consensus document on frailty in general cardiology is lacking. Moreover, new options linked with eHealth are going to better define and manage frailty. This consensus document on definition, assessment, clinical implications, and management of frailty provides an input to integrate strategies pre- and post-acute CV events with a comprehensive view including out of hospital, office-based diagnostic and therapeutic choices, and based on a multidisciplinary team approach (general cardiologists, nurses, and general practitioners).

Many biomarkers that could be used to assess ejection fraction, heart failure, or myocardial infarction fail to translate into clinical practice because they lack essential performance characteristics or fail to meet regulatory standards for approval. Despite their potential, new technologies have added to the complexities of successful translation into clinical practice. Biomarker discovery and implementation requires a standardised approach that includes: identification of a clinical need; identification of a valid surrogate biomarker; stepwise assay refinement, demonstration of superiority over current standard-of-care; development and understanding of a clinical pathway; and demonstration of real-world performance. Successful biomarkers should improve efficacy or safety of treatment, while being practical at a realistic cost. Everyone involved in cardiovascular healthcare, including researchers, clinicians, and industry partners, are important stakeholders in facilitating the development and implementation of biomarkers. This paper provides suggestions for a development pathway for new biomarkers, discusses regulatory issues and challenges, and suggestions for accelerating the pathway to improve patient outcomes. Real life examples of successful biomarkers-high sensitivity cardiac troponin (hs-cTn), T2* cardiovascular magnetic resonance (CMR) imaging, and echocardiography-are used to illustrate the value of a standardised development pathway in the translation of concepts into routine clinical practice.

Commercially available health technologies such as smartphones and smartwatches, activity trackers and eHealth applications, commonly referred to as wearables, are increasingly available and used both in the leisure and healthcare sector for pulse and fitness/activity tracking. The aim of the Position Paper is to identify specific barriers and knowledge gaps for the use of wearables, in particular for heart rate (HR) and activity tracking, in clinical cardiovascular healthcare to support their implementation into clinical care. The widespread use of HR and fitness tracking technologies provides unparalleled opportunities for capturing physiological information from large populations in the community, which has previously only been available in patient populations in the setting of healthcare provision. The availability of low-cost and high-volume physiological data from the community also provides unique challenges. While the number of patients meeting healthcare providers with data from wearables is rapidly growing, there are at present no clinical guidelines on how and when to use data from wearables in primary and secondary prevention. Technical aspects of HR tracking especially during activity need to be further validated. How to analyse, translate, and interpret large datasets of information into clinically applicable recommendations needs further consideration. While the current users of wearable technologies tend to be young, healthy and in the higher sociodemographic strata, wearables could potentially have a greater utility in the elderly and higher-risk population. Wearables may also provide a benefit through increased health awareness, democratization of health data and patient engagement. Use of continuous monitoring may provide opportunities for detection of risk factors and disease development earlier in the causal pathway, which may provide novel applications in both prevention and clinical research. However, wearables may also have potential adver

Commercially available health technologies such as smartphones and smartwatches, activity trackers and eHealth applications, commonly referred to as wearables, are increasingly available and used both in the leisure and healthcare sector for pulse and fitness/activity tracking. The aim of the Position Paper is to identify specific barriers and knowledge gaps for the use of wearables, in particular for heart rate (HR) and activity tracking, in clinical cardiovascular healthcare to support their implementation into clinical care. The widespread use of HR and fitness tracking technologies provides unparalleled opportunities for capturing physiological information from large populations in the community, which has previously only been available in patient populations in the setting of healthcare provision. The availability of low-cost and high-volume physiological data from the community also provides unique challenges. While the number of patients meeting healthcare providers with data from wearables is rapidly growing, there are at present no clinical guidelines on how and when to use data from wearables in primary and secondary prevention. Technical aspects of HR tracking especially during activity need to be further validated. How to analyse, translate, and interpret large datasets of information into clinically applicable recommendations needs further consideration. While the current users of wearable technologies tend to be young, healthy and in the higher sociodemographic strata, wearables could potentially have a greater utility in the elderly and higher-risk population. Wearables may also provide a benefit through increased health awareness, democratization of health data and patient engagement. Use of continuous monitoring may provide opportunities for detection of risk factors and disease development earlier in the causal pathway, which may provide novel applications in both prevention and clinical research. However, wearables may also have potential adverse, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Diagnostic tests including echocardiography, albuminuria, electrocardiogram (ECG), high-sensitivity troponin I (hs-TnI), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) have been suggested as cardiovascular (CV) risk predictors in type 2 diabetes. We studied the separate and combined prognostic yield of these risk markers. Methods: In all, 1030 patients with type 2 diabetes were recruited from specialized clinics in this prospective cohort study. Full echocardiographic evaluation was feasible in 886 patients in sinus rhythm with adequate image quality. ECG was performed in 998 patients. Albuminuria was measured in 1009 and NT-proBNP/hs-TnI in 933 patients. The end point was a composite of CV events. Results: The median follow-up was 4.7 years (interquartile range: 4.0-5.3), and 174 patients experienced a CV disease event. All considered markers, except hs-TnI, were significantly (P <.001) associated with the outcome: abnormal echocardiogram (hazard ratio 2.40 [1.70-3.39]), albuminuria 2.01 (1.47-2.76), abnormal ECG (2.27 [1.66-3.08]), high NT-proBNP (>150 pg/mL) 3.05 (2.11-4.40), and hs-TnI 1.12 (0.79-1.59). After adjusting for clinical variables, all remained significantly associated with the end point. However, after adjusting for each other, only NT-proBNP >150 pg/mL remained significantly associated with the end point (2.07 [1.28-3.34], P <.001). Measured by C-statistics, model performance was highest with log2 (NT-proBNP) (0.70 [0.65-0.75]) and similar to clinical variables alone (0.71 [0.67-0.76]). Combining all risk markers only resulted in a very limited increase in C-statistics (0.69 [0.64-0.74]). Conclusions: This study identified NT-proBNP over echocardiography, ECG, and albuminuria in risk prediction in patients with type 2 diabetes. The diagnostic yield in considering more than one risk marker was limited in this population.

AIMS: In type 1 diabetes mellitus (T1DM), recent findings suggest that women have a greater excess risk of cardiovascular diseases (CVDs) compared to men. Impaired diastolic function is a common feature in T1DM. We investigated the association between myocardial function by echocardiography and outcomes in T1DM males and females without known heart disease.METHODS AND RESULTS: A prospective cohort of individuals with T1DM without known heart disease from the outpatient clinic of Steno Diabetes Center Copenhagen. Follow-up was performed through Danish national registers. Outcomes, major adverse cardiovascular events (MACE) and all-cause mortality, were investigated. A total of 1079 participants (mean age: 49.6 ± 14.5 years, 52.6% male, mean duration of diabetes 25.8 ± 14.6 years) were included in the study. During follow-up (median 6.3 years, interquartile range 5.7-6.9), 142 (13.2%) experienced MACE and 63 (5.8%) died. Gender modified the relationship between E/e' and both MACE and all-cause mortality (P = 0.016 and 0.007, respectively). In females, after multivariable adjustment, both E/e' and global longitudinal strain (GLS) were significantly associated with MACE [E/e': hazard ratio (HR) 1.15 confidence interval (CI) 95%: 1.07-1.24, per 1unit increase; and GLS: HR 1.19 CI 95%: 1.04-1.35, per 1% decrease] and with all-cause mortality (E/e': HR 1.26 CI 95%: 1.11-1.44; and GLS: HR 1.27 CI 95%: 1.03-1.56). In males, the association between E/e' and GLS and outcomes did not reach statistical significance.CONCLUSION: In female individuals with T1DM both E/e' and GLS provided independent prognostic information, whereas the associations were not significant in males. These results suggest that T1DM affects myocardial function differently in males and females, which may be related to the observed sex difference in CVD risk in T1DM.

Background: Patients with type 2 diabetes (T2D) have increased risk for subclinical myocardial disease. Early systolic lengthening (ESL), a paradoxical stretch of myocardial fibers, is a sensitive marker of myocardial dysfunction. The aims of this study were to investigate the prognostic value of ESL in patients with T2D and to determine if global longitudinal strain (GLS) modifies this relationship. Methods: In this prospective study, speckle-tracking echocardiography was conducted in 703 patients with T2D (62% men; mean age, 63 ± 10 years; median diabetes duration, 11 years; interquartile range, 6–17 years). Patients had no histories of significant heart disease. ESL index was assessed as [−100 × (peak positive systolic strain/maximal strain)] and ESL duration as time from QRS complex on the electrocardiogram to time of peak positive systolic strain. P values ≤ .004 were considered to indicate statistical significance. Results: During a median follow-up time of 4.8 years (interquartile range, 4.1–5.3 years), 86 patients (12%) experienced major adverse cardiovascular events (MACE), a composite of incident heart failure, myocardial infarction, and cardiovascular death. In multivariate models, only the ESL index (hazard ratio [HR], 1.06 per 1% increase; 95% CI, 1.01–1.010; P = .004) but not ESL duration (HR, 1.02 per 1-ms increase; 95% CI, 1.00–1.03; P = .036) were associated with MACE. GLS modified this relationship (P for interaction < .05) such that in patients with low GLS (>−18%), ESL index (HR, 1.06 per 1% increase; 95% CI, 1.02–1.10; P = .003) was associated with MACE, but ESL duration was not (HR, 1.02 per 1-ms increase; 95% CI, 1.00–1.04; P = .005). No associations were found for high GLS (<−18%). Conclusions: In patients with T2D and no histories of heart disease, ESL provides prognostic information on MACE and may potentially aid in cardiovascular risk stratification.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) are undertreated with beta-blockers following myocardial infarction (MI), possibly due to fear for acute exacerbations of COPD (AECOPD). Is beta-blocker use associated with increased risk of AECOPD in patients following first-time MI?METHODS: Danish nationwide study of patients with COPD following hospitalisation for MI from 2003 to 2015. Multivariable, time-dependent Cox regression accounting for varying beta-blocker use based on claimed prescriptions during up to 13 years of follow-up.RESULTS: A total of 10 884 patients with COPD were discharged after first-time MI. The 1-year rate of AECOPD was 35%, and 65% used beta-blockers at 1 year. Beta-blocker use was associated with a lower risk of AECOPD (multivariable-adjusted HR 0.78, 95% CI 0.74-0.83). This association was independent of the type of MI (HR 0.70, 95% CI 0.59-0.83 in ST-elevation MI (STEMI) and HR 0.80, 95% CI 0.75-0.84 in non-STEMI), presence or absence of heart failure (HR 0.82, 95% CI 0.74-0.90 and HR 0.77, 95% CI 0.72-0.82, respectively), beta-blocker dosage and type, as well as exacerbation severity. Results were similar in 1118 patients with full data on COPD severity and symptom burden (median forced expiratory volume in 1 s as percentage of predicted was 46 and majority had moderate dyspnoea), and in 1358 patients with severe COPD and frequent AECOPD with a high 1-year rate of AECOPD of 70%.DISCUSSION: Beta-blocker use was not associated with increased risk of AECOPD following MI. This finding was independent of COPD severity, symptom burden and exacerbation history, and supports the safety of beta-blockers in patients with COPD, including high-risk patients with severe disease.

Aims: Sodium glucose transport inhibitors (SGLT2i) can reduce risk of heart failure (HF) and cardiovascular death in people with type 2 diabetes (T2D) and existing cardiovascular disease. Our aim was to examine the effect of the SGLT2i dapagliflozin on cardiac function in people with T2D and albuminuria. Methods: A secondary analysis of a double-blind, randomized, cross-over study of 12 weeks treatment with dapagliflozin 10 mg versus placebo. Myocardial function was assessed by echocardiography and biomarkers of cardiac risk were measured. An exploratory diastolic composite of echocardiographic variables was computed. Results: Of the 36 participants completing the study 89% were male, mean age 64 ± 8 years, diabetes duration 16.4 ± 4.7 years and HbA1c 73 ± 15 mmol/mol (8.9 ± 1.4%), 30.6% had former cardiovascular events and 32% had macroalbuminuria. Mean left ventricular ejection fraction (LVEF) was 55.4% after placebo and 54.3% after dapagliflozin (p = 0.15), global longitudinal strain −16.1 vs. −15.9, (p = 0.64), E/e′ 7.6 vs. 7.6 (p = 0.082), and tissue Doppler velocity e′ 10.0 vs. 10.6 (p = 0.05). The composite score showed diastolic function improvement of 19.8% (p = 0.021). No other significant changes were observed. Conclusions: Dapagliflozin may have minor effects on diastolic function in people with T2D, albuminuria and preserved LVEF.