Aortic Root Dimension Using Transthoracic Echocardiography: Results from the Copenhagen City Heart Study.

Findings regarding the relation between aortic size and risk factors are heterogeneous. This study aimed to generate new insights from a population-based adult cohort on aortic root dimensions and their association with age, anthropometric measures, and cardiac risk factors and evaluate the incidence of acute aortic events. Participants from the fifth examination round of the Copenhagen City Heart study (aged 20 to 98 years) with applicable echocardiograms and no history of aortic disease or valve surgery were included. Aorta diameter was assessed at the annulus, sinus of Valsalva, sinotubular junction, and the tubular part of the ascending aorta. The study population comprised 1,796 men and 2,316 women; mean age: 56.4 ± 17.0 and 56.9 ± 18.1 years, respectively. Men had larger aortic root diameters than women regardless of height indexing (p <0.01). Age, height, weight, systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, hypertension, diabetes, ischemic heart disease, and smoking were positively correlated with aortic sinus diameter in the crude and gender-adjusted analyses. However, after full adjustment, only height, weight, and diastolic blood pressure remained significantly positively correlated with aortic sinus diameter (p <0.001). For systolic blood pressure and pulse pressure, the correlation was inverse (p <0.001). During follow-up (median 5.4 [quartile 1 to quartile 3 4.5 to 6.3] years), the incidence rate of first-time acute aortic events was 13.6 (confidence interval 4.4 to 42.2) per 100,000 person-years. In conclusion, beyond anthropometric measures, age, and gender, diastolic blood pressure was the only cardiac risk factor that was independently correlated with aortic root dimensions. The number of aortic events during follow-up was low.

Normal values for left atrial strain, volume, and function derived from 3D echocardiography: the Copenhagen City Heart Study.

AIMS: 3D echocardiographic (3DE) assessment of the left atrium (LA) is a new modality of potential clinical value. Age- and sex-based normative values are needed to benchmark these parameters for clinical use. METHODS AND RESULTS: Of 4466 participants in the 5th Copenhagen City Heart Study, a prospective longitudinal cohort study on the general population, 2082 participants underwent 3DE of the LA. Healthy participants were included to establish normative values for LA strain, volume, and function by 3DE. The effects of age and sex were also evaluated. After excluding participants with comorbidities, 979 healthy participants (median age 44 years, 39.6% males) remained. The median and limits of normality (2.5th and 97.5th percentiles) for functional and volumetric measures were as follows: LA reservoir strain (LASr) 30.8% (18.4-44.2%), LA conduit strain (LAScd) 19.1% (6.8-32.0%), LA contractile strain 11.7% (4.3-22.2%), total LA emptying fraction (LAEF) 61.4% (47.8-71.0%), passive LAEF 37.7% (17.4-53.9%), active LAEF 37.4% (22.2-52.5%), LA minimum volume index (LAVimin) 10.2 (5.9-18.5) mL/m2, and LA maximum volume index (LAVimax) 26.8 (16.5-40.1) mL/m2. All parameters changed significantly with increasing age (P value for all <0.001). Significant sex-specific differences were observed for all parameters except active LAEF and LAVimax. Sex significantly modified the association between age and LASr (P for interaction < 0.001), LAScd (P for interaction < 0.001), LAVimin (P for interaction = 0.037), and total LAEF (P for interaction = 0.034) such that these parameters deteriorated faster with age in females than males. CONCLUSION: We present age- and sex-specific reference material including limits of normality for LA strain, volume, and function by 3DE.

NatIonal Danish endocarditis stUdieS - Design and objectives of the NIDUS registry.

AIMS: The NatIonal Danish endocarditis stUdieS (NIDUS) registry aims to investigate the mechanisms contributing to the increasing incidence of infective endocarditis (IE) and to discover risk factors associated to the course, treatment and clinical outcomes of the disease. METHODS: The NIDUS registry was created to investigate a nationwide unselected group of patients hospitalized for IE. The National Danish healthcare registries have been queried for validated IE diagnosis codes (International Classification of Disease, 10th edition [ICD-10]: DI33, DI38, and DI398). Subsequently, a team of 28 healthcare professionals, including experts in endocarditis, will systematically review and evaluate all identified patient records using the modified Duke Criteria and the 2015 European Society of Cardiology modified diagnostic criteria. The registry will contain all cases with definite or possible IE found in primary data sources in Denmark between January 1, 2016, and December 31, 2021. We will gather individual patient data, such as clinical, microbiological, and echocardiographic characteristics, treatment regimens, and clinical outcomes. A digital data collection form will be used to the gathering of data. A sample of approximately 4,300 individual patients will be evaluated using primary data sources. CONCLUSIONS AND PERSPECTIVES: The NIDUS registry will be the first comprehensive nationwide IE registry, contributing critical knowledge about the course, treatment, and clinical outcomes of the disease. Additionally, it will significantly aid in identifying areas in which future research is needed.

Temporal Trends in Patient Characteristics and Outcomes of Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement: A Nationwide Study.

With increased use of transcatheter aortic valve implantation (TAVI) in treatment of aortic stenosis, it is important to evaluate real life data trends in outcomes. This nationwide register-based study aimed to present an outlook on temporal trends in characteristics and outcomes, including mortality. First-time consecutive Danish patients who underwent TAVI from 2010 to 2019 were included in this study. The chi-square and Kruskal-Wallis tests were performed to assess the differences in the characteristics over time and Cochrane-Armitage trend tests were used to examine changes in complications and mortality. Between 2010 and 2019, 4,847 patients (54.6% men, median age 82 [quartile 1 to quartile 3: 77 to 85] years) underwent first-time TAVI. A statistically significant decrease over time was observed for preprocedural hypertension, ischemic heart disease, and heart failure, whereas preexisting chronic obstructive lung disease and preprocedural pacemaker remained stable. We observed a significant decrease in 30- and 90-day postoperative preprocedural pacemaker implantation from 2011 to 2017, with 15.1% and 15.9% in 2011 and 8.6% and 8.9% in 2017, respectively. The incidence of for 30- and 90-day heart failure significantly decreased from 19.3% and 20.3% to 8.5% and 9.1%, respectively. We observed significant changes for 30-day atrial fibrillation, whereas the changes over time for 90-day atrial fibrillation and 30- and 90-day stroke/transient ischemic attack remained insignificant. The all-cause mortality within 30- and 90 days significantly decreased over time from 6.7% and 9.2% in 2011 to 1.5% and 2.7% in 2019 and 2016, respectively. In conclusion, this national study provides general insight on the trends of complications and mortality of TAVI, demonstrating significant reductions over time.

Comparative outcomes in patients with preexisting heart failure to those without heart failure after out-of-hospital cardiac arrest: A nationwide registry study.

BACKGROUND: The knowledge of prognosis following out-of-hospital cardiac arrest (OHCA) in patients with heart failure heart failure (HF) is sparse. The objective of this study was to compare the outcome after OHCA among patients with and without HF. METHODS: We studied 45,293 patients who were included for the Danish cardiac arrest registry between 2001 and 2014. Patients were stratified into two groups based on the presence of HF prior to cardiac arrest. The primary outcome was 30-day survival and secondary outcome was anoxic brain damage or permanent nursing home admission at 1-year among 30-day survivors. RESULTS: Among the final 28,955 patients included, 6675 (23%) patients had prior HF and 22,280 (77%) patients had no prior HF. At 30 days, 616 (9.2%) patients survived among the patients with HF and 1916 (8.6%) among the patients without HF. There was a significant interaction between atrial fibrillation (AF) and HF for primary outcome and therefore it was assessed separately between the two study groups stratified based on AF. Among patients without AF a significantly higher odds of 30-day survival were observed among patients with HF (OR 2.69, 95% CI 2.34-3.08, P < 0.001), but no difference was observed among the patients from two study groups with no AF. No significant difference in risk for secondary outcome was observed among the two study groups. In multivariable average treatment effect modeling, all the results largely remain unchanged. CONCLUSIONS: Outcome following OHCA among patients with and without HF is found to be similar in this large Danish OHCA registry.

Association between myocardial work indices and cardiovascular events according to hypertension in the general population.

AIMS: Pressure-strain loop (PSL) analysis is a novel echocardiographic tool capable of assessing myocardial work non-invasively. In this study, we aim to evaluate the prognostic value of myocardial work indices in the general population. METHODS AND RESULTS: This was a prospective community-based cohort study (n = 4466). PSL analyses were performed to acquire global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE). The endpoint was a composite of heart failure or cardiovascular death (HF/CVD). Survival analysis was applied. A total of 3932 participants were included in this analysis (median age: 58 years, 43% men). Of these, 124 (3%) experienced the outcome during a median follow-up period of 3.5 years [interquartile range (IQR): 2.6-4.4 years]. Hypertension significantly modified the association between all work indices and outcome (P for interaction < 0.05), such that work indices posed a higher risk of outcome in non-hypertensive than in hypertensive participants. After adjusting for Atherosclerosis Risk in Communities (ARIC)-HF risk variables, all work indices predicted outcome in non-hypertensive participants, but only GWI, GCW, and GWE predicted outcome in hypertensive participants [GWI: hazard ratio (HR) = 1.12 (1.07-1.16), per 100 mmHg% decrease; GCW: HR = 1.12 (1.08-1.17), per 100 mmHg% decrease; GWE: HR = 1.08 (1.04-1.12), per 1% decrease]. Only GWE significantly increased C-statistics when added to ARIC-HF risk variables in hypertensive participants (C-stat 0.865 vs. 0.877, P for increment = 0.003). CONCLUSION: Hypertension modifies the association between myocardial work indices and HF/CVD in the general population. All work indices are associated with outcome in normotensive participants. GWI, GCW, and GWE are independently associated with outcome in hypertension, but only GWE improves risk prediction.

Electrocardiographic Markers of Adverse Left Ventricular Remodeling and Myocardial Fibrosis in Severe Aortic Stenosis.

The optimal timing for aortic valve replacement (AVR) in aortic stenosis (AS) is still controversial and may be guided by markers of adverse left ventricular (LV) remodeling. We aim to assess electrocardiographic (ECG) strain in relation to LV remodeling and myocardial fibrosis. 83 severe AS patients underwent surgical AVR, with preoperative 12-lead ECG, cardiovascular magnetic resonance with T1 mapping and echocardiography with global longitudinal strain analysis. Collagen volume fraction (CVF) was measured in myocardial biopsies sampled during AVR. Patients with ECG strain had more severe AS, more advanced LV remodeling and evidence of heart failure. Patients with ECG strain had more diffuse fibrosis, as evident by higher mean native T1 values (974.8 ± 34 ms vs. 946.5 ± 28 ms, p < 0.001). ECG strain was the only predictor of increased LV mass index on multivariate regression analysis (OR = 7.10, 95% CI 1.46-34.48, p = 0.02). Patients with persistent ECG strain at 1 year following AVR had more advanced LV remodeling and more histological fibrosis (CVF 12.5% vs. 7.3%, p = 0.009) at baseline assessment. Therefore, ECG strain is a marker of adverse LV remodeling and interstitial myocardial fibrosis. Lack of improvement in ECG strain following AVR indicates more advanced baseline LV injury and higher levels of myocardial fibrosis.

Trends in Medical and Device Therapies Following Incident Heart Failure in Denmark during 1996-2019: A Nationwide Register-Based Follow-Up Study.

Introduction: Data on temporal trends in guideline-based medical and device therapies in real-world chronic heart failure (HF) patients are lacking. Methods: Register-based nationwide follow-ups of temporal trends in characteristics, guideline-recommended therapies, one-year all-cause mortality, and HF rehospitalizations in incident HF patients in Denmark during 1996-2019. Results: Among 291,720 incident HF patients, the age at the onset of HF was stable over time. While initially fairly equal, the sex distribution markedly changed over time with more incidents occurring in men overall. Hypertension and diabetes increased significantly over time, while other comorbidities remained stable. Between 1996 and 2019, significant increases in angiotensin-converting enzyme inhibitor and angiotensin II-receptor blocker (ACEi/ARB) therapy (38.2% to 69.9%), beta-blocker therapy (15.5% to 70.6%), and mineralocorticoid receptor antagonist (MRA) therapy (11.8% to 34.5%) were seen. Angiotensin receptor-neprilysin inhibitor (ARNI) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were introduced in the middle of the past decade, with minor increases but overall low uses: ARNI (2015: 0.1% vs. 2019: 3.9%) and SGLT2i (2012: <0.1% vs. 2019: 3.9%). Between 1999 and 2019, implantable cardioverter-defibrillator (ICD) use increased significantly: 0.1% to 3-4%. Cardiac resynchronization therapy (CRT) use similarly increased between 2000 and 2019: 0.2% to 2.3%. Between 1996 and 2019, one-year all-cause mortality decreased significantly: 34.6% to 20.9%, as did HF rehospitalizations (6% to 1.3%). Conclusions: Among 291,720 incident HF patients in Denmark during 1996-2019, significant increases in the use of ACEi/ARB, beta-blockers, MRAs, and devices were seen, with concurrent significant decreases in the one-year all-cause mortality and HF rehospitalization rates. The use of CRT, ARNI, and SGLT2i remained low, and MRAs were relatively underutilized, thereby representing future targets to potentially further improve HF prognoses.

Education level and the use of coronary computed tomography, functional testing, coronary angiography, revascularization, and outcomes-a 10-year Danish, nationwide, registry-based follow-up study.

BACKGROUND AND AIMS: Coronary computed tomography angiography (CCTA) can guide downstream preventive treatment and improve patient prognosis, but its use in relation to education level remains unexplored. METHODS: This nationwide register-based cohort study assessed all residents in Denmark between 2008-2018 without coronary artery disease (CAD) and 50-80 years of age (n = 1 469 724). Residents were divided according to four levels of education: low, lower-mid, higher-mid, and high. Outcomes were CCTA, functional testing, invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: Individuals with the lowest education level underwent CCTA (absolute risk [AR] 3.95% individuals aged ≥ 50-59, AR 3.62% individuals aged ≥ 60-69, AR 2.19% individuals aged ≥ 70-80) less often than individuals of lower-mid (AR 4.16%, AR 3.90%, AR 2.41%), higher-mid (AR 4.38%, AR 4.30%, AR 2.45%) and highest education level (AR 3.98%, AR 4.37%, AR 2.30%). Similar differences were observed for functional testing. Conversely, use of ICA, and risks of revascularization and MACCE were more common among individuals of lowest education level. Among patients examined with CCTA (n = 50 234), patients of lowest education level less often underwent functional testing and more likely initiated preventive medication, underwent ICA, revascularization, and experienced MACCE. CONCLUSION: Despite tax-financed healthcare in Denmark, individuals of lowest education level were less likely to undergo CCTA and functional testing than persons of higher education level. ICA utilization, revascularization and MACCE risks were higher for individuals of lowest education level. Among CCTA-examined patients, patients of lowest education level were more likely to initiate preventive medication and had the highest risks of revascularization and MACCE when compared to higher education level groups. These findings suggest that the preventive potential of CCTA is underutilized in individuals of lower education level, a proxy for socioeconomic status. Socioeconomic differences in CAD assessment, care, and outcomes are likely even larger without tax-financed healthcare.

Takotsubo syndrome and stroke risk: A nationwide register-based study.

AIMS: Previous small-scale studies have indicated a short-term stroke incidence of 1.0-1.3% following Takotsubo (syndrome). In this nationwide register-based study, we investigated the 90-day risk of ischemic stroke (IS) or transient ischemia attack (TIA) and mortality of patients with Takotsubo. METHODS AND RESULTS: Patients with incident Takotsubo between January 1st 2009 to September 30th 2018 were identified from Danish nationwide registries. Takotsubo patients were age- and sex-matched with background-, atrial fibrillation/flutter- (AF) and myocardial infarction (MI) cohorts. Cumulative incidences and Cox proportional-hazard regression models were used to analyze the following outcomes: 1) composite of IS/TIA and 2) all-cause mortality. A total of 890 patients with Takotsubo were followed for 90 days. The cumulative 90-day incidence of IS/TIA in the Takotsubo-, background-, AF- and MI cohort, was 2.1% (n = 19), 0.1% (n = 4), 1.1% (n = 47) and 1.5% (n = 66), respectively. The cumulative 90-day mortality in the Takotsubo-, background-, AF- and MI cohort was 5.1% (n = 45), 0.3% (n = 13), 1.7% (n = 75) and 5.6% (n = 230), respectively. The adjusted hazard ratio (HR) for 90-day IS/TIA was when compared to the background-, AF- and MI cohort, 26.43 (95% CI: 8.82-79.24), 1.91 (95% CI: 1.09-3.35) and 2.06 (95% CI: 1.12-3.79), respectively. The adjusted HR for 90-day mortality was when compared to the background-, AF- and MI cohort, 14.19 (95% CI: 7.43-27.09), 0.73 (95% CI: 0.52-1.02) and 1.96 (95% CI: 1.25-3.07), respectively. CONCLUSION: Patients with Takotsubo had an increased 90-day hazard for IS/TIA when compared to age- and sex-matched background-, AF- and MI cohorts.

Short-term prognosis of changes in plasma potassium following an episode of hyperkalaemia in patients with chronic heart failure.

BACKGROUND/AIM: There is an increasing prevalence of chronic heart failure (HF). It is well known that patients with HF and disturbances in the potassium level have an increased mortality risk. The aim of this study was to investigate the prognosis of a second plasma-potassium measurement after an episode with hyperkalaemia on short-term mortality in patients with chronic HF. METHODS AND RESULTS: From Danish national registers, 2,339 patients with chronic HF and hyperkalaemia (>4.6 mmol/L) at first potassium measurement within 14-365 days from concomitant treatment were identified. To be included, a second measurement was required within 6-30 days subsequent to the first measurement and the 60-day mortality was observed. Based on the second measurement, the patients were divided into five groups: <3.5 mmol/L (n = 257), 3.5-4.0 mmol/L (n = 709), 4.1-4.6 mmol/L (n = 1,204, reference), 4.7-5.0 mmol/L (n = 89) and >5.0 mmol/L (n = 80). To assess all-cause and cardiovascular mortality, we used the Cox regression model. The multivariable analysis showed that patients with potassium concentrations <3.5 mmol/L (hazard ratio (HR): 3.03; 95% CI: 2.49-3.70) and 3.5-4.0 mmol/L (HR: 1.81; 95% CI: 1.54-2.14) had a worse prognosis compared to the reference. We observed similar results when calculating the risk of cardiovascular mortality. A restricted cubic spline curve showed a U-shaped relationship between plasma-potassium and all-cause mortality. CONCLUSION: Patients with chronic HF and hyperkalaemia who became hypokalaemic after 6-30 days were associated with a higher 60-day all-cause and cardiovascular mortality compared to the reference. This also applied for patients with low normal potassium concentrations (3.5-4.0 mmol/L).

Age- and sex-based normal reference ranges of the cardiac time intervals: the Copenhagen City Heart Study.

BACKGROUND: Color tissue Doppler imaging (TDI) M-mode can be used to measure the cardiac time intervals including the isovolumic contraction time (IVCT), the left ventricular ejection time (LVET), the isovolumic relaxation time (IVRT), and the combination of all the cardiac time intervals in the myocardial performance index (MPI) defined as [(IVCT + IVRT)/LVET]. The aim of this study was to establish normal age- and sex-based reference ranges for the cardiac time intervals. METHODS AND RESULTS: A total of 1969 participants free of cardiovascular diseases and risk factors from the general population with limited age range underwent an echocardiographic examination including TDI. The median age was 46 years (25th-75th percentile: 33-58 years), and 61.5% were females. In the entire study population, the IVCT was observed to be 40 ± 10 ms [95% prediction interval (PI) 20-59 ms], the LVET 292 ± 23 ms (95% PI 248-336 ms), the IVRT 96 ± 19 ms (95% PI 59-134 ms) and MPI 0.47 ± 0.09 (95% PI 0.29-0.65). All the cardiac time intervals differed significantly between females and males. With increasing age, the IVCT increased in females, but not in males. The LVET did not change with age in both sexes, while the IVRT increased in both sexes with increasing age. Furthermore, we developed regression equations relating the heart rate to the cardiac time intervals and age- and sex-based normal reference ranges corrected for heart rate. CONCLUSION: In this study, we established normal age- and sex-based reference ranges for the cardiac time intervals. These normal reference ranges differed significantly with sex.

Characteristics and Outcomes in Patients With Acute Aortic Dissection: A Nationwide Registry Study.

BACKGROUND: We aimed to describe characteristics and outcomes in a nationwide population of patients with acute type A and type B aortic dissection. METHODS: All patients in Denmark with a first-time diagnosis of acute aortic dissection between 2006 and 2015 were identified by national registries. The main outcomes were in-hospital mortality and long-term survival in hospital survivors. RESULTS: The study population comprised 1157 (68%) patients with type A aortic dissection and 556 (32%) patients with type B aortic dissection, median age of 66 (57-74) years and 70 (61-79) years, respectively. Men accounted for 64%. Median follow-up was 8.9 (6.8-11.5) years. Of patients with type A aortic dissection, 74% were managed surgically, whereas 22% of the patients with type B aortic dissection were managed with surgery or endovascular technique. In-hospital mortality was 27% for type A aortic dissection overall (surgery, 18%; no surgery, 52%) and 16% for type B aortic dissection (surgery or endovascular treatment, 13%; conservative treatment, 17%; P < .001, type A vs type B). Of patients discharged alive, survival was persistently better for type A aortic dissection than for type B aortic dissection (P < .001). Unadjusted 1- and 3-year survival of patients with type A aortic dissection discharged alive was 96% and 91%, respectively, for surgically managed and 88% and 78% without surgery. For type B aortic dissection, the numbers were 89% and 83% for endovascular/surgically managed and 89% and 77% for conservatively managed. CONCLUSIONS: We found higher in-hospital mortality for type A and type B aortic dissection than is reported from referral center registries. Type A aortic dissection had the highest mortality rate during the acute phase, whereas for patients who were discharged alive, the mortality rate was higher for patients with type B aortic dissection.

The role of contractile dyssynchrony in pacing-induced cardiomyopathy: detailed assessment using index of contractile asymmetry.

AIMS: The pathophysiological effects of chronic right ventricular pacing and the role of right ventricular lead position are not well understood. Therefore, we investigated the association between left ventricular contractile dyssynchrony and pacing-induced cardiomyopathy (PICM) in patients with chronic right ventricular pacing. Furthermore, we assessed the association between right ventricular lead location and left ventricular contractile dyssynchrony. METHODS: This was a retrospective study using data from 153 pacemaker patients with normal (≥ 50%) pre-implant left ventricular ejection fraction (LVEF). Baseline and follow-up echocardiograms were analyzed, and PICM was defined as LVEF < 50% with ≥ 10% decrease in LVEF after pacemaker implantation. Relative index of contractile asymmetry (rICA), a novel strain rate-based method, was calculated to quantify left ventricular contractile dyssynchrony between opposing walls in the three apical views. Right ventricular lead position was categorized into anterior septum, posterior septum, free wall, and apex based on contrast-enhanced cardiac computed tomography. RESULTS: Forty-seven (31%) developed PICM. Overall contractile dyssynchrony, measured by mean rICA, was higher in the PICM group compared with the non-PICM group (1.19 ± 0.21 vs. 1.03 ± 0.19, p < 0.001). Left ventricular anterior-inferior dyssynchrony, assessed in the apical two-chamber view, was independently associated with PICM (p < 0.001). Thirty-seven (24%) leads were implanted anterior septal, 11 (7.2%) posterior septal, 74 (48.4%) apical, and 31 (20.3%) free wall. Left ventricular anterior-inferior dyssynchrony was significantly different between the four pacing lead locations (p < 0.01) with the highest rICA observed in the posterior septal group (1.30 ± 0.37). CONCLUSIONS: PICM is significantly associated increased contractile dyssynchrony assessed by rICA. This study suggests that especially left ventricular dyssynchrony in the anterior-inferior direction is associated with PICM, and pacing the right ventricular posterior septum resulted in the highest degree of anterior-inferior dyssynchrony. Quantification of left ventricular dyssynchrony by rICA provides important insights to the potential pathophysiology of PICM and the impact of right ventricular lead position.

Changes in cardiac time intervals over a decade and the risk of incident heart failure: The Copenhagen City Heart Study.

BACKGROUND: The cardiac time intervals include the isovolumic contraction time (IVCT), the left ventricular ejection time (LVET), the isovolumic relaxation time (IVRT) and the combination of all the cardiac time intervals in the myocardial performance index (MPI) (defined as [(IVCT+IVRT)/LVET)]. Whether the cardiac time intervals change over time and which clinical factors that accelerate these changes is not well-established. Additionally, whether these changes are associated with subsequent heart failure (HF), remains unknown. METHODS: We investigated participants from the general population (n = 1064) who had an echocardiographic examination including color tissue Doppler imaging performed in both the 4th and 5th Copenhagen City Heart Study. The examinations were performed 10.5 years apart. RESULTS: The IVCT, LVET, IVRT and MPI increased significantly over time. None of the investigated clinical factors were associated with increase in IVCT. Systolic blood pressure (standardized ß= - 0.09) and male sex (standardized ß= - 0.08) were associated with an accelerated decrease in LVET. Age (standardized ß=0.26), male sex (standardized ß=0.06), diastolic blood pressure (standardized ß=0.08), and smoking (standardized ß=0.08) were associated with an increase in IVRT, while HbA1c (standardized ß= - 0.06) was associated with a decrease in IVRT. Increasing IVRT over a decade was associated with an increased risk of subsequent HF in participants aged <65 years (per 10 ms increase: HR 1.33; 95%CI (1.02-1.72), p = 0.034). CONCLUSION: The cardiac time increased significantly over time. Several clinical factors accelerated these changes. An increase in IVRT was associated with an increased risk of subsequent HF in participants aged <65 years.

Does targeted positioning of the left ventricular pacing lead towards the latest local electrical activation in cardiac resynchronization therapy reduce the incidence of death or hospitalization for heart failure?

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms, health-related quality of life and long-term survival in patients with systolic heart failure (HF) and shortens QRS duration. However, up to one third of patients attain no measurable clinical benefit from CRT. An important determinant of clinical response is optimal choice in left ventricular (LV) pacing site. Observational data have shown that achieving an LV lead position at a site of late electrical activation is associated with better clinical and echocardiographic outcomes compared to standard placement, but mapping-guided LV lead placement towards the site of latest electrical activation has never been investigated in a randomized controlled trial (RCT). The purpose of this study was to evaluate the effect of targeted positioning of the LV lead towards the latest electrically activated area. We hypothesize that this strategy is superior to standard LV lead placement. METHODS: The DANISH-CRT trial is a national, double-blinded RCT (ClinicalTrials.gov NCT03280862). A total of 1,000 patients referred for a de novo CRT implantation or an upgrade to CRT from right ventricular pacing will be randomized 1:1 to receive conventional LV lead positioning preferably in a nonapical posterolateral branch of the coronary sinus (CS) (control group) or targeted positioning of the LV lead to the CS branch with the latest local electrical LV activation (intervention group). In the intervention group, late activation will be determined using electrical mapping of the CS. The primary endpoint is a composite of death and nonplanned HF hospitalization. Patients are followed for a minimum of 2 years and until 264 primary endpoints occurred. Analyses will be conducted according to the intention-to-treat principle. Enrollment for this trial began in March 2018, and per April 2023, a total of 823 patients have been included. Enrollment is expected to be complete by mid-2024. CONCLUSIONS: The DANISH-CRT trial will clarify whether mapping-guided positioning of the LV lead according to the latest local electrical activation in the CS is beneficial for patients in terms of reducing the composite endpoint of death or nonplanned hospitalization for heart failure. Results from this trial are expected to impact future guidelines on CRT. GOV IDENTIFIER: NCT03280862.

Impact of Percutaneous Intervention Compared to Pharmaceutical Therapy on Complex Arrhythmias in Patients With Chronic Total Coronary Occlusion. Rationale and Design of the CTO-ARRHYTHMIA Study.

Chronic total coronary occlusions (CTO) occur in up to 50 % of patients with coronary artery disease by angiography. In CTO-patients, clinically significant arrhythmia is potentially important and insufficiently investigated. Therefore, the purpose of the CTO-ARRHYTHMIA study was to investigate the incidence of loop recorder detected clinically significant arrhythmias and the effect on arrhythmias of revascularization by CTO-PCI. The study is an independent sub-study of the NOrdic-Baltic Randomized Registry Study for Evaluation of PCI in Chronic Total Coronary Occlusion (NOBLE-CTO); ClinicalTrials.gov Identifier NCT03392415. NOBLE-CTO prospectively collects procedural data, quality of life measures, echocardiographic and cardiac MRI findings before and after treatment as well as clinical outcomes in all CTO patients that may be treated by PCI.

Novel non-invasive ECG imaging method based on the 12-lead ECG for reconstruction of ventricular activation: A proof-of-concept study.

Aim: Current non-invasive electrocardiographic imaging (ECGi) methods are often based on complex body surface potential mapping, limiting the clinical applicability. The aim of this pilot study was to evaluate the ability of a novel non-invasive ECGi method, based on the standard 12-lead ECG, to localize initial site of ventricular activation in right ventricular (RV) paced patients. Validation of the method was performed by comparing the ECGi reconstructed earliest site of activation against the true RV pacing site determined from cardiac computed tomography (CT). Methods: This was a retrospective study using data from 34 patients, previously implanted with a dual chamber pacemaker due to advanced atrioventricular block. True RV lead position was determined from analysis of a post-implant cardiac CT scan. The ECGi method was based on an inverse-ECG algorithm applying electrophysiological rules. The algorithm integrated information from an RV paced 12-lead ECG together with a CT-derived patient-specific heart-thorax geometric model to reconstruct a 3D electrical ventricular activation map. Results: The mean geodesic localization error (LE) between the ECGi reconstructed initial site of activation and the RV lead insertion site determined from CT was 13.9 ± 5.6 mm. The mean RV endocardial surface area was 146.0 ± 30.0 cm2 and the mean circular LE area was 7.0 ± 5.2 cm2 resulting in a relative LE of 5.0 ± 4.0%. Conclusion: We demonstrated a novel non-invasive ECGi method, based on the 12-lead ECG, that accurately localized the RV pacing site in relation to the ventricular anatomy.

Recurrent syncope in patients with a pacemaker and bradyarrhythmia.

Background. Pacemakers are used to treat syncope in patients with bradyarrhythmia; however, the risk of recurrent syncope has only been investigated in few and smaller studies. Objective. The aim of this study was to investigate the risk of recurrent syncope after pacemaker implantation in patients with bradyarrhythmia and prior syncope. Methods. This retrospective, population-based cohort study included patients with a prior syncope and implantation of a pacemaker using data from the Danish nationwide registers from 1996 to 2017. Cumulative incidence and cox regression was used to estimate the 5-year incidence and the risk of recurrent syncope, respectively. Results. In total, 11,126 patients (median age: 78 years, interquartile range: 69-85, 56% male) were included and the 5-year cumulative incidence of recurrent syncope was 19.6% (95% confidence interval (CI): 18.8-20.3%). Sinus node dysfunction (hazard ratio [HR]: 1.29, 95%CI: 1.17-1.42) and unspecified type of bradyarrhythmia (HR: 1.32, 95%CI: 1.15-1.52) were associated with an increased risk of syncope compared to advanced atrioventricular (AV) block. Male sex (HR: 1.22, 95%CI: 1.22-1.34), cerebrovascular disease (HR: 1.17, 95%CI: 1.05-1.30), and prior number of syncopes were significantly associated with a higher HR of recurrent syncope. Conclusion. Almost one-in-five patients with bradyarrhythmia and prior syncope who had a pacemaker implanted had a recurrent syncope within five years. A higher risk of syncope was observed among patients with sinus node dysfunction and unspecified type of bradyarrhythmia compared to AV block. Male sex, cerebrovascular disease, and prior number of syncopes were associated risk factors of recurrent syncope.

Electrocardiographic P terminal force in lead V1, its components, and the association with stroke and atrial fibrillation or flutter.

BACKGROUND: The electrocardiographic (ECG) marker P terminal force V1 (PTFV1) is generally perceived as a marker of left atrial pathology and has been associated with atrial fibrillation or flutter (AF). OBJECTIVE: The purpose of this study was to determine the association between PTFV1 components (duration and amplitude) and incident AF and stroke/transient ischemic attack (TIA). METHODS: The study included patients with an ECG recorded at the Copenhagen General Practitioners Laboratory in 2001 to 2011. PTFV1 ≥4 mV·ms was considered abnormal. Patients with abnormal PTFV1 were stratified into tertiles based on duration (PTDV1) and amplitude (PTAV1) values. Cox regressions adjusted for age, sex, and relevant comorbidities were used to investigate associations between abnormal PTFV1 components and AF and stroke/TIA. RESULTS: Of 267,636 patients, 5803 had AF and 18,176 had stroke/TIA (follow-up 6.5 years). Abnormal PTFV1 was present in 44,549 subjects (16.7%) and was associated with an increased risk of AF and stroke/TIA. Among patients with abnormal PTFV1, the highest tertile of PTDV1 (78-97 ms) was associated with the highest risk of AF (hazard ratio [HR] 1.37; 95% confidence interval [CI] 1.23-1.52) and highest risk of stroke/TIA (HR 1.13; 95% CI 1.05 -1.20). For PTAV1, the highest tertile (78-126 µV) conferred the highest risk of AF and stroke/TIA (HR 1.20; 95% CI 1.09-1.32; and HR 1.21; 95% CI 1.14-1.25, respectively). CONCLUSION: Abnormal PTFV1 was associated with an increased risk of AF and stroke/TIA. Increasing PTDV1 showed a dose-response relationship with the development of AF and stroke/TIA, whereas the association between PTAV1 and AF was less apparent.