Cardiovascular events according to blood pressure thresholds recommended by ACC/AHA.

AIM: The latest guidelines from ACC/AHA define hypertension at systolic blood pressure (SBP) 130-139 mmHg or diastolic blood pressure (DBP) 80-89 mmHg in contrast to guidelines from ESC/ESH defining hypertension at SBP ≥ 140 mmHg or DBP ≥ 90 mmHg. The aim was to determine whether the ACC/AHA definition of hypertension identifies persons at elevated risk for future cardiovascular outcome. METHODS: In a Danish prospective cardiovascular study, 19,721 white men and women aged 20-98 years were examined up to five occasions between 1976 and 2015. The population was followed until December 2018. The ACC/AHA definition of the BP levels were applied: Normal: SBP <120 mmHg and DBP <80 mmHg, Elevated: SBP 120-129 mmHg and DBP <80 mmHg, Stage 1: SBP 130-139 mmHg or DBP 80-89 mmHg, Stage 2: SBP ≥140 mmHg or DBP ≥90 mmHg. Absolute 10-year risk was calculated taking repeated examinations, covariates, and competing risk into account. RESULTS: For all outcomes, the 10-year risk in stage 1 hypertension did not differ significantly from risk in subjects with normal BP: The 10-year risk of cardiovascular events in stage 1 hypertension was 14.1% [95% CI 13.2;15.0] and did not differ significantly from the risk in normal BP at 12.8% [95% CI 11.1;14.5] (p = 0.19). The risk was highest in stage 2 hypertension 19.4% [95% CI 18.9;20.0] and differed significantly from normal BP, elevated BP, and stage 1 hypertension (p < 0.001). The 10-year risk of cardiovascular death was 6.6% [95% CI 5.9;7.4] in stage 1 hypertension and did not differ significantly from the risk in normal BP at 5.7% [95% CI 4.1;7.3] (p = 0.33). CONCLUSIONS: Stage 1 hypertension as defined by the ACC/AHA guidelines has the same risk for future cardiovascular events as normal BP. In contrast, the definition of hypertension as suggested by ESC/ESH identifies patients with elevated risk of cardiovascular events.

Until 2017, there was worldwide agreement on defining hypertension at systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg.In 2017, the American Cardiology Societies (ACC and AHA) lowered the threshold for defining hypertension at SBP 130-139 mmHg or DBP 80-89 mmHg.Lowering the threshold might make healthy persons sick if the thresholds do not identify persons at high risk.Unnecessary medical treatment is associated with high economic cost for the health care systems.We wanted to explore whether applying the American BP definition in a Scandinavian population identified persons with elevated risk for cardiovascular disease.As part of the Copenhagen City Heart study, 19,721 men and women aged 20-98 years were followed from 1976.They went through up to five examinations between 1976 and 2018 including BP measurements.We applied the American BP thresholds and followed the persons until death or 2018.In Denmark all citizens have a unique identification number which is linked to all health care contacts and administrative registers.We used advanced statistical methods and linked the BP measurements with the data for cardiovascular disease and death date from the Danish registries for each person.The results showed that the American definition of hypertension has same risk for future cardiovascular disease as the definition of normal BP.This means that healthy persons will be diagnosed with hypertension if the US guidelines were applied in Denmark.

Left atrial functional measurements' utility in predicting long-term risk of atrial fibrillation after isolated CABG.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia following coronary artery bypass grafting (CABG). We hypothesized that measures of left atrial (LA) function would be useful in predicting AF in patients undergoing CABG. METHODS AND RESULTS: In the study, 611 patients were included after CABG. All patients had echocardiograms performed preoperatively and LA functional measurements were assessed. These measurements were LA maximum volume index (LAVmax), LA minimum volume index (LAVmin) and LA emptying fraction (LAEF). The endpoint was AF occurring >14 days after surgery. During the follow-up period of a median of 3.7 years, 52 (9%) developed AF. The mean age was 67 years, 84% were male and the average left ventricle ejection fraction was 50%. Patients who developed AF had a lower CCS class and lower LAEF (40 vs. 45%), otherwise no clinical differences were observed between outcome groups. No functional LA measurements were significant predictors of AF in the whole CABG population. However, in patients with normal-sized LA (n = 532, events: 49), both LAEF and LAVmin were univariable predictors of AF. When the functional measurements were adjusted for the CHADS2 score, both LAVmin (HR = 1.07 [1.01-1.13], p = .014) and LAEF (HR: 1.02 [1.00-1.03], p = .023), remained significant predictors. CONCLUSION: No echocardiographic measurements were significant predictors of AF after CABG. In patients with a normal LA size, LAVmin as well as LAEF were significant predictors of AF.

Effect of Influenza Vaccination on Risk of Coronavirus Disease 2019: A Prospective Cohort Study of 46†000 Healthcare Workers.

BACKGROUND: The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19). METHODS: A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination. RESULTS: The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56-1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found. CONCLUSIONS: The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.

Echocardiographic predictors of long-term adverse cardiovascular outcomes in participants with and without diabetes mellitus: A follow-up analysis of the Copenhagen City Heart Study.

BACKGROUND: Previous studies have identified several echocardiographic markers of cardiac dysfunction in participants with diabetes mellitus, including E/e'. However, previous studies have been limited by short follow-up duration or low statistical power, and none have assessed whether echocardiographic predictors of adverse cardiovascular outcome differ between individuals with DM and individuals without DM. METHODS: A total of 1997 individuals from the general population without heart disease had an echocardiogram performed in 2001 to 2003. Diabetes was defined as HbA1c ≥6.5% (≥48 mmol/mol), non-fasted blood glucose ≥11.1 mmol/L or the use of glucose lowering medication. The end-point was a composite of heart failure (HF), ischemic heart disease (IHD) and cardiovascular death (CVD). RESULTS: At baseline, a total of 292 participants (15%) had diabetes. Median follow-up time was 12.4 years (interquartile-range: 9.8-12.8 years) and follow-up was 100%. During follow-up, 101 participants (35%) with diabetes and 281 participants without diabetes (16%) reached the composite end-point. The prognostic value of E/e' was significantly modified by diabetes (p for interaction: 0.003). In participants with diabetes, only E/e' remained an independent predictor of outcome in a final multivariable model adjusted for clinical and echocardiographic parameters (HR 1.08, 95% CI 1.00-1.17, p = 0.0041, per 1 increase). In participants without diabetes, left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and a' remained independent predictors of outcome when adjusted for clinical and echocardiographic parameters. In individuals with diabetes, only E/e' added incremental prognostic value to risk factors from the SCORE risk chart and the ACC/AHA Pooled Cohort Equation. CONCLUSION: In individuals with diabetes from the general population, E/e' is a stronger predictor of cardiovascular mortality and morbidity than in individuals without diabetes and contributes with incremental prognostic value in addition to established cardiovascular risk factors.

Diabetic microvascular complications are associated with reduced global longitudinal strain independent of atherosclerotic coronary artery disease in asymptomatic patients with diabetes mellitus: a cross-sectional study.

BACKGROUND: Reduced left ventricular function, assessed by global longitudinal strain (GLS), is sometimes observed in asymptomatic patients with diabetes mellitus (DM) and is often present in patients with diabetes-related microvascular complications. Our aim was to assess the association between microvascular complications, coronary artery plaque burden (PB) and GLS in asymptomatic patients with DM and non-obstructive coronary artery disease (CAD). METHODS: This cross-sectional study included patients with DM without any history, symptoms or objective evidence of obstructive CAD. All patients were identified in the outpatient Clinic of Endocrinology at Odense University Hospital Svendborg. An echocardiography and a coronary computed tomography angiography were performed to assess GLS and the degree of CAD, respectively. A coronary artery stenosis < 50% was considered non-obstructive. A linear regression model was used to evaluate the impact of potential confounders on GLS with adjustment of body mass index (BMI), mean arterial pressure (MAP), microvascular complications, type of diabetes, tissue Doppler average early diastolic mitral annulus velocity (e') and PB. RESULTS: Two hundred and twenty-two patients were included, of whom 172 (77%) had type 2 DM and 50 (23%) had type 1 diabetes. One hundred and eleven (50%) patients had microvascular complications. GLS decreased as the burden of microvascular complications increased (P-trend = 0.01): no microvascular complications, GLS (- 16.4 ± 2.5%), 1 microvascular complication (- 16.0 ± 2.5%) and 2-3 microvascular complications (- 14.9 ± 2.8%). The reduction in GLS remained significant after multivariable adjustment (ß 0.50 [95% CI 0.11-0.88], p = 0.01). BMI (ß 0.12 [95% CI 0.05-0.19]) and MAP (ß 0.05 [95% CI 0.01-0.08]) were associated with reduced GLS. In addition, an increased number of microvascular complications was associated with increased PB (ß 2.97 [95% CI 0.42-5.51], p = 0.02) in a univariable linear regression model, whereas there was no significant association between PB and GLS. CONCLUSIONS: The burden of microvascular complications was associated with reduced GLS independent of other cardiovascular risk factors in asymptomatic patients with DM and non-obstructive CAD. In addition, the burden of microvascular complications was associated with increasing PB, whereas PB was not associated with GLS.

Prognostic value of suPAR and hsCRP on acute kidney injury after cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) represents a serious complication following cardiac surgery. Adverse outcome after cardiac surgery has been observed in the presence of elevated levels of soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-Reactive Protein (hsCRP). The aim of study was (i) to investigate the relationship between preoperative elevated levels of suPAR and hsCRP and postoperative AKI in unselected cardiac surgery patients and (ii) to assess whether the concentration of the biomarkers reflected severity of AKI. METHODS: In a retrospective observational study, biobank blood plasma samples (n = 924) from patients admitted for elective on-pump cardiac surgery were analysed for suPAR and hsCRP levels. The relation between suPAR and hsCRP-values and AKI (any stage), defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria, was assessed using adjusted logistic regression. Further, the association between biomarkers and severity (KDIGO 1, KDIGO 2-3 and renal replacement therapy (RRT)) was assessed using adjusted logistic regression. RESULTS: Postoperative AKI (any stage) was observed in 327 patients (35.4 %). A doubling of preoperative suPAR corresponded to an adjusted odds ratio (OR) for postoperative AKI (any stage) of 1.62 (95 % CI 1.26-2.09, p < 0.001). Furthermore, a doubling of suPAR had an adjusted OR of 1.50 (95 % CI 1.16-1.93, p = 0.002), 2.44 (95 % CI 1.56-3.82, p < 0.001) and 1.92 (95 % CI 1.15-3.23, p = 0.002), for KDIGO 1, KDIGO 2-3 and need for RRT, respectively. No significant association was found between elevated levels of hsCRP and any degree of AKI. CONCLUSIONS: Increasing levels of suPAR, but not hsCRP, were associated with development and severity of AKI following on-pump cardiac surgery.

Diastolic function assessed with speckle tracking over a decade and its prognostic value: The Copenhagen City Heart Study.

BACKGROUND: The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) may be a more accurate measure of LV filling pressure then ratio of early filling pressure to early tissue velocity. The aim of the study was to investigate the impact of age, sex, obesity, smoking, hypertension, hypercholesterolemia, diabetes, physical activity level, socioeconomic, and psychosocial status on E/e'sr over a decade. Additionally, the predictive value of ΔE/e'sr on future major adverse cardiovascular events (MACE) has never been explored. METHOD: The study included 623 participants from the general population, who participated in the 4th and 5th Copenhagen City Heart Study (CCHS4 and CCHS5). Examinations were median 10 years apart. MACE was the composite endpoint of heart failure, myocardial infarction, and all-cause death. RESULTS: Follow-up time was median 5.7 years, and 43 (7%) experienced MACE. Mean age was 51 ± 14 years, and 43% were male. Mean ΔE/e'sr was 2.1 ± 23.0 cm. After multivariable adjustment for demographic, clinical, and biochemistry variables, high age (stand. ß-coef. = .24, P < .001) and mean arterial blood pressure (MAP) (stand. ß-coef. = .17, P < .001) were significantly associated with an accelerated increase in E/e'sr In multivariable Cox regression, E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of MACE (HR = 1.20, 95% CI [1.01; 1.42] per 10 cm increase for both). ΔE/e'sr did only provide incremental prognostic value to change in left atrial volume index of the conventional diastolic measurements. CONCLUSION: In the general population, age and MAP were predictors of an accelerated increase in E/e'sr over a decade. E/e'sr at CCHS5 and ΔE/e'sr were independent predictors of future MACE.

Prognostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor and High-Sensitivity C-Reactive Protein on Postoperative Mortality in Patients Undergoing Elective On-Pump Cardiac Surgery.

OBJECTIVES: Elevated soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) have been associated with increased mortality in patients with cardiovascular disease. The aim of the present study was to explore the relationship between suPAR and hsCRP values and associated mortality after elective cardiac surgery. A secondary aim was to assess whether a combined risk model of European System for Cardiac Operative Risk Evaluation (EuroSCORE II), suPAR, and/or hsCRP would improve the prognostic accuracy compared with EuroSCORE II alone. DESIGN: Retrospective observational study. SETTING: Single-center, university hospital. PARTICIPANTS: Adult patients admitted for elective on-pump cardiac surgery were included. Biobank blood samples were obtained from previous research projects at a tertiary heart center from 2012 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 931 patients were included. Kaplan-Meier and Cox proportional hazard analyses were used to explore a potential association between preoperative suPAR and hsCRP values and all-cause mortality up to one year after surgery. Thirty-day mortality was predicted from suPAR, hsCRP, and EuroSCORE II by logistic regression and compared using area under the receiver operating characteristics curve and Brier scores. After adjustment for known confounders, a doubling of suPAR and hsCRP corresponded to a hazard ratio for all-cause mortality of 2.27 (95% confidence interval 1.65-3.11; p < 0.001) and 1.26 (95% confidence interval 1.07-1.49; p = 0.005), respectively. However, adding the biomarkers to EuroSCORE II did not improve prediction/discrimination with respect to 30-day mortality. CONCLUSIONS: Elevated preoperative levels of suPAR and hsCRP were associated with all-cause mortality in elective cardiac surgery patients. However, inclusion of biomarkers did not improve the prognostic accuracy of EuroSCORE II.

Cardiovascular and metabolic health effects of team handball training in overweight women: Impact of prior experience.

PURPOSE: We tested the hypothesis that participation in small-sided team handball training could provide beneficial effects on cardiovascular and metabolic parameters in overweight premenopausal women with special focus on the importance of prior team handball experience. METHODS: A 16-week RCT training intervention was conducted in overweight premenopausal women randomized into three groups: a team handball training group without prior experience (UN; n = 13), a team handball group with prior experience (EXP; n = 10), and an inactive control group (CON; n = 9). Both UN and EXP completed 1.6 ± 0.3 training sessions per week with average heart rates of 84 ± 5 and 85 ± 9% of maximal heart rate, respectively. Cardiovascular and metabolic parameters were assessed before and after the intervention. RESULTS: Compared to CON, UN had significant increases in VO2max  (7 ± 4%) and intermittent endurance performance (26 ± 14%) as well as reduced total fat mass (4 ± 6%), total fat percentage (4 ± 5%), and android fat mass (7 ± 12%), respectively (all P < .05). Compared to UN and CON, EXP displayed increased left ventricular mass and left ventricular mass index (both P < .05) after the training period. There were no significant changes between any of the groups in muscle mass, blood lipids, resting heart rate, and blood pressure (all P > .05). CONCLUSION: Small-sided team handball training in overweight premenopausal women resulted in improvement of VO2max and body composition for participants with minimal team handball experience, indicating that prior team handball experience is not a prerequisite for improving physiological parameters of importance for health. Furthermore, EXP displayed cardiac adaptations, including increased left ventricular mass and left ventricular mass index.

Ratio of transmitral early filling velocity to early diastolic strain rate predicts long-term risk of cardiovascular morbidity and mortality in the general population.

Aims: It has previously been demonstrated that the ratio of early mitral inflow velocity to global diastolic strain rate (E/e'sr) is a significant predictor of cardiac events in specific patient populations. The utility of this measurement to predict cardiovascular events in a general population has not been evaluated. Methods and results: A total of 1238 participants in a general population study underwent a health examination including echocardiography where global longitudinal strain (GLS) and E/e'sr were determined. The primary endpoint was the composite of incident heart failure (HF), acute myocardial infarction (AMI) or cardiovascular death (CVD). During follow-up (median 11 years), 140 (11.3%) participants reached the composite endpoint. E/e'sr was associated with adverse outcome [HR 1.17 95% CI (1.13-1.21); P < 0.001, per 10 cm increase]. After multivariable adjustment for echocardiographic and clinical parameters, E/e'sr remained an independent predictor of the composite endpoint [HR 1.08, 95% CI (1.02-1.13); P = 0.003] as opposed to E/e' [HR 1.03, 95% CI (0.99-1.06); P = 0.11 per 1 unit increase]. Global longitudinal strain modified the relationship between E/e'sr and outcome (P for interaction = 0.015). E/e'sr was a stronger predictor in participants with good systolic function as determined by GLS (GLS > 18%) after multivariable adjustment, when compared to participants with reduced systolic function (GLS < 18%) [HR 1.28 95% CI (1.06-1.54); P = 0.011, and HR 1.08 95% CI (1.02-1.14); P = 0.012, respectively). E/e'sr provided incremental information [Harrell's C-index: 0.839 (0.81-0.87) vs. 0.844 (0.82-0.87); P = 0.045] beyond the SCORE risk chart. Conclusion: In the general population, E/e'sr provides independent and incremental prognostic information regarding cardiovascular morbidity and mortality. Additionally, E/e'sr is a stronger predictor of cardiac events than E/e'.

Left ventricular concentric geometry predicts incident diabetes mellitus independent of established risk factors in the general population: the Copenhagen City Heart Study.

BACKGROUND: Subtle impairments in left ventricular (LV) function and geometry are common findings in individuals with diabetes. However, whether these impairments precede the development of diabetes mellitus (DM) is not entirely clear. METHODS: Echocardiograms from 1710 individuals from the general population free of prevalent diabetes mellitus were analyzed. Left ventricular (LV) concentric geometry was defined as either LV concentric remodeling or LV concentric hypertrophy as directed in contemporary guidelines. The severity of LV concentricity was assessed by relative wall thickness (RWT) calculated as posterior wall thickness (PWT) indexed to left ventricular internal diameter at end diastole (LVIDd) (RWT = 2 * PWT/LVIDd). End-point was incident DM. RESULTS: Median follow-up time was 12.6 years (IQR: 12.0-12.8 years). Follow-up was a 100%. A total of 55 participants (3.3%) developed DM during follow-up. At baseline, the prevalence of a concentric LV geometric pattern was significantly higher (41.8% vs 20.3%, p < 0.001) in individuals who developed DM during follow-up. In a final multivariable model adjusting for established DM risk factors including HbA1c, BMI and plasma glucose, LV concentric geometry and RWT remained significantly associated with incident DM (LV concentric geometry: HR 1.99, 95% CI 1.11-3.57, p = 0.021) (RWT: HR 1.41, 95% CI 1.06-1.86, p = 0.017, per 0.1 increase). This association remained despite adjustment for established risk factors for DM. CONCLUSION: Altered LV geometry may precede the development of DM. LV concentric geometry determined by echocardiography and the severity of LV concentricity evaluated as RWT are associated with incident DM in the general population.

Cardiac left ventricular myocardial tissue density, evaluated by computed tomography and autopsy.

BACKGROUND: Left ventricular mass (LVM) is an independent risk factor for the prediction of cardiac events. Its assessment is a clinically important diagnostic procedure in cardiology and may be performed by Computed Tomography (CT). The aim of this study was to assess the correlation between the cardiac left ventricular shell volume (LVShV) determined by postmortem Computed Tomography (PMCT) and the anatomic LVM obtained at autopsy and to calculate the myocardial tissue density. METHODS: A total of 109 deceased individuals were examined with a 64-slice CT scanner and LVShV was determined. At autopsy, the left ventricle was dissected and weighted. The correlation between LVShV and the anatomic LVM was analysed. Asymmetric left ventricular (LV) hypertrophy was recorded. Inter-observer variability was evaluated, and a density value for myocardial tissue was calculated. RESULTS: The mean age of the deceased was 55 ± 16 years, and 58% was men. We found 30 cases of asymmetric LV hypertrophy. A highly positive correlation existed between LVShV and anatomic LVM (r = 0.857; p < 0.0001), regardless of hypertrophy, asymmetric hypertrophy and gender. The mean difference in the inter-observer variability for LVShV assessment was - 4.4 ml (95% CI: -26.4; 17.6). A linear regression analysis was performed, resulting in a value of 1.265 g/ml for myocardial tissue density. Applying the hitherto used myocardial tissue density of 1.055 g/ml underestimated the anatomic LVM by 18.1% (p < 0.0001). CONCLUSION: PMCT is a helpful tool for the assessment of LVM, and LVShV is highly correlated with LVM as assessed by subsequent autopsy. The correlation between the two was independent of gender, hypertrophy and LV asymmetric hypertrophy. We found a higher myocardial tissue density of 1.265 g/ml compared to previous studies. We show that PMCT combined with autopsy may contribute not only to anatomical but also clinical knowledge.

Global longitudinal strain before cardiac surgery: Improving feasibility, reproducibility, and variability.

BACKGROUND: Global longitudinal strain (GLS) is a predictor of outcome after cardiac surgery. If integrated into clinical decision-making and timing of surgery, it is important to evaluate the feasibility, reproducibility, and variation of GLS in this selection of patients, where poor image quality and nontraceable segments are frequent. METHODS AND RESULTS: Two-dimensional strain analysis was performed on 250 patients planned to undergo open-heart surgery. Intra- and inter-examiner retest variability was assessed in 50 consecutive patients. All myocardial segments were traceable in 119 patients, and GLS of those served as a reference in comparison with alternative strain models with nontraceable segments. Global longitudinal strain estimation by the recommended method of a maximum of one nontraceable segment per view was only feasible in 64% of cases (mean GLS -16%). Reproducibility was moderate (intra-observer coefficient of variation [CV] 8%; inter-observer CV 10%) and variation of GLS showed bias ± 95% limits of agreement (LOA) of 0.6 ± 1.1 (P < .05). Accepting three nontraceable segments in total increased feasibility to 77% with similar reproducibility (intra-observer CV 8%; inter-observer CV 11%) and variation (bias ± LOA: 0.6 ± 1.3, P < .05). A model with a maximum of one apical, one mid, and one basal nontraceable segment increased feasibility to 72% with similar reproducibility (intra-observer CV 8%; inter-observer CV 10%) and variation (bias ± LOA: 0.4 ± 1.2, P < .05). CONCLUSION: Global longitudinal strain estimation in patients prior to cardiac surgery is challenged by moderate feasibility, retest variation as well as variation in cases of nontraceable segments. We suggest alternative strain models with improved feasibility without compromising reproducibility and variation.

Transjugular intrahepatic portosystemic shunt: impact on systemic hemodynamics and renal and cardiac function in patients with cirrhosis.

Transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension and possibly increases central blood volume (CBV). Moreover, renal function often improves; however, its effects on cardiac function are unclear. The aims of our study were to examine the effects of TIPS on hemodynamics and renal and cardiac function in patients with cirrhosis. In 25 cirrhotic patients, we analyzed systemic, cardiac, and splanchnic hemodynamics by catheterization of the liver veins and right heart chambers before and 1 wk after TIPS. Additionally, we measured renal and cardiac markers and performed advanced echocardiography before, 1 wk after, and 4 mo after TIPS. CBV increased significantly after TIPS (+4.6%, P < 0.05). Cardiac output (CO) increased (+15.3%, P < 0.005) due to an increase in stroke volume (SV) (+11.1%, P < 0.005), whereas heart rate (HR) was initially unchanged. Cardiopulmonary pressures increased after TIPS, whereas copeptin, a marker of vasopressin, decreased (-18%, P < 0.005) and proatrial natriuretic peptide increased (+52%, P < 0.0005) 1 wk after TIPS and returned to baseline 4 mo after TIPS. Plasma neutrophil gelatinase-associated lipocalin, renin, aldosterone, and serum creatinine decreased after TIPS (-36%, P < 0.005; -65%, P < 0.05; -90%, P < 0.005; and -13%, P < 0.005, respectively). Echocardiography revealed subtle changes in cardiac function after TIPS, although these were within the normal range. TIPS increases CBV by increasing CO and SV, whereas HR is initially unaltered. These results indicate an inability to increase the heart rate in response to a hemodynamic challenge that only partially increases CBV after TIPS. These changes, however, are sufficient for improving renal function. NEW & NOTEWORTHY For the first time, we have combined advanced techniques to study the integrated effects of transjugular intrahepatic portosystemic shunt (TIPS) in cirrhosis. We showed that TIPS increases central blood volume (CBV) through improved cardiac inotropy. Advanced echocardiography demonstrated that myocardial function was unaffected by the dramatic increase in preload after TIPS. Finally, renal function improved due to the increase in CBV. Recognition of these physiological changes significantly contributes to our clinical understanding of TIPS.

Semi-automated estimation of left ventricular ejection fraction by two-dimensional and three-dimensional echocardiography is feasible, time-efficient, and reproducible.

PURPOSE: To compare two-dimensional (2D) and three-dimensional (3D) methods to estimate left ventricular ejection fraction (LVEF) with respect to feasibility, time consumption, and retest reproducibility. METHODS: A total of 100 patients planned to undergo coronary artery bypass grafting and/or aortic valve replacement were included consecutively. 2D and 3D echocardiography was performed on all patients. Acquisition and analysis time as well as intra- and inter-examiner variability were assessed in 50 consecutive patients with 3 repeated echocardiographic examinations and analyses. LVEF was estimated by five different methods: uniplane, biplane, and single-beat triplane (SB3P), as well as semi-automated biplane (AutoEF) and 3D volumetric tracings (4D Auto LVQ). All methods were compared to Simpson's biplane method and feasibility was determined. RESULTS: Feasibility of Simpson's uniplane method, Simpson's biplane method, AutoEF, SB3P, and 4D Auto LVQ was 97%, 92%, 86%, 70%, and 89%, respectively. All methods evaluated were 18%-33% faster (P < 0.001) than Simpson's biplane method (115 seconds, standard deviation 15 seconds). Compared to Simpson's biplane method mean LVEF was slightly underestimated by 4D Auto LVQ (-2 ± 8%, P = 0.02), but not significantly different when assessed by the other methods. AutoEF and 4D Auto LVQ showed the lowest test variability (intra-examiner coefficient of variation (CV) 10%-11%; inter-examiner CV 10%-12% vs intra-examiner CV 12%-18%; inter-examiner CV 12%-20%). CONCLUSIONS: Estimation of LVEF by modern semi-automated 2D and 3D echocardiographic modalities is feasible, time-efficient, and reproducible.

Diastolic dysfunction revisited: A new, feasible, and unambiguous echocardiographic classification predicts major cardiovascular events.

BACKGROUND: Echocardiographic classification of DDF has been widely discussed. The aim of this study was to investigate the independent prognostic value of established echocardiographic measures in a community-based population and create a new classification of DDF. METHODS: Within the Copenhagen City Heart Study, a prospective, community-based study, 1851 participants were examined by echocardiography including Tissue Doppler Imaging (TDI) in 2001 to 2003 and followed with regard to MACE (median, 10.9 years). RESULTS: We found that persons with impaired myocardial relaxation as defined by low peak early diastolic mitral annular velocity e' by TDI had higher incidence of clinical and echocardiographic markers of cardiac dysfunction and increased risk of MACE. Among persons with impaired relaxation, only echocardiographic indices of increased filling pressures such as LAVi≥34 mL/m2 (HR 1.97 (1.13-3.45, P=.017), E/e' ≥ 17 (HR 1.89 (1.34-2.65), P<.001), and E/A>2 (HR 5.24 (1.91-14.42), P=.001) provided additional and independent prognostic information on MACE. Based on these findings, we created a new classification of DDF where all grades were significant predictors of MACE independently of age, sex, and cardiac clinical risk markers (Mild DDF: HR 1.99 (1.23-3.21), P=.005; Moderate DDF: HR 3.11 (1.81-5.34), P<.001; Severe DDF: HR 4.20 (1.81-9.73), P<.001). Increasing severity of DDF was linearly associated with increasing plasma proBNP concentrations. CONCLUSIONS: In the general population, the presence of echocardiographic markers of elevated filling pressures in persons with impaired relaxation increased the risk of MACE significantly. Based on this, we present a new, feasible, and unambiguous classification of DDF capable of accurate risk prediction in the community.

Cholesterol remnants and triglycerides are associated with decreased myocardial function in patients with type 2 diabetes.

BACKGROUND: Recently, genetic studies have suggested a causal relationship between cholesterol remnants and ischemic heart disease. We aimed to determine whether cholesterol remnants and its marker, triglyceride levels, are associated with cardiac function as determined by sensitive echocardiographic measures in a population of patients with type 2 diabetes. METHODS: Comprehensive echocardiography including 2D-speckle tracking echocardiography was performed on a representative sample of 924 patients with type 2 diabetes-730 of whom were treated with statins. These were recruited from two large secondary care centers. RESULTS: In multivariable analyses, triglycerides and cholesterol remnants were not associated with left ventricular ejection fraction, but with subtle measures of systolic function, including global longitudinal strain by speckle tracking and longitudinal displacement by tissue Doppler echocardiography: global longitudinal strain [0.33 % (0.14), p = 0.02 per doubling in cholesterol remnants and 0.28 % (0.13), p = 0.03 per doubling in triglyceride levels] and with longitudinal displacement [-0.25 mm (0.10), p = 0.01 per doubling in cholesterol remnants and -0.25 mm (0.09), p = 0.005 per doubling in triglyceride levels]. Subgroup analyses of patients receiving statin therapy and patients without known heart disease revealed similar results, but the association was not present in patients with known heart disease. CONCLUSION: In patients with type 2 diabetes, subtle decrease in left ventricular function is present with increasing levels of cholesterol remnants and triglyceride levels indicating an effect of these on cardiac function that is not detectable by conventional echocardiography.

Total average diastolic longitudinal displacement by colour tissue doppler imaging as an assessment of diastolic function.

BACKGROUND: The current method for a non-invasive assessment of diastolic dysfunction is complex with the use of algorithms of many different echocardiographic parameters. Total average diastolic longitudinal displacement (LD), determined by colour tissue Doppler imaging (TDI) via the measurement of LD during early diastole and atrial contraction, can potentially be used as a simple and reliable alternative. METHODS: In 206 patients, using GE Healthcare Vivid E7 and 9 and Echopac BT11 software, we determined both diastolic LD, measured in the septal and lateral walls in the apical 4-chamber view by TDI, and the degree of diastolic dysfunction, based on current guidelines. Of these 206 patients, 157 had cardiac anomalies that could potentially affect diastolic LD such as severe systolic heart failure (n = 45), LV hypertrophy (n = 49), left ventricular (LV) dilation (n = 30), and mitral regurgitation (n = 33). Intra and interobserver variability of diastolic LD measures was tested in 125 patients. RESULTS: A linear relationship between total average diastolic LD and the degree of diastolic dysfunction was found. A total average diastolic LD of 10 mm was found to be a consistent threshold for the general discrimination of patients with or without diastolic dysfunction. Using linear regression, total average diastolic LD was estimated to fall by 2.4 mm for every increase in graded severity of diastolic dysfunction (ß = -0.61, p-value <0.001). Patients with LV hypertrophy had preserved total average diastolic LD despite being classified as having diastolic dysfunction. Reproducibility of LD measures was acceptable. CONCLUSIONS: There is strong evidence suggesting that patients with a total average diastolic LD under 10 mm have diastolic dysfunction.

Predicting Paroxysmal Atrial Fibrillation in Cerebrovascular Ischemia Using Tissue Doppler Imaging and Speckle Tracking Echocardiography.

BACKGROUND: Often the underlying cause of cerebral ischemia (CI) cannot be found during a routine diagnostic investigation, but paroxysmal atrial fibrillation (PAF) could be the culprit. AIM: The objective of the study is to investigate whether advanced echocardiography improves the diagnostic approach for PAF in CI. METHODS: The study included 286 CI patients with an echocardiogram in sinus rhythm. Patients were divided by PAF occurrence (PAF: n = 86, non-PAF: n = 200). PAF was defined as 1 or more reported episodes of atrial fibrillation. Echocardiograms consisted of conventional measures, tissue Doppler imaging (TDI), and speckle tracking. TDI was performed to acquire myocardial peak velocities during systole/ventricular contraction (global s'), early diastole/ventricular filling (global e'), and late diastole/atrial contraction (global a'). Speckle tracking was performed for myocardial strain analysis, thereby retrieving global longitudinal strain and global strain rate (s, e, a) values. RESULTS: Patients with PAF exhibited significantly impaired atrial contractile measures: global a' (-7.0 cm/second versus -5.7 cm/second, P < .001) and global strain rate a (.97 second(-1) versus .81 second(-1), P < .001). Both were univariable markers of PAF, and along with age remained the only independent significant determinants of PAF after multivariable logistic regression. Area under the curve (AUC) for age, global a', and global strain rate a significantly exceeded AUC for age alone (.79 versus .76, P = .032). Cutoff values with the highest sensitivity and specificity for these 3 parameters improved the diagnostic accuracy (sensitivity = 97%, specificity = 32%, negative predictive value = 95%, and positive predictive value = 38%). CONCLUSIONS: Atrial contractile measures by advanced echocardiography are significant determinants of PAF in CI. However, there is no discriminatory power to make them clinically useful at the current moment.

Plasma neutrophil gelatinase-associated lipocalinin in the general population: association with inflammation and prognosis.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein stored in granules of neutrophil leukocytes participating in inflammatory and atherosclerotic processes and possibly plaque rupture. Despite the putative role of NGAL in atherosclerosis and acute myocardial infarction, human studies of plasma NGAL are still limited. APPROACH AND RESULTS: We prospectively followed 5599 randomly selected men and women from the community in the fourth Copenhagen Heart Study. Plasma NGAL was measured at study entry. Participants were followed for 10 years. During follow-up, 20% died (n=1120) and 15% (n=884) developed a major adverse cardiovascular event. Plasma NGAL associated strongly with all inflammatory markers (high-sensitivity C-reactive protein, total leukocyte count, neutrophil count) and inversely with estimated glomerular filtration rate (all, P<0.001). Multivariate analysis identified neutrophil leukocyte count as the main determinant of plasma NGAL. During follow-up, participants with increasing NGAL had increased risk of all-cause mortality and major adverse cardiovascular event (both, P<0.001). Even after adjustment for confounding risk factors by Cox regression analysis, NGAL remained an independent predictor of both all-cause mortality and major adverse cardiovascular event. When added to the Framingham risk score, NGAL improved c-statistics and correctly reclassified ≈15% into more appropriate risk groups. In comparison with high-sensitivity C-reactive protein, when both markers were added to the Framingham risk score, NGAL conferred 3× to 4× the risk. CONCLUSIONS: Plasma NGAL is strongly associated with inflammation in the general population. NGAL independently associated with 10-year outcome, and when added to the Framingham risk score, NGAL both improves c-statistics and correctly reclassifies participants into more accurate risk categories.