Tor Biering-Sørensen | University of Copenhagen (original) (raw)

Papers by Tor Biering-Sørensen

Circulation, 2016

-While age-associated changes in LV diastolic function are well-recognized, limited data exist ch... more -While age-associated changes in LV diastolic function are well-recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident HF, as well as their associations with circulating biomarkers of heart failure (HF) risk. -Among 5,801 elderly participants in the Atherosclerosis Risk in Communities (ARIC) study (age range 67-90, mean age 76 ± 5, 42% male, 21% black), we determined the continuous association of diastolic measures (TDI e', E/e', and left atrial size) with concomitant NT-proBNP and subsequent HF hospitalization or death. We also determined sex-specific 10(th) and 90(th) percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. -Each measure of diastolic function was robustly associated with NT-proBNP and incident HF or death. ARIC-based reference limits for TDI e' (4.6 and 5.2 cm/sec for septal and lateral TDI e', respectively) were substantially lower than guideline cutpoints (7 and 10 cm/sec, respectively), while E/e' and LA size demonstrated good agreement with guideline cutpoints. TDI e' was non-linearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cutpoints based on the IDI (p<0.001) and continuous NRI (p<0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. Using these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/year over a mean 1.7 year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/year), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/year). -Our findings suggest that LV longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.

Cardiovascular Ultrasound, 2015

The current method for a non-invasive assessment of diastolic dysfunction is complex with the use... more 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. 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. 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 (β = -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. There is strong evidence suggesting that patients with a total average diastolic LD under 10 mm have diastolic dysfunction.

JACC: Cardiovascular Imaging, 2016

Journal of the American College of Cardiology, 2016

Cardiovascular diabetology, Jan 22, 2016

Recently, genetic studies have suggested a causal relationship between cholesterol remnants and i... more 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. 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. 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 0.2...

Circulation. Cardiovascular imaging, 2016

Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, all... more Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the current moment. Numerous studies, however, have shown that functional measures may be superior to the maximal LA volume in several aspects and to possess clinical value even in the absence of structural abnormalities. Such functional measures could prove particularly useful in the setting of predicting atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked a...

International Journal of Cardiology, 2016

Contemporary treatment of type 2 diabetes (T2D) has improved patient outcome and may also have af... more Contemporary treatment of type 2 diabetes (T2D) has improved patient outcome and may also have affected myocardial structure and function. We aimed to describe the effect of T2D and T2D duration on cardiac structure and function in a large outpatient population. We performed comprehensive echocardiography on a representative sample of 1004 persons including a representative sample of 770 patients with T2D without known heart disease and 234 age- and sex-matched controls. T2D was associated with increased left ventricular (LV) wall thicknesses and decreased LV internal diameter and the changes were pronounced with increasing diabetes duration (P<0.01 for all) but not with increased LV mass (P=0.74). It was also significantly associated with the prevalence of diastolic dysfunction (16.5% vs. 4.0%; P<0.001), with indices of LV relaxation and elevated filling pressures expressed as e'septal (mean: 6.9 (SD: 1.9) cm/s vs. 7.5 (2.4); P<0.001) and E/e'septal (median: 10.8 (interquartile range (IQR): 9.1-13.3) vs. 9.1 (7.2-11.1); P<0.001) and global longitudinal strain (mean: -14.1 (SD: 2.4) vs. -15.0 (2.0), P<0.001) but not with LV ejection fraction (median: 60.8 (IQR: 56.5-65.1) vs. 62.1 (57.9-65.4), P=0.28). With the exception of global longitudinal strain, this was pronounced with increasing diabetes duration for all measures including increasing diastolic dysfunction (<10years: 10.8%, 10-20years: 18.5%, >20years: 24.8%; P<0.001). The increased risk of diastolic dysfunction persisted after multivariable adjustment (P=0.013). In patients with T2D, LV structural and functional alterations persist and are accentuated with increasing diabetes duration despite reductions in overall risk of cardiovascular disease in this patient population.

Journal of Hypertension, 2015

The aim of this study was to evaluate the performance of common carotid artery diameter, flow vel... more The aim of this study was to evaluate the performance of common carotid artery diameter, flow velocity and flow velocity/artery diameter ratio as predictors of major adverse cardiovascular events (MACEs) in a sample of hypertensive patients. A cohort of 403 hypertensive patients was followed up for a median of 1260 (714) days, and 27 suffered MACEs. At baseline, participants were evaluated by clinical, laboratory, echocardiographic and carotid ultrasound analysis. Patients with peak-systolic flow velocity (sFV) less than the median value and systolic artery diameter (sAD) greater than the median value presented the worst clinical outcome compared to those with isolated sFV less than the median value or sAD greater than the median value, suggesting an additive effect of these two variables. Further, Kaplan-Meier analysis demonstrated worse outcome for individuals with sFV/sAD ratio less than 85.7/s (optimal cut-off point obtained by receiver-operating characteristic analysis) compared to those with higher sFV/sAD values (log-rank test: P < 0.0001). In stepwise multivariable Cox-regression analyses, sFV/sAD was significantly associated with MACEs (P < 0.001), whereas carotid intima-media thickness and clinically defined high cardiovascular risk did not. Furthermore, area under the receiver-operating characteristic curve for sFV/sAD was higher than that for Framingham risk score (0.77 versus 0.64; P = 0.045), whereas adding sFV/sAD to the Framingham risk factors resulted in increased net reclassification improvement (P = 0.041) and integrated discrimination improvement (P < 0.001). Lower carotid sFV/sAD was associated with MACEs in hypertensive patients independent of cardiovascular prediction models and carotid intima-media thickness. These findings suggest that this index may be a promising approach to identify hypertensive subjects at increased risk for future cardiovascular events.

PLOS ONE, 2016

Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognos... more Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI). The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information. In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI) and two-dimensional strain echocardiography (2DSE). During a median-follow-up of 5.3 (IQR 2.5-6.1) years the primary endpoint (death, heart failure or a new MI) was reached by 145 (38.9%) patients. After adjustment for significant confounders (including conventional echocardiographic parameters) and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS) remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell's c-statistics: 0.63 vs. 0.67, p = 0.032). In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p<0.05 for all deformation parameters). Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse outcome.

European heart journal cardiovascular Imaging, Jan 15, 2016

Only 30% of patients receiving an implantable cardioverter defibrillator (ICD) for primary preven... more Only 30% of patients receiving an implantable cardioverter defibrillator (ICD) for primary prevention receive appropriately therapy. We sought to investigate the value of tissue Doppler imaging (TDI) to predict ventricular tachycardia (VT), ventricular fibrillation (VF), and cardiovascular mortality (CVD) in patients with primary prevention ICD. In total, 151 ICD patients meeting primary prevention criteria and with no history of ventricular arrhythmias were included. All participants were examined by conventional 2D echocardiography and TDI echocardiography. Longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities were measured using TDI at six mitral annular sites and averaged to provide global estimates. Forty patients experienced the combined endpoint of VT, VF, or CVD during a median follow-up of 2.3 years. Left ventricular ejection fraction, global longitudinal strain, E/e', global s', and global e' were not signif...

PloS one, 2016

To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-... more To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI) and the conventional method of obtaining MPI (MPIConv), with established echocardiographic and invasive measures of systolic and diastolic function. In a large community based population study (n = 974), where all are free of any cardiovascular disease and cardiovascular risk factors, cardiac time intervals, including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI M-mode through the MV. IVCT/ET, IVRT/ET and the MPI ((IVRT+IVCT)/ET) were calculated. We also included a validation population (n = 44) of patients who underwent left heart catheterization and had the MPITDI and MPIConv measured. IVRT, IVRT/ET and MPI all increased significantly with increasing age in both gender...

Diabetes & vascular disease research, Jan 21, 2016

We aimed to determine the prevalence of echocardiographic abnormalities and their relation to cli... more We aimed to determine the prevalence of echocardiographic abnormalities and their relation to clinical characteristics and cardiac symptoms in a large, contemporary cohort of patients with type 2 diabetes. A total of 1030 patients with type 2 diabetes participated. Echocardiographic abnormalities were present in 513 (49.8%) patients, mainly driven by a high prevalence of diastolic dysfunction 178 (19.4%), left ventricular hypertrophy 213 (21.0%) and left atrial enlargement, 200 (19.6%). The prevalence increased markedly with age from 31.1% in the youngest group (<55 years) to 73.9% in the oldest group (>75 years) (p < 0.001) and was equally distributed among the sexes (p = 0.76). In univariate analyses, electrocardiographic abnormalities, age, body mass index, known coronary heart disease, hypertension, albuminuria, diabetes duration and creatinine were associated with abnormal echocardiography along with dyspnoea and characteristic chest pain (p < 0.05 for all). Neither...

European heart journal. Acute cardiovascular care, Jan 10, 2016

Rheumatologic disorders are characterised by inflammation and an increased risk of coronary arter... more Rheumatologic disorders are characterised by inflammation and an increased risk of coronary artery disease (CAD). However, the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing percutaneous coronary intervention (PCI) is unknown. Thus, we aimed to examine the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing PCI. A post-hoc analysis was performed in 4605 patients (age: 63.3 ± 11.0 years; male: 76.6%) with ST-segment elevation myocardial infarction (STEMI; n = 1396), non-STEMI (n = 1541), and stable CAD (n = 1668) from the all-comer stent trials, the BAsel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination (BASKET-PROVE) I and II trials. We evaluated the association between rheumatologic disorders and 2-year major adverse cardiac events (MACEs; cardiac death, nonfatal myocardial infarction (MI), and target vessel revascularisation (TVR)) by Cox regression analysis. Patients with...

Circulation, Jan 14, 2016

-Asymptomatic individuals account for a majority of sudden cardiac deaths (SCDs). Development of ... more -Asymptomatic individuals account for a majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and non-invasive SCD risk stratification tools are necessary. -Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20,177; age 59.3±10.1 years; age range 44-100; 56% female; 77% white) were followed for 14.0 years (median). Five ECG markers of global electrical heterogeneity (GEH) (sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient (SVG) magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH ECG parameters and SCD. A SCD competing risks score was derived using demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1,000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes, hypertension, coronary heart disease, and stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C-statistic increased from 0.777 to 0.790 (p=0.008), the risk score classified 10-year SCD risk as high (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high- to intermediate-risk. Net reclassification index was 18.3%. -Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. Addition of GEH parameters to clinical characteristics improves SCD risk prediction.

Cardiorenal Medicine, 2016

Journal of the American College of Cardiology, 2016

Future Cardiology, 2016

It is often difficult to provide an exact echocardiographic measure of left ventricular systolic ... more It is often difficult to provide an exact echocardiographic measure of left ventricular systolic function in patients with atrial fibrillation, partly because of the varying cycle length affecting pre and afterload and partly because of the increased heart rate often accompanying this arrhythmia. We sought to elucidate two points: whether it would be possible to correct for the cyclic variance in systolic output, and if global longitudinal strain is preferable to the left ventricular ejection fraction at evaluating systolic function during atrial fibrillation.

Journal of the American Heart Association, 2016

We hypothesized that the cardiac time intervals reveal reduced myocardial function in persons wit... more We hypothesized that the cardiac time intervals reveal reduced myocardial function in persons with hypertension and are strong predictors of future ischemic cardiovascular diseases in the general population. In a large community-based population study, cardiac function was evaluated in 1915 participants by using both conventional echocardiography and tissue Doppler imaging (TDI). The cardiac time intervals, including the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET), were obtained by TDI M-mode through the mitral leaflet. IVCT/ET, IVRT/ET, and myocardial performance index [MPI=(IVRT+IVCT)/ET] were calculated. After multivariable adjustment for clinical variables the IVRT, IVRT/ET, and MPI, remained significantly impaired in persons with hypertension (n=826) compared with participants without hypertension (n=1082). Additionally, they displayed a significant dose-response relationship, between increasing severity of elevated blood pressure and increasing left ventricular mass index (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001 for all). Further, during follow-up of a median of 10.7 years, 435 had an ischemic cardiovascular disease (ischemic heart disease, peripheral arterial disease, or stroke). The IVRT/ET and MPI were powerful and independent predictors of future cardiovascular disease, especially in participants with known hypertension. They provide prognostic information incremental to clinical variables from the Framingham Risk Score, the SCORE risk chart, and the European Society of Hypertension/European Society of Cardiology risk chart. The cardiac time intervals identify impaired cardiac function in individuals with hypertension, not only independent of conventional risk factors but also in participants with a normal conventional echocardiographic examination. The IVRT/ET and MPI are independent predictors of future cardiovascular disease especially in participants with known hypertension.

The international journal of cardiovascular imaging, Jan 21, 2016

Cardiac time intervals (CTI) are prognostic above and beyond conventional echocardiographic measu... more Cardiac time intervals (CTI) are prognostic above and beyond conventional echocardiographic measures. The explanation may be that CTI contain information about both systolic and diastolic measures; this is, however, unknown. The relationship between the CTI and systolic and diastolic function assessed by conventional, tissue Doppler (TDI) and speckle-tracking echocardiography (STE) was investigated. CTI and echocardiographic measurements, including conventional, STE, and TDI echocardiography, were studied in 1088 type 1 diabetes patients without known heart disease randomly selected from the out-patient clinic at Steno Diabetes Center. The CTI were obtained by TDI M-mode through the mitral leaflet and included the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and the myocardial performance index (MPI = (IVRT + IVCT)/ejection time). Standardized beta-values were assessed. Both systolic and diastolic measures associated with CTI. Conventional measures: left ve...

Circulation. Cardiovascular imaging, 2015

Circulation, 2016

-While age-associated changes in LV diastolic function are well-recognized, limited data exist ch... more -While age-associated changes in LV diastolic function are well-recognized, limited data exist characterizing measures of diastolic function in older adults, including both reference ranges reflecting the older adult population and prognostically relevant values for incident HF, as well as their associations with circulating biomarkers of heart failure (HF) risk. -Among 5,801 elderly participants in the Atherosclerosis Risk in Communities (ARIC) study (age range 67-90, mean age 76 ± 5, 42% male, 21% black), we determined the continuous association of diastolic measures (TDI e&#39;, E/e&#39;, and left atrial size) with concomitant NT-proBNP and subsequent HF hospitalization or death. We also determined sex-specific 10(th) and 90(th) percentile limits for these measures using quantile regression in 401 participants free of prevalent cardiovascular disease and risk factors. -Each measure of diastolic function was robustly associated with NT-proBNP and incident HF or death. ARIC-based reference limits for TDI e&#39; (4.6 and 5.2 cm/sec for septal and lateral TDI e&#39;, respectively) were substantially lower than guideline cutpoints (7 and 10 cm/sec, respectively), while E/e&#39; and LA size demonstrated good agreement with guideline cutpoints. TDI e&#39; was non-linearly associated with incident HF or death, with inflection points for risk supportive of ARIC-based limits. ARIC-based limits for diastolic function improved risk discrimination over guideline-based cutpoints based on the IDI (p&lt;0.001) and continuous NRI (p&lt;0.001), reclassifying 42% of the study population as having normal diastolic function. We replicate these findings in the Copenhagen City Heart Study. Using these limits, 46% had normal diastolic function and were at low risk of HF hospitalization or death (1%/year over a mean 1.7 year follow-up), 49% had 1 or 2 abnormal measures and were at intermediate risk (2.4%/year), and all 3 diastolic measures were abnormal in 5% who were at high risk (7.5%/year). -Our findings suggest that LV longitudinal relaxation velocity declines as a part of healthy aging and is largely prognostically benign. The use of age-based normative values when considering an elderly population improves the risk discrimination of diastolic measures for incident HF or death.

Cardiovascular Ultrasound, 2015

The current method for a non-invasive assessment of diastolic dysfunction is complex with the use... more 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. 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. 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 (β = -0.61, p-value &amp;amp;lt;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. There is strong evidence suggesting that patients with a total average diastolic LD under 10 mm have diastolic dysfunction.

JACC: Cardiovascular Imaging, 2016

Journal of the American College of Cardiology, 2016

Cardiovascular diabetology, Jan 22, 2016

Recently, genetic studies have suggested a causal relationship between cholesterol remnants and i... more 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. 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. 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 0.2...

Circulation. Cardiovascular imaging, 2016

Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, all... more Several cardiac imaging modalities are able to visualize the left atrium (LA) and, therefore, allow for quantification of both structural and functional properties of this cardiac chamber. In echocardiography, only the maximal LA volume is included in the assessment of diastolic function at the current moment. Numerous studies, however, have shown that functional measures may be superior to the maximal LA volume in several aspects and to possess clinical value even in the absence of structural abnormalities. Such functional measures could prove particularly useful in the setting of predicting atrial fibrillation, which will be a point of focus in this review. Pivotal cardiac magnetic resonance imaging studies have revealed high correlation between LA fibrosis and risk of atrial fibrillation recurrence after catheter ablation, and subsequent multimodality imaging studies have uncovered an inverse relationship between LA reservoir function and degree of LA fibrosis. This has sparked a...

International Journal of Cardiology, 2016

Contemporary treatment of type 2 diabetes (T2D) has improved patient outcome and may also have af... more Contemporary treatment of type 2 diabetes (T2D) has improved patient outcome and may also have affected myocardial structure and function. We aimed to describe the effect of T2D and T2D duration on cardiac structure and function in a large outpatient population. We performed comprehensive echocardiography on a representative sample of 1004 persons including a representative sample of 770 patients with T2D without known heart disease and 234 age- and sex-matched controls. T2D was associated with increased left ventricular (LV) wall thicknesses and decreased LV internal diameter and the changes were pronounced with increasing diabetes duration (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01 for all) but not with increased LV mass (P=0.74). It was also significantly associated with the prevalence of diastolic dysfunction (16.5% vs. 4.0%; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), with indices of LV relaxation and elevated filling pressures expressed as e&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;septal (mean: 6.9 (SD: 1.9) cm/s vs. 7.5 (2.4); P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and E/e&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;septal (median: 10.8 (interquartile range (IQR): 9.1-13.3) vs. 9.1 (7.2-11.1); P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) and global longitudinal strain (mean: -14.1 (SD: 2.4) vs. -15.0 (2.0), P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) but not with LV ejection fraction (median: 60.8 (IQR: 56.5-65.1) vs. 62.1 (57.9-65.4), P=0.28). With the exception of global longitudinal strain, this was pronounced with increasing diabetes duration for all measures including increasing diastolic dysfunction (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;10years: 10.8%, 10-20years: 18.5%, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;20years: 24.8%; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001). The increased risk of diastolic dysfunction persisted after multivariable adjustment (P=0.013). In patients with T2D, LV structural and functional alterations persist and are accentuated with increasing diabetes duration despite reductions in overall risk of cardiovascular disease in this patient population.

Journal of Hypertension, 2015

The aim of this study was to evaluate the performance of common carotid artery diameter, flow vel... more The aim of this study was to evaluate the performance of common carotid artery diameter, flow velocity and flow velocity/artery diameter ratio as predictors of major adverse cardiovascular events (MACEs) in a sample of hypertensive patients. A cohort of 403 hypertensive patients was followed up for a median of 1260 (714) days, and 27 suffered MACEs. At baseline, participants were evaluated by clinical, laboratory, echocardiographic and carotid ultrasound analysis. Patients with peak-systolic flow velocity (sFV) less than the median value and systolic artery diameter (sAD) greater than the median value presented the worst clinical outcome compared to those with isolated sFV less than the median value or sAD greater than the median value, suggesting an additive effect of these two variables. Further, Kaplan-Meier analysis demonstrated worse outcome for individuals with sFV/sAD ratio less than 85.7/s (optimal cut-off point obtained by receiver-operating characteristic analysis) compared to those with higher sFV/sAD values (log-rank test: P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). In stepwise multivariable Cox-regression analyses, sFV/sAD was significantly associated with MACEs (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), whereas carotid intima-media thickness and clinically defined high cardiovascular risk did not. Furthermore, area under the receiver-operating characteristic curve for sFV/sAD was higher than that for Framingham risk score (0.77 versus 0.64; P = 0.045), whereas adding sFV/sAD to the Framingham risk factors resulted in increased net reclassification improvement (P = 0.041) and integrated discrimination improvement (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Lower carotid sFV/sAD was associated with MACEs in hypertensive patients independent of cardiovascular prediction models and carotid intima-media thickness. These findings suggest that this index may be a promising approach to identify hypertensive subjects at increased risk for future cardiovascular events.

PLOS ONE, 2016

Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognos... more Global longitudinal systolic strain (GLS) has recently been demonstrated to be a superior prognosticator to conventional echocardiographic measures in patients after myocardial infarction (MI). The aim of this study was to evaluate the prognostic value of regional longitudinal myocardial deformation in comparison to GLS, conventional echocardiography and clinical information. In total 391 patients were admitted with ST-Segment elevation myocardial infarction (STEMI), treated with primary percutaneous coronary intervention and subsequently examined by echocardiography. All patients were examined by tissue Doppler imaging (TDI) and two-dimensional strain echocardiography (2DSE). During a median-follow-up of 5.3 (IQR 2.5-6.1) years the primary endpoint (death, heart failure or a new MI) was reached by 145 (38.9%) patients. After adjustment for significant confounders (including conventional echocardiographic parameters) and culprit lesion, reduced longitudinal performance in the anterior septal and inferior myocardial regions (but not GLS) remained independent predictors of the combined outcome. Furthermore, inferior myocardial longitudinal deformation provided incremental prognostic information to clinical and conventional echocardiographic information (Harrell&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s c-statistics: 0.63 vs. 0.67, p = 0.032). In addition, impaired longitudinal deformation outside the culprit lesion perfusion region was significantly associated with an adverse outcome (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05 for all deformation parameters). Regional longitudinal myocardial deformation measures, regardless if determined by TDI or 2DSE, are superior prognosticators to GLS. In addition, impaired longitudinal deformation in the inferior myocardial segment provides prognostic information over and above clinical and conventional echocardiographic risk factors. Furthermore, impaired longitudinal deformation outside the culprit lesion perfusion region seems to be a paramount marker of adverse outcome.

European heart journal cardiovascular Imaging, Jan 15, 2016

Only 30% of patients receiving an implantable cardioverter defibrillator (ICD) for primary preven... more Only 30% of patients receiving an implantable cardioverter defibrillator (ICD) for primary prevention receive appropriately therapy. We sought to investigate the value of tissue Doppler imaging (TDI) to predict ventricular tachycardia (VT), ventricular fibrillation (VF), and cardiovascular mortality (CVD) in patients with primary prevention ICD. In total, 151 ICD patients meeting primary prevention criteria and with no history of ventricular arrhythmias were included. All participants were examined by conventional 2D echocardiography and TDI echocardiography. Longitudinal systolic (s'), early diastolic (e'), and late diastolic (a') myocardial velocities were measured using TDI at six mitral annular sites and averaged to provide global estimates. Forty patients experienced the combined endpoint of VT, VF, or CVD during a median follow-up of 2.3 years. Left ventricular ejection fraction, global longitudinal strain, E/e', global s', and global e' were not signif...

PloS one, 2016

To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-... more To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI) and the conventional method of obtaining MPI (MPIConv), with established echocardiographic and invasive measures of systolic and diastolic function. In a large community based population study (n = 974), where all are free of any cardiovascular disease and cardiovascular risk factors, cardiac time intervals, including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI M-mode through the MV. IVCT/ET, IVRT/ET and the MPI ((IVRT+IVCT)/ET) were calculated. We also included a validation population (n = 44) of patients who underwent left heart catheterization and had the MPITDI and MPIConv measured. IVRT, IVRT/ET and MPI all increased significantly with increasing age in both gender...

Diabetes & vascular disease research, Jan 21, 2016

We aimed to determine the prevalence of echocardiographic abnormalities and their relation to cli... more We aimed to determine the prevalence of echocardiographic abnormalities and their relation to clinical characteristics and cardiac symptoms in a large, contemporary cohort of patients with type 2 diabetes. A total of 1030 patients with type 2 diabetes participated. Echocardiographic abnormalities were present in 513 (49.8%) patients, mainly driven by a high prevalence of diastolic dysfunction 178 (19.4%), left ventricular hypertrophy 213 (21.0%) and left atrial enlargement, 200 (19.6%). The prevalence increased markedly with age from 31.1% in the youngest group (<55 years) to 73.9% in the oldest group (>75 years) (p < 0.001) and was equally distributed among the sexes (p = 0.76). In univariate analyses, electrocardiographic abnormalities, age, body mass index, known coronary heart disease, hypertension, albuminuria, diabetes duration and creatinine were associated with abnormal echocardiography along with dyspnoea and characteristic chest pain (p < 0.05 for all). Neither...

European heart journal. Acute cardiovascular care, Jan 10, 2016

Rheumatologic disorders are characterised by inflammation and an increased risk of coronary arter... more Rheumatologic disorders are characterised by inflammation and an increased risk of coronary artery disease (CAD). However, the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing percutaneous coronary intervention (PCI) is unknown. Thus, we aimed to examine the association between rheumatologic disorders and long-term prognosis in CAD patients undergoing PCI. A post-hoc analysis was performed in 4605 patients (age: 63.3 ± 11.0 years; male: 76.6%) with ST-segment elevation myocardial infarction (STEMI; n = 1396), non-STEMI (n = 1541), and stable CAD (n = 1668) from the all-comer stent trials, the BAsel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination (BASKET-PROVE) I and II trials. We evaluated the association between rheumatologic disorders and 2-year major adverse cardiac events (MACEs; cardiac death, nonfatal myocardial infarction (MI), and target vessel revascularisation (TVR)) by Cox regression analysis. Patients with...

Circulation, Jan 14, 2016

-Asymptomatic individuals account for a majority of sudden cardiac deaths (SCDs). Development of ... more -Asymptomatic individuals account for a majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and non-invasive SCD risk stratification tools are necessary. -Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20,177; age 59.3±10.1 years; age range 44-100; 56% female; 77% white) were followed for 14.0 years (median). Five ECG markers of global electrical heterogeneity (GEH) (sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient (SVG) magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH ECG parameters and SCD. A SCD competing risks score was derived using demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1,000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes, hypertension, coronary heart disease, and stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C-statistic increased from 0.777 to 0.790 (p=0.008), the risk score classified 10-year SCD risk as high (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high- to intermediate-risk. Net reclassification index was 18.3%. -Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. Addition of GEH parameters to clinical characteristics improves SCD risk prediction.

Cardiorenal Medicine, 2016

Journal of the American College of Cardiology, 2016

Future Cardiology, 2016

It is often difficult to provide an exact echocardiographic measure of left ventricular systolic ... more It is often difficult to provide an exact echocardiographic measure of left ventricular systolic function in patients with atrial fibrillation, partly because of the varying cycle length affecting pre and afterload and partly because of the increased heart rate often accompanying this arrhythmia. We sought to elucidate two points: whether it would be possible to correct for the cyclic variance in systolic output, and if global longitudinal strain is preferable to the left ventricular ejection fraction at evaluating systolic function during atrial fibrillation.

Journal of the American Heart Association, 2016

We hypothesized that the cardiac time intervals reveal reduced myocardial function in persons wit... more We hypothesized that the cardiac time intervals reveal reduced myocardial function in persons with hypertension and are strong predictors of future ischemic cardiovascular diseases in the general population. In a large community-based population study, cardiac function was evaluated in 1915 participants by using both conventional echocardiography and tissue Doppler imaging (TDI). The cardiac time intervals, including the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET), were obtained by TDI M-mode through the mitral leaflet. IVCT/ET, IVRT/ET, and myocardial performance index [MPI=(IVRT+IVCT)/ET] were calculated. After multivariable adjustment for clinical variables the IVRT, IVRT/ET, and MPI, remained significantly impaired in persons with hypertension (n=826) compared with participants without hypertension (n=1082). Additionally, they displayed a significant dose-response relationship, between increasing severity of elevated blood pressure and increasing left ventricular mass index (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001 for all). Further, during follow-up of a median of 10.7 years, 435 had an ischemic cardiovascular disease (ischemic heart disease, peripheral arterial disease, or stroke). The IVRT/ET and MPI were powerful and independent predictors of future cardiovascular disease, especially in participants with known hypertension. They provide prognostic information incremental to clinical variables from the Framingham Risk Score, the SCORE risk chart, and the European Society of Hypertension/European Society of Cardiology risk chart. The cardiac time intervals identify impaired cardiac function in individuals with hypertension, not only independent of conventional risk factors but also in participants with a normal conventional echocardiographic examination. The IVRT/ET and MPI are independent predictors of future cardiovascular disease especially in participants with known hypertension.

The international journal of cardiovascular imaging, Jan 21, 2016

Cardiac time intervals (CTI) are prognostic above and beyond conventional echocardiographic measu... more Cardiac time intervals (CTI) are prognostic above and beyond conventional echocardiographic measures. The explanation may be that CTI contain information about both systolic and diastolic measures; this is, however, unknown. The relationship between the CTI and systolic and diastolic function assessed by conventional, tissue Doppler (TDI) and speckle-tracking echocardiography (STE) was investigated. CTI and echocardiographic measurements, including conventional, STE, and TDI echocardiography, were studied in 1088 type 1 diabetes patients without known heart disease randomly selected from the out-patient clinic at Steno Diabetes Center. The CTI were obtained by TDI M-mode through the mitral leaflet and included the isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and the myocardial performance index (MPI = (IVRT + IVCT)/ejection time). Standardized beta-values were assessed. Both systolic and diastolic measures associated with CTI. Conventional measures: left ve...

Circulation. Cardiovascular imaging, 2015