Peter Godsk Jørgensen

Global Longitudinal Strain Is a Superior Predictor of All-Cause Mortality in Heart Failure With Reduced Ejection Fraction

OBJECTIVES The purpose of this study was to investigate the prognostic value of global longitudinal strain (GLS) in heart failure with reduced ejection fraction (HFrEF) patients in relation to all-cause mortality. BACKGROUND Measurement of myocardial deformation by 2-dimensional speckle tracking echocardiography, specifically GLS, may be superior to conventional echocardiographic parameters, including left ventricular ejection fraction, in predicting all-cause mortality in HFrEF patients. METHODS Transthoracic echocardiographic examinations were retrieved for 1,065 HFrEF patients admitted to a heart failure clinic. The echocardiographic images were analyzed, and conventional and novel echocardiographic parameters were obtained. RESULTS Many of the conventional echocardiographic parameters proved to be predictors of mortality. However, GLS remained an independent predictor of mortality in the multivariable model after adjusting for age, sex, body mass index, total cholesterol, mean arterial pressure, heart rate, ischemic cardiomyopathy, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, noninsulin dependent diabetes mellitus, and conventional echocardiographic parameters (hazard ratio [HR]: 1.15; 95% confidence interval [CI]: 1.04 to 1.27; p = 0.008, per 1% decrease). No other echocardiographic parameter remained an independent predictor after adjusting for these variables. Furthermore, GLS had the highest C-statistics of all the echocardiographic parameters and added incremental prognostic value with a significant increase in the net reclassification improvement (p = 0.009). Atrial fibrillation (AF) modified the relationship between GLS and mortality (p value for interaction = 0.036); HR: 1.08 (95% CI: 0.97 to 1.19), p = 0.150 and HR: 1.22 (95% CI: 1.15 to 1.29), p < 0.001, per 1% decrease in GLS for patients with and without AF, respectively. Sex also modified the relationship between GLS and mortality (p value for interaction = 0.047); HR: 1.23 (95% CI: 1.16 to 1.30), p < 0.001 and HR: 1.09 (95% CI: 0.99 to 1.20), p = 0.083, per 1% decrease in GLS for men and women, respectively. CONCLUSIONS GLS is an independent predictor of all-cause mortality in HFrEF patients, especially in male patients without AF. Furthermore, GLS was a superior prognosticator compared with all other echocardiographic parameters.

Prognostic value of cardiac time intervals by tissue Doppler imaging M-mode in patients with acute ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention.

Background— Color tissue Doppler imaging M-mode through the mitral leaflet is an easy and precise method to estimate all cardiac time intervals from 1 cardiac cycle and thereby obtain the myocardial performance index (MPI). However, the prognostic value of the cardiac time intervals and the MPI assessed by color tissue Doppler imaging M-mode through the mitral leaflet in patients with ST-segment–elevation myocardial infarction (MI) is unknown. Methods and Results— In total, 391 patients were admitted with an ST-segment–elevation MI, treated with primary percutaneous coronary intervention, and examined by echocardiography a median of 2 days after the ST-segment–elevation MI. Outcome was assessed according to death (n=33), hospitalization with heart failure (n=53), or new MI (n=25). Follow-up time was a median of 25 months. The population was stratified according to tertiles of the MPI. The risk of new MI, being admitted with congestive heart failure or death, increased with increasing tertile of MPI, being ≈3 times as high for the third tertile compared with the first tertile (hazard ratio, 2.8; 95% confidence interval, 1.7–4.7; P<0.001). MPI provided independent prognostic information in a multivariable Cox regression model adjusted for age, sex, previous MI, peak troponin, and systolic and diastolic echocardiographic parameters, with a hazard ratio of 1.24 (P=0.005) for the combined end point per each 0.1 increase in MPI. Conclusions— MPI assessed by tissue Doppler imaging M-mode is a simple and reproducible measure that provides independent prognostic information, regardless of rhythm, incremental to conventional and novel echocardiographic parameters of systolic and diastolic function in patients with ST-segment–elevation MI treated with primary percutaneous coronary intervention.

Global Longitudinal Strain by Echocardiography Predicts Long-Term Risk of Cardiovascular Morbidity and Mortality in a Low-Risk General PopulationCLINICAL PERSPECTIVE: The Copenhagen City Heart Study

Background— Global longitudinal strain (GLS) is prognostic of adverse cardiovascular outcomes in various patient populations, but the prognostic utility of GLS for long-term cardiovascular morbidity and mortality in the general population is unknown. Methods and Results— A total of 1296 participants in a general population study underwent a health examination, including echocardiography measurement of GLS. The primary end point was the composite of incident heart failure, acute myocardial infarction, or cardiovascular death. During a median follow-up of 11 years, 149 (12%) participants were diagnosed with heart failure, acute myocardial infarction, or cardiovascular death. Lower GLS was associated with a higher risk of the composite end point (hazard ratio, 1.12; 95% confidence interval, 1.08–1.17; P<0.001 per 1% decrease), an association that persisted after multivariable adjustment for age, sex, heart rate, hypertension, systolic blood pressure, left ventricular ejection fraction, left ventricular mass index, left ventricular dimension, deceleration time, left atrium dimension, E/e′, and pro B-type natriuretic peptide (hazard ratio, 1.05; 95% confidence interval, 1.00–1.11; P=0.045 per 1% decrease). GLS provided incremental prognostic information beyond the Framingham Risk Score, the Systemic Coronary Evaluation risk chart, and the modified American College of Cardiology/American Heart Association Pooled Cohort Equation for the composite outcome and incident heart failure. Sex modified the relationship between GLS and outcome such that after multivariable adjustment, GLS was an independent predictor of outcomes in men but not in women (hazard ratio, 1.14; 95% confidence interval, 1.06–1.24; P=0.001, and hazard ratio, 0.99; 95% confidence interval, 0.92–1.07; P=0.81, respectively; P for interaction =0.032). Conclusions— In the general population, GLS provides independent and incremental prognostic information regarding long-term risk of cardiovascular morbidity and mortality. GLS seems to be a stronger prognosticator in men than in women.

Abnormal echocardiography in patients with type 2 diabetes and relation to symptoms and clinical characteristics

Objectives: 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. Results: 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 of the cardiac symptoms nor clinical characteristics had sufficient sensitivity and specificity to accurately identify patients with abnormal echocardiography. Conclusion: Echocardiographic abnormalities are very common in outpatients with type 2 diabetes, but neither cardiac symptoms nor clinical characteristics are effective to identify patients with echocardiographic abnormalities.

Low cardiac output as physiological phenomenon in hibernating, free-ranging Scandinavian brown bears (Ursus arctos) - an observational study

BackgroundDespite 5-7 months of physical inactivity during hibernation, brown bears (Ursus arctos) are able to cope with physiological conditions that would be detrimental to humans. During hibernation, the tissue metabolic demands fall to 25% of the active state. Our objective was to assess cardiac function associated with metabolic depression in the hibernating vs. active states in free-ranging Scandinavian brown bears.MethodsWe performed echocardiography on seven free-ranging brown bears in Dalarna, Sweden, anesthetized with medetomidine-zolazepam-tiletamine-ketamine during winter hibernation in February 2013 and with medetomidine-zolazepam-tiletamine during active state in June 2013. We measured cardiac output noninvasively using estimates of hemodynamics obtained by pulsed wave Doppler echocardiography and 2D imaging. Comparisons were made using paired T-tests.ResultsDuring hibernation, all hemodynamic indices were significantly decreased (hibernating vs. active state): mean heart rate was 26.0 (standard deviation (SD): 5.6) beats per min vs. 75.0 (SD: 17.1) per min (P = 0.002), mean stroke volume 32.3 (SD: 5.2) ml vs. 47.1 (SD: 7.9) ml (P = 0.008), mean cardiac output 0.86 (SD: 0.31) l/min vs. 3.54 (SD: 1.04) l/min (P = 0.003), and mean cardiac index 0.63 (SD: 0.21) l/min/kg vs. 2.45 (SD: 0.52) l/min/ m2 (P < 0.001). Spontaneous echo contrast was present in all cardiac chambers in all seven bears during hibernation, despite the absence of atrial arrhythmias and valvular disease.ConclusionFree-ranging brown bears demonstrate hemodynamics comparable to humans during active state, whereas during hibernation, we documented extremely low-flow hemodynamics. Understanding these physiological changes in bears may help to gain insight into the mechanisms of cardiogenic shock and heart failure in humans.

Impact of type 2 diabetes and duration of type 2 diabetes on cardiac structure and function

BACKGROUND 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. METHODS 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. RESULTS 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 eseptal (mean: 6.9 (SD: 1.9) cm/s vs. 7.5 (2.4); P<0.001) and E/eseptal (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). CONCLUSIONS 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.

Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes.

To investigate the effects of exercise in combination with a glucagon‐like peptide‐1 receptor agonist (GLP‐1RA), liraglutide, or placebo for the treatment of type 2 diabetes.

Long-term outcomes in patients with rheumatologic disorders undergoing percutaneous coronary intervention: a BAsel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination (BASKET-PROVE) sub-study.

Aims: 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. Methods and results: 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 rheumatologic disorders (n = 197) were older, more often female, had a higher prevalence of renal disease, multi-vessel coronary disease, and bifurcation lesions, and had longer total stent lengths. During the 2-year follow-up, the MACE rate was 8.6% in the total cohort. After adjustment for potential confounders, rheumatologic disorders were associated with MACEs in the total cohort (adjusted hazard ratio: 1.55; 95% confidence interval (CI): 1.04–2.31) driven by the STEMI subgroup (adjusted hazard ratio: 2.38; 95% CI: 1.26–4.51). In all patients, rheumatologic disorders were associated with all-cause death (adjusted hazard ratio: 2.05; 95% CI: 1.14–3.70), cardiac death (adjusted hazard ratio: 2.63; 95% CI: 1.27–5.43), and non-fatal MI (adjusted hazard ratio: 2.64; 95% CI: 1.36–5.13), but not with TVR (adjusted hazard ratio: 0.81; 95% CI: 0.41–1.58). Conclusions: The presence of rheumatologic disorders appears to be independently associated with worse outcome in CAD patients undergoing PCI. This calls for further studies and focus on this high-risk group of patients following PCI.

Effect of exercise combined with glucagon‐like peptide‐1 receptor agonist treatment on cardiac function: A randomized double‐blind placebo‐controlled clinical trial

In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon‐like peptide‐1 (GLP‐1) receptor agonist (GLP‐1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP‐1RA liraglutide or placebo, combined with supervised exercise, in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (mean ± standard deviation [s.d.] −7.1 ± 1.6 to −7.7 ± 1.8 cm/s, P  = .01), but not in the liraglutide group (−7.1 ± 1.4 to −7.0 ± 1.4 cm/s, P  = .60; between groups, P  = .02). Similarly, the mean ± s.d. ratio of early and atrial mitral annular tissue velocities improved in the placebo group (1.0 ± 0.4 to 1.2 ± 0.4, P  = .003), but not in the liraglutide group (1.0 ± 0.3 to 1.0 ± 0.3, P  = .87; between groups, P  = .03). We found no significant differences in heart rate, left ventricular (LV) structure or function within or between the groups. In conclusion, the addition of liraglutide to exercise in sedentary patients with dysregulated type 2 diabetes may blunt the suggested beneficial effect of exercise on LV diastolic function.

Echocardiographic quantification of systolic function during atrial fibrillation: probing the 'ten heart cycles' rule

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.