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The prevalence of diabetic metabolic derangement (DMetD) has increased dramatically over the last decades. Although there is increasing evidence that DMetD is associated with cardiac dysfunction, the early DMetD-induced myocardial alterations remain incompletely understood. Here, we studied early DMetD-related cardiac changes in a clinically relevant large animal model. DMetD was established in adult male Göttingen miniswine by streptozotocin injections and a high-fat, high-sugar diet, while control animals remained on normal pig chow. Five months later left ventricular (LV) function was assessed by echocardiography and hemodynamic measurements, followed by comprehensive biochemical, molecular and histological analyses. Robust DMetD developed, evidenced by hyperglycemia, hypercholesterolemia and hypertriglyceridemia. DMetD resulted in altered LV nitroso-redox balance

Background: Elderly heart failure (HF) patients are underrepresented in clinical trials, though are a large proportion of patients in real-world practice. We investigated practice-based, secondary care HF management in a large group of chronic HF patients aged ≥ 80 years (octogenarians). Methods: We analyzed electronic health records of 3490 octogenarians with chronic HF at 34 Dutch outpatient clinics in the period between 2013 and 2016 , 49% women. Study patients were divided into HFpEF [LVEF ≥ 50%; n = 911 (26.1%)], HFrEF [LVEF < 40%; n = 2009 (57.6%)] and HF with mid-range EF [HFmrEF: LVEF 40–49%; n = 570 (16.3%)]. Results: Most HFrEF patients aged ≥ 80 years received a beta blocker and a renin–angiotensin system (RAS) inhibitor (angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker), i.e. 78.3% and 72.8% respectively, and a mineralocorticoid receptor antagonist (MRA) was prescribed in 52.0% of patients. All three of these guideline-recommended medications (triple therapy) were given in only 29.9% of octogenarians with HFrEF, and at least 50% of target doses of triple therapy, beta blockers, RAS inhibitor and MRA, were prescribed in 43.8%, 62.2% and 53.5% of the total group of HFrEF patients. Contraindications or intolerance for beta blockers was present in 3.5% of the patients, for RAS inhibitors and MRAs in, 7.2% and 6.1% Conclusions: The majority of octogenarians with HFrEF received one or more guideline-recommended HF medications. However, triple therapy or target doses of the medications were prescribed in a minority. Comorbidities and reported contraindications and tolerances did not fully explain underuse of recommended HF therapies. Graphic abstract: [Figure not available: see fulltext.].

Aims: Obesity doubles the lifetime risk of developing heart failure. Current knowledge on the role of obesity in causing cardiac dysfunction is insufficient for optimal risk stratification. The aim of this study was first to estimate the prevalence of subclinical cardiac dysfunction in obesity patients and second to investigate the underlying pathophysiology. Methods and results: The CARDIOBESE study is a cross-sectional multicentre study of 100 obesity patients [body mass index (BMI) ≥ 35 kg/m2] without known cardiovascular disease and 50 age-matched and gender-matched non-obese controls (BMI ≤ 30 kg/m2). Echocardiography was performed, blood samples were collected, and a Holter monitor was affixed. Fifty-nine obesity patients [48 (42–50) years, 70% female] showed subclinical cardiac dysfunction: 57 patients had decreased global longitudinal strain (GLS), and two patients with normal GLS had either diastolic dysfunction or increased brain natriuretic peptide (BNP). Only one non-obese control had diastolic dysfunction, and none had another sign of cardiac dysfunction. Multivariable logistic analysis identified male gender and standard deviation of all NN intervals (SDNN) index, which is a measure of autonomic dysfunction, as independent significant risk factors for subclinical cardiac dysfunction in obesity patients. Conclusions: There was a high prevalence (61%) of subclinical cardiac dysfunction in obesity patients without known cardiovascular disease, which appeared to be best identified by GLS. Subclinical cardiac dysfunction in obesity was linked to autonomic dysfunction and male gender, and not to the presence of traditional cardiac risk factors, increased C-reactive protein, increased BNP, increased high-sensitivity troponin I, or increased left ventricular mass.

Background: Despite a generally high specificity, electrocardiographic (ECG) criteria for the detection of left ventricular hypertrophy (LVH) lack sensitivity, particularly in obesity patients. Objectives: The aim of the study was to evaluate the accuracy of the most commonly used ECG criteria (Cornell voltage and Sokolow-Lyon index), the recently introduced Peguero-Lo Presti criteria and the correction of these criteria by body mass index (BMI) to detect LVH in obesity patients and to propose adjusted ECG criteria with optimal accuracy. Methods: The accuracy of the ECG criteria for the detection of LVH was retrospectively tested in a cohort of obesity patients referred for a transthoracic echocardiogram based on clinical grounds (test cohort, n = 167). Adjusted ECG criteria with optimal sensitivity for the detection of LVH were developed. Subsequently, the value of these criteria was prospectively tested in an obese population without known cardiovascular disease (validation cohort, n = 100). Results: Established ECG criteria had a poor sensitivity in obesity patients in both the test cohort and the validation cohort. The adjusted criteria showed improved sensitivity, with optimal values for males using the Cornell voltage corrected for BMI, (RaVL+SV3)*BMI ≥700 mm*kg/m2; sensitivity 47% test cohort, 40% validation cohort; for females, the Sokolow-Lyon index corrected for BMI, (SV1 + RV5/RV6)*BMI ≥885 mm*kg/m2; sensitivity 26% test cohort, 23% validation cohort. Conclusions: Established ECG criteria for the detection of LVH lack sufficient sensitivity in obesity patients. We propose new criteria for the detection of LVH in obesity

We apply a high frame rate (over 500 Hz) tissue Doppler method to measure the propagation velocity of naturally occurring shear waves (SW) generated by aortic and mitral valves closure. The aim of this work is to demonstrate clinical relevance. We included 45 healthy volunteers and 43 patients with hypertrophic cardiomyopathy (HCM). The mitral SW (4.68 ± 0.66 m/s) was consistently faster than the aortic (3.51 ± 0.38 m/s) in all volunteers (p < 0.0001). In HCM patients, SW velocity correlated with E/e’ ratio (r = 0.346, p = 0.04 for aortic SW and r = 0.667, p = 0.04 for mitral SW). A subgroup of 20 volunteers were matched for age and gender to 20 HCM patients. In HCM, the mean velocity of 5.1 ± 0.7 m/s for the aortic SW (3.61 ± 0.46 m/s in matched volunteers, p < 0.0001) and 6.88 ± 1.12 m/s for the mitral SW(4.65 ± 0.77 m/s in matched volunteers, p < 0.0001). A threshold of 4 m/s for the aortic SW correctly classified pathologic myocardium with a sensitivity of 95% and specificity of 90%. Naturally occurring SW can be used to assess differences between normal and pathologic myocardium.

Introduction In view of the increasing occurrence of both obesity and heart failure, a growing overlap of these two clinical entities in the near future is expected. Significant advances in our understanding of the pathophysiological consequences of obesity for the cardiovascular system have been made over the past two decades. However, to optimise management and treatment of obesity patients, further research is required to improve early identification of cardiac dysfunction in obesity and to gain insight in the underlying pathophysiology. The CARdiac Dysfunction In OBesity - Early Signs Evaluation (CARDIOBESE) study has been designed to address these issues. Methods and analysis CARDIOBESE is a cross-sectional multicentre study of 100 obesity patients scheduled for bariatric surgery (body mass index (BMI) ≥35 kg/m 2) without known cardiovascular disease, and 50 age-matched and gender-matched non-obese controls (BMI <30 kg/m 2). Echocardiography, blood and urine biomarkers and Holter monitoring will be used to identify parameters that are able to show cardiac dysfunction at a very early stage in obesity patients (primary objective). Furthermore, a prospective follow-up study of obesity patients before and 1 year after bariatric surgery will be done to gain insight in the pathophysiology of obesity causing cardiac dysfunction (secondary objective). Ethics and dissemination The study was approved by the Medical Ethics Committee Toetsingscommissie Wetenschappelijk Onderzoek Rotterdam e.o. (TWOR). Inclusion of patients and controls is almost complete. Analyses of the investigations are currently being performed, and dissemination through peer-reviewed publications and conference presentations is expected from the first quarter of 2019. By identifying early markers of cardiac dysfunction in obesity, and by understanding the underlying pathophysiology of the abnormalities of these markers, the CARDIOBESE study may provide guidance for risk stratification, monitoring and

Cardiac muscle stiffness can potentially be estimated non-invasively with shear wave elastography. Shear waves are present on the septal wall after mitral and aortic valve closure, thus providing an opportunity to assess stiffness in early systole and early diastole. We report on the shear wave recordings of 22 minipigs with high-frame-rate echocardiography. The waves were captured with 4000 frames/s using a programmable commercial ultrasound machine. The wave pattern was extracted from the data through a local tissue velocity estimator based on one-lag autocorrelation. The wave propagation velocity was determined with a normalized Radon transform, resulting in median wave propagation velocities of 2.2 m/s after mitral valve closure and 4.2 m/s after aortic valve closure. Overall the velocities ranged between 0.8 and 6.3 m/s in a 95% confidence interval. By dispersion analysis we found that the propagation velocity only mildly increased with shear wave frequency.

Background The echocardiographic focus to detect abnormalities in genetically hypertrophic cardiomyopathy (HCM) affected subjects without left ventricular (LV) hypertrophy (G+/LVH-) has been on diastolic abnormalities in transmitral flow and longitudinal myocardial function with tissue Doppler imaging. The aim of this study was to assess diastolic LV unstrain and untwist. Methods and results Forty-one consecutive genotyped family members of HCM patients (mean age 37611 years, 16 men) and 41 ageand gender-matched healthy volunteers underwent speckle-tracking echocardiography to measure untwist and unstrain. No significant differences between G+/LVH- and control subjects were seen in maximal systolic twist and global longitudinal strain. In diastole, the early peak untwist rate was significantly lower in G+/LVH- subjects compared with control subjects (62±19°s-1 vs. 76±30°s-1, P<0.05), whereas the late peak untwist rate tended to be higher. Untwist from maximal twist until the first 20% of diastole was delayed in G+/LVH- subjects (39.3612.9% vs. 51.3±15.6%, P<0.005). Late diastolic unstrain rate was significantly higher in G+/LVH- subjects in the inferoseptal wall (111±33 s-1 vs. 94±32 s-1, P=0.024), the inferolateral wall (105±42 vs. 75±35 s-1, P=0.007) and the anteroseptal wall (97±26 vs. 80±23 s-1, P=0.010). Unstrain from maximal twist until the first 20% of diastole was delayed in G+/LVH- subjects in the inferoseptal (18.9614.0% vs. 30.1±17.7%, P=0.005), inferolateral (27.1±16.3% vs. 39.2±18.0%, P=0.015) and anteroseptal (19.1±14.7% vs. 35.8±18.5%, P=0.0003) segments. Conclusions In mutation carriers, for HCM LV, untwist and unstrain are delayed and untwist rate

Objective: To assess the image quality of coronary CT angiography (CCTA) for suspected acute coronary syndrome (ACS) outside office hours. Methods: Patients with symptoms suggestive of an ACS underwent CCTA at the emergency department 24 hours, 7 days a week. A total of 118 patients, of whom 89 (75 %) presented during office hours (weekdays between 07:00 and 17:00) and 29 (25 %) outside office hours (weekdays between 17:00 and 07:00, weekends and holidays) underwent CCTA. Image quality was evaluated per coronary segment by two experienced readers and graded on an ordinal scale ranging from 1 to 3. Results: There were no significant differences in acquisition parameters, beta-blocker administration or heart rate between patients presenting during office hours and outside office hours. The median quality score per patient was 30.5 [interquartile range 26.0–33.5] for patients presenting during office hours in comparison to 27.5 [19.75–32.0] for patients presenting outside office hours (p=0.043). The number of non-evaluable segments was lower for patients presenting during office hours (0 [0–1.0] vs. 1.0 [0–4.0], p=0.009). Conclusion: Image quality of CCTA outside office hours in the diagnosis of suspected ACS is diminished. Key Points: • Quality scores were higher for coronary-CTA during office hours.• There were no differences in acquisition parameters.• There was a non-significant trend towards higher heart rates outside office hours.• Coronary-CTA on the ED requires state-of-the-art scanner technology and sufficiently trained staff.• Coronary-CTA on the ED needs preparation time and optimisation of

Background: Speckle tracking echocardiography (STE) is an echocardiography modality that is able to measure left ventricular (LV) characteristics, including rotation, strain and strain rate. Strain measures myocardial fibre contraction and relaxation. This study aims to assess the effect of renal sympathetic denervation (RDN) on functional myocardial parameters, including STE, and to identify potential differences between responders and non-responders. Methods: The study population consisted of 31 consecutive patients undergoing RDN in the context of treatment for resistant hypertension. Patients were included between December 2012 and June 2014. Transthoracic echocardiography and speckle tracking analysis was performed at baseline and at 6 months follow-up. Results: The study population consisted of 31 patients with treatment-resistant hypertension treated with RDN (mean age 64 ± 10 years, 15 men). The total study population could be divided into responders (n = 19) and non-responders (n = 12) following RDN. RDN reduced office blood pressure by 18.9 ± 26.8/8.5 ± 13.5 mmHg (p < 0.001). A significant decrease was seen in LV posterior wall thickness (LVPWd) (0.47 ± 1.0 mm; p = 0.020), without a significant change in the LV mass index (LVMI). In the total cohort, only peak late diastolic filling velocity (A-wave velocity) decreased significantly by 5.3 ± 13.2 cm/s (p = 0.044) and peak untwisting velocity decreased significantly by 14.5 ± 28.9°/s (p = 0.025). Conclusion: RDN reduced blood pressure and significantly improved functional myocardial parameters such as A-wave velocity and peak untwisting velocity in patients with treatment-resistant hypertension, suggesting a potential beneficial effect of RDN on myocardial mechanics.

The American Society of Echocardiography and European Association of Echocardiography (ASE/EAE) have published an algorithm for the grading of diastolic function. However, the ability to use this algorithm effectively in daily clinical practice has not been investigated. We hypothesized that in some patients it may be difficult to grade diastolic dysfunction with this scheme, since there may be discrepancies in the assessed parameters. The aim of the current study was to test the feasibility of the ASE/EAE algorithm and to compare this with a new Thoraxcenter (TXC) algorithm. The ASE/EAE and TXC algorithms were applied to 200 patients. The ASE/EAE algorithm starts with assessment of diastolic myocardial wall velocities and left atrial (LA) volumes with subsequent assessment of E/A ratio, E-wave deceleration time and pulmonary venous flow. The TXC algorithm reverses these steps, uses LA dimension instead of volume and does not include a Valsalva manoeuvre and pulmonary venous flow. Due to inconsistencies between diastolic myocardial wall velocities and LA volumes and a not covered E/A ratio in the range of 1.5–2 it was not possible to classify 48 % of patients with the ASE/EAE algorithm, as opposed to only 10 % by the TXC algorithm. LA volume was always needed in the ASE/EAE algorithm. In only 64 % of patients LA size was necessary by the TXC algorithm. When LA volume would have been used instead of LA dimension, grading of LV diastolic function would have been different in only 2 % of patients without apparent improvement. Assessment of LA dimension was considerably faster than LA volume. The TXC algorithm to grade LV diastolic dysfunction was compared to the ASE/EAE algorithm simpler, faster, better reproducible and yields a higher diagnostic outcome.

Background: Symptoms in the elderly patients with severe aortic stenosis (AS) and co-morbidities seem to lack in specificity. Therefore, objective parameters for increased left ventricular(LV) filling pressures are needed. The aim of this study was to investigate the correlation between the septal, lateral and average E/e' ratio and the value of the N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP). Methods: Two-hundred-fifty consecutive symptomatic patients (mean age 80 ± 8 years, 52 % men) with severe AS underwent transthoracic echocardiography and NT-proBNP measurement. Results: In the overall population the septal E/e' (r = 0,459, r2 = 0,21, P <0,0001), lateral E/e' (r = 0,322, r2 = 0,10, P <0,0001), and the average E/e' (r = 0,432, r2 = 0,18, P <0,0001) were all significantly correlated to NT-proBNP. After the exclusion of patients with confounders (more than mild aortic or mitral regurgitation, severe renal dysfunction, obesity or severe COPD) the septal E/e' (r = 0,584, r2 = 0,34, P <0,0001), lateral E/e' (r = 0,377, r2 = 0,14, P <0,0001), and the average E/e' (r = 0,487, r2 = 0,24, P <0,0001) were all significantly better correlated to NT-proBNP. In obese patients no significant correlations were seen. Previous bypass surgery did not alter the correlations. Conclusions: In elderly patients with severe symptomatic AS there is a significant correlation between the E/e' ratio and NT-proBNP, in particular after exclusion of confounders. The correlation was best for the septal E/e' ratio and was preserved in patients with a history of bypass surgery.

The dynamic interaction between subendocardial and subepicardial fibre helices in the left ventricle (LV) leads to a twisting deformation, which has an important role in LV function. This study sought to assess the influence of cardiac shape on LV twist in the normal and dilated human heart. The study comprised 45 dilated cardiomyopathy (DCM) patients and 60 for age- and gender-matched healthy volunteers. Speckle tracking echocardiography was used to determine basal and apical LV peak systolic rotation (Rotmax) and instantaneous LV peak systolic twist (Twistmax). LV sphericity index was calculated by dividing the LV maximal long-axis internal dimension by the maximal short-axis internal dimension at end-diastole. A parabolic relation between the sphericity index and apical Rotmaxor Twistmaxwas identified in the total study population (R2= 0.56 and R2= 0.54, respectively; both P < 0.001) and healthy volunteers (R2= 0.39 and R2= 0.25, respectively; both P < 0.001), whereas these relations were linear in DCM patients (R2= 0.40 and R2= 0.43, respectively; both P < 0.001). In a multivariate analysis, LV sphericity index was the strongest independent predictor of apical Rotmaxand Twistmax. In conclusion, LV apical rotation and twist are significantly influenced by LV configuration. Taking the important function of LV twist into account, this finding highlights the vital influence of cardiac shape on LV systolic function. Copyright

Left ventricular (LV) twist describes the instantaneous circumferential motion of the apex with respect to the base of the heart and has an important role in LV function. LV twist originates from the dynamic interaction between oppositely wound subepicardial and subendocardial myocardial fibres. The direction of LV twist is governed by the subepicardial fibres, mainly owing to their longer arm of movement. Recently, speckle tracking echocardiography has been introduced as a new method for angle-independent quantification of LV twist. The aim of the thesis was to investigate the acquisition of LF twist by speckle tracking echocardiography and the physiology and clinical application of LV twist. A more caudal transducer position, as compared to the standard transducer position, was associated with increased measured LV twist. Therefore, in each patient the most caudal available transducer position should be used. Assessment of LV twist by speckle tracking echocardiography appeared to be feasible in approximately two thirds of subjects and had a good intraobserver, interobserver and temporal reproducibility, allowing to study changes over time in LV twist in an individual patient. Several physiological aspects of LV twist were studied. Differences in the extent and timing of de-rotation at the LV apical level as compared to

The increasing number and proportion of aged individuals in the population warrants knowledge of normal physiological changes of left ventricular (LV) biomechanics with advancing age. LV twist describes the instantaneous circumferential motion of the apex with respect to the base of the heart and has an important role in LV ejection and filling. This study sought to investigate the biomechanics behind age-related changes in LV twist by determining a broad spectrum of LV rotation parameters in different age groups, using speckle tracking echocardiography (STE). The final study population consisted of 61 healthy volunteers (16-35 yr, n = 25; 36-55 yr, n = 23; 56-75 yr, n = 13; 31 men). LV peak systolic rotation during the isovolumic contraction phase (Rotearly), LV peak systolic rotation during ejection (Rotmax), instantaneous LV peak systolic twist (Twistmax), the time to Rotearly, Rotmax, and Twistmax, and rotational deformation delay (defined as the difference of time to basal Rotmaxand apical Rotmax) were determined by STE using QLAB Advanced Quantification Software (version 6.0; Philips, Best, The Netherlands). With increasing age, apical Rotmax(P < 0.05), time to apical Rotmax(P < 0.01), and Twistmax(P < 0.01) increased, whereas basal Rotearly(P < 0.001), time to basal Rotearly(P < 0.01), and rotational deformation delay (P < 0.05) decreased. Rotational deformation delay was significantly correlated to Twistmax(R2= 0.20, P < 0.05). In conclusion, Twistmaxincreased with aging, resulting from both increased apical Rotmaxand decreased rotational deformation delay between the apex and the base of the LV. This may explain the preservation of LV ejection fraction in the elderly. Copyright

Background: Noncompaction cardiomyopathy (NCCM) is a rare disorder with persistance of the embryonic pattern of myoarchitecture. NCCM is characterized by loosened, spongy myocardium associated with a high incidence of systolic and diastolic left ventricular (LV) dysfunction and heart failure (HF). It is known that LV dysfunction contributes to elevated left atrial (LA) and pulmonary vascular pressures, however atrial function has not been examined in NCCM. The objective of the present study was to assess LA systolic function characterized by LA ejection force (LAEF) in NCCM patients using real-time three-dimensional echocardiography (RT3DE) and to compare to control subjects. Methods: The study comprised 17 patients with an established diagnosis of NCCM and their results were compared to 17 healthy age-matched controls with no evidence of cardiovascular disease. Forty-one percent of NCCM patients were in NYHA functional class II/III HF. Previously proposed echocardiographic diagnostic criteria for NCCM were used. All patients underwent conventional two-dimensional echocardiography and RT3DE. LAEF was measured based on MA annulus diameter (LAEF3D-MAD) and area (LAEF3D-MAA) using RT3DE. Results: The presence and severity of mitral regurgitation were more frequent in NCCM patients than in control subjects. LV diameters and mitral annulus were significantly increased in NCCM patients. Compared with control subjects, both LAEF3D-MAD(3.8 ± 2.2 vs 2.3 ± 1.0 kdyne P < 0.05 and LAEF3D-MAA(12.7 ± 7.6 vs 4.9 ± 2.1 kdyne, P < 0.01) were significantly increased in NCCM patients. Conclusions: LAEF as a characteristic of LA systolic function is increased in NCC