The plasma proteome is linked with left ventricular and left atrial function parameters in patients with chronic heart failure.

BACKGROUND: Examining the systemic biological processes in the heterogeneous syndrome of heart failure with reduced ejection fraction (HFrEF), as reflected by circulating proteins, in relation to echocardiographic characteristics, may provide insights into HF pathophysiology. OBJECTIVE: We investigated the link of 4210 repeatedly measured circulating proteins with repeatedly measured echocardiographic parameters, as well as with elevated left atrial pressure (LAP), in HFrEF patients, to provide insights into underlying mechanisms. METHODS: In 173 HFrEF patients, we performed six-monthly echocardiography and trimonthly blood sampling during a median follow-up of 2.7(IQR:2.5-2.8) years. We investigated circulating proteins in relation to echocardiographic parameters of left ventricular (left ventricular ejection fraction[LVEF], global longitudinal strain[GLS]), and left atrial function (left atrial reservoir strain[LASr]) and elevated LAP(E/e' ratio >15), and used gene enrichment analyses to identify underlying pathophysiological processes. RESULTS: We found 723, 249, 792 and 427 repeatedly measured proteins, with significant associations with LVEF, GLS, LASr and E/e' ratio, respectively. Proteins associated with LASr reflected pathophysiological mechanisms mostly related to the extracellular matrix (ECM). Proteins associated with GLS reflected cardiovascular biological processes and diseases, whereas those associated with LVEF reflected processes involved in the sympathetic nervous system. Moreover, 49 proteins were associated with elevated LAP; after correction for LVEF, three proteins remained: Cystatin-D, Fibulin-5 and HSP40. CONCLUSION: Circulating proteins show varying associations with different echocardiographic parameters in HFrEF patients. These findings suggest that pathways involved in atrial and ventricular dysfunction, as reflected by the plasma proteome, are distinct.

Prognostic value of temporal patterns of left atrial reservoir strain in patients with heart failure with reduced ejection fraction.

BACKGROUND: We investigated whether repeatedly measured left atrial reservoir strain (LASr) in heart failure with reduced ejection fraction (HFrEF) patients provides incremental prognostic value over a single baseline LASr value, and whether temporal patterns of LASr provide incremental prognostic value over temporal patterns of other echocardiographic markers and NT-proBNP. METHODS: In this prospective observational study, 153 patients underwent 6-monthly echocardiography, during a median follow-up of 2.5 years. Speckle tracking echocardiography was used to measure LASr. Hazard ratios (HRs) were calculated for LASr from Cox models (baseline) and joint models (repeated measurements). The primary endpoint (PEP) comprised HF hospitalization, left ventricular assist device, heart transplantation, and cardiovascular death. RESULTS: Mean age was 58 ± 11 years, 76% were men, 82% were in NYHA class I/II, mean LASr was 20.9% ± 11.3%, and mean LVEF was 29% ± 10%. PEP was reached by 50 patients. Baseline and repeated measurements of LASr (HR per SD change (95% CI) 0.20 (0.10-0.41) and (0.13 (0.10-0.29), respectively) were both significantly associated with the PEP, independent of both baseline and repeated measurements of other echo-parameters and NT-proBNP. Although LASr was persistently lower over time in patients with PEP, temporal trajectories did not diverge in patients with versus without the PEP as the PEP approached. CONCLUSION: LASr was associated with adverse events in HFrEF patients, independent of baseline and repeated other echo-parameters and NT-proBNP. Temporal trajectories of LASr showed decreased but stable values in patients with the PEP, and do not provide incremental prognostic value for clinical practice compared to single measurements of LASr.

Endovascular renal sympathetic denervation to improve heart failure with reduced ejection fraction: the IMPROVE-HF-I study.

INTRODUCTION: The aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: We randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I­MIBG) heart-to-mediastinum ratio (HMR) at 6 months. RESULTS: Mean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was -0.02 (95% CI: -0.08 to 0.12) in the RDN group, versus -0.02 (95% CI: -0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: -6.35 to 1.67) in the RDN group versus -2.59 (95% CI: -1.61 to 6.79) in the OMT group (p-value 0.09). CONCLUSION: RDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I­MIBG.

P1138Cardiac shear wave velocity in healthy individuals.

BACKGROUND: The closure of the valves generates shear waves in the heart walls. The propagation velocity of shear waves relates to stiffness. This could potentially be used to estimate the stiffness of the myocardium, with huge potential implications in pathologies characterized by a deterioration of the diastolic properties of the left ventricle. In an earlier phantom study we already validated shear wave tracking with a clinical ultrasound system in cardiac mode. PURPOSE: In this study we aimed to measure the shear waves velocity in normal individuals. METHODS: 12 healthy volunteers, mean age=37±10, 33% females, were investigated using a clinical scanner (Philips iE33), equipped with a S5-1 probe, using a clinical tissue Doppler (TDI) application. ECG and phonocardiogram (PCG) were synchronously recorded. We achieved a TDI frame rate of >500Hz by carefully tuning normal system settings. Data were processed offline in Philips Qlab 8 to extract tissue velocity along a virtual M-mode line in the basal third of the interventricular septum, in parasternal long axis view. This tissue velocity showed a propagating wave pattern after closure of the valves. The slope of the wave front velocity in a space-time panel was measured to obtain the shear wave propagation velocity. The velocity of the shear waves induced by the closure of the mitral valve (1st heart sound) and aortic valve (2nd heart sound) was averaged over 4 heartbeats for every subject. RESULTS: Shear waves were visible after each closure of the heart valves, synchronous to the heart sounds. The figure shows one heart cycle of a subject, with the mean velocity along a virtual M-mode line in the upper panel, synchronous to the ECG signal (green line) and phonocardiogram (yellow line) in the lower panel. The slope of the shear waves is marked with dotted lines and the onset of the heart sounds with white lines. In our healthy volunteer group the mean velocity of the shear wave induced by mitral valve closure was 4.8±0.7m/s, standard error of 0.14 m/s. The mean velocity after aortic valve closure was 3.4±0.5m/s, standard error of 0.09 m/s. We consistently found that for any subject the velocity after mitral valve closure was higher than after aortic valve closure. CONCLUSION: The velocity of the shear waves generated by the closure of the heart valves can be measured in normal individuals using a clinical TDI application. The shear wave induced after mitral valve closure was consistently faster than after aortic valve closure. Abstract P1138 Figure.Abstract P1138 Figure.

Contrast echocardiography: mechanism of action, safety and clinical applications.

Since its initial description by Gramiak and Shah in 1968, contrast echocardiography has become an established practice world-wide. Microbubbles have the unique property of being pure intravascular tracers. The basic rationale behind bubble imaging is the characteristic responses to ultrasound power that results in enhanced ultrasound images from the blood pool. Therefore, whenever there is blood pool there is a potential application for contrast ultrasound. Clinical applications of contrast echocardiography have been vastly grown from diagnostic applications such as detection of a persistent foramen ovale to drug delivery. This article reviews the mechanism of action, safety and clinical applications of contrast echocardiography.

Influence of the pattern of hypertrophy on left ventricular twist in hypertrophic cardiomyopathy.

BACKGROUND/OBJECTIVE: Left ventricular (LV) twist has an important role in LV function. The influence of the pattern of LV hypertrophy on LV twist in hypertrophic cardiomyopathy (HCM) patients is unknown. This study sought to assess LV twist in a large group of HCM patients according to the pattern of LV hypertrophy. METHODS: The final study population consisted of 43 patients with HCM (mean age 43 (15) years, 31 men) and a typical sigmoidal (n = 16) or reverse septal curvature (n = 27) and 43 age-matched and gender-matched healthy control subjects. LV peak systolic rotation (Rot(max)), LV peak systolic twist (Twist(max)) and untwisting at 5%, 10% and 15% of diastole were determined by speckle tracking echocardiography (STE). RESULTS: Compared to control subjects, HCM patients had increased basal Rot(max) (-5.5 degrees (2.3 degrees ) vs -3.4 degrees (1.7 degrees ), p<0.001) and comparable apical Rot(max) (7.3 degrees (3.1 degrees ) vs 7.0 degrees (2.2 degrees ), p = NS), resulting in increased Twist(max) (12.4 degrees (4.0 degrees ) vs 9.9 degrees (2.7 degrees ), p<0.01). Untwisting at 5%, 10% and 15% of diastole was decreased in HCM patients (all p<0.05). There was a striking difference in apical Rot(max )(9.4 degrees (2.8 degrees ) vs 6.0 degrees (2.6 degrees ), p<0.01) and Twist(max) (15.3 degrees (3.2 degrees ) vs 10.6 degrees (3.3 degrees ), p<0.01) between HCM patients with a sigmoidal and reverse septal curvature. CONCLUSIONS: STE may provide novel non-invasive indices to assess LV function in patients with HCM. Apical Rot(max) and Twist(max) in HCM patients are dependent on the pattern of LV hypertrophy.

Cardiac involvement in adults with Pompe disease.

BACKGROUND: Glycogen storage disease type II or Pompe disease is a neuromuscular disorder caused by deficiency of lysosomal acid alpha- glucosidase. Classic infantile Pompe disease results in massive left ventricular (LV) hypertrophy and failure. Although Pompe disease is often included in the differential diagnosis of LV hypertrophy the true frequency of cardiac involvement in adults with Pompe disease is not known. METHODS: Forty-six consecutive adult patients (mean age 48 +/- 12, 22 men) with Pompe disease were included. Each patient underwent a clinical examination, electrocardiography, and rest and low-dose dobutamine (in 20 patients) two-dimensional echocardiography including contrast and tissue Doppler imaging. RESULTS: All patients had limited exercise tolerance; a rollator walking aid was used in seven patients (15%), a wheelchair in 13 patients (28%), and assisted ventilation in 14 patients (30%). Prior to this study, one patient was known with permanent atrial fibrillation, His-bundle ablation and a VVI pacemaker and another patient was known with fluid retention. The first patient had increased LV end-diastolic diameter, impaired LV ejection fraction, low systolic mitral annular velocities and diastolic dysfunction grade II. The patient with fluid retention was wheelchair bound and dependent on 24-h assisted ventilation and showed right ventricular and LV hypertrophy (septum 16 mm, posterior wall 15 mm). LV hypertrophy was not seen in any of the other patients. One woman of advanced age had isolated low systolic mitral annular velocities. Mean global systolic LV function, including contractile reserve, was not decreased in patients with Pompe disease. Eight patients (17%) had mild diastolic dysfunction grade I, related to hypertension in four and advanced age in seven. CONCLUSIONS: In adult patients with Pompe disease without objective signs of cardiac affection by 12-leads electrocardiography or physical examination, echocardiographic screening for LV hypertrophy seems not effective.