Evaluation of left ventricular filling pressure by echocardiography in patients with atrial fibrillation.

BACKGROUND: Echocardiography is widely used to evaluate left ventricular (LV) diastolic function in patients suspected of heart failure. For patients in sinus rhythm, a combination of several echocardiographic parameters can differentiate between normal and elevated LV filling pressure with good accuracy. However, there is no established echocardiographic approach for the evaluation of LV filling pressure in patients with atrial fibrillation. The objective of the present study was to determine if a combination of several echocardiographic and clinical parameters may be used to evaluate LV filling pressure in patients with atrial fibrillation. RESULTS: In a multicentre study of 148 atrial fibrillation patients, several echocardiographic parameters were tested against invasively measured LV filling pressure as the reference method. No single parameter had sufficiently strong association with LV filling pressure to be recommended for clinical use. Based on univariate regression analysis in the present study, and evidence from existing literature, we developed a two-step algorithm for differentiation between normal and elevated LV filling pressure, defining values ≥ 15 mmHg as elevated. The parameters in the first step included the ratio between mitral early flow velocity and septal mitral annular velocity (septal E/e'), mitral E velocity, deceleration time of E, and peak tricuspid regurgitation velocity. Patients who could not be classified in the first step were tested in a second step by applying supplementary parameters, which included left atrial reservoir strain, pulmonary venous systolic/diastolic velocity ratio, and body mass index. This two-step algorithm classified patients as having either normal or elevated LV filling pressure with 75% accuracy and with 85% feasibility. Accuracy in EF ≥ 50% and EF < 50% was similar (75% and 76%). CONCLUSIONS: In patients with atrial fibrillation, no single echocardiographic parameter was sufficiently reliable to be used clinically to identify elevated LV filling pressure. An algorithm that combined several echocardiographic parameters and body mass index, however, was able to classify patients as having normal or elevated LV filling pressure with moderate accuracy and high feasibility.

Mechanical Dyssynchrony Combined with Septal Scarring Reliably Identifies Responders to Cardiac Resynchronization Therapy.

Background and aim: The presence of mechanical dyssynchrony on echocardiography is associated with reverse remodelling and decreased mortality after cardiac resynchronization therapy (CRT). Contrarily, myocardial scar reduces the effect of CRT. This study investigated how well a combined assessment of different markers of mechanical dyssynchrony and scarring identifies CRT responders. Methods: In a prospective multicentre study of 170 CRT recipients, septal flash (SF), apical rocking (ApRock), systolic stretch index (SSI), and lateral-to-septal (LW-S) work differences were assessed using echocardiography. Myocardial scarring was quantified using cardiac magnetic resonance imaging (CMR) or excluded based on a coronary angiogram and clinical history. The primary endpoint was a CRT response, defined as a ≥15% reduction in LV end-systolic volume 12 months after implantation. The secondary endpoint was time-to-death. Results: The combined assessment of mechanical dyssynchrony and septal scarring showed AUCs ranging between 0.81 (95%CI: 0.74-0.88) and 0.86 (95%CI: 0.79-0.91) for predicting a CRT response, without significant differences between the markers, but significantly higher than mechanical dyssynchrony alone. QRS morphology, QRS duration, and LV ejection fraction were not superior in their prediction. Predictive power was similar in the subgroups of patients with ischemic cardiomyopathy. The combined assessments significantly predicted all-cause mortality at 44 ± 13 months after CRT with a hazard ratio ranging from 0.28 (95%CI: 0.12-0.67) to 0.20 (95%CI: 0.08-0.49). Conclusions: The combined assessment of mechanical dyssynchrony and septal scarring identified CRT responders with high predictive power. Both visual and quantitative markers were highly feasible and demonstrated similar results. This work demonstrates the value of imaging LV mechanics and scarring in CRT candidates, which can already be achieved in a clinical routine.

Automatic Detection of Aortic Valve Events Using Deep Neural Networks on Cardiac Signals From Epicardially Placed Accelerometer.

BACKGROUND: Miniaturized accelerometers incorporated in pacing leads attached to the myocardium, are used to monitor cardiac function. For this purpose functional indices must be extracted from the acceleration signal. A method that automatically detects the time of aortic valve opening (AVO) and aortic valve closure (AVC) will be helpful for such extraction. We tested if deep learning can be used to detect these valve events from epicardially attached accelerometers, using high fidelity pressure measurements to establish ground truth for these valve events. METHOD: A deep neural network consisting of a CNN, an RNN, and a multi-head attention module was trained and tested on 130 recordings from 19 canines and 159 recordings from 27 porcines covering different interventions. Due to limited data, nested cross-validation was used to assess the accuracy of the method. RESULT: The correct detection rates were 98.9% and 97.1% for AVO and AVC in canines and 98.2% and 96.7% in porcines when defining a correct detection as a prediction closer than 40 ms to the ground truth. The incorrect detection rates were 0.7% and 2.3% for AVO and AVC in canines and 1.1% and 2.3% in porcines. The mean absolute error between correct detections and their ground truth was 8.4 ms and 7.2 ms for AVO and AVC in canines, and 8.9 ms and 10.1 ms in porcines. CONCLUSION: Deep neural networks can be used on signals from epicardially attached accelerometers for robust and accurate detection of the opening and closing of the aortic valve.

Determinants of left atrial reservoir and pump strain and use of atrial strain for evaluation of left ventricular filling pressure.

AIMS: The aim of this study is to investigate determinants of left atrial (LA) reservoir and pump strain and if these parameters may serve as non-invasive markers of left ventricular (LV) filling pressure. METHODS AND RESULTS: In a multicentre study of 322 patients with cardiovascular disease of different aetiologies, LA strain and other echocardiographic parameters were compared with invasively measured LV filling pressure. The strongest determinants of LA reservoir and pump strain were LV global longitudinal strain (GLS) (r-values 0.64 and 0.51, respectively) and LV filling pressure (r-values -0.52 and -0.57, respectively). Left atrial volume was another independent, but weaker determinant of both LA strains. For both LA strains, association with LV filling pressure was strongest in patients with reduced LV ejection fraction. Left atrial reservoir strain <18% and LA pump strain <8% predicted elevated LV filling pressure better (P < 0.05) than LA volume and conventional Doppler parameters. Accuracy to identify elevated LV filling pressure was 75% for LA reservoir strain alone and 72% for pump strain alone. When combined with conventional parameters, accuracy was 82% for both LA strains. In patients with normal LV systolic function by GLS, LA pump strain >14% identified normal LV filling pressure with 92% accuracy. CONCLUSION: Left atrial reservoir and pump strain are determined predominantly by LV GLS and filling pressure. Accuracy of LA strains to identify elevated LV filling pressure was best in patients with reduced LV systolic function. High values of LA pump strain, however, identified normal LV filling pressure with good accuracy in patients with normal systolic function.

Postnatal development of the molecular complex underlying astrocyte polarization.

Astrocytes are highly polarised cells with processes that ensheath microvessels, cover the brain surface, and abut synapses. The endfoot membrane domains facing microvessels and pia are enriched with aquaporin-4 water channels (AQP4) and other members of the dystrophin associated protein complex (DAPC). Several lines of evidence show that loss of astrocyte polarization, defined by the loss of proteins that are normally enriched in astrocyte endfeet, is a common denominator of several neurological diseases such as mesial temporal lobe epilepsy, Alzheimer's disease, and stroke. Little is known about the mechanisms responsible for inducing astrocyte polarization in vivo. Here we introduce the term endfoot-basal lamina junctional complex (EBJC) to denote the proteins that consolidate and characterize the gliovascular interface. The present study was initiated in order to resolve the developmental profile of the EBJC in mouse brain. We show that the EBJC is established after the first week postnatally. Through a combination of methodological approaches, including light microscopic and high resolution immunogold cytochemistry, quantitative RT-PCR, and Western blotting, we demonstrate that the different members of this complex exhibit distinct ontogenic profiles­with the extracellular matrix (ECM) proteins laminin and agrin appearing earlier than the other members of the complex. Specifically, while laminin and agrin expression peak at P7, quantitative immunoblot analyses indicate that AQP4, α-syntrophin, and the inwardly rectifying K(+) channel Kir4.1 expression increases towards adulthood. Our findings are consistent with ECM having an instructive role in establishing astrocyte polarization in postnatal development and emphasize the need to explore the involvement of ECM in neurological disease.