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.

Cardiac Valve Event Timing in Echocardiography Using Deep Learning and Triplane Recordings.

Cardiac valve event timing plays a crucial role when conducting clinical measurements using echocardiography. However, established automated approaches are limited by the need of external electrocardiogram sensors, and manual measurements often rely on timing from different cardiac cycles. Recent methods have applied deep learning to cardiac timing, but they have mainly been restricted to only detecting two key time points, namely end-diastole (ED) and end-systole (ES). In this work, we propose a deep learning approach that leverages triplane recordings to enhance detection of valve events in echocardiography. Our method demonstrates improved performance detecting six different events, including valve events conventionally associated with ED and ES. Of all events, we achieve an average absolute frame difference (aFD) of maximum 1.4 frames (29 ms) for start of diastasis, down to 0.6 frames (12 ms) for mitral valve opening when performing a ten-fold cross-validation with test splits on triplane data from 240 patients. On an external independent test consisting of apical long-axis data from 180 other patients, the worst performing event detection had an aFD of 1.8 (30 ms). The proposed approach has the potential to significantly impact clinical practice by enabling more accurate, rapid and comprehensive event detection, leading to improved clinical measurements.

Non-invasive myocardial work in aortic stenosis: validation and improvement in left ventricular pressure estimation.

AIMS: The non-invasive myocardial work index (MWI) has been validated in patients without aortic stenosis (AS). A thorough assessment of methodological limitations is warranted before this index can be applied to patients with AS. METHODS AND RESULTS: We simultaneously measured left ventricular pressure (LVP) by using a micromanometer-tipped catheter and obtained echocardiograms in 20 patients with severe AS. We estimated LVP curves and calculated pressure-strain loops using three different models: (i) the model validated in patients without AS; (ii) the same model, but with pressure at the aortic valve opening (AVO) adjusted to diastolic cuff pressure; and (iii) a new model based on the invasive measurements from patients with AS. Valvular events were determined by echocardiography. Peak LVP was estimated as the sum of the mean aortic transvalvular gradient and systolic cuff pressure. In same-beat comparisons between invasive and estimated LVP curves, Model 1 significantly overestimated early systolic pressure by 61 ± 5 mmHg at AVO compared with Models 2 and 3. However, the average correlation coefficients between estimated and invasive LVP traces were excellent for all models, and the overestimation had limited influence on MWI, with excellent correlation (r = 0.98, P < 0.001) and good agreement between the MWI calculated with estimated (all models) and invasive LVP. CONCLUSION: This study confirms the validity of the non-invasive MWI in patients with AS. The accuracy of estimated LVP curves improved when matching AVO to the diastolic pressure in the original model, mirroring that of the AS-specific model. This may sequentially enhance the accuracy of regional MWI assessment.

Pulse arrival time variation as a non-invasive marker of acute response to cardiac resynchronization therapy.

AIMS: Successful cardiac resynchronization therapy (CRT) shortens the pre-ejection period (PEP) which is prolonged in the left bundle branch block (LBBB). In a combined animal and patient study, we investigated if changes in the pulse arrival time (PAT) could be used to measure acute changes in PEP during CRT implantation and hence be used to evaluate acute CRT response non-invasively and in real time. METHODS AND RESULTS: In six canines, a pulse transducer was attached to a lower limb and PAT was measured together with left ventricular (LV) pressure by micromanometer at baseline, after induction of LBBB and during biventricular pacing. Time-to-peak LV dP/dt (Td) was used as a surrogate for PEP. In twelve LBBB patients during implantation of CRT, LV and femoral pressures were measured at baseline and during five different pacing configurations. PAT increased from baseline (277 ± 9 ms) to LBBB (313 ± 16 ms, P < 0.05) and shortened with biventricular pacing (290 ± 16 ms, P < 0.05) in animals. There was a strong relationship between changes in PAT and Td in patients (r2 = 0.91). Two patients were classified as non-responders at 6 months follow-up. CRT decreased PAT from 320 ± 41 to 298 ± 39 ms (P < 0.05) in the responders, while PAT increased by 5 and 8 ms in the two non-responders. CONCLUSION: This proof-of-concept study indicates that PAT can be used as a simple, non-invasive method to assess the acute effects of CRT in real time with the potential to identify long-term response in patients.

Tracking Early Systolic Motion for Assessing Acute Response to Cardiac Resynchronization Therapy in Real Time.

An abnormal systolic motion is frequently observed in patients with left bundle branch block (LBBB), and it has been proposed as a predictor of response to cardiac resynchronization therapy (CRT). Our goal was to investigate if this motion can be monitored with miniaturized sensors feasible for clinical use to identify response to CRT in real time. Motion sensors were attached to the septum and the left ventricular (LV) lateral wall of eighteen anesthetized dogs. Recordings were performed during baseline, after induction of LBBB, and during biventricular pacing. The abnormal contraction pattern in LBBB was quantified by the septal flash index (SFI) equal to the early systolic shortening of the LV septal-to-lateral wall diameter divided by the maximum shortening achieved during ejection. In baseline, with normal electrical activation, there was limited early-systolic shortening and SFI was low (9 ± 8%). After induction of LBBB, this shortening and the SFI significantly increased (88 ± 34%, p < 0.001). Subsequently, CRT reduced it approximately back to baseline values (13 ± 13%, p < 0.001 vs. LBBB). The study showed the feasibility of using miniaturized sensors for continuous monitoring of the abnormal systolic motion of the LV in LBBB and how such sensors can be used to assess response to pacing in real time to guide CRT implantation.

A high-throughput study of visceral organs in CT-scanned pigs.

It has been debated whether intensive selection for growth and carcass yield in pig breeding programmes can affect the size of internal organs, and thereby reduce the animal's ability to handle stress and increase the risk of sudden deaths. To explore the respiratory and circulatory system in pigs, a deep learning based computational pipeline was built to extract the size of lungs and hearts from CT-scan images. This pipeline was applied on CT images from 11,000 boar selection candidates acquired during the last decade. Further, heart and lung volumes were analysed genetically and correlated with production traits. Both heart and lung volumes were heritable, with h2 estimated to 0.35 and 0.34, respectively, in Landrace, and 0.28 and 0.4 in Duroc. Both volumes were positively correlated with lean meat percentage, and lung volume was negatively genetically correlated with growth (rg = - 0.48 ± 0.07 for Landrace and rg = - 0.44 ± 0.07 for Duroc). The main findings suggest that the current pig breeding programs could, as an indirect response to selection, affect the size of hearts- and lungs. The presented methods can be used to monitor the development of internal organs in the future.

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.

Shortening of time-to-peak left ventricular pressure rise (Td) in cardiac resynchronization therapy.

AIMS: We tested the hypothesis that shortening of time-to-peak left ventricular pressure rise (Td) reflect resynchronization in an animal model and that Td measured in patients will be helpful to identify long-term volumetric responders [end-systolic volume (ESV) decrease >15%] in cardiac resynchronization therapy (CRT). METHODS: Td was analysed in an animal study (n = 12) of left bundle-branch block (LBBB) with extensive instrumentation to detect left ventricular myocardial deformation, electrical activation, and pressures during pacing. The sum of electrical delays from the onset of pacing to four intracardiac electrodes formed a synchronicity index (SI). Pacing was performed at baseline, with LBBB, right and left ventricular pacing and finally with biventricular pacing (BIVP). We then studied Td at baseline and with BIVP in a clinical observational study in 45 patients during the implantation of CRT and followed up for up to 88 months. RESULTS: We found a strong relationship between Td and SI in the animals (R = 0.84, P < 0.01). Td and SI increased from narrow QRS at baseline (Td = 95 ± 2 ms, SI = 141 ± 8 ms) to LBBB (Td = 125 ± 2 ms, SI = 247 ± 9 ms, P < 0.01), and shortened with biventricular pacing (BIVP) (Td = 113 ± 2 ms and SI = 192 ± 7 ms, P < 0.01). Prolongation of Td was associated with more wasted deformation during the preejection period (R = 0.77, P < 0.01). Six patients increased ESV by 2.5 ± 18%, while 37 responders (85%) had a mean ESV decrease of 40 ± 15% after more than 6 months of follow-up. Responders presented with a higher Td at baseline than non-responders (163 ± 26 ms vs. 121 ± 19 ms, P < 0.01). Td decreased to 156 ± 16 ms (P = 0.02) with CRT in responders, while in non-responders, Td increased to 148 ± 21 ms (P < 0.01). A decrease in Td with BIVP to values similar or below what was found at baseline accurately identified responders to therapy (AUC 0.98, P < 0.01). Td at baseline and change in Td from baseline was linear related to the decrease in ESV at follow-up. All-cause mortality was high among six non-responders (n = 4), while no patients died in the responder group during follow-up. CONCLUSIONS: Prolongation of Td is associated with cardiac dyssynchrony and more wasted deformation during the preejection period. Shortening of a prolonged Td with CRT in patients accurately identifies volumetric responders to CRT with incremental value on top of current guidelines and practices. Thus, Td carries the potential to become a biomarker to predict long-term volumetric response in CRT candidates.

Lateral Wall Dysfunction Signals Onset of Progressive Heart Failure in Left Bundle Branch Block.

OBJECTIVES: This study sought to investigate if contractile asymmetry between septum and left ventricular (LV) lateral wall drives heart failure development in patients with left bundle branch block (LBBB) and whether the presence of lateral wall dysfunction affects potential for recovery of LV function with cardiac resynchronization therapy (CRT). BACKGROUND: LBBB may induce or aggravate heart failure. Understanding the underlying mechanisms is important to optimize timing of CRT. METHODS: In 76 nonischemic patients with LBBB and 11 controls, we measured strain using speckle-tracking echocardiography and regional work using pressure-strain analysis. Patients with LBBB were stratified according to LV ejection fraction (EF) ≥50% (EFpreserved), 36% to 49% (EFmid), and ≤35% (EFlow). Sixty-four patients underwent CRT and were re-examined after 6 months. RESULTS: Septal work was successively reduced from controls, through EFpreserved, EFmid, and EFlow (all p < 0.005), and showed a strong correlation to left ventricular ejection fraction (LVEF; r = 0.84; p < 0.005). In contrast, LV lateral wall work was numerically increased in EFpreserved and EFmid versus controls, and did not significantly correlate with LVEF in these groups. In EFlow, however, LV lateral wall work was substantially reduced (p < 0.005). There was a moderate overall correlation between LV lateral wall work and LVEF (r = 0.58; p < 0.005). In CRT recipients, LVEF was normalized (≥50%) in 54% of patients with preserved LV lateral wall work, but only in 13% of patients with reduced LV lateral wall work (p < 0.005). CONCLUSIONS: In early stages, LBBB-induced heart failure is associated with impaired septal function but preserved lateral wall function. The advent of LV lateral wall dysfunction may be an optimal time-point for CRT.

Myocardial Strain Measured by Epicardial Transducers-Comparison Between Velocity Estimators.

This study describes results from an experimental ultrasound system with miniature transducers sutured directly onto the epicardial surface and used to measure heart contractions continuously. This system was used to find velocity distributions through the myocardium. The resulting velocities were used to track the motion of four layers at different depths through the myocardium and to find the regional strain in each of the four layers. Velocities inside the myocardium vary from the epicardial to the endocardial borders. Conventional velocity estimators based on Doppler and on time delay estimation were modified to better handle these variations. Results from four different velocity estimators were tested against a simulation model for ultrasound echoes from moving tissue and on ultrasound recordings from five animals. We observed that the tested velocity estimators were able to reproduce the myocardial velocity distributions, track the myocardial layer motion and estimate strain at different positions inside the myocardium for both simulated and real ultrasound recordings. The most accurate results were obtained when the digitized ultrasound scanlines were upsampled by a factor of 10 before applying cross-correlation to estimate time delays. A modified Doppler algorithm allowing the velocity to vary linearly with time throughout the duration of the pulse packet (constant acceleration Doppler) was found to be better at capturing rapidly changing velocities compared with conventional Doppler processing. The best results were obtained using upsamling and time delay estimation, but the long computation time required by this method may make it best suited in a laboratory setting. In a real-time system, the computationally quicker constant acceleration Doppler may be preferred.

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.

Continuous Estimation of Acute Changes in Preload Using Epicardially Attached Accelerometers.

OBJECTIVE: A miniaturized accelerometer can be incorporated in temporary pacemaker leads which are routinely attached to the epicardium during cardiac surgery and provide continuous monitoring of cardiac motion during and following surgery. We tested if such a sensor could be used to assess volume status, which is essential in hemodynamically unstable patients. METHODS: An accelerometer was attached to the epicardium of 9 pigs and recordings performed during baseline, fluid loading, and phlebotomy in a closed chest condition. Alterations in left ventricular (LV) preload alter myocardial tension which affects the frequency of myocardial acceleration associated with the first heart sound ( fS1). The accuracy of fS1 as an estimate of preload was evaluated using sonomicrometry measured end-diastolic volume (EDV[Formula: see text]). Standard clinical estimates of global end-diastolic volume using pulse index continuous cardiac output (PiCCO) measurements (GEDV[Formula: see text]) and pulmonary artery occlusion pressure (PAOP) were obtained for comparison. The diagnostic accuracy of identifying fluid responsiveness was analyzed for fS1, stroke volume variation (SVV[Formula: see text]), pulse pressure variation (PPV[Formula: see text]), GEDV[Formula: see text], and PAOP. RESULTS: Changes in fS1 correlated well to changes in EDV[Formula: see text] ( r2=0.81, 95%CI: [0.68, 0.89]), as did GEDV[Formula: see text] ( r2=0.59, 95%CI: [0.36, 0.76]) and PAOP ( r2=0.36, 95%CI: [0.01, 0.73]). The diagnostic accuracy [95%CI] in identifying fluid responsiveness was 0.79 [0.66, 0.94] for fS1, 0.72 [0.57, 0.86] for SVV[Formula: see text], and 0.63 (0.44, 0.82) for PAOP. CONCLUSION: An epicardially placed accelerometer can assess changes in preload in real-time. SIGNIFICANCE: This novel method can facilitate continuous monitoring of the volemic status in open-heart surgery patients and help guiding fluid resuscitation.

The 'Digital Twin' to enable the vision of precision cardiology.

Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the 'digital twin' of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.

Mechanical Effects on Right Ventricular Function From Left Bundle Branch Block and Cardiac Resynchronization Therapy.

OBJECTIVES: The purpose of this study was to investigate how LBBB and CRT modify RV free wall function by direct ventricular interaction. BACKGROUND: Right ventricular (RV) function influences prognosis in patients with left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). There is, however, limited insight into how LBBB and CRT affect RV function. METHODS: In 24 patients with LBBB with nonischemic cardiomyopathy, RV and left ventricular (LV) strain by speckle-tracking echocardiography was measured before and after CRT. Underlying mechanisms were studied in 16 anesthetized dogs with ultrasonic dimension crystals and micromanometers. RESULTS: Patients with LBBB demonstrated distinct early systolic shortening in the RV free wall, which coincided with the typical abnormal early systolic septal shortening. In animals, this RV free wall contraction pattern resulted in reduced myocardial work as a large portion of the shortening occurred against low pressure during early systole, coinciding with abnormal leftward septal motion. RV systolic function was maintained by vigorous contraction in the late-activated LV lateral wall, which pushed the septum toward the RV. CRT reduced abnormal septal motion and increased RV free wall work because there was less inefficient shortening against low pressure. CONCLUSIONS: LBBB reduces workload on the RV free wall because of abnormal septal motion and delayed activation of the LV lateral wall. Restoring septal and LV function by CRT increases workload in RV free wall and may explain why patients with RV failure respond poorly to CRT. (Contractile Reserve in Dyssynchrony: A Novel Principle to Identify Candidates for Cardiac Resynchronization Therapy [CRID-CRT]; NCT02525185).