The Prognostic Role of Global Longitudinal Strain and NT-proBNP in Heart Failure Patients Receiving Cardiac Resynchronization Therapy.

BACKGROUND: We aimed to evaluate whether baseline GLS (global longitudinal strain), NT-proBNP, and changes in these after cardiac resynchronization therapy (CRT) can predict long-term clinical outcomes and the echocardiographic-based response to CRT (defined by 15% relative reduction in left ventricular end-systolic volume). METHODS: We enrolled 143 patients with stable ischemic heart failure (HF) undergoing CRT-D implantation. NT-proBNP and echocardiography were obtained before and 6 months after. The patients were followed up (median: 58 months) for HF-related deaths and/or HF hospitalizations (primary endpoint) or HF-related deaths (secondary endpoint). RESULTS: A total of 84 patients achieved the primary and 53 the secondary endpoint, while 104 patients were considered CRT responders and 39 non-responders. At baseline, event-free patients had higher absolute GLS values (p < 0.001) and lower NT-proBNP serum levels (p < 0001) than those achieving the primary endpoint. A similar pattern was observed in favor of CRT responders vs. non-responders. On Cox regression analysis, baseline absolute GLS value (HR = 0.77; 95% CI, 0.51-1.91; p = 0.002) was beneficially associated with lower primary endpoint incidence, while baseline NT-proBNP levels (HR = 1.55; 95% CI, 1.43-2.01; p = 0.002) and diabetes presence (HR = 1.27; 95% CI, 1.12-1.98; p = 0.003) were related to higher primary endpoint incidence. CONCLUSIONS: In HF patients undergoing CRT-D, baseline GLS and NT-proBNP concentrations may serve as prognostic factors, while they may predict the echocardiographic-based response to CRT.

From evidence-based medicine to digital twin technology for predicting ventricular tachycardia in ischaemic cardiomyopathy.

Survivors of myocardial infarction are at risk of life-threatening ventricular tachycardias (VTs) later in their lives. Current guidelines for implantable cardioverter defibrillators (ICDs) implantation to prevent VT-related sudden cardiac death is solely based on symptoms and left ventricular ejection fraction. Catheter ablation of scar-related VTs is performed following ICD therapy, reducing VTs, painful shocks, anxiety, depression and worsening heart failure. We postulate that better prediction of the occurrence and circuit of VT, will improve identification of patients at risk for VT and boost preventive ablation, reducing mortality and morbidity. For this purpose, multiple time-evolving aspects of the underlying pathophysiology, including the anatomical substrate, triggers and modulators, should be part of VT prediction models. We envision digital twins as a solution combining clinical expertise with three prediction approaches: evidence-based medicine (clinical practice), data-driven models (data science) and mechanistic models (biomedical engineering). This paper aims to create a mutual understanding between experts in the different fields by providing a comprehensive description of the clinical problem and the three approaches in an understandable manner, leveraging future collaborations and technological innovations for clinical decision support. Moreover, it defines open challenges and gains for digital twin solutions and discusses the potential of hybrid modelling.

Accuracy and Potential Benefit of Ultraselective Invasive Coronary Angiography Guided by Computed Tomographic Coronary Angiography.

OBJECTIVES: It is unknown whether computed tomographic coronary angiography (CTCA) can be used to perform ultraselective invasive coronary angiography (ICA) by only visualizing the abnormal coronary artery on CTCA and defer visualization of the normal contralateral coronary artery. This study assessed the accuracy of CTCA in patients with coronary artery disease (CAD) on CTCA limited to either the left (LCA) or right coronary artery (RCA) in predicting a contralateral coronary artery without abnormalities on CTCA determined to be normal by ICA. METHODS: This retrospective analysis included patients with CAD limited to the LCA or RCA on CTCA. Primary endpoint was the accuracy of CTCA to predict a contralateral coronary artery without abnormalities on CTCA to be normal by ICA. Secondary endpoints were potential reductions in procedure time and radiation exposure if an ultraselective ICA approach would be used compared to standard ICA. RESULTS: In total, 202 patients were included. CTCA was correct in predicting a normal contralateral coronary artery in 201 of the 202 patients (99.5%). Deferring ICA of the normal contralateral coronary artery on CTCA resulted in a potential reduction in procedure time and dose area product of 4.22 ± 2.67 minutes (61 ± 16% reduction) and 1501 ± 1304 mGy•cm² (29 ± 13% reduction). CONCLUSIONS: In this retrospective study, CTCA was extremely accurate in predicting a normal contralateral coronary artery in patients with LCA- or RCA-limited CAD on CTCA. A potential CTCA-guided ultraselective ICA approach was feasible and would have led to a considerable decrease in procedure time and radiation exposure.

Left atrial reverse remodeling predicts long-term survival after cardiac resynchronization therapy.

BACKGROUND: Left ventricular (LV) reverse remodeling has been identified as a strong predictor of long-term survival in patients receiving CRT. Interestingly, CRT induces reverse remodeling in the left atrium (LA) as well. It is currently unknown to what extent LA reverse remodeling is correlated to long-term survival after CRT. This study aims to assess the long-term prognostic value of left atrium (LA) reverse remodeling in patients undergoing cardiac resynchronization therapy (CRT). METHODS: Baseline and 3-months follow-up echocardiograms after CRT implantation were prospectively assessed to determine changes in left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), left atrial volume (LAV), and left atrial reservoir strain (LASr). Multivariate Cox regression analysis was performed to identify predictors for long-term survival. RESULTS: In our study population of 99 patients with a mean follow-up of 6.3 ± 2.1 years, 43 patients (43%) reached the end-point of all-cause mortality. More extensive LA reverse remodeling, as measured by a relative increase in LASr, was observed in survivors compared to non-survivors (43 [29-64] % vs. 8 [2-28] %, P < 0.001, respectively). After multivariate analysis, delta LASr remained the only significant predictor of mortality [HR per 5%: 0.90 (0.86-0.95); AUC 0.78 (0.68-0.88)]. CONCLUSION: An increase in LASr is associated with favorable long-term outcome after CRT. The observed clinical importance of LA reverse remodeling after CRT asks for further validation in larger prospective cohorts.

Echocardiographic Assessment of Left Bundle Branch-Related Strain Dyssynchrony: A Comparison With Tagged MRI.

Recent studies have shown the efficacy of myocardial strain estimated using speckle tracking echocardiography (STE) in predicting response to cardiac resynchronisation therapy. This study focuses on circumferential strain patterns, comparing STE-acquired strains to tagged-magnetic resonance imaging (MRI-T). Second, the effect of regularisation was examined. Two-dimensional parasternal ultrasound (US) and MRI-T data were acquired in the left ventricular short-axis view of canines before (n = 8) and after (n = 9) left bunch branch block (LBBB) induction. US-based strain analysis was performed on Digital Imaging and Communications in Medicine data at the mid-level using three overall methods ("Commercial software," "Basic block-matching," "regularised block-matching"). Moreover, three regularisation approaches were implemented and compared. MRI-T analysis was performed using SinMod. Normalised regional circumferential strain curves, based on standard six or septal/lateral segments, were analysed and cross-correlated with MRI-T data. Systolic strain (SS) and septal rebound stretch (SRS) were calculated and compared. Overall agreement of normalised circumferential strain was good between all methods on a global and regional level. All STE methods showed a bias (≥4% strain) toward higher SS estimates. Pre-LBBB, septal and lateral segment correlation was excellent between the Basic (mean ρ = 0.96) and regularised (mean ρ = 0.97) methods and MRI-T. The Commercial method showed a significant discrepancy between the two walls (septal ρ = 0.94, lateral ρ = 0.68). Correlation with MRI-T reduced between pre- and post-LBBB (Commercial ρ = 0.79, Basic ρ = 0.82, mean regularised ρ = 0.86). Septal strain patterns and SRS varied with the STE software and type of regularisation, with all STE methods estimating non-zero SRS values pre-LBBB. Absolute values showed moderate agreement, with a bias for higher strain from STE. SRS varied with the type of software and extra regularisation applied. Open efforts are needed to understand the underlying causes of differences between STE methods before standardisation can be achieved. This is particularly important given the apparent clinical value of strain-based parameters such as SRS.

Noninvasive pulmonary transit time: A new parameter for general cardiac performance.

INTRODUCTION: Pulmonary transit time (PTT) assessed with contrast-enhanced ultrasound (CEUS) is a novel tool to evaluate cardiac function. PTT represents the time for a bolus of contrast to pass from the right to the left ventricle, measured according to the indicator dilution principles using CEUS. We investigated the hypothesis that PTT is a measure of general cardiac performance in patient populations eligible for cardiac resynchronization therapy (CRT). METHODS: The study population consisted of heart failure patients referred for CRT with NYHA class II-IV, left ventricular ejection fraction (LVEF)≤35% and QRS≥120 ms. CEUS, ECG, and blood were analyzed, and participants completed a quality of life questionnaire at baseline and 3 months after CRT implantation. Normalized PTT (nPTT) was calculated to compensate for the heart rate. Correlations were assessed with Pearson's or Spearman's coefficients and stratified for rhythm and NYHA class. RESULTS: The study population consisted of 94 patients (67 men) with a mean age of 70±8.9 years. (n)PTT was significantly correlated with left ventricular parameters (rs =-.487, P<.001), right ventricular parameters (r=-.282, P=.004), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (rs =.475, P<.001), and quality of life (rs =.364, P<.001). Stronger significant correlations were found in patients in sinus rhythm. CONCLUSION: CEUS-derived PTT and nPTT correlate to a fair degree with measures of systolic and diastolic function, NT-pro-BNP, and quality of life. As CEUS-derived PTT can be obtained easily, noninvasively and at the bedside, it is a promising future measure of general cardiac performance.

Pulmonary transit time measurement by contrast-enhanced ultrasound in left ventricular dyssynchrony.

BACKGROUND: Pulmonary transit time (PTT) is an indirect measure of preload and left ventricular function, which can be estimated using the indicator dilution theory by contrast-enhanced ultrasound (CEUS). In this study, we first assessed the accuracy of PTT-CEUS by comparing it with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Secondly, we tested the hypothesis that PTT-CEUS correlates with the severity of heart failure, assessed by MRI and N-terminal pro-B-type natriuretic peptide (NT-proBNP). METHODS AND RESULTS: Twenty patients referred to our hospital for cardiac resynchronization therapy (CRT) were enrolled. DCE-MRI, CEUS, and NT-proBNP measurements were performed within an hour. Mean transit time (MTT) was obtained by estimating the time evolution of indicator concentration within regions of interest drawn in the right and left ventricles in video loops of DCE-MRI and CEUS. PTT was estimated as the difference of the left and right ventricular MTT. Normalized PTT (nPTT) was obtained by multiplication of PTT with the heart rate. Mean PTT-CEUS was 10.5±2.4s and PTT-DCE-MRI was 10.4±2.0s (P=0.88). The correlations of PTT and nPTT by CEUS and DCE-MRI were strong; r=0.75 (P=0.0001) and r=0.76 (P=0.0001), respectively. Bland-Altman analysis revealed a bias of 0.1s for PTT. nPTT-CEUS correlated moderately with left ventricle volumes. The correlations for PTT-CEUS and nPTT-CEUS were moderate to strong with NT-proBNP; r=0.54 (P=0.022) and r=0.68 (P=0.002), respectively. CONCLUSIONS: (n)PTT-CEUS showed strong agreement with that by DCE-MRI. Given the good correlation with NT-proBNP level, (n)PTT-CEUS may provide a novel, clinically feasible measure to quantify the severity of heart failure. CLINICAL TRIAL REGISTRY: NCT01735838.

A constitutive modeling interpretation of the relationship among carotid artery stiffness, blood pressure, and age in hypertensive subjects.

Aging has a profound influence on arterial wall structure and function. We have previously reported the relationship among pulse wave velocity, age, and blood pressure in hypertensive subjects. In the present study, we aimed for a quantitative interpretation of the observed changes in wall behavior with age using a constitutive modeling approach. We implemented a model of arterial wall biomechanics and fitted this to the group-averaged pressure-area (P-A) relationship of the "young" subgroup of our study population. Using this model as our take-off point, we assessed which parameters had to be changed to let the model describe the "old" subgroup's P-A relationship. We allowed elastin stiffness and collagen recruitment parameters to vary and adjusted residual stress parameters according to published age-related changes. We required wall stress to be homogeneously distributed over the arterial wall and assumed wall stress normalization with age by keeping average "old" wall stress at the "young" level. Additionally, we required axial force to remain constant over the cardiac cycle. Our simulations showed an age-related shift in pressure-load bearing from elastin to collagen, caused by a decrease in elastin stiffness and a considerable increase in collagen recruitment. Correspondingly, simulated diameter and wall thickness increased by about 20 and 17%, respectively. The latter compared well with a measured thickness increase of 21%. We conclude that the physiologically realistic changes in constitutive properties we found under physiological constraints with respect to wall stress could well explain the influence of aging in the stiffness-pressure-age pattern observed.