Showing papers by "Jens-Uwe Voigt published in 2022"

Right ventricular longitudinal strain in the clinical routine: a state-of-the-art review.

Abstract: Myocardial deformation imaging is a very attractive clinical tool for the assessment of right ventricular (RV) systolic performance, providing incremental diagnostic and prognostic information over the traditional indices of RV function. Among various imaging modalities, echocardiography is currently the method of choice for clinical assessment of RV longitudinal strain (RVLS). The methodology of 2D speckle-tracking echocardiography to obtain RVLS has been recently standardized and demonstrated to be feasible, accurate, and robust for clinical use. Inter-technique and inter-vendor comparability and reliability of RVLS are improving. RVLS is advantageous because it is more sensitive to subtle changes in myocardial function than conventional parameters used to assess RV function (i.e. tricuspid annular plane systolic excursion, tissue Doppler systolic velocity, fractional area change, or RV ejection fraction) representing a sensitive tool for the long-term follow-up of patients. Proper interpretation of measurements requires a deep understanding of RV mechanics and pathologic tissue characteristics in different cardiovascular conditions, as well as the influence of loading conditions, image properties, and tracking algorithms on RVLS measurements.

Right ventricular strain related to pulmonary artery pressure predicts clinical outcome in patients with pulmonary arterial hypertension.

Abstract: AIMS In pulmonary arterial hypertension (PAH), the right ventricle (RV) is exposed to an increased afterload. In response, RV mechanics are altered. Markers which would relate RV function and afterload could therefore aid to understand this complex response system and could be of prognostic value. The aim of our study was to (i) assess the RV-arterial coupling using ratio between RV strain and systolic pulmonary artery pressure (sPAP), in patients with PAH, and (ii) investigate the prognostic value of this new parameter over other echocardiographic parameters. METHODS AND RESULTS Echocardiograms of 65 pre-capillary PAH patients (45 females, age 61 ± 15 years) were retrospectively analysed. Fractional area change (FAC), sPAP, tricuspid annular plane systolic excursion, and RV free-wall (FW) longitudinal strain (LS) were measured. A primary endpoint of death or heart/lung transplantation described clinical endpoint. Patients who reached a clinical endpoint had worse functional capacity (New York Heart Association), reduced RV function, and higher sPAP. Left ventricle function was similar in both groups. Only RVFW LS/sPAP ratio was found as an independent predictor of clinical endpoint in multivariable analysis (hazard ratio 8.3, 95% confidence interval 3.2-21.6, P < 0.001). The RWFW LS/sPAP (cut-off 0.19) demonstrated a good accuracy for the prediction of reaching the clinical endpoint, with a sensitivity of 92% and specificity of 82.5%. CONCLUSION RVFW LS/sPAP ratio significantly predicts all-cause mortality and heart-lung transplantation, and was superior to other well-established parameters, in patients with pre-capillary PAH. We therefore propose RVFW LS/sPAP as a new prognostic echocardiographic marker.

Non-invasive imaging as the cornerstone of cardiovascular precision medicine.

Abstract: AIMS To provide an overview of the role of cardiovascular (CV) imaging in facilitating and advancing the field of precision medicine in CV disease. METHODS AND RESULTS Non-invasive CV imaging is essential to accurately and efficiently phenotype patients with heart disease, including coronary artery disease (CAD) and heart failure (HF). Various modalities, such as echocardiography, nuclear cardiology, cardiac computed tomography (CT), cardiovascular magnetic resonance (CMR), and invasive coronary angiography, and in some cases a combination, can be required to provide sufficient information for diagnosis and management. Taking CAD as an example, imaging is essential for the detection and functional assessment of coronary stenoses, as well as for the quantification of cardiac function and ischaemic myocardial damage. Furthermore, imaging may detect and quantify coronary atherosclerosis, potentially identify plaques at increased risk of rupture, and guide coronary interventions. In patients with HF, imaging helps identify specific aetiologies, quantify damage, and assess its impact on cardiac function. Imaging plays a central role in individualizing diagnosis and management and to determine the optimal treatment for each patient to increase the likelihood of response and improve patient outcomes. CONCLUSIONS Advances in all imaging techniques continue to improve accuracy, sensitivity, and standardization of functional and prognostic assessments, and identify established and novel therapeutic targets. Combining imaging with artificial intelligence, machine learning and computer algorithms, as well as with genomic, transcriptomic, proteomic, and metabolomic approaches, will become state of the art in the future to understand pathologies of CAD and HF, and in the development of new, targeted therapies.

Impact of Loading and Myocardial Mechanical Properties on Natural Shear Waves: Comparison to Pressure-Volume Loops.

Abstract: Shear wave elastography (SWE) has been proposed as a novel noninvasive method for the assessment of myocardial stiffness, a relevant determinant of diastolic function. It is based on tracking the propagation of shear waves, induced, for instance, by mitral valve closure (MVC), in the myocardium. The speed of propagation is directly related to myocardial stiffness, which is defined by the local slope of the nonlinear stress-strain relation. Therefore, the operating myocardial stiffness can be altered by both changes in loading and myocardial mechanical properties.This study sought to evaluate the capability of SWE to quantify myocardial stiffness changes in vivo by varying loading and myocardial tissue properties and to compare SWE against pressure-volume loop analysis, a gold standard reference method.In 15 pigs, conventional and high-frame rate echocardiographic data sets were acquired simultaneously with pressure-volume loop data after acutely changing preload and afterload and after inducting an ischemia/reperfusion (I/R) injury.Shear wave speed after MVC significantly increased by augmenting preload and afterload (3.2 ± 0.8 m/s vs 4.6 ± 1.2 m/s and 4.6 ± 1.0 m/s, respectively; P = 0.001). Preload reduction had no significant effect on shear wave speed compared to baseline (P = 0.118). I/R injury resulted in significantly higher shear wave speed after MVC (6.1 ± 1.2 m/s; P < 0.001). Shear wave speed after MVC had a strong correlation with the chamber stiffness constant β (r = 0.63; P < 0.001) and operating chamber stiffness dP/dV before induction of an I/R injury (r = 0.78; P < 0.001) and after (r = 0.83; P < 0.001).Shear wave speed after MVC was influenced by both acute changes in loading and myocardial mechanical properties, reflecting changes in operating myocardial stiffness, and was strongly related to chamber stiffness, invasively derived by pressure-volume loop analysis. SWE provides a novel noninvasive method for the assessment of left ventricular myocardial properties.

High-Frame-Rate Speckle Tracking for Echocardiographic Stress Testing.

Abstract: Stress echocardiography helps to diagnose cardiac diseases that cannot easily be detected or do not even manifest at rest. In clinical practice, assessment of the stress test is usually performed visually and, therefore, in a qualitative and subjective way. Although speckle tracking echocardiography (STE) has been proposed for the quantification of function during stress, its time resolution is inadequate at high heart rates. Recently, high-frame-rate (HFR) imaging approaches have been proposed together with dedicated STE algorithms capable of handling small interframe displacements. The aim of this study was to determine if HFR STE is effective in assessing strain and strain rate parameters during echocardiographic stress testing. Specifically, stress echocardiography, at four different workload intensities, was performed in 25 healthy volunteers. At each stress level, HFR images from the apical four-chamber view were recorded using the ULA-OP 256 experimental scanner. Then, the myocardium was tracked with HFR STE, and strain and strain rate biomarkers were extracted to further analyze systolic and diastolic (early and late) peaks, as well as a short-lived isovolumic relaxation peak during stress testing. The global systolic strain response was monophasic, revealing a significant (p < 0.001) increase at low stress but then reaching a plateau. In contrast, all strain rate indices linearly increased (p < 0.001) with increasing stress level. These findings are in line with those reported using tissue Doppler imaging and, thus, indicate that HFR STE can be a useful tool in assessing cardiac function during stress echocardiography.

Impaired biventricular contractile reserve in patients with diastolic dysfunction: insights from exercise stress echocardiography.

Abstract: AIMS Cardiac output limitation is a fundamental feature of heart failure with preserved ejection fraction (HFpEF) but the relative contribution of its determinants in symptomatic vs. asymptomatic stages are not well characterized. We aimed to gain insight into disease mechanisms by performing comprehensive comparative non-invasive exercise imaging in patients across the disease spectrum. METHODS AND RESULTS We performed bicycle stress echocardiography in 10 healthy controls, 13 patients with hypertensive left ventricular (LV) concentric remodelling and asymptomatic diastolic dysfunction (HTDD), 15 HFpEF patients, and 15 subjects with isolated right ventricular (RV) dysfunction secondary to chronic thromboembolic pulmonary hypertension (CTEPH). During exercise, ventricular performance differed across the groups (all P ≤ 0.01 for interaction). Notably in controls, LV and RV function significantly increased (all P < 0.05) while both LV systolic and diastolic reserve were significantly reduced in HFpEF patients. Likewise, RV systolic reserve was also impaired in HFpEF but not to the extent of CTEPH patients (P < 0.001 between groups). HTDD patients behaved as an intermediary group with borderline LV systolic and diastolic reserve and reduced RV systolic reserve. The increased pulmonary vascular (PV) load in HFpEF and CTEPH patients in combination with impaired RV reserve resulted in RV-pulmonary artery uncoupling during exercise. CONCLUSION The multifaceted decline of cardiac and PV function accompanying disease progression in HFpEF is unmasked by exercise and already emerges in preclinical disease. The revelation of these subtle abnormalities during exercise illustrates the benefit of exercise imaging and creates new prospects for early diagnosis and management.

Clinical and Experimental Evidence for a Strain-Based Classification of Left Bundle Branch Block-Induced Cardiac Remodeling

Abstract: Background: Septal strain patterns measured by echocardiography reflect the severity of left bundle branch block (LBBB)-induced left ventricular (LV) dysfunction. We investigated whether these LBBB strain stages predicted the response to cardiac resynchronization therapy in an observational study and developed a sheep model of LBBB-induced cardiomyopathy. Methods: The clinical study enrolled cardiac resynchronization therapy patients who underwent echocardiographic examination with speckle-tracking strain analysis before cardiac resynchronization therapy implant. In an experimental sheep model with pacing-induced dyssynchrony, LV remodeling and strain were assessed at baseline, at 8 and 16 weeks. Septal strain curves were classified into 5 patterns (LBBB-0 to LBBB-4). Results: The clinical study involved 250 patients (age 65 [58; 72] years; 79% men; 89% LBBB) with a median LV ejection fraction of 25 [21; 30]%. Across the stages, cardiac resynchronization therapy resulted in a gradual volumetric response, ranging from no response in LBBB-0 patients (ΔLV end-systolic volume 0 [−12; 15]%) to super-response in LBBB-4 patients (ΔLV end-systolic volume −44 [−64; −18]%) (P<0.001). LBBB-0 patients had a less favorable long-term outcome compared with those in stage LBBB≥1 (log-rank P=0.003). In 13 sheep, acute right ventricular pacing resulted in LBBB-1 (23%) and LBBB-2 (77%) patterns. Over the course of 8−16 weeks, continued pacing resulted in progressive LBBB-induced dysfunction, coincident with a transition to advanced strain patterns (92% LBBB-2 and 8% LBBB-3 at week 8; 75% LBBB-3 and 25% LBBB-4 at week 16) (P=0.023). Conclusions: The strain-based LBBB classification reflects a pathophysiological continuum of LBBB-induced remodeling over time and is associated with the extent of reverse remodeling in observational cardiac resynchronization therapy-eligible patients.

Can nuclear imaging accurately detect scar in ischemic cardiac resynchronization therapy candidates?

Abstract: Background Accurate scar assessment is crucial in cardiac resynchronization therapy (CRT) candidates, since its presence is a negative predictor for CRT response. Therefore, we assessed the performance of different PET parameters to detect scar in CRT candidates. Methods: Twenty-nine CRT candidates underwent 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT), resting 13N-NH3-PET/CT and cardiac magnetic resonance (CMR) prior to CRT implantation. Segmental 18F-FDG uptake, late 13N-NH3 uptake and absolute myocardial blood flow (MBF) were evaluated for scar detection using late gadolinium enhancement (LGE) CMR as reference. A receiver operator characteristic (ROC) area under the curve (AUC) ≥0.8 indicated a good accuracy of the methods evaluated. Results Scar was present in 111 of 464 segments. None of the approaches could reliably identify segments with nontransmural scar, except for 18F-FDG uptake in the lateral wall (AUC 0.83). Segmental transmural scars could be detected with all methods (AUC ≥ 0.8), except for septal 18F-FDG uptake and MBF in the inferior wall (AUC < 0.8). Late 13N-NH3 uptake was the best parameter for transmural scar detection, independent of its location, with a sensitivity of 80% and specificity of 92% using a cutoff of 66% of the maximum tracer activity. Conclusions Late 13N-NH3 uptake is superior to 13N-NH3 MBF and 18F-FDG in detecting transmural scar, independently of its location. However, none of the tested PET parameters was able to accurately detect nontransmural scar.

Comparing Myocardial Shear Wave Propagation Velocity Estimation Methods Based on Tissue Displacement, Velocity and Acceleration Data.

Abstract: Shear wave elastography (SWE) is a promising technique used to assess cardiac function through the evaluation of cardiac stiffness non-invasively. However, in the literature, SWE varies in terms of tissue motion data (displacement, velocity or acceleration); method used to characterize mechanical wave propagation (time domain [TD] vs. frequency domain [FD]); and the metric reported (wave speed [WS], shear or Young's modulus). This variety of reported methodologies complicates comparison of reported findings and sheds doubt on which methodology better approximates the true myocardial properties. We therefore conducted a simulation study to investigate the accuracy of various SWE data analysis approaches while varying cardiac geometry and stiffness. Lower WS values were obtained by the TD method compared with the FD method. Acceleration-based WS estimates in the TD were systematically larger than those based on velocity (∼10% difference). These observations were confirmed by TD analysis of 32 in vivo SWE mechanical wave measurements. In vivo data quality is typically too low for accurate FD analysis. Therefore, our study suggests using acceleration-based TD analysis for in vivo SWE to minimize underestimation of the true WS and, thus, to maximize the sensitivity of SWE to detect stiffness changes resulting from pathology.

Ischemic heart disease

Abstract: Ischemic disease results in global and regional strain changes. Global strain is typically reduced, which is an unspecific but very sensitive reaction. Regional myocardial dysfunction alters the morphology of segmental strain curves. Typical findings are an early systolic lengthening of varying degree, a reduced systolic shortening, and a postsystolic shortening. These can occur both in scar and acute ischemia.

Statistics and individuals.

Abstract: This editorial refers to ‘Clinical implications of left atrial reverse remodelling after cardiac resynchronization therapy’ by Stassen J. et al.https://doi.org/10.1093/ehjci/jeac042. Heart failure patients with reduced cardiac function and left bundle branch block-like conduction delay have a mechanical problem: The early activated septum contracts first, which ends left ventricular (LV) filling by closing the mitral valve, but does not lead to a relevant pressure rise in the LV as the contracting myocardial volume is too small. Only the delayed activation of the posterolateral myocardium enables LV ejection. Since the septum is already relaxing at this time, most of the ejection work is borne by the late contracting lateral regions which then hypertrophy while the unused septum virtually atrophies. In addition, the mutual stretching of opposing walls supports the further dilatation of the ventricle. LV dyssynchrony and dilatation cause or aggravate mitral leakage. The de-synchronization of the ventricle leads not only to a dissipation of contractile function but has also an effect on its diastole. Both, the isovolumic contraction and relaxation time are prolonged, and ventricular filling time becomes extremely short. Reduced systolic and diastolic function lead to elevated filling pressures and subsequent atrial dilatation, dysfunction, and, eventually, fibrillation.

Building up evidence.

Abstract: This editorial refers to ‘Reduced global longitudinal strain as a marker for early detection of Fabry cardiomyopathy’ D.-Y. Lu et al. pp. 487–95. Over two decades ago, strain and strain rate imaging was introduced to the world of clinical echocardiography.1 Post-processing of colour-tissue-Doppler was used to calculate myocardial deformation and deformation rate and allowed for the first time to quantify myocardial function on a regional (segmental) level. The method was immediately embraced by lovers of technological advances, but remained mainly a research tool. Focusing on regions of interest that had to be tracked manually throughout the cardiac cycle, the post-processing was time-consuming and not suited for a fast and comprehensive assessment of the entire left ventricle during a clinical routine examination. Nevertheless, strain and strain rate imaging has massively influence the way we look at myocardial function in echocardiography. We learned that regional dysfunction is more than hypo-,...

Echocardiographic assessment of mechanical dyssynchrony: are the new parameters better?

Abstract: Type of funding sources: None. Introduction - The high cost and important non-response rate are preventing optimal use of cardiac resynchronization therapy (CRT). Assessing mechanical dyssynchrony on echocardiography in candidates for CRT could remove these barriers by improving patient selection. In 2008 the PROSPECT study compared several old parameters of dyssynchrony in search of a reproducible parameter capable of better predicting response to CRT. Unfortunately, the results were disappointing and the assessment of dyssynchrony became discredited. Promising new parameters have been developed but a comparison with the old parameters is currently missing. Purpose - To compare the old and new parameters of mechanical dyssynchrony for (1) their effect on response to CRT as additional selection criteria, (2) predicting favourable long-term outcome after CRT and (3) their reproducibility. Methods - 146 CRT patients were analysed retrospectively in a multicentre setting. Mechanical dyssynchrony was assessed using three old parameters: septal-to-posterior wall motion delay (SPWMD), left ventricular filling time/cardiac cycle ratio (LVFT/RR), and intraventricular mechanical delay (IVMD); and three new parameters: systolic stretch index (SSI), myocardial work index (MWI), and visual presence of septal flash or apical rocking (SFoAR). Response to CRT was defined as a ≥15% decrease in LV end-systolic volume 1 year after CRT. For each parameter patients were categorized using previously published cut-offs as ‘eligible’ or ‘non-eligible’. The ‘non-eligible’ were considered untreated. Results were compared to the guidelines (Fig. 1). The hazard ratio (HR) for cardiac death within 5 years after implantation was computed for all patients (Fig. 2), and intra- and interrater agreement was determined. Results - 73% (n= 107) of patients showed response to CRT. The old parameters maintained less than 75% of the original responders. SFoAR preserved the highest proportion of responders (93%), while reducing the number of non-responders by 39% (Fig. 1). The prediction of cardiac death was significant for SFoAR (HR = 0.29; 95% CI: 0.12-0.74; P = 0.009) and IVMD (HR = 0.32; 95% CI: 0.13-0.79; P = 0.014) (Fig. 2). Intra- and interrater agreement was best for SFoAR (κ = 0.89; 95% CI: 0.67-1.0 and κ = 0.78; 95% CI: 0.50-1.0 respectively). Interrater agreement was poor for all old parameters (κ < 0.6). Conclusion - The new parameters for dyssynchrony are performing better. The visual presence of apical rocking or septal flash provided the most responders to CRT, predicted favourable long-term outcome and was highly reproducible. Our results show that future research should focus on the new parameters. Abstract Figure. Abstract Figure.

Model-based and Unsupervised Machine-learning Approaches for the Characterization of Responder Profiles for Cardiac Resynchronization Therapy

Abstract: The objective of this study is to improve the inter-pretability of a previous unsupervised clustering analysis of the CRT response through a physiological model-based approach. The developed clustering approach was applied on 250 CRT candidates based on clinical, original and classical echocardiographic features. Patient-specific computational models were proposed for patients associated of each cluster barycenter in order to provide an ex-plainable analysis in relation with physiological mecha-nisms. Five phenogroups were identified from the clustering approach with response rates ranging from 50% to 92.7%. Concerning the model-based approach, a match was observed between the 16 experimental and simulated myocardial strain curves pattern with a mean RMSE of 3.97%($\pm$ 1.74) on the five patients. Moreover, the identified model parameters provide us information about the mecano-electrical coupling and tissue properties. The gain of information provides by the parameters model identification, added to the clinical and classical echocar-diographic features is promising for an understanding of LV mechanical dyssynchrony and the identification of patients suitable for CRT.

Combined assessment of septal scar and septal flash by cardiac magnetic resonance identifies responders to cardiac resynchronization therapy

Abstract: Type of funding sources: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Regional Health Authority. Research grants of the University of Leuven. Left ventricular (LV) scar, particularly in the lateral wall and septum, reduces response rate to cardiac resynchronization therapy (CRT), whereas a dyssynchronous LV contraction pattern (septal flash) suggests good response. Lateral wall scar abolishes septal flash. Therefore, a combined approach of septal scar and septal flash may characterize the myocardial substrate responsive to CRT. Cardiac magnetic resonance (CMR) may assess both scar and contraction pattern. The present study aimed to determine if combined assessment of septal scar and septal flash by CMR as single image modality identifies responders to CRT. We investigated all CRT recipients with available CMR from a prospective, multicenter study (n = 136), with both ischemic and non-ischemic heart failure. Septal scar was assessed by late gadolinium enhancement (LGE) from a stack of short axis slices (n = 128) and septal flash determined visually on ordinary cine sequences (n = 136). CRT response was defined as ≥15% reduction in LV end-systolic volume by echocardiography at 6 months follow-up. We also assessed heart transplantation or death of any cause 39 ± 13 months after device implantation. In multivariate analysis including percentage septal scar (LGE), septal flash, QRS-duration and QRS-morphology, septal LGE and septal flash were the only independent predictors of CRT response (both p < 0.001). A combined approach of septal LGE and septal flash predicted CRT response with area under the curve 0.86 (95% confidence interval (CI): 0.78-0.94) and long-term survival without heart transplantation with hazard ratio 0.18 (95% CI: 0.05-0.61). A practical approach to selection of CRT candidates by septal LGE and septal flash is illustrated in the present figure. As shown, absence of septal LGE indicated excellent response rate (93%) to CRT independent of other parameters. When septal LGE was present, however, overall response rate was substantially lower (58%), but presence or absence of septal flash separated responders from non-responders with high accuracy. This sequential approach correctly classified 86% of patients. Importantly, the approach was equally accurate in patients with intermediate QRS duration (130-150ms), where 93% of patients were correctly classified. Combined assessment of septal LGE and septal flash by CMR as single image modality identifies CRT responders with high accuracy and predicts long-term survival. Abstract Figure.