Hemodynamic Forces in Cardiac Resynchronization Therapy: Implications and Future Directions

The intricacies of intracardiac fluid dynamics hold the key to understanding various cardiovascular pathologies and their management. Echocardiography-derived hemodynamic forces (HDF) have emerged as a noninvasive technique to measure intracardiac hemodynamics characterizing the relation between wall mechanics and fluid dynamics of the left ventricle (LV), thus providing insight into mechanical synchrony in the context of ventricular remodeling.¹ This technique builds on existing modalities of cardiac deformation analysis (i.e., strain and LV ejection fraction [LVEF]) by its ability to temporally quantify the interplay between blood flow and the endocardium of the LV. The noninvasive nature of this technique offers several advantages: (1) minimizing patient discomfort and risk, (2) repeated measurements with limited cumulative harm, (3) is cost-effective, and (4) providing a readily accessible means of monitoring cardiac performance. The significance of this technique lies in the changes in HDF which become apparent before pathologic alterations in myocardial deformation. In recent years, computational advancements have facilitated the calculation of HDF in the LV by drawing correlations with established imaging modalities such as 4-dimensional flow cardiac magnetic resonance imaging.²

In the previous issue, Laenens et al³ evaluated the HDF application in patients who underwent cardiac resynchronization therapy (CRT). Previous studies have evaluated HDF changes after CRT in small cohorts⁴; however, this study presents a detailed, time-specific assessment with an emphasis on both immediate and longer-term effects of CRT. The study evaluated 197 patients with LVEF ≤35%, QRS duration ≥130 ms, and left bundle branch block from a single center between 2000 to 2014 at Leiden University Medical Center, The Netherlands.

The study compared HDF parameters from the CRT cohort alongside 30 healthy controls, who were matched for age, gender, and body mass index; additionally, the control group was followed longitudinally alongside the CRT cohort to explore the evolution of HDF over time. Transthoracic echocardiography was performed at 3 stages: pre-CRT, immediately post-CRT, and at 6 months post-CRT. Echocardiographic data underwent a detailed HDF analysis at 4 different time points: (1) at baseline pre-CRT, (2) at baseline post-CRT, (3) at 6 months with CRT ON, and (4) at 6 months with CRT OFF. Each of these temporal milestones provided a comprehensive view of the HDF dynamics in relation to CRT, which captured both immediate and long-term impact. The 4-chamber, 3-chamber, and 2-chamber views were evaluated utilizing proprietary software (QStrain Echo Research Edition, Medis Medical Imaging, Leiden, The Netherlands). The endocardial boundary was delineated at both LV end-systolic and LV end-diastolic phases.

Patients in the study had a mean age of 64 ± 11 years with 38% female patients. Comparisons revealed patients with heart failure (HF) exhibited significantly reduced force magnitudes in both apical-basal (AB) and lateral-septal (LS) directions relative to healthy controls. The LS-AB ratio was notably elevated, with a decreased angle in CRT recipients, suggesting HDF misalignment pre-CRT implantation. Additionally, the AB impulse during systolic thrust was significantly diminished in patients with HF, mirroring reduced AB forces in propulsive phase of systole. Furthermore, a decreased systolic force vector angle in patients with HF indicated aberrant HDF orientation during the propulsive phase of systole compared with healthy controls. Immediately post-CRT implantation, there was a marked enhancement in HDF, particularly in the AB impulse (p = 0.002) and systolic force vector angle (p = 0.03) during the systolic thrust phase but not in other parts of cardiac cycle. Six months post-CRT implantation demonstrated significant clinical improvements in quality of life with features suggestive of reversal of LV remodeling (significant reduction in LV volume, improved LVEF and LV global longitudinal strain, and reduction in mitral regurgitation, p <0.001). HDF dynamics revealed an increase in the AB strength and an improved alignment toward the apex-base direction. However, upon temporary deactivation of the CRT device at the 6 months, LS forces became prominent (p = 0.007) indicating recurrence of mechanical dyssynchrony with a trend toward recurrent misalignment of HDF evidenced by the increased force vector angle during the systolic thrust (p = 0.01).

The study had several strengths. First, the study population was homogeneous and robust with the inclusion of 197 patients with CRT. Second, the novel echocardiographic approach incorporating intracardiac hemodynamics in the LV without flow measurements using the QStrain software. Third, the longitudinal evaluation of HDF at 4 distinct time points—pre-CRT, immediately post-CRT, 6 months post-CRT with the device ON, and 6 months post-CRT with the device OFF provided the study provides a comprehensive understanding of HDF dynamics relative to CRT. This temporal analysis enabled the assessment of both the immediate and long-term impact of CRT on HDF. The decision to temporarily deactivate the CRT device at the 6 months and analyze the subsequent changes offered additional insight into the acute effects of CRT versus the persistent effects of LV remodeling, which is an important distinction for therapeutic considerations.

Despite the strengths of the study, limitations were present. The study had an observational, retrospective design which inherently introduces potential biases limiting inference to causality. Second, the study was from a single center which limits broader applicability of the findings, given heterogeneity in patient populations and clinical practices across centers. Third, whereas the study provided in-depth insight into the complete cardiac cycle and systolic changes, there was a lack of a thorough evaluation of diastolic HDF changes as improvements in hemodynamics were observed during the complete cardiac cycle and cannot be attributable to systolic thrust alone. Finally, exclusion of patients with significant valvulopathy, arrhythmias, or insufficient imaging quality prevalent in the clinical population where CRT is indicated, limits the evaluation of HDF because of changes in LV geometry which could introduce both selection bias and estimation errors. Lastly, derivation of HDF is associated with its own technical challenges which require future studies to evaluate its performance which may be additive to speckle-tracking echocardiography.¹

Nonetheless, Laenens et al³ provide novel insight into the alteration in HDF’s magnitude and orientation in patients with HF and objectively capture the changes post-CRT implantation. Their findings provide evidence to support that longitudinal changes in HDF are associated with the reversal of LV remodeling and the role of electromechanical synchrony achieved through CRT. Thus, echocardiography-derived HDF has the potential to guide the optimization of CRT therapy. The results of the study may aid clinicians in tailoring CRT protocols and ensuring therapies align with each patient’s distinct cardiovascular HDF profile enhancing precision strategies in this population. This approach could maximize CRT’s efficacy and optimize patient outcomes.

Although the assessment of HDF presents a novel avenue in assessing CRT and its efficacy, the incorporation of techniques such as artificial intelligence (AI) and machine learning (ML) would further enhance our understanding and management of CRT in an agnostic, precision medicine-driven pathway. AI-driven algorithms trained on HDF-derived data could predict patient-specific HDF shifts, offering tailored CRT optimization potentially limiting adverse events. Concurrently, ML models might also enable real-time patient monitoring, alerting clinicians to nuanced changes in HDF identifying precursors to significant myocardial changes.

In summary, this study by Laenens et al³ illuminates the potential of echocardiography-derived HDF in assessing the impact of CRT. Their analysis suggests that HDF can refine CRT therapies for optimized patient outcomes. Further investigation is necessary to determine the added utility compared with existing echocardiographic parameters. Integration of AI and ML methodologies may further enhance CRT management requiring the need for ethical, patient-centered care.