Understudied factors in drug-coated balloon design and evaluation: A biophysical perspective.

Drug-coated balloon (DCB) percutaneous interventional therapy allows for durable reopening of the narrowed lumen via physical tissue expansion and local anti-restenosis drug delivery, providing an alternative to traditional uncoated balloons or a permanent indwelling implant such as a conventional metallic drug-eluting stent. While DCB-based treatment of peripheral arterial disease (PAD) has been incorporated into clinical guidelines, DCB use has been recently curtailed due to reports that showed evidence of increased mortality risk in patients treated with paclitaxel (PTX)-coated balloons. Given the United States Food and Drug Administration's 2019 consequent warning regarding PTX-eluting DCBs and the subsequent marked reduction in clinical DCB use, there is now a critical need to better understand the compositional and mechanical factors underlying DCB efficacy and safety. Most work to date on DCB refinement has focused on designing both the enabling balloon catheter and alternate coatings composed of various drugs and excipients, followed by device evaluation in preclinical and clinical studies. We contend that improvement in DCB performance will require a better understanding of the biophysical factors operative during and following balloon deployment, and moreover that the elaboration and demonstrated control of these factors are needed to address current concerns with DCB use. This article provides a perspective on the biophysical interactions that govern DCB performance and offers new design strategies for the development of next-generation DCB devices.

Changes in Myocardial Microstructure and Mechanics With Progressive Left Ventricular Pressure Overload.

This study assessed the regional changes in myocardial geometry, microstructure, mechanical behavior, and properties that occur in response to progressive left ventricular pressure overload (LVPO) in a large animal model. Using an index of local biomechanical function at early onset of LVPO allowed for prediction of the magnitude of left ventricular chamber stiffness (Kc) and left atrial area at LVPO late timepoints. Our study found that LV myocardial collagen content alone was insufficient to identify mechanisms for LV myocardial stiffness with progression to heart failure with preserved ejection fraction (HFpEF). Serial assessment of regional biomechanical function might hold value in monitoring the natural history and progression of HFpEF, which would allow evaluation of novel therapeutic approaches.

Speckle-Tracking Echocardiography Enables Model-Based Identification of Regional Stiffness Indices in the Left Ventricular Myocardium.

INTRODUCTION: Left ventricular (LV) remodeling is a critical process underlying heart failure (HF) development and progression. While LV global longitudinal strain determined by speckle-tracking echocardiography (STE) provides a promising basis to monitor LV remodeling, reported strain measures are limited by the masking of regional differences and a dependency on hemodynamic load. OBJECTIVES: Our goal is to extend two-dimensional STE to enhance regional mechanical assessment of the LV myocardium-providing clinically accessible and load-independent response variables that directly reflect the LV remodeling process. METHODS: An inverse finite element analysis was employed with a pattern search optimization algorithm to identify regional indices of LV myocardial stiffness based on STE-derived regional LV longitudinal strains and wall geometries. Our framework was applied in two distinct porcine models of early LV remodeling, specifically following myocardial infarction and onset of LV pressure overload. RESULTS: Regional and temporal changes in computed indices of LV myocardial stiffness over diastolic pressures correlate with conventional indices of LV remodeling and show enhanced early sensitivity as compared to LV global longitudinal strain. CONCLUSION: Our findings suggest that STE-integrated computational modeling can be used to track indices of LV myocardial stiffness and, thus, is a potential tool for HF diagnosis and prognosis.

Geometric determinants of local hemodynamics in severe carotid artery stenosis.

In cases of severe carotid artery stenosis (CAS), carotid endarterectomy (CEA) is performed to recover lumen patency and alleviate stroke risk. Under current guidelines, the decision to surgically intervene relies primarily on the percent loss of native arterial lumen diameter within the stenotic region (i.e. the degree of stenosis). An underlying premise is that the degree of stenosis modulates flow-induced wall shear stress elevations at the lesion site, and thus indicates plaque rupture potential and stroke risk. Here, we conduct a retrospective study on pre-CEA computed tomography angiography (CTA) images from 50 patients with severe internal CAS (>60% stenosis) to better understand the influence of plaque and local vessel geometry on local hemodynamics, with geometrical descriptors that extend beyond the degree of stenosis. We first processed CTA images to define a set of multipoint geometric metrics characterizing the stenosed region, and next performed computational fluid dynamics simulations to quantify local wall shear stress and associated hemodynamic metrics. Correlation and regression analyses were used to relate obtained geometric and hemodynamic metrics, with inclusion of patient sub-classification based on the degree of stenosis. Our results suggest that in the context of severe CAS, prediction of shear stress-based metrics can be enhanced by consideration of readily available, multipoint geometric metrics in addition to the degree of stenosis.

Regional and temporal changes in left ventricular strain and stiffness in a porcine model of myocardial infarction.

The aim of the present study was to serially track how myocardial infarction (MI) impacts regional myocardial strain and mechanical properties of the left ventricle (LV) in a large animal model. Post-MI remodeling has distinct regional effects throughout the LV myocardium. Regional quantification of LV biomechanical behavior could help explain changes in global function and thus advance clinical assessment of post-MI remodeling. The present study is based on a porcine MI model to characterize LV biomechanics over 28 days post-MI via speckle-tracking echocardiography (STE). Regional myocardial strain and strain rate were recorded in the circumferential, radial, and longitudinal directions at baseline and at 3, 14, and 28 days post-MI. Regional myocardial wall stress was calculated using standard echocardiographic metrics of geometry and Doppler-derived hemodynamic measurements. Regional diastolic myocardial stiffness was calculated from the resultant stress-strain relations. Peak strain and phasic strain rates were nonuniformly reduced throughout the myocardium post-MI, whereas time to peak strain was increased to a similar degree in the MI region and border zone by 28 days post-MI. Elevations in diastolic myocardial stiffness in the MI region plateaued at 14 days post-MI, after which a significant reduction in MI regional stiffness in the longitudinal direction occurred between 14 and 28 days post-MI. Post-MI biomechanical changes in the LV myocardium were initially limited to the MI region but nonuniformly extended into the neighboring border zone and remote myocardium over 28 days post-MI. STE enabled quantification of regional and temporal differences in myocardial strain and diastolic stiffness, underscoring the potential of this technique for clinical assessment of post-MI remodeling. NEW & NOTEWORTHY For the first time, speckle-tracking echocardiography was used to serially track regional biomechanical behavior and mechanical properties postmyocardial infarction (post-MI). We found that changes initially confined to the MI region extended throughout the myocardium in a nonuniform fashion over 28 days post-MI. Speckle-tracking echocardiography-based evaluation of regional changes in left ventricular biomechanics could advance both clinical assessment of left ventricular remodeling and therapeutic strategies that target aberrant biomechanical behavior post-MI.