Transcatheter targeted myocardial restoration using hydrogel-based cell-free compound: Toward an adoptable clinical protocol

Abstract

Background: There is a need for a targeted, comprehensive, minimally invasive myocardial restoration treatment aimed at patients with chronic postinfarction heart failure that can provide a sustained effect and be conveniently adopted with transcatheter techniques. Here we evaluated the effectiveness of a platelet-rich plasma hydrogel-based, cell-free therapeutic compound delivered with the aid of a 3-dimensional electromechanical mapping and catheter-based technique (NOGA) in a porcine translational model.

Methods: We assessed the feasibility of targeted, minimally invasive transcatheter NOGA-guided injections of the therapeutic compound in myocardial infarction (MI) survivors at 8 weeks post-MI.

Results: Animals undergoing NOGA-guided hydrogel injections at 8 weeks post-MI demonstrated a significant improvement of the selected left ventricular parameters at a 12-week follow-up. Compared to nonintervention, the hydrogel-based therapy provided significant improvements in end-diastolic volume (-11.0% ± 11.1% vs 6.3% ± 15.2%; P = .008) and ejection fraction (-9.1% ± 16% vs 12.7% ± 18.6%; P = .009). In the slice closest to the apex, significant differences in scar area were observed; the treatment group demonstrated a smaller mean scar area in the infarcted zone compared with the control group (47.1% ± 7.0% vs 59% ± 8.2%; P = .013) and a smaller mean scar area in the border zone compared with the saline group (31.4% ± 8.3% vs 42.6% ± 9.0%; P = .016).

Conclusions: The study implies a translational potential of the hydrogel-based therapy and should trigger clinical trials focused on establishing a restoration therapy that can be integrated into a clinical protocol.

Keywords: NOGA; hydrogel; myocardial infarction; myocardial restoration; transcatheter.

A method of evaluation of a platelet-rich plasma hydrogel-based compound in postinfarction heart failure.

Figure 1

A, Three-dimensional dynamic visualization of the scar area (<0.5 mV) (red) and viable tissue (>1.5 mV) (purple). B, Electromechanical assessment showing viability in the left column. The dense scar is visible at the apex and the anteroseptal wall; surrounding areas show a wall motion deficit (red in linear local shortening [LLS]): B1, unipolar voltage map; B2, bullseye view of unipolar voltage map; B3, wall movement map (LLS%); B4, LLS% bullseye view. C1, Intramyocardial injections; 10 injections within the infarct zone and the remaining 10 within the peri-infarct zone, identified as brown dots. C2 to C4, Electrical conduction propagation showing the delayed activation in the scar area (left anterior descending artery territory). D, Visualization of dyskinetic zones: D1, volume–time graph showing synchronous left ventricular (LV) volume (yellow line) and local wall movement (white line); D2, dyssynchronous LV volume (yellow line) and local wall movement (white line).

Figure 2

A, Cardiac magnetic resonance imaging (MRI) at 8 weeks after myocardial infarction (MI): A1, long axis (diastole); A2, long axis (systole), A3, short axis (diastole); A4, short axis (systole); A5, late gadolinium enhancement (LGE) showing the quantified area of scar tissue in the left ventricle. B, Cardiac MRI at 12 weeks after MI: B1, long axis (diastole); B2, long axis (systole); B3, short axis (diastole); B4, short axis (systole); B5, LGE.

Figure 3

Histologic assessment of the explanted myocardium. A1, The left ventricle was sectioned and sliced. A2, Transverse sections of the left ventricle. A3, Schematic of the 3 zones. B, Hematoxylin and eosin staining of slides from the 3 zones: B1, infarct; B2, remote; B3, border.

Figure 4

Comparison of changes in primary endpoints from 8 weeks to 12 weeks in the study groups. A, Percentage change in ejection fraction (EF) measured by magnetic resonance imaging (MRI) in all groups. B, Percentage change in EF measured by MRI in the nontreatment (control + saline) group and the treatment group. C, Percentage change in end-diastolic volume (EDV) measured by MRI in all groups. D, Percentage change in EDV measured by MRI in the nontreatment and treatment groups. In all the box-and-whisker plots, the lower and upper borders of the box represent the 25th and 75th percentiles, respectively, and the middle horizontal line represents the median. The lower and upper whiskers represent the minimum and maximum values of nonoutliers, and outliers were excluded.

Figure E1

Study flow diagram showing the evaluation and investigation of the study animals over 12 weeks. MI, Myocardial infarction; LCX, left circumflex branch; LAD, left anterior descending artery.

Figure E2

Fluoroscopy of the experimental large animal in left anterior oblique cranial view showing engagement of the left anterior descending artery (LAD) with a 6 Fr Amplatz right 1.0 guiding catheter (A1), initiation of deployment of a Nester or Tornado embolization coil (Cook Medical) into the mid-LAD region (A2), and completion view of the successful coil embolization and complete occlusion of the LAD (A3).

Figure E3

A, Periprocedural transthoracic echocardiography at 8 weeks after myocardial infarction (MI): A1, parasternal long-axis view; A2, pulsed-wave (PW) Doppler measurement; A3, short-axis view. B, Periprocedural transthoracic echocardiography at 12 weeks post-MI: B1, parasternal long-axis view; B2, PW Doppler measurement; B3, short-axis view. C, Statistical comparison of the changes from 8 weeks to 12 weeks post-MI in the study group: C1, end-diastolic volume (EDV) (P = .173); C2, end-systolic volume (ESV) (P = .292); C3, ejection fraction (EF) (P = .920).