Impella controller derived flow correlates well with pulsed-wave Doppler derived flow
All 10 pigs survived 15h post-ROSC and were successfully extubated. No complications due to TEE probe insertion or during TEE image acquisition were observed. Body surface area was similar between groups (0ppm: 1.2±0.1 vs. 20ppm: 1.3±0.1 m2, p=0.278). At least two different clear views of 4-CH, 2-CH, and LAX at all given time points were obtained in all animals.
The mean heart rate at baseline was 92±14 min-1. The systemic and pulmonary artery pressure at baseline did not differ between groups and are presented in Table 1. COPWD correlated well with the invasively measured COTD at baseline, 30min, 3h and 5h (r= 0.71, p= 0.021; r= 0.91, p<0.001; r= 0.93, p<0.001; r= 0.84, p<0.01, respectively) (Figure 2). The calculated pump flow displayed by the automated Impella controller correlated well with the PWD derived pulmonary flow following iCPR initiation (1.8±0.2 vs. 1.9±0.2 L/min, r=0.85, p=0.012).
Application of iNO significantly increases cardiac output and improves left ventricular systolic function recovery
At baseline, LVEDV, LV-EF and LV-GLS did not differ between groups. After induction of VF, LVEDV increased significantly in both groups compared to baseline (Figure 3A). Over the course of iCPR for 5 hours, LVEDV decreased and returned closer to baseline values in both groups (Figure 3A and Table 2). However, LVEDV in the 20ppm group was higher at all time points and was statistically significant at 3h post-ROSC (0ppm: 78.2±1.1 vs. 20ppm: 70.8±1.3 mL, p<0.001). LV-EF did not differ significantly between groups at all time points or within each group compared to baseline (Figure 3B). The LV-GLS improved throughout the duration of iCPR in both groups from baseline (Figure 3C). The LV-GLS values were significantly lower at 3h and 5h post-ROSC in the 20ppm group compared to the 0ppm group (5h: 0ppm: -13.1±2.4 vs. 20ppm: -18.2±3.4, p=0.025) (Figure 3C). The CO decreased in both groups at iCPR initiation and improved over the course of iCPR. The COPWD increased significantly in the 20ppm group at 3h and 5h post-ROSC compared to the 0ppm group (3h: 0ppm: 4.6±0.9 L/min vs. 20ppm: 6.6±1.1, p=0.016; 5h: 0ppm: 4.0±0.6 L/min vs. 20ppm: 5.8±1.0, p=0.036) (Figure 3D).
Application of iNO enhances right ventricular systolic function recovery
RV echocardiographic measurements, RV basal diameters at end-diastole (RVEDD), RV-FAC, TASV and RV-GLS, did not differ between the two groups at baseline (Figure 4A-D and Table 2). However, RV-FAC decreased significantly during CA and 30min post-ROSC. In the 0ppm group, RV-FAC was lower at all time-points compared to baseline (0ppm baseline vs. 30min, vs. 3h vs. 5h post-ROSC: 44.1±6.1% vs. 27.4±2.8%, p=0.004; vs. 32±5%, p=0.009; vs. 33.2±4.3%, p=0.001; see also table 2). In the 20ppm group, RV-FAC improved at 3h and recovered to baseline values at 5h post-ROSC (baseline: 42.9±6.6 % vs. 5h: 41.1±6.4; p=0.442) (Figure 4A). RVEDD increased significantly in both groups at iCPR initiation, and slowly recovered over time but did not differ between groups (Figure 4B and Table 2). Within the 0ppm group, TASV decreased significantly after CA and remained lower during the course of iCPR (baseline vs. 3h: 13.6±1.1 vs. 7.8±1.6 cm/s, p=0.024; baseline vs. 5h: 13.6±1.1 vs. 9.4±1.3 cm/s, p=0.009, respectively) (Figure 4A and Table 2). The TASV values in the 20ppm group were higher at 3h and 5h post-ROSC compared to the 0ppm group (20ppm vs. 0ppm at 3h: 11.4±1.1 vs. 7.8±1.6 cm/s, p=0.024; at 5h: 12.8±1.1 vs. 9.4±1.3 cm/s, p=0.012). The RV-GLS values were similar between the two groups at baseline and post-ROSC. However, RV-GLS at 5h post-ROSC was significantly lower in the 20ppm group than 0ppm (0ppm vs. 20ppm at 5h: -9±1.4% vs. -13±2.2%; p=0.007; Figure 4D).
LV myocardial work indices indicate recovery during and after ventricular unloading
At baseline, myocardial work indices (GWI, GWE, GCW, GWW) did not differ between the two groups (Figure 5A-D and Table 2). The LV-GWI did not differ between the two groups at any time. However, LV-GWI in the 20ppm group recovered after an initial decrease and began to recover at 30min post-ROSC to reach almost baseline values at 5h post-ROSC (baseline: 1,751±270 mmHg% vs. 5h: 1,529±274 mmHg%, p=0.401) (Figure 5A and Table 2), while in the 0ppm group, LV-GWI was significantly lower compared to baseline at all time-points (baseline: 1,835±305 mmHg%; 30min: 891.2±412 mmHg% (p=0.032), 3h: 896±129 mmHg% (p=0.011), and 5h: 1,125±214 mmHg% (p=0.011); Figure 5A). LV-GWE and LV-GCW had a similar time-course to LV-GWI and did not recover in the 0ppm group (Figure 5B). The LV-GWW did not differ between groups and did not increase significantly in both groups at all time-points compared to baseline (Figure 5C).
RV myocardial indices indicate a more complex pattern and slower recovery
At baseline, the RV myocardial work indices did not differ between groups (0ppm vs. 20ppm, Figure 6A-C and Table 2). At 3h and 5h post-ROSC, RV-GWI was significantly lower in the 0ppm group compared to the 20ppm group (0ppm: 108.4±22.6 vs. 20ppm: 189.6±43.6 mmHg%, p=0.049 and 0ppm: 152.6±42.4 vs. 261.6±54.2 mmHg%, p=0.041, respectively). Within the 0ppm group, the RV-GWI did not recover and remained significantly decreased at 30min, 3h and 5h post-ROSC compared to baseline (baseline: 338.2±45.3 mmHg% vs. 30min: 101.6±34.5 mmHg%, p<0.001; vs. 3h: 108.4±22.6 mmHg%, p<0.001; vs. 5h: 152.6±42.4 mmHg%, p=0.012, respectively; Figure 6B). In both groups, the RV-GCW decreased significantly after CA, but a slow recovery over time was noted in both groups with no difference between groups (Figure 6B and Table 2). The RV-GWW increased significantly in the 0ppm group compared to the 20ppm group at 3h and 5h post-ROSC: 69.6±11.9 vs. 47.4±6.7, p=0.049 and 77.8±14.8 vs. 50.2±8.2, p=0.046, respectively (Figure 6C). The RV-GWE increased significantly in the 20ppm group at 5h post-ROSC compared to the 0ppm group (80±5.2 vs. 73±5.7, p=0.042, respectively)
Diagnostic utilization of pressure-strain loops
Figure 7A is a representative overlay of the PS-loops of the LV. An acute injury following iCPR initiation is demonstrated by narrowing of the PS-loop (a sign of loss in maximally generated strain), thus explaining the ventricle´s inability to generate sufficient pressure [13-17].
The partially positive strain indicates a passive distention of the myocardium due to volume loading [15-17]. Unloading leads to slow recovery and progressive normalization of the PS-loop, which remains below (i.e., less negative) normal values but shows a curve pattern comparable to normal conditions [17, 18].
Figure 7B is a representative overlay of the PS-loops of the right ventricle. A pumping failure leads to increased RVP, and a loss in strain translates to a more complex strain-pressure relation [19, 20]. The RV strain reduction remains pronounced even after a longer duration of left ventricular support [20, 21].
Figure 7C demonstrates the spatial distribution of strain at different time-points. This allows differentiation of regional wall motion deterioration e.g., in acute myocardial infarction from global failure, thus providing a detailed perspective on myocardial recovery over time.