Invasive and non-invasive monitoring during mechanical circulatory support in cardiogenic shock

Acute myocardial infarction (AMI) presents with varying degrees of ischemicmyocardial damage and in cases with extensive myocardial damage, cardiogenicshock (CS) may develop. This is a state where damage to the heart reduces itsability to deliver oxygenated blood to meet the metabolic demand of end-organs.Classic signs of hypoperfusion is altered mental state, oliguria and cold andclammy skin. Hypoperfusion further reduces the hearts performance, leading toa downward spiral that causes multi-organ failure and death.Management of patients with CS due to AMI has two simultaneous paths, onewith the aim to restore coronary blood flow and one to provide therapy to supportthe heart and end-organs. Restoration of coronary blood flow, with percutaneouscoronary interventions or coronary artery bypass surgery, are the only therapiesproven to reduce mortality. Despite the lack of established benefit on mortality,several strategies exist for support of the heart and end-organs, includingvasopressors, inotropic agents and mechanical circulatory support (MCS). Thechoice of strategy depends on the location and degree of myocardial damage andthe presence of extracardial organ damage. To assess this, echocardiography isthe most widely used method in clinical practice, as it is possible to conduct abedside estimation of function of the left and right ventricle, assess gross valvularpathology and identify mechanical complications to AMI within minutes.However, when assessing left ventricular (LV) function there are two principlesused; one based on volume changes and one based on signs of contraction.Within both principles, several methods exist, but to which degree they areaffected by ischemia and their relation to invasive pressure and volume measuresare largely unknown.In CS after AMI, both the LV and right ventricle (RV) can be the primary oneaffected, with primary LV dysfunction being the most common. For primary LVdysfunction several options for MCS exist, but two systems are more commonlyused; the Impella® system and veno-arterial extracorporeal membraneoxygenation (VA-ECMO). The Impella® system is a percutaneous microaxialtransvalvular flow pump that drains blood from the LV and delivers it into theascending aorta. This has the advantage of unloading the LV. With VA-ECMO,blood is drained from the right atrium and inferior vena cava, is oxygenated, and With CS due to primary RV dysfunction, strategies for support and MCS optionsdiffers markedly. For MCS, Impella RP® is one option, as it drains blood from theright atrium and delivers it into the pulmonary artery, thereby bypassing the failingRV. This unloads the RV compared to a vasoactive strategy, but how it affectsthe echocardiographic measurements of the RV and LV function is unknown.The purpose of the present PhD study was to study the following aims, usingexperimental porcine models of CS due to coronary embolization:Study A - describe the association between speckle tracking echocardiography(STE) and Doppler based imaging and central hemodynamics assessed withconductance catheter technology during induction of severe ischemicdysfunction.Study B - compare the combination of VA-ECMO and Impella CP® (ECMELLA)to VA-ECMO alone on outcomes of myocardial energetics and end-organperfusion.Study C - compare the impact of either Impella RP® or vasoactive treatment onlongitudinal functions assessed by STE and tissue Doppler imaging (TDI) in CSwith predominant RV failure.

Methods
In all studies, Danish landrace pigs with a weight of 70-75 kg were used. Allinstrumentation was performed percutaneously and echocardiography wasperformed through a subxiphoid midline incision. For assessment ofintraventricular pressure and volume, we used conductance catheters in the LVin study A and B and in both the LV and RV in study C. CS was induced withstepwise injections of occlusive microspheres in the coronary arteries. For studyA and B, emboli was injected into the left main coronary artery and into the rightcoronary artery in study C. In all studies, CS was defined as a 50% or morereduction in cardiac output and/or mixed venous saturation or an absolute mixedvenous saturation below 30%.In study A, an echocardiogram was performed after each emboli from baseline toCS and analyzed with STE and TDI with simultaneous recording of pressurevolume relationship. In study B, VA-ECMO was initiated when CS was presentand embolization was continued until pulse pressure was below 10 mmHg. At thispoint, an Impella CP® was implanted in the ECMELLA arm. The interventions waskept running for four hours. In study C, the vasoactive treatment consisted ofnorepinephrine and milrinone. Either vasoactive treatment or Impella RP® wasinitiated when CS was obtained and the interventions was then kept running forthree hours before termination.

Results.
In study A, 10 animals were studied, and with induction of myocardial injury wefound large increases in longitudinal strain (LS) (-13.8±3.0 % to -6.1±2.0 %) anddecreases in LVOT VTI (16.9±2.6 cm to 7.8±1.8 cm) from baseline to time of CS.LS and LVOT VTI showed earlier and more pronounced changes from baselineto CS, compared to LVEF and s’. In univariate linear regression, LS and LVOTVTI demonstrated the strongest correlations with stroke work of the evaluatedmeasures, followed by systolic blood pressure.In study B, we induced severe LV dysfunction in 15 animals. At baseline, pressurevolume area (PVA) was 15553±4292 mmHg*mL) and 13161±4023 mmHg*mL) inthe VA-ECMO and ECMELLA arm, respectively. At time of CS, this was reduced to 8923±1975mmHg*mL and with continued embolization remained stable at8961±708 mmHg*mL in the VA-ECMO arm but decreased from 8436±2973mmHg*mL to 6921±5036 mmHg*mL in ECMELLA. The difference in PVA wassignificant after four hours (p
Conclusion
In conclusion, we found that LS is a sensitive echocardiographic marker ofdeclining LV function in an experimental model of myocardial infarction withprogressive LV dysfunction. In CS supported with VA-ECMO and low pulsepressure, the addition of Impella CP® lowered PVA, indicating better myocardialenergetics and we observed equal end-organ perfusion. In the case of CS withpredominant RV failure, vasoactive treatment increased LS in both the RV andLV but at the cost of increased stroke work. delivered into the descending aorta. This creates a retrograde flow towards theupper body and heart. VA-ECMO has the advantage of being able to deliverhigher flow rates than the Impella® and offers both oxygenation and biventricularsupport. However, the retrograde flow induces a risk of severe LV distension andpressure overload, especially with low intrinsic LV function, which in turn maylead to pulmonary congestion. To overcome this, the combination of VA-ECMOand Impella® (the ECMELLA configuration) has been proposed. In theory, thisshould ameliorate LV distension and offer better cardiac energetics, but thisremains to be scientifically proven.