Coronary and myocardial physiology of left ventricular unloading

Student thesis: Doctoral ThesisDoctor of Medicine by Research


Left ventricular unloading both pharmacologically and mechanically has been employed predominantly in the prevention and treatment of cardiogenic shock. Mechanical circulatory support devices deliver varying degrees of ventricular unloading through differing mechanisms of action. Despite their physiological promise of improved myocardial supply and demand, they have failed to make an impact on patient outcomes in randomised clinical trials. The main aim of this thesis was therefore to improve our understanding of the coronary and myocardial physiological mechanisms that underpin mechanical left ventricular unloading, to obtain a greater understanding of more established and new devices, and novel treatment uses. 
The physiological impact of left ventricular unloading through various mechanical circulatory support devices was evaluated in different clinical settings and models, through invasively acquired intra-coronary pressure and Doppler flow, alongside assessment of left ventricular mechanics through the acquisition of pressure volume loops. 
The impact of balloon counterpulsation was studied in a cohort of patients with ischaemic cardiomyopathy undergoing high-risk percutaneous coronary intervention in two parts. The first part involved a detailed physiological assessment of balloon counterpulsation, and through this defining and characterising responders to balloon counterpulsation in terms of their effects on coronary haemodynamics. Furthermore, a direct comparison between two different sized balloons employed during balloon counterpulsation on coronary physiology was undertaken. 
The effect of direct left ventricular unloading through the Impella device was studied in a similar clinical cohort, to understand its physiological effects on myocardial supply and demand. In addition, the impact of Impella left ventricular unloading prior to reperfusion during coronary occlusion on invasive coronary and myocardial physiology (including impact on coronary collateral flow index) and infarct size in a swine model of acute myocardial infarction (AMI) was examined. 
Finally, Percutaneous Heart Pump, a new potent left ventricular unloading device, was assessed for the first time in a pre-clinical model of acute myocardial infarction. 
Balloon counterpulsation has more profound effects on coronary and aortic haemodynamics than on myocardial demand. Coronary haemodynamic responders were more likely to have undergone complex PCI and have worse systemic haemodynamics at the outset, to suggest that those with the most disordered autoregulation stand to benefit most from counterpulsation. A larger capacity balloon as compared with the smaller balloon has more pronounced coronary haemodynamic effects. 
In the clinical study of Impella device in the setting of an open artery following PCI, mechanical left ventricular unloading favourably impacts the myocardial supply: demand ratio, through greater effects on myocardial demand rather than improved coronary perfusion. Left ventricular unloading during coronary occlusion prior to reperfusion increases coronary collateral flow to the infarct-related artery, correlating with improved left ventricular stroke work and reduction in infarct size. 
The Percutaneous Heart Pump provides potent left ventricular unloading, with little effect on overall coronary flow and results in a reduction in total coronary wave energy with increasing flow rates. There is an observed negative effect on physiology with an inactivated device across the aortic valve. 
Mechanical left ventricular unloading in its various forms have differing effects on myocardial supply and demand, which underpins the need for a more individualised approach to device therapy. The physiological benefits of balloon counterpulsation have been re-confirmed, and a cohort of patients clinically that have more disordered autoregulation at the outset stand to benefit most from this therapy. With an open coronary artery, direct left ventricular unloading devices have more profound effects on the myocardium and therefore may be of most benefit in cardiogenic shock, whereas when employed during occlusion (termed primary unloading) these devices improve myocardial supply through an increase in collateral flow. Primary unloading is a paradigm-changing concept that may become a new therapeutic indication for these devices, but will need to be tested in patients in a randomised fashion before it is introduced into the clinical arena. Overall, the importance of understanding the device physiology and patient physiology has been highlighted, in order to maximise the therapeutic impact.
Date of Award1 Sept 2019
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorDivaka Perera (Supervisor) & Michael Marber (Supervisor)

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