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Cardiac electro-mechanical coupling in relation to ventricular arrhythmias in the intact human heart: from cardiac mapping and speckle tracking echocardiography to biomarkers

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The balance of power in the heart

The electrical activity and mechanical function of the human heart are highly intertwined. Delineating the feedback mechanism between these processes is central to human health.

Fundamental Research
Health

The blood-pumping action of the heart is maintained through electrical impulses that originate in the right atrium. Under physiological conditions, electrical activation and repolarisation ensure cardiac relaxation and contraction. Mechanical deformation of the heart induces changes in cardiac electrophysiology, indicating a tight interaction between the two processes. This is called electro-mechanical feedback (MEF) of the heart and is poorly characterised in vivo. Scientists of the EU-funded CARDIO MEF project wished to investigate MEF in patients undergoing open heart cardiac surgery. To achieve this, they simultaneously assessed the electrical and mechanical activity via a multi-electrode heart sock and trans-oesophageal echocardiography. Specific focus was given to ventricular repolarisation, including beat-to-beat dynamics and spatial dispersion. Research teams hypothesised that alterations in the strain of the myocardium have a direct, predictable effect on electrophysiology, while in patients with coronary artery disease, mechanical heterogeneity may contribute to electrical heterogeneity, creating a pro-arrhythmic state. Analysis of the collected data showed a change in repolarisation and premature contractions during changes in ventricular loading. This was due to transient aortic occlusion and establishment and disconnection of cardio-pulmonary bypass. Using a combination of computational modelling and human experimental data, scientists studied MEF at the cellular level. The computational model showed that mechanical strain and adrenergic activation can affect cardiac repolarisation dynamics. Importantly, these two processes can act synergistically under pathological conditions and lead to dangerous arrhythmia. In another part of the project, scientists investigated the underlying mechanisms of repolarisation alternans, an electro-mechanical phenomenon that is associated with periodic beat-to-beat variability of T-waves on the electrocardiogram. Results indicated a role for calcequestrin and ryanodine, proteins involved in the handling of calcium ions. Overall, the study provided fundamental knowledge on the coupling between electrical activity and mechanical function of the human heart. Furthermore, these results are expected to have an impact on the prediction of ventricular arrhythmia and patient management.

Keywords

Heart, electro-mechanical feedback, CARDIO MEF, arrhythmia, repolarisation alternans

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