Biomechanics — the study and analysis of forces on the body — provides an important perspective for understanding the normally functioning heart as well as the diseased heart. This page will analyze the structural changes to the heart caused by HF, and how those changes affect the heart’s biomechanical function.

Normal Cardiac Function

Anatomy of the Heart:

At the most basic level, the heart consists of four chambers: the left atrium, the left ventricle, the right atrium, and the right ventricle. Blood enters the right atrium of the heart from the rest of the body through the superior and inferior venae cavae. The blood will drain from the right atrium through the tricuspid valve and enter the right ventricle. The pulmonary arteries bring the deoxygenated blood from the right side of the heart to the lungs, and the pulmonary veins transport the blood back to the heart into the left atrium. The purpose of the right side of the heart is to provide enough pressure to force the blood through the pulmonary circuit (Hill et al., 2016). Blood will leave the bottom of the atrium through the left atrioventricular valve and into the left ventricle. With each contraction, the blood will be pumped out of the systemic aorta, into the systemic circuit where oxygen will be supplied to all the tissues throughout the body.

Electrical System:

The heart is able to pump blood by forcefully contracting its muscular chambers, a process that is controlled by electric impulses. In humans, those electrical impulses originate in, and are initiated by, a central location known as the pacemaker cells. Since the muscle cells are electrically coupled, when one pacemaker cell is depolarized, it will cause the cells around it to also depolarize, creating an electrical reaction that will spread throughout the remaining parts of the heart until every cell is depolarized (Hill et al., 2016). The pacemaker cells are located in the right atrium, a location known as the sinoatrial node. The cells that make up the pacemaker have an increased frequency of spontaneous depolarization compared to the other myocytes, which is why they initiate the depolarization of the heart. As the depolarization spreads throughout the atria, they will start to contract and pump blood to the ventricles. The electrical signal spreads to the ventricles, which begin to contract, pumping blood to the lungs and the body. As ventricles eject blood, the atria start to become repolarized and relaxed, losing pressure until the venous pressure is sufficient to open valves that permit blood to refill the atria.

Myocytes:

The specialized cardiac muscle cells are called myofibers or myocytes. The myocytes have different orientations in different layers of the heart: from longitudinal to circumferential, and then back to longitudinal as they form layered sheets (Voorhees, 2015). In the sheets parallel to the epicardial surface, the individual myocytes are aligned at varying angles depending on their location within the heart. This orientation allows the heart to be stronger in the longitudinal and circumferential directions where the heart tends to undergo the most stress. The arrangement of the myocytes also produces ventricular torsion with the relaxation and contraction of the myocytes. Therefore, the outer and inner surfaces of the myocardium can contract in different circumferences, an arrangement that shrinks the volume of the chamber more efficiently than if the contractions occurred in one circumference. Pumping is also enhanced by ventricular torsion, created by the difference in the timing of the electrical contraction signals in the subepicardial and subendocardial layers, a twist which further shrinks the ventricular chamber, ejecting more of the blood to the aorta. 

Altered Cardia Function in Patients with Heart Failure

Titin:

Another important part of the myocardial tissue that has an effect on the mechanical properties of the heart is the molecule titin. It is a large elastic protein that stabilizes the sarcomere, the contractile building block, an intracellular unit of contracting myosin and actin molecules arrayed in series and parallel. By preventing the sarcomere from over-extending when the myocyte is stretched by an external force, the main role of titin is to protect the cells from damage (Voorhees, 2015). There are many isoforms of titin, some more flexible than others; the flexible isoforms may be unable to prevent overextension and may lead to heart failure and diastolic dysfunction in the future.

Myosin and Actin:

Contraction of a myocyte occurs when the myosin binds to actin, creating a cross-bridge, and then undergoes a conformational change, reconfiguring to pull on actin fibers. This is a repetitive process that contracts the sarcomere, shortening the whole myocyte when all the sarcomeres within the cell contract in concert. The quantity of cross bridges determines the magnitude of force and the stiffness of the myocardial wall. 

Collagen:

The structural protein collagen, which forms in large part the extracellular matrix of the myocardium, provides attachment sites for the myocytes and prevents the myocardium from overstretching. In a healthy individual, the collagen levels will be low relative to the volume of muscle. But diseases and old age can cause the levels of collagen to increase through fibrosis, the thickening of tissues in an organ (Voorhees, 2015). This process makes the tissues and the heart itself stiffer, resulting in a lower amount of blood entering the LV, which can be diagnosed as heart failure.

Left Ventricle Remodeling:

Heart failure is normally caused by abnormalities of the left ventricle. The main hypothesis of HF is that it is a progressive disorder caused by left ventricular remodeling, which is caused by a so-called index event. An index event is any acute injury to the heart, which can be a myocardial infarction, genetic variations that affect contractile function, and hemodynamic overload. The index event and cardiac remodeling then leads progressively to heart dysfunction, including impaired cardiac function and circulatory congestion. After an index event occurs, endogenous neurohormones and cytokines are activated as a response (Fomovsky, 2010). Due to heart dysfunction, there are drastic changes in the size and shape of the heart, which can include loss of myofilament, apoptosis, myocyte slippage, interstitial matrix growth, as well as many other mechanisms (Francis, 2001). With the loss of myocytes, the heart cannot generate the contractile force needed to effectively pump enough blood. But the process is not entirely clear. More work is needed on LV remodeling in order to explain why cardiac myocytes sometimes enter apoptotic pathways or why some myocytes will increase in size (hypertrophy). An analysis of patients with heart failure have shown that they have increased cardiac mass due to fibrosis and myocyte hypertrophy, leading to the chambers becoming more stiff (Orogo and Gustafsson, 2013). Hypertrophy is linked to mechanical deformation of the cell membrane and mechanical signals such as neuroendocrine factors, but more research still needs to be completed to understand the mechanisms behind hypertrophy.  

Excitation-contraction Coupling:

Another important consideration when discussing HF is cardiac mechanical contraction, which involves excitation-contraction coupling (ECC) to create the electrical activation, discussed above, that triggers the contraction of the heart. Poorly regulated cardiac myocyte intracellular calcium can lead to heart failure since the electrical delay can cause mechanical alterations and increase pump impairments. In order to have adequate ejection of blood from the heart, there must be synchronous contraction, and without it, the heart will not be able to eject blood efficiently. Asynchronous contraction eventually leads to decreased pump function. Roughly half of patients with HF have mechanical dyssynchrony (Pfeiffer, 2014). There have been numerous studies conducted to analyze ECC at the cellular level in patients with heart failure and other cardiac diseases, but more studies must be done in order to understand the effect of altered ECC on the mechanical function in the whole heart. 

References

  • Arackal, A., & Alsayouri, K. (2022). Histology, heart – statpearls – NCBI bookshelf. National Library of Medicine NIH. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK545143/ 
  • Centers for Disease Control. (2022, October 14). Heart failure. Centers for Disease Control and Prevention. Retrieved October 31, 2022, from https://www.cdc.gov/heartdisease/heart_failure.htm 
  • Fomovsky, G. M., Thomopoulos, S., & Holmes, J. W. (2010). Contribution of extracellular 
  • matrix to the mechanical properties of the heart. Journal of Molecular and Cellular 
  • Cardiology, 48(3), 490–496. https://doi.org/10.1016/j.yjmcc.2009.08.003
  • Francis, G. S. (2001). Pathophysiology of chronic heart failure. The American Journal of Medicine, 110(7), 37–46. https://doi.org/10.1016/S0002-9343(98)00385-4 
  • Hill, R. W., Wyse, G. A., & Anderson, M. (2016). Animal Physiology. Sinauer Associates, Inc. 
  • Orogo, A. M., & Gustafsson, Å. B. (2013, August). Cell death in the myocardium: My heart won’t go on. IUBMB Life. Retrieved November 21, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4074399/ 
  • Pfeiffer, E. R., Tangney, J. R., Omens, J. H., & McCulloch, A. D. (2014). Biomechanics of cardiac electromechanical coupling and mechanoelectric feedback. Journal of Biomechanical Engineering, 136(2), 021007. https://doi.org/10.1115/1.4026221
  • Voorhees, A. P., & Han, H. C. (2015). Biomechanics of cardiac function. Comprehensive Physiology, 5(4), 1623–1644. https://doi.org/10.1002/cphy.c140070