Physiological mechanism of HF and the rescuing treatment LVAD (Left Ventricular Assisting Device)

A 58 years old man, who had suffered from chronic chest pain and breath shortness for a few months, finally had enough of it and went to the hospital and seeked for help. The result of the medical checkup was astonishing. The hospital’s chief cardiothoracic surgeon found extensive signs of heart disease, with blockages in some of the man’s coronary arteries at well over 90 percent and systolic malfunction. The team removed two arteries from his chest and a vein from the leg and attached them to arteries serving the heart to detour around the blockages, saving his life just in time. This man is the two terms USA president, Bill Clinton, and one of the luckiest man in the world who was on the brink of heart failure only to recognize his cardio problem early enough and received well established treatment including a quadruple bypass operation.

        The scenario mentioned above isn’t happened coincidentally but is also happening right now and around the globe. So let us have a short insight into one of the most serious global health issue, Heart failure.

Epidemiology of heart failure 

Unfortunately, not everyone in the world is as lucky as Bill Clinton is. According to statistics, over 40 millions of people were affected by heart failure in 2015. As mentioned above, the overall onset percentage of heart failure in adult is around 2%, which is a really scary number by just calculating the total number of people affected by heart failure. In the chart below we can also notice that the differences between the onset percentage of Heart failure in men and women is quite different, in part which the men bear a higher risk than women. (Ref: [1], [3])

Figure 1Prevalence of heart failure by age and sex in the USA. Based on the National Health and Nutrition Examination Survey

Impact in Taiwan and world wide

Heart failure is one of the most serious health problem impacting not only Taiwan but worldwide. The fact that it is so dangerous is because it is both life threatening and cost a heavy burden on medical resources. According to the data of Ministry of health and welfare, Cardiovascular diseases is the second leading cause of the death in Taiwan. While in the meantime, heart failure is the major outcome in most of the end stage cardiovascular disease patient. We can claim that it is in our urgent need to develop a better strategy against Heart failure and cardiovascular disease. (Ref: [2])

 

                      Figure 2 Top 10 death cause in Taiwan.

Pathophysiology of heart failure

The pathophysiology of Heart failure is very complicated. However, we can still sort out the paradigm of the overall process in the malfunctioning heart. To be brief, the main outcome of heart failure is most common to be presented by the decrease in cardiac output. Since we know that cardiac output is the multiplication of stroke volume (SV) and heart rate (HR), we can infer that the main reason for the decline in cardiac output is originate from the decrease in stroke volume observing that there are no big differences in the heart rate of heart failure patients. Interestingly, in some cases of heart failure, it is observed that there is a correlation between higher heart rate and higher mortality rate in Chronic heart failure (CHF) patients. The finding is based on several cohort studies. (Ref: [3], [4], [5])

Figure 3the normal state of the circulation is venous return of 5 L/min and a right atrial pressure of 0 mm Hg.

        There are several reasons that will lead to decrease in stroke volume. Among these, the most frequently seen are systolic dysfunction, diastolic dysfunction, and the combination of these two. We will first focus on systolic dysfunction since it is the most common cause.

        In intuition, systolic dysfunction means the heart loses its contractility, or in a more specific physiologic term, “intrinsic inotropy”. The loss of contractility may be caused by either direct loss of cardiac muscle or the alteration in signal transduction pathways in the cardiac muscle. Take myocardial infarction as an example, stenosis or blockage in coronary arteries leads to the death of myocardia and result in cardiac muscle death.

        Diastolic dysfunction, in other words, can be viewed as the decrease in the blood volume that the ventricle can fill. This results from the decrease in compliance of the ventricle, and affect the end-diastolic volume of the heart. Another reason for diastolic dysfunction is because of overload exhaustion of heart that lead to abnormal ventricular hypertrophy and thus take up most of the space in ventricle.

        However, the dysfunctions mentioned above is only the beginning of the heart failure. The real problem is that the body’s compensatory response cannot rescue the process only to lead to a worse situation.

Figure 4Right atrial pressure and the progress of heart failure

The black line in the graph, represent a cardiac output level of 5 L/min. This level is approximately the critical cardiac output level that is required to make the kidneys keep a normal fluid balance. At cardiac outputs below this level, the kidney will go on a compensatory response to take in more body fluid volume. Because of this progressive increase in fluid volume, the systemic vascular pressure continues to rise, which forces progressively increasing quantities of blood from the person’s peripheral veins into the right atrium, thus increasing the right atrial pressure.

The rise in right atrial pressure will lead to less venous return. The less venous return will lead to the less preload, which in turns causes less cardiac output according to the Frank-Starling law. It is now clear that further retention of fluid will be more detrimental than beneficial to the circulation. The excessive retention body fluid will not only cause a burden to heart but caused edema in the heart to affect its performance. In this case, there is no return of cardiac function unless medical treatment interferes. (Ref: [7])

Treatment to rescue heart failure

Among the many treatments rescuing heart failure, most of them could be categorized into two groups: Pharmacological and surgical. In pharmacological treatments, several strategies can be taken by increasing heart systolic function. Beta adrenergic agonist and Digoxin are the two most common examples. ACE inhibitor (Angiotensin-converting enzyme (ACE) inhibitors) is also used clinically, by inhibiting the Renin-Angiotensin-Aldosterone system. Diuretics are also important in the treatment of heart failure, used in combination with the other medicine. As it can mitigate the overload in ventricle caused by compensatory response.

LVAD, the acronym for Left Ventricular Assist Device, is an artificial pump that can serve the function of left ventricular. Patients with severe heart failure and incapable of controlling the symptoms with drug can be rescued by LVAD, while waiting for heart transplantation. Since the heart transplantation has reached a plateau in recent years, LVAD is not only considered a bridge between heart transplant but also a life-prolong device.

                            Figure 5 Left Ventricular Assist Device

The basic design is to direct the blood flow in the left ventricle directly into the aorta, with a pump providing work to pump out the blood. This device requires a mild surgery to apply to patient.

The physiological circulation is quite different in patients with LVAD. For example, it is observed that by increasing pump speed and LVAD flow the Left ventricular volume evidently decreased. This is due to the fact that LVAD and native LV compete for the same preload. This reduction in LV volume can been seen from the shift in the pressure-volume loop. The original pattern of normal heart moves left and downward, becoming triangular-shaped. The reason why it becomes triangular-shaped is because with continuous flow LVAD the iso-volumic phases of the cardiac cycle will no longer exist.

Because of the partial blood flow bypassed the left ventricle. There is a reduction in preload for the native LV. Assuming contractility and afterload are unchanged, the stroke volume of native LV is sure to decline leading to reduction in systolic pressure. If the pulse pressure is too low, the aortic valve will fail to open, and that will cause the increase in pulsatility of the arterial blood pressure. That is, the pulsatility of the blood pressure is directly related to pump speed and flow.

Figure  6The effect of increasing pump speed/flow on the left ventricular pressure-volume loop.

Conclusion

        Cardiovascular disease such as heart failure are on the rise due to the aging population in the world. With the effort of numerous cardiologist, doctors, and experts from all the field, however, heart failure is no longer an opponent that we cannot combat. The complicated physiological process of cardiovascular disease is well-studied, but far from enough. I believe with this momentum, we are on the right track of fighting circulation problems. And as a medical student, I look upon myself to someday have the power to contribute to this field and bring people a higher quality of life.

Reference:

1.        Mosterd, Arend, and Arno W. Hoes. "Clinical epidemiology of heart failure." Heart 93.9 (2007): 1137-1146.

2.        https://www.mohw.gov.tw/cp-3795-41794-1.html

3.        Kannel, William B., et al. "Heart rate and cardiovascular mortality: the Framingham Study." American heart journal 113.6 (1987): 1489-1494.

4.        Hori, Masatsugu, and Hiroshi Okamoto. "Heart rate as a target of treatment of chronic heart failure." Journal of cardiology 60.2 (2012): 86-90.

5.        Kleiger, Robert E., et al. "Decreased heart rate variability and its association with increased mortality after acute myocardial infarction." The American journal of cardiology 59.4 (1987): 256-262.

6.        Lim, Hoong Sern, Neil Howell, and Aaron Ranasinghe. "The physiology of continuous-flow left ventricular assist devices." Journal of cardiac failure 23.2 (2017): 169-180.

7.        Hall, John E. Guyton and Hall textbook of medical physiology e-Book. Elsevier Health Sciences, 2015.