A research study, conducted by Witte, Levy, Lindsay, and Clark in 2007, on the biomechanics and metabolic efficiency in patients with chronic heart failure is linked below. The study explores the differences between patients with HF and control subjects during percentages of their peak workload. The key findings showed that patients with HF are less efficient at lower workloads, they have a higher total oxygen consumption per unit of work, and they shift to anaerobic metabolism quicker than the controls. Patients also take an increased amount of time to repay their oxygen debt. To find out more specifics about the study itself, read below! This presentation was created with a target audience of college-educated individuals.
Presentation:
We are going to look at how the cardiac function, which is the ability of the heart to meet the metabolic demands of the body, is impaired in patients with chronic heart failure, or CHF. Thus, we will look at a scientific article that investigates this topic!As a reminder, this semester I’ve been addressing these two questions: “What are the structural changes to the heart caused by CHF and how do those changes affect the biomechanical function of the heart? How do these changes also affect other systems in the body?” Today, I will be addressing the second question of how it affects other parts of the body. If you are curious about how the biomechanical function of the heart is altered in patients with CHF, feel free to read my review paper on that topic! Now to the research paper. I picked the article called Biomechanical efficiency is impaired in patients with chronic heart failure written in 2007 by Witte, Levy, Lindsay, and Clark. Before we get into the scientific paper, it is first important to understand what chronic heart failure is! When an individual’s heart is unable to pump enough blood to meet the demands of the body, then the person is in heart failure. Most causes of heart failure are from LV remodeling, which means there are changes to the left ventricular myocardium that leads to a decline in the performance of the left ventricle. People who have heart failure have reduced ejection fraction. Ejection fraction is the percentage of blood that leaves the left ventricle with each contraction. Patients with low ejection fraction means their hearts are not pumping enough blood from the left ventricle. Typically, people with heart failure have an ejection fraction below 40%, while the average individual has an ejection fraction between 55% and 75%. Patients who have a history of CAD, hypertension, diabetes, obesity, myocardial infarction and other cardiac related diseases are the most at risk of developing CHF. On the right is a picture of a normal heart and a picture of a heart that is in heart failure. As you can see, the left ventricle (which will be on your right when you are looking at it) appears to be thickened. The ventricle also has a smaller volume. On the left, we see the basic anatomy of the heart. Blood flow enters the heart into the right atria from the superior and inferior vena cavas. It will flow through the tricuspid valve (right atrioventricular valve) into the right ventricle. From there, the pulmonary valve opens, and the blood will go to the lungs through the pulmonary artery. Then the blood will leave the lungs through the pulmonary veins and enter the left atria. Once the mitral valve opens, the blood flows into the left ventricle. Lastly, once the aortic valve opens, the blood leaves the heart through the aorta. The figure on the right shows the dynamics of the left side of the heart. The arrow at the bottom of the graphs marks the start of ventricular systole, which is when the left ventricle starts to contract. Once the pressure in the ventricle is greater than the pressure in the atria, the atrioventricular valve closes, stopping more blood from flowing into the ventricle. For about 0.05 seconds, the ventricular pressure is lower than the systemic aorta pressure. During this time period, the volume of blood in the ventricle is constant since the inflow and outflow valves are closed. However, once the pressure exceeds the pressure in the aorta by contraction of the constant volume of blood, known as isometric contraction, the aortic valve will open and blood will leave the heart and increase the pressure in the aorta. Once the aortic valve opens, the ventricular ejection phase starts. During the end of this phase, the ejection of the blood will occur at a slower rate due to momentum. Once the aortic pressure is greater than the ventricular pressure again, the valve will shut, and the ventricle will relax. Then this whole process will start again. If you look at the very bottom graph, the area under the curve will be the amount of blood in mL that is ejected. Thus, this curve will be smaller in patients with heart failure since they have a reduced ejection fraction. One of the most common symptoms of CHF is shortness of breath since there is an insufficient amount of blood that flows to the organs for oxygen exchange. A lot of patients also have a fast heart beat, which is called tachycardia, since the heart will try to compensate for less blood leaving the ventricle by beating faster. However, this also prevents the ventricle from filling with as much blood as it normally would. Another symptom is fluid retention. Fluid builds up in the body since there is reduced urine output caused by the buildup of blood in the kidneys too. Thus, the kidneys are not able to filter the blood efficiently, leading to the retention of fluids throughout the body. This is why a lot of patients with CHF limit their fluid intake, as well as their salt intake. Other symptoms include fatigue/weakness, cough with pink mucus, weight gain (from fluid retention), nausea, chest pain, and difficulty in concentrating. On this diagram you can see jugular vein distention, known as JVD, which is when the major veins in your neck is bulging. As an example (click for picture to appear), this is what it will look like in a patient with heart failure. This occurs when there is blood backed up in the superior vena cava or in the heart. There is an alarming amount of people who are affected by CHF every year. Just in America, there are 6.5 million people over the age of 20 that suffer from CHF. In addition, there are 960,000 people who are diagnosed with CHF every year. As you can see from the graphic, 1 in 5 people will develop HF in their lifetime. Half of the people over 65 who have heart failure will die within five years of the onset. The graph on the right shows the amount of people who have heart failure in each area of the country. Since there are so many people who have CHF, it is probably not surprising that it is the number one cause of hospitalizations in America. Due to heart failure, there are so many hospitalizations. There were 1.1 million hospital stays in 2017, as well as 11.2 billion dollars spent on treating heart failure. It is an expensive condition to have! As you saw in the previous symptoms slides, shortness of breath and fatigue both affect people who have been diagnosed with chronic heart failure. Since the heart muscle is not pumping efficiently, the tissues and organs are not getting enough oxygen since the blood builds up in the lungs. Thus, carbon dioxide also builds up in the body since the exchange of oxygen and carbon dioxide in the lungs is impaired. Patients will have an increased ventilatory response, which means they will try to inhale more oxygen since they feel short of breath. Oxygen consumption is a proxy for the metabolic rate. Thus, it makes sense that patients with CHF have a lower peak oxygen consumption: their entire energy metabolism is impacted negatively. Other findings from previous studies have shown that patients with CHF take longer to reach their steady state will exercising, and they also take longer to return to their baseline. In this case, steady state refers to reaching a point while exercising where the heart rate and oxygen consumption are constant. The baseline is the resting oxygen consumption.
Other studies have also shown that patients with CHF have an increase in biomechanical efficiency due to their lower oxygen consumption. However, they have a decrease in metabolic efficiency since patients with CHF consume more ATP. Researchers believe that biomechanical efficiency is increased in patients with CHF since they perform more anaerobically than the general population, which means they produce ATP without oxygen. However, this study is investigating the biomechanical efficiency between controls and patients with chronic heart failure. The researchers did not used fixed values but instead used workloads that were related to the peak work of each individual. For each subject, they measured the total oxygen consumption, sum of oxygen debt, oxygen consumption, and oxygen uptake during recovery (after done exercising). This study analyzed 13 patients with what they considered was “stable” CHF and compared them to a control of 12 males. The researchers defined stable as patients who did not have any changes to their therapy or any hospital admissions during the 3 month time period leading up to the study. The controls were randomly picked off of a list of general practitioners, and they were not on any medications, no did they ever show signs/symptoms of any cardiac diseases. All of the CHF patients were on beta blockers during the study. Beta blockers block effects of epinephrine, which is the body’s adrenaline. They make the heart beat slower and reduces the force, which means it also reduces the blood pressure. Beta blockers also help improve the blood flow by widening veins and arteries. Therefore, these drugs help reduce the risk of disease progression in patients with HF. They also help improve some symptoms, such as tachycardia and hypertension. They can help with the symptoms of heart failure but cannot reverse damage the heart has already sustained. Each participant in the study had their metabolic gas exchange measured during peak exercise testing. They also had an echocardiogram taken, which is an ultrasound of the heart that shows the researchers how blood is moving through the heart’s chambers and valves. The patients also underwent standard spirometry, which assesses how well the lungs function by measuring the airflow into and out of the lungs. Also the researchers determined that any respiratory exchange ratio, which is the ratio between the volume of CO2 produced and the O2 consumed, greater than 1 will be interpreted as maximal effort. This ratio reveals whether the body is functioning aerobically or anaerobically. Thus, a ratio greater than 1 indicates that anaerobic respiration is occurring in the body. Each subject was exercised at a percentage of their own peak capacity so individuals could be compared at similar degrees of relative work. For a perfectly healthy individual without HF, they will be able to perform more than an individual with CHF. After the initial visits, patients performed steady state exercise tests at 15%, 25% and 50% of workload determined during the initial peak test. Between each test, patients were given 30 minutes of rest, and the order of the tests were randomized. Gas exchange was measured at three different points during each test: 3 minutes of rest before exercise, the entire duration of exercise, and then 5 minutes after the cessation of exercise. During exercise, the steady state was described as no change in the intake of oxygen for at least a minute. The exercise continued for 3 minutes after the participant hit the steady state. This is an example of an EPOC graph, which stands for excess post-exercise oxygen consumption. The oxygen debt, known as the EPOC, is the amount of oxygen a body needs in order to go back to its normal metabolic function. Depending on the type of exercise, as well as the individual, these graphs may look slightly different. Figure 1 from the research paper shows the graph they used to calculate the oxygen consumption for each individual. The curves were fitted based on the raw oxygen uptake data. As you can see, it is the same type of graph we saw on the previous slide. Area D represents the oxygen deficit when exercise starts and area C represents the recovery after the cessation of exercise. These two areas were calculated for each peak and submaximal tests. Areas A and B represent the oxygen consumption during exercise. More specifically, area B shows oxygen consumption when the individual reaches his steady state. Total oxygen uptake was calculated from areas A, B and C. E represents the resting level. The oxygen deficit was calculated by D/[(A+B+C)/exercise time] and the oxygen debt was calculated by C/[(A+B+C)/exercise time]. The amount of work produced was represented by the total energy expended in joules. The biomechanical efficiency was then calculated by “the oxygen required to perform work for the time of exercise (exercise/watt areas A+B), for recovery (recovery/watt), and for the whole exercise session including recovery (A+B+C) (total/watt).” Also used this data to calculate the average oxygen consumption per joule of work. A t-test was used to compare the values between groups and LSLR was used to interpret the relationship between peak oxygen consumption and biomechanical efficiency. P values less than 0.05 were considered to be statistically significant. If you think back to the slide where I discussed what CHF was, it makes sense that the patients showed impaired ventricular function. In addition, they showed lower peak oxygen consumption, as well as lower peak workload. Again, RER is the respiratory exchange ratio. Since they are higher in patients than in the control subjects, the patients with CHF perform more anaerobically. The oxygen deficit and debt as a percentage of total oxygen consumed per minute were not significantly different between groups. But when the workload tests were controlled based on peak performance, then the O2 deficit, debt and uptake were greater in the patients for each of the lower workload tests (15, 25, and 50%)
The first significant subject characteristic is LVEF, which is the left ventricle ejection fraction. As discussed in previous slides, patients with CHF have a reduced ejection fraction, which is why the average for the patients is much lower than the average for the controls. The second significant characteristic is the LVEDD, which is the left ventricular end-diastolic diameter. This is an important indicator in an echocardiogram, and it tells the researcher how wide the left ventricle is, which also reflects the left ventricular function. Dilation is associated with CHF, which is why the patients have a larger average of 6.1 than the controls. The last significant finding is the peak workload. Since patients with chf have impaired hearts, they are not able to perform as much work as healthy individuals. As you can see, their peak load is less than half of the peak workload that the controls can perform.
Again, you can see in table 2 that there are a bunch of significant results. For example, the absolute workload (W) is significantly different between the two groups, with the controls being almost double for percentage of the peak. The ml/kg/min represents the relative VO2 which is the amount of relative oxygen that the body can use while exercising. For all workloads, the patients utilized less oxygen. Then the exercise, debt, total/watt, and average O2 uptake is only significant between groups for the two lower workloads with all the values for the patients being higher than the values for the controls. As we can see in the lower values, the O2 deficit, debt and uptake at steady state greater in patients for the workload tests
In figure 2, the unfilled circles represent the patients with CHF while the filled circles represent the controls. Figure 2a and b show that biomechanical efficiency (total oxygen uptake per joule) is inversely related to peak oxygen consumption for all populations for the 15% and 25% tests. At the highest workload, there is no relationship between peak oxygen consumption and biomechanical efficiency. In both groups, there was a relationship between absolute workload and biomechanical efficiency. They were also significantly different between the groups with a p-value less than 0.001. Figure 2 suggests that there is optimal efficiency of 0.25.
Figure 3 shows the graph of absolute workload vs biomechanical efficiency. The unfilled circles represent the patients with CHF while the filled circles represent the control subjects. This graph reveals that the individuals with CHF reached optimal efficiency earlier at lower workloads than the control subjects. This research paper suggests that the patients have reduced biomechanical efficiency since they have a higher oxygen consumption than controls. These results are different from previous studies that suggested patients have an increased biomechanical efficiency. However, this study is different from past research since workloads were matched as a percentage of peak exercise, rather than using fixed numbers. Patients being less efficient at lower workloads suggests that resting oxygen consumption forms a greater proportion of total oxygen consumption at lower workloads. However, at higher workloads, the resting oxygen consumption is not as important, which also supports why at higher workloads there is no significant differences between the groups. Since respiratory exchange ratios are higher for patients when the workloads are the same, this suggests the control are less anaerobic than the patients. Thus, CHF patients shift to anaerobic metabolism earlier than the controls. Therefore, the delay in recovery for patients may be due to patients having higher anaerobic metabolism during lower levels of exercise. Since there is a shift to anaerobic metabolism faster in patients with CHF, this suggests that there may be changes in the skeletal muscle ultrastructure. The researchers believe there is a shift from type 1 fibers, which are capable of prolonged aerobic metabolism, to type 2b fibers, which have a lower mitochondrial density, twice oxygen requirement, and higher ATP consumption. Thus, this means there will be a higher dependence on anaerobic metabolism during exercise. The study shows that patients with CHF perform activities at lower absolute levels of work. Thus, these individuals require more time to repay their oxygen debt compared to a normal healthy individual. This finding suggests that patients with CHF may begin another period of work before they fully recovered from their last period of work.
Patients with CHF have an impaired biomechanical efficiency at reduced levels of work, and they require more oxygen. Thus, they shift to anaerobic metabolism quicker. However, anaerobic metabolism produces less ATP than aerobic metabolism, which may explain why patients with CHF have fatigue.
