Introduction

The left ventricle is an integral part of the cardiovascular system. Left ventricular contraction forces oxygenated blood through the aortic valve to be distributed to the entire body. With such an important role, decreased function caused by injury or maladaptive change can induce disease symptoms.

Issues of Concern

Heart failure (HF) often results from poor left ventricular function. Reduced diastolic filling and ejection fraction can lead to less blood leaving the heart into systemic circulation. HF correlates with structural changes in the ventricular wall, such as dilation and mural thinning. Alterations in various components of the myocardium precede these ventricular changes, such as focal myocyte loss and fibrotic replacement, as well as hypertrophic myocyte activity, leading to a thicker ventricular wall. These myocardial changes lead to a decrease in the ability of the individual myocytes to contract with sufficient speed and force to maintain the cardiac output necessary to meet bodily needs.[1]

Cellular Level

Cardiac muscle tissue is only found in the heart. Each myocyte contains a single nucleus and many mitochondria for high energy output. Cardiac muscle is involuntary, striated, and possesses an extensive capillary network. Cardiomyocytes are individual muscle cells organized into sarcomeres and interconnected via intercalated discs. The interconnections allow synchronized contraction of the cardiac myofibrils. Each contraction is initiated by the release of calcium into the cytosol. T-tubules facilitate the conversion of electrical impulses from Purkinje fibers into mechanical contraction, called excitation-contraction coupling, by activating L-type calcium channels to allow calcium into the cytosol. This calcium binds to ryanodine receptors in the sarcoplasmic reticulum, which induces ventricular contraction.[2] The amount of calcium transiently determines the contractility of the heart. Physiological or pathological increases in cardiac demand, such as greater afterload, induce adaptive changes in the left ventricle, including myocyte hypertrophy or fibroblast proliferation, leading to fibrosis, vascularization, and even cell death.[3]

Development

From conception, the cells from the primary cardiac crescent form bilaterally within the embryonic disc and migrate to the cervical region to form the primary heart tube. Subsequent divisions and contributions from the bulbus cordis develop into the right ventricle, while the primitive ventricle of the primary cardiac crescent forms the left ventricle. During subsequent weeks, the primitive heart folds into an "s" shape, which places the chambers and major vessels into alignment and shape that mirrors an adult heart. The partitioning of the atria and ventricles by the interatrial, interventricular, and atrioventricular septum proceed, followed by the formation of the semilunar valves.[4]

Congenital defects of the left ventricle include hypoplastic left heart syndrome. This condition is characterized by an underdeveloped left ventricle secondary to a small, poorly formed mitral valve, aortic valve, and/or ascending aorta. The number of affected structures coincides with the severity of this defect. The underdeveloped left ventricle cannot adequately pump blood to the body, so the newborn undergoes surgery to bypass the poorly functioning left side of the heart and make the right ventricle the main pump to the body.[5] Most affected newborns also have an atrial septal defect, so medication is given to help the foramen ovale remain patent as well as help lower their blood pressure and remove excess fluid.

Organ Systems Involved

The left ventricle connects nearly all organ systems through its function to pump oxygenated blood to the body. Left ventricular failure would likely result in impairment of all other organ systems. Organs may react to low ventricular function by initiating mechanisms to increase blood delivery. A person might experience syncopal episodes due to a lack of blood flow to the brain, or their kidneys might start to release renin to elevate blood pressure. Decreased cardiac output can also lead to the adrenal release of epinephrine to increase heart rate and blood pressure, thus increasing blood supply to vital organs such as the brain. Left ventricular failure may cause blood to go back into the lungs and cause pulmonary edema. This edema can lead to pulmonary hypertension and excessive strain to the right atrium and ventricle. The fluid again backs up, this time into the vena cava, and can cause liver pathologies and portal hypertension.

Function

The primary function of the left ventricle is to provide sufficient cardiac output to maintain blood flow to other organ systems. Cardiac output results from systolic contraction of the left ventricle, which can be influenced by preload, afterload, and contractility.

Cardiac output (CO) is the amount of blood pumped out of the heart in a given time. Heart rate (HR) is the number of heartbeats in a given time, often recorded as beats per minute (bpm). Stroke volume (SV) is blood ejected in a single ventricular contraction. Cardiac output can be calculated using the following equations:

• CO = HR * SV
• SV = end-diastolic volume (EDV) – end-systolic volume (ESV)

Cardiac output cannot be measured clinically, so ejection fraction is a commonly used index to estimate heart contractility. Left ventricular ejection fraction (LVEF) is the volume of blood pumped out of the heart during systole relative to the volume in the left ventricle at the end of diastole. LVEF is calculated using the following equation:

• LVEF = SV / EDV

Factors Affecting Cardiac Output

Preload is the load on ventricular muscle during diastole. The load is caused by the volume of blood that fills the ventricle as it rests between contractions. Higher preload volumes generally increase contractility through the Frank-Starling mechanism. This mechanism occurs when the preload volume lengthens the myocyte sarcomere length closer to the optimal overlap of actin and myosin.

Afterload is the pressure the left ventricle must push against during each contraction. Conditions like hypertension, atherosclerosis, and aortic stenosis all require the left ventricle to work harder to overcome the elevated afterload pressure. If this occurs chronically, the left ventricle undergoes hypertrophic adaptations, which can lead to pathology.

Contractility is the inotropic state of the heart muscle. The intracellular calcium levels greatly influence heart contractility with higher levels inducing a stronger contraction. Medications like digoxin are given to increase heart contractility via myocyte contractile performance, and electrophysiological variables do so by raising intracellular calcium levels. These medications are therapeutic for those who suffer from chronic left ventricular dysfunction. Therapy can normalize action potential characteristics and improve left ventricular pump function in the setting of left ventricular failure.[6]

Evaluation of left ventricular function results from 3 indices: end-diastolic left ventricular chamber size, LVEF, and mean velocity of circumferential fiber shortening (MVCFc), which reflects heart muscle performance. These measurement indices are preload and afterload-dependent and, therefore, can influence contractility or relative inotropic sensitivity.[7]

Mechanism

The left ventricle pumps blood at higher pressures than the rest of the heart chambers, as it faces a much higher workload and mechanical afterload. The free wall of the left ventricle is much thicker than that of the right ventricle.

The electrophysiology of the left ventricle starts at the sinoatrial (SA) node, which initiates an action potential. This action potential is carried across the atria, causing contraction, to the atrioventricular (AV) node. The AV node delays the electrical current by about 100ms before transmitting the impulse to the atrioventricular bundle of His. The electrical impulse travels down the right and left bundle branches to the Purkinje fibers. When the action potential reaches the ventricular contractile fibers, excitation-contraction coupling induces calcium influx causing synchronized contraction starting at the heart apex and progressing upwards.[8][9]

Related Testing

Heart disease can manifest in different ways, such as electrocardiogram (ECG) abnormalities, palpitations, wall motion abnormalities, or a change in chamber geometry. For example, heart failure is a clinical diagnosis that can be the result of a multitude of different structural and functional cardiac disorders that affect intrinsic myocardial contractility. It is largely a clinical diagnosis and is characterized by the ventricle's inability to fill with or eject blood properly. A patient might exhibit systolic as well as diastolic dysfunction and present with dyspnea, fatigue, and fluid retention. ECGs may assess heart electrical activity and unearth findings that may result in heart failure, like ventricular tachycardia, ventricular fibrillation, left ventricular hypertrophy, and myocardial infarctions. Stress testing and echocardiograms are noninvasive diagnostic exam methods used to assess for cardiac lesions and monitor myocardial functionality and may reveal chamber size abnormalities, wall motion abnormalities, or improper valve function. It has been shown that stress echocardiography, in combination with various stressors, can detect significant coronary stenosis with accuracy ranging from 80 to 90%, making it a powerful prognostic tool in those with chronic coronary artery disease.[10]

Important to the diagnosis of heart failure is left ventricular ejection fraction (LVEF), which is evaluated with an echocardiogram. It is a load-dependent test and indicator of left ventricular performance. The fraction percentage identifies the different categories of heart failure: preserved ejection fraction greater than or equal to 50%, mid-range left ventricular ejection fraction 41-49%, and reduced ejection fraction less than or equal to 40%.[11][12] This differentiation between the preserved, midrange, and reduced LVEF is important for continued quality of care performance and measurement in heart failure patients.

The circumferential fiber shortening (MCVFc) is another measurement that can aid in determining ventricular performance as a direct relation to muscle function. It is an index of myocardial performance relative to wall stress. There is an inverse linear relationship between end-systolic wall stress and the velocity of circumferential fiber shortening, the index of which is a sensitive measure of the cardiac contractile state independent of preload and accounting for afterload.[13]

Tissue Doppler is another noninvasive method of testing the left ventricle's systolic and diastolic function and performance. It is used to assess for changes in the myocardium due to strain, twists, and rotations that are distinct from previous tests.

Pathophysiology

Left ventricular heart failure can result from a variety of pathologies such as ischemia, excessive peripheral demands, high output failure, volume overload, pressure and volume overload, and primary muscle disease. Four determinants of left ventricular performance are an intrinsic decrease in muscle contractility, an increase in systemic afterload causing decreased cardiac output, an increased preload that pushes fluid into the lungs, causing pulmonary congestion, and an increased heart rate associated with sympathetic tone.[14]  

Left ventricular hypertrophy can occur when the heart contracts against high pressure chronically. The high pressure can be attributed to conditions like hypertension or aortic stenosis. Over time, the heart adapts to this stress through myocyte hypertrophy. However, this process is a pathologic mechanism as the ventricular wall thickens, which decreases overall left ventricular function. On the contrary, non-pathologic hypertrophy can result from exercise where the myocytes increase in size but do not cause wall thickening associated with decreased ventricular function.

Clinical Significance

Per the CDC, 1 in 4 people with heart disease die each year in the United States, making it the leading cause of death in both men and women. Heart failure is still a challenge to many healthcare providers and is associated with higher rates of readmissions and increased morbidity and mortality. Treatment methods vary based on the nature and extent of the pathophysiology. The primary goals of management are to improve prognosis and reduce morbidity and mortality with appropriate therapies.[15] If the patient is admitted to the hospital, an additional goal would be to reduce the rates of readmission as well as the length of stay. Addressing and managing other comorbidities that could enhance cardiac dysfunction is important for positive outcomes.[16]