Tricuspid Regurgitation

Overview

Definition and epidemiology

Tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) (TR) is the backflow of blood through the tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy into the right atrium during ventricular systole Ventricular systole Cardiac Cycle. 

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency for physiologically significant TR worldwide is < 1%.
• 70% of normal adults will have a minimal degree of TR.
• Similar incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency rates in men and women

Etiology

• Most commonly due to dilation of the valve annulus from right ventricular dilation:
  • Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
  • Mitral or pulmonary stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS)
  • Ischemic or idiopathic Idiopathic Dermatomyositis dilated cardiomyopathy Dilated Cardiomyopathy Dilated cardiomyopathy (DCM) is the most common type of non-ischemic cardiomyopathy and a common cause of heart failure (HF). The cause may be idiopathic, familial, or secondary to a variety of underlying conditions. The disease is characterized by the enlargement of 1 or both ventricles and reduced systolic function. Dilated Cardiomyopathy
  • Left ventricular heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
• Structural anomalies:
  • Tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy prolapse
  • Papillary muscle dysfunction:
    • Myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
    • Fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans
    • Infiltrative diseases
  • Ebstein anomaly
    • Congenital Congenital Chorioretinitis abnormalities of the tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy and the right ventricle
    • Often associated with other congenital Congenital Chorioretinitis heart defects
• Inflammatory or systemic disease:
  • Rheumatic heart disease Rheumatic Heart Disease Cardiac manifestation of systemic rheumatological conditions, such as rheumatic fever. Rheumatic heart disease can involve any part the heart, most often the heart valves and the endocardium. Rheumatic Fever
  • Infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis
  • Connective-tissue diseases:
    • Marfan syndrome Marfan syndrome Marfan syndrome is a genetic condition with autosomal dominant inheritance. Marfan syndrome affects the elasticity of connective tissues throughout the body, most notably in the cardiovascular, ocular, and musculoskeletal systems. Marfan Syndrome
    • Ehlers-Danlos syndrome Ehlers-Danlos syndrome Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective tissue disorders that are characterized by hyperextensible skin, hypermobile joints, and fragility of the skin and connective tissue. Ehlers-Danlos Syndrome
    • Osteogenesis imperfecta Osteogenesis imperfecta Osteogenesis imperfecta (OI), or “brittle bone disease,” is a rare genetic connective tissue disorder characterized by severe bone fragility. Although OI is considered a single disease, OI includes over 16 genotypes and clinical phenotypes with differing symptom severity. Osteogenesis Imperfecta
  • Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
• Iatrogenic Iatrogenic Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment. Anterior Cord Syndrome:
  • Pacemaker Pacemaker A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external). Bradyarrhythmias leads
  • Endomyocardial biopsy Endomyocardial biopsy Myocarditis
• Medications:
  • Phentermine Phentermine A central nervous system stimulant and sympathomimetic with actions and uses similar to those of dextroamphetamine. It has been used most frequently in the treatment of obesity. Stimulants
  • Fenfluramine

Pathophysiology

• Backflow of blood into the right atrium during systole Systole Period of contraction of the heart, especially of the heart ventricles. Cardiac Cycle → increased right atrial pressure → increased venous pressure → systemic venous congestion (can lead to right ventricular systolic dysfunction Systolic dysfunction Dilated Cardiomyopathy and low cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics)
• Inspiration Inspiration Ventilation: Mechanics of Breathing widens the right ventricle → enlarges the tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy annulus → worsens regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)

Clinical Presentation

Symptoms

• Mild or moderate TR is usually asymptomatic.
• Severe TR is associated with right heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) symptoms:
  • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea on exertion
  • Orthopnea Orthopnea Pulmonary Edema
  • Paroxysmal nocturnal dyspnea Paroxysmal nocturnal dyspnea A disorder characterized by sudden attacks of respiratory distress in at rest patients with heart failure and pulmonary edema. It usually occurs at night after several hours of sleep in a reclining position. Patients awaken with a feeling of suffocation, coughing, a cold sweat, and tachycardia. When there is significant wheezing, it is called cardiac asthma. Pulmonary Edema
  • Abdominal distension
  • Peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia

Physical exam

• Blowing holosytolic murmur at the lower left sternal border:
• Carvallo’s sign Carvallo’s sign Accentuation of the murmur during inspiration, leg raise, squatting, and exercise. Tricuspid Stenosis:
  • Murmur augmented with inspiration Inspiration Ventilation: Mechanics of Breathing
  • Murmur reduced when standing or during the Valsalva maneuver Valsalva maneuver Forced expiratory effort against a closed glottis. Rectal Prolapse
• S3 S3 Heart Sounds and/or S4 gallop S4 gallop Heart Sounds that increases with inspiration Inspiration Ventilation: Mechanics of Breathing
• Signs of systemic venous congestion:
  • Jugular venous distention
  • Hepatomegaly
  • Hepatojugular reflux 
  • Abdominal distension and ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
  • Peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema
• If febrile, consider infective endocarditis Infective endocarditis Infective endocarditis (IE) is caused by infection or inflammation of the inner lining of the heart (endocardium), most commonly affecting the heart valves. Endocarditis.

Diagnosis and Management

Diagnosis

• Echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) (modality of choice)
  • Right atrial and right ventricular dilation
  • Tricuspid annulus dilation
  • Prolapsing, displaced, or scarred leaflets
  • Vegetations → endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis
  • Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography):
    • Establish the severity.
    • Evaluate for pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension.
• Cardiac magnetic resonance Cardiac magnetic resonance Aortic Regurgitation imaging
  • Can help with the diagnosis if echo imaging is suboptimal or inconclusive
  • Gives a quantitative assessment of:
    • Amount of blood regurgitating back into the right atrium
    • Ratio of TR volume to stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle
    • Right ventricular volumes and ejection fraction Ejection fraction Cardiac Cycle
• Cardiac catheterization Cardiac Catheterization Procedures in which placement of cardiac catheters is performed for therapeutic or diagnostic procedures. Cardiac Surgery (not used for the diagnosis of TR, but may assist in finding the underlying cause):
  • Measures pulmonary pressures → possible diagnosis of pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
  • Evaluates for coronary artery Coronary Artery Truncus Arteriosus disease and left-sided heart disease
• Electrocardiogram Electrocardiogram An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) (no characteristic findings, but may point to the underlying cause):
  • Q-waves in inferior leads → right ventricular myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
  • Right ventricular hypertrophy Right Ventricular Hypertrophy Tetralogy of Fallot with right axis deviation → pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
  • Right bundle branch block Right bundle branch block Bundle Branch and Fascicular Blocks with preexcitation → Ebstein anomaly

Management

• Systemic volume overload treatment:
  • Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia restriction
  • Fluid restriction
  • Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication 
• Treat underlying causes, such as left heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) and pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension.
• Surgery (repair or replacement) for moderate-to-severe TR is considered if:
  • Left-sided valve surgery is also needed
  • Endocarditis Endocarditis Endocarditis is an inflammatory disease involving the inner lining (endometrium) of the heart, most commonly affecting the cardiac valves. Both infectious and noninfectious etiologies lead to vegetations on the valve leaflets. Patients may present with nonspecific symptoms such as fever and fatigue. Endocarditis

Differential Diagnosis

• Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR): results when the heart cannot maintain a normal cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics. Etiologies can include ischemic, structural, inflammatory, and valvular disease. Symptoms depend on the side of involvement, but include dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, orthopnea Orthopnea Pulmonary Edema, and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. Diagnosis is made by echocardiogram Echocardiogram Transposition of the Great Vessels, and treatment involves diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication and salt/fluid restriction. Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) can occur in conjunction with tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD), and will be established by echocardiogram Echocardiogram Transposition of the Great Vessels.
• Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis: chronic disease of the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy marked by fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans of the parenchyma and impaired function. Symptoms include jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites, hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus, and edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. Diagnosis is made based on liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function test anomalies and an ultrasound showing distorted hepatic architecture with portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension. Treatment includes management of the underlying cause, diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication, and salt restriction. Echo findings will help distinguish this condition from tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD).
• Mitral regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD): valve disorder where blood refluxes from the left ventricle to the left atrium during systole Systole Period of contraction of the heart, especially of the heart ventricles. Cardiac Cycle. Signs and symptoms are based on severity and can include exertional dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, or edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. Exam will be notable for a systolic murmur at the cardiac apex, and echocardiogram Echocardiogram Transposition of the Great Vessels can establish the diagnosis and differentiate the condition from tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD). Treatment includes sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia restriction, diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication, and surgery for severe cases.
• Mitral stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS): narrowing of the mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy, which results in obstruction of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure from the left atrium to the left ventricle. Rheumatic heart disease Rheumatic Heart Disease Cardiac manifestation of systemic rheumatological conditions, such as rheumatic fever. Rheumatic heart disease can involve any part the heart, most often the heart valves and the endocardium. Rheumatic Fever is the most common cause. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be asymptomatic or present with dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea. Exam may reveal a low-pitched, rumbling, diastolic murmur at the cardiac apex. Diagnosis is made by echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA), and will differentiate this condition from tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD).
• Tricuspid stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS): narrowing of the tricuspid valve Tricuspid valve The valve consisting of three cusps situated between the right atrium and right ventricle of the heart. Heart: Anatomy, which prevents normal blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure from the right atrium to the right ventricle. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be asymptomatic or present with signs and symptoms of systemic venous congestion. A mid-diastolic murmur at the left lower sternal border distinguishes this condition from tricuspid regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD). Echocardiogram Echocardiogram Transposition of the Great Vessels will establish the diagnosis. Management includes sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia restriction, diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication, and surgery for severe cases.