Heart failure (HF), also known as chronic heart failure (CHF), is when the heart is unable to pump sufficiently to maintain blood flow to meet the body's needs. Signs and symptoms of heart failure commonly include shortness of breath, excessive tiredness, and leg swelling. The shortness of breath is usually worse with exercise, while lying down, and may wake the person at night. A limited ability to exercise is also a common feature. Chest pain, including angina, does not typically occur due to heart failure.
Common causes of heart failure include coronary artery disease including a previous myocardial infarction (heart attack), high blood pressure, atrial fibrillation, valvular heart disease, excess alcohol use, infection, and cardiomyopathy of an unknown cause. These cause heart failure by changing either the structure or the functioning of the heart. The two types of heart failure – heart failure with reduced ejection fraction (HFrEF), and heart failure with preserved ejection fraction (HFpEF) – are based on whether the ability of the left ventricle to contract is affected, or the heart's ability to relax. The severity of disease is graded by the severity of symptoms with exercise. Heart failure is not the same as myocardial infarction (in which part of the heart muscle dies) or cardiac arrest (in which blood flow stops altogether). Other diseases that may have symptoms similar to heart failure include obesity, kidney failure, liver problems, anemia, and thyroid disease. Heart failure is diagnosed based on the history of the symptoms and a physical examination, with confirmation by echocardiography. Blood tests, electrocardiography, and chest radiography may be useful to determine the underlying cause.
Treatment depends on the severity and cause of the disease. In people with chronic stable mild heart failure, treatment commonly consists of lifestyle modifications such as stopping smoking, physical exercise, and dietary changes, as well as medications. In those with heart failure due to left ventricular dysfunction, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or valsartan/sacubitril along with beta blockers are recommended. For those with severe disease, aldosterone antagonists, or hydralazine with a nitrate may be used. Diuretics are useful for preventing fluid retention and the resulting shortness of breath. Sometimes, depending on the cause, an implanted device such as a pacemaker or an implantable cardiac defibrillator (ICD) may be recommended. In some moderate or severe cases, cardiac resynchronization therapy (CRT) or cardiac contractility modulation may be of benefit. A ventricular assist device or occasionally a heart transplant may be recommended in those with severe disease that persists despite all other measures.
Heart failure is a common, costly, and potentially fatal condition. In 2015, it affected about 40 million people globally. Overall around 2% of adults have heart failure and in those over the age of 65, this increases to 6–10%. Rates are predicted to increase. The risk of death is about 35% the first year after diagnosis; while by the second year the risk of death is less than 10% for those who remain alive. This degree of risk of death is similar to some cancers. In the United Kingdom, the disease is the reason for 5% of emergency hospital admissions. Heart failure has been known since ancient times, with the Ebers papyrus commenting on it around 1550 BCE.
|Synonyms||Chronic heart failure (CHF), congestive cardiac failure (CCF)|
|The major signs and symptoms of heart failure|
|Symptoms||Shortness of breath, feeling tired, leg swelling|
|Causes||Heart attack, high blood pressure, abnormal heart rhythm, excessive alcohol use, infection, heart damage|
|Risk factors||Smoking, sedentary lifestyle|
|Differential diagnosis||Kidney failure, thyroid disease, liver disease, anemia, obesity|
|Medication||Diuretics, cardiac medications|
|Frequency||40 million (2015), 2% of adults (developed countries)|
|Deaths||35% risk of death in first year|
Heart failure is a pathophysiological state in which cardiac output is insufficient to meet the needs of the body and lungs. The term "congestive heart failure" is often used, as one of the common symptoms is congestion, or build-up of fluid in a person's tissues and veins in the lungs or other parts of the body. Specifically, congestion takes the form of water retention and swelling (edema), both as peripheral edema (causing swollen limbs and feet) and as pulmonary edema (causing breathing difficulty), as well as ascites (swollen abdomen). This is a common problem in old age as a result of cardiovascular disease, but it can happen at any age, even in fetuses.
The term "acute" is used to mean rapid onset, and "chronic" refers to long duration. Chronic heart failure is a long-term condition, usually kept stable by the treatment of symptoms. Acute decompensated heart failure is a worsening of chronic heart failure symptoms which can result in acute respiratory distress. High-output heart failure can occur when there is an increased cardiac output. The circulatory overload caused, can result in an increased left ventricular diastolic pressure which can develop into pulmonary congestion (pulmonary edema).
Heart failure is divided into two types based on ejection fraction, which is the proportion of blood pumped out of the heart during a single contraction. Ejection fraction is given as a percentage with the normal range being between 50 and 75%. The two types are:
1) Heart failure due to reduced ejection fraction (HFrEF). Synonyms no longer recommended are "heart failure due to left ventricular systolic dysfunction" and "systolic heart failure". HFrEFe is associated with an ejection fraction of less than 40%.
2) Heart failure with preserved ejection fraction (HFpEF). Synonyms no longer recommended include "diastolic heart failure" and "heart failure with normal ejection fraction". HFpEF occurs when the left ventricle contracts normally during systole, but the ventricle is stiff and does not relax normally during diastole, which impairs filling.
Heart failure symptoms are traditionally and somewhat arbitrarily divided into "left" and "right" sided, recognizing that the left and right ventricles of the heart supply different portions of the circulation. However, heart failure is not exclusively backward failure (in the part of the circulation which drains to the ventricle).
There are several other exceptions to a simple left-right division of heart failure symptoms. Additionally, the most common cause of right-sided heart failure is left-sided heart failure. The result is that people commonly present with both sets of signs and symptoms.
The left side of the heart is responsible for receiving oxygen-rich blood from the lungs and pumping it forward to the systemic circulation (the rest of the body except for the pulmonary circulation). Failure of the left side of the heart causes blood to back up (be congested) into the lungs, causing respiratory symptoms as well as fatigue due to insufficient supply of oxygenated blood. Common respiratory signs are increased rate of breathing and increased work of breathing (non-specific signs of respiratory distress). Rales or crackles, heard initially in the lung bases, and when severe, throughout the lung fields suggest the development of pulmonary edema (fluid in the alveoli). Cyanosis which suggests severe low blood oxygen, is a late sign of extremely severe pulmonary edema.
Additional signs indicating left ventricular failure include a laterally displaced apex beat (which occurs if the heart is enlarged) and a gallop rhythm (additional heart sounds) may be heard as a marker of increased blood flow or increased intra-cardiac pressure. Heart murmurs may indicate the presence of valvular heart disease, either as a cause (e.g. aortic stenosis) or as a result (e.g. mitral regurgitation) of the heart failure.
Backward failure of the left ventricle causes congestion of the lungs' blood vessels, and so the symptoms are predominantly respiratory in nature. Backward failure can be subdivided into the failure of the left atrium, the left ventricle or both within the left circuit. The person will have dyspnea (shortness of breath) on exertion and in severe cases, dyspnea at rest. Increasing breathlessness on lying flat, called orthopnea, occurs. It is often measured in the number of pillows required to lie comfortably, and in orthopnea, the person may resort to sleeping while sitting up. Another symptom of heart failure is paroxysmal nocturnal dyspnea: a sudden nighttime attack of severe breathlessness, usually several hours after going to sleep. Easy fatigability and exercise intolerance are also common complaints related to respiratory compromise.
Right-sided heart failure is often caused by pulmonary heart disease (cor pulmonale), which is typically caused by difficulties of the pulmonary circulation, such as pulmonary hypertension or pulmonic stenosis.
Physical examination may reveal pitting peripheral edema, ascites, and liver enlargement. Jugular venous pressure is frequently assessed as a marker of fluid status, which can be accentuated by eliciting hepatojugular reflux. If the right ventricular pressure is increased, a parasternal heave may be present, signifying the compensatory increase in contraction strength.
Backward failure of the right ventricle leads to congestion of systemic capillaries. This generates excess fluid accumulation in the body. This causes swelling under the skin (termed peripheral edema or anasarca) and usually affects the dependent parts of the body first (causing foot and ankle swelling in people who are standing up, and sacral edema in people who are predominantly lying down). Nocturia (frequent nighttime urination) may occur when fluid from the legs is returned to the bloodstream while lying down at night. In progressively severe cases, ascites (fluid accumulation in the abdominal cavity causing swelling) and liver enlargement may develop. Significant liver congestion may result in impaired liver function (congestive hepatopathy), and jaundice and even coagulopathy (problems of decreased or increased blood clotting) may occur.
Dullness of the lung fields to finger percussion and reduced breath sounds at the bases of the lung may suggest the development of a pleural effusion (fluid collection between the lung and the chest wall). Though it can occur in isolated left- or right-sided heart failure, it is more common in biventricular failure because pleural veins drain into both the systemic and pulmonary venous systems. When unilateral, effusions are often right sided.
If a person with a failure of one ventricle lives long enough, it will tend to progress to failure of both ventricles. For example, left ventricular failure allows pulmonary edema and pulmonary hypertension to occur, which increase stress on the right ventricle. Right ventricular failure is not as deleterious to the other side, but neither is it harmless.
Heart failure may also occur in situations of "high output" (termed "high-output heart failure"), where the amount of blood pumped is more than typical and the heart is unable to keep up. This can occur in overload situations (blood or serum infusions), kidney diseases, chronic severe anemia, beriberi (vitamin B1/thiamine deficiency), hyperthyroidism, cirrhosis, Paget's disease, multiple myeloma, arteriovenous fistulae, or arteriovenous malformations.
Viral infections of the heart can lead to inflammation of the muscular layer of the heart and subsequently contribute to the development of heart failure. Heart damage can predispose a person to develop heart failure later in life and has many causes including systemic viral infections (e.g., HIV), chemotherapeutic agents such as daunorubicin, cyclophosphamide, and trastuzumab, and abuse of drugs such as alcohol, cocaine, and methamphetamine. An uncommon cause is exposure to certain toxins such as lead and cobalt. Additionally, infiltrative disorders such as amyloidosis and connective tissue diseases such as systemic lupus erythematosus have similar consequences. Obstructive sleep apnea (a condition of sleep wherein disordered breathing overlaps with obesity, hypertension, and/or diabetes) is regarded as an independent cause of heart failure.
Chronic stable heart failure may easily decompensate. This most commonly results from an intercurrent illness (such as myocardial infarction (a heart attack), pneumonia), abnormal heart rhythms, uncontrolled hypertension, or a person's failure to maintain a fluid restriction, diet, or medication. Other factors that may worsen CHF include: anemia, hyperthyroidism, excessive fluid or salt intake, and medication such as NSAIDs and thiazolidinediones. NSAIDs increase the risk twofold.
A number of medications may cause or worsen the disease. This includes NSAIDS, a number of anesthetic agents such as ketamine, thiazolidinediones, a number of cancer medications, salbutamol, and tamsulosin.
Heart failure is caused by any condition which reduces the efficiency of the heart muscle, through damage or overloading. As such, it can be caused by a wide number of conditions, including myocardial infarction (in which the heart muscle is starved of oxygen and dies), hypertension (which increases the force of contraction needed to pump blood) and amyloidosis (in which misfolded proteins are deposited in the heart muscle, causing it to stiffen). Over time these increases in workload will produce changes to the heart itself:
The heart of a person with heart failure may have a reduced force of contraction due to overloading of the ventricle. In a healthy heart, increased filling of the ventricle results in increased contraction force (by the Frank–Starling law of the heart) and thus a rise in cardiac output. In heart failure, this mechanism fails, as the ventricle is loaded with blood to the point where heart muscle contraction becomes less efficient. This is due to reduced ability to cross-link actin and myosin filaments in over-stretched heart muscle.
No system of diagnostic criteria has been agreed on as the gold standard for heart failure. The National Institute for Health and Care Excellence recommends measuring brain natriuretic peptide (BNP) followed by ultrasound of the heart if positive. This is recommended in those with shortness of breath. In those with heart failure which worsen both a BNP and a troponin are recommended to help determine likely outcomes.
Echocardiography is commonly used to support a clinical diagnosis of heart failure. This modality uses ultrasound to determine the stroke volume (SV, the amount of blood in the heart that exits the ventricles with each beat), the end-diastolic volume (EDV, the total amount of blood at the end of diastole), and the SV in proportion to the EDV, a value known as the ejection fraction (EF). In pediatrics, the shortening fraction is the preferred measure of systolic function. Normally, the EF should be between 50% and 70%; in systolic heart failure, it drops below 40%. Echocardiography can also identify valvular heart disease and assess the state of the pericardium (the connective tissue sac surrounding the heart). Echocardiography may also aid in deciding what treatments will help the person, such as medication, insertion of an implantable cardioverter-defibrillator or cardiac resynchronization therapy. Echocardiography can also help determine if acute myocardial ischemia is the precipitating cause, and may manifest as regional wall motion abnormalities on echo.
Chest X-rays are frequently used to aid in the diagnosis of CHF. In a person who is compensated, this may show cardiomegaly (visible enlargement of the heart), quantified as the cardiothoracic ratio (proportion of the heart size to the chest). In left ventricular failure, there may be evidence of vascular redistribution ("upper lobe blood diversion" or "cephalization"), Kerley lines, cuffing of the areas around the bronchi, and interstitial edema. Ultrasound of the lung may also be able to detect Kerley lines.
An electrocardiogram (ECG/EKG) may be used to identify arrhythmias, ischemic heart disease, right and left ventricular hypertrophy, and presence of conduction delay or abnormalities (e.g. left bundle branch block). Although these findings are not specific to the diagnosis of heart failure a normal ECG virtually excludes left ventricular systolic dysfunction.
Blood tests routinely performed include electrolytes (sodium, potassium), measures of kidney function, liver function tests, thyroid function tests, a complete blood count, and often C-reactive protein if infection is suspected. An elevated B-type natriuretic peptide (BNP) is a specific test indicative of heart failure. Additionally, BNP can be used to differentiate between causes of dyspnea due to heart failure from other causes of dyspnea. If myocardial infarction is suspected, various cardiac markers may be used.
BNP is a better indicator than N-terminal pro-BNP (NTproBNP) for the diagnosis of symptomatic heart failure and left ventricular systolic dysfunction. In symptomatic people, BNP had a sensitivity of 85% and specificity of 84% in detecting heart failure; performance declined with increasing age.
Hyponatremia (low serum sodium concentration) is common in heart failure. Vasopressin levels are usually increased, along with renin, angiotensin II, and catecholamines in order to compensate for reduced circulating volume due to inadequate cardiac output. This leads to increased fluid and sodium retention in the body; the rate of fluid retention is higher than the rate of sodium retention in the body, this phenomenon causes "hypervolemic hyponatremia" (low sodium concentration due to high body fluid retention). This phenomenon is more common in older women with low body mass. Severe hyponatremia can result in accumulation of fluid in the brain, causing cerebral oedema and intracranial haemorrhage.
Angiography is the X-ray imaging of blood vessels which is done by injecting contrast agents into the bloodstream through a thin plastic tube (catheter) which is placed directly in the blood vessel. X-ray images are called angiograms. Heart failure may be the result of coronary artery disease, and its prognosis depends in part on the ability of the coronary arteries to supply blood to the myocardium (heart muscle). As a result, coronary catheterization may be used to identify possibilities for revascularisation through percutaneous coronary intervention or bypass surgery.
Various measures are often used to assess the progress of people being treated for heart failure. These include fluid balance (calculation of fluid intake and excretion), monitoring body weight (which in the shorter term reflects fluid shifts). Remote monitoring can be effective to reduce complications for people with heart failure.
There are many different ways to categorize heart failure, including:
Functional classification generally relies on the New York Heart Association functional classification. The classes (I-IV) are:
This score documents the severity of symptoms and can be used to assess response to treatment. While its use is widespread, the NYHA score is not very reproducible and does not reliably predict the walking distance or exercise tolerance on formal testing.
The ACC staging system is useful in that Stage A encompasses "pre-heart failure" – a stage where intervention with treatment can presumably prevent progression to overt symptoms. ACC Stage A does not have a corresponding NYHA class. ACC Stage B would correspond to NYHA Class I. ACC Stage C corresponds to NYHA Class II and III, while ACC Stage D overlaps with NYHA Class IV.
There are various algorithms for the diagnosis of heart failure. For example, the algorithm used by the Framingham Heart Study adds together criteria mainly from physical examination. In contrast, the more extensive algorithm by the European Society of Cardiology (ESC) weights the difference between supporting and opposing parameters from the medical history, physical examination, further medical tests as well as response to therapy.
By the Framingham criteria, diagnosis of congestive heart failure (heart failure with impaired pumping capability) requires the simultaneous presence of at least 2 of the following major criteria or 1 major criterion in conjunction with 2 of the following minor criteria. Major criteria include an enlarged heart on a chest x-ray, an S3 gallop (a third heart sound), acute pulmonary edema, episodes of waking up from sleep gasping for air, crackles on lung auscultation, central venous pressure of more than 16 cm H
2O at the right atrium, jugular vein distension, positive abdominojugular test, and weight loss of more than 4.5 kg in 5 days in response to treatment (sometimes classified as a minor criterion). Minor criteria include an abnormally fast heart rate of more than 120 beats per minute, nocturnal cough, difficulty breathing with physical activity, pleural effusion, a decrease in the vital capacity by one third from maximum recorded, liver enlargement, and bilateral ankle swelling.
Minor criteria are acceptable only if they can not be attributed to another medical condition such as pulmonary hypertension, chronic lung disease, cirrhosis, ascites, or the nephrotic syndrome. The Framingham Heart Study criteria are 100% sensitive and 78% specific for identifying persons with definite congestive heart failure.
|Assessment||Diagnosis of heart failure|
|Supports if present||Opposes if normal or absent|
|Cardiac dysfunction on echocardiography||+++||+++|
|Response of symptoms or signs to therapy||+++||++|
|Low blood sodium||+||+|
|Mild elevations of troponin||+||+|
|Reduced exercise capacity||+++||++|
|Abnormal pulmonary function tests||+||+|
|Abnormal hemodynamics at rest||+++||++|
|+ = some importance; ++ = intermediate importance; +++ = great importance.|
There are several terms which are closely related to heart failure and may be the cause of heart failure, but should not be confused with it. Cardiac arrest and asystole refer to situations in which there is no cardiac output at all. Without urgent treatment, these result in sudden death. Myocardial infarction ("Heart attack") refers to heart muscle damage due to insufficient blood supply, usually as a result of a blocked coronary artery. Cardiomyopathy refers specifically to problems within the heart muscle, and these problems can result in heart failure. Ischemic cardiomyopathy implies that the cause of muscle damage is coronary artery disease. Dilated cardiomyopathy implies that the muscle damage has resulted in enlargement of the heart. Hypertrophic cardiomyopathy involves enlargement and thickening of the heart muscle.
A person's risk of developing heart failure is inversely related to their level of physical activity. Those who achieved at least 500 MET-minutes/week (the recommended minimum by U.S. guidelines) had lower heart failure risk than individuals who did not report exercising during their free time; the reduction in heart failure risk was even greater in those who engaged in higher levels of physical activity than the recommended minimum. Heart failure can also be prevented by lowering high blood pressure, high blood cholesterol, and controlling diabetes. Also, remaining at the right weight and reducing obesity can help. Lowering salt, alcohol, quitting smoking, and lowering sugar intake may help.
Treatment focuses on improving the symptoms and preventing the progression of the disease. Reversible causes of the heart failure also need to be addressed (e.g. infection, alcohol ingestion, anemia, thyrotoxicosis, arrhythmia, hypertension). Treatments include lifestyle and pharmacological modalities, and occasionally various forms of device therapy and rarely cardiac transplantation.
In acute decompensated heart failure (ADHF), the immediate goal is to re-establish adequate perfusion and oxygen delivery to end organs. This entails ensuring that airway, breathing, and circulation are adequate. Immediate treatments usually involve some combination of vasodilators such as nitroglycerin, diuretics such as furosemide, and possibly noninvasive positive pressure ventilation (NIPPV). Supplemental oxygen is indicated in those with oxygen saturation levels below 90% but is not recommended in those with normal oxygen levels on room air.
The goals of treatment for people with chronic heart failure are the prolongation of life, the prevention of acute decompensation and the reduction of symptoms, allowing for greater activity.
Heart failure can result from a variety of conditions. In considering therapeutic options, it is important to first exclude reversible causes, including thyroid disease, anemia, chronic tachycardia, alcohol abuse, hypertension and dysfunction of one or more heart valves. Treatment of the underlying cause is usually the first approach to treating heart failure. However, in the majority of cases, either no primary cause is found or treatment of the primary cause does not restore normal heart function. In these cases, behavioral, medical and device treatment strategies exist which can provide a significant improvement in outcomes, including the relief of symptoms, exercise tolerance, and a decrease in the likelihood of hospitalization or death. Breathlessness rehabilitation for chronic obstructive pulmonary disease (COPD) and heart failure has been proposed with exercise training as a core component. Rehabilitation should also include other interventions to address shortness of breath including psychological and education needs of people and needs of carers.
Behavioral modification is a primary consideration in chronic heart failure management program, with dietary guidelines regarding fluid and salt intake. Fluid restriction is important to reduce fluid retention in the body and to correct the hyponatremic status of the body. The evidence of benefit of reducing salt however is poor as of 2018.
Exercise should be encouraged and tailored to suit individual capabilities. The inclusion of regular physical conditioning as part of a cardiac rehabilitation program can significantly improve quality of life and reduce the risk of hospital admission for worsening symptoms; however, there is no evidence for a reduction in mortality rates as a result of exercise. Furthermore, it is not clear whether this evidence can be extended to people with heart failure with preserved ejection fraction (HFpEF) or to those whose exercise regimen takes place entirely at home.
First-line therapy for people with heart failure due to reduced systolic function should include angiotensin-converting enzyme (ACE) inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) if the person develops a long term cough as a side effect of the ACE-I. Use of medicines from this class is associated with improved survival and quality of life in people with heart failure.
Beta-adrenergic blocking agents (beta blockers) also form part of the first line of treatment, adding to the improvement in symptoms and mortality provided by ACE-I/ARB. The mortality benefits of beta blockers in people with systolic dysfunction who also have atrial fibrillation (AF) is more limited than in those who do not have AF. If the ejection fraction is not diminished (HFpEF), the benefits of beta blockers are more modest; a decrease in mortality has been observed but reduction in hospital admission for uncontrolled symptoms has not been observed.
In people who are intolerant of ACE-I and ARBs or who have significant kidney dysfunction, the use of combined hydralazine and a long-acting nitrate, such as isosorbide dinitrate, is an effective alternate strategy. This regimen has been shown to reduce mortality in people with moderate heart failure. It is especially beneficial in African-Americans (AA). In AAs who are symptomatic, hydralazine and isosorbide dinitrate (H+I) can be added to ACE-I or ARBs.
Second-line medications for CHF do not confer a mortality benefit. Digoxin is one such medication. Its narrow therapeutic window, a high degree of toxicity, and the failure of multiple trials to show a mortality benefit have reduced its role in clinical practice. It is now used in only a small number of people with refractory symptoms, who are in atrial fibrillation and/or who have chronic low blood pressure.
Diuretics have been a mainstay of treatment for treatment of fluid accumulation, and include diuretics classes such as loop diuretics, thiazide-like diuretic, and potassium-sparing diuretic. Although widely used, evidence on their efficacy and safety is limited, with the exception of mineralocorticoid antagonists such as spironolactone. Mineralocorticoid antagonists in those under 75 years old appear to decrease the risk of death. A recent Cochrane review found that in small studies, the use of diuretics appeared to have improved mortality in individuals with heart failure. However, the extent to which these results can be extrapolated to a general population is unclear due to the small number of participants in the cited studies.
Anemia is an independent factor in mortality in people with chronic heart failure. The treatment of anemia significantly improves quality of life for those with heart failure, often with a reduction in severity of the NYHA classification, and also improves mortality rates. The latest European guidelines (2012) recommend screening for iron-deficient anemia and treating with parenteral iron if anemia is found.
The decision to anticoagulate people with HF, typically with left ventricular ejection fractions <35% is debated, but generally, people with coexisting atrial fibrillation, a prior embolic event, or conditions which increase the risk of an embolic event such as amyloidosis, left ventricular noncompaction, familial dilated cardiomyopathy, or a thromboembolic event in a first-degree relative.
Vasopressin receptor antagonist can also be used to treat heart failure. Conivaptan is the first drug approved by US Food and Drug Administration for the treatment of euvolemic hyponatremia in those with heart failure. In rare cases hypertonic 3% saline together with diuretics may be used to correct hyponatremia.
Sacubitril/valsartan is a combination medication for the treatment of heart failure with reduced left ventricular ejection fraction. It has been in use as an alternative to ACE inhibitors and beta blockers.
In people with severe cardiomyopathy (left ventricular ejection fraction below 35%), or in those with recurrent VT or malignant arrhythmias, treatment with an automatic implantable cardioverter defibrillator (AICD) is indicated to reduce the risk of severe life-threatening arrhythmias. The AICD does not improve symptoms or reduce the incidence of malignant arrhythmias but does reduce mortality from those arrhythmias, often in conjunction with antiarrhythmic medications. In people with left ventricular ejection (LVEF) below 35%, the incidence of ventricular tachycardia (VT) or sudden cardiac death is high enough to warrant AICD placement. Its use is therefore recommended in AHA/ACC guidelines.
Cardiac contractility modulation (CCM) is a treatment for people with moderate to severe left ventricular systolic heart failure (NYHA class II–IV) which enhances both the strength of ventricular contraction and the heart's pumping capacity. The CCM mechanism is based on stimulation of the cardiac muscle by non-excitatory electrical signals (NES), which are delivered by a pacemaker-like device. CCM is particularly suitable for the treatment of heart failure with normal QRS complex duration (120 ms or less) and has been demonstrated to improve the symptoms, quality of life and exercise tolerance. CCM is approved for use in Europe, but not currently in North America.
About one third of people with LVEF below 35% have markedly altered conduction to the ventricles, resulting in dyssynchronous depolarization of the right and left ventricles. This is especially problematic in people with left bundle branch block (blockage of one of the two primary conducting fiber bundles that originate at the base of the heart and carries depolarizing impulses to the left ventricle). Using a special pacing algorithm, biventricular cardiac resynchronization therapy (CRT) can initiate a normal sequence of ventricular depolarization. In people with LVEF below 35% and prolonged QRS duration on ECG (LBBB or QRS of 150 ms or more) there is an improvement in symptoms and mortality when CRT is added to standard medical therapy. However, in the two-thirds of people without prolonged QRS duration, CRT may actually be harmful.
People with the most severe heart failure may be candidates for ventricular assist devices (VAD). VADs have commonly been used as a bridge to heart transplantation, but have been used more recently as a destination treatment for advanced heart failure.
In select cases, heart transplantation can be considered. While this may resolve the problems associated with heart failure, the person must generally remain on an immunosuppressive regimen to prevent rejection, which has its own significant downsides. A major limitation of this treatment option is the scarcity of hearts available for transplantation.
People with heart failure often have significant symptoms, such as shortness of breath and chest pain. Palliative care should be initiated early in the HF trajectory, and should not be an option of last resort. Palliative care can not only provide symptom management, but also assist with advanced care planning, goals of care in the case of a significant decline, and making sure the person has a medical power of attorney and discussed his or her wishes with this individual. A 2016 and 2017 review found that palliative care is associated with improved outcomes, such as quality of life, symptom burden, and satisfaction with care.
Without transplantation, heart failure may not be reversible and cardiac function typically deteriorates with time. The growing number of people with Stage IV heart failure (intractable symptoms of fatigue, shortness of breath or chest pain at rest despite optimal medical therapy) should be considered for palliative care or hospice, according to American College of Cardiology/American Heart Association guidelines.
Prognosis in heart failure can be assessed in multiple ways including clinical prediction rules and cardiopulmonary exercise testing. Clinical prediction rules use a composite of clinical factors such as lab tests and blood pressure to estimate prognosis. Among several clinical prediction rules for prognosticating acute heart failure, the 'EFFECT rule' slightly outperformed other rules in stratifying people and identifying those at low risk of death during hospitalization or within 30 days. Easy methods for identifying people that are low-risk are:
A very important method for assessing prognosis in people with advanced heart failure is cardiopulmonary exercise testing (CPX testing). CPX testing is usually required prior to heart transplantation as an indicator of prognosis. Cardiopulmonary exercise testing involves measurement of exhaled oxygen and carbon dioxide during exercise. The peak oxygen consumption (VO2 max) is used as an indicator of prognosis. As a general rule, a VO2 max less than 12–14 cc/kg/min indicates a poor survival and suggests that the person may be a candidate for a heart transplant. People with a VO2 max<10 cc/kg/min have a clearly poorer prognosis. The most recent International Society for Heart and Lung Transplantation (ISHLT) guidelines also suggest two other parameters that can be used for evaluation of prognosis in advanced heart failure, the heart failure survival score and the use of a criterion of VE/VCO2 slope > 35 from the CPX test. The heart failure survival score is a score calculated using a combination of clinical predictors and the VO2 max from the cardiopulmonary exercise test.
Heart failure is associated with significantly reduced physical and mental health, resulting in a markedly decreased quality of life. With the exception of heart failure caused by reversible conditions, the condition usually worsens with time. Although some people survive many years, progressive disease is associated with an overall annual mortality rate of 10%.
Approximately 18 of every 1000 persons will experience an ischemic stroke during the first year after diagnosis of HF. As the duration of follow-up increases, the stroke rate rises to nearly 50 strokes per 1000 cases of HF by 5 years.
In 2015 heart failure affected about 40 million people globally. Overall around 2% of adults have heart failure and in those over the age of 65, this increases to 6–10%. Above 75 years old rates are greater than 10%.
Rates are predicted to increase. Increasing rates are mostly because of increasing life span, but also because of increased risk factors (hypertension, diabetes, dyslipidemia, and obesity) and improved survival rates from other types of cardiovascular disease (myocardial infarction, valvular disease, and arrhythmias). Heart failure is the leading cause of hospitalization in people older than 65.
In the United States, heart failure affects 5.8 million people, and each year 550,000 new cases are diagnosed. In 2011, heart failure was the most common reason for hospitalization for adults aged 85 years and older, and the second most common for adults aged 65–84 years. It is estimated that one in five adults at age 40 will develop heart failure during their remaining lifetime and about half of people who develop heart failure die within 5 years of diagnosis. Heart failure is much higher in African Americans, Hispanics, Native Americans and recent immigrants from the eastern bloc countries like Russia. This high prevalence in these ethnic minority populations has been linked to high incidence of diabetes and hypertension. In many new immigrants to the U.S., the high prevalence of heart failure has largely been attributed to lack of preventive health care or substandard treatment. Nearly one out of every four people (24.7%) hospitalized in the U.S. with congestive heart failure are readmitted within 30 days. Additionally, more than 50% of people seek re-admission within 6 months after treatment and the average duration of hospital stay is 6 days.
Heart failure is a leading cause of hospital readmissions in the U.S. People aged 65 and older were readmitted at a rate of 24.5 per 100 admissions in 2011. In the same year, people under Medicaid were readmitted at a rate of 30.4 per 100 admissions, and uninsured people were readmitted at a rate of 16.8 per 100 admissions. These are the highest readmission rates for both categories. Notably, heart failure was not among the top ten conditions with the most 30-day readmissions among the privately insured.
In the UK, despite moderate improvements in prevention, heart failure rates have increased due to population growth and ageing. Overall heart failure rates are similar to the four most common causes of cancer (breast, lung, prostate and colon) combined. People from deprived backgrounds are more likely to be diagnosed with heart failure and at a younger age.
In tropical countries, the most common cause of HF is valvular heart disease or some type of cardiomyopathy. As underdeveloped countries have become more affluent, there has also been an increase in the incidence of diabetes, hypertension and obesity, which have in turn raised the incidence of heart failure.
Men have a higher incidence of heart failure, but the overall prevalence rate is similar in both sexes since women survive longer after the onset of heart failure. Women tend to be older when diagnosed with heart failure (after menopause), they are more likely than men to have diastolic dysfunction, and seem to experience a lower overall quality of life than men after diagnosis.
Some sources state that people of Asian descent are at a higher risk of heart failure than other ethnic groups. Other sources however have found that rates of heart failure are similar to rates found in other ethnic groups.
In 2011, non-hypertensive heart failure was one of the ten most expensive conditions seen during inpatient hospitalizations in the U.S., with aggregate inpatient hospital costs of more than $10.5 billion.
Heart failure is associated with a high health expenditure, mostly because of the cost of hospitalizations; costs have been estimated to amount to 2% of the total budget of the National Health Service in the United Kingdom, and more than $35 billion in the United States.
There is low-quality evidence that stem cell therapy may help. Although this evidence positively indicated benefit, the evidence was of lower quality than other evidence that does not indicate benefit. A 2016 Cochrane review found tentative evidence of longer life expectancy and improved left ventricular ejection fraction in persons treated with bone marrow-derived stem cells.
An angiotensin-converting-enzyme inhibitor (ACE inhibitor) is a pharmaceutical drug used primarily for the treatment of hypertension (elevated blood pressure) and congestive heart failure.
This group of drugs causes relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart. They inhibit the angiotensin-converting enzyme, an important component of the renin–angiotensin system.
Frequently prescribed ACE inhibitors include benazepril, zofenopril, perindopril, trandolapril, captopril, enalapril, lisinopril, and ramipril.Alcoholic cardiomyopathy
Alcoholic cardiomyopathy is a disease in which the chronic long-term abuse of alcohol (i.e., ethanol) leads to heart failure. Alcoholic cardiomyopathy is a type of dilated cardiomyopathy. Due to the direct toxic effects of alcohol on heart muscle, the heart is unable to pump blood efficiently, leading to heart failure. It can affect other parts of the body if the heart failure is severe. It is most common in males between the ages of 35–50.Aortic stenosis
Aortic stenosis (AS or AoS) is the narrowing of the exit of the left ventricle of the heart (where the aorta begins), such that problems result. It may occur at the aortic valve as well as above and below this level. It typically gets worse over time. Symptoms often come on gradually with a decreased ability to exercise often occurring first. If heart failure, loss of consciousness, or heart related chest pain occurs due to AS the outcomes are worse. Loss of consciousness typically occurs with standing or exercise. Signs of heart failure include shortness of breath especially when lying down, at night, or with exercise, and swelling of the legs. Thickening of the valve without narrowing is known as aortic sclerosis.Causes include being born with a bicuspid aortic valve, and rheumatic fever. A bicuspid aortic valve affects about one to two percent of the population. As of 2014 rheumatic heart disease mostly occurs in the developing world. A normal valve may also harden over the decades. Risk factors are similar to those of coronary artery disease and include smoking, high blood pressure, high cholesterol, diabetes, and being male. The aortic valve usually has three leaflets and is located between the left ventricle of the heart and the aorta. AS typically results in a heart murmur. Its severity can be divided into mild, moderate, severe, and very severe, distinguishable by ultrasound of the heart.Aortic stenosis is typically followed using repeated ultrasound scans. Once it has become severe, treatment primarily involves valve replacement surgery, with transcatheter aortic valve replacement (TAVR) being an option in some who are at high risk from surgery. Valves may either be mechanical or bioprosthetic, with each having risks and benefits. Another less invasive procedure, balloon aortic valvuloplasty (BAV), may result in benefit, but for only a few months. Complications such as heart failure may be treated in the same way as in those with mild to moderate AS. In those with severe disease a number of medications should be avoided, including ACE inhibitors, nitroglycerin, and some beta blockers. Nitroprusside or phenylephrine may be used in those with decompensated heart failure depending on the blood pressure.Aortic stenosis is the most common valvular heart disease in the developed world. It affects about 2% of people who are over 65 years of age. Estimated rates were not known in most of the developing world as of 2014. In those who have symptoms, without repair the chance of death at five years is about 50% and at 10 years is about 90%. Aortic stenosis was first described by French physician Lazare Rivière in 1663.Beta blocker
Beta blockers, also written β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack (myocardial infarction) after a first heart attack (secondary prevention). They are also widely used to treat high blood pressure (hypertension), although they are no longer the first choice for initial treatment of most patients.Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1, β2 and β3 receptors. β1-adrenergic receptors are located mainly in the heart and in the kidneys. β2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal muscle. β3-adrenergic receptors are located in fat cells.Beta receptors are found on cells of the heart muscles, smooth muscles, airways, arteries, kidneys, and other tissues that are part of the sympathetic nervous system and lead to stress responses, especially when they are stimulated by epinephrine (adrenaline). Beta blockers interfere with the binding to the receptor of epinephrine and other stress hormones, and weaken the effects of stress hormones.
In 1964, James Black synthesized the first clinically significant beta blockers—propranolol and pronethalol; it revolutionized the medical management of angina pectoris and is considered by many to be one of the most important contributions to clinical medicine and pharmacology of the 20th century.For the treatment of primary hypertension, meta-analyses of studies which mostly used atenolol have shown that although beta blockers are more effective than placebo in preventing stroke and total cardiovascular events, they are not as effective as diuretics, medications inhibiting the renin–angiotensin system (e.g., ACE inhibitors), or calcium channel blockers.Bisoprolol
Bisoprolol, marketed under the tradename Zebeta among others, is a medication most commonly used for heart diseases. This specifically includes high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.Common side effects include headache, feeling tired, diarrhea, and swelling in the legs. More severe side effects include worsening asthma, blocking the ability to recognize low blood sugar, and worsening heart failure. There are concerns that use during pregnancy may be harmful to the baby. Bisoprolol is in the beta blocker family of medications and is of the β1 selective type.Bisoprolol was patented in 1976 and approved for medical use in 1986. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Bisoprolol is available as a generic medication. The wholesale cost in the developing world is about US$2.98–4.94 per month. In the United States, as of 2015, it costs about $25–50 a month.Brain natriuretic peptide
Brain natriuretic peptide (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. BNP is named as such because it was originally identified in extracts of pig brain.
The 32-amino acid polypeptide BNP is secreted attached to a 76–amino acid N-terminal fragment in the prohormone called NT-proBNP (BNPT), which is biologically inactive. Once released, BNP binds to and activates the atrial natriuretic factor receptor NPRA, and to a lesser extent NPRB, in a fashion similar to atrial natriuretic peptide (ANP) but with 10-fold lower affinity. The biological half-life of BNP, however, is twice as long as that of ANP, and that of NT-proBNP is even longer, making these peptides better targets than ANP for diagnostic blood testing.
The physiologic actions of BNP are similar to those of ANP and include decrease in systemic vascular resistance and central venous pressure as well as an increase in natriuresis. The net effect of these peptides is a decrease in blood pressure due to the decrease in systemic vascular resistance and, thus, afterload. Additionally, the actions of both BNP and ANP result in a decrease in cardiac output due to an overall decrease in central venous pressure and preload as a result of the reduction in blood volume that follows natriuresis and diuresis.Cardiac asthma
Cardiac asthma is a medical diagnosis of wheezing, coughing or shortness of breath due to congestive heart failure. It is known as cardiac asthma because the symptoms mimic ordinary asthma (bronchial asthma). One study found that patients with cardiac asthma represented one third of congestive heart failure in elderly patients.Depending on severity, it may be classified as a medical emergency, as it can be a symptom of acute heart failure leading to the buildup of fluid in the lungs (pulmonary edema) as well as within and around the airways.
The distinction between bronchial asthma and cardiac asthma is especially important because some treatments for bronchial asthma, including inhalers, may worsen cardiac asthma or cause severe heart arrhythmias.
Bronchial asthma, in contrast, is caused by the inflammation and narrowing of pulmonary airways, causing the characteristic breathing difficulties. Bronchial asthma has nothing to do with fluid in the lungs or heart disease, or even the heart failure associated with cardiac asthma.Congestive hepatopathy
Congestive hepatopathy, also known as nutmeg liver and chronic passive congestion of the liver, is liver dysfunction due to venous congestion, usually due to congestive heart failure. The gross pathological appearance of a liver affected by chronic passive congestion is "speckled" like a grated nutmeg kernel; the dark spots represent the dilated and congested hepatic venules and small hepatic veins. The paler areas are unaffected surrounding liver tissue. When severe and longstanding, hepatic congestion can lead to fibrosis; if congestion is due to right heart failure, it is called cardiac cirrhosis.Digoxin
Digoxin, sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is taken by mouth or by injection into a vein.Common side effects include breast enlargement with other side effects generally due to an excessive dose. These side effects may include loss of appetite, nausea, trouble seeing, confusion, and an irregular heartbeat. Greater care is required in older people and those with poor kidney function. It is unclear whether use during pregnancy is safe. Digoxin is in the cardiac glycoside family of medications.Digoxin was first isolated in 1930 from the foxglove plant, Digitalis lanata. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$0.21–6.60 a month. In the United States it generally costs less than $25 per month, as of 2015.Dilated cardiomyopathy
Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Complications can include heart failure, heart valve disease, or an irregular heartbeat.Causes include genetics, alcohol, cocaine, certain toxins, complications of pregnancy, and certain infections. Coronary artery disease and high blood pressure may play a role, but are not the primary cause. In many cases the cause remains unclear. It is a type of cardiomyopathy, a group of diseases that primarily affects the heart muscle. The diagnosis may be supported by an electrocardiogram, chest X-ray, or echocardiogram.In those with heart failure, treatment may include medications in the ACE inhibitor, beta blocker, and diuretic families. A low salt diet may also be helpful. In those with certain types of irregular heartbeat, blood thinners or an implantable cardioverter defibrillator may be recommended. If other measures are not effective a heart transplant may be an option in some.About 1 per 2,500 people are affected. It occurs more frequently in men than women. Onset is most often in middle age. Five-year survival rate is about 50%. It can also occur in children and is the most common type of cardiomyopathy in this age group.Dronedarone
Dronedarone (development codename SR33589 and marketed as Multaq) is a drug by Sanofi-Aventis, mainly for the indication of cardiac arrhythmias. It was approved by the FDA on July 2, 2009. It was recommended as an alternative to amiodarone for the treatment of atrial fibrillation and atrial flutter in people whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment i.e. direct current cardioversion (DCCV) to maintain normal rhythm. It is a class III antiarrhythmic drug. In the United States, the FDA approved label includes a claim for reducing hospitalization, but not for reducing mortality, as a reduction in mortality was not demonstrated in the clinical development program. A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in patients with moderate to severe CHF.The U.S. label for dronedarone includes a boxed warning, stating that dronedarone is contraindicated in patients with NYHA Class IV heart failure, with NYHA Class II–III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic, or with permanent atrial fibrillation." Dronedarone is also associated with rare cases of severe liver damage, including liver failure.Edema
Edema, also spelled oedema or œdema, is an abnormal accumulation of fluid in the interstitium, located beneath the skin and in the cavities of the body, which can cause severe pain. Clinically, edema manifests as swelling. The amount of interstitial fluid is determined by the balance of fluid homeostasis and the increased secretion of fluid into the interstitium. The word is from Greek οἴδημα oídēma meaning "swelling". The condition is also known (mostly archaic) as dropsy.Ejection fraction
An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, ventricle, gall bladder, or leg veins, although if unspecified it usually refers to the left ventricle of the heart. EF is widely used as a measure of the pumping efficiency of the heart and is used to classify heart failure types. It is also used as an indicator of the severity of heart failure, although it has recognized limitations.The EF of the left heart, known as the left ventricular ejection fraction (LVEF), is calculated by dividing the volume of blood pumped from the left ventricle per beat (stroke volume) by the volume of blood collected in the left ventricle at the end of diastolic filling (end-diastolic volume). LVEF is an indicator of the effectiveness of pumping into the systemic circulation. The EF of the right heart, or right ventricular ejection fraction (RVEF), is a measure of the efficiency of pumping into the pulmonary circulation. A heart which cannot pump sufficient blood to meet the body's requirements (i.e., heart failure) will often, but not invariably, have a reduced ventricular ejection fraction.Heart
The heart is a muscular organ in most animals, which pumps blood through the blood vessels of the circulatory system. Blood provides the body with oxygen and nutrients, as well as assisting in the removal of metabolic wastes. In humans, the heart is located between the lungs, in the middle compartment of the chest.In humans, other mammals, and birds, the heart is divided into four chambers: upper left and right atria; and lower left and right ventricles. Commonly the right atrium and ventricle are referred together as the right heart and their left counterparts as the left heart. Fish, in contrast, have two chambers, an atrium and a ventricle, while reptiles have three chambers. In a healthy heart blood flows one way through the heart due to heart valves, which prevent backflow. The heart is enclosed in a protective sac, the pericardium, which also contains a small amount of fluid. The wall of the heart is made up of three layers: epicardium, myocardium, and endocardium.The heart pumps blood with a rhythm determined by a group of pacemaking cells in the sinoatrial node. These generate a current that causes contraction of the heart, traveling through the atrioventricular node and along the conduction system of the heart. The heart receives blood low in oxygen from the systemic circulation, which enters the right atrium from the superior and inferior venae cavae and passes to the right ventricle. From here it is pumped into the pulmonary circulation, through the lungs where it receives oxygen and gives off carbon dioxide. Oxygenated blood then returns to the left atrium, passes through the left ventricle and is pumped out through the aorta to the systemic circulation−where the oxygen is used and metabolized to carbon dioxide. The heart beats at a resting rate close to 72 beats per minute. Exercise temporarily increases the rate, but lowers resting heart rate in the long term, and is good for heart health.Cardiovascular diseases (CVD) are the most common cause of death globally as of 2008, accounting for 30% of deaths. Of these more than three quarters are a result of coronary artery disease and stroke. Risk factors include: smoking, being overweight, little exercise, high cholesterol, high blood pressure, and poorly controlled diabetes, among others. Cardiovascular diseases frequently do not have symptoms or may cause chest pain or shortness of breath. Diagnosis of heart disease is often done by the taking of a medical history, listening to the heart-sounds with a stethoscope, ECG, and ultrasound. Specialists who focus on diseases of the heart are called cardiologists, although many specialties of medicine may be involved in treatment.Heart failure with preserved ejection fraction
Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure in which the ejection fraction - the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the left ventricle is maximally filled - is normal, defined as greater than 50%; this may be measured by echocardiography or cardiac catheterization. Approximately half of people with heart failure have preserved ejection fraction, while the other half have a reduction in ejection fraction, called heart failure with reduced ejection fraction (HFrEF).Risk factors for HFpEF include hypertension, hyperlipidemia, diabetes, smoking, and obstructive sleep apnea.
HFpEF is characterized by abnormal diastolic function: there is an increase in the stiffness of the left ventricle, which causes a decrease in left ventricular relaxation during diastole, with resultant increased pressure and/or impaired filling. There is an increased risk for atrial fibrillation and pulmonary hypertension.
There is controversy regarding the relationship between diastolic heart failure and HFpEF.Hypertensive heart disease
Hypertensive heart disease includes a number of complications of high blood pressure that affect the heart. While there are several definitions of hypertensive heart disease in the medical literature, the term is most widely used in the context of the International Classification of Diseases (ICD) coding categories. The definition includes heart failure and other cardiac complications of hypertension when a causal relationship between the heart disease and hypertension is stated or implied on the death certificate. In 2013 hypertensive heart disease resulted in 1.07 million deaths as compared with 630,000 deaths in 1990.According to ICD-10, hypertensive heart disease (I11), and its subcategories: hypertensive heart disease with heart failure (I11.0) and hypertensive heart disease without heart failure (I11.9) are distinguished from chronic rheumatic heart diseases (I05-I09), other forms of heart disease (I30-I52) and ischemic heart diseases (I20-I25). However, since high blood pressure is a risk factor for atherosclerosis and ischemic heart disease, death rates from hypertensive heart disease provide an incomplete measure of the burden of disease due to high blood pressure.Rheumatic fever
Rheumatic fever (RF) is an inflammatory disease that can involve the heart, joints, skin, and brain. The disease typically develops two to four weeks after a streptococcal throat infection. Signs and symptoms include fever, multiple painful joints, involuntary muscle movements, and occasionally a characteristic non-itchy rash known as erythema marginatum. The heart is involved in about half of the cases. Damage to the heart valves, known as rheumatic heart disease (RHD), usually occurs after repeated attacks but can sometimes occur after one. The damaged valves may result in heart failure, atrial fibrillation and infection of the valves.Rheumatic fever may occur following an infection of the throat by the bacterium Streptococcus pyogenes. If the infection is untreated rheumatic fever can occur in up to three percent of people. The underlying mechanism is believed to involve the production of antibodies against a person's own tissues. Due to their genetics, some people are more likely to get the disease when exposed to the bacteria than others. Other risk factors include malnutrition and poverty. Diagnosis of RF is often based on the presence of signs and symptoms in combination with evidence of a recent streptococcal infection.Treating people who have strep throat with antibiotics, such as penicillin, decreases the risk of developing rheumatic fever. In order to avoid antibiotic misuse this often involves testing people with sore throats for the infection, which may not be available in the developing world. Other preventive measures include improved sanitation. In those with rheumatic fever and rheumatic heart disease, prolonged periods of antibiotics are sometimes recommended. Gradual return to normal activities may occur following an attack. Once RHD develops, treatment is more difficult. Occasionally valve replacement surgery or valve repair is required. Otherwise complications are treated as per normal.Rheumatic fever occurs in about 325,000 children each year and about 33.4 million people currently have rheumatic heart disease. Those who develop RF are most often between the ages of 5 and 14, with 20% of first-time attacks occurring in adults. The disease is most common in the developing world and among indigenous peoples in the developed world. In 2015 it resulted in 319,400 deaths down from 374,000 deaths in 1990. Most deaths occur in the developing world where as many as 12.5% of people affected may die each year. Descriptions of the condition are believed to date back to at least the 5th century BCE in the writings of Hippocrates. The disease is so named because its symptoms are similar to those of some rheumatic disorders.Serelaxin
Serelaxin (brand name Reasanz; developmental code name RLX-030) is a medication which is marketed in Russia for the treatment of acute heart failure (AHF), targeting the relaxin receptor. It was also under development in other places in the world, including in the United States, Europe, and Asia, but ultimately was not marketed in these areas.Serelaxin is a recombinant form of human relaxin-2, a hormone that (among other functions) is produced during pregnancy and mediates the haemodynamic changes that occur during this time, such as increased blood output of the heart and blood flow in the kidney. Human-relaxin-2 mediates vasodilation (widening of blood vessels) by increasing the production of nitric oxide (NO), a potent vasodilator. Activation of the relaxin receptor RXFP1 activates several enzymes in a phosphorylation cascade that eventually results in the activation of NO synthase in endothelial cells and the subsequent production of NO. Relaxin can also bind to a secondary receptor, endothelial B receptor, which is upregulated as a result of the previous pathway. Relaxin binding to endothelial B receptor on endothelial cells also induces vasodilation.Relaxin causes vasodilation by an indirect mechanism, where it inhibits the potent vasoconstrictors angiotensin II and endothelin. In addition to vasodilation, the effects of relaxin are also seen in the kidneys, by significantly increasing creatinine clearance, which is a measure of kidney function, as well as increased renal blood flow. Relaxin also functions as a cardiac stimulant. Studies have demonstrated that relaxin increases calcium sensitivity of cardiac myofilaments as well as increasing phosphorylation of the myofilaments by protein kinase C (PKC). These modifications both function to increase the force generated by the myofilaments without increasing the energy consumption of the cardiac myocytes. Thus relaxin and serelaxin can increase stroke volume, the amount of blood pumped per heart beat, without increasing the energy demand on the already strained heart of acute heart failure patients.Shortness of breath
Shortness of breath, also known as dyspnea, is the feeling that one cannot breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity", and recommends evaluating dyspnea by assessing the intensity of the distinct sensations, the degree of distress involved, and its burden or impact on activities of daily living. Distinct sensations include effort/work, chest tightness, and air hunger (the feeling of not enough oxygen).Dyspnea is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations or light exertion. In 85% of cases it is due to asthma, pneumonia, cardiac ischemia, interstitial lung disease, congestive heart failure, chronic obstructive pulmonary disease, or psychogenic causes, such as panic disorder and anxiety. Treatment typically depends on the underlying cause.