inhibiting the formation of prostaglandins, nsaids may exacerbate heart failure through several mechanisms, including promotion of fluid retention, increasing blood pressure, and decreasing a person's response to diuretic medications. similarly, the acc/aha recommends against the use of cox-2 inhibitor medications in people with heart failure. thiazolidinediones have been strongly linked to new cases of heart failure and worsening of pre-existing congestive heart failure due to their association with weight gain and fluid retention. certain calcium channel blockers, such as diltiazem and verapamil, are known to decrease the force with which the heart ejects blood, thus are not recommended in people with heart failure with a reduced ejection fraction. supplements certain alternative medicines carry a risk of exacerbating existing heart failure, and are not recommended. this includes aconite, ginseng, gossypol, gynura, licorice, lily of the valley, tetrandrine, and yohimbine. aconite can cause abnormally slow heart rates and abnormal heart rhythms such as ventricular tachycardia. ginseng can cause abnormally low or high blood pressure, and may interfere with the effects of diuretic medications. gossypol can increase the effects of diuretics, leading to toxicity. gynura can cause low blood pressure. licorice can worsen heart failure by increasing blood pressure and promoting fluid retention. lily of the valley can cause abnormally slow heart rates with mechanisms similar to those of digoxin. tetrandrine can lead to low blood pressure through inhibition of l-type calcium channels. yohimbine can exacerbate heart failure by increasing blood pressure through alpha-2 adrenergic receptor antagonism. pathophysiology main article: pathophysiology of heart failure model of a normal heart (left); and a weakened heart, with over-stretched muscle and dilation of left ventricle (right); both during diastole heart failure is caused by any condition that reduces the efficiency of the heart muscle, through damage or overloading. over time, these increases in workload, which are mediated by long-term activation of neurohormonal systems such as the renin–angiotensin system and the sympathoadrenal system, lead to fibrosis, dilation, and structural changes in the shape of the left ventricle from elliptical to spherical. the heart of a person with heart failure may have a reduced force of contraction due to overloading of the ventricle. in a normal 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 myofilaments in over-stretched heart muscle. diagnosis no diagnostic criteria have been agreed on as the gold standard for heart failure, especially heart failure with preserved ejection fraction (hfpef). in the uk, the national institute for health and care excellence recommends measuring n-terminal pro-bnp (nt-probnp) followed by an ultrasound of the heart if positive. in europe, the european society of cardiology, and in the united states, the aha/acc/hfsa, recommend measuring nt-probnp or bnp followed by an ultrasound of the heart if positive. this is recommended in those with symptoms consistent with heart failure such as shortness of breath. the european society of cardiology defines the diagnosis of heart failure as symptoms and signs consistent with heart failure in combination with "objective evidence of cardiac structural or functional abnormalities". this definition is consistent with an international 2021 report termed "universal definition of heart failure".: 3613 score-based algorithms have been developed to help in the diagnosis of hfpef, which can be challenging for physicians to diagnose.: 3630 the aha/acc/hfsa defines heart failure as symptoms and signs consistent with heart failure in combination with shown "structural and functional alterations of the heart as the underlying cause for the clinical presentation", for hfmref and hfpef specifically requiring "evidence of spontaneous or provokable increased left ventricle filling pressures".: e276–e277 algorithms the european society of cardiology has developed a diagnostic algorithm for hfpef, named hfa-peff.: 3630 hfa-peff considers symptoms and signs, typical clinical demographics (obesity, hypertension, diabetes, elderly, atrial fibrillation), and diagnostic laboratory tests, ecg, and echocardiography.: e277 classification one historical method of categorizing heart failure is by the side of the heart involved (left heart failure versus right heart failure). right heart failure was thought to compromise blood flow to the lungs compared to left heart failure compromising blood flow to the aorta and consequently to the brain and the remainder of the body's systemic circulation. however, mixed presentations are common and left heart failure is a common cause of right heart failure. more accurate classification of heart failure type is made by measuring ejection fraction, or 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 types are: heart failure with reduced ejection fraction (hfref): synonyms no longer recommended are "heart failure due to left ventricular systolic dysfunction" and "systolic heart failure". hfref is associated with an ejection fraction less than 40%. heart failure with mildly reduced ejection fraction (hfmref), previously called "heart failure with mid-range ejection fraction", is defined by an ejection fraction of 41–49%. 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 may also be classified as acute or chronic. 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 increased cardiac demand that results in increased left ventricular diastolic pressure which can develop into pulmonary congestion (pulmonary edema). several terms 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 no cardiac output occurs at all. without urgent treatment, these events 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. ultrasound an echocardiogram (ultrasound of the heart) is commonly used to support a clinical diagnosis of heart failure. this can 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 specific treatments, 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. ultrasound showing severe systolic heart failure chest x-ray chest radiograph of a lung with distinct kerley b lines, as well as an enlarged heart (as shown by an increased cardiothoracic ratio, cephalization of pulmonary veins, and minor pleural effusion as seen for example in the right horizontal fissure. yet, no obvious lung edema is seen. overall, this indicates intermediate severity (stage ii) heart failure. 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, evidence may exist 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. congestive heart failure with small bilateral effusions kerley b lines electrophysiology an electrocardiogram (ecg or 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 n-terminal pro-bnp (nt-probnp) is the favoured biomarker for the diagnosis of heart failure, according to guidelines published 2018 by nice in the uk. brain natriuretic peptide 32 (bnp) is another biomarker commonly tested for heart failure. an elevated nt-probnp or bnp is a specific test indicative of heart failure. additionally, nt-probnp or 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. 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. hyponatremia (low serum sodium concentration) is common in heart failure. vasopressin levels are usually increased, along with renin, angiotensin ii, and catecholamines 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 edema and intracranial hemorrhage. angiography 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. staging heart failure is commonly stratified by the degree of functional impairment conferred by the severity of the heart failure, as reflected in the new york heart association (nyha) functional classification. the nyha functional classes (i–iv) begin with class i, which is defined as a person who experiences no limitation in any activities and has no symptoms from ordinary activities. people with nyha class ii heart failure have slight, mild limitations with everyday activities; the person is comfortable at rest or with mild exertion. with nyha class iii heart failure, a marked limitation occurs with any activity; the person is comfortable only at rest. a person with nyha class iv heart failure is symptomatic at rest and becomes quite uncomfortable with any physical activity. 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. in its 2001 guidelines, the american college of cardiology/american heart association working group introduced four stages of heart failure: stage a: people at high risk for developing hf in the future, but no functional or structural heart disorder stage b: a structural heart disorder, but no symptoms at any stage stage c: previous or current symptoms of heart failure in the context of an underlying structural heart problem, but managed with medical treatment stage d: advanced disease requiring hospital-based support, a heart transplant, or palliative care the acc staging system is useful since stage a encompasses "pre-heart failure" – a stage where intervention with treatment can presumably prevent progression to overt symptoms. acc stage a does not