Identifying HFmrEF as a separate group will stimulate research into the underlying characteristics, pathophysiology and treatment of this group of patients. Patients without detectable LV myocardial disease may have other cardiovascular causes for HF e. Occasionally, however, a patient may have HF due to a problem that resolves completely e.
Many or all of these terms may be accurately applied to the same patient at different times, depending upon their stage of illness.
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However, symptom severity correlates poorly with many measures of LV function; although there is a clear relationship between the severity of symptoms and survival, patients with mild symptoms may still have an increased risk of hospitalization and death. Compared with HFrEF, patients with HFpEF are older, more often women and more commonly have a history of hypertension and atrial fibrillation AF , while a history of myocardial infarction is less common. The aetiology of HF is diverse within and among world regions. Identification of these diverse pathologies should be part of the diagnostic workup, as they may offer specific therapeutic opportunities.
Many patients with HF and ischaemic heart disease IHD have a history of myocardial infarction or revascularization. However, a normal coronary angiogram does not exclude myocardial scar e. In clinical practice, a clear distinction between acquired and inherited cardiomyopathies remains challenging. Over the last 30 years, improvements in treatments and their implementation have improved survival and reduced the hospitalization rate in patients with HFrEF, although the outcome often remains unsatisfactory.
Estimation of prognosis for morbidity, disability and death helps patients, their families and clinicians decide on the appropriate type and timing of therapies in particular, decisions about a rapid transition to advanced therapies and assists with planning of health and social services and resources. However, their clinical applicability is limited and precise risk stratification in HF remains challenging. In recent decades, several multivariable prognostic risk scores have been developed for different populations of patients with HF, 36 - 41 and some are available as interactive online applications.
Multivariable risk scores may help predict death in patients with HF, but remain less useful for the prediction of subsequent HF hospitalizations. Signs, such as elevated jugular venous pressure and displacement of the apical impulse, may be more specific, but are harder to detect and have poor reproducibility. A detailed history should always be obtained. HF is unusual in an individual with no relevant medical history e. At each visit, symptoms and signs of HF need to be assessed, with particular attention to evidence of congestion. Symptoms and signs are important in monitoring a patient's response to treatment and stability over time.
Persistence of symptoms despite treatment usually indicates the need for additional therapy, and worsening of symptoms is a serious development placing the patient at risk of urgent hospital admission and death and merits prompt medical attention. Patients with normal plasma NP concentrations are unlikely to have HF. Among them, AF, age and renal failure are the most important factors impeding the interpretation of NP measurements.
An abnormal electrocardiogram ECG increases the likelihood of the diagnosis of HF, but has low specificity. Echocardiography is the most useful, widely available test in patients with suspected HF to establish the diagnosis. It provides immediate information on chamber volumes, ventricular systolic and diastolic function, wall thickness, valve function and pulmonary hypertension.
The information provided by careful clinical evaluation and the above mentioned tests will permit an initial working diagnosis and treatment plan in most patients. Other tests are generally required only if the diagnosis remains uncertain e. The diagnosis of HF in the acute setting is discussed in Section If all elements are normal, HF is highly unlikely and other diagnoses need to be considered. If at least one element is abnormal, plasma NPs should be measured, if available, to identify those who need echocardiography an echocardiogram is indicated if the NP level is above the exclusion threshold or if circulating NP levels cannot be assessed.
The diagnosis of HFpEF remains challenging. This section summarizes practical recommendations necessary for proper diagnosis of this clinical entity in clinical practice.
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To improve the specificity of diagnosing HFpEF, the clinical diagnosis needs to be supported by objective measures of cardiac dysfunction at rest or during exercise. Objective evidence of other cardiac functional and structural alterations underlying HF for details, see below. In case of uncertainty, a stress test or invasively measured elevated LV filling pressure may be needed to confirm the diagnosis for details, see below. Not all of the recommended values are identical to those published in previous guidelines, because of the inclusion of new data published in recent reports, in particular by Cabarello et al.
Patients with HFpEF are a heterogeneous group with various underlying aetiologies and pathophysiological abnormalities. Cardiac imaging plays a central role in the diagnosis of HF and in guiding treatment. Of several imaging modalities available, echocardiography is the method of choice in patients with suspected HF, for reasons of accuracy, availability including portability , safety and cost.
In general, imaging tests should only be performed when they have a meaningful clinical consequence. The reliability of the outcomes is highly dependent on the imaging modality, the operator and centre experience and imaging quality.
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Normal values may vary with age, sex and imaging modality. It is probably most useful in identifying an alternative, pulmonary explanation for a patient's symptoms and signs, i. For the diagnosis of asthma or chronic obstructive pulmonary disease COPD , pulmonary function testing with spirometry is needed. Transthoracic echocardiography TTE is the method of choice for assessment of myocardial systolic and diastolic function of both left and right ventricles.
This method relies on accurate tracing of endocardial borders. In case of poor image quality, contrast agents should be used to improve endocardial delineation. Doppler techniques allow the calculation of haemodynamic variables, such as stroke volume index and cardiac output, based on the velocity time integral at the LV outflow tract area.
In recent years, tissue Doppler parameters S wave and deformation imaging techniques strain and strain rate have been shown to be reproducible and feasible for clinical use, especially in detecting subtle abnormalities in systolic function in the preclinical stage; however, measurements may vary among vendors and software versions.
LV diastolic dysfunction is thought to be the underlying pathophysiological abnormality in patients with HFpEF and perhaps HFmrEF, and thus its assessment plays an important role in diagnosis. Although echocardiography is at present the only imaging technique that can allow for the diagnosis of diastolic dysfunction, no single echocardiography variable is sufficiently accurate to be used in isolation to make a diagnosis of LV diastolic dysfunction. An obligatory element of echocardiography examination is the assessment of right ventricle RV structure and function, including RV and right atrial RA dimensions, an estimation of RV systolic function and pulmonary arterial pressure.
Transoesophageal echocardiography TOE is not needed in the routine diagnostic assessment of HF; however, it may be valuable in some clinical scenarios of patients with valve disease, suspected aortic dissection, suspected endocarditis or congenital heart disease and for ruling out intracavitary thrombi in AF patients requiring cardioversion.
When the severity of mitral or aortic valve disease does not match the patient's symptoms using TTE alone, a TOE examination should be performed. CMR is acknowledged as the gold standard for the measurements of volumes, mass and EF of both the left and right ventricles. CMR is the preferred imaging method to assess myocardial fibrosis using late gadolinium enhancement LGE along with T1 mapping and can be useful for establishing HF aetiology.
CMR may also be used for the assessment of myocardial ischaemia and viability in patients with HF and CAD considered suitable for coronary revascularization. However, limited evidence from RCTs has failed to show that viability assessed by CMR or other means identified patients who obtained clinical benefit from revascularization. Clinical limitations of CMR include local expertise, lower availability and higher costs compared with echocardiography, uncertainty about safety in patients with metallic implants including cardiac devices and less reliable measurements in patients with tachyarrhythmias.
Claustrophobia is an important limitation for CMR. Limited availability, radiation exposure and cost are the main limitations. Indications for coronary angiography in patients with HF are in concordance with the recommendations of other relevant ESC guidelines. Coronary angiography is also recommended in patients with a history of symptomatic ventricular arrhythmia or aborted cardiac arrest.
However, the test is only required when its results might affect a therapeutic decision. The most important clinical indications for the applicability of certain imaging methods in patients with suspected or confirmed HF are shown in the recommendations table. Recommendations for cardiac imaging in patients with suspected or established heart failure. Comprehensive assessment of patients with HF comprises, besides medical history and physical examination, including adequate imaging techniques, a set of additional diagnostic tests, i.
The major typical indications are summarized in the recommendations table for diagnostic tests in patients with HF. Although there is extensive research on biomarkers in HF e. ST2, galectin 3, copeptin, adrenomedullin , there is no definite evidence to recommend them for clinical practice. Recommendations for diagnostic tests in patients with heart failure.
Molecular genetic analysis in patients with cardiomyopathies is recommended when the prevalence of detectable mutations is sufficiently high and consistent to justify routine targeted genetic screening. There are already more than 50 genes identified that are associated with DCM. Many genes are related to the cytoskeleton. ARVC is hereditary in most cases and is caused by gene mutations that encode elements of the desmosome. Counselling should be performed by someone with sufficient knowledge of the specific psychological, social and medical implications of a diagnosis.
Determination of the genotype is important, since some forms [e. DNA analysis could also be of help to establish the diagnosis of rare forms, such as mitochondrial cardiomyopathies. There is considerable evidence that the onset of HF may be delayed or prevented through interventions aimed at modifying risk factors for HF or treating asymptomatic LV systolic dysfunction see recommendations table. Many trials show that control of hypertension will delay the onset of HF and some also show that it will prolong life.
Intensification of hypoglycaemic therapy to drive down glycated haemoglobin HbA1c with agents other than empagliflozin does not reduce the risk of developing HF for details see Section Although smoking cessation has not been shown to reduce the risk of developing HF, the epidemiological associations with the development of cardiovascular disease suggest that such advice, if followed, would be beneficial. An inverse relationship between physical activity and the risk of HF has been reported.
Statins reduce the rate of cardiovascular events and mortality; there is also reasonable evidence that they prevent or delay the onset of HF. Obesity is also a risk factor for HF, but the impact of treatments of obesity on the development of HF is unknown. The goals of treatment in patients with HF are to improve their clinical status, functional capacity and quality of life, prevent hospital admission and reduce mortality. However, it is now recognized that preventing HF hospitalization and improving functional capacity are important benefits to be considered if a mortality excess is ruled out.
The recommendations for each treatment are summarized below. Therapeutic algorithm for a patient with symptomatic heart failure with reduced ejection fraction. Green indicates a class I recommendation; yellow indicates a class IIa recommendation. For further details, see Sections 7 and 8 and corresponding web pages.
Ivabradine reduces the elevated heart rate often seen in HFrEF and has also been shown to improve outcomes, and should be considered when appropriate. The use of diuretics should be modulated according to the patient's clinical status. The recommendations given in Sections 7. ACEIs have been shown to reduce mortality and morbidity in patients with HFrEF 2 , 5 , - and are recommended unless contraindicated or not tolerated in all symptomatic patients.
There is evidence that in clinical practice the majority of patients receive suboptimal doses of ACEI. MRAs spironolactone and eplerenone block receptors that bind aldosterone and, with different degrees of affinity, other steroid hormone e. Regular checks of serum potassium levels and renal function should be performed according to clinical status. Diuretics are recommended to reduce the signs and symptoms of congestion in patients with HFrEF, but their effects on mortality and morbidity have not been studied in RCTs.
Loop diuretics produce a more intense and shorter diuresis than thiazides, although they act synergistically and the combination may be used to treat resistant oedema. However, adverse effects are more likely and these combinations should only be used with care. The aim of diuretic therapy is to achieve and maintain euvolaemia with the lowest achievable dose. The dose of the diuretic must be adjusted according to the individual needs over time. A new therapeutic class of agents acting on the RAAS and the neutral endopeptidase system has been developed [angiotensin receptor neprilysin inhibitor ARNI ].
The first in class is LCZ, which is a molecule that combines the moieties of valsartan and sacubitril neprilysin inhibitor in a single substance. By inhibiting neprilysin, the degradation of NPs, bradykinin and other peptides is slowed. Also, the number of African American patients, who are at a higher risk of angioedema, was relatively small in this study. Ivabradine slows the heart rate through inhibition of the I f channel in the sinus node and therefore should only be used for patients in sinus rhythm.
Additionally, a combination of hydralazine and isosorbide dinitrate may be considered in symptomatic patients with HFrEF who can tolerate neither ACEI nor ARB or they are contraindicated to reduce mortality. However, this recommendation is based on the results of the Veterans Administration Cooperative Study, which recruited symptomatic HFrEF patients who received only digoxin and diuretics.
This section describes treatments that have shown benefits in terms of symptomatic improvement, reduction in HF hospitalizations or both, and are useful additional treatments in patients with HFrEF. In patients with symptomatic HF and AF, digoxin may be useful to slow a rapid ventricular rate, but it is only recommended for the treatment of patients with HFrEF and AF with rapid ventricular rate when other therapeutic options cannot be pursued.
A resting ventricular rate in the range of 70—90 bpm is recommended based on current opinion, although one trial suggested that a resting ventricular rate of up to bpm might still be acceptable. Digitalis should always be prescribed under specialist supervision. Given its distribution and clearance, caution should be exerted in females, in the elderly and in patients with reduced renal function. In the latter patients, digitoxin should be preferred. Although statins reduce mortality and morbidity in patients with atherosclerotic disease, statins are not effective in improving the prognosis in patients with HFrEF.
Most statin trials excluded patients with HF because it was uncertain that they would benefit. Patients with HFrEF receiving oral anticoagulation because of concurrent AF or risk of venous thromboembolism should continue anticoagulation. Detailed information is provided in Section Similarly, there is no evidence on the benefits of antiplatelet drugs including acetylsalicylic acid in patients with HF without accompanying CAD, whereas there is a substantial risk of gastrointestinal bleeding, particularly in elderly subjects, related with this treatment.
Aliskiren direct renin inhibitor failed to improve outcomes for patients hospitalized for HF at 6 months or 12 months in one study and is not presently recommended as an alternative to an ACEI or ARB. Diltiazem and verapamil have been shown to be unsafe in patients with HFrEF. There is a variety of dihydropyridine CCBs; some are known to increase sympathetic tone and they may have a negative safety profile in HFrEF. There is only evidence on safety for amlodipine and felodipine in patients with HFrEF, and they can be used only if there is a compelling indication in patients with HFrEF.
Currently, the evidence is considered insufficient to support specific guideline recommendations for other therapeutic technologies, including baroreflex activation therapy, vagal stimulation, diaphragmatic pacing , and cardiac contractility modulation; , further research is required. Implantable devices to monitor arrhythmias or haemodynamics are discussed elsewhere in these guidelines.
A high proportion of deaths among patients with HF, especially those with milder symptoms, occur suddenly and unexpectedly. Many of these are due to electrical disturbances, including ventricular arrhythmias, bradycardia and asystole, although some are due to coronary, cerebral or aortic vascular events. Treatments that improve or delay the progression of cardiovascular disease will reduce the annual rate of sudden death, but they may have little effect on lifetime risk and will not treat arrhythmic events when they occur.
ICDs are effective in preventing bradycardia and correcting potentially lethal ventricular arrhythmias. Some antiarrhythmic drugs might reduce the rate of tachyarrhythmias and sudden death, but they do not reduce overall mortality and may increase it. Compared with amiodarone treatment, ICDs reduce mortality in survivors of cardiac arrest and in patients who have experienced sustained symptomatic ventricular arrhythmias.
Accordingly, an ICD is contraindicated in this time period. A wearable defibrillator may be considered if the patient is deemed to be at high risk of ventricular fibrillation, although evidence from randomized trials is lacking. See the guideline on CRT for further details Section 8. ICD therapy is not recommended in patients in NYHA Class IV with severe symptoms refractory to pharmacological therapy who are not candidates for CRT, a ventricular assist device or cardiac transplantation, because such patients have a very limited life expectancy and are likely to die from pump failure.
Patients should be counselled as to the purpose of an ICD, complications related to implantation and device activation predominantly inappropriate shocks and under what circumstances it might be deactivated terminal disease or explanted infection, recovery of LV function. If HF deteriorates, deactivation of a patient's ICD may be considered after appropriate discussion with the patient and caregiver s. If the ICD generator reaches its end of life or requires explantation, it should not automatically be replaced. It is a matter of some controversy whether patients whose LVEF has greatly improved and who have not required device therapy during the lifetime of the ICD should have another device implanted.
Subcutaneous defibrillators may be as effective as conventional ICDs with a lower risk from the implantation procedure. Patients must be carefully selected, as they have limited capacity to treat serious bradyarrhythmia and can deliver neither antitachycardia pacing nor CRT. Substantial RCTs with these devices and more data on safety and efficacy are awaited. Recommendations for cardiac resynchronization therapy implantation in patients with heart failure.
The prevention of lethal bradycardia might be an important mechanism of benefit shared by all pacing devices. Not all patients respond favourably to CRT. Patients with ischaemic aetiology will have less improvement in LV function due to myocardial scar tissue, which is less likely to undergo favourable remodelling. Clinical practice varies widely among countries. It is unclear whether CRT reduces the need for an ICD by reducing the arrhythmia burden or increases the benefit from an ICD by reducing mortality rates from worsening HF, leading to longer exposure to the risk of arrhythmia.
This can be prevented by CRT, which might improve patient outcomes. Only two small trials have compared pharmacological therapy alone vs. CRT in patients with AF, with conflicting results. This observation has not been confirmed in a randomized trial. Imaging tests for dyssynchrony have not yet been shown to be of value in selecting patients for CRT.
The reader is directed to guidelines on pacing and CRT for recommendations on device implantation procedures. For patients with HFrEF who remain symptomatic despite OMT and do not have an indication for CRT, new device therapies have been proposed and in some cases are approved for clinical use in several European Union EU countries but remain under trial evaluation. Most other devices under evaluation involve some modification of the activity of the autonomic nervous system ANS by targeted electrical stimulation.
As new data and analyses become available, it might be possible to make recommendations for each phenotype separately. The pathophysiology underlying HFpEF and HFmrEF is heterogeneous, and they are associated with different phenotypes including diverse concomitant cardiovascular diseases e. Diuretics will usually improve congestion, if present, thereby improving symptoms and signs of HF. The evidence that diuretics improve symptoms is similar across the spectrum of LVEF.
For patients in sinus rhythm, there is some evidence that nebivolol, , , digoxin, spironolactone and candesartan might reduce HF hospitalizations. Patients in AF should receive an anticoagulant to reduce the risk of thromboembolic events for details, see the ESC guidelines of AF ]. Antiplatelet agents are ineffective for this purpose. Renal dysfunction, which is common in this population, may contraindicate or increase the risk of haemorrhage with NOACs. Recently, a trial of empagliflozin showed a reduction in blood pressure and body weight, probably by inducing glycosuria and osmotic diuresis.
Its use was associated with a reduction in hospitalization for HF and in cardiovascular mortality. Myocardial ischaemia may contribute to symptoms, morbidity and mortality and should be considered when assessing patients. However, there is only anecdotal evidence that revascularization improves symptoms or outcome. Patients with angina should follow the same management route as patients with HFrEF. Patients with HFpEF and HFmrEF have impaired exercise tolerance, commonly accompanied by an augmented blood pressure response to exercise and chronotropic incompetence.
There is no evidence that clinical decisions based on routine ambulatory electrocardiographic monitoring improve outcomes for patients with HF. Ambulatory electrocardiographic recording detects premature ventricular complexes in virtually all patients with HF. AF is the most common arrhythmia in HF irrespective of concomitant LVEF; it increases the risk of thromboembolic complications particularly stroke and may impair cardiac function, leading to worsening symptoms of HF.
The following issues need to be considered in patients with HF presenting with AF, irrespective of LVEF, especially with a first diagnosed episode of AF or paroxysmal AF: identification of potentially correctable causes e. Dronedarone is contraindicated in patients with HF and AF. For patients with marked congestion who nonetheless have few symptoms at rest, initial treatment with oral or intravenous i.
For patients in haemodynamic instability, an i. In patients with haemodynamic collapse, emergency electrical cardioversion is recommended see also Section Assessment of ventricular rate control from the radial pulse is not ideal, especially in patients with HF, as ventricular activation may not always generate a palpable pulse. Rate control should be documented electrocardiographically.
A wearable device enables ventricular rate to be assessed during rest, exercise and sleep, but the value of routine monitoring has not yet been established. The optimal resting ventricular rate in patients with AF and HF is uncertain but may be between 60— bpm. Rarely, ventricular rate cannot be reduced below — bpm by pharmacological means alone and AV node ablation with ventricular pacing may be considered; in this situation, for patients with HFrEF, CRT should be considered instead of conventional RV pacing.
In patients with chronic HF, a rhythm control strategy including pharmacological or electrical cardioversion has not been shown to be superior to a rate control strategy in reducing mortality or morbidity. A rhythm control strategy is probably best reserved for patients with a reversible secondary cause of AF e.
The use of class I antiarrhythmic agents and dronedarone increases morbidity and mortality in patients with HF and AF and should be avoided. The safety and efficacy of catheter ablation in the atria and pulmonary veins PV as a rhythm control strategy in HF is at present uncertain except for tachycardia induced cardiomyopathy. Two small studies of AF ablation compared with rate control met with mixed success in terms of procedural complications and success in improving symptoms.
Recommendations for a rhythm control management strategy in patients with atrial fibrillation, symptomatic heart failure NYHA Class II—IV and left ventricular systolic dysfunction and no evidence of acute decompensation. In patients with HF and AF who have mechanical heart valves or at least moderate mitral stenosis, only oral vitamin K antagonists should be used for prevention of thromboembolic stroke.
The dabigatran dose should be reduced to mg b. Randomized trials of revascularization for patients with HFrEF have not reduced overall mortality, , even in subgroups of patients with angina or myocardial ischaemia, , but further analysis did suggest a reduction in sudden deaths. Seeking the advice of the members of the HF Team with expertise in electrophysiology is recommended in patients with recalcitrant ventricular arrhythmias. When the cause of bradycardia or pauses is sinus node disease with intact AV conduction, then therapeutic strategies that avoid inducing ventricular dyssynchrony are preferred, although clinical trial evidence to support this expert opinion for patients with HF is sparse.
This may be because either safety or efficacy may be different in the presence of HF or may simply be unknown or because of evidence of particular effects in an HF population, either beneficial or detrimental. In HFpEF patients, they may also be used for angina relief, although this has never been formally tested.
For indications for invasive coronary angiography in patients with HF, please refer to Section 5.
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Percutaneous and surgical revascularization are complementary approaches for symptomatic relief of angina in HFpEF, but whether these interventions improve outcomes is not entirely clear. Recent ESC guidelines on myocardial revascularization recommended coronary artery bypass grafting CABG for patients with significant left main stenosis and left main equivalent proximal stenosis of both the left anterior descending and left circumflex arteries to improve prognosis.
Post hoc analyses from the STICH trial revealed that the presence of inducible myocardial ischaemia either on radionuclide stress test or dobutamine stress echocardiogram or angina does not identify those with worse prognosis and greater benefit from CABG over OMT. Cachexia is a generalized wasting process affecting all body compartments [i.
The causes are multifactorial, and in individual patients they are difficult to determine. Certain chemotherapeutic agents can cause or aggravate LV systolic dysfunction and HF. The best recognized of these are the anthracyclines e. If LV function improves, the risks and benefits of further chemotherapy need to be reconsidered. Cardiac biomarkers NPs and troponins can be used to identify patients at higher risk of cardiotoxicity and may be helpful in monitoring the use and dosing of cardiotoxic cytotoxics.
Stroke and HF commonly coexist because of an overlap of shared risk factors. Both contribute to a worse prognosis. Autonomic dysfunction is common in HFrEF, especially when severe. Diuretic dosage may be reduced to reduce the severity of postural hypotension. Depression is common and is associated with worse clinical status and a poor prognosis in HF. A high index of suspicion is needed to make the diagnosis, especially in the elderly.
Routine screening using a validated questionnaire is good practice. Until now, the Beck Depression Inventory BDI and Cardiac Depression Scale have been formally validated as reliable tools for the assessment of depressive mood in patients with HF, , but other questionnaires have been broadly used in this group of patients e. Psychosocial intervention and pharmacological treatment are helpful, as well as exercise training, in patients with HFrEF and depression. Selective serotonin reuptake inhibitors are thought to be safe, although the Sertraline Antidepressant Heart Attack Randomized Trial did not confirm that sertraline provides a greater reduction in depressive symptoms or improvement in cardiovascular status compared with placebo in HFrEF patients, but this trial was not powered enough to prove the latter.
Importantly, tricyclic antidepressants should be avoided, because they may cause hypotension, worsening HF and arrhythmias. Dysglycaemia and diabetes are very common in HF, and diabetes is associated with poorer functional status and worse prognosis. In patients with HFrEF, interventions that reduce morbidity and mortality confer similar benefit in the presence or absence of diabetes. Whether strict glycaemic control alters the risk of cardiovascular events in patients with HF is uncertain. In patients with diabetes and HF, glycaemic control should be implemented gradually and moderately, giving preference to those drugs, such as metformin, that have been shown to be safe and effective.
In contrast to what was previously believed, metformin is safe to use in patients with HFrEF, and it should be the treatment of choice in patients with HF , but is contraindicated in patients with severe renal or hepatic impairment, because of the risk of lactic acidosis. Sulphonylurea derivatives have also been associated with an increased risk of worsening HF and should be used with caution.
Thiazolidinediones glitazones cause sodium and water retention and increased risk of worsening HF and hospitalization and are not recommended in patients with HF. Erectile dysfunction is a common and important component of quality of life in men with HF. Some drugs applied for HF therapy e.
Hyperuricaemia and gout are common in HF and may be caused or aggravated by diuretic treatment. Hyperuricaemia is associated with a worse prognosis in HFrEF. Xanthine oxidase inhibitors allopurinol, oxypurinol may be used to prevent gout, although their safety in HFrEF is uncertain. Rheumatoid arthritis is associated with an increased risk of HFpEF. Both hypokalaemia and hyperkalaemia are associated with HF and with many drugs used for HF treatment. Amiloride and triamterene are sometimes used as adjunct diuretics in resistant oedema and to assist in preventing hypokalaemia.
The treatment of hypokalaemia can involve recommending high potassium foods or prescribing potassium supplements. A Cochrane review found no trial evidence of major outcome benefits for any emergency therapy regimen for hyperkalaemia. Two new potassium binders patiromer and sodium zirconium cyclosilicate are currently under consideration for regulatory approval. However, in patients who are already receiving a statin for CAD, a continuation of this therapy may be considered. Negatively inotropic CCBs i. The blood pressure targets recommended in hypertension guidelines are applicable to HF.
In contrast, treatment of hypertension is an important issue in patients with HFpEF. In patients with AHF, i. Treatment was also associated with a significant reduction in hospitalizations for worsening HF. The number of deaths and the incidence of adverse events were similar. Neither i. The safety of i. It is more common in women, the elderly and in patients with renal impairment and is associated with advanced myocardial remodelling, inflammation and volume overload.
A diagnostic workup to seek a cause for any finding of anaemia is indicated e. HF and CKD frequently coexist, share many risk factors diabetes, hypertension, hyperlipidaemia and interact to worsen prognosis. The importance of these apparently small changes is that they are frequent, they promote the development and progression of CKD and, as a consequence, can worsen the prognosis of HF. Increases in creatinine during an AHF hospitalization are not always clinically relevant, especially when they are accompanied by appropriate decongestion, diuresis and haemoconcentration.
Large increases in serum creatinine, termed acute kidney injury AKI , are relatively rare in HF and are probably associated with the combination of diuretic therapy with other potentially nephrotoxic drugs such as some antibiotics gentamicin and trimethoprim , contrast media, ACEIs, ARBs, NSAIDs, etc. Of relevance, some of these drugs may accumulate if they are renally excreted. Despite the fact that RAAS blockers can frequently cause a decrease in GFR in patients with HF, this reduction is usually small and should not lead to treatment discontinuation unless there is a marked decrease, as the treatment benefit in these patients is probably largely maintained.
Diuretics, especially thiazides, but also loop diuretics, may be less effective in patients with a very low GFR, and if used, should be dosed appropriately higher doses to achieve similar effects. Renally excreted drugs e. Renal dysfunction and worsening renal function is further discussed in the section about AHF see Section Prostatic obstruction is common in older men and can interfere with renal function; it should therefore be ruled out in men with HF with deteriorating renal function.
Therefore, according to the GINA global strategy report, , asthma is not an absolute contraindication, but these medications should only be used under close medical supervision by a specialist, with consideration of the risks for and against their use. Oral corticosteroids can cause sodium and water retention, potentially leading to worsening of HF, but this is not believed to be a problem with inhaled corticosteroids.
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Turner, Ralph King John: England's Evil King? Stroud, UK: History Press. Vincent, Nicholas In Vincent, Nicholas ed. Magna Carta: The Foundation of Freedom, — London: Third Millennium Publishing. Warren, W. Lewis King John. London: Methuen. White, Albert Beebe Woolwrych, Austin Herbert Smith, David Lee ed. Cromwell and Interregnum: The Essential Readings. Wright, Herbert G. Book on Demand. Wright, Patrick The River: A Thames Journey. London: BBC Books. Category Index Outline Portal. Legislation of the United Kingdom. United Kingdom portal Law portal. Namespaces Article Talk. Views Read View source View history.
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Repealed by Statute Law Repeals Act Regulated Jewish money lending, stating that children would not pay interest on a debt they had inherited while they were under age. Further addressed Jewish money lending, stating that a widow and children should be provided for before paying an inherited debt.
Determined that scutage or aid, forms of medieval taxation, could be levied and assessed only by the common consent of the realm. Confirmed the liberties and customs of the City of London and other boroughs. Described how senior churchmen and barons would be summoned to give consent for scutage and aid. Placed limits on the level of service required for a knight's fee. Repealed by Statute Law Revision Act Stated that an amercement, a type of medieval fine, should be proportionate to the offence, but even for a serious offence the fine should not be so heavy as to deprive a man of his livelihood.
Determined that the size of a fine on a member of the clergy should be independent of the ecclesiastical wealth held by the individual churchman. Prohibited royal officials, such as sheriffs, from trying a crime as an alternative to a royal judge. Repealed by Crown Proceedings Act Laid out the process for dealing with intestacy. Determined that a royal officer requisitioning goods must offer immediate payment to their owner. Regulated the exercise of castle-guard duty. Prevented the Crown from confiscating the lands of felons for longer than a year and a day, after which they were to be returned to the relevant feudal lord.
Ordered the removal of all fish weirs from rivers. Forbade the issuing of writ precipes if doing so would undermine the right of trial in a local feudal court. Stated that no one should be put on trial based solely on the unsupported word of a royal official. Stated that no free man could be imprisoned or stripped of his rights or possessions without due process being legally applied. Permitted men to leave England for short periods without prejudicing their allegiance to the King, with the exceptions for outlaws and wartime.