7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Heart Failure Contents Introduction History Framingham heart study Definition and diagnosis Definition of heart failure Prevalence Acute and chronic heart failure Systolic versus diastolic heart failure Pathophysiology of heart failure Management Clinical aspects History Symptoms and signs Severity of HF Physical examination Additional diagnostic tests Electrocardiogram Chest X-ray Echocardiography Laboratory tests Exercise test Heart catheterization Etiology of heart failure Coronary heart disease Hypertension Heart rhythm disorders Valvular disease Cardiomyopathies Pericardial disease and Tamponade Drugs Toxins Endocrine disorders Nutritional status Infiltrative and storage disorders Infectious disease Management in investigating etiology of heart failure https://www.textbookofcardiology.org/wiki/Heart_Failure 1/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Therapy of heart failure Non-pharmacological treatment Education Fluid and sodium restriction Body weight Alcohol and tobacco Exercise Other Pharmacological treatment Angiotensin-converting enzyme (ACE) inhibitors Beta Blockers Diuretics (Loop of Henle diuretics, Thiazides, Aldosterone antagonists) Loop of Henle diuretics Thiazides Aldosterone antagonists Choice and combination of diuretics Angiotensin receptor blockers (ARBs) Digoxin Ivabradine Hydralazine and isosorbide dinitrate (H-ISDN) Other Therapy of acute heart failure Management of HF beyond medication Device treatment Timing of ICD implantation Heart transplantation and Left Ventricular Assist Devices Management of HF patients with preserved LVEF (HFPEF) Prognosis References Ineke Nederend MSc, Peter Damman MD, W.E.M. Kok MD PhD Introduction History In 1628, William Harvey first described the circulation. Before this time, there was very little understanding of the nature of heart failure (HF). There are, however, accounts of a disease that now would be called heart failure, and herbal medicines such as the ancient boiled bulb of squill, or, later on, the broom plant (Cytisus scoparius) and the foxglove (Digitalis purpura) were used as diuretics to treat https://www.textbookofcardiology.org/wiki/Heart_Failure 2/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology heart failure or dropsy (edema). Foxglove was described as a diuretic by William Withering in 1785.[1] The essential glycoside substance digitalis of the leaves of the plant improves contractility of the cardiac muscle and has important parasympathetic effects, particularly on the atrioventricular node. In the 1950s, thiazide diuretics were introduced, and in the 1960s furosemide became available. For a long time, diuretics and digitalis were the main treatment options for HF. Vasodilator therapy for HF was introduced around 1960, and the first randomized trial showing a mortality benefit with nitrates and alphablockers for HF was published in 1986. In 1975, the first ACE inhibitor, captopril, was developed and it was approved for human use in 1981, in 1987. with data from the first randomized trial being published Spironolacton, introduced in 1959, was used (in low dose) for HF only after the introduction of ACE inhibitors. Beta blockers were hardly used in heart failure even though they were shown to beneficial in the 1970s. It was only in 1994 that data from the first randomized trial demonstrated a mortality benefit with beta blocker therapy. Foxglove (digitalis), used as a medicine for heart failure. Framingham heart study In 1948, the Framingham heart study was launched. At its start, 5209 residents of the town Framingham in the USA, aged between 30 and 62 years, were included in the study in an attempt to determine risk factors for cardiac disease. The study is still in progress today and long term data from the lengthy follow up have been published. This study is considered to be the most important longitudinal source of data on the epidemiology of heart failure[2]. Definition and diagnosis Definition of heart failure The term heart failure (HF) (congestive heart failure or cardiac decompensation or decompensatio cordis) describes an acute or chronic situation in which the amount of blood pumped through the circulation by the heart, is insufficient to meet the body s demands at a normal cardiac filling pressure. According to the guidelines of the European Society of Cardiology, HF is defined as a syndrome in which the patient has the following triad of features: (1) symptoms typical of HF; (2) signs typical of HF; and most importantly (3) objective evidence of a structural or functional abnormality of the heart at rest (Table 1). https://www.textbookofcardiology.org/wiki/Heart_Failure 3/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Table 1. Definition of heart failure Heart failure is a clinical syndrome in which patients have the following features: Symptoms typical of heart failure Breathlessness Orthopnoea Paroxysmal nocturnal dyspnoea Reduced exercise tolerance Fatigue Tiredness Ankle swelling And Signs typical of heart failure Elevated jugular venous pressure Hepatomegaly Third heart sound Pulmonary rales Pleura effusion Peripheral oedema Hepatojugular reflux Cardiomegaly on X-ray of the thorax And Objective evidence of a structural or functional abnormality of the heart at rest Abnormal echocardiogram Abnormal pump function on nuclear imaging or on MRI Prevalence The prevalence of HF in the Western world is estimated to be 1-2%, and the incidence is approximately 5-10 per 1000 persons per year (7,9). Coronary heart disease at a young age is more prevalent in men than women, and so the prevalence of HF is also higher in this group compared to age matched women. In older age groups, the prevalence of HF is equal between the sexes. Acute and chronic heart failure Heart failure may become a chronic condition, in which HF is persistent either with recurrences or with slow progression. A patient may be described as decompensated when chronic stable HF deteriorates. Acute HF has traditionally been used to describe the nature of the clinical presentation, as severe or of recent onset. Different clinical presentations fall under this definition. Systolic versus diastolic heart failure https://www.textbookofcardiology.org/wiki/Heart_Failure 4/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Heart failure patients may be broadly classified into one of two groups, or a combination of both, depending on the left ventricular ejection fraction (LVEF). The LVEF is most often assessed with echocardiography (see Table 3). When the LVEF is less than 45%, systolic pump function is abnormal and it is named systolic HF.[3] If LVEF is preserved (>50%), symptoms are attributed to impaired relaxation of the heart during diastole and therefore this condition is diagnosed as diastolic HF or HF with a preserved LVEF.[3][4] As a result of impaired relaxation, end diastolic pressure and, subsequently, left atrial- and pulmonary pressure will rise; alveolar pulmonary edema develops as a consequence of these changes. LF diastolic dysfunction may be present in asymptomatic patients, and it is considered an important precursor of heart failure.[5] Frequently, patients have both systolic and diastolic heart failure at the same time, but the term for this ailment is still systolic heart failure. The term heart failure is not limited to a failing left ventricle; the right ventricle may also be involved in the process and there may also be isolated right ventricular heart failure. Pathophysiology of heart failure HF is caused by a loss of cardiac pump function, which can be due to a structural abnormality of the heart muscle (e.g. myocardial infarction) or a change in the heart function (and often structure) in response to an abnormal load (e.g. aortic valve stenosis). The relationship between loading the ventricle (by filling it) and its output was described by Frank and Starling in 1918 and has become the cornerstone in understanding heart failure and how to treat it. The relationship states that as a result of loading the heart (increasing its filling or its pressure), the output increases (Figure 1). A heart that has a lower output can be improved by increasing loading its volume and pressure. This is what naturally happens filling (LV dilatation and pressure) when the heart does not pump out enough volume, and, in the first phase of disease, compensates for the loss of contractility. It takes more energy from the heart to work at an increased loading, but the heart has a reasonable energy reserve. In a chronic situation, remodeling of the heart progresses (by hypertrophy of the myocytes and dilatation by increasing myocyte length and matrix changes), which, in the long term, leads to a further loss in function. The result of this dysfunction is further increased loading pressures in the heart and, by communicating the diastolic loading pressures to the left atrium and pulmonary veins, the pulmonary capillaries may become overloaded and leak water into the lungs. This is the practical restriction of further filling the heart as a tool to improve its function; even poor left ventricles may be filled more to increase their output [6] but the patients pulmonary capillaries cannot tolerate these hydrostatic pressures and start to leak water. its Figure 1. Frank-Starling curve increased Hemodynamic explanations (the heart as a pump) use the concept of preload (filling) and afterload (workload of the heart, which is wall tension and arterial pressure or vascular resistance). In this way, the progression of left sided heart failure towards right sided heart failure is explained as follows: prolonged left ventricular failure increases pressures in the left atrium (preload), which in time leads to a https://www.textbookofcardiology.org/wiki/Heart_Failure 5/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology subsequent increased resistance in the pulmonary vascular system (which is the the right ventricle) and afterload of right lead eventually may also ventricular failure. Another relevant issue is afterload of the left ventricle influencing the output of the heart: as the afterload of the aortic pressure also influences the timing of closure of the aortic valve, a high aortic pressure will close the aortic valve early and will, therefore, diminish the output. Decreasing (theoretically diastolic, but more practically systolic) aortic pressure will increase the stroke volume by latter closure of the aortic valves. (Figure 2) to system sympathetic Hormonal/ mechanisms Sympathetic (RAAS/ overstimulation) of heart failure are as hemodynamic important mechanisms of heart failure. as the Figure 2. Effects of decreased afterload. Red arrows indicate aortic valve opening, which occurs later and at higher LV systolic pressure when the diastolic aortic pressure is higher. Blue arrows indicate closing of the aortic valve. Bidirectional arrows represent stroke volume. When aortic pressure is decreased, stroke volume increases as a result of a lower aortic pressure during closure of the aortic valve. A decreased cardiac output to diminished renal perfusion and release of hormones in the RAA-system: renin is released into the circulation by the renal juxtaglomerular which stimulates the cleavage of angiotensinogen into angiotensin I and II during its passage through II stimulates vasoconstriction in the kidneys, and in other vascular systems, increasing blood pressure; the second effect of angiotensin is to stimulate the release of aldosterone from the adrenals into the plasma, which retains sodium from the kidney tubules in the blood and thereby water. The RAA system, which works as a compensatory mechanism for heart failure to increase blood pressure and blood volume, also stimulates hypertrophy of muscle cells and the formation of fibrosis, which in the long term are detrimental to heart failure. leads apparatus, the lungs. Angiotensin Figure 3. Management in heart failure. The other compensatory mechanism for heart the sympathetic nervous system, increases heart rate to increase cardiac output, which is a powerful compensatory mechanism. However, chronic stimulation of the sympathetic nerves to the heart, leading to higher heart rates, is toxic to the heart, because of continuous release of norepinephrine to the failure, stimulation of https://www.textbookofcardiology.org/wiki/Heart_Failure 6/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology myocyte. In addition, as a result of their continued stimulation, the betareceptors for norepinephrine are downregulated in heart failure, which further diminishes the function and functional reserve of the heart. Management When a patient presents with symptoms of heart failure, it is worthwhile to have a dedicated diagnostic and therapeutic plan, in the order as indicated below (Figure 3). Clinical aspects are important for diagnosis, but the final diagnosis is only made after objective evidence of heart dysfunction. Clinical aspects History A careful history of the patient is important for the diagnosis and in order to identify the cause of HF. The history (and physical examination) can be used to differentiate between the abovementioned potential causes of HF (refer to Etiology of heart failure). Family history of HF, smoking status, hyperlipidaemia, hypertension and diabetes mellitus are factors that should be taken into account during the assessment of the patient history in order to draw a risk profile of the patient. Finally, the history should include previous events and the response to therapy. Symptoms and signs HF can manifest with a multitude of different symptoms and signs, but shortness of breath and tiredness are the most characteristic. The Framingham Heart Study defined major and minor diagnostic criteria for HF. Major criteria: Paroxysmal nocturnal dyspnea Neck vein distention Pulmonaty rales Radiographic cardiomegaly (increasing heart size on chest radiography) Acute pulmonary edema S3 gallop Increased central venous pressure (>16 cm H2O at right atrium) Hepatojugular reflux Weight loss >4.5 kg in 5 days in response to treatment Minor criteria: Bilateral ankle edema Nocturnal cough Dyspnea on ordinary exertion Hepatomegaly Pleural effusion https://www.textbookofcardiology.org/wiki/Heart_Failure 7/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Tachycardia (heart rate>120 beats/min.) Minor criteria are acceptable only if they cannot be attributed to another medical condition (such as pulmonary hypertension, chronic lung disease, cirrhosis, ascites, or the nephrotic syndrome). Diagnosis of HF requires the simultaneous presence of at least 2 major criteria or 1 major criterion in conjunction with 2 minor criteria. The Framingham Heart Study criteria are 100% sensitive and 78% specific for identifying persons with definite congestive heart failure in an outpatient population.[7] Severity of HF In general, correlation between the severity of symptoms and the severity of HF in terms of loss of maximal oxygen consumption is weak.[3] The New York Heart Association functional classification is used most frequently to classify the severity of HF (Table 2). Assessing severity is needed for the proper therapy/ medication to be chosen. Table 2. NYHA functional classification Severity based on symptoms and physical activity No limitation of physical activity. Ordinary physical activity does not cause undue palpitation, or dyspnoea. fatigue, Class I Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnoea. Class II Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity results in fatigue, palpitation, or dyspnoea. Class III Unable to carry on any physical activity without discomfort. Symptoms at rest. Class IV If any physical activity is undertaken, discomfort is increased. Physical examination https://www.textbookofcardiology.org/wiki/Heart_Failure 8/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology There are several key features in the clinical examination of a patient presenting with HF. The physical examination should focus on the general appearance of the patient, pulse and blood pressure, signs of fluid overload (increased jugular venous pressure, peripheral edema, ascites and hepatomegaly), the lungs, and the heart (apex, Gallop rhythm, third heart sound, murmurs). Additional diagnostic tests In order to assist in the diagnosis of HF and to differentiate between possible causes of HF, the following tests are available. Electrocardiogram An electrocardiogram (ECG) should be performed on every patient suspected of HF. Several common abnormalities (including possible causes) indicative of HF on the ECG include but are not limited to: sinus tachy- or bradycardia, atrial tachycardia, -flutter, or fibrillation, ventricular arrhythmias, ischemia (including myocardial infarction), abnormal Q waves, left ventricular hypertrophy, micro voltages, and QRS length >120 ms. Although an abnormal ECG (excluding arrhythmias) has a low positive predictive value for HF, a normal ECG is highly indicative of the absence of HF. Chest X-ray A chest X-ray is a part of the standard examination in potential HF patients. Importantly, the X-ray is a tool to detect cardiomegaly (defined as a cardiac: thoracic ratio of > 0,5) or other clues (redistribution, Kerley B-lines and pleural effusion) that indicate HF. It is also important to rule out other causes of dyspnea. Echocardiography Echocardiography is the cornerstone in the diagnosis of HF, and should be performed routinely, because ventricular function can be evaluated accurately with this technique. It can provide objective evidence of a structural or functional abnormality of the heart at rest, besides signs and symptoms that are typical of heart failure. Important parameters that can be assessed include, but are not limited to, wall motion, valve function, left ventricular ejection fraction and diastolic function. Diastolic dysfunction might be an important finding in symptomatic patients with a preserved ejection fraction. Refer to Table 3 for common echocardiographic findings in HF. Transesophageal echocardiography is indicated in patients with an inadequate transthoracic echo window, suspected endocarditis, complicated valvular disease or to exclude a LV thrombus. If echocardiography provides inadequate information or in patients with suspected coronary artery disease, additional imaging includes CT scanning, cardiac magnetic resonance imaging or radionuclide imaging. Laboratory tests A standard blood assessment includes a complete blood count, electrolytes, renal function, glucose and liver function. Furthermore, urinalysis and other tests, depending on the clinical condition of the patient, complete the laboratory assessment. For example, cardiac troponins must be sampled if an ACS is in the differential diagnosis. In patients suspected of HF, values of natriuretic peptides (such as B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP)) can provide important information https://www.textbookofcardiology.org/wiki/Heart_Failure 9/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology regarding the diagnosis, management and prognosis of HF. Natriuretic peptides are enzymes, secreted by the atria or ventricles in response to myocardial wall stress. The most commonly used tests are BNP and NT-proBNP measurements, which despite their different half-lives in the plasma, do not differ substantially terms of diagnostic ability. Cut-off values are different in acute settings with acute dyspnea compared to chronic settings. Normal values are almost 100% specific, and exclude heart failure in patients >18 year old. Abnormal values do not have a 100% predictive value, and objective evidence for heart failure is still needed. The values for BNP and NTproBNP are also used to evaluate the prognosis in patients with known HF, in whom higher values carry a worse prognosis. in Exercise test Figure 4. Flowchart suspected heart failure [3] An exercise test is not diagnostic for HF, but may be used to identify ischemia as the cause of heart failure, or it can be used to assess the severity of HF, usually in conjunction with maximal oxygen uptake (VO2max) measurement. This test is performed on a treadmill or on a bicycle ergo meter. The patient is asked to give maximal effort while the workload gradually increases. During the test, the ECG is monitored for ischemia. When possible, oxygen consumption should also be measured during the test. Not only is an oxygen consumption test a good tool to discriminate between lung- peripheral- or heart problems, but the obtained value for maximal oxygen uptake (VO2max) has an important prognostic value. Heart catheterization Heart catheterization is not always part of the routine diagnosis and work-up of patients with HF. It should be considered however to exclude coronary heart disease (Class of recommendation IIa, level of evidence C, see Table 4). Coronary angiography is recommended in patients at high risk of coronary artery disease (Class of recommendation I, level of evidence C) and in HF patients with significant valvular disease (Class of recommendation IIa, level of evidence C). https://www.textbookofcardiology.org/wiki/Heart_Failure 10/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Table 3. Common echocardiographic abnormalities in heart failure Measurement Abnormality Clinical implications Left ventricular ejection fraction (LVEF) Left ventricular global systolic dysfunction Reduced (< 50%) Myocardial infarction/ischaemia, Cardiomyopathy, Left ventricular wall motion Akinesis, hypokinesis, dyskinesis Myocarditis Left ventricular end- diastolic diameter Increased ( 60 mm/>32 mm/m2)) Volume overload HF likely Volume overload Left ventricular end- systolic diameter Increased ( 45 mm/>25 mm/m2,) HF likely Left ventricular fractional shortening Reduced (<25%) Left ventricular systolic dysfunction Increased filling pressures, Left atrial volume index Increased (volume >34 mL/m2) Mitral valve dysfunction Hypertention, Aortic stenosis, Left ventricular thickness Hypertrophy (>11 12 mm) Hypertrophic cardiomyopathy May be primary cause of HF or complicating factor Valvular stenosis or regurgitation (especially aortic stenosis and mitral insufficiency) Asses consequences haemodynamic Valvular structure and function Consider surgery Mitral diastolic flow profile Abnormalities of the early and late diastolic filling patterns Indicates diastolic dysfunction and suggests mechanism Tricuspid regurgitation peak velocity Increased right ventricular systolic pressure Increased (>3.4 m/s) Pericardium Effusion, Consider tamponade, Haemopericardium, Malignancy, Calcification Systemic disease, Acute or chronic pericarditis, https://www.textbookofcardiology.org/wiki/Heart_Failure 11/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Constrictive pericarditis Aortic outflow velocity time integral Reduced (<15 cm) Reduced low stroke volume Right ventricular function (e.g. TAPSE) Reduced (TAPSE < 16 mm) RV systolic dysfunction Increased right atrial pressures, Right ventricular dysfunction, Inferior vena cava Dilated, with no respiratory collapse Volume overload Pulmonary hypertention possible Etiology of heart failure Coronary heart disease The most important cause (50% of the cases) of HF in the Western world is ischemic heart disease, including myocardial infarction. These patients mainly suffer from systolic HF due to wall motion abnormalities of the affected area and re-modeling of the non-affected parts of the myocardium. Hypertension In patients with a high systolic blood pressure (BP), the left ventricle faces an increased afterload (a higher workload pumping the blood against the increased vascular resistance). Over a certain period of time, this will lead to hypertrophy of the cardiac myocardium, and longer term remodeling may lead to pump function disorders (diastolic or systolic). In as many as 60-70% of patients suffering HF, hypertension is the primary or secondary cause of the condition. Heart rhythm disorders Atrial fibrillation is a common rhythm disorder in the elderly. With this condition, the atria do not contract in the coordinated fashion as they would in normal sinus rhythm, and therefore the atria never optimally empty. Normally, the atrial kick contributes approximately 15% of the stroke volume. The absence of the atrial kick during atrial fibrillation can contribute to a reduced LVEF. However, atrial fibrillation is seldom the cause of heart failure, but more often a trigger of heart failure in already existing structural heart disease. Valvular disease https://www.textbookofcardiology.org/wiki/Heart_Failure 12/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Valvular disease, especially mitral- or aortic, can cause volume and pressure overload of the left ventricle of the heart. This overload causes dilation and / or hypertrophy of the left ventricle, which in the long term decreases the pump function. Cardiomyopathies Dilated cardiomyopathy (DCM) is characterized by dilatation of one or both of the ventricles of the heart, with a general decrease in contractility and consequently a decreased pump function. In approximately 30% of the cases, DCM is hereditary. Hypertrophic cardiomyopathy (see also Hypertension) is characterized by hypertrophy, which may be concentric or asymmetric. The asymmetric form is usually hereditary. Restrictive cardiomyopathy is characterized by a primary diastolic dysfunction of one or more of the ventricles, leading to increased filling pressures and hypertrophy, and initially a preserved systolic function. Arrhythmogenic right ventricular cardiomyopathy is characterized by fatty infiltration and fibrosis of the right ventricle or the left ventricle or both and is usually hereditary. Pericardial disease and Tamponade Restriction of ventricular filling by a tight (inflamed or constrictive) pericardium or by pericardial effusion and tamponade can be the cause of diastolic HF. Drugs Drugs that can cause HF are: Cytotoxic agents (chemotherapy, especially doxorubicin) The antipsychotic agent clozapine Drugs that can aggravate HF are: Beta blockers Calcium antagonist Antiarrhythmics Disulfiram Toxins Alcohol Cocaine, Trace elements (mercury, cobalt, arsenic). Endocrine disorders Diabetes mellitus https://www.textbookofcardiology.org/wiki/Heart_Failure 13/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Hypo- or hyperthyroidism Cushing syndrome Adrenal insufficiency Excessive growth hormone in acromegaly Phaeochromocytoma Nutritional status Deficiency of thiamine, selenium, or camitine, in states of severe cachexia. Infiltrative and storage disorders Sarcoidosis Amyloidosis Haemochromatosis Connective tissue disease Infectious disease Chagas disease HIV infection Viral, bacterial or protozoal diseases causing myocarditis. Management in investigating etiology of heart failure 1. Assess globally: are there triggers of heart failure. Hypertension, infection, anemia, rhythm disorders. Perform standard laboratory tests: in addition to hemoglobin, leukocytes, thrombocytes, creatinin, sodium and potassium levels, also liver function, thyroid function (TSH), glucose. 2. Assess ischemia: are there indications of ischemic etiology (ECG: Q s or significant and changing ST segments, laboratory: troponins, and echocardiogram: segmental wall motion abnormality in coronary territory areas) ? If yes, then proceed with further coronary artery or myocardial perfusion imaging. 3. Are there no indications for ischemic etiology? Classify phenotype of cardiomyopathy: dilated, hypertrophic, restrictive, arrhytmogenic right ventricular cardiomyopathy. Then assess with additional laboratory tests, including creatinin kinase, autoimmune markers, eosinophilia, ferritin and iron saturation. In some suspected cases: calcium and albumin. Look for clues of etiologies: history, family history (including maternal inheritage of diabetes in a family) In case of fever look for infectious etiology, MRI confirmation for possible myocarditis, plasma serology. Look for clues on ECG: microvoltage on the ECG, AV block in combination with later atrial fibrillation. Additional lab may be warranted (monoclonal proteins in case of microvoltage in the presence of sufficient amounts of myocardium and the absence of pericardial fluid or pulmonary emphysema) https://www.textbookofcardiology.org/wiki/Heart_Failure 14/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology MRI for further classification of cardiomyopathy and assessment of presence and localization of delayed contrast enhancement Coronary arteriography or coronary CT scan to exclude coronary artery disease Myocardial biopsy in cases where the suspicion of severe underlying disease is high (e.g. fulminant myocarditis, sarcoidosis suspicion on MRI with no other organ involved). Genetic testing after counseling Therapy of heart failure The therapeutic management of HF involves both pharmacological and non-pharmacological treatment. The goal is reduction in mortality and morbidity, prevention of the progression of HF, and the treatment of (non-) cardiovascular co-morbidities. Non-pharmacological treatment Non-pharmacological management is of great importance for HF patients. It can have a significant impact on symptoms, functional capacity, wellbeing, morbidity, and prognosis. The most important non- pharmacological options are described below. Education Education of both the patient and their family about HF and its symptoms is important. The patient and/or the caregiver should be able to undertake appropriate actions such as adjusting the diuretic dose or contact the physician when necessary. (Class I recommendation, level of evidence C; see Table 4) Education on the importance and (side) effects of medication should be provided to the patient in order to increase compliance. (Class I recommendation, level of evidence C) Fluid and sodium restriction In patients with severe symptoms of HF, restriction of fluid intake (to 1500 ml/day) may be considered. (Class IIa recommendation, level of evidence C). Also, patients should be educated about the salt content of food and advised to minimize their salt intake (< 2 gram/ day) in order to prevent fluid retention. (Class I recommendation, level of evidence C) Body weight CHF patients should carefully monitor their body weight. A sudden increase in weight is a potential consequence of fluid retention and deterioration of HF. If patients notice a weight gain of >2kg in 3 days, they should consult their physician. (Class I recommendation, level of evidence C). In obese patients (body mass index >30 kg/m2), weight reduction should be promoted to prevent progression of HF, decrease symptoms and improve the overall wellbeing of the patient. (Class IIa recommendation, level of evidence C). Also, attention should be paid to weight loss due to malnutrition, which is frequently https://www.textbookofcardiology.org/wiki/Heart_Failure 15/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology observed in severe HF. An altered metabolism, inflammatory mechanisms or a decreased food intake may be important factors in the pathophysiology of cardiac cachexia in HF. (Class I recommendation, level of evidence C) Alcohol and tobacco Alcohol intake should be minimized, as it may increase blood pressure and/or have a negative inotropic effect. (Class IIa recommendation, level of evidence C). Smoking cessation should be encouraged. It is recommended that patients with HF receive support and advice on this topic. (Class I recommendation, level of evidence C). A reduction in alcohol and tobacco intake might also improve co-morbidities, including sleep disorders. Exercise Exercise training is recommended to all chronic stable HF patients. Twenty years ago, exercise was strongly discouraged in patients with HF as it was considered to be harmful. Nowadays, numerous studies have demonstrated the opposite. Rehabilitation programs have shown to increase exercise capacity and health related quality of life, and decrease hospitalization rates and symptoms. (Class I recommendation, level of evidence A) Other Other non-pharmacological treatment recommendations include immunization of HF patients (pneumococcal- and influenza vaccination should be considered), the consulting of a physician around pregnancy, the screening for depression and sleep disorders that require additional medical attention. Pharmacological treatment A flowchart for the treatment of patients presenting with systolic HF is depicted in Figure 5. Medications with a class I indication in patients with systolic heart failure are summarized in Table 5. Indications, mode of action, contraindications of the medication, and possible side effects of drugs included in this algorithm are discussed below. https://www.textbookofcardiology.org/wiki/Heart_Failure 16/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Figure 5. Treatment options for patients with chronic systolic HF https://www.textbookofcardiology.org/wiki/Heart_Failure 17/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology NYHA I & EF <40% NYHA II NYHA III NYHA IV Diuretic ACE-inhib AT-II antagonist Alternative Alternative Alternative Post infarction Betablocker Aldosteron antagonist EF < 35% EF < 35% EF < 35% Nitrate / Hydralazine Afro-American Afro-American Afro-American SR>75/min & EF<35% SR>75/min & EF<35% SR>75/min & EF<35% Ivabradine Digoxin Table 5. Medication with a class I indication in patients with systolic heart failure. Note that AT-II antagonists are alternative medicine for ACE inhibitors in case of intolerance (coughing, allergy). Nitrates and Hydralazine are added therapy for patients of Afro-American descent, and alternative therapy for patients that cannot tolerate ACE-inhibitors and AT-II antagonists). Digoxin can also be seen as symptomatic (instead of added preventive) treatment, not always necessary in NYHA III or even IV. Angiotensin-converting enzyme (ACE) inhibitors An ACE inhibitor is indicated for every patient with symptomatic systolic HF and an EF 40 % (NYHA class II-IV). (Class I recommendation, level of evidence A) Contraindications for the use of ACE inhibitors are: History of angioedema Bilateral renal artery stenosis Serum potassium concentration >5.0 mmol/L Serum creatinine >220 mol/L Severe aortic stenosis ACE inhibitors relieve the heart by decreasing the preload and afterload. This is achieved through two mechanisms. Firstly, conversion of angiotensin-I to angiotensin II is inhibited, which reduces vasoconstriction and lowers BP. Secondly, production of aldosterone is decreased, as angiotensin II induces this production. Aldosterone stimulates sodium- and water retention. Possible side effects are symptomatic hypotension (dizziness), hyperkalemia, worsening renal function and cough. In patients with congestive HF, total mortality and hospitalization are significantly reduced by ACE inhibitors.[8] Beta Blockers Beta blockade (in addition to an ACE inhibitor or ARB when ACE inhibitor is not tolerated) is indicated for every patient with symptomatic systolic HF and an EF 40 % (NYHA class II-IV) and in asymptomatic patients with a LVEF 40% after a MI. (Class I recommendation, level of evidence A).[9] https://www.textbookofcardiology.org/wiki/Heart_Failure 18/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Contraindications are: Bronchial asthma Second - or third degree heart block, sick sinus syndrome, sinus bradycardia Beta blockers mainly exert their effect by reducing the toxic effects of the sympathetic nervous stimulation on the heart and by deactivating the renin-angiotensin system. Possible side effects include (symptomatic) hypotension, worsening of HF and bradycardia. The recommendation is start low, go slow , i.e. start with a low dose, and titrate every two weeks. In patients with persistent symptoms after treatment with a combination of beta blocker and ACE inhibitor or ARB, a mineralocorticoid/aldosterone receptor antagonist (MRA) is recommended. (Class I recommendation, level of evidence A) Diuretics (Loop of Henle diuretics, Thiazides, Aldosterone antagonists) Diuretics reduce preload by venous vasodilatation and by increasing diuresis. As a result, filling pressures of the heart lung vasculature decrease. the and Although the effects of diuretics on mortality and morbidity have not been studied in patients with HF (irrespective of EF), it is recommended in patients with signs and symptoms of congestion as diuretics relieve dyspnea and edema. Figure 6 depicts the nephron and the sites where different diuretics work. Loop of Henle diuretics Figure 6. Diuretics and site of action in the nephron. Loop of Henle diuretics act on ascending loop of Henle in the kidney tubules to inhibit sodium and chloride (and indirectly calcium and magnesium) reabsorption. This will ultimately result in increased urine production of sodium and water. Compared to thiazides, loop diuretics produce a more intense and shorter diuresis. the Thiazides Thiazide increases urine production by decreasing reabsorption of sodium in the distal tubule. This type of diuretic is often used in combination with loop diuretics to enhance their effects, but may be less effective in patients with a severely reduced kidney function. Aldosterone antagonists Adding this drug is suggested for patients with moderate to severe symptomatic HF (NYHA class II to IV, refer to Table 2) and an LVEF < 35%. (Class I recommendation, level of evidence A) Contraindications: https://www.textbookofcardiology.org/wiki/Heart_Failure 19/30 7/3/23, 11:59 PM Heart Failure - Textbook of Cardiology Serum potassium concentration > 5.0 mmol/L Serum creatinine > 220 mol/L Concomitant potassium sparing diuretic or potassium supplements Combination of an ACEI and ARB Aldosterone antagonists reduce sodium retention by the kidney, and inhibit fibrosis formation in the heart. Possible side effects include hyperkalemia, hyponatremia, worsening renal function, and breast tenderness and/or enlargement. Eplerenon has less mastopathy side effects and is an alternative to spironolacton. In patients with severe heart failure, spironolactone in addition to standard therapy, reduces morbidity and mortality. [10] Choice and combination of diuretics Patients with heart failure may be treated with a thiazide diuretic, which should be switched to a loop diuretic if a suboptimal response occurs. In patients with a decreased renal function, a loop diuretic is the mainstay of treatment. Addition of a thiazide diuretic to a loop diuretic can be considered in case of a suboptimal response of loop diuretic alone, when given in sufficient doses (furosemide 250 mg twice daily), suggesting that diuretic resistance is due to distal tubular increased activity of retaining sodium. In all patients with NYHA II or more, except in those with a creatinine clearance < 20 ml/min (creatinine > 220 micromol/L), addition of an aldosterone antagonist should be considered. In special cases in which hypercapnia plays a role, metabolic alkalosis can result from diuretics, and acetazolamide, a reversible carbonic anhydrase inhibitor, is then prescribed as an alternative diuretic. Angiotensin receptor blockers (ARBs)