European Heart Journal Advance Access originally published online on January 28, 2005
European Heart Journal 2005 26(4):384-416; doi:10.1093/eurheartj/ehi044
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Executive summary of the guidelines on the diagnosis and treatment of acute heart failure
The Task Force on Acute Heart Failure of the European Society of Cardiology
Endorsed by the European Society of Intensive Care Medicine (ESICM) Authors/Task Force Members,
ESC Committee for Practice Guidelines (CPG),
Document Reviewers,
* Corresponding author. Chairperson: Markku S. Nieminen, Division of Cardiology, Helsinki University Central Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland. Tel.: +358 94717 22 00; fax: +358 9 4717 40 15. E-mail address: markku.nieminen{at}hus.fi
Guidelines and Expert Consensus documents aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making.
A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) and by different organizations and other related societies. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents.
In spite of the fact that standards for issuing good quality Guidelines and Expert Consensus Documents are well defined, recent surveys of Guidelines and Expert Consensus Documents published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied with in the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilization of health resources.
The ESC Committee for Practice Guidelines (CPG) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups or consensus panels. The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.
The Task Force has classified and ranked the usefulness or efficacy of the recommended procedure and/or treatments and the Level of Evidence as indicated in the tables below:
|
|
1. Introduction
The aim of these guidelines is to describe the rationale behind the diagnosis and treatment of acute heart failure (AHF) in the adult population.
The Committee for Practice Guidelines (CPG) of the European Society of Cardiology nominated the Task Force for the AHF Guidelines. The Task Force included representatives from the Heart Failure Association of the ESC and members of the European Society of Intensive Care Medicine (ESICM). The Task Force recommendations were circulated among a review board and approved by the CPG of the ESC and by the ESICM. Together with the Guidelines for the diagnosis and treatment of chronic heart failure1 these Guidelines form the recommendations on diagnosis and treatment of heart failure.
The recommendations are also published as an unabridged version of the document,2 as a pocket guideline, and as an ESC educational product CD.
2. Epidemiology, aetiology, and clinical context
The combination of the aging of the population in many countries, and improved survival after acute myocardial infarction (AMI)3 has created a rapid growth in the number of patients currently living with chronic heart failure (CHF),4 with a concomitant increase in the number of hospitalizations for decompensated heart failure. Coronary heart disease is the aetiology of AHF in 60–70% of patients,5–7 particularly in the elderly population. In younger subjects, AHF is frequently caused by dilated cadiomyopathy, arrhythmia, congenital or valvular heart disease, or myocarditis. The causes and complications of AHF are described in Table 1.
|
The management of heart failure consumes 1–2% of health care expenditure in European countries,8,9 with around 75% relating to inpatient care. Advanced heart failure and related acute decompensation have become the single most costly medical syndrome in cardiology.10,11
Patients with AHF have a very poor prognosis. Mortality is particularly high in patients with acute myocardial infarction (AMI) accompanied by severe heart failure, with a 30% 12 month mortality.12 Likewise, in acute pulmonary oedema a 12% in-hospital and 40% 1 year mortality have been reported.13
About 45% of patients hospitalized with AHF will be rehospitalized at least once (and 15% at least twice) within twelve months.14,15 Estimates of the risk of death or rehospitalization within 60 days of admission vary from 30 to 60%, depending on the population studied.5,6,16–19
I. Definitions, diagnostic steps, instrumentation and monitoring of the patient with AHF
3. Definition and clinical classification of AHF
3.1. Definition
Acute heart failure is defined as the rapid onset of symptoms and signs secondary to abnormal cardiac function. It may occur with or without previous cardiac disease. The cardiac dysfunction can be related to systolic or diastolic dysfunction, to abnormalities in cardiac rhythm, or to pre-load and after-load mismatch. It is often life threatening and requires urgent treatment.
AHF can present itself as acute de novo (new onset of acute heart failure in a patient without previously known cardiac dysfunction) or acute decompensation of chronic heart failure.
The patient with acute heart failure may present with one of several distinct clinical conditions (Table 2):
- Acute decompensated heart failure (de novo or as decompensation of chronic heart failure) with signs and symptoms of acute heart failure, which are mild and do not fulfil criteria for cardiogenic shock, pulmonary oedema or hypertensive crisis.
- Hypertensive AHF: Signs and symptoms of heart failure are accompanied by high blood pressure and relatively preserved left ventricular function with a chest radiograph compatible with acute pulmonary oedema.
- Pulmonary oedema (verified by chest X-ray) accompanied by severe respiratory distress, with crackles over the lung and orthopnoea, with O2 saturation usually <90% on room air prior to treatment.
- Cardiogenic shock: Cardiogenic shock is defined as evidence of tissue hypoperfusion induced by heart failure after correction of pre-load. There is no clear definition for haemodynamic parameters, which explains the differences in prevalence and outcome reported in studies (Table 2), but cardiogenic shock is usually characterized by reduced blood pressure (systolic BP <90 mmHg or a drop of mean arterial pressure>30 mmHg) and/or low urine output (<0.5 ml/kg/h), with a pulse rate >60 b.p.m. with or without evidence of organ congestion. There is a continuum from low cardiac output syndrome to cardiogenic shock.
- High output failure is characterized by high cardiac output, usually with high heart rate (caused by arrhythmias, thyrotoxicosis, anaemia, Paget's disease, iatrogenic or by other mechanisms), with warm peripheries, pulmonary congestion, and sometimes with low BP as in septic shock.
- Right heart failure is characterized by low output syndrome with increased jugular venous pressure, increased liver size and hypotension.
|
Various other classifications of the acute heart failure syndrome are utilized in coronary care and intensive care units. The Killip classification is based on clinical signs and chest X-ray findings, and the Forrester classification is based on clinical signs and haemodynamic characteristics. These classifications have been validated in acute heart failure after AMI and thus are best applied to acute de novo heart failure. The third ‘clinical severity’ classification has been validated in a cardiomyopathy service20 and is based on clinical findings.21 It is most applicable to chronic decompensated heart failure.22
3.1.1. Killip classification.
The Killip classification was designed to provide a clinical estimate of the severity of myocardial derangement in the treatment of AMI:23
- StageI—No heart failure. No clinical signs of cardiac decompensation;
- StageII—Heart failure. Diagnostic criteria include rales, S3 gallop and pulmonary venous hypertension. Pulmonary congestion with wet rales in the lower half of the lung fields;
- StageIII—Severe heart failure. Frank pulmonary oedema with rales throughout the lung fields;
- StageIV—Cardiogenic shock. Signs include hypotension (SBP
90mmHg), and evidence of peripheral vasoconstriction such as oliguria, cyanosis and diaphoresis.
3.1.2. Forrester classification.
The Forrester AHF classification was also developed in AMI patients, and describes four groups according to clinical and haemodynamic status24 (Figure 1). Patients are classified clinically on the basis of peripheral hypoperfusion (filliform pulse, cold clammy skin, peripheral cyanosis, hypotension, tachycardia, confusion, oliguria) and pulmonary congestion (rales, abnormal chest X-ray), and haemodynamically on the basis of a depressed cardiac index (2.2 L/min/m2) and elevated pulmonary capillary pressure (>18 mmHg). The original paper defined the treatment strategy according to the clinical and haemodynamic status. Mortality was 2.2% in group I, 10.1% in group II, 22.4% in group III, and 55.5% in group IV.
|
3.1.3. ‘Clinical severity’ classification.
The clinical severity classification is based on observation of the peripheral circulation (perfusion) and on auscultation of the lungs (congestion). The patients can be classified as Class I (Group A) (warm and dry), Class II (Group B) (warm and wet), Class III (Group L) (cold and dry), and Class IV (Group C) (cold and wet). This classification has been validated prognostically in a cardiomyopathy service,20 and is therefore applicable to patients with chronic heart failure, whether hospitalized or outpatients.
3.2. The clinical syndrome of AHF
AHF is a clinical syndrome, with reduced cardiac output, tissue hypoperfusion, increase in the pulmonary capillary wedge pressure (PCWP), and tissue congestion. The underlying mechanism may be cardiac or extra-cardiac, and may be transient and reversible with resolution of the acute syndrome, or may induce permanent damage leading to chronic heart failure. The cardiac dysfunction can be related to systolic or diastolic myocardial dysfunction (mainly induced by ischaemia or infection), acute valvular dysfunction, pericardial tamponade, abnormalities of cardiac rhythm, or pre-load/after-load mismatch. Multiple extra-cardiac pathologies may result in acute heart failure by changing the cardiac loading conditions for example (i) increased after-load due to systemic or pulmonary hypertension or massive pulmonary emboli, (ii) increased pre-load due to increased volume intake or reduced excretion due to renal failure or endocrinopathy, or (iii) high output state due to infection, thyrotoxicosis, anaemia, Paget's disease. Heart failure can be complicated by co-existing end-organ disease. Severe heart failure can also induce multi-organ failure, which may be lethal.
Appropriate long-term medical therapy and, if possible, anatomical correction of the underlying pathology may prevent further AHF syndrome ‘attacks’ and improve the poor long-term prognosis associated with this syndrome.
The clinical AHF syndrome may be classified as predominantly left or right forward failure, left or right backward failure, or a combination of these.
3.2.1. Forward (left and right) AHF.
Forward acute heart failure may be mild-to-moderate with only effort fatigue, up to severe with manifestations of reduced tissue perfusion at rest with weakness, confusion, drowsiness, paleness with peripheral cyanosis, cold clammy skin, low blood pressure, filliform pulse, and oliguria, culminating in the full blown presentation of cardiogenic shock.
This syndrome may be induced by a large variety of pathologies. An adequate history may indicate the main diagnosis for example (i) acute coronary syndrome with the relevant risk factors, past history, and suggestive symptoms; (ii) acute myocarditis with a recent history suggestive of acute viral infection; (iii) acute valvular dysfunction with a history of chronic valve disease or valve surgery, infection with the possibility of bacterial endocarditis, or chest trauma; (iv) pulmonary embolism with a relevant history and suggestive symptoms; or (v) pericardial tamponade.
Physical examination of the cardiovascular system may be indicative of the main diagnosis, for example by distended neck veins and paradoxical pulse (pericardial tamponade), muffled heart sounds related to myocardial systolic dysfunction, or the disappearance of artificial valve sounds or an appropriate murmur indicating a valvular problem.
In forward AHF immediate management should include supportive treatment to improve cardiac output and tissue oxygenation. This can be achieved with vasodilating agents, fluid replacement to achieve an optimal pre-load, short-term inotropic support and (sometimes) intra-aortic balloon counterpulsation.
3.2.2. Left-heart backward failure.
Left-heart backward failure may be related to left ventricular dysfunction with varying degrees of severity, from mild-to-moderate with only exertional dyspnoea, to pulmonary oedema presenting with shortness of breath (dry cough, sometimes with frothy sputum), pallor or even cyanosis, cold clammy skin, and normal or elevated blood pressure. Fine rales are usually audible over the lung fields. Chest X-ray shows pulmonary congestion/oedema.
Pathology of the left heart may be responsible for this syndrome, including: myocardial dysfunction related to chronic existing conditions; acute insult such as myocardial ischaemia or infarction; aortic and mitral valve dysfunction; cardiac rhythm disturbances; or tumours of the left heart. Extra-cardiac pathologies may include severe hypertension, high output states (anaemia, thyrotoxicosis) and neurogenic states (brain tumours or trauma).
Physical examination of the cardiovascular system, including the apex beat, the quality of the heart sounds, the presence of murmurs, and auscultation of the lungs for fine rales and expiratory wheezing (‘cardiac asthma’) may be indicative of the main diagnosis.
In left heart backward failure patients should be treated mainly with vasodilation and the addition of diuretics, bronchodilators and narcotics, as required. Respiratory support may be necessary. This can either be with continuous positive airway pressure (CPAP) or non-invasive positive pressure ventilation, or in some circumstances invasive ventilation may be required following endotracheal intubation.
3.2.3. Right-heart backward failure.
The syndrome of acute right heart failure is related to pulmonary and right heart dysfunction, including exacerbations of chronic lung disease with pulmonary hypertension, or acute massive lung disease (e.g. massive pneumonia or pulmonary embolism), acute right ventricular infarction, tricuspid valve malfunction (traumatic or infectious), and acute or sub-acute pericardial disease. Advanced left heart disease progressing to right-sided failure should also be considered, and similarly long-standing congenital heart disease with evolving right ventricular failure should be taken into account. Non-cardiopulmonary pathologies include nephritic/nephrotic syndrome and end-stage liver disease. Various vasoactive peptide-secreting tumours should also be considered.
The typical presentation is with fatigue, pitting ankle oedema, tenderness in the upper abdomen (due to liver congestion), shortness of breath (with pleural effusion) and distension of the abdomen (with ascites). The full-blown syndrome includes anasarca with liver dysfunction and oliguria.
History and physical examination should confirm the syndrome of acute right heart failure, indicate the suspected diagnosis and guide further investigation, which is likely to include ECG, blood gases, D-dimer, chest X-ray, cardiac Doppler-echocardiography, angiography or chest CT scan.
In right heart backward failure fluid overload is managed with diuretics, including spironolactone, and sometimes with a short course of low dose (‘diuretic dose’) of dopamine. Concomitant treatment may include: antibiotics for pulmonary infection and bacterial endocarditis; Ca++ channel blockers, nitric oxide, or prostaglandins for primary pulmonary hypertension; and anticoagulants, thrombolytics, or thrombectomy for acute pulmonary embolism.
4. Pathophysiology of AHF
4.1. The vicious circle in the acute failing heart
The final common denominator in the syndrome of AHF is a critical inability of the myocardium to maintain a cardiac output sufficient to meet the demands of the peripheral circulation. Irrespective of the underlying cause of AHF, a vicious circle is activated that, if not appropriately treated, leads to chronic heart failure and death. This is shown in Figure 2, and is described in detail elsewhere.2
|
In order for patients with AHF to respond to treatment the myocardial dysfunction must be reversible. This is particularly important in AHF due to ischaemia, stunning or hibernation, where a dysfunctional myocardium can return to normal when appropriately treated.
4.2. Myocardial stunning
Myocardial stunning is the myocardial dysfunction that occurs following prolonged ischaemia, which may persist in the short-term even when normal blood flow is restored.25,26 The intensity and duration of stunning is dependent on the severity and duration of the preceding ischaemic insult.26
4.3. Hibernation
Hibernation is defined as an impairment of myocardial function due to severely reduced coronary blood flow although myocardial cells are still intact. By improving blood flow and oxygenation, hibernating myocardium can restore its normal function.27
Hibernating myocardium and stunning can co-exist. Hibernation improves in time with reinstitution of blood flow and oxygenation, whilst stunned myocardium retains inotropic reserve and can respond to inotropic stimulation.26,28 Since these mechanisms depend on the duration of myocardial damage, a rapid restoration of oxygenation and blood flow is mandatory to reverse these pathophysiological alterations.
5. Diagnosis of AHF
The diagnosis of AHF is based on the symptoms and clinical findings, supported by appropriate investigations such as ECG, chest X-ray, biomarkers, and Doppler-echocardiography (Figure 3). The patient should be classified according to previously described criteria for systolic and/or diastolic dysfunction (Figure 4), and by the characteristics of forward or backward left or right heart failure.
|
|
5.1. Clinical evaluation
Systematic clinical assessment of the peripheral circulation, venous filling, and peripheral temperature are important.
Right ventricular (RV) filling in decompensated heart failure may usually be evaluated from the central jugular venous pressure. When the internal jugular veins are impractical for evaluation (e.g. due to venous valves) the external jugular veins can be used. Caution is necessary in the interpretation of high measured central venous pressure (CVP) in AHF, as this may be a reflection of decreased venous compliance together with decreased RV compliance even in the presence of low RV filling.
Left sided filling pressure is assessed by chest auscultation, with the presence of wet rales in the lung fields usually indicating raised pressure. The confirmation, classification of severity, and clinical follow-up of pulmonary congestion and pleural effusions should be done using the chest X-ray.
Class I recommendation, level of evidence C
Again, in acute conditions the clinical evaluation of left-sided filling pressure may be misleading due to the rapidly evolving clinical situation. Cardiac palpation and auscultation for ventricular and atrial gallop rhythms (S3, S4) should be performed. The quality of the heart sounds, and the presence of atrial and ventricular gallops and valvular murmurs are important for diagnosis and clinical assessment. Assessment of the extent of arteriosclerosis by detecting missing pulses and the presence of carotid and abdominal bruits is often important, particularly in elderly subjects.
5.2. Electrocardiogram (ECG)
A normal ECG is uncommon in acute heart failure. The ECG is able to identify the rhythm, and may help determine the aetiology of AHF and assess the loading conditions of the heart. It is essential in the assessment of acute coronary syndromes.29–31 The ECG may also indicate acute right or left ventricular or atrial strain, perimyocarditis and pre-existing conditions such as left and right ventricular hypertrophy or dilated cardiomyopathy. Cardiac arrhythmia should be assessed in the 12-lead ECG as well as in continuous ECG monitoring.
5.3. Chest X-ray and imaging techniques
Chest X-ray and other imaging should be performed early for all patients with AHF to evaluate pre-existing chest or cardiac conditions (cardiac size and shape) and to assess pulmonary congestion. It is used both for confirmation of the diagnosis, and for follow-up of improvement or unsatisfactory response to therapy. Chest X-ray allows the differential diagnosis of left heart failure from inflammatory or infectious lung diseases. Chest CT scan with or without contrast angiography and scintigraphy may be used to clarify the pulmonary pathology and diagnose major pulmonary embolism. CT scan or transesophageal echocardiography should be used in cases of suspicion of aortic dissection.
5.4. Laboratory tests
A number of laboratory tests should be performed in AHF patients (Table 3). Arterial blood gas analysis (Astrup) enables assessment of oxygenation (pO2), respiratory adequacy (pCO2), acid–base balance (pH), and base deficit, and should be performed in all patients with severe heart failure. Non-invasive measurement with pulse oximetry and end-tidal CO2 can often replace Astrup (Level of evidence C) but not in very low output, vasocontricted shock states. Measurement of venous O2 saturation (i.e. in the jugular vein) may be useful for an estimation of the total body oxygen supply-demand balance.
|
Plasma B-type natriuretic peptide (BNP) is released from the cardiac ventricles in response to increased wall stretch and volume overload and has been used to exclude and/or identify congestive heart failure (CHF) in patients admitted, for dyspnoea, to the emergency department.1,32 Decision cut points of 300 pg/mL for NT-proBNP and 100 pg/mL for BNP have been proposed, but the older population has been poorly studied. During ‘flash’ pulmonary oedema, BNP levels may remain normal at the time of admission. Otherwise, BNP has a good negative predictive value to exclude heart failure.33 Various clinical conditions may affect the BNP concentration including renal failure and septicaemia. If elevated concentrations are present, further diagnostic tests are required. If AHF is confirmed, increased levels of plasma BNP and NT-pro BNP carry important prognostic information. The exact role of BNP remains to be fully clarified.34
5.5. Echocardiography
Echocardiography is an essential tool for the evaluation of the functional and structural changes underlying or associated with AHF, as well as in the assessment of acute coronary syndromes.
Class I recommendation, level of evidence C
Echocardiography with Doppler imaging should be used to evaluate and monitor regional and global left and right ventricular function, valvular structure and function, possible pericardial pathology, mechanical complications of acute myocardial infarction and—on rare occasions—space occupying lesions. Cardiac output can be estimated by appropriate Doppler aortic or pulmonary time velocity contour measurements. An appropriate echo-Doppler study can also estimate pulmonary artery pressures (from the tricuspid regurgitation jet) and has also been used for the monitoring of left ventricular pre-load.35–37 Echocardiography has not been validated with right heart catheterization in patients with AHF.38
5.6. Other investigations
In cases of coronary-artery-related complications such as unstable angina or myocardial infarction, angiography is important and angiography-based revascularization therapy has been shown to improve prognosis.29,30
Class I recommendation, level of evidence B
Coronary arteriography is also often indicated in prolonged AHF, unexplained by other investigations, as recommended in the guidelines for diagnosis of CHF.1
Insertion of a pulmonary artery catheter (PAC) may assist in making the diagnosis of AHF. See Section 7.2.3 for further details.
6. Goals of the treatment of AHF
The immediate goals are to improve symptoms and to stabilize the haemodynamic condition (Table 4, Figure 5).40–51 An improvement in haemodynamic parameters only may be misleading, however, and a concomitant improvement in symptoms (dyspnoea and/or fatigue) is generally required.52 These short-term benefits must also be accompanied by favourable effects on longer-term outcomes. This is likely to be achieved by avoidance, or limitation, of myocardial damage.
|
|
Another objective of treatment is reduction in the clinical signs of HF. A reduction in body weight, and/or an increase in diuresis, are beneficial effects of therapy in congestive and oliguric patients with AHF.44,53 Similarly, an improvement in oxygen saturation, renal and/or hepatic function, and/or serum electrolytes are meaningful goals of treatment. Plasma BNP concentration can reflect haemodynamic improvement and decreased levels are beneficial.
Beneficial effects of therapy on outcome include reductions in the duration of intravenous vasoactive therapy, the length of stay, and the readmission rate with an increase in the time to readmission.52,54,55 A reduction in both in-hospital and long-term mortality is also a major goal of treatment.
Lastly, a favourable safety and tolerability profile is also necessary for any treatment used in patients with AHF. Any agent used in this condition should be associated with a low withdrawal rate with a relatively low incidence of untoward side effects.
6.1. Organization of the treatment of AHF
Best results are achieved if patients with AHF are treated promptly by expert staff in areas reserved for heart failure patients. An experienced cardiologist and/or other suitably trained staff should treat AHF patients. The diagnostic services should provide early access to diagnostic procedures such as echocardiography and coronary angiography, as needed.
Treatment of patients with AHF requires a treatment plan in the hospital system.50
Class I recommendation, level of evidence B
Comparative studies have shown shorter hospitalization time in patients treated by staff trained in heart failure management.17 The treatment of AHF should be followed by a subsequent HF clinic programme when applicable and as recommended by ESC guidelines.1
The care and information needs of the acutely ill patient and his/her family will usually be addressed by expert nurses.
Heart failure staff nurses and cardiology/heart failure/intensive care specialists should be given the opportunity for continuing professional education.
Recommendations on the standard structure, nursing staff and equipment requirements in intensive cardiology care units and relevant step-down care units based on the expert opinion of the Working Group of Acute Cardiac Care are under preparation.
7. Instrumentation and monitoring of patients in AHF
Monitoring of the patient with AHF should be initiated as soon as possible after his/her arrival at the emergency unit, concurrently with ongoing diagnostic measures addressed at determining the primary aetiology. The types and level of monitoring required for any individual patient vary widely depending on the severity of the cardiac decompensation and the response to initial therapy. Local logistic issues may also be relevant. The guidelines on monitoring discussed here are based on expert opinion.
7.1. Non-invasive monitoring
In all critically ill patients, BP measurements should be made routinely; blood pressure, temperature, respiratory rate, heart rate, the electrocardiogram and blood pressure is mandatory. Some laboratory tests should be done repeatedly i.e. electrolytes, creatinine and glucose or markers for infection or other metabolic disorders. Hypo– or hyperkalaemia must be controlled. These can all be monitored easily and accurately with modern automated equipment. If the patient becomes more unwell, the frequency of these observations will need to be increased.
ECG monitoring (arrhythmias and ST segment) is necessary during the acute decompensation phase, particularly if ischaemia or arrhythmia is responsible for the acute event.
Class I recommendation, level of evidence C
Maintenance of normal blood pressure is critical during the initiation of therapy, and consequently it should be measured regularly (e.g. every 5 minutes), until the dosage of vasodilators, diuretics or inotropes has been stabilized. The reliability of non-invasive, automatic plethysmographic measurement of blood pressure is good in the absence of intense vasoconstriction and very high heart rate.
Class I recommendation, level of evidence C
The pulse oximeter is a simple non-invasive device that estimates the arterial saturation of haemoglobin with oxygen (SaO2). The estimate of the SaO2 is usually within 2% of a measured value from a co-oximeter, unless the patient is in cardiogenic shock. The pulse oximeter should be used continuously on any unstable patient who is being treated with a fraction of inspired oxygen (FiO2) that is greater than in air. It should also be used at regular intervals (every hour) on any patient receiving oxygen therapy for an acute decompensation.
Class I recommendation, level of evidence C
Cardiac output and pre-load can be monitored non-invasively with the use of Doppler techniques (see Section 5.5.). There is little to no evidence to help choose which of these to monitor and it makes no difference as long as the limitations of individual monitoring devices are understood and the data are used appropriately.
Class IIb recommendation, level of evidence C
7.2. Invasive monitoring
7.2.1. Arterial line.
The indications for the insertion of an in-dwelling arterial catheter are the need for either continuous beat-to-beat analysis of arterial blood pressure due to haemodynamic instability or the requirement for multiple arterial blood analyses. The complication rate for the insertion of a 20-gauge 2-inch radial artery catheter is low.
Class IIb recommendation, level of evidence C
7.2.2. Central venous pressure lines.
Central venous lines provide access to the central venous circulation and are therefore useful for the delivery of fluids and drugs and can also be used to monitor the CVP and venous oxygen saturation (SvO2) in the superior vena cava (SVC) or right atrium, which provides an estimate of oxygen transport.
Class II b recommendation, level of evidence C
Caution has to be advised, however, to avoid the over-interpretation of right atrial pressure measurements, as these rarely correlate with left atrial pressures, and therefore left ventricular (LV) filling pressures, in patients with AHF. CVP measurements are also affected by the presence of significant tricuspid regurgitation and positive end-expiratory pressure (PEEP) ventilation.
Class I recommendation, level of evidence C
7.2.3. Pulmonary artery catheter.
The pulmonary artery catheter (PAC) is a balloon flotation catheter that measures pressures in the superior vena cava (SVC), right atrium, right ventricle and pulmonary artery as well as cardiac output. Modern catheters can measure the cardiac output semi-continuously as well as the mixed venous oxygen saturation and right ventricular end diastolic volume and ejection fraction.
Although the insertion of a PAC for the diagnosis of AHF is usually unnecessary, it can be used to distinguish between a cardiogenic and a non-cardiogenic mechanism in complex patients with concurrent cardiac and pulmonary disease. The PAC is also frequently used to estimate PCWP, cardiac output and other haemodynamic variables and therefore guide therapy in the presence of severe diffuse pulmonary pathology or ongoing haemodynamic compromise not resolved by initial therapy.57,58 PCWP is not an accurate reflection of left ventricular end–diastolic pressure (LVEDP) in patients with mitral stenosis (MS) aortic regurgitation (AR), ventricular interdependence, high airway pressure, or stiff LV, due to, for example, left ventricular hypertrophy (LVH), diabetes, fibrosis, inotropes, obesity, ischaemia. Severe tricuspid regurgitation, frequently found in patients with AHF, can overestimate or underestimate cardiac output measured by thermodilution.
Several retrospective studies assessing the use of the PAC in acute myocardial infarction demonstrated increased mortality with the PAC. These observations were partially explained by case-mix differences between the groups of the study.59–61 Similar observational findings have subsequently been reported in other groups of patients.47,61,62 A recent prospective randomized study enrolling a mixed group of critically ill patients failed to demonstrate a difference in outcome, although randomization to the PAC led to increased fluid resuscitation within the first 24 h. The PAC did not cause harm to patients, rather it was the use of the information derived from the catheter (sometimes in an inappropriate fashion) that was detrimental.48
The use of a PAC is recommended in haemodynamically unstable patients who are not responding in a predictable fashion to traditional treatments, and in patients with a combination of congestion and hypoperfusion. In these cases it is inserted in order to ensure optimal fluid loading of the ventricles and to guide49 vasoactive therapies and inotropic agents (Table 5). Because the complications increase with the duration of its use, it is critical to insert the catheter when specific data are needed (usually regarding the fluid status of the patient) and to remove it as soon as it is of no further help (i.e. when diuretic and vasodilating therapy have been optimized).
|
Class IIb recommendation, level of evidence C
In cardiogenic shock and prolonged severe low output syndrome it is recommended that the mixed venous oxygen saturation from the pulmonary artery be measured as an estimation of oxygen extraction (SpO2–SvO2). The aim should be to maintain SvO2 above 65% in patients with AHF.
8. General medical issues in the treatment of AHF
Infections: Patients with advanced AHF are prone to infectious complications, commonly respiratory or urinary tract infections, septicaemia, or nosocomial infection with Gram positive bacteria. An increase in C-reactive protein (CRP) and a decrease in general condition may be the only signs of infection—fever may be absent. Meticulous infection control and measures to maintain skin integrity are mandatory. Routine cultures are recommended. Prompt antibiotic therapy should be given when indicated.
Diabetes: AHF is associated with impaired metabolic control. Hyperglycaemia occurs commonly. Routine hypoglycaemic drugs should be stopped and glycaemic control should be obtained by using short-acting insulin titrated according to repeated blood glucose measurements. Normoglycaemia improves survival in diabetic patients who are critically ill.50
Catabolic state: negative caloric and nitrogen balance is a problem in ongoing AHF. This is related to reduced caloric intake due to reduced intestinal absorption. Care should be undertaken to maintain calorie and nitrogen balance. Serum albumin concentration, as well as nitrogen balance, may help to monitor metabolic status.
Renal failure: a close interrelationship exists between AHF and renal failure. Both may cause, aggravate, and influence, the outcome of the other. Close monitoring of renal function is mandatory. Preservation of renal function is a major consideration in the selection of the appropriate therapeutic strategy for these patients.
9. Oxygen and ventilatory assistance
9.1. Rationale for using oxygen in AHF
The maintenance of an SaO2 within the normal range (95–98%) is important in order to maximize oxygen delivery to the tissues and tissue oxygenation, thus helping to prevent end-organ dysfunction and multiple organ failure.
Class I recommendation, level of evidence C
This is best achieved first by ensuring that there is a patent airway and then by administration of an increased FiO2. Endotracheal intubation is indicated if these measures fail to improve tissue oxygenation.
Class IIa recommendation, level of evidence C
Despite this intuitive approach to giving oxygen, there is little to no evidence available that giving increasing doses of oxygen results in an improved outcome. Studies have demonstrated that hyperoxia can be associated with reduced coronary blood flow, reduced cardiac output, increased blood pressure, increased systemic vascular resistance, and a trend to higher mortality.51
The administration of increased concentrations of oxygen to hypoxaemic patients with acute cardiac failure is unquestionably warranted.
Class IIa recommendation, level of evidence C
The use of increased concentrations of oxygen in patients without evidence of hypoxaemia is more controversial and may cause harm.63
9.2. Ventilatory support without endotracheal intubation (non-invasive ventilation)
Two techniques are used for ventilatory support: CPAP or non-invasive positive pressure ventilation (NIPPV). NIPPV is a method of providing mechanical ventilation to patients without the need for endotracheal intubation. There is a strong consensus that one of these two techniques should be used before endotracheal intubation and mechanical ventilation. Utilization of non-invasive techniques dramatically reduce the need for endotracheal intubation and mechanical ventilation.
9.2.1. Rationale.
Application of CPAP can cause pulmonary recruitment and is associated with an increase in the functional residual capacity. The improved pulmonary compliance, reduced transdiaphragmatic pressure swings, and decreased diaphragmatic activity can lead to a decrease in the overall work of breathing and therefore a decreased metabolic demand from the body. NIPPV is a more sophisticated technique that requires a ventilator. Addition of a PEEP to the inspiratory assistance results in a CPAP mode (also known as bilevel positive pressure support, BiPAP). The physiological benefits of this mode of ventilation are the same as for CPAP but also include the inspiratory assist which further reduces the work of breathing and the overall metabolic demand.
9.2.2. Evidence for the use of CPAP and NIPPV in left ventricular failure.
CPAP in patients with cardiogenic pulmonary oedema improves oxygenation, decreases symptoms and signs of AHF, and results in a decreased need for endotracheal intubation.64–68 The studies have been relatively small and therefore have not reported a statistically significant reduction in mortality. A systematic review69 following the first three trials suggested that CPAP was associated with a decreased need for intubation and a trend to decreased in-hospital mortality compared to standard therapy alone. Evidence was lacking, however, on the potential for CPAP to actually cause harm.
There have been three randomized controlled trials of the use of NIPPV in the setting of acute cardiogenic pulmonary oedema.70–72 NIPPV appears to decrease the need for endotracheal intubation, but this does not translate into a reduction in mortality or improvement in long-term function.
9.2.3. Conclusions.
The use of CPAP and NIPPV in acute cardiogenic pulmonary oedema is associated with a significant reduction in the need for tracheal intubation and mechanical ventilation.
Class IIa recommendation, level of evidence A
There are insufficient data to demonstrate a significant reduction in mortality; however, the data do not trend in that direction.
9.3. Mechanical ventilation with endotracheal intubation in AHF
Invasive mechanical ventilation (with endotracheal intubation) should not be used to reverse hypoxaemia that could be better restored by oxygen therapy, CPAP, or NIPPV, but rather to reverse AHF-induced respiratory muscle fatigue. The latter is the most frequent reason for endotracheal intubation and mechanical ventilation. Respiratory muscle fatigue may be diagnosed by a decrease in respiratory rate, associated with hypercapnia and confused state of mind.
Invasive mechanical ventilation should only be used if acute respiratory failure does not respond to vasodilators, oxygen therapy, and/or CPAP, or NIPPV. Another consideration should be the need for immediate intervention in a patient with pulmonary oedema secondary to ST-elevation acute coronary syndrome.
10. Medical treatment
10.1. Morphine and its analogues in AHF
Morphine is indicated in the early stage of the treatment of a patient admitted with severe AHF, especially if associated with restlessness and dyspnoea.
Class IIb recommendation, level of evidence B
Morphine induces venodilatation and mild arterial dilatation, and reduces heart rate.73 In most studies, iv boluses of morphine 3 mg were administered as soon as the intravenous line was inserted. This dosing can be repeated if required.
10.2. Anticoagulation
Anticoagulation is well established in acute coronary syndrome with or without heart failure.29 The same is true in atrial fibrillation.31 There is less evidence for the initiation of unfractionated heparin or low molecular weight heparin (LMWH) in AHF. A large placebo-controlled trial of enoxaparine 40 mg subcutaneoulsy in acutely ill and hospitalized patients, including a major group of heart failure patients, showed no clinical improvement but less venous thrombosis.74 There are no large comparative studies comparing LMWH to unfractionated heparin (given as 5000 IU twice or thrice daily). Careful monitoring of the coagulation system is mandatory in AHF as there is often concomitant liver dysfunction. LMWH is contraindicated if the creatinine clearance is below 30 mL/min or should be used with extreme care with monitoring of the anti-Factor Xa level.
10.3. Vasodilators in the treatment of AHF
Vasodilators are indicated in most patients with acute heart failure as first line therapy, if hypoperfusion is associated with an adequate blood pressure and signs of congestion with low diuresis, to open the peripheral circulation and to lower pre-load (Table 6).
|
10.3.1. Nitrates.
Nitrates relieve pulmonary congestion without compromising stroke volume or increasing myocardial oxygen demand in acute left heart failure, particularly in patients with acute coronary syndrome. At low doses they only induce venodilation, but as the dose is gradually increased they cause the arteries, including the coronary arteries, to dilate. With appropriate doses, nitrates exert balanced vasodilation of the venous and arterial sides of the circulation, thereby reducing LV pre-load and after-load, without impairing tissue perfusion. Their effect on cardiac output depends on pre-treatment pre-load and after-load and the ability of the heart to respond to baroreceptor-induced increases in sympathetic tone.
Initially nitrates may be given orally but intravenous nitrates are also well tolerated in AMI. Two randomized trials in AHF have established the efficacy of intravenous nitrates in combination with furosemide and have demonstrated that titration to the highest haemodynamically tolerable dose of nitrates with low dose furosemide is superior to high dose diuretic treatment alone.
Class I recommendation, level of evidence B
In one of these randomized studies furosemide and isosorbide dinitrate as bolus injections were tested and it was reported that intravenous high dose nitrate was more effective than furosemide treatment in controlling severe pulmonary oedema.75
In practical use nitrates have a U-shaped curve effect. If given in sub-optimal doses vasodilators may have a limited effect in preventing AHF recurrences. However, administration of high doses may also reduce their effectiveness. One disadvantage of nitrates is the rapid development of tolerance especially when given intravenously in high doses, limiting their effectiveness to 16–24 h only. Nitrates should be given at doses aimed at achieving optimal vasodilation, leading to an increase in cardiac index (CI) and decrease in pulmonary wedge pressure. Inappropriate vasodilation may induce a steep reduction in blood pressure, which may result in haemodynamic instability.
Nitroglycerin can be administered orally or by inhalation [glyceryl trinitrate (GTN) spray 400 µg (2 puffs) every 5–10 min], or buccally (isosorbide dinitrate 1 or 3 mg), while monitoring blood pressure. The intravenous administration and dosing of nitrates (glycerylnitrate 20 µg/min increasing dose to 200 µg/min, or isosorbide dinitrate 1–10 mg/h) should be done with extreme caution, under careful blood pressure monitoring, titrating the dose administered against blood pressure decrease. One should be particularly cautious when administering nitrates to a patient with aortic stenosis, although this therapy may help in these complex situations. The dose of nitrates should be reduced if systolic blood pressure falls below 90–100 mmHg and discontinued permanently if blood pressure drops further. From a practical point of view a reduction of 10 mmHg in mean arterial pressure should be achieved.
10.3.2. Sodium nitroprusside.
Sodium nitroprusside (SNP) (0.3 µg/kg/min up-titrating carefully to 1 µg/kg/min up to 5 µg/kg/min) is recommended in patients with severe heart failure, and in patients with predominantly increased after-load such as hypertensive heart failure or mitral regurgitation.
Class I recommendation, level of evidence C
SNP should be titrated cautiously and usually requires invasive arterial monitoring and close supervision. Prolonged administration may be associated with toxicity from its metabolites, thiocyanide and cyanide, and should be avoided especially in patients with severe renal or hepatic failure. Controlled trials with SNP in AHF are lacking and its administration in AMI has yielded equivocal results.76 SNP should be tapered down to avoid rebound effects. In AHF caused by acute coronary syndromes, nitrates are favoured over SNP as SNP may cause ‘coronary steal syndrome’.77,78
10.3.3. Nesiritide.
Recently, nesiritide, a new class of vasodilator, has been developed for the treatment of AHF.40 Nesiritide is a recombinant human brain or B-type natriuretic peptide (BNP) that is identical to the endogenous hormone. Nesiritide has venous, arterial, and coronary vasodilatory properties that reduce pre-load and after-load, and increase cardiac output without direct inotropic effects.
Systemic infusion of nesiritide in patients with CHF has beneficial haemodynamic actions, results in an enhanced sodium excretion, and suppression of the renin–angiotensin–aldosterone and sympathetic nervous systems.79 Nesiritide was compared to intravenous nitroglycerin and resulted in improvement in haemodynamics more effectively and with fewer adverse effects, although this did not translate into improvement in clinical outcome. Nesiritide may cause hypotension and some patients are non-responders.
10.3.4. Calcium antagonists.
Calcium antagonists are not recommended in the treatment of AHF. Diltiazem and verapamil, and dihydropyridines, should be considered contraindicated.
10.4. Angiotensin converting enzyme (ACE)-inhibitors in AHF
10.4.1. Indications.
ACE-inhibitors are not indicated in the early stabilization of patients with AHF.
Class IIb recommendation, level of evidence C
However, as these patients are at high risk, ACE-inhibitors have a role in early management of AHF patients and AMI. There is still debate on the selection of patients and the timing of initiation of ACE-inhibitor therapy.
10.4.2. Effects and mechanism of action.
The haemodynamic effects of ACE-inhibitors result from decreased formation of AII and increased levels of bradykinin, which in turn decreases total peripheral vascular resistances and promotes natriuresis. Short-term treatment is accompanied by a decrease in angiotensin II (AII) and aldosterone and an increase in angiotensin I and plasma renin activity.
There have been no efficacy studies of ACE-inhibitors in AHF to date. Studies with ACE-inhibitors in heart failure after myocardial infarction have focused on long-term effects.80,81 A recent meta-analysis found that mortality at 30 days was reduced from 7.6% in the placebo group to 7.1% in the ACE-inhibitor group [relative risk reduction 7% (95% CI 2–11%, P<0.004)]. This equates to about five fewer deaths per 1000 patients treated for 4–6 weeks [number needed to treat (NNT) to prevent one death=200]. The trials which selected high-risk patients found that ACE-inhibitors led to large relative and absolute reductions in mortality.82
10.4.3. Practical use.
Intravenous ACE-inhibition should be avoided. The initial dose of the ACE-inhibitor should be low and increased progressively after early stabilization within 48 h with monitoring of blood pressure and renal function. The duration of therapy, when initiated, should be at least six weeks.
Class I recommendation, level of evidence A
ACE-inhibitors should be used with caution in patients with marginal cardiac output as they may significantly reduce glomerular filtration.The risk of intolerance to the ACE-inhibitors is increased by the concomitant administration of non-steroid anti-inflammatory agents, and in the presence of bilateral renal artery stenosis.
10.5. Diuretics
10.5.1. Indications.
Administration of diuretics is indicated in patients with acute and acutely decompensated heart failure in the presence of symptoms secondary to fluid retention.
Class I recommendation, level of evidence B
The symptomatic benefits and their universal clinical acceptance have precluded a formal evaluation in large-scale randomized clinical trials.
10.5.2. Effects and mechanisms of action.
Diuretics increase the urine volume by enhancing the excretion of water, sodium chloride and other ions, leading to a decrease in plasma and extracellular fluid volume, total body water and sodium, a reduction in right and left ventricular filling pressures and a decrease in peripheral congestion and pulmonary oedema.83,84 Intravenous administration of loop diuretics also exerts a vasodilating effect, manifested by an early (5–30 min) decrease in right atrial and pulmonary wedge pressure as well as pulmonary resistances.85 With high bolus doses (>1 mg/kg) there is a risk of reflex vasoconstriction. As opposed to chronic use of diuretics, in severe decompensated heart failure the use of diuretics normalizes loading conditions and may reduce neurohormonal activation in the short term.86 Especially in acute coronary syndromes diuretics should be used in low doses and preference given to vasodilator therapy.87
10.5.3. Practical use.
Intravenous administration of loop diuretics (furosemide, bumetanide, torasemide), with a strong and brisk diuretic effect is the preferred choice in patients with AHF. Therapy can safely be initiated before hospital admission75,88–90 and the dose should be titrated according to the diuretic response and relief of congestive symptoms. Administration of a loading dose followed by continued infusion of furosemide or torasemide have been shown to be more effective than bolus alone.87,91–95 Thiazides96–98 and spironolactone99 can be used in association with loop diuretics, the combination in low doses being more effective and having with fewer secondary effects than the use of higher doses of a single drug.96–99 Combination of loop diuretics with dobutamine, dopamine92 or nitrates88 is also a therapeutic approach that is more effective and produces fewer secondary effects than increasing the dose of the diuretic.100
Class IIb recommendation, level of evidence C
Table 7 lists the recommendations for the practical use of diuretics. Table 8 gives the recommended doses of commonly used diuretics in heart failure.
|
|
10.5.4. Diuretic resistance.
Diuretic resistance is defined as the clinical state in which diuretic response is diminished or lost before the therapeutic goal of oedema relief has been achieved.101 Such resistance is associated with a poor prognosis.102 It is more frequent in patients with chronic, severe heart failure on long-term diuretic therapy, although it has also been reported with acute volume depletion after intravenous administration of loop diuretics.103 Diuretic resistance can be attributed to a number of factors (Table 9).101,103 A number of therapeutic approaches to overcome diuretic resistance have been explored (Table 10), and in clinical practice different strategies may be of value in a particular patient. Continuous infusion of furosemide is more effective than individual boluses.104
|
|
10.5.5. Secondary effects, drug interactions.
Although diuretics can be used safely in the majority of patients, secondary effects are frequent and may be life-threatening. They include neurohormonal activation, especially of the angiotensin–aldosterone system and the sympathetic nervous system97, hypokalaemia, hypomagnesaemia, and hypochloraemic alkalosis that may lead to severe arrhythmias92, and nephrotoxicity and aggravation of renal failure.100,105 Excessive diuresis may reduce venous pressure, pulmonary wedge pressure and diastolic filling excessively, leading to a reduction in stroke volume and cardiac output, particularly in patients with severe heart failure and predominant diastolic failure or ischaemic RV dysfunction. Intravenous administration of acetazolamide (1 or 2 doses) may be helpful for the correction of alkalosis.106
10.5.6. New diuretic agents.
Some new compounds with diuretic and other effects are under investigation, including vasopressin V2 receptor antagonists, brain natriuretic peptides (see Section 10.3.3) and adenosine receptor antagonists.
10.6. ß-blocking agents
10.6.1. Indications and rationale for ß-blocking agents.
There has been no study with ß-blocker therapy in AHF targeted to acutely improve the condition. On the contrary, AHF has been considered a contraindication for this treatment. Patients with more than basal pulmonary rales, or hypotension, have been excluded from trials early after AMI. In patients with AMI who are not in overt heart failure or hypotensive, ß-blockers limit infarct size, reduce life-threatening arrhythmias and relieve pain.30,107–109
Intravenous administration should be considered in patients with ischaemic chest pain resistant to opiates, recurrent ischaemia, hypertension, tachycardia, or arrhythmia. In the Gothenburg metoprolol study, intravenous metoprolol or placebo was initiated early after an AMI and followed by oral therapy for three months. Fewer patients developed heart failure in the metoprolol group.110 In patients with signs of pulmonary congestion with basal rales and/or treatment with intravenous furosemide, metoprolol therapy had even greater effects and reduced mortality and morbidity.111 There is experience with the short acting ß-blocker esmolol mainly in the setting of cardiac surgery. One small study has compared celiprolol and esmolol in severe heart failure. Celiprolol reduced CI less at similar heart rate reduction, which was claimed to be due to differences in the vasodilation effect.112 The clinical importance of this difference is unclear. Invasive haemodynamic monitoring was carried out in the MIAMI trial on patients with elevated pulmonary wedge pressures up to 30 mmHg. These patients when treated with metoprolol showed a decrease in filling pressures.113
10.6.2. Practical use.
In patients with overt AHF and more than basal pulmonary rales, ß-blockers should be used cautiously. Among such patients in whom ongoing ischaemia and tachycardia are present, intravenous metoprolol can be considered.
Class IIb recommendation, level of evidence C
However, in patients with an AMI who stabilize after developing AHF, ß-blockers should be initiated early.
Class IIa recommendation, level of evidence B
In patients with chronic heart failure, ß-blockers should be initiated when the patient has stabilized after the acute episode (usually after 4 days).
Class I recommendation, level of evidence A
The initial oral dose of bisoprolol, carvedilol, or metoprolol should be small and increased slowly and progressively to the target dose used in the large clinical trials. Up-titration should be adapted to individual response. ß-blockers may reduce blood pressure and heart rate excessively. As a general rule, patients on ß-blockers admitted to hospital due to worsening heart failure should be continued on this therapy unless inotropic support is needed but the dose could be reduced if signs of excessive dosage are suspected (i.e. bradycardia and hypotension).
10.7. Inotropic agents
10.7.1. Clinical indications.
Inotropic agents are indicated in the presence of peripheral hypoperfusion (hypotension, decreased renal function) with or without congestion or pulmonary oedema refractory to diuretics and vasodilators at optimal doses (Figure 6).
|
Class IIa recommendation, level of evidence C
Their use is potentially harmful as they increase oxygen demand and calcium loading and they should be used with caution.114
In patients with decompensated CHF the symptoms, clinical course, and prognosis of the disease may become critically dependent on the haemodynamics. Thus, improvements in the haemodynamic parameters may become a goal of treatment and inotropic agents may be useful and life-saving in this setting. The beneficial effects of an improvement in the haemodynamic parameters is, however, partially counteracted by the risks of arrhythmias and, in some cases, myocardial ischaemia and by the possible long-term progression of myocardial dysfunction caused by an excessive increase in energy expenditure.114,115 The risk-benefit ratio may not, however, be the same for all the inotropic agents. Those acting through the stimulation of the ß1-adrenergic receptors which increase cytoplasmic myocardial cell Ca++ concentration may be associated with the greatest risk.116,117 Lastly, only a few controlled trials with inotropic agents in patients with AHF have been performed, and very few have assessed their effects on the symptoms and signs of heart failure and their long-term effects on prognosis.117
10.7.2. Dopamine.
At low doses (<2 µg/kg/min i.v.) dopamine acts only on peripheral dopaminergic receptors and lowers peripheral resistance both directly and indirectly. Vasodilation occurs predominantly in the renal, splanchnic, coronary, and cerebral vascular beds. At this dosage, its action may cause an improvement in renal blood flow, glomerular filtration rate, diuresis, and sodium excretion rate, with an increased response to diuretic agents, in patients with renal hypoperfusion and failure.118–121
At higher doses (>2 µg/kg/min i.v.) dopamine stimulates the ß-adrenergic receptors both directly and indirectly with a consequent increase in myocardial contractility and cardiac output. At doses >5 µg/kg/min dopamine acts on 
-adrenergic receptors with an increase in the peripheral vascular resistance which, though potentially useful in hypotensive patients, may be deleterious in patients with AHF, as it may augment the LV after-load, pulmonary artery pressure, and pulmonary resistance.122
10.7.3. Dobutamine.
Dobutamine is a positive inotropic agent acting mainly through stimulation of ß1-receptors and ß2-receptors to produce dose-dependent positive inotropic and chronotropic effects,123,124 and a reflex decrease in sympathetic tone, and thus vascular resistance.<