teaser
S Russell
Wales Heart Research Institute
Cardiff
R McArtney and Z Yousef
University Hospital of Wales
Cardiff
Heart failure is a common clinical condition affecting at least 15m people in Europe. The prevalence increases steeply with age and rises sharply at the age of 75 years. The prevalence of heart failure between the ages of 70–80 years is between 10–20% compared to 2–3% below the age of 75 years1.
The clinical presentation is typically with symptoms of breathlessness, lethargy and/or ankle swelling with signs of fluid accumulation on clinical examination or chest radiograph. The presence of fluid overload is suggested by a raised heart and/or respiratory rate, pleural effusions or pulmonary oedema, raised central venous pressure or a palpable liver. A diagnosis of heart failure is supported by an abnormal electrocardiogram (ECG), and/or ultrasound scan of the heart (echocardiogram). More recently brain naturetic peptide (BNP) a neurohormone, has been shown to be raised in the presence of heart failure. However, many other clinical conditions are also associated with a raised BNP. A diagnosis of acute heart failure is unlikely with a normal BNP measurement.
Acute heart failure is defined as a rapid onset or change in signs or symptoms of heart failure requiring urgent medical treatment.1 It has multiple aetiologies including: acute coronary syndromes, hypertension, abnormal heart rhythms, heart valve dysfunction and sepsis. Therefore, effective treatment involves the recognition of the heart failure substrate (aetiology) and identification of the trigger responsible for the acute decompensation. For example, acute ventricular septal defects or acute severe mitral regurgitation are recognised complications of acute myocardial infarction and may require surgical correction. In other cases, abnormal heart rhythms including atrial fibrillation can act as the decompensation trigger and require rate or rhythm control with anti-arrhythmic medications. Haemodynamically unstable arrhythmias are an indication for urgent electrical cardioversion.
There are several classifications of acute heart failure including the Killip and the Forrester classification.2,3 Stage 4 of the Killip classification describes the most severe presentation of acute heart failure called ‘cardiogenic shock’. This is diagnosed in the presence of hypotension (systolic BP <90mmHg), evidence of peripheral vasoconstriction including oliguria, cyanosis and sweating. The Forrester classification divides patients into subgroups based on pulmonary congestion and tissue perfusion. This helps to direct the initial management strategy of acute heart failure. Pulmonary congestion is reversed with diuretics and IV nitrates to reduce loading of the heart. Tissue hypoperfusion may require inotropic agents to improve cardiac output, see figure below.
The management of acute heart failure is based on consensus of opinion (class II/III evidence) rather than multiple randomised control trials (class I/II evidence). Hypoxaemia should be corrected with supplementary oxygen and non-invasive ventilation may be necessary. The British Thoracic Society guidelines 2008 recommend supplementary oxygen to a target saturation of 92–96% or 88–92% if the patient is at high risk of hypercapnic respiratory failure.4 The use of supplementary oxygen in normoxaemic subjects is controversial. There is evidence to suggest that hyperoxaemia is detrimental to patients after a stroke and no clear benefit after an acute myocardial infarction.5,6
Opiates, e.g. morphine are indicated for the treatment of breathlessness and chest pain and may facilitate the use of non-invasive ventilation because of their sedative and anxiolytic effect. Opiates also cause venodilation, which reduces the volume of blood returned to the heart (preload), which is beneficial for the treatment of acute heart failure.
Diuretics
Loop diuretics are used to treat congestion and volume over-load (see figure above). Initial bolus therapy, giving IV furosemide 20–40mg bolus should achieve an adequate diuresis. Higher doses or even infusions may be necessary for patients who have been on long-term oral loop diuretics. The dose of loop diuretic may be reduced by concurrent administration of a thiazide diuretic (e.g. metolazone) or vasodilator (IV nitrates).
In subjects with acute myocardial infarction, reduced heart function (ejection fraction <40%) and either clinical or radiographic evidence of heart failure, eplerenone a selective aldosterone antagonist has been shown to improve mortality over a mean 16 month follow up (relative risk 0.85; 95% confidence interval, 0.75 to 0.94; p=0.005).7 Eplerenone was added to standard post myocardial infarction medications with careful monitoring for hyperkalaemia, serum potassium ≥6mmol/l, (5.5% in eplerenone group v 3.9% in the placebo group, p=0.002).
Vasopressin antagonist, tolvaptan, is an oral vasopressin (V2) antagonist and licensed for use in subjects with hypervolaemia or euvolaemic hyponatremia. The V2 receptor is located predominantly in the principal cells of the renal-collecting duct system and induces free water diuresis. In the EVEREST trial,8 tolvaptan decreased body weight and improved patient symptoms and/or breathlessness but had no mortality advantage. Tolvaptan significantly reduced the requirement for furosemide compared to placebo (-55.8mg/day v -42.9mg/day, p=0.002) and the incidence of hyponatraemia at day 1 and discharge v placebo (p<0.001).
Vasodilators
Vasodilators are recommended in the early phase of acute heart failure without hypotension (systolic BP <90mmHg).1 This group of medications include IV glyceryl trintitate, and sodium nitroprusside. N-acetylcysteine can be used in combination with IV nitrates to reduce tolerance and therefore potentiate the effect of organic nitrates.9
The heart is surrounded by a protective sac called the pericardium. The pericardium allows a finite volume of blood into both ventricles. IV nitrates cause venodilation, reducing the volume of blood returning to the right ventricle. This allows the left ventricle to receive more blood and augments the filling of the left ventricle. This increases the volume of blood that is ejected by the left ventricle around the systemic circulation – diastolic interaction. Relief of the diastolic interaction is beneficial to the decompensated heart and helps to reverse acute pulmonary oedema and symptoms of breathlessness.
Nesiritide is a recombinant form of brain or B-type natriuretic peptide (BNP), which causes significant vasodilation, salt and water excretion and improved heart filling properties. It is efficacious in improving breathlessness in acute heart failure. Clinical trials are in progress to ascertain whether nesiritide reduces 30 day mortality or rehospitalisation after acute decompensated heart failure.10
Inotropes
Inotropic agents should be used in low output/hypotensive states (cold section – Forrester figure), to correct the signs of hypoperfusion or signs of congestion despite the use of diuretics and vasodilators. Although inotropes help improve cardiac output in acute heart failure they increase myocardial oxygen demand and can increase mortality. Therefore, inotropes should be used sparingly and discontinued at the earliest opportunity (see Table 1).
Dopamine and dobutamine use the β receptors to exert their effect. In addition, dopamine acts on dopaminergic receptors in the kidney and at low dose has a diuretic effect. Both of these inotropes have a dose dependent mechanism of action, with dopamine causing vasoconstriction at higher doses. Tachyphylaxis is observed with longterm or recurrent use of these inotropes.
Phosphodiesterase inhibitors are a newer class of inotrope. Their mode of action is independent of the β receptor and leads to an increase in cardiac output. The loading of the left heart is reduced – there is a concomitant decline in pulmonary capillary wedge pressure and the tightness of the systemic and pulmonary vessels (resistance) is reduced. These effects are beneficial in acute heart failure.
Levosimendan is a calcium channel sensitiser and it increases the affinity of Troponin-C (an intracellular cardiac protein) to bind calcium. This enhances myocardial contractility and causes vasodilatation. Levosimendan differs from the classical inotropes because of its ability to improve myocardial efficiency without increasing oxygen demand. Randomised clinical trials have shown Levosimendan to have beneficial effects on symptoms, haemodynamics and neurohormones but no beneficial effects on mortaility.11 For completeness, vasopressors such as norepinephrine can be used in combination with inotropes in cardiogenic shock to augment blood pressure.
Devices
Intra-aortic balloon pump
The intra-aortic balloon pump is a mechanical device that augments the systemic circulation of blood and enhances coronary perfusion. The pump is usually inserted via the femoral artery and the balloon is advanced into the proximal section of the descending aorta. The balloon inflated during diastole (the filling phase of the cardiac cycle). The device can detect diastole either by monitoring the ECG or arterial pressure wave forms.
During diastole the coronary arteries ‘suck’ blood from the aorta. Inflation of the balloon augments coronary perfusion. In addition, the balloon circulates blood to the distal target organs. The balloon deflates before systole (the contraction phase of the cardiac cycle), so not to obstruct the flow of blood from the left ventricle into the aorta.
Biventricular pacing
Biventricular pacing is a treatment for chronic heart failure. This is achieved by placing pacing wires into the heart usually via the subclavian vein or one of its branches. Conventional pacing requires the pacing wires to be placed in the right atrium and right ventricle to treat heart block.
With the addition of a third wire that is placed on the posterior/lateral wall of the left ventricle via the coronary veins both cardiac ventricles can be stimulated. This is an effective treatment for patients with chronic heart failure and helps to prevent episodes of acute heart failure. Biventricular pacing fine tunes the heart to contract in an efficient manner – this is called resynchronisation.
The failing heart can develop a condition called ‘dysynchrony’ where the heart contraction is poorly co-ordinated and there is regional variation in left ventricular contraction. This is associated with dilation of the left ventricular cavity and a reduction in the ability of the heart to eject blood – ejection fraction. Markers of dysynchrony can be found on an electrocardiogram (ECG) – left bundle branch block or measured on a transthoracic echocardiogram to focus on the timing of events in the cardiac chambers.
Biventricular pacing (which is also called ‘cardiac resynchronisation therapy’) has been evaluated in several randomised control trials. The vast majority of trials have concentrated on subjects in sinus rhythm and excluded permanent atrial arrhythmias.
Two large randomised control trials have shown a mortality benefit with biventricular pacing in subjects with symptomatic heart failure, reduced ejection fraction and broadened QRS/left bundle branch block on ECG.12,13 The National Institute for Clinical Excellence (NICE) and the European Society of Cardiology (ESC) have issued guidelines on which patients should be selected for biventricular pacing.1
More recent trials have investigated the benefit of biventricular pacing in subjects with less symptomatic heart failure but severely reduced ejection fraction and markers of dysynchrony. The Cardiac-Resynchronisation Therapy for the Prevention of Heart Failure Events trial (MADIT-CRT)14 reported a significant reduction in a composite primary endpoint of death or heart failure events, 17.2% v 25.3%, p=0.001. This was driven by a 41% reduction in heart failure events in the group of patient receiving biventricular pacing.
References
1.
Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail. Oct 2008;10(10):933-989.
2.
Killip T, 3rd, Kimball JT. Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol. Oct 1967;20(4):457-464.
3.
Forrester JS, Diamond GA, Swan HJ. Correlative classification of clinical and hemodynamic function after acute myocardial infarction. Am J Cardiol. Feb 1977;39(2):137-145.
4.
O’Driscoll BR, Howard LS, Davison AG. BTS guideline for emergency oxygen use in adult patients. Thorax. Oct 2008;63 Suppl 6:vi1-68.
5.
Ronning OM, Guldvog B. Should stroke victims routinely receive supplemental oxygen? A quasi-randomized controlled trial. Stroke. Oct 1999;30(10):2033-2037.
6.
Rawles JM, Kenmure AC. Controlled trial of oxygen in uncomplicated myocardial infarction. Br Med J. May 8 1976;1(6018):1121-1123.
7.
Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. Apr 3 2003;348(14):1309-1321.
8.
Gheorghiade M, Konstam MA, Burnett JC, Jr., et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. Mar 28 2007;297(12):1332-1343.
9.
Mehra A, Shotan A, Ostrzega E, et al. Potentiation of isosorbide dinitrate effects with N-acetylcysteine in patients with chronic heart failure. Circulation. Jun 1994;89(6):2595-2600.
10.
Hernandez AF, O’Connor CM, Starling RC, et al. Rationale and design of the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial (ASCEND-HF). Am Heart J. Feb 2009;157(2):271-277.
11.
Mebazaa A, Nieminen MS, Packer M, et al. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. May 2 2007;297(17):1883-1891.
12.
Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. Apr 14 2005;352(15):1539-1549.
13.
Bristow MR, Feldman AM, Saxon LA. Heart failure management using implantable devices for ventricular resynchronization: Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure (COMPANION) trial. COMPANION Steering Committee and COMPANION Clinical Investigators. J Card Fail. Sep 2000;6(3):276-285.
14.
Moss AJ, Hall WJ, Cannom DS, et al. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med. Oct 1 2009;361(14):1329-1338.
