Department of Anaesthesia and Intensive Care Medicine, Royal Brompton and Harefield NHS Trust, Harefield Hospital, Harefield, Middlesex, UB9 6JH, UK.
*Corresponding author. E-mail: dave{at}tharg.demon.co.uk
Keywords: complications, heart, failure; equipment, assist devices; treatment
Congestive heart failure is a complex clinical syndrome characterized by impaired ventricular performance, exercise intolerance, a high incidence of ventricular arrhythmias and shortened life expectancy. Congestive heart failure is common and is estimated to affect five million people in the US, 300 000 of whom die per year.34 Hospitalizations and mortality from heart failure have increased steadily since 1968, despite the overall improvement in mortality from cardiovascular disease. Among adults over 65 yr of age, heart failure is the commonest reason for admission to a hospital.11
Heart failure may occur suddenly or develop gradually and is the final common pathway of a variety of primary cardiovascular disease entities. Coronary artery disease and hypertension are the two major risk factors for the development of heart failure in the elderly. Other common aetiologies include diabetes mellitus, valvular heart disease, especially aortic stenosis and mitral regurgitation, and non-ischaemic myopathies.8 It is often multifactorial, but specific independent risk factors are male gender, hypertension, coronary artery disease, diabetes mellitus and age.7 At present, the only cure for end-stage congestive heart failure is cardiac transplantation.
Heart failure can be broadly subdivided into two distinct forms (although other classification schemes exist) and distinguishing between the two forms is often difficult. The first form is termed diastolic dysfunction or diastolic heart failure and is due to inadequate ventricular relaxation preventing adequate end-diastolic filling. This type of heart failure affects the left ventricle. The second is the more common systolic dysfunction or systolic heart failure due to inadequate force generation to eject blood normally. This type of heart failure can affect either ventricle but failure of the left heart is more common.
Pathophysiology of heart failure
The principle problems associated with the aging and failing heart are changes in shape, associated with chamber enlargement, and ventricle wall thickness and stiffness. As humans age they progressively lose cardiac myocytes. Their maximal heart rate and cardiac output decrease, while systemic vascular resistance and left ventricular (LV) stiffness, systolic arterial pressure and LV wall thickness increase.4 Myocellular hypertrophy and increased myocellular mass result from increased wall stress and reduction of contractility; this in turn leads to chamber enlargement due to cell slippage and sarcomere growth.5
Increased interstitial fibrosis and cross-linking of collagen in the heart are also associated with aging and this contributes to increased LV stiffness.54 In addition, prolongation of isovolaemic relaxation time and slowing of the rate at which calcium is sequestered by the sarcoplasmic reticulum after myocardial relaxation result in poor LV relaxation. The compliance and early diastolic filling of the left ventricle is decreased and, because LV relaxation is impaired, a significantly greater percentage of LV filling is due to atrial contraction.4 In addition to the decreased early diastolic filling, increased LV stiffness and prolonged relaxation time cause raised LV pressures at rest and during exercise.53
The major neurohumoral systems activated in response to a reduction in cardiac output are the sympathetic nervous system and reninangiotensinaldosterone (RAA) system. In addition, modifications to endothelin receptors, natriuretic peptides and tumour necrosis factor receptors are now recognized to be involved in the secondary response.5 Stimulation of the sympathetic nervous system causes peripheral vasoconstriction and retention of sodium and water by the kidney.22 Plasma norepinephrine levels correlate directly with prognosis in congestive heart failure patients.22 Sympathetic activity also activates the RAA. While these responses have an initial benefit to the patient, they also compound the injury to the heart so that in heart failure the reflex activation of the neurohumoral systems eventually contributes to detrimental effects instead of maintaining arterial pressure and cardiac output. LV remodelling and LV systolic dysfunction occur as a consequence of activation of neurohumoral activation. These deleterious effects are related to alterations in afterload, preload, stretch, increased wall tension, interstitial collagen deposits and through direct toxic effects. Increased wall tension and myocardial oxygen consumption, together with reduced subendocardial perfusion, combine to reduce myocyte shortening and with remodelling, the LV dilates and becomes more spherical.
Diagnosis
The signs and symptoms of heart failure include tachycardia, decreased exercise tolerance, shortness of breath, peripheral and pulmonary oedema and cardiomegaly. There are a number of precipitating factors for acute-on-chronic organ failure. Examples include inadequate compliance with medication, hot weather, uncontrolled hypertension, anaemia, infection with fever, hypoxia, alcohol intake, myocardial infarction (MI), pulmonary embolism, renal insufficiency and thyroid abnormalities.5 One of the most common precipitating factors is the development of an arrhythmia, especially an atrial arrhythmia. The prevalence of atrial fibrillation increases with age from 5% at age 60 yr to about 22% by the age of 90 yr.6 Atrial fibrillation may suddenly worsen heart failure by reducing cardiac output because of a shortened diastolic filling time and a loss of the atrial kick that was contributing to late diastolic filling. The single most useful diagnostic test in the evaluation of patients with heart failure is echocardiography, particularly transoesophageal echocardiography (TOE) coupled with Doppler flow studies. These tests determine whether the primary abnormality is pericardial, myocardial or valvular, and if myocardial, whether the dysfunction is primarily systolic or diastolic. The functional information gained from the echocardiogram is the measurement of LV ejection fraction; patients with an ejection fraction less than 40% are generally considered to have systolic dysfunction. In addition, the echocardiogram allows for the quantitative assessment of the dimensions, geometry, thickness and regional motion of the right and left ventricles and the qualitative evaluation of the atria, pericardium, valves and vascular structures. Such a comprehensive evaluation is important, since it is not uncommon for patients to have more than one cardiac abnormality that can cause or contribute to the development of heart failure.
LV size is assessed by measuring the inside diameter at the junction of the basal and mid third at end diastole. This value should be less than 5.5 cm with a wall thickness of 1.2 cm or less at end diastole. Systolic LV global function can be assessed quantitatively or qualitatively.
Fractional area change (FAC) is a two-dimensional TOE equivalent of ejection fraction. It is obtained by measuring the LV chamber cross-sectional area at the transgastric mid short axis view at end-systole and end-diastole to get the end-diastolic area (EDA) and end-systolic area (ESA). FAC=EDAESA/EDA and is normally greater than 0.5. This method is not as accurate when regional wall motion abnormalities are present. A qualitative assessment is done by examination of all areas of the ventricle and estimation of ejection fraction as normal (>55%), mildly decreased, moderately decreased, moderately severely decreased or severely decreased (<25%). This method in experienced hands correlates well with other non-echocardiographic methods of ejection fraction measurement such as ventriculography.
Diastolic LV function can be assessed using pulse wave Doppler echocardiography. The transmitral inflow velocity profile during diastole in the normal patient has an E wave corresponding to early passive filling of the ventricle, followed by an A wave corresponding to atrial contraction (Fig. 1). Impaired relaxation patterns with decreased peak E-to-A velocity ratio and prolonged E wave deceleration time signify mild diastolic dysfunction. A restrictive pattern, with raised filling pressures and severe diastolic dysfunction, is associated with an increased peak E-to-A velocity ratio and decreased E wave deceleration time. A period where the mitral inflow pattern appears normal may occur as diastolic dysfunction progresses from mild to severe. The pulmonary venous inflow velocity profile may help to distinguish between these two.
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No cure exists for most people with heart failure but much can be done to make physical activity more comfortable and improve the quality and duration of life. The American College of Cardiology and American Heart Association have described four stages of heart failure (Table 1).34 Patients in stage A have a known risk factor. Those in stage B are known to have LV dysfunction but have not developed heart failure. Those in stage C have current or previous evidence of heart failure with known LV dysfunction and the stage D patients have refractory end-stage heart failure. Although this is a useful classification to differentiate between various management strategies, it is also obvious that the symptomatic and pathological development of heart failure is on a continuum.
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Patients with stage-A heart failure without contraindications, who have exercise-limiting angina pectoris or frequent angina at rest should have angiography with a view to revascularization. A few patients with ischaemia of effort present not with chest pain but with shortness of breath. These patients also warrant investigation and possible angiography. Patients with stage-B heart failure and haemodynamically significant valvular regurgitation or stenosis are candidates for valve replacement or repair.
Anaesthetic considerations for stage-A patients undergoing cardiac or major non-cardiac surgery mainly centre around the therapy they are receiving. The majority will be being treated for hypertension (diuretics, angiotensin-converting enzyme (ACE) inhibitors and beta blockers), diabetes, or both.34
For stage B-heart failure, all measures used for stage A are recommended. If ACE inhibitors and beta blockers have not already been started their addition to the patients medication should be considered. Patients are usually anticoagulated with oral anticoagulants to an international normalized ratio of 23. Medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and all antiarrhythmic drugs other than beta blockers, digoxin and amiodarone should be stopped as they aggravate heart failure.34
Anaesthetic implications for patients with impaired ventricular function or stage-C heart failure
If the patient does present for surgery that is unrelated to their heart failure, the two principal cardiovascular events to control during anaesthesia are myocardial depression and peripheral vasodilatation. Any changes in either of these variables should be minimized. Historically drugs such as etomidate and ketamine have been suggested as useful in this regard. However, there is a lack of evidence to support these in the patient whose cardiac condition has been optimized with currently advocated preoperative pharmacological interventions.
The majority of patients with impaired LV function are dependent on their preload to maintain ventricular filling and many patients with heart failure also rely on increased sympathetic tone to maintain tissue perfusion and cardiac output. Patients with severe impairment of LV function are therefore extremely sensitive to changes in the fine balance in which they exist. Moreover, the underlying cardiomyopathy leading to heart failure has different aetiology and thus different problems of management. Cardiomyopathy is associated with a high incidence of heart failure and may be restrictive, dilated or hypertrophic.
Restrictive cardiomyopathy is the most difficult to deal with and is characterized by stiff ventricles that impair ventricular filling; pronounced right heart failure is a frequent problem. If the technique of general anaesthesia produces myocardial depression, vasodilatation and reduced venous return allied to increased intrathoracic pressure from IPPV, then this may lead to circulatory arrest. Spontaneous ventilation is therefore preferred while maintaining an elevated right heart pressure by administration of fluid.
Dilated cardiomyopathy manifests as a large, poorly contractile heart, with stroke volume preserved by dilatation and increased LV end-diastolic volume. Functional mitral and tricuspid incompetence is common due to the dilatation of the annulus of the valve, and exacerbates the problem. Arrhythmias are frequent and may be life-threatening. Amiodarone is the drug of choice to treat these arrhythmias as it has the least myocardial depressant effect.14 Inhalational anaesthetics reduce myocardial contractility in a dose-dependent manner, but effects differ between the different agents. Isoflurane is a popular anaesthetic for patients undergoing coronary revascularization and appears to have certain cardioprotective properties. Sevoflurane, unlike isoflurane and desflurane, does not induce a tachycardia. Recent human studies have also suggested that isoflurane and sevoflurane have cardioprotective effects similar to those induced by ischaemic preconditioning.24 70 71 Because of the extreme sensitivity to negative inotropic agents, these patients frequently require inotropic support.14
Hypertrophic cardiomyopathy is characterized by outflow tract obstruction produced by septal hypertrophy. Impaired diastolic function is an important feature, and diastolic filling of the ventricles may rely on atrial systole (atrial kick) for up to 75% of end-diastolic volume (Fig. 1), therefore sinus rhythm is very important. Tachycardia may also be a problem, as it reduces diastolic filling time of both the coronaries and the ventricle. Inotropic support may worsen outflow obstruction and increase myocardial oxygen demand at the same time as lessening oxygen supply by increasing ventricular wall tension.14 In general, vasodilators that do not induce a tachycardia should be useful here.
Interventions with grade-D heart failure
These patients are most likely to present to the anaesthetist in intensive care rather than for elective surgery, as mortality following anaesthesia and surgical interventions in this group is extremely high.
Pharmacological interventions
The cardiac glycosides have been the mainstay of treatment for those with chronic heart failure.14 Their mechanisms of action leading to subjective reduction in symptoms in heart failure are multiple.42 In addition to effects on ion exchange channels, it is hypothesized that digoxin also provides a reduction in the sympathetic hyperactivity associated with congestive heart failure.27 Diuretics should be given for patients with evidence of fluid retention, and spirinolactone is often used in patients with recurrent symptoms and preserved renal function. Patients should also be treated with neurohormonal blockade with an ACE inhibitor (or angiotensin receptor blocker in patients with persistent cough or angioedema) and a beta blocker. Calcium channel blockers (except amlodipine) and NSAIDs should not be given.
The basis of added therapy in advanced heart failure is interventions to increase inotropy and reduce preload.
Inotropy
The fundamental mechanism to improve inotropy is to increase myocyte intracellular cyclic AMP. Figure 2 shows the various pathways that can be used to achieve this effect. In the acute setting the usual inotropic support is from catecholamines acting through the beta adrenoceptor. I.V. dobutamine has been used for short-term support in severe heart failure and LV dysfunction, but older patients treated with dobutamine commonly develop arrhythmias,60 and there is evidence that an increased rate of ventricular arrhythmias and subsequent mortality are associated with use of dobutamine. The FIRST study showed that long-term use of dobutamine in heart failure patients was an independent predictor of mortality, and did not improve quality of life.52
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Recently there has been a resurgence of interest in the use of nutritional and metabolic support in heart failure. Nutritional supplements (such as coenzyme Q10, carnitine, taurine and antioxidants) have been the subject of small-scale studies. The administration of glucose-insulin-potassium (GIK) may be of benefit. First suggested as an intervention for improving ventricular function and reducing infarct size in the 1970s,44 57 GIKs popularity waned because of concerns about various safety issues.50 However in 1987, a study advocated the use of GIK following coronary thrombolysis with streptokinase, stating that its use improved ejection fraction and reduced segmental wall motion abnormalities.63
A further approach to improving carbohydrate utilization is to cause the myocyte to metabolize carbohydrate as its principal substrate in preference to fatty acids. One approach to increase glucose oxidation is to inhibit fatty acid oxidation; three agents that work in this manner are trimetazidine, etomoxir and ranolizine. Trimetazidine is widely available for clinical use.43 It optimizes cardiac metabolism by inhibition of fatty acid oxidation through inhibition of mitochondrial palmitoylcarnitine oxidation, while only partially inhibiting pyruvate oxidation and preserving mitochondrial oxidation.26 37 A European collaborative working group on trimetazidine has undertaken a number of trials. These have confirmed earlier findings for this class of compound and showed that in patients with angina, the effects of trimetazidine are not only equivalent to nifedipine23 and propranol25 but also that it does not reduce coronary blood flow or rate pressure product. It is synergistic with diltiazem in reducing angina and appears to be effective in patients with LV dysfunction.65 Patients with chronically dysfunctional myocardium have also been studied, and administration of trimetazidine caused significant improvement in function and symptomatology.65 Evidence therefore suggests that agents such as trimetazidine improve the dysfunctional heart without increasing oxygen demand and may have an important therapeutic role.
L-carnitine and its analog proprionyl L-carnitine increase glucose oxidation and benefit myocardial function by reducing mitochondrial acetyl CoA.64 Animal studies have demonstrated a myocardial benefit,28 and a multicentre trial showed that L-carnitine may reduce ventricular end-diastolic pressure and slow the progression of LV dilatation in patients who have suffered an MI.35
Direct stimulation of the pyruvate dehydrogenase (PDH) complex to increase glucose oxidation may also be effective, and the prototype drug in this class is dichloroacetate, which acts by inhibiting PDH kinase and therefore prevents inhibition of the PDH complex. This drug has been shown clinically to have beneficial effects in patients with LV functional abnormalities in heart failure.12
Reduced preload
The mechanism for reduction in vascular tone that may benefit patients with heart failure is to increase the intracellular concentration of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation and vasodilation. This is usually achieved using a nitrate vasodilator or sometimes with sodium nitroprusside infusion.
As an alternate, human brain natriuretic peptide (hBNP) binds to the particulate guanylate cyclase receptor of vascular smooth muscle and endothelial cells, leading to increased intracellular concentrations of cGMP and smooth muscle cell relaxation (Fig. 3).
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Nesiritide achieves the majority of its effect within 15 min of injection.46 The offset of the haemodynamic effect of nesiritide is longer than the kinetic half-life would predict. For example, in patients who developed symptomatic hypotension in the VMAC trial,1 half of the recovery of systolic arterial pressure toward the baseline value after discontinuation or reduction of the dose of nesiritide was observed in about 60 min. When higher doses of nesiritide were infused, the duration of hypotension was sometimes several hours.
Non-pharmacological interventions in heart failure
Synchronized pacing
Sudden cardiac death due to arrhythmias is a common problem in patients with heart failure. Such patients should be treated aggressively, and sinus rhythm, which is crucial in those patients who rely on synchronized atrial systole for ventricular filling, should be restored, and rate optimized, typically to a rate of about 80 beats min1.
In chronic atrial fibrillation, the use of TOE facilitates earlier cardioversion by allowing examination of the heart and especially the atrial appendages for clot, and therefore safe DC cardioversion without anticoagulation.
Optimization of the synchronization of myocardial contraction has been studied recently, with promising results.13 Many patients with chronic heart failure have ECG evidence of an interventricular conduction delay, which may worsen LV systolic dysfunction; this is most often in the form of left bundle branch block. This is caused by asynchronous ventricular contraction and occurs in up to one-third of chronic heart failure patients.17 Permanent pacing has been used for many years to treat symptomatic bradycardia and may be useful to alleviate heart failure associated with heart block.18 A number of studies have examined the use of dual chamber pacing in heart failure patients to improve cardiac performance. Results have varied, with apical right-sided pacing causing worsening haemodynamics or poorer LV function.31 40 These effects are thought to be a result of asynchrony of the ventricles, so many centres now advocate pacing from the interventricular septum in the hope of providing a more physiological pattern of contraction. From this grew the idea that cardiac resynchronization could be achieved with biventricular pacing. Significant improvement can be shown in patients who have cardiac resynchronization through atrial-synchronized biventricular pacing.2 17 41 This is achieved through the use of dual chamber pacing placed in the usual way (transvenous), with a third wire, also transvenous, placed in the LV venous circulation via the coronary sinus. Biventricular pacing has been shown to allow the heart to contract more efficiently to increase LV ejection fraction and cardiac output while consuming less oxygen.51 Other benefits include increased diastolic ventricular filling time, decreased PCWP and reduced mitral regurgitation.18 Newer devices allow more control of atrioventricular contraction for further optimization of function. Several clinical trials have studied the use of biventricular pacing in left bundle branch block. The MUSTIC and MIRACLE studies showed significant improvements in quality-of-life scores, exercise tolerance, peak oxygen uptake and ejection fraction with biventricular pacing.17 41 There were also impressive reductions in hospital admission and hospital stay. Mortality data from the COMPANION study showed a reduction in mortality of 20% in the biventricular pacing group; the trial was consequently halted.15 In those who had implantable biventricular cardiac defibrillators, the all-cause mortality was reduced by 40%. The CARE heart failure study is underway, but evidence thus far seems to show a definite benefit in morbidity and mortality with biventricular pacing.19
Unfortunately as many as 20% of those patients who fulfill the criteria for biventricular pacing derive no benefit from it, and new techniques of patient selection are being sought.59 The current criteria that suggest greatest benefits following biventricular pacing and internal cardiodefibrillator implantation are systolic heart failure, non-reversible causes for failure, a patient who is highly symptomatic and has optimized medical therapy, and should be in sinus rhythm with significant mitral regurgitation, and ventricular dysynchrony (left bundle branch block induced by right ventricular apical pacing).18
Implantable cardioverter defibrillators are being advocated in heart failure because severe LV failure, an independent predictor of cardiac mortality, causes death by progressive heart failure or malignant ventricular arrhythmias.18 The National Institute for Clinical Evidence has recommended the use of these devices in cases of high-risk heart failure, following the publication of large randomized controlled trials showing benefits in mortality in high-risk ischaemic patients.49 The MADIT-II trial showed a relative risk reduction of 31% in heart failure patients with ischaemic heart disease and poor LV function when automatic defibrillators were implanted.48
Biventricular pacing and implantable cardioverter defibrillators have also been used in the acute setting; a case report of a patient weaned from cardiopulmonary bypass with biventricular pacing was published recently,39 and bi-atrial pacing has been used to prevent recurrence of atrial fibrillation in the intensive care unit after surgery.29
Surgical ventricular restoration
Anterior myocardial infarction leads to changes in the ventricular architecture and volume. The proposed pathophysiology is for the development of dyskinesia or akinesia that leads to heart failure by myocardial dysfunction of the remote muscle.9 Ventricular remodelling is designed to return the ventricle to a more normal shape. Patients undergoing anterior ventricular endocardial restoration showed significant improved 18-month survival and reduction in hospital re-admission when associated with coronary revascularization or mitral valve repair.9 The Surgical Treatment of Heart Failure Trial has been started and will investigate long-term outcomes of patients with heart failure and abnormal LV ejection fraction.
Mechanical assistance
This is a more radical and invasive method of support and protection of the failing heart. Mechanical assist devices are designed to decrease the mechanical work of the heart and improve coronary perfusion. The main problem for the clinician is to assess how much potential the patients heart function (together with the resultant multi-organ failure related to the low output state) has for recovery and if a mechanical support device will achieve this. The increasing variety and availability of these devices will allow the selection of the most appropriate system for each patient. Predictability of the devices performance and available resources are essential for effective use of mechanical support.47
Intra-aortic balloon counterpulsation, commonly referred to as an intra-aortic balloon pump (IABP), has been the mainstay of perioperative short-term treatment of the failing heart. Although IABPs are not suitable for all critically ill patients, their use is becoming more widespread, with good results reported.13 Further study on balloon pump use has generated evidence that may allow the use of an IABP on an ambulatory, longer term basis.20 36 IABP is a proven technology that is often used as a comparator to assess the ability of other systems to unload the heart and maintain coronary filling whilst maintaining cardiac output. It is an effective treatment for intractable angina and cardiogenic shock,32 and has been shown to have a considerable benefit in cases of acute MI in combination with either percutaneous transluminal coronary angioplasty or thrombolysis.10 However, dopamine has been shown to be more effective in the case of myocardial stunning following resuscitation.67 For perioperative protection, it is clear that the effectiveness of IABP is greatest when introduced before surgery: institution 2 h before surgery conveyed a highly significant benefit when compared with institution at weaning from cardiopulmonary bypass.45 Other modalities of protection (pharmacological and metabolic modulation) should always accompany IABP use.47 The overall morbidity (e.g. limb ischaemia or bleeding) from IABP use is 35%, and risk must be balanced against benefits.
LV assist devices (LVAD) have become increasingly used for end-stage heart failure because of the shortage of organs available for transplantation. While certain devices have been approved by the US Food and Drug Administration (FDA) for short-term support or as a bridge to transplant, none has received a licence for permanent replacement therapy. The REMATCH trial sponsored by the US National Institutes of Health was designed to compare permanent LVAD placement against optimal medical management in patients not suitable for cardiac transplantation.61 62 Analysis of data from these studies showed a 48% reduction in the risk of death from any cause in the group that received LVADs compared with the medical-therapy group. The survival rate at 1 yr was 52% in the device group and 25% in the medical-therapy group, and at 2 yr was 23% and 8%, respectively. The frequency of serious adverse events in the device group was 2.35 times that in the medical-therapy group, with a predominance of infection, bleeding and malfunction of the device.
Indications for device placement include postcardiotomy shock, acute MI and myocarditis. In many cases, short-term support as a bridge to recovery is replaced by a longer-term device as a bridge to transplant. Reduced ventricular function before surgery may mean that longer-term devices are used at the outset. One of the most common indications is severe cardiogenic shock associated with acute coronary syndrome.56 Revascularization is often not appropriate in these patients, and a bridge to transplant is required. The Shock trial demonstrated the ineffectiveness of medical and surgical revascularization in these patients, but device implantation is not yet considered the optimal option. Patients with long-term heart failure awaiting transplantation frequently receive implants because of clinical deterioration. More time is provided to evaluate these patients because of their chronic clinical deterioration, and this approach often allows a period for recovery of end-organ failure before transplantation. Patients considered ineligible for transplantation may be improved by the implantation of a device to the point where they can be listed for transplantation.69 More recently, a team at Harefield Hospital has been using an aggressive medical therapy including the anabolic beta-adrenoceptor agonist clenbuterol. This has been associated with exceptional recovery of the patients native heart function, allowing removal of the LVAD without clinical deterioration.33 Patient selection is critical. Early implantation in a patient soon to receive an organ, or with a chance of recovery, subjects the patient to an expensive and complex procedure with its own morbidity and mortality. Conversely, a delay in device placement may result in multi-organ failure that precludes further intervention for the patient. The decision-making process is complicated and clinically challenging. The appropriate device to implant depends on variables such as the planned duration of support, patient body surface area and need for uni- or bi-ventricular support. Criteria have been developed to help these decisions. Haemodynamic elements include systolic arterial pressure, PCWP and cardiac index, with consideration of inotropic or balloon pump support, or both. Other end-organ function, including cognitive function, are essential considerations. Preoperative factors that have an impact on LVAD effectiveness include ventilatory support, coagulopathy, right heart function, infection and renal function.69 Most patients with heart failure have mild pulmonary hypertension, which resolves over time with placement of an LVAD and unloading of the left heart. However, the right heart may not be able to tolerate this reactive pulmonary hypertension and may need support for a few days. Right heart failure can be catastrophic and support can be with inotropic agents (typically PDIs are used as first-line intervention because of their combined inotropic and vasodilator actions) or right VAD insertion. The simplest protection is to ensure that the patients cardiac index is not raised precipitously following LVAD placement, which might cause the right ventricle to fail.69
Temporary neurological damage is not a contraindication to device placement where there are reasonable grounds to expect recovery, but if there is no recovery the patient should not receive a transplant. Aortic valvular insufficiency is a contraindication, as the low pressure ventricle will allow a preferential flow of pumped blood in a circuit from the left ventricle through the device and back to the aortic root rather than around the body. The valve leaflets may be sewn together when a device that does not require valve opening is implanted. Aortic stenosis may be repaired if myocardial recovery is possible, and this may convey some protection in the event of device failure.69 Mitral stenosis or regurgitation should also be corrected and a tricuspid annuloplasty ring may be placed to prevent the development of insufficiency. A patent foramen ovale must be diagnosed and closed, as with unloading of the left atrium significant intracardiac right-to-left shunting may occur.
Choice of device
Devices can be divided into site of placement (extra- and intra-corporeal) and type of flow generator system (centrifugal, axial and diaphragm). Centrifugal pumps utilize the pump mechanism of standard heart bypass. Two of the most common are the Biomedicus Bio-pump and the Sarns/3M Centrifugal system; new centrifugal systems include the bearingless Levitronix system. These drive systems are magnetically coupled to an external power source and pump flow is related to rotation speed. They can be used uni- or bi-ventricularly. Their main disadvantages are the need for heparinization, difficulty in chest closure, the need for intensive monitoring and inability to generate pulsatile flow. They are used primarily as a bridge to recovery in cardiogenic shock, but may be followed by a longer-term device if recovery does not occur in 714 days.
Examples of other extracorporeal devices include the Thoratec/Pierce-Donachy device and the Abiomed Bi-ventricular support (BVS) 5000. The Abiomed is a pneumatic device with two pumps, each with two chambers: the top (atrial) fills by gravity, and the lower (ventricular) has a bladder that is compressed with gas to expel the contained blood. The machine can generate flows up to 6 litre min1 and the central console regulates the flow based on preload filling. The device is approved for post-cardiotomy support but has been used for bridging to transplantation; it is relatively safe, being filled passively, and simple to maintain in the patient. It provides pulsatile flow. Its disadvantages include a fixed stroke volume that may be problematic in the very small or large patient, the need for anticoagulation, the requirement for intensive care unit support and the inability for patient mobilization. This device is ideal for short-term support (average 7 days) and as a bridge to recovery or to transplantation. The Thoratec/Pierce-Donachy VAd can also be used for left, right or bi-ventricular support. It is a polyurethane-lined, pneumatically driven, pusher-plate device, with a stroke volume of 65 ml and generates flows up to 7 litre min1. The pump itself is extracorporeal but like the BVS 5000, the chest may be closed over the inflow and outflow cannulae, which exit the body through the abdominal wall. The cannulae have a coating to allow reduced levels of anticoagulation This device is approved for post-cardiotomy support and is frequently used as a bridge to transplant. It has been implanted for up to 515 days, and has been reported as having up to 38% weaning rate in some studies. Advantages include versatility and suitability for small patients. It is the only device approved for those in need of longer support. Disadvantages include infective risk with the abdominal exit site, anticoagulation need and a large cumbersome drive console.69
Intracorporeal devices include the Novacor Left Ventricular Assist System (LVAS) and The Heartmate LVAD systems. The Novacor is FDA approved for bridge to transplant. This device works by a dual pusher plate with a polyurethane-lined blood-contact surface and two porcine valves. Flows are up to 10 litre min1 with a stroke volume of 70 ml. Similar to the Heartmate system, it is only available as a left-sided support device and it can be triggered with ECG or intrinsic ventricular contractile synchronization. Newer devices may become completely implantable, but for now drive gases and electrical connections to the device that is implanted in the abdominal cavity must pass through the skin. Patients under 60 kg in weight are usually considered too small for implantation of this device. Advantages include the almost free ambulation so that selected patients can be discharged home. Anticoagulation is the primary drawback of LVAS, and despite this being adequate based on laboratory criteria, the incidence of thrombotic stroke is high (about 26%). The percutaneous line is a route for infection, as with the Heartmate and other transcutaneous systems. Reliability is excellent and support has been up to 4 yr.69 The Heartmate LVAD is available in two versions: the implantable pneumatic (IP) and vented electric (VE). The device is unique in that it uses a sintered titanium housing that stimulates formation of a pseudo-intimal layer. This is combined with xenograft valves to avoid the need for anticoagulation. The IP device is driven by a pneumatic driver and is thus less portable than the VE device. An external pneumatic pump may drive the IP device in an emergency, since it is vented. Flow rates as high as 10 litre min1 can be achieved and the stroke volume is 85 ml; there are two modes. The driveline is tunnelled and exits the abdomen. Advantages include a very low rate of thromboembolic events (2.7%) despite the avoidance of anticoagulation.66 A hand pump can operate both devices in the event of a failure, and patients can be discharged home while awaiting an organ. Disadvantages include limitation on patient size, percutaneous driveline and the requirement for another type of device if right-sided support is required. These devices have proven themselves reliable and versatile, and patients who go on to transplantation do as well as those who have transplantation initially.16
Implantable axial flow pumps (Jarvik 2000, DeBakey VAD, Kriton and the Heartmate II) are the latest technology to be employed. These systems are very light, simple, small, lack valves, can generate flows up to 10 litre min1 and have minimal blood contact areas.38 They show minimal haemolysis but require anticoagulation (except the Kriton). The Kriton is exceptional as it has a pump with no mechanical wear, and therefore no heat, and no area of stagnant blood to stimulate clotting. The main advantage of these pumps is their small size, which simplifies implantation and explantation, and makes them suitable for smaller patients. Their simplicity should aid reliability but in the event of a failure, replacement is the only option. These devices are in clinical use now and are under evaluation. There is some concern that these devices are not pulsatile and this may have implications for end organs, but this is a theoretical issue and the evidence appears good in studies to date.58
Postoperative management of patients after implantation is often difficult because of multiple organ dysfunction. Bleeding and worsening right ventricular disease contribute to difficult patient management. Avoidance of transfusion where possible in patients who will be transplanted, and the implications for pulmonary vascular resistance with transfusion, are major concerns. Aprotinin has been shown to be effective in reducing bleeding in these patients30 and anticoagulation is only begun after surgery when patients have ceased to bleed. Right-hearted failure is the most dangerous complication of LVAD insertion, as mentioned previously; an atrial pressure above 20 mm Hg with a low PCWP are cardinal signs. Inhaled nitric oxide may be valuable in this setting. Pacing, biventricular if indicated, may also be instituted. Biventricular support will be necessary if aggressive pharmacological support is unsuccessful despite careful regulation of left-sided flows.69 Vasodilatory hypotension is common in these patients and if traditional vasopressors fail, arginine vasopressin may be useful.3
Summary
The heart failure epidemic is now a major cause of mortality and morbidity and is responsible for many hundreds of thousands of deaths throughout the world each year. Anaesthetists and intensivists encounter this condition on an almost daily basis and not infrequently it contributes to or causes the death of the patients for whom we are responsible. However, our understanding of this complex illness is steadily improving and the medical armamentarium to alleviate symptoms and improve outcome is expanding. New surgical and medical treatments and new and more sophisticated medical devices all have the potential to prolong and improve the lives of heart failure patients. Future therapy for this distressing condition holds out much promise.
References
1 Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002; 287: 153140
2 Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002; 346: 184553
3 Argenziano M, Choudhri AF, Oz MC, et al. A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement. Circulation 1997; 96: II-28690
4 Aronow W. Effects of aging on the heart. In: Tallis R, Fillit H, Broccklehurst J, eds. Brocklehursts Textbook of Geriatric Medicine and Gerontology. Edinburgh: Churchill Livingstone, 1998; 25562
5 Aronow WS. Epidemiology, pathophysiology, prognosis and treatment of systolic and diastolic heart failure in elderly patients. Heart Dis 2003; 5: 27994[Medline]
6 Aronow WS, Ahn C, Gutstein H. Prevalence of atrial fibrillation and association of atrial fibrillation with prior and new thromboembolic stroke in older patients. J Am Geriatr Soc 1996; 44: 5213[ISI][Medline]
7 Aronow WS, Ahn C, Kronzon I. Comparison of incidences of congestive heart failure in older African-Americans, Hispanics and whites. Am J Cardiol 1999; 84: 61112, A9[CrossRef][ISI][Medline]
8 Aronow WS, Ahn C, Kronzon I, Koenigsberg M. Congestive heart failure, coronary events and atherothrombotic brain infarction in elderly blacks and whites with systemic hypertension and with and without echocardiographic and electrocardiographic evidence of left ventricular hypertrophy. Am J Cardiol 1991; 67: 2959[CrossRef][ISI][Medline]
9 Athanasuleas CL, Stanley AW Jr, Buckberg GD, et al. Surgical anterior ventricular endocardial restoration (SAVER) in the dilated remodeled ventricle after anterior myocardial infarction. RESTORE group. Reconstructive Endoventricular Surgery, returning Torsion Original Radius Elliptical Shape to the LV. J Am Coll Cardiol 2001; 37: 1199209[CrossRef][ISI][Medline]
10 Barron HV, Every NR, Parsons LS, et al. The use of intra-aortic balloon counterpulsation in patients with cardiogenic shock complicating acute myocardial infarction: data from the National Registry of Myocardial Infarction 2. Am Heart J 2001; 141: 9339[CrossRef][ISI][Medline]
11 Berry C, Murdoch DR, McMurray JJ. Economics of chronic heart failure. Eur J Heart Fail 2001; 3: 28391[CrossRef][ISI][Medline]
12 Bersin RM, Wolfe C, Kwasman M, et al. Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate. J Am Coll Cardiol 1994; 23: 161724[ISI][Medline]
13 Bosenberg C, Royston D. Protect the heart in the intensive care unit but how? Curr Opin Crit Care 2002; 8: 41720[CrossRef][Medline]
14 Bovill J. Anesthesia for patients with impaired ventricular function. Semin Cardiothorac Vasc Anesth 2003; 7: 4954
15 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 2000; 6: 27685[CrossRef][ISI][Medline]
16 Cantanese K, Morales D. Outpatient left ventricular assist therapy. In: Goldstein D, Ox M, eds. Cardiac Assist Devices. Armonk, NY: Futura, 2000: 15365
17 Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 2001; 344: 87380
18 Chow AW, Lane RE, Cowie MR. New pacing technologies for heart failure. BMJ 2003; 326: 10737
19 Cleland JG, Daubert JC, Erdmann E, et al. The CARE-HF study (CArdiac REsynchronisation in Heart Failure study): rationale, design and end-points. Eur J Heart Fail 2001; 3: 4819[CrossRef][ISI][Medline]
20 Cochran RP, Starkey TD, Panos AL, Kunzelman KS. Ambulatory intraaortic balloon pump use as bridge to heart transplant. Ann Thorac Surg 2002; 74: 74651
21 Cohn JN, Goldstein SO, Greenberg BH, et al. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators. N Engl J Med 1998; 339: 181016
22 Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984; 311: 81923[Abstract]
23 Dalla-Volta S, Maraglino G, Della-Valentina P, Viena P, Desideri A. Comparison of trimetazidine with nifedipine in effort angina: a double-blind, crossover study. Cardiovasc Drugs Ther 1990; 4 (Suppl 4): 8539[ISI][Medline]
24 De Hert SG, ten Broecke PW, Mertens E, et al. Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology 2002; 97: 429[ISI][Medline]
25 Detry JM, Sellier P, Pennaforte S, et al. Trimetazidine: a new concept in the treatment of angina. Comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group. Br J Clin Pharmacol 1994; 37: 27988[ISI][Medline]
26 Fantini E, Demaison L, Sentex E, Grynberg A, Athias P. Some biochemical aspects of the protective effect of trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation. J Mol Cell Cardiol 1994; 26: 94958[CrossRef][ISI][Medline]
27 Ferguson D. Sympathetic mechanisms in heart failure. Circulation 1993; 87: 6875[ISI]
28 Ferrari R, Anard I. Utilisation of propionyl L-carnitine for the treatment of heart failure. In: de Jong J, Ferrari R, eds. A New Therapeutic Approach to Cardiac Diseases. Dordrecht: Kluwer Academic, 1995; 32336
29 Gerstenfeld EP, Khoo M, Martin RC, et al. Effectiveness of bi-atrial pacing for reducing atrial fibrillation after coronary artery bypass graft surgery. J Intervent Cardiol Electrophysiol 2001; 5: 27583[CrossRef][ISI][Medline]
30 Goldstein DJ, Oz MC, Smith CR, et al. Safety of repeat aprotinin administration for LVAD recipients undergoing cardiac transplantation. Ann Thorac Surg 1996; 61: 6925
31 Hochleitner M, Hortnagl H, Ng CK, Gschnitzer F, Zechmann W. Usefulness of physiologic dual-chamber pacing in drug-resistant idiopathic dilated cardiomyopathy. Am J Cardiol 1990; 66: 198202[ISI][Medline]
32 Hollenberg SM. Cardiogenic shock. Crit Care Clin 2001; 17: 391410[ISI][Medline]
33 Hon JK, Yacoub MH. Bridge to recovery with the use of left ventricular assist device and clenbuterol. Ann Thorac Surg 2003; 75: S3641
34 Hunt SA, Baker DW, Chin MH, et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation 2001; 104: 29963007
35 Iliceto S, Scrutinio D, Bruzzi P, et al. Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial. J Am Coll Cardiol 1995; 26: 3807[CrossRef][ISI][Medline]
36 Jeevanandam V, Jayakar D, Anderson AS, et al. Circulatory assistance with a permanent implantable IABP: initial human experience. Circulation 2002; 106: I1838[CrossRef][ISI][Medline]
37 Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res 2000; 86: 5808
38 Kaplon RJ, Oz MC, Kwiatkowski PA, et al. Miniature axial flow pump for ventricular assistance in children and small adults. J Thorac Cardiovasc Surg 1996; 111: 1318
39 Kleine P, Doss M, Aybek T, Wimmer-Greinecker G, Moritz A. Biventricular pacing for weaning from extracorporeal circulation in heart failure. Ann Thorac Surg 2002; 73: 9602
40 Linde C, Gadler F, Edner M, et al. Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure. Am J Cardiol 1995; 75: 91923[CrossRef][ISI][Medline]
41 Linde C, Leclercq C, Rex S, et al. Long-term benefits of biventricular pacing in congestive heart failure: results from the MUltisite STimulation in cardiomyopathy (MUSTIC) study. J Am Coll Cardiol 2002; 40: 11118[CrossRef][ISI][Medline]
42 Lonn E, McKelvie R. Drug treatment in heart failure. BMJ 2000; 320: 118892
43 Lopaschuk G, Manzilli M. Mode of action of trimetazidine and other metabolic agents in the treatment of ischaemic heart disease. Semin Cardiothorac Vasc Anesth 2003; 7: 916
44 Mantle JA, Rogers WJ, Smith LR, et al. Clinical effects of glucose-insulin-potassium on left ventricular function in acute myocardial infarction: results from a randomized clinical trial. Am Heart J 1981; 102: 31324[CrossRef][ISI][Medline]
45 Marra C, De Santo LS, Amarelli C, et al. Coronary artery bypass grafting in patients with severe left ventricular dysfunction: a prospective randomized study on the timing of perioperative intraaortic balloon pump support. Int J Artif Organs 2002; 25: 1416[ISI][Medline]
46 Mills RM, Hobbs RE. Nesiritide in perspective: Evolving approaches to the management of acute decompensated heart failure. Drugs Today (Barc) 2003; 39: 76774[Medline]
47 Mol B. Mechanical support in acute perioperative heart failure: Are assist devises smart enough to heal the heart? Semin Cardiothorac Vasc Anesth 2003; 7: 1059
48 Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002; 346: 87783
49 National Institute for Clinical Excellence. Guidance on the use of implantable cardioverter defibrillators. Technological appraisal guidance no. 11. London: NICE, 2000; 15
50 Neely JR, Grotyohann LW. Role of glycolytic products in damage to ischemic myocardium. Dissociation of adenosine triphosphate levels and recovery of function of reperfused ischemic hearts. Circ Res 1984; 55: 81624[Abstract]
51 Nelson GS, Berger RD, Fetics BJ, et al. Left ventricular or biventricular pacing improves cardiac function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-branch block. Circulation 2000; 102: 30539
52 OConnor CM, Gattis WA, Uretsky BF, et al. Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST). Am Heart J 1999; 138: 7886[ISI][Medline]
53 Ogawa T, Spina RJ, Martin WH 3rd, et al. Effects of aging, sex and physical training on cardiovascular responses to exercise. Circulation 1992; 86: 494503[Abstract]
54 Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res 1991; 68: 15608[Abstract]
55 Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 1991; 325: 146875[Abstract]
56 Park SJ, Nguyen DQ, Bank AJ, Ormaza S, Bolman RM 3rd. Left ventricular assist device bridge therapy for acute myocardial infarction. Ann Thorac Surg 2000; 69: 114651
57 Rackley CE, Russell RO Jr, Rogers WJ, et al. Clinical experience with glucose-insulin-potassium therapy in acute myocardial infarction. Am Heart J 1981; 102: 103849[CrossRef][ISI][Medline]
58 Reddy RC, Goldstein AH, Pacella JJ, et al. End organ function with prolonged nonpulsatile circulatory support. Asaio J 1995; 41: M54751[Medline]
59 Reuter S, Garrigue S, Barold SS, et al. Comparison of characteristics in responders versus nonresponders with biventricular pacing for drug-resistant congestive heart failure. Am J Cardiol 2002; 89: 34650[CrossRef][ISI][Medline]
60 Rich MW, Woods WL, Davila-Roman VG, et al. A randomized comparison of intravenous amrinone versus dobutamine in older patients with decompensated congestive heart failure. J Am Geriatr Soc 1995; 43: 2714[ISI][Medline]
61 Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med 2001; 345: 143543
62 Rose EA, Moskowitz AJ, Packer M, et al. The REMATCH trial: rationale, design and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure. Ann Thorac Surg 1999; 67: 72330
63 Satler LF, Green CE, Kent KM, et al. Metabolic support during coronary reperfusion. Am Heart J 1987; 114: 548[CrossRef][ISI][Medline]
64 Schonekess BO, Allard MF, Lopaschuk GD. Propionyl L-carnitine improvement of hypertrophied heart function is accompanied by an increase in carbohydrate oxidation. Circ Res 1995; 77: 72634
65 Sellier P. The effects of trimetazidine on ergometric parameters in exercise-induced angina. Controlled multicenter double blind versus placebo study. Arch Mal Coeur Vaiss 1986; 79: 13316[ISI][Medline]
66 Slater JP, Rose EA, Levin HR, et al. Low thromboembolic risk without anticoagulation using advanced-design left ventricular assist devices. Ann Thorac Surg 1996; 62: 13217
67 Tennyson H, Kern KB, Hilwig RW, Berg RA, Ewy GA. Treatment of post resuscitation myocardial dysfunction: aortic counterpulsation versus dobutamine. Resuscitation 2002; 54: 6975[CrossRef][ISI][Medline]
68 Uretsky BF, Jessup M, Konstam MA, et al. Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure. Lack of benefit compared with placebo. Enoximone Multicenter Trial Group. Circulation 1990; 82: 77480[Abstract]
69 Williams M, Oz M, Mancini D. Cardiac assist devices for end-stage heart failure. Heart Dis 2001; 3: 10915[Medline]
70 Zaugg M, Lucchinetti E, Garcia C, et al. Anaesthetics and cardiac preconditioning. Part II. Clinical implications. Br J Anaesth 2003; 91: 56676
71 Zaugg M, Lucchinetti E, Uecker M, Pasch T, Schaub MC. Anaesthetics and cardiac preconditioning. Part I. Signalling and cytoprotective mechanisms. Br J Anaesth 2003; 91: 55165