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Journal of Perioperative Science REVIEW

A Practical Approach to the Perioperative Management of Heart Failure John H. Eisenach* Abstract Demographic aging and its implications for healthcare delivery is a global concern. Heart failure is the leading cause of hospital admission in patients older than age 65. It is a major risk factor for postoperative morbidity and mortality, representing one of the most challenging and expensive problems in medicine and surgery. Every anesthesia provider must be familiar with the definition, classification, pathogenesis, and perioperative management associated with heart failure. This review will focus on five key questions that anesthesiologists can incorporate into a strategic approach to managing the surgical patient with heart failure. Keywords: systolic heart failure; diastolic heart failure; cardiomyopathy; anesthesia; preoperative evaluation; blood volume management ( J Perioper Sci 2014, 1:4 )

Introduction The terms “coronary

artery disease” and “congestive heart failure” are common listings on the pre-anesthesia medical record. Coronary artery disease is a structural and readily conceptual diagnosis. In contrast, the term “CHF” is often vaguely listed on the pre-anesthesia record and poorly characterized in patients for non-cardiac surgery. Furthermore, many aspects of heart failure (HF) are poorly understood. Every anesthesia provider must be familiar with the definition, classification, pathogenesis, and treatment strategies associated with HF. Comprehensive guidelines for the diagnosis and treatment of HF were first published in 1995, were revised in 2001, 2009, and recently in 2013 [1,2]. As survival in patients with coronary disease has increased, so has the prevalence of heart failure [3]. Patients with HF have a significantly higher risk of From the *Departments of Anesthesiology, Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905 Accepted for publication July 13, 2014. Reprints will not be available from the authors. Address correspondence to John H. Eisenach Departments of Anesthesiology, Physiology and Biomedical Engineering, Mayo Clinic. Address e-mail to [email protected]

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postoperative mortality than patients with coronary disease, even in minor procedures [4]. From the year 2010 to 2030 the prevalence of all cardiovascular disease is projected to increase by 10%, but the prevalence of HF is projected to increase by 25%, such that 1 in 33 Americans will have heart failure [5]. In the same time frame, total costs for HF are estimated to increase from $31 billion to $70 billion [3]. Heart failure is the most common reason for hospital admission in patients older than age 65 [6]. Taken together, HF is emerging as one of the most challenging and expensive problems in medicine and surgery. In a recent surgical outcomes study of HF patients, adverse events within one month of non-cardiac surgery occurred in 30%; of these were death (8%), myocardial infarction (15%), and HF exacerbation (25%). Patient factors that increased risks of these complications included age>80, diabetes, and ejection fraction (EF) less that 30% [7]. Due to the broad nature of this topic, this review will focus on five key questions that anesthesiologists can incorporate into a strategic approach to managing the surgical patient with heart failure. What is the type and cause of heart failure? The common definitions used to classify the type of HF are summarized in Table 1. Heart failure is the

Eisenach. J Perioperative Science 2014, 1:4 http://www.perioperative-science.com/content/01/04

syndrome that results from a reduced filling of blood, or reduced ejection of blood from the ventricle. The unifying theme in HF is the clinical presentation of dyspnea and fatigue which may limit exercise tolerance. Fluid retention may lead to pulmonary venous congestion and peripheral edema. Together, the ultimate consequence is a reduction in quality of

life and life expectancy [8]. While there is no single test that confirms the diagnosis of HF, the categorical feature of systolic HF is an EF less than 40%, compared to an EF greater than 50% in diastolic HF, while individuals with an EF between 41 and 49% are considered intermediate.

Table 1. Definitions of common terms and some key features of HF Term

Definition

Comments/features

Heart Failure

Structural or functional impairment of Lifetime risk is 20% for Americans ventricular filling or ejection over age 40. Mortality is 50% within 5 years of diagnosis.

HFrEF

HF with reduced EF, formerly systolic EF typically < 40% Prevalence less than HF: Inability of heart to move blood half of HF cases. Major causes are forward at a sufficient rate to meet the ischemic heart disease and idiopathic. metabolic demands of the body

HFpEF

EF typically > 50% Prevalence more than half of HF cases and more common in women. Major cause is hypertension. EF between 41-49%. Treated similarly to HFpEF

HF with preserved EF, formerly diastolic HF: Ability of heart to move blood forward only if the cardiac filling pressures are abnormally high HF intermediate HF with intermediate EF EF Cardiomyopathy, LV dysfunction

Structural and functional disorders of Includes a wide range of abnormalities the myocardium that cause HF

Dilated Cardiomyopathy

Myocardial dysfunction characterized Most commonly idiopathic in origin by ventricular dilatation and and associated with better survival decreased contractility than other causes of cardiomyopathy; 25% of cases improve in a short time

Peripartum cardiomyopathy

LV dysfunction in the last trimester of pregnancy, unknown cause but risk factors include multiparity, advanced maternal age, African descent, longterm tocolysis. Moving up the Frank-Starling curve (Na+ and water retention), LV hypertrophy, neurohumoral activation Increased cardiac workload due to increases in metabolic demand, increased circulating volume, decreased contractility

Compensated HF

Decompensated HF

The heart consumes more energy than any other organ, pumping about ten tons of blood throughout the body per day. When cells in the myocardium become deprived of energy, this abnormality of “myocardial energetics” plays a major role in progression of HF. There are three components of cellular energy metabolism: 1) substrate utilization: Journal of Perioperative Science

After 6 months: improved LV function in 50% of patients; much worse prognosis if LV function does not improve (6 year mortality 50%) Improving NYHA class

Worsening NYHA class

the uptake and conversion of free fatty acids and glucose into the Kreb’s cycle; 2) oxidative phosphorylation: producing ATP from the mitochondrial respiratory chain; and 3) transfer and utilization of high-energy phosphates (ATP) to the myofibrils [9]. Dysfunction in all three components of myocardial energetics is early and integral to HF ２

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pathogenesis. Future therapeutic approaches will target these molecular and metabolic pathways. In contrast to the common clinical presentation of HF, the causes of HF are widely variable. Growing evidence suggests that there are unique characteristics in risk factors, pathophysiology, treatment, and outcomes in systolic vs. diastolic heart failure [10]. Figure 1 displays common and contrasting features of systolic and diastolic HF.

Causes of HF can be classified as cardiogenic or non-cardiogenic. Cardiogenic causes of HF are inherently related to pathophysiology of the myocardium, the valves, and the pericardium, and can be classified as structural and functional. Noncardiogenic causes of HF are non-cardiac pathologies that are injurious to myocardium or evoke a physiological state that resembles heart failure.

Figure 1. Common and contrasting features of heart failure with reduced HF (HFrEF) and heart failure with preserved HF (HFpEF). HFrEF or systolic HF is generally associated with an acute injury to myocardium, or a genetic abnormality injurious to myocardium. The pathophysiology of HFpEF, or diastolic HF, is insidious in onset primarily from poorly controlled hypertension, but also confounded by aging and poorly controlled comorbidities. While initial physiologic adaptations are common between syndromes, the maladaptive processes distinguish the two. The arrows represent the cycle of heart failure that continues when inadequate therapies exacerbate the syndrome.

For structural changes in systolic HF, ischemic heart disease is the leading cardiogenic cause. Myocardial infarction changes the ventricular geometry within hours to days. The area of myocardium expands and becomes thinner. Global remodeling results in ventricular dilatation (eccentric hypertrophy), decreased systolic function, mitral valve dysfunction, and aneurysm formation [11]. For diastolic HF, hypertensive heart disease is the leading cardiogenic cause associated with remodeling, as the ventricular walls become thickened (concentric hypertrophy) and ejection fraction is preserved. Chemotherapy induced cardiomyopathy can be attributed to a variety of agents, with the most established class being anthracyclines. Doxorubicin (Adriamycin) toxicity is thought to be due to Journal of Perioperative Science

oxidative stress, decreased antioxidant enzymes, and possibly iron accumulation in cardiomyocytes [12,13]. The incidence of heart failure after doxorubicin is dependent on age and dose, with an accelerated risk of myocardial toxicity when doses exceed 550 mg/m2 [14]. Trastuzumab (Herceptin) is a monoclonal antibody against HER2 protein for the treatment of positive HER2 breast cancer [15]. Trastuzumab myocardial toxicity is not related to dose, but potential cardiotoxicity increases when combined with anthracycline therapy, and the effects are greater if the cumulative doxorubicin dose is > 300 mg/m² [16]. Other common chemotherapy agents that are associated with myocardial depression are mitoxantrone (Novantrone), cyclophosphamide (Cytoxan), ３

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ifosfamide (Ifex), all-trans retinoic acid (Tretinoin), and imatinib (Gleevec) [17]. Detailed examples of additional structural causes of HF are beyond the scope of this review but include: gene mutations, inborn errors of metabolism, toxins (i.e., alcohol, smoking, illicit drugs, lead poisoning), infections such as viral (i.e, HIV), bacterial, Lyme disease, fungal, parasitic (i.e., Chagas disease), and idiopathic. Indeed, the leading cause of non-ischemic dilated cardiomyopathy is idiopathic, present in up to 50% of patients where no definitive cause is found [18]. Functional causes of HF are illustrated in Figure 2. Functional causes may overlap with structural

causes that reduce contractile function, such as myocardial infarction. However, a major cause of non-ischemic contractile dysfunction is chronic volume overload due to either severe mitral regurgitation or severe aortic regurgitation. This leads to chamber dilation and eccentric hypertrophy. Pressure overload is a functional cause of diastolic HF, where chronic hypertension or chronic aortic stenosis lead to ventricular remodeling which increases wall thickness in attempt to reduce the wall stress through LaPlace’s relation for a hollow sphere:

σ = P x r / 2h, where σ = wall tension, P = pressure, r = radius, and h = wall thickness.

Figure 2. Functional causes of left sided heart failure. Impaired contractility results from a combination of structural damage to myocardium, most commonly by myocardial infarction and ischemic heart disease, with functional causes that perpetuate the syndrome of heart failure, such as increased sympathetic nervous system activity and neurohormonal activation. Pressure overload can induce left ventricular (LV) systolic or diastolic dysfunction. Diastolic dysfunction is the abnormal relaxation or myocardial stiffness associated with chronic hypertension, pressure overload, and myocardial thickening. Without proper management diastolic dysfunction can progress to LV systolic dysfunction or HF with preserved EF.

Diastolic dysfunction is the abnormal relaxation associated with chronic hypertension, pressure overload, and myocardial thickening. Without proper management it can progress to HF with preserved EF. Other causes of diastolic dysfunction that aren’t directly caused from pressure overload

Journal of Perioperative Science

include hypertrophic cardiomyopathy and restrictive cardiomyopathy. Another common functional cause of HF relevant to the anesthesiologist is tachyarrhythmia-induced cardiomyopathy. A typical surgical presentation of tachyarrhythmia-induced cardiomyopathy is atrial fibrillation with rapid ventricular response and ４

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associated arterial thrombosis (i.e., ischemic stroke, mesenteric ischemia, or cold leg). Emergency echocardiography may reveal severe global hypokinesis with a severely depressed ejection fraction. When caught early, these tachyarrhythmiainduced cardiomyopathies are at least partially reversible with rate control and medical management [19]. The pathophysiology of systolic HF.is a complex interaction between injury of the myocytes and extracellular matrix, ventricular remodeling, sympathetic nervous system activation, and activation of the renin-angiotensin-aldosterone system [20]. Sympathetic nerve activity is normally increased in aging, but substantially increased during HF [21]. Circulating catecholamine levels (norepinephrine, epinephrine) are increased, which leads to salt and fluid retention, peripheral vasoconstriction, and down-regulation of beta-1 adrenergic receptors in the heart [22]. Vagal function in the heart is also reduced in proportion to the severity of heart failure [23,24]. Concomitant with overdriving sympathetic nerve traffic, HF is associated with an over-active renal angiotensin-aldosterone system (RAAS) [25]. This further increases salt and fluid retention, and the RAAS hormones mediate some of the maladaptive effects on the myocardium[26,27]. Natriuretic peptides are released, and circulating cytokines such as interferons and tumor necrosis factor further mediate dysfunctional myocardial remodeling [28]. Interestingly, co-morbid conditions tend to segregate between systolic and diastolic HF. Previous myocardial infarction is the major risk factor for systolic HF, followed by sleep apnea, hypertension, and diabetes. Diastolic HF is associated with a greater variety of diseases, with the major risks being obesity, hypertension, and diabetes, followed by chronic lung disease, dialysis, and sleep apnea [11].

and optimization of HF before elective surgery [30]. Compensated HF or prior HF is now considered a clinical risk factor warranting further assessment of functional capacity, other clinical risk factors, and surgical risk. Adapted from the original Goldman criteria, the Revised Cardiac Risk Index (RCRI) lists “History of HF” as one of six independent predictors of cardiac risk in the determination of an individual’s RCRI [31]. More recently, Sabate and colleagues identified HF as an independent risk factor for major adverse cardiac and cerebrovascular events following non-cardiac surgery [32]. Class: The New York Heart Association (NYHA) functional classification correlates with quality of life and survival. Because the paramount symptom of HF is dyspnea on exertion, the NYHA class stratifies patients based on the symptom severity as described in Table 2. Class IV HF has a worse prognosis than most cancers in the U.S., with a oneyear mortality approaching 45% [11]. Stage: Historically, there have not been widespread screening efforts for HF. Risk factors for HF were either poorly defined or poorly publicized. In an attempt to prevent or reverse HF progression, the ACCF/AHA guidelines developed clinical staging criteria to identify patients at risk for—or in early stages of—HF [1]. The staging criteria allow for patients to be stratified into clinical trials. Results of these trials form the guidelines for medical management. In contrast to NYHA class where patients can move up or down a continuum of functional status, patients move through the stages of HF in one direction, not reverse. What are the current medications? By understanding the treatment strategy, summarized in Table 2, one can determine a patient’s current HF stage. The medications in HF serve to reduce cardiac sympathetic stimulation, lessen sodium and water retention, and decrease afterload, collectively breaking the cycle of physiological adaptations and pathologic maladaptations depicted in Figure 1. On the electrocardiogram, a prolonged QRS complex is present in approximately 1/3 of HF patients, which is associated with worse outcome [33]. The associated bundle branch block produces a loss of ventricular coordination called dyssynchrony or mechanoenergetic uncoupling which hastens maladaptive remodeling [34]. Cardiac resynchronization therapy (CRT) is an attempt to coordinate ventricular depolarization. With pacer

What is the stage and class of heart failure? The patient’s functional status remains a key feature in preoperative cardiac evaluation. In previous ACC/AHA guidelines for preoperative clinical predictors of anesthesia risk, decompensated HF was classified as a major clinical risk factor, and compensated or prior HF, an intermediate risk factor [29]. The most recent ACC/AHA guidelines for preoperative cardiovascular evaluation list decompensated HF as an “active cardiac condition,” for which the HF patient should undergo evaluation Journal of Perioperative Science

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leads in both ventricles, CRT brings synchronized contraction to the ventricles, which reverses pathologic remodeling, may improve mitral

regurgitation if present, improve ejection fraction, and can improve symptoms and NYHA class [35].

Table 2. Stage, class, and treatment algorithm of HF NYHA Functional Classifications

ACCF/AHA Stages of HF

Treatment Algorithm

A

At high risk for HF but without structural heart disease or symptoms of HF

Risk-factor reduction, education; treat hypertension, diabetes, dyslipidemia. Smoking cessation and avoidance of cardiotoxic agents ACE inhibitor or ARB in all patients; betablocker in select patients; statins; ICD in patients with ischemic cardiomyopathy and at least 40 days postMI and EF < 30%

I

No limitations of physical activity. Ordinary physical activity does not cause symptoms of HF.

B

Structural heart disease but without signs or symptoms of HF

I

No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. Slight limitation of physical activity, Comfortable at rest, but ordinary physical activity results in symptoms of HF. Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF. Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.

C

Structural heart disease with prior or current symptoms of HF

II

III

IV

ACE inhibitors and beta-blockers in all patients; Dietary sodium restriction, diuretics, and digoxin; Hydralazine and isosorbide dinitrate in African Americans; Aldosterone antagonist; Cardiac resynchronization if bundlebranch block present Revascularization, mitral-valve surgery

D

Refractory HF requiring specialized interventions

Inotropes, ventricular assist device, transplantation Hospice

ACCF, American College of Cardiology Foundation; AHA, American Heart Association; HF, heart failure; NYHA, New York Heart Association; MI, myocardial infarction; ARB, angiotension receptor blocker. Table adapted from reference [1].

There is strong evidence to suggest that CRT is indicated in patients with left ventricular EF less than or equal to 35%, a QRS complex greater than 120 milliseconds, a left bundle branch pattern on Journal of Perioperative Science

ECG, sinus rhythm, and NYHA class II or III symptoms [1]. Weaker evidence suggests a benefit of CRT in patients with atrial fibrillation with EF less than 35%, optimal medical therapy, and fully ６

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dependent on ventricular pacing [1]. Importantly, approximately 80% of biventricular pacers will include an automated internal cardiac defibrillator (ICD). There are two strong indications for ICD’s in HF. This first is to prevent sudden cardiac death in patients with non-ischemic cardiomyopathy, ischemic cardiomyopathy > 40 days post myocardial infarction, an EF less than or equal to 35%, and have a NYHA class II or III with a reasonably predicted survival beyond one year [1]. The second indication is to prevent sudden cardiac death in patients with an EF less than or equal to 30%, with NYHA class I symptoms while receiving optimal medical management, who are also expected to live beyond one year [1] . CRT is not indicated for patient with comorbidities and an poor expected survival. One must weigh the benefits against the potential for worsening quality of life because of the discomfort from shock delivery.

in exercise tolerance; 2) Fluid retention; 3) With no symptoms or with symptoms of another cardiac disorder or noncardiac disorder. The complete history and physical exam will delineate cardiac versus noncardiac causes of presentation. The routine ECG and chest X-ray have low sensitivity and specificity for diagnosing a cardiac cause of HF, but are useful in the general assessment of cardiac and pulmonary pathology. The most useful diagnostic test is echocardiography to address three main questions: 1) ejection fraction; 2) left ventricular structure, dimension, wall motion; and 3) non-left ventricular abnormalities (i.e., valve, pericardium, right ventricle). Additional echocardiography indices will include atrial size and pressure, characteristics of LV filling, and pulmonary arterial pressure. The comprehensive echocardiogram will also provide a baseline for future comparison and therapeutic management. Laboratory testing will include natriuretic peptides (BNP and/or NT-proBNP)Figure 3, complete blood count, urinalysis, electrolyte panel, hemoglobin A-1c, lipid panel, renal, liver, and thyroid function, as well as viral screening.

What workup does this patient need before surgery? The patient with HF presents in one of three ways: 1) A noticeable onset of exertional dyspnea or decrease

Figure 3. Brain-type natriuretic peptide. BNP is also called brain type natriuretic peptide because it was first discovered in brain tissue. In cardiac myocytes, dilation and pressure overload on the cell causes expression of the gene that translates the pro-hormone. The pro-hormone gets cleaved into an N-terminal pro-BNP that is inactive but measurable, and C-terminal BNP which is the active hormone that inhibits the renin angiotensin aldosterone system (RAAS), promotes diuresis and vasodilation, and thereby decreases preload and afterload. NT-proBNP has a half-life of 1-2 hours and BNP has a half-life of 20 minutes. Journal of Perioperative Science

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The pre-operative holding area: Is this patient in heart failure? Certainly patients in acute HF should not undergo elective procedures, and anesthesia providers must be prepared to diagnose and triage HF patients in the holding area. A meta-analysis of HF diagnostic criteria in patients presenting to the emergency room with dyspnea can be extrapolated to our pre-operative evaluations [36]. If a patient is dyspneic, the positive predictors that suggest HF are listed in Table 3. The strongest predictor of HF in a dyspneic patient is medication non-adherence. Atrial fibrillation is an important predictor of HF because

the prevalence of a-fib in patients with acute HF is greater than 30% [37]. Of note, the reason serum BNP or NT-proBNP is not listed as a positive predictor is because it can also be elevated in advanced age and critical illness. This would include renal failure, acute coronary syndrome, lung disease with cor pulmonale, acute pulmonary embolus, and high output cardiac states such as sepsis. However, if BNP is low, this suggests that a patient does not have HF. The most negative predictors that would dissuade the diagnosis of HF are also listed in Table 3.

Table 3. Is this patient in heart failure…do I cancel this case? Suggested of systolic HF (HFrEF): Comorbidities

Suggestive of HFpEF:

Hypertension, Obesity, chronic lung Poorly controlled hypertension, disease, chronic kidney disease, diabetes, previous MI, sleep apnea, diabetes, sleep apnea, hyper/hypothyroidism, obesity acromegaly, alcohol, cocaine, cancer agents, tachydysrhythmias, myocarditis, AIDS, Chaga’s disease, peripartum cardiomyopathy, amyoid, sarcoid, Takotsubo Predictors of acute decompensated HF Positive predictors:

Negative predictors:

History

History of HF, past or present atrial fibrillation or other tachyarrhythmias, peripheral edema, sleep disordered breathing

No history of HF No dyspnea on exertion

Physical exam

Presence of an S3 gallop Jugular venous distention Irregular pulse rhythm Presence of right ventricular heave Cold extremities

No rales/crackles auscultation

Chest X-Ray

Congestion (cardiomegaly with a heart to No cardiomegaly thorax ratio of less than 1:2, cephalization No congestion of flow or batwing or butterfly appearance, Kerley B lines, prominent horizontal fissure, pleural effusions)

Electrocardiography

Abnormal rhythm, ventricular morphology

No abnormalities

Monitors/Laboratory

BNP or N-terminal pro-BNP elevated* Cardiac troponins elevated

A normal BNP

on

lung

*indicates that while BNP and/or NT-proBNP is elevated in acute HF, there are many other conditions associated with an elevation of these markers.

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Preoperative medications: For preoperative continuation of anti-hypertensive agents, concerns have arisen with respect to profound and refractory intraoperative hypotension in patients who take an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB). A study at our institution found that discontinuation of ACEI/ARB therapy at least 10 hour before anesthesia was associated with a reduced risk of immediate postinduction hypotension [38]. Therefore, our pre-operative evaluation clinic recommends that patients hold their ACEI and ARB on the day of surgery, provided that their blood pressure is well-controlled. If their hypertension is poorly controlled at the time of their preoperative visit, these medications are continued on the day of surgery. The lipid-lowering agent is generally taken at night, and while postoperative outcomes data are less clear on HF patients, the use of preoperative statins has shown a reduction in postoperative atrial fibrillation and hospital length-of-stay in cardiac surgery patients [39]and therefore can be continued up to surgery. Specific beta-blockers in HF management are bisoprolol, carvedilol, or sustained-release metoprolol [1]. These medications should be continued on the day of surgery [40,41]. Diuretics should be held on the morning of surgery, primarily because patients are fasting and therefore may be at risk of volume depletion with the use of their diuretic. Aldosterone antagonists (i.e., spironolactone, eplerenone), digoxin, and longacting nitrates can be continued on the day of surgery. Pacemaker interrogation: Pacemaker settings vary by patient and device manufacturer. Interrogation of these devices is essential to determine whether a patient’s heart rhythm is pacemaker dependent and if so, the device should be re-programmed to asynchronous demand pacing (e.g., VOO). The device settings and magnet responses should be reviewed with the manufacturer and/or the hospital pacemaker service. If neither is available and the device is a single chamber (right atrium) or dualchamber (right atrium + right ventricle) pacemaker, a magnet placed on the chest should convert a pacemaker to VOO. Importantly, these responses are not universal, particularly for older devices. This stresses the importance of reviewing all pacemakers prior to surgery. Stage B patients with asymptomatic ischemic cardiomyopathy, who are at least 40 days after myocardial infarction, and have an LVEF ≤30%, may have an internal cardiac defibrillator (ICD) to Journal of Perioperative Science

prevent sudden cardiac death. Defibrillators are accompanied by either single chamber, dual chamber, or biventricular pacemakers. If a biventricular pacemaker device has an ICD, a magnet should inactivate the defibrillator but may not change the pacemaker settings. To prevent unnecessary shocks the ICD should be inactivated in the holding area. Continuous ECG monitoring is indicated until reactivation. Stage C patients may have a biventricular pacemaker with or without an implantable defibrillator. Again, magnet placement should deactivate the defibrillator, but will not change the pacemaker settings. For electrical interference, these devices are programmed with a ventricular noise reversion back-up mode, referred to as the “VNR.” This is the automatic default setting when the pacemaker senses electrical noise such as electrocautery. When electrical interference is sensed, the device typically converts to VOO at a rate between 60-90 bpm. These devices should be interrogated postoperatively to confirm the desired settings and reactivation of the ICD. How should I care for this patient during and after surgery? Induction and maintenance of anesthesia: An awake arterial catheter prior to induction is helpful for any patient in acute or decompensated HF presenting for emergency surgery, for any HF patient in a higher functional class or stage of HF, and for any HF patient with severe systolic or diastolic dysfunction, pulmonary hypertension, or significant valvular disease. Rapid atrial fibrillation in a HF patient would also indicate arterial line placement, with aggressive attempts to adequately stabilize ventricular rate control prior to surgery. The choice of medications for induction is less critical when real-time monitoring of heart rate and arterial pressure allow for careful titration of these agents. For example, propofol or thiopental have the potential to cause profound hypotension in the HF patient because of the chronically elevated sympathetic nervous system activity [42,43]. These agents can be given simultaneously with pressor administration. Etomidate and ketamine have less effect on sympathetic-mediated maintenance of blood pressure [42,44]. The sympathomimetic effect of ketamine may increase myocardial oxygen demand, but this can be offset by short-acting betablockade. Maintenance of anesthesia in HF patients is generally dependent on the surgical procedure, the expected duration of procedure, blood loss, fluid

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shifts, and the need for additional monitoring techniques. Hemodynamic supportive infusions for perioperative management: The agents useful for maintaining cardiac performance and blood pressure support are listed in Table 4. Patients with severe systolic dysfunction or dilated cardiomyopathy may

develop hypotension secondary to low cardiac output. If the patient has adequate intravascular volume, then inotropes (dopamine, dobutamine) should be initiated. If blood pressure is stable, then these patients may benefit from the vasodilatory and inotropic effect of milrinone. Milrinone may be bolused over 10 minutes prior to infusion.

Table 4. Intraoperative supportive medications and considerations Indication / Drug

Mech. Action

Goal / Effect

Starting Dose

Dopamine

DA1, β1, α1, α2 ag.

Inotropy, pressor

5 mcg/kg/min

Dobutamine

β1 agonist

Inotropy

2 mcg/kg/min

Milrinone

PDE III inhibitor

Inotropy,

Bolus: 50 mcg/kg over 10 min

vasodilation

Infusion:

Systolic dysfunction (↓ CO + congestion)

0.5 mcg/kg/min Diastolic dysfunction (↑ BP + congestion) Nitroprusside Nitroglycerin

NO donor, veno- &

Preload < afterload

0.5 mcg/kg/min

arteriodilator

reduction

NO donor, veno- &

Preload > afterload

arteriodilator

reduction

Loop diuretic

Plasma volume

Initial I.V. bolus one-half

reduction

patient’s daily oral dose

0.5 mcg/kg/min

Volume Overload Furosemide

For patients with diastolic HF, an imbalance in myocardial oxygen supply and demand, particularly in the setting of volume overload and severe hypertension, may lead to deterioration of cardiac function and flash pulmonary edema. Nitroglycerin generally decreases preload by venodilation in order to reduce myocardial oxygen demand, while the arteriodilator effect reduces afterload. Nitroprusside provides potent afterload reduction. Both agents must be titrated with caution as patients with diastolic HF are particularly volume sensitive. With either decompensated systolic or diastolic HF, furosemide is the agent of choice for diuresis. Based on the oral bioavailability (60%), the initial I.V. bolus dose is approximately one-half the daily Journal of Perioperative Science

oral dose, with additional doses titrated to effect. Nesiritide is a recombinant natriuretic peptide that has been shown to improve dyspnea and hemodynamic parameters in patients with decompensated heart failure [45]but no improvement in renal function or mortality [46]. Because the half-life and duration of action of nesiritide is longer than the nitric oxide mediated vasodilators, it’s use is limited in the perioperative period. Monitors: Regardless of surgery, the ACCF/AHA guidelines recommend invasive hemodynamic monitoring in HF patients whose fluid status, perfusion, or systemic or pulmonary vascular resistance is uncertain; whose systolic pressure １０

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remains low, or is associated with symptoms, despite initial therapy; whose renal function is worsening with therapy; or those who require parenteral vasoactive agents[1]. Because of pathophysiologic relevance of intravascular volume for both systolic and diastolic HF, the most critical aspect of intraoperative and postoperative monitoring for HF patients involves careful fluid management. “Static” variables are those that estimate cardiac filling pressure or cardiac filling volume (as an estimate of end-diastolic volume, or preload) [47]. Central venous catheters are placed for tracking changes in filling pressure but in isolation will not discriminate between changes in ventricular dysfunction and volume overload. The pulmonary arterial catheter estimates changes in left ventricular filling pressure (pulmonary diastolic and wedge pressure) and provides thermodilution-based measures of cardiac output. Even with minimal user training, transesophageal echocardiography (TEE) provides real-time image estimates of end-diastolic ventricular volume, and global and regional ventricular contractile function [48]. TEE is often considered the monitor of choice to differentiate between cardiogenic, hypovolemic, and vasodilatory causes of shock. The intrathoracic thermodilution method utilizes a central venous line for injection of iced saline, and a thermodilution catheter in a proximal artery (i.e., femoral or axillary) to sense the temperature change from the cold saline injection [49]. The accompanying commercial monitor module estimates stroke volume and intrathoracic blood volume and global end-diastolic volume without dependence on the respiratory cycle. “Dynamic” variables estimate changes in intravascular volume based on characteristics of the arterial waveform that vary with the respiratory cycle [47]. A regular rhythm is also necessary. During positive pressure ventilation, systolic blood pressure variation is the difference between the maximum and minimum systolic pressure values over the respiratory cycle. Hypovolemia is suggested when systolic pressure variation is greater than 10 mmHg. Similarly, pulse pressure (PP) will vary over the respiratory cycle in accord with hypovolemia. Pulse pressure variability can also be derived from one respiratory cycle and is calculated as the maximal PP minus the minimal PP, divided by the average of these two pressures, expressed as a percentage. Similarly, stroke volume (SV) varies over the respiratory cycle in accord with hypovolemia. The calculation of SV variability requires a commercial module on the arterial line Journal of Perioperative Science

that analyzes the pulse contour to estimate SV. SV variability is derived from one respiratory cycle and is calculated as the maximal SV minus the minimal SV divided by the average of these two pressures. It is also expressed as a percentage. Finally, commercial modules exist that determine variability in the amplitude of the pulse oximetry waveform. The variability in pulse oximeter plethysmography waveform (ΔPOP) is calculated as the maximal minus minimal plethysmographic amplitude, divided by the maximal amplitude. This too can be determined over one respiratory cycle. All of the examples of static and dynamic methods of tracking intravascular volume changes have advantages and disadvantages, including cost and training expertise. Moreover, ventricular systolic and diastolic dysfunction associated with HF may have a confounding effect on these variables. No readily available technique has demonstrated superiority. In this context, one must practice the basics of fluid management, including maintenance fluid requirements, surgery-specific insensible losses, urine output, estimated blood loss, and careful fluid resuscitation. Postoperative Management: Postoperative planning for HF patients depends on the preoperative functional status, the complexity of the procedure including intravascular fluid shifts, and potential for postoperative acute decompensating HF. Cardiac devices must be interrogated and reactivated when available. Large intraoperative fluid shifts increase the risk for major adverse cardiac events and acute congestion. The entire clinical picture must be considered for postoperative monitoring with a low threshold for intensive care. In summary, HF is a syndrome with multiple classifications, etiologies, and treatment strategies. Understanding the recently-standardized treatment algorithm will facilitate the preoperative evaluation. Anesthesia providers need to recognize compensated versus decompensated HF in order to guide decision-making. Careful anesthetic planning, device interrogation, fluid management, and postoperative monitoring will optimize perioperative management.

Competing interests The authors declare that they have no conflict of interests.

References

１１

Eisenach. J Perioperative Science 2014, 1:4 http://www.perioperative-science.com/content/01/04

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013. Yancy CW, Jessup M, Bozkurt B, Masoudi FA, Butler J, McBride PE, Casey DE, Jr., McMurray JJ, Drazner MH, Mitchell JE, Fonarow GC, Peterson PN, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL. 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013. Heidenreich PA, Albert NM, Allen LA, Bluemke DA, Butler J, Fonarow GC, Ikonomidis JS, Khavjou O, Konstam MA, Maddox TM, Nichol G, Pham M, Pina IL, Trogdon JG. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6(3):606-19. van Diepen S, Bakal JA, McAlister FA, Ezekowitz JA. Mortality and readmission of patients with heart failure, atrial fibrillation, or coronary artery disease undergoing noncardiac surgery: an analysis of 38 047 patients. Circulation. 2011;124(3):289-96. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, Finkelstein EA, Hong Y, Johnston SC, Khera A, Lloyd-Jones DM, Nelson SA, Nichol G, Orenstein D, Wilson PW, Woo YJ. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation. 2011;123(8):933-44. Alla F, Zannad F, Filippatos G. Epidemiology of acute heart failure syndromes. Heart Fail Rev. 2007;12(2):91-5. Healy KO, Waksmonski CA, Altman RK, Stetson PD, Reyentovich A, Maurer MS. Perioperative outcome and long-term mortality for heart failure patients undergoing intermediate- and high-risk noncardiac surgery: impact of left ventricular ejection fraction. Congest Heart Fail. 2010;16(2):45-9. PMCID: 2945730. Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, Ganiats TG, Goldstein S, Gregoratos G, Jessup ML, Noble RJ, Packer M, Silver MA, Stevenson LW, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Jacobs AK, Hiratzka LF, Russell RO, Smith SC, Jr. 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). J Am Coll Cardiol. 2001;38(7):2101-13. Neubauer S. The failing heart--an engine out of fuel. N Engl J Med. 2007;356(11):1140-51.

Journal of Perioperative Science

[10] Borlaug BA, Redfield MM. Diastolic and systolic heart failure are distinct phenotypes within the heart failure spectrum. Circulation. 2011;123(18):2006-13; discussion 14. PMCID: 3420141. [11] Jessup M, Brozena S. Heart failure. N Engl J Med. 2003;348(20):2007-18. [12] Kwok JC, Richardson DR. Anthracyclines induce accumulation of iron in ferritin in myocardial and neoplastic cells: inhibition of the ferritin iron mobilization pathway. Mol Pharmacol. 2003;63(4):849-61. [13] Singal PK, Deally CM, Weinberg LE. Subcellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol. 1987;19(8):817-28. [14] Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869-79. [15] Chien KR. Herceptin and the heart--a molecular modifier of cardiac failure. New Engl J Med. 2006;354(8):789-90. [16] Saidi A, Alharethi R. Management of chemotherapy induced cardiomyopathy. Curr Cardiol Rev. 2011;7(4):245-9. PMCID: 3322442. [17] Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, Durand JB, Gibbs H, Zafarmand AA, Ewer MS. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004;109(25):3122-31. [18] Felker GM, Thompson RE, Hare JM, Hruban RH, Clemetson DE, Howard DL, Baughman KL, Kasper EK. Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy. N Engl J Med. 2000;342(15):1077-84. [19] Nerheim P, Birger-Botkin S, Piracha L, Olshansky B. Heart failure and sudden death in patients with tachycardia-induced cardiomyopathy and recurrent tachycardia. Circulation. 2004;110(3):247-52. [20] McMurray JJ. Clinical practice. Systolic heart failure. N Engl J Med. 2010;362(3):228-38. [21] Leimbach WN, Jr., Wallin BG, Victor RG, Aylward PE, Sundlof G, Mark AL. Direct evidence from intraneural recordings for increased central sympathetic outflow in patients with heart failure. Circulation. 1986;73(5):913-9. [22] Fowler MB, Laser JA, Hopkins GL, Minobe W, Bristow MR. Assessment of the beta-adrenergic receptor pathway in the intact failing human heart: progressive receptor down-regulation and subsensitivity to agonist response. Circulation. 1986;74(6):1290-302. [23] Eckberg DL, Drabinsky M, Braunwald E. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med. 1971;285(16):877-83. [24] Saul JP, Arai Y, Berger RD, Lilly LS, Colucci WS, Cohen RJ. Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis. Am J Cardiol. 1988;61(15):1292-9. [25] Dzau VJ, Colucci WS, Hollenberg NK, Williams GH. Relation of the renin-angiotensin-aldosterone system

１２

Eisenach. J Perioperative Science 2014, 1:4 http://www.perioperative-science.com/content/01/04

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

to clinical state in congestive heart failure. Circulation. 1981;63(3):645-51. Baig MK, Mahon N, McKenna WJ, Caforio AL, Bonow RO, Francis GS, Gheorghiade M. The pathophysiology of advanced heart failure. Am Heart J. 1998;135(6 Pt 2 Su):S216-30. Weber KT. Aldosterone in congestive heart failure. The New England journal of medicine. 2001;345(23):168997. Onwuanyi A, Taylor M. Acute decompensated heart failure: pathophysiology and treatment. Am J Cardiol. 2007;99(6B):25D-30D. Eagle KA, Berger PB, Calkins H, Chaitman BR, Ewy GA, Fleischmann KE, Fleisher LA, Froehlich JB, Gusberg RJ, Leppo JA, Ryan T, Schlant RC, Winters WL, Jr., Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Jacobs AK, Hiratzka LF, Russell RO, Smith SC, Jr. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery--executive summary a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation. 2002;105(10):1257-67. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC, Jr., Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Md RN, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW. ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): Developed in Collaboration With the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation. 2007;116(17):1971-96. Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, Sugarbaker DJ, Donaldson MC, Poss R, Ho KK, Ludwig LE, Pedan A, Goldman L. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation. 1999;100(10):1043-9. Sabate S, Mases A, Guilera N, Canet J, Castillo J, Orrego C, Sabate A, Fita G, Parramon F, Paniagua P, Rodriguez A, Sabate M. Incidence and predictors of major perioperative adverse cardiac and cerebrovascular events in non-cardiac surgery. Br J Anaesth. 2011;107(6):879-90. Young JB, Abraham WT, Smith AL, Leon AR, Lieberman R, Wilkoff B, Canby RC, Schroeder JS, Liem LB, Hall S, Wheelan K. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced

Journal of Perioperative Science

[34] [35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]

１３

chronic heart failure: the MIRACLE ICD Trial. JAMA. 2003;289(20):2685-94. Hare JM. Cardiac-resynchronization therapy for heart failure. New Engl J Med. 2002;346(24):1902-5. Linde C, Ellenbogen K, McAlister FA. Cardiac resynchronization therapy (CRT): clinical trials, guidelines, and target populations. Heart Rhythm. 2012;9(8 Suppl):S3-S13. Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergency department have congestive heart failure? JAMA. 2005;294(15):1944-56. Gheorghiade M, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, She L, Stough WG, Yancy CW, Young JB, Fonarow GC. Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure. JAMA : the journal of the American Medical Association. 2006;296(18):2217-26. Comfere T, Sprung J, Kumar MM, Draper M, Wilson DP, Williams BA, Danielson DR, Liedl L, Warner DO. Angiotensin system inhibitors in a general surgical population. Anesth Analg. 2005;100(3):636-44, table of contents. Liakopoulos OJ, Kuhn EW, Slottosch I, Wassmer G, Wahlers T. Preoperative statin therapy for patients undergoing cardiac surgery. Cochrane Database Syst Rev. 2012;4:CD008493. Fonarow GC, Abraham WT, Albert NM, Stough WG, Gheorghiade M, Greenberg BH, O'Connor CM, Sun JL, Yancy CW, Young JB. Influence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with heart failure: findings from the OPTIMIZE-HF program. J Am Coll Cardiol. 2008;52(3):190-9. Kwon S, Thompson R, Florence M, Maier R, McIntyre L, Rogers T, Farrohki E, Whiteford M, Flum DR. betablocker continuation after noncardiac surgery: a report from the surgical care and outcomes assessment program. Arch Surg. 2012;147(5):467-73. Ebert TJ, Muzi M, Berens R, Goff D, Kampine JP. Sympathetic responses to induction of anesthesia in humans with propofol or etomidate. Anesthesiology. 1992;76(5):725-33. Sellgren J, Ponten J, Wallin BG. Percutaneous recording of muscle nerve sympathetic activity during propofol, nitrous oxide, and isoflurane anesthesia in humans. Anesthesiology. 1990;73(1):20-7. Kienbaum P, Heuter T, Pavlakovic G, Michel MC, Peters J. S(+)-ketamine increases muscle sympathetic activity and maintains the neural response to hypotensive challenges in humans. Anesthesiology. 2001;94(2):252-8. Gassanov N, Biesenbach E, Caglayan E, Nia A, Fuhr U, Er F. Natriuretic peptides in therapy for decompensated heart failure. Eur J Clin Pharmacol. 2012;68(3):223-30. O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, Heizer GM, Komajda M, Massie BM, McMurray JJ, Nieminen MS, Reist CJ,

Eisenach. J Perioperative Science 2014, 1:4 http://www.perioperative-science.com/content/01/04

Rouleau JL, Swedberg K, Adams KF, Jr., Anker SD, Atar D, Battler A, Botero R, Bohidar NR, Butler J, Clausell N, Corbalan R, Costanzo MR, Dahlstrom U, Deckelbaum LI, Diaz R, Dunlap ME, Ezekowitz JA, Feldman D, Felker GM, Fonarow GC, Gennevois D, Gottlieb SS, Hill JA, Hollander JE, Howlett JG, Hudson MP, Kociol RD, Krum H, Laucevicius A, Levy WC, Mendez GF, Metra M, Mittal S, Oh BH, Pereira NL, Ponikowski P, Tang WH, Tanomsup S, Teerlink JR, Triposkiadis F, Troughton RW, Voors AA, Whellan DJ, Zannad F, Califf RM. Effect of nesiritide in patients with acute decompensated heart failure. N Eng J Med. 2011;365(1):32-43. [47] Guerin L, Monnet X, Teboul JL. Monitoring volume and fluid responsiveness: From static to dynamic indicators. Best Pract Res Clin Anaesthesiol. 2013;27(2):177-85. [48] Guarracino F, Baldassarri R. Transesophageal echocardiography in the OR and ICU. Minerva Anestesiol. 2009;75(9):518-29. [49] Muller L, Louart G, Bengler C, Fabbro-Peray P, Carr J, Ripart J, de La Coussaye JE, Lefrant JY. The intrathoracic blood volume index as an indicator of fluid responsiveness in critically ill patients with acute circulatory failure: a comparison with central venous pressure. Anesth Analg. 2008;107(2):607-13.

Journal of Perioperative Science

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