PROSTHETIC HEART VALVES 201 Figure 4.5 Common types of heart valve prostheses (from top left clockwise): St. Jude \200 \231s Medical bilea \202 et, Starr \200\223Edwards ball and cage, Bjork \200\223Shiley til ting disk, stented porcine prosthesis. Reproduced with permission from Bloom \201 eld P (2 002). Heart 87(6):583 \200\223589. Table 4.4 Class I and II AHA/ACC recommendations for choice of prosthetic valve(cid:13) Recommendations for valve replacement with a mechanical prosthesis Patients with expected long lifespan Patients with a mechanical valve already in place in a different position than the valve being replaced Patients with renal failure on hemodialys is or with hypercalcemia Patients requiring anticoagulation due to risk factors for thrombo embolism \200 Patients <65 years for AVR and <0 years for MVR I I II IIa IIa Recommendations for valve replacement with a bioprosthesis Patients who cannot or will not take warfarin treatment Patients >65 years needing AVR with no risk factors for thromboembolism \200 Patients considered to have possible compliance problems with warfarin Patients > 70 years needing MVR with no risk factors for thromboembo lism \200 Valve replacement for thrombosed mechanical valve I I IIa IIa IIb Reproduced with permission from Bloom \201 eld P (2002). Heart 87(6):583 \200\223589. \200 Risk factors: atrial \201 brillation, severe LV dysfunction, previous thromboemboli sm, hypercoagulable condition. AVR (aortic valve replacement); MVR (mitral valve replacemen t). CHAPTER 4 Valvular heart disease 202 TEE is better at assessing prosthetic mitral valve function than it is for prosthetic aortic valves. MRI is safe for modern mechanical valves, but is expensive and time consuming, therefore reserved for cases when TTE/TEE is inconclusive. Cardiac catheterization This modality can be used to assess valve gradient (and thus valve area). It can quantify the degree of regurgitation. Because there is a risk of passing the catheter across mechanical valves, it is used prior to reoperation or when noninvasive tests are inconclusive. PROSTHETIC HEART VALVES: COMPLICATIONS 203 Prosthetic heart valves: complications Valve thrombosis \200 \200 Incidence: Risks: similar rates for bioprosthetic valves and mechanical valves receiving ad equate anticoagulation. There is no difference in rates between different types of mechanic al valves receiving adequate anticoagulation. Clinical presentation: pulmonary edema, syste mic embolism, sudden death Investigation: decreased intensity of valve sounds, decreased le a \202 et motion on TTE or \202 uoroscopy, and increased valve gradient on TTE Treatment : TTE then anticoagulation may suf \201 ce. If >5 mm, then will need further treatment (th rombolysis, thrombectomy or valve replacement). Prognosis: valve replacement for valve thro mbus has a mortality rate of <15%, thrombolysis has a mortality rate of <10% (with emboliza tion in <20%). Thrombolysis is more effective for aortic valve thrombosis and in recent (<2 week) onset. 0.1% \200\2235.7% per patient-year. inadequate anticoagulation and mitral prostheses. There are \200 anticoagulation with heparin. If thrombus is <5 mm on Systemic embolization The most common manifestation is TIA or stroke. \200 Incidence: year on aspirin, and 1% per patient-year on warfarin. AF, age >70 years, depress ed LV function, mitral prostheses, Risks: ball and cage valves, >1 valve, suboptimal antico agulation, infective endocarditis. 4% per patient-year with no anticoagulation, 2% per patient- Hemolysis A low level of background hemolysis is common in patients with mechani- cal prost heses (even when functioning normally). Severe hemolysis is uncommon and is usually seconda ry to valve dysfunction (paravalvular leak, dehiscence, infection). Hemolysis is uncommon i n tissue prostheses. \200 Investigation: reticulocytosis, schistocytes on peripheral smear. Treatment: needed); give blood transfusion, folic acid, and iron supplementation. anemia, elevated LDH, low serum haptoglobin level, treat underlying problem (including further valve surgery if Endocarditis Prevalence Endocarditis occurs at some point in 3% \200\2236% of patients with prosthetic valves. Risk is greatest <3 months after implantation. Early endocarditis occurs within 60 days of valve surgery and late endo- carditis occurs >60 days since surgery. Early prosthetic valve endocarditis (PVE) usually arises from skin or wound infections or i ndwelling IV catheters and is commonly due to S. aureus, S. epidermidis, gram-negative bact eria, and fungi. Late PVE has similar microbiology to that of native valve endocarditis. Th e risk is similar for tissue and mechanical valves. All patients with prosthetic valves should receive antibiotic prophylaxis during dental procedures. CHAPTER 4 Valvular heart disease 204 Infective endocarditis Epidemiology There are approximately 15,000 new cases diagnosed in the United States annual ly with a male predominance (M:F 2.5:1). Mitral valve prolapse with MR and degenerative aor tic valve disease are the leading predisposing conditions. The incidence of nosocomial and iatrogenic infections is rising due to the increased use of dialysis catheters, permanent pacemakers, and other indwelling central venous catheters (s ee Table 4.5). The mitral valve is most commonly involved, followed by the aortic valve. Right-sided endocarditis, usually tricuspid valve, generally occurs in IV drug users. The m ajority of patients (75%) with infective endocarditis (IE) have underlying structural heart disease. Pathogenesis Valvular endothelium is damaged from local trauma, turbulence or meta- bolic c hanges leading to platelet and \201 brin deposition, which results in nonbacterial thromb otic lesions. These areas are subsequently colonized during an episode of bacteremia result ing from trauma to mucous mem- branes or other colonized tissue. Once colonization of the valve occurs, bacterial division and further platelet/ \201 brin deposition results in a mature vegetation that can lead to valve ring abscess, valve regurg itation, and valve perforation. Staphylococci and streptococci account for most cases (Table 4.6). Vegetations are usually localized downstream from regurgitant \202 ow along lines of valve closure. Both humoral and cellular immunity are stimulated. Symptoms Noncardiac symptoms are constitutional and include malaise, anorexia, weight loss, fever, rigors, and night sweats. Cardiovascular symptoms depend on the valve involved and the sever- ity of valve destructio n and include CHF, syncope, and chest pain from pericarditis or myocardial ischemia. Patients may also have pulmonary symptoms in right-sided endocar- ditis. Embolic phenomena are common (up to 1/3 patients) and may be asymptomatic. Physical exam In addition to nonspeci \201 c \201 ndings associated with systemic infect ion (i.e., fever, tachycardia), the following \201 ndings are unique (see also Table 4.7) : \200 Osler node and toes. They are often multiple and are due to immune complex deposition. Jane way lesions: palms and soles. They are due to peripheral embolization. Splinter hemorrhage nails due to vasculitis or microemboli. Roth spots: are located near the optic disk. : small, painful nodular lesions on the pads of \201 ngers hemorrhagic macular painless plaques seen on the : narrow, reddish-brown lines of blood beneath the oval, pale retinal lesions surrounded by hemorrhage. They INFECTIVE ENDOCARDITIS 205 Table 4.5 Risk factors for infective endocarditis High risk Prosthetic valves Previous bacterial endocarditis Aortic valve disease Mitral regurgitation or mixed mitral disease Cyanotic congenital heart disease Patent ductus arteriosis Uncorre cted L-to-R shunt Intracardiac and systemic-pulmonary shunts MVP with regurgitation or valv e thickening Isolated mitral stenosis Tricuspid valve disease Pulmonic stenosis Hypertrophi c cardiomyopathy Bicuspid aortic valve disease Degenerative valve disease in elderly Mural thrombus (e.g., post-infarction) MVP without regurgitation Tricuspid incompetence without s tructural abnormality Isolated ASD Surgically corrected L-to-R shunt with no residual shunt Calci \201 cation of MV annulus Ischemic heart disease and/or previous CABG Permanent pac emaker Atrial myxoma Moderate risk Low risk Other predisposing factors \200 \200 Arterial prostheses or arteriovenous \201 stulas Recurrent bacteremia (e.g., IV-drug user s, severe periodontal disease, colon carcinoma) Conditions predisposing to infections (e.g. , diabetes, renal failure, alcoholism, immunosuppression) Recent central line In many cases no obvious risk factor is identi \201 ed. Table 4.6 Microbiology of infective endocarditis 40% Streptococci (especially Strep. viridans group) Enterococci Staphylococci S. aureus = coagu lase positive S. epidermidis = coagulase negative Culture negative Gram-negative bacilli Mu ltiple organisms Diptheroids Fungi 10% 30% \200\22340% 5 \200\22310% <1% <1% <1% <1% CHAPTER 4 Valvular heart disease 206 Table 4.7 Extracardiac manifestations in infective endocarditis Central nervous system \200 Cerebral emboli/infarction, arteritis, abscess, mycotic aneurysm, intracerebral hemorrhage, cerebritis/meningitis Kidney \200 Glomerulonephritis, infarcts, abscess Spleen \200 Abscess, infarct Lung \200 Pulmonary emboli, pleural effusion Skin \200 Osler nodes, Janeway lesions, splinter hemorrhages, palatal petechiae Eye \200 Roth spots, conjunctival petechiae Musculoskeletal \200 Mono- or oligoarthritis Patients with signi \201 cant cardiac complications may have rales, S3 (if CHF), pericardi al rub (if abscess, pericarditis), hypotension, tachycardia, altered mental status, decreas ed urine output (if cardiogenic shock), and wide pulse pressure (in severe acute AR). Uniqu e exam \201 ndings may be seen following systemic embolization (i.e., focal neurological de \201 cits). Cardiac complications These occur in up to 50% of patients and include the following: \200 CHF leading cause of death in patients with IE. Perivalvular abscess: S. aureus with increa sed mortality. Aortic valve involvement and IV drug use are risk factors. It may extend int o the septum and cause conduction abnormalities, including AV block. Myocardial infarction: Pericarditis: Hemopericardium/ \201 stulas: of Valsalva. These have a high mortality of > 40%. : due to acute valvular insuf \201 ciency, aortic > mitral. This is the is most common. Abscess is associated \200 \200 rare complication of IE due to coronary emboli associated with myocardial abscess. due to rupture of mycotic aneurysm on sinus Systemic embolization This is a common complication, occurring in one-third of patients. Le ft- sided endocarditis, especially mitral valve, is the most common predispos- ing lesion. Other factors associated with increased risk include vegetation size >10 mm; highly mobile vegetations; S. bovis, S. aureus, and Candida infection; and antiphospholipid antibodies. Anticoagulation is not indicated and may increase the risk of hemor- rhagic stroke and death. INFECTIVE ENDOCARDITIS 207 Diagnosis Diagnosis is based on clinical history and physical exam as well as blood culture and echocardiographic \201 ndings. The modi \201 ed Duke criteria system (Box 4.6) is t he most widely used classi \201 cation scheme and is highly spe- ci \201 c (99%) and sens itive (92%). Echocardiography TTE has a low sensitivity of <50% but a high speci \201 city of 98% for t he diagnosis of infective endocarditis. TEE has a sensitivity of 75% \200\22395% and a spec i \201 city of 85% \200\22398% and is the recommended diagnostic imaging test in patients with prosthetic valves, cases rated at least possible IE by clinical criteria, and patients with complications. TEE is also recommended when the clinical suspicion for IE is high des pite a negative TTE. Box 4.6 Duke criteria De \201 nite endocarditis Direct evidence of endocarditis from his- tological or microbiological \201 ndings from s urgical or autopsy specimens. Clinical diagnosis requires 2 major criteria, 1 major and 3 m inor criteria, or 5 minor criteria. Findings that fall short of de \201 nite endocarditis but are not rejected. Requires 1 major and 1 or 2 minor clinical criteria or 3 minor criter ia Firm alternative diagnosis, or sustained resolution of clinical features with <4 days of antibiotic therapy Possible endocarditis Rejected diagnosis Major criteria \200 Positive blood culture \200 \200 \200 Evidence of endocardial involvement \200 Typical microorganism for IE from two separate blood cultures Persistently positive blood c ulture Single positive blood culture or titer for Q fever Positive echocardiogram. \200\224Oscillating intracardiac mass (vegetation) \200\224Absce ss \200\224New partial dehiscence of prosthetic valve New valve regurgitation Minor criteria \200 \200 \200 Predisposing condition or IV drug use Fever >38 C Vascular phenomena: arterial emboli, sep tic pulmonary infarcts, mycotic aneurysm, intracranial and conjunctival hemorrhage, Janeway lesions Immunological phenomena: glomerulonephritis, Osler \200\231s nodes, Roth spots, rh eumatoid factor Positive blood cultures not meeting major criteria CHAPTER 4 Valvular heart disease 208 Medical therapy Intravenous bactericidal antibiotics are the cornerstone of therapy and sho uld be guided by the suspected organism and local resistance patterns (see Table 4.8). Bloo d culture data, including antibiotic susceptibility and minimum inhibitory concentration, s hould be used to tailor therapy to the causative organisms. Antibiotics are typically continued for 4 \200\2236 weeks. Surveillance blood cultures should be obtained to document clearance of the bacteremia. Indications for surgery \200 \200 \200 \200 \200 Hemodynamic instability (CHF, AV block) Severe valvular insuf \201 ciency Abscess, \201 stulas Fungal endocarditis Other organisms ( Coxiella burnetii) Recurrent emboli Persistent bacteremia despite antibiotics Large, mobile vegetations >10 mm in size Prosthetic valve e ndocarditis if dehiscence, valve obstruction or worsening regurgitation Pseudomonas aeruginosa, Brucella species, \200 \200 \200 Prognosis Overall mortality can be as high as 20% \200\22325% and depends on co-morbid- iti es, the presence of cardiac complications, and the causative organism. S. aureus, fungi, an d gram-negative organisms are associated with higher mortality than that with streptococcal species. Antibiotic prophylaxis during dental procedures Current recommendations (2007 AHA guideline s) for antimicrobial proph- ylaxis for dental and other procedures are limited to cardiac c onditions associated with the highest risk for adverse outcomes from endocarditis: \200 P rosthetic cardiac valve or prosthetic material used for valve repair \200 Previous infect ive endocarditis \200 Congenital heart disease \200 \200 \200 Cardiac transplant re cipients with valvulopathy Dental procedures involving gingival manipulation and respirator y tract procedures involving incision or biopsy require prophylaxis. Unrepaired cyanotic lesions Repaired defects using prosthetic material or devices for 6 mon ths Residual defects following repair \200 Routine prophylaxis is no longer recommended for gastrointestinal or genitourinary procedur es. The primary antibiotic regimen for most patients is amoxicillin, 2 g po 30 \200\22360 m inutes before the procedure. Cephalexin, azithromycin, or clindamycin can be used in penicillin- allergic patients. INFECTIVE ENDOCARDITIS 209 Table 4.8 Antibiotic regimens Penicillin-susceptible streptococci (MIC (cid:100)0.12 g/mL) Penicillin-intermediate susc eptible streptococci (MIC >0.12 g/mL but <0.5 g/mL) Penicillin-susceptible enterococci Penicillin G or ceftriaxone or vancomycin for 4 weeks Either penicillin G or ceftriaxone fo r 4 weeks plus gentamicin for 2 weeks, or monotherapy with vancomycin 4 weeks Gentamicin fo r 4 \200\2236 weeks plus either penicillin G, ampicillin, or vancomycin for 4 \200\2236 wee ks Gentamicin for 6 weeks plus either ampicillin-sulbactam (if B-lactamase producing) or va ncomycin for 6 weeks Penicillin-resistant enterococci Vancomycin/penicillin/ aminoglycoside resistant enterococc i E. faecium Linezolid (cid:116)8 weeks or quinupristin- dalfopristin (cid:116)8 weeks Imipenem/cilastat in plus ampicillin (cid:116)8 weeks or ceftriaxone plus ampicillin (cid:116)8 weeks Nafcill in, oxacillin, or cefazolin for 6 weeks plus gentamicin for 3 \200\2235 days Vancomycin for 6 weeks E. faecalis Oxacillin-susceptible staphylococci Oxacillin-resistant staphylococci HACEK organisms Ceftriaxone, ampicillin-sulbactam, or cipro \202 oxacin for 4 weeks Ampicillin-sulbactam p lus gentamicin for 4 \200\2236 weeks or vancomycin plus gentamicin plus cipro \202 oxacin 4 \200\2236 weeks Culture-negative endocarditis Adapted from AHA Scienti \201 c Statement on Infective Endocarditis, Circulation 2005; 111 (23):3167 \200\2233184. This page intentionally left blank 211 Chapter 5 Heart failure Introduction 212 Forms of heart failure 215 Causes and precipitants 217 Diagnosis and initi al workup 219 Management 222 Diuretics in heart failure 224 ACE inhibitors for heart failur e 226 B-Blockers for heart failure 229 Angiotensin II receptor antagonists for heart failur e 232 Aldosterone receptor antagonists in heart failure 233 Digoxin in heart failure 235 Va sodilators in heart failure 235 Phosphodiesterase inhibitors in heart failure 236 Positive inotropic support 236 Antiplatelet agents and anticoagulants 236 Miscellaneous drugs for he art failure 236 Device therapy for heart failure 237 Surgery for heart failure 238 Palliati ve care for heart failure 240 Worsening heart failure 241 Diastolic heart failure 242 High- output heart failure 244 CHAPTER 5 Heart failure 212 Introduction De \201 nition Heart failure (HF) is a progressive condition with several sta ges as outlined by the ACC/AHA Task Force (stages A \200\223D, see Fig. 5.1). Heart failure can be de \201 ned as a clinical syndrome that results from any structural or func- tiona l abnormality of the heart that impairs the ability of the left ventricle to \201 ll with or to eject blood. It is characterized by dyspnea and/or fatigue on exertion (and occasion ally at rest) and evidence of \202 uid retention that may lead to peripheral edema or pul monary congestion. A clinical response to treatment directed at heart failure alone (e.g., diuretic use) is not suf \201 cient for diagnosis. Epidemiology and prognosis The development of new therapeutic innovations for coronary arte ry disease coupled with an aging population has led to an increase in the prevalence of hea rt failure. There are currently over 5 million cases in the United States and an estimated 23 million people with heart failure world- wide. Nearly one million new cases are diagnose d annually worldwide. The lifetime risk of developing heart failure for all comers over the age of 40 is 20%. The prevalence increases with age, with the mean age of the heart failure population being in their mid-70s. Despite improvement in prognosis in coronary artery disease, the prog- nosis in heart failu re remains poor with over 50% of all patients hospital- ized for the \201 rst time with h eart failure dying within 5 years. Patients with heart failure can die suddenly (as the result of ventricu- lar tachyarrhythmi as) or with worsening heart failure symptoms and \202 uid overload. Pathophysiology The origin of symptoms in heart failure is poorly understood. An initial ev ent (infarction, in \202 ammation, pressure/volume overload) causes myo- cardial damage re sulting in an increase in myocardial wall stress. This is fol- lowed by the activation of m ultiple neuroendocrine systems including the renin \200\223angiotensin \200\223aldosterone system, the sympathetic nervous system, and the release of cytokines such as tumor necrosis factor (TNF). Neuroendocrine activation is also accompanied by structural and metabolic changes in the pe ripheral skeletal muscle and by abnormalities in cardiopulmonary re \202 ex function, such as the barore \202 ex and chemore- \202 ex. These produce further wall stress perpetuat ing this vicious cycle (see Fig. 5.2). At Risk for Heart Failure Heart Failure STAGE A At high risk for HF but without structural heart disease or synmptoms of HF. STAGE D Refractory HF requiring specialized interventions. STAGE B Structural heart disease but without signs or symptoms of HF. STAGE C Structural heart disease with prior or current symptoms of HF. e.g., Patients who have marked symptoms at rest despite maximal medical therapy (e.g., thos e who are recurrently hospitalized or cannot be safely discharged from the hospital without specialized interventions) e.g., Patients with: \200 hypertension \200 atherosclerotic disease \200 obesity \200 metabolic syndrome or Patients \200 using cardiotoxins \200 with FHx CM e.g., Patients with: \200 known structural heart disease and \200 shortness of breath a nd fatigue, reduced exercise tolerance e.g., Patients with: \200 previous MI \200 LV remodeling including LVH and low EF \200 asymptomatic valvular disease Refractory symptoms of HF at rest Structural heart disease Development of symptoms of HF THERAPY THERAPY THERAPY THERAPY GOALS All measures under Stage A and B \200 Dietary salt restriction GOALS \200 Treat hypertensions \200 Encourage smoking cessation \200 Treat lipid diso rders \200 Encourage regular exercise \200 Discourage alcohol intake, illicit drug use \200 Control metabolic syndrome GOALS \200 All measures under Stage A GOALS \200 Appropriate measures under Stages A, B, C \200 Decision re: appropriate leve l of care DRUGS \200 ACEI or ARB in appropriate patients (see text) \200 Beta-blockers in appropr iate patients (see text) DRUGS FOR ROUTINE USE \200 Diuretics for fluid retention \200 ACEI \200 Beta-blockers OPTIONS \200 Compassionate end-of- life care/hospice \200 Extraordinary measures \200 heart transplant \200 chronic inotropes \200 permanent mechanical support \200 exper imental surgery or drugs DRUGS IN SELECTED PATIENTS DEVICES IN SELECTED PATIENTS \200 Implantable defibrillators Aldosterone antagonist \200 ARBs \200 Digitalis \200 Hydralazine/nitrates DRUGS I N T R O D U C T O N ACEI or ARB in appropriate patients (see text) for vascular disease or diabetes DRUGS IN SELECTED PATIENTS Biventricular pacing \200 Implantable defibrillators Figure 5.1 Stages of heart failure. ACE-I, angiotensin-converting enzyme inhibitor; ARB, an giotensin receptor blocker; HF, heart failure. Reprinted with permission from the ACC/AHA G uidelines 2005. Circulation 2005; 112:e154 \200\223e235. 2005, American Heart Association , Inc. I 2 1 3 CHAPTER 5 Heart failure 214 d Stroke volume d Arterial perfusion Neuroendocrine activation Starling effect i Wall stress Remodeling Compensated Normalized wall stress Restoration of stroke volume Limited volume/shape change Limited d in LVEF Non-compensated Persistent in i wall stress Persistent neuroendocrine activation ii LV volu me dd LVEF HEART FAILURE Figure 5.2 Pathophysiology of heart failure. FORMS OF HEART FAILURE 215 Forms of heart failure Acute vs. chronic heart failure The clinical manifestations depend on the speed with which the syndrome develops. Acute heart failure is often used to describe the patient with acute -onset dyspnea and pulmonary edema, but it can also apply to cardio- genic shock where the patient is hypotensive and oliguric. Compensatory mechanisms have not yet become operative. Acute deterioration may be a consequence of myocardial infarction (MI), arrhythmia, or acute valve dysfunction (e.g., endocarditis). Systolic vs. diastolic heart failure Most patients with heart failure have impaired LV syst olic function: there is a failure of the LV to eject blood. However, there is a group of patients with signs and symptoms of heart failure but apparent ly preserved LV systolic function. These patients are said to have diastolic heart failure: there is an abnormality in the ability of the LV to \201 ll in diastole. This may be tra nsient (e.g., acute ischemia) or persistent (restrictive or in \201 ltrative cardiomyopath y, or LVH). Right vs. left heart failure Right and left heart failure refers to whether the patient has either pre- dominantly systemic venous congestion (swollen ankles, hepatome- galy) or pulm onary venous congestion (pulmonary edema), respectively. These terms do not necessarily ind icate which ventricle is most seriously affected. Fluid retention in heart failure is due to a combination of factors: reduced GFR (glomerula r \201 ltration rate) and activation of the renin \200\223angiotensin \200\223 aldosteron e system and sympathetic system. However, there are causes for swollen ankles other than he art failure (gravitational disorder, e.g., immo- bility; venous thrombosis or obstruction; varicose veins; hypoproteinemia, e.g., nephrotic syndrome or liver disease; or lymphatic ob struction; see also Box 5.1). High-output vs. low-output heart failure A variety of high-output states may lead to heart failure, e.g., thyrotoxico- sis, Paget \200\231s disease, beriberi, and anemia. High-output failure is character- ized by warm extremities and normal or widened pulse pressure. In contrast, low-output states are characterized by cool, pale extremi- ties, cyanosis due to systemic vasoconstriction, and low pulse volume. The mixed venous oxygen saturation (a marker of the ability of the heart to deliver oxygen to the metabolizing tissues) is typically abnormally low in low-output states but normal or even high in high-output states. CHAPTER 5 Heart failure 216 Box 5.1 Conditions mimicking heart failure \200 \200 \200 \200 \200 Intrinsic renal disease Intrinsic hepatic disease Pulmonary embolic disease Depression and/ or anxiety disorders Severe anemia Thyroid disease Bilateral renal artery stenosis Obesity Chest disease, including lung, diaphragm, or chest wall Venous insuf \201 ciency i n lower limbs Drug-induced ankle swelling (e.g., dihydropyridine calcium blockers) Drug-ind uced \202 uid retention (e.g., NSAIDs) Hypoalbuminemia \200 \200 \200 CAUSES AND PRECIPITANTS 217 Causes and precipitants In all patients with heart failure it is important to carefully con sider the underlying etiology, as there may be speci \201 c exacerbating factors or other diseases that in \202 uence the patients \200\231 management. A nonexhaustive list is give n in Box 5.2. Patients with compensated heart failure have a high rate of readmission to hospital with ac ute exacerbations. A number of studies have demon- strated that a precipitating cause for e mergency admission to the hospital with heart failure can be identi \201 ed in up to two-t hirds of patients. \200 Inappropriate reduction in therapy: withdrawal of diuretics, ACE-I, digoxin, and dietary ex cess of salt are recognized precipitants. Education of the patient and family is important. Cardiac arrhythmias: will further reduce LV \201 lling and stroke volume, and may exacer bate ischemia. Marked bradycardia reduces cardiac output especially if stroke volume cannot increase any further. Myocardial ischemia or infarction worsen mitral regurgitation due to ischemia of papillary muscles. Infection: systemic infection can precipitate heart failure through a combination of factors, including direct myocardial depression from in \202 amm atory cytokines, sinus tachycardia, and fever. Anemia: failure and may exacerbate underlyin g ischemia. Concomitant drug therapy: function (e.g., calcium antagonists \200\224verapamil , diltiazem; many antiarrhythmics, anesthetics, overenthusiastic initiation of B-blockers, etc.) as well as drugs causing salt and water retention (e.g., NSAIDs, estrogens, steroids, COX-2 antagonists) may precipitate heart failure. Alcohol: function and predispose to arrh ythmias. Pulmonary embolism: low-output state and atrial \201 brillation. self-discontinuation or iatrogenic most commonly AF, but any tachyarrhythmia exacerbates LV dysfunction and may respiratory infections are a common precipitant, but any this causes a high-output state that may precipitate acute heart drugs that directly depress myocardial this is directly toxic and in excess can depress myocardial the risk increases in the immobile patient with It is very important to look for precipitating causes in all patients with heart failure (s ee Table 5.1). Once the precipitant has been identi \201 ed and treated, appropriate measu res (patient and family education, adjustment of therapy) should be put into place to preve nt recurrence. CHAPTER 5 Heart failure 218 Box 5.2 Etiology of heart failure \200 \200 \200 \200 \200 \200 \200 \200 \200 Hemachromatosis Familial In \201 ltration (amyloid/sarcoid) Valve disease Postpartum Chemo therapy Radiotherapy Infections (Chagas disease) Nutritional (beriberi) Ischemic heart disease (most common cause in developed world) Dilated cardiomyopathy Post v iral Alcohol Hypothyroidism Hypertension \200 \200 \200 \200 Table 5.1 Population-attributable risk of heart failure related to various risk factors* Risk factor Attributable risk (%) Coronary disease 61.6 Cigarette smoking 17.1 Hypertension 10.1 Physical inactivity 9.2 Male sex 8.9 Less than high school education 8.9 Overweight 8.0 Diabetes 3.1 Valvular heart disease 2.2 Reproduced with permission from He J, Ogden LG, Bazzano LA, et al. (2001). Arch Intern Med 161:996. Copyright 2001 American Medical Association. All rights reserved. DIAGNOSIS AND INITIAL WORKUP 219 Diagnosis and initial workup Signs and symptoms The diagnosis of heart failure is a clinica l diagnosis, using the history, phys- ical exam, chest X-ray (CXR) and other diagnostic tes ts (i.e., transthoracic echocardiogram [TTE]) to make the diagnosis. Box 5.3 provides a lis t of some of the most common signs and symptoms of heart failure. Symptoms alone can be used to classify the severity of congestive heart failure (CHF) and t o monitor the effect of treatment. The New York Heart Association classi \201 cation (NYHA ) is widely used (Table 5.2). Investigations for all patients with heart failure (see Fig. 5.3) ECG Although there are no speci \201 c changes in CHF, a completely normal ECG should encourage you to reconsider t he diagnosis. Look for AF or other tachy- or bradyarrhythmias, conduction system defects, e vidence of previ- ous MI, or ongoing ischemia. CXR See Figure 5.4. A normal CXR and ECG make the diagnosis of heart failure very unlikely. Echocardiogram This is the key investigation in patients with heart failure. It is used to evaluate resting LV size and function and to rule out valvular heart disease, pericardial d isease and myocardial diseases. Absolute values for ejection fraction do not necessarily re \202 ect the clinical severity of heart failure. Box 5.3 Common signs and symptoms of heart failure \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Hepatomegaly Peripheral edema Chest pain Cachexia Sleep apnea Dyspnea (exertion or at rest) Fatigue Paroxysmal nocturnal dyspnea Orthopnea Palpitations R aised JVP Third heart sound Table 5.2 NYHA classi \201 cation of heart failure Class I No limitation of physical activity Class II Slight limitation of physical activity \200\224symptoms with ordinary levels of exertion (e .g., walking up stairs) Class III Marked limitation of physical activity \200\224symptoms with minimal levels of exertion (e. g., dressing) Class IV Symptoms at rest CHAPTER 5 Heart failure 220 Suspected heart failure because of history, symptoms, and signs. Seek to exclude heart failure Other recommended tests: (mostly to exclude other conditions) through: 12 lead ECG \200 and/or natriuretic peptides (BNP or NT proBNP) \200\223where available. chest X-ray \200 blood tests: U&ES, creatinine, FBC, RFTs, LFTs, glucose, and lipids \200 urinalysis, peak flow or spirometry One or more abnormal Both normal Heart failure unlikely, Consider alternative diagnosis, Imaging by echocardiography* Abnormal Assess HF severity, etiology, precipitating and exacerbating factors and type of c ardiac dysfunction. Correctable causes must be identified. Consider referral. No abnormality detected Heart failure unlikely, but if diagnostic doubt persists consider d iastolic dysfunction and consider referral for specialist assessment. Figure 5.3 Algorithm summarizing recommendations for the diagnosis of heart failure. Altern ative methods of imaging the heart should be considered when a poor image is produced by tr ansthoracic Doppler 2D echocardiography. Alternatives include transesophageal echocardi- og raphy (TEE), radionuclide imaging, or cardiac magnetic resonance imaging. BNP, B-type natri - uretic peptide; ECG, electrocardiogram; CBC, complete blood count; LFTs, liver function t ests; NTproBNP, N-terminal pro-B-type natriuretic peptide; TFTs, thyroid function tests; U& Es, urea and electrolytes. (a) (b) Figure 5.4 CXR \201 ndings in heart failure. (a) There is cardiomegaly with prominent upp er lobe vessels and alveolar edema ( \200\234bat \200\231s wing shadowing \200\235). (b) Ma gni \201 cation of right costophrenic angle showing septal lines (Kerley B lines) due to i nterstitial edema. DIAGNOSIS AND INITIAL WORKUP 221 Blood tests These may alert you to possible underlying etiologies for heart failure as well as establishing a baseline prior to initiation of therapy. \200 CBC (anemia), Chem7, glucose, liver function tests (LFTs), thyroid function tests (TFTs) (h ypo- or hyperthyroidism), uric acid BNP has a high negative predictive value if <100 pg/mL. Investigations for selected patients with heart failure \200 \200 \200 \200 Ferritin Immunoglobulins and protein electrophoresis Viral titers BNP: serum levels of natr iuretic peptides are frequently elevated in patients with impaired LV function. They appear to have a useful role in identifying patients who merit more extensive investigation of ca rdiac function. Coronary angiography Holter monitoring ( QT dispersion, heart rate variab ility) Cardiopulmonary exercise testing or 6-minute walk test Pulmonary function tests Radi onuclide ventriculography Stress imaging (for assessment of viable/hibernating myocardium) Cardiac magnetic resonance \200 \200 \200 \200 \200 \200 By using these signs and symptoms as well as initial basic diagnostic tests, one can make t he diagnosis of heart failure with reasonable certainty (see Table 5.3). Table 5.3 Framingham criteria for diagnosis of heart failure* Major criteria \200 \200 \200 \200 \200 \200 \200 Paroxysmal nocturnal dyspnea Raised JVP; distended neck veins Crackles in lung \201 elds Cardiomegaly on CXR Acute pulmonary edema S3 gallop rhythm Hepatojugular re \202 ux Weight loss >4.5 kg in 5 days in response to tre atment of heart failure Minor criteria \200 \200 \200 \200 \200 \200 Bilateral ankle edema Nocturnal cough Dyspnea on ordinary exertion Hepatomegaly Pleural effusion Tachycardia rate >120/min Decrease in vital capacity by one-third This table was published in Ho KL (1993). The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol, 22(Suppl A):6A. Copyright Elsevier 1993. CHAPTER 5 Heart failure 222 Management Management outline \200 \200 Establish that the patient has heart failure. Ascertain severity of symptoms and presenting features: pulmonary edema, exertional breathlessness, fatigue, peripheral edema. Try to de termine the etiology of heart failure. Identify precipitating and exacerbating factors and any concomitant diseases relevant to heart failure and its management. Estimate prognosis. Anticipate complications. Counsel the patient and relatives. Choose appropriate management (e.g., see Fig. 5.5). Monitor progress and manage accordingly. \200 \200 \200 \200 \200 Aims of treatment 1. Prevention of heart failure \200 Prevention and/or controlling of diseases leading to cardiac dysfunction and heart failure Prevention of progression to heart failure once cardiac dysfunction is established 2. Maintenance or improvement in quality of life 3. Increased duration of life It is always better to try and prevent heart failure than to treat it once it has developed. This includes management of risk factors for ischemic heart disease, treatment of ischemia and revascularization where appro- priate, early reperfusio n therapy for acute MI, aggressive management of hypertension, and management of diabetes a nd valvular heart disease. Stop exacerbating drugs if possible (NSAIDs, steroids, negative inotropes). Education of the patient and relatives is an important aspect of manage- ment of patients w ith heart failure. Many hospitals now employ heart fail- ure specialist nurses who are able to provide excellent service and should be used whenever possible. Formal cardiac rehabili tation classes may be bene \201 cial. It is important to explain the diagnosis and symptom s, how the treatment will help, the role of self-weighing, and the importance of exer- cise . Mild to moderate aerobic exercise can increase functional capacity in these patients. General measures include restriction of dietary salt and water intake, smoking cessation, r educing alcohol intake (stopping completely if alcohol is implicated in the etiology of HF) , addressing obesity with a weight- reducing program, and vaccinations (Pneumovax once and in \202 uenza yearly). Patients should also be counseled about their drug therapy. The desired effects and potenti al side effects need to be explained, as well as the fact that while effects may take some time to become apparent, it is import- ant to stay adherent to the therapy. Self-management of diuretics may be appropriate for some patients. Patients also need to be aware of drug interactions (e.g., with over-the-counter NSAIDs). MANAGEMENT 223 Generalist New diagnosis Add Diuretic Diuretic therapy is likely to be required to control congestive symptoms and f luid retention Add Digoxin If a patient is sinus rhythm remains symptomatic despite therapy with a diuretic, ACE inhibitor (or angiotensin-II receptor antagonist) and B-blocker, OR i f a patient is in atrial fibriallation then use as first line therapy Or if ACE inhibitor not tolerated (e.g., due to severe cough) Consider angiotensin-II recep tor antagonist Start ACE inhibitor and titrate upward t u p n Add B-blocker and titrate upward i t s i l a i c e p S Add spironolactone If patient remains moderately to severely symptomatic despite optimal dr ug therapy listed above Specialist Seek specialist advice for further options Figure 5.5 Seeking a specialist opinion for patients with heart failure. Reproduced with pe rmission from NICE guidelines. www.nice.org.uk CHAPTER 5 Heart failure 224 Diuretics in heart failure Diuretics are used for the symptomatic treatment of \202 uid o verload (either pulmonary congestion or peripheral edema). With the exception of aldos- ter one antagonists, there are no randomized, controlled trials that have shown any prognostic bene \201 t. However, they do improve symptoms and may slow the progression of LV remodeli ng.