53314 Chronic Bundle Branch Block Chronic Coronary Artery Disease (CAD)complications and prognosis■ Progression of bifascicular block to complete heart block: slow.■ Syncope in the presence of bifascicular block: increased incidenceof sudden cardiac death.CHRONIC CORONARY ARTERY DISEASE (CAD)JOEL S. KARLINER, MDhistory & physicalHistory■ Risk factors: hypertension, abnormal lipids, smoking, diabetes, priorMI, revascularization, obesity, family history■ Associations: peripheral vascular and cerebral vascular disease,chronic renal disease, especially dialysis■ Complaint: chest discomfort with exertion, and/or at rest (mixedangina)■ Squeezing,burning,substernal.Canradiate tothroat,jaws, shoulder,arm (usually left), back■ Emotion (anger) also a cause■ Anginal equivalent: exertional dyspnea due to LV ischemiaSigns & Symptoms■ May be normal. Hypertension common.■ Signs of valvular heart disease (e.g., aortic stenosis)■ Mitral insufﬁciency usually secondary■ Signs of CHF (see CHF chapter)tests■ Basic blood tests➣Hct, Hgb, smear (R/O anemia)➣Lipid and renal panels➣Glucose, Hgb A1C■ Basic test➣resting ECG■ Specific Diagnostic Tests➣Treadmill exercise test: alone or with imaging➣If pt unable to walk, do pharmacologic imaging test (e.g., dobu-tamine echocardiography, persantine-thallium study).➣Gold standard: coronary angiography
3Chronic Coronary Artery Disease (CAD) 315differential diagnosis■ Non-cardiac:➣Gastroesophageal reﬂux: do EGD➣Chest wall pain: may be apparent on physical exam.➣Cervical spondylitis: do x-ray or MRI■ Cardiac:➣Pericarditis (especially after CABG): do ECG and echo.➣Tachyarrhythmias: 24-h Holter monitor; event monitor➣Substance abuse, especially cocaine: toxicology screenmanagementWhat to Do First■ Resting ECG■ Exercisetestwith or without scintigraphy;pharmacologic stressechoor scintigram■ If younger with convincing history, coronary angiography may beindicated without stress testGeneral Measures■ Dietary counseling: reduce fat intake, weight loss■ Discontinue tobacco; may need group Rx■ Exercise prescription■ Optimal diabetes controlspeciﬁc therapy■ Indication for following is diagnosis of chronic CAD:➣ASA➣Statin, ﬁbrate, and/or niacin depending on lipid proﬁle➣Prophylactic and therapeutic sublingual nitroglycerin➣Beta-blocker Rx➣Optimal BP control with additional medications as necessary(long-acting dihydropyridine calcium channel antagonist, ACEinhibitor, hydrochlorothiazide, angiotensin II antagonist, cloni-dine [oral or patch])➣If ACE inhibitor not necessary for BP control, add low-dose ACEinhibitor for cardiac and renal protection, especially in patientswith left ventricular dysfunction. Patients with normal left ven-tricular function may not beneﬁt.➣Long-acting nitrates➣Hormone replacement therapy: controversial. May have adversecardiovascular effects. Use only for serious menopausal symp-toms, not for prevention of heart attack or stroke.
3316 Chronic Coronary Artery Disease (CAD)➣Revascularization if symptoms not controlled or patient has pro-gressive symptoms despite optimal Rx and is not febrile, anemic,or thyrotoxic, and is compliant with mediations (see ACS chap-ter).rDrug eluting stent, bare metal stent, or balloon angioplasty(see ACS chapter)rCoronary bypass surgerySide Effects & Complications■ ASA: bleeding, allergy■ Statin, ﬁbrate: abnormal LFTs; rhabdomyolysis■ Niacin: abnormal LFTs; glucose intolerance■ NTG and long-acting nitrates: headaches; nitrate tolerance; hypo-tension■ Beta-blockade: bradycardia, hypotension, fatigue, decreased libidoand cognition; exacerbation of asthma; decreased LV function anddiabetes are not contraindications■ Calcium antagonists: bradycardia (except dihydropyridines); ortho-static hypotension; amlodipine OK in CHF; short-acting prepara-tions contraindicated■ ACE inhibitors: renal dysfunction; hyperkalemia; cough■ Hydrochlorothiazide: worsening diabetes, gout, renal insufﬁciency,hypokalemia■ Angiotensin II receptor antagonists: renal dysfunction; hyper-kalemia■ Clonidine: bradycardia, fatigue, decreased congnition■ Hormone replacement therapy: higher morbidity and mortality vs.control in pts when started long after menopause. Long-term beneﬁtnot proved if started at time of menopause(see above).■ Angioplasty/stent: Acute MI. Restenosis with recurrent angina (usu-ally in ﬁrst 6 months, more likely in diabetics; incidence less withdrug eluting stents and clopidogrel Rx)■ Coronary bypass surgery: Acute: arrhythmias, bleeding, pericarditis,MI, stroke. Chronic: graft occlusion (usually venous graft); dimin-ished cognition.■ Avoid COX-2 inhibitors unless arthritic symptoms are otherwise notcontrollable; if used, employ lowest possible dose for shortest pos-sible time.follow-up■ History at each visit regarding stability of symptoms,➣compliance with medications and lifestyle changes
3Chronic Coronary Artery Disease (CAD) Chronic Granulomatous Disease 317■ Vital signs to assure optimal heart rate and BP control■ Yearly renal panel in diabetes■ Yearly lipid panel in all patients■ Exercise test every 1–3 years depending on symptoms.complications and prognosis■ Chronic stable angina by itself: good prognosis■ Prognosis worse with increasing age, diabetes, prior MI withdecreased LV function, multivessel disease, poorly controlled BP,continued smoking, female gender, renal failure, noncompliancewith medications, and progressive symptoms despite optimal med-ical managementCHRONIC GRANULOMATOUS DISEASENANCY BERLINER, MDhistory & physical■ Severe bacterial and fungal infections from early childhood■ Family history of the disorder: usually X-linked, but autosomal reces-sive inheritance also occurs■ Examine for evidence of infection. Most common infections: pneu-monia, lymphadenitis, cutaneous infections, hepatic abscesses,osteomyelitis, aphthous ulcers, perirectal abscessestests■ Diagnosis conﬁrmed by tests of neutrophil oxidative metabolism:nitroblue tetrazolium (NBT) slide test or measurements of superox-ide or peroxide production.differential diagnosis■ Heterogeneous group of rare disorders■ Defective production of superoxide (O2−) by neutrophils, mono-cytes, and eosinophils■ Caused by mutations in any of four genes encoding the respiratoryburst oxidase.■ Also evaluate for other immunodeﬁciency syndromes and neutro-phil functional defectsmanagement■ Aggressive prophylaxis with prophylactic trimethoprim-sulfame-thoxazole or dicloxacillin
3318 Chronic Granulomatous Disease Chronic Heart Failure■ Prompt treatment of infection with parenteral antibiotics■ Surgical interventions including drainage of abscesses and resectionof infected tissuespeciﬁc therapy■ Prophylaxis with interferon-gamma helps decreases infections insome patients■ Stem cell transplantation➣A potential target for gene therapyfollow-upn/acomplications and prognosis■ Life-threatening infections shorten life expectancyCHRONIC HEART FAILUREJOHN R. TEERLINK, MDhistory & physicalHistory■ Prior/current evidence of coronary artery disease (and related riskfactors, such as smoking, dyslipidemias, etc.), valvular disease, con-genital heart disease, hypertension, myocarditis, thyroid disease,alcohol or other cardiotoxic (cocaine, anthracyclines) ingestion orexposure, inﬁltrative disease (amyloid, hemochromatosis, etc.)■ Family h/o cardiomyopathy, myocardial infarction■ Progressive increase in weight, peripheral edema, bloating, dyspnea■ Relatively gradual onset of symptoms■ Episodic symptoms suggestive of underlying ischemia■ Exacerbations often preceded by:➣Excessive salt and/or ﬂuid intake➣Changes in therapy (or non-compliance)➣Excessive activity➣Progression of disease➣Other precipitating causes (arrhythmias, infection, pulmonaryemboli)Signs & Symptoms■ Dyspnea: exertional, orthopnea, paroxysmal nocturnal, “cardiacasthma”
3Chronic Heart Failure 319■ Chronic non-productive cough■ Reduced exercise capacity■ Generalized weakness and fatigue■ Nocturia, oliguria■ Confusion, poor memory, insomnia, anxiety, headache, delirium■ Nausea, abdominal discomfort, anorexia, right upper quadrant pain■ Consistent with underlying or inciting pathophysiology■ General: distressed, dyspnea, pallor, diaphoresis, cachexia, jaundice(acute hepatic congestion)■ Vital signs: tachycardia (usually), hypotension or hypertension, nar-row pulse pressure, tachypnea, diaphoresis, low grade fever.■ Respiratory: rales, pleural effusion, Cheyne-Stokes respiration pat-tern■ CV: jugular venous distension, hepatojugular reﬂux, pulsus alter-nans (indicates severe LV dysfunction), cardiomegaly, LV heave, RVlift, loud P2, S3, S4, systolic murmur (functional MR/TR)■ Abd: hepatomegaly, ascites■ Extrem: peripheral edema, cool/ poorly perfusedtests■ Basic Blood Tests➣Usually normal, except for other comorbidities➣Electrolytes: Hyponatremia (dilutional), secondary hyperal-dosteronism, Hypokalemia (diuretic use), hypophosphatemia,hypomagnesemia (diuretics, alcohol)➣BUN/creatinine: Prerenal azotemia➣BNP (B-type natriuretic peptide) or nt-pro-BNP: suggestiveof elevated cardiac ﬁlling pressures or ventricular wall stress;usually only used for acute exacerbations; may be elevatedin right-sided heart failure (i.e., cor pulmonale, pulmonaryembolus)➣Cardiac enzymes: elevated troponins or CK-MB (myocardialinjury)➣Liver function tests: AST, ALT, LDH, direct and indirect bilirubinelevated in congestive hepatopathy➣TSH: hypo- or hyperthyroidism■ Basic Urine Tests➣Proteinuria, high speciﬁc gravity, acellular casts■ Speciﬁc Diagnostic Tests➣Chest X-ray: cardiomegaly (size and shape can assist withdx); pulmonary vascular redistribution, interstitial pulmonary
3320 Chronic Heart Failureedema (Kerley B lines, perivascular, subpleural effusion), alveo-lar edema (“butterﬂy pattern”)➣Electrocardiogram: ischemia/infarction; evidence of LVH, priorMI➣Echocardiogram(2-D with Doppler ﬂow study): single most use-ful diagnostic test; cardiac function, structure, wall motion andvalvular abnormalities■ Other Tests as Appropriate➣Radionuclide ventriculogram (RVG; MUGA): cardiac function,wall motion abnormalities➣Exercise or pharmacologic stress testing: assess myocardialischemia risk➣Cardiac catheterization: deﬁne coronary anatomy, possibleinterventions;➣Good distal targets, absent scintigraphic perfusion + radioactiveglucose uptake in “dead” region = hibernating myocardium;good response to revascularization likely.differential diagnosis■ Abnormal ventricular or atrial rhythm■ Chronic pulmonary emboli■ Chronic obstructive pulmonary disease■ Pneumonia■ Sepsis■ Cardiogenic shockmanagement[also see Heart Failure Society Of America. Executive summary: HFSA2006 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2006Feb;12(1):10–38; Hunt SA, et al. ACC/AHA 2005 guideline update for thediagnosis and management of chronic heart failure in the adult: a reportoftheAmericanCollegeof Cardiology/AmericanHeartAssociationTaskForce on Practice Guidelines (Writing Committee to Update the 2001Guidelines for the Evaluation and Management of Heart Failure). J AmColl Cardiol. 2005 Sep 20;46(6):e1–82; and Swedberg K, et al. Guidelinesfor the diagnosis and treatment of chronic heart failure: executive sum-mary (update 2005): The Task Force for the Diagnosis and Treatment ofChronic Heart Failure of the European Society of Cardiology. Eur HeartJ. 2005 Jun;26(11):1115–40.]What to Do First■ Identify nature and severity of cardiac abnormality: combine historyand physical examination with echocardiographic and other diag-nostic studies, as necessary
3Chronic Heart Failure 321■ Assess nature and degree of patient’s functional limitation, NYHAClass (a dynamic scale)➣I: no limitation of physical activity, no symptoms with ordinaryphysical activity➣II: slight limitation of physical activity, comfortable at rest, symp-tomatic with ordinary activity➣III: marked limitation of physical activity, comfortable at rest,symptomatic with less than ordinary activity➣IV: inability to perform physical activity without discomfort,symptoms may be present at rest■ Assess ACC/AHA clinical stage of heart failure (a one-way scale)➣A: High risk for developing heart failure without current struc-tural heart disease or symptoms of heart failure (i.e., patientswith hypertension, atherosclerosis, diabetes, obesity, metabolicsyndrome, etc.)➣B: Structural heart disease without signs or symptoms of heartfailure (prior myocardial infarction, left ventricular hypertrophyor enlargement, reduced ejection fraction, valvular disease)➣C: Structural heart disease with prior or current signs or symp-toms of heart failure (known structural heart disease and dysp-nea, exercise intolerance, etc.)➣D: Refractory heart failure requiring specialized interventions(marked symptoms at rest despite maximal therapy)■ Assess presence and severity of ﬂuid retention: body weight (maydecrease long-term solely due to cardiac cachexia), physical exam-ination, especially jugular venous distention, hepatojugular reﬂux,rales, hepatomegaly, edemaGeneral Measures■ Prevent development of heart failure:➣Control coronary risk factors (smoking, hyperlipidemia, hyper-tension, weight reduction in obese patients, diabetes)➣Discontinue alcohol use➣In acute MI patients, limit MI size with reperfusion (thrombolyt-ics, PTCA) and adverse ventricular remodeling/neurohormonalactivation (ACE inhibitors, beta blockers, aldosterone antago-nists, ARB)➣Inpatients with asymptomatic LV dysfunction, limit adverseven-tricular remodeling/neurohormonal activation (ACE inhibitors[ARB if intolerant to ACE inhibitor], beta blockers)■ Correct reversible causes: valvular, ischemia, arrhythmia, alcoholor drug use, high output states, cardiac shunts, drugs that cause/
3322 Chronic Heart Failureexacerbate heart failure (NSAIDs, calcium channel blockers, anti-arrhythmics), treat hemochromatosis, sarcoidosis, amyloidosis,pericardial disease hypertension■ Maintain ﬂuid balance:➣Restrict salt intake (≤3 g salt/d)➣Daily weights (same time of day, post-voiding, nude)■ Improvephysicalconditioning: encourage moderatedegrees ofexer-cise to prevent/reverse deconditioning■ Speciﬁc measures➣Control ventricular response in atrial ﬁbrillation or other SVT➣Anti-coagulation in atrial ﬁbrillation or previous embolic event➣Coronary revascularization in patients with angina or if survivalbeneﬁt anticipated■ Avoid certain medications➣Anti-arrhythmic agents to suppress asymptomatic ventriculararrhythmias➣Most calcium channel blockers➣Nonsteroidal anti-inﬂammatory drugs■ Other general measures include inﬂuenza and pneumococcal vac-cination, close outpatient surveillancespeciﬁc therapyTreatment Options, including Side Effects and Contraindications: Gen-eral information on drug classes, check for more complete prescrib-ing information, see also Chapter on Hypertension and Acute HeartFailure■ Approved Therapies:■ Diuretics: thiazides (hydrochlorothiazide), loop diuretics (furo-semide, torsemide, bumetanide), metolazone, potassium-sparing.If patient–properly instructed and motivated, may use a prn dosefor transient increases in body weight.➣Indication: Volume overload, reduce preload. Thiazides or meto-lazone alone in mild ﬂuid retention, loop diuretics in mostpatients (mild-severe); metolazone and loop diuretic in severecases. Rapidly improve symptoms.➣SideEffectsand Complications:renalfailure,thrombocytopenia,orthostatic hypotension, dizziness, dry mouth, headache, nau-sea/vomiting, dyspepsia, impotence, rash, hypokalemia, musclecramps, ototoxicity.➣Absolute Contraindications: hepatic coma➣Relative Contraindications: anuria, severe electrolyte depletion
3Chronic Heart Failure 323■ ACE inhibitors: Improve morbidity and mortality. Captopril, enal-april, lisinopril, quinapril, fosinopril (ramipril for heart failure afteracute MI) FDA approved; full symptomatic improvement may takeweeks to months➣Indication: Left ventricular dysfunction (asymptomatic or symp-tomatic), heart failure➣Side effects: Hyperkalemia (especially with Type IV RTA), hypo-tension, chronic dry cough (causes ∼5% to discontinue inblinded trials; should rechallenge later to establish diagnosis),angioedema, dizziness, skin rash, dysgusia (captopril; often re-solves spontaneously)➣Absolute Contraindications: Any prior angioedema, pregnancy,hyperkalemia, renovascular disease➣Relative Contraindications: Renal failure (although ACEinhibitors may improve renal dysfunction), volume depletion■ Beta-blockers: improve morbidity and mortality, may improve dis-ease progression independent of symptoms; agents with beneﬁcialresults in large clinical trials include carvedilol, metoprolol succi-nate, bisoprolol. “Start low, go slow” titration. Advise patients of pos-sible early side effects which do not generally prevent long-time use.Symptomatic improvement may take months.➣Indication:Heartfailuredue to systolicdysfunction(stable NYHAclass II–IV)➣Side effects: hypotension, ﬂuid retention and worsening ofheart failure, bradycardia and heart block, worsens bron-chospasm, CNS symptoms (depression,nightmares, excitement,confusion), fatigue, lethargy, impotence, increase triglycerides(depression of HDL).➣Absolute Contraindications: Severe peripheral vascular disease,severe bronchospastic disease, sick sinus syndrome or advancedheart block (unless treated with pacemaker), unstable NYHA IVCHF.➣Relative Contraindications: Types I and II diabetes, depression,dyslipidemia, peripheral vascular disease.■ Digoxin: improves symptoms, minimal effect on survival; use inconjunction with diuretics, ACE inhibitor, and beta blockers; dose-adjustment required for many medications; serum levels not usefulin guiding therapy. Side effects may occur at any level, though morefrequent >2 ng/mL and in elderly.➣Indication: Heart failure due to systolic dysfunction (NYHA classII–IV) for symptom improvement
3324 Chronic Heart Failure➣Side effects: cardiac arrhythmias (ectopic and reentrant tachy-cardias), bradycardia and heart block, anorexia, nausea, vomit-ing, visual disturbances (“yellow halo”), disorientation, con-fusion, hypotension, ﬂuid retention and worsening of heartfailure, worsens bronchospasm, CNS symptoms (depression, ni-ghtmares, excitement, confusion), fatigue, lethargy, impotence,increase triglycerides (depression of HDL).➣Absolute Contraindications: Ventricular ﬁbrillation, ventriculartachycardia, signiﬁcant AV block, anuria.➣Relative Contraindications: Renal failure■ Angiotensin II receptor blockers: Candesartan and valsartan FDAapproved for heart failure treatment. Use in addition to optimalstandard therapy (ACE inhibitor, beta blocker) or substitute forACE inhibitor in patients who are ACE inhibitor intolerant due tocough or angioedema (ARB may also cause angioedema). Improvesmorbidity; in patients unable to take ACE inhibitor, improves mor-tality.➣Indications:Heart failureduetosystolicdysfunction(NYHAclassII–IV) for symptom improvement, as add-on to standard care orreplace ACE inhibitor (IF ACE intolerant)➣Side Effects and Complications: Hyperkalemia (especially withType IV RTA), hypotension, angioedema (less frequent than ACEinhibitor), dizziness, skin rash (less frequent than ACE inhibitor),hepatotoxicity➣Absolute Contraindications: Any prior angioedema, pregnancy,hyperkalemia, renovascular disease➣Relative Contraindications: Renal failure, volume depletion■ Aldosterone antagonists: spironolactone, eplerenone (FDA ap-proved for post-myocardial heart failure), neurohormonal antag-onist, weak potassium-sparing diuretic. Improves morbidity andmortality in advanced heart failure patients (spironolactone) and inpost-myocardialinfarction heart failure patients (eplerenone). Care-fully monitor potassium.➣Indications:Heart failureduetosystolicdysfunction(NYHAclassIIIB–IV) or post-myocardial infarction; consider in patients withless severe heart failure symptoms who require potassium sup-plementation➣Side Effects and Complications: Hyperkalemia (especially withType IVRTA), agranulocytosis, anaphylaxis, gynecomastia, hypo-tension, headache, dizziness, confusion, skin rash, impotence,irregular menstrual bleeding
3Chronic Heart Failure 325➣Absolute Contraindications: Anuria, hyperkalemia, acute renalinsufﬁciency➣Relative Contraindications: Hepatic insufﬁciency■ Isosorbide dinitrate and hydralazine: combination of vasodilators,though biochemical effects may be more important. FDA approvedfor treatment of symptomatic heart failure in addition to standardtherapy (ACE inhibitors, beta blockers, etc.).➣Indication: Consider if truly intolerant to ACE inhibitors andangiotensin II receptor blockers; addition to ACE inhibitor,diuretic, beta blocker, ARB, digoxin, if still symptomatic➣Side Effects and Complications: hemolytic anemia, methe-moglobinemia, headache, dizziness, hypotension, syncope,angina, reﬂextachycardia, nausea/vomiting,edema,rash,GI dis-tress, rash; agranulocytosis, SLE-like syndrome (hydralazine)➣Absolute Contraindications: Increased intracerebral pressure,cerebral hemorrhage, symptomatic hypotension, angle-closureglaucoma, stenotic valvular disease➣Relative Contraindications: stroke, hypotension, severe anemia,impaired renal function, acute MI (hydralazine)■ Unapproved drugs used in treatment of patients with heart failure■ Calcium channel blockers: Generally contraindicated in heart fail-ure. May consider Amlodipine, which has demonstrated no adverseeffect on survival (also perhaps felodipine).➣Indication: Angina, hypertension➣Side Effects and Complications: Hypotension, headache, ﬂush-ing, congestive heart failure, peripheral edema, bradycardia withsinus/AV node depression (especially verapamil and diltiazem),palpitations/reﬂex tachycardia, constipation (especially vera-pamil in elderly), GI distress, exacerbate heart failure in patientswith systolic dysfunction, possible increase in myocardial infarc-tion in diabetics with renal disease (nisoldipine, amlodipine)➣Absolute Contraindications: 2nd/3rd-degree AV block, sick sinussyndrome, systolic dysfunction (perhaps except amlodipine),post-myocardialinfarction,hypotension,pulmonary congestion➣Relative Contraindications: Impaired liver or renal function■ Anti-arrhythmic therapy: Drugs generally contraindicated in heartfailure. Treatment for asymptomatic or nonsustained ventriculararrhythmias not indicated. Beta-blockers reduce sudden death inCHF. Class I agents (quinidine, procainamide, ﬂecainide, encainide)increase risk of death. May consider amiodarone for atrial arrhyth-mias, but not for general use to prevent death/sudden death.
3326 Chronic Heart Failure➣Indication: Atrial arrhythmias, symptomatic ventricular arrhyth-mias (consider AICD)➣Side Effects and Complications: arrhythmias, SA and AV block,hepaticfailure, severepulmonarytoxicity,cornealdeposits;blue-gray skin discoloration, peripheral neuropathy, ataxia, edema,dizziness, hyper/hypothyroidism➣Absolute Contraindications: Severe SA node disease, 2nd/3rd-degree AV block, sick sinus syndrome, bradycardia-induced syn-cope➣Relative Contraindications: Thyroid disease, pulmonary disease,impaired liver or renal function, elderly■ Device Therapy■ Implantable Cardioverter Deﬁbrillators (ICD): Improve survival inselected patients;multipleguidelinesandindications; decision mustbe individualized➣Indications: Secondary prevention of sudden death with noknown reversible causes; primary prevention in patients with:rClass II or III heart failure + LVEF ≤35% ORrPrior MI LVEF ≤30% ORrPrior MI LVEF ≤35% + inducible sustained VT or VF➣Contraindications:rCardiogenic shock or symptomatic hypotensionrNIDCM with symptoms <3 monthsrCABG or PTCA within the past 3 monthsrAcute MI within the past 40 daysrCandidate for coronary revascularizationrIrreversible brain damage from preexisting cerebral diseaserNoncardiac disease with a likely survival <1 year➣SideEffectsand Complications: Acute: infection and local woundcomplications, myocardial perforation with pericardial tampon-ade, VT/VF induced during testing. Chronic: Infection, inappro-priate shocks, system failure (leads, generator).■ Biventricular pacemakers (BiV)/Cardiac Resynchronization Ther-apy (CRT): Reduce CHF hospitalizations and improve survival inselected patients;multipleguidelinesandindications; decision mustbe individualized➣Indications: Patients with symptomatic Class III–IV heart failuredespitestable,optimalheartfailuredrug therapyANDLVejectionfraction ≤0.35 AND QRS ≥120 milliseconds➣Contraindications: As above for ICD; must be individualized➣SideEffectsand Complications: Acute: infection and local wound
3Chronic Heart Failure Chronic Kidney Disease 327complications, myocardial perforation with pericardial tampon-ade, VT/VF induced during placement. Chronic: Infection, inap-propriate pacing, pacemaker syndrome, system failure (leads,generator).follow-upDuring Treatment■ Often require weekly or bi-weekly visits during titration of medica-tions, especially beta blockers■ Monitor electrolytes, especially potassium, and renal function■ Emphasize lifestyle changes such as reduced sodium intake, aerobicexercise, compliance with medications, daily weights.■ Educate patient about pathophysiology of heart failure and reasonfor medications (improves outcomes and compliance).Routine■ Follow-up at least every 6 months■ Improved outcomes noted when followed by cardiologist, heart fail-ure specialist.■ Repeat evaluation of LV function generally not indicated, unlessmajor intercurrent event or deterioration, although rechecking 6months after beta blocker therapy may demonstrate signiﬁcantimprovement.■ If ICD or CRT device in place, requires follow-up with qualiﬁed car-diologist to interrogate and check settingscomplications and prognosis■ Complications usually related to underlying pathophysiology, alsosudden death (about 50% of overall mortality) and death due to pro-gressive heart failure■ 50% 5-year mortality in some seriesCHRONIC KIDNEY DISEASEROBERT D. TOTO, MDhistory & physicalHistory■ Infections, toxins, environment: hepatitis B and C, lead, mercury, sili-con; Drugs: acetaminophen/paracetamol/caffeine combinations,
3328 Chronic Kidney DiseaseNSAIDS, lithium, cancer chemotherapeutic agents, pamidronate,lithium, herbal (e.g., some Chinese herbs) remediesRisk Factors for Progressive Renal Disease■ Age, male gender, diabetes mellitus, hypertension, family his-tory (pattern of inheritance); African-American, Hispanic, cigarettesmoking, persistent albuminuria, nephrotoxin exposure (e.g., anal-gesics).Signs & Symptoms■ May be asymptomatic; symptoms usual when estimated glomerularﬁltration rate ≤25 mL/min/1.73 m2■ General: fatigue, malaise, weakness, fever (systemic diseases andretroperitoneal ﬁbrosis)■ HEENT: headache, visual disturbances, periorbital edema, retinalchanges of hypertensive/diabetic retinopathy, cholesterol emboli,uremic fetor■ CV and PULM: dyspnea, edema, chest pain, hypertension, hemopt-ysis, hyperpnea (metabolic acidosis) pulmonary edema■ GI: dysgeusia, anorexia, nausea, vomiting, diarrhea, occult GI hem-orrhage■ GU: Nocturia, foamy urine, dysuria, hematuria, stranguria, painfulurination, ﬂank or back pain, hypospadias, urethral stricture,prostate enlargement■ MS: lower extremity edema, bone and articular pain, generalizedmuscle wasting and weakness■ NS: encephalopathy: difﬁculty concentrating, insomnia, daytimedrowsiness, seizures, coma; peripheral neuropathy■ SKIN: pruritus, easy bruising, petechiae, cutaneous infarcts, palpa-ble purpura, calcinosistestsLaboratory■ Basic blood tests:➣Early disease: estimated GFR <60 ml/min/1.73 m2, elevatedserum creatinine, elevated BUN➣Advanced disease: early disease + hyperkalemia, hypobicar-bonatemia, hyperphosphatemia, hypocalcemia, hypercalcemia,hypermagnesemia, elevated serum PTH, decreased serum 1,25(OH)2 vitamin D3, elevated alkaline phosphatase, normo-chromic normocytic anemia
3Chronic Kidney Disease 329■ Basic urine tests:➣Early disease: microalbuminuria/proteinuria, microhematuria,pyuria; casts including red blood cells (RBCs), white blood cells(WBCs), granular; crystalluria➣Advanced disease: same as early and hyaline casts➣Urinalysis Patterns:➣Glomerulonephritis: hematuria, dysmorphic RBC, heavy pro-teinuria (urine protein/creatinine ratio ≥3.0), RBC casts➣Tubulointerstitial nephritis: microhematuria, pyuria, + WBCcasts, mild proteinuria (urine protein/creatinine ratio ≤2.0) andwaxy casts➣Renal ischemia (vasculitis, atheroembolism, renal artery steno-sis) or urinary obstruction: minimal cellular elements + protein-uria➣Urine [Na] and fractional Na excretion (FENa) not helpful inchronic kidney diseaseSpeciﬁc Diagnostic Tests:■ Estimated glomerular ﬁltration rate (eGFR), creatinine clearance(Ccr)■ Spot urine albumin mg/creatinine g ratio (>30 and <300 = micro-albuminuria; >300 = macroalbuminuria); spot urine total proteinmg/creatinine g ratio, >200 abnormal■ Anti-nuclear antibodies (SLE), anti-glomerular basement mem-brane antibody, anti-neutrophil cytoplasmic antibody (ANCA),hepatitis B surface antigen, anti-hepatitis C antibody; HIV, comple-ment components 3 and 4, anti-topoisomeraseantibody, cryoglobu-lins, serum and urine protein electrophoresis,urine immunoﬁxation(light chain deposition disease)Imaging:■ CXR to evaluate heart and lungs (see management)■ Renal ultrasound➣Early disease: Normal or enlarged kidneys; cystic-autosomaldominant polycystic kidney disease (ADPKD); hydronephrosis,increased echogenicity➣Advanced disease: small shrunken kidneys, increased echo-genicity; normal or enlarged kidneys in ADPKD, diabetes HIVnephropathy: hydronephrosis■ CT/MRI/MRA: angiomyolipomas, ADPKD; papillary necrosis, renalartery stenosis (MRA)
3330 Chronic Kidney Disease■ Voiding cystourethrogram■ Renal Biopsy:➣Useful when kidneys normal size to make speciﬁc diagnosis –e.g., SLE, glomerulonephritis. When kidneys small (e.g., ≤9cm)usual ﬁnding is end-stage kidney – i.e. global glomerulosclerosis+ tubulointerstitial nephritisdifferential diagnosis■ Chronic kidney disease (CKD) symptoms mimicked by systemicdiseases, cancer, wasting illnesses, depression, hypothyroidism,chronic heart failure, chronic liver disease. Elevated BUN and crea-tinine point to kidney, adrenocortical insufﬁciency.Causes of Chronic Kidney Disease■ Systemic disease: Diagnosis usually established by history, exam,sonogram and speciﬁc laboratory tests: diabetes mellitus, hyperten-sion, systemic lupus erythematosus, Sjogren’s syndrome, systemicnecrotizing vasculitides, atheroembolic renal disease, myeloma,light chain deposition disease, amyloidosis, genetic disease – e.g.,polycystic disease, tuberous sclerosis, cystinosis, Fabry’s disease,sickle cell disease, heart failure, cirrhosis■ Primary renal and urinary tract disease: Speciﬁc glomerular dis-ease usually requires renal biopsy; obstructive uropathy by sono-gram or CT scan (e.g., retroperitoneal ﬁbrosis), vesicoureteral reﬂux(detected by voiding cystourethrogram), prostate disease, recurrentUTI or voiding dysfunction (Hx, exam, voiding study)managementWhat to Do First■ Assess cardiovascular and volume status by physical exam and CXR,and determine if dialysis is indicated because of:■ a) hypertension and/or pulmonary edema; b) hyperkalemia; c)pericarditis; d) metabolic acidosis; e) altered MSGeneral Measures■ Dialysis not indicated:➣Restore volume status with conservative measures (e.g., diureticsin patient with volume overload).➣Treat hypertension (present in >90% of cases).rTarget blood pressure <130/80 mmHg with (in order):ACE inhibitor/angiotensin II receptor blocker + thiazide(serum creatinine ≤1.8 mg/dl) or loop diuretic (serum
3Chronic Kidney Disease 331creatinine >1.8 mg/dl), calcium channel blocker, central-acting alpha-agonist/peripheral alpha-blocker/beta-blocker,then vasodilator (e.g., minoxidil) and dietary Na restriction(2 g/day).➣Treat hyperkalemia and acidosis (see below).speciﬁc therapy■ eGFR or Ccr 25–75 ml/min/1.73 m2, see “Preserve renal function”■ eGFR or Ccr <25 ml/min/1.73 m2, consult access surgeon, dieticianand social worker to assist in preparing for dialysis■ eGFR or Ccr <20 ml/min/1.73 m2, place vascular access (hemodial-ysis) or plan peritoneal catheter in 6–12 months■ eGFR or Ccr in range of 8–12 ml/min/1.73 m2, initiate mainte-nance renal replacement therapy unless: a) patient’s weight is stable;b) serum albumin is at least at lower limit of normal range forlaboratory; c) patient is symptom-freePreserve (Remaining) Renal Function for All Levels of CKD■ Treat underlying disease process – e.g. treat SLE, relieve obstruction,identify and discontinue nephrotoxin (e.g., lithium) whenever pos-sible■ Normalize BP using ACE inhibitor unless: a) patient has knownallergy; b) cough intolerable; c) hyperkalemic with K ≥6.0 on K-restricted diet; d) known or suspected critical renal artery stenosis■ Optimize glycemic control in diabetic (HgbA1c ≤6.5%)■ Cease cigarette smoking (hard evidence)■ Improve dyslipidemia with low-saturated-fat diet and statin drug forLDL-cholesterol (≤70 for highest risk [e.g., diabetic] and ≤100 mg/dlfor non-diabetic) and triglyceride <150 mg/dl■ Dietary protein intake: 0.8 g/kg/day prior to dialysis. After initiationof dialysis 1.0–1.4 g/kg/d for hemodialysis and 1.4–1.6 g/kg/d forperitoneal dialysis.Preserve Cardiac Function■ 50% of deaths in patients with ESRD are cardiac in origin.■ Normalize BP, manage dyslipidemia with statins (see above); ﬁbricacid derivative for uncontrolled hypertriglyceridemia, stop smoking,folic acid 5 mg/day to reduce risk of hyperhomocysteinemiaManage Acid-Base and Electrolyte Disturbances■ Hyperkalemia: +EKG changes: IV Calcium gluconate, insulin,inhaled beta-2 agonist, oral or rectal Kayexalate and dietary potas-sium restriction (0.8 mEq/kg/day). - EKG change: diet/Kayexalate.
3332 Chronic Kidney Disease■ Acidosis: Check ABG, treat with oral sodium bicarbonate: 1 mEq/kg/day as Shohl’s solution (1 mEq/ml); baking soda (60 mEq/tsp)or NaHCO3 tabs (8 mEq/650 mg tab). For pH <7.15. consider intra-venous NaHCO3 therapy. Renal osteodystrophy: Goal to normalizecalcium and phosphorus, lower PTH and increase vitamin D: Dietaryphosphate restriction to 12 mg/kg/day. Add Ca- based binder (CaAcetate of Ca Carbonate) or non-Ca-based binder such as sevalemerHCl (Renalgel) 1–4 tablets with meals. Measure PTH and 25(OH)2vitamin D3. If PTH elevated and 25 (OH)2 vitamin D3 low, admin-ister ergocalciferol 50,000 units monthly for 6 months and repeatPTH. If still elevated, administer active vitamin D such as calcitriolor paricalcitriol.■ Avoid malnutrition: 0.8 g/kg/day protein, 35 kcal/kg/day prior todialysis (see above). Monitor body weight, muscle mass, serum albu-min, BUN (protein intake) and Scr (muscle mass).Anemia■ Measure serum Fe, TIBC and ferritin.■ Treat hemoglobin <11 g/dl with subcutaneous erythropoietin or dar-bepoietin subcutaneously along with oral or intravenous iron ther-apy.■ No contraindications; BP may increase in 20–25% of patients.follow-up■ Every 3 months for patients with eGFR or Ccr ≤25 ml/min/1.73 m2■ Increase frequency as needed as patient approaches ESRD■ Labs at visit: chemistries, iron stores, hemoglobin, spot urine albu-min or protein/creatinine ratio. Goals: urine albumin/creatinineratio <300 mg/g, urine protein/creatinine <200 mg/g.complications and prognosisAdverse drug events:■ ACEinhibitors:cough, hyperkalemia,rarelyangioedema(morecom-mon in African-Americans)■ HMG-CoA reductase inhibitors: rhabdomyolysis, muscle pain orasymptomatic CK elevation■ Active vitamin D3 (e.g., calcitriol) may cause hypercalemia.■ Loop diuretics: hypokalemia, hypomagnesemia, hypochloremicmetabolic alkalosis■ ESRD: nearly all patients with Ccr <25 ml/min/1.73 m2reach ESRDwithin 2 years. Mortality rate on dialysis at 5 years is about 50%.
3Chronic Lymphocytic Leukemia 333CHRONIC LYMPHOCYTIC LEUKEMIAKANTI R. RAI, MDhistory & physicalHistory■ Characteristically, a disease of elderly■ Predominant in malesSigns & Symptoms■ Often diagnosed in an asymptomatic patient on routine CBC■ Usually has an indolent course■ Patients may present with “B” symptoms and abdominal fullness(secondary to splenomegaly)■ Physical exam may be normal at initial diagnosis➣Some patients may have some or all of the following: pallor, lym-phadenopathy, splenomegaly, skin involvementtestsEssential Criteria for Diagnosis■ Absolute lymphocytosis (≥5,000/microliter) persistent for >4 weeks■ More than 30% involvement of the bone marrow by CLL■ Characteristic phenotypic proﬁle of the lymphocytes on ﬂowcytometry: CD5(+), CD19(+), CD20(+), CD23(+), dim expressionof monoclonal surface immunoglobulinOther Lab Findings■ Absolute lymphocytosis with mature appearing lymphocytes inperipheral blood■ Anemia, thrombocytopenia may be seen■ Hypogammaglobulinemia may be seenBone Marrow■ Hypercellular or normocellular■ Marked lymphoid inﬁltration■ Flow cytometry: as abovedifferential diagnosis■ Other lymphoproliferative disorders (see table)
3334 Chronic Lymphocytic LeukemiaCLL■ sIg: W■ CD5: +■ CD23: +■ CD20: +■ CD10: −■ CD103: −HCL■ sIg: B■ CD5: −■ CD23: −■ CD20: +++■ CD10: −■ CD103: +PLL■ sIg: B■ CD5: +/−■ CD23: −■ CD20: +++■ CD10: −■ CD103: −SLVL■ sIg: B■ CD5: +/−■ CD23: −■ CD20: +++■ CD10: −■ CD103: −MCL-L■ sIg: B■ CD5: +++■ CD23: −■ CD20: ++■ CD10: −■ CD103: −FCL-L■ sIg: B■ CD5: −■ CD23: −■ CD20: ++++■ CD10: −■ CD103: −■ SIg – surface immunoglobulin, W – weak,B–bright, HCL – Hairy cellleukemia,PLL–Prolymphocytic leukemia,SLVL –Spleniclymphomawith villous lymphocytes, MCL – Mantle cell lymphoma-leukemicphase, FCC – Follicular center lymphoma-leukemic phaseStaging■ Rai stage Clinical features➣Stage 0 lymphocytosis only➣Stage I lymphocytosis + enlarged lymph nodes➣Stage II lymphocytosis + enlarged spleen or liver with or withoutenlarged nodes➣Stage III lymphocytosis + anemia with or without enlargednodes, liver, spleen➣Stage IV lymphocytosis + thrombocytopenia with or withoutenlarged nodes, spleen, liver and anemia■ Modiﬁed Rai criteria➣Stage 0 = low risk; Stage I/II = intermediate risk; Stage III/IV =high risk
3Chronic Lymphocytic Leukemia 335managementWhat to Do First■ To decide if the patient needs treatmentIndications■ Disease related symptoms (weight loss, fever, fatigue)■ Progressive increase in lymphocytosis with a rapid LDT■ Worsening of anemia and or thrombocytopenia■ Auto-immune anemia or thrombocytopenia■ Symptomatic bulky lymphadenopathy or splenomegaly■ Recurrent infectionsTreatment Strategy Based on Stage■ Low risk and Intermediate risk - Observation, unless any of the aboveindication is present■ High risk – Initiate cytotoxic therapyspeciﬁc therapy■ Chlorambucil PO Q 3–4 weeks or■ Cyclophosphamide PO/iv Q3–4 weeks or■ Fludarabine iv QD × 5 days q month for 4–6 months■ Glucocorticoids: Prednisone alone or combination with alkylatingagents (not with Fludarabine)■ Monoclonal antibodies:➣Campath-1H (anti-CD52) – for Fludarabine failures given iv or scat 30 mg each dose 3 timesa week (usually Mondays, Wednesdaysand Fridays) for up to 8 weeks➣Rituximab (anti-CD20) (in clinical trials) – In combination withﬂudarabine (given at standard dosage as described above, onmonthly basis), and rituximab given on day 1 of each month’sﬂudarabine, at 375 mg/M2 iv, for 4–6 monthsfollow-upDuring Treatment■ CBC and physical exam at 2–3 weeks■ Coombs, quantitative immunoglobulins periodically■ Bone marrow biopsy at complete remission (CR) by all other criteriaRoutine■ Once in CR: CBC, physical exam q 2–3 months