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Heart Failure findings on ECG and echocardiogrant also may suggest an TEY POIXIS ischen.ric cause for LV dysfunction. . B type natriuretic peptide measurement is a sensitive Patients with exertional chest pain, history of myocar and specific test for the diagnosis of heart failure in dial infarction, or other symptoms suggesting CAD should patients with dyspnea of unknown etiolosr. undergo further evaluation with tunctional or anatomic o Echocardiography is the primary diagnostic modality assessment for obstructive CAD as clinically appropriate (see fbr er,aluation of heart failurel it provides information Diagnostic Testing in Cardiology). Identification of significant on chamber size and thickness. systolic and diastolic CAD is important because LV dysf unction caused by ischemia function. valvular patholos/, and regional $all motion may lessen or resolve with appropriate medical therapl' or abnormalities. revascu I a ri zat ion.

findings on ECG and echocardiogrant also may suggest an TEY POIXIS ischen.ric cause for LV dysfunction. . B type natriuretic peptide measurement is a sensitive Patients with exertional chest pain, history of myocar and specific test for the diagnosis of heart failure in dial infarction, or other symptoms suggesting CAD should patients with dyspnea of unknown etiolosr. undergo further evaluation with tunctional or anatomic o Echocardiography is the primary diagnostic modality assessment for obstructive CAD as clinically appropriate (see fbr er,aluation of heart failurel it provides information Diagnostic Testing in Cardiology). Identification of significant on chamber size and thickness. systolic and diastolic CAD is important because LV dysf unction caused by ischemia function. valvular patholos/, and regional $all motion may lessen or resolve with appropriate medical therapl' or abnormalities. revascu I a ri zat ion. Classification Management The severity of heart failure is categorized according to the New York Heart Association (NYt{A) functional classifica Heart Failure With Reduced Ejection Fraction 'fhe treatment of HFrEF includes long term therap]' to tion (Table 11) and the American College of Cardiology (ACC)/American Heart Association (AHA) heart failure decreirse morbidity and mortality and reliere s!'mptoms as stages (Table 12). Patients can move between NYHA classes r,r,ell as nlanagement of acute exacerbations. Treatment of depending on fluid status and progression of heart failure: stage B IIFTEF entails RAAS inhibition (ACE inhibitor. ARB. or

Classification Management The severity of heart failure is categorized according to the New York Heart Association (NYt{A) functional classifica Heart Failure With Reduced Ejection Fraction 'fhe treatment of HFrEF includes long term therap]' to tion (Table 11) and the American College of Cardiology (ACC)/American Heart Association (AHA) heart failure decreirse morbidity and mortality and reliere s!'mptoms as stages (Table 12). Patients can move between NYHA classes r,r,ell as nlanagement of acute exacerbations. Treatment of depending on fluid status and progression of heart failure: stage B IIFTEF entails RAAS inhibition (ACE inhibitor. ARB. or however, they can only progress in the ACC,'AHA stages. ARNI) and p blockade; therapies fbr stage C (s1'mptomatic) Both the patient's functional class and stage affect the choice []FrEt are outlined in Figure 13. <-rf therapy. Medical Therapy ACE lnhibitors and Angiotensin Receptor Blockers TABLE 1 1 . New York Heart Association Functional ACE inhibitors reduce morbidity and mofiality in patients Classification with tlFrEF and should be used in both symptomatic and Class Description ,synlptomatic patients. ACE inhibitors block the conversion of No limitations of physical activity angiotensin I to angiotensin II. inhibiting the upregulation ol Slight limitation of physical activity the RAAS pathway. The primary adverse effects are hypoten sion. kidney dysfunction. ACE inhibitor induced cough. and Marked limitation of physical activity angioedema. iltA Symptoms with less than ordinary activity Although an ACE inhibitor should be considered in every' iltB Symptoms with minimal exertion patient \\,ith HFTEF. worsening kidney function and h1'per Unable to carry on any physical activity without kalen.ria may prevent its use. Many physicians do not recom symptoms n.rer.rd initiating or increasing the dosage if the creatinine level rises to 2.5 mg/dl (221 pmol/L) or the estimated glomerular filtration rate (eGFR) falls below 30 mlrminil.73 m2. 'l'he TABLE 12. American College of Cardiology/American eGFR should be monitored fbr decline during uptitration of' Heaft Association Stages of Heart Failure therapy. Stage Description An ACE inhibitor induced cough. occurring in up to Stage A At risk for heart failure but without structural heart 20')1, of patients, is the primary reason to su,itch therapy from changes (e.9., patients with diabetes mellitus, an ACE inhibitor to an angiotensin receptor blocker (ARB). coronary artery disease, hypertension, or vascular Although fen,er data support the use of ARBs in asymptomatic disease) patients with reduced LVEFI there is consensus that all patients Stage B Structural heart disease (e.9., reduced ejection fraction, left ventricu lar hypertrophy, cham ber with an ACE inhibitor induced cough should receive an ARB. enlargement) but without heart failure symptoms Patients who develop angioedema lvhile taking an ACE inhibi Stage C Structural heart disease with current or prior heart tor are often switched to an ARB: however. there are rare failure symptoms reports of ARB induced angioedema. and patients should be Stage D Refractory heart failure requiring advanced infbrmed of this risk. intervention (e.9., biventricular pacemakel left ventricular assist device, transplantation) Angiotensin Receptor Neprilysin lnhibitor lnformation from Hunt SA, Abraham WT, Ch n MH, et al. 2009 Focused update 'lhe ARNI valsartan sacubitril belongs to a ne\\' drug class incorporated into the ACC/AHA 2005 gu delines for the dragnosis and management of hean failure ln adults: a report o{ the American Col ege of Cardiology Foundation/ that combines an ARB with a nepril_rsin inhibitor. Nepril-rsin American Heart Assoc atlon Task Force on Practrce Guidelrnes: developed in colLaboration with the lnternational Society for Heaft and Lung Transplanrarron. is a neutral endopeptidase that degrades natriuretic peptides I Crculation.2009;119:e391479.IPMID:19324966]doi:10.1161/CIRCULATIONAHA. and bradykinin. Inhibition of neprilysin increases levels ol 109.192065 these substances, leading to enhanced diuresis, natriuresis,

however, they can only progress in the ACC,'AHA stages. ARNI) and p blockade; therapies fbr stage C (s1'mptomatic) Both the patient's functional class and stage affect the choice []FrEt are outlined in Figure 13. <-rf therapy. Medical Therapy ACE lnhibitors and Angiotensin Receptor Blockers TABLE 1 1 . New York Heart Association Functional ACE inhibitors reduce morbidity and mofiality in patients Classification with tlFrEF and should be used in both symptomatic and Class Description ,synlptomatic patients. ACE inhibitors block the conversion of No limitations of physical activity angiotensin I to angiotensin II. inhibiting the upregulation ol Slight limitation of physical activity the RAAS pathway. The primary adverse effects are hypoten sion. kidney dysfunction. ACE inhibitor induced cough. and Marked limitation of physical activity angioedema. iltA Symptoms with less than ordinary activity Although an ACE inhibitor should be considered in every' iltB Symptoms with minimal exertion patient \\,ith HFTEF. worsening kidney function and h1'per Unable to carry on any physical activity without kalen.ria may prevent its use. Many physicians do not recom symptoms n.rer.rd initiating or increasing the dosage if the creatinine level rises to 2.5 mg/dl (221 pmol/L) or the estimated glomerular filtration rate (eGFR) falls below 30 mlrminil.73 m2. 'l'he TABLE 12. American College of Cardiology/American eGFR should be monitored fbr decline during uptitration of' Heaft Association Stages of Heart Failure therapy. Stage Description An ACE inhibitor induced cough. occurring in up to Stage A At risk for heart failure but without structural heart 20')1, of patients, is the primary reason to su,itch therapy from changes (e.9., patients with diabetes mellitus, an ACE inhibitor to an angiotensin receptor blocker (ARB). coronary artery disease, hypertension, or vascular Although fen,er data support the use of ARBs in asymptomatic disease) patients with reduced LVEFI there is consensus that all patients Stage B Structural heart disease (e.9., reduced ejection fraction, left ventricu lar hypertrophy, cham ber with an ACE inhibitor induced cough should receive an ARB. enlargement) but without heart failure symptoms Patients who develop angioedema lvhile taking an ACE inhibi Stage C Structural heart disease with current or prior heart tor are often switched to an ARB: however. there are rare failure symptoms reports of ARB induced angioedema. and patients should be Stage D Refractory heart failure requiring advanced infbrmed of this risk. intervention (e.9., biventricular pacemakel left ventricular assist device, transplantation) Angiotensin Receptor Neprilysin lnhibitor lnformation from Hunt SA, Abraham WT, Ch n MH, et al. 2009 Focused update 'lhe ARNI valsartan sacubitril belongs to a ne\\' drug class incorporated into the ACC/AHA 2005 gu delines for the dragnosis and management of hean failure ln adults: a report o{ the American Col ege of Cardiology Foundation/ that combines an ARB with a nepril_rsin inhibitor. Nepril-rsin American Heart Assoc atlon Task Force on Practrce Guidelrnes: developed in colLaboration with the lnternational Society for Heaft and Lung Transplanrarron. is a neutral endopeptidase that degrades natriuretic peptides I Crculation.2009;119:e391479.IPMID:19324966]doi:10.1161/CIRCULATIONAHA. and bradykinin. Inhibition of neprilysin increases levels ol 109.192065 these substances, leading to enhanced diuresis, natriuresis, 32

L t L Heart Failure t HFrEF Stage C Treatment L t t ARNI/ACEI/ARB t (ARNI prefened') AND evidence-based p-blockeP t with diuretic agent as needed i

t t ARNI/ACEI/ARB t (ARNI prefened') AND evidence-based p-blockeP t with diuretic agent as needed i I For patients with For persistently eGFR >30/mVmin/1.73 m2 or For patients For patients with For patients with symptomatic Black I creatinine meeting eGFR persistent volume resting HR >70/min, patients despite s2.5 mg/dL(221 pmol/L) criteria", NYHA overload, NYHA on maximally ARNI/p-blocker/ in males or <2.0 mg/dL class ll-lV tolerated p-blocker class ll-lV aldosterone (176.8 pmol/L) in females or dose in antagonisVSGLT2 sinus rhythm, K. <5.0 mEq/L (5.0 mmol/L), inhibitor, NYHA NYHA class ll-lll NYHA class ll-lV class lll-lV

I For patients with For persistently eGFR >30/mVmin/1.73 m2 or For patients For patients with For patients with symptomatic Black I creatinine meeting eGFR persistent volume resting HR >70/min, patients despite s2.5 mg/dL(221 pmol/L) criteria", NYHA overload, NYHA on maximally ARNI/p-blocker/ in males or <2.0 mg/dL class ll-lV tolerated p-blocker class ll-lV aldosterone (176.8 pmol/L) in females or dose in antagonisVSGLT2 sinus rhythm, K. <5.0 mEq/L (5.0 mmol/L), inhibitor, NYHA NYHA class ll-lll NYHA class ll-lV class lll-lV Add Add Titrate Add Add

I For patients with For persistently eGFR >30/mVmin/1.73 m2 or For patients For patients with For patients with symptomatic Black I creatinine meeting eGFR persistent volume resting HR >70/min, patients despite s2.5 mg/dL(221 pmol/L) criteria", NYHA overload, NYHA on maximally ARNI/p-blocker/ in males or <2.0 mg/dL class ll-lV tolerated p-blocker class ll-lV aldosterone (176.8 pmol/L) in females or dose in antagonisVSGLT2 sinus rhythm, K. <5.0 mEq/L (5.0 mmol/L), inhibitor, NYHA NYHA class ll-lll NYHA class ll-lV class lll-lV Add Add Titrate Add Add Aldosterone 5GLT2 Diuretic Hydralazine antagonist inhibitor agent + isosorbide lvabradine dinitrate

Aldosterone 5GLT2 Diuretic Hydralazine antagonist inhibitor agent + isosorbide lvabradine dinitrate receptor-neprilysin inhibitor; eGFR = estimated glomerularfiltration rate; HR = heart rate; NYHA= NewYork HeartAssociation; SGLT2 = sodium,glucose cotransporter 2. 'An ACEI/ARB should only be considered in patients with contraindications, intolerance, or inaccessibility to an ARNI. bCaruedilol.netoprolol succinate.o, b'soprolo.. 'tnsure eGtR >30 mUmin/1 73 m2 for dapagliflozin and eGFR >20 mUmin/1 73 m'? for empaglillozin before initiation College of Cardiology Foundation.

receptor-neprilysin inhibitor; eGFR = estimated glomerularfiltration rate; HR = heart rate; NYHA= NewYork HeartAssociation; SGLT2 = sodium,glucose cotransporter 2. 'An ACEI/ARB should only be considered in patients with contraindications, intolerance, or inaccessibility to an ARNI. bCaruedilol.netoprolol succinate.o, b'soprolo.. 'tnsure eGtR >30 mUmin/1 73 m2 for dapagliflozin and eGFR >20 mUmin/1 73 m'? for empaglillozin before initiation College of Cardiology Foundation. and myocardial relaxation. In the PARADIGM HF trial of include patients with chronic heart failure and any LVEF, patients with symptomatic heart failure and LVEF below although the benefits are most evident in patients with LVEF 40'X,, valsartan-sacubitril reduced mortality and heart failure below normal. Caution should be used in patients with hypo- hospitalizationby 2O'1, compared with enalapril. In patients tension. Valsartan sacubitril should not be administered to taking valsartan sacubitril, the incidence of hypotension patients with a history of angioedema (even if tolerant of an was increased, while acute kidney injury hyperkalemia, and ARB) or within 36 hours of the last dose of an ACE inhibitor cough were reduced. because of the risk for angioedema with the combination of an Guidelines recommend replacing an ACE inhibitor or ACE inhibitor and ARNI. ARB with valsartan sacubitril in patients with chronic symp tomatic HFrEF (NYHA class II-IV heart failure symptoms and B Blockers LVEF <40'1,) or initiating valsartan-sacubitril instead of an ACE p Blockers should be initiated in all patients with HFTEF. inhibitor or ARB in patients with new-onset HFTEF. The FDA p Blockers improve remodeling, increase LVEE, and reduce has expanded the indications for valsartan sacubitril to hospitalization and mortality when added to ACE inhibitor

and myocardial relaxation. In the PARADIGM HF trial of include patients with chronic heart failure and any LVEF, patients with symptomatic heart failure and LVEF below although the benefits are most evident in patients with LVEF 40'X,, valsartan-sacubitril reduced mortality and heart failure below normal. Caution should be used in patients with hypo- hospitalizationby 2O'1, compared with enalapril. In patients tension. Valsartan sacubitril should not be administered to taking valsartan sacubitril, the incidence of hypotension patients with a history of angioedema (even if tolerant of an was increased, while acute kidney injury hyperkalemia, and ARB) or within 36 hours of the last dose of an ACE inhibitor cough were reduced. because of the risk for angioedema with the combination of an Guidelines recommend replacing an ACE inhibitor or ACE inhibitor and ARNI. ARB with valsartan sacubitril in patients with chronic symp tomatic HFrEF (NYHA class II-IV heart failure symptoms and B Blockers LVEF <40'1,) or initiating valsartan-sacubitril instead of an ACE p Blockers should be initiated in all patients with HFTEF. inhibitor or ARB in patients with new-onset HFTEF. The FDA p Blockers improve remodeling, increase LVEE, and reduce has expanded the indications for valsartan sacubitril to hospitalization and mortality when added to ACE inhibitor 33

Heart Failure TABLE 1 3. Therapeutic Dosages of B-Blockers for Aldosterone antagonists can cause hyperkalemia and Treatment of Heart Failure With Reduced Ejection Fraction should be used cautiously in patients with kidnel'dysfunc Agent Target Dosage tion. In clinical trials, potassium supplementation \^Ias rou tinely discontinued at the beginning oftherapy. and electrolyte Carvedilol 25 mg twice daily (50 mg twice daily if weight >85 k9 [187 lb)) measurement was repeated within I week of initiation. Aldosterone antagonists should not be considered diuretic Metoprolol 200 mg daily succrnate therapy. and patients with volume overload should be treated

TABLE 1 3. Therapeutic Dosages of B-Blockers for Aldosterone antagonists can cause hyperkalemia and Treatment of Heart Failure With Reduced Ejection Fraction should be used cautiously in patients with kidnel'dysfunc Agent Target Dosage tion. In clinical trials, potassium supplementation \^Ias rou tinely discontinued at the beginning oftherapy. and electrolyte Carvedilol 25 mg twice daily (50 mg twice daily if weight >85 k9 [187 lb)) measurement was repeated within I week of initiation. Aldosterone antagonists should not be considered diuretic Metoprolol 200 mg daily succrnate therapy. and patients with volume overload should be treated Bisoprolol 10 mg daily with a loop or thiazide diuretic. Of the two agents. eplerenone is a more selective aldosterone antagonist and is associated with lort'er incidence of grnecomastia and breast tenderness. and diuretic therapy. In contrast to ACE inhibitors, the benefits of p blocker therapy do not appear to be a class effect, and one Isoso rbide D initrate - H y d ralazine of three agents shown to have a mortality benefit (bisoprolol, In Black patients with NYHA functional class III to lV symp carvedilol, and metoprolol succinate) should be used. toms. isosorbide dinitrate hydralazine used in combination p-Blockers are generally well tolerated but should not be with an ACE inhibitor, p-blocker, and aldosterone antagonist started when the patient is acutely decompensated. These has been shown to reduce mortality compared with placebo. agents have negative inotropic properties and may exacerbate Guidelines recommend the addition of isosorbide dinitrate heart failure in patients with acute volume overload. p blockers hydralazine in Black patients who remain s)'mptomatic on should be initiated at low doses and slowly uptitrated over maximal doses of a B-blocker: ACE inhibitor. ARB. or ARNI: weeks (not days) until the patient achieves the guideline and aldosterone antagonist. In patients who are intolerant of directed target dose or maximum tolerable dose (Table 13) ACE inhibitor or ARB therapy. especially those u'ith chronic while monitoring for light headedness. hypotension. and kidney disease, isosorbide dinitrate hydralazine may be bradyarrhythmia. Contraindications to B-blocker therapy considered as a therapeutic option. Headache is a common include cardiogenic shock and second- or third degree atrio- adverse effect. ventricular block. In patients with reactive airways disease or Because patients may have difficulty adhering to a thrice COPD, B-blockers should not be initiated if the patient has daily dosing regimen, physicians might consider switching to acute bronchospasm or evidence of pulmonary disease exac once daily therapy with isosorbide mononitrate. However. erbation. Hospitalized patients generally should be started on there is no experimental evidence that isosorbide mononitrate p blocker therapy before discharge. plus hydralazine is as effective as isosorbide dinitrate plus hydralazine or that adherence is improved. Initiating and Managing ACE lnhibitor andB BlockerTherapy Diuretics An ACE inhibitor (or ARB or ARNI) and a p blocker are indi Loop diuretics are the primary diuretic therapy for volume over cated in all patients with HFTEF. Either drug may be initiated load in heart failure because of increased potency compared first, although it is reasonable to select the first agent based on with other diuretics. Of the four loop diuretics, furosemide is patient factors. For example, a B blocker should be started first most commonly used; however, some studies have shown tor in patients with CAD or atrial fibrillation who require heart semide and bumetanide to be more effective because of their rate control. Conversely, an ACE inhibitor should be started increased bioavailability and longer half lives. Occasionally. loop first in patients with diabetes for the additional renal benefits. and thiazide diuretics are combined to potentiate diuresis. The Studies have shown that patients receive additive benefit from lowest dosage that achieves euvolemia should be used. Major the second agent regardless ofthe order ofinitiationi however, side effects include hypokalemia and hypomagnesemia. the second drug should be started befbre the dosage of the first Electrollte levels should be monitored. In patients lvho are eu agent is maximized, especially if the patient has or is at risk for volemic following diuresis and able to adhere to a rigorous salt hypotension. For both drugs, studies suggest that higher doses restricted diet, diuretic dosage may be reduced or discontinued. are associated with reduced hospitalizations and improved symptoms. luabradine Ivabradine is a sinoatrial node modulator that selectively Aldosterone Antagonists inhibits the 11 current in the sinoatrial node. causing a reduc Aldosterone antagonists (spironolactone, eplerenone) reduce tion in heart rate. It has no negative inotropic effects. In mortality and heart failure hospitalizations in patients with patients with HFrEF (LVEF <35')(,) and NYHA functional class symptomatic HFrEF (NYHA functional class II IV) and in II to III symptoms who are in sinus rhyhm u,ith a heart rate patients with HFrEF after acute myocardial infarction. Despite ol at least 7Oimin and taking maximally tolerated doses of a their proven efficacy, they are underused. Current guidelines p blocker, ivabradine reduces heart failure associated hospi recommend initiating these agents in patients with sympto talizations and the combined end point of mortality and heart matic HFrEF and an eGFR of at least 30 ml/min/1.73 m2. tailure hospitalization.

Bisoprolol 10 mg daily with a loop or thiazide diuretic. Of the two agents. eplerenone is a more selective aldosterone antagonist and is associated with lort'er incidence of grnecomastia and breast tenderness. and diuretic therapy. In contrast to ACE inhibitors, the benefits of p blocker therapy do not appear to be a class effect, and one Isoso rbide D initrate - H y d ralazine of three agents shown to have a mortality benefit (bisoprolol, In Black patients with NYHA functional class III to lV symp carvedilol, and metoprolol succinate) should be used. toms. isosorbide dinitrate hydralazine used in combination p-Blockers are generally well tolerated but should not be with an ACE inhibitor, p-blocker, and aldosterone antagonist started when the patient is acutely decompensated. These has been shown to reduce mortality compared with placebo. agents have negative inotropic properties and may exacerbate Guidelines recommend the addition of isosorbide dinitrate heart failure in patients with acute volume overload. p blockers hydralazine in Black patients who remain s)'mptomatic on should be initiated at low doses and slowly uptitrated over maximal doses of a B-blocker: ACE inhibitor. ARB. or ARNI: weeks (not days) until the patient achieves the guideline and aldosterone antagonist. In patients who are intolerant of directed target dose or maximum tolerable dose (Table 13) ACE inhibitor or ARB therapy. especially those u'ith chronic while monitoring for light headedness. hypotension. and kidney disease, isosorbide dinitrate hydralazine may be bradyarrhythmia. Contraindications to B-blocker therapy considered as a therapeutic option. Headache is a common include cardiogenic shock and second- or third degree atrio- adverse effect. ventricular block. In patients with reactive airways disease or Because patients may have difficulty adhering to a thrice COPD, B-blockers should not be initiated if the patient has daily dosing regimen, physicians might consider switching to acute bronchospasm or evidence of pulmonary disease exac once daily therapy with isosorbide mononitrate. However. erbation. Hospitalized patients generally should be started on there is no experimental evidence that isosorbide mononitrate p blocker therapy before discharge. plus hydralazine is as effective as isosorbide dinitrate plus hydralazine or that adherence is improved. Initiating and Managing ACE lnhibitor andB BlockerTherapy Diuretics An ACE inhibitor (or ARB or ARNI) and a p blocker are indi Loop diuretics are the primary diuretic therapy for volume over cated in all patients with HFTEF. Either drug may be initiated load in heart failure because of increased potency compared first, although it is reasonable to select the first agent based on with other diuretics. Of the four loop diuretics, furosemide is patient factors. For example, a B blocker should be started first most commonly used; however, some studies have shown tor in patients with CAD or atrial fibrillation who require heart semide and bumetanide to be more effective because of their rate control. Conversely, an ACE inhibitor should be started increased bioavailability and longer half lives. Occasionally. loop first in patients with diabetes for the additional renal benefits. and thiazide diuretics are combined to potentiate diuresis. The Studies have shown that patients receive additive benefit from lowest dosage that achieves euvolemia should be used. Major the second agent regardless ofthe order ofinitiationi however, side effects include hypokalemia and hypomagnesemia. the second drug should be started befbre the dosage of the first Electrollte levels should be monitored. In patients lvho are eu agent is maximized, especially if the patient has or is at risk for volemic following diuresis and able to adhere to a rigorous salt hypotension. For both drugs, studies suggest that higher doses restricted diet, diuretic dosage may be reduced or discontinued. are associated with reduced hospitalizations and improved symptoms. luabradine Ivabradine is a sinoatrial node modulator that selectively Aldosterone Antagonists inhibits the 11 current in the sinoatrial node. causing a reduc Aldosterone antagonists (spironolactone, eplerenone) reduce tion in heart rate. It has no negative inotropic effects. In mortality and heart failure hospitalizations in patients with patients with HFrEF (LVEF <35')(,) and NYHA functional class symptomatic HFrEF (NYHA functional class II IV) and in II to III symptoms who are in sinus rhyhm u,ith a heart rate patients with HFrEF after acute myocardial infarction. Despite ol at least 7Oimin and taking maximally tolerated doses of a their proven efficacy, they are underused. Current guidelines p blocker, ivabradine reduces heart failure associated hospi recommend initiating these agents in patients with sympto talizations and the combined end point of mortality and heart matic HFrEF and an eGFR of at least 30 ml/min/1.73 m2. tailure hospitalization. 34

Heart Failure Digoxin cotransporter 2 (SGLI2) inhibitors (empagliflozin, canagliflozin, Digoxin reduces the risk fbr hearl failure hospitalization but does and dapagliflozin). SGLI2 inhibitors also appear to reduce the risk not reduce mortality. It is occasionally used in patients with for heart failure hospitalization by 35'1,. The mechanisms of this HFrEF and concomitant atrial fibrillation for rate control and in reduction are unclear but are thought to be independent of patients with heart failure symptoms refractory to optimal ther increased diuresis due to glucose excretion. The DAPA HF trial apy with an ACE inhibitor and B blocker. Because of its associ. showed that dapagliflozin reduced the risk for worsening heafi ated toxicity, digoxin should be managed carefully, and drug failure or cardiovascular death in patients with HFTEE, independ levels should be monitored. Toxicity is more common in patients ent of underVing glucose control. SGLI2 inhibitors should be with impaired kidney lunction, older adults, and women. initiated for patients with hearl lailure and NYHA functional class II to IV symptoms with or without tlpe 2 diabetes, in addition to Calcium Channel Blockers guideline directed medical therapy, to reduce the risk for worsen The nondihydropyridine calciunr channel blockers verapamil ing hearl failure and cardiovascular death. An eGFR of at least and diltiazem are detrimental in patients with HFTEF, proba 30 ml/min/1.73 m2 for dapagliflozin and at least 20 ml/min/ bly related to negative inotropic eflfects, and should not be 1.73 m2 for empagliflozin is recommended before initiation. used. Amlodipine and f'elodipine have shown neither benefit nor harm and can be used in patients with persistent hyper lron Therapy tension despite therapy with other agents at maximal dosage. All patients should be evaluated at baseline for anemia, which is independently associated with heart failure severity. Iron Stotins deficiency has been linked with reduced lunctional capacity, Two large clinical trials have shown no benefit'a.hen rosuva- and multiple small studies in patients with heart failure and statin is added to standard medical therapy in patients with concomitant iron deficiency have shown an improvement in lIFrEF, and statins should not be used routinely in patients f'unctional capacity and quality of life with iron replacement. with heart failure without another accepted indication. Some experts contend that impaired iron absorption should Moderate intensity statin therapy can be considered in prompt intravenous rather than oral iron therapy. patients with HFrEF attributable to ischemic heart disease if life expectancy is reasonable (S 5 years). t(EY POtltTS o Guidelines recommend replacing an ACE inhibitor or Sodium-Glu cose Cotransporter 2 Inhibitors angiotensin receptor blocker (ARB) with valsartan Glucose lowering medications have been evaluated fbr their sacubitril in patients with chronic symptomatic heart effect on cardiovascular outcomes, including heafi failure failure with reduced ejection fraction who tolerate ACE (Table 14). Multiple studies have documented significant reduc inhibitor or ARB therapy. tions in cardiovascular events with use of sodium glucose . In patients with heart failure with reduced ejection TABLE 14. Glucose-Lowering Medications in Patients fraction, p blockers prolong survival and are generally With Heart Failure well tolerated, but they should not be initiated in patients Drug Class Considerations with acute decompensation. Biguanides Survival benefit in patients with HF o Aldosterone antagonists reduce mortality and heart fail (metformin) Discontinue in patients with lactic acidosis ure hospitalizations in patients with symptomatic heart or cardiogenic shock failure but are underused. Sulfonylureas No randomized data in patients with HF . In Black patients with New York Heart Association func Th iazolid ined iones Not recommended because of increased tional class III to IV symptoms, isosorbide dinitrate risk or worsening of HF hydralazine used in combination with an ACE inhibitor, ln ulin Observational studies suggest an p blocker, and aldosterone antagonist has been shown increase in HF with insulin therapy to reduce mortality. GLP-1 receptor Reduce major adverse cardiovascular antagonists events but no impact or detriment in o Ivabradine should be considered for patients with patients with HF symptomatic heart failure and an ejection fraction of lf recent HF hospitalization, use with 35'7, or less who have an elevated heart rate (>7Olmin) caution based on two smalltrials in sinus rhythm and are taking maximally tolerated DPP-4 inhibitors No evidence of cardiovascular benefit B blockertherapy. 5GLT2 inhibitors Reduce risk for worsening HF and . The goal treatment regimen for mortality reduction in cardiovascular death in patients with HF patients with heart failure with reduced ejection frac with reduced ejection fraction with or without type 2 diabetes mellitus tion comprises an angiotensin receptor-neprilysin inhibitor, a p-blocker, an aldosterone antagonist, and a DPP-4 = dipeptidyl peptidase 4; GLP 1 = glucagon like peptide 1; HF = heart failure; SGLT2 = sodium glucose cotransporter 2. sodium glucose cotransporter 2 inhibitor.

Digoxin cotransporter 2 (SGLI2) inhibitors (empagliflozin, canagliflozin, Digoxin reduces the risk fbr hearl failure hospitalization but does and dapagliflozin). SGLI2 inhibitors also appear to reduce the risk not reduce mortality. It is occasionally used in patients with for heart failure hospitalization by 35'1,. The mechanisms of this HFrEF and concomitant atrial fibrillation for rate control and in reduction are unclear but are thought to be independent of patients with heart failure symptoms refractory to optimal ther increased diuresis due to glucose excretion. The DAPA HF trial apy with an ACE inhibitor and B blocker. Because of its associ. showed that dapagliflozin reduced the risk for worsening heafi ated toxicity, digoxin should be managed carefully, and drug failure or cardiovascular death in patients with HFTEE, independ levels should be monitored. Toxicity is more common in patients ent of underVing glucose control. SGLI2 inhibitors should be with impaired kidney lunction, older adults, and women. initiated for patients with hearl lailure and NYHA functional class II to IV symptoms with or without tlpe 2 diabetes, in addition to Calcium Channel Blockers guideline directed medical therapy, to reduce the risk for worsen The nondihydropyridine calciunr channel blockers verapamil ing hearl failure and cardiovascular death. An eGFR of at least and diltiazem are detrimental in patients with HFTEF, proba 30 ml/min/1.73 m2 for dapagliflozin and at least 20 ml/min/ bly related to negative inotropic eflfects, and should not be 1.73 m2 for empagliflozin is recommended before initiation. used. Amlodipine and f'elodipine have shown neither benefit nor harm and can be used in patients with persistent hyper lron Therapy tension despite therapy with other agents at maximal dosage. All patients should be evaluated at baseline for anemia, which is independently associated with heart failure severity. Iron Stotins deficiency has been linked with reduced lunctional capacity, Two large clinical trials have shown no benefit'a.hen rosuva- and multiple small studies in patients with heart failure and statin is added to standard medical therapy in patients with concomitant iron deficiency have shown an improvement in lIFrEF, and statins should not be used routinely in patients f'unctional capacity and quality of life with iron replacement. with heart failure without another accepted indication. Some experts contend that impaired iron absorption should Moderate intensity statin therapy can be considered in prompt intravenous rather than oral iron therapy. patients with HFrEF attributable to ischemic heart disease if life expectancy is reasonable (S 5 years). t(EY POtltTS o Guidelines recommend replacing an ACE inhibitor or Sodium-Glu cose Cotransporter 2 Inhibitors angiotensin receptor blocker (ARB) with valsartan Glucose lowering medications have been evaluated fbr their sacubitril in patients with chronic symptomatic heart effect on cardiovascular outcomes, including heafi failure failure with reduced ejection fraction who tolerate ACE (Table 14). Multiple studies have documented significant reduc inhibitor or ARB therapy. tions in cardiovascular events with use of sodium glucose . In patients with heart failure with reduced ejection TABLE 14. Glucose-Lowering Medications in Patients fraction, p blockers prolong survival and are generally With Heart Failure well tolerated, but they should not be initiated in patients Drug Class Considerations with acute decompensation. Biguanides Survival benefit in patients with HF o Aldosterone antagonists reduce mortality and heart fail (metformin) Discontinue in patients with lactic acidosis ure hospitalizations in patients with symptomatic heart or cardiogenic shock failure but are underused. Sulfonylureas No randomized data in patients with HF . In Black patients with New York Heart Association func Th iazolid ined iones Not recommended because of increased tional class III to IV symptoms, isosorbide dinitrate risk or worsening of HF hydralazine used in combination with an ACE inhibitor, ln ulin Observational studies suggest an p blocker, and aldosterone antagonist has been shown increase in HF with insulin therapy to reduce mortality. GLP-1 receptor Reduce major adverse cardiovascular antagonists events but no impact or detriment in o Ivabradine should be considered for patients with patients with HF symptomatic heart failure and an ejection fraction of lf recent HF hospitalization, use with 35'7, or less who have an elevated heart rate (>7Olmin) caution based on two smalltrials in sinus rhythm and are taking maximally tolerated DPP-4 inhibitors No evidence of cardiovascular benefit B blockertherapy. 5GLT2 inhibitors Reduce risk for worsening HF and . The goal treatment regimen for mortality reduction in cardiovascular death in patients with HF patients with heart failure with reduced ejection frac with reduced ejection fraction with or without type 2 diabetes mellitus tion comprises an angiotensin receptor-neprilysin inhibitor, a p-blocker, an aldosterone antagonist, and a DPP-4 = dipeptidyl peptidase 4; GLP 1 = glucagon like peptide 1; HF = heart failure; SGLT2 = sodium glucose cotransporter 2. sodium glucose cotransporter 2 inhibitor. 35

Heart Failure Despite many studies of therapeutic agents, no drug has classified as "warm" (adequate perfusion) or "cold" (inade been shown to reduce morbidity or mortality in patients with quate perfusion). Signs of inadequate perfusion include cool HFpEF a finding that may reflect the heterogeneity of HFpEF extremities. narrow pulse pressure. poor mentation. and etiologz. The TOPCAT trial showed no difference in the pri worsening kidney function. Intravenous inotropes or other mary combined end point of death, aborted cardiac arrest. or advanced therapies should be considered in patients with poor heart failure hospitalization with spironolactone versus pla perfusion to improve cardiac function. cebo. In retrospective analysis, there was an unusual amount In patients with decompensated heart failure with fluid of regional variation in efficacy. Specially, a mortality advan overload. effectire diuresis is essential (Figure la). Loop diuret tage was noted in the United States but not confirmed in ics are the principal therapy. ln a study evaluating different European patients. According to ACC/AHA guidelines. in strategies fbr diuresis, including varied diuretic dosages and select patients with HFpEF with an elevated BNP level or heart bolus versus continuous therapy, high dose diuretics (2.5 failure hospitalization within 1 year, aldosterone antagonists times the outpatient oral daily dosage) were associated r,r,ith might be considered to decrease hospitalizations. The con increased diuresis but also transient worsening of kidney traindications for aldosterone antagonists in patients with function. No differences were observed between bolus and HFpEF are the same as those for patients with HFTEF. continuous intravenous infusion groups, and length ofstay did ln 2021. based on the results of the PARAGON HF trial. not differ regardless of the strateg, used. ln patients '*'ho do which demonstrated a nonsignificant reduction in the primary not achieve adequate diuresis with a loop diuretic. increasing end point of heart failure hospitalization or cardiovascular the dosage or adding a thiazide diuretic may be considered. death, the FDA expanded the indication for valsartan sacubitril Notably, administering low dose dopamine to improve diure to include all patients with heart failure, regardless of ejection sis and preserve kidney function offers no benefit. fraction. This decision was primarily based on the finding that Many patients with acute decompensated heart failure patients with an LVEF between 45'7, and 55'2, appeared to ben either present with or develop concomitant acute kidney d1's- efit from the drug. function, termed cardiorenal s1'ndrome. Cardiorenal s1'n drome is related to neurohormonal activation. abdominal XEY POIlII vascular congestion leading to decreased renal perfusion, and . The primary therapies for heart failure with preserved worsening cardiac function (see MKSAP 19 Nephrologr). Often, ejection fraction are diuretics to control symptoms of continued diuresis with higher diuretic doses is required volume overload and antihypertensive agents to target a despite worsening kidney function. Withholding ACE inhibi systolic blood pressure of less than 130 mm Hg. tors and aldosterone antagonists may be reasonable until kid ney function improves. If kidney function '"torsens as the Acute Decompensated Heart Failure patient approaches euvolemia, withholding diuretics for 1 day Initial management of acute decompensated heart failure to allow extravascular fluid to redistribute into the vascular focuses on identifying the cause of the heart failure exacerba space should be considered. tion, determining the patient's current physiologic state, Standard heart failure therapy including ACE inhibitor removing fluid to improve congestion, and optimizing medical (or ARB) therapy, p blockers. and aldosterone antagonists. therapy before discharge. should be maintained throughout hospitalization or restarted Common causes of acute decompensation include fluid before discharge. If p-blockers are discontinued at admission overload in the setting of nonadherence to dietary fluid or salt because ofsigns oflow cardiac output, therapy should not be intake recommendations and recurrent ischemia in patients reinitiated until the patient improves. If the patient is admitted with ischemic cardiomyopathy. Fluid overload may be related with volume overload without signs of low cardiac output. to an inability to tolerate previous levels offluid and salt intake B blocker therapy can usually be maintained at the same or a due to progression of LV dysfunction or may occur after an lower dosage during hospitalization. unintentional increase in salt intake. Other causes of decon.r In patients with respiratory distress not requiring pensation include hypertension, concomitant illness, and mechanical ventilation, noninvasive positive pressure ventila nonadherence to therapy with diuretics and other medica tion is associated with reduced need for intubation and. tions. Identifying the cause of decompensation may mitigate according to some data. a reduction in mortality. It is unclear risk and prevent recurrence. ilnoninvasive positive pressure ventilation results in a shorter Volume status should be assessed in all patients hospital length of hospital stay. ized for heart failure. Symptoms of volume overload include BNP level should be measured on admission and before orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, discharge for prognostic purposes. High BNP levels on admis weight gain, and progressive exertional dyspnea. On physical sion are linked with increased mortality and rehospitalization. examination. jugular venous distention is usually present. Likewise, BNP levels that fail to decrease during hospitaliza Patients may have crackles (which are much more likely in tion are associated with a higher mortality rate. Serum tro acute than chronic heart failure), ascites, or peripheral edema. ponin measurement on admission also can be used for Perfusion also should be assessed, and patients may be prognostication; patients with elevated troponin levels have

Despite many studies of therapeutic agents, no drug has classified as "warm" (adequate perfusion) or "cold" (inade been shown to reduce morbidity or mortality in patients with quate perfusion). Signs of inadequate perfusion include cool HFpEF a finding that may reflect the heterogeneity of HFpEF extremities. narrow pulse pressure. poor mentation. and etiologz. The TOPCAT trial showed no difference in the pri worsening kidney function. Intravenous inotropes or other mary combined end point of death, aborted cardiac arrest. or advanced therapies should be considered in patients with poor heart failure hospitalization with spironolactone versus pla perfusion to improve cardiac function. cebo. In retrospective analysis, there was an unusual amount In patients with decompensated heart failure with fluid of regional variation in efficacy. Specially, a mortality advan overload. effectire diuresis is essential (Figure la). Loop diuret tage was noted in the United States but not confirmed in ics are the principal therapy. ln a study evaluating different European patients. According to ACC/AHA guidelines. in strategies fbr diuresis, including varied diuretic dosages and select patients with HFpEF with an elevated BNP level or heart bolus versus continuous therapy, high dose diuretics (2.5 failure hospitalization within 1 year, aldosterone antagonists times the outpatient oral daily dosage) were associated r,r,ith might be considered to decrease hospitalizations. The con increased diuresis but also transient worsening of kidney traindications for aldosterone antagonists in patients with function. No differences were observed between bolus and HFpEF are the same as those for patients with HFTEF. continuous intravenous infusion groups, and length ofstay did ln 2021. based on the results of the PARAGON HF trial. not differ regardless of the strateg, used. ln patients '*'ho do which demonstrated a nonsignificant reduction in the primary not achieve adequate diuresis with a loop diuretic. increasing end point of heart failure hospitalization or cardiovascular the dosage or adding a thiazide diuretic may be considered. death, the FDA expanded the indication for valsartan sacubitril Notably, administering low dose dopamine to improve diure to include all patients with heart failure, regardless of ejection sis and preserve kidney function offers no benefit. fraction. This decision was primarily based on the finding that Many patients with acute decompensated heart failure patients with an LVEF between 45'7, and 55'2, appeared to ben either present with or develop concomitant acute kidney d1's- efit from the drug. function, termed cardiorenal s1'ndrome. Cardiorenal s1'n drome is related to neurohormonal activation. abdominal XEY POIlII vascular congestion leading to decreased renal perfusion, and . The primary therapies for heart failure with preserved worsening cardiac function (see MKSAP 19 Nephrologr). Often, ejection fraction are diuretics to control symptoms of continued diuresis with higher diuretic doses is required volume overload and antihypertensive agents to target a despite worsening kidney function. Withholding ACE inhibi systolic blood pressure of less than 130 mm Hg. tors and aldosterone antagonists may be reasonable until kid ney function improves. If kidney function '"torsens as the Acute Decompensated Heart Failure patient approaches euvolemia, withholding diuretics for 1 day Initial management of acute decompensated heart failure to allow extravascular fluid to redistribute into the vascular focuses on identifying the cause of the heart failure exacerba space should be considered. tion, determining the patient's current physiologic state, Standard heart failure therapy including ACE inhibitor removing fluid to improve congestion, and optimizing medical (or ARB) therapy, p blockers. and aldosterone antagonists. therapy before discharge. should be maintained throughout hospitalization or restarted Common causes of acute decompensation include fluid before discharge. If p-blockers are discontinued at admission overload in the setting of nonadherence to dietary fluid or salt because ofsigns oflow cardiac output, therapy should not be intake recommendations and recurrent ischemia in patients reinitiated until the patient improves. If the patient is admitted with ischemic cardiomyopathy. Fluid overload may be related with volume overload without signs of low cardiac output. to an inability to tolerate previous levels offluid and salt intake B blocker therapy can usually be maintained at the same or a due to progression of LV dysfunction or may occur after an lower dosage during hospitalization. unintentional increase in salt intake. Other causes of decon.r In patients with respiratory distress not requiring pensation include hypertension, concomitant illness, and mechanical ventilation, noninvasive positive pressure ventila nonadherence to therapy with diuretics and other medica tion is associated with reduced need for intubation and. tions. Identifying the cause of decompensation may mitigate according to some data. a reduction in mortality. It is unclear risk and prevent recurrence. ilnoninvasive positive pressure ventilation results in a shorter Volume status should be assessed in all patients hospital length of hospital stay. ized for heart failure. Symptoms of volume overload include BNP level should be measured on admission and before orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, discharge for prognostic purposes. High BNP levels on admis weight gain, and progressive exertional dyspnea. On physical sion are linked with increased mortality and rehospitalization. examination. jugular venous distention is usually present. Likewise, BNP levels that fail to decrease during hospitaliza Patients may have crackles (which are much more likely in tion are associated with a higher mortality rate. Serum tro acute than chronic heart failure), ascites, or peripheral edema. ponin measurement on admission also can be used for Perfusion also should be assessed, and patients may be prognostication; patients with elevated troponin levels have 38

Heart Failure Continue diuretics Trajectory: lmproving . Target relief of congestion towards target o Plan for transition to oral therapy lnitiate lV loop diuretics early (ED or immediately after admission) lnitial dose usually 1-2.5 times Escalate diuretics . Usually increase loop total daily oral loop diuretic in Monitor symptoms, signs, Trajectory: lnitial IV furosemide equivalents diuretic dose by 50o/o-1OO% Diuretics urine output, BP, electrolytes, improvement, then o Consider metolazone and assess trajectory stalled Prescribe lV diuretics (every 8-1 2 2.5-5 mg 1-2x daily h or continuous), depending on r Consider other thiazides patient characteristics, diuretic response, kidney function

lnitial dose usually 1-2.5 times Escalate diuretics . Usually increase loop total daily oral loop diuretic in Monitor symptoms, signs, Trajectory: lnitial IV furosemide equivalents diuretic dose by 50o/o-1OO% Diuretics urine output, BP, electrolytes, improvement, then o Consider metolazone and assess trajectory stalled Prescribe lV diuretics (every 8-1 2 2.5-5 mg 1-2x daily h or continuous), depending on r Consider other thiazides patient characteristics, diuretic response, kidney function Change course . Escalate diuretics Trajectory: Not o Consider other improved/worsening decongestion strategies o Consider hemodynamic monitoring . Consider inotropes . Consider advanced therapies

Change course . Escalate diuretics Trajectory: Not o Consider other improved/worsening decongestion strategies o Consider hemodynamic monitoring . Consider inotropes . Consider advanced therapies tIGURE 14. Diuretictherapyindifferentclinicaltrajectories.BP=bloodpressure; ED-emergencydepartment; lV=intravenous.

Change course . Escalate diuretics Trajectory: Not o Consider other improved/worsening decongestion strategies o Consider hemodynamic monitoring . Consider inotropes . Consider advanced therapies tIGURE 14. Diuretictherapyindifferentclinicaltrajectories.BP=bloodpressure; ED-emergencydepartment; lV=intravenous. worse clinical outcomes and a higher risk for death. Currently, function. Treatment initially fbcuses on reversing the cause there are no absolute cutoff values for these biomarkers, and ofshock, such as reperfusion in the setting ofacute coronary measurement data should be used in combination with clini syndrome. Intravenous inotropic agents are often required cal judgment to guide management. to improve hemodynamic status, including cardiac output and urine output (Table 15) (see MKSAP 19 Pulmonary and Cardiogenic Shock Critical Care Medicine). Routine invasive pulmonary artery Cardiogenic shock is characterized by signs and symptoms of' catheterization to monitor hemodynamics does not improve low cardiac output with hypotension (systolic blood pressure survival or reduce future hospitalization in patients with <90 mm Hg or support to maintain blood pressure) and evi decompensated heart lailure. Pulmonary artery catheteriza dence of end organ hypoperfusion. Laboratory evaluation tion should be used only when hemodynamic and volume includes assessment of BNP. lactate, and kidney and liver status is unclear or when hemodynamic data may lead to

worse clinical outcomes and a higher risk for death. Currently, function. Treatment initially fbcuses on reversing the cause there are no absolute cutoff values for these biomarkers, and ofshock, such as reperfusion in the setting ofacute coronary measurement data should be used in combination with clini syndrome. Intravenous inotropic agents are often required cal judgment to guide management. to improve hemodynamic status, including cardiac output and urine output (Table 15) (see MKSAP 19 Pulmonary and Cardiogenic Shock Critical Care Medicine). Routine invasive pulmonary artery Cardiogenic shock is characterized by signs and symptoms of' catheterization to monitor hemodynamics does not improve low cardiac output with hypotension (systolic blood pressure survival or reduce future hospitalization in patients with <90 mm Hg or support to maintain blood pressure) and evi decompensated heart lailure. Pulmonary artery catheteriza dence of end organ hypoperfusion. Laboratory evaluation tion should be used only when hemodynamic and volume includes assessment of BNP. lactate, and kidney and liver status is unclear or when hemodynamic data may lead to TABLE 15. lntravenousVasoactive Medications Used forTreatment of Cardiogenic Shock Medication Mechanism lnotropy Vasodilation Milrinone Phosphodiesterase inhibition +-t- + Dobutamine B1, p2 Receptor agonism # (+)(at low dose) - (vasoconstriction at high dose) Sodium nitroprusside Nitric oxide production 0 + Nitroglycerin Nitric oxide production 0 +r (mainly venous) Vasopressin Arginine vasopressin receptor (V receptor) agonism - (vasoconstriction) Dopamine Dopaminergic receptor (D receptor) agonism + - (vasoconstriction at high dose) p1 Receptor agonism at intermediate dose

TABLE 15. lntravenousVasoactive Medications Used forTreatment of Cardiogenic Shock Medication Mechanism lnotropy Vasodilation Milrinone Phosphodiesterase inhibition +-t- + Dobutamine B1, p2 Receptor agonism # (+)(at low dose) - (vasoconstriction at high dose) Sodium nitroprusside Nitric oxide production 0 + Nitroglycerin Nitric oxide production 0 +r (mainly venous) Vasopressin Arginine vasopressin receptor (V receptor) agonism - (vasoconstriction) Dopamine Dopaminergic receptor (D receptor) agonism + - (vasoconstriction at high dose) p1 Receptor agonism at intermediate dose cr1 Receptor agonism at high dose Norepinephrine cr1, cr2 Receptor agonism greaterthan p1 receptor + - (vasoconstriction) agonism Strength of effect: + indicates very strong; + indicates strong; (+) indicates weak; 0 ind cates neutral; indicates opposite effect. 39

Heart Failure advanced mechanical circulatory support or consideration of Advanced Refractory Heart Failure heart transplantation. Patients with persistent severe l.reart failure symptoms despite Percutaneous mechanical support during acute exacerba maximal medical therapy (ACC/AHA stage D) are candidates tions has greatly increased in recent years. Intra aortic balloon for advanced treatment. Cardiac transplantation remains the pumps, percutaneous ventricular assist devices' and extracor gold standard therapy tbr patients with end stage heart failure: poreal membrane oxygenators can be quickly placed to sup however. because of a lack of appropriate donors. only 3500 port the critically ill patient. Treatment by a team comprising heart transplantations are performed in the United States each a heart failure physician, critical care physician. and cardiac ,ear. accounting for approximately 50'),, of eligible patients surgeon is suggested to rapidly deploy therapy and provide awaiting transplantation. Acceptable candidates for transplan postprocedure care. Consideration of'longer term options for tation generally are younger than 65 to 70,€ars $'ith no medi advanced heart failure (heart transplantation or LVAD place cal contraindications (e.g.. diabetes with end organ complica ment) is an important aspect o1'management for patients tions. malignancies within 5 years. kidney dysfunction. or receiving mechanical support in the acute setting. For patients other chronic illnesses that will decrease survival) and good who do not show clinical improvement, there should be daily social support and adherence. Many patients awaiting trans discussions about treatment options and goals of care, includ- plant also require an LVAD for support until an organ becomes ing transplantation, permanent device placement, and pallia- available. Hospice may be considered as an option in shared tive or hospice care. decision making discussions.

advanced mechanical circulatory support or consideration of Advanced Refractory Heart Failure heart transplantation. Patients with persistent severe l.reart failure symptoms despite Percutaneous mechanical support during acute exacerba maximal medical therapy (ACC/AHA stage D) are candidates tions has greatly increased in recent years. Intra aortic balloon for advanced treatment. Cardiac transplantation remains the pumps, percutaneous ventricular assist devices' and extracor gold standard therapy tbr patients with end stage heart failure: poreal membrane oxygenators can be quickly placed to sup however. because of a lack of appropriate donors. only 3500 port the critically ill patient. Treatment by a team comprising heart transplantations are performed in the United States each a heart failure physician, critical care physician. and cardiac ,ear. accounting for approximately 50'),, of eligible patients surgeon is suggested to rapidly deploy therapy and provide awaiting transplantation. Acceptable candidates for transplan postprocedure care. Consideration of'longer term options for tation generally are younger than 65 to 70,€ars $'ith no medi advanced heart failure (heart transplantation or LVAD place cal contraindications (e.g.. diabetes with end organ complica ment) is an important aspect o1'management for patients tions. malignancies within 5 years. kidney dysfunction. or receiving mechanical support in the acute setting. For patients other chronic illnesses that will decrease survival) and good who do not show clinical improvement, there should be daily social support and adherence. Many patients awaiting trans discussions about treatment options and goals of care, includ- plant also require an LVAD for support until an organ becomes ing transplantation, permanent device placement, and pallia- available. Hospice may be considered as an option in shared tive or hospice care. decision making discussions. Strategies to Prevent Readmission Mechanical Circulatory SupPort The first step in preventing heart lailure readmission is to treat Clinical outcomes in patients rn,ith advanced heart failure hare reversible causes of the exacerbation. Discharge should not markedly improved u'ith the use of LVADs. With neu€r occur until the patient has approached euvolemia with diure- continuous flow devices, patients have 1 year sun'ival approx sis. Medication reconciliation befbre discharge should ensure imating that of cardiac transplant recipients and substantial that the patient is taking the appropriate medications, particu improvements in functional capacity and quality of life. The larly those that reduce mortality and morbidity in heart failure. use ofLVADs as destination therapy rather than as a bridge to Education on heart failure physiologr. the importance of medi transplant is increasing. LVAD placement is currently indi cation and dietary adherence, signs and symptoms of worsen cated in patients with LVEF less than 25'1, and poor exercise ing hearl failure, and when to contact a physician should be tolerance (NYHA functional class lll,'lV) despite maximal provided. A home nurse, in follow up after discharge, can tolerated therapy. r,r,ith either a high predicted 1 to 2 year ct-rntinue patient education, provide confirmation that dis mortality or inotrope dependency. rtho continue to desire charge medications coincide with home medications. and aggressive restorative care.

Strategies to Prevent Readmission Mechanical Circulatory SupPort The first step in preventing heart lailure readmission is to treat Clinical outcomes in patients rn,ith advanced heart failure hare reversible causes of the exacerbation. Discharge should not markedly improved u'ith the use of LVADs. With neu€r occur until the patient has approached euvolemia with diure- continuous flow devices, patients have 1 year sun'ival approx sis. Medication reconciliation befbre discharge should ensure imating that of cardiac transplant recipients and substantial that the patient is taking the appropriate medications, particu improvements in functional capacity and quality of life. The larly those that reduce mortality and morbidity in heart failure. use ofLVADs as destination therapy rather than as a bridge to Education on heart failure physiologr. the importance of medi transplant is increasing. LVAD placement is currently indi cation and dietary adherence, signs and symptoms of worsen cated in patients with LVEF less than 25'1, and poor exercise ing hearl failure, and when to contact a physician should be tolerance (NYHA functional class lll,'lV) despite maximal provided. A home nurse, in follow up after discharge, can tolerated therapy. r,r,ith either a high predicted 1 to 2 year ct-rntinue patient education, provide confirmation that dis mortality or inotrope dependency. rtho continue to desire charge medications coincide with home medications. and aggressive restorative care. assess the patient's condition. If home nurse follow up is not Because these devices provide continuous flow. most instituted, a phone call within 48 hours of discharge may be use patients no longer have a palpable pulse. and blood pressure ful to confirm a safe transition ofcare. Finally, an early follow must be measured by Doppler. Therapy includes anticoagula up appointment (within 7 days) should be scheduled to review tion to prevent pump thrombus formation; continued heart the medication list, assess volume status and adherence to diet failure therapy with an ACE inhibitor. ARB. or ARNI and and medications, and reinforce patient education points. p blocker; and management of fluid overload with diuretics. Clinicians caring for hospitalized patients with an LVAD XEY POITIIS require specialized training and continuous emergency access . Management of patients with acute decompensated to an LVAD specialist. heart failure focuses on identifying the cause ofthe LVADs have several potential major complications related to heart failure exacerbation, determining the patient's either the pump itself or the driveline. r.thich passes through the physiologic state, treating fluid overload, and optimizing skin and connects the internal pump to a po\ er source. Major medical therapy before discharge. complications at 2 years reported with a current generation HVC o Routine invasive pulmonary artery catheterization for device include hemorrhagic and thrombotic strokes (9.9'7,)r hemodynamic monitoring is not recommended in inf'ections (skin or at the pump) (58.3'7,); pump thrombosis patients with decompensated heart failure. (1.4'){,); arrh}'thmias (gs.g'it,): and gastrointestinal bleeding (24.5'X,) . which is usually associated with small bouel arterio . In patients hospitalized with acute heart failure, early venous malformations. The incidence of these complications follow-up with home nurse visits, phone contact within is decreasing as pump technologr'improres. 48 hours ofdischarge, and a prompt physician appoint ment (within 7 days) to review the medication list, Management of Posttransplant Patients assess volume status and adherence to diet and medica- Most patients who undergo heart transplantation quickly tions, and reinforce patient education reduces the risk recover physical activity and have normal quality of life, with for heart failure readmission. a mean survival of more than 1l years. The most frequent

assess the patient's condition. If home nurse follow up is not Because these devices provide continuous flow. most instituted, a phone call within 48 hours of discharge may be use patients no longer have a palpable pulse. and blood pressure ful to confirm a safe transition ofcare. Finally, an early follow must be measured by Doppler. Therapy includes anticoagula up appointment (within 7 days) should be scheduled to review tion to prevent pump thrombus formation; continued heart the medication list, assess volume status and adherence to diet failure therapy with an ACE inhibitor. ARB. or ARNI and and medications, and reinforce patient education points. p blocker; and management of fluid overload with diuretics. Clinicians caring for hospitalized patients with an LVAD XEY POITIIS require specialized training and continuous emergency access . Management of patients with acute decompensated to an LVAD specialist. heart failure focuses on identifying the cause ofthe LVADs have several potential major complications related to heart failure exacerbation, determining the patient's either the pump itself or the driveline. r.thich passes through the physiologic state, treating fluid overload, and optimizing skin and connects the internal pump to a po\ er source. Major medical therapy before discharge. complications at 2 years reported with a current generation HVC o Routine invasive pulmonary artery catheterization for device include hemorrhagic and thrombotic strokes (9.9'7,)r hemodynamic monitoring is not recommended in inf'ections (skin or at the pump) (58.3'7,); pump thrombosis patients with decompensated heart failure. (1.4'){,); arrh}'thmias (gs.g'it,): and gastrointestinal bleeding (24.5'X,) . which is usually associated with small bouel arterio . In patients hospitalized with acute heart failure, early venous malformations. The incidence of these complications follow-up with home nurse visits, phone contact within is decreasing as pump technologr'improres. 48 hours ofdischarge, and a prompt physician appoint ment (within 7 days) to review the medication list, Management of Posttransplant Patients assess volume status and adherence to diet and medica- Most patients who undergo heart transplantation quickly tions, and reinforce patient education reduces the risk recover physical activity and have normal quality of life, with for heart failure readmission. a mean survival of more than 1l years. The most frequent 40

Heart Failure complication within the first year after transplant is infection. Black Patients Cytomegalovirus (CMV) infection is common, and patients at Black patients have been underrepresented in many hearl tailure moderate risk (CMV positive donor/CMV-positive recipient) clinical trials, including those involving valsartan-sacubitril, SGLI2 and high risk (CMV-positive donor/CMV,negative recipienr) inhibitors, ivabradir.re, and long acting metoprolol. Based on the should receive antiviral prophylaxis (valganciclovir or ganci benefits observed ir.r the general population, recent guidelines rec clovir) for 6 months. ommend that tslack patients also receive these medications. Expert Incidence of rejection is highest in the first 6 months after consensus suggests first initiating an ARNI, ACE inhibitor, or ARB transplantation. Because most patients with early rejection are (ARNI preferred); a p blockeri alt aldosterone antagonist; and an asymptomatic, regularly scheduled endomyocardial biopsies SGLI2 inhibitor. Once target or maxin-rally tolerated doses of an or gene expression profiling tests are performed to detect RAAS inhibitor, p blocker, and aldosterone antagonist are achieved, rejection for the first few years after transplant. Severe rejec adding isosorbide dinitrate hydralazine is recommended for Black tion is characterized by acute heart failure and atrial arrhyth patients with HFrEF who remain qrn.rptomatic. Black patients mias or conduction abnormalities. have a higher incidence of angioedenra while taking RAAS inhibi Early complications related to immunosuppressive ther tors (ACE inhibitors, ARBs. ARNI); hol,rever, these agents should be apy include hypertension (more than 90"/,, of patients) and initiated despite the increased risk. diabetes (15'X, 2O"1, of patients). Long-term complications after transplantation include CAD and an increased incidence of malignancies, including skin cancer (common) and B-cell lym Specific Ca rd iomyopath ies phoma related to immunosuppressive therapy (less common). Fbr a discussion of'hypertrophic cardiomyopathy and restric

complication within the first year after transplant is infection. Black Patients Cytomegalovirus (CMV) infection is common, and patients at Black patients have been underrepresented in many hearl tailure moderate risk (CMV positive donor/CMV-positive recipient) clinical trials, including those involving valsartan-sacubitril, SGLI2 and high risk (CMV-positive donor/CMV,negative recipienr) inhibitors, ivabradir.re, and long acting metoprolol. Based on the should receive antiviral prophylaxis (valganciclovir or ganci benefits observed ir.r the general population, recent guidelines rec clovir) for 6 months. ommend that tslack patients also receive these medications. Expert Incidence of rejection is highest in the first 6 months after consensus suggests first initiating an ARNI, ACE inhibitor, or ARB transplantation. Because most patients with early rejection are (ARNI preferred); a p blockeri alt aldosterone antagonist; and an asymptomatic, regularly scheduled endomyocardial biopsies SGLI2 inhibitor. Once target or maxin-rally tolerated doses of an or gene expression profiling tests are performed to detect RAAS inhibitor, p blocker, and aldosterone antagonist are achieved, rejection for the first few years after transplant. Severe rejec adding isosorbide dinitrate hydralazine is recommended for Black tion is characterized by acute heart failure and atrial arrhyth patients with HFrEF who remain qrn.rptomatic. Black patients mias or conduction abnormalities. have a higher incidence of angioedenra while taking RAAS inhibi Early complications related to immunosuppressive ther tors (ACE inhibitors, ARBs. ARNI); hol,rever, these agents should be apy include hypertension (more than 90"/,, of patients) and initiated despite the increased risk. diabetes (15'X, 2O"1, of patients). Long-term complications after transplantation include CAD and an increased incidence of malignancies, including skin cancer (common) and B-cell lym Specific Ca rd iomyopath ies phoma related to immunosuppressive therapy (less common). Fbr a discussion of'hypertrophic cardiomyopathy and restric Careful attention must be paid to the medication regimen tive cardiomyopathy, refer to Myocardial Disease. Peripartum I cardiomyopathy is discussed in Pregnancy and Cardiovascular of cardiac transplant recipients to avoid drug drug interac tions. Cyclosporine and tacrolimus, two agents commonly Disease.

Careful attention must be paid to the medication regimen tive cardiomyopathy, refer to Myocardial Disease. Peripartum I cardiomyopathy is discussed in Pregnancy and Cardiovascular of cardiac transplant recipients to avoid drug drug interac tions. Cyclosporine and tacrolimus, two agents commonly Disease. i used for immunosuppression, are metabolized by the CYP3A4 system ancl are subject to substantial drug interactions with Ta kotsu bo Ca rd iomyopathy ; 'lakotsubo cardiomyopathy. also knou,n as stress induced car both inhibitors and inducers of this isoenzyme. An extensive list of drugs that can interact through the CYP3A4 isoenzyme diomyopathy or apical ballooning syndrome, is a clinical syn I drome associrrted with reduced LVEF. elevated cardiac enzyme can be found at http:/lmedicine.iupui.edu/clinpharm/ddis. t levels, and sigr.rs of ischen.ria on E(l(1. It typically occurs in KEY PO I l{TS older women and is usually precipitated by a stressful physical I

i used for immunosuppression, are metabolized by the CYP3A4 system ancl are subject to substantial drug interactions with Ta kotsu bo Ca rd iomyopathy ; 'lakotsubo cardiomyopathy. also knou,n as stress induced car both inhibitors and inducers of this isoenzyme. An extensive list of drugs that can interact through the CYP3A4 isoenzyme diomyopathy or apical ballooning syndrome, is a clinical syn I drome associrrted with reduced LVEF. elevated cardiac enzyme can be found at http:/lmedicine.iupui.edu/clinpharm/ddis. t levels, and sigr.rs of ischen.ria on E(l(1. It typically occurs in KEY PO I l{TS older women and is usually precipitated by a stressful physical I I . Patients with severe heart failure symptoms despite or emotional event, such as the death ofa loved one or a sud : maximal medical therapy are candidates for advanced den surprise. The patl-rogenesis of takotsubo cardiomyopatlry I treatment, including placement of a left ventricular assist is unknown. but the condition is postulated to result from t device and heart transplantation. reversible myocarclial toxicity induced by very high catechola I . Patients who undergo heart transplantation have a mine levels. Cardiac irnaging shows wall motion abnormalities median survival of 11 years and, typically, a normal that do not follow ir coronary artery territory (typically, apical i quality of life. dyskinesis or ballooning) with preservation of bas;rl wall r In cardiac transplant recipients, cltomegalovirus infec- motion (Figure 15). Because takotsubo cardiomyopathy resem t bles an acute coronary syndrome, enrergent coronary angiog i tion (within the first year) and rejection (within the first I raphy is often perfbrmed. Treatment is largely supportive and 6 months) are important complications. is similar to that fbr heafi failure of other causes. Most patients ; o Endomyocardial biopsy or gene expression profiling recover cardiac function over the course of a few weeks to I should be routinely performed after heart transplanta- months. As with other forms of new onset heart failure, repeat i tion to diagnose early asymptomatic rejection. echocardiography should be perfbrmed in 3 to 6 months to I evaluate recovery. It is unclear for how long medical therapy 1 Specific Populations should continue in patients with recovery of cardiac function, Patients With Diabetes Mellitus but most clinicians continue therapy fbr at least 1 year. I I Patients with diabetes have a more than twofold increased risk t for heart failure and experience worse outcomes, more hospi Acute Myocarditis t

I . Patients with severe heart failure symptoms despite or emotional event, such as the death ofa loved one or a sud : maximal medical therapy are candidates for advanced den surprise. The patl-rogenesis of takotsubo cardiomyopatlry I treatment, including placement of a left ventricular assist is unknown. but the condition is postulated to result from t device and heart transplantation. reversible myocarclial toxicity induced by very high catechola I . Patients who undergo heart transplantation have a mine levels. Cardiac irnaging shows wall motion abnormalities median survival of 11 years and, typically, a normal that do not follow ir coronary artery territory (typically, apical i quality of life. dyskinesis or ballooning) with preservation of bas;rl wall r In cardiac transplant recipients, cltomegalovirus infec- motion (Figure 15). Because takotsubo cardiomyopathy resem t bles an acute coronary syndrome, enrergent coronary angiog i tion (within the first year) and rejection (within the first I raphy is often perfbrmed. Treatment is largely supportive and 6 months) are important complications. is similar to that fbr heafi failure of other causes. Most patients ; o Endomyocardial biopsy or gene expression profiling recover cardiac function over the course of a few weeks to I should be routinely performed after heart transplanta- months. As with other forms of new onset heart failure, repeat i tion to diagnose early asymptomatic rejection. echocardiography should be perfbrmed in 3 to 6 months to I evaluate recovery. It is unclear for how long medical therapy 1 Specific Populations should continue in patients with recovery of cardiac function, Patients With Diabetes Mellitus but most clinicians continue therapy fbr at least 1 year. I I Patients with diabetes have a more than twofold increased risk t for heart failure and experience worse outcomes, more hospi Acute Myocarditis t : talizations, and a worse prognosis than those without diabe Myocarditis is a clinical syndrome ol acute onset heart failure. I t tes. Even when blood glucose levels are controlled, patients Causes include viral. bacterial. or other inf'ections: toxins; and I I with diabetes have a higher incidence of heart failure. immunologic syndromes. The classic fbrm is viral in origir.r and Aggressive blood glucose control has not been associated with is preceded by a typical upper respiratory tract infection caused l i better outcomes. Implementing therapy with agents shown to by adenovirus, echovirus, or coxsackievirus. Patients may have improve cardiovascular and heart failure outcomes is prudent no antecedent symptoms or have a viral prodrome with fever, (see Table 1.1). myalgia, and respiratory symptoms. Although the pathogenesis

: talizations, and a worse prognosis than those without diabe Myocarditis is a clinical syndrome ol acute onset heart failure. I t tes. Even when blood glucose levels are controlled, patients Causes include viral. bacterial. or other inf'ections: toxins; and I I with diabetes have a higher incidence of heart failure. immunologic syndromes. The classic fbrm is viral in origir.r and Aggressive blood glucose control has not been associated with is preceded by a typical upper respiratory tract infection caused l i better outcomes. Implementing therapy with agents shown to by adenovirus, echovirus, or coxsackievirus. Patients may have improve cardiovascular and heart failure outcomes is prudent no antecedent symptoms or have a viral prodrome with fever, (see Table 1.1). myalgia, and respiratory symptoms. Although the pathogenesis 41 I

Heart Failure FIGURE 15. Leftventriculogramshowingtakotsubo(stress) cardiomyopathyduringsystole(/ef)anddiastole(lght). lnsystole,thebasal segmentsof theheartcontract well, while the apical portion of the heart is dyskinetic (bulges outward as opposed to inward) (arrows).

Heart Failure FIGURE 15. Leftventriculogramshowingtakotsubo(stress) cardiomyopathyduringsystole(/ef)anddiastole(lght). lnsystole,thebasal segmentsof theheartcontract well, while the apical portion of the heart is dyskinetic (bulges outward as opposed to inward) (arrows). is not completely understood, it is thought that acute viral Sarcoidosis infection causes early destruction of myocytes followed by an Cardiac sarcoidosis is found at autopsy in up to 25% ofpatients immune response that causes further destruction. with systemic sarcoidosis. Cardiac manifestations include ven- Echocardiography helps rule out other causes of heart tricular tachycardia, second- or third degree atrioventricular failure. Definitive diagnosis may require CMR imaging or endo- block, and HFTEF. Diagnosis is made by the presence of non myocardial biopsy. Biopsy is recommended for patients with caseating granuloma with no alternative cause identified on recent-onset heart failure (<2 weeks) accompanied by hemo extracardiac or endomyocardial biopsy and clinical cardiac dynamic compromise and patients with unexplained new- manifestations. Cardiac imaging studies for diagnosis include onset heart failure of 2 weeks' to 3 months' duration who PET and CMR imaging. Therapy for patients with sarcoidosis develop new arrhl.thmias or do not respond to evidence based and heart failure includes standard heart failure therapy and therapy within 2 weeks. Standard therapy for heart failure is immunosuppressive medications. For acute flares of either recommended; anti inflammatory agents do not offer benefit. heart failure (decline in LVEF) or arrhythmias, high dose prednisone is typically initiated, followed by tapering over 3 to Giant Cell Myocarditis 6 months. Giant cell myocarditis is an acute and often fatal form of myo- carditis that typically occurs in younger persons. It is often Tachycardia-Mediated Cardiomyopathy rapidly progressive and can cause both left and right ventricu- Tachycardia-mediated cardiomyopathy has been associated lar dysfunction. Giant cell myocarditis is also associated with with supraventricular and ventricular arrhl.thmias. Reversible an increased incidence of high-grade atrioventricular block causes of tachycardia (e.g., hyperthyroidism) should be and ventricular arrhythmias. Patients with acute heart failure excluded. Importantly, rate control (B blockers) or rhythm unresponsive to usual care or with accompanying arrhy.thmias control (catheter ablation) improves LV function in these should undergo endomyocardial biopsy for diagnosis. Initial patients. In patients with atrial fibrillation associated with biopsy findings may be negative because of the patchy nature rapid ventricular response, no evidence shows that convert of the inflammation. Unlike in acute myocarditis, aggressive ing to sinus rhythm is more efficacious than controlling immunosuppressive therapy has some benefit and should be heart rate. In patients with ventricular arrhl.thmias or fre- initiated. Patients often require percutaneous or surgical ven quent premature ventricular contractions. cardiomyopathy tricular support until they recover or need heart transplanta is generally thought to develop when the burden of prema tion or LVAD placement. If giant cell myocarditis is suspected, ture ventricular contractions is more than 10,000 per day prompt transfer to a hospital equipped with mechanical sup or more than 10% of all beats; ablation, especially if the port should be considered because patients can progress from premature ventricular contractions are unifocal, should be feeling well to moribund within hours. considered.

is not completely understood, it is thought that acute viral Sarcoidosis infection causes early destruction of myocytes followed by an Cardiac sarcoidosis is found at autopsy in up to 25% ofpatients immune response that causes further destruction. with systemic sarcoidosis. Cardiac manifestations include ven- Echocardiography helps rule out other causes of heart tricular tachycardia, second- or third degree atrioventricular failure. Definitive diagnosis may require CMR imaging or endo- block, and HFTEF. Diagnosis is made by the presence of non myocardial biopsy. Biopsy is recommended for patients with caseating granuloma with no alternative cause identified on recent-onset heart failure (<2 weeks) accompanied by hemo extracardiac or endomyocardial biopsy and clinical cardiac dynamic compromise and patients with unexplained new- manifestations. Cardiac imaging studies for diagnosis include onset heart failure of 2 weeks' to 3 months' duration who PET and CMR imaging. Therapy for patients with sarcoidosis develop new arrhl.thmias or do not respond to evidence based and heart failure includes standard heart failure therapy and therapy within 2 weeks. Standard therapy for heart failure is immunosuppressive medications. For acute flares of either recommended; anti inflammatory agents do not offer benefit. heart failure (decline in LVEF) or arrhythmias, high dose prednisone is typically initiated, followed by tapering over 3 to Giant Cell Myocarditis 6 months. Giant cell myocarditis is an acute and often fatal form of myo- carditis that typically occurs in younger persons. It is often Tachycardia-Mediated Cardiomyopathy rapidly progressive and can cause both left and right ventricu- Tachycardia-mediated cardiomyopathy has been associated lar dysfunction. Giant cell myocarditis is also associated with with supraventricular and ventricular arrhl.thmias. Reversible an increased incidence of high-grade atrioventricular block causes of tachycardia (e.g., hyperthyroidism) should be and ventricular arrhythmias. Patients with acute heart failure excluded. Importantly, rate control (B blockers) or rhythm unresponsive to usual care or with accompanying arrhy.thmias control (catheter ablation) improves LV function in these should undergo endomyocardial biopsy for diagnosis. Initial patients. In patients with atrial fibrillation associated with biopsy findings may be negative because of the patchy nature rapid ventricular response, no evidence shows that convert of the inflammation. Unlike in acute myocarditis, aggressive ing to sinus rhythm is more efficacious than controlling immunosuppressive therapy has some benefit and should be heart rate. In patients with ventricular arrhl.thmias or fre- initiated. Patients often require percutaneous or surgical ven quent premature ventricular contractions. cardiomyopathy tricular support until they recover or need heart transplanta is generally thought to develop when the burden of prema tion or LVAD placement. If giant cell myocarditis is suspected, ture ventricular contractions is more than 10,000 per day prompt transfer to a hospital equipped with mechanical sup or more than 10% of all beats; ablation, especially if the port should be considered because patients can progress from premature ventricular contractions are unifocal, should be feeling well to moribund within hours. considered. 42

Arrhythmias Arrhythmias Sinus Bradycardia Sinus bradycardia is defined as the presence ofsinus rhythm lntroduction with a heart rate below 50/min. Sinus bradycardia may be Disruptions in cardiac rhythm or rate occur in seven basic pat appropriate in trained athletes and during sleep. Inappropriate terns: early beats, bigeminal beats, grouped beats, pauses, or patholoqic sinus bradycardia is most commonly caused by bradycardia, tachycardia, and chaotic rhythms. This section sinus node dysfunction due to age related myocardial fibrosis. Less commonly, sinus node dysfunction may result from right provides an approach to arrhythmias and discusses the diag nosis and management of specific rhythm disorders. coronary ischemia, hypothyroidism, intracranial hyperten sion. postoperative scarring or fibrosis from cardiothoracic surgery or infiltrative or inflammatory disorders (e.g., sar Approach to the Patient coidosis). The most common extrinsic cause is medication use With Bradycardia (B blockers, donepezil, neostigmine, pyridostigmine).

Arrhythmias Sinus Bradycardia Sinus bradycardia is defined as the presence ofsinus rhythm lntroduction with a heart rate below 50/min. Sinus bradycardia may be Disruptions in cardiac rhythm or rate occur in seven basic pat appropriate in trained athletes and during sleep. Inappropriate terns: early beats, bigeminal beats, grouped beats, pauses, or patholoqic sinus bradycardia is most commonly caused by bradycardia, tachycardia, and chaotic rhythms. This section sinus node dysfunction due to age related myocardial fibrosis. Less commonly, sinus node dysfunction may result from right provides an approach to arrhythmias and discusses the diag nosis and management of specific rhythm disorders. coronary ischemia, hypothyroidism, intracranial hyperten sion. postoperative scarring or fibrosis from cardiothoracic surgery or infiltrative or inflammatory disorders (e.g., sar Approach to the Patient coidosis). The most common extrinsic cause is medication use With Bradycardia (B blockers, donepezil, neostigmine, pyridostigmine). Clinical Presentation and Evaluation Bradycardia (heart rate <50/min) may be asymptomatic or asso Atrioventricular Block ciatecl with light headedness, syncope, exertional inttilerance, AV block may be classified as first degree, second degree, or dyspnea, or fatigue. It can be a normal finding or result lrom third degree. First degree AV block is defined by a delay in AV disease in the sinus node, atrioventricular (AV) node. or His conduction (PR interval >200 ms). In large cohort studies, Purkinje system or from dysfunction of'the autonomic system. first degree AV block has been associated with an increased Diagnostic evaluaticin consists of a thorough history, risk for atrial flbrillation (AF) and all-cause mortality. physicat examination, focused laboratory testing (electrolyte In second degree AV block, only some P waves conduct to levels, thyroid function testing). and resting 12 lead ECC. the ventricles. Mobitz type I second degree (Wenckebach) AV Severe or unstable conduction abnormalities that require block is characterized electrocardiographically by a PR interval urgent intervention must be identified.'[he evaluation should that progressively prolongs until a QRS complex is dropped, also include investigation for extrinsic and reversible causes of resulting in grouped beating (Figure 16). Mobitz type 2 second- bradycardia, including ischemia, myocarditis, endocarditis, degree AV block is typitied by intermittent nonconducted P hypothyroidism, infecticlus diseases, neurologic events, elec waves with unchanging PR intervals (Figure 17). When 2:1 trolyte disturbances, and medication use (especially AV nodal block is present, the Mobitz type cannot be determined defini blockers and parasympathomimetics). Echocardiography is tively. However, the distinction between types is important fiequently performed, and exercise stress testing to assess Mobitz fype 2 AV block usually occurs below the AV node and chronotropic competence as well as ambulatory ECG monitor has a higher risk for progression to complete heart block. ing may be helpful. Clues fiom the history and physical exami tligh degree AV block ref'ers to the presence of more than one nation (e.g., rash suggestive of' Lyme disease) may dictate successive nonconducted P wave, resulting in several consecu further testing. In patients with nocturnal bradycardia or con tive P waves without QRS complexes. duction disturbances, sleep apnea should be considered and, In third degree AV block, also termed complete heart ifappropriate, evaluated and treated. Isolated nocturnal brad block. no P waves conduct to the ventricles. AV dissociation is yarrhythmias are unlikely to require a permanent pacemaker. observed on the ECG (Figure 18).

Clinical Presentation and Evaluation Bradycardia (heart rate <50/min) may be asymptomatic or asso Atrioventricular Block ciatecl with light headedness, syncope, exertional inttilerance, AV block may be classified as first degree, second degree, or dyspnea, or fatigue. It can be a normal finding or result lrom third degree. First degree AV block is defined by a delay in AV disease in the sinus node, atrioventricular (AV) node. or His conduction (PR interval >200 ms). In large cohort studies, Purkinje system or from dysfunction of'the autonomic system. first degree AV block has been associated with an increased Diagnostic evaluaticin consists of a thorough history, risk for atrial flbrillation (AF) and all-cause mortality. physicat examination, focused laboratory testing (electrolyte In second degree AV block, only some P waves conduct to levels, thyroid function testing). and resting 12 lead ECC. the ventricles. Mobitz type I second degree (Wenckebach) AV Severe or unstable conduction abnormalities that require block is characterized electrocardiographically by a PR interval urgent intervention must be identified.'[he evaluation should that progressively prolongs until a QRS complex is dropped, also include investigation for extrinsic and reversible causes of resulting in grouped beating (Figure 16). Mobitz type 2 second- bradycardia, including ischemia, myocarditis, endocarditis, degree AV block is typitied by intermittent nonconducted P hypothyroidism, infecticlus diseases, neurologic events, elec waves with unchanging PR intervals (Figure 17). When 2:1 trolyte disturbances, and medication use (especially AV nodal block is present, the Mobitz type cannot be determined defini blockers and parasympathomimetics). Echocardiography is tively. However, the distinction between types is important fiequently performed, and exercise stress testing to assess Mobitz fype 2 AV block usually occurs below the AV node and chronotropic competence as well as ambulatory ECG monitor has a higher risk for progression to complete heart block. ing may be helpful. Clues fiom the history and physical exami tligh degree AV block ref'ers to the presence of more than one nation (e.g., rash suggestive of' Lyme disease) may dictate successive nonconducted P wave, resulting in several consecu further testing. In patients with nocturnal bradycardia or con tive P waves without QRS complexes. duction disturbances, sleep apnea should be considered and, In third degree AV block, also termed complete heart ifappropriate, evaluated and treated. Isolated nocturnal brad block. no P waves conduct to the ventricles. AV dissociation is yarrhythmias are unlikely to require a permanent pacemaker. observed on the ECG (Figure 18). 2nd A I Bate 58 BPM 10 mm'mv 02:10:10 5,24'2017

Clinical Presentation and Evaluation Bradycardia (heart rate <50/min) may be asymptomatic or asso Atrioventricular Block ciatecl with light headedness, syncope, exertional inttilerance, AV block may be classified as first degree, second degree, or dyspnea, or fatigue. It can be a normal finding or result lrom third degree. First degree AV block is defined by a delay in AV disease in the sinus node, atrioventricular (AV) node. or His conduction (PR interval >200 ms). In large cohort studies, Purkinje system or from dysfunction of'the autonomic system. first degree AV block has been associated with an increased Diagnostic evaluaticin consists of a thorough history, risk for atrial flbrillation (AF) and all-cause mortality. physicat examination, focused laboratory testing (electrolyte In second degree AV block, only some P waves conduct to levels, thyroid function testing). and resting 12 lead ECC. the ventricles. Mobitz type I second degree (Wenckebach) AV Severe or unstable conduction abnormalities that require block is characterized electrocardiographically by a PR interval urgent intervention must be identified.'[he evaluation should that progressively prolongs until a QRS complex is dropped, also include investigation for extrinsic and reversible causes of resulting in grouped beating (Figure 16). Mobitz type 2 second- bradycardia, including ischemia, myocarditis, endocarditis, degree AV block is typitied by intermittent nonconducted P hypothyroidism, infecticlus diseases, neurologic events, elec waves with unchanging PR intervals (Figure 17). When 2:1 trolyte disturbances, and medication use (especially AV nodal block is present, the Mobitz type cannot be determined defini blockers and parasympathomimetics). Echocardiography is tively. However, the distinction between types is important fiequently performed, and exercise stress testing to assess Mobitz fype 2 AV block usually occurs below the AV node and chronotropic competence as well as ambulatory ECG monitor has a higher risk for progression to complete heart block. ing may be helpful. Clues fiom the history and physical exami tligh degree AV block ref'ers to the presence of more than one nation (e.g., rash suggestive of' Lyme disease) may dictate successive nonconducted P wave, resulting in several consecu further testing. In patients with nocturnal bradycardia or con tive P waves without QRS complexes. duction disturbances, sleep apnea should be considered and, In third degree AV block, also termed complete heart ifappropriate, evaluated and treated. Isolated nocturnal brad block. no P waves conduct to the ventricles. AV dissociation is yarrhythmias are unlikely to require a permanent pacemaker. observed on the ECG (Figure 18). 2nd A I Bate 58 BPM 10 mm'mv 02:10:10 5,24'2017 i

Clinical Presentation and Evaluation Bradycardia (heart rate <50/min) may be asymptomatic or asso Atrioventricular Block ciatecl with light headedness, syncope, exertional inttilerance, AV block may be classified as first degree, second degree, or dyspnea, or fatigue. It can be a normal finding or result lrom third degree. First degree AV block is defined by a delay in AV disease in the sinus node, atrioventricular (AV) node. or His conduction (PR interval >200 ms). In large cohort studies, Purkinje system or from dysfunction of'the autonomic system. first degree AV block has been associated with an increased Diagnostic evaluaticin consists of a thorough history, risk for atrial flbrillation (AF) and all-cause mortality. physicat examination, focused laboratory testing (electrolyte In second degree AV block, only some P waves conduct to levels, thyroid function testing). and resting 12 lead ECC. the ventricles. Mobitz type I second degree (Wenckebach) AV Severe or unstable conduction abnormalities that require block is characterized electrocardiographically by a PR interval urgent intervention must be identified.'[he evaluation should that progressively prolongs until a QRS complex is dropped, also include investigation for extrinsic and reversible causes of resulting in grouped beating (Figure 16). Mobitz type 2 second- bradycardia, including ischemia, myocarditis, endocarditis, degree AV block is typitied by intermittent nonconducted P hypothyroidism, infecticlus diseases, neurologic events, elec waves with unchanging PR intervals (Figure 17). When 2:1 trolyte disturbances, and medication use (especially AV nodal block is present, the Mobitz type cannot be determined defini blockers and parasympathomimetics). Echocardiography is tively. However, the distinction between types is important fiequently performed, and exercise stress testing to assess Mobitz fype 2 AV block usually occurs below the AV node and chronotropic competence as well as ambulatory ECG monitor has a higher risk for progression to complete heart block. ing may be helpful. Clues fiom the history and physical exami tligh degree AV block ref'ers to the presence of more than one nation (e.g., rash suggestive of' Lyme disease) may dictate successive nonconducted P wave, resulting in several consecu further testing. In patients with nocturnal bradycardia or con tive P waves without QRS complexes. duction disturbances, sleep apnea should be considered and, In third degree AV block, also termed complete heart ifappropriate, evaluated and treated. Isolated nocturnal brad block. no P waves conduct to the ventricles. AV dissociation is yarrhythmias are unlikely to require a permanent pacemaker. observed on the ECG (Figure 18). 2nd A I Bate 58 BPM 10 mm'mv 02:10:10 5,24'2017 i tIGURE 16. ECGshowingMobitztypelsecond'degreeatrioventricularblock(Wenckebachblock),whichmanifestsasaprogressiveprolongationof thePRinterval until . there is a dropped ventricular beat (arrow).

2nd A I Bate 58 BPM 10 mm'mv 02:10:10 5,24'2017 i tIGURE 16. ECGshowingMobitztypelsecond'degreeatrioventricularblock(Wenckebachblock),whichmanifestsasaprogressiveprolongationof thePRinterval until . there is a dropped ventricular beat (arrow). 43