Update in Congestive Hear Failure DRAGOS VESBIANU MD

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1 Update in Congestive Hear Failure DRAGOS VESBIANU MD

2 Case 58 yo AAM c/o shortness of breath for 3 weeks. Used to walk one mile per day and now he has noticed that he gets short of breath after 2 blocks. He also has a hard time climbing steps. Denies cough and has occasional wheezing. He usually sleeps on 2 pillows because of back problems. Has gained 10 lbs in the last month, but it s not unusual for his weight to fluctuate.

3 Case PMH: HTN, DM 2, HLD, COPD Meds: Lipitor, HCTZ, Metformin, Lantus, Advair, Albuterol BID Physical exam: Comfortable, not SOB at rest Bilateral wheezing and rales lower lungs S1, S2, RRR +1 b/l LE pitting edema

4 Symptoms in HF Common Symptoms: -dyspnea -edema -fatigue -wheezing Subtle symptoms: -abdominal pain, nausea, anorexia -confusion -lethargy

5 Initial Workup of Stage C HF After detailed history; Initial laboratory evaluation: CBC, urinalysis, CMP (including calcium and magnesium), fasting lipid profile, TSH, iron panel, Serial monitoring, when indicated, should include serum electrolytes and renal function, BNP, +/-CE A 12-lead ECG should be performed initially on all patients presenting with HF. Chest X-ray in all patients with new onset HF. Echocardiogram in all patients with new dx of HF (MUGA in some) Repeat echo usually for a significant change in clinical status or for consideration of changes after therapy or to evaluate for device therapy. Noninvasive stress imaging or cardiac cath is reasonable in HF and suspected CAD

6 Role of BNP in chronic HF BNP and NT-proBNP are sensitive (92-93%) and can help rule out heart failure BNP has prognostic value and can be used for risk stratification BNP guided therapy may play a role especially in hospitalized patients.

7 Case You start the patient on Lasix 40 mg BID. He calls in 5 days to let you know he is doing much better. You check an Echocardiogram that shows, LVH, bilateral atrial enlargement, EF of 30% What do you do next?

8 Definition of Heart Failure Classification I. Heart Failure with Reduced Ejection Fraction (HFrEF) Ejection Fraction Description 40% Also referred to as systolic HF. Randomized clinical trials have mainly enrolled patients with HFrEF and it is only in these patients that efficacious therapies have been demonstrated to date. II. Heart Failure with Preserved Ejection Fraction (HFpEF) 50% Also referred to as diastolic HF. Several different criteria have been used to further define HFpEF. The diagnosis of HFpEF is challenging because it is largely one of excluding other potential noncardiac causes of symptoms suggestive of HF. To date, efficacious therapies have not been identified. a. HFpEF, Borderline 41% to 49% These patients fall into a borderline or intermediate group. Their characteristics, treatment patterns, and outcomes appear similar to those of patient with HFpEF. b. HFpEF, Improved >40% It has been recognized that a subset of patients with HFpEF previously had HFrEF. These patients with improvement or recovery in EF may be clinically distinct from those with persistently preserved or reduced EF. Further research is needed to better characterize these patients.

9 Classification of Heart Failure A B C D ACCF/AHA Stages of HF At high risk for HF but without structural heart disease or symptoms of HF. Structural heart disease but without signs or symptoms of HF. Structural heart disease with prior or current symptoms of HF. Refractory HF requiring specialized interventions. None I I II III IV NYHA Functional Classification No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF. Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF. Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF. Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.

10 Pharmacological Treatment for Stage C HFrEF Tequila shot vs Penicillin shot I IIa IIb III Diuretics are recommended in patients with HFrEF who have evidence of fluid retention, unless contraindicated, to improve symptoms. I IIa IIb III ACE inhibitors are recommended in patients with HFrEF and current or prior symptoms, unless contraindicated, to reduce morbidity and mortality. I IIa IIb III ARBs are recommended in patients with HFrEF with current or prior symptoms who are ACE inhibitor-intolerant, unless contraindicated, to reduce morbidity and mortality.

11 Pharmacological Treatment for Stage C HFrEF (cont.) Tequila shot vs Penicillin shot I IIa IIb III Harm Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is potentially harmful for patients with HFrEF. I IIa IIb III Use of 1 of the 3 beta blockers proven to reduce mortality (i.e., bisoprolol, carvedilol, and sustainedrelease metoprolol succinate) is recommended for all patients with current or prior symptoms of HFrEF, unless contraindicated, to reduce morbidity and mortality.

12 Neprilysin as a Therapeutic Target Neprilysin breaks down endogenous vasoactive peptides, including the natriuretic peptides Inhibition of neprilysin potentiates the action of those peptides Because angiotensin II is also a substrate for neprilysin, neprilysin inhibitors must be co-administered with a RAAS blocker The combination of a neprilysin inhibitor and an ACEI is associated with unacceptably high rates of angioedema Natriuretic peptides Adrenomedullin Bradykinin Substance P (angiotensin II) Neprilysin Inactive fragments Sacubitril/Valsartan (LCZ696): Angiotensin Receptor Neprilysin Inhibitor (ARNI) Corti R et al. Circulation. 2001;104:

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14 PARADIGM-HF: CV Death or HF Hospitalization (Primary Endpoint) 1. McMurray JJ et al. N Engl J Med. 2014;371:

15 SHIFT Trial Primary Composite Endpoint: CV Death or Hospitalization for Worsening HF Swedberg K et al. Lancet. 2010;376:

16 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure COR LOE Recommendation I B-R ACEI or ARB or ARNI in conjunction with β blockers + MRA (where appropriate) is recommended for patients with chronic HFrEF to reduce morbidity and mortality I B-R In patients with chronic, symptomatic HFrEF NYHA class II or III who tolerate an ACEI or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality III B-R ARNI should NOT be administered concomitantly with ACEI or within 36 hours of last ACEI dose III C-EO ARNI should NOT be administered to patients with a history of angioedema COR LOE Recommendations IIa B-R Ivabradine can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II-III), stable, chronic HFrEF (LVEF 35%) who are receiving GDMT, including a β blocker at maximally tolerated dose, and who are in sinus rhythm with a heart rate 70 bpm at rest 1. Yancy CW et al. J Am Coll Cardiol. 2016;68:

17 Pharmacological Treatment for Stage C HFrEF (cont.) I IIa IIb III Aldosterone receptor antagonists [or mineralocorticoid receptor antagonists (MRA)] are recommended in patients with NYHA class II-IV and who have LVEF of 35% or less, unless contraindicated, to reduce morbidity and mortality. Patients with NYHA class II should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to be considered for aldosterone receptor antagonists. Creatinine should be 2.5 mg/dl or less in men or 2.0 mg/dl or less in women (or estimated glomerular filtration rate >30 ml/min/1.73m2) and potassium should be less than 5.0 meq/l. Careful monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia and renal insufficiency.

18 Pharmacological Treatment for Stage C HFrEF (cont.) I IIa IIb III Aldosterone receptor antagonists are recommended to reduce morbidity and mortality following an acute MI in patients who have LVEF of 40% or less who develop symptoms of HF or who have a history of diabetes mellitus, unless contraindicated. I IIa IIb III Harm Inappropriate use of aldosterone receptor antagonists is potentially harmful because of life-threatening hyperkalemia or renal insufficiency when serum creatinine greater than 2.5 mg/dl in men or greater than 2.0 mg/dl in women (or estimated glomerular filtration rate <30 ml/min/1.73m2), and/or potassium above 5.0 meq/l.

19 Pharmacological Treatment for Stage C HFrEF (cont.) I IIa IIb III The combination of hydralazine and isosorbide dinitrate is recommended to reduce morbidity and mortality for patients self-described as African Americans with NYHA class III IV HFrEF receiving optimal therapy with ACE inhibitors and beta blockers, unless contraindicated. I IIa IIb III A combination of hydralazine and isosorbide dinitrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated.

20 Medical Therapy for Stage C HFrEF: Magnitude of Benefit Demonstrated in RCTs GDMT RR Reduction in Mortality NNT for Mortality Reduction (Standardized to 36 mo) RR Reduction in HF Hospitalizations ACE inhibitor or ARB 17% 26 31% Beta blocker 34% 9 41% Aldosterone antagonist 30% 6 35% Hydralazine/nitrate 43% 7 33%

21 Case Your guy had a few no shows in the clinic and you get a call from your hospitalist colleagues that he got admitted for CHF exacerbation. He presented to the hospital with shortness of breath and 30 lbs weight gain. BP is 160/96, HR is 93, sat 90% on RA. Positive JVDs, crackles bilaterally. BNP is Now on Coreg 6.25 mg, Lisinopril 10 mg and Spironolactone 25 mg How should approach his CHF exacerbation.

22 Triggers for acute decompensation Non compliance with medications Non compliance with diet Poorly controlled HTN Ischemia/ACS Afib Infections (demand ischemia) PE Worsening renal function

23 Management of acute decompensation Volume control Afterload and preload reduction Positive pressure ventilation Initiation of neuro-hormonal drugs Morphine use

24 Implantable Cardiac Defibrillators (ICD) Sustained ventricular tachycardia is associated with sudden cardiac death in HF. About one-third of mortality in HF is due to sudden cardiac death. ICDs for primary prevention have been shown to improve survival in selected patients with HF

25 Indications for ICD Therapy ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 days post- MI with LVEF 35%, and NYHA class II or III symptoms on chronic GDMT, who are expected to live 1 year ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 days post- MI with LVEF 30%, and NYHA class I symptoms while receiving GDMT, who are expected to live 1 year ** ICDs do not improve symptoms; most patients should be on GDMT; should have an expected lifeexpectancy of at least 1 year 2013 ACCF/AHA Guideline for the Management of Heart Failure

26 Sinus node Cardiac Resynchronization Pacing: Consequences of a Prolonged QRS Delayed Ventricular Activation Delayed lateral wall contraction Disorganized ventricular contraction Decreased pumping efficiency AV node Conduction block Reduction in diastolic filling times Prolongation of the duration of mitral regurgitation

27 Mechanism: Ventricular Resynchronization Sinus node AV node Conduction block Stimulation therapy Intraventricular Activation Organized ventricular activation sequence Coordinated septal and freewall contraction Improved pumping efficiency

28 Device Therapy for Stage C HFrEF I IIa IIb III I IIa IIb III ICD therapy is recommended for primary prevention of SCD to reduce total mortality in selected patients with nonischemic DCM or ischemic heart disease at least 40 days post-mi with LVEF of 35% or less, and NYHA class II or III symptoms on chronic GDMT, who have reasonable expectation of meaningful survival for more than 1 year. NYHA Class III/IV I IIa IIb III CRT is indicated for patients who have LVEF of 35% or less, sinus rhythm, left bundle-branch block (LBBB) with a QRS duration of 150 ms or greater, and NYHA class II, III, or ambulatory IV symptoms on GDMT. NYHA Class II

29 HFpEF THERAPY Goals Control symptoms Improve HRQOL Prevent hospitalization Prevent mortality Strategies Identification of comorbidities Treatment Diuresis to relieve symptoms of congestion Follow guideline driven indications for comorbidities, e.g., HTN, AF, CAD, DM Revascularization or valvular surgery as appropriate HFpEF HFrEF Trials THERAPY have not shown Goals Control symptoms Patient education Prevent hospitalization Prevent specifically mortality in HFpEF significant mortality or morbidity benefit with use of ACEI/ARB No trials showing definite benefit of Beta blockers, Drugs for routine use Diuretics for fluid retention ACEI sildenafil or ARB Beta blockers Aldosterone antagonists TOPCAT trial: Randomizeddouble blind trial of spironolactone (15-45 mg) vs. placebo in HFpEF patients (LVEF >45%) with Prior HF hospitalization or BNP > 100 pg/ml Drugs for use in selected patients Hydralazine/isosorbide dinitrate ACEI and ARB Digoxin In selected patients CRT ICD Revascularization or valvular surgery as appropriate Goals Con Imp Red rea Est of-li Optio Adv mea Hea Chr Tem MC Exp dru Pal hos ICD

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