Acute Decompensated Heart Failure PDF

Acute Decompensated Heart Failure JULIE DIBRIDGE CLARKSON, PHARMD, BCCP, BCCCP 1 Learning Objectives Identify precipitating causes of acute decompensated heart failure Design diuretic treatment regimens to manage acute decompensated he...

Acute Decompensated Heart Failure JULIE DIBRIDGE CLARKSON, PHARMD, BCCP, BCCCP 1 Learning Objectives Identify precipitating causes of acute decompensated heart failure Design diuretic treatment regimens to manage acute decompensated heart failure. Recommend appropriate treatment goals and pharmacotherapy for acute heart failure 2 Epidemiology Approximately 6 million Americans are diagnosed with heart failure Heart failure is one of the leading causes for hospital admission Responsible for 6.5 million hospital days annually High risk of readmission presentsasvolume overload denovoHF worseningHFhashighriskofreadmission 3  starts Progressive Nature of Heart Failure Structural Heart Disease Excessive Salt/Water Intake Damage to heart muscle (MI) Medications (NSAIDs) Left ventricular hypertrophy (LVH) Non-adherence to heart failure Cardiomyopathies Decreased cardiac output Valvular disease exacerbation development ofsympt pain De Novo Heart Failure Chronic Acute Heart Heart Failure Failure Heart Failure medications End Stage Lifestyle modifications ACC/AHA Stage? CTD Salt/water restrictions Heart Failure NYHA FC? Discontinuing medications that can 111th exacerbate heart failure 4 Acute Heart Failure Definition: Sudden or gradual worsening of signs and symptoms of Heart Failure Compensation mechanisms and medications are overcome out ofbalance Results in unplanned medical interventions ◦ Medical office visits ◦ Emergency room visits ◦ Hospitalizations Severe episodes can result in cardiogenic shock 5 Acute Heart Failure Chronic Heart Failure Acute Heart Failure (stable, compensated) (decompensated) ◦ Baseline symptoms ◦ Worsening signs and symptoms ◦ SOB/dyspnea ◦ Increased pulmonary edema patifferan ◦ Peripheral edema ◦ Increased peripheral edema there'ja ◦ Baseline exercise capacity ◦ Decrease in exercise capacity ay forfluid ◦ Baseline NYHA-FC (I-III) ◦ Worsening NYHA-FC (II-IV) accumulation ◦ Baseline BNP level ◦ Increased BNP used yeasure Acute heart failure can only refer to ACC/AHA Stages C and D Why? mustbe symptomatic 6  a normal Exacerbation Etiology station 7 Common Causes Non-adherence ◦ Pneumonia ◦ GDMT Left ventricular dysfunction ◦ Dietary restrictions (Na, water) ◦ CAD Medications ◦ Acute MI ◦ Negative inotrope dropCO ◦ Arrhythmia ◦ Meds that cause NA/fluid ◦ Endocarditisinflammationofliningoftheheart retention NSAIDS steroids ◦ Valvular disease Illicit Drugs Acute Illnesses ◦ COPD exacerbation pneumoniaUTI sepsis 8  Common Causes - Medications Avoid Analgesics: NSAIDS, COX-2 inhibitors Immunomodulating therapies ◦ VEGF inhibitors: Avastin (bevacizumab) Avoid Calcium Channel Blockers (CCB): Both ◦ Tyrosine kinase inhibitors: (dasatinib) DHP and Non-DHP ◦ PDL-1 inhibitors: Keytruda (pembrolizumab) ◦ Amlodipine is generally considered safest in heart failure TNF-alpha inhibitors Avoid Diabetes Medications: ◦ Humira (adalimumab), Remicade (infliximab) Thiazolidinediones, DPP-IV inhibitors Rapid titration of beta blockers Glucocorticoid steroids 9h pain ploglitaz.in Stimulants cocaine 9  ? Patient Case EK is a 60 YOM with HF is admitted onto your service. He says he spent the day at Heinz Stadium watching the Steeler’s play drinking Soda and eating Hotdogs. Medication Last filled date (90-day supply) i m in salt Valsartan 40 mg BID 10/1/23 Metformin 1000 mg BID 10/1/23 Ibuprofen Clopidogrel 75 mg daily 9/24/23 Furosemide 40 mg daily 6/16/23 Potassium 20 mEq daily 9/24/23 Ibuprofen 800 mg daily 10/1/23 Metoprolol Tartrate 50 mg BID 10/1/23 Spironolactone 25 mg BID 10/1/23 10 What risk factors for ADHF for this patient? A. Arrhythmia 0 B. NSAID use C. TZD Use D. Alcohol use What risk factors for ADHF for this patient? A. Arrhythmia B. NSAID use C. TZD Use D. Alcohol use Questions related to risk factors Pathophysiology Activation of sympathetic nervous symptom → ◦ increased HR, vasoconstriction ◦ increased preload→ increased O2 demand, decreased renal blood flow Increased HR → sympathetic ◦ decreased CO → negative nervous system remodeling (LVH) ◦ (LVH) hypertrophy→ increased contractility ◦ Increased contractility→ increased O2 demand/cardiac workload Decreased renal blood flow → activation of RAAS ◦ Aldosterone increases preload ◦ Angiotensin II increases afterload pressure  Decompensated Heart Failure – Signs & Symptoms FACES Fluid FLUID OVERLOAD h mn IMPAIRED CARDIAC OUTPUT nauseous Dyspnea SOB Cold extremities Orthopnea SOB layingdown Hypotension Edema Renal dysfunction Elevated jugular venous pressure Altered mental status Rales Cyanosis c Narrow pulse pressureiaii.in esusto Helan'tpee m piisIpEdieiHaitaitYeaim umY nonmoneley bint Signs and symptoms – Fluid Overload Fatigue Dyspnea At rest On exertion ii iii in Paroxysmal nocturnal Orthopnea Bendopnea Fluid Retention iouro.br iiii Peripheral edema Pulmonary edema Bibasilar crackles/rales Tachypnea Cough Rapid weight gain Elevated jugular venous distension (JVD) 15 Signs and symptoms – Low Cardiac Output Organ dysfunction Worsening renal function (↑ SCr) Altered mental status (confusion) Liver dysfunction (↑ LFT) hepatil Hypotension (SBP 5.5 mEq/L) Beta Blockers ADHF caused by recent drug initiation or increase, evidence of new or worsening low output or cardiogenic shock, symptomatic hypotension or bradycardia Aldosterone Worsening renal function, severe hyperkalemia (K+ >5.5 mEq/L) Antagonists Nitrates/Hydralazine Symptomatic hypotension Ivabradine YILYL Contraindicated (per FDA label), other scenarios include blood pressureemassioffman Digoxin Symptomatic bradycardia, life-threatening arrhythmias, elevated serum concentrations (>1.0 ng/mL), or signs/symptoms of digoxin toxicity  ? Should we hold GDMT? EK is admitted for acute decompensated heart failure Medication Continue or 1/2 beta-blocker Valsartan 40 mg BID What if he was admitted for Metformin 1000 mg BID Clopidogrel 75 mg daily cardiogenic shock with a severe AKI Furosemide 40 mg daily Hold beta-blocker, ACE/ARB/ARNi, MRA Potassium 20 mEq daily Metoprolol Tartrate 50 mg BID Spironolactone 25 mg BID 28 Pharmacotherapy options Loop diuretics ◦ Furosemide, bumetanide, torsemide ◦ Decreases fluid volume (preload) 9ht t leftside whichdecreasespulmonarycapillarywedgepf u Vasodilators ◦ Nitroglycerin (NTG), Nitroprusside (NTP) ◦ Decreases preload and afterload Inotropes ◦ Dobutamine, milrinone ◦ Increase contractility sayfnymial monitorfor arrihymias Ynergagerty n'f creasingrer contractility 29 Monitoring Fluid balance 400mLW in Labs ◦ Urine Output: 0.5 mL/kg/hr 2hours ◦ Lactate 90% Hemodynamics ◦ Blood pressure (MAP) ◦ Heart Rate ◦ RHC (PCWP, CO/CI) Tight heartcarnerer 30  Pharmacotherapy based on Forrester Subset 1. Warm and Dry chronicstable Optimize oral medications PCWP 90 Diuresis, vasodilator, inotropic agent 3 4 SBP 80% >80% Clinical Pearls Max IVP: 160 mg Liver metabolism Max IVP: 4 mg (limited by (limited by ototoxicity) myalgia) Max rate: 40 mg/min Max rate: 1mg/min Dose Equivalency (mg) 20 (IV) / 40 (PO) 20 1 If a patient is on a diuretic at home, best practice is to double their home dose 36 Diuretic Threshold and Ceiling Effect Threshold dose ◦ Dosage required to achieve adequate response ◦ Frequency is increased to achieve desired amount of diuresis Ceiling effect patientstop responding dropoffin to output ◦ Increase in dose no longer has an added effect Dose and route matter! ◦ Furosemide 20mg TID ≠ furosemide 60mg ◦ IV bumetanide 1mg ≠ PO bumetanide 1mg Ceiling and threshold doses are patient specific 37  Sequential Nephron Blockade Combining diuretics that act on different segments of the nephron Diuretic resistance ◦ Volume depletion leads to renin release → more reabsorption of Na ◦ Decreased response to loop diuretics over time mustaddonathiazide so Add on therapy to loop diuretics ◦ Continuation of MRA and SGLT2i when possible ◦ Thiazides + Loop Diuretics ◦ Monitor K and Mg levels ◦ Acetazolamide increasepatientsresponse releasesrenin 38  switchingfromlisinoprilclomy to Entresto vaisariah I 160mg 24126titrateup Add on Diuretics Drug Initial Dose (PO) Maximum Daily Dose (PO) Duration of Effect Thiazide Diuretics* cangive insoomy Chlorothiazide 250 – 500 mg daily or BID 1000 mg 6-12 hours IV Metolazone PO 2.5 mg daily 20 mg 12-24 hours Carbonic Anhydrase Inhibitor Acetazolamide 250 mg – 500 mg daily or dropsserumbilarb BID shelf *3T Trial found no to diuresepatient tcontrolacidbaselevels difference in weight loss or urine output between chlorothiazide and metolazone after 48 hours moved expensive tothiazide 39  Diuretics in decompensated HF – Sequential Nephron Blockade Greater risk of electrolyte abnormalities Kt Not Metolozone, chlorothiazide most commonly used for this purpose (in combination with loop diuretic) 3T’s Trial – no difference in diuretic efficacy between metolazone and chlorothiazide Timing of thiazide administration (30 min before loop diuretic) makes theoretical sense Acetazolamide – may provide additional augmentation of diuresis andcontrolandbaselevels  Treating HFrEF – Diuretics furosemide ◦ If patient is NOT taking diuretics – 20-40 mg IV x1 ◦ If patient is taking a diuretic – first hospital dose will be INCREASED by 1–2.5 times outpatient dose ◦ All subsequent doses are determined based on clinical response ◦ After 2 hours if UOP < 400 mL consider: ◦ Increase IV loop diuretic – insufficient response should be treated by doubling dose (note frequency) ◦ Switch to IV loop continuous infusion ◦ Add thiazide diuretic, sequential nephron blockade ◦ Consider adjunct (NTG, NTP) vasodilators ◦ Higher doses provide greater diuresis and more rapid dyspnea relief ◦ May transiently increase risk of worsening renal function  ? Patient Case How would you treat EK’s acute heart failure exacerbation? Medication list Valsartan 40 mg BID Metformin 1000 mg BID 1 2 Clopidogrel 75 mg daily Furosemide 40 mg daily give40mgIV Potassium 20 mEq daily Metoprolol Tartrate 50 mg BID (held) 3 4 Spironolactone 25 mg BID 42 Case Which initial diuretic regimen would be best to acutely address EK’s decompensated heart failure? A. Furosemide 60 mg PO BID B. Furosemide 80 mg PO BID 0 C. Furosemide 40 mg IV BID D. Chlorothiazide 500 mg IV BID Case Which initial diuretic regimen would be best to acutely address EK’s decompensated heart failure? A. Furosemide 60 mg PO BID B. Furosemide 80 mg PO BID C. Furosemide 40 mg IV BID D. Chlorothiazide 500 mg IV BID  ? Patient Case After diuresis EK’s symptoms resolve. How would you optimize EK’s oral medications? Medication list Valsartan 40 mg BID Metformin 1000 mg BID 1 2 Clopidogrel 75 mg daily Furosemide 40 mg daily Potassium 20 mEq daily succinate Metoprolol Tartrate 50 mg BID (held) 3 4 Spironolactone 25 mg BID 45  Witer Diuretics in Decompensated HF Loops Furosemide monitorweightSerUOPpotassium -IV bolus: 20-120 mg daily-TID 400mi -Continuous infusion: 5-20 mg/hour goalVOP Bumetanide thiazide Metolazone -IV bolus: 1-4 mg daily-TID -2.5 mg – 20 mg PO daily -Continuous infusion 0.5-2 mg/hour Chlorothiazide omg -IV bolus: 250 mg – 500 mg IV daily-BID torsemidezonffffem.ae *Acetazolamide -IV bolus: 250 mg – 500 mg daily-BID Diuretic Resistance, cont’d. ◦ Ultrafiltration is reasonable to consider (Unload Trial) (class 2b) - for diuretic resistance and cardiorenal syndrome ◦ Adjunct Therapies: everybasic high pH ◦ Acetazolamide – If alkalosis + persistent congestion ◦ Vasopressin antagonism – EVEREST trial = improved weight loss but no other outcome ◦ Class IIb recommendation: If severe persistent hyponatremia with risk of cognitive symptoms with volume overload lessthan120 ◦ IV Vasodilators: ◦ Class II recommendation - for treatment of ADHF and relief of dyspnea5013 ◦ In hypertensive patients ◦ In those with pulmonary congestion, not responsive to initial diuretics ◦ Beneficial effects: ◦ Decrease BP and improve efficiency of cardiac work ◦ Speed symptom relief ◦ No change in mortality Vasodilators wiser Initial Dose Titration Max Dose Monitoring Adverse Effects Increase 5-10 Headache Nitroglycerin 10-20 mcg/min 200 Hemodynamics: BP, Hypotension (NTG) mcg/min every 5-10 mcg/min HR, PCWP, CO Reflex tachycardia minutes Increase by 5 As above + Nitroprusside 0.5 mcg/kg/min 2 As above + Thiocyanate or (NTP) mcg/kg/min every 5-10 mcg/kg/min Renal function cyanide toxicity minutes don'tuse in lowCrCL 51  Decompensated HF: Vasopressin Antagonists Arginine vasopressin antagonists: conivaplanToivaptan - Not recommended for routine use due to increased risk for WRF, high cost, and no long term benefit - Does not improve dyspnea symptoms, only associated with increased serum sodium and reduction in laboratory markers of congestion May have benefit for severely hyponatremic patients with, or at risk for, cognitive symptoms despite fluid restriction sodium increasesserum only Mechanism of Action: antagonism of V2 receptor in the collecting ducts, promoting free water excretion without electrolyte loss Medications: avoidsodiumincreased time in anoun a Conivaptan 20 mg IV loading dose, followed by 20-40 mg given via continuous infusion over 24 hours Tolvaptan 15 mg PO daily monitorserumNat -May be increased by 15 mg increments to maximum of 60 mg/day Must monitor serum -Caution: can cause hepatotoxicity (limit use to NMT 30 days) sodium; avoid hyponatremia overcorrection -Avoid with strong CYP34A inhibitors or inducers w volume (> 12 mEq/24 hours) overload J Am Coll Cardiol. 2017 Mar 21;69(11):1399–406. JAMA. 2007 Mar 28;297(12):1332–43. Basic Treatment Strategies: Vasodilators Adjuncts  Parenteral therapy in decompensated HF: Vasodilators Nitroglycerin (intravenous) 154995m b de k i gsvr Mechanism of Benefit: reduction in preload mediated primarily through venodilation, resulting in decreased pulmonary congestion Primarily venodilation at low doses and mild arterial vasodilation at higher doses (preferred agent for preload reduction) Caution: tachyphylaxis may occur, frequently underdosed, dose-limiting symptoms, hypotension tolerance don'tuse inborderlinepressure Sodium nitroprusside Mechanism of Benefit: balanced venous and arterial dilation, leading to reduction in preload and afterload reducing 9589 09 8 48 dgheghehaaftopumr.by Balanced arterial and venous vasodilator which results in augmentation of cardiac output and reduction in filling pressure Caution: may cause significant hypotension, prolonged infusions may result in thiocyanate toxicity (especially with impaired renal function), avoid if severe renal/liver dysfunction Patient Case A 59-year-old woman, BB, presents to the emergency department with worsening dyspnea and lower extremity edema. Her home medication list includes furosemide 40 mg PO daily, amlodipine 10 mg daily, and Lisinopril 5 mg daily. She is hypertensive on arrival. After starting IV diuresis with furosemide 40 mg IV BID, the patient was transferred to the CCU for possible swan placement. Her SBP on the unit was 185/110 mm Hg, HR 100 bpm. Laboratory values: Na+ 142 mEq/L, K+ 4.4 mEq/L, SCr 2 mg/dL (1.2 baseline), and BNP 1200 pg/mL elegged elevated After 4 hours, this patients UOP was < 200 mL (indicating inadequate diuresis) Which of the following is an appropriate treatment plan for ADHF? A. Furosemide 10 mg/hour IV infusion B. Milrinone 0.125 mcg/kg/hr IV infusion C. Furosemide 80 mg IV bolus followed by 10 mg/hour IV infusion plus nitroglycerin 10 mcg/min titrated to SBP goal D. Furosemide 40 mg IV TID Which of the following is an appropriate treatment plan for this patients ADHF A. Furosemide 10 mg/hour IV infusion B. Milrinone 0.125 mcg/kg/hr IV infusion C. Furosemide 80 mg IV bolus followed by 10 mg/hour IV infusion plus nitroglycerin 10 mcg/min titrated to SBP goal D. Furosemide 40 mg IV TID Patient Case BB is started on a furosemide drip as previously described and continued to respond poorly. Her blood pressures began to drop and she was sent to the ICU for urgent Swan placement. PCWP = 12 mmHg; CI = 1.2 L/min/m2; PA = 6 mmHg, MAP = 65 mmHg, SCr increased from 0.7 to 1.2/24 hr. Basic Treatment Strategies: Inotropes Basic Treatment Strategies: Subset III (Not address in detail in guidelines) Liberalize fluid restrictions Gentle fluid administration Hold diuresis Evaluate likely cause Basic Treatment Strategies: Cardiogenic Shock Cardiogenic Shock (CS) not responsivetofluidalone Decreased systemic CO in presence of adequate intravascular volume leading to tissue hypoxia Caused by ◦ Left ventricular failure (typically MI and to a lesser extent advanced heart failure) ◦ Right ventricular failure (pulmonary hypertension) ◦ Severe mitral regurgitation ◦ Ventricular septal rupture ◦ Pericardial tamponade ◦ Cardiomyopathy o Not responsive to fluid administration alone o Secondary to cardiac dysfunction o Associated with signs of hypoperfusion: CI 18 mmHg cold wet Inotropes Majority of patients will not require inotropic agents ◦ Enhance cardiac output in low-output patients ◦ Reserved for refractory acute heart failure Place in therapy ◦ Short-term: maintains perfusion in patients with low BP and low CO with reversible causes ◦ Bridge: used while patients await definitive therapies (mechanical circulatory support or heart transplant) ◦ Palliative: used to help improve symptoms All patients receiving inotropes should be monitored for arrythmias 60  2016 European Society of Cardiology Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure Strength Recommendation Class I (C ) Fluid challenge is recommended as first‐line treatment if no signs of overt fluid overload Class IIb ( C ) Dobutamine may be considered to increase cardiac output Class I (C ) Recommend ECG monitoring and blood pressure when using inotropic agents and vasopressors, as they can cause arrhythmia, myocardial ischemia, and hypotension. Class IIb ( B ) A vasopressor (norepinephrine preferably over dopamine) may be considered in patients who have cardiogenic shock, despite treatment with another inotrope, to increase blood pressure and organ I perfusion (IIB, LOE B) consider adding ifnotresponding Ponikowski P, Voors AA, Anker SD et al. European Heart Journal (2016) 37, 2129–2200.  Inotropic Agents calcitropes Dobutamine: beta-1 and beta-2 agonist iBlunted effects itrecievingbeta blocker Milrinone: phosphodiesterase 3 (PDE3) inhibitor → increases cAMP → increases contractile force increasecytosoliccalciumAvailable Agent Dose T½ CO HR SVR PVR BP Monitoring Adverse Effects (mcg/kg/min) Dobutamine 2.5-7.5 2-3 ↑ ↑ ↑/↓ EKG Ventricular minutes Hemodynamics: BP, arrhythmias 290 aBf mSBP HR, PCWP, CO Tachycardia Milrinone 0.125-0.5 2.5 hours ↑ ↑ ↓ ↓ As above + Myocardial ischemia renal function (increased myocardial inIrei therapy beranioner oxygen supply) Adverse effects: all inotropes carry risk of arrhythmia Milrinone, dobutamine carry small risk of hypotension Milrinone – caution with renal dysfunction (due to renal elimination) alsonitroprusideavoidinrenalfailure 62  Selecting an Inotrope ❑SBP >90 + chronic beta blocker therapy – consider milrinone PDE3inhibitor ◦ Milrinone is a phosphodiesterase-III inhibitor that blocks the degradation of cyclic adenosine monophosphate ◦ Inotrope with systemic and pulmonary vasodilating effects. ◦ Leads to increase in CI, decrease in arteriolar resistance, decrease in pulmonary pressures, no change in mean arterial pressure (possibly hypotension and reflex tachycardia dt vasodilation) ◦ DOC if concomitant beta blockade ❑If SBP < 90 or symptomatic hypotension – consider dobutamine ◦ Dobutamine, a synthetic β1- and β2-receptor agonist, is an inotrope with vasodilatory effects at higher doses ◦ Blunted effects if receiving beta blockade ❑If severe hypotension (MAP B2 receptor activity 1st line in septic shock after volume resuscitation worksmovein periphery Phenylephrine 0.1 - 10 mcg/kg/min Pure alpha 1 agonist No inotropic or chronotropic effects No effect on HR Dopamine 2-20 mcg/kg/min Arrhythmogenic at any dose (does not provide exclusive receptor activity across dosing ranges) Useful for bradycardia + hypotension 2-5 mcg/kg/min - dopamine receptor 5-10 mcg/kg/min - B1R > 10 mcg/kg/min a1R Vasopressin 0.04-0.08 units/min V-1R agonist -->stimulate smooth muscle contraction of the vessels + V-2 receptors in the kidneys as an anti-diuretic No inotropic or chronotropic effects Transition Home after Hospitalization Patient has returned to baseline Exacerbating factors addressed Plans for follow up in clinic Medication Action Plan ◦ Changes to previous home diuretic dosing ◦ Instructions for weight increases caning 3 lbsin ◦ Maintenance of electrolytes (potassium supplementation) 598neck Clinicvisitoneweek afterdischarge 68  Summary 1. Warm and Dry Optimize oral medications PCWP 90 imilrinore Diuresis, vasodilator, inotropic agent 3 4 SBP