Disclosures I have nothing to disclose “ Heart Failure Pearls for the Hospitalist ” Ronald Witteles, M.D. Stanford University School of Medicine October 21, 2017 @Ron_Witteles Outline Patient 1 n Admission for “Heart Failure Exacerbation”? • 68 y.o. man with dilated nonischemic cardiomyopathy • Baseline echo: Moderate LV dilatation, LVEF 25% n Three different patient types, three different problems • Comes to ER for gradually worsening SOB/edema – How can we provide the best possible care for each patient? • Baseline meds (stable over last 6 months): • Carvedilol 25 mg bid n Final thoughts • Lisinopril 20 mg bid • Furosemide 40 mg bid • Spironolactone 25 mg qd • Digoxin 0.25 mg qd 1
Exam & Labs What Do You Do? • Physical exam: The patient says he wants to stop any medications which • Wt 90 kg (up from 85 kg one month ago) aren’t clearly helping him. What do you do with the • BP 115/65, HR 65, SaO2 94% RA digoxin? • Scant bibasilar crackles 1) Stop digoxin • No significant murmurs/gallops 2) Continue digoxin • 3+ LE edema • Labs: • Na 137, K 4.1, Cr 1.3 (baseline 1.4) • NT-Pro BNP 6100, Troponin I <0.1 • Digoxin level (random): 0.3 (subtherapeutic) • CXR: Cardiomegaly, mild pulmonary edema • ECG: Sinus rhythm at 65 bpm, old LBBB What Do You Do? Digoxin – DIG Trial (1997) • 6800 patients with EF ≤ 45% The patient says he wants to stop any medications which aren’t clearly helping him. What do you do with the • Digoxin vs. placebo digoxin? • All patients in sinus rhythm • Outcomes: 1) Stop digoxin • Primary: All-cause mortality 2) Continue digoxin • Secondary: CV death, worsened HF & hospitalizations 2
All-Cause Mortality Death or HF Hospitalization placebo digoxin Adapted from NEJM. 1997;336:525-33. Adapted from NEJM. 1997;336:525-33. Cochrane Review: A Recent Story… Risk of Clinical Deterioration if Stop Dig Adapted from Hood et al. Cochrane Library. 2004, Issue 4. 3
A Recent Story… A Recent Story… I was nervously thinking about this talk… I was nervously thinking about this talk… • • • Will they like it? A Recent Story… A Recent Story… I was nervously thinking about this talk… I was nervously thinking about this talk… • • • Will they like it? • Will they like it? • Will my jokes fall flat? • Will my jokes fall flat? I developed a tension headache. • 4
A Recent Story… A Recent Story… I was nervously thinking about this talk… I was nervously thinking about this talk… • • • Will they like it? • Will they like it? • Will my jokes fall flat? • Will my jokes fall flat? I developed a tension headache. I developed a tension headache. • • I took 600 mg of ibuprofen. I took 600 mg of ibuprofen. • • My headache went away. I was happy. • A Recent Story… A Recent Story… I was nervously thinking about this talk… I was nervously thinking about this talk… • • • Will they like it? • Will they like it? • Will my jokes fall flat? • Will my jokes fall flat? I developed a tension headache. I developed a tension headache. • • I took 600 mg of ibuprofen. I took 600 mg of ibuprofen. • • My headache went away. I was happy. My headache went away. I was happy. • • • Note: I never thought I was going to live longer by taking the ibuprofen. 5
A Recent Story… A Recent Story… I was nervously thinking about this talk… I was nervously thinking about this talk… • • • Will they like it? • Will they like it? • Will my jokes fall flat? • Will my jokes fall flat? I developed a tension headache. I developed a tension headache. • • I took 600 mg of ibuprofen. I took 600 mg of ibuprofen. • • My headache went away. I was happy. My headache went away. I was happy. • • • Note: I never thought I was going to live • Note: I never thought I was going to live longer by taking the ibuprofen. longer by taking the ibuprofen. Should I have been denied the opportunity to Should I have been denied the opportunity to • • take the ibuprofen??? take the ibuprofen??? Why do we hold digoxin to such a higher • standard? What Do You Do? What Do You Do? What should you do with the digoxin dose? What should you do with the digoxin dose? 1) Continue digoxin at 0.25 mg qd 1) Continue digoxin at 0.25 mg qd 2) Increase to 0.50 mg qd 2) Increase to 0.50 mg qd 3) Check a true digoxin trough level & increase dose to 3) Check a true digoxin trough level & increase dose to 0.50 mg qd if still subtherapeutic 0.50 mg qd if still subtherapeutic 6
High Digoxin Doses: High Digoxin Doses: Beware Eggerthella Lenta Beware Eggerthella Lenta Purpose in life: To break down digoxin! Purpose in life: To break down digoxin! • • 1970s: 10% of individuals found to excrete inactive 1970s: 10% of individuals found to excrete inactive • • dihydrodigoxin when given digoxin. dihydrodigoxin when given digoxin. 1983: Manuscript in Science identifies Eubacterium 1983: Manuscript in Science identifies Eubacterium • • lentum as the culprit lentum as the culprit • “Fresh stool samples from two human volunteers • “Fresh stool samples from two human volunteers who were known to be heavy digoxin reduction who were known to be heavy digoxin reduction product excretors were cultured anaerobically in product excretors were cultured anaerobically in chopped meat glucose broth containing chopped meat glucose broth containing digoxin…” digoxin…” • God bless the basic scientists!!! Adapted from Saha et al. Science. 1983;220:325-327. Adapted from Saha et al. Science. 1983;220:325-327. An Inevitable Sequence of Events... An Inevitable Sequence of Events... Well-meaning physician targets digoxin levels Well-meaning physician targets digoxin levels • • for treatment of HF or atrial fibrillation for treatment of HF or atrial fibrillation A patient with eggerthella lenta ends up on an A patient with eggerthella lenta ends up on an • • extremely high dose of digoxin extremely high dose of digoxin Patient receives antibiotics (Z-pack, etc.) Patient receives antibiotics (Z-pack, etc.) • • Patient gets dig-toxic Patient gets dig-toxic • • 7
An Inevitable Sequence of Events... An Inevitable Sequence of Events... Well-meaning physician targets digoxin levels Well-meaning physician targets digoxin levels • • for treatment of HF or atrial fibrillation for treatment of HF or atrial fibrillation A patient with eggerthella lenta ends up on an A patient with eggerthella lenta ends up on an • • extremely high dose of digoxin extremely high dose of digoxin Patient receives antibiotics (Z-pack, etc.) Patient receives antibiotics (Z-pack, etc.) • • Patient gets dig-toxic Patient gets dig-toxic • • An Inevitable Sequence of Events... An Inevitable Sequence of Events... Well-meaning physician targets digoxin levels Well-meaning physician targets digoxin levels • • for treatment of HF or atrial fibrillation for treatment of HF or atrial fibrillation A patient with eggerthella lenta ends up on an A patient with eggerthella lenta ends up on an • • extremely high dose of digoxin extremely high dose of digoxin Patient receives antibiotics (Z-pack, etc.) Patient receives antibiotics (Z-pack, etc.) • • Patient gets dig-toxic Patient gets dig-toxic • • NOTE: This is the reason for antibiotic-digoxin • medication interactions! 8
DIG Trial: Post-hoc Analysis of Mortality How to Avoid This? vs. 1-month Digoxin Levels Step 1: Recognize we live in a world of antibiotics. • • It is not realistic to think your patient will not ultimately get an antibiotic prescription. Step 2: Don’t target digoxin levels! • • You can estimate daily dose by 2 main things: • GFR • Amiodarone use • Nobody should require a maintenance dose > 0.25 mg • Remember: For the most part, low levels are okay! • Particularly true if using for heart failure indication rather than rate control Reasons for checking digoxin levels: • • You suspect toxicity • To check medication adherence Adapted from Adams et al. J Am Coll Cardiol. 2005;46:497-504. What Do You Do? What Do You Do? What about the lisinopril? What about the lisinopril? 1) Continue lisinopril unchanged 1) Continue lisinopril unchanged 2) Decrease lisinopril dose to 10 mg bid 2) Decrease lisinopril dose to 10 mg bid 3) Change lisinopril to ARB 3) Change lisinopril to ARB 4) Stop lisinopril & start sacubitril/valsartan next day 4) Stop lisinopril & start sacubitril/valsartan next day 5) Change lisinopril to ARB x 36 hours, then change to 5) Change lisinopril to ARB x 36 hours, then change sacubitril/valsartan to sacubitril/valsartan 9
Breakdown of Outcomes PARADIGM-HF Neprilysin: Breaks down natriuretic peptides & • angiotensin II Trial: Sacubitril-valsartan vs. Enalapril • Double-blind, randomized trial of 8442 patients • • LVEF ≤ 40% • NYHA II-IV Primary end-point: Time to CV death or HF • hospitalization Stopped early after median follow-up of 27 months • ACC/AHA/HFSA Guidelines: • • SWITCH NYHA Class 2-3 HFrEF patients from ACEi or ARB to sacubitril-valsartan (Class 1 recommendation!) Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. Breakdown of Outcomes Breakdown of Outcomes Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. Adapted from McMurray et al. New Engl J Med. 2014;371:993-1004. 10
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