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clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Acute Heart Failure: Current
S...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
About These Slides
 Users are...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Faculty
Javed Butler, MD, MPH,...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Disclosures
Javed Butler, MD, ...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Patient Case: History
 71-yr-...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Biomarkers in Diagnosis and
Pr...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Natriuretic Peptides in AHF Di...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Additional Biomarkers in AHF D...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Impact of Troponin Release on ...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Clinical Considerations
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Stratification of Pts With AHF...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Systolic Blood Pressure at Adm...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Precipitating Causes of AHF Ar...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
ACCF/AHA Definitions of HFrEF ...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Distribution of LVEF in AHF Pt...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
ADHERE CART Analysis: In-Hospi...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Worsening Renal Function as a
...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Patient Case: Initial Assessme...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Current Treatment Options
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Diuretics in Hospitalized Pts
...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
DOSE: Loop Diuretics in AHF
 ...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Vasodilators in AHF
 ACCF/AHA...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
8.69.5
10
ASCEND-HF: 6- and 24...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
 1-yr mortality rates did not...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Inotropic Support
 ACCF/AHA g...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
AERate(%)
Treatment Failure
Fr...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Ultrafiltration
 ACCF/AHA gui...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Weight
Gain
(lb)
CARRESS: Chan...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
CARRESS: Change in Creatinine ...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Patient Case: Treatment
 Echo...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Investigational Agents
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Ularitide
 Natriuretic peptid...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
1. Stewart DR, et al. J Clin E...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
RELAX-AHF: CV Death Through Da...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
120
160
40
80
140
180
20
60
10...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Omecamtiv Mecarbil
 Selective...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
ATOMIC-AHF
 Randomized, place...
clinicaloptions.com/cardiology
Acute Heart Failure: Current Standards and Evolution of Care
Postdischarge Outcomes in AHF
...
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Acute Heart Failure: Current Standards and Evolution of Care
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Acute Heart Failure: Current Standards and Evolution of Care.2015

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Обсуждение последних данных, касающиеся диагностики и лечения острой сердечной недостаточности, в том числе использование биомаркеров для диагностики и оценке прогноза , преимущества и ограничения действующих стандартами медицинской помощи, и доказательств данных по современной терапии острой сердечной недостаточности.
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Acute Heart Failure: Current Standards and Evolution of Care.2015

  1. 1. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Acute Heart Failure: Current Standards and Evolution of Care This program is supported by educational grants from Amgen and Novartis.
  2. 2. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.
  3. 3. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Faculty Javed Butler, MD, MPH, MBA Professor of Medicine Chief of Cardiology Division of Cardiology Stony Brook University Stony Brook, New York G. Michael Felker, MD, MHS, FACC, FAHA Professor of Medicine Chief, Heart Failure Section Division of Cardiology Duke University Durham, North Carolina
  4. 4. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Disclosures Javed Butler, MD, MPH, MBA, has disclosed that that he has received consulting fees from Amgen, Bayer, CardioCell, Celladon, Novartis, Stealth Peptides, Trevena, Zensun, and ZS Pharma and fees for non-CME/CE services from Novartis. G. Michael Felker, MD, MHS, FACC, FAHA, has disclosed that he has received consulting fees from Amgen, Bristol-Myers Squibb, Celladon, Merck, Novartis, Relypsa, Roche Diagnostics, Singulex, Stealth Peptides, and Trevena and funds for research support from Amgen, Novartis, Otsuka, and Roche Diagnostics.
  5. 5. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Patient Case: History  71-yr-old woman with history of hypertension, diabetes, and obesity  No prior history of HF  Presents to emergency department with chief complaint of breathlessness that has gradually progressed over 4 days; has also noticed some peripheral edema  ROS: no chest pain + orthopnea  Current medicines at home: ASA, insulin, lisinopril
  6. 6. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Biomarkers in Diagnosis and Prognosis
  7. 7. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Natriuretic Peptides in AHF Diagnosis  ACCF/AHA guidelines: measurement of BNP or NT-proBNP is useful in aiding a diagnosis of ADHF[1]  Breathing Not Properly study: prospective study assessing the use of BNP in diagnosing pts with HF (N = 1586) 1. Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239. 2. Maisel AS, et al. N Engl J Med. 2002;347:161-167. Levels of BNP Differentiating Dyspnea due to CHF vs Other Causes[2] BNP (pg/mL) Accuracy 50 79 80 83 100 83 125 83 150 84 *Pts had a history of ventricular dysfunction. 1400 1200 1000 800 600 400 200 0 Dyspnea due to CHF (N = 744) Dyspnea due to Noncardiac Causes* (n = 72) No CHF (n = 770) Median BNP Levels[2] BNP(pg/mL)
  8. 8. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Additional Biomarkers in AHF Diagnosis and Risk Stratification  Cardiac troponins[1] – Markers of myocardial injury; increased circulating levels are associated with poorer clinical outcomes and mortality – ACCF/AHA: assessment recommended for additive risk stratification  Galectin-3 and sST2[1] – Markers of myocardial fibrosis; prognostic for hospitalization and mortality – ACCF/AHA: assessment recommended for additive risk stratification  Additional prognostic biomarkers[2] – Cystatin C, AST, ALT 1. Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239. 2. Metra M, et al. J Am Coll Cardiol. 2013;61:196-206.
  9. 9. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Impact of Troponin Release on Survival in AHF  Analysis of the ADHERE registry for pts hospitalized for ADHF who had troponin measurements at initial evaluation Peacock WF, et al. N Engl J Med. 2008;358:2117-2126. 0 2 4 6 8 2.0 2.7 3.4 5.3 > 0.20> 0.10- 0.20 > 0.04- 0.10 ≤ 0.04 Troponin I Quartile 9534932310,36711,090Pts, n In-HospitalMortality(%)
  10. 10. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Clinical Considerations
  11. 11. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Stratification of Pts With AHF Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239. No Warm and Dry Yes Warm and Wet Cold and Dry Cold and WetYes No Congestion at Rest? (eg, orthopnea, elevated jugular venous pressure, pulmonary rales, S3 gallop, edema) LowPerfusionatRest? (eg,narrowpulsepressure, coolextremities,hypotension)
  12. 12. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Systolic Blood Pressure at Admission in Pts Hospitalized for AHF  Data from the OPTIMIZE- HF registry (48,612 pts)  ~ 75% pts with SBP ≥ 120 mm Hg Gheorghiade M, et al. JAMA. 2006;296:2217-2226. 24.9% 25.2% 24.9% 24.9% SBP < 120 mm Hg SBP 140-161 mm Hg SBP 120-139 mm Hg SBP > 161 mm Hg
  13. 13. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Precipitating Causes of AHF Are Poorly Understood  Increased sodium diet  Myocardial ischemia  Mild respiratory or urinary tract infection  Arrhythmia (eg, atrial fibrillation )  Poorly controlled hypertension  Pneumonia  Noncompliance with chronic medications Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239.
  14. 14. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care ACCF/AHA Definitions of HFrEF and HFpEF Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239. Classification EF, % Description I. HFrEF ≤ 40 Also referred to as systolic HF. Randomized controlled trials have mainly enrolled pts with HFrEF, and it is only in these pts that efficacious therapies have been demonstrated to date II. 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 41-49 These pts fall into a borderline or intermediate group. Their characteristics, treatment patterns, and outcomes appear similar to those of pts with HFpEF b. HFpEF, improved > 40 It has been recognized that a subset of pts with HFpEF previously had HFrEF. These pts 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 pts
  15. 15. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Distribution of LVEF in AHF Pts LVEF (%) 0- 5 6- 10 11- 15 16- 20 21- 25 26- 30 31- 35 36- 40 41- 45 46- 50 51- 55 56- 60 61- 65 66- 70 71- 75 76- 80 81- 85 86- 90 91- 95 96- 100 Pts(n) Documented LVEF Measured Prior to or During Hospitalization HFrEF HFpEF Fonarow GC, et al. J Am Coll Cardiol. 2007;50:768-777. 5000 4000 3000 2000 1000 0
  16. 16. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care ADHERE CART Analysis: In-Hospital Mortality  Assessed 33,046 pts hospitalized with AHF  Pts could be classified as having a low, intermediate, or high risk of in-hospital mortality based on admission levels of: – BUN – SBP – Serum creatinine  Pats with lowest mortality risk (2.14% crude mortality [445/20,834]): – BUN < 43 mg/dL – SBP ≥ 115 mm Hg  Pts with highest mortality risk (21.94% crude mortality [136/620]): – BUN ≥ 43 mg/dL – SBP < 115 mm Hg – Serum creatinine ≥ 2.75 mg/dL Fonarow G, et al. JAMA. 2005;293:572-580.
  17. 17. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Worsening Renal Function as a Prognostic Indicator for Pts With AHF  Study assessed 1681 pts 65 yrs of age or older Krumholz H, et al. Am J Cardiol. 2000;85:1110-1113. Outcome RF Not Worse (n = 1212) RF Worse (n = 469) OR (95% CI) In-hospital mortality, % 3 7 2.7 (1.6-4.6) 30-day mortality, % 6 10 1.9 (1.3-2.8) 6-mo mortality, % 19 25 1.6 (1.2-2.1) Length of hospital stay, days 6.93 9.14
  18. 18. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Patient Case: Initial Assessment  Exam – BP 174/93, HR 90, BMI 39 – JVP difficult to assess due to body habitus – RRR: no murmurs or gallops – Basilar rales – 2+ lower extremity edema to knees  Labs and Imaging – Serum creatinine 1.8 mg/dL – Troponin levels not elevated – ECG shows NSR and narrow QRS, with nonspecific ST-T wave changes – CXR shows cardiomegaly with increased interstitial markings
  19. 19. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Current Treatment Options
  20. 20. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Diuretics in Hospitalized Pts  ACCF/AHA guidelines (Class I, LOE B recommendation) – Pts with HF admitted with evidence of significant fluid overload should be promptly treated with IV loop diuretics to reduce morbidity – If pts are already receiving loop diuretic therapy, the initial IV dose should equal or exceed their chronic oral daily dose and should be given as either intermittent boluses or continuous infusion. Urine output and signs and symptoms of congestion should be serially assessed, and the diuretic dose should be adjusted accordingly to relieve symptoms, reduce volume excess, and avoid hypotension Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239.
  21. 21. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care DOSE: Loop Diuretics in AHF  Double-blind, randomized trial of low- vs high-dose IV furosemide via bolus or continuous infusion in AHF pts (N = 308)  Coprimary endpoints: pts’ global assessment of symptoms and change in serum creatinine level from baseline to 72 hrs 0.08 0.10 ChangeinCreatinine(mg/dL) Low Dose P = .21 Felker GM, et al. N Engl J Med. 2011;364:797-805. 0.05 0 0.04 100 80 60 40 20 0 GlobalAssessmentof Symptoms(GlobalVASScore) 0 10 20 30 40 50 60 70 Hrs AUC with low-dose strategy: 4171 ± 1436 AUC with high-dose strategy: 4430 ± 1401 P = .06 High dose Low dose High Dose
  22. 22. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Vasodilators in AHF  ACCF/AHA guidelines (Class IIb, LOE A recommendation) – If symptomatic hypotension is absent, IV nitroglycerin, nitroprusside or nesiritide may be considered an adjuvant to diuretic therapy for relief of dyspnea in pts admitted with acutely decompensated HF Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239.
  23. 23. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care 8.69.5 10 ASCEND-HF: 6- and 24-Hr Dyspnea and Mortality/Rehospitalization  Randomized, placebo-controlled phase III study of nesiritide for 24-168 hrs in hospitalized pts with AHF (N = 7141) O’Connor CM, et al. N Engl J Med. 2011;365:32-43. 12 10 8 6 4 2 0 10.1 4.0 9.4 6.1 3.6 6.0 Death or Rehospitalization for HF Death Rehospitalization for HF Death From Any Cause or Rehospitalization for HF at 30 Days -0.4 (-1.3 to 0.5) -0.7 (-2.1 to 0.7) -0.1 (-1.2 to 1.0) Percentage point difference (95% CI) P = .31 HR: 0.93 (95% CI: 0.8-1.08) Placebo Nesiritide 42.1 13.4 28.7 34.1 21.7 44.5 15.0 29.5 32.8 20.3 70 60 50 40 30 20 0 10 20 30 40 50 60 Placebo (n = 3444) Nesiritide (n = 3416) 66.1 27.5 38.6 22.1 68.2 30.4 37.8 21.2 Placebo (n = 3398) Nesiritide (n = 3371) 6 Hrs P = .03 24 Hrs P = .007 Self-Assessed Change in Dyspnea Markedly better Moderately better Minimally better No change Minimally worse Moderately worse Markedly worse Pts(%) Pts(%)
  24. 24. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care  1-yr mortality rates did not change over the last decade[2]  Nearly 1 in 4 AHF pts readmitted within 30 days[1] 1. Dharmarajan K, et al. JAMA. 2013;309:355-363. 2. Chen J, et al. JAMA. 2011;306:1669-1678. Postdischarge Outcomes in AHF 30 0 5 25 10 20 15 PtsReadmitted(%) Days Following Hospital Discharge 20100 30 40 100 0 20 Risk-Adjusted MortalityRate*(%) Yr 2003 2002 1999 2001 2005 2000 2008 2007 40 2006 2004 80 60 *Risk-adjusted rates relative to 1999.
  25. 25. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Inotropic Support  ACCF/AHA guidelines (Class IIb, LOE B recommendation) – Short-term, continuous IV inotropic support may be reasonable in those hospitalized pts presenting with documented severe systolic dysfunction who present with low blood pressure and significantly depressed cardiac output to maintain systemic perfusion and preserve end- organ performance Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239.
  26. 26. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care AERate(%) Treatment Failure From AE (48 hrs) Sustained Hypotension Acute MI Mortality Milrinone Placebo Afib P < .001 P < .001 P = .18 P = .004 P = .19 12.6 2.1 10.7 3.2 1.5 0.4 4.6 1.5 3.8 2.3 0 5 10 15 20 OPTIME-CHF: In-Hospital AEs  Randomized, double-blind, placebo-controlled trial of short-term IV milrinone in pts hospitalized due to chronic heart failure exacerbation (N = 951) Cuffe MS, et al. JAMA. 2002;287:1541-1547.
  27. 27. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Ultrafiltration  ACCF/AHA guidelines – Ultrafiltration may be considered for pts with obvious volume overload to alleviate congestive symptoms and fluid weight (Class IIb, LOE B recommendation) – Ultrafiltration may be considered for pts with refractory congestion not responding to medical therapy (Class IIb, LOE C recommendation) Yancy CW, et al. J Am Coll Cardiol. 2013;62:e147-e239.
  28. 28. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Weight Gain (lb) CARRESS: Change in Creatinine and Weight at 96 Hrs  Randomized trial of ultrafiltration vs stepped pharmacologic therapy in pts with AHF, worsened renal function, and persistent congestion (N = 188) Bart BA, et al. N Engl J Med. 2012;367:2296-2304. P = .003 Weight Loss (lb) Creatinine Increase (mg/dL) Creatinine Decrease (mg/dL) 1.0 0.8 0.6 0.4 0.2 0 -0.2 -0.4 -0.6 -0.8 0-2-4-6-8-10-12-14-16-18-20 Ultrafiltration (n = 92) Pharmacologic therapy (n = 94)
  29. 29. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care CARRESS: Change in Creatinine Over 60 Days Bart BA, et al. N Engl J Med. 2012;367:2296-2304. 0.30 0.20 0.10 0 -0.10 -0.20 -0.30 -0.40 -0.50 P = .35 72 Hrs 48 Hrs 24 Hrs 96 Hrs 7 Days 30 Days 60 Days Serum Creatinine P = .048 P = .007 P = .002 P = .50 P = .17 P = .03 MeanCreatinineChangeFrom Baseline(mg/dL) Pharmacologic therapy Ultrafiltration
  30. 30. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Patient Case: Treatment  Echocardiogram shows EF 30% with global hypokinesis, mild MR/TR  Treated with IV furosemide and continuation of oral medications  Responds with brisk diuresis and improvement in symptoms  Pt is discharged with improved symptoms on hospital Day 6  Added carvedilol and spirolactone to outpatient regimen
  31. 31. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Investigational Agents
  32. 32. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Ularitide  Natriuretic peptide with vasodilating and diuretic properties  Previously assessed in the randomized, double-blind, placebo-controlled phase II SIRIUS trial (N = 221)[1] – Standard of care + IV ularitide improved dyspnea and decreased PWCP vs placebo in hospitalized pts with AHF  TRUE-AHF[2] – Multicenter, randomized, double-blind, placebo- controlled phase III study – Pts will receive IV ularitide or placebo for 48 hrs within 12 hrs of ED admission – Pts will have persisting dyspnea at rest despite standard therapy for AHF  Primary endpoints – Clinical composite including dyspnea relief, worsening of heart failure, and all-cause mortality – CV mortality1. Mitrovic V, et al. Eur Heart J. 2006;27:2823-2832. 2. Clinicaltrials.gov. NCT01661634.
  33. 33. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care 1. Stewart DR, et al. J Clin Endocrinol Metab. 1990;70:1771-1773. 2. Szlachter BN, et al. Obstet Gynecol. 1982;59:167-170. 3. Teerlink JR, et al. Lancet. 2013;381:29-39. Serelaxin  Relaxin: naturally occurring peptide; normal hormone of pregnancy[1,2]  Benign safety profile  RELAX-AHF[3] – Randomized, placebo-controlled trial of standard of care + 48 hrs IV serelaxin or placebo in hospitalized pts w/AHF (N = 1161) – Serelaxin treatment improved dyspnea, as measured by VAS AUC (19.4% increase in AUC with serelaxin from baseline through Day 5 vs placebo)
  34. 34. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care RELAX-AHF: CV Death Through Day 180 0 14 12 10 8 6 4 2 CVDeath(ITT)(%) 0 14 30 60 90 120 150 180 HR: 0.63 (95% CI: 0.41-0.96; P = .028) 55 (9.6) 35 (6.1) Placebo (n = 580) Serelaxin (n = 581) Events, n (%) NNT = 29 Days Teerlink JR, et al. Lancet. 2013;381:29-39.
  35. 35. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care 120 160 40 80 140 180 20 60 100 0 Prognostic Indicators of 180-Day Mortality Metra M, et al. J Am Coll Cardiol. 2013;61:196-206. < 30% decrease ≥ 30% decrease NT-proBNP < 22 nmo/L Increase (0.3 mg/L) ≥ 22 nmo/L Increase (0.3 mg/L) Cystatin C CumulativeRisk Study Day < 20% increase ≥ 20% increase ALT CumulativeRisk < 20% increase ≥ 20% increase Troponin T 0 No WHF to Day 5 WHF to Day 5 Worsening Heart Failure 0 < 20% increase ≥ 20% increase AST 0.47 (0.31-0.69) P = .0001 2.10 (1.38-3.20) P = .0004 1.96 (1.13-3.40) P = .0152 1.80 (1.16-2.78) P = .0076 1.66 (0.92-3.00) P = .0987 1.90 (1.11-3.22) P = .0164 120 160 40 80 140 180 20 60 100 0 120 160 40 80 140 180 20 60 100 0 120 160 40 80 140 180 20 60 100 0 0 0.20 0.15 0.10 0.05 0 120 160 40 80 140 180 20 60 100 0 0.20 0.15 0.10 0.05 0 120 160 40 80 140 180 20 60 100 0 Study Day 0 Study Day
  36. 36. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Omecamtiv Mecarbil  Selective activator of cardiac myosin  In a placebo-controlled study in healthy volunteers (N = 34), 6-hr infusions of omecamtiv mecarbil – Prolonged systole ejection time – Increased stroke volume – Increased fractional shortening – Increased ejection fraction Teerlink JR, et al. Lancet. 2011;378:667-675.
  37. 37. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care ATOMIC-AHF  Randomized, placebo-controlled phase II study of omecamtiv mecarbil for treating AHF (N = 606)  3 sequential dose-escalation cohorts received 48-hr IV OM infusion (cohorts 1-3 targeted median OM plasma concentrations of 115, 230, and 310 ng/mL, respectively)  Primary endpoint: dyspnea symptom response (7-point Likert scale) through 48 hrs Teerlink JR, et al. ESC 2013. Abstract 709. Response Rate Ratio* (95% CI) Cohort 1 1.03 (0.79-1.35) Cohort 2 1.15 (0.90-1.47) Cohort 3 1.23 (0.97-1.55) Pooled Placebo (n = 303) OM Cohort 1 (n = 103) OM Cohort 2 (n = 99) OM Cohort 3 (n = 101) *Relative to pooled placebo. 100 0 41 42 47 51 Overall P = .33 DyspneaResponseRate (%Responders) 20 40 60 80
  38. 38. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Postdischarge Outcomes in AHF  Nearly 1 in 4 AHF pts readmitted within 30 days Dharmarajan K, et al. JAMA. 2013;309:355-363. 30 0 5 25 10 20 15 PtsReadmitted(%) Days Following Hospital Discharge 20100 30 40
  39. 39. clinicaloptions.com/cardiology Acute Heart Failure: Current Standards and Evolution of Care Go Online for Additional Discussion of Acute Heart Failure CME-certified video Downloadable PowerPoint slideset ClinicalThought commentary clinicaloptions.com/cardiology

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