Stopping the Revolving Door of ADHF Ileana L. Piña, MD, MPH Professor of Medicine and Epidemiology/Population Health Associate Chief for Academic Affairs -- Cardiology Montefiore-Einstein Medical Center Bronx, NY
HF Incidence In the United States: Incidence of first hospitalization for HF approaching 400 per 100,000 population 1 Incidence of second hospitalization for HF approaching 1,000 per 100,000 1 Age-adjusted hospitalization rates for HF, 1979-2004 2 1. Blair JE, et al. Curr Cardiol Rev. 2013;9(2):128-146. 2. Fang J, et al. J Am Coll Cardiol. 2008;52(6):428 434.
Why the high incidence? 1) Chronic HF treatment is improving 2) Improved survival from acute coronary syndrome (ACS) 1 22% males and 46% females with acute myocardial infarction (AMI) will be disabled with HF within 6 years 3) Population is aging (increasing risk factors) 1,2 Millions of persons 65 years old 3 80 60 40 20 0 25.5 16.6 11.3 9.2 Millions of persons 53.7 34.8 16.5 12.7 77.2 20.5 Percent of population 1960 1980 2000 2020 2040 Year 80 60 40 20 0 Percent of population 65 years old 3 1. Roger VL, et al. Circulation 2012;125(1):e2 220 2. YancyCW, et al. J Am Coll Cardiol 2013;62(16);e147-239. 3. Ortman JM, et al. US Census Bureau May 2014.
Estimated Direct and Indirect Costs of HF in US Hospitalization $20.9 53% Total Cost $39.2 billion 14% Nursing Home $4.7 8% Lost Productivity/ Mortality* $4.1 Home Healthcare $3.8 Heart Disease and Stroke Statistics 2010 Update 8% 10% 7% Physicians/Other Professionals $2.5 Drugs/Other Medical Durables $3.2
Acute Heart Failure (AHF) Defined as a rapid or gradual change in signs and symptoms in patients with chronic HF or de novo HF that necessitates urgent therapy and/or hospitalization 1 Leading medical cause of hospitalization among people 65 years 2 Presentation of AHF represents a period of very high risk, during which the likelihood of death and re-hospitalization is significantly greater than for a comparable period of chronic but stable HF Treatment is highly variable and needs to improve 1 1. Gheorghiade M, et al. Circulation. 2005;112(25):3958-3968. 2. Gheorghiade M, et al. J Am Coll Cardiol. 2009;53(7):557-573. 6
Mortality in HF Adjusted changes in outcomes between 1999 and 2011 13% Decline Krumholz HM, et al. Circulation. 2014;130(12):966-975.
Trends in HF: Mortality and Disposition 8
Heart Failure is the most common reason for 30 day reshospitalization Jencks et al. N Engl J Med 2009;360:1418-28.
the first 30 days after a hospitalization Jencks et al. N Engl J Med 2009;360:1418-28
30 day Readmission and 30 day Mortality Butler et al. 11
First Point of Care for AHF Inpatient Unit / Obs Status 1% Observation Unit < 1% Inpatient Unit 20% N=187,565 Emergency Department 78% The ADHERE Registry
Lower-risk patients exist Are ED MDs ready to discharge from ED? 23 hours clinical stability and self-care barriers addressed Collins JACC 2013 61(2):121-6 13
Clinical Characteristics of ADHF Data from almost 200,000 patients hospitalized for heart failure 1 ADHERE 2 Euro-HF 3 OPTIMIZE-HF 4 (105,388 pts) (11,327 pts) (48,612 pts) Median age, y 75 Hx of atrial fibrillation 30% Women >50% Renal abnormalities 30% Hx of CAD/MI 60% SBP >140 mm Hg 50% Hx of hypertension 70% SBP 90-140 mm Hg 45% Hx of diabetes 40% SBP <90 mm Hg 5% 1. Gheorghiade M, et al. Circulation. 2005;112(25):3958-3968. 2. Adams KF Jr, et al. Am Heart J. 2005;149(2):209-216. 3. Cleland JG, Eur Heart J. 2003;24(5):442-463. 4. Fonarow GC, et al. JAMA. 2007;297(1):61-70. 14
MedPac report March 2013
Comorbidities in AHF >40% of patients age 65 years and up with HF have more than 5 comorbidities 1 Significant independent predictors of mortality: 1 Chronic kidney disease Chronic obstructive pulmonary disease Peripheral arterial disease Warrants heightened level of clinical suspicion and appropriate screening
AHF in the ED Emergency department (ED) is the first point of care for 78% of AHF patients 1 Misdiagnosis rate in the ED around 14% 2 N= 439 ED patients with signs/symptoms of HF Cardiology criterion Standard diagnosis Primary HF Non-primary HF ED diagnosis Primary HF 115 (26.3%) 5 (1.1%) Non-primary HF 58 (13.2%) 260 (59.4%) 1. ADHERE National Registry Benchmark Report; December 2014. 2. Collins SP, et al. BMC Emerg Med. 2006;6:11.
Biomarkers in AHF Biomarker Diagnosis Risk stratification Treatment Natriuretic peptides +++ +++ +++ Procalcitonin -pulm infxn NGAL -AKI ++ ++ ++ ++ ++ ++ MR-proADM +++ + Copeptin +++ ++ ST2 +++ + Galectin-3 +++ + ctn -cardiac myonecrosis +++ +++ +++ Adapted from Maisel AS, Choudhary R. Nat Rev Cardiol. 2012;9(8):478-490.
Initial Assessment and Management: 5 Questions to Ask 1) Stable? NIV, IV vasoactives 2) SBP >140 mmhg? Yes? SLNTG followed by IV NTG No? 2x home diuretic 3) Vitals? Tachycardia, low BP (not shock) 4) Cause? Nonadherence (self-care)? ACS, Infxn? 5) Test results? Tn, Na 2+ BUN/Cr Response to therapy Gheorghiade M, Braunwald E. JAMA. 2011;305(16):1702-1703.
Risk Assessment and Disposition Two pieces to risk-stratification: 1. Immediate risk measures of ACUTE severity Hypoxia, hypotension, respiratory distress, hypertension? Immediate intermediate 2. Intermediate risk (5-days through 30 60 days) Renal dysfunction Hyponatremia Ischemia on ECG / elevated Tn Low BP (not shock) BNP Collins SP, et al. Crit Pathways Cardiol. 2008;7(2):96-102.
Selected ED-based risk stratification studies from the last 8 years which examine events within 30 days or less of index ED presentation Author/year N Predicted outcome Variables in final model Lassus et al. 441 4,450 2013 1 (pooled analysis, total no. varied by biomarker evaluated) 30-day and 1-year mortality Lower risk: Elevated BP Normal troponin Normal renal function Stiell et al. 2013 2 559 30-day death and 14-day serious nonfatal events ST2, MR-proADM, CRP, NTproBNP, BNP, MR-proANP h/o TIA/CVA, vital signs, ECG and laboratory findings Lee et al. 2012 3 12,591 7-day mortality Creatinine, BP, O 2 satn, Tn, h/o cancer, home metolazone, EMS, transport Hsieh et al. 8,384 In patient mortality or serious medical 2008 4 complications, 30-day mortality Diercks et al. 499 Stay <24 h in observation and no 30-day 2006 5 adverse cardiac events Auble et al. 33,533 In patient mortality or serious medical 2005 6 complications, 30-day mortality and AHF readmission ph, pulse, renal function, WBC, glucose, sodium Low-risk markers No 1, 2, 4 No 2, 4 Yes 2, 3 Yes 2, 3, 4 Tn, systolic BP Yes 2, 4 ph, pulse, renal function, WBC, glucose, sodium Yes 2, 3, 4 Fonarow et al. 65,275 In-hospital mortality BUN, systolic BP, creatinine No 2, 3, 4 2005 7 Limitations Collins and Storrow. JACC HF 2013;1:273 80 1. Lassus J, et al. Int J Cardiol. 2013;168(3):2186-2194. 2. Stiell IG, et al. Acad Emerg Med. 2013;20(1):17-26. 3. Lee DS, et al. Ann Intern Med. 2012;156(11):767-775. 4. Hsieh M, et al. Ann Emerg Med. 2008;51(1):37-44. 5. Diercks DB, et al. Am J Emerg Med. 2006;24(3):319-324. 6. Auble TE, et al. Acad Emerg Med. 2005;12(6):514-521. 7. Fonarow GC, et al. JAMA. 2005;239(5):572-580.
AHF in the ED: Risk Stratification Algorithm From Collins S, et al. J Card Fail. 2015;21(1):27-43; with permission.
Therapy: No new therapies approved since nesiritide Diuretics! Diuretics! Diuretics! Vasodilators Nitrates Nesiritide Nitroprusside Inodilators Milrinone Inotropes Dobutamine, dopamine Novel agents serelaxin 23
SAEM/HFSA 2015 Guidelines ED Presentation Phenotype Low BP (SBP <100) Normal BP (SBP 100-140) High BP (SBP >140) Clinical Characteristics - Known/suspected low LVEF - Likely CAD or CRI -Sub-acute symptoms - Preserved or reduced LVEF -Dietary/medical indiscretion -History of HTN -Abrupt symptom Treatment -Diuretics (+++) -Inotropes/pressors (++) - Mechanical support (+) -Diuretics (++) -IV vasodilators (+) -Topical nitrates (++) -Topical/SL nitrates (++) +, Relative intensity of use; NIV, non-invasive ventilation; HTN, hypertension; CAD, coronary artery disease; LVEF, left ventricular ejection fraction; CRI, chronic renal insufficiency; SL, sublingual; BP, blood pressure Adapted from Collins S, et al. J Card Fail. 2015;21(1):27-43.
Diuretic Strategies: Protocol Comparison No significant differences in patients global assessment of symptoms or in the change of renal function when diuretic therapy was administered by bolus as compared with continuous infusion or at high dose as compared with a low dose. Kaplan Meier Curves for the Clinical Composite End Point of Death, Rehospitalization, or Emergency Department Visit From Felker GM, et al. N Engl J Med. 2011;364(9):797-805; with permission.
Mean Change in Serum Creatinine Level. Felker GM et al. N Engl J Med 2011;364:797-805
Safety of Loop Diuretics in HF Activate the renin-angiotensin-aldosterone system and sympathetic nervous system 1 Both play a fundamental role in HF progression Administration may result in significant decrease in glomerular filtration rate in some patients 1 May lead to electrolyte imbalances 1 Relationship between maximum in-hospital diuretic dose and mortality in the ESCAPE study. 2 1. Felker GM, et al. Circulation: Heart Failure. 2009;2:56-62. 2. Hasselblad V, et al. Eur J Heart Fail. 2007;9(10):1064-1069; with permission.
2010 HFSA Recommendations for Vasodilator Therapy IV vasodilators and diuretics recommended for rapid symptom relief in patients with acute pulmonary edema or severe hypertension In the absence of symptomatic hypotenstion, IV nitroglycerin, nitroprusside, or nesiritide may be considered as an addition to diuretic therapy for rapid improvement of congestive symptoms Frequent blood pressure monitoring recommended Decrease dosage if symptomatic hypotension develops IV nitroprusside, nitroglycerin, or nesiritide may be considered in patients with AHF and advanced HF who have persistent severe HF despite aggressive treatment with diuretics and standard oral therapies Lindenfeld J, et al. J Card Fail. 2010;16(6):e1.
Co-Primary outcome: 30-day all-cause mortality or HF rehospitalization 12 P=0.31 Hazard Ratio 0.93 (95% CI: 0.8,1.08) 10 10.1 9.4 Placebo 8 Nesiritide % 6 6.1 6.0 4 4.0 3.6 2 0 30-day Death/HF Rehospitalization 30-day Death HF Rehospitalization Risk Diff (95 % CI) -0.7 (-2.1; 0.7) -0.4 (-1.3; 0.5) -0.1 (-1.2; 1.0)