Advanced Care for Decompensated Heart Failure Sara Kalantari MD Assistant Professor of Medicine, University of Chicago Advanced Heart Failure, Mechanical Circulatory Support and Cardiac Transplantation
Disclosures I have no relevant financial relationships with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial services discussed in this CME activity. I do not intend to discuss an unapproved/investigative use of a commercial product/device in my presentation.
Learning Objectives At the end of my presentation you (the learner) will be able to: 1. Understand the physiology of acute and chronic heart failure 2. Understand the signs and symptoms of decompensated heart failure and hemodynamic profiles 3. Identify therapies for advanced heart failure patients
Heart Failure Statistics 5.8 million people have HF 670,000 new cases each year 3.4 million outpatient visits per year 1.1 million hospitalizations per year $39 billion in 2010 Prevalence of Common Cardiovascular and Lung Diseases, U.S., 2004, NHLBI report Death from specific cardiovascular, Lung and Blood Diseases, U.S., 2004 NHLBI report AHA Statistical Update: Circulation. 2009;119:e21-e181
Risk Factors for Cardiomyopathy Major causes of CMP/HF Ischemic heart disease (e.g., coronary artery disease) Nonischemic underlying diseases (e.g., hypertension, valvular heart disease) Risk factors for cardiomyopathy/hf History of or active coronary artery disease Hypertension (75% of patients) Genetic predisposition, congenital heart defects Diabetes Valvular heart disease Thyroid disease Hyperlipidemia Sleep apnea Overweight (elevated body mass index [BMI]) Sedentary lifestyle Advanced age Viral Others (e.g., smoking, alcohol, illicit or therapeutic cardiotoxic drugs) Chang, 2007; DeMartinis et al, 2003; Hunt et al, 2005
Nomenclature Stage vs. Class ACC-AHA Stage A At high risk for HF but without structural heart disease or symptoms of HF (e.g. patients with hypertension or CAD) NYHA Functional Class B Structural heart disease but without symptoms of HF I Asymptomatic II Symptomatic with moderate exertion C Structural heart disease with prior or current symptoms of HF III Symptomatic with minimal exertion D Refractory HF requiring specialized interventions IV Symptomatic at rest Farrell MH, Foody JM, Krumholz HM. JAMA 2002;287:890
Heart Failure is Progressive
Prognosis in Advanced Heart Failure Unchanged in 20 years Stage D, NYHA Class IV Acute cardiogenic shock End organ dysfunction Inotrope-dependent ACE-inhibitor intolerant Cachexia, hyponatremia, CKD Tolerating oral therapies Stabilized to NYHA Class III Median Survival Imminent 1 month 3-6 months 6 months 6-12 months ± 12 months > 24 months Stevenson LW, Rose EA. Circulation 2003;108:3059
Pathologic Progression of CV Disease Coronary artery disease Sudden Death Hypertension Diabetes Myocardial injury Pathologic remodeling Low ejection fraction Death Cardiomyopathy Valvular disease Pump failure Neurohormonal stimulation Myocardial toxicity Symptoms: Dyspnea Fatigue Edema Chronic heart failure Cohn JN. N Engl J Med. 1996;335:490 498. 9
Overactivation of the RAAS and SNS is detrimental in HFrEF Neuropeptides are Protective Natriuretic peptide system 1 Sympathetic nervous system NPRs NPs Epinephrine Norepinephrine α 1, β 1, β 2 receptors Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy HFrEF SYMPTOMS & PROGRESSION Vasoconstriction RAAS activity Vasopressin Heart rate Contractility Renin-angiotensinaldosterone-system Ang II AT 1 R The crucial importance of the RAAS is supported by the beneficial effects of ACEIs, ARBs and MRAs 1 Benefits of β-blockers indicate that the SNS also plays a key role 1 Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis 1. McMurray et al. Eur Heart J 2012;33:1787 847; Figure References: Levin et al. N Engl J Med 1998;339:321 8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27 42; Kemp & Conte. Cardiovascular Pathology 2012;365 71; 10 Schrier & Abraham. N Engl J Med 2009;341:577 85
Pressure Volume Relationship - Weak (poor contractility) - Over-worked (too much preload and afterload) 11
Treatment Approach for the Patient with Heart Failure Stage A Stage B Stage C Stage D At high risk, no structural disease Structural heart disease, asymptomatic Structural heart disease with prior/current symptoms of HF Refractory HF requiring specialized interventions Therapy Treat Hypertension Treat lipid disorders Encourage regular exercise Discourage alcohol intake ACE inhibition Therapy All measures under stage A ACE inhibitors in appropriate patients Beta-blockers in appropriate patients Therapy All measures under stage A Drugs: Diuretics ACEI, ARB, ARNI MRA Beta-blockers Ivabridine Digitalis Salt restriction Therapy All measures under stages A,B, and C Mechanical assist devices Heart transplantation Continuous (not intermittent) IV inotropic infusions for palliation Hospice care Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management 12of Chronic Heart Failure in the Adult, 2005
Hemodynamic Profile Stevenson et al. JAMA. 2002;287;5:628 640. 13
Failed or Neutral Trials in ADHF: Trial Intervention Patients (n) Journal/Year OPTIME Milrinone 951 JAMA/2002 SURVIVE Levosimendan 1,327 JAMA/2007 ESCAPE PA Catheter guided management 433 JAMA/2005 PROTECT Rolofylline 2,033 NEJM/2010 EVEREST Tolvaptan 4,133 JAMA/2007 ASTRONAUT Aliskiren 1,615 JAMA/2013 ROSE Dopamine 360 JAMA/2013 ASCEND Nesiritide 7,151 NEJM/2011
% of Patients Patterns of Therapy for Acute Decompensated Heart Failure 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 88% 14.20% 11.70% ADHERE Registry: Fonarrow, GC et al. AHJ 2007.
Diuretics Diuretics and salt restriction are indicated in patients with current or prior symptoms of HF and reduced LVEF who have evidence of fluid retention (Class I; LOE C) Use until euvolemic stage is achieved Continue to prevent recurrence of fluid retention Increase urinary sodium excretion Improve pulmonary and peripheral congestion Decrease preload No mortality benefit Activates the RAAS system ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult http://www.acc.org/clinical/guidelines/failure/hf_index.htm
Dosing Oral Diuretics ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult 17 http://www.acc.org/clinical/guidelines/failure/hf_index.htm
Dosing IV Diuretics ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult 18 http://www.acc.org/clinical/guidelines/failure/hf_index.htm
Beta-Blockers Cardioprotective effects due to blockade of excessive SNS stimulation In the short-term, beta blocker decreases myocardial contractility; increase in EF after 1-3 months of use Long-term, placebo-controlled trials have shown symptomatic improvement in patients treated with certain beta-blockers 1 When combined with conventional HF therapy, betablockers reduce the combined risk of morbidity and mortality, or disease progression 1 1 Hunt, SA, et al ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult, 2001 p. 20.
Inotropes and Intracellular Signaling Francis et al. JACC 63;20;2014.
Inotropes: Mechanism and Outcome Studies Francis et al. JACC 63;20;2014.
Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS)
MECHANICAL DEVICES FOR ADHF AND SHOCK
Current percutaneous mechanical support options * Investigational device IABP Impella TandemHeart ECMO / ECLS Impella 2.5 Impella CP Impella 5.0 Impella RP
Percutaneous Short-term VAD VA ECMO Surgical Short-term VAD Long-term VAD 25
Summary Acute and chronic heart failure physiology Hemodynamic profile of decompensated heart failure Therapies for advanced heart failure patients