Speaker Disclosures. Managing the Patient with Congestive Heart Failure. Objectives. Etiology of Cardiomyopathy 7/15/2015

Transcription

1 Speaker Disclosures Managing the Patient with Congestive Heart Failure I disclose that I am a Consultant for St Jude Medical. I disclose that I am a member of the speaker s bureaus for Gilead, United Therapeutics, Bayer and Actelion Pharmaceuticals. I will not discuss off-label or unapproved usage. Javier Jimenez MD PhD FACC Director, Advanced Heart Failure and Pulmonary Hypertension Miami Cardiac & Vascular Institute South Miami Hospital 2 Objectives Stages, Phenotypes and Treatment of HF Discuss common causes of Heart Failure Review what is an appropriate evaluation and management of a heart failure patient Learn about new drug therapies Develop strategies to prevent rehospitalizations Etiology of Cardiomyopathy Cardiomyopathy Primary Cardiomyopathy GENETIC RVD HCM Mytochondrial MIXED Dillated Cardiomyopathy Restrictive-Non hyperthopied Ischemic Non-Ischemic ADQUIRED Myocarditis Takotsubo Peripartum 1

2 Hypertensive Valvular Drug related: chemo, etoh Non Compaction Amyloid, Sarcoid Thyroid, DM RA, Lupus Hemochromatosis Tuberous Sclerodis Esosinophylic MELAS Diagnostic Testing Electrocardiography (EKG) Echocardiography (E) Nuclear Imaging (NI) Angiography (CA) Cardiac CT (CCT) Cardiac MRI (MRI) Endomyocardial Biopsy (BX) Laboratory testing (LAB) Ischemic Cardiomyopathy What kind of cardiomyopathy A-HCM NON -OBS B-HTN CM C-AMYLOID D-MUCHOPOLYS E-OXALOSIS F-FRIEDIREICH ATX Non CompactionCardiomyopathy Hyperthrophic Cardiomyopathy 2

3 Cardiac Amyloidosis Arrhythmogenic Right Ventricular Cardiomyopathy Prognosis depends on Etiology History and Physical Exam in HF 1230 pts. referred for unexplained CM. Felker GM. NEJM 2000;342:1077 Clues suggesting etiology of HF Duration of illness Severity, triggers and associated symptoms Weight changes Palpitations, syncope Volume status Disorders breathing at night Prior hospitalizations for HF Discontinuation of medications CASE 1-Initial Evaluation 75 year old female 2 months worsening SOB/orthopnea Presented to ED after eating at a BBQ Past Hx bordeline HTN, COPD, no meds Physical exam HR 98, BP 150/82, RR 28, temp 36.0C JVP elevated, crackles, pulses 2+, legs warm and LEE1+ CASE 1-Initial Evaluation 74 year old female CXR = pending Labs = pending 3

4 How confident are you that it is AHF? 1. < >8 No right answer AHF Dx Scoring systems Predictor Points Our Case Elevated NT-proBNP 4? Interstitial edema on CXR 2? Orthopnea 2 - Absence of fever 2 2 Current loop diuretic use 1 - Age > 75 years 1 - Rales on lung examination 1 1 Absence of cough 1 1 Interpretation 4 e.g. At a score of 9, PPV 92%, NPV 82%, sens 70, spec 93 Baggish AL, et al. Am Heart J 2006; 151: 48-54]. CASE-1 More information 75 year old female CXR = increased pulmonary markings c/w edema, no evidence of COPD Labs = troponin I 0.20 BNP 728 pg/ml Creatinine 1.30 AHF Dx Scoring systems Predictor Points Our Case Elevated NT-proBNP 4 4 Interstitial edema on CXR 2 2 Orthopnea 2 - Absence of fever 2 2 Current loop diuretic use 1 - Age > 75 years 1 - Rales on lung examination 1 1 Absence of cough 1 1 Interpretation 10 e.g. At a score of 9, PPV 92%, NPV 82%, sens 70, spec 93 Baggish AL, et al. Am Heart J 2006; 151: 48-54]. Risk Scores to Predict Outcomes in HF -SEATTLE HEART FAILURE MODEL -HEART FAILURE SURVIVAL SCORE -CHARM RISK SCORE -CORONA RISK SCORE -HPRESERVE SCORE -ADHERE CLASSIFICATION -AHA GET WITH THE GUIDELINES -EFFECT RISK SCORE -OPTIMIZE HF RISK PREDICTION SCORE J Am CollCardiol. 2013;62(16):e147-e239. doi: /j.jacc What is BNP? A 32 amino acid polypeptide Secreted by cardiac myocytes in response to excessive distension of the Heart ventricles Named after extracts found in Pig-brain What is NT-proBNP? NT-proBNP is a biologically inactive 76 amino acid N-terminal fragment Co-secreted with BNP Even longer t 1/2 than BNP (~1-2hrs vs ~20mins) Biological effects of Cardiac Natriuretic peptides Increase Natriuresis Decrease peripheral vascular resistance 4

5 Recommendation Recommendation -Use a validated diagnostic scoring system for patients in whom the diagnosis of AHF is being considered -This recommendation places a relatively high value on evaluating the constellation of clinical findings in a patient with suspected AHF and less value on an individual physical examination finding, presenting symptom or investigation. In the clinical scenario when the clinical diagnosis of AHF is of intermediate pre-test probability, a BNP level can be obtained to rule-out AHF (BNP <100 pg/ml; NTproBNP <300 pg/ml) or rule-in AHF (BNP >500 pg/ml; NT-proBNP >900 pg/ml if age years, NT-proBNP >1800 if age >75 years) as the cause for the presenting symptoms suspicious of AHF Practical Tips What additional tests should we order? A precipitating cause for AHF should be sought. An ECG and a chest x-ray should be performed within 2 hours of initial presentation. Initial blood tests should include: complete blood count, creatinine, blood urea nitrogen, glucose, sodium, potassium, and troponin. A-Echocardiogram B-Coronary CT angiogram C-Nuclear Stress test D-All of them Non Invasive testing Echocardiogram Initial CHF presentation Repeat if change in clinical status Nuclear Cardiac Imaging If suspected myocardial ischemia Viability Cardiac MRI Viability Infiltrative cardiomyopathies Invasive testing Hemodynamics Guide therapy Impaired perfusion Assessment volume status Coronary Angiography Suspected ischemia Planned revascularization 5

6 Practical Tips A transthoracic echocardiogram should be performed within 72 hours of presentation. For patients with a prior echocardiogram, another is not required unless there has been a significant change in clinical status requiring investigation, a lack of clinical response to appropriate therapy and/or it is greater than 12 months since the prior echocardiogram. CASE 2-Management of AHF 50 year old male with history of congestive heart failure Presents to ER after the Miami Heat wins the season SOB on minimal exertion, orthopnea HR 105, BP 99/52, RR 24, temp 98.6F JVP difficult to assess (thick neck) Crackles both lungs pulses weak, legs cool and LLEE 1+ Trop: 0.15 Pro-BNP 12,000 CXR=CHF How much diuretic will you give and how? BACKGROUND 1. IV furosemide 20 mg bid 2. IV furosemide 40 mg bid 3. IV furosemide 80 mg bid 4. IV furosemide 10 mg/hour infusion 5. Other choice IV loop diuretics are standard on the current treatment of AHF Data to guide the use of loop diuretics are sparse. Guidelines are based primarily on expert opinion. Clinical practice varies widely with regard to both the mode and dose of administration. High doses of loop diuretics may have harmful effects Activation of the renin angiotensin and sympathetic systems, Electrolyte disturbances Worsening of renal function. Low Dose (1 x oral) Q12 IV bolus DOSE: Study Design Acute Heart Failure (1 symptom AND 1 sign) <24 hours after admission 2x2 factorial randomization Low Dose (1x oral) Continuous infusion High Dose (2.5 x oral) Q12 IV bolus 48 hours 1) Change to oral diuretics 2) continue current strategy 3) 5 increase in dose 72 hours Co-primary endpoints High Dose (2.5 x oral) Continuous infusion DOSE: Co-Primary Endpoints Efficacy: Patient Global Assessment by visual analog scale over 72 hours using area under the curve Safety: Change in creatinine from baseline to 72 hours 60 days Felker, NEJM 2011 Clinical endpoints 6

7 DOSE: patient global assessment DOSE: DOSE: Death, Rehosp DOSE-AHF Conclusions Recommendations: Diuretics There was no statistically significant difference in global symptom relief or change in renal function at 72 hours for either: bolus vs. infusion or low vs. high No clinical differences but High was associated with favorable trends: Symptom relief (global assessment and dyspnea) Weight loss and net volume loss Proportion free from signs of congestion Reduction in NT-proBNP We recommend intravenous diuretics be given as first line therapy for patients with congestion (Strong Recommendation, Moderate Quality Evidence). We recommend for patients requiring intravenous diuretic therapy, furosemide may be dosed intermittently (e.g. twice daily) or as a continuous infusion (Strong Recommendation, Moderate Quality Evidence). Diuretic Resistant Patient?? Assess volume status Restrict Na2+/H2O intake Add another type of diuretic with different site of action (thiazides, spironolactone). Hemodynamic assessment and/or positive inotropic agents. Hemodialysis, or ultrafiltration The patient remains persistently symptomatic with Heart Failure, what is next option? 1. Add digoxin 2. Increase ACEI 3. Reduce beta blockers 4. Add inotropic agent 5. Call for help 7

8 Oral vasodilators Optimize ACE inhibitors/arb dosing Add oral hydralazine Add oral nitrates Add phophodiesterase inhibitors but do not worry about low blood pressure unless symtomatic Intravenous Vasodilators a)nitroglycerin (Strong Recommendation, Moderate Quality Evidence); b)nesiritide (Weak Recommendation, High Quality Evidence); c)nitroprusside (Weak Recommendation, Low Quality Evidence). AHA 2012: RELAX-AHF, CARRESS Inotropes Do I stop the beta-blockers on admission? Hemodynamically stable patients do not routinely receive inotropes like dobutamine, dopamine or milrinone (Strong Recommendation, High Quality Evidence). Values and Preferences These recommendations for inotropes place high value on the potential harm demonstrated when systematically studied in clinical trials and less value on potential short term hemodynamic effects of inotropes. but they may be very helpful in the appropriate patient specially if you know the hemodynamics Cohorts suggest continuing beta-blockers advantageous RCT: B-CONVINCED Keep vs. Stop strategy in known HF pts on beta-blockers Keep was non-inferior to Stop. Does not delay clinical improvement Predicts staying on BB in the longer term EurHeart J 2009; 30: Case 3-Something in the horizon Is there anything else you can do? 65 years old female, previous MI Stable NYHA II, LVEF 30-35%. Two recent hospitalizations. On optimal dose of lisinopril, andmetoprolol, intermediate dose of diuretics Pt with prior ICD implanted BP 99/67 mmhg, HR 85 bpm K, 4.7 meq/l; NT-proBNP 1500 pg/ml EKG: old anterior MI, LBBB QRS 155 ms. 1.Add an aldostenore inhibitor 2.Upgrade to a BiV ICD 3.Leave patient alone since he is FC -2 4.Add digoxin 5.Anything else? 8

9 RALES: Study Design RALES-All-Cause Mortality Aldactone 25 mg/day (n = 822) NYHA III* or IV heart failure LVEF 35% ACE-I + loop diuretic ± digoxn 3 years Placebo (n = 841) Primary Endpoint Total mortality Secondary Endpoint Cardiac mortality Cardiac hospitalization Cardiac mortality or cardiac hospitalization Changes from baseline in NYHA classification Pitt et al, N Engl J Med, *History of NYHA IV within 6 months before first dose RALES Combined Endpoint of Cardiac Mortality or Cardiac Hospitalization CRT in Patients with Mild HF Symptoms: MADIT-CRT 25% reduction in mortality 1820 pts, mostly NYHA II, CRT+ICD vs. ICD alone Low risk population, annual mortality ~3% 4 reduction in HF events in CRT-ICD group Moss et al, NEJM 2009 Reduces Risk of Hospital Admission (The DIG Trial) Placebo (n=3403) Digoxin (n=3397) Heart Failure 35% 27% 8% All-Cause 67% 64% 3% Absolute Risk Difference Hazard ratio (95% CI) 0.72 ( ) 0.92 ( ) P value < Does Not Increase Mortality (The DIG Trial) HR = 0.99; 95% CI = ; P = 0.80 Digoxin significantly reducedthe risk of hospitalizationdue to heart failureby 28%during 37 months of average follow-up, but its effect on hospitalization due to all causes was more modest (a 8% reduction) N EnglJ Med. 1997; 336: N EnglJ Med. 1997; 336:

10 Systolic Heart failure treatment with the I f inhibitor ivabradine Trial Heart rate at baseline influences the effect of ivabradineon cardiovascular outcomes in chronic heart failure: Effect of ivabradineon outcomes in patients with chronic heart failure (LVEF <35%), one hospital admission for HF within 12 months and HR 75 bpm % Decrease in Mortality Drugs That Reduce Mortality in Heart Failure With Reduced Ejection Fraction Angiotensin receptor blocker ACE inhibitor Drugs that inhibit the renin-angiotensin system have modest effects on survival Beta blocker Mineralocorticoid receptor antagonist Based on results of SOLVD-Treatment, CHARM-Alternative, COPERNICUS, MERIT-HF, CIBIS II, RALES and EMPHASIS-HF One Enzyme Neprilysin Degrades Many Endogenous Vasoactive Peptides Neprilysin Inhibition Potentiates Actions of Endogenous Vasoactive Peptides That Counter Maladaptive Mechanisms in Heart Failure Endogenous vasoactive peptides (natriuretic peptides, adrenomedullin, bradykinin, substance P, calcitonin gene-related peptide) Inactive metabolites Neprilysin Endogenous vasoactive peptides (natriuretic peptides, adrenomedullin, bradykinin, substance P, calcitonin gene-related peptide) Inactive metabolites Neprilysin Neurohormonal activation Vascular tone Cardiac fibrosis, hypertrophy Sodium retention Neprilysin inhibition LCZ696: Angiotensin Receptor Neprilysin Inhibition LCZ696 Aim of the PARADIGM-HF Trial Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF) Angiotensin receptor blocker Inhibition of neprilysin LCZ mg daily Enalapril 20 mg daily SPECIFICALLY DESIGNED TO REPLACE CURRENT USE OF ACE INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERS AS THE CORNERSTONE OF THE TREATMENT OF HEART FAILURE 10

11 PARADIGM-HF: Entry Criteria NYHA class II-IV heart failure LV ejection fraction 4 35% BNP 150 (or NT-proBNP 600), but one-third lower if hospitalized for heart failure within 12 months Any use of ACE inhibitor or ARB, but able to tolerate stable dose equivalent to at least enalapril 10 mg daily for at least 4 weeks Guideline-recommended use of beta-blockers and mineralocorticoid receptor antagonists Systolic BP 95 mm Hg, egfr 30 ml/min/1.73 m 2 and serum K 5.4 meq/l at randomization PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint) Kaplan-Meier Estimate of Cumulative Rates (%) LCZ696 Enalapril Patients at Risk 8 0 Enalapril (n=4212) Days After Randomization LCZ696 (n=4187) HR = 0.80 ( ) P = Number needed to treat = Kaplan-Meier Estimate of Cumulative Rates (%) HR = 0.80 ( ) P = Number need to treat = 32 Enalapril (n=4212) LCZ696 (n=4187) Days After Randomization Patients at Risk LCZ696 Enalapril PARADIGM-HF: Cardiovascular Death Angiotensin Neprilysin Inhibition With LCZ696 Doubles Effect on Cardiovascular Death of Current Inhibitors of the Renin-Angiotensin System % Decrease in Mortality Angiotensin receptor blocker 15% ACE inhibitor 18% 2 Angiotensin neprilysin inhibition Effect of ARB vs placebo derived from CHARM-Alternative trial Effect of ACE inhibitor vs placebo derived from SOLVD-Treatment trial Effect of LCZ696 vs ACE inhibitor derived from PARADIGM-HF trial Case 4-Rehospitalization 74 year old female with NYHA FC II-III HF with LVEF 20-25% BP 90/70, HR 85, Na 130, Creat 2.1mg/dL, K Euvolemic, Fith day after admission. Feeling back to her baseline. Third hospital admission in two months. Ready for discharge Worsening Chronic Heart Failure: The Major Reason for Heart Failure Hospitalizations What should you do next? A.Arrange for hospice care B.Start intravenous outpatient inotropes C.Change cardiologist D.Refer to an outpatient heart failure program 11

12 Causes of Hospital Readmission for Congestive Heart Failure Over 2/3 of HF Hospitalizations Preventable Diet Noncompliance 24% 16% Inappropriate Rx 19% Failure to Seek Care Rx Noncompliance 24% 17% Other Heart Failure Management Issues High Mortality High re-admission rates Poor understanding of disease Poor Rx adherence On-going symptoms Reduced Quality of Life More relevant in the Elderly Annals of Internal Medicine 122:415-21, 1995 Medication Adherence Gap Cost of medications Complacency-patient and physician Side effects Lack of understanding Infrequent monitoring intervals Lack of reinforcement What can we do about it? Pt follow up soon after discharge Medication Reconciliation Assessment of volume status Make your life easy and refer to a heart failure program Heart Failure Clinic Team Nurse Practitioners Registered Nurses Social work services Nutritionists Pharmacists Physician Supervising Heart Failure Clinic Team MCVI- South Miami Hospital Nurse Practitioners Registered Nurses Social work services Nutritionists Pharmacists Physician Supervising 2,000 patients/year 12

13 25% 2 15% 1 5% 10/13 Implemented HF Education Program 4% 5% Miami Cardiac & Vascular Institute South Miami Hospital 1 October, September, 2014 HF Clinic Education Only Patients 5% 6% 2% 12% HF Clinic Treatment Program National Readmit Rates = 23% SMH Readmit Rates = 2 5% 9% 3% Oct-13 Nov-13 Dec-13 Jan-14 Feb-14 Mar-14 Apr-14 May-14 Jun-14 Jul-14 Aug-14 Sep % Role of Heart Failure Clinics Pre-transplant/ pre LVAD eligibility and work-up Out-patient chronic parenteral inotropic therapy Medication titration Patient education High risk (CHF) rehabilitation programs Out patient LVAD chronic care Volume management (outpatient iv diuretics) Management of social issues Role of Primary Care Physician Summary High risk CHF Patient identification Assessment/modification of underlying etiology Promt follow up after discharge Medication titration Patient education Management of comorbitiies Family integration When heart failure cannot be controlled look for unsual etiologies Follow the guidelines, learn about new drugs Discharge the patient in a euvolemic state If available seek the support of a specialized Heart Failure Clinic 13