Heart Failure: IS It A Death Sentence? Collaborative ... · 10/2/2019 2 Prevalence and Economic Burden About 5.7 million adults in the United States have heart failure.1 1 in 9 deaths

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Heart Failure: IS It A Death Sentence?Collaborative Diagnosis, Management and Treatment Options in 2019

Sridevi Durga, MD, FACC, RPVI

Interventional Cardiologist

Medical Director, Heart Failure Program

Cox South Hospital

Objectives

� Definition and classification of heart failure

� Guideline based treatment strategies

� Recognize Novel medical therapies and device options

� Ventricular assist devices and Cardiac transplantation

ACC/AHA definition

� Complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill or eject blood.

� Clinical diagnosis that is based on a careful history and physical examination.

� Chronic, progressive condition in which the heart muscle is unable to pump enough blood through the heart to meet the body's needs for blood and

oxygen.

� Heart failure usually results in an enlarged heart.

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Prevalence and Economic Burden

� About 5.7 million adults in the United States have heart failure.1

� 1 in 9 deaths in the United States is due to heart failure. 1

� About half of people who develop heart failure die within 5 years of diagnosis.1

� Heart failure costs the nation an estimated $30.7 billion each year.2 This total includes the cost of health care services, medications to treat heart failure, and missed days of work.

� The mean cost of heart failure related hospitalizations is $23,077 per patient. 2

1. Mozzafarian D, Benjamin EJ, Go AS, et al. on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016;133:e38-e360.2. Heidenreich PA, Trogdon JG, Khavjou OA, Butler J, Dracup K, Ezekowitz MD, et al. Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart AssociationExternal. Circulation. 2011;123(8):933–44.

Risk Factors for Heart Failure

� Advanced age

� Hypertension

� Diabetes

� Coronary artery disease

� Lifestyle factors – Smoking, Drugs, Alcohol

� Sedentary lifestyle and obesity

� Eating foods high in sodium, high cholesterol

� Valvular and congenital heart disease

� Family history

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How to describe Heart Failure

� Acute (decompensated) or chronic (compensated) or both

� Right sided or left sided or both

� Decreased (systolic) or preserved (diastolic) ejection fraction or both

� Stage and class

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HFpEF vs. HFrEF

� Heart failure with preserved ejection fraction (HFpEF), heart failure with normal ejection fraction (HFnEF), or diastolic heart failure

EF > or =50%

*Don’t confuse with diastolic dysfunction – abnormal mechanical property (in absence of clinical syndrome)

� Heart Failure with reduced ejection fraction (HFrEF): (“systolic heart failure”)

EF < 50%

Yancy CW et al. Circulation 2013.

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Treatment options for Heart Failure

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Magnitude of Benefit of Pharmacological Therapy in Stage C Heart Failure

Fonarow GC et al. Am Heart J. 2011Yancy CW et al. Circulation 2013

Response to treatment in HFrEF vs. HFpEF

Borlaug BA et al. Circulation 2011

Clyde W. Yancy et al. JACC 2013;62:e147-e239

American College of Cardiology Foundation and the American Heart Association, Inc.

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NOVEL MEDICAL THERAPIES FOR HEART FAILURE

� Neprilysin inhibitor / Angiotensin receptor blocker

� Ivabradine

� SGLT2 receptor inhibitors - Dapagliflozin

Neprilysin inhibitor / Angiotensin receptor blocker - Sacubitril-Valsartan (ENTRESTO)

� Sacubitril (LCZ696) is a prodrug that is activated to LBQ657 by de-ethylationvia esterases. LBQ657 inhibits the enzyme neprilysin.

� Neprilysin is a natural enzyme that degrades several endogenous vasoactive peptides, including natriuretic peptides, bradykinin, and adrenomedullin.

� Inhibition of Neprilysin increases the levels of these substances, countering the neurohormonal overactivation that contributes to vasoconstriction,

sodium retention, and maladaptive cardiac and vascular remodeling

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� 8442 patients with class II (71%) and III (23%) heart failure� EF < 40%, HF symptoms, BNP >150pg/ml

� Compared to ‘Standard of Care’ Enalapril (10 mg BID)� Primary outcome: Composite of death from CV causes or

hospitalization from HF

PARADIGM-HF Trial

Results:

McMurray J et al. NEJM 2014

Results:

Angiotensin receptor–neprilysin inhibition was superior to ACE-I alone in reducing the risks of death and of hospitalization for heart failure

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Pharmacological Treatment for Stage C HF With Reduced EF

Renin-Angiotensin System Inhibition With ACE-Inhibitor or ARB

or ARNI


I

ACE-I: A

The clinical strategy of inhibition of the renin-angiotensin system with ACE

inhibitors (Level of Evidence: A), ORARBs (Level of Evidence: A), OR ARNI (Level of Evidence: B-R) in conjunction with evidence-based beta blockers, and aldosterone antagonists in selected patients, is recommended for patients with chronic HFrEF to reduce morbidity and mortality.

NEW: New clinical trial

data prompted clarification and important updates.

ARB: A

ARNI: B-R

COR LOE RecommendationsComment/Rationale



Renin-Angiotensin System Inhibition With ACE-Inhibitor

or ARB or ARNI

Ivabradine

� Selectively inhibits the If current in the sinoatrial node, providing heart rate reduction

� Heart rate lowering reduces myocardial oxygen demand, simultaneously improving oxygen supply

� No negative inotropic or lusitropic (myocardial relaxation) effects

� Reduction in HF hospitalization

� Side Effects: bradycardia, hypertension, atrial fibrillation, and temporary visual disturbance entailing seeing flashes of light

Swedberg Ket al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376:875–85.

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BEAUTIFUL Trial

� Randomized, double blinded, placebo controlled trial

� Patients with coronary artery disease and a left-ventricular ejection fraction of less than 40%

� 5 mg ivabradine, with the intention of increasing to the target dose of 7·5 mg twice a day in addition to appropriate cardiovascular medication.

� Primary endpoint: composite of cardiovascular death, admission to hospital for acute myocardial infarction, and admission to hospital for new onset or

worsening heart failure.

Fox K et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL)a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807–16.

Results and Interpretation

� In patients with HR > 70 bpm

� No effect on primary outcome: composite of cardiovascular death, or admission to hospital for new-onset or worsening heart failure (hazard ratio 0·91, 95% CI 0·81–1·04, p=0·17)

� Reduction in secondary end points: admission to hospital for fatal and non-fatal myocardial infarction (0·64, 95% CI 0·49–0·84, p=0·001) and coronary revascularisation (0·70, 95% CI 0·52–0·93, p=0·016)

� Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have

heart rates of 70 bpm or greater.

Fox K et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL)a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807–16.


Ivabradine


COR LOE RecommendationsComment/Rationale

IIa B-R

Ivabradine can be beneficial to reduce HF hospitalization for

patients with symptomatic (NYHA class II-III) stable chronic HFrEF(LVEF ≤35%) who are receiving GDEM*, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest.

NEW: New clinical trial data.

*In other parts of the document, the term “GDMT” has been used to denote guideline-directed management and

therapy. In this recommendation, however, the term “GDEM” has been used to denote this same concept in order to reflect the original wording of the recommendation that initially appeared in the “2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure”.

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NOVEL DEVICE THERAPIES FOR HEART FAILURE

� CardioMEMs

� Ventricular assist devices

CardioMEMS™ HF System for the Management of HF

Delivers insight into the early onset of worsening HF to more proactively manage HF

patients and improve outcomes

21

Abraham WT, Lancet, 2011.

27382-SJM-MEM-0814-0012(1)a(10) | Item approved for global use.

PULMONARY

ARTERY PRESSURE

SENSOR

PATIENT

ELECTRONICS

SYSTEM

MERLIN.NET™

PCN

TARGET LOCATION FOR

PA PRESSURE SENSOR

Slide Courtesy: ABBOTT

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Microelectrical Mechanical System (MEMS)No lead or battery, no need for replacement



Inclusion Criteria:� NYHA III symptoms for at least 3 months

� Irrespective of LVEF� HF hospitalization in last 12 months� Reduced EF patients had to be on stable medical

therapy

Abraham WT et al. Lancet 2011

� Primary efficacy endpoint : rate of heart-failure-related hospitalizations at 6 months.

� Safety endpoints : freedom from device-related or system-related complications (DSRC) and freedom from pressure-sensor failures.

� All analyses were by intention to treat

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RESULTS OF CHAMPION TRIAL


� Treatment group had 3X’s the changes to medical regimen vs. control group

� LOS for HF related hospitalizations was shorter in treatment group � 37% reduction in overall HF related hospitalizations!� NNT to prevent one HF related hospitalization = 4

Monitoring with CardioMEMS™ HF System Leads to Reduction in Mean PA Pressure from Baseline

PART 1: RANDOMIZED ACCESS

30

Abraham WT, et al. Lancet, 2011.


SECONDARY ENDPOINT: Targeting PA pressures and titrating medications results in reduction of mean PA pressure over time.

PA Mean Pressure AUC (mmHg days)


RESULTS OF CHAMPION TRIAL

Pulmonary Artery Pressure

Medication Changes Based on Pulmonary

Artery Pressure (p < 0.0001)

Pulmonary Artery Pressure Reduction

(p = 0.008)

Reduction in Heart Failure Hospitalizations

(p < 0.0001)

Quality of Life Improvement

(p = 0.024)

MANAGING PRESSURES TO TARGET

GOAL RANGES:

• PA pressure systolic 15–35 mmHg

• PA pressure diastolic 8–20 mmHg

• PA pressure mean 10–25 mmHg

Using diuretics and vasodilators,

in addition to guideline-directed

medical therapies

Summary of CHAMPION Randomized Clinical Trial:550 PREVIOUSLY HOSPITALIZED NYHA CLASS III PATIENTS

1. Abraham WT, et al. Lancet, 2011.

2. Abraham WT, et al. Lancet, 2016.

3. Adamson PB, et al. J Card Fail, 2010.

27382-SJM-MEM-0814-0012(1)a(10) | Item approved for global use. 25


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PRE-SPECIFIED SUB-GROUP ANALYSIS:Rate of HF hospitalizations by baseline EF


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Indications for Device Therapy

Heart Failure Continuum

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Clinical Events and Findings Useful for Identifying Patients With Advanced HF

� Repeated (≥2) hospitalizations or ED visits for HF in the past year

� Progressive deterioration in renal function (e.g., rise in BUN and creatinine)

� Weight loss without other cause (e.g., cardiac cachexia)

� Intolerance to ACE inhibitors due to hypotension and/or worsening renal function

� Intolerance to beta blockers due to worsening HF or hypotension

� Frequent systolic blood pressure <90 mm Hg

� Persistent dyspnea with dressing or bathing requiring rest

� Inability to walk 1 block on the level ground due to dyspnea or fatigue

� Recent need to escalate diuretics to maintain volume status, often reaching daily furosemide equivalent dose >160 mg/d and/or use of

supplemental metolazone therapy

� Progressive decline in serum sodium, usually to <133 mEq/L

� Frequent ICD shocks

Intravenous Inotropic Agents Used in Management of Heart Failure

Mechanical Circulatory Support (MCS) Devices: Class IIa Recommendations

� MCS is beneficial in carefully selected patients with stage D HFrEF in whom definitive management (e.g., cardiac transplantation) or cardiac recovery is

anticipated or planned (Level of Evidence: B)

� Nondurable MCS, including the use of percutaneous and extracorporeal

ventricular assist devices (VADs), is reasonable as a “bridge to recovery” or “bridge to decision” for carefully selected‡ patients with HFrEF with acute, profound hemodynamic compromise (Level of Evidence: B)

� Durable MCS is reasonable to prolong survival for carefully selected patients with stage D HFrEF (Level of Evidence: B)

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Cardiac Transplantation: Class I recommendation

� Evaluation for cardiac transplantation is indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management (Level of

Evidence: C)

Indications for LVAD or Heart Transplantation

� Class IIIb / IV NYHA heart failure

� Failed OMT for at least 45 of 60 days, or has been IABP dependent for 7 days or IV inotrope dependent for 14 days

� LVEF < 25%

� Functional limitation with peak VO2 max < 14 ml/kg/min unless IABP or inotrope dependent or physically unable to perform testing

Slaughter MS et al JHLT 2010

Mechanical circulatory support (MCS) devices

� Non Durable MCS devices

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Impella CP

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Mechanical circulatory support (MCS) devices� Durable MCS devices - LVAD

1st GenerationPulsatile Pumps

2nd GenerationAxial Flow

Continuous Flow

3rd Generation Centrifugal Flow

HeartMate 3™HeartMate 3™

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MECHANICAL CIRCULATORY SUPPORT AS BRIDGE TO TRANSPLANTATION

0

10

20

30

40

50

60

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

% o

f P

atie

nts

Year of Transplant

ECMOVAD+ECMOTAHLVAD+RVADRVAD

JHLT. 2017 Oct; 36(10): 1037-1079

Cardiac TransplantationThe gold standard treatment for end-stage heart failure

Cardiac Transplantation

Additional Imaging studies :- Abd US- ABI’s- Carotid US- Panorex- Chest / Abd / Pelvis CT

Additional Consultations: - Renal- Psychiatry- Palliative Care- Financial- Social- Pulmonary- Hepatology

Selection process involves multidisciplinary group:

• Surgeons• Cardiologists• Social workers• Financial workers• Transplant coordinators• Nutrition• Pharmacy• Palliative Care

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National Heart Failure Awareness Week

The week of Valentine’s Day

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In Conclusion….

� Heart failure is no longer the grim death sentence it was once thought to be.

� With the right treatment, patients with heart failure can stabilize their condition and often improve heart function and quality of life.

That’s alllll

Folks!

That’s all folks!

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THERAPY RECOMMENDATIONS FOR THE HOSPITALIZED PATIENT

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SHFM website - https://depts.washington.edu/shfm/?width=1024&height=768

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Biomarkers Indications for Use

*Other biomarkers of injury or fibrosis include soluble ST2 receptor, galectin-3, and high-sensitivity troponin.ACC indicates American College of Cardiology; AHA, American Heart Association; ADHF, acute decompensated heart failure; BNP, B-type natriuretic peptide; COR, Class of Recommendation; ED, emergency department; HF, heart failure; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; and pts, patients.

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Documents

Heart Failure: IS It A Death Sentence? Collaborative ... · 10/2/2019 2 Prevalence and Economic Burden About 5.7 million adults in the United States have heart failure.1 1 in 9 deaths