Post on 03-Jul-2022
Michael Zacharias, D.O., F.A.C.C.Assistant Professor of Medicine
Section of Heart Failure and Heart TransplantationMedical Director of Mechanical Circulatory Support (MCS)
Assistant Program Director Advanced Heart Failure/Transplant Fellowship
New Options for HF“Drugs & Devices”
March 20, 2021
New Options for HF “Drugs and Devices”
Michael Zacharias DO, Cardiologist, UH Harrington Heart & Vascular Institute, Assistant Professor of Medicine, Case Western Reserve University School of Medicine
Disclosures:Commercial Support / Sponsorship: None
Conflict of Interest: None
Overview
• Case
• Background of HF
• Advances in heart failure management• Medications• Devices
• Revisit the case
• When to refer to AHF
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Overview
• Case
• Background of HF
• Advances in heart failure management• Medications• Devices
• Revisit the case
• When to refer to AHF
4
Case• 58M
– CAD/MI w/prior remote PCI– Ischemic cardiomyopathy (LVEF 30%)– Primary prevention ICD
• Hospitalized three times in the last year for ADHF• Not able to “enjoy life” because of SOB• Also has noted worsening LE edema and has been
sleeping in his recliner to “breath easier”
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Case
• Medications– Metoprolol succinate 100 mg daily– Lisinopril 10 mg daily– Furosemide 80 mg twice a day– ASA 81 mg daily– Atorvastatin 80 mg daily
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Case
• Labs:– Na: 132– Cr 1.6
• Repeat echo shows LVEF 25-30% with worsening MR and further dilatation of his left ventricle
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Case
• Despite adjustments in diuretic therapy he continues to retain fluid with evidence of worsening renal function
• He has a resting HR of 75 and SBP 115
• He is referred to the Heart Failure clinic looking for help
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Questions to consider
• Why is he failing medical therapy?
• Can we optimize his medical therapy?
• Aside from medication, is there anything else we can pursue to help guide his management?
• When should we consider advanced heart failure therapies?
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Overview
• Case
• Background of HF
• Advances in heart failure management• Medications• Devices
• Revisit the case
• When to refer to AHF
10
Background
• Growing prevalence of heart failure– Currently 5.7 million Americans– Estimated to grow to >30 million by 2030– Only form of heart disease increasing in
prevalence
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Circ Heart Fail. 2013;6(3):606-619.
Background
• Most common cause of hospitalization– Primary diagnosis in >1 million discharges per
year– Affects 10% of men, 8% women over age 60– 30-Day readmission rate 20-25%– Of those hospitalized:
–HFrEF: 53% –HFpEF: 47%
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Circ Heart Fail. 2013;6(3):606-619.
Background
• Why?– Increasing prevalence of risk factors– Improved survival post-MI– Aging population
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Circ Heart Fail. 2013;6(3):606-619.
Background
Mortality of patients hospitalized for AHF• 10% within 30 days• 22% within 1 year• 42% within 5 years
• Higher 5-year mortality rate than many cancers including leukemia, lymphoma, colon, or breast
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Circ Heart Fail. 2012;5(4):414-421.JAMA. 2004;292(3):344-350.http://seer.cancer.gov/statfacts.
HF Therapy Timeline
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1980s 1990s 2000s 2010-PresentPre-1980s
DiureticsDigitalis
ACEi β-blockerICD
CRTARBMRALVAD
Pressure monitorARNIFunny channel (If)SGLT2 inhibitors
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Circulation. 2001;104:2996-3007
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N Engl J Med 2003; 348:2007-2018
Overview
• Case
• Background of HF
• Advances in heart failure management• Medications• Devices
• Revisit the case
• When to refer to AHF
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Advances in Heart Failure Management
• Medications– Neprolysin inhibition– Heart rate modulation via funny channel (If)– Sodium-glucose co-transporter-2 (SGLT2) inhibitors
• Devices– Pulmonary arterial pressure monitoring system – Left ventricular assist device (LVAD)
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Sacubitril/Valsartan
•Formerly “LCZ-696” now Entresto®
•ARNi• Angiotensin Receptor-Neprilysin Inhibitor
•PARADIGM-HF Trial (NEJM 2014)
•PARAGON-HF Trial (NEJM 2019)
Sacubitril/Valsartan
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JACC HF 2014
•NYHA class II-IV and LVEF <40%
•8442 pts
•LCZ 696 (200 mg bid) vs Enalapril (10 mg bid)
•Mean duration of follow up: 27 months
•Primary outcome: CV death or first HF hospitalization
NEJM 2014
NEJM 2014
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•NYHA class II-IV and LVEF >45%•4822 pts•Entresto (97/103 mg bid) vs Valsartan (160 mg bid)•Mean duration of follow up: 4 years•Primary outcome: total hospitalizations for HF and death from CV causes
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2/2021: Entresto approved for HFpEF. FDA “Benefits are most clearly evident in patients with LVEF below normal (45-57%)”
Heart rate modulation
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Framingham Data
Am Heart J.1993;125:1148-1154
• Heart rate is determined by spontaneous electrical pacemaker activity in the sinoatrial node controlled by the If current
• Prior data indicates that increasing HR is associated with worsened cardiac outcomes
• Recent literature supports that a HR <70 may be beneficial in pts with HFrEF
Heart rate modulation
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Lancet 2008
•LVEF <40% and stable CAD
•5438 pts
•HR >70 vs <70
•Cardiovascular outcomes
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Lancet 2008
HR >70:34% increased risk of CV death 53% increase in heart failure hospitalizations
Lancet 2008
Ivabradine (Corlanor®)
• Selectively blocks funny current (If)– Reduces slope of diastolic
repolarization reducing HR• Independent effect of β-blocker
• No effect on blood pressure
• No negative inotropic, lusitropic, or contractility effects
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Curr Med Res Opin. 2005
•Symptomatic heart failure, LVEF <35%, hospitalized within the last year, SR with HR >70 bpm on stable beta blocker
•6558 pts
•Mean duration of follow up: 22.9 months
•Primary outcome: CV death or HF hospitalization
Lancet 2010
Lancet 2010
Lancet 2010
18% reduction in primary endpoint (CV death or HF hospitalization)26% reduction in HF death or hospitalization
DM Drug Trials
• Meta-analysis of 42 trials of Rosiglitazone suggested increased risks of both MI and CV mortality
• 2008: FDA requires diabetic trials to assess CV risk
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CVOT
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Cochrane UK
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SGLT2
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•NYHA class II-IV and LVEF <40%•4744 pts (with/without DM)•Dapagliflozin (10 mg daily) vs Placebo•Mean duration of follow up: 18 months•Primary outcome: worsening HF or CV death
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Cardiovascular Diabetology 2019
Why we do what we do
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Key Points for Med Mgt of HFrEF
• RAAS and sympathetic systems are the enemy– There is no such thing as “low” blood pressure,
unless the patient is symptomatic. • If symptomatic, think:
– Hypovolemia– RV dysfunction/failure– Advanced/stage D HF
• Minimize loop diuretics to maximize vasodilator, MRA, SGLT2
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Devices
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Symptoms are late in the game
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CardioMEMs®
• Continuous monitoring
• RHC
• Implanted into left PA
• No battery/replacement
• Remote monitoring
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CardioMEMs
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•NYHA class III for at least 3 months, no LVEF cutoff, and hospitalized within the last year for HF
•550 pts implanted– 270 randomized to treatment– 280 pts randomized to control group– Post-procedure medication
• prior anticoagulants resumed• otherwise ASA 81 + Clopidogrel 75 x30 days, then ASA 81
alone
•Mean duration of follow up: 15 months
Lancet 2011
Lancet 2011
• 28% reduction in HF hospitalizations within the first 6 months and 37% by 15 months
• Improved QOL• Treatment group required <1
medication adjustment per patient per month vs. control
• No PE or pulm infarct during study time
Left ventricular assist device (LVAD)
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• Intra-corporeal pump• 1st generation: pulsatile• 2nd/3rd generation: continuous• Axial or Centrifugal pump• Constant power source• Antiplatelet/anticoagulant
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ISHLTJHLT. 2017.
~2500-3000/yr
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NEJM 2001
• 129 patients with NYHA IV, stage D HF who were ineligible for cardiac transplantation
• Primary endpoint: death from any cause
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NEJM. 2009.
LVAD Thrombosis
53AJMedSci. 2015.NEJM. 2014.
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NEJM. 2017.
• Investigate the effectiveness of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis.
• 294 patients, 152 were assigned to the centrifugal-flow pump group and 142 to the axial-flow pump group
HeartMate 3TM LVAD
• Fully magnetically levitated
• Larger gaps in pump housing
• Built-in pulsatility
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RR (95%CI) = 0.21 (0.11 – 0.38)P<0.0001
HeartMate 3(N=515)
HeartMate II(N=505)
Significantly lower rate of pump replacement at 2 years
Only 3 HeartMate 3™ LVAD exchanges for suspected pump
thrombosis or elevated LDH
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Current FDA Approved Durable MCS
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HeartMate IITM LVAD Total Artificial Heart (TAH)
• BTT• DT
• BTT• DT
• BTT
HeartMate 3TM LVAD
• BTT• DT
Heartware HVADTM
Overview
• Case
• Background of HF
• Advances in heart failure management• Medications• Devices
• Revisit the case
• When to refer to AHF
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Case
• Worsening symptoms
• Multiple hospitalizations in last year
• Worsening LV function/MR
• Cardio-renal
• Hyponatremia
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Case
• Identify reasons for worsening symptoms • Medication optimization
– Transition to ARNi– Add MRA– Uptitrate beta blocker (once euvolemic)– Ivabradine (after uptitration of β-B, if needed)– Initiate SGLT2
• Consider device therapy (CardioMEMs) • For persistent symptoms; refer for Advanced Therapies
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Patients with any of the following should be referred for evaluation for advanced heart failure therapies1
Reference: 1. 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment: Answers to 10 Pivotal Issues About Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. Yancy CW, Januzzi JL Jr, Allen LA, Butler J, Davis LL, Fonarow GC, et al. J Am Coll Cardiol. 2018 Jan 16;71(2):201-230.
I IV inotropesN NYHA IIIB/IV or persistently elevated natriuretic peptidesE End-organ dysfunction (Cr > 1.8 mg/dL or BUN > 43 mg/dL)E Ejection fraction ≤ 35%D Defibrillator shocksH Hospitalizations > 1E Edema (or elevated PA pressure) despite escalating diureticsL Low blood pressure, high heart rateP Prognostic medication — progressive intolerance or down-titration
GDMT
Additional patient considerations for referral:• CRT non-responder• Physical activity limited or impaired quality of life
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I NEED HELP
When to refer
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“SHARK”
When to refer
• S odium (hyponatremia Na<136)
• H ospitalizations • readmit in 30 days or ≥ 2 hospital stays in 6 months
• A rrhythmias (atrial/ventricular)
• R efractory to meds (ACE/ARB/BB)
• K idney failure (Cr ≥1.2, or >0.3 from b/l)
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In conclusion
• New therapies (both medical and device) are reshaping the landscape of HF management
• Given the limitations of transplant, LVAD therapy has continued to improve and now provides a viable alternative as either a bridge or permanent treatment
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