advanced medicine 2017 diastolic heart failure dr
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Diastolic Heart Failure
Dr. Alexander Lyon Senior Lecturer and Consultant Cardiologist
Royal Brompton Hospital and Imperial College, London
Clinical Lead for Cardio-Oncology
Heart Failure Association of ESC Board Member
Advanced Medicine 2017
Heart Failure with Preserved Ejection Fraction
Dr. Alexander Lyon Senior Lecturer and Consultant Cardiologist
Royal Brompton Hospital and Imperial College, London
Clinical Lead for Cardio-Oncology
Heart Failure Association of ESC Board Member
Advanced Medicine 2017
Overview
• What is ventricular diastole?
• What is Heart Failure with Preserved Ejection Fraction (HFpEF)?
• Mechanisms
• Treatment options
• Management plan
What is ventricular diastole?
• Ventricular filling
• AV closure - Isovolumic relaxation
• MV opening – Early filling – active
relaxation – E wave
– Late filling – passive (ventricle), active atria – A wave
• Isovolumic contraction
• Ends with AV opening
DIASTOLE DIASTOLE
Normal Diastolic Ventricular Filling
E A E A E A
Typical Modern Echo report
Diastolic Function / Dysfunction
Diagnostic algorithm for a diagnosis of heart failure
Piotr Ponikowski et al. Eur Heart J 2016;37:2129-2200
Left Ventricular Ejection Fraction
Ejection Fraction LVEF = LVEDV-LVESV
LVEDV
EuroHeart Failure Survey
Healthy Subjects
Classification of Heart Failure based upon Left Ventricular Ejection Fraction
Structural cardiac remodelling • Left atrial dilatation and/or • Left ventricular hypertrophy Functional diastolic dysfunction • Elevated E/E’
Normal vs HFpEF
HFpEF Pathophysiology Cardiac Non Cardiac
Borlaug, Nature Reviews Cardiology, 2013 Sharma K. Circ Res 2014
Hierarchy of mechanisms of diastolic dysfunction
David A. Kass et al. Circulation Research. 2004;94:1533-1542
What is HFpEF?
Patel HC et al Eur J Heart Fail. 2014 Jul;16(7):767-71.
1. 22% of HHF have an EF>50%
2. 0.6% of HHF cohort suitable for RDT-HFpEF
What is HFpEF?
Patel HC et al Eur J Heart Fail. 2014 Jul;16(7):767-71.
One syndrome, multiple causes and phenotypes
• Elderly – ageing • COPD • Chronic renal failure • Diabetes • Obesity • Obstructive Sleep Apnoea • Previous cancer therapy
– Chemotherapy – doxorubicin, epirubicin – Radiotherapy – left breast DXT
• Post myocardial infarction • Post AVR for severe aortic stenosis • Cardiac amyloidosis • Hypertrophic Cardiomyopathy • Reverse remodelled HFrEF
How to treat HFpEF?
Phase III studies HFpEF All NEGATIVE:
Also:
SWEDIC (carvedilol)
J-DHF (carvedilol)
ELANDD (nebevilol)
ALDO DHF (spironolactone)
Hong Kong DHF
irbesartan/ramipirl
RAAM (eplerenone)
RELAX (sildenafil)
Why? 1. Suboptimal trial design:
- Targeting wrong patients (some were HF-REF or did not have HF) - Patients already on RAAS drugs prior to randomisation - Intolerance of study drug/optimal dose not achieved - Underpowered
2. Inadequate attenuation of the intended pathway
Open label phase 2 trial to assess safety and efficacy of RSD in symptomatic stable ambulatory patients with HFpEF
Randomised 2:1 RSD vs control (no sham)
POBA design
Do we have any options?
• 3,445 participants randomised to spironolactone (target dose 30mg OD) vs placebo
• HFpEF – EF>45%, either HHF or elevated BNP (>100pg/ml or NT-proBNP >360) • 1o endpoint composite
– CV mortality, aborted cardiac arrest or HF hospitalisation
• No difference in 1o endpoint • Reduction in HF hospitalisations (12 vs 14% p=0.04) • Pts enrolled with high BNP – significant benefit • HOWEVER
– All cause hospitalisations no difference – Geographical variation
• 2/3 US patients – enrolled with BNP – benefit • 1/3 Russia/Georgia – enrolled with HHF – no benefit
– ~33% off study drug at end of trial
Pitt et al NEJM 2014
Who develops HFpEF?
Kaplan–Meier Estimates of the Rate of End Points, According to Study Group. BP Control with Indapamide +/- Perindopril prevents HF in the Elderly
Beckett NS et al. NEJM 2008;358:1887-1898.
The all-cause mortality treatment effect of
ACE inhibitor and ARB hypertension trials.
van Vark L C et al. Eur Heart J 2012;33:2088-2097
Zinman B et al. N Engl J Med 2015;373:2117-2128
Empagliflozin reduced new onset heart failure and CV mortality in Type 2 Diabetes
New guideline recommendations to prevent heart failure
Piotr Ponikowski et al. Eur Heart J 2016;37:2129-2200
Practical Guide to Symptomatic Patients with HFpEF
• Diuretics for oedema or hypertension – Indapamide if elderly >80 years – HYVET trial – Thiazide if younger – Spironolactone* TOPCAT trial BNP subgroup
• ACE inhibitors for hypertension – irrespective of age – HYVET trial
• ARBs acceptable if intolerant of ACE I – losartan effect from LIFE trial
• Empagliflozin for type 2 diabetics with CV risk factors • Exclude
– Ischaemia – Chronotropic incompetence
• Avoid rate controlling medication
– Exaggerated HR or BP response
• ?Target Co-morbidities • Research trials – HFpEF service at Royal Brompton Hospital
HFpEF – not so easy….
29 April – 2 May 2017 PARIS, France
Abstract submission deadline: 13 January
4 days of scientific exchange
6 100+ healthcare professionals
2 000+ abstracts and cases submitted
110+ scientific sessions
300+ expert faculty members
100+ countries represented
45+ industry sessions/workshops
Topics include:
• How to deliver a Cardio-Oncology service
• Training in Cardio-Oncology
• eHealth and Cardio-Oncology
• How do I measure the quality of my service?
• Role of primary care in cancer survivors
• Immunotherapy and emerging cardiotoxicity
• Personalised medicine & genetics
• EP session –who should have ablation, ICDs, CRT?
• Anticoagulation and antithrombotic (AF, ACS)
• Radiation-induced cardiotoxicity
• Managing cardiac issues during BMSC transplants
• Cardiac tumours, carcinoid valvular disease, amyloid
• Hormone therapy and CV risk
September 20-21, 2017