HFpEF: How to optimise management

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HFpEF: How to optimise management Burkert Pieske M.D. Berlin, Germany Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité University Medicine Berlin, and Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany

Disclosures Speaker Bureau, Consultancy, Advisory Board/Committee for: Bayer Healthcare, MSD, Novartis, Astra-Zeneca, Stealth Peptides, Servier, DaiichiSankyo, Biotronic, Abbott Vascular

ESC 2016: How to optimize management 1. Identify the patient Diagnosis 2. Classify the patient Etiology and Stratification 3. General principles of management 4. Specific therapeutic approaches

ESC 2016: Typical demographics and co-morbidities associated with HFpEF Who are these patients?

ESC HF GL 2016: Definition of heart failure with preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction (HFrEF) ESC 2016: Signs and symptoms of HF are often non-specific and do not discriminate well between HF and other clinical conditions

Diagnostic algorithm for HF of non-acute onset

ESC 2016 Key Diagnostic HFpEF Criteria Preserved EF 50% Structural alterations: LAVI >34 ml/m2 or LVMI 115 (males) / 95 (females) mg/m2 Functional alterations: E/é 13 é (mean septal and lateral) <9 cm/s NTproBNP: BNP: >125 pg/ml or >35 pg/ml (SR; increase with Afib!)

ESC 2016: Normal & abnormal echocardiographic indices of diastolic function according to age categories, differentiated for gender

ESC 2016 Additional Diagnostic HFpEF Criteria Longitudinal strain Tricuspid regurgitation velocity Diastolic stress test: Semi-supine exercise echocrdiography Invasive hemodynamics at rest (PCWP 15 mmhg) and with exercise

Exercise echocardiography (Diastolic stress test)

ESC 2016: How to optimize management 1. Identify the patient Diagnosis 2. Classify the patient Etiology and Stratification 3. General principles of management 4. Specific therapeutic approaches

Senni & Pieske, Eur Heart J 2014

Prospective cross-sectional study, symptomatic HFpEF including LVH (LVEDWT 12mm) 99mTc-3,3-diphosphono-1,2-propanodi-carboxylic Genetic analysis for mutations in the TTR gene acid scintigraphy (99mTc-DPD)

Wild-type transthyretrin amyloidosis: Scintigraphy 99mTc-3,3-diphosphono-1,2-propanodi-carboxylic scintigraphy (severe 99mTc-DPD cardiac uptake) acid Gonzáles-López E et al. Eur Herat J 2015; 36:2585-2594

Summary: Diagnosis of HFpEF 120 HFpEF patients included 16 patients (13.3%) with moderate-severe 99mTc-DPD cardiac uptake No mutations found on genetic testing EMB in 4 patients demonstrated ATTR WT in all cases

ESC 2016: Diagnostic tests for specific causes of HFpEF

ESC 2016: How to optimize management 1. Identify the patient Diagnosis 2. Classify the patient Etiology and Stratification 3. General principles of management 4. Specific therapeutic approaches

ESC 2016: How to optimize management Only slightly fewer patients with HFpEF appear to receive diuretics, beta-blockers, MRAs, ACEI, or ARBs - comorbidities or extrapolation? Screen and treat cardiovascular comorbidities Arterial hypertension, CAD, pulmonary hypertension Screen and treat non-cardiovascular comorbidities (diabetes, CKD, anaemia, iron deficiency, COPD, obesity) Hospitalisations/death in HFpEF more likely to be non-cardiovascular than in HFrEF

Importance of co-morbidities in patients with HF

Recommendations for treatment of patients with HFpEF and HFmrEF

ESC 2016: Management of specific comorbidities

Treatments not recommended for co-morbidities in patients with HF

General principles of management 1.Optimal control of risk factors and comorbidities? BP<130/80 mmhg (preferentially by RAS blocker) HBA1c < 6.5 mg% (Metformin, SGL2-Inhibitor; avoid insulin wherever possible) Statin therapy in indicated Correct myocardial ischemia Treat pulmonary disease 2.Inadequate hypertensive blood pressure response to exercise? Stress test optimize BP response 3.Heart rate response to exercise? Tachycardic control inadequate increases in heart rate Chronotropic incompetence? Reduce bradycardic agents, consider PM

General principles of management 4.Atrial fibrillation? Restore SR if possible Anticoagulation as indicated 5.Signs of hypervolemia or pulmonary congestion? Loop diuretics Restrict volume and salt intake 6.Physical inactivity/overweight? Implement physical activity/exercise training programs Initate weight loss preferably by structured programs

Targeting therapies to the HFpEF phenotype Senni M & Pieske B, Eur Heart J 2014

ESC 2016: How to optimize management 1. Identify the patient Diagnosis 2. Classify the patient Etiology and Stratification 3. General principles of management 4. Specific therapeutic approaches

ESC 2016: Specific HFpEF therapies? ESC 2016: No treatment has been shown, convincingly, to reduce morbiditiy and mortality in patients with HFpEF or HFmrEF

Mitter SS and Shah SJ., Curr Atheroscler Rep, 2015 Nov, 17(11):64

TOPCAT: Heart Failure Hospitalizations Total HF Hosp Spiro : 394 Placebo: 475 P<0.01* Placebo Spironolactone HR = 0.83 (0.69 0.99) 245/1723 (14.2%) 206/1722 (12.0%) p=0.042 *poisson regression

Suggested algorithm for Sprinolactone in HFpEF Mitter SS and Shah SJ., Curr Atheroscler Rep, 2015 Nov, 17(11):64

Generation of an inter-atrial shunt Hasenfuss G et al., J Card Fail, 2015 Jul, 21(7):594-600

Hasenfuß Lancet 2016

Kitzman DW et al., JAMA, 2016 Jan 5, 315(1):36-46

Ex-DHF pilot: Exercise training in elderly HFpEF Primary Endpoint: peak VO2 HFpEF=heart failure with preserved ejection fraction Maximum Workload Edelmann F et al., JACC 2011;58:1780 91

Summary: ESC 2016 Management of HFpEF New definitions: HFpEF vs. HFmrEF, more specific imaging cutoffs Exercise stress test (echo, invasive, mentioned for first time) Mandates for etiological workup to target therapies Mandates for minute assessment and therapy of comorbidities Give general management recommendations, including loop diuretics State that no specific therapies are available yet