REDUCE LAP HF 2 year Outcomes Professor David Kaye Director, - PowerPoint PPT Presentation

Baker Heart and Diabetes Institute REDUCE LAP HF 2 year Outcomes Professor David Kaye Director, Department of Cardiology, Alfred Hospital Head, Heart Failure Research Lab, BHDI (david.kaye@baker.edu.au)

HFpEF, Physiology and the IASD Approach Elevated left atrial pressure (PCWP>25), especially during exercise, is a near- universal finding in patients with HFPEF. p<0.01 40 Δ = 19 ± 3 mmHg PCWP (mmHg) 30 Δ = 8 ± 2 mmHg 20 10 0 Healthy HFPEF Peak Work (114+12W) (43+8W) Van Empel JAHA 2014

Inclusion/Exclusion for REDUCE LAP HF 1. Chronic symptomatic heart failure documented by one or more of the following : a. NYHA Class III/ambulatory functional class IV symptoms One hospital admission for HF within the last 12 months On-going management with recommended heart failure medications 2. Age ≥ 40 years . 3. LVEF ≥ 40% as determined by echocardiography . 4. Hemodynamic inclusion criteria a. PCWP (end expiratory) or LVEDP (end expiratory) at rest ≥15 mmHg, and greater than CVP, OR b. PCWP (end expiratory) during supine bike exercise ≥25mm Hg. Exclusions Severe heart failure (stage D heart failure), CI < 2.0 L/min/m² , inotropes Presence of significant valve disease Right ventricular dysfunction incl. TAPSE < 1.4 cm, CVP >14 mmHg

Study End-points (6 month 1 o EPs) DEVICE SAFETY • Peri-procedural and 6 months MACCE & systemic embolic events • Need for removal DEVICE PERFORMANCE • % of patients who have successful device implantation • % of patients with reduction of PCWP, and left to right flow at 6 months

Study Population Age (Y) 69±8 Gender (% Female/Male) 66 / 34 LVEF (%) 47±7 NYHA Class (n, II/III/IV) 18/46/0 Minnesota Living with HF Score 49 ± 20 BMI kg/m 2 33 ± 6 Permanent AF (%) 36 NT-Pro BNP (median, IQR pg./ml) 377 (222-925) Hypertension (%) 81 Diabetes (%) 33 Coronary artery disease (%) 36 Diuretics at baseline (%) 91 Resting CVP (mm Hg) 9 ± 4 Resting PCWP (mm Hg) 17 ± 5

6 month and 1 year Top Line results MACCE event Six months % One year % Death 0 4.7 (3/64) MOF; stroke; unknown Stroke 0 1.5 (1/64)* (pt died) No MIs, device removal, systemic emboli MLWHF Score 6MWD NYHA Class *** *** 80 500 ** ** 100 *** *** 60 400 metres I 40 % II 50 300 III 20 IV 200 0 0 Baseline 6M 12M Baseline 6M 12M Baseline 6M 12M Mean D at 1 year: 15 points Mean D at 1 year: 33m **p<0.01, ***p<0.001 vs baseline

Hemodynamics to 1 Year Exercise Work indexed Exercise time Workload PCWP * 15 150 * ** ** mmHg/(W/kg) 80 minutes * ** 10 100 Watts 60 40 5 50 20 0 0 0 Baseline 6M 12M Baseline 6M 12M Baseline 6M 12M PCWP Cardiac Output ** 15 * p<0.05, ** p<0.01 vs baseline 40 * mmHg L/min 10 20 5 0 0 Baseline 6M 12M Baseline 6M 12M 7

Echo to 1 Year LVEF RVEF 60 ** 80 * 60 40 % % 40 20 20 0 0 Baseline 6M 12M Baseline 6M 12M LVEDVI RVEDVI ** 80 *** *** 40 *** 60 30 ml/m 2 ml/m 2 40 20 20 10 0 0 Baseline 6M 12M Baseline 6M 12M No change in atrial volumes *p<0.05, **p<0.01, ***p<0.001

2 Year Follow-up Questions: Safety and durability of effect? AVAILABLE • Safety: Death, device events • Efficacy: NYHA class, HFH/other hospitalization NOT REQUIRED PER PROTOCOL • Echo • Hemodynamics • BNP/NT-pro BNP ESC Heart Failure 2018 (in press)

NYHA Status at >2 years Minimum f/u 2 years, median 739 days 0.0% 0.0% 0.0% 1.6% 0.0% 0.0% 100% 90% 18.3% 28.1% 25.8% 31.0% 33.8% 80% 70% 71.2% 60% 50% 61.7% 46.9% 54.8% 40% 55.2% 53.8% 30% 20% 28.8% 10% 25.0% 20.0% 17.7% 13.8% 12.3% 0% Baseline 1 Month 3 Month 6 Month 12 Month 24 Month NYHA I NYHA II NYHA III NYHA IV

Outcomes summary Outcome measure @6M @12M @24M Survival 100% 95.3% (61/64) 92.2% (59/64) All cause mortality 0% 4.7% (3/64) 7.8% (5/64) HF related mortality 0% 0% 3.1% (2/64) Total follow up: Median 739 days, 177.2 pt years f/u: 6 deaths: = 3.4 deaths/100 yrs (3 HF, 2 non HF, 1 CVA) • 42 HFH events in 19 patients •

Predicting HF Outcomes – MAGGIC Scores Parameter For REDUCE LAP HF population: LVEF Age SBP BMI Predicted mortality rate: 10.2/100pt years (95% CI 6.1- Creatinine NYHA 16.9). Gender Smoking Observed rate: 33% lower mortality rate (95% CI 0.09- Diabetes COPD 0.89) across the full observation period (p=0.02). HF duration GDMT

Observed vs MAGGIC Predicted KM Curves Percent survival 100 Observed 80 p=0.014 Predicted 60 0 6 12 18 24 30 36 Months

Survival benefit of IASD? Work&corrected& 100 Six minute walk (meters) PCWP<25.5&mmHg/W/kg | 600 r= -0.47 90 p<0.001 | Survival&(%) 400 80 p=0.03 | 70 | Work&corrected& 200 PCWP>25.5&mmHg/W/kg 60 | 0 50 | 0 100 200 300 | | | | | | | | Workload corrected PCWP 2 4 6 8 10 12 14 16 (mmHg/W/kg) Years

Survival benefit of IASD? Work&corrected& 100 PCWP<25.5&mmHg/W/kg | 90 18% (117/662) of patients had ePAD | Survival&(%) decreased 3 mmHg or more from baseline to month 6 p=0.03 80 | 70 | Work&corrected& PCWP>25.5&mmHg/W/kg 60 | 29% (193/662) of patients had ePAD increased 50 | 3 mmHg or more from baseline to month 6 | | | | | | | | 2 4 6 8 10 12 14 16 Years < -6 -5 -4 -3 0 3 4 5 6 Change in ePAD from baseline to 6-months (mmHg)

IASD and HF Hospitalization TABLE 1. Baseline features according to HFH status No HFH HFH P value Echocardiography No HFH p (n=45) (n=19) HFH value LVEF (%) 47±1 47±1 0.66 Age (years) 69±1 71±2 0.37 Body mass index (kg/m 32±1 34±2 0.27 LAVI (ml/m sq) 34±3 34±3 0.88 sq) RAVI (ml/m sq) 35±3 35±3 0.95 NT-proBNP (pg/ml) 332 595 0.24 TAPSE (cm) 2.0±0.1 1.9±0.1 0.52 Resting hemodynamics Atrial fibrillation (%) 36 37 0.92 RA pressure (mmHg) 9±1 10±1 0.15 Hypertension (%) 80 84 0.69 PAm pressure (mmHg) 23±1 25±1 0.39 IHD (%) 31 32 0.97 PCWP (mmHg) 17±1 18±1 0.40 eGFR 65±3 54±4 0.08 Cardiac Index (L/min/m sq) 2.7±0.1 2.7±0.2 0.78 6 MWD (meters) 335±16 316±18 0.49 Peak exercise workload 44±3 40±4 0.48 (Watts)

IASD and HF Hospitalization Resting Echo and HD at 6 months (post IASD) not associated with HFH, but: A B Right atrial pressure mean PA pressure 30 50 40 mmHg 20 mmHg 30 20 10 10 0 0 No HFH HFH No HFH HFH D C PCWP Work indexed 40 150 PCWP mmHg/W/kg 30 p=0.021 mmHg 100 20 50 10 0 0 No HFH HFH No HFH HFH