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

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)

Baker

Heart and Diabetes Institute

HFpEF, Physiology and the IASD Approach

Healthy HFPEF 10 20 30 40

PCWP (mmHg)

Peak Work (114+12W) (43+8W)

Δ= 8±2 mmHg Δ= 19±3 mmHg

p<0.01

Van Empel JAHA 2014

Elevated left atrial pressure (PCWP>25), especially during exercise, is a near- universal finding in patients with HFPEF.

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 1oEPs)

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/m2 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

MACCE event Six months % One year % Death 4.7 (3/64) MOF; stroke; unknown Stroke 1.5 (1/64)* (pt died)

6 month and 1 year Top Line results

**p<0.01, ***p<0.001 vs baseline

Baseline 6M 12M 50 100 % NYHA Class I II III IV

*** ***

Baseline 6M 12M 20 40 60 80 MLWHF Score

*** ***

Baseline 6M 12M 200 300 400 500 metres 6MWD

** **

Mean D at 1 year: 15 points Mean D at 1 year: 33m

No MIs, device removal, systemic emboli

7

Hemodynamics to 1 Year

Baseline 6M 12M 5 10 15 minutes Exercise time

* *

Baseline 6M 12M 20 40 mmHg PCWP Baseline 6M 12M 20 40 60 80 Watts Workload

** **

Baseline 6M 12M 5 10 15 L/min Cardiac Output

** *

Exercise

* p<0.05, ** p<0.01 vs baseline Baseline 6M 12M 50 100 150 mmHg/(W/kg) Work indexed PCWP

* **

Echo to 1 Year

Baseline 6M 12M 20 40 60 % LVEF Baseline 6M 12M 20 40 60 80 ml/m2 LVEDVI

** ***

Baseline 6M 12M 20 40 60 80 % RVEF

* **

Baseline 6M 12M 10 20 30 40 ml/m2 RVEDVI

*** ***

*p<0.05, **p<0.01, ***p<0.001

No change in atrial volumes

AVAILABLE

• Safety: Death, device events
• Efficacy: NYHA class, HFH/other hospitalization

NOT REQUIRED PER PROTOCOL

• Echo
• Hemodynamics
• BNP/NT-pro BNP

2 Year Follow-up

Questions: Safety and durability of effect?

ESC Heart Failure 2018 (in press)

NYHA Status at >2 years

Minimum f/u 2 years, median 739 days

12.3% 25.0% 17.7% 20.0% 13.8%

28.8% 53.8% 46.9% 54.8% 61.7% 55.2% 71.2% 33.8% 28.1% 25.8% 18.3% 31.0% 0.0% 0.0% 0.0% 1.6% 0.0% 0.0%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

Baseline 1 Month 3 Month 6 Month 12 Month 24 Month

NYHA I NYHA II NYHA III NYHA IV

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)

Outcomes summary

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

LVEF Age SBP BMI Creatinine NYHA Gender Smoking Diabetes COPD HF duration GDMT

For REDUCE LAP HF population:

Predicted mortality rate: 10.2/100pt years (95% CI 6.1- 16.9). Observed rate: 33% lower mortality rate (95% CI 0.09- 0.89) across the full observation period (p=0.02).

Observed vs MAGGIC Predicted KM Curves

6 12 18 24 30 36 60 80 100 Months Percent survival

Observed Predicted p=0.014

Survival benefit of IASD?

100 200 300 200 400 600 Workload corrected PCWP (mmHg/W/kg) Six minute walk (meters) r= -0.47 p<0.001

| | | | | | | |

| | | | | |

2 4 6 8 10 12 14 16 100 90 80 70 60 50 Work&corrected& PCWP>25.5&mmHg/W/kg Work&corrected& PCWP<25.5&mmHg/W/kg p=0.03

Years Survival&(%)

Survival benefit of IASD?

| | | | | | | |

| | | | | |

2 4 6 8 10 12 14 16 100 90 80 70 60 50 Work&corrected& PCWP>25.5&mmHg/W/kg Work&corrected& PCWP<25.5&mmHg/W/kg p=0.03

Years Survival&(%) < -6

• 5
• 4
• 3

3 4 5 6

18% (117/662) of patients had ePAD decreased 3 mmHg or more from baseline to month 6 29% (193/662) of patients had ePAD increased 3 mmHg or more from baseline to month 6

Change in ePAD from baseline to 6-months (mmHg)

IASD and HF Hospitalization

No HFH (n=45) HFH (n=19) P value Age (years) 69±1 71±2 0.37 Body mass index (kg/m sq) 32±1 34±2 0.27 NT-proBNP (pg/ml) 332 595 0.24 Atrial fibrillation (%) 36 37 0.92 Hypertension (%) 80 84 0.69 IHD (%) 31 32 0.97 eGFR 65±3 54±4 0.08 6 MWD (meters) 335±16 316±18 0.49 Peak exercise workload (Watts) 44±3 40±4 0.48

TABLE 1. Baseline features according to HFH status

Echocardiography No HFH HFH p value LVEF (%) 47±1 47±1 0.66 LAVI (ml/m sq) 34±3 34±3 0.88 RAVI (ml/m sq) 35±3 35±3 0.95 TAPSE (cm) 2.0±0.1 1.9±0.1 0.52 Resting hemodynamics RA pressure (mmHg) 9±1 10±1 0.15 PAm pressure (mmHg) 23±1 25±1 0.39 PCWP (mmHg) 17±1 18±1 0.40 Cardiac Index (L/min/m sq) 2.7±0.1 2.7±0.2 0.78

IASD and HF Hospitalization

Resting Echo and HD at 6 months (post IASD) not associated with HFH, but:

No HFH HFH 10 20 30

mmHg Right atrial pressure

No HFH HFH 10 20 30 40

mmHg PCWP

No HFH HFH 10 20 30 40 50

mmHg mean PA pressure

No HFH HFH 50 100 150

mmHg/W/kg Work indexed PCWP

p=0.021

A B C D