Device based approach for treating Diastolic Heart Failure

Amir Elami, MD * Department of Cardiothoracic Surgery

Hebrew University – Hadassah School of Medicine

* Member of Scientific Advisory Board, CorAssist Ltd.

CHF patients

>40% EF < 0.50

SHF - “Systolic HF”

•  Systolic Dysfunction

•  Diastolic Dysfunction

•  Dilated LV

EF > 0.50 DHF - “Diastolic HF”

•  Diastolic Dysfunction

•  LV not Dilated

•  High LV Mass/EDV

•  Hypertension

Mechanisms of Diastolic Dysfunction

Resistance to filling by:

•  Impaired relaxation (early to mid-diastole) •  Reduced compliance (mid- and late diastole)

Elevated diastolic pressures, limited ability to increase stroke volume through the Frank-Starling mechanism during exercise

Exertional fatigue, dyspnea and pulmonary congestion

DHF and SHF patients similar characteristics

Kitzman W et al JAMA 2002 Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure

•  Reduced exercise capacity •  Reduced peak oxygen consumption •  Marked Neuro-endocrine activation •  Reduced Quality of Life

DHF Vs SHF: Mortality and Hospitalization

•  Lower short-term mortality •  Similar long-term mortality •  Similar hospitalization rates

Pernenkil et al. Am J Cardiol 1997 Philbin et al. Am J Med 2000

Do they need the same treatment?

•  SHF •  Medications

•  ACE-I / ARB •  β-Blocker •  Aldosteron Blocker

•  Devices •  LVAD’s •  BiV Pace (CRT)

•  DHF •  Medical treatment is empirical •  No devices are available.

DHF Vs SHF: Treatment

Aim of CorAssist project

• Develop a mechanical solution for a mechanical problem

Diastolic Pressure Normal: 6-12mmHg DHF: 25mmHg

Systolic Pressure

120 - 140mmHg

7-8%

Pressure reduction 10 mmHg

40%

Recruiting force developed during (normal) systole and transferring it to assist (impaired) diastole

Device Concept •  Facilitating LV filling, utilizing a passive,

elastic mechanical device

•  The device stores energy during systole and releases it in a recoiling force during diastole

Animal Experiments Stage 1: Safety and Feasibility

•  5 healthy sheep* (35 – 45 kg)

•  LV pressures were measured to evaluate whether the device restricts the heart at two extreme conditions •  Accelerated heart rate

•  Volume overload

* can’t decrease much the low diastolic pressures

Results (1)

•  Attachment procedure was technically simple

•  All animals exhibited good clinical recuperation •  Ejection fraction was preserved up to 180-day

follow-up

•  There were no valve motion disturbances

•  Histopathology at 6 months confirms only minimal local tissue reaction around the attachment screws.

Movie

Movie 2

Results (2)

•  Angiography demonstrated normal coronary flow

Results (3) •  Device energy transfer remained constant

3/2007 summary

0

500

1000

1500

2000

2500

0 20 40 60 80 100 120 140 160 180

Average FU Period [Days]

AverageEstimated

Device Elastic Energy Transfer

[gr*mm]

IFU

Energy Transfer

Results (4) •  The EDP response to extreme conditions was similar in

animals before implantation (Table 1) and animals 90 days after implantation (Table 2)

Animal ID 7369 4301 5202 LV EDP (mmHg) EF (%) HR LV EDP

(mmHg) EF (%) HR LV EDP (mmHg) EF (%) HR

Base 10.7 63 84 13 62 72 8.9 57 80 Dobutamine 10.2 83 135 13 79 120 10.2 61 130

Fluid 19.7 57 96 19.5 62 87 14.3 65 110

Animal ID 3350 5247 LV EDP (mmHg) EF

(%) HR LV EDP (mmHg) EF

(%) HR Base 5 74 82 6.7 64 95

Dobutamine 1 68 137 6.9 64 150 Fluid 15 72 82 19.1 63 100

Before

90 Days After

Conclusion

This study demonstrates for the first time that a passive mechanical device, applying outward force on the LV can be safely implanted without evidence of restriction during extreme stress conditions.

Thank You