Innovation therapy in Heart Failure

Transcription

1 Innovation therapy in Heart Failure P. Laothavorn September 2015

2 Topics of discussion Basic Knowledge about heart failure Standard therapy New emerging therapy

3 References: standard Therapy in Heart Failure ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure ACCF/AHA Guideline for the management of Heart Failure NICE: Acute heart failure diagnosing and managing acute heart failure in adults 2014

4 Definition of Heart Failure A pathophysiological state in which the heart is unable to pump blood at a rate sufficient to meet the metabolic needs of the body Congestive heart failure (CHF) is common terminology, but Heart Failure is preferred, as not all patients present with congestion ภาวะท ห วใจไม สามารถบ บเล อดไปเล ยงร างกายได เพ ยงพอ 2001 CCS Consensus Guideline update. Can J Cardiol 2001;17(Suppl E);5E-24E.

5 Forms of Heart Failure (Clinical approach) Systolic & Diastolic Heart Failure HFpEF, HFrEF, High Output Failure & Low Output Failure Pregnancy, anemia, thyrotoxicosis, A/V fistula, Beriberi, Pagets disease, CM Acute & Chronic Heart Failure Acute MI, myocarditis Large or multiple MI, VHD, CM Right sided & Left sided Heart Failure Most common cause is secondary to left sided failure, Other causes included: PE, PHT, RVI, MS

6 Terminology related to Heart Failure Related to ejection fraction (EF) HF-NEF (EF > 50%), HF-REF (EF < 35%- 45%), HF-PEF (EF > 40% Related to time-course Asymptomatic LVD, Chronic HF, Acute HF Related to symptoms NYHA functional classification 6

7 Systolic failure (HFrEF) Forms of Heart Failure Coronary Artery Disease (MI) Idiopathic dilated cardiomyopathy (DCM) Hypertension» 50% idiopathic (at least 25% familial)» 9 % myocarditis (viral), Ischemic heart disease, peripartum, hypertension, HIV, connective tissue disease, substance abuse, doxorubicin Valvular Heart Disease Diastolic failure (HFpEF) Hypertension Coronary artery disease (earliest change after ischemia) Hypertrophic obstructive cardiomyopathy (HCM) Restrictive cardiomyopathy

8 Objective of Heart Failure treatment 1] PROGNOSIS Reduce mortality 2] MORBIDITY Relieve symptoms and signs Improve quality of life Reduce hospitalisation 3] PREVENTION Progression of myocardial damage Remodeling Hospitalization ESC. Guidelines 2008

9 TREATMENT Correction of reversible causes Ischemia Valvular heart disease Thyrotoxicosis and other high output status Shunts Arrhythmia A fib, flutter, PJRT Medications Ca channel blockers, some antiarrhythmics

10 General Measures - Diet and Activity Salt restriction Fluid restriction Daily weight (tailor therapy) Gradual exertion programs

11 Orders of Medical Therapy 1. Loop diuretics 2. ACE inhibitor (or ARB if not tolerated) 3. Beta blockers 4. Hydralazine, Nitrate 5. Aldosterone antagonists (MRA) 6. Ivabradine (Digoxin) 7. CRT-D / ICD

12 12 Treatment for patients with HF-REF. ESC Guidelines for Diagnosis and treatment of acute and chronic heart failure 2012 EHJ 2012, 33:

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14 HFpEF No definite medications that prove benefit in prolonging survival Diuretics is the main stay. Vasodilator improve the symptoms Treat underlying diseases

15 Acute Heart Failure NICE 2014 : Recommendations 12. Offer intravenous diuretic therapy to people with acute heart failure. Start treatment using either a bolus or infusion strategy. 13. For people already taking a diuretic, consider a higher dose of diuretic than that on which the person was admitted unless there are serious concerns with patient adherence to diuretic therapy before admission. 14. Closely monitor the person s renal function, weight and urine output during diuretic therapy. 15. Discuss with the person the best strategies of coping with an increased urine output.

16 Acute Heart Failure NICE 2014 : Recommendations 16. Do not routinely offer nitrates to people with acute heart failure. 17. If intravenous nitrates are used in specific circumstances, such as for people with concomitant myocardial ischaemia, severe hypertension or regurgitant aortic or mitral valve disease, monitor blood pressure closely in a setting where at least level 2 caree can be provided. 18. Do not offer sodium nitroprusside to people with acute heart failure.

17 Acute Heart Failure NICE 2014 : Recommendations 19. Do not routinely offer inotropes or vasopressors to people with acute heart failure. 20. Consider inotropes or vasopressors in people with acute heart failure with potentially reversible cardiogenic shock. Administer these treatments in a cardiac care unit or high dependency unit or an alternative setting where at least level 2 caref can be provided.

18 Acute Heart Failure NICE 2014 : Recommendations 26. In a person presenting with acute heart failure who is already taking beta-blockers, continue the beta-blocker treatment unless they have a heart rate less than 50 beats per minute, second or third degree atrioventricular block, or shock. 27. Start or restart beta-blocker treatment during hospital admission in people with acute heart failure due to left ventricular systolic dysfunction, once their condition has been stabilised for example, when intravenous diuretics are no longer needed. 28. Ensure that the person s condition is stable for typically 48 hours after starting or restarting beta-blockers and before discharging from hospital. 29. Closely monitor the person s renal function, electrolytes, heart rate, blood pressure and overall clinical status during treatment with beta-blockers, aldosterone antagonists or angiotensinconverting enzyme inhibitors.

19 Acute Heart Failure NICE 2014 : Recommendations 30. Offer an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker if there are intolerable side effects) and an aldosterone antagonist during hospital admission to people with acute heart failure and reduced left ventricular ejection fraction. If the angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker) is not tolerated an aldosterone antagonist should still be offered.

20 New Emerging Therapy (Innovation therapy) MODULATION OF HEART RATE OR AUTONOMIC TONE VASODILATORS HORMONES CELL THERAPY GENE THERAPY IMMUNOTHERAPY NUTRITIONAL SUPPLEMENTS MECHANICAL THERAPIES

21 New Emerging Therapy (Innovation therapy) HORMONES Testosterone Growth Hormone IMMUNOTHERAPY Intravenous Immune Globulin Immunoadabsorption

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23 New Emerging Therapy (Innovation therapy) NUTRITIONAL SUPPLEMENTS CELL THERAPY, GENE THERAPY MODULATION OF HEART RATE OR AUTONOMIC TONE VASODILATORS MECHANICAL THERAPIES

24 Emerging Therapy (Innovation therapy) NUTRITIONAL SUPPLEMENTS Coenzyme Q10 Vitamin C Vitamin E Probocol Allopurinol

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28 Autonomic Modulation Therapy Reduce sympathetic stimulation Add vagal parasympathetic stimulation Vagal Stimulation Spinal Stimulation Baroreceptor Stimulation Renal Denervation

29 Implant and Stimulation Protocol VNS Implanted System Implant duration Mean: 85 min Min: 36 min Max: 225 min Implants by surgical specialty 34 by neurosurgeons 62 by cardiac or vascular surgeons Anesthesia General: 89 Local/Sedation: 7 VNS Cuff Stimulation protocol Frequency = 20 Hz Pulse Width = 300 µs Duty Cycle = 10s ON / 50s OFF Current: highest tolerable (up to 4mA)

30 NECTAR-HF Study Flowchart Enrollment: NYHA Class II-III; EF 35%; Optimal Therapy NECTAR-HF System Implant ~2 Weeks Recovery Baseline Evaluation and Randomization 3x Therapy Titration Visits (including sham)* Follow-up: 3M and 6M Therapy ON for All Patients Post-6M FU Follow-up: 9M, 12M, 15M and 18M *6 month window begins after last titration

31 Primary Endpoint LVESD LVESD (cm) Baseline 6 Months Baseline 6 Months Therapy Control

32 Conclusions Although robust pre-clinical data showed the benefit of VNS, NECTAR-HF, the first VNS randomized sham controlled trial, failed to demonstrate a successful clinical translation of VNS therapy to the primary endpoint of cardiac remodelling. There were statistically significant improvements seen in the quality of life measures. There were no significant safety concerns through 6 months (primary safety will be assessed at 18 months). Additional clinical research may provide additional insights into the effectiveness of VNS for heart failure. Sham control and checking for blinding are critical

33 Thoracic Spinal Cord Stimulation for Heart Failure as a Restorative Treatment (SCS HEART study): First-in-man experience Heart Rhythm Volume 12, Issue 3, March 2015, Pages

34 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care Intra-Aortic Balloon Pump Left Atrial to Aorta Assist Devices LV to Aorta-Assist Devices Extracorporeal Membrane Oxygenation Right-Sided Support

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49 SUMMARY AND RECOMMENDATIONS Investigational and emerging therapies for patients with heart failure (HF) include vasodilators, hormones, cell therapy, gene therapy, immunotherapy, antiviral therapy, and mechanical therapies. While beneficial effects have been seen with some of these interventions in small studies, the risk/benefit ratio and true efficacy remain to be proven.

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