1. A History of Dropsy: From Edema to Transplant
Timothy A. Denton, M.D.
Attending Cardiologist
High Desert Heart Institute
Victorville, CA

2. Outline History Physiopathology Evaluation Medical therapy
Other therapies

3. Independent program at UCLA associated with a significant increase in drug utilization in patients with CAD at the time of hospital discharge and during long term follow-up.
Increase in the number of these patients reaching the NCEP target of LDL-C < 100 during follow-up.
Demonstrates that a protocol for initiation of comprehensive risk factor management prior to hospital discharge can be considerably more effective than usual care for modification of coronary risk in AMI patients.

4. Independent program at UCLA associated with a significant increase in drug utilization in patients with CAD at the time of hospital discharge and during long term follow-up.
Increase in the number of these patients reaching the NCEP target of LDL-C < 100 during follow-up.
Demonstrates that a protocol for initiation of comprehensive risk factor management prior to hospital discharge can be considerably more effective than usual care for modification of coronary risk in AMI patients.

5. The Time Line BC AD 500 500 1000 1500 2000 dropsy Socrates
500
1000
1500
2000
dropsy
Socrates
( BC)
Hippocrates
( BC)
Galen
(180)
Harvey
(1616)
Independent program at UCLA associated with a significant increase in drug utilization in patients with CAD at the time of hospital discharge and during long term follow-up.
Increase in the number of these patients reaching the NCEP target of LDL-C < 100 during follow-up.
Demonstrates that a protocol for initiation of comprehensive risk factor management prior to hospital discharge can be considerably more effective than usual care for modification of coronary risk in AMI patients.
Laënnec
(1700)

6. Heart Failure ~400 B.C. – SOB, edema, rales
First described by Hippocrates
Ear directly on chest
How to drain effusions
caused by excess of “phlegm” (cold humor)
Moving from brain to chest

7. Dropsy A morbid condition characterized by the accumulation
of watery fluid in the serous cavities
or the connective tissue of the body.
Hydrops, Idropsie
First use in 1290 – “Some fullen in-to be dropesie”
OED

8. “A Treatise on the Diseases of the Chest”
Dropsy
A woman, 50 years of age, had been affected for twelve years with all the symptoms of disease of the heart, in a very high degree, viz. strong and frequent palpitations, habitual dyspnoea, breathlessness on using the least exercise, sudden startings from sleep, almost constant edema of the lower extremities, and lividity of the cheeks, nose and lips. Laennec
“A Treatise on the Diseases of the Chest”
1821

9. Dropsy Treatment of the Weak and probably Dilated Heart…
During this treatment, and especially when free diuresis is established, it is necessary that wine or some other diffusible stimulus should be carefully administered, and the system supported by a proper aliment… Stokes
“Diseases of the Heart and the Aorta”
1853

10. William Harvey
1639: De Motu Cordis

11. Groucho on the Circulation
“We then come to the bloodstream.
The blood rushes from the head, down to the feet…
gets a look at those feet,
and rushes back to the head again.”
from “Horse Feathers” 1932
(Julius Henry Marx)

12. William Withering Born: 1741 - 1799
1775: Obtained first “tea” from gypsy
From German: Fingerhut (finger hat or thimble)
Mid-1500’s: Latinized to “digitalis” – finger (digitus)
Digitalis purpurea – a common variety
1775 – William Withering

13. Heart Failure - Etiology Treat the underlying cause
“Pure” LV Heart failure
_________________
Systolic dysfuntion
Diastolic dysfunction
Ischemic LV Heart failure
_________________
Prior MI Ongoing ischemia Large vessel disease Small vessel disease
Mechanical Heart failure
_________________
AS MR Pericardium Endocardium Myocardium
Treat the underlying cause

14. Definition of Heart Failure
Clinical syndrome resulting from a structural or functional disorder
that impairs the heart from filling or ejecting blood
Clinical syndrome includes Symptoms (dyspnea, fatigue) and
Signs (fluid retention)
Heart failure ≠ congestive heart failure
2005 ACC/AHA HF Guidelines

15. AHA CHF Guidelines Stage A – Risk for CHF
Stage B – Heart disease, no symptoms
Stage C – Heart disease, symptoms
Stage D – Heart disease, refractory symptoms
ACC/AHA CHF Guidelines –

16. Heart Failure Diagnosis Clinical SOB, DOE Orthopnea Edema CxR BNP
Echo (or equivalent)
Is there another cause of symptoms?

17. New York Heart Association Classes
I – symptoms similar to normal patients
II – symptoms with ordinary exertion
III – symptoms at less-than-ordinary exertion
IV – symptoms at rest
2005 ACC/AHA HF Guidelines

18. Heart Failure
Diagnosis
What is the EF?
Echo
MUGA
Low
Normal High

19. Heart Failure
Diagnosis
Is there ischemia?
Yes No
PTCA
CABG
EECP

20. Heart Failure
Normal Heart Enlarged Heart

21. Heart Failure
Dilated Normal Hypertrophic

22. Heart Failure Systole = contraction (inotropy)
Diastole = relaxation (lusitropy)

23. What is diastolic dysfunction?
Heart Failure
What is diastolic dysfunction?

24. Heart Failure
Dilated Normal Hypertrophic

25. Systolic vs Diastolic Failure
Heart Failure
Systolic vs Diastolic Failure
Systolic
Diastolic
*No valvular or mechanical causes
Kitzman,et al., Am J Cardiol, 2001;87:

26. LV Systolic Heart Failure
It’s a hemodynamic disease Preload Contractility Afterload
It’s a neurohormonal disease
Other factors affecting therapy

27. It’s a hemodynamic disease !
Heart Failure
It’s a hemodynamic disease !
Afterload
Preload
Contractility

28. Preload Inpatient and Outpatient Therapy
IV diuretics Lasix (20,40,80,160,320) Lasix drip Combination (Lasix / zaroxolyn)
Naturetic peptic (nesiritide)
Dialysis / Ultrafiltration
Nitrates

29. Control of Volume Status
Patient Responsibilities
Weight yourself every day
Write it down
2,000 mg of Sodium per day
2,000 cc of fluids per day
If your weight goes up by “X”, change your diuretics

30. 0.5 – 1.0 qd BID 20 – 40 qd BID 10 – 20 qd 25-50 qd BID
Diuretics
Drug
Dosing
Max
Duration
Loop
Bumetanide Furosemide Torsemide Ethacrynic acid
0.5 – 1.0 qd BID 20 – 40 qd BID 10 – 20 qd qd BID
10 mg 600 mg 200 mg 200 mg
4-6 h 6-8 h h 6-7 h
Thiazide
Chlorothiazide Chlorthalidone HCTZ Indapamide Metolazone
qd BID 12.5 – 25 qd 25 qd BID 1.5 qd 2.5 qd
1000 mg 100 mg 200 mg 5 mg
20 mg
6 – 12 h h 6-12 h 36 h h
Potassium sparing
Amiloride Spironolactone Triamterene
5 qd 12.5 – 25 qd 50 – 75 qd BID
20 mg 50 mg 200 mg
24 h 2-3 days 7-9 h

31. Preload
Southey’s Tubes
Used into the late 1950’s

32. Ultrafiltration
CHF Solutions, Inc.

33. Dialysis / Ultrafiltration

34. It’s a hemodynamic disease !
Heart Failure
It’s a hemodynamic disease !
Afterload
Preload
Contractility

35. Contractility Digoxin Dobutamine Milrinone Epinephrine Dopamine LVAD
Heart transplantation

36. Ambulatory Infusion Pumps
Dobutamine
Milrinone

37. LV Assist Devices
Bridge to Transplant
Destination therapy

38. Heart Transplantation
Ejection fraction
Cardiopulmonary exercise testing – VO2 < 14 (???)
Other risk factors
“Risk Score”
Referral to transplant team
Local “work-up”
ISHLT Guidelines – 2006
Heart and Lung Transplantation 2006;25:1024

39. HEART TRANSPLANTATION Kaplan-Meier Survival (1/1982-6/2004)20 40 60 80
100 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 21 22
Years
Survival (%) .
Half-life = 9.9 years
Conditional Half-life = 13 years
N=69,536
N followed at longest time point: 28,463
Survival was calculated using the Kaplan-Meier method, which incorporates information from all transplants for whom any follow-up has been provided. Since many patients are still alive and some patients have been lost to follow-up, the survival rates are estimates rather than exact rates because the time of death is not known for all patients. Therefore, 95% confidence limits are provided about the survival rate estimate; the survival rate shown is the best estimate but the true rate will most likely fall within these limits.
The half-life is the estimated time point at which 50% of all of the recipients have died. The conditional half-life is the estimated time point at which 50% of the recipients who survive to at least 1 year have died. Because the decline in survival is greatest during the first year following transplantation, the conditional survival provides a more realistic expectation of survival time for recipients who survive the early post-transplant period.
ISHLT
2006
J Heart Lung Transplant 2006;25:869-79

40. It’s a hemodynamic disease !
Heart Failure
It’s a hemodynamic disease !
Afterload
Preload
Contractility

41. Afterload
Lowered afterload improves hemodynamics in MR (Ann Int Med 1975;83:312)
Vasodilator therapy in heart failure (Ann Int Med 1975;83:421)
Hydralazine / Minoxidil in refractory CHF (Ann Int Med 1976;85:467)
Lowered afterload improves hemodynamics in AI (Circulation 1976;53:879)
Lowered afterload improves hemodynamics in CHF (Ann Rev Physiology 1977;39:277
CONSENSUS I

42. Afterload
Nitroprusside
ACE inhibitors
ARB’s
Hydralazine / nitrates

43. Heart Failure
SOLVD NEJM 1991;325:

44. ACE / ARB Drug Dosing Max ACE
Captopril Enalapril Fosinopril Lisinopril Perindopril Quinapril Ramipril Trandolapril
6.25 tid 2.5 bid 5-10 qd qd 2 qd 5 bid qd 1 qd
50 tid bid 40 qd qd 8-16 qd 20 bid 10 qd 4 qd
ARB
Candesartan Losartan Valsartan
4-8 qd qd bid
32 qd qd 160 bid

45. It’s a neurohormonal disease !
Heart Failure
It’s a neurohormonal disease !
1963 – Plasma norepinephrine elevated in CHF (NEJM 1963;269:653)
1970’s digoxin reduces plasma renin and norepinephrine levels

46. Neurohormonal Beta blocker Spironolactone / eplerenone ACE inhibitors
ARB’s

47. Randomised Aldactone Evaluation Study (RALES)
Davies, M K et al. BMJ 2000;320:

48. Is there a BEST Beta Blocker?
Carvedilol
Bisoprolol
Metroprolol succinate

49. Is there a BEST Beta Blocker?
17% Reduction
Carvedilol or Metoprolol European Trial (COMET) Lancet 2003; 362:7

50. Beta Blockers Drug Dosing Max
Bisoprolol Carvedilol Metoprolol succinate (CR/XL)
1.25 qd bid 12.5 – 25 qd
10 qd 25 bid 200 qd

51. CHF with or without Dysrhythmia
ICD
Antiarrhythmics
Beta blockers

52. ICD’s and Survival
MADIT II Survival N Engl J Med. 2002;346:

53. Dysynchrony
Bi-V pacing

54. Heart Failure Clinic Central location with ICU nurses
Drug infusion diuretics dobutamine nesiritide (Fusion II)
Education
“CAREFUL” follow-up

55. Medical Therapy Preload + Lasix + Ultrafiltration + Nitrates
Contractility
Digoxin
Transplant evaluation / LVAD
Afterload
ACE / ARB
Hydralazine
Neurohormonal
Beta blocker
Spironolactone / eplerinone
Dysrhythmia
ICD
+ Antiarrhythmics
Dysynchrony
BiV Pacing

56. Therapy of Heart Failure
Systolic Dysfunction
Diastolic Dysfunction
Normal
Range
Ejection Fraction

57. Therapy of Heart Failure
ICD
Heart transplant
BiV pacer
Aggressive MedRx
Systolic Dysfunction
Diastolic Dysfunction
Normal
Range
Ejection Fraction

58. Therapy of Heart Failure
Medical therapy N Y H A C L S II
BiV ICD
III
ICD and
Transplant evaluation IV
Ejection Fraction

59. The END