1. Cardiac Investigation in
Heart Failure
What Internist Needs to
know
Sarinya Puwanant, MD, FASE

3. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare disease and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?

4. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare disease and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?

5. Assessment of CAD in HF
 Is the patient a potential
revascularization candidate?
 Recommendations linked to proof that
revasc alters outcomes.
EST
Perfusion
Stress Echo

6. Get Angiogram First
 Angina (I)
 Atypical Chest Pain (IIa)
 Known CAD + No chest pain
(IIa)
 Suspected CAD with Chest pain
(IIa)

7. Stress Test, Viability, Perfusion
Study
 Known CAD (extent) (IIa)
 Diagnostic CAD (IIb)

8. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare disease and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?

9.  Spotty Disease
 Sensitivity 50%
 False negative 40%

10.  No specific Rx even immunosuppressive Rx
does not improved outcomes
 Giant Cell Myocarditis
Trial Immunosuppressive
LVAD
OHTx
 GCM- Young, Female, rapid deterioration
(VT, CHB, rapid drop of EF)

11. Biopsy is useful for
 Confirm diagnosis (Strongly
suspected)
 Altered management
– Anthracycline toxicity
– Affect Suitability for OHTX ( Amyloid)
– GCM

12. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare disease and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?

13. B-Natriuretic Peptide in HF
Physiology
Caveats of Natriuretic Peptide
Clinical Utility of Natriuretic Peptide
and
Landmark Trials
When should we order Natriuretic
Peptide?

14. B-Natriuretic Peptide in HF
Physiology
Caveats of Natriuretic Peptide
Clinical Utility of Natriuretic Peptide
and
Landmark Trials
When should we order Natriuretic
Peptide?

15. BNP Release
Atrial stretch
Not always =
pressure
i.e., tamponade
Increased LV wall
stress

16. Pre-ProBNP
ProBNP
NT-ProBNP
-In-active
-Half Life 90 min BNP
-Active
-Half Life 20 min

17. B-Natriuretic Peptide in HF
Physiology
CaveatS of Natriuretic Peptide
Clinical Utility of Natriuretic Peptide
and
Landmark Trials
When should we order Natriuretic
Peptide?

18. High BNP Low BNP
Elderly Tamponade
Female Constriction
Pulmonary Emboli Obesity –NPR-C
Renal Failure
H/o HF w/ undiagnosed dyspnea
Anemia NT 1200 pg/ml-se 89, sp 72
Hyperthyroid (NT)
400 pg/ml pg/ml-se 87, sp 76

19. B-Natriuretic Peptide in HF
Physiology
Caveat of Natriuretic Peptide
Clinical Utility of Natriuretic
Peptide
and Landmark Trials
When should we order Natriuretic
Peptide?

20. Clinical Utility of Natriuretic Peptide
in Heart Failure
1. Diagnosis  Ruling out
2. Risk Stratification
3. Screening Cardiac Dysfunction
4. Guiding Management of Heart
Failure

21. Clinical Utility of Natriuretic Peptide
in Heart Failure
1. Diagnosis  Ruling out
2. Risk Stratification
3. Screening Cardiac Dysfunction
4. Guiding Management of Heart
Failure

22. Clinical Utility of Natriuretic Peptide
in Heart Failure
Confirm or Rule out HF
Diagnosis
Ambiguous signs and symptoms
Acute Setting

23. BNP Cut – Off
BNP Study
N=1586
Maisel. N Engl J Med 2002;347:161

24. References Ranges BNP
(pg/ml)
767 Subjects w/o CV diseases or LV
dysfunction (5th-95th percentile)
Age 45-54 55-64 65-75 74-
83
Female 8-73 10-93 13-120 16-
155
Male 4-40 5-52 7-67 JACC 2002
Redfield

25. NT-Pro BNP Cut - Off
PRIDE STUDY
N=600
Am J Cardiol 2005;95:948

26. Pro-NT BNP Cut - Off
The International Collaborative of NT-proBNP
Study
N=1256
Januzzi EHJ 2006:27:330

27. Preserved EF HF - BNP Sub-study
JACC 2003;
41:2010 –7

28. BASEL STUDY
• N=452, ER w/ acute dyspnea, Biosite Essay
• 2 Diagnostic strategies- BNP and no BNP
• BNP group
- Less need for hospitalization (75% vs. 85%, p< 0.05)
- Less need for intensive care (15 vs. 24%, p<0.05)
- Rapid time to discharge (8 vs. 11 days, p<0.05)
- Less total cost of treatment (5410 $ vs. 7264$, p<0.05)
- Similar 30- day mortality

29. Clinical Utility of Natriuretic Peptide
in Heart Failure
Confirm or Rule out HF
Diagnosis
Ambiguous signs and symptoms
Non- Acute Setting

30. Clinical Utility of Natriuretic Peptide in
Diagnosis of Heart Failure in Non-Acute Setting
1. Class II a, Level of evidence C
2. Skeptical, various cut-off values (80-300 pg/ml)
3. Lack of good prospective randomized control trials
4. Presently, NT pro-BNP improved HF diagnostic
accuracy (21 vs. 8%, p<0.002). Number needed to
Dx =7
5. Great impact on ruling out HF
6. Lower cut-off compared to those in acute setting

31. N=306
ESC HF criteria
Zaphirio European Journal of Heart Failure 7 (2005)
537– 541

32. NT-pro BNP <11 pg/ml NT-pro BNP <17 pg/ml
Age >=50 Age >=50
N= 345, ESC HF Dx
Sens 95% Spect 68% PPV 54% NPV 97%
Nielsen et al. The European Journal of Heart Failure 6 (2004) 63–70

33. • N=558, Chronic stable systolic HF
• Asymptomatic (n=60)  BNP 5-572 pg/ml, median
147
• Symptomatic (n=498)  21% had BNP <100
pg/ml

34. r=0.32 r=0.69
• Weak correlation of BNP and PCWP in ICU pts with LV
dysfx -Circulation. 2004;109:2432-2439
• Poor correlation of BNP, pro BNP and LVEDP (r=0.05-
0.08)
-Am Heart J 2006; 152:107126

35. Clinical Utility of Natriuretic Peptide
in Heart Failure
1. Diagnosis  Ruling out
2. Risk Stratification
3. Screening Cardiac Dysfunction
4. Guiding Management of Heart
Failure

36. Risk Stratification
• Provide robust prognostic information
- Normal Population
- ACS
- CAD
- CRT
- HF
- PE
for both BNP and proBNP
for both absolute values and delta values on
F/U
• Provide incremental prognostic information
• Lack of clear clinical utility of guiding of clinical
management

37. N=4300 HF patients
Valheft Study
(Circulation. 2003;107:1278-1283.)

38. • N= 72, NYHA class 3-4
• Last BNP strongly associate combine endpoints
(death, re-HF hospitalization)
• BNP @ DC = strong predictor of re-admission
J Am Coll Cardiol 2001;37:386 –91

39. Clinical Utility of Natriuretic Peptide
in Heart Failure
1. Diagnosis  Ruling out
2. Risk Stratification
3. Screening Cardiac Dysfunction
4. Guiding Management of Heart
Failure

40. Screening for Cardiac Dysfunction
AHA/ACC Stage
A CV Risk Factors
?
B Asymptomatic LV dysfx
C Overt Heart Failure
D Advanced/Terminal Heart Failure

41. Screening for Cardiac Dysfunction
Approach 1 – Post MI w/o overt HF
• Inconclusive data (vary ranges, cost
effectiveness)
• Pro and Con
Approach 2- Other Population
• Class II b Higher BNP, higher LV abn.
Olmsted
• Still not warranted/recommended

42. LV diastolic dysfunction
N=294
Circulation. 2002;105:595-601

43. Clinical Utility of Natriuretic Peptide
in Heart Failure
1. Diagnosis  Ruling out
2. Risk Stratification
3. Screening Cardiac Dysfunction
4. Guiding Management of Heart
Failure

44. N=220
NYHA 2-3
LVEF <45%
BNP <100 = target
Median 15 months FU
JACC 2007;49:1733–9

46. Clinical Utility of Natriuretic Peptide
in Heart Failure
? Track changes in Clinical Status

47. Track changes in Risk and Clinical Status
• BNP falls rapidly after diuretics
- Independent of hemodynamic status
- vary widely
- Lag period?
• BNP correlates w/ functional status in OPD
pts.
- High intra-individual variability

48. • BNP is not a perfect surrogate for intravascular volume
• Driving down BNP at all costs may be potentially harmful
• NT pro-BNP comes down slower than BNP
• What is optimal level?
• Therefore … at best this is an unproven concept
•Pre DC BNP is superior to Admission BNP in predicting of
death, HF hospitalization in pts with acute LVF

49. B-Natriuretic Peptide in HF
Physiology
Caveats of Natriuretic Peptide
Clinical Utility of Natriuretic Peptide
and
Landmark Trials
When should we order Natriuretic
Peptide?

50. When Should we order
BNP/NT- proBNP ?
1. To exclude or diagnose HF patients presented with acute dyspnea and
ambiguous signs and symptoms of HF (Ruling out > Diagnose)
2. To exclude HF in patient presented with non-acute dyspnea and ambiguous
signs and symptoms of HF in some patients (not routine !)
3. To assess risk stratification if needed in selected patients (not routine !)
Adapted from Tang Circulation July 31, 2007

51. Not Recommend ordering
BNP/NT-PBNP :
1. Routine BNP/NT-pro BNP testing for screening of asymptomatic LV
dysfunction
2. Routine blood biomarker testing for the sole purpose of risk
stratification in patients with HF
3. Routine blood BNP or NT-proBNP testing for making specific
therapeutic decisions for patients with acute or chronic heart failure
(Reasons: still emerging but incomplete data as well as intra- and inter-individual
variations)
Adapted from Tang Circulation July 31, 2007

52. Have to ask before
interpretation
1. NT pro BNP vs. BNP?
2. What kind of essay?
Research [Shionogi®] vs. Commercial [Abbots®,
Biosite®]
3. Any factors affecting BNP/ pro BNP level?
4. Is ordering physician clever ? Why did he/she order?

53. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare diseases and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?

54. When should I screen for rare diseases
and comorbidities?
 Anthracycline
 Herceptin
 Cyclophosphamide
 Chloroquine
 ETOH, Cocain
 NSAIDS-Cox2
 XRT
 Premature CAD
 Valvular disease
 CP

55. HF and systemic disease
 Recognize Clinical Clue
 Routine screening not recommended if
nothing suggested in clinical history
Hemochromatosis
HIV
CNTD
Amyloid
Pheochromocytoma
Familial CM

56. ROUTINE LAB:
CBC, UA, BUN, Cr, Elyte
BG, Lipid, LFT, TSH
12 lead EG
CXR PA, lat

57. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare diseases and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?
 Hot Topic-Sleep and HF

58. When should I get metabolic
stress testing ?
 Vo2 max < 14 ml/k/min or
 <50% age and sex matched
 RER >=1.15
 Don’t do until medical Rx
optimized.

59. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare diseases and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?
 Hot Topic-Sleep and HF

60. Systolic dysfunction Structural Abnormalities
Heart
Failure
Diastolic dysfunction •RV
- LV filling pressure
- Exercise/rest •Pericardial disease

61. Diastolic LV filling pressure ?
Mitral E = 110 cm/s
110/5
E/e’ = 22
Critical LM CAD
Mitral e’ = 5 cm/s LVEDP 28 mmHg

62. Estimation of
LV Filling Pressure
mLAP PCWP
LVEDP

63. E / E’ ratio

64. M-LVDP vs. Groups Defied by
Values of Septal E/E’
M -LVDP (m m Hg)
40
Patients with EF < 50%
w ith
35 Patients w ith EF > 50%
with
30
25
20
15
10
5
0
E/E’ < 8 E/E’ 8-15 E/E’ > 15
Ommen et al. Circulation 2000 110-103

65. Omens SR Circ 102: 10/10/2000

66. Septal vs. Lateral
Omens SR Circ 102: 10/10/2000

68. Diastolic Dysfunction
 Lateral E/E’ >10 predicts LVEDP
>12 mmHg
 Sensitivity 91%
 Specificity 81%
Nagueh et al. JACC 1997; 30:1527-33

69. Correlations between
PCWP and BNP vs. Mitral
E/e’

70. Echocardiography is now able to estimated
LV filling pressure under various conditions

71. RA pressure
RA
IVC ∆ with resp
pressure
<1.5 cm collapse 0-5 mmhg
nl (1.5-2.5) >50% 5-10
nl <50% 11-15
>2.5 <50% 16-20
>2.5 no change >20
Note in intubated patients, IVC size is not reliable for RA
pressure assessment (unless it is small).

72. RV
RA
mRAP =5 mmHg
RVSP-RASP = Peak gradient TR= 85 mmHg
RVSP = 85 + RASP
= 85+5= 90

73. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare diseases and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?
 Hot Topic-Sleep and HF

74. Right Atrial
Lead
Left Ventricular
Lead
Right Ventricular
Lead

75. (Death and hospitalization) (Death from any cause)
•NYHA class III •PR 150 •NSR
•QRS 120 •LVEF < 35% •VDD pacing
COMPANION study N Engl J Med 2004;350:2140-50.

76. •NYHA class III •QRS 120-149 plus echo criteria •QRS > 149
•LVEF < 35% •LVEDD 30 mm
CARE-HF N Engl J Med 2005;352:1539-49.

79. Cardiac Resynchronization Therapy* in
Patients With Severe Systolic Heart
Failure
I IIa IIb III
IIb III 1. LVEF <=35%
2. QRS >=120 ms
3. Sinus rhythm
4. NYHA III or ambulatory IV
5. Optimal medical Rx
I IIa IIb III
IIb III
1. LVEF <=35%
2. QRS >=120 ms
3. AFib
4. NYHA III or ambulatory IV
5. Optimal medical Rx
I IIa IIb III
1. LVEF <=35%
2. QRS >=120 ms
3. V pacing dependent
4. NYHA III or ambulatory IV
5. Optimal medical Rx

80. Cardiac Resynchronization Therapy*
in Patients With Severe Systolic Heart
Failure
I IIa IIb III
For patients with LVEF less than or equal to 35% with
NYHA functional Class I or II symptoms who are receiving
optimal recommended medical therapy and who are
undergoing implantation of a permanent pacemaker
and/or ICD with anticipated frequent ventricular pacing,
I IIa IIb III CRT may be considered.
CRT is not indicated for asymptomatic patients with
reduced LVEF in the absence of other indications for
I IIa IIb III pacing.
CRT is not indicated for patients whose functional status
and life expectancy are limited predominantly by chronic
noncardiac conditions.

81. N=2521
LVEF 35%
NYHA class II
N Engl J Med 2005;352:225-37

82. Evaluation /Investigation
 How do I assess CAD in HF ?
 When should I do endomyocardial biopsy ?
 When should I order BNP?
 When should I screen for rare diseases and
comorbidities?
 When should I get metabolic stress testing ?
 When should I use echo for guiding
management?
 When should I place CRT/ICD?
 Hot Topic-Sleep and HF

83. Sleep and HF
 OSA
 Central Apnea- Chyne stroke
Resp

84. Sleep and HF
 Sleep Disordered Breathing (SDB)
[Apnea-Hypopnea syndrome]
 SDB – apnea or hypopnea
 AH index (Apnea/hypopnea index)
 5-15 Mild
 >15 Moderate or severe
 AH syndrome (SDB)  Daytime somnolence

85. Sleep and HF
 Polysomnogram

86. Sleep and HF
 General pop
 SDB 24% men, 9% women
 OSAH syndrome 4% male, 2 % female.
 HF with low LVEF
 Prevalence is higher
 SDB = 51%
(78% CSA, 22% OSAH)

87. Sleep and HF
 CSA caused by HF
 OSA caused HF

88. Sleep and HF Rx
 OSAHS
 Weight Loss
 CPAP
 CSR-CSA
Nocturnal O2
CPAP needed?
Theophylline
ASV-Alternating servo ventilation