1. DYSPNEA : Is it the Heart or the Lung?
Prof. Roland KASSAB
Head of Division of Cardiology
HDF
CARDIOPACE, Le Royal Hotel, 11/03/2011

3. Definitions Dyspnea: Hypoxia: Subjective experience of breathing
discomfort that consists of
qualitative sensations that vary in intensity
(American Thoracic Society)
Deficiency in oxygen as measured by pulse oxymetry (SpO2)

4. Dyspnea - common complaint/symptom
“shortness of breath” or “breathlessness”
Defined as abnormal/uncomfortable breathing
Multiple etiologies -
2/3 of cases - cardiac or pulmonary etiology

5. Differential Diagnosis
Dyspnea
Cardiac:
Other:
Pulmonary:
COPD
Asthma
OSA
Pneumonia
Interstitial Lung Disease
Pulmonary Embolism
Pneumothorax
Pleural effusion
Chest wall deformity
Pulmonary HTN
ACS/AMI
CHF
Pericardial effusion/
tamponade
Arrhythmia
Pericarditis
Valvular disease
Anemia
Anxiety
Ascites
Acidosis
CVA
Iatrogenic/Drugs
* Many of these will also cause hypoxia

6. Initial Approach History: How does patient describe sensation?
When did it start? (acute vs. subacute vs. chronic)
Precipitating factors?
Past Medical history
Review recent events
Meds given
Trend of vital signs : tachycardia, tachypnea, high/low BPs, hypoxia

7. Physical Exam General Appearance: Respiratory: Cardiac:
Speaking in full sentences?
Use of accessory muscles?
Cyanosis?
Respiratory:
Diminished/absent breath sounds?
Wheezes, rales, or rhonchi?
Cardiac:
Heart sounds: rate, rhythm, murmurs, rub, S3/S4
JVP
Peripheral pulses/edema

8. Easily Performed Diagnostic Tests
Chest radiographs
Electrocardiograph
Screening spirometry

9. Other Diagnostic Testing
ABG
Labs: CBC, Renal function panel, BNP, Cardiac enzymes?
Further imaging as warranted:
PE protocol CT vs. V/Q scan
Transthoracic Echo

10. ABGs Commonly used to evaluate acute dyspnea
Can provide information about altered pH, hypercapnia, hypocapnia or hypoxemia
Normal ABGs do not exclude cardiac/pulmonary dx as cause of dyspnea
Remember- ABGs may be normal even in cases of acute dyspnea - ABGs do not evaluate breathing

11. PULSE OX
Rapid, widely available, noninvasive means of assessment in most clinical situations-
Insensitive (may be normal in acute dyspnea)
The % of Oxygen saturation does not always correspond to PaO2
The hemoglobin desaturation curve can be shifted depending on the pH, temperature or arterial carbon monoxide or carbon dioxide levels

12. Echocardiography
The first approach to assess left ventricular and valvular function in patients in whom the history, physical and laboratory examinations, and the chest radiograph do not establish the cause of dyspnea
Less sensitive in identifying diastolic dysfunction
Does not rule out cardiogenic pulmonary edema

14. Case 1
A 60 year old non-smoking woman complained of cough, dyspnoea and right sided pleuritic chest pain for 3 days. She was pyrexial (39.3 C) and a pleural rub was audible at the right lung base. Her white cell count was raised.
What are the notable observations ?

15. Case 1
A 60 year old non-smoking woman complained of cough, dyspnoea and right sided pleuritic chest pain for 3 days. She was pyrexial (39.3 C) and a pleural rub was audible at the right lung base. Her white cell count was raised.

17. Case 1 diagnosis
Right lower lobe pneumonia

18. Case 2
This 22 year old woman complained of sudden onset right sided chest pain, followed by progressive dyspnoea. By admission, she was in distress and appeared cyanosed. Her pulse was 140, with respiratory rate 40. On chest auscultation, breath sounds were noted to be quiet, especially on the right

19. Case 2
This 22 year old woman complained of sudden onset right sided chest pain, followed by progressive dyspnoea. By admission, she was in distress and appeared cyanosed. Her pulse was 140, with respiratory rate 40. On chest auscultation, breath sounds were noted to be quiet, especially on the right.

21. Case 2 diagnosis
Tension pneumothorax

22. Case 3
This 68 year old man was admitted with a myocardial infarct 5 days ago. He became acutely breathless at 3am. On examination he was sitting up in bed and sweating. His respiratory rate was 40 and pulse 130. His chest was dull to percussion at the bases and crackles were heard there on auscultation.

23. Case 3
This 68 year old man was admitted with a myocardial infarct 5 days ago. He became acutely breathless at 3am. On examination he was sitting up in bed and sweating. His respiratory rate was 40 and pulse 130. His chest was dull to percussion at the bases and crackles were heard there on auscultation.

25. Case 3 diagnosis
Acute pulmonary oedema due to congestive cardiac failure.

26. Case 4
78yo male heavy smoker with h/o COPD, CAD and ICM EF 40% presented with chest pain and was admitted to the ED for r/o ACS. Overnight he developed dyspnea and noted that his chest “felt funny”
Differential?
What do you do?

27. Case 4
SEE THE PATIENT!
VS: T 37 P 130 R 20 BP 140/85 O2 Sat 90% PaCO2 46 HCO3 35
CV: irregular pulse, tachycardic, 2+ pulses, normal S1/S2, 2/6 SEM RUSB, no rubs or gallops
Resp: faint rales at bases, diffuse ↓ of VM

29. CXR

31. The Limited Reliability of the Physical Examination in Heart Failure
Prospectively compared physical signs with hemodynamic measurements in 50 hospitalized patients
Rales, edema, jugular venous pulse elevation absent in 18 of 43 patients with pulmonary capillary wedge >24mmHg
Sensitivity 58%, Specificity 100%
Slide 12
HF symptoms are non-specific and relatively insensitive. Frequently, establishing the diagnosis of HF is clinically challenging.
Stevenson and Perloff. JAMA. 1989;261:

32. Methods Used in the Differential Diagnosis of Heart Failure
Electrocardiogram
Chest x-ray
Echocardiogram
Stress test (echo / nuclear imaging)
Spiral computed tomography (CT) scanning
Right heart catheterization (Swan-Ganz)
Left heart catheterization
Several tools are available to aid in diagnosing heart failure. Some of these tools,such as the ECG, Cardiac Enzymes, and cultures, are non-specific for heart failure.
Echocardiograms are expensive and are usually not available in the emergency department. Right Heart Catheterization procedures measure pulmonary and atrial wedge pressures, but require lengthy hospital visits and are an expensive tool for the initial diagnosis of heart failure

33. Clinical Indecision in the Emergency Room
Physician Report on Clinical Probability of Congestive Heart Failure
Significant Indecision Exists - 43% 50
100
150
200
250
300
350
Number of Cases 10 20 30 40 60 70 80 90
Pretest Probability of CHF

34. Assessment of Severity and Progression of Congestive Heart Failure
Symptoms do not correlate well with left ventricular dysfunction or with prognosis
Many “markers” are elevated in CHF (cytokines, catecholamines, etc) but are not useful in assessing severity or following progression:
Wide variability in values
Difficult to measure
Not often elevated until CHF is severe
Determining the severity of HF is very difficult because symptoms often do not correlate directly with severity of disease or with a patient’s prognosis. Many markers currently used to assess the severity of disease are difficult to measure and are not elevated until HF is very severe.

36. B-Type Natriuretic Peptide (BNP)
32-amino acid peptide secreted primarily from the ventricles of the heart
Released in response to stretch and increased volume in the ventricles
BNP levels correlate with:
Left ventricular end-diastolic pressure and volume
New York Heart Association (NYHA) functional classification
Extent of reversible ischemia
Rapid, point-of-care assay for BNP now available to facilitate diagnosis of CHF and use as a prognostic marker
Slide 13
Natriuretic Peptides (NP) are hormones that are manufactured and released by the heart muscle cells, in response to extra fluid volume, which causes an increased stretch on the heart muscle and its chambers. B-type natriuretic peptide (BNP) is produced by the heart ventricles in response to ventricular volume expansion and pressure overload.
BNP is not secreted under normal circumstances, nor in response to routine activities of daily living, such as hydration status and physical activity. BNP is only generated and secreted in response to excess ventricular stretch and pressure as occurs in HF. In addition, it is not stored but is generated and secreted in direct response to the severity of the HF as it progresses or improves. Therefore, elevated levels are diagnostic for HF, under all circumstances and levels of severity of HF, for which a patient might present to a health care facility.
There is a positive relationship between disease severity and BNP levels. In addition, blood BNP levels correlate positively with left ventricular end diastolic pressure, and there is an inverse correlation to left ventricular function and BNP following acute myocardial infarction.

37. Natriuretic Peptides
Listed here are the three common natriuretic peptides. Structurally, the natriuretic peptides are similar. All have a 17 AA ring structure with 11 identical AA. This ring structure is essential for receptor binding (Guanylate cyclase linked receptor).
The first natriuretic peptide that was identified in the late 1960s was the Atrial Natriuretic Peptide , a 28-amino acid hormone found predominantly in the atrium of the heart. ANP is increased in volume overload conditions in normal patients, as well as patients with CHF. The B-type, or formerly called Brain Natriuretic Peptide, has been found to be a more useful marker for congestive heart failure because the hormone is elevated in patients with congestive heart failure. BNP is secreted from the ventricles of the heart in response to ventricular stretch and volume overload. BNP has been synthesized and developed as a therapeutic tool for use in congestive heart failure. The C-type natriuretic peptide is found in the endothelium of the heart, has a very low concentration in plasma, and is not elevated in CHF.
Other members of the natriuretic peptide family such as Urodilatin are still being identified and characterized. This family of hormonally active peptides clearly has a regulatory role in cardiovascular disease.
The Triage® BNP Test is indicated for use as an aid in the diagnosis of congestive heart failure.

38. DIAGNOSTIC VALUE : BNP

39. BNP Levels in Non-CHF Patients
All non-CHF
Non-CHF Female
Non-CHF Male
100
(n=478)
BNP (pg/mL) 50
All
55-64
65-74
75+
Age

40. BNP Levels in Other Common Conditions
Yes No 60 50 40
BNP (pg/mL) 30 20 10
Hypertension
Diabetes
COPD
African
American
Caucasian

41. Relationship of BNP and NYHA Classification
1200
977.7
1000
800
Mean
678.6
BNP (pg/mL)
600
396.5
400
167.5
200
Class I
Class II
Class III
Class IV
Triage® BNP package insert. Data on File at Biosite Diagnostics Inc.

42. BNP Levels in Patients with Dyspnea Secondary to CHF or COPD
1200
1076 +/- 138
1000
800
BNP (pg/mL)
600
400
The ability to differentiate dyspnea due to COPD vs. CHF is a major diagnostic dilemma in the E.D. The rapid whole blood assay provides a strong indication of symptom origin. Patients who presented with dyspnea from pulmonary origin without cardiac involvement had normal BNP levels in the blood, whereas patients with dyspnea as a symptom of congestive heart failure had markedly elevated BNP levels.
200
86 +/- 39
COPD
n=56
CHF
n=94
Cause of Dyspnea
Dao Q, Maisel A, et al. J. Am Coll Cardio. 2001;37(2):
The Triage® BNP Test is indicated for use as an aid in the diagnosis of congestive heart failure.

43. BNP Concentration for the Degree of CHF Severity
2500
2013 ± 266
2000
1500
BNP Concentration (pg/mL)
791 ± 165
1000
Slide 15
B-type natriuretic peptide (BNP) is elevated in HF. In this study, three tertiles exhibited a relative increase in BNP levels with increased severity of heart failure. An increase in BNP level in heart failure is a physiologic response to this condition.
500
186 ± 22
Mild
(n=27)
Moderate
(n=34)
Severe
(n=36)
Dao Q, Maisel A, et al. J. Am Coll Cardio. 2001;37(2):

44. BNP Assay for Differentiating Heart Failure from Lung Disease
1000
900
800
700
600
BNP (pg/mL)
500
400
300
200
Slide 15
B-type natriuretic peptide (BNP) is elevated in HF. In this study, three tertiles exhibited a relative increase in BNP levels with increased severity of heart failure. An increase in BNP level in heart failure is a physiologic response to this condition.
100
CHF
COPD
Asthma
Act Bronch
Pneumonia PE
Cause of Dyspnea
321 Patients with dyspnea (gold standard dx of CHF, pts with COPD with RHF dx with CHF).
Morrison LK et al. J Am Coll Cardiol. 2002;39:

45. Multivariate Analysis with BNP Analyzed Last
All 250 Cases
Chi- Sens Spec Accuracy
Variable Square Significances (%) (%) (%)
History of CHF
Heart size
Murmurs
Pulm. Venous Hypertension
EKG-Atrial Fibrillation
Pedal Edema
BNP
In the multivariate analysis, the combined explanatory power of history, symptoms, signs, radiological studies and lab findings was evaluated. Additions of BNP levels to the model substantially increased the explanatory power of the model, suggesting that BNP measurements provided meaningful diagnostic information not available from other clinical variables.
Dao Q, Maisel A, et al. J. Am Coll Cardio. 2001;37(2):
The Triage® BNP Test is indicated for use as an aid in the diagnosis of congestive heart failure.

46. BNP Combined with Clinical Judgment
BNP improves diagnostic
accuracy
AUC
.86 ( ) ED Probability
.90 ( ) BNP
.93 ( ) Combined

47. Clarification of Diagnosis and BNP45 43 40
BNP Reduces Clinical Indecision by 74% 35 30 25
Indecision (%) 20 15 11 10 5
* P<0.0001
Clinical
Evaluation
Clinical Evaluation
and BNP

48. BNP Elevations Right sided heart failure Non heart failure elevations
Cor pulmonale: pg/mL
Primary pulmonary hypertension: pg/mL
Acute pulmonary embolism: pg/mL
Non heart failure elevations
Acute coronary syndromes: pg/mL
Acute myocardial infarction: 40 - >1300 pg/mL
End-stage renal disease: 80 - >1300 pg/mL

49. Heart Failure Diagnostic Algorithm
Patient presenting with dyspnea
Physical examination,
chest x-ray, ECG,
BNP level
BNP <100 pg/mL
BNP pg/mL
BNP > 400 pg/mL
CHF very unlikely
(2%)
Baseline LV dysfunction,
underlying cor pulmonale or
acute pulmonary embolism?
CHF very likely
(95%)
Yes No
Possible
exacerbation of CHF
(25%)
CHF likely
(75%)
Maisel A. Rev Cardiovasc Med. 2002;3(suppl 4):S13.

50. Patients with Acute Dyspnea
Brain Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL)
Patients with Acute Dyspnea
Randomized
Clinical group n=227
BNP group n=225
Time to discharge
History, Physical Exam, ECG, Chest X-ray, Blood Tests, SaO2
Rapid BNP Test (15min)
Start of Specific Treatment
Hospital Discharge
30 Day Outcomes
N Engl J Med. 2004;350:

51. Brain Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL)
N Engl J Med. 2004;350:

52. Brain Natriuretic Peptide for Acute Shortness of Breath Evaluation (BASEL)
8000
14,0 ]
7000
12,0
-23%
-26%
6000
-26%
10,0 ]
5000
Total Treatment Cost ($)
8,0
Time to Discharge (days)
4000
6,0
P=0.009
3000
P=0.006
4,0
2000
2,0
1000
7264
5410
13.7
10.6
0,0
Clinical group
BNP group
Clinical group
BNP group
n=227
n=225
n=227
n=225
N Engl J Med. 2004;350:

53. PROGNOSTIC VALUE : BNP

54. Natriuretic peptides: NT-proBNP
propeptide 1
NH2
COOH
disulfide bridge 98
126
N-terminal (NT) propeptide
biological active
peptide
BNP
NT-proBNP
Serum or plasma samples
Required volume 20 ml
Time for evaluation 18 min
Elecsys-proBNP
Advantages of NT-proBNP:
Longer half-life
Higher stability

55. BNP versus NT-BNP Assay for HF
Characteristic
BNP
NT-proBNP
Components
BNP molecule
NT fragment (1-76)
NT-proBNP (1-108)
Molecular Weight
3.5 kilodaltons
8.5 kilodaltons
Hormonally Active
Yes
No, inactive peptide
Genesis
Cleavage from NT-proBNP
Release from ventricular myocytes
Half-life
20 minutes
120 minutes
Clearance mechanism
Neutral Endopeptidase
Clearance Receptors
Renal Clearance
Increases with Normal Aging +
++++
Approved cutoff(s) for CHF diagnosis
100 pg/mL
Age <75: 125 pg/mL
Age ≥75: 450 pg/mL
Available at the Point-of-Care No
Studies Completed
1370 39
Entry on US Market
November 2000
December 2002
McCullough. Rev Cardiovasc Med

56. DIAGNOSTIC VALUE : pro-BNP

57. NT-proBNP in CHF: Verification
1028
1000
800
600
NT-proBNP (median) (pmol/l)
340
400
217
200
101 12
Control I II
III IV
NYHA Class
n = 408; LVEF < 45%
n = 16; controls
Haass M et al. Medimont Publ 2001; Zugck C et al. JACC 2002

58. NT-proBNP in CHF: Early Identification*
120
1000 80
800
(pmol/l) 40
600
NT-proBNP (median) (pmol/l)
Control
NYHA I
400
200 I II
III IV
Control
NYHA Class
n = 408; LVEF < 45%
n = 16; controls
Haass M et al. Medimont Publ 2001; Zugck C et al. JACC 2002

59. Northern Glasgow MONICA NT-BNP, Symptoms and LVD7 6 6 5
LOG NT-BNP (95%CI) 5 4 4 3
P < ANOVA 3
No LVD
ASLVD
SLVD
Median conc (pg/ml) No
LVD
22.00
ASLVD
77.00
ASLVD - Asymptomatic LVD
SLVD - Symptomatic LVD
SLVD
215.50
P <

60. BNP vs pro-BNP

61. PRIDE study (Massach. Gen. Hosp)
Rate of False-Negative Natriuretic-Peptide test for a diagnosis of HF:
Higher sensitivity of NT-proBNP in
Preserved EF
Marker
Nonsystolic HF
n = 76
Systolic HF
n = 77
NT-proBNP (%)
9 * 7
BNP (%) 20

62. BNP vs NT-proBNP
♥ Use of NT-proBNP in routine testing and comparison to BNP: no clinically significant advantage of BNP testing could be found.
Pfister and al. Eur J Heart Fail 2004; 6 :289-93
♥ BNP and NT-proBNP may be equally useful as an aid in the diagnosis of CHF in short of breath patients.
Mueller J and al. Heart 2005; 91:
♥ Pro-BNP more stable but less reliable in elderly.

63. Role of the BNP Assay
Diagnosis: BNP levels accurately reflect the cause of dyspnea in patients presenting to the ED and add additional information beyond standard Hx, PE, and diagnostic testing
Screening: BNP accurately detects abnormal left ventricular function in patients with or without Sx of CHF or a previous history of CHF
Risk Stratification: BNP levels are associated with risk of hospitalization and death in patients with heart failure and risk of CV events and death in patients with AMI and ACS
Treatment Guide: Early studies suggest BNP may guide initiation and titration of heart failure therapy

64. GUIDELINES

66. HFSA 2010 Practice Guideline
Recommendation 4.6
It is recommended that BNP or NT ProBNP levels be assessed in all patients suspected of having HF when the diagnosis is not certain.
Strenght of Evidence = B
J Card Fail 2010 Jun; 16(6): e44-56

67. ACC/AHA Guidelines
Measurement of BNP or NT-ProBNP can be useful in the evaluation of patients presenting in the urgent care setting in whom the clinical diagnosis of HF is uncertain. Should not be used in isolation to confirm or exclude the presence of HF.
(Class IIa; Level of Evidence: A)

68. Conclusions and Recommendations
Dyspnea situation : Treatment can be provided while the diagnostic steps are taken
Begin with a careful History and Physical Examination
Electrocardiogram
ABG and Laboratory exams
Measurement of plasma BNP
Chest radiograph
Transthoracic Echocardiogram
Pulmonary-artery catheter

70. Thank you