3 Definitions Dyspnea: Hypoxia: Subjective experience of breathing discomfort that consists ofqualitative 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 breathingMultiple etiologies -2/3 of cases - cardiac or pulmonary etiology
5 Differential Diagnosis DyspneaCardiac:Other:Pulmonary:COPDAsthmaOSAPneumoniaInterstitial Lung DiseasePulmonary EmbolismPneumothoraxPleural effusionChest wall deformityPulmonary HTNACS/AMICHFPericardial effusion/tamponadeArrhythmiaPericarditisValvular diseaseAnemiaAnxietyAscitesAcidosisCVAIatrogenic/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 historyReview recent eventsMeds givenTrend 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/S4JVPPeripheral pulses/edema
8 Easily Performed Diagnostic Tests Chest radiographsElectrocardiographScreening spirometry
9 Other Diagnostic Testing ABGLabs: CBC, Renal function panel, BNP, Cardiac enzymes?Further imaging as warranted:PE protocol CT vs. V/Q scanTransthoracic Echo
10 ABGs Commonly used to evaluate acute dyspnea Can provide information about altered pH, hypercapnia, hypocapnia or hypoxemiaNormal ABGs do not exclude cardiac/pulmonary dx as cause of dyspneaRemember- ABGs may be normal even in cases of acute dyspnea - ABGs do not evaluate breathing
11 PULSE OXRapid, 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 PaO2The hemoglobin desaturation curve can be shifted depending on the pH, temperature or arterial carbon monoxide or carbon dioxide levels
12 EchocardiographyThe 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 dyspneaLess sensitive in identifying diastolic dysfunctionDoes not rule out cardiogenic pulmonary edema
14 Case 1A 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 1A 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.
18 Case 2This 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 2This 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.
22 Case 3This 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 3This 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 diagnosisAcute pulmonary oedema due to congestive cardiac failure.
26 Case 478yo 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 4SEE THE PATIENT!VS: T 37 P 130 R 20 BP 140/85 O2 Sat 90% PaCO2 46 HCO3 35CV: irregular pulse, tachycardic, 2+ pulses, normal S1/S2, 2/6 SEM RUSB, no rubs or gallopsResp: faint rales at bases, diffuse ↓ of VM
31 The Limited Reliability of the Physical Examination in Heart Failure Prospectively compared physical signs with hemodynamic measurements in 50 hospitalized patientsRales, edema, jugular venous pulse elevation absent in 18 of 43 patients with pulmonary capillary wedge >24mmHgSensitivity 58%, Specificity 100%Slide 12HF 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 ElectrocardiogramChest x-rayEchocardiogramStress test (echo / nuclear imaging)Spiral computed tomography (CT) scanningRight heart catheterization (Swan-Ganz)Left heart catheterizationSeveral 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 FailureSignificant Indecision Exists - 43%50100150200250300350Number of Cases1020304060708090Pretest Probability of CHF
34 Assessment of Severity and Progression of Congestive Heart Failure Symptoms do not correlate well with left ventricular dysfunction or with prognosisMany “markers” are elevated in CHF (cytokines, catecholamines, etc) but are not useful in assessing severity or following progression:Wide variability in valuesDifficult to measureNot often elevated until CHF is severeDetermining 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 heartReleased in response to stretch and increased volume in the ventriclesBNP levels correlate with:Left ventricular end-diastolic pressure and volumeNew York Heart Association (NYHA) functional classificationExtent of reversible ischemiaRapid, point-of-care assay for BNP now available to facilitate diagnosis of CHF and use as a prognostic markerSlide 13Natriuretic 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 PeptidesListed 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.
39 BNP Levels in Non-CHF Patients All non-CHFNon-CHF FemaleNon-CHF Male100(n=478)BNP (pg/mL)50All55-6465-7475+Age
40 BNP Levels in Other Common Conditions YesNo605040BNP (pg/mL)302010HypertensionDiabetesCOPDAfricanAmericanCaucasian
41 Relationship of BNP and NYHA Classification 1200977.71000800Mean678.6BNP (pg/mL)600396.5400167.5200Class IClass IIClass IIIClass IVTriage® BNP package insert. Data on File at Biosite Diagnostics Inc.
42 BNP Levels in Patients with Dyspnea Secondary to CHF or COPD 12001076 +/- 1381000800BNP (pg/mL)600400The 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.20086 +/- 39COPDn=56CHFn=94Cause of DyspneaDao 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 25002013 ± 26620001500BNP Concentration (pg/mL)791 ± 1651000Slide 15B-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.500186 ± 22Mild(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 1000900800700600BNP (pg/mL)500400300200Slide 15B-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.100CHFCOPDAsthmaAct BronchPneumoniaPECause of Dyspnea321 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 CasesChi- Sens Spec AccuracyVariable Square Significances (%) (%) (%)History of CHFHeart sizeMurmursPulm. Venous HypertensionEKG-Atrial FibrillationPedal EdemaBNPIn 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 diagnosticaccuracyAUC.86 ( ) ED Probability.90 ( ) BNP.93 ( ) Combined
47 Clarification of Diagnosis and BNP 454340BNP Reduces Clinical Indecision by 74%353025Indecision (%)201511105* P<0.0001ClinicalEvaluationClinical Evaluationand BNP
49 Heart Failure Diagnostic Algorithm Patient presenting with dyspneaPhysical examination,chest x-ray, ECG,BNP levelBNP <100 pg/mLBNP pg/mLBNP > 400 pg/mLCHF very unlikely(2%)Baseline LV dysfunction,underlying cor pulmonale oracute pulmonary embolism?CHF very likely(95%)YesNoPossibleexacerbation 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 DyspneaRandomizedClinical group n=227BNP group n=225Time to dischargeHistory, Physical Exam, ECG, Chest X-ray, Blood Tests, SaO2Rapid BNP Test (15min)Start of Specific TreatmentHospital Discharge30 Day OutcomesN 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) 800014,0]700012,0-23%-26%6000-26%10,0]5000Total Treatment Cost ($)8,0Time to Discharge (days)40006,0P=0.0093000P=0.0064,020002,010007264541013.710.60,0Clinical groupBNP groupClinical groupBNP groupn=227n=225n=227n=225N Engl J Med. 2004;350:
54 Natriuretic peptides: NT-proBNP propeptide1NH2COOHdisulfide bridge98126N-terminal (NT) propeptidebiological activepeptideBNPNT-proBNPSerum or plasma samplesRequired volume 20 mlTime for evaluation 18 minElecsys-proBNPAdvantages of NT-proBNP:Longer half-lifeHigher stability
55 BNP versus NT-BNP Assay for HF CharacteristicBNPNT-proBNPComponentsBNP moleculeNT fragment (1-76)NT-proBNP (1-108)Molecular Weight3.5 kilodaltons8.5 kilodaltonsHormonally ActiveYesNo, inactive peptideGenesisCleavage from NT-proBNPRelease from ventricular myocytesHalf-life20 minutes120 minutesClearance mechanismNeutral EndopeptidaseClearance ReceptorsRenal ClearanceIncreases with Normal Aging+++++Approved cutoff(s) for CHF diagnosis100 pg/mLAge <75: 125 pg/mLAge ≥75: 450 pg/mLAvailable at the Point-of-CareNoStudies Completed137039Entry on US MarketNovember 2000December 2002McCullough. Rev Cardiovasc Med
61 PRIDE study (Massach. Gen. Hosp) Rate of False-Negative Natriuretic-Peptide test for a diagnosis of HF:Higher sensitivity of NT-proBNP inPreserved EFMarkerNonsystolic HFn = 76Systolic HFn = 77NT-proBNP (%)9 *7BNP (%)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 AssayDiagnosis: BNP levels accurately reflect the cause of dyspnea in patients presenting to the ED and add additional information beyond standard Hx, PE, and diagnostic testingScreening: BNP accurately detects abnormal left ventricular function in patients with or without Sx of CHF or a previous history of CHFRisk 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 ACSTreatment Guide: Early studies suggest BNP may guide initiation and titration of heart failure therapy
66 HFSA 2010 Practice Guideline Recommendation 4.6It 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 = BJ Card Fail 2010 Jun; 16(6): e44-56
67 ACC/AHA GuidelinesMeasurement 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 takenBegin with a careful History and Physical ExaminationElectrocardiogramABG and Laboratory examsMeasurement of plasma BNPChest radiographTransthoracic EchocardiogramPulmonary-artery catheter