Acute heart failure: new diagnostic perspectives for the emergency physician

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1 Intern Emerg Med (2008) 3:37 41 DOI /s EM - REVIEW Acute heart failure: new diagnostic perspectives for the emergency physician Gino Soldati Æ Luna Gargani Æ Fernando R. Silva Received: 2 June 2007 / Accepted: 1 November 2007 / Published online: 9 February 2008 Ó SIMI 2008 Abstract The topic of heart failure (HF) in the emergency department is today relevant, since there are new serum markers and imaging techniques that may help in the diagnosis of this disease. Natriuretic peptides have now entered the flowchart for etiologic diagnosis in patients with acute dyspnea, when technical facilities are available. Recently, chest ultrasonography has been shown to be useful for the noninvasive assessment of extravascular lung water. Starting from this practical standpoint, we propose that simple chest ultrasonogrpahic signs can provide a totally noninvasive characterization of pulmonary congestion in patients with HF. Keywords Chest sonography B-lines Ultrasound lung comets Heart failure Lung ultrasound Introduction The emergency physician often makes the diagnosis and manages many acute heart failure (HF) patients. Rapid G. Soldati Emergency Department, ASL 2, Ospedale di Castelnuovo Garfagnana, Lucca, Italy L. Gargani Institute of Clinical Physiology, National Research Council, Pisa, Italy F. R. Silva Department of Emergency Medicine, New York Hospital Queens, Flushing, NY, USA G. Soldati (&) Valle del Serchio General Hospital, Via Nazionale, 106, Pieve Fosciana Lucca, Italy g.soldati@usl2.toscana.it diagnosis of decompensated HF is important for prompt, appropriate therapy, but it is often difficult to detect [1]. The topic of decompensated HF diagnosis in the emergency department (ED) is today relevant, since plasma levels of B-type natriuretic peptide (BNP) and its aminoterminal fragment N-terminal probnp (NT-proBNP) have been proposed, in addition to clinical judgement, to facilitate this diagnosis [2 4]. BNP and NT-proBNP have a very high negative predictive value in excluding HF, thus the diagnosis of acute HF with normal values of natriuretic peptides is very unlikely. On the contrary, in many circumstances they may be elevated in absence of HF, i.e. in patients with renal failure [5]. In these cases and in the presence of slightly abnormal values, the gray zone of natriuretic peptides, diagnosis and management of patients with dyspnea should be integrated with other parameters. Recently, chest ultrasonography imaged as Ultrasound Lung Comets (ULCs or B-lines) has been proposed as a very simple method [6] for assessment of pulmonary congestion in HF patients [7]. ULCs have been found to be related to New York Heart Association (NYHA) functional class [8], to radiographic signs of pulmonary congestion on chest X-ray [9], to invasive measurement of extravascular lung water (EVLW) [10], and to systolic and diastolic dysfunction [8]. The aim of this discussion is to underline the potential usefulness of chest ultrasonography in the diagnosis of acute HF in the ED. The clinical entity Among all cardiovascular diseases, HF is the only one increasing in prevalence, incidence, hospitalization rate, total burden of mortality, and costs. It is estimated that the

2 38 Intern Emerg Med (2008) 3:37 41 USA has more than 5 million cases, with 500,000 new cases diagnosed each year. At least 20 million people are asymptomatic patients with HF that will become symptomatic within 1 5 years [11, 12]. After the initial symptoms the mortality rate at 6 years is very high (80% in men, 65% in women), and 1 year after the first pulmonary edema only half the patients are alive [13]. Acute HF is a highly recurrent disease: only 21% of the cases in the ED are actually the first event [14]. Physiopathology Regardless of its many different causes, HF results from a dysfunction of the systolic or diastolic phase of cardiac function. Independent of the primary cause of HF, there are two fundamental consequences: an increase in left ventricular filling pressure, leading to pulmonary congestion and edema, causing the respiratory symptoms, and the induction of a pathological neuroendocrine activation, leading to the production of numerous substances, including cathecolamines, angiotensin II, aldosterone, endothelin, cytokines, and alpha-tnf [15]. This activation leads to many pathological consequences, including left ventricular remodeling with fibrosis, apoptosis, contraction and geometry changes, and peripheral vascular modifications. In this context, natriuretic peptides positively affect the body fluid and sodium homeostasis, through an inhibitory action on the neurohormonal and immunological systems, especially the renin angiotensin aldosterone system, with diuresis and natriuresis [16]. They also exert a fundamental role in regulating the vascular tone and remodeling, by decreasing shear stress, modulating coagulation and fibrinolysis pathways, and inhibiting platelet activation [17]. In HF patients, BNP and NT-proBNP serum levels increase after myocardial stretch, following pressure or volume overload; they correlate with the severity of ventricular dysfunction and with the NYHA class of dyspnea [18, 19]. Diagnosis The absence of standardization for the diagnosis of acute decompensated HF makes this diagnosis a challenge for clinicians. In the ED setting, diagnosis of acute HF has usually been based on clinical examination. Unfortunately, signs and symptoms of acute HF are non-specific. Dyspnea, for example, characterizes a wide range of diseases that includes bronchial and pulmonary diseases, acute coronary syndromes, pulmonary embolism, dysrhythmias, obesity, psychiatric disorders, and physical deconditioning [1]. Even the chest X-ray study is often not very helpful in the diagnosis: it fails to demonstrate at least 20% of cardiomegalies further diagnosed by ultrasound and 50% of pleural effusions, especially if small; in chronic HF, sensitivity and specificity of radiological signs in predicting increased pulmonary capillary wedge pressure (PCWP) is low [20, 21]. The echocardiographic estimation of ejection fraction (EF) has been considered the most important measure in heart failure [22], but there is not a clear correlation between symptoms and EF values [11]. In cases of preserved systolic function, the echocardiographic assessment of diastolic function would require more expertise. Finally, echocardiography is not widely available in the ED. According to previous registries, it is estimated that over one-third of acute HF diagnoses are mistaken; about half are COPD [23]. BNP in the reality of emergency medicine Given this clinical challenge, the blood-based measurement of BNP and NT-proBNP has emerged as part of the diagnostic tools available for the diagnosis of patients presenting with acute onset of dyspnea in the ED. Many studies have compared BNP and NT-proBNP accuracy to the clinical judgment of physicians [2 4, 24 27]. Measurement of either BNP or NT-proBNP outperformed the clinician who integrated the history, physical examination, and other diagnostic test findings (i.e. chest X-ray). Thus, in the 2005 update of the ACC/AHA guidelines for the diagnosis and treatment of HF, it is stated that measurement of BNP is considered useful in the evaluation of patients presenting in the urgent care setting in whom the clinical diagnosis of HF is uncertain, although it should not be used in isolation to confirm or exclude the presence of HF [11]. The multicenter breathing not properly trial established an optimal cut-off value for BNP of 100 pg/ ml for the diagnosis of decompensated HF [2], while The International Collaborative of NT-proBNP (ICON) study established optimal age-based cut-offs for NT-proBNP to rule in acute decompensated HF, and a single cut-off to rule out HF [28]. In case of very high BNP or NTproBNP values, even more than ten times below these cut-offs, diagnosis of HF is almost certain, as well as values beyond them, almost always exclude HF, unless a flash pulmonary edema is present (when we may hypothize that there is no time for the polypeptide synthesis). On the contrary, it is challenging to interpretate values that fall between the lower rule-out and higher rule-in values found in HF patients. This range is often referred to as the gray zone. In this range, integration with clinical and other diagnostic tools is mandatory, especially because BNP can be elevated in many other circumstances [29], as listed on Table 1. It is especially

3 Intern Emerg Med (2008) 3: Table 1 Situations that can increase serum BNP levels Old age Renal failure Hypertension with LV hypertrophy Cirrhosis Pulmonary hypertension Pulmonary embolism Myocardial ischemia Sustained arrhythmias important to interpretate BNP and NT-proBNP values, always considering the renal function. Chest ultrasonography Currently, there is evidence that chest ultrasonography may be very helpful in differentiating cardiogenic dyspnea, associated with increased EVLW, from non-cardiogenic dyspnea. This distinction is based on the presence of ULCs or B-lines [7, 30], a pathological expression of enlarged pulmonary interstitium or alveolar interstitial syndrome (AIS). The ULCs or B-lines are defined as echogenic, coherent, wedge-shaped signals with a narrow origin in the near field of the image (Figs. 1, 2). They represent one of the lung ultrasound artefacts produced by normal and pathologic pleural and subpleural points of high impedance, that act as ultrasound resonators. In a normal aerated lung, we can only visualize a black screen, where at least only the normal A-lines are visible (Fig. 3); A-lines are horizontal reverberation artefacts that reproduce the Fig. 2 In this image several merging ultrasound lung comets or B-lines are visible, creating almost homogenous echogenic fields (white lung) normal pleural line (the basic physiological linear reflector). The ULCs or B-lines are focal resonance of subpleural interlobular septa thickened by water (similar to traditional Kerley B-lines) or, as EVLW increases and fill the alveolar space, they represent acoustic resonance in the alveolar spaces surrounded by water. The interstitial syndrome is characterized by separated ULCs or B-lines, while the involvement of the alveolar spaces leads to the coalescence of ULCs or B-lines, appearing as a white screen ( the white lung ). Fig. 1 Heart failure with pulmonary edema. Septal ultrasound lung comets or B-lines, arising from the pleural line and erasing the A-lines Fig. 3 An intercostal space showing a normal lung pattern, where horizontal artefacts (A-lines) are visible beyond the pleural line

4 40 Intern Emerg Med (2008) 3:37 41 Table 2 Chest sonography results showing a correlation between cardiogenic dyspnea, B-Lines (ULCs), BNP values and radiographic findings of acute heart failure ED emergency department, BNP brain natriuretic peptide, HF heart failure, ULCs ultrasound lung comets, ROC receiver operating characteristic Study 83 patients with dyspnea: chest sonography identification of pulmonary edema, correlation with clinical presentation and chest X-ray [31] 52 patients with dyspnea in ED: BNP values among subjects with final diagnosis of HF and with other diagnosis [36] 52 patients with dyspnea in ER: chest sonography edema score in subjects with and without final diagnosis of HF [36, 37] 27 patients with dyspnea in ER: ROC curve analysis of BNP levels and chest sonography edema score versus final diagnosis of HF [36] Results Sensitivity 96%, specificity 100% of ultrasound versus chest X-ray Subjects with HF: BNP 905 pg/dl Subjects without HF: 140 pg/dl (P \ 0.01) BNP values in the gray zone ( pg/dl): 40% Mean ULCs or B-Lines in subjects without HF: 8 Mean ULCs or B-Lines in subjects with HF: 55 Correlation between ultrasound score and BNP serum levels: 0.7 (P \ 0.01) BNP [118 pg/dl: sensitivity 100%, specificity 64% for diagnosis of HF Over 20 bilateral ULCs or B-lines: specificity 100%, sensitivity 84% for diagnosis of HF Cardiologists have become aware of the potential importance of the echographic pattern of the edematous lung. Several studies from the late 1990s have confirmed a good correlation of this echographic sign with the clinical and radiographic presentation of cardiogenic pulmonary edema [9, 31 33]. Picano and coworkers find a significant correlation between the number of ULCs or B-lines with a score of radiographic signs of pulmonary congestion [9], and also with EVLW volume, invasively quantified by the indicator diluition method, and with the PCWP obtained by right heart catheterization [10]. Volpicelli et al. [34] in an ED setting, find a sensitivity of 85.7% and a specificity of 97.7% for ULCs or B-Lines to detect AIS. A small pivotal study in patients with dyspnea, find a significant correlation between ULCs number and NT-proBNP values (r = 0.69, P \ ); with receiver operating characteristic (ROC) analysis, ULCs showed an area under the curve of.893, and NT-proBNP of (P = 0.001), in predicting the cardiac origin of dyspnea [35]. Other chest sonography findings at the ED, in HF patients, also confirm these first results, and are synthesized in Table 2 [31, 36, 37]. Basing on these initial data, although on small numbers of patients, a 2- or 3-min chest ultrasonographic scanning may elucidate a doubtful clinical presentation or a grayzone BNP/NT-proBNP level. Although ULCs or B-lines with a considerable number (at least more than 5, bilaterally) can quickly identify pulmonary congestion, we must remember that they are a non-specific echographic sign of pulmonary edema, including non-cardiogenic forms as acute lung injury/acute respiratory distress syndrome [38]. Moreover, they may be also present in interstitial pneumonia and other interstitial and fibrogenic granulomatous diseases [39]. In these cases, together with clinical information and history, other chest ultrasonographic signs may be helpful, such as presence or absence of pleural effusion, and the different patterns of ultrasonographic findings (homogeneous, inhomogeneous, focal or diffuse) [37, 40]. Conclusions In the challenging task of diagnosing acute HF at the ED, especially in case of gray zone levels of BNP/NTproBNP, pulmonary congestion detected by ULCs or B- lines, could be definitive for the diagnosis of HF. Moreover, a normal lung echographic pattern (with less than 5 ULCs or B-lines on the whole thorax) in a patient with BNP [ 100 pg/dl may suggest a right-ventricle origin of the peptide (pulmonary hypertension and pulmonary embolism). References 1. Stevenson LW, Perloff JK (1989) The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA 261: Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrmann HC, McCullough PA (2002) Breathing not properly multinational study investigators. Rapid measurement of B-Type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 347: Mueller C, Scholer A, Laule-Kilian K, Martina B, Schindler C, Buser P, Pfisterer M, Perruchoud AP (2004) Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. N Engl J Med 350: McCullough PA, Nowak RM, McCord J, Hollander JE, Herrmann HC, Steg PG, Duc P, Westheim A, Omland T, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, Perez A, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS (2002) B- type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation 106:

5 Intern Emerg Med (2008) 3: Anwaruddin S, Lloyd-Jones DM, Baggish A, Chen A, Krauser D, Tung R, Chae C, Januzzi JL Jr (2006) Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study. J Am Coll Cardiol 47: Bedetti G, Gargani L, Corbisiero A, Frassi F, Poggianti E, Mottola G (2006) Evaluation of ultrasound lung comets by handheld echocardiography. Cardiovasc Ultrasound 4:34 7. Picano E, Frassi F, Agricola E, Gligorova S, Gargani L, Mottola G (2006) Ultrasound lung comets: a clinically useful sign of extravascular lung water. J Am Soc Echocardiogr 19: Frassi F, Gargani L, Gligorova S, Ciampi Q, Mottola G, Picano E (2007) Clinical and echocardiographic determinants of ultrasound lung comets. Eur J Echocardiogr 8: Jambrik Z, Monti S, Coppola V, Agricola E, Mottola G, Miniati M, Picano E (2004) Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water. Am J Cardiol 93: Agricola E, Bove T, Oppizzi M, Marino G, Zangrillo A, Margonato A, Picano E (2005) Ultrasound comet-tail images : a marker of pulmonary edema: a comparative study with wedge pressure and extravascular lung water. Chest 127: Hunt SA (2005) ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to update the 2001 guidelines for the evaluation and management of heart failure). J Am Coll Cardiol 46:e1 e American Heart Association (2007) Heart disease and stroke statistics 2007 update. American Heart Association, Dallas 13. Peacock WF (2004) Heart failure management in the Emergency Department Observation Unit. Progr Cardiovasc Dis 46: Aghababian R (2002) Acutely decompensated heart failure: opportunities to improve care and outcomes in the emergency department. Rev Cardiovasc Med 3(suppl 4): Braunwald E (2005) Heart disease, 7th edn. Elsevier, Amsterdam 16. de Bold AJ, Ma KK, Zhang Y, de Bold ML, Bensimon M, Khoshbaten A (2001) The physiological and pathophysiological modulation of the endocrine function of the heart. Can J Physiol Pharmacol 79: Clerico A, Recchia FA, Passino C, Emdin M (2006) Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications. Am J Physiol Heart Circ Physiol 290:H17 H Panteghini M (2004) Role and importance of biochemical markers in clinical cardiology. Eur Heart J 25: Struthers AD (1994) Ten years of natriuretic peptide research: a new dawn for their diagnostic and therapeutic use? BMJ 308: Ruskin JA, Gurney JW, Thorsen MK, Goodman LR (1987) Detection of pleural effusions on supine chest radiographs. Am J Roentgenol 148: Chakko S, Woska D, Marinez H de Marchena E, Futterman L, Kessler KM, Myerberg RJ (1991) Clinical, radiographic and hemodynamic correlations in chronic congestive heart failure: conflicting results may lead to inappropriate care. Am J Med 90: Packer M, Cohn JN (1999) Consensus recommendations for the management of chronic heart failure. Am J Cardiol 83:1A 38A 23. Remes J, Miettinen H, Reunanen A, Pyörälä K (1991) Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J 12: Januzzi JL Jr, Camargo CA, Anwaruddin S et al (2005) The N- terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol 95: Lainchbury JG, Campbell E, Frampton CM, Yandle TG, Nicholls MG, Richards AM (2003) Brain natriuretic peptide and n-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath. J Am Coll Cardiol 42: Zaphiriou A, Robb S, Murray-Thomas T et al (2005) The diagnostic accuracy of plasma BNP and NTproBNP in patients referred from primary care with suspected heart failure: results of the UK natriuretic peptide study. Eur J Heart Fail 7: Maisel A, Hollander JE, Gauss D et al (2004) Primary results of the rapid emergency department heart failure outpatient trial (REDHOT): a multicenter study of B-type natriuretic peptide levels, emergency decision making and outcomes in patients presenting with shortness of breath. J Am Coll Cardiol 44: Januzzi JL, van Kimmenade R, Lainchbury J et al (2006) NTproBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study. Eur Heart J 27: Emdin M, Clerico A, Clemenza F, Galvani M, Latini R, Masson S, Mule P, Panteghini M, Valle R, Zaninotto M, Ganau A, Mariotti R, Volpe M, Aspromonte N, Cacciatore G, Cappelletti P, L Abbate A, Miglio F, Ottani F, Pagani F, Passino C, Plebani M, Sarzani R, Zucchelli G (2005) Italian Association of Hospital Cardiologists; Italian Society of Cardiology; Italian Federation of Cardiology; Italian Society of Clinical Chemistry and Molecular Biology; Italian Society of Laboratory Medicine; Italian Society of Emergency Medicine. Recommendations for the clinical use of cardiac natriuretic peptides. Ital Heart J 6: Lichtenstein D, Meziere G, Biderman P, Gepner A, Barre O (1997) The comet-tail artifact. An ultrasound sign of alveolar interstitial syndrome. Am J Respir Crit Care Med 156: Soldati G, Rossi M (1999) Wet and dry lungs. A useful sonographic distinction. Crit Care 3(suppl 1):P Soldati G (2001) Lung ultrasound: movement, artifact or echotexture? Giornale Italiano Ecografia 4: Lichtenstein D, Meziere G (1998) A lung ultrasound sign allowing bedside distinction between pulmonary edema and COPD: the comet tail artifact. Intensive Care Med 24: Volpicelli G, Mussa A, Garofalo G, Cardinale L, Casoli G, Perotto F, Fava C, Frascisco M (2006) Bedside lung ultrasound in the assessment of alveolar interstitial syndrome. Am J Emerg Med 24: Gargani L, Soldati G, Frassi F, Agrusta M, Tesorio P, Mottola G, Picano E (2006) Ultrasound lung comets for differential diagnosis of dyspnea: comparison with plasma cardiac peptides. Circulation (November supplement: 3589) 36. Soldati G, Bergamini C (2006) A sonographic lung score for the detection of extravascular lung water in patients with CHF. Acad Emerg Med 13: Soldati G, Bergamini C (2006) Chest sonography in the diagnosis of congestive heart failure. Acad Emerg Med 13: Soldati G, Testa A, Silva FR, Carbone L, Portale G, Silveri NG (2006) Chest ultrasonography in lung contusion. Chest 130: Reissig A, Kroegel C (2003) Transthoracic sonography of diffuse parenchymal lung disease: the role of comet tail artifacts. J Ultrasound Med 22: Soldati G, Copetti R (2006) Ecografia toracica. GCEMS Ed. Medico Scientifiche, Torino