dell’ecocardiografia nella valutazione cardiologica di prima linea aumenterà nettamente e
lo studio delle comete polmonari potrebbe ulteriormente espandere la sua applicazione
clinica. D’altro canto l’ecografia, al giorno d’oggi, deve essere considerata come uno strumento “che il medico porta nella tasca come se fosse un superstetoscopio”, e che deve
poter essere utilizzato anche da medico di medicina generale.125
La possibilità di ottenere informazioni sull’acqua extravascolare polmonare, ricorrendo ad una tecnologia molto semplice, che può essere essere eseguita al letto del paziente, consentirà di espandere ulteriormente l’utilizzo degli ultrasuoni, con la possibilità di valutare la presenza di cardiomegalia, di versamento pleurico e di congestione polmonare, che sono parametri fondamentali nella diagnosi e nel follow-up dei pazienti con insufficienza cardiaca, permettendoci di instaurare una terapia ottimizzata.
Ovviamente l’utilizzo di questa metodica, così come in generale di tutti gli altri
esami strumentali, non deve mai sostituire la valutazione clinica del paziente, che rimane il caposaldo da cui iniziare eventualmente le successive indagini. L’esperienza e il buon senso del medico sono gli strumenti indispensabili affinchè gli stessi esami strumentali siano appropriati e apportatori di informazioni aggiuntive. Ci sono però delle fasi pre- cliniche anche nel paziente con insufficienza cardiaca, nelle quali l’integrazione di un esame strumentale semplice e poco costoso potrebbe risultare di notevole ausilio.
4.c.
LIMITI DELLO STUDIO
Il contesto ideale di questo studio sarebbe stato il pronto soccorso, dove il paziente con dispnea acuta viene visitato per la prima volta dal medico, e non ha ancora ricevuto alcuna terapia specifica. I pazienti con dispnea di questo studio provenivano o dal pronto soccorso, dove spesso avevano già intrapreso terapia con diuretici dell’ansa, oppure si
ricoveravano per peggioramento della sintomatologia, fra cui dispnea, nell’ultimo periodo.
Un altro limite dello studio è che su 205 pazienti considerati, quelli con dispnea non cardiogena sono in numero piuttosto inferiore rispetto a quelli con dispnea cardiogena, per
un’ovvia selezione iniziale, provenendo, per la maggior parte, da una corsia cardiologica.
In questo studio, il tempo intercorso fra il prelievo di sangue venoso per il dosaggio del NT-proBNP e l’esame ecografico del torace per il conteggio delle comete, è stato sempre inferiore a 4 ore. Tuttavia, vista la dinamicità di questo segno, serebbe ottimale un confronto su valutazione simultanea dei due parametri.
In conclusione le comete polmonari sono un metodo ecografico affidabile ma estremamente semplice, veloce e poco costoso, di valutazione semi-quantitativa dell’acqua extravascolare polmonare, le cui caratteristiche fanno ipotizzare la possibilità, in futuro, di un vasto impiego clinico, a integrazione dell’ecografia classica, nella gestione del paziente con scompenso cardiaco.
5.
BIBLIOGRAFIA
1. Wendell BA. Ultrasonic appearance of metallic foreign bodies in parenchymal organs. J Clin Ultrasound. 1981 Mar;9:133-5.
2. Ziskin MC, Thickman DI, Goldenberg NJ, Lapayowker MS, Becker JM. The comet tail artifact. J Ultrasound Med. 1982 Jan-Feb;1:1-7.
3. Thickman DI, Ziskin MC, Goldenberg NJ, Linder BE. Clinical manifestations of the comet tail artifact. J Ultrasound Med. 1983 May;2:225-30.
4. Kremkau FW, Taylor KJ. Artifacts in ultrasound imaging. J Ultrasound Med. 1986 Apr;5:227-37.
5. Targhetta R, Bourgeois JM, Chavagneux R, Coste E, Amy D, Balmes P, Pourcelot L. Ultrasonic signs of pneumothorax: preliminary work. J Clin Ultrasound. 1993 May;21:245-50.
6. Reissig A, Kroegel C. Transthoracic sonography of diffuse parenchymal lung disease: the role of comet tail artifacts. J Ultrasound Med. 2003 Feb;22:173-80. 7. Kohzaki S, Tsurusaki K, Uetani M, Nakanishi K, Hayashi K. The aurora sign: an
ultrasonographic sign suggesting parenchymal lung disease. Br J Radiol. 2003 Jul;76:437-43.
8. Lichtenstein D et al. The comet-tail artifact: an ultrasound sign of alveolar- interstitial syndrome. Am J Respir Crit Care Med. 1997;156:1640-1646.
9. Felson, B. Chest Roentgenology, 1st ed. W. B. Saunders, Philadelphia, 1973, pagg. 244–245.
10. Gattinoni A, Pesenti A, Torresin A, Vesconi S, Rossi GP, Fumagalli R, Marcolin R, Mascheroni D, Langer D, Iapichino G, Rossi F, Baglioni S, CT in acute respiratory failure, in Kox W, Boultbee J, Donaldson R, Imaging and Labelling Techniques in
the Critically Ill, 1st ed., Springer-Verlag, New York, pagg. 67–75.
11. Rouby JJ, Puybasset L, Nieszkowska A, Lu Q. Acute respiratory distress syndrome: lessons from computed tomography of the whole lung. Crit Care Med. 2003;31(Suppl.4):S285-95.
12. Cittadini Giorgio, Diagnostica per immagini e radioterapia, Genova, Edizioni Culturali Internazionali Genova, V ed., 2003, pag.277.
13. Rigler LG. Roentgen examination of the chest: its limitations in the diagnosis of disease. JAMA. 1950;142:773.
14. Tagliabue M, Casella TC, Zincone GE, Fumagalli R, Salvini E. CT and chest radiography in the evaluation of adult respiratory distress syndrome. Acta Radiol. 1994;35:230-4.
15. Lichtenstein D, Meziere G. A lung ultrasound sign allowing bedside distinction between pulmonary edema and COPD: the comet-tail artifact. Intensive Care Med. 1998;24:1331-4.
16. Jambrik Z, Monti S, Coppola V, Agricola E, Mottola G, Miniati M, Picano E. Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water. Am J Cardiol. 2004;93:1265-70.
17. Giuntini C, Pistolesi M, Miniati M, Fazio F. Theoretical and practical considerations of measuring extravascular lung water. J Thorac Imaging 1988;3:36–43.
18. Pistolesi M, Giuntini C. Assessment of extravascular lung water. Radiol Clin North
Am 1978;15:551–574.
19. Agricola E, Bove T, Oppizzi M, Marino G, Zangrillo A, Margonato A, Picano E. "Ultrasound comet-tail images": a marker of pulmonary edema: a comparative study with wedge pressure and extravascular lung water. Chest. 2005;127:1690-5. 20. Lewis FR, Elings VB, Sturm JA: Bedside measurement of lung water. J Surg Res
1979, 27:250–261.
21. Sivak ED, Starr NJ, Graves JW, Cosgrove DM, Borsh J, Estafanous FG. Extravascular lung water values in patients undergoing coronary artery bypass surgery. Crit Care Med. 1982;10:593-6.
22. Sibbald WJ, Warshawski FJ, Short AK, Harris J, Lefcoe MS, Holliday RL. Clinical studies of measuring extravascular lung water by the thermal dye technique in critically ill patients. Chest. 1983;83:725-31.
23. Gallagher JD, Moore RA, Kerns D, Jose AB, Botros SB, Clark DL. Effects of advanced age on extravascular lung water accumulation during coronary artery bypass surgery. Crit Care Med. 1985;13:68-71.
24. Agricola E, Picano E, Oppizzi M, Pisani M, Meris A, Fragasso G, Margonato A. Assessment of stress-induced pulmonary interstitial edema by chest ultrasound during exercise echocardiography and its correlation with left ventricular function.
J Am Soc Echocardiogr. 2006;19:457-63.
25. Nagueh SF, Middleton KJ, Kopelen HA, Zoghbi WA, Quinones MA. Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol 1997;30:1527-33.
26. Picano E, Frassi F, Agricola E, Gligorova S, Gargani L, Mottola G. Ultrasound lung comets: a clinically useful sign of extravascular lung water. J Am Soc
Echocardiogr. 2006;19:356-63.
27. Picano E. Sustainability of medical imaging. BMJ. 2004;328:578-80.
29. Miller WS, The Lung, Springfield, IL, Charles C Thomas, 1937.
30. Fraser RS, Parè PD, Diagnosis of diseases of the chest, Philadelphia, W.B. Saunders Company, 2000, pagg.25-29.
31. Kasper DL, Harrison’s Principles of Internal Medicine, 16th ed., New York, The McGraw-Hill Companies, 2005, pag. 1561.
32. Società Italiana di Ultrasonologia in Medicina e Biologia, Trattato Italiano di
Ecografia, Roma, SIUMB 1993.
33. Roelandt JRTC, Sutherland GR, Iliceto S, Linker DT. Cardiac ultrasound. Curchill Livingstone, 1993.
34. Soldati G. Sonographic findings in pulmonary diseases. Radiol Med 2006;111:507- 15.
35. Soldati G, Copetti R, Ecografia toracica, Edizioni Medico Scientifiche, Torino, 2006.
36. Feigenbaum H., Echocardiography, 5thed., Malvern, Pennsylvania, Lea & Febiger, 1994.
37. Stone KC, Mercer RR, Freeman BA, Chang LY, Crapo JD. Distribution of lung cell numbers and volumes between alveolar and nonalveolar tissue. Am Rev Respir
Dis. 1992;146:454-6.
38. Lange NR, Schuster DP. The measurement of lung water. Crit Care. 1999;3:R19- R24.
39. Hopkins SR, Schoene RB, Martin TR. Intense exercise impairs the integrity of the pulmonary blood-gas barrier in elite atletes. Am J Respir Crit Care Med. 1997; 155: 1090- 1094.
40. Maisel A. The coming of age of natriuretic peptides: the emperor does have clothes! J Am Coll Cardiol. 2006;47:61-4.
41. Staub NC, Nagano H and Pearce MC. Pulmonary edema in dogs , especially the sequence of fluid accumulation in lungs. J Appl Physiol 1967; 22:222-247.
42. Staub NC. Pulmonary edema. Physiol Rev. 1974; 54: 678-811.
43. Starling EH. On the absorption of fluid from the connective tissue spaces. J Phisiol 1896;19:312-317.
44. Staub NC. Pathophysiology of pulmonary edema. In: Staub NC and Taylor AE (eds). Edema. New York Raven Press,1984.
45. Schneeberger EE, Karnovsky MJ. Substructure of intercellular functions in freeze- fractured alveolar-capillary membranes of mouse lung. Circ res 1976;38:404-411.
46. Tsukimoto K, Mathieu-Costello O, Prediletto R, Elliot AR, West JB. Ultrastructural appareances of pulmonary capillaries at high transmural pressures. J
Appl Physiol 1991;71:573-582.
47. Gee MH and Williams DO. Effect of lung inflation on perivascular cuff fluid volume in isolated dog lung lobes. Microvasc Res.1979;19:209-216.
48. Garr KA, Taylor AE, Owens LJ et al. Pulmonary capillary pressure and filtration coefficient in the isolated perfused lung. Am J Phisiol 1967;213:910-914.
49. Milne ENC, Pistolesi M. Reading the chest radiograph: a physiologic approach. St Louis, Mo: Mosby –Year Book.1993;9-50.
50. Nettelbladt O, Tengblad A, Hallgren R. Lung accumulation of hyaluronan parallels pulmonary edema in experimental alveolitis. Am J Physiol Lung Cell Mol Physiol 1989;257:L379-L384.
51. Mauch C. Regulation of connective tissue turnover by cell-matrix interactions.
Arch Dermatol Res. 1998;290:S30-S36.
52. Bhattacharya J, Cruz T, Bhattacharya S, Bray BA. Hyaluronan affects extravascular water in lungs of unanestetized rabbits. J Appl Physiol. 1989;66:2595-2599.
53. Bhattacharya J , Gropper MA Staub NC. Interstitial fluid pressure gradient measured by micropucture of in the excised dog lung. J Appl Physiol. 1984:56:271- 277.
54. Nieman GF, Bredemberg CE. High surface tension pulmonary edema induced by detergent aerosol. J Appl Physiol. 1980;58:129-136.
55. Bland RD, McMillan DD, Bressack MA, Dong L. Clearance of liquid from lungs of newborn rabbits. J Appl Physiol. 1980;49:171-7.
56. Bland RD, Hansen TN, Haberkern CM, Bressack MA, Hazinski TA, Raj JU, Goldberg RB. Lung fluid balance in lambs before and after birth. J Appl Physiol. 1982;53:992-1004.
57. Daluz P, Shubia H, Weil M. Pulmonary edema related to changes in colloid osmotic and pulmonary artery pressure in patients after acute myocardial infarction.
Circulation. 1975;51:350-356.
58. Brigham KL, Woolverton WC, Blake LH, Staub NC. Increased sheep lung vascular permeability caused by pseudomonas bacteremia. J Clin Invest. 1974;54:792-804. 59. Fein A, Grossman RF, Jones JG, Overland E, Pitts L, Murray JF, Staub NC. The
value of edema fluid protein measurement in patients with pulmonary edema. Am J
Med. 1979;67:32-8.
60. Matthay MA, Hopewell PC, Adult respiratory distress syndrome. Pathogenesis and treatment. In: Simmons DH, Current Pulmology, Vol. 3, New York, John Wiley and Sons, 1981.
61. Petty TL, Asbaugh DG. The adult respiratory distress syndrome. Chest. 1971;70:233-239.
62. Hurley JV. Current views on mechanisms of pulmonary edema. J Pathol. 1978;125:59-79.
63. Mayo JR: Magnetic resonance imaging of the chest. Where we stand. Radiol Clin
North Am 1994;32:795–809.
64. Morris AH, Blatter DD, Case TA, Cutillo AG, Ailion DC, Durney CH, Johnson SA. A new nuclear magnetic resonance property of lung. J Appl Physiol.1985;58:759-62.
65. Cutillo AG, Morris AH, Ailion DC, Durney CH, Case TA. Determination of lung water content and distribution by nuclear magnetic resonance imaging. J Thorac
Imag. 1986;1:39–51.
66. Mayo JR, Muller NL, Forster BB, Okazawa M, Pare PD. Magnetic resonance imaging of hydrostatic pulmonary edema in isolated dog lungs: comparison with computed tomography. Can Assoc Radiol J 1990;41:281–286.
67. Wexler HR, Nicholson RL, Prato FS. Quantitation of lung water by nuclear magnetic resonance imaging. A preliminary study. Invest Radiol 1985;20:583–590. 68. Phillips DM, Allen PS, Man SF. Assessment of temporal changes in pulmonary
edema with NMR imaging. J Appl Physiol. 1989; 66:1197–1208.
69. Caruthers SD, Paschal CB, Pou NA, Roselli RJ, Harris TR. Regional measurements of pulmonary edema by using magnetic resonance imaging. J Appl Physiol. 1998; 84:2143–2153.
70. Cutillo AG, Morris AH, Ailion DC. Assessment of lung water distribution by nuclear magnetic resonance. A new method for quantifying and monitoring experimental lung injury. Am Rev Respir Dis. 1988;137:1371–1378.
71. Rhodes CG. Measurement of lung water using nuclear magnetic resonance imaging [letter]. Br J Radiol 1986;59:1135–1136.
72. Cutillo A, Goodrich K, Krishnamurthy G. Lung water measurement by nuclear magnetic resonance: correlation with morphometry. J Appl Physiol. 1995;79:2163– 2168.
73. Berthezene Y, Vexler V, Jerome H. Differentiation of capillary leak and hydrostatic pulmonary edema with a macromolecular MR imaging contrast agent. Radiology. 1991;181:773–777.
74. Cutillo AG, Goodrich KC, Ganesan K. Alveolar air/tissue interface and nuclear magnetic resonance behavior of normal and edematous lungs. Am J Respir Crit
75. Schuster DP. Positron emission tomography: theory and its application to the study of lung disease. Am Rev Respir Dis. 1989;139:818–840.
76. Schuster DP, Marklin GF, Mintun MA. Regional changes in extravascular lung water detected by positron emission tomography. J Appl Physiol. 1986;60:1170– 1178.
77. Velazquez M, Haller J, Amundsen T, Schuster DP. Regional lung water measurements with PET: accuracy, reproducibility, and linearity. J Nucl Med. 1991; 32:719–725.
78. Spinale FG, Reines HD, Cook MC, Crawford FA. Noninvasive estimation of extravascular lung water using bioimpedance. J Surg Res. 1989;47:535–540.
79. Zellner JL, Spinale FG, Crawford FA. Bioimpedance: a novel method for the determination of extravascular lung water. J Surg Res. 1990;48:454–459.
80. Nierman DM, Eisen DI, Fein ED, Hannon E, Mechanick JI, Benjamin E. Transthoracic bioimpedance can measure extravascular lung water in acute lung injury. J Surg Res. 1996;65:101–108.
81. Adler A, Amyot R, Guardo R, Bates JHT, Berthiaume Y. Monitoring changes in lung air and liquid volumes with electrical impedance tomography. J Appl
Physiol.1997;83:1762–1767.
82. Commissione europea, Linee guida di riferimento per la diagnostica mediante immagini. Protezione dalle radiazioni 118, Ufficio delle pubblicazioni ufficiali della Comunità Europea, Lussemburgo 2002.
83. Bock J, Lewis FR . Clinical rilevance of lung water measurement with the termal dye diluition technique. J Surg Res. 1990;48:254-265.
84. Mihm FG, Feeley TW, Jamieson SW. Thermal dye double indicator dilution measurement of lung water in man:comparison with gravimetric measurements.
Thorax. 1987;42:72-6.
85. Boyle J. Indicator mixing in the left heart and reexamination of mean circulation time. J Appl Physiol. 1974;4:541-6
86. Godje O, Peyerl M, Seebauer T, Dewald O, Reichart B. Reproducibility of double indicator dilution measurements of intrathoracic blood volume compartments, extravascular lung water and liver function. Chest. 1998;113:1070-77.
87. Sakka SG, Ruhl CC, Pfeiffer UJ, Beale R, McLuckie A, Reinhart K, Meier- Hellmann A. Assessment of cardiac preload and extravascular lung water by single transpulmonary thermodilution. Intensive Care Med. 2000;26:180-7.
88. Mulrow C, Lucey C, Farnett L. Discriminating causes of dyspnea through the clinical examination. J Gen Intern Med. 1993;8:383–92.
89. Schmitt B, Kushner M, Wiener S. The diagnostic usefulness of history of the patient with dyspnea. J Gen Intern Med. 1986;1:386–93.
90. Kasper DL, Harrison’s Principles of Internal Medicine, 16th ed., New York, The McGraw-Hill Companies, 2005, pag. 202.
91. Lien CT, Gillespie ND, Struthers AD, McMurdo ME. Heart failure in frail elderly patients: diagnostic difficulties, co-morbidities, polypharmacy and treatment dilemmas. Eur J Heart Fail. 2002;4:91-8.
92. Render ML, Weinstein AS, Blaustein AS. Left ventricular dysfunction in deteriorating patients with chronic obstructive pulmonary disease. Chest. 1995;107:162-8.
93. Stevenson LW. The limited availability of physical signs for estimating hemodynamics in chronic heart failure. JAMA 1989;261:884–8.
94. Deveraux RB, Liebson PR, Horan MJ. Recommendations concerning use of echocardiography in hypertension and general population research. Hypertension. 1987;9:97–104.
95. Wuerz RC, Meador SA. Effects of prehospital medications on mortality and length of stay in congestive heart failure. Ann Emerg Med. 1992;21:669-74.
96. Myocardial Infarction Redefined—A Consensus Document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redefinition of Myocardial Infarction. J Am Coll Cardiol. 2000;36:959-69.
97. Hunt SA; 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). 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. 2005;46:e1-82.
98. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, Smiseth OA, Gavazzi A, Haverich A, Hoes A, Jaarsma T, Korewicki J, Levy S, Linde C, Lopez-Sendon JL, Nieminen MS, Pierard L, Remme WJ; Task Froce for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur
Heart J. 2005;26:1115-40.
99. NICE. Clinical Guideline 5. Chronic heart failure. Management of chronic heart failure in adults in primary and secondary care. London, July 2003, 1-44.
100. Bonomo L, Del Favero C, Pesce B, Tamburrini O, Scotti G, Salvatore M, et al. Agenzia per i Servizi Sanitari Regionali. La diagnostica per immagini. Linee
guida. Disponibile presso il sito: www.sirm.org/professione.
101. Cowie MR, Mendez GF. BNP and congestive heart failure. Prog Cardiovasc Dis. 2002;44:293-321.
102. Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A. Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. J Am Coll Cardiol. 2002;39:202-9.
103. Wuerz RC, Meador SA. Effects of prehospital medications on mortality and length of stay in congestive heart failure. Ann Emerg Med. 1992;21:669-74. 104. 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; Breathing Not Properly Multinational Study Investigators. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J
Med. 2002;347:161-7.
105. Cowie MR, Wood DA, Coats AJ, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC. Survival of patients with a new diagnosis of heart failure: a population based study. Heart. 2000;83:505-10.
106. Nieminen MS, Bohm M, Cowie MR, Drexler H, Filippatos GS, Jondeau G, Hasin Y, Lopez-Sendon J, Mebazaa A, Metra M, Rhodes A, Swedberg K, Priori SG, Garcia MA, Blanc JJ, Budaj A, Cowie MR, Dean V, Deckers J, Burgos EF, Lekakis J, Lindahl B, Mazzotta G, Morais J, Oto A, Smiseth OA, Garcia MA, Dickstein K, Albuquerque A, Conthe P, Crespo-Leiro M, Ferrari R, Follath F, Gavazzi A, Janssens U, Komajda M, Morais J, Moreno R, Singer M, Singh S, Tendera M, Thygesen K; ESC Committe for Practice Guideline (CPG). Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology.
Eur Heart J. 2005;26:384-416.
107. Belenky A, Smith A, Zhang B, Lin S, Despres N, Wu ALH, Bluestein BL. The effect of class-specific protease inhibitors on the stabilization of B-type natriuretic peptide in human plasma. Clin Chim Acta 2004;340:163-72.
108. Shimizu H, Masuta K, Aono K, Asada H, Sasakura K, Tamaki M, et al. Molecular forms of human brain natriuretic peptide in plasma. Clin Chim Acta 2002;316:129- 35.
109. Shimizu H, Masuta K, Asada H, Sugita K, Sairenji T. Characterization of molecular forms of probrain natriuretic peptide in human plasma. Clin Chim Acta 2003;334:233-9.
110. Goetze JP. Biochemistry of Pro-B-Type natriuretic peptide-derived peptides: the endocrine heart revisited. Clin Chem 2004;50:1503-10.
111. Hunt PJ, Espiner EA, Nicholls MG, Richards AM, Yandle TG. The role of the circulation in processing pro-brain natriuretic peptide (proBNP) to ammino- terminal BNP and BNP-32. Peptides 1997;18:1475-81.
112. Wu AH, Smith A, Apple FS. Optimum blood collection intervals for B-type natriuretic peptide testing in patients with heart failure. Am J Cardiol. 2004;93:1562-3.
113. Wu AH, Smith A. Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure. Eur J Heart Fail. 2004;6:355-8.
114. Clerico A, Emdin M. Diagnostic accuracy and prognostic relevance of the measurement of the cardiac natriuretic peptides: a review. Clin Chem 2004;50:33- 50.
115. Clerico A, Recchia FA, Passino C, Emdin M. Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications. Am J Physiol Heart Circ Physiol. 2006;290:H17-29.
116. Richards M, Nicholls MG, Espiner EA, Lainchbury JG, Troughton RW, Elliott J, Frampton CM, Crozier IG, Yandle TG, Doughty R, MacMahon S, Sharpe N; Christchurch Cardioendocrine Research Group; Australia-New Zealand Heart Failure Group. Comparison of B-type natriuretic peptides for assessment of cardiac function and prognosis in stable ischemic heart disease. J Am Coll Cardiol. 2006;47:52-60.
117. Braunwald E, Zipes DP, Libby P, Heart diseases, 6th edition, WB Saunders Company, Philadelphia 2001, pagg. 534-5.
118. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440-63.
119. Zoghbi WA, Enriquez-Sarano M, Foster E, Grayburn PA, Kraft CD, Levine RA, Nihoyannopoulos P, Otto CM, Quinones MA, Rakowski H, Stewart WJ, Waggoner A, Weissman NJ; American Society of Echocardiography. Recommendations for evaluation of the severity of native valvular regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr. 2003;16:777-802.
120. Emdin M, Iervasi G, Scompenso cardiaco e sistema neuroendocrino, Pisa, Primula, 2001, pp. 76-85.
121. 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