Review of Current and Investigational Pharmacologic Agents for Acute Heart Failure Syndromes

American Journal of Cardiology

Volumn 99, Issue 2 SUPPL., 2007, Pages

  Shin, David D ^a   Brandimarte, Filippo ^b   De Luca, Leonardo ^c   Sabbah, Hani N ^d   Fonarow, Gregg C ^e   Filippatos, Gerasimos ^f   Komajda, Michel ^g   Gheorghiade, Mihai ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c EUROPEAN HOSPITAL   (Italy)

^d HENRY FORD HEALTH SYSTEM   (United States)

^e UNIVERSITY OF CALIFORNIA   (United States)

^f UNIVERSITY OF ATHENS   (Greece)

^g PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE RECEPTOR BLOCKING AGENT; CAPTOPRIL; CONIVAPTAN; DARUSENTAN; DIGOXIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; DOBUTAMINE; DOPAMINE; ENALAPRIL; ENALAPRILAT; ENDOTHELIN RECEPTOR ANTAGONIST; FUROSEMIDE; GLYCERYL TRINITRATE; INOTROPIC AGENT; ISOSORBIDE DINITRATE; MILRINONE; NAXIFYLLINE; NESIRITIDE; NITRATE; NITROPRUSSIDE SODIUM; PHOSPHODIESTERASE INHIBITOR; PLACEBO; TEZOSENTAN; TOLVAPTAN; UNINDEXED DRUG; URODILATIN; VASODILATOR AGENT; VASOPRESSIN ANTAGONIST; ZOFENOPRIL;

ACUTE HEART FAILURE; ACUTE HEART FAILURE SYNDROME; AGED; ANGINA PECTORIS; ANKLE EDEMA; ARTICLE; CARDIOVASCULAR EFFECT; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; DYSPNEA; FEMALE; FORWARD HEART FAILURE; GLOMERULUS FILTRATION RATE; HEADACHE; HEART ARRHYTHMIA; HEART ATRIUM ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART ATRIUM FLUTTER; HEART MUSCLE OXYGEN CONSUMPTION; HEART PERFORMANCE; HEART VENTRICLE ARRHYTHMIA; HEART VENTRICLE FIBRILLATION; HEART VENTRICLE TACHYCARDIA; HIGH RISK POPULATION; HOSPITAL ADMISSION; HUMAN; HYPERTENSION; HYPOTENSION; LUNG EDEMA; MAJOR CLINICAL STUDY; MALE; MORTALITY; NAUSEA; OUTCOME ASSESSMENT; PERFUSION; PRACTICE GUIDELINE; PRIORITY JOURNAL; SAFETY; SIDE EFFECT; SODIUM EXCRETION; SYNDROME; SYSTOLIC BLOOD PRESSURE; TACHYCARDIA; TREATMENT DURATION; TREATMENT OUTCOME; URINE VOLUME; VOMITING; WEIGHT REDUCTION;

AGED; BLOOD PRESSURE; CARDIAC OUTPUT, LOW; CARDIOTONIC AGENTS; FEMALE; HEART FAILURE, CONGESTIVE; HOSPITALIZATION; HUMANS; MALE; RANDOMIZED CONTROLLED TRIALS; REGISTRIES; SYNDROME;

EID: 33846219165     PISSN: 00029149     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.amjcard.2006.11.025     Document Type: Article

References (170)

1. Gheorghiade M., Zannad F., Sopko G., Klein L., Pina I.L., Konstam M.A., Massie B.M., Roland E., Targum S., Collins S.P., Filippatos G., Tavazzi L., and International Working Group on Acute Heart Failure Syndromes. Acute heart failure syndromes: current state and framework for future research. Circulation 112 (2005) 3958-3968
2. Fonarow G.C. The Acute Decompensated Heart Failure National Registry (ADHERE): opportunities to improve care of patients hospitalized with acute decompensated heart failure. Rev Cardiovasc Med 4 suppl 7 (2003) S21-S30
3. Adams Jr. K.F., Fonarow G.C., Emerman C.L., LeJemtel T.H., Costanzo M.G., Abraham W.T., Berkowitz R.L., Galvao M., Horton D.P., and ADHERE Scientific Advisory Committee and Investigators. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 149 (2005) 209-216
4. Fonarow G.C., Abraham W.T., Albert N.M., Gattis W.A., Gheorghiade M., Greenberg B., O'Connor C.M., Yancy C.W., and Young J. Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF): rationale and design. Am Heart J 148 (2004) 43-51
5. Cleland J.G., Swedberg K., Follath F., Komajda M., Cohen-Solal A., Aguilar J.C., Dietz R., Gavazzi A., Hobbs R., Korewicki J., et al., Study Group on Diagnosis of the Working Group on Heart Failure of the European Society of Cardiology. The EuroHeart Failure Survey programme: a survey on the quality of care among patients with heart failure in Europe. Part 1: patient characteristics and diagnosis. Eur Heart J 24 (2003) 442-463
6. Tavazzi L., Maggioni A.P., Lucci D., Cacciatore G., Ansalone G., Oliva F., and Porcu M. Nationwide survey on acute heart failure in cardiology ward services in Italy. Eur Heart J 27 (2006) 1207-1215
7. Zannad F., Mebazaa A., Juilliere Y., Cohen-Solal A., Guize L., Alla F., Rouge P., Blin P., Barlet M.H., Paolozzi L., et al., EFICA [Etude Française de l'Insuffisance Cardiaque Aiguë] Investigators. Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: the EFICA study. Eur J Heart Fail 8 (2006) 697-705
8. Gheorghiade M., Abraham W., Albert N., Greenberg B., O'Connor C., She L., Stough W., Yancy C., Young J., Fonarow G., and OPTIMIZE-HF [Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure] Investigators and Coordinators. Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute heart failure. JAMA 296 (2006) 2217-2226
9. Bayram M., De Luca L., Massie M.B., and Gheorghiade M. Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes. Am J Cardiol 96 suppl (2005) 47G-58G
10. Brater D.C. Diuretic therapy. N Engl J Med 339 (1998) 387-395
11. Stough W.G., O'Connor C.M., and Gheorghiade M. Overview of current noninodilator therapies for acute heart failure syndromes. Am J Cardiol 96 suppl (2005) 41G-46G
12. Lahav M., Regev A., Ra'anani P., and Theodor E. Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure. Chest 102 (1992) 725-731
13. Dormans T.P., van Meyel J.J., Gerlag P.G., Tan Y., Russel F.G., and Smits P. Diuretic efficacy of high dose furosemide in severe heart failure: bolus injection versus continuous infusion. J Am Coll Cardiol 28 (1996) 376-382
14. Cotter G., Weissgarten J., Metzkor E., Moshkovitz Y., Litinski I., Tavori U., Perry C., Zaidenstein R., and Golik A. Increased toxicity of high-dose furosemide versus low-dose dopamine in the treatment of refractory congestive heart failure. Clin Pharmacol Ther 62 (1997) 187-193
15. Cotter G., Metzkor E., Kaluski E., Faigenberg Z., Miller R., Simovitz A., Shaham O., Marghitay D., Koren M., Blatt A., et al. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. Lancet 351 (1998) 389-393
16. Hasselblad V., Stough W.G., Shah M.R., Lokhnygina J.C., Burnett J.C., Gheorghiade M., Rayburn B., Adams Jr. K.F., Francis G.S., and Califf R.M. Relation between diuretic dose and outcome in a heart failure population: results of the ESCAPE trial [abstract]. J Card Fail 11 (2005) S157
17. Emerman C.L., Marco T.D., Costanzo M.R., Peacock W.F., and ADHERE Scientific Advisory Committee. Impact of intravenous diuretics on the outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE Registry [abstract]. J Card Fail 10 (2004) S116
18. Costanzo M.R., Heywood J.T., DeMarco T., Fonarow G.C., and Wynne J.S. Impact of renal insufficiency and chronic diuretic therapy on outcome and resource utilization in patients with acute decompensated heart failure [abstract]. J Am Coll Cardiol 43 (2004) 180A
19. Ahmed A., Husain A., Love T.E., Gambassi G., Dell'italia L.J., Francis G.S., Gheorghiade M., Allman R.M., Meleth S., and Bourge R.C. Heart failure, chronic diuretic use, and increase in mortality and hospitalization: an observational study using propensity score methods. Eur Heart J 27 (2006) 1431-1439
20. Domanski M., Tian X., Haigney M., and Pitt B. Diuretic use, progressive heart failure, and death in patients in the DIG [Digitalis Investigation Group] study. J Card Fail 12 (2006) 327-332
21. Cooper H.A., Dries D.L., Davis C.E., Shen Y.L., and Domanski M.J. Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction. Circulation 100 (1999) 1311-1315
22. Eshaghian S., Horwich T.B., and Fonarow G.C. Relation of loop diuretic dose to mortality in advanced heart failure. Am J Cardiol 97 (2006) 1759-1764
23. Adams K.F., Lindenfeld J., Arnold J.M.O., Baker D.W., Barnard D.H., Baughman K.L., Boehmer J.P., Deedwania P., Dunbar S.B., Elkayam U., et al., Heart Failure Society of America. HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Cardiac Failure 12 (2006) e1-e122
24. Nieminen M.S., Bohm M., Cowie M.R., Drexler H., Filippatos G.S., Jondeau G., Hasin Y., Lopez-Sendon J., Mebazaa A., Metra M., and 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 26 (2005) 384-416
25. Moazemi K., Chana J.S., Willard A.M., and Kocheril A.G. Intravenous vasodilator therapy in congestive heart failure. Drugs Aging 20 (2003) 485-508
26. Elkayam U., Bitar F., Akhter M.W., Khan S., Patrus S., and Derakhshani M. Intravenous nitroglycerin in the treatment of decompensated heart failure: potential benefits and limitations. J Cardiovasc Pharmacol Ther 9 (2004) 227-241
27. Thadani U. Nitrate tolerance, rebound, and their clinical relevance in stable angina pectoris, unstable angina, and heart failure. Cardiovasc Drugs Ther 10 (1997) 735-742
28. Dupuis J., Lalonde G., Lemieux R., and Rouleau J.L. Tolerance to intravenous nitroglycerin in patients with congestive heart failure: role of increased intravascular volume, neurohumoral activation and lack of prevention with N-acetylcysteine. J Am Coll Cardiol 16 (1990) 923-931
29. Pizzulli L., Hagendorff A., Zirbes M., Jung W., and Luderitz B. N-acetylcysteine attenuates nitroglycerin tolerance in patients with angina pectoris and normal left ventricular function. Am J Cardiol 79 (1997) 28-33
30. Armstrong P.W., Walker D.C., Burton J.R., and Parker J.O. Vasodilator therapy in acute myocardial infarction: a comparison of sodium nitroprusside and nitroglycerin. Circulation 52 (1975) 1118-1122
31. Rossen R.M., Alderman E.L., and Harrison D.C. Circulatory response to vasodilator therapy in congestive cardiomyopathy. Br Heart J 38 (1976) 695-700
32. Hockings B.E., Cope G.D., Clarke G.M., and Taylor R.R. Randomized controlled trial of vasodilator therapy after myocardial infarction. Am J Cardiol 48 (1981) 345-352
33. Cohn J.N., Franciosa J.A., Francis G.S., Archibald D., Tristani F., Fletcher R., Montero A., Cintron G., Clarke J., Hager D., et al. Effect of short-term infusion of sodium nitroprusside on mortality rate in acute myocardial infarction complicated by left ventricular failure: results of a Veterans Administration cooperative study. N Engl J Med 306 (1982) 1129-1135
34. Johnson W., Omland T., Hall C., Lucas C., Myking O.L., Collins C., Pfeffer M., Rouleau J.L., and Stevenson L.W. Neurohormonal activation rapidly decreases after intravenous therapy with diuretics and vasodilators for class IV heart failure. J Am Coll Cardiol 39 (2002) 1623-1629
35. Levin E.R., Gardner D.G., and Samson W.K. Natriuretic peptides. N Engl J Med 339 (1998) 321-328
36. Mills R.M., LeJemtel T.H., Horton D.P., Liang C., Lang R., Silver M.A., Lui C., Chatterjee K., and Natrecor Study Group. Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol 34 (1999) 155-162
37. Colucci W.S., Elkayam U., Horton D.P., Abraham W.T., Bourge R.C., Johnson A.D., Wagoner L.E., Givertz M.M., Liang C.S., Neibaur M., Haught W.H., LeJemtel T.H., and Nesiritide Study Group. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. N Engl J Med 343 (2000) 246-253
38. Publication Committee for the VMAC [Vasodilatation in the Management of Acute CHF] Investigators. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 287 (2002) 1531-1540
39. Burger A.J., Horton D.P., LeJemtel T., Ghali J.K., Torre G., Dennish G., Koren M., Dinerman J., Silver M., Cheng M.L., Elkayam U., and Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Natrecor Therapy. Effect of nesiritide (B-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: the PRECEDENT [Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Natrecor Therapy] study. Am Heart J 144 (2002) 1102-1108
40. Topol E.J. Nesiritide-not verified. N Engl J Med 353 (2005) 113-116
41. Sackner-Bernstein J.D., Skopicki H.A., and Aaronson K.D. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 111 (2005) 1487-1491
42. Sackner-Bernstein J.D., Kowalski M., Fox M., and Aaronson K. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA 293 (2005) 1900-1905
43. Aaronson K.D., and Sackner-Bernstein J.D. Risk of death associated with nesiritide in patients with acutely decompensated heart failure [research letter]. JAMA 296 (2006) 1465-1466
44. Gheorghiade M., Hall V., Lakier J.B., and Goldstein S. Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure. J Am Coll Cardiol 13 (1989) 134-142
45. Annane D., Bellissant E., Pussard E., Asmar R., Lacombe F., Lanata E., Madonna O., Safar M., Giudicelli J.F., and Gajdos P. Placebo-controlled randomized double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema. Circulation 95 (1996) 1316-1324
46. Swedberg K., Held P., Kjekshus J., Rasmussen K., Ryden L., and Wedel H. Effects of the early administration of enalapril on mortality in patients with acute myocardial infarction: results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med 327 (1992) 678-684
47. Ambrosioni E., Borghi C., Magnani B., and The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators. The effect of the angiotensin-converting enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med 332 (1995) 80-85
48. Latini R., Tognoni G., Maggioni A.P., et al., Angiotensin-converting Enzyme Inhibitor MyocardialInfarction Collaborative Group. Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. J Am Coll Cardiol 35 (2000) 1801-1807
49. Hunt S.A., Abraham W.T., Chin M.H., Feldman A.M., Francis G.S., Ganiats T.G., Jessup M., Konstam M.A., Mancini D.M., Michl K., et al., American College of Cardiology/ American Heart Association Task Force on Practice Guidelines. 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). Circulation 112 (2005) e154-e235
50. Adams Jr. K.F., De Marco T., Berkowitz R., and Chand S. Inotrope use and negative outcomes in treatment of acute heart failure in patients with preserved systolic function: data from the ADHERE database [abstract]. Circulation 108 (2003) IV-695
51. Abraham W.T., Adams Jr. K.F., Fonarow G.C., Costanzo M.R., Berkowitz R.L., Lejemtel T.H., Cheng M.L., and Wynne J. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol 46 (2005) 57-64
52. Perna E.R., Macin S.M., Parras J.I., Pantich R., Farias E.F., Badaracco J.R., Jantus E., Medina F., and Brizuela M. Cardiac troponin T levels are associated with poor short- and long-term prognosis in patients with acute cardiogenic pulmonary edema. Am Heart J 143 (2002) 814-820
53. Horwich T.B., Patel J., MacLellan W.R., and Fonarow G.C. Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 108 (2003) 833-838
54. Perna E.R., Macin S.M., Cimbaro Canella J.P., Alvarenga P.M., Rios N.G., Pantich R., Augier N., Farias E.F., Jantus E., Brizuela M., and Medina F. Minor myocardial damage detected by troponin T is a powerful predictor of long-term prognosis in patients with acute decompensated heart failure. Int J Cardiol 99 (2005) 253-261
55. Gheorghiade M., Gattis Stough W., Adams Jr. K.F., Jaffe A.S., Hasselblad V., and O'Connor C.M. The Pilot Randomized Study of Nesiritide Versus Dobutamine in Heart Failure (PRESERVD-HF). Am J Cardiol 96 suppl (2005) 18G-25G
56. Treasure C.B., Vita J.A., Cox D.A., Fish R.D., Gordon J.B., Mudge G.H., Colucci W.S., Sutton M.G., Selwyn A.P., Alexander R.W., et al. Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy. Circulation 81 (1990) 772-779
57. Unverferth D.V., Magorien R.D., Lewis R.P., and Leier C.V. The role of subendocardial ischemia in perpetuating myocardial failure in patients with nonischemic congestive cardiomyopathy. Am Heart J 105 (1983) 176-179
58. van den Heuvel A.F., van Veldhuisen D.J., van der Wall E.E., Blanksma P.K., Siebelink H.M., Vaalburg W.M., van Gilst W.H., and Crijns H.J. Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy. J Am Coll Cardiol 35 (2000) 19-28
59. Guth B.D., Schulz R., and Heusch G. Time course and mechanisms of contractile dysfunction during acute myocardial ischemia. Circulation 87 suppl (1993) IV35-IV42
60. Schulz R., Rose J., Martin C., Brodde O.E., and Heusch G. Development of short-term myocardial hibernation: its limitation by the severity of ischemia and inotropic stimulation. Circulation 88 (1993) 684-695
61. Brunton L.L., Lanzo J.S., and Parker K.L. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 11th ed. (2006), McGraw-Hill, Inc, New York 2021
62. Jain P., Massie B.M., Gattis W.A., Klein L., and Gheorghiade M. Current medical treatment for the exacerbation of chronic heart failure resulting in hospitalization. Am Heart J 145 suppl (2003) S3-S17
63. Packer M., Carver J.R., Rodeheffer R.J., Ivanhoe R.J., DiBianco R., Zeldis S.M., Hendrix G.H., Bommer W.J., Elkayam U., Kukin M.L., et al., PROMISE Study Research Group. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med 325 (1991) 1468-1475
64. Lubsen J., Just H., Hjalmarsson A.C., La Framboise D., Remme W.J., Heinrich-Nols J., Dumont J.M., and Seed P. Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial. Heart 76 (1996) 223-231
65. Hampton J.R., van Veldhuisen D.J., Kleber F.X., Cowley A.J., Ardia A., Block P., Cortina A., Cserhalmi L., Follath F., Jensen G., et al., Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME II) Investigators. Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Lancet 349 (1997) 971-977
66. Cohn J.N., Goldstein S.O., Greenberg B.H., Lorell B.H., Bourge R.C., Jaski B.E., Gottlieb S.O., McGrew III F., DeMets D.L., White B.G., and Vesnarinone Trial Investigators. A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. N Engl J Med 339 (1998) 1810-1816
67. Califf R.M., Adams Jr. K.F., McKenna W.J., Gheorghiade M., Uretsky B.F., McNulty S.E., Darius H., Schulman K., Zannad F., Handberg-Thurmond E., et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: the Flolan International Randomized Survival Trial (FIRST). Am Heart J 134 (1997) 44-54
68. O'Connor C.M., Gattis W.A., Uretsky B.F., Adams Jr. K.F., McNulty S.E., Grossman S.H., McKenna W.J., Zannad F., Swedberg K., Gheorghiade M., and Califf R.M. Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST). Am Heart J 138 (1999) 78-86
69. Liang C.S., Sherman L.G., Doherty J.U., Wellington K., Lee V.W., and Hood Jr. W.B. Sustained improvement of cardiac function in patients with congestive heart failure after short-term infusion of dobutamine. Circulation 69 (1984) 113-119
70. Dies F., Krell M.J., and Whitlow P. Intermittent dobutamine in ambulatory outpatients with chronic cardiac failure [abstract]. Circulation 74 (1986) II-38
71. Elis A., Bental T., Kimchi O., Ravid M., and Lishner M. Intermittent dobutamine treatment in patients with chronic refractory congestive heart failure: a randomized, double-blind, placebo-controlled study. Clin Pharmacol Ther 63 (1998) 682-685
72. Maskin C.S., Ocken S., Chadwick B., and LeJemtel T.H. Comparative systemic and renal effects of dopamine and angiotensin-converting enzyme inhibition with enalaprilat in patients with heart failure. Circulation 72 (1985) 846-852
73. Baim D.S., McDowell A.V., Cherniles J., Monrad E.S., Parker J.A., Edelson J., Braunwald E., and Grossman W. Evaluation of a new bipyridine inotropic agent-milrinone-in patients with severe congestive heart failure. N Engl J Med 309 (1983) 748-756
74. Monrad E.S., Baim D.S., Smith H.S., and Lanoue A.S. Milrinone, dobutamine, and nitroprusside: comparative effects on hemodynamics and myocardial energetics in patients with severe congestive heart failure. Circulation 73 (1986) III-168-III-174
75. Anderson J.L. Hemodynamic and clinical benefits with intravenous milrinone in severe chronic heart failure: results of a multicenter study in the United States. Am Heart J 121 (1991) 1956-1964
76. Cuffe M.S., Califf R.M., Adams Jr. K.F., Benza R., Bourge R., Colucci W.S., Massie B.M., O'Connor C.M., Pina I., Quigg R., Silver M.A., and Gheorghiade M. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA 287 (2002) 1541-1547
77. Felker G.M., Benza R.L., Chandler A.B., Leimberger J.D., Cuffe M.S., Califf R.M., Gheorghiade M., and O'Connor C.M. Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study. J Am Coll Cardiol 41 (2003) 997-1003
78. Gheorghiade M., van Veldhuisen D.J., and Colucci W.S. Contemporary use of digoxin in the management of cardiovascular disorders. Circulation 113 (2006) 2556-2564
79. Goldstein R.A., Passamani E.R., and Roberts R. A comparison of digoxin and dobutamine in patients with acute infarction and cardiac failure. N Engl J Med 303 (1980) 846-850
80. Tisdale J.E., and Gheorghiade M. Acute hemodynamic effects of digoxin alone or in combination with other vasoactive agents in patients with congestive heart failure. Am J Cardiol 69 (1992) 34G-47G
81. Singh K., Xiao L., Remondino A., Sawyer D.B., and Colucci W.S. Adrenergic regulation of cardiac myocyte apoptosis. J Cell Physiol 189 (2001) 257-265
82. Goldsmith S.R. Vasopressin: a therapeutic target in congestive heart failure?. J Card Fail 5 (1999) 347-356
83. Szatalowicz V.L., Arnold P.E., Chaimovitz C., Bichet D., and Schrier R.W. Radioimmunoassay of plasma arginine vasopressin in hyponatremic patients with congestive heart failure. N Engl J Med 305 (1981) 263-266
84. Riegger G.A.J., Liebau G., and Kochsiek K. Antidiuretic hormone in congestive heart failure. Am J Med 72 (1982) 49-52
85. Schrier R.W., and Abraham W.T. Hormones and hemodynamics in heart failure. N Engl J Med 341 (1999) 577-585
86. Klein L., O'Connor C.M., Leimberger J.D., Gattis-Stough W., Pina I.L., Felker G.M., Adams Jr. K.F., Califf R.M., Gheorghiade M., and OPTIME-CHF Investigators. Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study. Circulation 111 (2005) 2454-2460
87. 2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 107 (2003) 2690-2696
88. Gheorghiade M., Gattis W.A., O'Connor C.M., Adams Jr. K.F., Elkayam U., Barbagelata A., Ghali J.K., Benza R.L., McGrew F.A., Klapholz M., Ouyang J., Orlandi C., and Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure (ACTIV in CHF) Investigators. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 291 (2004) 1963-1971
89. Gheorghiade M., Orlandi C., Burnett J.C., Demets D., Grinfeld L., Maggioni A., Swedberg K., Udelson J.E., Zannad F., Zimmer C., and Konstam M.A. Rationale and design of the multicenter, randomized, double-blind, placebo-controlled study to evaluate the Efficacy of Vasopressin antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST). J Card Fail 11 (2005) 260-269
90. 2 vasopressin receptor antagonist, in patients with advanced heart failure. Circulation 104 (2001) 2417-2423
91. 1 receptor antagonists and the kidney. Curr Opin Nephrol Hypertens 12 (2003) 497-502
92. 1-receptor antagonists in congestive heart failure. Drugs 61 (2001) 1387-1393
93. 1 receptor blockade induces natriuresis with a favorable renal hemodynamic profile in SHHF/Mcc-fa(cp) rats chronically treated with salt and furosemide. J Pharmacol Exp Ther 299 (2001) 978-987
94. 1 on ventricular and renal function. J Cardiovasc Pharmacol 38 (2001) 618-624
95. 1-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure. J Am Coll Cardiol 35 (2000) 56-59
96. 1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation 105 (2002) 1348-1353
97. 1 receptor attenuates cardiac hypertrophy and prevents heart failure in murine left ventricular pressure-overload model. Circ Res 93 (2003) 759-766
98. Forssmann W., Meyer M., and Forssmann K. The renal urodilatin system: clinical implications. Cardiovasc Res 51 (2001) 450-462
99. Saxenhofer H., Raselli A., Weidmann P., Forssmann W.G., Bub A., Ferrari P., and Shaw S.G. Urodilatin, a natriuretic factor from kidneys, can modify renal and cardiovascular function in men. Am J Physiol 259 (1990) F832-F838
100. Kentsch M., Ludwig D., Drummer C., Gerzer R., and Muller-Esch G. Haemodynamic and renal effects of urodilatin in healthy volunteers. Eur J Clin Invest 22 (1992) 319-325
101. Bestle M.H., Olsen N.V., Christensen P., Jensen B.V., and Bie P. Cardiovascular, endocrine, and renal effects of urodilatin in normal humans. Am J Physiol 276 (1999) R684-R695
102. Kentsch M., Ludwig D., Drummer C., Gerzer R., and Muller-Esch G. Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure. Eur J Clin Invest 22 (1992) 662-669
103. Elsner D., Muders F., Muntze A., Kromer E.P., Forssmann W.G., and Riegger G.A. Efficacy of prolonged infusion of urodilatin [ANP-(95-126)] in patients with congestive heart failure. Am Heart J 129 (1995) 766-773
104. Mitrovic V., Luss H., Nitsche K., Forssmann K., Maronde E., Fricke K., Forssmann W.G., and Meyer M. Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial [clinical investigation]. Am Heart J 150 (2005) 1239
105. Mitrovic V., Seferovic P.M., Simeunovic D., Ristic A.D., Miric M., Moiseyev V.S., Kobalava Z., Nitsche K., Forssmann W.G., Luss H., and Meyer M. Haemodynamic and clinical effects of ularitide in decompensated heart failure. Eur Heart J 27 (2006) 2823-2832
106. Levin E.R. Endothelins. N Engl J Med 333 (1995) 356-363
107. Teerlink J.R. The role of endothelin in the pathogenesis of heart failure. Curr Cardiol Rep 4 (2002) 206-212
108. Aronson D., and Burger A.J. Neurohumoral activation and ventricular arrhythmias in patients with decompensated congestive heart failure role of endothelin. PACE Pacing Clin Electrophysiol 26 (2003) 703-710
109. Aronson D., and Burger A.J. Neurohormonal prediction of mortality following admission for decompensated heart failure. Am J Cardiol 91 (2003) 245-248
110. Clozel M., Ramuz H., Clozel J.P., Breu V., Hess P., Loffler B.M., Coassolo P., and Roux S. Pharmacology of tezosentan, new endothelin receptor antagonist designed for parenteral use. J Pharmacol Exp Ther 290 (1999) 840-846
111. Teerlink J.R., Massie B.M., Cleland J.G.F., Tzivoni D., and RITZ-1 Investigators. A double-blind, parallel-group, multi-center, placebo-controlled study to investigate the efficacy and safety of tezosentan in reducing symptoms in patients with acute decompensated heart failure [abstract]. Circulation 104 (2001) II-526
112. Torre-Amione G., Young J.B., Colucci W.S., Lewis B.S., Pratt C., Cotter G., Stangl K., Elkayam U., Teerlink J.R., Frey A., Rainisio M., and Kobrin I. Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol 42 (2003) 140-147
113. O'Connor C.M., Gattis W.A., Adams Jr. K.F., Hasselblad V., Chandler B., Frey A., Kobrin I., Rainisio M., Shah M.R., Teerlink J., and Gheorghiade M. Tezosentan in patients with acute heart failure and acute coronary syndromes: results of the Randomized Intravenous TeZosentan Study (RITZ-4). J Am Coll Cardiol 41 (2003) 1452-1457
114. Kaluski E., Kobrin I., Zimlichman R., Marmor A., Krakov O., Milo O., Frey A., Kaplan S., Krakover R., Caspi A., Vered Z., and Cotter G. RITZ-5: randomized intravenous TeZosentan (an endothelin-A/B antagonist) for the treatment of pulmonary edema: a prospective, multicenter, double-blind, placebo-controlled study. J Am Coll Cardiol 41 (2003) 204-210
115. Teerlink J.R., McMurray J.J., Bourge R.C., Cleland J.G., Cotter G., Jondeau G., Krum H., Metra M., O'Connor C.M., Parker J.D., et al. Tezosentan in patients with acute heart failure: design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study (VERITAS). Am Heart J 150 (2005) 46-53
116. Niu C, Cox D, Lee K, Sylvester S, Sueoka S, Qian X, Feng B, Malik F, Morgans D Jr, Hartman J, Sakowicz R, Elias K. Cellular responses of the myosin activator CK-0689705 in normal and heart failure models. Presented at the 44th Annual Meeting of the American Society of Cell Biology; December 4-8, 2004; Washington, DC.
117. Rodriguez H, Sylvester S, Qian X, Morgan B, Morgans D Jr, Malik F, Sakowicz R. Activation of cardiac sarcomere ATPase by CK-1122534, a small molecule agent that specifically targets cardiac myosin. Presented at the 44th Annual Meeting of the American Society of Cell Biology; December 4-8, 2004; Washington, DC.
118. Niu C, Anderson R, Cox D, Qian X, Morgan B, Malik F, Morgans D, Jr, Elias K. The cardiac myosin activator, CK-1122534, increases contractility in adult cardiac myocytes without altering the calcium transient. Presented at the 44th Annual Meeting of the American Society of Cell Biology; December 4-8, 2004; Washington, DC.
119. Malik F, Elias KA, Finer JT, Morgan BP, Sakowicz R, Anderson R, Baliga R, Conn L, Cox D, Garard M, et al. Direct activation of cardiac myosin by CK-1827452 improves cardiac function in a dog heart failure model. Presented at the 9th Annual Scientific Meeting of the Heart Failure Society of America; September 18-21, 2005; Boca Raton, Florida.
120. Anderson RL, Sueoka SH, Rodriguez HM, Lee KH, Cox DR, Kawas R, Morgan BP, Sakowicz R, Morgans DJ, Jr, Malik F, Elias KA. In vitro and in vivo efficacy of the cardiac myosin activator CK-1827452. Presented at the 45th Annual Meeting of the American Society of Cell Biology; December 10-14, 2005; San Francisco, California.
121. Stanley W.C., Lopaschuk G.D., Hall J.L., and McCormack J.G. Regulation of myocardial carbohydrate metabolism under normal and ischemic conditions: potential for pharmacological interventions. Cardiovasc Res 33 (1997) 243-257
122. Liedtke A.J. Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog Cardiovasc Dis 23 (1981) 321-336
123. Stanley W.C. Cardiac energetics during ischaemia and the rationale for metabolic interventions. Coron Artery Dis 12 suppl (2001) S3-S7
124. Taegtmeyer H., Roberts A.F., and Raine A.E. Energy metabolism in reperfused heart muscle: metabolic correlates to return of function. J Am Coll Cardiol 6 (1985) 864-870
125. Depre C., Vanoverschelde J.L., and Taegtmeyer H. Glucose for the heart. Circulation 99 (1999) 578-588
126. Lopaschuk G.D., Wambolt R.B., and Barr R.L. An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effects of high levels of fatty acids during aerobic reperfusion of ischemic hearts. J Pharmacol Exp Ther 264 (1993) 135-144
127. Murnaghan M.F. Effect of fatty acids on the ventricular arrhythmia threshold in the isolated heart of the rabbit. Br J Pharmacol 73 (1981) 909-915
128. Kennedy J.A., Kiosoglous A.J., Murphy G.A., Pelle M.A., and Horowitz J.D. Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart. J Cardiovasc Pharmacol 36 (2000) 794-801
129. Cole P.L., Beamer A.D., McGowan N., Cantillon C.O., Benfell K., Kelly R.A., Hartley L.H., Smith T.W., and Antman E.M. Efficacy and safety of perhexiline maleate in refractory angina. Circulation 81 (1990) 1260-1270
130. Barry W.H., Horowitz J.D., and Smith T.W. Comparison of negative
131. Jeffrey F.M., Alvarez L., Diczku V., Sherry A.D., and Malloy C.R. Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. J Cardiovasc Pharmacol 25 (1995) 469-472
132. Horowitz J.D., and Mashford M.L. Perhexiline maleate in the treatment of severe angina pectoris. Med J Aust 1 (1979) 485-488
133. Roberts R.K., Cohn D., Petroff V., and Seneviratne B. Liver disease induced by perhexiline maleate. Med J Aust 2 (1981) 553-554
134. Bouche P., Bousser M.G., Peytour M.A., and Cathala H.P. Perhexiline maleate and peripheral neuropathy. Neurology 29 (1979) 739-743
135. Lee L., Campbell R., Scheuermann-Freestone M., Taylor R., Gunaruwan P., Williams L., Ashrafian H., Horowitz J., Fraser A.G., Clarke K., and Frenneaux M. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation 112 (2005) 3280-3288
136. Gheorghiade M., Teerlink J.R., and Mebazaa A. Pharmacology of new agents for acute heart failure syndromes. Am J Cardiol 96 (2005) 68G-73G
137. De Luca L., Colucci W.S., Nieminen M.S., Massie B.M., and Gheorghiade M. Evidence-based use of levosimendan in different clinical settings. Eur Heart J 27 (2006) 1908-1920
138. Haikala H., and Linden I.B. Mechanisms of action of calcium-sensitizing drugs. J Cardiovasc Pharmacol 26 suppl 1 (1995) S10-S19
139. Tachibana H., Cheng H., Ukai T., Igawa A., Zhang Z., Little W., and Cheng C. Levosimendan improves left ventricular systolic and diastolic performance at rest and during exercise after heart failure. Am J Physiol Heart Circ Physiol 288 (2005) H914-H922
140. Hasenfuss G., Pieske B., Castell M., Kretschmann B., Maier L.S., and Just H. Influence of the novel inotropic agent levosimendan on isometric tension and calcium cycling in failing human myocardium. Circulation 98 (1998) 2141-2147
141. Ukkonen H., Saraste M., Akkila J., Knuuti M.J., Lehikoinen P., Nagren K., Lehtonen L., and Voipio-Pulkki L.M. Myocardial efficiency during calcium sensitization with levosimendan: a noninvasive study with positron emission tomography and echocardiography in healthy volunteers. Clin Pharmacol Ther 61 (1997) 596-607
142. Ukkonen H., Saraste M., Akkila J., Knuuti J., Karanko M., Iida H., Lehikoinen P., Nagren K., Lehtonen L., and Voipio-Pulkki L.M. Myocardial efficiency during levosimendan infusion in congestive heart failure. Clin Pharmacol Ther 68 (2000) 522-531
143. Kersten J.R., Montgomery M.W., Pagel P.S., and Warltier D.C. Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of KATP channels. Anesth Analg 90 (2000) 5-11
144. Sonntag S., Sundberg S., Lehtonen L.A., and Kleber F.X. The calcium sensitizer levosimendan improves the function of stunned myocardium after percutaneous transluminal coronary angioplasty in acute myocardial ischemia. J Am Coll Cardiol 43 (2004) 2177-2182
145. Kivikko M., Lehtonen L., and Colucci W.S. Sustained hemodynamic effects of intravenous levosimendan. Circulation 107 (2003) 81-86
146. McBride B.F., and White C.M. Levosimendan: implications for clinicians. J Clin Pharmacol 43 (2003) 1071-1081
147. Nieminen M.S., Akkila J., Hasenfuss G., Kleber F.X., Lehtonen L.A., Mitrovic V., Nyquist O., and Remme W.J. Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. J Am Coll Cardiol 36 (2000) 1903-1912
148. Slawsky M.T., Colucci W.S., Gottlieb S.S., Greenberg B.H., Haeusslein E., Hare J., Hutchins S., Leier C.V., LeJemtel T.H., Loh E., et al., Study Investigators. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Circulation 102 (2000) 2222-2227
149. Moiseyev V.S., Poder P., Andrejevs N., Ruda M.Y., Golikov A.P., Lazebnik L.B., Kobalava Z.D., Lehtonen L.A., Laine T., Nieminen M.S., Lie K.I., and RUSSLAN [Randomised stUdy on Safety and effectivenesS of Levosimendan in patients with left ventricular failure due to an Acute myocardial iNfarct] Study Investigators. Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction: a randomized, placebo-controlled, double-blind study (RUSSLAN). Eur Heart J 23 (2002) 1422-1432
150. Follath F., Cleland J.G., Just H., Papp J.G., Scholz H., Peuhkurinen K., Harjola V.P., Mitrovic V., Abdalla M., Sandell E.P., and Lehtonen L. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomized double-blind trial. Lancet 360 (2002) 196-202
151. Zairis MN, Apostolatos C, Anastassiadis F, Kouris N, Grassos H, Sifaki M, Babalis D, Foussas S. Comparison of the effect of levosimendan, or dobutamine or placebo in chronic low output decompensated heart failure: CAlcium Sensitizer or Inotrope or NOne in low output heart failure (CASINO) study. In: Program and Abstracts of the European Society of Cardiology, Heart Failure Update 2004; June 12-15, 2004; Wroclaw, Poland. Abstract 273.
152. Cleland J.G., Ghosh J., Freemantle N., Kaye G.C., Nasir M., Clark A.L., and Coletta A.P. Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-Lipids and cardiac resynchronisation therapy in heart failure. Eur J Heart Fail 6 (2004) 501-508
153. Coletta A.P., Cleland J.G., Freemantle N., and Clark A.L. Clinical trials update from the European Society of Cardiology Heart Failure meeting: SHAPE, BRING-UP 2 VAS, COLA II, FOSIDIAL, BETACAR, CASINO and meta-analysis of cardiac resynchronisation therapy. Eur J Heart Fail 6 (2004) 673-676
154. Packer M., Colucci W.S., Fisher L., Massie B.M., Teerlink J.R., Young J.B., and Garratt C.J. Development of a comprehensive new endpoint for the evaluation of new treatments for acute decompensated heart failure: results with levosimendan in the REVIVE-1 study [abstract]. J Card Fail 9 (2003) S61
155. Johansson S., Apajasalo M., Sarapohja T., and Garratt C. Effect of levosimendan treatment on length of hospital and intensive care stay in the REVIVE I study [abstract]. Crit Care 8 suppl 1 (2004) P88
156. Packer M. The Randomized multicenter EValuation of Intravenous leVosimendan Efficacy-2 (REVIVE-2) trial [late-breaking clinical trial]. American Heart Association, Annual Scientific Session; November 13-16, 2005; Dallas, Texas.
157. Mebazaa A., Cohen-Solal A., Kleber F.X., Nieminen M., Packer M., Pocock S.J., Põder P., Sarapohja T., and Kivikko M. Study design of a mortality trial with intravenous levosimendan (the SURVIVE study) in patients with acutely decompensated heart failure [abstract]. Crit Care 8 suppl 1 (2004) 87
158. Mebazaa A. The SURVival of Patients with Acute Heart Failure in Need of IntraVEnous Inotropic Support (SURVIVE) trial [late-breaking clinical trials]. American Heart Association, Annual Scientific Session; November 13-16, 2005; Dallas, Texas.
159. Micheletti R., Mattera G.G., Rocchetti M., Schiavone A., Loi M.F., Zaza A., Gagnol R.J., De Munari S., Melloni P., Carminati P., Bianchi G., and Ferrari P. Pharmacological profile of the novel inotropic agent (E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride (PST2744). J Pharmacol Exp Ther 303 (2002) 592-600
160. +-ATPase inhibitors derived from a 5α,14α -androstane scaffold as positive inotropic compounds. J Med Chem 56 (2003) 3644-3654
161. + pump inhibition: evaluation of electrophysiological mechanisms. J Pharmacol Exp Ther 305 (2003) 765-771
162. + pump inhibitors with different toxicity: digoxin and PST2744 [(E,Z)-3-((2-aminoethoxy)imino)androstane-6,17-dione hydrochloride]. J Pharmacol Exp Ther 313 (2005) 207-215
163. Adamson P.B., Vanoli E., Mattera G.G., Germany R., Gagnol J.P., Carminati P., and Schwartz P.J. Hemodynamic effects of a new inotropic compound, PST-2744, in dogs with chronic ischemic heart failure. J Cardiovasc Pharmacol 42 (2003) 169-173
164. Barassi P., Ferrandi M., Bianchi G., and Ferrari P. Istaroxime stimulates SERCA2a activity in animal and human failing heart preparations [abstract]. J Card Fail 11 (2005) S154
165. Imai M., Gheorghiade M., Cowart D., Zhang D., Amato A., Carminati P., and Sabbah H.N. Intravenous istaroxime improves left ventricular systolic function in dogs with advanced heart failure without increasing myocardial oxygen consumption [abstract]. J Card Fail 11 (2005) S95
166. Makato I., Gheorghiade M., Cowart D., Zhang D., Amato A., Carminati P., and Sabbah H.N. Intravenous istaroxime improves left ventricular lusitropic properties in dogs with advanced heart failure [abstract]. J Card Fail 11 (2005) S154
167. Mattera G.G., Loi F., Adamson P.B., Gagnol J.P., Vanoli E., Borsini F., and Carminati P. Istaroxime, a novel luso-inotropic agent, improves cardiac function in dogs with acute LV dysfunction: a pilot study [abstract]. J Card Fail 11 (2005) S160
168. Micheletti R., Palazzo F., Barassi P., Giacalone G., Ferrandi M., Schiavone A., Moro B., Parodi O., Ferrari P., and Bianchi G. Istaroxime, a stimulator of sarcoplasmic reticulum calcium adenosine triphosphatase isoforms 2a activity, as a novel therapeutic approach to heart failure. Am J Cardiol 99 suppl (2007) 24A-32A
169. Mattera G.G., Lo Giudice P., Loi F.M.P., Vanoli E., Gagnol J.-P., Borsini F., and Carminati P. Istaroxime: a new luso-inotropic agent for heart failure. Am J Cardiol 99 suppl (2007) 33A-40A
170. Sabbah H.N., Imai M., Cowart D., Amato A., Carminati P., and Gheorghiade M. Hemodynamic properties of a new generation positive luso-inotropic agent for the acute treatment of advanced heart failure. Am J Cardiol 99 suppl (2007) 41A-46A