Traditional heart failure medications and sudden cardiac death prevention: A review

Journal of Cardiovascular Pharmacology and Therapeutics

Volumn 18, Issue 5, 2013, Pages 412-426

  Al Chekakie, M Obadah ^a  

^a Cheyenne Regional Medical Center   (United States)

Author keywords

heart failure; renin angiotensin aldosterone system; statin; sudden cardiac death

Indexed keywords

ANGIOTENSIN II; ANTIARRHYTHMIC AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BISOPROLOL; BUCINDOLOL; C REACTIVE PROTEIN; CANDESARTAN; CAPTOPRIL; CARVEDILOL; CATECHOLAMINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; ENDOTHELIAL NITRIC OXIDE SYNTHASE; EPLERENONE; HYDRALAZINE PLUS ISOSORBIDE DINITRATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; METOPROLOL; METOPROLOL SUCCINATE; NEBIVOLOL; NORADRENALIN; PERINDOPRIL; PLACEBO; POTASSIUM; PROPRANOLOL; RAMIPRIL; RENIN; ROSUVASTATIN; TRANDOLAPRIL; TRANSFORMING GROWTH FACTOR BETA1; VALSARTAN;

ATRIOVENTRICULAR CONDUCTION; AUTOPSY; BLOOD BRAIN BARRIER; CARDIAC RESYNCHRONIZATION THERAPY; CARDIOVASCULAR MORTALITY; CORONARY ARTERY DISEASE; DIABETES MELLITUS; DIASTOLIC DYSFUNCTION; DRUG DOSAGE FORM COMPARISON; DRUG EFFICACY; DYING; EXERCISE; FOLLOW UP; FUNDING; HEART ARREST; HEART CATHETERIZATION; HEART FAILURE; HEART INFARCTION; HEART LEFT VENTRICLE EJECTION FRACTION; HEART LEFT VENTRICLE FUNCTION; HEART MUSCLE ISCHEMIA; HEART MUSCLE OXYGEN CONSUMPTION; HEART RATE; HEART VENTRICLE ARRHYTHMIA; HEART VENTRICLE ENDDIASTOLIC PRESSURE; HEART VENTRICLE REMODELING; HIGH RISK PATIENT; HUMAN; IMPLANTABLE CARDIOVERTER DEFIBRILLATOR; KIDNEY FUNCTION; LIPID PEROXIDATION; MITOGENESIS; MORTALITY; POSITIVE FEEDBACK; PRIMARY PREVENTION; PRIORITY JOURNAL; PROGNOSIS; PROTEIN EXPRESSION; RECEPTOR DENSITY; REVIEW; RISK FACTOR; SECONDARY PREVENTION; SUDDEN CARDIAC DEATH; SYSTOLIC HEART FAILURE;

HEART FAILURE; RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM; STATIN; SUDDEN CARDIAC DEATH;

ANIMALS; ANTI-ARRHYTHMIA AGENTS; CARDIOVASCULAR AGENTS; DEATH, SUDDEN, CARDIAC; DEFIBRILLATORS, IMPLANTABLE; HEART FAILURE; HUMANS; INCIDENCE; PRACTICE GUIDELINES AS TOPIC;

EID: 84882256450     PISSN: 10742484     EISSN: 19404034     Source Type: Journal    
DOI: 10.1177/1074248413491496     Document Type: Review

References (147)

1. Escobedo LG, Zack MM. Comparison of sudden and nonsudden coronary deaths in the united states. Circulation. 1996 ; 93 (11). 2033-2036
2. Zheng ZJ, Croft JB, Giles WH, Mensah GA. Sudden cardiac death in the United States, 1989 to 1998. Circulation. 2001 ; 104 (18). 2158-2163
3. Chugh SS, Jui J, Gunson K, et al. Current burden of sudden cardiac death: multiple source surveillance versus retrospective death certificate-based review in a large U.S. community. J Am Coll Cardiol. 2004 ; 44 (6). 1268-1275
4. Cobb LA, Fahrenbruch CE, Olsufka M, Copass MK. Changing incidence of out-of-hospital ventricular fibrillation, 1980-2000. JAMA. 2002 ; 288 (23). 3008-3013
5. Zipes DP, Camm AJ, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American college of cardiology/American heart association task force and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death). J Am Coll Cardiol. 2006 ; 48 (5). e247 - e346
6. Kong MH, Fonarow GC, Peterson ED, et al. Systematic review of the incidence of sudden cardiac death in the united states. J Am Coll Cardiol. 2011 ; 57 (7). 794-801
7. Every NR, Parsons L, Hlatky MA, et al. Use and accuracy of state death certificates for classification of sudden cardiac deaths in high-risk populations. Am Heart J. 1997 ; 134 (6). 1129-1132
8. Engel LW, Strauchen JA, Chiazze L, Heid M. Accuracy of death certification in an autopsied population with specific attention to malignant neoplasms and vascular diseases. Am J Epidemiol. 1980 ; 111 (1). 99-112
9. Modelmog D, Rahlenbeck S, Trichopoulos D. Accuracy of death certificates: a population-based, complete-coverage, one-year autopsy study in east Germany. Cancer Causes & Control. 1992 ; 3 (6). 541-546
10. Roulson J, Benbow EW, Hasleton PS. Discrepancies between clinical and autopsy diagnosis and the value of post mortem histology; a meta-analysis and review. Histopathology. 2005 ; 47 (6). 551-559
11. Nichol G, Thomas E, Callaway CW, et al. Regional variation in out-of-hospital cardiac arrest incidence and outcome. JAMA. 2008 ; 300 (12). 1423-1431
12. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005 ; 352 (3). 225-237
13. Buxton AE, Lee KL, Hafley GE, et al. Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease: lessons from the MUSTT study. J Am Coll Cardiol. 2007 ; 50 (12). 1150-1157
14. Stecker EC, Vickers C, Waltz J, et al. Population-based analysis of sudden cardiac death with and without left ventricular systolic dysfunction: two-year findings from the Oregon sudden unexpected death study. J Am Coll Cardiol. 2006 ; 47 (6). 1161-1166
15. Cabassi A, Vinci S, Calzolari M, Bruschi G, Borghetti A. Regional sympathetic activity in pre-hypertensive phase of spontaneously hypertensive rats. Life Sci. 1998 ; 62 (12). 1111-1118
16. Quinones MA, Greenberg BH, Kopelen HA, et al. Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: Significance of left ventricular hypertrophy. Studies of left ventricular dysfunction. J Am Coll Cardiol. 2000 ; 35 (5). 1237-1244
17. Turakhia MP, Schiller NB, Whooley MA. Prognostic significance of increased left ventricular mass index to mortality and sudden death in patients with stable coronary heart disease (from the heart and soul study). Am J Cardiol. 2008 ; 102 (9). 1131-1135
18. Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002 ; 106 (17). 2194-2199
19. Lindenfeld J, Feldman AM, Saxon L, et al. Effects of cardiac resynchronization therapy with or without a defibrillator on survival and hospitalizations in patients with New York Heart Association Class IV Heart Failure. Circulation. 2007 ; 115 (2). 204-212
20. Rouleau J, Shenasa M, de Champlain J, et al. Predictors of survival and sudden death in patients with stable severe congestive heart failure due to ischemic and nonischemic causes: a prospective long term study of 200 patients. Can J Cardiol. 1990 ; 6 (10). 453-460
21. Carmeliet E. Cardiac ionic currents and acute ischemia: from channels to arrhythmias. Physiol Rev. 1999 ; 79 (3). 917-1017
22. Kleber AG, Rudy Y. Basic mechanisms of cardiac impulse propagation and associated arrhythmias. Physiol Rev. 2004 ; 84 (2). 431-488
23. Reiken S, Wehrens XH, Vest JA, et al. Beta-blockers restore calcium release channel function and improve cardiac muscle performance in human heart failure. Circulation. 2003 ; 107 (19). 2459-2466
24. Pereira L, Cheng H, Lao DH, et al. Epac2 mediates cardiac beta1-adrenergic-dependent sarcoplasmic reticulum Ca2+ leak and arrhythmia. Circulation. 2013 ; 127 (8). 913-922
25. Tomaselli GF, Zipes DP. What causes sudden death in heart failure?. Circ Res. 2004 ; 95 (8). 754-763
26. Huikuri HV, Castellanos A, Myerburg RJ. Sudden death due to cardiac arrhythmias. N Engl J Med. 2001 ; 345 (20). 1473-1482
27. Mann DL. Basic mechanisms of disease progression in the failing heart: the role of excessive adrenergic drive. Prog Cardiovasc Dis. 1998 ; 41 (1 suppl 1). 1-8
28. Chidsey CA, Sonnenblick EH, Morrow AG, Braunwald E. Norepinephrine stores and contractile force of papillary muscle from the failing human heart. Circulation. 1966 ; 33 (1). 43-51
29. Hasegawa K, Iwai-Kanai E, Sasayama S. Neurohormonal regulation of myocardial cell apoptosis during the development of heart failure. J Cell Physiol. 2001 ; 186 (1). 11-18
30. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the studies of left ventricular dysfunction (SOLVD). Circulation. 1990 ; 82 (5). 1724-1729
31. Calvert JW, Condit ME, Aragon JP, et al. Exercise protects against myocardial ischemia-reperfusion injury via stimulation of beta(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols. Circ Res. 2011 ; 108 (12). 1448-1458
32. Gorre F, Vandekerckhove H.. Beta-blockers: Focus on mechanism of action. Which beta-blocker, when and why?. Acta Cardiol. 2012 ; 65 (5). 565-570
33. Swedberg K, Viquerat C, Rouleau JL, et al. Comparison of myocardial catecholamine balance in chronic congestive heart failure and in angina pectoris without failure. Am J Cardiol. 1984 ; 54 (7). 783-786
34. Gorre F, Vandekerckhove H. Beta-blockers: focus on mechanism of action. Which beta-blocker, when and why?. Acta Cardiol. 2010 ; 65 (5). 565-570
35. Gilbert EM, Abraham WT, Olsen S, et al. Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart. Circulation. 1996 ; 94 (11). 2817-2825
36. Hall SA, Cigarroa CG, Marcoux L, et al. Time course of improvement in left ventricular function, mass and geometry in patients with congestive heart failure treated with beta-adrenergic blockade. J Am Coll Cardiol. 1995 ; 25 (5). 1154-1161
37. Bello D, Shah DJ, Farah GM, et al. Gadolinium cardiovascular magnetic resonance predicts reversible myocardial dysfunction and remodeling in patients with heart failure undergoing beta-blocker therapy. Circulation. 2003 ; 108 (16). 1945-1953
38. Yaoita H, Sakabe A, Maehara K, Maruyama Y. Different effects of carvedilol, metoprolol, and propranolol on left ventricular remodeling after coronary stenosis or after permanent coronary occlusion in rats. Circulation. 2002 ; 105 (8). 975-980
39. Wilber DJ, Zareba W, Hall WJ, et al. Time dependence of mortality risk and defibrillator benefit after myocardial infarction. Circulation. 2004 ; 109 (9). 1082-1084
40. Seidl K, Hauer B, Schwick NG, et al. Comparison of metoprolol and sotalol in preventing ventricular tachyarrhythmias after the implantation of a cardioverter/defibrillator. Am J Cardiol. 1998 ; 82 (6). 744-748
41. Jimenez-Candil J, Hernandez J, Martin A, et al. Influence of beta-blocker therapy on antitachycardia pacing effectiveness for monomorphic ventricular tachycardias occurring in implantable cardioverter-defibrillator patients: a dose-dependent effect. Europace. 2012 ; 12 (9). 1231-1238
42. Snow PJ. Effect of propranolol in myocardial infarction. Lancet. 1965 ; 2 (7412). 551-553
43. N Engl J Med. 1981 ; 304 (14). 801-807
44. Morbidity results. JAMA. 1983 ; 250 (20). 2814-2819
45. Vantrimpont P, Rouleau JL, Wun CC, et al. Additive beneficial effects of beta-blockers to angiotensin-converting enzyme inhibitors in the survival and ventricular enlargement (SAVE) study. SAVE investigators. J Am Coll Cardiol. 1997 ; 29 (2). 229-236
46. Spargias KS, Hall AS, Greenwood DC, et al. Beta blocker treatment and other prognostic variables in patients with clinical evidence of heart failure after acute myocardial infarction: evidence from the AIRE study. Heart. 1999 ; 81 (1). 25-32
47. Freemantle N, Cleland J, Young P, Mason J, Harrison J.. Beta blockade after myocardial infarction: Systematic review and meta regression analysis. BMJ. 1999 ; 318 (7200). 1730-1737
48. Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med. 1998 ; 339 (8). 489-497
49. Chadda K, Goldstein S, Byington R, Curb JD. Effect of propranolol after acute myocardial infarction in patients with congestive heart failure. Circulation. 1986 ; 73 (3). 503-510
50. Dargie HJ. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial. Lancet. 2001 ; 357 (9266). 1385-1390
51. McMurray J, Kober L, Robertson M, et al. Antiarrhythmic effect of carvedilol after acute myocardial infarction: results of the carvedilol post-infarct survival control in left ventricular dysfunction (CAPRICORN) trial. J Am Coll Cardiol. 2005 ; 45 (4). 525-530
52. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol heart failure study group. N Engl J Med. 1996 ; 334 (21). 1349-1355
53. Packer M, Coats AJ, Fowler MB, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 ; 344 (22). 1651-1658
54. The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. Lancet. 1999 ; 353 (9146). 9-13
55. Hjalmarson A, Goldstein S, Fagerberg B, et al. Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). MERIT-HF study group. JAMA. 2000 ; 283 (10). 1295-1302
56. A trial of the beta-blocker Bucindolol in patients with advanced chronic heart failure. N Engl J Med. 2001 ; 344 (22). 1659-1667
57. Domanski MJ, Krause-Steinrauf H, Massie BM, et al. A comparative analysis of the results from 4 trials of beta-blocker therapy for heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS. J Card Fail. 2003 ; 9 (5). 354-363
58. Ohlstein EH, Douglas SA, Sung CP, et al. Carvedilol, a cardiovascular drug, prevents vascular smooth muscle cell proliferation, migration, and neointimal formation following vascular injury. Proc Natl Acad Sci USA. 1993 ; 90 (13). 6189-6193
59. Neil-Dwyer G, Bartlett J, McAinsh J, Cruickshank JM. Beta-adrenoceptor blockers and the blood-brain barrier. Br J Clin Pharmacol. 1981 ; 11 (6). 549-553
60. Metra M, Giubbini R, Nodari S, Boldi E, Modena MG, Dei Cas L. Differential effects of beta-blockers in patients with heart failure: a prospective, randomized, double-blind comparison of the long-term effects of metoprolol versus carvedilol. Circulation. 2000 ; 102 (5). 546-551
61. Fonarow GC, Abraham WT, Albert NM, et al. Influence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with heart failure: findings from the OPTIMIZE-HF program. J Am Coll Cardiol. 2008 ; 52 (3). 190-199
62. Fiuzat M, Wojdyla D, Kitzman D, et al. Relationship of beta-blocker dose with outcomes in ambulatory heart failure patients with systolic dysfunction: results from the HF-action (heart failure: a controlled trial investigating outcomes of exercise training) trial. J Am Coll Cardiol. 2012 ; 60 (3). 208-215
63. Fonarow GC, Abraham WT, Albert NM, et al. Dosing of beta-blocker therapy before, during, and after hospitalization for heart failure (from organized program to initiate lifesaving treatment in hospitalized patients with heart failure). Am J Cardiol. 2008 ; 102 (11). 1524-1529
64. Jessup M, Abraham WT. Casey DE, et al. 2009 focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the American college of cardiology foundation/American heart association task force on practice guidelines: developed in collaboration with the international society for heart and lung transplantation. Circulation. 2009 ; 119 (14). 1977-2016
65. Anderson JL, Hallstrom AP, Epstein AE, et al. Design and results of the antiarrhythmics vs implantable defibrillators (AVID) registry. The AVID investigators. Circulation. 1999 ; 99 (13). 1692-1699
66. Hreybe H, Bedi M, Ezzeddine R, et al. Indications for internal cardioverter defibrillator implantation predict time to first shock and the modulating effect of beta-blockers. Am Heart J. 2005 ; 150 (5). 1064
67. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 ; 355 (3). 251-259
68. Paulus WJ, Tschope C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the heart failure and echocardiography associations of the European society of cardiology. Eur Heart J. 2007 ; 28 (20). 2539-2550
69. van Heerebeek L, Borbely A, Niessen HW, et al. Myocardial structure and function differ in systolic and diastolic heart failure. Circulation. 2006 ; 113 (16). 1966-1973
70. Cameron JS, Kimura S, Jackson-Burns DA, et al. ATP-sensitive k+ channels are altered in hypertrophied ventricular myocytes. Am J Physiol. 1988 ; 255 (5 pt 2). H1254 - H1258
71. Rials SJ, Wu Y, Xu X, Filart RA, Marinchak RA, Kowey PR. Regression of left ventricular hypertrophy with captopril restores normal ventricular action potential duration, dispersion of refractoriness, and vulnerability to inducible ventricular fibrillation. Circulation. 1997 ; 96 (4). 1330-1336
72. Koyanagi S, Eastham C, Marcus ML. Effects of chronic hypertension and left ventricular hypertrophy on the incidence of sudden cardiac death after coronary artery occlusion in conscious dogs. Circulation. 1982 ; 65 (6). 1192-1197
73. Martins JB, Kim W, Marcus ML. Chronic hypertension and left ventricular hypertrophy facilitate induction of sustained ventricular tachycardia in dogs 3 hours after left circumflex coronary artery occlusion. J Am Coll Cardiol. 1989 ; 14 (5). 1365-1373
74. Kohya T, Kimura S, Myerburg RJ, et al. Susceptibility of hypertrophied rat hearts to ventricular fibrillation during acute ischemia. J Mol Cell Cardiol. 1988 ; 20 (2). 159-168
75. Dobre D, van Veldhuisen DJ, DeJongste MJ, et al. Prescription of beta-blockers in patients with advanced heart failure and preserved left ventricular ejection fraction. Clinical implications and survival. Eur J Heart Fail. 2007 ; 9 (3). 280-286
76. Massie BM, Nelson JJ, Lukas MA, et al. Comparison of outcomes and usefulness of carvedilol across a spectrum of left ventricular ejection fractions in patients with heart failure in clinical practice. Am J Cardiol. 2007 ; 99 (9). 1263-1268
77. Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of Nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (seniors). Eur Heart J. 2005 ; 26 (3). 215-225
78. Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med. 1999 ; 341 (8). 577-585
79. Sadoshima J, Izumo S.. Molecular characterization of angiotensin II - induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the at1 receptor subtype. Circ Res. 1993 ; 73 (3). 413-423
80. Urata H, Healy B, Stewart RW, et al. Angiotensin II-forming pathways in normal and failing human hearts. Circ Res. 1990 ; 66 (4). 883-890
81. Fang KC, Raymond WW, Blount JL, et al. Dog mast cell alpha-chymase activates progelatinase b by cleaving the phe88-gln89 and phe91-glu92 bonds of the catalytic domain. J Biol Chem. 1997 ; 272 (41). 25628-25635
82. Hunyady L, Catt KJ. Pleiotropic AT1 receptor signaling pathways mediating physiological and pathogenic actions of angiotensin II. Mol Endocrinol. 2006 ; 20 (5). 953-970
83. van Kats JP, Duncker DJ, Haitsma DB, et al. Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent cardiac remodeling in pigs after myocardial infarction: role of tissue angiotensin II. Circulation. 2000 ; 102 (13). 1556-1563
84. Zhang TT, Takimoto K, Stewart AF, et al. Independent regulation of cardiac Kv4.3 potassium channel expression by angiotensin II and phenylephrine. Circ Res. 2001 ; 88 (5). 476-482
85. McIntosh MA, Cobbe SM, Kane KA, et al. Action potential prolongation and potassium currents in left-ventricular myocytes isolated from hypertrophied rabbit hearts. J Mol Cell Cardiol. 1998 ; 30 (1). 43-53
86. Tomita F, Bassett AL, Myerburg RJ, et al. Diminished transient outward currents in rat hypertrophied ventricular myocytes. Circ Res. 1994 ; 75 (2). 296-303
87. Nabauer M, Kaab S. Potassium channel down-regulation in heart failure. Cardiovasc Res. 1998 ; 37 (2). 324-334
88. Tsai CT, Wang DL, Chen WP, et al. Angiotensin II increases expression of alpha1C subunit of L-type calcium channel through a reactive oxygen species and cAMP response element-binding protein-dependent pathway in HL-1 myocytes. Circ Res. 2007 ; 100 (10). 1476-1485
89. Xiao HD, Fuchs S, Campbell DJ, et al. Mice with cardiac-restricted angiotensin-converting enzyme (ACE) have atrial enlargement, cardiac arrhythmia, and sudden death. Am J Pathol. 2004 ; 165 (3). 1019-1032
90. Vermes E, Tardif JC, Bourassa MG, et al. Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the studies of left ventricular dysfunction (SOLVD) trials. Circulation. 2003 ; 107 (23). 2926-2931
91. Pedersen OD, Bagger H, Kober L, et al. Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction. Circulation. 1999 ; 100 (4). 376-380
92. Madrid AH, Bueno MG, Rebollo JM, et al. Use of Irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation. 2002 ; 106 (3). 331-336
93. Minisi AJ, Thames MD. Distribution of left ventricular sympathetic afferents demonstrated by reflex responses to transmural myocardial ischemia and to intracoronary and epicardial bradykinin. Circulation. 1993 ; 87 (1). 240-246
94. Thai H, Castellano L, Juneman E, et al. Pretreatment with angiotensin receptor blockade prevents left ventricular dysfunction and blunts left ventricular remodeling associated with acute myocardial infarction. Circulation. 2006 ; 114 (18). 1933-1939
95. Zannad F, Dousset B, Alla F.. Treatment of congestive heart failure: Interfering the aldosterone-cardiac extracellular matrix relationship. Hypertension. 2001 ; 38 (5). 1227-1232
96. Zannad F, Alla F, Dousset B, et al. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the Randomized Aldactone Evaluation Study (RALES). RALES investigators. Circulation. 2000 ; 102 (22). 2700-2706
97. Rutherford JD, Pfeffer MA, Moye LA, et al. Effects of captopril on ischemic events after myocardial infarction. Results of the survival and ventricular enlargement trial. SAVE investigators. Circulation. 1994 ; 90 (4). 1731-1738
98. Kober L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril cardiac evaluation (TRACE) study group. N Engl J Med. 1995 ; 333 (25). 1670-1676
99. Cleland JG, Erhardt L, Murray G, et al. Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE study investigators. Eur Heart J. 1997 ; 18 (1). 41-51
100. Domanski MJ, Exner DV, Borkowf CB, et al. Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials. J Am Coll Cardiol. 1999 ; 33 (3). 598-604
101. The consensus trial study group. N Engl J Med. 1987 ; 316 (23). 1429-1435
102. The SOLVD investigators. N Engl J Med. 1992 ; 327 (10). 685-691
103. Cohn JN, Johnson G, Ziesche S, et al. A comparison of Enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991 ; 325 (5). 303-310
104. Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (evaluation of losartan in the elderly study, ELITE). Lancet. 1997 ; 349 (9054). 747-752
105. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of Candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-ADDED trial. Lancet. 2003 ; 362 (9386). 767-771
106. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001 ; 345 (23). 1667-1675
107. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003 ; 349 (20). 1893-1906
108. Pitt B, Poole-Wilson PA, Segal R, et al. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial - the losartan heart failure survival study ELITE II. Lancet. 2000 ; 355 (9215). 1582-1587
109. Konstam MA, Neaton JD, Dickstein K, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009 ; 374 (9704). 1840-1848
110. Granger CB, McMurray JJ, Yusuf S, et al. Effects of Candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-alternative trial. Lancet. 2003 ; 362 (9386). 772-776
111. Gring CN, Francis GS. A hard look at angiotensin receptor blockers in heart failure. J Am Coll Cardiol. 2004 ; 44 (9). 1841-1846
112. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study investigators. N Engl J Med. 1999 ; 341 (10). 709-717
113. Pitt B, Remme W, Zannad F, et al. eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003 ; 348 (14). 1309-1321
114. O'Meara E, Khairy P, Blanchet MC, et al. Mineralocorticoid receptor antagonists and cardiovascular mortality in patients with atrial fibrillation and left ventricular dysfunction: insights from the atrial fibrillation and congestive heart failure trial. Circ Heart Fail. 2012 ; 5 (5). 586-593
115. Wachtell K, Okin PM, Olsen MH, et al. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE study. Circulation. 2007 ; 116 (7). 700-705
116. Cleland JG, Tendera M, Adamus J, Freemantle N, Polonski L, Taylor J. The Perindopril in elderly people with chronic heart failure (PEP-CHF) study. Eur Heart J. 2006 ; 27 (19). 2338-2345
117. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of Candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-preserved trial. Lancet. 2003 ; 362 (9386). 777-781
118. Persson H, Lonn E, Edner M, et al. Diastolic dysfunction in heart failure with preserved systolic function: need for objective evidence: results from the CHARM Echocardiographic Substudy-CHARMES. J Am Coll Cardiol. 2007 ; 49 (6). 687-694
119. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification. Eur J Echocardiogr. 2006 ; 7 (2). 79-108
120. Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008 ; 359 (23). 2456-2467
121. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4s). Lancet. 1994 ; 344 (8934). 1383-1389
122. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events trial investigators. N Engl J Med. 1996 ; 335 (14). 1001-1009
123. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with Atorvastatin in patients with stable coronary disease. N Engl J Med. 2005 ; 352 (14). 1425-1435
124. Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the asteroid trial. JAMA. 2006 ; 295 (13). 1556-1565
125. Cascio WE. Myocardial ischemia: what factors determine arrhythmogenesis?. J Cardiovasc Electrophysiol. 2001 ; 12 (6). 726-729
126. Laufs U, La Fata V, Plutzky J, et al. Upregulation of endothelial nitric oxide synthase by hmg coa reductase inhibitors. Circulation. 1998 ; 97 (12). 1129-1135
127. Rikitake Y, Kawashima S, Takeshita S, et al. Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis. 2001 ; 154 (1). 87-96
128. Ridker PM, Rifai N, Pfeffer MA, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and recurrent events (CARE) investigators. Circulation. 1998 ; 98 (9). 839-844
129. Weber KT, Anversa P, Armstrong PW, et al. Remodeling and reparation of the cardiovascular system. J Am Coll Cardiol. 1992 ; 20 (1). 3-16
130. Lee TM, Chou TF, Tsai CH. Effects of pravastatin on cardiomyocyte hypertrophy and ventricular vulnerability in normolipidemic rats after myocardial infarction. J Mol Cell Cardiol. 2003 ; 35 (12). 1449-1459
131. Sola S, Mir MQ, Lerakis S, et al. Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol. 2006 ; 47 (2). 332-337
132. Node K, Fujita M, Kitakaze M, Hori M, Liao JK. Short-term statin therapy improves cardiac function and symptoms in patients with idiopathic dilated cardiomyopathy. Circulation. 2003 ; 108 (7). 839-843
133. Suzuki G, Iyer V, Cimato T, Canty JM. Pravastatin improves function in hibernating myocardium by mobilizing CD133+ and cKit+ bone marrow progenitor cells and promoting myocytes to reenter the growth phase of the cardiac cell cycle. Circ Res. 2009 ; 104 (2). 255-264
134. Vrtovec B, Okrajsek R, Golicnik A, et al. Atorvastatin therapy increases heart rate variability, decreases QT variability, and shortens QTC interval duration in patients with advanced chronic heart failure. J Card Fail. 2005 ; 11 (9). 684-690
135. Pehlivanidis AN, Athyros VG, Demitriadis DS, Papageorgiou AA, Bouloukos VJ, Kontopoulos AG. Heart rate variability after long-term treatment with Atorvastatin in hypercholesterolaemic patients with or without coronary artery disease. Atherosclerosis. 2001 ; 157 (2). 463-469
136. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose Atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the ideal study: a randomized controlled trial. JAMA. 2005 ; 294 (19). 2437-2445
137. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with Atorvastatin in patients with stable coronary disease. N Engl J Med. 2005 ; 352 (14). 1425-1435
138. Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol. 2005 ; 96 (5). 611-616
139. Mitchell LB, Powell JL, Gillis AM, Kehl V, Hallstrom AP. Are lipid-lowering drugs also antiarrhythmic drugs? An analysis of the antiarrhythmics versus implantable defibrillators (AVID) trial. J Am Coll Cardiol. 2003 ; 42 (1). 81-87
140. Vyas AK, Guo H, Moss AJ, et al. Reduction in ventricular tachyarrhythmias with statins in the multicenter automatic defibrillator implantation trial (MADIT)-II. J Am Coll Cardiol. 2006 ; 47 (4). 769-773
141. Dickinson MG, Ip JH, Olshansky B, et al. Statin use was associated with reduced mortality in both ischemic and nonischemic cardiomyopathy and in patients with implantable defibrillators: mortality data and mechanistic insights from the sudden cardiac death in heart failure trial (SCD-HEFT). Am Heart J. 2007 ; 153 (4). 573-578
142. Goldberger JJ, Subacius H, Schaechter A, et al. Effects of statin therapy on arrhythmic events and survival in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol. 2006 ; 48 (6). 1228-1233
143. Buber J, Goldenberg I, Moss AJ, et al. Reduction in life-threatening ventricular tachyarrhythmias in statin-treated patients with nonischemic cardiomyopathy enrolled in the MADIT-CRT (multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy). J Am Coll Cardiol. 2012 ; 60 (8). 749-755
144. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007 ; 357 (22). 2248-2261
145. Gissi HFI, Tavazzi L, Maggioni AP, et al. Effect of Rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008 ; 372 (9645). 1231-1239
146. Tuzcu EM, Kapadia SR, Tutar E, et al. High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation. 2001 ; 103 (22). 2705-2710
147. Wilson PW, D'Agostino RB, Levy D, et al. Prediction of coronary heart disease using risk factor categories. Circulation. 1998 ; 97 (18). 1837-1847