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Is Dressler Syndrome Dead?* FREE TO VIEW

Karim Bendjelid, MD, MS; Jérôme Pugin, MD
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*From the Divisions of Surgical Intensive Care (Dr. Bendjelid) Medical Intensive Care (Dr. Pugin), Geneva University Hospitals, Geneva, Switzerland.

Correspondence to: Karim Bendjelid, MD, MS, Chef de Clinique Scientifique, Surgical Intensive Care Division, University Hospital of Geneva, CH-1211 Geneva 14, Switzerland; e-mail: karim.bendjelid@hcuge.ch



Chest. 2004;126(5):1680-1682. doi:10.1378/chest.126.5.1680
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Published online

Post-acute myocardial infarction (AMI) syndrome was first described by Dressler in 1956. Its incidence has decreased in the reperfusion era, most likely because of the extensive use of thrombolysis and coronary balloon angioplasty, therapies that dramatically decreased the size of myocardial necrosis. The authors suggest that drugs that have been prescribed in previous decades as the post-AMI “standard-of-care,” such as angiotensin-converting enzyme inhibitors, β-blockers, and statins, may also play an important role in the disappearance of Dressler syndrome due to their immunomodulatory effects.

Dressler’s description,1> 40 years ago, of a clinical entity following an acute myocardial infarction (AMI) continues to be indelibly evoked at bedside and in the standard cardiology literature. Clinical features of this post-AMI syndrome include fever, chest pain, pericarditis, pleurisy occurring 2 to 3 weeks after the AMI, and a tendency for recurrence.2 Prior to the reperfusion era, the reported incidence of Dressler syndrome (DS) ranged from 1 to 5% of patients with AMI.25 The incidence of DS, however, has decreased in the reperfusion era, most likely due to the widespread use of therapy with thrombolysis67 and balloon angioplasty.8Supporting this, in a prospective study of 201 patients with AMI who had undergone thrombolysis, Shahar et al9found that no patient showing clinical signs of early reperfusion had DS. The only patient who developed DS in the latter study had had an extensive anterior AMI without evidence of reperfusion. Before the reperfusion era, Lichstein and colleagues10 suggested that the decreased incidence of DS was related to the modification of the treatment of patients with AMI. The use of novel therapies, such as nonsteroidal antiinflammatory agents, steroids, and salicylates, and the decreased use of oral anti-coagulants were evoked. In addition to the two mechanisms discussed above, which may account for the observed decrease in the incidence of DS,910 the authors propose a third hypothesis. We think that drugs that have been prescribed in previous decades as post-AMI “standard-of-care” may also play an important role in the disappearance of DS.

Before the Era of Coronary Reperfusion

Several pathogenic mechanisms have been proposed for DS, including local inflammation,11autoimmune reaction,12and latent viruses.13 Irritant pericarditis due to the presence of blood in the pericardial space induced by anticoagulation therapy was at that time anticipated as a likely mechanism.1 However, anticoagulation therapy could not be related to all cases since > 25% of patients in the original report of Dressler1did not receive anticoagulants.2 In addition, nowadays, a significant number of patients still receive anticoagulants after experiencing anterior AMIs,14 yet DS is not observed in this patient population. These two facts seem to rule out anticoagulants as the drugs playing a major role in the pathogenesis of DS.

Since the Era of Coronary Reperfusion

The decrease of the incidence of DS has been viewed as another beneficial effect of early and aggressive coronary reperfusion therapy, which decreased mortality and improved cardiac function.9 It was postulated9 that the diminution of the infarct size and the shortened time of exposure of the myocardial antigens to the immune system accounted for the decreased incidence of DS. Although the reduction in both the number of patients with AMI and in the infarct size following coronary reperfusion may play a role in the observed decrease of the incidence of DS,1516 this can hardly explain the quasi-complete disappearance of the syndrome. Indeed, even in the reperfusion era, a significant number of patients will develop large AMIs due to unsuccessful or late reperfusion. The quasi-absence of DS in this patient population calls for another mechanism to explain their protection against DS.

The Authors’ Hypothesis

DS is a recurrent immunoinflammatory syndrome that has similarities with other syndromes occurring after myocardial injury, such as postcardiotomy syndrome and posttraumatic pericarditis.17 Following myocardial injury or AMI, myocardial antigens are exposed and/or released, and, in some cases, an immune complex can form. This immune activation triggers a local inflammatory reaction, and may involve remote organs such the pleura and synovia, due to molecular mimicry and immune cross-reactions.12 The time needed for the immune reaction to develop may account for the observed latency period of 2 to 3 weeks between the AMI and the onset of DS. The duration of DS may be explained by the limited time during which myocardial antigens are exposed to the immune system and corresponds grossly to the time necessary for the myocardium to heal after an AMI. Interestingly, the hypothesis proposed herein suggests that this immune reaction has been minimized by novel therapies administered in the last 1 or 2 decades in the vast majority of patients who have experienced AMIs. These therapies include the use of angiotensin-converting enzyme (ACE) inhibitors, statins, and β-blockers. All of these drugs have been proposed to carry immunomodulatory properties.1822 These drugs also lower the risk of recurrent AMI in addition to their effect on all-cause mortality. A direct relationship between systemic inflammation and myocardial ischemia has been highlighted by several authors.2327 Interestingly, Gullestad et al19 have shown that circulating levels of proinflammatory cytokines were reduced by high doses of ACE inhibitors in patients with heart failure. Other authors demonstrated that ACE inhibitors reduced myocardial injury in cell cultures and in isolated hearts.18 In similar studies, β-blockers have been shown to decrease circulating levels of proinflammatory cytokines.20,22 Statins, a new class of lipid-lowering drugs that reduces cardiovascular-related morbidity and mortality,2829 are now widely used for treatment after an AMI. Although these agents have not directly been shown to decrease the levels of systemic proinflammatory mediators in patients with AMI, they carry unequivocal protective antiinflammatory and immunomodulatory properties.21 Moreover, statin therapy has been found to lower levels of C-reactive protein,25,30and Nahrendorf et al31 have demonstrated that left ventricular remodeling after AMI was profoundly changed by statin treatment in rats.

Another explanation for the post-AMI syndrome could be the close proximity between the myocardium and the pericardium. The inflammatory process that affects the cardiac muscle could propagate a nonspecific inflammatory response to the neighboring pericardium. However, the usual latency period of 2 to 3 weeks between the AMI and the onset of DS makes this hypothesis less likely, and corresponds more to the pathogenesis of the acute pericarditis observed within the 5-day period after the AMI.

Historically, attempts to understand the quasi-complete disappearance of the DS have focused on early coronary reperfusion therapy, and less attention has been given to drugs with immunomodulatory properties. We hypothesize that the most likely disappearance of DS following a correctly treated AMI is related to drugs that have a strong defensive effect by virtue of diverse antiinflammatory effects.

Abbreviations: ACE = angiotensin-converting enzyme; AMI = acute myocardial infarction; DS = Dressler syndrome

Dressler, W (1956) A post-myocardial infarction syndrome: preliminary report of a complication resembling idiopathic, recurrent, benign pericarditis.JAMA160,1379-1383. [CrossRef]
 
Dressler, W The post-myocardial infarction syndrome.Arch Intern Med1959;103,28-42. [CrossRef]
 
Davidson, CO, Oliver, MF, Robertson, RF Post-myocardial infarction syndrome.BMJ1961;2,535-539. [CrossRef] [PubMed]
 
Welin, L, Vedin, A, Wilhelmsson, C Characteristics, prevalence, and prognosis of postmyocardial infarction syndrome.Br Heart J1983;50,140-145. [CrossRef] [PubMed]
 
Northcote, RJ, Hutchison, SJ, McGuinness, JB Evidence for the continued existence of the postmyocardial infarction (Dressler’s) syndrome.Am J Cardiol1984;53,1201-1202. [CrossRef] [PubMed]
 
GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction.N Engl J Med1993;329,1615-1622. [CrossRef] [PubMed]
 
Ross, AM, Coyne, KS, Moreyra, E, et al Extended mortality benefit of early postinfarction reperfusion: GUSTO-I Angiographic Investigators; Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial.Circulation1998;97,1549-1556. [CrossRef] [PubMed]
 
Stone, GW, Grines, CL, Cox, DA, et al Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.N Engl J Med2002;346,957-966. [CrossRef] [PubMed]
 
Shahar, A, Hod, H, Barabash, GM, et al Disappearance of a syndrome: Dressler’s syndrome in the era of thrombolysis.Cardiology1994;85,255-258. [CrossRef] [PubMed]
 
Lichstein, E, Arsura, E, Hollander, G, et al Current incidence of postmyocardial infarction (Dressler’s) syndrome.Am J Cardiol1982;50,1269-1271. [CrossRef] [PubMed]
 
Thadani, U, Chopra, MP, Aber, CP, et al Pericarditis after acute myocardial infarction.BMJ1971;2,135-137. [PubMed]
 
Earis, JE, Marcuson, EC, Bernstein, A Complement activation after myocardial infarction.Chest1985;87,186-190. [CrossRef] [PubMed]
 
Kossowsky, WA, Lyon, AF, Spain, DM Reappraisal of the postmyocardial infarction Dressler’s syndrome.Am Heart J1981;102,954-956. [CrossRef] [PubMed]
 
Weinreich, DJ, Burke, JF, Pauletto, FJ Left ventricular mural thrombi complicating acute myocardial infarction: long-term follow-up with serial echocardiography.Ann Intern Med1984;100,789-794. [PubMed]
 
Correale, E, Maggioni, AP, Romano, S, et al Comparison of frequency, diagnostic and prognostic significance of pericardial involvement in acute myocardial infarction treated with and without thrombolytics: Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI).Am J Cardiol1993;71,1377-1381. [CrossRef] [PubMed]
 
Oliva, PB, Hammill, SC, Talano, JV Effect of definition on incidence of postinfarction pericarditis: it is time to redefine postinfarction pericarditis?Circulation1994;90,1537-1541. [CrossRef] [PubMed]
 
Versey, JM, Gabriel, R Soluble-complex formation after myocardial infarction.Lancet1974;2,493-494. [PubMed]
 
Linz, W, Wiemer, G, Scholkens, BA ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts.J Mol Cell Cardiol1992;24,909-919. [CrossRef] [PubMed]
 
Gullestad, L, Aukrust, P, Ueland, T, et al Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure.J Am Coll Cardiol1999;34,2061-2067. [CrossRef] [PubMed]
 
Prabhu, SD, Chandrasekar, B, Murray, DR, et al Beta-adrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling.Circulation2000;101,2103-2109. [CrossRef] [PubMed]
 
Kwak, B, Mulhaupt, F, Myit, S, et al Statins as a newly recognized type of immunomodulator.Nat Med2000;6,1399-1402. [CrossRef] [PubMed]
 
Ohtsuka, T, Hamada, M, Hiasa, G, et al Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy.J Am Coll Cardiol2001;37,412-417. [CrossRef] [PubMed]
 
Neumann, FJ, Ott, I, Gawaz, M, et al Cardiac release of cytokines and inflammatory responses in acute myocardial infarction.Circulation1995;92,748-755. [CrossRef] [PubMed]
 
Ridker, PM, Hennekens, CH, Buring, JE, et al C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.N Engl J Med2000;342,836-843. [CrossRef] [PubMed]
 
Ridker, PM, Rifai, N, Clearfield, M, et al Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.N Engl J Med2001;344,1959-1965. [CrossRef] [PubMed]
 
Cusack, MR, Marber, MS, Lambiase, PD, et al Systemic inflammation in unstable angina is the result of myocardial necrosis.J Am Coll Cardiol2002;39,1917-1923. [CrossRef] [PubMed]
 
Kinlay, S, Timms, T, Clark, M, et al Comparison of effect of intensive lipid lowering with atorvastatin to less intensive lowering with lovastatin on C-reactive protein in patients with stable angina pectoris and inducible myocardial ischemia.Am J Cardiol2002;89,1205-1207. [CrossRef] [PubMed]
 
Schwartz, GG, Olsson, AG, Ezekowitz, MD, et al Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.JAMA2001;285,1711-1718. [CrossRef] [PubMed]
 
Olsson, AG, Schwartz, GG Early initiation of treatment with statins in acute coronary syndromes.Ann Med2002;34,37-41. [CrossRef] [PubMed]
 
Albert, MA, Danielson, E, Rifai, N, et al Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study.JAMA2001;286,64-70. [CrossRef] [PubMed]
 
Nahrendorf, M, Hu, K, Hiller, KH, et al Impact of hydroxymethylglutaryl coenzyme a reductase inhibition on left ventricular remodeling after myocardial infarction: an experimental serial cardiac magnetic resonance imaging study.J Am Coll Cardiol2002;40,1695-1700. [CrossRef] [PubMed]
 

Figures

Tables

References

Dressler, W (1956) A post-myocardial infarction syndrome: preliminary report of a complication resembling idiopathic, recurrent, benign pericarditis.JAMA160,1379-1383. [CrossRef]
 
Dressler, W The post-myocardial infarction syndrome.Arch Intern Med1959;103,28-42. [CrossRef]
 
Davidson, CO, Oliver, MF, Robertson, RF Post-myocardial infarction syndrome.BMJ1961;2,535-539. [CrossRef] [PubMed]
 
Welin, L, Vedin, A, Wilhelmsson, C Characteristics, prevalence, and prognosis of postmyocardial infarction syndrome.Br Heart J1983;50,140-145. [CrossRef] [PubMed]
 
Northcote, RJ, Hutchison, SJ, McGuinness, JB Evidence for the continued existence of the postmyocardial infarction (Dressler’s) syndrome.Am J Cardiol1984;53,1201-1202. [CrossRef] [PubMed]
 
GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function, and survival after acute myocardial infarction.N Engl J Med1993;329,1615-1622. [CrossRef] [PubMed]
 
Ross, AM, Coyne, KS, Moreyra, E, et al Extended mortality benefit of early postinfarction reperfusion: GUSTO-I Angiographic Investigators; Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Trial.Circulation1998;97,1549-1556. [CrossRef] [PubMed]
 
Stone, GW, Grines, CL, Cox, DA, et al Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction.N Engl J Med2002;346,957-966. [CrossRef] [PubMed]
 
Shahar, A, Hod, H, Barabash, GM, et al Disappearance of a syndrome: Dressler’s syndrome in the era of thrombolysis.Cardiology1994;85,255-258. [CrossRef] [PubMed]
 
Lichstein, E, Arsura, E, Hollander, G, et al Current incidence of postmyocardial infarction (Dressler’s) syndrome.Am J Cardiol1982;50,1269-1271. [CrossRef] [PubMed]
 
Thadani, U, Chopra, MP, Aber, CP, et al Pericarditis after acute myocardial infarction.BMJ1971;2,135-137. [PubMed]
 
Earis, JE, Marcuson, EC, Bernstein, A Complement activation after myocardial infarction.Chest1985;87,186-190. [CrossRef] [PubMed]
 
Kossowsky, WA, Lyon, AF, Spain, DM Reappraisal of the postmyocardial infarction Dressler’s syndrome.Am Heart J1981;102,954-956. [CrossRef] [PubMed]
 
Weinreich, DJ, Burke, JF, Pauletto, FJ Left ventricular mural thrombi complicating acute myocardial infarction: long-term follow-up with serial echocardiography.Ann Intern Med1984;100,789-794. [PubMed]
 
Correale, E, Maggioni, AP, Romano, S, et al Comparison of frequency, diagnostic and prognostic significance of pericardial involvement in acute myocardial infarction treated with and without thrombolytics: Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI).Am J Cardiol1993;71,1377-1381. [CrossRef] [PubMed]
 
Oliva, PB, Hammill, SC, Talano, JV Effect of definition on incidence of postinfarction pericarditis: it is time to redefine postinfarction pericarditis?Circulation1994;90,1537-1541. [CrossRef] [PubMed]
 
Versey, JM, Gabriel, R Soluble-complex formation after myocardial infarction.Lancet1974;2,493-494. [PubMed]
 
Linz, W, Wiemer, G, Scholkens, BA ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts.J Mol Cell Cardiol1992;24,909-919. [CrossRef] [PubMed]
 
Gullestad, L, Aukrust, P, Ueland, T, et al Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure.J Am Coll Cardiol1999;34,2061-2067. [CrossRef] [PubMed]
 
Prabhu, SD, Chandrasekar, B, Murray, DR, et al Beta-adrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling.Circulation2000;101,2103-2109. [CrossRef] [PubMed]
 
Kwak, B, Mulhaupt, F, Myit, S, et al Statins as a newly recognized type of immunomodulator.Nat Med2000;6,1399-1402. [CrossRef] [PubMed]
 
Ohtsuka, T, Hamada, M, Hiasa, G, et al Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy.J Am Coll Cardiol2001;37,412-417. [CrossRef] [PubMed]
 
Neumann, FJ, Ott, I, Gawaz, M, et al Cardiac release of cytokines and inflammatory responses in acute myocardial infarction.Circulation1995;92,748-755. [CrossRef] [PubMed]
 
Ridker, PM, Hennekens, CH, Buring, JE, et al C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.N Engl J Med2000;342,836-843. [CrossRef] [PubMed]
 
Ridker, PM, Rifai, N, Clearfield, M, et al Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.N Engl J Med2001;344,1959-1965. [CrossRef] [PubMed]
 
Cusack, MR, Marber, MS, Lambiase, PD, et al Systemic inflammation in unstable angina is the result of myocardial necrosis.J Am Coll Cardiol2002;39,1917-1923. [CrossRef] [PubMed]
 
Kinlay, S, Timms, T, Clark, M, et al Comparison of effect of intensive lipid lowering with atorvastatin to less intensive lowering with lovastatin on C-reactive protein in patients with stable angina pectoris and inducible myocardial ischemia.Am J Cardiol2002;89,1205-1207. [CrossRef] [PubMed]
 
Schwartz, GG, Olsson, AG, Ezekowitz, MD, et al Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial.JAMA2001;285,1711-1718. [CrossRef] [PubMed]
 
Olsson, AG, Schwartz, GG Early initiation of treatment with statins in acute coronary syndromes.Ann Med2002;34,37-41. [CrossRef] [PubMed]
 
Albert, MA, Danielson, E, Rifai, N, et al Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study.JAMA2001;286,64-70. [CrossRef] [PubMed]
 
Nahrendorf, M, Hu, K, Hiller, KH, et al Impact of hydroxymethylglutaryl coenzyme a reductase inhibition on left ventricular remodeling after myocardial infarction: an experimental serial cardiac magnetic resonance imaging study.J Am Coll Cardiol2002;40,1695-1700. [CrossRef] [PubMed]
 
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