Statins and coronary microvascular dysfunction in patients with acute ST segment elevation myocardial infarction

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Letters to the Editor

Statins and coronary microvascular dysfunction in patients with acute ST segment elevation myocardial infarction Turgay Celik a,⁎, Sait Demirkol a, Murat Celik b, U. Cagdas Yuksel a, Atila Iyisoy c a b c

Gulhane Military Medical Academy, School of Medicine, Department of Cardiology, Etlik-Ankara, Turkey Van Army District Hospital, Department of Cardiology, Van, Turkey Gulhane Military Medical Academy, School of Medicine, Department of Cardiology, Etlik-Ankara, Turkey

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Article history: Received 18 December 2011 Accepted 21 December 2011 Available online 14 January 2012 Keywords: Statins Coronary microvascular dysfunction Acute ST segment elevation myocardial infarction

In their recently published well-designed and well-presented article Ishida and coworkers tried to elucidate the effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in 35 acute myocardial infarction (AMI) patients undergoing successful primary percutaneous coronary intervention (pPCI) [1]. They demonstrated that statin treatment appears to beneficially attenuate left ventricular remodeling after AMI, which may be associated with restoring coronary endothelial function via endogenous nitric oxide. Although statin role in acute coronary syndromes is less clear, they seem to be beneficial [2]. However, plaque regression induced by cholesterol reduction alone is not considered sufficient to explain the striking benefit in these patients [3]. Chronic administration of simvastatin has been shown to preserve myocardial response and coronary microvascular integrity during cardiac stress in experimental hypercholesterolemia, independent of lipid lowering [4]. In addition, previous experimental studies of statin in ischemia/ reperfusion injury have clearly demonstrated cardioprotective effects of statins despite unaltered cholesterol levels [5–7]. It has been previously demonstrated that atorvastatin attenuates lethal reperfusion induced injury in rat model [8]. In a nicely designed clinical study, it was found that pravastatin increased microvascular perfusion in normocholesterolemic patients with single-vessel disease after successful elective PTCA [9]. At the end of 6-month follow-up period myocardial perfusion imaging still showed reversible perfusion defects in 29% of patients receiving placebo versus 3% receiving statins. In a previously published clinical study we aimed to investigate the effects of prior statin use on coronary blood flow after pPCI in patients with AMI using Thrombolysis In Myocardial Infarction (TIMI) frame count method [10]. The study population consisted of 200 patients (161 men; mean age 62±7 years) referred to cardiology clinics with AMI and underwent subsequently successful pPCI. The study population was divided into two groups according to statin use before pPCI. Group 1 consisted of 98 patients (75 men; mean age 63 ± 7 years) not taking statin and Group 2 consisted of 102 patients (86 men; mean age 61 ± 7 years) taking daily dose of at least 40 mg atorvastatin for at least 6 months. Coronary blood flow was determined by TIMI frame count method using the angiographic images obtained just after PCI and stenting. Only mean TIMI frame count was detected to be significantly lower in patients taking at least 40 mg atorvastatin for at least 6 months compared with that of the patients taking no statin (p b 0.001). After

confounding variables were controlled for, the mean TIMI frame count of patients in Group 2 was significantly lower than that of the patients in Group 1 (p = 0.001). Pain to balloon time and vessel type were detected as important confounding variables of TIMI frame count after analysis of covariances. In our study TIMI frame counts in patients taking at least 40 mg atorvastatin for at least 6 months before pPCI were significantly lower than those of the patients taking no statin. This finding may be attributed to the potential beneficial effects of atorvastatin mentioned above on coronary microcirculation. The improvement of microvascular function by prior statin use in patients with AMI who underwent PCI is of considerable concern because microvascular integrity plays a significant role in reducing both short and long term morbidity and mortality of these patients. TIMI frame counts have been reported to be very useful in predicting clinical outcomes [11]. In a well-designed clinical study Ishii and coworkers investigated whether administration of chronic statin therapy before AMI was associated with a reduction in reperfusion injury in AMI patients undergoing PCI [12]. Electrocardiographic ST-segment resolution after PCI was observed in 87.5% and 69.9% of the statin and nonstatin groups, respectively (HR: 3.01). Achievement of TIMI grade 3 flow after PCI was seen in 95.0% of the statin group and 83.5% of the nonstatin group (HR: 3.75). Patients treated with a statin had a significantly lower mean (SD) maximum CK level compared with the nonstatin group (2300 [1449] vs 3538 [3170] IU/mL, respectively) and a lower CTFC after PCI (18.8 [4.0] vs 24.2 [14.2]). The difference in reperfusion arrhythmias between groups was not statistically significant. After adjustment for baseline covariates, pretreatment with a statin was found to be an independent predictor of ST-segment resolution after PCI (HR: 2.95) and prevention of impaired coronary flow (HR: 3.00). In another study, Iwakura and coworkers performed intracoronary myocardial contrast echocardiography in 293 consecutive patients with AMI undergoing successful pPCI [13]. There were no significant differences in the incidence of the no-reflow between the patients with and without hypercholesterolemia. The 33 patients receiving chronic statin treatment before admission had lower incidence of the no-reflow than those without it (9.1 and 34.6%). They also showed better wall motion, smaller left ventricular dimensions, and better ejection fraction at 4.9 + 2.2 months later. Multivariable logistic regression analysis revealed that statin pre-treatment was a significant predictor of the no-reflow along with anterior wall infarction, ejection fraction on admission, and additional ST-elevation after reperfusion, whereas total cholesterol was not. In conclusion, receipt of chronic statin therapy before the onset of AMI was associated with improvement in epicardial perfusion and a reduction in myocardial necrosis after PCI. More importantly chronic pre-treatment with statins could preserve the microvascular integrity after AMI independent of lipid lowering, leading to better functional recovery. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology (Shewan and Coats 2010; 144: 1–2). References

⁎ Corresponding author at: Department of Cardiology, Gulhane School of Medicine, 06018 Etlik-Ankara, Turkey. Tel.: +90 312 3044268; fax: +90 312 3044250. E-mail address: [email protected] (T. Celik).

[1] Ishida K, Geshi T, Nakano A, et al. Beneficial effects of statin treatment on coronary microvascular dysfunction and left ventricular remodeling in patients with acute myocardial infarction. Int J Cardiol 2012;155(3):442–7.

Letters to the Editor [2] Schwartz GG, Olsson AG, Ezekowitz MD, et al. Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001;285:1711–8. [3] Aengevaeren WR. Beyond lipids — the role of the endothelium in coronary artery disease. Atherosclerosis 1999;147(Suppl 1):S11–6. [4] Bonetti PO, Wilson SH, Rodriguez-Porcel M, Holmes Jr DR, Lerman LO, Lerman A. Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering. J Am Coll Cardiol 2002;40:546–54. [5] Endres M, Laufs U, Huang Z, et al. Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci U S A 1998;95:8880–5. [6] Di Napoli P, Antonio Taccardi A, Grilli A, et al. Simvastatin reduces reperfusion injury by modulating nitric oxide synthase expression: an ex vivo study in isolated working rat hearts. Cardiovasc Res 2001;51:283–93. [7] Lefer AM, Siegfried MR, Ma XL. Protection of ischemia–reperfusion injury by sydnonimine NO donors via inhibition of neutrophil–endothelium interaction. J Cardiovasc Pharmacol 1993;22(Suppl 7):S27–33.

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[8] Bell RM, Yellon DM. Atorvastatin, administered at the onset of reperfusion, and independent of lipid lowering, protects the myocardium by up-regulating a prosurvival pathway. J Am Coll Cardiol 2003;41:508–15. [9] Manfrini O, Pizzi C, Morgagni G, Fontana F, Bugiardini R. Effect of pravastatin on myocardial perfusion after percutaneous transluminal coronary angioplasty. Am J Cardiol 2004;93 1391–3, A6. [10] Celik T, Kursaklioglu H, Iyisoy A, et al. The effects of prior use of atorvastatin on coronary blood flow after primary percutaneous coronary intervention in patients presenting with acute myocardial infarction. Coron Artery Dis 2005;16:321–6. [11] Gibson CM, Murphy SA, Rizzo MJ, et al. Relationship between TIMI frame count and clinical outcomes after thrombolytic administration. Thrombolysis In Myocardial Infarction (TIMI) Study Group. Circulation 1999;99:1945–50. [12] Ishii H, Ichimiya S, Kanashiro M, et al. Effects of receipt of chronic statin therapy before the onset of acute myocardial infarction: a retrospective study in patients undergoing primary percutaneous coronary intervention. Clin Ther 2006;28:1812–9. [13] Iwakura K, Ito H, Kawano S, et al. Chronic pre-treatment of statins is associated with the reduction of the no-reflow phenomenon in the patients with reperfused acute myocardial infarction. Eur Heart J 2006;27:534–9.

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Two-dimensional speckle tracking echocardiography: A novel approach to evaluate left atrial mechanical function Huaying Fu 1, Tong Liu 1, Changyu Zhou, Chenghuan Zheng, Guangping Li ⁎ Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China

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Article history: Received 11 December 2011 Accepted 21 December 2011 Available online 12 January 2012 Keywords: Two-dimensional speckle tracking echocardiography Left atrial function Atrial fibrillation

Atrial fibrillation (AF) remains the most common clinically encountered arrhythmia associated with increased morbility and mortality. Unlike the other supraventricular arrhythmias, the underlying mechanisms of AF are still not clearly elucidated. Atrial remodeling process including electrical, structural and mechanical remodeling remains the cornerstone in the development and maintenance of AF. Among them, mechanical remodeling manifests as decreased atrial contractility and increased atrial compliance which lead to a stretch of the atrial myocardium, may also contribute to the occurrence of cardiogenic stroke [1]. Left atrial (LA) mechanical function includes reservoir, conduit and pump function which contribute to left ventricular filling at different stages of cardiac cycle. LA mechanical function can be evaluated by two-dimensional (2D) echocardiography, Doppler analysis of transmitral and pulmonary vein flow, and Tissue Doppler assessment of LA myocardial velocities [2–4]. However, the quantification of effective LA function still remains a challenging task. Two-dimensional strain imaging is an echocardiographic technique that uses standard B-mode images for speckle tracking analysis. The speckle pattern is followed frame-by-frame, using a statistical approach based on the detection of the best matching area. The displacement of this speckled

⁎ Corresponding author. Tel.: +86 22 88328368; fax: +86 22 28261158. E-mail address: [email protected] (G. Li). 1 The first 2 authors contributed equally to this work.

pattern is considered to follow myocardial movement, and a change between speckles is assumed to represent myocardial deformation [5,6]. Quantification of LA mechanical function by 2D speckle tracking has been recently proposed [7–9], and the assessment of global strain and strain rate (SR) using this new imaging technique has been utilized to predict new-onset non-valvular AF [10], postoperative AF [11] and AF recurrence following catheter ablation [12,13] and electrical cardioversion [14,15]. In a recent paper published in the International Journal of Cardiology, Henein et al. [16] assessed the LA mechanical function in 23 patients with paroxysmal atrial fibrillation (PAF) using 2D speckle tracking echocardiography. They demonstrated that global LA strain and strain rate (SR) were both decreased in patients with PAF compared with healthy controls. Further analysis in regional strain and SR showed lateral S and SR were also reduced. Both septal and lateral wall SR correlated with E/A. However, the PAF patients enrolled in this study all suffered from hypertension, which may also be a possible reason for the reduction of global LA strain and SR [17,18]. Furthermore, the number of patients with diabetes, which may decrease LA strain and SR [18], was not described in the paper. Also, none of the controls had any cardiovascular risk factors. Hypertension and other cardiovascular risk factors such as diabetes may also contribute to the reduced strain and SR in the PAF group. We recently performed another study to observe the LA mechanical function in patients with PAF using 2D speckle tracking echo. Our study population consisted of 33 patients with paroxysmal atrial fibrillation and 30 age, sex-matched controls in sinus rhythm who were referred to our echocardiography laboratory. LA wall strain in the longitudinal direction obtained using 2D speckle tracking. We measured both peak atrial longitudinal strain (PALS) and atrial contraction longitudinal strain (ACLS) in apical 4-chamber view and apical 2-chamber view. Time to peak longitudinal strain (TPLS) was also measured in the apical 4-chamber view and the apical 2-chamber view. △TPLS was defined as the difference between the TPLS in apical 4-chamber view and apical 2-chamber view. There were no significant differences between the 2 groups regarding age (63 ± 12 vs 60 ± 9 yrs), sex (males 48% vs 60%) and