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Serum Amyloid a Protein As a Predictor of Cardiac Rupture in Acute Myocardial Infarction Patients Following Primary Coronary Angioplasty

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Serum Amyloid a Protein As a Predictor of Cardiac Rupture in Acute Myocardial Infarction Patients Following Primary Coronary Angioplasty Circ J 2006; 70: 530–535 Serum Amyloid A Protein as a Predictor of Cardiac Rupture in Acute Myocardial Infarction Patients Following Primary Coronary Angioplasty Toshiro Katayama, MD; Hiroshi Nakashima, MD*; Chisa Takagi, MD*; Yukiharu Honda, MD*; Shin Suzuki, MD*; Yoshihiro Iwasaki, MD**; Tadashi Yamamoto, MD**; Masato Yoshioka, MD**; Katsusuke Yano, MD Background The predictors of cardiac rupture (CR) in patients with acute myocardial infarction (AMI) treated with successful primary coronary angioplasty have not been identified. Methods and Results Of 433 consecutive AMI subjects who underwent reperfusion by primary coronary angioplasty within 24 h of onset, CR occurred in 11 (2.5%), free wall rupture in 9, and ventricular septal perfora- tion in 2. Rates of females, diabetes mellitus and anterior infarction were higher in the group of CR patients than in the others (p<0.05). There were no significant differences between the 2 groups in terms of left ventricular (LV) function soon after recanalization, such as LV ejection fraction, regional wall motion, or end-diastolic volume index. Plasma levels of both high-sensitivity C-reactive protein (hsCRP) and serum amyloid-A protein (SAA) were significantly higher in the CR patients than in the others (hsCRP: 6.7±6.7mg/dl vs 3.3±3.8 mg/dl, p=0.007; SAA: 699±812μg/dl vs 208±273μg/dl, p<0.0001). Multivariate analysis identified SAA as an indepen- dent predictor of CR (risk ratio: 8.8, 95%confidence interval: 1.7–25.6, p<0.05). Conclusions In patients with AMI treated with primary coronary angioplasty, inflammation may be closely related to CR, for which SAA is a useful predictor. (Circ J 2006; 70: 530–535) Key Words: Cardiac rupture; C-reactive protein; Myocardial infarction; Serum amyloid-A protein n acute myocardial infarction (AMI), early recanaliza- of SAA are similar to those of CRP, but the clinical impli- tion of the culprit coronary artery is vital for the pres- cation of the relationship between SAA and CR in AMI I ervation of cardiac function and patient prognosis.1,2 patients is unknown. One method is direct percutaneous coronary intervention (PCI), now widely recognized as a useful and effective ther- apeutic strategy, and one associated with good outcomes Methods for the patient.3,4 Although rare, cardiac rupture (CR) is a Patient Population major adverse clinical consequence that is difficult to Between October 1999 and August 2005, 461 consecu- predict, and almost always fatal. tive patients with AMI who were admitted to hospital Current thinking suggests systemic inflammation is asso- within 24h of onset were enrolled in the study. The study ciated with ischemic heart diseases, including AMI.5,6 Pre- protocol, which included blood sampling for CRP and vious studies have demonstrated that C-reactive protein SAA, was approved by the hospital ethics committee, and (CRP), an acute phase representative protein, is associated informed consent was given by each patient and/or the with various complications in AMI, including cardiac family to 1 of the investigators before entry into the study. events.7,8 It has been reported that the peak CRP concentra- Diagnosis of AMI was based on: (1) complaint of chest tion in plasma is an important predictor of CR,9,10 but serum pain; (2) electrocardiographic ST segment elevation of amyloid A protein (SAA) is also an important acute phase >0.1mV in 2 or more limb leads, or >0.2mV in 2 or more inflammatory protein that has an expanded dynamic range precordial leads, or presentation of left-bundle branch with different kinetics compared with CRP and is reported block; and (3) elevated peak-serum creatine kinase (CK) to be a more sensitive indicator of inflammation in some more than twice the upper limit of the patient’s normal noncardiovascular conditions.11 When in vivo inflammation range. We excluded patients with renal failure on admission occurs, synthesis of SAA, as well as CRP, in the liver is (serum CK >2.5mg/dl), patients admitted >24h after onset, accelerated by inflammatory cytokines; that is, the kinetics patients who died <24h after onset (ie, after blood samples had been taken) and patients who underwent drug-eluting (Received October 26, 2005; revised manuscript received January 5, stent implantation. Furthermore, to avoid other variables 2006; accepted February 15, 2006) that could influence the serum levels of high-sensitivity Department of Cardiovascular Medicine and Course of Medical and CRP (hsCRP) or SAA, we excluded patients with a history Dental Science, Graduate School of Biomedical Science, Nagasaki of recent surgery or trauma within the preceding 2 months, University, *Department of Cardiology, Nagasaki Citizens Hospital and **Department of Cardiology, Nagasaki Kouseikai Hospital, malignancy or liver cirrhosis, acute or chronic inflammatory Nagasaki, Japan disease, or collagen disease. We had no patients with Mailing address: Toshiro Katayama, MD, 2-5-5-1615 Akasako, primary or secondary amyloidosis. In the end, 433 is the Nagasaki 852-8156, Japan. E-mail: [email protected] number of patients after exclusions. There were 224 cases Circulation Journal Vol.70, May 2006 Predictors of Cardiac Rupture in AMI 531 Table 1 Patient and Lesion Characteristics in Cases of CR Case Age Culprit location SAA Peak CK BNP hs-CRP at 24 h Day of occurrence Type Previous Diabetes Hyper Gender Hypertension Outcome no. (years) (segment no.) (μg/dl) (IU/L) (pg/ml) since onset (mg/dl) of CR of CR MI mellitus lipidemia 1 F 70 6 371 12,199 325 6.79 4 FWR(B) – – + – Dead 2 M 88 5 546 9,425 195 11.28 3 FWR(B) – – + – Dead 3 M 69 5 373 2,039 73 1.00 7 VSP – + + + Alive 4 M 71 6 493 2,748 434 0.15 3 FWR(B) – + – – Dead 5 F 89 7 940 8,414 221 12.32 2 FWR(O) – – – – Alive 6 M 56 6 328 2,311 183 4.11 5 VSP + + – + Alive 7 F 67 7 460 3,426 461 4.01 6 FWR(B) – + + + Dead 8 F 81 6 1,605 1,110 136 14.27 2 FWR(B) – + – – Alive 9 F 85 2 110 4,056 441 5.02 9 FWR(O) – – + – Dead 10 F 75 7 592 4,263 748 13.86 2 FWR(O) + – + + Alive 11 F 91 11 1,603 2,601 230 3.23 3 FWR(B) – + + + Dead CR, cardiac rupture; segment no., location of coronary artery by American Heart Association; SAA, serum amyloid A protein; Peak CK, peak value of creatine kinase; BNP, brain natriuretic peptide; CRP, C-reactive protein; Previous MI, previous myocardial infarction; FWR, free wall rupture; B, blow-out type free wall rupture; VSP, ventricular septal perforation; O, oozing type free wall rupture. of anterior myocardial infarction (MI). type), ventricular septal perforation (VSP) and papillary muscle rupture. The diagnosis of free wall rupture was Treatment Strategy based on echocardiography followed by pericardiocentesis Following oral administration of 200mg of aspirin and or surgical or postmortem examination. The blow-out type 200mg of ticlopidine, all patients underwent direct PCI of rupture was defined as a free wall rupture with electro- within 2h of admission. For 72h after reperfusion therapy, mechanical dissociation, and sudden onset of severe hypo- all patients were given intravenous nicorandil (96mg/day) tension without ECG change. The oozing type rupture was and heparin (10,000units/day). We did not use abciximab. defined as a gradual bleeding into the pericardial sac, causing progressive or recurrent cardiac tamponade. VSP Blood Sampling was diagnosed on the basis of abnormal shunt-flow at the On admission, blood samples were taken while patients interventricular septum on color Doppler echocardiogra- were supine, for analysis of hsCRP, CK, and troponin-T. phy. Our follow-up period was 30 days after onset of AMI. For 3 days after admission hsCRP was serially determined The primary endpoint was CR or cardiac death. every 24h, and CK every 4h. At 24h after onset, blood samples were taken, again while patients were supine, for Statistical Analysis analysis of brain natriuretic peptide (BNP), atrial natri- Values are expressed as mean±standard-deviation. All uretic peptide (ANP), renin, aldosterone, epinephrine, statistical tests were 2-tailed, and a p-value <0.05 was con- norepinephrine, and SAA. The SAA assay by the latex sidered statistically significant. The chosen cut-off points agglutination nephelometric immunoassay was contracted for the concentrations of the hsCRP at 24-h since onset, out (BioMedical Laboratories Inc). SAA, peak-CK, and BNP were based on the highest tertiles in the overall sample. Multivariate logistic regression Hemodynamics and Cardiac Function analyses were performed, with the independent variables On admission, we used the Killip classification to assess including age, gender, diabetes mellitus, culprit lesion loca- the severity of the patient’s condition. We also evaluated tion, the number of vessels involved, Killip classification major complications, defined as ventricular arrhythmia on admission, ANP, BNP, peak-CK value, hsCRP at 24-h (except reperfusion arrhythmia), pulmonary edema, car- since onset, and SAA. The odds ratios and 95%confidence diogenic shock, sub-acute thrombosis and cardiac death. intervals (CI) were also calculated. We defined cardiogenic shock as systolic blood pressure <90 mmHg (without inotropic or intra-aortic balloon (IABP) support), signs of hypoperfusion (cold extremities, Results impaired mental status, or urine output <30 ml/h), and A total of 433 patients with AMI were analyzed (291 evidence of pulmonary congestion on chest X-ray. male, 142 female; mean age 69±12 years). Before PCI ther- All subjects, except 29 with cardiogenic shock, under- apy, simple aspiration thrombectomy catheters were used went left ventriculography soon after recanalization from a in 184 patients with massive visible thrombus, but distal single plane with a right anterior deviation of 30° to evalu- protection devices were not used.
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