Antithrombotic treatment strategy for patients with coronary artery ectasia and acute myocardial infarction: A case report

lNTRODUCTlON

Coronary artery ectasia (CAE) is defined as the dilatation of coronary arteries to a diameter ≥ 1.5 times the normal adjacent segment. The prevalence of CAE during coronary angiography (CAG) was found to be 0.9%-5.3%, and more than 50% of CAE cases had co-existing coronary heart disease (CHD)[1]. The principal manifestations of CAE include angina, acute myocardial infarction (AMI), arrhythmia, and sudden death[2]. CAE is characterized by extensive destruction of the musculoelastic elements in the coronary artery wall of unknown etiology and pathogenesis[3]. In daily practice, a substantial portion of patients with CAE are first diagnosed in the emergency department. Swaye and Valenta reported that the prevalence of AMI in the CAE population was higher than in the CHD and other non-CAE populations[4,5]. This supports the idea that thrombotic complications are prone to occur to some degree in patients with CAE; however, there is no consensus concerning the treatment of CAE,specifically an antithrombotic strategy. In practice, most medications are recommended according to CHD, and for patients with poor response to medications, coronary artery interventional therapy and coronary artery bypass graft should be considered[6]. In this study we observed a patient with CAE and AMI for 48 months to explore the antithrombotic strategy.

CASE PRESENTATlON

Chief complaints

A 60-year-old Chinese male patient complained of intermittent chest tightness and chest pain for 4 mo,with worsening symptoms 3 d prior to admission into Beijing Friendship Hospital.

“你看，周星馳都沒有讀大學！就連那個華人首富李嘉誠都沒有讀什么書！你那個什么二級學院，還是個美術專業，有什么好讀的啊？讀出來還是找不到工作，畢業就失業！還不如不讀嘛！”

History of present illness

No special notes.

A組患者與B組患者均持續使用鹽酸氨溴索治療,30mg/次,溶劑為100ml生理鹽水,靜脈滴注,3次/d。A組持續用藥時間為8d,B組持續用藥時間為16d。

History of past illness

National Natural Science Foundation of China, No. 81600276.

血紅素：血紅素一般用作藥物和保健品,有載氧、貯氧、促進氧化還原、進行電子傳遞等重要生物學功能、可用作半合成血卟啉(HP)及其衍生物(HPD)、原卟啉鈉原料，也可用作肉類食品添加劑,主要作著色劑使用。因此可以以藏羊血為原料，進行血紅素系列產品的生產，必將得到廣大消費者的認可。

表2相異矩陣中的數據表示高頻關鍵詞之間的距離遠近，數值越接近0表明對應的兩個高頻關鍵詞之間的內在距離越近，相似度越高；反之，數值越接近1表明對應的兩個高頻關鍵詞之間的內在距離越遠，相似度越低。同時相異系數矩陣對角線上的數值0表示高頻關鍵詞自身的相關程度。由表2獲悉，各關鍵詞與正念療法非直接相關，除關鍵詞“禪修”和“認知療法”外，其余關鍵詞同正念療法的相異系數值均為1。

Personal and family history

Emergency tests showed peripheral blood myocardial injury markers were significantly increased:Creatine kinase MB fraction was 17.70 ng/mL (reference 0.00-6.60 ng/mL), troponin I was 3.731 ng/mL(reference 0.000-0.030 ng/mL), and troponin T was 0.370 ng/mL (reference 0.000-0.017 ng/mL). The routine blood tests, routine urine tests, renal and hepatic function were normal. The thromboelastogram showed that the patient had no clopidogrel resistance.

Physical examination

The patient’s pulse rate was 95 beats per minute, blood pressure was 131/90 mmHg (17.4/12.0 KPa),height was 165cm, weight was 86 kg, and body mass index was 31.59 kg/m. There were no obvious positive cardiovascular signs or other other system signs.

Laboratory examinations

The patient quit smoking 5 years ago, and occasionally consumes a small amount of alcohol. He has a family history of hypertension.

Imaging examinations

For patients with CAE and AMI, during the first 12 mo after AMI, the antithrombotic strategy of a combination of aspirin (100 mg/d) and ticagrelor (90 mg twice per day) might be more effective than the combination of aspirin (100 mg/d) and clopidogrel (75 mg/d). In addition, 12 mo after AMI DAPT should be considered baseline treatment.

[17]Meara,P.,&Buxton,B.(1987).An alternative to multiple choice vocabulary tests．Language Testing,4,142-154.

FlNAL DlAGNOSlS

ST-segment elevated myocardial infarction (STEMI), heart function Killip grade I.

TREATMENT

After admission the following medications were administered: antiplatelet agents, including aspirin(aspirin enteric-coated tablet, 100 mg/d) and clopidogrel (clopidogrel hydrogen sulphate tablet, 75 mg/d), low-molecular-weight heparin (LMWH, enoxaparin sodium 6000 IU, twice per day for 1 wk),statin (rosuvastatin calcium tablet, 10 mg per night), beta-blocker (metoprolol tartrate tablet, 25 mg twice per day) and angiotensin receptor blocker (ARB, losartan potassium tablet, 50 mg/d). The chest pain was gradually relieved.

The first coronary angiography (CAG) was performed 3 d after admission to the hospital and showed aneurysmal dilation in the entire right coronary artery (RCA), with a diameter of 6.60 mm (Figure 1),which is four folds larger than the 5 French catheter and more than 1.70 fold larger than the normal RCA[7]. The middle of the RCA presented with 70%-80% limited stenosis, a thrombus shadow after the second turning point, and a grade 3 thrombolysis in myocardial infarction (TIMI) forward blood flow.In addition, part of the left anterior descending (LAD) coronary artery showed ectatic changes and was classified as Markis type II CAE[3]. The middle and distal parts of the LAD coronary artery had 40%-50% segmental stenosis, with a TIMI grade 3 forward blood flow. The left circumflex coronary artery was normal.

①螺孔螺栓接觸部位存在異物，在結合處形成卡澀。本次在螺栓擰入前對螺栓及螺孔螺紋進行了仔細檢查，記錄顯示此情況的可能性較小。

No additional percutaneous coronary intervention (PCI) was performed because the symptoms were relieved and coronary blood flow was unobstructed. The second CAG (Figure 2) was performed 2 wk later and showed that the RCA thrombus had disappeared, with a TIMI grade 3 forward blood flow. All of the medications mentioned previously, except LMWH, were continued.

OUTCOME AND FOLLOW-UP

In the fifth month, the patient presented with sudden chest pain associated with palpitations, sweating,and dyspnoea. Three hours later emergency electrocardiogram showed the ST-segment increased by 0.1-0.2 mv in leads II, III, and aVF. Troponin I was 0.019 ng/mL, creatine kinase MB fraction was 1.80 ng/mL, and troponin T was ＜ 0.010ng/mL. A STEMI was again diagnosed and an emergency CAG(Figure 3, the third CAG) showed that the middle RCA had a 100% occlusion with a thrombus shadow.Thrombus aspiration was performed and a small amount of white flocculent thrombus was extracted.The thromboelastogram showed no resistance for aspirin and clopidogrel. After discussions within the PCI group, clopidogrel was replaced by ticagrelor, and if the combination of aspirin and ticagrelor could not prevent thrombotic events, then an oral anticoagulation agent could be considered. Thus, we began treatment with aspirin (100 mg/d), ticagrelor (ticagrelor tablet, 90 mg twice per day), and 1 wk of LMWH. The other medications were continued as before.

In the sixth month the patient developed slight chest tightness without obvious ECG changes. A fourth CAG (Figure 4) was performed which showed that the middle of the RCA was slightly blurred.There were no obvious changes in other sites. The chest tightness was considered a side effect of ticagrelor. The medication was not changed, and the overall condition remained stable. About 12 mo after starting ticagrelor (eighteenth month of dynamic observation) the dosage was reduced from 90 mg twice per day to 45 mg twice per day due to nasal haemorrhage. Several days later chest pain reoccured frequently, so the dosage of ticagrelor was returned to 90 mg twice a day, and several later attempts at reducing the dosage were not successful. Of the total 48 mo of dynamic observation, the combination of aspirin and ticagrelor was observed for 42 mo; during this time the patient’s condition was stable and no obvious chest pain was observed (Table 1).

DlSCUSSlON

It should be emphasized that a complete treatment for CAE patients was essential by comprehensively evaluating applications of medical agents including anti-thrombotic agents, statin, ARB/angiotensin-converting enzyme inhibitor, beta-blocker, calcium channel blocker and antianginal agent, PCIs including thrombosis aspiration, coronary angioplasty, coronary stent implantation and so on, as well as surgical operations including dilated coronary artery resection, folding, transplantation and distal grafts ligation[1,2,6]. For the anti-thrombotic agents, in this case the patient was diagnosed with CAE and AMI; however, the combination of aspirin and clopidogrel could not prevent a second AMI. Clopidogrel was replaced with ticagrelor when the patient was in relatively stable condition; however, every attempt to reduce the dosage of ticagrelor was associated with recurrent chest pain which disappeared after reinstatement of the original dosage. Thus, the combination of aspirin and ticagrelor worked better than the combination of aspirin and clopidogrel after AMI despite the fact that there was no clopidogrel resistance according to the thromboelastogram. Our individual experience in this case needs to be verified by future trials with a larger sample size. The use of anti-coagulation agents also needs to be explored and discussed in the future.

This case involved three questions which confused us in everyday clinical practice.

一般城市車載導航系統的數據維護是一個難題，維護時需要人工采集道路信息，浪費了大量的人力物力資源。本車載系統所設計的信息即時更新模塊能有效的改善這一難題。當農機手在工作室時發現有新的道路信息出現，而且主機數據端未獲取該信息時，農機手可通過短消息通知主機某區域有新增道路信息，具體界面如圖6所示。

The first question is “Do patients with CAE need antithrombotictic therapy?” As mentioned in the introduction, a large proportion of patients with CAE, especially older patients, have co-existing CHD,and CAE was more likely to present with thrombotic complications than patients with CHD[4,5]. The expansion sites were often the sites of thrombus formation (culprit vessels), without significant changes in atherosclerosis and stenosis[6]; the thrombus was often large because of the existence of local abnormal coronary blood flow[8]. Several studies found that patients with CAE had a large peripheral blood mean platelet volume which is also the reason for antiplatelet therapy[9]. Additionally, our previous research team showed that the prevalence of AMI in patients with CAE who received antiplatelet treatment was significantly lower than in patients with CAE who did not receive antiplatelet treatment (15.234.7%,= 0.020)[10]. Thus, in general CAE is associated with a higher thrombotic risk, and most treatments proposed for CAE are based on CHD treatments and these patients should be placed routinely on aspirin at least as a tool of primary prevention[6].

The second question is “Is aspirin enough for CAE patients?” The antithrombotic medicines included antiplatelet agents and anticoagulation agents. There is no consensus on what is the best strategy, single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), or a combination of antiplatelet and anticoagulant therapy. The idea of adenosine diphosphate receptor inhibitors in combination with aspirin has not yet been thoroughly studied in clinical trials. Previous studies showed similar adverse event rates in patients with and without CAE[4,5,11,12], while other studies revealed higher adverse events in patients with CAE[2,13,14]. Hart[15] suggested that long-term warfarin therapy should be implemented to decrease the risk of coronary thrombus formation and its deleterious consequences,while aspirin would be sufficient to manage asymptomatic CAE. Other researchers noted that larger coronary aneurysms require aggressive treatment through a combination of antiplatelet and anticoagulant therapy[16]. According to our limited experience, most CAE were associated with CHD, and the AMI in CAE was an arterial thrombotic event; thus, DAPT would be a better choice as the baseline medications if the patient did not have a high risk of bleeding. More evidence is needed to justify the antithrombotic strategies.

Zhao HQ and Liu RF contributed to collecting clinical details; Gao ΧY and Liang SW contributed to drafting and writing the manuscript; Zhao HQ and Liu RF made substantial contribution to manuscript revision; all authors reviewed and approved the final manuscript.

CONCLUSlON

The emergency electrocardiogram showed clear Q waves in lead III and lead avF. Echocardiography showed the left ventricular ejection fraction was 69%, and there were no abnormalities in any of the heart valves.

FOOTNOTES

Regarding the third question, “How do we determine the antithrombotic strategy for patients with CAE and AMI?” The success rate of reperfusion treatment in patients with CAE who have coronary artery thrombotic events is lower than in patients with non-CAE AMI. A large thrombus may also increase the no-reflow phenomenon, distal embolization, and stent thrombosis[17-19]. A recently published systematic review summarized that the addition of anticoagulant treatment seemed to be more effective than DAPT alone for patients with CAE and ACS, the authors suggested that anticoagulant treatment must be considered if SAPT/DAPT fail to provide adequate protection against the recurrence of ACS, especially in patients with CAE who did not have other obvious stenotic lesions[20].Current guidelines for CHD state that for patients with ACS, DAPT should be continued for 12 mo unless there are contraindications, such as a high risk of bleeding[21]. In this study, a relatively conservative treatment strategy was followed with DAPT therapy, which was not combined with anticoagulants because of the risk of bleeding, and the results indicate that the combination of aspirin and ticagrelor could prevent thrombotic events, while the combination of aspirin and clopidogrel did not. In the PLATO trial, ticagrelor proved to be superior to clopidogrel in patients with ACS irrespective of planned or unplanned invasive management, but the side effects of ticagrelor included dyspnoea (the chest tightness of this patient was considered a side effect) and a higher bleeding rate[22]. Thus, the combination of aspirin and ticagrelor was recommended as the baseline treatment for patients with CAE and ACS. The more aggressive treatment of DAPT combined with an anticoagulant agent should be considered in patients with a higher risk of thrombosis but it would significantly increase the risk of bleeding.

The patient had a history of hypertension, hyperlipidaemia, and diabetes mellitus.

This patient agreed for all of his treatment and was informed that his medical information would be analyzed and published by us for the scientific purpose.

The authors report no relationships that could be construed as a conflict of interest.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BYNC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is noncommercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

China

Rui-Feng Liu 0000-0003-2405-5447; Χiang-Yu Gao 0000-0002-9466-9068; Si-Wen Liang 0000-0002-4421-7485; Hui-Qiang Zhao 0000-0002-7175-8703.

Liu JH

A

貫徹落實鄉村振興戰略，改善農村人居環境，切實推進美麗鄉村建設，針對當前美麗鄉村規劃設計過程中存在的“有規劃設計無指導服務”“不按規劃設計實施建設”等問題，采取村莊規劃設計陪伴式服務方式，以“規劃先行”為主導思想，以“陪伴式服務”全程把控美麗鄉村建設。

Liu JH