Dose All of the Coronary Fistulas been Created by the Reopening Wire After Successful Revascularization of Chronic Total Occlusion?

Background: Coronary stulas may be congenital or acquired generally as consequence of coronary interventions, mainly chronic total occlusion (CTO) reopening. When the reopening wire passes through the occlusion it may microperforate the advential vascular layers, favoring the stulous communication between coronary vessel and cardiac chambers. But some of acquired coronary stulas (ACFs) had been already present at the CTO vessels and would been seen after revascularization. This study was designed to investigate the characteristics of ACFs, which albeit mostly benign can cause concern and unnecessary treatment post successful CTO percutaneous coronary intervention (PCI). Methods: Data, including clinical and procedural characteristics, medical history, and ndings in electrocardiography, echocardiography and coronary angiography, from 2169 consecutive patients undergoing CTO PCI between January 2018 and December 2019 were analyzed retrospectively. Results: 1844 (85.0%) underwent successful CTO PCI with complete revascularization. Among them, there were 49 cases (mean age, 62.80 ± 11.24 years; 40 men) of ACFs: 24 (49%) involved the right coronary artery, 19 (38.8%) the left anterior descending artery, and 6 (12.2%) the circumex branch; and 38 (77.6%) were coupled with multiple stulas (>3), and 29 (59.2%) affected multiple branches of the CTO vessel (>3). The majority of patients with ACFs had a history of MI or Q-wave (n=34, 69.4%), and angina was the most common complaint (n=41, 83.7%). None of them had pericardial effusion, tamponade and Hemodynamic abnormalities before or after PCI. Conclusion: ACFs after successful CTO PCI mostly developed in patients with MI history, originated from the right coronary artery or left anterior descending artery, and involved multiple stulas and CTO vessel branches. rich


Introduction
Coronary stulas rst described as congenital and abnormal vascular connections between coronary arteries and cardiac chambers or with other vessels, were later found to have other etiologies [1], including trauma, surgery, severe coronary atherosclerosis and myocardial infarction (MI). As rst reported by Ryan in 1977 [2] and later by others [3][4][5], MI is a common cause of acquired coronary stulas (ACFs). ACFs secondary to MI are harmless, common in patients with chronic total occlusion (CTO), and hard to nd before complete revascularization because of insu cient collateral lling. With higher rates of successful percutaneous coronary intervention (PCI) of CTO with new equipment and techniques, more ACFs are visualized after CTO PCI. It is important to distinguish ACF from coronary perforation (CP), a rare but potentially serious complication in PCI which can lead to pericardial effusion and tamponade, often necessitating medical treatment and even emergency pericardiocentesis or cardiac surgery [6]. To this end, there has not been a systematic description of imaging characteristics, medical history, and predictors of ACFs in a real-word cohort of patients who underwent successful CTO revascularization, which is therefore the subject of this study.

Patients
We retrospectively analyzed 2169 consecutive patients who underwent CTO PCI at ZhongShan Hospital of Fudan University from January 2018 to December 2019. Patients were excluded if the PCI was undertaken in the setting of an acute coronary syndrome. All original angiograms were reviewed by two physicians to con rm ACFs and to extract other clinical information. The study was approved by the institutional review board and all patients signed a general informed consent form.

Procedure
All patients were treated with oral dual antiplatelet drug before the procedure, unfractionated heparin was administered intravenously at 100 IU/Kg followed by further heparin as necessary to achieve a target activated clotting time of 250-350 s. Microcatheter include Finecross (Terumo, Japan) and Corsair (Asahi, Japan), and CTO guidewire include Fielder XT (Asahi, Janpan), Fielder XTR (Asahi, Janpan), Gaia 2 and 3 (Asahi, Janpan), Pilot 150 and 200 (Abbott, America) had been used widely during the procedure.
Study de nitions CTO was de ned as a complete occlusion with thrombolysis in myocardial infarction (TIMI) ow grade 0 antegrade for ≥ 3 months [7]. Procedural success was de ned as < 50% residual stenosis with antegrade TIMI ow grade 3 at the end of the procedure [8]. ACF was de ned as an abnormal connection between coronary arteries and cardiac chambers or with other vessels, which are secondary to exogenous or endogenous injury [1]. History of myocardial infarction was identi ed by past medical record including STsegment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) based on initial ECG, and clinical and laboratory ndings. Adverse events captured included death from all causes, stent thrombosis (ST)/Q-wave myocardial infarction, emergent cardiac surgery and cardiac tamponade. Degree of development of coronary collaterals in CTO was classi ed using Rentrop Grade as follows [9]: 0 = none; 1 = lling of side branches of the artery to be dilated via collateral channels without visualization of the epicardial segment; 2 = partial epicardial lling of the occluded artery; and 3 = complete epicardial lling of the occluded artery.

Data collection
Demographic, procedural, and medical data were obtained from review of the catheterization laboratory database and medical records of patients.

Statistical analysis
Continuous variables are presented as mean ± SD and were compared using t-test. Categorical variables are presented as counts and percentages and were compared using X 2 test of Fisher's exact test. All analyses were performed using SPSS V26, and p < 0.05 was considered statistically signi cant.

Baseline clinical characteristics
Among the 2169 consecutive patients who underwent CTO PCI, procedural success was achieved in 1844 (85.0%). Among these 1844 patients, ACFs were found at the end of the procedure in 49 cases with mean age of 62.80 ± 11.24 years; 40 men (81.6%); 25 (51.0%) hypertensives, 15 (30.6%) diabetics, 5 (10.2%) with hyperlipidemia; 23 long-term smokers; and 10 with previous PCI and none with previous coronary artery bypass surgery (CABG); microcatheter and guidewire which had been used to cross the occlusion are listed in Table 1.

Electrocardiogram (ECG) and Echocardiography
As shown in Fig. 1 Table 1. None pericardial effusion and tamponade had been found in patients with ACFs.
As shown in Table 3, clinical and imaging characteristics and medical history parameters were similarly distributed among cases of ACF originating from RCA, LAD and LCX, except for smoking that was more frequent in cases of ACFs originating in RCA and LAD than LCX. The mean length of hospital stay was 4.45 days, and there were no in-hospital cases of death, emergent cardiac surgery or MI.

Discussion
In the present study, the most common characteristics of ACFs in successful CTO PCI patients included: multiplicity and diffusibility with three or more branch vessels and drainage sites; and a history of MI or Q-Wave (69.4% vs. 56.3%-58.4% in the overall CTO population) [10,11]. Smoking is a risk factor for coronary artery disease (CHD), and is more frequent among ACFs originating from LAD and RCA, which could be secondary to smaller sample size or lower incidence in LCX. In the presence of ACFs, the contrast agent quickly diffuses out of the coronary artery without retention during angiography.
In our data, the prevalence of ACFs in successful CTO PCI patients was 2.60%, which is lower than that the up to 8.9% one for CP during CTO PCI [12]. On occasions, CP and ACFs have similar angiographic appearance, and Ellis classi cation has been used to classify CP as type - [13]. Unlike CP, ACFs drain into the cardiac chambers, and therefore pericardial effusion and tamponade do not develop thereby rendering procedures safe. Wrong judgment of operator and lack of bedside echocardiography may lead to concern and unnecessary treatment, such as coil embolization which would be feasible and effective in treating CP, but useless and unnecessary in ACFs (Fig. 3, Movie S7 and S8 in Supplementary). It is therefore important to distinguish ACFs from CP during CTO PCI.
ACFs could result from MI, hypertrophic cardiomyopathy, dilated cardiomyopathy, tumor, PCI, CABG, cardiac transplant, cardiac biopsy, and pacemaker placement, among other etiologies [14][15][16]. Rupture of the microvasculature may be the most important cause of ACFs [17,18]. A sudden total occlusion of a coronary artery blocks blood ow to the heart muscle leading to tissue death. Because of extensive myocardial cell necrosis, myocardial rupture will occur within the rst two weeks in 90% of MI [19,20]. Complete rupture triggers hemopericardium and sudden death, and incomplete rupture will become a ventricular aneurysm because the pericardium seals the ventricular perforation. In CTO patients, in contrast, the coronary artery obturates slowly allowing development of collateral circulation, and myocardial death does not cause symptoms and patients can survive the attack, but death of endocardium damages the microvasculature. Myocardial scarring and rupture of the microvasculature causes ACFs, which become apparent by coronary angiography after successful CTO-PCI. In some of the patients with ACFs and good collaterals and no history of MI or Q-Wave, other underlying mechanisms for ACFs include newly developed collaterals, neo-vascularization of mural thrombus formation and reopening of the thebesian vessels [21].
ACFs caused by MI drain into LV more than right ventricle (RV) [5,22], possibly because: (a) right ventricular myocardial infarction may not result in signi cant ischemia or infarction; the thin walls of the RV require less oxygen, and the ability of RV to extract oxygen is increased during MI; rich collaterals from LAD reduce infarct size, and the RV has direct blood supply from the RV cavity through the thebesian veins, with coronary perfusion of the RV occurring both in systole and diastole [23,24]; and (b) most of the ACFs are located at the end of the coronary arteries which mainly supply the LV. Moreover, no coronary steal syndrome or hemodynamic impairment was apparent after CTO PCI in our patients with ACFs.

Limitations
Because the drainage sites were tiny, we couldn't clear and con rm where the drainage sites of ACFs located by Transthoracic Echocardiogram (TTE), but no pericardial effusion and tamponade had been con rm after PCI. ACFs have been reported to cause myocardial ischemia, endocarditis and congestive heart failure [25], but long-term tracking are needed to evaluate whether ACFs are associated with poor prognosis in CTO patients.

Conclusion
In the present study, It is very important to recognize ACFs, which is di cult to distinguish with CP during CTO PCI. ACFs albeit mostly benign can cause concern and unnecessary treatment, such as coil embolization. The characteristic of ACFs are diffusibility, asymptomatic, distal coronary artery-left ventricular stulas in patients with history of MI.
Declarations Figure 1 The