| Introduction:Atrial fibrillation(AF)is the most common sustained cardiac arrhythmia encountered in clinical practice.AF patients confer markedly increased morbidity and mortality due to its most feared complications stroke and systemic thromboembolism.The pathophysiological mechanism of increased prothrombotic tendency is multifactorial and complex in AF patients.However,increasing evidence suggests that hyperactive platelets and abnormal inflammatory response play an important role in thrombus formation in AF patients through the prospect of Virchow's Triad.AF can be initiated by ectopic beats from the pulmonary veins(PVs)has led to the development of catheter ablation(CA)as a curative treatment option.CA has been reported with prolonged maintenance of sinus rhythm;decreased number of AF events,and improved quality of life as compared to anti-arrhythmic drugs.Radiofrequency(RF)point-by-point ablation is the most common energy used worldwide to achieve PVs isolation during CA.However,RF ablation is associated with major risk of complications,typically within first two weeks after the procedure.These complications include permanent injury,esophageal fistulas,cardiac perforation,ischemic stroke,or death.To avoid such complications,there is a continuing search for alternative techniques that should be more effective and easily be performed with fewer procedure complications.Recently,cryoballoon(CB)ablation has emerged as a highly effective alternative technique to RF ablation.CB ablation is a simple and single shot procedure for creating circumferential transmural lesions to achieve effective PVs isolation in paroxysmal AF patients.Previous studies investigating prothrombotic state measured by platelet and inflammatory biomarkers yielded opposite results at short-term after CB and RF ablation.Furthermore,whether CA for PV isolation withCB and RF energies will impact on prothrombotic state at long-term is still unknown.In addition,there is an increasing concern that similar pathophysiological mechanism of thrombus formation on left atrial appendage might be possible on right atrial appendage in AF patients,which could lead to pulmonary embolism(PE).Traditionally,PE is thought to stem from an underlying,silent or overt deep vein thrombosis(DVT).But,the majority of publishing data found DVT in 50%of patients with proven PE via extensive detection methods including ultrasonography,contrast venography,and magnetic resonance imaging.However,there are limited studies to evaluate the most common risk factors of PE in patients with or without AF patients.Objectives:This thesis aimed to evaluate three main objectives1.The objective was to evaluate multiple platelet activation biomarkers change at long-term after catheter ablation in patients with paroxysmal AF.2.The aim was to evaluate the short and long-term response of platelet and inflammatory biomarkers after CB and RF ablation in paroxysmal AF patients.3.The purpose was to conduct a retrospective case-control study to investigate the most common risk factors and clinical characteristics of PE patients with and without AF.Methodology:In order to achieve three main objectives,this thesis used the different methodology for each objective.Which were conducted at The First Affiliated Hospital of Dalian Medical University.1.We recruited fifty patients with drug-refractory paroxysmal AF who were scheduled for the first time CA during Sep 2016 to Sep 2017.Exclusion criteria including long-standing(>12 months)and persistent AF,acute cause of AF,heart failure,inflammatory condition,cancer,left atrial diameter>55mm,and having previous history cerebrovascular events within the last 3 months.Platelet surface expression of P-selectin(CD62P),CD40 ligand(CD40L),platelet factor-4(PF-4),mean platelet volume(MPV),platelet-leukocyte ratio(P-LCR),and platelet distribution width(PDW)were measured at baseline(before ablation)and 6-Months postablation.Serial 7-day Holter monitoring and 12 leads ECG were performed at 1,3,and 6 months after the procedure during follow up.2.Fifty-eight patients with drug-refractory paroxysmal AF were randomly selected to perform PV isolation either via CB or RF ablation.Exclusion criteria and follow-up protocol were similar as mentioned above.However,biomarkers of platelet activation CD62P,CD40L,PF-4,MPV,P-LCR,and PDW,and inflammatory[high sensitivity CRP(hs-CRP)and interleukin 6(IL-6)]were measured at baseline(before ablation),18-24h and 6-Months postablation3.We retrospectively analyzed medical records of patients with confirmed diagnosis of PE with AF(Study Group)from 2002-2015.Patients with PE without AF,matched by age and sex,served as controls(Control Group).AF diagnosis was confirmed by 12-lead electrocardiography(ECG)or Holter,and PE diagnosis was considered to be confirmed when there was clinical manifestation with combined objective confirmation test by CT pulmonary angiogram(CTPA)or spiral computed tomography,perfusion-ventilation scan,high D-dimer>500 ug/L,low P02<80 and electrocardiographic signs(S1Q3T3).All demographic and clinical characteristic including potential risk factors for PE such as newly and previous history of DVT,active malignancy,history of recent surgery(previous 8 weeks)and smoking were obtained in both groups.Furthermore,the CHA2DS2-VASc and CHADS2 scores were calculated and classified into 2 categories,low-intermediated(<2 points)and high-risk(?2 points)for Study Group.Results:1.1.1.In all,41(85.4%)patients maintained sinus rhythm(SR group),whereas 7(14.6%)patients sustained a recurrence of AF(AFR group)at 6 months follow up.There were no significant differences in demographic,clinical characteristics and baseline level of all biomarkers in both groups(p>0.05).However,mean fluoroscopy time(minutes 22±11 vs.14±5,p = 0.004)was significantly longer in AFR than SR group.1.2.At 6-Month postablation,a significant decrease was observed in CD62P(%17.7±4.3 vs.19.1±4.8,p = 0.032),CD40L(pg/mL 28±25 vs.71±37 p<0.001),PF-4(pg/mL 75.8±32 vs.102±20,p<0.001),and MPV(fL 9.9±0.5 vs.10.1±0.7,p = 0.047),compared to baseline in SR group.Though,SR group was trend to decrease in PDW(fL 11.3±1.2 vs.11.9± 1.3,p = 0.104),and P-LCR(%24.5±5vs.25.4±5.7,p = 0.221),with no statistical difference.1.3.Despite less number of patients in AFR group,no significant difference was noted in CD62P(%17.5±4.6 vs.18.8±3.4,p = 0.386),CD40L(pg/mL 41±19.4 vs.56±34 p = 0,142),PF-4(pg/mL 106±20 vs.120±12,p = 0.215),and MPV(fL 10.5±0.6 vs.10.1 10.5,p = 0.203),PDW(fL 29.7±5.6 vs.27.3±5.6,p = 0.062),and P-LCR(%12.5±1.2 vs.11.9±1.3,p = 0.062)compared to baseline.2.2.1.All patients except one in CB group couldn't complete 6 months follow up.Twenty-four(86.2%)and twenty-six(89.7%)patients maintained sinus rhythm,whereas,4(13.8%)and 3(10.3%)patients sustained a recurrence of AF in CB and RF group respectively(p = 0.500).No significant differences were found in the clinical characteristics and at baseline biomarkers in both groups(p>0.05).2.2.Significant activations were noted in CD62P,CD40L,PF-4,IL-6,and hs-CRP at 18-24h postablation in both groups(p<0.001).However,CD62P(%29.1±5.4 vs.34.4±7.7,p = 0.005)was significantly decreased in CB than RF group.In addition,PDW(fL 11.4±1.1 vs.11.9±1.1,p = 0.025)significant decrease compared to baseline in CB.No change was observed in MPV and P-LCR in both groups(p>0.05).2.3.At 6-Month postablation,a significant decrease was observed in CD62P(%18.5±4.4p vs.16.4±3.8,p = 0.021),CD40L(pg/mL 68±33.8 vs.23.8±19.6,p<0.001),PF-4(pg/mL 102±23.5 vs.72.7±34.8,p<0.001),MPV(fL 9.9±0.5 vs.10.1 ±0.5,p = 0.010),PDW(fL 11.3±1.1 vs.11.9±1.1,p = 0.004),and P-LCR(%24.3±4.5 vs.25.9±5.2,p=0.033)compared to baseline levels in maintained sinus rhythm patients of CB group.2.4.There was a significant decreased in CD40L(pg/mL 31.6±29.7 vs.70.3±47.8 p<0.001),PF-4(pg/mL 87±26.5 vs.108.5±18.3,p<0.001),an elevation in CD62P level(%21.3±6.1 vs.17.9±5.9,p = 0.022),and no change in MPV and P-LCR(p>0.05)compared to baseline levels in maintained sinus rhythm patients of RF group.2.5.IL-6,and hs-CRP were comparable to baseline levels in both groups(p>0.05).However,an increased trend was noted in mean IL-6[mg/L 3.9(2.1-8.6)vs.3(1.9-6.7)p = 0.399]and hs-CRP[pg/mL 1(0.5-1.2)vs.0.6(0.4-2.1),p = 0.959]compared to baseline in maintained sinus rhythm patients of RF group,with no statistical significant.3.3.1.A total of 330 patients(110 in Study Group and 220 in Control Group)were selected in this work.The Study Group had significantly lower incidence of newly diagnosed DVT(21%vs.44%,P<0.001),previous history of DVT(6%vs.17%,P = 0.006)and recent surgery or trauma(10%vs.23%,P =0.004)compared to the Control Group.3.2.When stratified by The CHADS2 score,49 patients(44.5%)were considered low-intermediate risk.This proportion significantly differed when stratified using CHA2DS2-VASc,in which 13 patients(13.6%)were considered low-intermediate risk,P<0.001.Conclusions:1.In the first study,a significant decrease in multiple platelet biomarkers further supports the notion that AF directly contribute to abnormal platelet activation and that could be decreased by maintenance of sinus rhythm after catheter ablation.2.In the second study,CB group was associated with less platelet activation after PV isolation and decreased platelet activation in maintained sinus rhythm patients at long-term than RF group.These encouraging results of CB may make it a better choice of energy to treat AF in the future.Which are clinically relevant for patient's disease state,may influence risk of thromboembolism and health economic burden.3.In the third study,the incidence of deep vein thrombosis was much lower in the Study Group,suggesting the possibility of clots originated from the right heart that may increase the risk of pulmonary embolism.The CHA2DS2-VASc scoring system might be more sensitive for prediction and stratification of the PE in AF patients than the CHADS2 score. |
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