Atrial fibrillation and coronary artery disease:An integrative review focusing on therapeutic implications of this relationship

The incidence of both atrial fibrillation(AF)and coronary artery disease(CAD)increases with advancing age.They share common risk factors and very often coexist.Evidence points to an intricate relationship between atrial tissue excitability and neuronal remodeling with ischemia at the microcirculatory level.In this review,we delineated this complex relationship,identified a common theme between the two,and discussed how the knowledge of this relationship translates into a positive and meaningful impact in patient management.Recent research indicates a high prevalence of CAD among AF patients undergoing coronary angiography.Further,the incidence of AF is much higher in those suffering from CAD compared to age-matched adults without CAD underlying this reciprocal relationship.CAD adversely affects AF by promoting progression via re-entry and increasing excitability of atrial tissue as a result of ischemia and electrical inhomogeneity.AF in turn accelerates atherosclerosis via endothelial dysfunctional and inflammation and together with enhanced thrombogenicity and hypercoagulability contribute to micro and macrothrombi throughout cardiovascular system.In a nutshell,the two form a vicious cycle wherein one disease promotes the other.Most AF recommendations focuses on rate/rhythm control and prevention of thromboembolism.Very few studies have discussed the importance of unmasking coexistent CAD and how the treatment of underlying ischemia will impact the burden of AF in these patients.Inflammation and endothelial dysfunction remain central to both disease processes and form a handsome therapeutic target in the management of the two diseases.The relationship between AF and CAD is complex and much more than mere coincidence.The two diseases share common risk factor and pathophysiology.Hence,it is impractical to treat them in isolation.Accordingly,we share the implications of managing underlying ischemia and inflammation to positively impact and improve quality of life among AF patients.

PCI compared with medical therapy in elderly patients with chronic symptomatic coronary artery disease

Objective The aim of this study was to assess quality of results of elderly patients with coronary disease after medical or revascularisation therapy. Methods In this study, we enrolled 103 patients aged 75 years or older with chronic angina in which 47 patients were assigned coronary angiography and revascularisation and 56 patients with optimised medical therapy. The primary endpoint was quality of life after 6 months, as assessed by questionnaire and the presence of major adverse cardiac events (death, non fatal myocardial infarction, or hospital admission for acute coronary syndrome with or without the need for revascularisation). Results After 6 months follow up, angina severity decreased and measures of quality of life increased in both treatment groups( P <0.05 ); however, these improvements were significantly greater after revascularisation( P <0.01 ). Major adverse cardiac events occurred in 30 ( 53.6% ) of patients in the medical group and 9 ( 19.1% ) in the invasive group ( P <0.01 ).Conclusions Patients aged 75 years or older with angina benefit more from revascularisation than from optimised medical therapy in terms of symptom relief and quality of life. Therefore, these patients should be offered invasive assessment despite their high risk profile followed by revascularisation if feasible.

Optimization of the pharmacological therapy in patients with polyvascular disease: A multidisciplinary approach

The recent shift of the concept of cardiovascular disease as a chronic progressive condition,potentially involving multiple districts,has driven attention to the optimal management of patients with concomitant coronary and peripheral artery disease,representing a subset of patients with an increased risk of events and impaired survival.Recent pharmacological achievements in terms of antithrombotic therapy and lipid-lowering drugs allow multiple therapeutical combinations,thus requiring optimizing the treatment in a tailored fashion according to patients’risk profiles.Nevertheless,data dedicated to this specific subset of patients are still modest.We summarize currently available strategies and indications for the management of antithrombotic and lipid-lowering drugs in patients with the poly-vascular disease.

Advances in Drug Therapy for Alzheimer’s Disease

Alzheimer’s disease(AD)is a chronic neurodegenerative disease that mainly causes dementia.It is a serious threat to the health of the global elderly population.Considerable money and effort has been invested in the development of drug therapy for AD worldwide.Many drug therapies are currently under development or in clinical trials,based on two known mechanisms of AD,namely,Aβtoxicity and the abnormal Tau hyperphosphorylation.Numerous drugs are also being developed for other AD associated mechanisms such as neuroinflammation,neurotransmitter imbalance,oxidative damage and mitochondrial dysfunction,neuron loss and degeneration.Even so,the number of drugs that can successfully improve symptoms or delay the progression of the disease remains very limited.However,multi-drug combinations may provide a new avenue for drug therapy for AD.In addition,early diagnosis of AD and timely initiation of treatment may allow drugs that act on the early pathological processes of AD to help improve the symptoms and prevent the progression of the condition.

Applications and developments of gene therapy drug delivery systems for genetic diseases

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

Effectiveness of cognitive behavioral therapy-based interventions on health outcomes in patients with coronary heart disease:A metaanalysis

BACKGROUND Recently,the efficacy of cognitive behavioral therapy(CBT)-based intervention on health outcomes in patients with coronary heart disease(CHD)has been recognized in randomized controlled trials(RCTs),but no comprehensive systematic review has been conducted.To address this research gap,our study aimed to evaluate whether comprehensive CBT-based interventions positively affect health outcomes in CHD patients.It was hypothesized that CBT-based interventions are effective in:(1)Reducing depression,anxiety,and stress symptoms;(2)Reducing body mass index,blood pressure,and lipid levels;and(3)Improving quality of life,and exercise endurance.AIM To verify the effectiveness of CBT-based interventions on CHD patients through a meta-analysis of previous publications.METHODS Relevant RCTs published in English were obtained by searching electronic databases,including PubMed,Embase,Cochrane Central Register of Controlled Trials,Scopus,and Proquest,with the retrieval time from inception to August 2020.The primary outcomes were psychological factors(depression,anxiety,and stress symptoms),physiological factors(body mass index,blood pressure,blood lipids).The secondary outcomes included quality of life and exercise endurance.We used Review Manager 5.3 to conduct the meta-analysis and used the Physiotherapy Evidence Database tool to evaluate the quality of studies.RESULTS A total of 22 RCTs comprising 4991 patients with CHD were included in the systematic review and meta-analysis.The main analysis revealed that CBT-based intervention can reduce depression symptoms:-2.00[95%confidence interval(CI):-2.83 to-1.16,P<0.001];anxiety symptoms:-2.07(95%CI:-3.39 to-0.75,P=0.002);stress symptoms:-3.33(95%CI:-4.23 to-2.44,P<0.001);body mass index:-0.47(95%CI:-0.81 to-0.13,P=0.006);and improve physical functioning:3.36(95%CI:1.63 to 5.10,P=0.000)and mental functioning:6.91(95%CI:4.10 to 9.73,P<0.001).Moreover,subgroup analysis results showed that CBT-based interventions were more effective for symptoms of depression and anxiety in CHD patients when individual,as opposed to group treatment,and psycho-education,behavioral and cognitive strategies were applied as the core treatment approaches.CONCLUSION CBT-based interventions are effective treatment strategies for CHD patients,significantly improving their symptoms of depression,anxiety and stress,body mass index,and health-related quality of life.

Long-term outcomes of high-risk elderly male patients with multivessel coronary disease： optimal medical therapy versus revascularization

Background Many studies have indicated that medical therapy and percutaneous coronary intervention have similar effects in terms of the long-term prognosis of patients with stable coronary artery disease. This study investigated the effects of optimal medical therapy （OMT） and revascularization-plus-OMT in elderly patients with high-risk angina. Methods In this prospective non-randomized study, 241 consecutive high-risk elderly male patients （65-92 years of age） with angiographically confirmed multivessel disease were enrolled in the registry from January 2004 to April 2005. Of these, 98 patients underwent OMT and 143 underwent revascularization therapy plus OMT. Results After 6.5 years of follow-up, we found that the rate of long-term cardiac mortality was significantly higher in patients who under- went OMT than in those who underwent revascularization （6.5-year unadjusted mortality rate, 14.3% for OMT vs. 7.0% for revascularization patients; log-rank P = 0.04）. However, the overall risks of major adverse cardiac cerebrovascular events （MACCE） were similar among all patients （6.5-year unadjusted mortality rate, 29.6% for OMT vs. 27.3% for revascularization patients; log-rank P = 0.67）. Conclusions OMT was associated with an increase in cardiac death but a similar 6.5-year risk of MACCE compared with revascularization in high-risk elderly male patients with coronary multivessel disease.

The impact of optimal medical therapy at discharge on mortality in patients with coronary artery disease

Objective To analyze the current usage of optimal medical therapy （OMT）, influencing factors, and the predictive value of OMT for all-cause mortality in coronary artery disease （CAD） patients with different subgroups. Methods A total of 3176 CAD patients confirmed by coronary angiography were included. OMT was defined as the combination of anti-platelet drugs, statins, beta blockers, and angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Factors for OMT and its prognostic value were analyzed in CAD patients across different subgroups. Results Out of 3176 patients, only 39.8% （n = 1265） were on OMT at discharge. Factors associated with OMT at discharge were pre-admission OMT and discharge department. All-cause mortality occurred in 6.8% （n = 217） of patients. Multivariate analyses indicated that OMT was significantly associated with reduced all-cause mortality （HR： 0.65, 95% CI： 0.45~0.95; P = 0.025）. Sub-group analyses indicate that male acute coronary syndrome （ACS） patients were more likely to receive survival benefits with OMT at discharge. The positive impact of OMT at discharge was more apparent after 24 months, regardless of revascularization therapy. Four-drug combination of OMT was superior to 3-drug combination therapy in ACS patients but not in stable patients. Conclusions OMT was asso- ciated with significant improvement in survival in patients with CAD. The positive impact of OMT was distinct in the CAD patients with different characteristics.

Safety and efficacy of dual antiplatelet therapy after percutaneous coronary interventions in patients with end-stage liver disease

The prevalence of coronary artery disease(CAD)increases in patients with endstage liver disease,with part of them receiving the percutaneous coronary intervention(PCI)as a treatment option.Dual antiplatelet therapy(DAPT),a standard of care after PCI,could result in catastrophic consequences in this population.Before PCI and the start of DAPT,it is recommended to assess patient bleeding risk.Based on novel findings,liver cirrhosis does not necessarily lead to a significant increase in bleeding complications.Furthermore,conventional methods,such as the international normalized ratio,might not be appropriate in assessing individual bleeding risk.The highest bleeding risk among cirrhotic patients has a subgroup with severe thrombocytopenia(<50×10^(9)/L)and elevated portal pressure.Therefore,every effort should be made to maintain thrombocyte count above>50×10^(9)/L and prevent variceal bleeding.There is no solid evidence for DAPT in patients with cirrhosis.However,randomized trials investigating short(one month)DAPT duration after PCI with new drug-eluting stents(DES)in a high bleeding risk patient population can be implemented in patients with cirrhosis.Based on retrospective studies(with older stents and protocols),PCI and DAPT appear to be safe but with a higher risk of bleeding complications with longer DAPT usage.Finally,novel methods in assessing CAD severity should be performed to avoid unnecessary PCI and potential risks associated with DAPT.When indicated,PCI should be performed over radial artery using contemporary DES.Complementary medical therapy,such as proton pump inhibitors and beta-blockers,should be prescribed for lower bleeding risk patients.Novel approaches,such as thromboelastography and“preventive”upper endoscopies in PCI circumstances,warn clinical confirmation.

Current evidence of drug-elution therapy for infrapopliteal arterial disease

New and sophisticated endovascular devices, such as drug-eluting stents(DES)and drug-coated balloons(DCB), provide targeted drug delivery to affected vessels. The invention of these devices has made it possible to address the reparative cascade of arterial wall injury following balloon angioplasty that results in restenosis. DESs were first used for the treatment of infrapopliteal lesions almost 20 years ago. More recently, however, DCB technology is being investigated to improve outcomes of endovascular below-the-knee arterial procedures, avoiding the need for a metallic scaffold. Today, level IA evidence supports the use of infrapopliteal DES for short to medium length lesions,although robust evidence that justifies the use of DCBs in this anatomical area is missing. This review summarizes and discusses all available data on infrapopliteal drug-elution devices and highlights the most promising future perspectives.

Drug eluting balloons for the treatment of coronary artery disease: What can we expect?

Drug-eluting balloons (DEBs) represent an enhancement of the therapeutic repertoire for the interventional cardiologist. The therapeutic concept of DEBs is promising, notably on the basis of initial studies in patients with diffuse in-stent restenosis (ISR). At present, however, a number of questions regarding long-term efficacy and safety remain, specifically in indications other than diffuse ISR. The results of the evaluation of different substances, balloon systems and clinical indications will determine the long-term success of DEBs.

Meta-analysis on Efficacy of Yiqi Huoxue Chinese Drugs in the Treatment of Coronary Heart Disease after Coronary Revascularization

[Objectives] To make a systematic evaluation on the therapeutic efficacy and safety of Yiqi Huoxue traditional Chinese drugs combined with western medicine in treatment of coronary heart disease( CHD) after coronary revascularization. [Methods] The literatures were retrieved from China Knowledge Infrastructure( CNKI),Chinese science and technology journal full-text database( VIP database,VIP),Wanfang Data,the Chinese biomedical Database,Pub Med,Embase,and the Cochrane Library. The retrieval time was set to the creation of the database to January 2017. The randomized controlled trial( RCT) was conducted on the comparison between Yiqi Huoxue Chinese drugs combined with western medicine and the western medicine alone in the treatment of CHD after coronary revascularization. The literature information was extracted and the methodological quality of the included literature was evaluated according to the bias risk assessment tool developed by the Cochrane Collaboration. Meta-analysis was performed with the aid of Rev Man 5. 3 software. Coronary artery restenosis rate,angina pectoris treatment efficiency,left ventricular ejection fraction( LVEF),left ventricular end-diastolic volume( LVEDV),B-type natriuretic peptide( BNP),6-minute walk test( 6 MWT),and adverse reactions were analyzed. [Results] A total of 29 articles were included,a total of2 518 patients,the literature quality was low. Meta-analysis results showed that compared with the treatment by western medicine alone,Yiqi Huoxue Chinese drugs combined with western medicine could further reduce coronary restenosis rate[RR = 0. 45,95% CI( 0. 34,0. 60),P <0. 000 01],improve the angina pectoris treatment efficiency[RR = 1. 13,95% CI( 1. 05,1. 21),P = 0. 000 5],raise LVEF[WMD = 4. 25,95% CI( 3. 46,5. 04),P < 0. 000 01],reduce LVEDV[WMD =-10. 41,95% CI(-17. 88,-2. 95),P = 0. 006],decrease the plasma BNP level[WMD =-32. 32,95% CI(-44. 92,-19. 72),P < 0. 000 01],and increase 6 MWT distance(WMD = 62. 25,95% CI( 21. 71,102. 78),P = 0. 003)[Conclusions]Yiqi Huoxue Chinese drugs combined with western medicine can alleviate the symptoms of angina pectoris,reduce the rate of coronary restenosis,improve heart function and improve exercise capacity,thereby improving clinical efficacy in patients with CHD after coronary revascularization.

Percutaneous Coronary Interventional Treatment for Coronary Artery Disease and the Role of Antiplaplatelets Therapy: A Review of the Literature

Uses of balloon catheters or BMS for the treatment of coronary artery lesions shows good short-term results but long-term follow up revealed restenosis in up to 20%-30% of patients. Thus new improvements to balloons and stents are always necessary to achieve the best results from percutaneous coronary intervention (PCI). Drug-eluting stents (DES) improved the principles of bare metal stents (BMS) by local drug release to inhibit neointimal growth. DES reduced the incidence of in-stent restenosis. These benefits and lower costs compared to surgical treatment make the DES an attractive alternative for the treatment of coronary artery disease. Different components of DES which include the polymers, drugs and the stents underwent progressive evolution, and these led to development of new generations of DES with variable types of drugs and polymers to fully absorbable stents. The concern of stent thrombosis still an issue and dual antiplatlets therapy (DAPT) is mandatory for variable time ranging from one month to one year. This article discusses the main available clinical trials in the developments of BMS, DES and the comparison between both with a prospective look at future technologies in the field, in addition to reviewing the current guideline in the uses of DAPT after PCI.

Clinical follow up of patients with premature coronary artery disease (PCAD) implanted with drug-eluting stents

Background: Drug-eluting stents (DESs) are associated with lower restenosis rates. However, minimal data on the follow up results of premature coronary artery disease (PCAD) treated with DESs exist. This study was to evaluate clinical characteristics and one- year prognosis of PCAD implanted with DESs in a Chinese population. Methods: 282 patients with PCAD, of which 177 implanted with DESs and 105 prescribed medicine alone were enrolled and analyzed. Major adverse cardiovascular events (MACEs) and the use of medications for secondary prevention were collected and analyzed. Results: Compared with those receiving medicine alone, patients implanted with DESs had higher ratios of males than females, they also had acute coronary syndromes, multi-vessel disease, higher values of cardiac troponin I, longer hospital stays, higher aspirin and clopidogrel use (all P β-blockers and statins use during follow-up, they had higher ratios of recurrent angina and composite MACEs during one-year follow- up (all P y syndrome (OR 1.716, 95% CI: 1.011 - 2.913) and reduced left ventricular ejection fraction (OR 2.539, 95% CI: 1.180 - 5.463) predict MACEs in a one-year follow-up among patients with PCAD. Conclusions: PCAD patients implanted with DESs have more unstable clinical phenotypes and higher MACEs during a one-year follow-up period, though they were prescribed higher ratios of optimal therapeutic medicine. Further enhanced strategies should be made for secondary prevention.

Real world studies are essential for drug therapy in Parkinson's disease

Prospective real-world data from large patient samples, which re- port on the long-term effectiveness of the employed different drug therapies, are rare in Parkinson＇s disease （PD）. The non interven- tional ＂Transdermal Rotigotine User Surveillance Study＂ （TRUST） trial represents such a real-world study. It investigated long-term treatment with different dopamine substituting treatment regimens in 2195 PD patients （Mfiller et al., 2018）. Participation in TRUST meant that the treating neurologists were only asked to document and modify the dopaminergic drug regimen without any prior PD patient selection criteria. Thus this unique trial design reflects the real world of patient maintenance.

The Effect of EDTA Chelation Therapy in Symptomatic Coronary Heart Disease: An Observational Study

Ethylene Diamine Tetra Acetic Acid (EDTA) chelation therapy has been considered a definitive alternative therapy for by-pass surgery in atherosclerotic cardiovascular disease for more than four decades. It is a relatively inexpensive method believed to restore blood flow in atherosclerotic vessels. However, the benefits of chelation therapy yet remain controversial in the treatment of ischemic heart disease. We observed the effect of EDTA chelation therapy on exercise tolerance in 13 volunteering patients receiving conventional treatment for established symptomatic coronary heart disease. Each patient received 30 weekly infusions of EDTA followed by monthly 12 boosters according to the ACAM protocol (American College for Advancement in Medicine). This was in addition to the conventional therapies they received from their respective physician in hospital. Stress ECG, echocardiography and coronary angiogram findings were obtained at the beginning of treatment. The distance that a patient could walk on level ground at moderate speed and the number of steps he/she can climb up on a staircase until he/she begins to feel either chest pain or breathlessness were the two clinical parameters of exercise tolerance recorded to grade angina. Liver and renal functions were tested at 1st, 5th, 10th, 15th and 30th infusions. Of the 13 patients, 11 showed improvement in angina grading whilst 2 experienced no effect. One patient improved from angina grade IV to I, 6 from grade III to I, 1 from grade III to II and 3 from grade II to I. A statistically significant reduction in the mean score (p = 0.002) was noticed at 6th month of treatment when compared to that of the first month. A significant 1.7 fold increase (p = 0.009) in the mean SGPT level was observed at the 30th infusion when compared to the pre-treatment values. The SGOT level showed no significant change (p = 0.664). None of the patients showed clinical features of hepato-cellular damage. The mean serum creatinine level showed a trend for reduction (p = 0.083) with treatment. The recognized side effects of intravenous EDTA chelation therapy such as liver damage, renal damage, hypersensitivity, symptomatic hypocalcaemia, and thrombophlebitis were not encountered. Thus, EDTA chelation therapy as prescribed by the ACAM protocol seems safe and effective in improving exercise tolerance in ischemic heart disease when administered concurrently with conventional therapy.

Effects of Ticagrelor on oxidative stress, coagulation function, platelet function and related factors in patients with coronary artery disease undergoing interventional therapy

Objective: To explore the effects of Ticagrelor on oxidative stress, coagulation function, platelet function and related factors in patients with coronary artery disease undergoing interventional therapy. Methods: A total of 140 patients with coronary artery disease who underwent percutaneous coronary intervention in our hospital from October 2016 to March 2018 were selected as the study subjects and were divided into control group (70 cases) and observation group (70 cases) by drawing lots. Both groups were treated with symptomatic routine therapy before operation. On this basis, the control group was treated with clopidogrel before operation, and the observation group was treated with Ticagrelor before operation on the basis of routine treatment. The changes of oxidative stress, coagulation index, platelet function and related factors were compared between the two groups before and after treatment. Results: Before treatment, there were no significant differences in oxidative stress factors, coagulation parameters, platelet parameters and related factors factors between the two groups. After treatment, the levels of MDA, MPAR, VEGF and MMP-9 in the two groups were lower than those before treatment, while the levels of SOD, APTT, TT and PT were higher than those before treatment;and the levels of MDA, MPAR, VEGF, MMP-9, APTT and PT in the observation group were significantly lower than those in the control group after treatment, while the levels fo SOD, TT and IPA in the observation group were significantly higher than those in the control group. Conclusions: Ticagrelor can better reduce oxidative stress injury, improve coagulation function and coronary stenosis, and inhibit platelet aggregation in patients with coronary heart disease undergoing PCI than clopidogrel. It has clinical popularization significance.

Application progress of cognitive behavioral therapy in coronary heart disease

To As one of the most common cardiovascular diseases,coronary heart disease has a high morbidity and mortality.In recent years,non-drug therapy has been put on equal importance with drug therapy due to its simple operation and fast onset.Cognitive behavioral therapy,as a kind of non-drug therapy,has been widely used to improve the physical and mental symptoms of patients with coronary heart disease.This article reviews the origin,concept,theoretical basis,characteristics,technology,and current research status of cognitive behavioral therapy in patients with coronary heart disease,in order to provide a reference for the clinical development of cognitive behavioral therapy.

Current status of high on-treatment platelet reactivity in patients with coronary or peripheral arterial disease:Mechanisms,evaluation and clinical implications

Antiplatelet therapy with aspirin or clopidogrel or both is the standard care for patients with proven coronary or peripheral arterial disease,especially those undergoing endovascular revascularization procedures. However,despite the administration of the antiplatelet regiments,some patients still experience recurrent cardiovascular ischemic events. So far,it is well documented by several studies that in vitro response of platelets may be extremely variable. Poor antiplatelet effect of clopidogrel or high on-treatment platelet reactivity(HTPR) is under investigation by numerous recent studies. This review article focuses on methods used for the ex vivo evaluation of HTPR,as well as on the possible underlying mechanisms and the clinical consequences of this entity. Alternative therapeutic options and future directions are also addressed.

Cholestatic liver diseases:An era of emerging therapies

Recently the field of cholestasis has expanded enormously reflecting an improved understanding of the molecular mechanisms underlying bile secretion and its perturbation in chronic cholestatic disease. Novel anti-cholestatic therapeutic options have been developed for patients not favorably responding to ursodeoxycholic acid (UDCA), the current standard treatment for cholestatic liver disease. Important novel treatment targets now also include nuclear receptors involved in bile acid (BA) homoeostasis like farnesoid X receptor and G proteincoupled receptors e.g., the G-protein-coupled BA receptor “transmembrane G coupled receptor 5”. Fibroblast growth factor-19 and enterohepatic BA transporters also deserve attention as additional drug targets as does the potential treatment agent norUDCA. In this review, we discuss recent and future promising therapeutic agents and their potential molecular mechanisms in cholestatic liver disorders.