Osimertinib,a third-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs),is approved globally as the first-line treatment for patients with EGFR mutations(EGFRm:Ex19del/L858R)and T790M resi...Osimertinib,a third-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs),is approved globally as the first-line treatment for patients with EGFR mutations(EGFRm:Ex19del/L858R)and T790M resistance mutations in advanced non-small cell lung cancer(NSCLC).[1−3]With its widespread use,the cardiotoxicity of osimertinib has been of great concern.According to the U.S.Food and Drug Administration Adverse Events Reporting System(FAERS),the main cardiac-related adverse events with EGFR-TKIs are heart failure,QT prolongation,atrial fibrillation,acute myocardial infarction and pericardial effusion,and osimertinib has a higher incidence of QT prolongation,heart failure and atrial fibrillation than other EGFR-TKIs.展开更多
BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is uncertain.This Mendelian randomization(MR)study investigated th...BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is uncertain.This Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.METHODS Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies.Individuals without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset.The dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.RESULTS In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni adjustment.Conversely,no significant relationships were observed between other iron and LV parameters.After Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the analysis.CONCLUSIONS We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.展开更多
To explore the effects of total flavonoids of Hippophae rhamnoides L. (TFH) quercetin (Que) and isorhamnetin (Isor) on the intracellular free calcium ([Ca^2+]) in vascular smooth muscle cells (VSMC) of spon...To explore the effects of total flavonoids of Hippophae rhamnoides L. (TFH) quercetin (Que) and isorhamnetin (Isor) on the intracellular free calcium ([Ca^2+]) in vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Metheds: Fluo 3-acetoxymethylester(Fluo-3/AM) was used to observe the effects of TFH (100mg/L) and its essential monomers, namely Que (10^-4mol/L) and Isor (10^-4mol/L) on changes of [Ca^2+]1 in cultured SHR and WKY VSMC (abbr. to Ca-SHR & Ca-WKY) following exposure to high K^+, norepinephrine (NE) and angiotensin Ⅱ (AngⅡ), and to compare with the effects of verapamil (Ver). Results: (1) TFH, Que and Isor had inhibitory effects on resting Ca-SHR (P〈0.05), but had no significant effects on Ca-WKY (P〉0.05). (2) High K^+ could increase Ca-SHR more significantly than Ca-WKY (P〈0.05); TFH, Que and Isor could inhibit the elevation of [Ca^2+]1 induced by high K^+ -depolarization, with the effects similar to that of Ver, and the effect on Ca-SHR was more significant than that on Ca-WKY (P〈0.05). (3) NE and Ang Ⅱ could increase Ca-SHR more significantly than Ca-WKY (P〈0.05), TFH, Que and Isor had remarkably inhibitory effect on the elevation of Ca-SHR and Ca-WKY induced by NE or Ang Ⅱ. (4) In the absence of extracellular Ca^2+ , TFH, Que and Isor also had certain inhibitory effect on Ca-SHR and Ca-WKY induced by NE, and the effect on the former was more significant than that on the latter(P〈0.05). Ceaclusiea: TFH, Que and Isor might decrease the levels of [Ca^2+], in VSMCs by blocking both voltage-dependent calcium channels (VDC) and receptoroperated calcium channels (ROC) in physiological or pathological state, which may be one of the important mechanisms of their hypotensive and protective effects on target organs in patients with hypertension.展开更多
Arrhythmogenic right ventricular cardiomyopathy(ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages an...Arrhythmogenic right ventricular cardiomyopathy(ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular(RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involvement. The identification of ARVC can be often challenging, because of the heterogeneous clinical presentation, highly variable intra- and inter-family expressivity and incomplete penetrance. This genotypephenotype "plasticity" is largely unexplained. A familial history of ARVC is present in 30% to 50% of cases, and the disease is considered a genetic cardiomyopathy, usually inherited in an autosomal dominant pattern with variable penetrance and expressivity; in addition, autosomal recessive forms have been reported(Naxos disease and Carvajal syndrome). Diagnosis of ARVC relays on a scoring system, with major or minorcriteria on the Revised Task Force Criteria. Implantable cardioverter defibrillators(ICDs) are increasingly utilized in patients with ARVC who have survived sudden death(SD)(secondary prevention). However, there are few data available to help identifying ARVC patients in whom the prophylactic implantation of an ICD is truly warranted. Prevention of SD is the primary goal of management. Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and ICD are the mainstay of treatment of ARVC.展开更多
Dual antiplatelet therapy(DAPT)with aspirin and clopidogrel has been widely used after percutaneous coronary intervention(PCI).The bleeding complications caused by it cannot be ignored and the incidence is as high as ...Dual antiplatelet therapy(DAPT)with aspirin and clopidogrel has been widely used after percutaneous coronary intervention(PCI).The bleeding complications caused by it cannot be ignored and the incidence is as high as 32.4%.[1]Among them,spinal cord hemorrhage is rare,acute and life-threatening.We herein report a case of spinal cord hemorrhage caused by DAPT with aspirin and clopidogrel used after PCI for non-ST elevation myocardial infarction(NSTEMI).展开更多
Behcet’s disease (BD) is a chronic inflammatory disorder that can affect many systems in the body. Cardiac involvement increases the risk of cardiovascular mortality and occurs in 1%-5% of patients with BD. Ventricul...Behcet’s disease (BD) is a chronic inflammatory disorder that can affect many systems in the body. Cardiac involvement increases the risk of cardiovascular mortality and occurs in 1%-5% of patients with BD. Ventricular arrythmias are believed to be the cause of this increased risk of cardiovascular mortality and it is also thought to be related with cardiac autonomic dysfunction. Heart rate turbulence (HRT) is a new predictor of cardiac autonomic activity. HRT is an independent and powerful predictor of mortality. In this study, we investigated the cardiac autonomic activity which can be determined by HRT in patients with BD. Forty patients with BD (20 men, mean age: 40 ± 9 years, range: 27-55 years) were diagnosed according to the International Study Group Criteria (ISGC) and gender and age matched healthy volunteers (20 men, mean age: 39 ± 8 years, range: 26-56 years) were included in this study. All of the participants (patients and controls) underwent 24 hours Holter electrocardiogram. HRT parameters, turbulence onset (TO) and turbulence slope (TS) were calculated with HRT (View Version 0.60-0.1 of Software Program). There were no significant differences in TO and TS values between patients with BD and control subject (TO-BD: 0.014 ± 0.03, TO-Control: 0.011 ± 0.04;TS-BD: 7.88 ± 4.9, TS-Control: 9.42 ± 6.7 respectively). Although increased cardiovascular mortality rates in BD have been shown in many studies, HRT values—detecting the risk of sudden death—do not seem to be altered in this disease.展开更多
Objective:To explore the effect of establishing a WeChat platform for a chest pain center as a medium to increase the treatment speed and improve the prognosis of patients with acute ST-segment elevation myocardial in...Objective:To explore the effect of establishing a WeChat platform for a chest pain center as a medium to increase the treatment speed and improve the prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI)undergoing primary percutaneous coronary intervention(PPCI).Methods:The chest pain center,established by the creation of a WeChat group,included primary hospitals in Chongqing that are not able to perform PPCI and the First Affi liated Hospital of Chongqing Medical University,which is the core of the center and which includes medical staff of the catheter laboratory,the cardiology department,the emergency,the vascular surgery department,and the cardiothoracic surgery department.Patients with acute STEMI who underwent PPCI from January 2017 to November 2018 in the First Affi liated Hospital of Chongqing Medical University were enrolled.The patients(including emergency department visitors,120 callers,and patients transferred from the critical care unit or other departments)were divided into a WeChat pre-admission startup group(n=311)and a non-WeChat pre-admission startup group(control group,n=172).Patients’door-to-balloon time,standard door-toballoon time achievement rate,artery puncture to balloon dilation time,heart failure rate,length of stay,and incidence of adverse events(including fatal arrhythmia,cardiogenic shock,and death)during hospitalization were compared between the two groups.Results:Four hundred eight-three consecutive patients were enrolled.There was no signifi cant difference in patients’sex,age,length of stay,and cardiovascular events during hospitalization between the two groups(P>0.05).The door-to-balloon time of the patients in the WeChat pre-admission startup group was much shorter than that of patients in the non-WeChat pre-admission startup group(27.35±10.58 min vs.88.15±53.79 min,P<0.05).The standard door-to-balloon time achievement rate was signifi cantly higher in the WeChat pre-admission startup group than in the non-WeChat pre-admission startup group(100%vs.72.09%,P<0.05).Conclusion:The application of a WeChat platform signifi cantly shortened the door-to-balloon time of patients receiving PPCI and increased the standard door-to-balloon time achievement rate for patients with STEMI.In addition,the platform is also conducive to integrating medical resources and sharing medical information.The establishment of the platform increased the treatment speed and improved the prognosis of patients with STEMI.展开更多
Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding ...Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils(i.e. amyloid). Apart from the common Val30 Met mutation there is a very heterogeneous group of non-Val30 Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122 del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results: Three patients needed a staged(1 patient) or simultaneous(2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac(allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions: This is the first report in(liver) transplant literature about the rare Val122 del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.展开更多
Background Prior studies have demonstrated that the achievement of faster coronary artery flow following reperfusion therapies is associated with improved outcomes among ST-elevation myocardial infarction (STEMI) pati...Background Prior studies have demonstrated that the achievement of faster coronary artery flow following reperfusion therapies is associated with improved outcomes among ST-elevation myocardial infarction (STEMI) patients. The association of patient age with angiographic characteristics of flow and perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) following the administration of fibrinolytic therapy has not been previously investigated. Objectives and Methods We examined the association between age (≥ 70 years or < 70years)and clinical and angiographic outcomes in 1472 STEMI patients who underwent rescue/adjunctive PCI following fibrinolytic therapy in 7 TIMI trials. We hypothesized that elderly patients would have slower post-PCI epicardial flow and worsened outcomes compared to younger patients. Results The 218 patients aged ≥ 70 years (14.8%) had more comorbidities than younger patients. Although these patients had significant angiographic improvement in TIMI frame counts and rates of TIMI Grade 3 flow following rescue/adjunctive PCI, elderly patients had higher (slower)post-PCI TIMI frame counts compared to the younger cohort (25 vs 22 frames, P = 0.039), and less often achieved post-PCI TIMI Grade 3 flow (80.1 vs 86.4%, P = 0.017). The association between age ( ≥70 years) and slower post-PCI flow was independent of gender, time to treatment, left anterior descending (LAD) lesion location, and pulse and blood pressure on admission. Elderly patients also had 4-fold higher mortality at 30 days (12.0 vs 2.7%,P = 0. 001 ). Conclusions This study suggests one possible mechanism underlying worsened outcomes among elderly STEMI patients insofar as advanced chronological age was associated with higher TIMI frame counts and less frequent TIMI Grade 3 flow after rescue/adjunctive PCI.展开更多
Chronic total occlusive disease of the coronary artery belongs to the category of"chest palsy"and"true heart pain"in traditional Chinese medicine.Its etiology has two aspects:deficiency of blood,bl...Chronic total occlusive disease of the coronary artery belongs to the category of"chest palsy"and"true heart pain"in traditional Chinese medicine.Its etiology has two aspects:deficiency of blood,blood stasis,qi stagnation,and phlegm.Failure can be caused by deficiency or disease.The pathogenesis of this disease is caused by obstruction of the heart pulse,and its pathogenesis can be transformed into each other.The theory of traditional Chinese medicine believes that the general rule is not painful.Therefore,the treatment of coronary CTO lesions should be based on the combination of Tong and Tong tonic.The chronic complete occlusive disease of the coronary artery can be treated through Xuanbi Tongyang,Huoxue Tongluo,and Aroma Wentong.Based on the Chinese medicine's understanding of the etiology and pathogenesis of coronary CTO lesions,it provides a basis for the diagnosis and treatment of traditional Chinese medicine,solves the problems of interventional medicine in western medicine,and gives play to the unique advantages of traditional Chinese medicine for clinical diagnosis and treatment.展开更多
Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been sho...Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.展开更多
Background and Aim: The Button technique was the operative technique generally used for the reimplantation of coro- nary arteries in the aortic root replacement because of reduced anastomotic complications respect to ...Background and Aim: The Button technique was the operative technique generally used for the reimplantation of coro- nary arteries in the aortic root replacement because of reduced anastomotic complications respect to the original wrapped operation described by Bentall and De Bono. The “Button Inside” technique is a modified Button technique recently performed in all consecutive series of patients operated on aortic root replacement at our Institution. In this study we report early postoperative angiographic results of patients operated on aortic root replacement using the “But- ton Inside” technique. Methods: Magnetic Resonance Imaging angiography was achieved in all patients operated on aortic root replacement. Morphological characteristics of the site of coronary buttons reattachment were accurately evaluated. Results: No postoperative anastomotic leakages were detected at the site of coronary buttons anastomosis. Moreover, in this first series of postoperative control aneurisms of coronary buttons were not detected. Conclusions: Early postoperative non-invasive angiographic results of the “Button Inside” technique are encouraging. This surgical approach for the reattachment of coronary arteries is suggested in aortic root replacement when is possible to mobilize coronary arteries in order to reduce coronary artery anastomotic complications.展开更多
Objectives To observe the expression of β3-adrenoceptor (β3-AR) of left ventricle and the effect on heart function by stimulating β3-AR in rats with experimental heart failure. Methods Rats were randomly divided ...Objectives To observe the expression of β3-adrenoceptor (β3-AR) of left ventricle and the effect on heart function by stimulating β3-AR in rats with experimental heart failure. Methods Rats were randomly divided into heart failure group and control group. Heart failure models were built up by ligating coronary artery in rats. The expression of β3-AR mRNA were detected with RT-PCR; The change of heart function were observed after administration of BRL37344 (β3-AR agonist) by measuring left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), the maximum pressure ascending rate of left ventricle (+dp/ dtmax) and the maximum pressure descending rate of left ventricle(-dp/dtmax). Results The expression of β3-AR mRNA (β3/β-actin) was 0.028±0.005 and the proportion of β3-AR (β3/β1+β2+β3) was 5.4%±0.06% in failure rats while the expression of β3-AR mRNA was 0.011 ±0.004 and the proportion was 1.2%±0.04% in control rats; The descending percentage of LVESP, + dp/dtmax and -dp/dtmax were 16.1%, 21.7% and 13.2% respectively with administration of BRL37344 in failure rats, while 12.2%, 15.8% and 11.5% in control rats. Conclusions Compared with control group the expression of β3-AR mRNA of left ventricle was obviously increased and the negative inotropic function with exciting β3-AR was obviously enhanced in failure groups.展开更多
Objective:To study the correlation of endothelial nitric oxide synthase (eNOS) gene G894T locus polymorphism with the oxidative and inflammatory endothelial function injury in patients with myocardial infarction.Metho...Objective:To study the correlation of endothelial nitric oxide synthase (eNOS) gene G894T locus polymorphism with the oxidative and inflammatory endothelial function injury in patients with myocardial infarction.Methods:87 patients with acute myocardial infarction treated in our hospital between May 2012 and December 2015 were selected as acute myocardial infarction (AMI) group and 90 healthy volunteers receiving physical examination during the same period were selected as control group. Peripheral arterial blood was collected to extract genomic DNA and then determine eNOS gene G894T locus polymorphism;peripheral venous blood was collected to separate serum and then determine endothelial injury, oxidative stress and inflammatory reaction indexes.Results:GG genotype proportion and G allele frequency of eNOS gene G894T locus of AMI group were significantly lower than those of control group (P<0.05) while the GT genotype and TT genotype proportion as well as T allele frequency were significantly higher than those of control group (P<0.05);serum nitric oxide (NO), SOD and GSH content of patients with GG genotype were significantly higher than those of patients with GT genotype and TT genotype (P<0.05) while vWF, ET-1, ox-LDL, MDA, -COOH, NF-κB, MCP-1, IL-6 and IL-18 content were significantly lower than those of patients with GT genotype and TT genotype (P<0.05).Conclusions: The proportion of eNOS gene G894T locus G mutation into T significantly increases in patients with myocardial infarction, and G894T locus G mutation into T can aggravate the endothelial injury caused by oxidative stress and inflammation.展开更多
Objectives To observe the effect of β3-Adrenoceptor (AR) on ventricle fibrillation threshold (VFT) and effective refractory period (ERP) in rats with heart failure. Methods Rats were randomized into control gro...Objectives To observe the effect of β3-Adrenoceptor (AR) on ventricle fibrillation threshold (VFT) and effective refractory period (ERP) in rats with heart failure. Methods Rats were randomized into control group and heart failure group. The expression of β3-ARmRNA was detected with RTPCR; The VFT, ERP, LVESP,LVEDP, +dp/dtmax and -dp/dtmax was measured at the same time with administration of BRL37344 ( 2 nmol / kg, β3- AR agonist). Results ①Both the expression of β3-AR mRNA and the proportion increased in rats with heart failure in comparison with control rats (0.028 vs. 0.011 and 5.4% vs 1.2%, P 〈 0.05);② ERP was longer in rats with heart failure than control group (70.5±5.5 ms vs 59.5±6.4ms, P 〈 0.05) and there was no difference of ERP in rats with heart failure with administration of BRL37344 (73.0±4.8 ms vs 70.5± 5.5 ms, P 〉0.05); ③VFT was lower in rats with heart failure than control group(10.9±0.8 mv vs 30.5± 1.3 mv, P〈 0.05) and decreased obviously in rats with heart failure with administration of BRL37344 (7.1±0.6 mv vs 10.9±0.8 mv, P 〈 0.05) ; The decrease of VFT correlated with the effect on LVESP, +dp/ dtmax,-dp/dtmax of BRL37344 and the expression of β3-AR mRNA (correlation coefficient: 0.788, 0.708, 0.759, 0.787; P 〈 0.05). Conclusions The expression of β3-AR mRNA of left ventricle was obviously increased in rats with heart failure, and activation of β3-AR had no effect on ERP but could decreased VFT which correlated with the effect of β3-AR on LVESP, +dp/dtmax, -dp/dtmax and the expression of β3-AR mRNA.展开更多
Objective:To study the effect of milrinone on the cardiac function and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with senile refractory heart failure. Methods:90 patients with senile refr...Objective:To study the effect of milrinone on the cardiac function and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with senile refractory heart failure. Methods:90 patients with senile refractory heart failure who were treated in our hospital between August 2013 and August 2016 were collected and divided into control group (n=45) and observation group (n=45) according to the random number table. The control group received regular clinical treatment, and the observation group received regular + milrinone treatment. The cardiac function and serum NT-proBN contents were compared between two groups of patients before and after treatment.Results: Before treatment, the differences in ultrasound and serum cardiac function indexes and serum NT-proBN levels were not statistically significant between two groups of patients. After treatment, ultrasound serum cardiac function parameter LVEDD level in observation group was lower than that in control group while CI and SV levels were higher than those in control group;serum cardiac function indexes Cys-C, GDF-15, sST2 and H-FABP contents were lower than those in control group;serum NT-proBNP content was lower than that in control group.Conclusion: Milrinone therapy can optimize the cardiac function and reduce the serum NT-proBN levels in patients with senile refractory heart failure.展开更多
文摘Osimertinib,a third-generation epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs),is approved globally as the first-line treatment for patients with EGFR mutations(EGFRm:Ex19del/L858R)and T790M resistance mutations in advanced non-small cell lung cancer(NSCLC).[1−3]With its widespread use,the cardiotoxicity of osimertinib has been of great concern.According to the U.S.Food and Drug Administration Adverse Events Reporting System(FAERS),the main cardiac-related adverse events with EGFR-TKIs are heart failure,QT prolongation,atrial fibrillation,acute myocardial infarction and pericardial effusion,and osimertinib has a higher incidence of QT prolongation,heart failure and atrial fibrillation than other EGFR-TKIs.
基金funded by the Key Research and Development of the Gansu Province(No.20YF8FA 079)the Construction Project of the Gansu Clinical Medical Research Center(No.18JR2FA003).
文摘BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is uncertain.This Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.METHODS Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies.Individuals without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset.The dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.RESULTS In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni adjustment.Conversely,no significant relationships were observed between other iron and LV parameters.After Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the analysis.CONCLUSIONS We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.
基金Supported by One-hundred-people Plan of Hygiene Systemin Shanghai (No .990122)
文摘To explore the effects of total flavonoids of Hippophae rhamnoides L. (TFH) quercetin (Que) and isorhamnetin (Isor) on the intracellular free calcium ([Ca^2+]) in vascular smooth muscle cells (VSMC) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Metheds: Fluo 3-acetoxymethylester(Fluo-3/AM) was used to observe the effects of TFH (100mg/L) and its essential monomers, namely Que (10^-4mol/L) and Isor (10^-4mol/L) on changes of [Ca^2+]1 in cultured SHR and WKY VSMC (abbr. to Ca-SHR & Ca-WKY) following exposure to high K^+, norepinephrine (NE) and angiotensin Ⅱ (AngⅡ), and to compare with the effects of verapamil (Ver). Results: (1) TFH, Que and Isor had inhibitory effects on resting Ca-SHR (P〈0.05), but had no significant effects on Ca-WKY (P〉0.05). (2) High K^+ could increase Ca-SHR more significantly than Ca-WKY (P〈0.05); TFH, Que and Isor could inhibit the elevation of [Ca^2+]1 induced by high K^+ -depolarization, with the effects similar to that of Ver, and the effect on Ca-SHR was more significant than that on Ca-WKY (P〈0.05). (3) NE and Ang Ⅱ could increase Ca-SHR more significantly than Ca-WKY (P〈0.05), TFH, Que and Isor had remarkably inhibitory effect on the elevation of Ca-SHR and Ca-WKY induced by NE or Ang Ⅱ. (4) In the absence of extracellular Ca^2+ , TFH, Que and Isor also had certain inhibitory effect on Ca-SHR and Ca-WKY induced by NE, and the effect on the former was more significant than that on the latter(P〈0.05). Ceaclusiea: TFH, Que and Isor might decrease the levels of [Ca^2+], in VSMCs by blocking both voltage-dependent calcium channels (VDC) and receptoroperated calcium channels (ROC) in physiological or pathological state, which may be one of the important mechanisms of their hypotensive and protective effects on target organs in patients with hypertension.
文摘Arrhythmogenic right ventricular cardiomyopathy(ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular(RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involvement. The identification of ARVC can be often challenging, because of the heterogeneous clinical presentation, highly variable intra- and inter-family expressivity and incomplete penetrance. This genotypephenotype "plasticity" is largely unexplained. A familial history of ARVC is present in 30% to 50% of cases, and the disease is considered a genetic cardiomyopathy, usually inherited in an autosomal dominant pattern with variable penetrance and expressivity; in addition, autosomal recessive forms have been reported(Naxos disease and Carvajal syndrome). Diagnosis of ARVC relays on a scoring system, with major or minorcriteria on the Revised Task Force Criteria. Implantable cardioverter defibrillators(ICDs) are increasingly utilized in patients with ARVC who have survived sudden death(SD)(secondary prevention). However, there are few data available to help identifying ARVC patients in whom the prophylactic implantation of an ICD is truly warranted. Prevention of SD is the primary goal of management. Pharmacologic treatment of arrhythmias, catheter ablation of ventricular tachycardia, and ICD are the mainstay of treatment of ARVC.
文摘Dual antiplatelet therapy(DAPT)with aspirin and clopidogrel has been widely used after percutaneous coronary intervention(PCI).The bleeding complications caused by it cannot be ignored and the incidence is as high as 32.4%.[1]Among them,spinal cord hemorrhage is rare,acute and life-threatening.We herein report a case of spinal cord hemorrhage caused by DAPT with aspirin and clopidogrel used after PCI for non-ST elevation myocardial infarction(NSTEMI).
文摘Behcet’s disease (BD) is a chronic inflammatory disorder that can affect many systems in the body. Cardiac involvement increases the risk of cardiovascular mortality and occurs in 1%-5% of patients with BD. Ventricular arrythmias are believed to be the cause of this increased risk of cardiovascular mortality and it is also thought to be related with cardiac autonomic dysfunction. Heart rate turbulence (HRT) is a new predictor of cardiac autonomic activity. HRT is an independent and powerful predictor of mortality. In this study, we investigated the cardiac autonomic activity which can be determined by HRT in patients with BD. Forty patients with BD (20 men, mean age: 40 ± 9 years, range: 27-55 years) were diagnosed according to the International Study Group Criteria (ISGC) and gender and age matched healthy volunteers (20 men, mean age: 39 ± 8 years, range: 26-56 years) were included in this study. All of the participants (patients and controls) underwent 24 hours Holter electrocardiogram. HRT parameters, turbulence onset (TO) and turbulence slope (TS) were calculated with HRT (View Version 0.60-0.1 of Software Program). There were no significant differences in TO and TS values between patients with BD and control subject (TO-BD: 0.014 ± 0.03, TO-Control: 0.011 ± 0.04;TS-BD: 7.88 ± 4.9, TS-Control: 9.42 ± 6.7 respectively). Although increased cardiovascular mortality rates in BD have been shown in many studies, HRT values—detecting the risk of sudden death—do not seem to be altered in this disease.
文摘Objective:To explore the effect of establishing a WeChat platform for a chest pain center as a medium to increase the treatment speed and improve the prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI)undergoing primary percutaneous coronary intervention(PPCI).Methods:The chest pain center,established by the creation of a WeChat group,included primary hospitals in Chongqing that are not able to perform PPCI and the First Affi liated Hospital of Chongqing Medical University,which is the core of the center and which includes medical staff of the catheter laboratory,the cardiology department,the emergency,the vascular surgery department,and the cardiothoracic surgery department.Patients with acute STEMI who underwent PPCI from January 2017 to November 2018 in the First Affi liated Hospital of Chongqing Medical University were enrolled.The patients(including emergency department visitors,120 callers,and patients transferred from the critical care unit or other departments)were divided into a WeChat pre-admission startup group(n=311)and a non-WeChat pre-admission startup group(control group,n=172).Patients’door-to-balloon time,standard door-toballoon time achievement rate,artery puncture to balloon dilation time,heart failure rate,length of stay,and incidence of adverse events(including fatal arrhythmia,cardiogenic shock,and death)during hospitalization were compared between the two groups.Results:Four hundred eight-three consecutive patients were enrolled.There was no signifi cant difference in patients’sex,age,length of stay,and cardiovascular events during hospitalization between the two groups(P>0.05).The door-to-balloon time of the patients in the WeChat pre-admission startup group was much shorter than that of patients in the non-WeChat pre-admission startup group(27.35±10.58 min vs.88.15±53.79 min,P<0.05).The standard door-to-balloon time achievement rate was signifi cantly higher in the WeChat pre-admission startup group than in the non-WeChat pre-admission startup group(100%vs.72.09%,P<0.05).Conclusion:The application of a WeChat platform signifi cantly shortened the door-to-balloon time of patients receiving PPCI and increased the standard door-to-balloon time achievement rate for patients with STEMI.In addition,the platform is also conducive to integrating medical resources and sharing medical information.The establishment of the platform increased the treatment speed and improved the prognosis of patients with STEMI.
文摘Background: Hereditary transthyretin(ATTRv) amyloidosis is an autosomal dominant disease linked to transthyretin gene mutations which cause instability of the transthyretin tetramer. After dissociation and misfolding they reassemble as insoluble fibrils(i.e. amyloid). Apart from the common Val30 Met mutation there is a very heterogeneous group of non-Val30 Met mutations. In some cases, the clinical picture is dominated by a rapidly evolving restrictive and hypertrophic cardiomyopathy. Methods: A case series of four liver recipients with the highly clinically relevant, rare and particularly aggressive Val122 del mutation is presented. Medical and surgical therapeutic options, waiting list policy for ATTRv-amyloidosis, including the need for heart transplantation, and status of heart-liver transplantation are discussed. Results: Three patients needed a staged(1 patient) or simultaneous(2 patients) heart-liver transplant due to rapidly progressing cardiac failure and/or neurologic disability. Domino liver transplantation was impossible in two due to fibrotic hepatic transformation caused by cardiomyopathy. After a follow-up ranging from 3.5 to 9.5 years, cardiac(allograft) function was maintained in all patients, but neuropathy progressed in three patients, one of whom died after 80 months. Conclusions: This is the first report in(liver) transplant literature about the rare Val122 del ATTRv mutation. Due to its aggressiveness, symptomatic patients should be prioritized on the liver and, in cases with cardiomyopathy, heart waiting lists in order to avoid the irreversible neurological and cardiac damage that leads to a rapid lethal outcome.
文摘Background Prior studies have demonstrated that the achievement of faster coronary artery flow following reperfusion therapies is associated with improved outcomes among ST-elevation myocardial infarction (STEMI) patients. The association of patient age with angiographic characteristics of flow and perfusion after rescue/adjunctive percutaneous coronary intervention (PCI) following the administration of fibrinolytic therapy has not been previously investigated. Objectives and Methods We examined the association between age (≥ 70 years or < 70years)and clinical and angiographic outcomes in 1472 STEMI patients who underwent rescue/adjunctive PCI following fibrinolytic therapy in 7 TIMI trials. We hypothesized that elderly patients would have slower post-PCI epicardial flow and worsened outcomes compared to younger patients. Results The 218 patients aged ≥ 70 years (14.8%) had more comorbidities than younger patients. Although these patients had significant angiographic improvement in TIMI frame counts and rates of TIMI Grade 3 flow following rescue/adjunctive PCI, elderly patients had higher (slower)post-PCI TIMI frame counts compared to the younger cohort (25 vs 22 frames, P = 0.039), and less often achieved post-PCI TIMI Grade 3 flow (80.1 vs 86.4%, P = 0.017). The association between age ( ≥70 years) and slower post-PCI flow was independent of gender, time to treatment, left anterior descending (LAD) lesion location, and pulse and blood pressure on admission. Elderly patients also had 4-fold higher mortality at 30 days (12.0 vs 2.7%,P = 0. 001 ). Conclusions This study suggests one possible mechanism underlying worsened outcomes among elderly STEMI patients insofar as advanced chronological age was associated with higher TIMI frame counts and less frequent TIMI Grade 3 flow after rescue/adjunctive PCI.
基金National natural science foundation of China(No.81774247)
文摘Chronic total occlusive disease of the coronary artery belongs to the category of"chest palsy"and"true heart pain"in traditional Chinese medicine.Its etiology has two aspects:deficiency of blood,blood stasis,qi stagnation,and phlegm.Failure can be caused by deficiency or disease.The pathogenesis of this disease is caused by obstruction of the heart pulse,and its pathogenesis can be transformed into each other.The theory of traditional Chinese medicine believes that the general rule is not painful.Therefore,the treatment of coronary CTO lesions should be based on the combination of Tong and Tong tonic.The chronic complete occlusive disease of the coronary artery can be treated through Xuanbi Tongyang,Huoxue Tongluo,and Aroma Wentong.Based on the Chinese medicine's understanding of the etiology and pathogenesis of coronary CTO lesions,it provides a basis for the diagnosis and treatment of traditional Chinese medicine,solves the problems of interventional medicine in western medicine,and gives play to the unique advantages of traditional Chinese medicine for clinical diagnosis and treatment.
文摘Statins, 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase enzyme inhibitors, are lipid-lowering drugs, often used in the treatment of cardiovascular diseases (hyperlipidemia, atherosclerosis). It has been shown that statins have antiinflammatory effects independent of their lipid-lowering effects and these anti-inflammatory effects inhibit the inflammation and pain process. This study evaluated the antinociceptive and anti-inflammatory effects of rosuvastatin using the acetic acid writhing, the formalin hind paw, the orofacial formalin and the hot plate tests. The following experimental group were used: control, acute (1 day) and chronic (3 days) after oral gavage with rosuvastatin (3, 10, 30, 100 and 300 mg/kg). Rosuvastatin produced a dose-dependent antinociception, with different potency, in all the tests. Additionally, nitric oxide synthase inhibitors (Abbreviationsand aminoguanidine) were used to assess the nitric oxide participation on this induced rosuvastatin antinociception. The data demonstrated the antinociceptive and anti-inflammatory activity of rosuvastatin in algesiometer models of tonic or phasic pain. These activities seem to be induced by modulation of iNOS expression, a result that may be relevant in the pharmacological treatment of human pain where rosuvastatin and nitric oxide synthase inhibitors must be used.
文摘Background and Aim: The Button technique was the operative technique generally used for the reimplantation of coro- nary arteries in the aortic root replacement because of reduced anastomotic complications respect to the original wrapped operation described by Bentall and De Bono. The “Button Inside” technique is a modified Button technique recently performed in all consecutive series of patients operated on aortic root replacement at our Institution. In this study we report early postoperative angiographic results of patients operated on aortic root replacement using the “But- ton Inside” technique. Methods: Magnetic Resonance Imaging angiography was achieved in all patients operated on aortic root replacement. Morphological characteristics of the site of coronary buttons reattachment were accurately evaluated. Results: No postoperative anastomotic leakages were detected at the site of coronary buttons anastomosis. Moreover, in this first series of postoperative control aneurisms of coronary buttons were not detected. Conclusions: Early postoperative non-invasive angiographic results of the “Button Inside” technique are encouraging. This surgical approach for the reattachment of coronary arteries is suggested in aortic root replacement when is possible to mobilize coronary arteries in order to reduce coronary artery anastomotic complications.
文摘Objectives To observe the expression of β3-adrenoceptor (β3-AR) of left ventricle and the effect on heart function by stimulating β3-AR in rats with experimental heart failure. Methods Rats were randomly divided into heart failure group and control group. Heart failure models were built up by ligating coronary artery in rats. The expression of β3-AR mRNA were detected with RT-PCR; The change of heart function were observed after administration of BRL37344 (β3-AR agonist) by measuring left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP), the maximum pressure ascending rate of left ventricle (+dp/ dtmax) and the maximum pressure descending rate of left ventricle(-dp/dtmax). Results The expression of β3-AR mRNA (β3/β-actin) was 0.028±0.005 and the proportion of β3-AR (β3/β1+β2+β3) was 5.4%±0.06% in failure rats while the expression of β3-AR mRNA was 0.011 ±0.004 and the proportion was 1.2%±0.04% in control rats; The descending percentage of LVESP, + dp/dtmax and -dp/dtmax were 16.1%, 21.7% and 13.2% respectively with administration of BRL37344 in failure rats, while 12.2%, 15.8% and 11.5% in control rats. Conclusions Compared with control group the expression of β3-AR mRNA of left ventricle was obviously increased and the negative inotropic function with exciting β3-AR was obviously enhanced in failure groups.
文摘Objective:To study the correlation of endothelial nitric oxide synthase (eNOS) gene G894T locus polymorphism with the oxidative and inflammatory endothelial function injury in patients with myocardial infarction.Methods:87 patients with acute myocardial infarction treated in our hospital between May 2012 and December 2015 were selected as acute myocardial infarction (AMI) group and 90 healthy volunteers receiving physical examination during the same period were selected as control group. Peripheral arterial blood was collected to extract genomic DNA and then determine eNOS gene G894T locus polymorphism;peripheral venous blood was collected to separate serum and then determine endothelial injury, oxidative stress and inflammatory reaction indexes.Results:GG genotype proportion and G allele frequency of eNOS gene G894T locus of AMI group were significantly lower than those of control group (P<0.05) while the GT genotype and TT genotype proportion as well as T allele frequency were significantly higher than those of control group (P<0.05);serum nitric oxide (NO), SOD and GSH content of patients with GG genotype were significantly higher than those of patients with GT genotype and TT genotype (P<0.05) while vWF, ET-1, ox-LDL, MDA, -COOH, NF-κB, MCP-1, IL-6 and IL-18 content were significantly lower than those of patients with GT genotype and TT genotype (P<0.05).Conclusions: The proportion of eNOS gene G894T locus G mutation into T significantly increases in patients with myocardial infarction, and G894T locus G mutation into T can aggravate the endothelial injury caused by oxidative stress and inflammation.
文摘Objectives To observe the effect of β3-Adrenoceptor (AR) on ventricle fibrillation threshold (VFT) and effective refractory period (ERP) in rats with heart failure. Methods Rats were randomized into control group and heart failure group. The expression of β3-ARmRNA was detected with RTPCR; The VFT, ERP, LVESP,LVEDP, +dp/dtmax and -dp/dtmax was measured at the same time with administration of BRL37344 ( 2 nmol / kg, β3- AR agonist). Results ①Both the expression of β3-AR mRNA and the proportion increased in rats with heart failure in comparison with control rats (0.028 vs. 0.011 and 5.4% vs 1.2%, P 〈 0.05);② ERP was longer in rats with heart failure than control group (70.5±5.5 ms vs 59.5±6.4ms, P 〈 0.05) and there was no difference of ERP in rats with heart failure with administration of BRL37344 (73.0±4.8 ms vs 70.5± 5.5 ms, P 〉0.05); ③VFT was lower in rats with heart failure than control group(10.9±0.8 mv vs 30.5± 1.3 mv, P〈 0.05) and decreased obviously in rats with heart failure with administration of BRL37344 (7.1±0.6 mv vs 10.9±0.8 mv, P 〈 0.05) ; The decrease of VFT correlated with the effect on LVESP, +dp/ dtmax,-dp/dtmax of BRL37344 and the expression of β3-AR mRNA (correlation coefficient: 0.788, 0.708, 0.759, 0.787; P 〈 0.05). Conclusions The expression of β3-AR mRNA of left ventricle was obviously increased in rats with heart failure, and activation of β3-AR had no effect on ERP but could decreased VFT which correlated with the effect of β3-AR on LVESP, +dp/dtmax, -dp/dtmax and the expression of β3-AR mRNA.
文摘Objective:To study the effect of milrinone on the cardiac function and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with senile refractory heart failure. Methods:90 patients with senile refractory heart failure who were treated in our hospital between August 2013 and August 2016 were collected and divided into control group (n=45) and observation group (n=45) according to the random number table. The control group received regular clinical treatment, and the observation group received regular + milrinone treatment. The cardiac function and serum NT-proBN contents were compared between two groups of patients before and after treatment.Results: Before treatment, the differences in ultrasound and serum cardiac function indexes and serum NT-proBN levels were not statistically significant between two groups of patients. After treatment, ultrasound serum cardiac function parameter LVEDD level in observation group was lower than that in control group while CI and SV levels were higher than those in control group;serum cardiac function indexes Cys-C, GDF-15, sST2 and H-FABP contents were lower than those in control group;serum NT-proBNP content was lower than that in control group.Conclusion: Milrinone therapy can optimize the cardiac function and reduce the serum NT-proBN levels in patients with senile refractory heart failure.