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1.
Int J Cardiol ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31668660

RESUMO

AIMS: To recapitulate progressive human dilated cardiomyopathy (DCM) and heart block in the Lmna R225X mutant mice model and investigate the molecular basis of LMNA mutation induced cardiac conduction disorders (CD); To investigate the potential interventional impact of exercise endurance. METHODS AND RESULTS: A Lmna R225X knock-in mice model in either heterozygous or homozygous genotype was generated. Electrical remodeling was observed with higher occurrence of AV block from neonatal and aged mutant mice as measured by surface electrocardiogram and atrio-ventricular Wenckebach point detection. Histological and molecular profiles revealed an increase in apoptotic cells and activation of caspase-3 activities in heart tissue. Upon aging, extracellular cellular matrix (ECM) remodeling appeared with accumulation of collagen in Lmna R225X mutant hearts as visualized by Masson's trichrome stain. This could be explained by the upregulated ECM gene expression, such as Fibronectin: Fn1, collagen: Col12a1, intergrin: Itgb2 and 3, as detected by microarray gene chip. Also, endurance exercise for 3 month improved the ventricular ejection fraction, attenuated fibrosis and cardiomyocytes apoptosis in the aged mutant mice. CONCLUSIONS: The mechanism of LMNA nonsense mutation induced cardiac conduction defects through AV node fibrosis is due to upregulated ECM gene expression upon activation of cardiac apoptosis. Lmna R225X mutant mice hold the potential for serving as in vivo models to explore the mechanism and therapeutic methods for AV block or myopathy associated with the aging process.

2.
Sci Rep ; 9(1): 16814, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728003

RESUMO

Implementation of a critical care pathway (CCP) for acute coronary syndrome (ACS) has been shown to improve early compliance to guideline-directed therapies and reduce early mortality. Nevertheless its long-term impact on the compliance with medications or clinical outcomes remains unknown. Between 2004 and 2015, 2023 consecutive patients were admitted to our coronary care unit with ACS. We retrospectively compared the outcomes of 628 versus 1059 patients (mean age 66.1 ± 13.3 years, 74% male) managed before and after full implementation of a CCP. Compared with standard care, implementation of the CCP significantly increased coronary revascularization and long-term compliance with guideline-directed medical therapy (both P < 0.01). After a mean follow-up of 66.5 ± 44.0 months, 46.7% and 22.2% patients admitted before and after implementation of the CCP, respectively, died. Kaplan-Meier analyses showed that patients managed by CCP had better overall survival (P = 0.03) than those managed with standard care. After adjustment for clinical covariates and coronary anatomy, CCP remained independently predictive of better survival from all-cause mortality [hazard ratio (HR): 0.75, 95%confidence intervals (CI): 0.62-0.92, P < 0.01]. Stepwise multivariate cox regression model showed that both revascularization (HR: 0.55, 95%CI: 0.45-0.68, P < 0.01) and compliance to statin (HR: 0.70, 95%CI: 0.58-0.85, P < 0.01) were accountable for the improved outcome.

3.
BMJ Open ; 9(8): e027193, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31375608

RESUMO

INTRODUCTION: Methamphetamine misuse is classified as a 'likely' risk factor for pulmonary arterial hypertension (PAH). Nevertheless, the actual prevalence of and a screening strategy for PAH in methamphetamine users have not been established. We plan to study the prevalence of PAH and identify its independent risk factors among methamphetamine users. METHODS AND ANALYSIS: The Screening Of Pulmonary Hypertension in Methamphetamine Abusers (SOPHMA) study will be a multicentre, cross-sectional screening study that will involve substance abuse clinics, hospitals and rehabilitation facilities in Hong Kong that cater to more than 20 methamphetamine users. A total of 400 patients who (1) are ≥18 years at enrolment; (2) report methamphetamine use in the last 2 years; (3) are diagnosed with methamphetamine use disorder; and (4) voluntarily agree to participate by providing written informed consent will be included. Patients will undergo standard echocardiography-based PAH screening procedures recommended for those with systemic sclerosis. Right heart catheterisation will be offered to participants with intermediate or high echocardiographic probability of PAH. For participants with a low echocardiographic probability of PAH, rescreening will be performed within 1 year. The primary measure will be the prevalence of PAH in methamphetamine users. The secondary measures will be the risk factors and a prediction model for PAH in methamphetamine users. ETHICS AND DISSEMINATION: The SOPHMA study has been approved by the institutional review board. The findings of this study will provide the necessary evidence to establish universal guidelines for screening of PAH in methamphetamine users. Our results will be disseminated through immediate feedback to study participants, press release to the general public, as well as presentation in medical conferences and publications in peer-reviewed journals to healthcare providers and academia worldwide.

4.
BMC Cardiovasc Disord ; 19(1): 168, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307391

RESUMO

BACKGROUND: The prognostic implication of statin in tolerance (SI) in those with stable CAD remains unclear. We hypothesized that SI is of higher prognostic significance in stable CAD patients with elevated high-sensitive cardiac troponin I (hs-cTnI). METHODS: A total of 952 stable CAD patients from the prospective Hong Kong CAD study who had complete clinical data, biomarker measurements and who were prescribed statin therapy were studied. RESULTS: We identified 13 (1.4%) and 125 (13.1%) patients with complete and partial SI, respectively. At baseline, patients with SI were more likely to have diabetes mellitus and a higher hs-cTnI level, but no difference in LDL-C level compared with those without SI. After 51 months of follow-up, patients with SI had a higher mean LDL-C level than those without SI. A total of 148 (15.5%) patients developed major adverse cardiovascular events (MACEs). Both SI (HR 1.52, 95% CI 1.06-2.19, P = 0.02) and elevated hs-cTnI (HR 3.18, 95% CI 2.07-4.89, P < 0.01) were independent predictors of a MACE in patients with stable CAD. When stratified by hs-cTnI level, SI independently predicted MACE-free survival only in those with elevated hs-cTnI (HR 1.51, 95% CI 1.01-2.24, P = 0.04). CONCLUSIONS: SI independently predicted MACE in patients with stable CAD and high hs-cTnI, but not in those with low hs-cTnI. Hs-cTnI may be used to stratify stable CAD patients who have SI for intensive lipid-lowering therapy using non-statin agents.

5.
Postgrad Med J ; 95(1125): 372-377, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31123174

RESUMO

BACKGROUND: Patients who survive non-ST-elevation myocardial infarction (NSTEMI) are at heightened risk of recurrent cardiovascular events. Data on long-term secondary atherothrombotic risk stratification are limited. OBJECTIVES: To stratify post-NSTEMI patients for risk of recurrent cardiovascular events to maximise benefit from aggressive secondary prevention strategies using the TIMI Risk Score for Secondary Prevention (TRS 2°P) score in a real-world cohort of NSTEMI patients. METHODS AND RESULTS: This was a single-centre observational study of 891 post-NSTEMI patients (73.7 ± 12.7 years; male: 54.2%). The TRS 2°P is a nine-point risk stratification tool to predict cardiovascular events in patients with established cardiovascular disease. The primary outcome was a composite endpoint of cardiovascular death, non-fatal MI and non-fatal ischaemic stroke. After a median follow-up of 31 months (IQR: 11.4 - 60.2), 281 patients (31.5%) had developed a primary outcome (13.3%/year) including 196 cardiovascular deaths, 94 non-fatal MIs and 22 non-fatal strokes. The TRS 2°P score was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P score =0 was 1.6%, and increased progressively to 47.4% for those with a TRS 2°P score ≥6 (HR: 20.18, 95% CI: 4.85 to 84.05, p<0.001). Similar associations were also observed between the TRS 2°P score and cardiovascular death and MI (fatal and non-fatal), but not non-fatal ischaemic stroke. CONCLUSION: The TRS 2°P score stratified post-NSTEMI patients for risk of future cardiovascular events and potentially help guide the selection of more aggressive secondary prevention therapy.

6.
Hypertension ; 74(1): 47-55, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31132949

RESUMO

Emerging preclinical data suggest that splanchnic sympathetic nerve activation may play an important role in the pathophysiology of hypertension. We sought to determine the potential therapeutic application of catheter-based splanchnic denervation in a clinically relevant large animal model of hypertensive cardiomyopathy (hCMP). Sustained elevated blood pressure was induced in adult pigs using a combination of intravenous infusion of Ang II (angiotensin II) and subcutaneous implantation of deoxycorticosterone acetate pellets to establish a large animal model of hCMP. Serial changes in cardiac echocardiographic and invasive hemodynamic parameters and neurohumoral biomarkers were investigated in animals with hypertension alone (n=9) and hypertension with catheter-based splanchnic denervation (n=6). Another 6 pigs without hypertension induction served as controls. At 10 weeks, hypertensive animals developed sustained elevated blood pressure and phenotype of hCMP with significant systolic and diastolic dysfunction, and left ventricular remodeling and hypertrophy as determined by invasive hemodynamic and echocardiogram assessments, respectively, and increased venoarterial norepinephrine gradient over the myocardium, kidneys, and splanchnic organs compared with baseline. Catheter-based splanchnic denervation decreased the venoarterial norepinephrine gradient over the splanchnic organs associated with the reduced splenic sympathetic nerve innervation; attenuated the elevated blood pressure, left ventricular remodeling, and hypertrophy; and preserved left ventricular systolic and diastolic function at 20 weeks in pigs with hCMP. Our results provide novel mechanistic insight into the role of splenic sympathetic nerve innervation in hypertension and important proof-of-principle data for the therapeutic application of catheter-based splanchnic denervation in a large animal model of hCMP.

7.
Circ J ; 83(4): 809-817, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30799311

RESUMO

BACKGROUND: Patients who survive myocardial infarction (MI) are at risk of recurrent cardiovascular (CV) events. This study stratified post-MI patients for risk of recurrent CV events using the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P). Methods and Results: This was an observational study that applied TRS 2°P to a consecutive cohort of post-MI patients. The primary outcome was a composite endpoint of CV death, non-fatal MI, and non-fatal ischemic stroke. A total of 1,688 post-MI patients (70.3±13.6 years; male, 63.1%) were enrolled. After a mean follow-up of 41.5±34.4 months, 405 patients (24.0%) had developed a primary outcome (9.3%/year) consisting of 278 CV deaths, 134 non-fatal MI, and 33 non-fatal strokes. TRS 2°P was strongly associated with the primary outcome. The annual incidence of primary composite endpoint for patients with TRS 2°P 0 was 1.0%, and increased progressively to 39.9% for those with TRS 2°P ≥6 (HR, 27.6; 95% CI: 9.87-77.39, P<0.001). The diagnostic sensitivity of TRS 2°P for the primary composite endpoint was 76.3% (95% CI: 72.1-80.5%). Similar associations were also observed between TRS 2°P and CV death and non-fatal MI, but not non-fatal ischemic stroke. CONCLUSIONS: TRS 2°P reliably stratified post-MI patients for risk of future CV events.

8.
Heart Rhythm ; 16(6): 896-902, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30550834

RESUMO

BACKGROUND: The major risk of implanting a leadless pacemaker at the right ventricular (RV) apex is cardiac perforation. OBJECTIVE: The purpose of this study was to describe and prospectively evaluate the safety and feasibility of a technique for midseptal implantation of the Micra leadless pacemaker. METHODS: We positioned the device at the center of the cardiac silhouette in the right anterior oblique (RAO) view, toward the left in the left anterior oblique (LAO) view, and away from the sternum in the left lateral view. RESULTS: Among the 51 patients (mean age 81.3 ± 9.3 years; 47% men) included in the study, 29 (57%) were >80 years old, 7 (14%) had body mass index <20 kg/m2, 48 (94%) had renal dysfunction, and 33 (65%) had valvular heart disease. The implantation sites were mid and apical septum in 46 (90%) and 5 (10%) patients, respectively. Although RAO and LAO views suggested a septal location, 9 (17.6%) devices were found to be directing at the free wall in the left lateral view and required repositioning. One patient (2%) developed cardiac perforation due to contrast injection against the RV anterior wall before verification of sheath location by lateral view. Mean R-wave sensing and pacing threshold at implantation were 9.7 ± 4.0 mV and 0.61 ± 0.31 V/0.24 ms, respectively. After median follow-up of 218.7 days, the pacing threshold remained stable. CONCLUSION: In this high-risk patient cohort, midseptal implantation of a leadless pacemaker as guided by RAO, LAO, and left lateral views was achieved in 90% of patients, with a low risk of complications.

9.
Int Heart J ; 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518718

RESUMO

The incidence of atrial tachycardia (AT) after rheumatic mitral valvular (RMV) surgery has been well described. However, there have been few reports on the characteristics, mechanism, and long-term ablation outcome of ATs after RMV surgery and concomitant Cox-MAZE IV procedure.The present study reviewed consecutive patients who underwent AT ablation between May 2008 and July 2013. All patients were refractory to antiarrhythmic drugs (AADs) and had a history of RMV surgery and Cox-MAZE IV procedure. A total of 34 patients underwent AT ablation after RMV surgery and concomitant Cox-MAZE IV procedure, and presented 57 mappable and 2 unmappable ATs. The 57 mappable ATs included 14 focal-ATs and 43 reentry-ATs. Ten of the 14 focal-like ATs were located at the pulmonary vein (PV) antrum and border of a box lesion. Of the 43 reentry-ATs, 16 were marco-reentrant around the mitral annulus (MA) and 16 around the tricuspid annulus. There were 41 atypical ATs (non-cavotricuspid isthmus related) including 16 ATs related to the box lesion and 21 ATs related to other Cox-MAZE IV lesions. The AT were successfully terminated in 33 (97.1%) patients. After mean follow-up of 46.9 ± 15.7 months, 25 (73.5%) patients maintained sinus rhythm without AADs after a single procedure and 28 (82.4%) patients after repeated procedures.The recurrent ATs after RMV surgery and concomitant Cox-MAZE IV were mainly reentry mechanism, and largely related to LA. An incomplete lesion or re-conductive gaps in a prior lesion might be the predominant mechanisms for these ATs. Catheter-based mapping and ablation of these ATs seems to be effective and safe during a long-term follow-up.

11.
12.
Diabetes ; 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305369

RESUMO

Elevated circulating levels of pigment epithelium-derived factor (PEDF) have been reported in patients with type 2 diabetes (T2DM) and its associated microvascular complications. This study aimed to (i) identify the genetic determinants influencing circulating PEDF level in a clinical setting of T2DM; (ii) examine the relationship between circulating PEDF and diabetic complications; and (iii) explore the causal relationship between PEDF and diabetic complications. An exome-chip association study on circulating PEDF leve1 was conducted in 5385 Chinese subjects with T2DM. A meta-analysis of the association results of the discovery stage (n=2936) and replication stage (n=2449) was performed. The strongest association was detected at SERPINF1 (p.Met72Thr; P combined =2.06x10-57; ß[SE]:-0.33[0.02]). Two missense variants of SMYD4 (p.Arg131Ile; P combined =7.56x10-25; ß[SE]:0.21[0.02]) and SERPINF2 (p.Arg33Trp; P combined =8.22x10-10; ß[SE]:-0.15[0.02]) respectively, showed novel associations at genome-wide significance. Elevated circulating PEDF level was associated with increased risks of diabetic nephropathy (DN) and sight-threatening diabetic retinopathy (STDR). Mendelian randomization analysis showed suggestive evidence of a protective role of PEDF on STDR (P=0.085). Our study had provided new insights into the genetic regulation of PEDF and further support for its potential application as a biomarker for DN and STDR. Further studies to explore the causal relationship of PEDF with diabetic complications are warranted.

13.
Arterioscler Thromb Vasc Biol ; 38(10): 2519-2527, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30354221

RESUMO

Objective- In patients with stable coronary artery disease, conventional risk factors provide limited incremental predictive value for cardiovascular events. We sought to investigate whether a panel of cardiometabolic biomarkers alone or combined with conventional risk factors would exhibit incremental value in the prediction of cardiovascular events. Approach and Results- In the discovery cohort, we measured serum adiponectin, A-FABP (adipocyte fatty acid-binding protein), lipocalin-2, FGF (fibroblast growth factor)-19 and 21, plasminogen activator inhibitor-1, and retinol-binding protein-4 in 1166 Chinese coronary artery disease patients. After a median follow-up of 35 months, 170 patients developed new-onset major adverse cardiovascular events (MACE). In the model with age ≥65 years and conventional risk factors, area under the curve for predicting MACE was 0.68. Addition of lipocalin-2 to the age-clinical risk factor model improved predictive accuracy (area under the curve=0.73). Area under the curve further increased to 0.75 when a combination of lipocalin-2, A-FABP, and FGF-19 was added to yield age-biomarkers-clinical risk factor model. The adjusted hazard ratio on MACEs for lipocalin-2, A-FABP, and FGF-19 levels above optimal cutoffs were 2.23 (95% CI, 1.62-3.08), 1.99 (95% CI, 1.43-2.76), and 1.65 (95% CI, 1.15-2.35), respectively. In the validation cohort of 1262 coronary artery disease patients with type 2 diabetes mellitus, the age-biomarkers-clinical risk factor model was confirmed to provide good discrimination and calibration over the conventional risk factor alone for prediction of MACE. Conclusions- A combination of the 3 biomarkers, lipocalin-2, A-FABP, and FGF-19, with clinical risk factors to yield the age-biomarkers-clinical risk factor model provides an optimal and validated prediction of new-onset MACE in patients with stable coronary artery disease.

14.
J Geriatr Cardiol ; 15(6): 408-412, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30108612

RESUMO

Objective: To evaluate the predictive value of red cell distribution width (RDW) on left atrial thrombus (LAT) or left atrial spontaneous echo contrast (LASEC) in patients with non-valvular atrial fibrillation (AF). Methods: We reviewed 692 patients who were diagnosed as non-valvular AF and underwent transesophageal echocardiography (TEE) in Guangdong Cardiovascular Institute from April 2014 to December 2015. The baseline clinical characteristics, laboratory test of blood routine, electrocardiograph measurements were analyzed. Results: Eighty-four patients were examined with LAT/LASEC under TEE. The mean RDW level was significantly higher in LAT/LASEC patients compared with the non-LAT/LASEC patients (13.59% ± 1.07% vs. 14.34% ± 1.34%; P < 0.001). Receiver-operating characteristic curve analysis was performed and indicated the best RDW cut point was 13.16%. Furthermore, multivariate logistic regression analysis indicated that RDW level > 13.16% could be an independent risk factor for LAT/LASEC in patients with AF. Conclusion: Elevated RDW level is associated with the presence of LAT/LASEC and could be with moderate predictive value for LAT/LASEC in patients with non-valvular AF.

15.
Sci Rep ; 8(1): 10846, 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30022097

RESUMO

Targeted next generation sequencing of gene panels has become a popular tool for the genetic diagnosis of hypertrophic (HCM) and dilated cardiomyopathy (DCM). However, it is uncertain whether the use of Whole Exome Sequencing (WES) represents a more effective approach for diagnosis of cases with HCM and DCM. In this study, we performed indirect comparisons of the coverage and diagnostic yield of WES on genes and variants related to HCM and DCM versus 4 different commercial gene panels using 40 HCM and DCM patients, assuming perfect coverage in those panels. We identified 6 pathogenic or likely pathogenic among 14 HCM patients (diagnostic yield 43%). 3 pathogenic or likely pathogenic were found among the 26 DCM patients (diagnostic yield 12%). The coverage was similar to that of four existing commercial gene panels due to the clustering of mutation within MYH7, MYBPC3, TPM1, TNT2, and TTN. Moreover, the coverage of WES appeared inadequate for TNNI3 and PLN. We conclude that most of the pathogenic variants for HCM and DCM can be found within a small number of genes which were covered by all the commercial gene panels, and the application of WES did not increase diagnostic yield.

16.
JAMA Cardiol ; 3(7): 661-662, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29710190
17.
Int J Cardiol ; 258: 103-108, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29467096

RESUMO

OBJECTIVES: To investigate the relationship between hyperuricemia and left atrial thrombus (LAT)/spontaneous echo contrast (SEC) and to determine the predictive value of hyperuricemia in non-valvular (NV) atrial fibrillation (AF) patients. METHODS: The study retrospectively reviewed 1198 consecutive patients (male 801, female 397, and mean age of 56.84 ±â€¯12.22) who were diagnosed with AF and accepted transesophageal echocardiography (TEE) prior to catheter ablation, appendage occlusion and electrical cardioversion using a single-center database. The clinical baseline characteristics were collected from medical record review and analyzed. Patients were categorized into an LAT/SEC group and a normal group. RESULTS: According to the TEE examination, there were 97 (8.1%) patients with abnormality; of these, 49 were with LAT and 48 with SEC. The mean serum uric acid (SUA) level and hyperuricemia proportion were markedly higher in patients with LAT/SEC. The significant predictive effect was observed in the SUA level (OR = 1.006) and hyperuricemia (OR = 2.04). After adjustment for persistent/permanent-AF, age, gender, LA dimension > 40 mm, previous stroke, hypertension and diabetes, the SUA level (OR = 1.004) and hyperuricemia (OR = 1.69) were independent predictors for LAT/SEC. The SUA level (OR = 1.004) and hyperuricemia (OR = 1.69) were independent predictors for LAT/SEC, Further subgroup analysis in different CHA2DS2-VASc categories, it might be helpful to refine the LAT/SEC risk via combination area CHA2DS2-VASc score and hyperuricemia, especially in those with CHA2DS2-VASc score < 2. CONCLUSIONS: The SUA level and hyperuricemia proportion are closely associated with LA stasis. Hyperuricemia might independently predict and refine LA stasis risk among NVAF patients, especially in those with CHA2DS2-VASc score < 2.


Assuntos
Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Hiperuricemia/sangue , Hiperuricemia/diagnóstico por imagem , Adulto , Idoso , Fibrilação Atrial/epidemiologia , Ecocardiografia/tendências , Feminino , Humanos , Hiperuricemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Ácido Úrico/sangue
18.
Heart Rhythm ; 15(6): 822-829, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29454138

RESUMO

BACKGROUND: The prognostic implication of early ventricular tachyarrhythmias (VTs) after acute coronary syndrome (ACS) remains unclear. OBJECTIVE: We sought to investigate the clinical outcomes of early monomorphic and non-monomorphic VTs that occur within 48 hours in patients after ACS. METHODS: We retrospectively reviewed the clinical outcomes of 2033 [mean age 67.0 ± 13.4 years; 1486 (73.1%) men] consecutive patients who presented with ACS from 2004 to 2015. RESULTS: A total of 67 (3.3%) and 90 (4.4%) patients developed early monomorphic or non-monomorphic VT, respectively. Killip class IV (odds ratio [OR] 3.05; 95% confidence interval [CI] 1.47-6.36; P < .01), creatine kinase level (OR 1.01; 95% CI 1.00-1.02 per 100 IU/L; P = .01), and left ventricular ejection fraction (OR 0.96; 95% CI 0.94-0.99; P < .01) were independently associated with early monomorphic VT, whereas age (OR 0.98; 95% CI 0.97-0.99; P = .04), ST elevated myocardial infarction (OR 3.53; 95% CI 1.71-7.27; P < .01), Killip class IV (OR 4.91; 95% CI 2.76-8.74; P < .01), diabetes mellitus (OR 0.48; 95% CI 0.28-0.81; P < .01), and left ventricular ejection fraction (OR 0.97; 95% CI 0.95-0.99; P < .01) were independently associated with early non-monomorphic VT. More patients with early monomorphic VT (n = 22 [32.8%]) died in hospital than those with non-monomorphic VT (n = 16 [17.8%]) or without early VT (n = 133 [7.1%]; P < .01). After a mean follow-up of 67.8 ± 43.2 months, 21 patients with early monomorphic VT (46.7%), 22 patients with early non-monomorphic VT (29.7%), and 552 patients without early VT (31.7%) died. Both early monomorphic and non-monomorphic VTs were associated with a long-term increase in sudden arrhythmic deaths and recurrent VTs. Nevertheless, only early monomorphic VT was shown to independently predict overall survival (hazard ratio 1.62; 95% CI 1.03-2.55; P = .04). CONCLUSION: Early monomorphic VT, but not early non-monomorphic VT, independently predicted all-cause mortality in patients with ACS who survived to hospital discharge.

19.
Europace ; 19(suppl_4): iv25-iv31, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29220424

RESUMO

Aims: Low vitamin D level is associated with atrial fibrillation (AF) and may be implicated in its pathogenesis. Methods and results: We studied single nucleotide polymorphisms (SNPs) of vitamin D mechanistic pathways and serum 25-hydroxyvitamin D [25(OH)D] levels in an age- and gender-matched case-control study (controls without AF: mean age 68.6 ± 8.7 years, female 25%; n = 1019; with AF: mean age 69.7 ± 9.5 years, female 30%; n = 156) recruited from a Chinese clinical cohort of patients with stable coronary artery disease. Twelve SNPs involved in the vitamin D mechanistic pathways were studied [biosynthetic: rs4646536, rs10877012, rs3829251, rs1790349; activation: rs2060793, rs1993116; vitamin D-binding protein (VBP)/group-specific component (GC): rs4588, rs7041, rs2282679, rs1155563; and vitamin D receptor: rs1544410, rs10735810]. A genetic risk score (GRS) (0-8) was constructed from SNPs associated with serum 25(OH)D as a proxy to lifelong vitamin D-deficient state. All 4 SNPs involved in the VBP/GC were significantly associated with serum 25(OH)D (rs4588, P < 0.001; rs2282679, P < 0.001; rs7041, P = 0.011; rs1155563, P < 0.001; all other SNPs, P > 0.05). Vitamin D GRS (points 0-8) generated from these 4 SNPs was independently predictive of serum 25(OH)D [B = 0.54, 95% confidence interval (CI) 0.30-0.79; P < 0.001]. Genetically deprived vitamin D status as denoted by a low GRS (0-3) independently predicted an increased risk of AF, compared to a high GRS (4-8) (odds ratio = 1.848, 95% CI 1.217-2.805; P = 0.004). Conclusion: Genetically deprived vitamin D exposure predisposes to increased AF among patients with coronary artery disease. Whether VBP/GC may alter the risk of AF via alternative mechanisms warrants further studies.


Assuntos
Fibrilação Atrial/etiologia , Polimorfismo de Nucleotídeo Único , Deficiência de Vitamina D/genética , Idoso , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , China , Doença das Coronárias/complicações , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/diagnóstico
20.
BMC Cardiovasc Disord ; 17(1): 233, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28836952

RESUMO

BACKGROUND: Whether PR prolongation independently predicts new-onset ischemic events of myocardial infarction and stroke was unclear. Underlying pathophysiological mechanisms of PR prolongation leading to adverse cardiovascular events were poorly understood. We investigated the role of PR prolongation in pathophysiologically-related adverse cardiovascular events and underlying mechanisms. METHODS: We prospectively investigated 597 high-risk cardiovascular outpatients (mean age 66 ± 11 yrs.; male 67%; coronary disease 55%, stroke 22%, diabetes 52%) for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and cardiovascular death. Vascular phenotype was determined by carotid intima-media thickness (IMT). RESULTS: PR prolongation >200 ms was present in 79 patients (13%) at baseline. PR prolongation >200 ms was associated with significantly higher mean carotid IMT (1.05 ± 0.37 mm vs 0.94 ± 0.28 mm, P = 0.010). After mean study period of 63 ± 11 months, increased PR interval significantly predicted new-onset ischemic stroke (P = 0.006), CHF (P = 0.040), cardiovascular death (P < 0.001), and combined cardiovascular endpoints (P < 0.001) at cut-off >200 ms. Using multivariable Cox regression, PR prolongation >200 ms independently predicted new-onset ischemic stroke (HR 8.6, 95% CI: 1.9-37.8, P = 0.005), cardiovascular death (HR 14.1, 95% CI: 3.8-51.4, P < 0.001) and combined cardiovascular endpoints (HR 2.4, 95% CI: 1.30-4.43, P = 0.005). PR interval predicts new-onset MI at the exploratory cut-off >162 ms (C-statistic 0.70, P = 0.001; HR: 8.0, 95% CI: 1.65-38.85, P = 0.010). CONCLUSIONS: PR prolongation strongly predicts new-onset ischemic stroke, MI, cardiovascular death, and combined cardiovascular endpoint including CHF in coronary patients or risk equivalent. Adverse vascular function may implicate an intermediate pathophysiological phenotype or mediating mechanism.


Assuntos
Isquemia Encefálica/etiologia , Doença da Artéria Coronariana/complicações , Bloqueio Cardíaco/complicações , Insuficiência Cardíaca/etiologia , Frequência Cardíaca , Infarto do Miocárdio/etiologia , Acidente Vascular Cerebral/etiologia , Potenciais de Ação , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Isquemia Encefálica/fisiopatologia , Espessura Intima-Media Carotídea , Causas de Morte , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Eletrocardiografia , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/mortalidade , Bloqueio Cardíaco/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Pacientes Ambulatoriais , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo
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