Background -Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone-binding globulin(SHBG) as potential mediators of increasing cardiovascular(CV) risk in women at midlif...Background -Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone-binding globulin(SHBG) as potential mediators of increasing cardiovascular(CV) risk in women at midlife. Methods and Results -The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic(white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol(E2) were evaluated along with SHBG and the free androgen index(FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors(higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index(P< 0.001 for all). Low levels of E2 were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI. Conclusions -Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women.展开更多
Aims: We conducted a multi- centre, prospective, controlled, randomize d rial to investigate the adjunctive role of ablation therapy to antiarrhythmic drug therapy in preventing atrial fibrillation(AF) relapses in pat...Aims: We conducted a multi- centre, prospective, controlled, randomize d rial to investigate the adjunctive role of ablation therapy to antiarrhythmic drug therapy in preventing atrial fibrillation(AF) relapses in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy had already failed. Methods and results: One hundred and thirty seven patients were randomized to ablation and antiarrhythmic drug therapy(ablation group) or antiarrhythmic drug therapy alone(control group). In the ablation group, patients underwent cavo- tricuspid and left inferior pulmonary vein(PV)- mitral isthmus ablation plus circumferential PV ablation. The primary end- point of the study was the absence of any recurrence of atrial arrhythmia lasting >30s in the 1- year follow- up period, after 1- month blanking period. Three(4.4% ) major complications were related to ablation: one patient had a stroke during left atrium ablation, another suffered transient phrenic paralysis, and the third had a pericardial effusion which required pericardiocentesis. After 12 months of follow- up, 63/69(91.3% ) control group patients had at least one AF recurrence, whereas 30/68(44.1% )(P < 0001) ablation group patients had atrial arrhythmia recurrence(four patients had atrial flutter, 26 patients AF). Conclusion: Ablation therapy combined with antiarrhythmic drug therapy is superior to antiarrhythmic drug therapy alone in preventing atrial arrhythmia recurrences in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy has already failed.展开更多
Background/Aims We performed the current study to assess the intestinal activity of enterocyte phosphate-activated glutaminase(PAG) in cirrhosis. Methods Forty-nine cirrhotic patients and 36 control subjects underwent...Background/Aims We performed the current study to assess the intestinal activity of enterocyte phosphate-activated glutaminase(PAG) in cirrhosis. Methods Forty-nine cirrhotic patients and 36 control subjects underwent endoscopic duodenal biopsies. Minimal hepatic encephalopathy (MHE) was evaluated using three psychometric tests. Oral glutamine challenge(OGC) was performed and MELD, Child-Pugh and the presence of esophageal varices were recorded. PAG was measured by enzymatic methods. Cerebral magnetic resonance spectroscopy was performed in 10 cirrhotics. Results PAG was found to be higher in cirrhotics than control subjects 2.4± 1.51vs.0.68± 0.57 IU/mg protein (P < 0.001). PAG was also increased in patients with MHE and correlated with MELD, INR,esophageal varices and serum bile acids. A negative correlation was observed between PAG activity and intra-cerebral choline/creatine ratio (r=-0.67; P=0.035) and a positive correlation with glutamine plus glutamate/creatine ratio (r=0.78; P=0.007). In multivariate analysis using backward logistic regression,presence of MHE was the only variable independently related to altered enterocyte PAG. Conclusions Enterocyte PAG is increased in cirrhotic patients and correlates with MHE. These data support a possible role for intestinal glutaminase in the pathogenesis of hepatic encephalopathy (HE) and could be a new target for future therapies.展开更多
Background: Health- related quality of life(HRQOL) among long- term survivors of coronary artery bypass surgery is an important outcome that has been little studied at the population level. Methods: A postal survey wa...Background: Health- related quality of life(HRQOL) among long- term survivors of coronary artery bypass surgery is an important outcome that has been little studied at the population level. Methods: A postal survey was conducted in 1999 to 2000 in patients 6 to 20 years after coronary artery bypass graft(CABG) surgery in Western Australia. A random stratified sample of 2500 was drawn from 8910 patients who had their first CABG surgery in 1980 to 1993. Health- related quality of life was measured with Short Form 36 and EuroQol visual analogue scale. Results: Response was 82% (n=2061). Health- related quality of life declined with age and was similar for men and women, although scores for women were worse for physical functioning. Compared with Australian population norms, the age- and sex- standardized scores of survivors of CABG were generally worse, mainly in the physical domain. Reported angina at the time of follow- up(33% ), symptoms of heart failure equivalent to New York Heart Association(NYHA) classes II to IV(34% ), and comorbidities such as diabetes and hypertension were associated with poorer HRQOL. For both men and women without angina or heart failure at follow- up,HRQOL was no different from that of the general population. Conclusion: Overall, the quality of life among long- term survivors of CABG is worse than that of the general population, the difference being mainly attributable to recurrent symptoms and comorbidities. Quality of life for those without angina or heart failure at follow- up was equivalent to the population norms, providing an incentive to maximize efforts to abolish angina and ameliorate heart failure symptoms.展开更多
Background: Electrical cardioversion in patients with atrial fi- brillation(AF) is associated with an increased risk of stroke. We compared a transesophageal echocardiography(TEE)- guided strategy with a conventional ...Background: Electrical cardioversion in patients with atrial fi- brillation(AF) is associated with an increased risk of stroke. We compared a transesophageal echocardiography(TEE)- guided strategy with a conventional strategy in patients with AF >2 days’ duration undergoing electrical cardioversion over a 6- month follow- up. Methods: The ACUTE study was a multicenter, randomized, clinical trial, with 1222 patients. Six- month follow- up was available in 1034 patients(85% ), 525 in the TEE group and 509 in the conventional group. The primary composite end points were cerebrovascular accident, transient ischemic attack, and peripheral embolism at 6 months, which was a prespecified time point. Secondary end points were hemorrhage, mortality, and sinus rhythm. Results: At 6 months, there was no difference in composite embolic events between the TEE group and the conventional group(10 [2% ] vs 4 [0.8% ]; risk ratio(RR) 2.47, 95% CI 0.78- 7.88; P=.11). However, the hemorrhagic rate was significantly lower in the TEE group(23 [4.4% ] vs 38 [7.5% ]; RR 0.58, 96% CI 0.35- 0.97; P=.04). There was no difference between the 2 treatment groups in all- cause mortality(21 [4% ] vs 14 [2.8% ]; RR 1.48, 95% CI 0.76- 2.92; P=.25) and in the occurrence of normal sinus rhythm between the 2 groups(305 [62.2% ] vs 280 [58.1% ]; P=.51). Sinus rhythm at 6 months was more common in the TEE- guided group, in those patients who had direct current cardioversion(238 [62.5% ] vs 151 [53.9% ]; P=.03). Conclusion: The TEE- guided strategy may be considered a clinically effective alternative to a conventional anticoagulation strategy for patients with AF of >2 days’ duration undergoing electrical cardioversion over a 6- month period.展开更多
Background: This study aimed to determine the epidemiologic, clinical, microbiologic characteristics, and inhospital outcome of infective endocarditis(IE) in Argentina and compare the results with those of the 1992 IE...Background: This study aimed to determine the epidemiologic, clinical, microbiologic characteristics, and inhospital outcome of infective endocarditis(IE) in Argentina and compare the results with those of the 1992 IE national survey. Methods: A prospective, multicenter study was conducted in 82 hospitals representing 16 of 24 provinces of Argentina. Patients with diagnosis of IE according to the Duke criteria were surveyed during an 18- month period. Results: From 470 surveyed episodes of IE, 390 cases were classified as definite and 80 as possible IE. The mean age of the definite IE cases was 58.5± 17.3 years; male sex, 70.0% ; and male- female ratio, 2.3 ∶ 1. Pathological evidence of IE was available in 26.2% . There was no previously known heart disease in 35.1% , and the proportion of prosthetic valve IE was 15.9% . Causative microorganisms were streptococci, 38.3% (Streptococcus viridans 27.0% , Streptococcus bovis 5.2% , others 6.1% ); enterococci, 10.2% ; staphylococci, 36.7% (Staphylococcus aureus 29.8% , coagulase- negative sta- phylococci 6.9% );HACEK group, 6.1% ; fungal, 1.4% ; and polymicrobial, 2.0% . Blood culture results were negative in 10.8% . Surgical treatment was performed in 26.2% , and the overall inhospital mortality was 24.6% . Patients from the 2002 survey were older(58.5± 17.3 vs 51.3± 18.7 years, P< .01) and more frequently had underlying heart disease(64.9% vs 55.0% , P< .01): degenerative valve disease(11.5% vs 4.8% , P< .01), congenital heart disease(9.5% vs 4.2% , P< .01), and prosthetic valve IE(15.9% vs 8.5% , P< .01). Conversely, the prevalence of rheumatic valve disease was significantly less than in the 1992 survey(5.4% vs 13.0% , P< .01). Conclusions: The EIRA- 2 survey shows that the clinical profile of IE has changed in Argentina. Currently, patients with IE are older and have a higher frequency of underlying heart disease, degenerative valve disease, and prosthetic valve IE than previously. The incidence of staphylococcal IE has increased. Inhospital mortality remains high, suggesting that more aggressive measures are needed for the early identification, prevention, and treatment of IE.展开更多
Aims: Recent data from the COMPANION trial have documented that cardiac resynchronization therapy(CRT) with biventricular(BiV) pacing reduces mortality and hospitalization in patients with advanced CHF, but little is ...Aims: Recent data from the COMPANION trial have documented that cardiac resynchronization therapy(CRT) with biventricular(BiV) pacing reduces mortality and hospitalization in patients with advanced CHF, but little is known regarding thecellular and molecular mechanisms of CRT. Our aim is to evaluate interstitial remodelling, tumor necrosis factor- α (TNF- α ) expression, and apoptosis in patients with advanced CHF treated with CRT. Methods and results: We performed endomyocardial biopsies in 10 patients, aged 62, with dilated cardiomyopathy before and 6 months after the implantation of a BiV pacing device. Clinical status and left ventricular(LV)architecture and function were assessed as well as myocardial histology, TNF- α expression, and apoptotic index. CRT improved clinical status, as shown by a significant reduction of the Minnesota living with heart failure questionnaire(MLHFQ)score(from 53 to 40) and 6- min walked distance(from 290 to 330 m)(all P < 0.05 vs. baseline). This was associated with reverse LV remodelling substantiated by significant reductions of LV volumes and end- systolic circumferential wall stress. Examination of myocardial tissue revealed a significant decrease of collagen volume fraction(CVF)(from 25.16 to 18.0% ), TNF- α expression(from 9.5 to 3.6 pixel × 103), and apoptotic index(from 2030 to 1408 apoptotic nuclei/106), with increased capillary density(from 1801 to 2011 capillary/mm2) after 6 months of CRT(all P < 0.05 vs. baseline). Moreover, changes in TNF- α expression were positively correlated with both CVF and end- systolic circumferential wall stress(r=0.80 and 0.70, respectively). Conclusion: We provide the first evidence that CRT reduces interstitial remodelling, TNF- α expression, and apoptosis. The data may explain the beneficial effects of CRT on CHF progression and survival.展开更多
文摘Background -Recent clinical trials have shifted attention away from estrogens and toward androgens and sex hormone-binding globulin(SHBG) as potential mediators of increasing cardiovascular(CV) risk in women at midlife. Methods and Results -The correlation between reproductive hormones and CV risk factors was evaluated in a multiethnic(white, black, Hispanic, Chinese, and Japanese) sample of 3297 premenopausal and perimenopausal women. Testosterone and estradiol(E2) were evaluated along with SHBG and the free androgen index(FAI), the amount of testosterone not bound by SHBG. Low SHBG and high FAI were strongly and consistently related to elevated CV risk factors(higher insulin, glucose, and hemostatic and inflammatory markers and adverse lipids) even after controlling for body mass index(P< 0.001 for all). Low levels of E2 were associated with elevated CV risk factors to a lesser degree. These observations were consistent across the 5 ethnic groups. Compared with whites, blacks had higher levels of SHBG and lower levels of FAI, and Chinese had lower levels of SHBG and higher levels of FAI. Conclusions -Low SHBG and high FAI are strongly associated with CV risk factors in racially diverse women, and thus, androgens likely play a role in the CV risk profile of perimenopausal women.
文摘Aims: We conducted a multi- centre, prospective, controlled, randomize d rial to investigate the adjunctive role of ablation therapy to antiarrhythmic drug therapy in preventing atrial fibrillation(AF) relapses in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy had already failed. Methods and results: One hundred and thirty seven patients were randomized to ablation and antiarrhythmic drug therapy(ablation group) or antiarrhythmic drug therapy alone(control group). In the ablation group, patients underwent cavo- tricuspid and left inferior pulmonary vein(PV)- mitral isthmus ablation plus circumferential PV ablation. The primary end- point of the study was the absence of any recurrence of atrial arrhythmia lasting >30s in the 1- year follow- up period, after 1- month blanking period. Three(4.4% ) major complications were related to ablation: one patient had a stroke during left atrium ablation, another suffered transient phrenic paralysis, and the third had a pericardial effusion which required pericardiocentesis. After 12 months of follow- up, 63/69(91.3% ) control group patients had at least one AF recurrence, whereas 30/68(44.1% )(P < 0001) ablation group patients had atrial arrhythmia recurrence(four patients had atrial flutter, 26 patients AF). Conclusion: Ablation therapy combined with antiarrhythmic drug therapy is superior to antiarrhythmic drug therapy alone in preventing atrial arrhythmia recurrences in patients with paroxysmal or persistent AF in whom antiarrhythmic drug therapy has already failed.
文摘Background/Aims We performed the current study to assess the intestinal activity of enterocyte phosphate-activated glutaminase(PAG) in cirrhosis. Methods Forty-nine cirrhotic patients and 36 control subjects underwent endoscopic duodenal biopsies. Minimal hepatic encephalopathy (MHE) was evaluated using three psychometric tests. Oral glutamine challenge(OGC) was performed and MELD, Child-Pugh and the presence of esophageal varices were recorded. PAG was measured by enzymatic methods. Cerebral magnetic resonance spectroscopy was performed in 10 cirrhotics. Results PAG was found to be higher in cirrhotics than control subjects 2.4± 1.51vs.0.68± 0.57 IU/mg protein (P < 0.001). PAG was also increased in patients with MHE and correlated with MELD, INR,esophageal varices and serum bile acids. A negative correlation was observed between PAG activity and intra-cerebral choline/creatine ratio (r=-0.67; P=0.035) and a positive correlation with glutamine plus glutamate/creatine ratio (r=0.78; P=0.007). In multivariate analysis using backward logistic regression,presence of MHE was the only variable independently related to altered enterocyte PAG. Conclusions Enterocyte PAG is increased in cirrhotic patients and correlates with MHE. These data support a possible role for intestinal glutaminase in the pathogenesis of hepatic encephalopathy (HE) and could be a new target for future therapies.
文摘Background: Health- related quality of life(HRQOL) among long- term survivors of coronary artery bypass surgery is an important outcome that has been little studied at the population level. Methods: A postal survey was conducted in 1999 to 2000 in patients 6 to 20 years after coronary artery bypass graft(CABG) surgery in Western Australia. A random stratified sample of 2500 was drawn from 8910 patients who had their first CABG surgery in 1980 to 1993. Health- related quality of life was measured with Short Form 36 and EuroQol visual analogue scale. Results: Response was 82% (n=2061). Health- related quality of life declined with age and was similar for men and women, although scores for women were worse for physical functioning. Compared with Australian population norms, the age- and sex- standardized scores of survivors of CABG were generally worse, mainly in the physical domain. Reported angina at the time of follow- up(33% ), symptoms of heart failure equivalent to New York Heart Association(NYHA) classes II to IV(34% ), and comorbidities such as diabetes and hypertension were associated with poorer HRQOL. For both men and women without angina or heart failure at follow- up,HRQOL was no different from that of the general population. Conclusion: Overall, the quality of life among long- term survivors of CABG is worse than that of the general population, the difference being mainly attributable to recurrent symptoms and comorbidities. Quality of life for those without angina or heart failure at follow- up was equivalent to the population norms, providing an incentive to maximize efforts to abolish angina and ameliorate heart failure symptoms.
文摘Background: Electrical cardioversion in patients with atrial fi- brillation(AF) is associated with an increased risk of stroke. We compared a transesophageal echocardiography(TEE)- guided strategy with a conventional strategy in patients with AF >2 days’ duration undergoing electrical cardioversion over a 6- month follow- up. Methods: The ACUTE study was a multicenter, randomized, clinical trial, with 1222 patients. Six- month follow- up was available in 1034 patients(85% ), 525 in the TEE group and 509 in the conventional group. The primary composite end points were cerebrovascular accident, transient ischemic attack, and peripheral embolism at 6 months, which was a prespecified time point. Secondary end points were hemorrhage, mortality, and sinus rhythm. Results: At 6 months, there was no difference in composite embolic events between the TEE group and the conventional group(10 [2% ] vs 4 [0.8% ]; risk ratio(RR) 2.47, 95% CI 0.78- 7.88; P=.11). However, the hemorrhagic rate was significantly lower in the TEE group(23 [4.4% ] vs 38 [7.5% ]; RR 0.58, 96% CI 0.35- 0.97; P=.04). There was no difference between the 2 treatment groups in all- cause mortality(21 [4% ] vs 14 [2.8% ]; RR 1.48, 95% CI 0.76- 2.92; P=.25) and in the occurrence of normal sinus rhythm between the 2 groups(305 [62.2% ] vs 280 [58.1% ]; P=.51). Sinus rhythm at 6 months was more common in the TEE- guided group, in those patients who had direct current cardioversion(238 [62.5% ] vs 151 [53.9% ]; P=.03). Conclusion: The TEE- guided strategy may be considered a clinically effective alternative to a conventional anticoagulation strategy for patients with AF of >2 days’ duration undergoing electrical cardioversion over a 6- month period.
文摘Background: This study aimed to determine the epidemiologic, clinical, microbiologic characteristics, and inhospital outcome of infective endocarditis(IE) in Argentina and compare the results with those of the 1992 IE national survey. Methods: A prospective, multicenter study was conducted in 82 hospitals representing 16 of 24 provinces of Argentina. Patients with diagnosis of IE according to the Duke criteria were surveyed during an 18- month period. Results: From 470 surveyed episodes of IE, 390 cases were classified as definite and 80 as possible IE. The mean age of the definite IE cases was 58.5± 17.3 years; male sex, 70.0% ; and male- female ratio, 2.3 ∶ 1. Pathological evidence of IE was available in 26.2% . There was no previously known heart disease in 35.1% , and the proportion of prosthetic valve IE was 15.9% . Causative microorganisms were streptococci, 38.3% (Streptococcus viridans 27.0% , Streptococcus bovis 5.2% , others 6.1% ); enterococci, 10.2% ; staphylococci, 36.7% (Staphylococcus aureus 29.8% , coagulase- negative sta- phylococci 6.9% );HACEK group, 6.1% ; fungal, 1.4% ; and polymicrobial, 2.0% . Blood culture results were negative in 10.8% . Surgical treatment was performed in 26.2% , and the overall inhospital mortality was 24.6% . Patients from the 2002 survey were older(58.5± 17.3 vs 51.3± 18.7 years, P< .01) and more frequently had underlying heart disease(64.9% vs 55.0% , P< .01): degenerative valve disease(11.5% vs 4.8% , P< .01), congenital heart disease(9.5% vs 4.2% , P< .01), and prosthetic valve IE(15.9% vs 8.5% , P< .01). Conversely, the prevalence of rheumatic valve disease was significantly less than in the 1992 survey(5.4% vs 13.0% , P< .01). Conclusions: The EIRA- 2 survey shows that the clinical profile of IE has changed in Argentina. Currently, patients with IE are older and have a higher frequency of underlying heart disease, degenerative valve disease, and prosthetic valve IE than previously. The incidence of staphylococcal IE has increased. Inhospital mortality remains high, suggesting that more aggressive measures are needed for the early identification, prevention, and treatment of IE.
文摘Aims: Recent data from the COMPANION trial have documented that cardiac resynchronization therapy(CRT) with biventricular(BiV) pacing reduces mortality and hospitalization in patients with advanced CHF, but little is known regarding thecellular and molecular mechanisms of CRT. Our aim is to evaluate interstitial remodelling, tumor necrosis factor- α (TNF- α ) expression, and apoptosis in patients with advanced CHF treated with CRT. Methods and results: We performed endomyocardial biopsies in 10 patients, aged 62, with dilated cardiomyopathy before and 6 months after the implantation of a BiV pacing device. Clinical status and left ventricular(LV)architecture and function were assessed as well as myocardial histology, TNF- α expression, and apoptotic index. CRT improved clinical status, as shown by a significant reduction of the Minnesota living with heart failure questionnaire(MLHFQ)score(from 53 to 40) and 6- min walked distance(from 290 to 330 m)(all P < 0.05 vs. baseline). This was associated with reverse LV remodelling substantiated by significant reductions of LV volumes and end- systolic circumferential wall stress. Examination of myocardial tissue revealed a significant decrease of collagen volume fraction(CVF)(from 25.16 to 18.0% ), TNF- α expression(from 9.5 to 3.6 pixel × 103), and apoptotic index(from 2030 to 1408 apoptotic nuclei/106), with increased capillary density(from 1801 to 2011 capillary/mm2) after 6 months of CRT(all P < 0.05 vs. baseline). Moreover, changes in TNF- α expression were positively correlated with both CVF and end- systolic circumferential wall stress(r=0.80 and 0.70, respectively). Conclusion: We provide the first evidence that CRT reduces interstitial remodelling, TNF- α expression, and apoptosis. The data may explain the beneficial effects of CRT on CHF progression and survival.
