Vascular pedicle ligation techniques during laparoscopic colectomy. A prospective randomized trial.

BACKGROUND: A variety of devices are available for pedicle ligation during laparoscopic colectomy including vascular staplers, clips, and electrothermal bipolar vessel-sealing devices. This study assesses their speed, reliability, and cost to guide surgeons in their choice for intracorporeal pedicle ligation. METHODS: A prospective randomized study comparing laparoscopic vascular staplers and disposable clip appliers (S/C) with the LigaSure Atlas (LIG) was performed during elective right, left, and total colectomy. Cases were stratified by procedure. Failure was defined as any bleeding after proper pedicle ligation. RESULTS: The study included 48 S/C patients and 52 LIG patients with no differences in demographics, diagnosis, procedure, number of vessels ligated per procedure, or operative time. Failure occurred for 14 (9.2%) of the 152 vessels ligated in the S/C group, as compared with 5 (3%) of the 169 vessels ligated in the LIG group (p = 0.02). The median blood loss associated with device failure was 50 ml (range, 20-50 ml) in S/C group, as compared with 100 ml (range 25-800 ml) in the LIG group (p = 0.054). Major blood loss attributable to device failure and surgeon error occurred in only one LIG case. The mean cost per case of vessel ligation was significantly less in the LIG group (317 dollars +/- 0 dollars vs 400 dollars +/- 112 dollars; p < 0.001). The cost differences were greatest for total colectomy (LIG = 317 dollars +/- 0 dollars vs S/C = 565 dollars +/- 67 dollars; p = 0.002). CONCLUSION: Device failure, although more common in the S/C group, does not result in significant blood loss. The LigaSure Atlas is more cost effective during laparoscopic colectomy, especially total colectomy, and may allow the surgeon more versatility in its application.

Family history and colorectal cancer: predictors of risk.

INTRODUCTION: While the association between family history of colorectal cancer in first-degree relatives and risk of developing colon cancer has been well defined, the association with rectal cancer is much less clear. The purpose of this study is to define rectal cancer risk associated with family history of colorectal cancer in first-degree relatives. We also evaluate diet and lifestyle factors associated with developing colorectal cancer among participants with a positive family history. METHODS: Data were available from two population-based case--control studies of colon and rectal cancer. Participants were members of the Kaiser Permanente Medical Care Program (KPMCP) or residents of the state of Utah. Cases were first primary colon cancer diagnosed between 1991 and 1994 (n = 1308 cases and 1544 controls) or rectal cancer diagnosed between 1997 and 2001 (n = 952 cases and 1205 controls). RESULTS: A family history of colorectal cancer in any first-degree relatives slightly increased risk of rectal cancer (OR: 1.37 95% CI: 1.02-1.85). Family history of colorectal cancer was associated with the greatest risk among those diagnosed at age 50 or younger (OR: 2.09 95% CI: 0.94-4.65 for rectal tumors; OR: 3.00 95% CI: 0.98-9.20 for distal colon tumors; and OR: 7.88 95% CI: 2.62-23.7 for proximal colon tumors). Factors significantly associated with cancer risk among those with a family history of colorectal cancer, included not having a sigmoidoscopy (OR: 2.81 95% CI: 1.86-4.24): a diet not Prudent, i.e. high in fruits, vegetables, whole grains, fish and poultry, (OR: 2.79 95% CI: 1.40-5.56); smoking cigarettes (OR: 1.68 95% CI: 1.12-2.53), and eating a Western diet, i.e. a diet high in meat, refined grains, high-fat foods, and fast foods, (OR: 2.15 95% CI: 1.06-4.35). Physical inactivity was not associated with increased cancer risk among those with a positive family history of colorectal cancer. SUMMARY: These results confirm observations reported by others that a family history of colorectal cancer increases risk of cancer among those diagnosed at a younger age. Associations with family history are weakest for rectal cancer and strongest for proximal colonic tumors. Since several diet and lifestyle factors influence development of cancer among those with a family history of the disease, there appears to be practical approaches for individuals with a family history of colorectal cancer to reduce their cancer risk.

Physical activity and colorectal cancer.

Physical activity has been inconsistently associated with rectal cancer despite the consistent association between physical activity and colon cancer. In this study, the authors evaluated the association between physical activity and rectal cancer using the same questionnaire used to evaluate the previously reported association with colon cancer. A population-based study of 952 incident cases of cancer in the rectum and rectosigmoid junction and 1,205 age- and sex-matched controls was conducted in Utah and northern California at the Kaiser Permanente Medical Care Program between 1997 and 2002. Vigorous physical activity was associated with reduced risk of rectal cancer in both men and women (odds ratio (OR) = 0.60, 95% confidence interval (CI): 0.44, 0.81 for men; OR = 0.59, 95% CI: 0.40, 0.86 for women). Among men, moderate levels of physical activity also were associated with reduced risk of rectal cancer (OR = 0.70, 95% CI: 0.51, 0.97). Participation in vigorous activity over the past 20 years conferred the greatest protection for both men and women (OR = 0.55, 95% CI: 0.39, 0.78 for men; OR = 0.44, 95% CI: 0.30, 0.67 for women). In summary, physical activity was associated with reduced risk of rectal cancer in these data. The reduced risk was similar to that previously observed for colon cancer.

Effect of prior revascularization on outcome following percutaneous coronary intervention; NHLBI Dynamic Registry.

AIMS: An increasing number of patients undergoing percutaneous coronary intervention (PCI) have experienced previous revascularization procedures. Their outcome after PCI has seldom been compared to that of patients without prior procedures. This study investigates which elements of prior revascularization affect in-hospital and long-term outcome after PCI. METHODS AND RESULTS: Baseline characteristics as well as in-hospital and 1-year outcomes were compared in 4010 consecutive patients undergoing PCI in the NHLBI Dynamic Registry, categorized by type of prior procedure. In-hospital mortality was lowest and procedural success highest among patients with prior PCI only. Patients with prior coronary artery bypass grafting (CABG) had higher rates for the combined endpoint of death and myocardial infarction (MI) at 1 year compared to patients with no prior procedures. However, in multivariate regression analysis adjusting for potential confounders, neither prior PCI nor prior CABG were independent predictors of death or death/MI at 1 year. Patients with prior procedure had higher rates for repeat PCI and patients with prior PCI had higher rates for CABG during the year following the index procedures. These associations persisted after adjustment for potential confounders. Finally, patients with prior procedures had a higher prevalence of angina at 1 year. CONCLUSIONS: Due to adverse baseline characteristics, patients with prior CABG have higher rates for death/MI during the first year after PCI and both groups of patients with prior procedures have higher revascularization rates. However, only the associations with repeat revascularization persist after adjustment for baseline and procedural factors.

Benefit and safety of enhanced external counterpulsation in treating coronary artery disease patients with a history of congestive heart failure.

Enhanced external counterpulsation (EECP) is used to noninvasively treat refractory angina patients, including those with a history of heart failure. The International EECP Patient Registry was used to examine the benefit and safety of EECP treatment, including a 6-month follow-up, in 1,957 patients, 548 with a history of heart failure. The heart failure cohort was older, with more females, a greater duration of coronary artery disease, more prior infarcts and revascularizations. Significantly fewer heart failure patients completed the course of EECP, and exacerbation of heart failure was more frequent, though overall major adverse cardiac events (MACE, i.e. death, myocardial infarction, revascularization) during treatment were not significantly different. The angina class improved in 68%, with comparable quality of life benefit, in the heart failure cohort. At 6 months, patients with congestive heart failure maintained their reduction in angina but were significantly more likely to have experienced a MACE end point.

Differences in heart valve procedures between North American and European centers: a report from the Artificial Valve Endocarditis Reduction Trial (AVERT).

BACKGROUND AND AIM OF THE STUDY: Differences in heart valve procedures between North American (NA) and European (EU) centers were evaluated in a multicenter trial. METHODS: Between July 1998 and January 2000, 807 patients from 12 NA (n = 446) and seven EU centers (n = 361) were randomized to receive either Silzone or conventional valves in the Artificial Valve Endocarditis Reduction Trial (AVERT). Subanalysis was performed to compare demographics, patient risk profile, surgical techniques and perioperative management of patients in NA and EU centers. RESULTS: Mean age was significantly younger and body mass index higher in NA. Patients' risk profiles showed significantly higher incidences of previous myocardial infarction, congestive heart failure, angina, prior cardiovascular surgery, and history of smoking in NA. A different distribution of implant position was observed between groups: aortic valve/mitral valve/double valve replacement in 54.0, 35.7 and 10.3% in NA, and 64.5, 27.4 and 8.0% in EU (p <0.01). Concomitant coronary artery bypass grafting was performed in 31.6% of NA patients and 19.4% of EU patients (p <0.001). Timing of surgery showed a higher incidence of urgent procedures in NA centers. Distribution of valve sizes and perioperative complication rate were similar, but length of hospital stay was longer in EU centers. CONCLUSION: Surprisingly, surgeons in NA and EU centers are faced by different patient populations requiring mechanical heart valve replacement. NA patients were younger, but required more extensive surgery. Surgical technique and perioperative management appear to differ in NA and EU centers. These differences in reporting heart valve procedures might have been influenced by variable interpretations of definitions and different patient expectations, although a uniform study protocol with consistent definitions was used at all sites.

The International EECP Patient Registry (IEPR): design, methods, baseline characteristics, and acute results.

BACKGROUND: In 1998, the International EECP Patient Registry (IEPR) was organized to document patient characteristics, safety, and efficacy during the treatment period, and long-term outcomes. All centers with EECP facilities were invited to join the voluntary Registry. The Registry population comprises all patients starting EECP therapy for treatment of angina pectoris in participating centers. HYPOTHESIS: The study was undertaken to determine whether EECP is a safe and effective treatment for patients with angina pectoris regardless of their suitability for revascularization by more conventional techniques. METHODS: After 18 months of operation, 43 clinical centers representing over half of clinical sites using the EECP system contributed cases. The data reported here were collected before the first EECP treatment and upon completion of final treatment. EECP can be used for patients ineligible for either coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), as well as for those who prefer noninvasive treatment to avoid or delay revascularization. In this report, patients considered to be candidates for revascularization are compared with those not considered suitable. RESULTS: Of the 978 patients analyzed, 70% had Canadian Cardiovascular Society Classification class III or IV angina before starting treatment, and 62% used nitroglycerin. Most (81%) had been previously revascularized, and 69% were considered unsuited for either PCI or CABG at the time of starting EECP. A full treatment course (usually 35 h) was completed in 86%, of whom 81% reported improvement of at least one angina class immediately after the last treatment. CONCLUSION: In a broad patient population, EECP has been shown to be a safe and effective treatment.

Does higher diastolic augmentation predict clinical benefit from enhanced external counterpulsation?: Data from the International EECP Patient Registry (IEPR).

BACKGROUND: Enhanced external counterpulsation (EECP) has been demonstrated to be an effective treatment for stable angina in patients with coronary disease. The hemodynamic effects of EECP are maximized when the ratio of diastolic to systolic pressure area is in the range of 1.5 to 2.0. HYPOTHESIS: It is hypothesized that patients undergoing EECP who are able to achieve higher diastolic augmentation (DA) ratios may derive greater clinical benefit. This study examines the relationship between the DA ratio and clinical outcomes in patients undergoing EECP. METHODS: We analyzed demographic, noninvasive hemodynamic, and clinical outcome data on 1,004 patients enrolled in the International EECP Patient Registry (IEPR) for treatment of chronic angina between January 1998 and August 1999. Blood pressure waveforms were recorded from finger plethysmography. Six-month clinical outcomes were obtained by telephone interview. RESULTS: At the end of EECP treatment, 370 (37%) patients had a higher DA ratio (defined as > or = 1.5) and 634 (63%) had a lower DA ratio (defined as < 1.5). Factors associated with a lower DA ratio included age > or =65 years (p <0.001), female gender (p < 0.001), left ventricular ejection fraction < 35% (p < 0.05), hypertension (p < 0.01), prior coronary bypass surgery (p < 0.01), noncardiac vascular disease (p < 0.001), multivessel disease (p < 0.01), congestive heart failure (p < 0.01), current smoking (p < 0.01), unsuitability for further revascularization (p < 0.001), and higher baseline angina class (p < 0.001). There were no significant differences regarding diabetes mellitus, prior coronary angioplasty, prior myocardial infarction, or antianginal medication use between patients with higher or lower DA ratios. Based on a multiple logistic regression model, independent predictors of a DA ratio < 1.5 at the end of EECP included current smoking (odds ratio 3.3; 95% confidence intervals 2.0-5.4); multivessel disease (1.7; 1.3-2.3); female gender (2.2; 1.7-3.0); no prior EECP (1.9; 1.1-3.3); noncardiac vascular disease (2.3; 1.7-2.9); age > or = 65 years (1.7; 1.4-2.2), and patients not suitable for revascularization (1.6; 1.2-2.0). By the end of therapy, there were no significant differences in myocardial infarction, revascularization rates, or nitroglycerin use with respect to higher DA ratios. At 6-month follow-up, patients with higher DA had a trend toward a greater reduction in angina class compared with those with lower DA (p = 0.069). There was a significantly higher rate of unstable angina and congestive heart failure in the group not achieving higher augmentation (p < 0.05). CONCLUSIONS: Patients who are younger, male, nonsmoking, and without multivessel coronary or noncardiac vascular disease are most likely to have higher DA with EECP. Patients with higher DA tended to have a greater reduction in angina class at 6-month follow-up compared with those with lower DA ratios. There is evidence that higher DA ratios are associated with improved short- or long-term clinical outcomes, suggesting that clinical benefit from EECP is associated with the magnitude of DA.

Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy.

BACKGROUND: This prospective placebo-controlled trial was designed to determine whether intravenous immune globulin (IVIG) improves left ventricular ejection fraction (LVEF) in adults with recent onset of idiopathic dilated cardiomyopathy or myocarditis. METHODS AND RESULTS: Sixty-two patients (37 men, 25 women; mean age +/-SD 43.0+/-12.3 years) with recent onset (/=0.10 from study entry, and 20 (36%) of 56 normalized their ejection fraction (>/=0.50). The transplant-free survival rate was 92% at 1 year and 88% at 2 years. CONCLUSIONS: These results suggest that for patients with recent-onset dilated cardiomyopathy, IVIG does not augment the improvement in LVEF. However, in this overall cohort, LVEF improved significantly during follow-up, and the short-term prognosis remains favorable.

Measurement variation of aortic pulse wave velocity in the elderly.

Accurate and reproducible measures are required to study arterial stiffness in human populations. The reproducibility of aortic pulse wave velocity was evaluated in 14 participants from a population-based study of cardiovascular disease in the elderly. Three data files were collected per participant by each of two sonographers and files were read by two readers. Seven of the 14 participants returned for a second visit 1 week later to assess between-visit variability. Reproducibility was evaluated with Pearson and intraclass correlations and by the absolute value of the difference between replicate values. The overall reliability coefficient was rI = 0.77. Between-sonographer, between-reader, and between-visit correlations were rP = 0.80 to 0.87, rP = 0.73 to 0.89 and rP = 0.63. The mean absolute value of the difference between replicates was 59.4 to 94.0 cm/sec and 88.7 to 112.8 cm/sec for sonographers and readers, respectively. These results indicate that the mean PWV measure is reproducible even when sonographers and readers are newly trained.

Coronary microvascular dysfunction is highly prevalent in women with chest pain in the absence of coronary artery disease: results from the NHLBI WISE study.

BACKGROUND: Chest pain in the absence of obstructive coronary artery disease (CAD) is common in women; it is frequently associated with debilitating symptoms and repeated evaluations and may be caused by coronary microvascular dysfunction. However, the prevalence and determinants of microvascular dysfunction in these women are uncertain. METHODS: We measured coronary flow velocity reserve (coronary velocity response to intracoronary adenosine) to evaluate the coronary microvasculature and risk factors for atherosclerosis in 159 women (mean age, 52.9 years) with chest pain and no obstructive CAD. All women were referred for coronary angiography to evaluate their chest pain as part of the Women's Ischemia Syndrome Evaluation (WISE) study. RESULTS: Seventy-four (47%) women had subnormal (<2.5) coronary flow velocity reserve suggestive of microvascular dysfunction (mean, 2.02 +/- 0.38); 85 (53%) had normal reserve (mean, 3.13 +/- 0.64). Demographic characteristics, blood pressure, ventricular function, lipid levels, and reproductive hormone levels were not significantly different between women with normal and those with abnormal microvascular function. Postmenopausal hormone use within 3 months was significantly less prevalent among those with microvascular dysfunction (40% vs 60%, P =.032). Age and number of years past menopause correlated with flow velocity reserve (r = -0.18, P =.02, and r = -0.30, P <.001, respectively). No significant associations were identified between flow velocity reserve and lipid and hormone levels, blood pressure, and left ventricular ejection fraction. CONCLUSIONS: Coronary microvascular dysfunction is present in approximately one half of women with chest pain in the absence of obstructive CAD and cannot be predicted by risk factors for atherosclerosis and hormone levels. Therefore, the diagnosis of coronary microvascular dysfunction should be considered in women with chest pain not attributable to obstructive CAD.

Detailed angiographic analysis of women with suspected ischemic chest pain (pilot phase data from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation [WISE] Study Angiographic Core Laboratory).

The purpose of this study is to provide a contemporary qualitative and quantitative analysis of coronary angiograms from a large series of women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) study who had suspected ischemic chest pain. Previous studies have suggested that women with chest pain have a lower prevalence of significant coronary artery disease (CAD) compared with men. Detailed analyses of angiographic findings relative to risk factors and outcomes are not available. All coronary angiograms were reviewed in a central core laboratory. Quantitative measurement of percent stenosis was used to assess the presence and severity of disease. Of the 323 women enrolled in the pilot phase, 34% had no detectable, 23% had measurable but minimal, and 43% had significant ( > 50% diameter stenosis) CAD. Of those with significant CAD, most had multivessel disease. Features suggesting complex plaque were identified in < 10%. Age, hypertension, diabetes mellitus, prior myocardial infarction (MI), current hormone replacement therapy, and unstable angina were all significant, independent predictors of presence of significant disease (p < 0.05). Subsequent hospitalization for a cardiac cause occurred more frequently in those women with minimal and significant disease compared with no disease (p = 0.001). The common findings of no and extensive CAD among symptomatic women at coronary angiography highlight the need for better clinical noninvasive evaluations for ischemia. Women with minimal CAD have intermediate rates of rehospitalization and cardiovascular events, and thus should not be considered low risk.

Usefulness of electron beam tomography to detect progression of coronary and aortic calcium in middle-aged women.

Electron beam tomography (EBT) permits the noninvasive quantification of coronary and aortic calcium as a marker of atherosclerosis. Coronary and aortic calcium are strongly related to premenopausal cardiovascular risk factors in middle-aged women. This report evaluates changes in coronary and aortic calcium over an average of 18 months in 80 women. Measurement variation over time and between readings is also evaluated in these women who were followed through the menopausal transition. Eight years after menopause, 80 women (average age 63 years) underwent serial EBT of the coronary arteries and aorta separated by 18 months. Calcium scores were based on the number and density of calcific deposits. Duplicate readings were obtained to evaluate the effect of reading variation on calcium scores. At baseline, the median calcium score was 0 in the coronary arteries and 58 in the aorta. Average change in coronary (+11) and aortic (+112) calcium were significantly different from zero (p < 0.001). Reading variability did not contribute significantly to the variation in calcium scores. Extent of calcium in the coronary arteries was associated with progression of calcium in the aorta (p = 0.013). Both coronary and aortic calcium were significantly associated with premenopausal cardiovascular risk factors. Thus, progression of coronary and aortic calcium using EBT can be observed over a short time in healthy middle- aged women.

Pharmacogenetic interactions between beta-blocker therapy and the angiotensin-converting enzyme deletion polymorphism in patients with congestive heart failure.

BACKGROUND: Activation of the renin-angiotensin and sympathetic nervous systems adversely affect heart failure progression. The ACE deletion allele (ACE D) is associated with increased renin-angiotensin activation; however, its influence on patient outcomes remains uncertain, and the pharmacogenetic interactions with beta-blocker therapy have not been previously evaluated. METHODS AND RESULTS: We prospectively followed 328 patients (age, 56.1+/-11.9 years) with systolic dysfunction (left ventricular ejection fraction, 0.24+/-0.08) to assess the impact of the ACE D allele on transplant-free survival (median follow-up, 21 months). Transplant-free survival was compared by genotype for the whole cohort and separately in patients with (n=120) and those without beta-blocker therapy (n=208) at the time of entry. Transplant-free survival was significantly poorer for patients with the D: allele (1-year percent survival II/ID/DD=94/77/75; 2-year=78/65/60; ordered log-rank test, P:=0.044). In patients not treated with beta-blockers, the adverse impact of ACE D allele was dramatically increased (1-year percent survival II/ID/DD=95/75/67; 2-year=81/61/48; P:=0.005). In contrast, in patients receiving beta-blocker therapy, no influence of ACE genotype on transplant-free survival was evident (1-year percent survival II/ID/DD=91/80/86; 2-year=70/71/77; P:=0.73). CONCLUSIONS: In a cohort of patients with systolic dysfunction, the ACE D allele was associated with a significantly poorer transplant-free survival. This effect was primarily evident in patients not treated with beta-blockers and was not seen in patients receiving therapy. These findings suggest a potential pharmacogenetic interaction between the ACE D/I polymorphism and therapy with beta-blockers in the determination of heart failure survival.

Percutaneous coronary intervention in the current era compared with 1985-1986: the National Heart, Lung, and Blood Institute Registries.

BACKGROUND: Although refinements have occurred in coronary angioplasty over the past decade, little is known about whether these changes have affected outcomes. METHODS AND RESULTS: Baseline features and in-hospital and 1-year outcomes of 1559 consecutive patients in the 1997-1998 Dynamic Registry who were having first coronary intervention were compared with 2431 patients in the 1985-1986 National Heart, Lung, and Blood Institute Registry. Compared with patients in the 1985-1986 Registry, Dynamic Registry patients were older (mean age, 62 versus 58 years; P:<0.001) and more often female (32.1% versus 25.5%; P:<0.001). In the Dynamic Registry, procedures were more often performed for acute myocardial infarction (22.9% versus 9.9%; P:<0.001) and treated lesions were more severe (84.5% versus 82.5% diameter reduction; P:<0.001), thrombotic (22.1% versus 11.3%; P:<0.001) or calcified (29.5% versus 10.8%; P:<0.001). Stents were used in 70.5% of Dynamic Registry patients, whereas 1985-1986 patients received balloon angioplasty alone. Procedural success was higher in the Dynamic Registry (92.0% versus 81.8%; P:<0.001) and the rate of in-hospital death, myocardial infarction, and emergency coronary bypass surgery combined was lower (4.9% versus 7.9%; P:=0.001) than in the 1985-1986 Registry. The 1-year rate for CABG was lower in the Dynamic Registry (6.9% versus 12.6%; P:<0.001). CONCLUSIONS: Although Dynamic Registry patients had more unstable and complex coronary disease than those in the 1985-1986 Registry, their rate of procedural success was higher whereas rates of complications and subsequent CABG were lower. Results of percutaneous coronary intervention have improved substantially over the past decade.

Expression of proinflammatory cytokines in the failing human heart: comparison of recent-onset and end-stage congestive heart failure.

BACKGROUND: Plasma levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, are elevated in patients with congestive heart failure (CHF). Recent studies suggest that the failing human heart is a source of proinflammatory cytokines in the end-stage failing heart. However, the relevance of plasma levels to those of the myocardium remains undefined. We sought to compare cytokine expression in early and end-stage CHF, and to evaluate the correlation of tissue expression to plasma levels. METHODS: Two patient populations were studied: patients with recent-onset CHF, all with symptoms less than 6 months (n = 17, duration of symptoms 2.1 +/- 1.6 months, range of New York Heart Association (NYHA) 1 to 3), and end-stage heart-failure patients (n = 7) who underwent left-ventricular assist-device (LVAD) implantation (Duration of symptoms 47.1 +/- 28.0 months, all NYHA class 4). Plasma levels of TNF-alpha and IL-6 proteins were evaluated by an Enzyme-Linked Immuno-Sorbent Assay (ELISA), while myocardial levels of cytokine transcripts were assessed by ribonuclease (Rnase) protection assay. RESULTS: In patients with end-stage heart failure, TNF-alpha and IL-6 were increased in the plasma as well as in the myocardium (plasma: TNF-alpha = 7.7 +/- 2.3 pg/ml, IL-6 = 45.0 +/- 47.1 pg/ml; myocardium: TNF-alpha = 0.31 +/- 0.15% of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression, IL-6 = 1.56 +/- 1.54% ). In contrast, despite elevated plasma levels of TNF-alpha and IL-6, the myocardium of patients with the recent onset of symptoms demonstrated minimal expression of TNF-alpha and IL-6 messenger ribonucleic acid (mRNA) (plasma: TNF-alpha = 4.3 +/- 1.7 pg/ml, IL-6 = 3.3 +/- 1.8 pg/ml; myocardium: TNF-alpha = 0.13 +/- 0. 04%, IL-6 = 0.02 +/- 0.04%). Plasma levels of TNF-alpha were significantly correlated with those in the myocardium when both populations were combined. (r = 0.69, p < 0.001). CONCLUSIONS: Cytokines are expressed in the myocardium in end-stage heart failure to a much greater degree than in patients with the recent-onset of symptoms. This suggests that induction of cytokines in the myocardium is a relatively late event in the pathogenesis of CHF. Furthermore, plasma levels of TNF-alpha correlates with mRNA expression in the myocardium and thus may serve as an appropriate marker of myocardial cytokine activation. Whether the production of cytokines in the failing human heart precedes the elevation of cytokines in the plasma remains undefined. Therefore, we studied expression of TNF-alpha and IL-6 in the myocardium as well as in the plasma in patients with early and end-stage CHF. The results have demonstrated that cytokines are expressed in the myocardium in end-stage heart failure to a much greater degree than in patients with the recent onset of symptoms. This suggests that induction of cytokines in the myocardium is a relatively late event in the pathogenesis of CHF.

Estrogen is associated with improved survival in aging women with congestive heart failure: analysis of the vesnarinone studies.

OBJECTIVES: This study sought to evaluate the effects of postmenopausal estrogen use on mortality in aging women with congestive heart failure (CHF). BACKGROUND: The age-related increase in CHF mortality in women may be related to a menopause-associated increased incidence of coronary artery disease. In addition to inhibiting coronary atherosclerosis, estrogen may also have protective effects on cardiac myocytes independent of the coronary vasculature. We hypothesized that estrogen use is associated with improved survival in elderly women with CHF. METHODS: Associations between survival, estrogen use and patient characteristics were assessed in 1,134 women who were at least 50 years of age, had CHF and left ventricular ejection fraction (EF) < or =30% and were enrolled in one of three clinical trials of vesnarinone. RESULTS: All-cause 12-month mortality was 15.0% among the 237 estrogen users versus 27.1% among the 897 estrogen nonusers (p = 0.004 for unadjusted comparison of survival). Similar results were observed for cardiac mortality. Regression analysis demonstrated that estrogen use was independently associated with improved survival (relative risk of mortality = 0.68, 95% confidence interval 0.48 to 0.96, p = 0.03). Advanced age, low EF, New York Heart Association class IV CHF, Caucasian race and abnormal serum creatinine, sodium, potassium and transaminase were independently associated with increased mortality. CONCLUSIONS: Estrogen use among older women with CHF is associated with decreased overall and cardiac mortality.

The effect of previous coronary-artery bypass surgery on the prognosis of patients with diabetes who have acute myocardial infarction. Bypass Angioplasty Revascularization Investigation Investigators.

BACKGROUND: Acute myocardial infarction in patients with diabetes is associated with high mortality. We studied whether previous revascularization by coronary-artery bypass grafting (CABG), as compared with percutaneous transluminal coronary angioplasty (PTCA), influences the prognosis in such patients. METHODS: We classified all patients eligible for the Bypass Angioplasty Revascularization Investigation who underwent coronary revascularization within three months after entry into the study according to whether they had diabetes and whether they had undergone CABG, either initially or after PTCA. The protective effect of CABG with regard to mortality in the presence and in the absence of subsequent spontaneous Q-wave myocardial infarction was estimated with the use of Cox regression models. RESULTS: Among the 641 patients with diabetes and the 2962 without diabetes, the cumulative five-year rates of death were 20 percent and 8 percent, respectively (P<0.001), and the five-year rates of spontaneous Q-wave myocardial infarction were 8 percent and 4 percent (P<0.001). CABG greatly reduced the risk of death after spontaneous Q-wave myocardial infarction in the patients with diabetes (relative risk, 0.09; 95 percent confidence interval, 0.03 to 0.29). Among patients with diabetes who had undergone CABG but did not have spontaneous Q-wave myocardial infarctions, the corresponding relative risk of death was 0.65 (95 percent confidence interval, 0.45 to 0.94). Among the patients without diabetes, no protective effect of CABG was evident. CONCLUSIONS: Among patients with diabetes, previous coronary bypass surgery, as compared with coronary angioplasty, has a highly favorable influence on prognosis after acute myocardial infarction and a smaller beneficial effect among patients who do not have infarction. These findings should influence the type of coronary revascularization procedure selected for patients with diabetes who have multivessel coronary artery disease.

Measurement of hemostatic indexes in conjunction with transcranial doppler sonography in patients with ventricular assist devices.

BACKGROUND AND PURPOSE: Clinical thromboembolism (TE) remains an impediment to the chronic application of ventricular assist devices (VADs). Microembolic signals (MES) have been detected by transcranial Doppler ultrasound (TCD) in patients with VADs, although their origin and relation to TE remain undefined. We have investigated the hypothesis that hemostatic alterations are related to MES and that MES are associated with TE in a group of 27 VAD patients. METHODS: Indexes of coagulation, fibrinolysis, and cellular activation and aggregation were measured before and during the VAD implantation period in conjunction with TCD. Groups were defined on the basis of presence of MES, degree of MES showering, and incidence of TE. RESULTS: MES were observed in 67 (58%) of 115 of individual postoperative TCD measurements and in 21 (78%) of 27 patients. Of patients with TE, 10 (83%) of 12 had detectable MES compared with 11 (73%) of 15 patients without TE (P=0.66). MES were significantly associated with elevated thrombin generation during the implantation period, as reflected by plasma prothrombin fragment F1.2. Elevations in indexes of coagulation, platelet activation, and fibrinolysis relative to normal control subjects were found for patients with VADs with and without detected MES. CONCLUSIONS: Although no significant relation between MES and TE in VAD patients was found, the data support the hypothesis that MES are related to increased hemostatic activity in this patient group despite aggressive anticoagulant therapy.

Effect of inotrope withdrawal on morbidity and mortality in patients with chronic heart failure: results of the vesnarinone trial withdrawal substudy. Vest Withdrawal Substudy Group.

BACKGROUND: The use of inotropic agents in the therapy of patients with congestive heart failure (CHF) is controversial. One concern regarding inotropic therapy has been that drug withdrawal could be associated with a worsening of symptoms. METHODS AND RESULTS: We took advantage of the discontinuation of the recent trial of vesnarinone in the therapy of CHF to assess the effects of withdrawal of the inotropic agent, vesnarinone, in patients with chronic CHF who had been randomized to receive either placebo or 30 or 60 mg of vesnarinone. Contrary to our initial hypothesis, withdrawal of vesnarinone did not impact on either morbidity or mortality over a period of 6 months. CONCLUSION: Although these results suggest vesnarinone withdrawal is safe, the applicability of these results to other inotropic agents remains unclear.