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Effect of candesartan on cause-specific mortality in heart failure patients: the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program.

BACKGROUND: Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure. We assessed the effect of candesartan on cause-specific mortality in patients enrolled in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program. METHODS AND RESULTS: The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure: CHARM-Alternative (n=2028; LVEF<=40% [corrected] and ACE intolerant), CHARM-Added (n=2548; LVEF<=40%, [corrected] already on ACE inhibitors), and CHARM-Preserved (n=3023; LVEF >40%). Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and were followed up for a median of 37.7 months. All deaths were reviewed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation. The number and rate of deaths by cause were calculated for each of the component trials and the overall program. Of all the patients, 8.5% died suddenly, and 6.2% died of progressive heart failure. Candesartan reduced both sudden death (HR 0.85 [0.73 to 0.99], P=0.036) and death from worsening heart failure (HR 0.78 [0.65 to 0.94], P=0.008). These reductions were most apparent in the patients with LVEF<=40% [corrected]. CONCLUSIONS: Candesartan reduced sudden death and death from worsening heart failure in patients with symptomatic heart failure, although this reduction was most apparent in patients with systolic dysfunction.

Aged↗

Heart failure progression due to secondary organ dysfunction in acute heart failure.

Although the pathophysiology of heart failure progression is important to survival it is not fully understood. In 92 patients with acute heart failure due to myocardial infarction or dilated cardiomyopathy, secondary organ dysfunction was evaluated to determine whether this factor contributed to heart failure progression and death. Forty-one patients had renal dysfunction, hepatic disease or loss of consciousness after the onset of the acute heart failure, and 26 of them (63%) died of progressive heart failure during the follow-up period of 20 months on average. The one-year survival rate was 22%. Although 51 other patients showed the same initial clinical features and cardiac function, they did not develop concurrent organ dysfunction during the course and only 11 (22%, p < 0.001) died of progressive heart failure. The one-year survival rate was 67%. The survival rate decreased in the order of renal dysfunction, hepatic disease and loss of consciousness. Transient low cardiac output of less than 2.2 l/min/m2 was more frequent in patients with organ dysfunction. It is suggested that heart failure progresses, in part, due to organ dysfunction secondary to heart failure and careful treatment to prevent organ dysfunction is important to long term survival.

Acute Disease↗

Clinical features and prognosis associated with a preserved left ventricular systolic function in a large cohort of congestive heart failure outpatients managed by cardiologists. Data from the Italian Network on Congestive Heart Failure.

BACKGROUND: The aim of this study was to evaluate the clinical characteristics, 1-year prognosis and therapeutic approach of heart failure with a preserved left ventricular systolic function in a large multicenter registry of patients referred to specialized heart failure clinics. METHODS: The study population consisted of 5164 outpatients (mean age 62 +/- 12 years, 78.8% male, 28.1% in NYHA functional class III-IV) with an available left ventricular ejection fraction (LVEF) measurement at the initial evaluation for enrollment in the Italian Network on Congestive Heart Failure. A 1-year follow-up was available for 2390 patients. RESULTS: 2859 out of 5164 patients (55.4%) had an LVEF < 35%, 1618 (31.3%) had an LVEF between 35 and 45%, and 687 patients (13.3%) had an LVEF > 45%. Patients with an LVEF > 45% were significantly older, more often female and presented a significantly higher prevalence of a hypertensive etiology, obesity and atrial fibrillation. The severity of the clinical picture, as indicated by a lower prevalence of NYHA class III-IV (17.2 vs 35.6%, p = 0.001) and a third heart sound (14.8 vs 33.5%, p = 0.001), was less in patients with an LVEF > 45%. The therapeutic approach differed significantly, with a larger use of calcium antagonists and beta-blockers in patients with an LVEF > 45%, while ACE-inhibitors, diuretics and digoxin were more often prescribed to those with an impaired LVEF. The 1-year mortality and morbidity (all cause and congestive heart failure worsening hospitalizations) were significantly lower in patients with a preserved left ventricular systolic function compared to those with left ventricular systolic dysfunction (8.9 vs 18.8% for mortality, p = 0.001, and 8.3 vs 16.5% for hospital readmissions due to worsening congestive heart failure, p = 0.001, respectively). CONCLUSIONS: Patients with congestive heart failure and a preserved left ventricular systolic function seem to constitute a distinct population not infrequently presenting even in the clinical setting of specialized heart failure clinics. Further studies are needed to establish a definitive and standardized diagnosis and the most appropriate therapy for congestive heart failure with a normal LVEF.

Aged↗

[A case of fulminant hepatic failure secondary to congestive heart failure].

It has been generally accepted that congestive heart failure does not lead to fulminant hepatic failure, unless it is associated with cardiac shock or low cardiac output. Only three cases have been reported, in which liver congestion is followed by fulminant hepatic failure without a history of shock or low cardiac output. Here we present a case of a 48-year-old man with dilated cardiomyopathy and pulmonary infarction, who developed fulminant hepatic failure from congestion. When he was admitted for the control of diabetes mellitus, hepatomegaly of 3-finger breadth and marked cardiomegaly without pulmonary congestion was noted. Diabetes was controlled using insulin. But 3 weeks after admission, he sometimes complained of back dullness because of pulmonary infarction. His heart gradually increased in size, and Jugular venous dilatation and pretibial pitting edema also worsened. Jaundice was noted and serum GOT and GPT increased. A large liver of 6-finger breath below the right costal margin was able to be felt. But within one week, the size of the liver markedly decreased and the signs of hepatic failure such as jaundice, hepatic encephalopathy and numerous petechiae appeared. Blood pressure was maintained and no hypotension or cardiac shock was noted. The patient died of fulminant hepatic failure on the 20th days after onset of the hepatic failure. The autopsy revealed liver atrophy with severe central lobular necrosis, and thrombus in the right main pulmonary artery which caused severe pulmonary infarction. The mechanism of fulminant hepatic failure not accompanied with low cardiac output is discussed.

Cardiomyopathy, Dilated↗

Right ventricular failure associated with left ventricular failure.

RV and LV failure frequently coexist. Experimental evidence suggests that RV failure results from a primary insult to the right ventricle and an increase in pulmonary vascular resistance. LV failure results in an elevation of the left atrial pressure and thereby a reduction in the transpulmonary hydrostatic gradient. Because RV function depends on the contraction of the left ventricle, this contribution is reduced during LV failure. Treatment should be aimed first at restoring LV function. If RV failure persists and is not due to a simple mechanical problem, treatment of RV failure should be commenced. If volume loading, inotropes, and pH adjustments do not result in adequate RV output, a mechanical assist device should be considered. RHBP is the most powerful device, and it is capable of restoring systemic perfusion even when there is no residual RV function. Clinical results with this device have been most encouraging--most patients demonstrate improved RV function and a decrease in pulmonary vascular resistance after several days of treatment, allowing them to be weaned from assist. However, this technique is very invasive and requires constant close attention. PABC is a simple but less powerful assist device. Experimental studies suggest that if RV function is not extremely depressed--cardiac output is greater than 50 percent of normal--PABC may be effective in restoring systemic perfusion to normal levels. Current results suggest that RHBP remains the gold standard for severe RV failure, but further clinical experience with PABC may more clearly define its role in the management of RV failure.

Heart Failure↗

Stage I, grade III adenocarcinoma of the endometrium treated with surgery and irradiation. Sites of failure and correlation of failure rate with irradiation technique.

Eighty-three patients treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH-BSO) and adjuvant irradiation for Stage I, grade III adenocarcinoma of the endometrium were reviewed. At 5 years, the overall survival was 71%, and the disease-free survival (excluding patients dying of intercurrent disease) was 79%. The failure rates for pelvis alone, pelvis plus distant, and distant alone were 4.8%, 4.8%, and 10.8%, respectively. The most common site of failure was the upper abdomen; 12% of all patients had a failure at this site, either alone or in conjunction with failure at another site. The 24% rate of failure in 50 patients receiving a preoperative implant and external irradiation was not significantly different from the 15% failure rate in 33 patients whose adjuvant irradiation consisted of a preoperative implant only. For the patients who had both an implant and external irradiation, the dose of external irradiation had no correlation with the rate of failure. In contrast, the number of milligram-hours delivered to the uterus by the preoperative implant had a strong inverse correlation with the rate of failure, both for patients receiving an implant only and for those receiving an implant plus external irradiation. The data suggest the following: (1) a high-intensity preoperative uterine implant may be an important adjunct to surgery; and (2) external pelvic irradiation in addition to the implant does not seem to be any more beneficial than an implant alone.

Adenocarcinoma↗

Confirmation of a heart failure epidemic: findings from the Resource Utilization Among Congestive Heart Failure (REACH) study.

OBJECTIVES: The purpose of this study was to create an automated surveillance tool for reporting the incidence, prevalence and processes of care for patients with heart failure. BACKGROUND: Previous epidemiologic studies suggest that the increasing prevalence of heart failure is a consequence of improved survival coupled with minimal changes in disease prevention. Developing new, efficient methods of assessing the incidence and prevalence of heart failure could allow continued surveillance of these rates during an era of rapidly changing treatments and health care delivery patterns. METHODS: Using administrative data sets, we created a definition of heart failure using diagnosis codes. After adjustment for patients leaving our health system or death, we derived the incidence, prevalence and mortality of the population with heart failure from 1989 to 1999. RESULTS: A total of 29,686 patients of all ages, 52.6% women and 47.4% men, met the definition of heart failure. Mean ages were 71.1 +/- 14.5 for women and 67.7 +/- 14.4 for men, p < 0.0001. Race proportions were 50.5% white, 44.6% African American and 4.9% other race. Incidence rates were higher in men and African Americans across all age groups. There was an annual increase in prevalence of 1/1,000 for women and 0.9/1,000 for men, p = 0.001 for both trends. CONCLUSIONS: Through the feasible and valid use of automated data, we have confirmed a chronic disease epidemic of heart failure manifested primarily by an increase in prevalence over the past decade. Our surveillance system mirrors the results of epidemiologic studies and may be a valid method for monitoring the impact of prevention and treatment programs.

Black or African American↗

Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure.

CONTEXT: Many older patients with symptoms of congestive heart failure have a preserved left ventricular ejection fraction (LVEF). However, the pathophysiology of this disorder, presumptively termed diastolic heart failure (DHF), is not well characterized and it is unknown whether it represents true heart failure. OBJECTIVE: To assess the 4 key pathophysiological domains that characterize classic heart failure by systematically performing measurements in older patients with presumed DHF and comparing these results with those from age-matched healthy volunteers and patients with classic systolic heart failure (SHF). DESIGN AND SETTING: Observational clinical investigation conducted in 1998 in a general community and teaching hospital in Winston-Salem, NC. PARTICIPANTS: A total of 147 subjects aged at least 60 years. Fifty-nine had isolated DHF defined as clinically presumed heart failure, LVEF of at least 50%, and no evidence of significant coronary, valvular, or pulmonary disease. Sixty had typical SHF (LVEF < or =35%). Twenty-eight were age-matched healthy volunteer controls. MAIN OUTCOME MEASURES: Left ventricular structure and function, exercise capacity, neuroendocrine function, and quality of life. RESULTS: By echocardiography, mean (SE) LVEF was 60% (2%) in patients with DHF vs 31% (2%) in those with SHF and 54% (2%) in controls. Mean (SE) LV mass-volume ratio was markedly increased in patients with DHF (2.12 [0.14] g/mL) vs those with SHF (1.22 [0.14] g/mL) (P<.001) and vs controls (1.49 [0.17] g/mL) (P =.002). Peak oxygen consumption by expired gas analysis during cycle ergometry was similar in the DHF and SHF groups (14.2 [0.5] and 13.1 [0.5] mL/kg per minute, respectively; P =.40) and in both was markedly reduced compared with healthy controls (19.9 [0.7] mL/kg per minute) (P =.001 for both). Ventilatory anaerobic threshold was similar in the DHF and SHF groups (9.1 [0.3] and 8.7 [0.3] mL/kg per minute, respectively; P<.001) and in both was reduced compared with healthy controls (11.5 [0.4] mL/kg per minute) (P<.001). Norepinephrine levels were similar in the DHF (306 [64] pg/mL) and SHF (287 [62] pg/mL) groups (P =.56) and in both were markedly increased vs healthy controls (169 [80] pg/mL) (P =.007 and.03, respectively). Brain natriuretic peptide was substantially increased in both the DHF (56 [30] pg/mL) and the SHF (154 [28] pg/mL) groups compared with healthy controls (3 [38] pg/mL) (P =.02 and.001, respectively). Quality-of-life decrement score as assessed by the Minnesota Living with Heart Failure Questionnaire was substantially increased from the benchmark score of 10 in both groups (SHF: 43.8 [3.9]; DHF: 24.8 [4.4]). CONCLUSION: Patients with isolated DHF have similar though not as severe pathophysiologic characteristics compared with patients with typical SHF, including severely reduced exercise capacity, neuroendocrine activation, and impaired quality of life.

Aged↗

Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT)

OBJECTIVES: This analysis sought to evaluate the clinical characteristics and outcome in heart failure with mild systolic dysfunction. BACKGROUND: Although heart failure with mild systolic dysfunction occurs commonly, this is an understudied area because clinical trials have usually excluded patients with ejection fraction >35%. METHODS: The 422 patients with left ventricular ejection fraction </=35% were compared with 172 with a left ventricular ejection fraction >35% in the Vasodilator in Heart Failure Trial (V-HeFT I), whereas in V-HeFT-II 554 patients with a left ventricular ejection fraction </=35% were compared with 218 patients with a left ventricular ejection fraction >35% for mortality and clinical care. For a left ventricular ejection fraction >35%, treatment with hydralazine/isosorbide dinitrate was compared with prazosin and placebo therapy in V-HeFT I, and hydralazine/isosorbide dinitrate was compared with enalapril in V-HeFT II for mortality, clinical course and change in physiologic variables: ejection fraction, plasma norepinephrine levels, ventricular tachycardia and echocardiographic variables. RESULTS: In both studies, patients with a left ventricular ejection fraction >35% differed principally in hypertensive history, higher functional capacity and radiographic and echocardiographic cardiac dimension from patients with a left ventricular ejection fraction </=35%, and plasma norepinephrine levels differed in V-HeFT II (p < 0.01). Patients with a left ventricular ejection fraction >35% had a lower cumulative mortality than those with a left ventricular ejection fraction </=35% (p < 0.0001) and less frequent hospital admissions for heart failure (p < 0.014, V-HeFT I; p < 0.005, V-HeFT II). Although cumulative mortality and morbidity did not differ between treatment groups in V-HeFT I, enalapril decreased overall mortality versus hydralazine/isosorbide dinitrate (p < 0.035) in V-HeFT II. For physiologic variables in V-HeFT II, enalapril decreased ventricular tachycardia at follow-up (p < 0.05). CONCLUSIONS: In V-HeFT, heart failure with mild systolic dysfunction was associated with different characteristics and a more favorable prognosis than heart failure with more severe systolic dysfunction. Enalapril decreased overall mortality and sudden death compared with hydralazine/isosorbide dinitrate. Prospective trials are needed to address therapy for heart failure with mild systolic dysfunction.

Aged↗

Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study.

AIMS: To determine the prevalence, incidence rate, lifetime risk and prognosis of heart failure. METHODS AND RESULTS: The Rotterdam Study is a prospective population-based cohort study in 7983 participants aged > or =55. Heart failure was defined according to criteria of the European Society of Cardiology. Prevalence was higher in men and increased with age from 0.9% in subjects aged 55-64 to 17.4% in those aged > or =85. Incidence rate of heart failure was 14.4/1000 person-years (95% CI 13.4-15.5) and was higher in men (17.6/1000 man-years, 95% CI 15.8-19.5) than in women (12.5/1000 woman-years, 95% CI 11.3-13.8). Incidence rate increased with age from 1.4/1000 person-years in those aged 55-59 to 47.4/1000 person-years in those aged > or =90. Lifetime risk was 33% for men and 29% for women at the age of 55. Survival after incident heart failure was 86% at 30 days, 63% at 1 year, 51% at 2 years and 35% at 5 years of follow-up. CONCLUSION: Prevalence and incidence rates of heart failure are high. In individuals aged 55, almost 1 in 3 will develop heart failure during their remaining lifespan. Heart failure continues to be a fatal disease, with only 35% surviving 5 years after the first diagnosis.

Age Distribution↗

Clinical studies on beta blockers and heart failure preceding the MERIT-HF Trial. Metoprolol CR/XL Randomized Intervention Trial in Heart Failure.

With greater understanding of the impact of neuroendocrine stimulation on the adverse outcomes of heart failure, especially lethal arrhythmias and sudden cardiac death, focus has returned to the potential benefits of beta-adrenergic blockade. In patients with myocardial infarction and left ventricular (LV) dysfunction, particularly those prone to life-threatening arrhythmias, beta-blocker therapy has been associated with a lower incidence of arrhythmias and improved survival. Even in the absence of angiotensin-converting enzyme (ACE) inhibition, beta blockade has improved cardiac function and LV contractility in nonischemic heart failure, leading to a decrease in LV end-diastolic pressure and improved clinical status. Both the Metoprolol in Dilated Cardiomyopathy (MDC) trial and the Cardiac Insufficiency Bisoprolol Study (CIBIS) found beta blockade to be associated with decreased mortality rates in patients with nonischemic heart failure. Of the 3 large randomized mortality trials now under way, the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) is specifically designed to investigate the effects of beta blockade on total mortality when used as an adjunct to ACE inhibition in patients with ischemic or nonischemic heart failure. Unresolved issues to be addressed include whether: (1) beta-blocker therapy in heart failure can improve survival and/or reduce the incidence of sudden cardiac death; (2) beta blockade is equally effective in ischemic and nonischemic heart failure; (3) any specific beta blocker may be better tolerated initially and cause fewer adverse effects; and (4) all beta blockers result in improved exercise tolerance and quality of life.

Adrenergic beta-Antagonists↗

Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study spell the end for non-selective endothelin antagonism in heart failure?

The last two decades have seen major advances in the treatment of chronic heart failure, primarily as a result of therapeutic manipulation of activated neurohormonal systems. Despite this progress, many patients still suffer significant morbidity and premature death. Antagonism of the biological effects of endothelin, a potent vasoconstrictor, represents a further potential target. To date, positive results from animal models of heart failure have not been translated into clinical practice, perhaps as a consequence of the high doses of drug used. The ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study evaluated the effects of low dose bosentan, a non-selective endothelin receptor antagonist, in patients with severe heart failure (left ventricular ejection fraction <35%, New York Heart Association class IIIb-IV). A total of 1,613 patients were randomized to receive either bosentan (125 mg twice a day) or placebo. The preliminary results were presented at the 51st Annual Scientific Session of the American College of Cardiology (17-20 March 2002, Atlanta, GA, USA). The primary endpoint of all-cause mortality or hospitalization for heart failure was reached in 321/808 patients on placebo and 312/805 receiving bosentan. Treatment with bosentan appeared to confer an early risk of worsening heart failure necessitating hospitalization, as a consequence of fluid retention. It has been suggested that further studies using even lower doses of bosentan or more aggressive concomitant diuretic therapy may avoid this adverse effect. The results from the ENABLE study have, however, thrown further doubt on the potential benefits of non-specific endothelin receptor blockade in heart failure.

Antihypertensive Agents↗

Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1-year period.

BACKGROUND: the incidence and prevalence of patients with advanced heart failure is increasing worldwide and the number of cardiac transplantations remains limited. AIMS: it was the aim of the study to describe our experience with the increasing number of available medical, interventional and cardiac surgery options, and to assess heart failure survival score predictability in an academic heart failure center within a 1-year follow-up. METHODS AND RESULTS: in all patients who were referred for cardiac transplant evaluation within a 12-month period between April 1998 and March 1999 at our Interdisciplinary Heart Failure and Transplant Program, our team assessed all medical interventions as well as interventional and surgical treatment options that were available, based on the clinical profile on initial presentation. In 92% of the 120 patients referred for cardiac transplantation evaluation, drug therapy could be optimized. A considerable number of patients could be subjected to an organ-preserving intervention or surgery, either PTCA (n=11), CABG (n=4), valve repair (n=7), multisite pacing (n=7), or partial ventricular resection (n=5). Only a small group of patients with the worst heart failure survival score were listed for heart transplantation (n=17) or received a ventricular assist device (n=3). CONCLUSIONS: within a contemporary cohort of advanced heart failure patients, only a small number of patients will undergo cardiac transplantation, which is predictable by the heart failure survival score. Most patients will undergo optimized medical therapy and a considerable number will be subjected to interventional or surgical treatment options.

Adrenergic beta-Antagonists↗

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

AIMS: Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. METHODS AND RESULTS: Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome. Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015). CONCLUSION: In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.

Death, Sudden, Cardiac↗

Randomized, controlled trial of integrated heart failure management: The Auckland Heart Failure Management Study.

AIMS: To determine the effect of an integrated heart failure management programme, involving patient and family, primary and secondary care, on quality of life and death or hospital readmissions in patients with chronic heart failure. METHODS AND RESULTS: This trial was a cluster randomized, controlled trial of integrated primary/secondary care compared with usual care for patients with heart failure. The intervention involved clinical review at a hospital-based heart failure clinic early after discharge, individual and group education sessions, a personal diary to record medication and body weight, information booklets and regular clinical follow-up alternating between the general practitioner and heart failure clinic. Follow-up was for 12 months. One hundred and ninety-seven patients admitted to Auckland Hospital with an episode of heart failure were enrolled in the study. There was no significant difference between the intervention and control groups for the combined end-point of death or hospital readmission. The physical dimension of quality of life showed a greater improvement in the intervention group from baseline to 12 months compared with the control group (-11.1 vs -5.8 respectively, 2 P=0.015). The main effect of the intervention was attributable to the prevention of multiple admissions (56 intervention group vs 95 control group, 2 P=0.015) and associated reduction in bed days. CONCLUSIONS: This integrated management programme for patients with chronic heart failure improved quality of life and reduced total hospital admissions and total bed days.

Adult↗

Organ system failures prediction model in intensive care patients with acute renal failure treated with dialysis.

OBJECTIVE: To evaluate the organ system failures hospital mortality predictions in critically ill patients with acute renal failure requiring dialysis. DESIGN: Prospective, cohort study. SETTING: Intensive care units in a tertiary care university hospital in Taiwan. PATIENTS: A total of 112 patients admitted to the intensive care units with acute renal failure who required dialysis from January 1999 through December 1999. INTERVENTIONS: Collection of information necessary to compute the number of failed organs. MEASUREMENTS AND RESULTS: Of the 112 patients studied, 75 were men and 37 were women. The mean age of survivors and non-survivors was 58.59 +/- 19.91 years and 58.76 +/- 19.62 years. The overall mortality rate was 67%. There were no significant differences between survivors and non-survivors in terms of age, gender, or indication for dialysis. The cause of death in the majority of patients was related to organ system failure during the 24 hours immediately preceding the initiation of acute hemodialysis, and carry mortality rates exceeding 83% with the coexistence of four or more failed organs. The area under the organ system failures prediction model receiver operating characteristic curve equaled 0.772 +/- 0.046. CONCLUSION: We conclude that mortality rate for acute renal failure in intensive care unit patients continues to be high. Organ system failures prediction model performed well and simple in its ability to identify patients who die in hospital. Mortality rate increases as number of failed organ increases.

Acute Kidney Injury↗

Laparoscopic fundoplication failures: patterns of failure and response to fundoplication revision.

OBJECTIVE: To determine rates and mechanisms of failure in 857 consecutive patients undergoing laparoscopic fundoplication for gastroesophageal reflux disease or paraesophageal hernia (1991-1998), and compare this population with 100 consecutive patients undergoing fundoplication revision (laparoscopic and open) at the authors' institution during the same period. SUMMARY BACKGROUND DATA: Gastroesophageal fundoplication performed through a laparotomy or thoracotomy has a failure rate of 9% to 30% and requires revision in most of the patients who have recurrent or new foregut symptoms. The frequency and patterns of failure of laparoscopic fundoplication have not been well studied. METHODS: All patients undergoing fundoplication revision were included in this study. Symptom severity was scored before and after surgery by patients on a 4-point scale. Evaluation of patients included esophagogastroscopy, barium swallow, esophageal motility, 24-hour ambulatory pH, and gastric emptying studies. Statistical analysis was performed with multiple chi-square analyses, Fisher exact test, and analysis of variance. RESULTS: Laparoscopic fundoplication was performed in 758 patients for gastroesophageal reflux disease and in 99 for paraesophageal hernia. Median follow-up was 2.5 years. Thirty-one patients (3.5%) have undergone revision for fundoplication failure. The mechanism of failure was transdiaphragmatic herniation of the fundoplication in 26 patients (84%). In 40 patients referred from other institutions, after laparoscopic fundoplication, only 10 (25%) had transdiaphragmatic migration (p < 0.01); a slipped or misplaced fundoplication occurred in 13 patients (32%), and a twisted fundoplication in 12 patients (30%). The failure mechanisms of open fundoplication (29 patients) followed patterns previously described. Fundoplication revision procedures were initiated laparoscopically in 65 patients, with six conversions (8%). The morbidity rate was 4% in laparoscopic procedures and 9% in open ones. There was one death, from aspiration and adult respiratory distress syndrome after open fundoplication. A year or more after revision operation, heartburn, chest pain, and dysphagia were rare or absent in 88%, 78%, and 91%, respectively, after laparoscopic revision, and were rare or absent in 91%, 83%, and 70%, respectively, after open revision, but 11 patients ultimately required additional operations for continued or recurrent symptoms, 3 after open revision (17%), and 8 after laparoscopic fundoplication (11%). CONCLUSIONS: Laparoscopic fundoplication failure is infrequent in experienced hands; the rate may be further reduced by extensive esophageal mobilization, secure diaphragmatic closure, esophageal lengthening (applied selectively), and avoidance of events leading to increased intraabdominal pressure. When revision is required, laparoscopic access may be used successfully by the laparoscopically experienced esophageal surgeon.

Fundoplication↗

Definitions of biochemical failure that best predict clinical failure in patients with prostate cancer treated with external beam radiation alone: a multi-institutional pooled analysis.

PURPOSE: Pooled data on 4,839 patients with T1-2 prostate cancer treated with external beam radiation therapy (RT) alone at 9 institutions have previously provided long-term biochemical failure (BF) and clinical outcomes using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition. In this report we determined the sensitivity and specificity of several BF definitions using distant failure (DF) alone or clinical failure (CF), defined as local failure (LF) and/or DF. MATERIALS AND METHODS: The pooled cohort was treated between 1986 and 1995 with external beam RT (60 Gy or greater) without pre-RT androgen suppression or planned post-RT adjuvant androgen suppression. Median followup was 6.3 years. The sensitivity and specificity of 102 definitions of BF relative to DF and LF were assessed. RESULTS: The BF definitions with higher sensitivity and specificity than the ASTRO definition for DF only and CF are reported. The sensitivity and specificity of the ASTRO definition to predict DF alone was 55% and 68%, respectively. Three definitions had higher sensitivity and specificity, namely prostate specific antigen (PSA) greater than current nadir (lowest PSA prior to current measurement) plus 3 ng/ml (sensitivity 76% and specificity 72%), dated at the call (failure date as the date when the criterion was met), PSA greater than absolute nadir plus 2 ng/ml (sensitivity 72% and specificity 70%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 69% and specificity 73%). The sensitivity and specificity of the ASTRO definition to predict CF was 60% and 72%, respectively. Three definitions had higher sensitivity and specificity, namely PSA greater than current nadir plus 3 ng/ml (sensitivity 66% and specificity 77%), dated at the call, PSA greater than absolute nadir plus 2 ng/ml (sensitivity 64% and specificity 74%), dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated (sensitivity 67% and specificity 78%). CONCLUSIONS: Using what is to our knowledge the largest data set of patients with prostate cancer treated with RT alone we correlated multiple definitions of BF with the strict clinical end points of DF alone and CF (DF or local failure). Defining BF as PSA greater than absolute nadir plus 2 ng/ml, dated at the call, PSA greater than current nadir plus 3 ng/ml, dated at the call, or 2 consecutive increases of at least 0.5 ng/ml, back dated, had higher sensitivity and specificity for DF alone or CF compared with the ASTRO definition. This information should contribute to the discussion regarding suggested modifications to the ASTRO definition of biochemical failure.

Adult↗