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At least 217 records · Page 12Linked to original sources

Pathology of late endothelial failure: late endothelial failure of penetrating keratoplasty: study with light and electron microscopy.

PURPOSE: Late endothelial failure of penetrating keratoplasty can be defined as gradual decompensation (increasing thickness with loss of clarity) of a previously clear graft without apparent cause. This study examined the possibility that a chronic subclinical rejection process may be occurring in grafts that fail from late endothelial failure. METHOD: Six patients fulfilling the diagnostic criteria for late endothelial failure who underwent repeated keratoplasty were studied. The clinical course and results of specular microscopy were reviewed. The failed corneal graft for each patient was examined by light and electron microscopy. RESULTS: Sequential specular microscopy demonstrated low initial postoperative endothelial cell density with continued decrease in density and increase in corneal thickness over the first 5 postoperative years. Electron microscopy revealed irregular-shaped cells of varying size with many abnormal features, lying on abnormal Descemet's membrane. Degenerating endothelial cells were commonly seen. There was no sign of acute or chronic inflammation. CONCLUSIONS: The pathologic findings are suggestive of an unstable and highly stressed endothelial cell population in late endothelial failure but are nonspecific. There was no evidence of acute or chronic rejection at the time of graft failure.

Adult↗

Bone marrow failure in children with acute liver failure.

BACKGROUND: Aplastic anemia is a rare but well-recognized complication of acute hepatitis and acute liver failure. The cause is unknown, and the condition is fatal without bone marrow recovery. Treatment includes immunosuppression regimens or bone marrow transplantation. The purpose of this study was to investigate the incidence, cause, treatment, and outcomes of this disorder in children. METHODS: Retrospective chart review of 75 patients with acute liver failure in a major pediatric liver center. RESULTS: Eight patients had evidence of bone marrow failure. Of those, six had aplastic anemia, and two had transient bone marrow suppression. There were five boys, median age 57 months (range, 36-132 months). Two had parvovirus B19, six had non-A, non-B, non-C hepatitis. Five underwent liver transplantation: auxiliary in one, orthotopic in four. The interval between initial symptoms and development of aplastic anemia and/or bone marrow suppression was 21 to 99 days (median, 39 days). Four patients with aplastic anemia received intravenous antithymocyte globulin (ATG) or antilymphocyte globulin (ALG). Median recovery period of granulopoiesis was 62 days (range, 27-115 days). Two made a full recovery, one had myelodysplasia, and one with unresponsive disease died of septic complications. Four did not receive ATG/ALG, two had aplastic anemia, and two had bone marrow suppression. Three underwent liver transplantation, and all four resumed granulopoiesis. One child who underwent liver transplantation died of sepsis with chronic rejection. Median recovery of granulopoiesis was 99 days (range, 20-153 days). CONCLUSIONS: Bone marrow failure occurs in 10.7% of children with acute liver failure. It sometimes occurs in association with non-A, non-B, non-C hepatitis and parvovirus B19 infection. Treatment with ATG/ALG is successful and is well tolerated in most cases.

Adolescent↗

Pathophysiology of heart failure update: the role of neurohumoral activation in the progression of heart failure.

Understanding the pathophysiologic mechanisms responsible for producing heart failure is necessary before effective treatments can be developed that increase survival and improve quality of life. Recent advances in the treatment of heart failure can be traced directly to improved appreciation of the role of neurohumoral activation in the pathophysiology of heart failure. Initially adaptive, neurohumoral activation ultimately results in a series of overadjustments that actively participate in the progression of heart failure. In this article, the role of neurohumoral activation, ventricular remodeling, and various peripheral vascular abnormalities in the pathophysiology of heart failure are explored.

Disease Progression↗

Resistance profiles and adherence at primary virological failure in three different highly active antiretroviral therapy regimens: analysis of failure rates in a randomized study.

OBJECTIVES: To investigate the interplay between resistance and adherence in the virological failure of three fundamentally different highly active antiretroviral therapy (HAART) regimens. METHODS: We retrospectively identified 56 verified primary virological failures (viral load >400 HIV-1 RNA copies/mL) among 293 patients randomized to two nucleoside reverse transcriptase inhibitors (NRTIs)+ritonavir+saquinavir (RS-arm) (n=115), two NRTIs+nevirapine+nelfinavir (NN-arm) (n=118), or abacavir+stavudine+didanosine (ASD-arm) (n=60) followed up for a median of 90 weeks. Data on adherence were collected from patient files, and genotyping was performed on plasma samples collected at time of failure. RESULTS: Treatment interruption or poor adherence was mainly caused by side effects and accounted for 74% of failures, and was associated with absence of resistance mutations. In the 30 failing patients not switched from randomized treatment, we found resistance in two of 12 patients in the RS-arm (M184 V only), four of six patients in the NN-arm [all four had non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations], and seven of 12 patients in the ASD-arm (NRTI mutations only). Two adherent patients on randomized treatment failed in the RS-arm, none in the NN-arm, and six in the ASD-arm. CONCLUSIONS: Primary virological failure was caused mainly by treatment interruption. No primary protease inhibitor (PI) mutations were found in patients failing on boosted saquinavir, whereas resistance to NNRTIs and NRTIs was prevalent in several patients failing on regimens based on these medications.

Adult↗

Congestive heart failure: potential role of arginine vasopressin antagonists in the therapy of heart failure.

Neurohormonal imbalances clearly contribute to the pathophysiology of chronic congestive heart failure. Agents that interfere with the generation or effects of angiotensin II and aldosterone, or which block the effects of excess sympathetic drive, all favorably affect mortality. Arginine vasopressin, through its V(1A) and V(2) receptor-mediated effects, could theoretically also contribute to progression of left ventricular dysfunction and heart failure by aggravating systolic and diastolic wall stress, and by directly stimulating myocardial hypertrophy. Arginine vasopressin levels are increased in congestive heart failure patients; acutely, both V(1A) and V(2) antagonists produce beneficial hemodynamic responses in both clinical and experimental congestive heart failure. Experimental studies also indicate beneficial effects of V(1A) and V(2) antagonists (alone or in combination) on hemodynamics and possibly ventricular remodeling after myocardial injury. Currently, there are no long-term studies of any type of arginine vasopressin antagonist in human heart failure, but both the theoretical rationale and preclinical data would appear to justify such efforts.

Animals↗

Early complete failures of fixed implant-supported prostheses in the edentulous maxilla: a 3-year analysis of 17 consecutive cluster failure patients.

BACKGROUND: Clusters of implant failures in the edentulous maxilla seem to occur in some patients. To create groups for analysis with higher numbers of these patients implies large original groups for inclusion. PURPOSE: The aim of this study was to retrospectively describe and compare a group of "cluster failure patients" with randomly selected patients treated in the edentulous maxilla. MATERIALS AND METHODS: From a group of 1,267 consecutively treated patients in one clinic, all patients presenting failing fixed implant-supported prostheses within the first 3 years of follow-up were included. All patients were treated with turned titanium implants using two-stage surgery. A control group of equal number of patients were created for comparison. Data on patients were retrospectively retrieved from their records, and compared. RESULTS: Seventeen patients (1.3%) met the inclusion criteria in the entire group. The bone resorption index revealed less bone quantity in the study group (p < .05) during implant placement, but there was no difference regarding primary implant stability at first-stage surgery. The distribution of short and long implants showed relatively higher number of short implants in the study group (p < .05), and more patients had a presurgical discussion on the risk of implant failure prior to treatment in this group (p < .05). Only 5 out of 102 implants (4.9%) were lost before prosthesis placement as compared to 38 and 25 lost implants during the following two years in the study group. Smoking habits and signs of bone loss related to periodontitis in the lower dentition were more frequent in the study group, but did not reach a significant level (p > .05). CONCLUSION: The results indicate that bone quantity, reflected in fixture length, has a significant impact on increased implant failure risk. Other factors of interest as predictors for implant failures could be smoking habits and also possibly signs of periodontitis in the opposing dentition.

Adult↗

Reversible renal failure after combined treatment with enalapril and frusemide in a patient with congestive heart failure.

A patient with congestive heart failure and moderate renal insufficiency developed severe reversible non-oliguric renal failure while on frusemide and enalapril. Renal failure developed when enalapril was given in the presence of pronounced sodium depletion. When positive sodium balance was restored the plasma creatinine concentration began to fall while angiotensin converting enzyme inhibition remained effective and blood pressure was stable. These observations suggest that the degree of sodium depletion plays an important role in the tendency for angiotensin converting enzyme inhibitors to induce renal failure in patients with congestive heart failure and moderate renal insufficiency. Restoration of a positive sodium balance promotes the recovery of renal function after the combined administration of angiotensin converting enzyme inhibitors and diuretics.

Acute Kidney Injury↗

Effect of discharge instructions on readmission of hospitalised patients with heart failure: do all of the Joint Commission on Accreditation of Healthcare Organizations heart failure core measures reflect better care?

BACKGROUND: Most nationally standardised quality measures use widely accepted evidence-based processes as their foundation, but the discharge instruction component of the United States standards of Joint Commission on Accreditation of Healthcare Organizations heart failure core measure appears to be based on expert opinion alone. OBJECTIVE: To determine whether documentation of compliance with any or all of the six required discharge instructions is correlated with readmissions to hospital or mortality. RESEARCH DESIGN: A retrospective study at a single tertiary care hospital was conducted on randomly sampled patients hospitalised for heart failure from July 2002 to September 2003. PARTICIPANTS: Applying the Joint Commission on Accreditation of Healthcare Organizations criteria, 782 of 1121 patients were found eligible to receive discharge instructions. Eligibility was determined by age, principal diagnosis codes and discharge status codes. MEASURES: The primary outcome measures are time to death and time to readmission for heart failure or readmission for any cause and time to death. RESULTS: In all, 68% of patients received all instructions, whereas 6% received no instructions. Patients who received all instructions were significantly less likely to be readmitted for any cause (p = 0.003) and for heart failure (p = 0.035) than those who missed at least one type of instruction. Documentation of discharge instructions is correlated with reduced readmission rates. However, there was no association between documentation of discharge instructions and mortality (p = 0.521). CONCLUSIONS: Including discharge instructions among other evidence-based heart failure core measures appears justified.

Academic Medical Centers↗

Sustained reduction of aldosterone in response to the angiotensin receptor blocker valsartan in patients with chronic heart failure: results from the Valsartan Heart Failure Trial.

BACKGROUND: Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure. METHODS AND RESULTS: Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150+/-160 pg/mL, mean+/-SD; n=2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137+/-124 pg/mL, mean+/-SD; n=2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8+/-3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8+/-3.0 pg/mL (SEM) (-17.4%) in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor beta-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs. CONCLUSIONS: Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.

Aldosterone↗

Clinical correlates of elevated plasma natriuretic peptides and Big endothelin-1 in a population of ambulatory patients with heart failure. A substudy of the Italian Network on Congestive Heart Failure (IN-CHF) registry. IN-CHF Investigators.

BACKGROUND: Activation of neuroendocrine factors plays a major role in the pathophysiology and progression of heart failure. The aim of the present study was 1) to assess the clinical correlates of elevated plasma natriuretic peptides [atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)] and Big endothelin-1 in a population of 180 ambulatory patients from the Italian registry of heart failure (Italian Network on Congestive Heart Failure, IN-CHF) in 22 clinical centers, 2) to assess the within-patient variability of plasma BNP concentration, and 3) to evaluate the analytical agreement for BNP determination between a core laboratory and local sites. METHODS: ANP and BNP were measured with specific immunoradiometric methods, Big endothelin-1 with an enzyme immunoassay. RESULTS: Elevated BNP was associated with severe mitral valve regurgitation (odds ratio 8.546, 95% confidence interval 1.879-38.510, p = 0.0052); high circulating concentrations of ANP and BNP were found in older patients, and in patients with higher NYHA functional class or reduced left ventricular ejection fraction. Elevated plasma concentration of Big endothelin-1 was a strong and independent predictor of atrial fibrillation (odds ratio 4.001, 95% confidence interval 1.531-10.454, p = 0.0047). Plasma concentration of BNP was reasonably stable at 3-month interval in patients with mild-to-moderate heart failure (mean between-visit difference -1.5+/-45 pg/ml, n = 96). There was a satisfactory analytical agreement between the central laboratory and sites, over a broad range of concentrations (2-1133 pg/ml, n = 283) with a slope for the best line fitted by linear regression of 1.09 (r2 = 0.96). CONCLUSIONS: BNP assay may become an appropriate tool for routine clinical practice in patients with congestive heart failure.

Aged↗

The Acute Decompensated Heart Failure National Registry (ADHERE): opportunities to improve care of patients hospitalized with acute decompensated heart failure.

Heart failure is a leading cause of hospitalization for adults in the United States. Patients hospitalized with acute decompensated heart failure (ADHF) face a substantial risk of in-hospital mortality and rehospitalization. Despite the large number of patients hospitalized and this substantial risk, data on these patients have been limited and there has been little effort to improve the quality of care for patients hospitalized with ADHF. The Acute Decompensated HEart Failure National REgistry (ADHERE(tm)) was designed to bridge this gap in knowledge and care by prospectively studying characteristics, management, and outcomes in a broad sample of patients hospitalized with ADHF. Participating community and university hospitals identified patients with a primary or secondary discharge diagnosis of heart failure and collected medical history, management, treatments, and health outcomes via secure web browser technology. As of July 2003, 65,180 patients have been enrolled from 263 hospitals. Initial data have provided important insights into the clinical characteristics, patterns of care, and outcomes of these patients. ADHERE documents significant delays in diagnosis and initiation of ADHF therapies as well as substantial under-use of evidence-based, guideline-recommended chronic heart failure therapies at hospital discharge. As such, there are substantial opportunities to improve the quality of care for ADHF patients in the nation's hospitals. The ADHERE Hospital Toolkit has been designed to provide hospital teams with effective proactive instruments to improve the quality of care for patients with ADHF. If successfully implemented, the improvements in short- and long-term clinical outcomes for ADHF patients are expected to be substantial.

Heart Failure↗

Pre-discharge initiation of beta-blocker therapy in elderly patients hospitalized for acute decompensation of chronic heart failure: an effective strategy for the implementation of beta-blockade in heart failure.

BACKGROUND: Current guidelines recommend beta-blockers in patients with heart failure and left ventricular systolic dysfunction. These agents, however, are largely underused in elderly patients because of the perception of up-titration complexity and the fear of side effects. METHODS: We prospectively assessed the feasibility, safety, tolerability, and 1-year outcome of the in-hospital initiation of carvedilol in elderly patients admitted for worsening heart failure. RESULTS: Among 164 eligible subjects (age > 70 years, left ventricular ejection fraction < 40% and no sign of congestion), 120 (73%) received carvedilol, on average 4.5 days after admission. The drug was permanently withdrawn in 10 out of 116 survivors (9%) at 60 days: 5 did not tolerate the starting dose because of worsening heart failure (n = 1), bradycardia (n = 1), and bronchospasm (n = 3). Two discontinued carvedilol during the in-hospital dose titration phase because of increasing premature ventricular beats and transient second degree atrioventricular block. The remaining 3 dropouts (fatigue in 2 and symptomatic bradycardia in 1 case) occurred after discharge. During the period between 60 days and 12 months, carvedilol was discontinued in 2 patients because of a depressive syndrome and symptomatic bradycardia. In no case these adverse events lead to death or were life-threatening, required hospitalization or resulted in any disability. The 1-year tolerability was 89%, the mortality was 17.5%, the frequency of hospitalization for worsening heart failure was 21%. CONCLUSIONS: Thus, our results show that the in-hospital initiation of carvedilol is feasible and well-tolerated in elderly patients with recent worsening heart failure, and allows rapid identification of the most intolerant patients. The proportion of subjects taking carvedilol after 1 year from discharge was very high. This unconventional approach could significantly modify the use of beta-blockers in clinical practice.

Adrenergic beta-Antagonists↗

[Kidney failure during acute pancreatitis. A unique aspect of multiple organ failure].

Eighty-two patients with acute pancreatis observed in the last seven years were included in prospective trial of monitoring protocol comprising: multiple organ failure and non invasive imaging of pancreatic lesion. One organ failure noted in the 60.9%, M.O.F. with three organ failure represented in the 21.9%. Renal failure was confirmed in 18.9%, trough nine clinical and biological index, become with shock in 73% and with extensive necrosis in 53%. ARF appeared with functional picture and normal diuresis in 73.3% and with organic failure in 26.7%. Index of specific mortality was 33.3%, while the comprehensive index of mortality in the study group was 12.9%, with a significant incidence in the half of deaths.

Acute Disease↗

Early recovery from heart failure: insights into the pathogenesis of experimental chronic pacing-induced heart failure.

Chronic rapid ventricular pacing (250 beats/min) induces severe heart failure in a canine model. To assess the potential for recovery after cessation of pacing, simultaneous hemodynamic and two-dimensional echocardiographic studies were conducted in nine conscious dogs paced to severe heart failure (4.3 +/- 1.7 weeks). Heart failure was characterized by elevated left and right ventricular filling pressures from 9 +/- 3 and 7 +/- 2 mm Hg to 25 +/- 6 and 15 +/- 3 mm Hg (both p less than 0.01), respectively. Left ventricular cross-sectional area (an estimate of preload) and systolic wall stress (an estimate of afterload) increased from 12 +/- 2 cm2 and 119 +/- 23 10(3) dynes/cm2 to 17 +/- 3 cm2 and 210 +/- 46 10(3) dynes/cm2 (both p less than 0.01), respectively. Left ventricular ejection fraction decreased from 54% +/- 7% to 13% +/- 5% (p less than 0.01). When pacing was discontinued to allow resumption of sinus rhythm, left and right ventricular filling pressures declined rapidly at 48 hours after resumption of sinus rhythm, by 36% and 53%, respectively. Ejection fraction doubled, although left ventricular cross-sectional area and wall stress remained elevated at 48 hours. The recovery of systolic function in the absence of major changes in loading conditions suggests that pacing-induced heart failure is mediated by a decrease in left ventricular contractility. Moreover, the persistent dilation of the left ventricle after cessation of pacing suggests that structural remodeling of the left ventricle occurs during the development of pacing-induced heart failure.

Animals↗

Studies on heart failure in old age (Part II). Hemodynamic effects of propranolol and isoproterenol in elderly patients with heart failure.

Hemodynamic responses to propranolol and isoproterenol were examined in elderly patients with heart failure. The results obtained are as follows: 1. Patients with mild heart failure showed greater reduction than control group in heart rate and cardiac output after intravenous propranolol. These enhanced hemodynamic responses to propranolol would be the evidence of increased adrenergic activity even in mild heart failure. 2. Intravenous propranolol in the small dosage of 0.03 mg/kg showed only a negligible hemodynamic deterioration even in patients with heart failure. 3. Hemodynamic responses to beta-adrenergic stimulator, isoproterenol, were depressed in severe heart failure.

Aged↗

Effects of carvedilol, a vasodilator-beta-blocker, in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.

BACKGROUND: beta-Blocker therapy has been shown to increase ejection fraction in patients with heart failure of idiopathic etiology. However, in patients with heart failure of ischemic etiology, the effects of this treatment on left ventricular function remain uncertain, as do the effects on exercise performance and symptoms. METHODS AND RESULTS: This study investigated the effects of carvedilol, a beta-blocker with alpha 1-blocking properties, on left ventricular size and function, maximal and submaximal exercise performance, and symptoms in 415 patients with stable heart failure of ischemic etiology (ejection fraction < 45%). After a 2- to 3-week run-in phase on open-label low-dose carvedilol, patients were randomized to continued treatment with carvedilol (up to 25 mg BID) or to matching placebo. After 6 months, left ventricular ejection fraction measured by radionuclide ventriculography had increased by 5.2% (2P < .0001) in the carvedilol group compared with the placebo group, and left ventricular end-systolic and end-diastolic dimensions measured by two-dimensionally guided M-mode echocardiography had decreased by 2.6 mm (2P = .0005) and 1.3 mm (2P = .05), respectively. There were no significant changes in either treadmill exercise duration or 6-minute walk distance between carvedilol and placebo groups (both 2P > .1); in the carvedilol group, exercise performance was therefore maintained with a 23% lower rate-pressure product. Symptoms assessed by the New York Heart Association (NYHA) scale and the Specific Activity Scale (SAS) were unchanged in two thirds of patients in both groups, but there was a small excess of patients whose symptoms worsened and a deficit of patients whose symptoms improved among those assigned carvedilol (NYHA, 2P = .05; SAS, 2P = .02). CONCLUSIONS: In patients with heart failure of ischemic etiology, 6-month treatment with carvedilol improved left ventricular function and maintained exercise performance at a lower rate-pressure product, but symptoms assessed by functional class were slightly worsened. A larger-scale trial is now required to determine whether this treatment will reduce serious morbidity and mortality from heart failure.

Adrenergic beta-Antagonists↗

[Acute liver failure secondary to cardiogenic shock in patients with congestive heart failure].

Fulminant hepatic failure is a complication of severe cardiocirculatory failure, with high morbidity and mortality, and is frequently misdiagnosed as fulminant viral hepatitis. We report three cases of patients with chronic severe heart failure who developed cardiogenic shock complicated by elevation of aminotransferase levels above 1,000 soon after the most severe episode of hypotension. All the three patients presented regression of hepatic enzymes 72h after admission. Two patients developed hepatic encephalopathy and renal failure. One underwent the implantation of an artificial left ventricle, followed by orthotopic heart transplantation. One died of systemic multiple organ failure, after he had showed improvement on his hepatic profile, and one was sent to the ward, after 15 days with marked improvement on his clinical status and no signs of hepatic disease.

Adult↗

Pathophysiology and therapy of heart failure, new insights and developments. Part II. Cardiac and peripheral alterations during progressive heart failure.

The initial phase of heart failure is characterized by peripheral mechanisms such as sympathetic stimulation and neuroendocrine activation, which attempt to compensate for the decline in cardiac pump function and tissue underperfusion. However, the resulting vasoconstriction and sodium and water retention lead to a vicious circle wherein the subsequent increase in afterload and in circulating volume eventually leads to a further decline in cardiac output, blood pressure and tissue perfusion on the one hand, and to systemic and pulmonary congestion on the other. Intrinsic cardiac alterations during progressive failure preclude efficient cardiac compensation. These alterations include downregulation of the beta-receptor, upregulation of its inhibitor subunit (Gi), changes in adenylate cyclase and phosphodiesterase activity, depletion of catecholamine stores, overexpression of abnormal contractile proteins and inherent changes in ATP-ase activity, a derangement of calcium cycling by the sarcoplasmic reticulum, and abnormalities in myocardial energy production and transfer. These multiple changes underline the importance of the heart per se in heart failure. However, it should be realized that the heart failure syndrome depends to a large extent on various intrinsic alterations in peripheral tissue function. Renal impairment, baroreceptor dysfunction, neuroendocrine activation, abnormalities in skeletal muscle metabolism and in vascular control, and electrolyte disturbances all add to the overall clinical picture. Both cardiac and peripheral alterations in heart failure will markedly affect future diagnostic and therapeutic approaches to this syndrome.

Adaptation, Physiological↗