Cases Of Congestive Heart Failure Research Articles

Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline‐related congestive heart failure after childhood cancer

Exposure to anthracyclines as part of cancer therapy has been associated with the development of congestive heart failure (CHF). The potential role of genetic risk factors in anthracycline-related CHF remains to be defined. Thus, in this study, the authors examined whether common polymorphisms in candidate genes involved in the pharmacodynamics of anthracyclines (in particular, the nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase 1 gene NQO1 and the carbonyl reductase 3 gene CBR3) had an impact on the risk of anthracycline-related CHF. A nested case-control study was conducted within a cohort of 1979 patients enrolled in the Childhood Cancer Survivor Study who received treatment with anthracyclines and had available DNA. Thirty patients with CHF (cases) and 115 matched controls were genotyped for polymorphisms in NQO1 (NQO1*2) and CBR3 (the CBR3 valine [V] to methionine [M] substitution at position 244 [V244M]). Enzyme activity assays with recombinant CBR3 isoforms (CBR3 V244 and CBR3 M244) and the anthracycline substrate doxorubicin were used to investigate the functional impact of the CBR3 V244M polymorphism. Multivariate analyses adjusted for sex and primary disease recurrence were used to test for associations between the candidate genetic polymorphisms (NQO1*2 and CBR3 V244M) and the risk of CHF. Analyses indicated no association between the NQO1*2 polymorphism and the risk of anthracycline-related CHF (odds ratio [OR], 1.04; P=.97). There was a trend toward an association between the CBR3 V244M polymorphism and the risk of CHF (OR, 8.16; P=.056 for G/G vs A/A; OR, 5.44; P=.092 for G/A vs A/A). In line, recombinant CBR3 V244 (G allele) synthesized 2.6-fold more cardiotoxic doxorubicinol per unit of time than CBR3 M244 (A allele; CBR3 V244 [8.26+/-3.57 nmol/hour.mg] vs CBR3 M244 [3.22+/-0.67 nmol/hour.mg]; P=.01). The functional CBR3 V244M polymorphism may have an impact on the risk of anthracycline-related CHF among childhood cancer survivors by modulating the intracardiac formation of cardiotoxic anthracycline alcohol metabolites. Larger confirmatory case-control studies are warranted.

High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly

Low levels of insulinlike growth factor 1 (IGF-I) may influence the development of age-related cardiovascular diseases including congestive heart failure (CHF). Insulinlike growth factor binding protein 1 (IGFBP-1), which increases during catabolic states and inhibits anabolic IGF-I effects, is increased in patients with CHF and has been associated prospectively with increased mortality among older adults and survivors of myocardial infarction. We investigated the association between fasting plasma levels of IGF-I, IGFBP-1, IGFBP-3, and insulin and risk of incident CHF in the prospective Cardiovascular Health Study. From among 5,888 adults 65 years old and older in the Cardiovascular Health Study, we studied 566 incident CHF cases and 1,072 comparison subjects after exclusion of underweight individuals (body mass index <18.5 kg/m(2)) and insulin users. Hazard ratios (HRs) with 95% CIs for CHF were estimated after adjustment for age, race, sex, hypertension, systolic blood pressure, lipid levels, left ventricular hypertrophy, coronary disease, C-reactive protein, health status, diabetes, and body mass index. High baseline IGFBP-1 level was a significant predictor of CHF, independent of established CHF risk factors and inflammation markers. The HR per SD of IGFBP-1 was 1.22 (95% CI 1.07-1.39, P < .01). Relative to the lowest IGFBP-1 tertile, the HR was 1.29 (95% CI 0.96-1.74, P = .09) for the second IGFBP-1 tertile and 1.47 (95% CI 1.06-2.04; P = .02) for the highest IGFBP-1 tertile (tertile cut points 19.5 and 35.8 ng/mL). Total IGF-I, IGFBP-3, or insulin levels had no association with CHF after adjustment for CHF risk factors. High circulating IGFBP-1 level may be a CHF risk factor among older adults.

Abstract 2710: Emergency Room Utilization of Continuous Intravenous Furosemide Together With the American Heart Association Get With the Guideline Heart Failure Care (GWTG-HF) Decreases Length of Stay for Hospitalized Heart Failure Patients at St. Joseph’s Regional Medical Center (SJRMC)

The main goals of therapy for hospitalized congestive heart failure (CHF) patients are to achieve euvolemia and to administer optimal standards of care. No study to date has examined ways to implement use of continuous intravenous furosemide (IVF) in the Emergency Room (ER) and ensure that each CHF patient consistently receives optimal standards of care throughout their hospitalization. Therefore, we hypothesized that a multi-disciplinary team approach with coordination of care from ER arrival to discharge (DC) with use of the AHA GWTG-HF Program will decrease length of stay (LOS) and provide optimal care for CHF patients as compared to usual care. METHODS: GWTG-HF was operational in 2006 with a multi-disciplinary team consisting of a Physician Champion, Advanced Practice Nurses (APNs), Case Managers and RNs. In June of 2006 the IVF program was implemented in coordination with the ER, Cardiology and Medicine Departments. ER physicians were prompted by an electronic medical record provider order entry (EMR-POE) CHF order set. GWTG-HF APNs followed these patients throughout their hospitalization. We compared the average LOS of CHF patients who received usual care in 2005 (Group I) to CHF patients who received IVF and GWTG-HF care from 6/06 to 4/07 (Group II). RESULTS: CHF cases in Group I equaled 773 as compared to 212 cases in Group II. Average LOS in I was 6.7 days as compared to 5.5 days in II (p = 0.001). Overall compliance with GWTG-HF Core Measures in 2006 was 98%. CONCLUSIONS: 1. Implementation of IVF in the ER with an EMR-POE order set helps ensure utilization of IVF in the ER at time of admission for CHF patients; 2. A multi-disciplinary team approach with use of IVF along with GWTG-HF is associated with a significant decrease in the LOS as compared to usual care; 3. A multi-disciplinary team approach to care for the CHF patient is superior to usual care with regards to LOS; and 4. GWTG-HF is associated with a high compliance with standards of hospitalized CHF care.

Late cardiotoxicity after treatment for Hodgkin lymphoma

AbstractWe assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks of myocardial infarction (MI) and congestive heart failure (CHF) were strongly increased compared with the general population (standardized incidence ratios [SIRs] = 3.6 and 4.9, respectively), resulting in 35.7 excess cases of MI and 25.6 excess cases of CHF per 10 000 patients/year. SIRs of all CVDs combined remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders from mediastinal RT (hazard ratios [HRs] were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared with the general population, even after prolonged follow-up, leading to increasing absolute excess risks over time. Anthracyclines further increase the elevated risks of CHF and valvular disorders from mediastinal radiotherapy.

Prognostic Value of Serial B-Type Natriuretic Peptide Testing During Follow-up of Patients With Unstable Coronary Artery Disease

Elevated concentrations of B-type natriuretic peptide (BNP) at presentation in patients with acute coronary syndrome (ACS) are associated with long-term mortality. Few data exist regarding serial assessment of BNP levels during follow-up. To determine whether concentrations of BNP at study entry (prior to hospital discharge for ACS) and at outpatient follow-up at 4 months and 12 months are associated with subsequent clinical outcomes. Prospective observational substudy of 4497 patients with non-ST-elevation or ST-elevation ACS who were enrolled in phase Z of the A to Z trial, which was conducted in 41 countries at 322 acute care hospitals between 1999 and 2003. Death from any cause or new onset of congestive heart failure (CHF) through 2 years. Levels of BNP were available in 4266 patients at study entry (prior to hospital discharge), 3618 patients at 4 months, and 2966 patients at 12 months. During follow-up there were 230 deaths and 163 incident cases of CHF. Adjusting for age, sex, index event, renal function, hypertension, prior heart failure, and diabetes, elevated levels of BNP (>80 pg/mL) were associated with subsequent death or new CHF when measured at study entry (111 [21%] vs 246 [7%]; adjusted hazard ratio [HR], 2.5; 95% confidence interval [CI], 2.0-3.3), at 4 months (34 [19%] vs 125 [4%]; adjusted HR, 3.9; 95% CI, 2.6-6.0), and at 12 months (19 [11%] vs 37 [1%]; adjusted HR, 4.7; 95% CI, 2.5-8.9). Patients with newly elevated levels of BNP at 4 months were at increased risk of death or new CHF (10 [15%] vs 105 [3%]); HR, 4.5; 95% CI, 2.3-8.6). Patients with elevated levels of BNP at study entry and with BNP levels lower than 80 pg/mL at 4 months tended to have only modestly increased risk (HR, 1.7; 95% CI, 1.0-2.9) compared with patients with BNP levels lower than 80 pg/mL at both visits. Serial determinations of BNP levels during outpatient follow-up after ACS predict the risk of death or new CHF. Changes in BNP levels over time are associated with long-term clinical outcomes and may provide a basis for enhanced clinical decision making in patients after onset of ACS.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00251576.

Multicenter phase II study of trastuzumab in combination with epirubicin and docetaxel as first-line treatment for HER2-overexpressing metastatic breast cancer

The primary objective of study is to evaluate cardiac safety of trastuzumab in combination with epirubicin and docetaxel. HER2-overexpressing metastatic breast cancer patients were enrolled in a two-stage, multicenter phase II trial with weekly trastuzumab (4 and then 2 mg/kg) with epirubicin and docetaxel (either 75 mg/m(2)) on day 1 every 3 weeks. After eight courses of chemotherapy, trastuzumab was continued as a single agent. To assess cardiotoxicity, patients were evaluated for left ventricular ejection fraction (LVEF) at baseline, every two cycles during chemotherapy and trastuzumab, and every 3 months during trastuzumab alone. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure (CHF) and/or an absolute decrease in LVEF of >or=20 units or a decline to <or=45%. In the first stage of the study, three episodes of cardiotoxicity were observed (two asymptomatic declines of LVEF and one CHF) in 29 patients, and recruitment continued. During follow-up of patients who continued trastuzumab after chemotherapy, seven further cardiologic events occurred (three asymptomatic decline of LVEF and four CHF). Therefore, recruitment was interrupted after the 45th patient. The majority of cardiac events occurred late during trastuzumab alone, half were asymptomatic and all cases of CHF were resolved using cardiac therapy. Complete and partial responses were 20 and 47%, respectively, and the median time to progression was 15.7 months (95% CI, 11.6-19.0 months). In light of the cardiotoxicity experienced during this study, we currently recommend that this combination be used only in controlled clinical trials under vigilant cardiac monitoring.

Selling Safety—Lessons From Muraglitazar

PEROXISOME PROLIFERATOR–ACTIVATED RECEPTORS (PPARs) are nuclear cell transcription factors with isoform agonists that exhibit clinical benefit. The PPARagonists increase insulin sensitivity, explaining the antidiabetic action of the thiazolidinediones rosiglitazone and pioglitazone. PPARagonists, including the fibrates, increase fatty acid oxidation, leading to a decrease in plasma triglycerides and a modest increase in highdensity lipoprotein cholesterol. Muraglitazar is the first dualPPAR agonist to be considered for general marketing both as monotherapy and combined therapy by the US Food and Drug Administration (FDA). Given the emerging epidemic of type 2 diabetes, it is easy to understand the enthusiasm for this new class of drugs. Tight glycemic control reduces diabetic microvascular complications, although both old and new studies have failed to convincingly show decreased macrovascular complications of stroke, cardiac disease, and peripheral vascular disease. On September 9, 2005, an FDA advisory committee reviewed muraglitazar’s efficacy and safety data and recommended approval and on October 18, 2005, it was reported that the FDA issued an “approvable letter” for this drug. However, in this issue of JAMA, Nissen and colleagues have reanalyzed these data and challenge the advisory board’s recommendation. Courtesy of a transparent FDA approval process that provides online submission information, Nissen et al were able to contrast the 2374 patients taking muraglitizar at 5 mg or less vs the combined 1351 patients exposed to either placebo or pioglitazone. Their analysis demonstrated a 2.23 (95% confidence interval, [CI], 1.07-4.06) increased risk in the composite outcome of death, myocardial infarction, or stroke and a 7.4 (95% CI, 0.97-56.8) relative risk of congestive heart failure (CHF). The authors rightly mention that a potential limitation of their analysis was their use of simple proportion tests and not the more informative survival time analysis. Nevertheless they feel confident in recommending that approval of muraglitazar be delayed pending a dedicated cardiovascular trial. In contrast, the sponsor’s presentation to the advisory committee concluded that no significant excess risk of deaths or cardiovascular events occurred with muraglitazar treatment. While there may be disagreement over which analysis to believe, a consensus should exist that these differences indicate less than robust data. Is it possible, at least partially, to reconcile these radically different interpretations of the same data? Unlike the report by Nissen et al, the sponsor presented the data as 3, not 2, distinct groups and calculated event rates per patient year of exposure (TABLE), thereby logically weighting by duration of exposure. However the 495 patients, representing 990 patient-years of exposure, with subtherapeutic doses of 2.5 mg or less were maintained in the denominator. Since FDA approval was not sought for these small doses of muraglitazar, the inclusion of these data in the safety analysis for the proposed marketed doses may be questioned. Because there were no associated cardiovascular events among these patients, the effect is a dilution of the clinically pertinent risk estimate. The recalculated event rate for the proposed marketed doses of muraglitazar is 97 events per 2447 patient-years, an excess of 20% compared with placebo alone and an excess of 67% compared with the combined placebopioglitazone control group. There is obvious variability in cardiovascular event rates across the 5 different trials, but this heterogeneity can only be properly explored with further studies. Muraglitazar users also had a 2to 4-kg increase in weight, a 10% incidence of edema, and 13 adjudicated cases of CHF (compared with 1 case in the control group) despite the strict exclusion of all patients with moderate or severe baseline CHF. Although patients with mild CHF symptoms (New York Heart Association class I and II) were eligible, only 25 were recruited and since their CHF risk was increased 10fold, the sponsor’s claim that safety has been demonstrated for this group rings hollow. Systematic baseline ejection fractions were not recorded but none of the patients had a value below 40%, implying that CHF risk prediction for future muraglitazar users will likely be problematic. These elevated CHF rates are possibly related to increased circulating volume and have been consistently observed with other PPARagonists. Moreover, the rates from these clinical

Erythropoietin in Heart Failure and Other Cardiovascular Diseases: Hematopoietic and Pleiotropic Effects

Erythropoietin is a hypoxia-induced hormone that is a major regulator of normal erythropoiesis. Over the last decade, the production of recombinant human erythropoietin has revolutionized the treatment of anemia associated with chronic renal failure, and has led to a greater understanding of anemia pathophysiology and to the elucidation of the interactions of erythropoietin, iron, and erythropoiesis. Anemia has been shown to be independently associated with increased mortality and disease progression. Potential survival benefits associated with correction of anemia have expanded considerably the indications of erythropoietin use in various patient populations and are leading to consideration of earlier, more aggressive treatment of mild to moderate anemia. The results of such treatment are promising in a variety of new clinical settings, including anemia associated with congestive heart failure. Furthermore, the erythropoietin receptor is widely distributed in the cardiovascular system, including endothelial cells, smooth muscle cells and cardiomyocytes and preclinical studies have established erythropoietin to be a pleiotropic cytokine with anti-apoptotic activity and tissue-protective actions in the cardiovascular system, beyond correction of hemoglobin levels. Despite some potential adverse effects, such as hypertension, and the occurrence of erythropoietin resistance, early studies in heart failure patients with anemia suggest that erythropoietin therapy is safe and effective in reducing left ventricular hypertrophy, enhancing exercise performance and increasing ejection fraction. Anemia is found in about one-third of all cases of congestive heart failure (CHF). The most likely common cause is chronic renal insufficiency, which is present in about half of all CHF cases. However, anemia can occur in CHF without renal insufficiency and is likely to be due to excessive cytokine production. The anemia itself can worsen cardiac function, both because it causes cardiac stress through tachycardia and increased stroke volume, and because it can cause a reduced renal blood flow and fluid retention, adding further stress to the heart. Long-standing anemia of any cause can cause left ventricular hypertrophy, which can lead to cardiac cell death through apoptosis and worsen CHF. Therefore, a vicious circle, cardio-renal anemia syndrome, is set up wherein CHF causes anemia, and the anemia causes more CHF and both damage the kidneys worsening the anemia and the CHF further and increasing mortality. There is now evidence that early correction of the CHF anemia with subcutaneous erythropoietin and intravenous iron improves shortness of breath and fatigue, cardiac function, renal function and exercise capacity, reducing the need for hospitalization and improving quality of life. In the present review we discuss the data on current clinical use of erythropoietin in cardiovascular disease, with the main focus on the treatment of congestive heart failure, and summarize the advances and progress made in the understanding of the hematopoietic and pleiotropic effects of erythropoietin in the cardiovascular system.

Congestive Heart Failure Incidence and Prognosis: Case Identification Using Central Adjudication Versus Hospital Discharge Diagnoses

We compared hospitalized congestive heart failure (CHF) incidence and prognosis estimates using hospital discharge diagnoses or central adjudication. We used the Cardiovascular Health Study (CHS), a population-based cohort study of 5888 elderly adults. A physician committee adjudicated potential CHF events, confirmed by signs, symptoms, clinical tests, and/or medical therapy. A CHF discharge diagnosis included any of these ICD-9 codes in any position: 428, 425, 398.91, 402.01, 402.11, 402.91, and 997.1. We constructed an inception cohort of 1209 hospitalized, nonfatal, incident CHF cases, identified by discharge diagnosis, adjudication, or both. Incidence rates for hospitalized CHF were 24.6 per 1000 person-years using discharge diagnoses and 17.1 per 1000 person-years using central adjudication. Compared to the group identified as having CHF by both methods, the group with only a discharge diagnosis (hazard ratio=0.77, 95% confidence interval=0.65-0.91) and the group with central adjudication only (hazard ratio=0.72, 95% confidence interval=0.55-0.94) had lower mortality rates. In the elderly, studies using only discharge diagnoses, as compared to central adjudication, may estimate higher rates of incident hospitalized CHF. Mortality following CHF onset may be similar for these methods and higher if both methods are used together.

Does Date Stamping ICD‐9‐CM Codes Increase the Value of Clinical Information in Administrative Data?

Comorbidity measures are designed to exclude complications when they map International Classification of Diseases (ICD-9-CM) codes to diagnostic categories. The use of data fields that indicates whether each secondary diagnosis was present at the time of hospital admission may lead to the more accurate identification of preexisting conditions. To examine the rate of misclassification of ICD-9-CM codes into diagnostic categories by the Dartmouth-Manitoba adaptation of the Charlson index and by the Elixhauser comorbidity algorithm. Analysis of 178,838 patients in the California State Inpatient Database (CA SID) admitted in 2000 for one of seven major medical and surgical conditions. The CA SID includes a condition present at admission (CPAA) modifier for each ICD-9-CM code. The Dartmouth/Charlson index and the Elixhauser comorbidity measure were used to map the ICD-9-CM codes into diagnostic categories for patients in each study population. We calculated the misclassification rate for each mapping algorithm, using information from the CPAA as the "gold standard." The Dartmouth/Charlson index underestimated the prevalence of hemiplegia/paraplegia by 70 percent, cerebrovascular disease by 70 percent, myocardial infarction by 65 percent, congestive heart failure (CHF) by 45 percent, and peptic ulcer disease by 34 percent. The Elixhauser algorithm misclassified complications as preexisting conditions for 43 percent of the coagulopathies, 25 percent of the fluid and electrolyte disorders, 18 percent of the cardiac arrhythmias, 18 percent of the cardiac arrhythmias, and 9 percent of the cases of CHF. Adding the CPAA modifier to administrative data would significantly enhance the ability of the Dartmouth/Charlson index and of the Elixhauser algorithm to map ICD-9-CM codes to diagnostic categories accurately.

Interim cardiac safety analysis of NCCTG N9831 Intergroup adjuvant trastuzumab trial

556 Background: NCCTG N9831 is a 3-arm randomized Phase III trial comparing safety and efficacy of AC followed by weekly paclitaxel (T) (Arm A) vs the same chemotherapy with 1 yr of trastuzumab (H) either after (Arm B) or starting with T (Arm C). Clinical and asymptomatic cardiac tolerability is the focus of this abstract. Methods: Women with normal left ventricular ejection fraction (LVEF) assessed by MUGA or echocardiogram scan were eligible. LVEF evaluation was repeated post-AC, 6, 9 and 18 months post entry. Clinical cardiac evaluation occurred as a continuum. A Cardiac Safety DMC reviewed asymptomatic and symptomatic LVEF changes monthly. Interim analyses were planned after 100, 300, and 500 evaluable pts per arm began post-AC therapy and were followed for additional 6 months. Primary endpoint was proportion of cardiovascular (CV) events in each arm (congestive heart failure (CHF) and definite or probable cardiac deaths). A difference of 4% would trigger suspension or closure of the H-containing study arms. Results: 3rd interim analysis comparing the cardiac safety on Arms A and B included 1126 women (544 on Arm A and 572 on Arm B) who had a satisfactory post-AC cardiac evaluation (7.3% on Arm A and 3.3% on Arm B were unsatisfactory (significant cardiac symptoms, LVEF below facility’s lower limit of normal, or LVEF drop >15 percentage points) and prohibited from taking H). There were 0 (0%; 95% CI: 0–0.7%) CV events on Arm A and 13 (2.2%; 95% CI: 1.2–3.8%) CV events on Arm B. Among the 13 CV events on Arm B, 12 pts had confirmed cases of CHF and 1 pt experienced a cardiac death. Follow-up data on pts experiencing CV events has been gathered and will be presented. The 3rd interim cardiac analysis comparing cardiac events in Arms A and C expected Spring 2005. Conclusions: There is an increase in cardiac toxicity with H but it remains less than the threshold of 4% prospectively designated as a stopping rule. By that criteria, AC → T vs AC → T → H manifests acceptable cardiac safety data in the adjuvant treatment setting. Enrollment continues for all arms anticipating completion in Spring 2005. Long-term follow-up is needed to determine the impact of the adverse CV events reported at this time. Supported by the Breast Cancer Research Foundation, Genentech, NIH CA25224. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Bristol-Myers Squibb, Eli Lilly, Genentech, Pfizer

Anti-rheumatic drug use and risk of hospitalization for congestive heart failure in rheumatoid arthritis

To assess the risk of hospitalization for congestive heart failure (CHF) associated with the use of disease-modifying anti-rheumatic drugs (DMARDs) and other medications used in RA. We used a case-control design nested within an administrative database cohort of patients with rheumatoid arthritis (RA) who were dispensed a DMARD between September 1998 and December 2001. Subjects identified with a prior history of CHF were excluded. For each hospitalized case of CHF identified during follow-up, 10 controls matched on age and time were randomly selected from the cohort. Conditional logistic regression was used to estimate the rate ratio (RR) of hospitalizations for CHF associated with the current use of specific drugs, adjusted for sex and co-morbidity. The cohort included 41 885 patients; 75% were women, with an average age at cohort entry of 51 yr. During follow-up, 520 hospitalizations for CHF occurred, for a rate of 10.1 per 1000 per year. The adjusted RR of CHF for current use of any DMARD was 0.7 (95% CI 0.6-0.9) relative to no current use. By DMARD category, there was evidence of a beneficial effect for both tumour necrosis factor-alpha antagonists (RR 0.5, 95% CI 0.2-0.9) and methotrexate monotherapy (RR 0.8, 95% CI 0.6-1.0). For non-DMARD medications, the rate of CHF was not clearly increased or decreased, except for COX-2 inhibitors. The data suggested an increased risk of CHF with rofecoxib (RR 1.3, 95% CI 1.0-3.1) and a decreased risk of CHF with celecoxib (RR 0.6, 95% CI 0.4, 1.0). The use of DMARDs was associated with a reduction in the risk of hospitalizations for CHF in this RA cohort. The increased risk with rofecoxib alongside a decreased risk with celecoxib suggests the absence of a class effect with respect to COX-II inhibitors for some types of cardiovascular morbidity.

Antidiabetic therapy and the risk of heart failure in type 2 diabetic patients: an independent effect or confounding by indication

This study assesses the effect of the type of antidiabetic treatment on the risk of developing congestive heart failure (CHF) in type 2 diabetes. The study was derived from the U.K.-based General Practice Research Database (GPRD) comprised of 3.5 million subjects followed between 1987 and 2001. A total of 21 888 type 2 diabetic patients were identified. A 6:1 matched nested case-control design was employed. Conditional logistic regression was used to derive adjusted odds ratios (ORs) for the association of drug treatment with CHF controlling for diabetes duration and for diseases known to affect the risk of CHF. Antidiabetic drug exposure was defined as the receipt of at least one prescription for an antidiabetic medication within the 3 months prior to the date of CHF diagnosis. There were 1301 incident cases of CHF in the cohort, matched to 7788 controls. After risk factor adjustment, there was a 1.2-fold increase in the risk of CHF for sulphonylureas (SUs) (OR = 1.17; 95%CI = 1.00-1.37) and metformin monotherapies (OR = 1.22; 95%CI = 0.97-1.52), a 1.6-fold increase with combinations of metformin and SUs (OR = 1.62; 95%CI = 1.30-2.02), a 2.2-fold increase with oral tricombinations (OR = 2.16; 95%CI = 0.96-4.86) and a 1.5-fold increase for insulin compared to no exposure (OR = 1.52; 95%CI = 1.06-2.17). Compared to SUs, bicombinations of metformin and SUs showed a statistically significant 1.4-fold increase in the odds of CHF (OR = 1.38; 95%CI = 1.13-1.69). All antidiabetic medications were associated with an increased likelihood of CHF compared to no antidiabetic exposure. The risk of CHF increased with the complexity of the antidiabetic regimen suggesting that it is the diabetes severity, which imparts risk and not necessarily the antidiabetic regimen itself.

Time trends in the use of β-blockers and other pharmacotherapies in older adults with congestive heart failure

Background Evidence supporting pharmacotherapy of congestive heart failure (CHF) has grown substantially over the past decade and includes large, placebo-controlled trials with mortality end points. We describe β-blocker and other medication temporal treatment trends of CHF in the Cardiovascular Health Study, a community-based cohort study of 5888 adults ≥65 years of age. Methods Prescription medication data were collected from hospital discharge summaries for incident CHF events and at in-study annual clinic visits for prevalent CHF cases from 1989 to 2000. Change in use of agents over time was estimated by using generalized estimating equations while adjusting for potential confounding factors of age, sex, race, and cardiovascular and pulmonary comorbidities. Results Among 1033 incident CHF events, β-blocker use after diagnosis increased an average of 2.4 percentage points annually (95% CI, 1.5 to 3.4 points) from 1989 to 2000. The increasing trend was consistent throughout follow-up. Among participants with coronary disease and/or hypertension and among those with low ejection fractions (<45%), β-blocker use remained flat from 1989 to 1994 and increased 4.7 points annually (2.5 to 6.9) and 10.0 points annually (6.1 to 13.8), respectively, from 1995 to 2000. Among participants without coronary disease or hypertension, there was no overall increase in use. Use of renin-angiotensin system inhibitors increased 2.3 points annually (1.0 to 3.5), digoxin use decreased 2.4 points annually (−3.6 to −1.1), and loop diuretic use remained flat between 1989 and 2000. In general, treatment trends were similar for prevalent CHF. Conclusions Treatment of CHF has changed gradually in the 1990s and may in part reflect the influence of CHF clinical trial evidence.

Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study

Background B-type natriuretic peptide (BNP) is secreted from the cardiac ventricles in response to increased wall tension. Methods The Breathing Not Properly Multinational Study was a 7-center, prospective study of 1586 patients who presented to the Emergency Department with acute dyspnea and had BNP measured with a point-of-care assay upon arrival. The gold standard for congestive heart failure (CHF) was adjudicated by two independent cardiologists, blinded to BNP results, who reviewed all clinical data and standardized scores. The current study explores the effect of these variables on BNP decision statistics as well as the impact that changing cutoffs might have on the cost-effectiveness of diagnostic decisions that use BNP information. Results Significant differences in CHF rates were found on the basis of age ( P < .001) and racial group ( P = .020) but not sex ( P = .424). BNP levels increased with increasing age ( P < .001). To evaluate potential differences in the diagnostic utility of BNP levels as a function of demographic variables, separate receiver operating characteristic curves were performed. BNP was a stronger predictor in younger subjects than in older subjects and slightly weaker for female patients than for male patients (area under the curve = 0.918 and 0.870, respectively). An even smaller difference was noted between the white and black racial groups (area under the curve = 0.888 and 0.903, respectively). The differences in specificity as a function of age are larger than other differences in specificity or sensitivity. When logistic regression was used in a multivariate approach to combine the demographic variables with BNP information in the prediction of CHF, only BNP contributed significantly to the prediction of acute CHF. When the model was expanded to include terms for the interaction of each of the demographic variables with log 10 BNP, a significant interaction was found for sex. Since the relative consequences of false-positives and false-negatives are unlikely to be equivalent, the BNP cut-points that would be selected based on the current data as a function of relative costs are presented. Sharply rising consequences are seen for BNP cut-points >100 pg/mL. Conclusions If one assumes that failing to treat cases of CHF is worse than treating negative cases, then relatively low BNP cut-points (eg, not >100 pg/mL) should be used in patients presenting to the Emergency Department with a chief complaint of dyspnea, regardless of age, sex, or ethnicity.

Clinical observation of the curative effect of Qiangxin Mixture on congestive heart failure

To investigate the efficacy of Qiangxin Mixture in patients with congestive heart failure (CHF). Sixty cases of CHF were randomly divided into Qiangxin Mixture group (treatment group, n=30) and digoxin group (control group, n=30). The total clinical effective rate, integra of the symptoms of kidney deficiency, classification of functional capacity of the New York Heart Association (NYHA), and echocardiogram [ejection fraction (EF), cardiac output (CO), interventricular septal thickness (IVST), posterior wall thickness (PWT), left ventricular mass index (LVMI)] as well as the measurement of plasma endothelin, angiotensin II and atrial natriuretic peptide were observed in both groups. The total clinical effective rate of Qiangxin Mixture group was 87%, and improvement was significantly observed in the Lee CHF score, classification of functional capacity of the NYHA, EF and CO (P<0.05, vs before treatment), but no significant improvement in digoxin group (P>0.05). The integra of the symptoms of kidney deficiency, the levels of plasma ET, Ang II and ANP decreased significantly (P<0.01, vs before treatment and digoxin group respectively). IVST, PWT and LVMI were also reduced significantly (P<0.01, vs before treatment; P<0.05 vs digoxin group). The Qiangxin Mixture is effective in enhancing cardiac contraction, improving hemodynamics in the short-term and rectifying some indexes in the long-term, so it could postpone the processes of CHF. This mechanism may be related to decreasing the stimulating factors (angiotensin, endothelin) which trigger the cardiac remodeling, delaying or reversing the cardiac remodeling.

Heart failure after myocardial infarction: Prevalence of preserved left ventricular systolic function in the community

Background Studies have reported that a large proportion of the cases of congestive heart failure (CHF) with mixed etiologies have preserved left ventricular systolic function. Whether this is the case in subjects with CHF after myocardial infarction (MI) is not known. This study was undertaken to examine the prevalence and characteristics associated with CHF in patients who had preserved ejection fraction (LVEF) after MI. Methods Clinical characteristics and LVEF were ascertained in a population-based cohort of patients with CHF after incident MI in Olmsted County, Minn. All MIs were validated by use of standardized epidemiological criteria, and all episodes of CHF were validated by use of Framingham criteria. Results Between 1979 and 1994, 1658 patients had an MI, and 644 of these patients (38%) had CHF during 7.4 ± 5.4 years of follow-up. Of these patients, 395 (61%) underwent LVEF assessment. Preserved LVEF (ie, ≥50%) was present in 30% of cases, and this proportion did not change with time. The proportion of women with CHF and preserved LVEF (37%) was greater than the proportion of men (23%, P = .002). The positive association between female sex and preserved LVEF remained significant after adjustment (odds ratio 1.97, 95% CI 1.26-3.07, P = .003). The highest tertile of peak creatinine phosphokinase level was negatively associated with preserved LVEF (odds ratio 0.51, 95% CI 0.29-0.89). Conclusion A notable proportion of cases of CHF after MI have preserved LVEF. This underscores the burden of CHF with preserved LVEF in a well-defined group of patients with documented coronary disease. CHF with preserved LVEF after MI is associated with female sex and smaller MI size. (Am Heart J 2003;145:742-8.)

Doxorubicin cardiotoxicity: Prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era

Background. Congestive heart failure (CHF) is among the most serious toxicities of doxorubicin, a potent cancer chemotherapeutic agent. Serial left ventricular ejection fraction (LVEF) monitoring during doxorubicin therapy for preventing CHF was proposed over 20 years ago. The current utility and cost-effectiveness of this approach in the present era are not known. Methods and Results. Clinical and follow-up data of 265 patients with cancer (age, 53 ± 14 years; 76% women) undergoing doxorubicin chemotherapy with serial equilibrium radionuclide angiocardiography (ERNA) monitoring (≥2 studies) were analyzed retrospectively. Patients with a normal baseline LVEF (≥50%) and a 10% or greater point fall in LVEF to a final value of less than 50% during doxorubicin therapy were considered “at risk” for CHF (n = 41). Over 679 ± 426 days of follow-up, 7 patients (2.6%) had CHF develop and 90 (34%) died (all cancer-related deaths, with none due to CHF). A comparison of “at-risk” (n = 41 [15%]) and “low-risk” (n = 224 [85%]) groups showed a higher incidence of CHF (12% vs 0.9%, P < .0001), lower baseline LVEF (58% ± 8% vs 64% ± 8%, P < .0001), lower value for the lowest LVEF (42% ± 8% vs 57% ± 7%, P < .0001), and higher rate of cancer-related deaths (59% vs 29%, P = .0003) in the former despite similar cumulative doxorubicin dose (304 ± 124 mg/m 2 vs 284 ± 110 mg/m 2, P = not significant). There were no differences in age, gender, cancer type, and co-morbidity. Cost analysis showed the overall cost of ERNA studies to be lower than the 1-year cost of caring for additional cases of CHF that would potentially be prevented by routine LVEF monitoring. Conclusions. An incipient fall in LVEF detected on serial ERNA during doxorubicin therapy provides an appropriate and cost-effective approach for predicting and preventing impending CHF. Use of this approach was associated with a low incidence of CHF (2.6%) and no CHF-related mortality in this study. (J Nucl Cardiol 2003;10:132-9)

Apnea‐Related Heart Rate Variability in Congestive Heart Failure Patients

Sleep‐disordered breathing (SDB) causes fluctuation of the RR interval. However, the details are uncertain. We studied the characteristics of sleep‐related heart rate variation (HRV) in congestive heart failure (CHF) patients with SDB. Ambulatory electrocardiograms and data on respiration (oronasal flow, trachea sound, abdominal wall movement, and oxygen saturation) were simultaneously recorded by a multi‐channel digital recorder for 13 CHF patients (8 men and 5 women; mean age, 68 ± 4 years). Heart rate variation occurred as a result of cyclical apnea attacks between 0.005 and 0.03 Hz (apnea band). The proportion of the apnea band (% apnea) increased with the number of apnea episodes, and SDB was highly likely when the % apnea was ≥80%. Low‐flow oxygen administration effectively reduced apnea frequency, and the apnea‐related HRV also decreased. We concluded that apnea‐related HRV was useful for detecting and following SDB in CHF cases.

Hyperthyroidism: A “Curable” Cause of Congestive Heart Failure—Three Case Reports and a Review of the Literature

With the increasing incidence of coronary artery disease and the aging population, the prevalence of congestive heart failure (CHF) is increasing. In the majority of these cases the etiology is underlying coronary artery disease. Other less common causes of CHF include valvular heart disease, hypertension, alcoholic cardiomyopathy, and dilated cardiomyopathy. In addition, there are rare causes, one of which is hyperthyroidism. Hyperthyroidism can affect the cardiovascular system in a variety of ways. The cardiovascular manifestations range from sinus tachycardia to atrial fibrillation and from a high cardiac output state to CHF due to systolic left ventricular dysfunction. If the underlying hyperthyroidism is recognized and treated early the CHF in such cases can be cured. The authors present three cases of CHF due to systolic left ventricular dysfunction secondary to hyperthyroidism, which showed considerable improvement in the left ventricular function once the hyperthyroidism was treated.