Subsequent Congestive Heart Failure Research Articles

Association of device detected atrial and ventricular tachyarrhythmia with adverse events in patients with an implantable cardioverter-defibrillator.

Heart failure patients with a history of atrial fibrillation (AF) and ventricular tachycardia/ventricular fibrillation (VT/VF) are known to have worse outcomes. However, there are limited data on the temporal relationship between development of these arrhythmias and the risk of subsequent congestive heart failure (CHF) exacerbation and death. The study cohort comprised 5511 patients implanted with an implantable cardioverter-defibrillator (ICD) in landmark clinical trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID) who were in sinus rhythm at enrollment. Multivariate cox analysis was performed to evaluate the time-dependent association between development of in-trial device detected AF and VT/VF with subsequent CHF exacerbation and death. Multivariate analysis showed that AF occurrence and VT/VF occurrence were both associated with a similar magnitude of risk for subsequent CHF exacerbation (HR = 1.73 and 1.87 respectively, p < .001 for both). In contrast, only in-trial VT/VF was associated with a significant > two-fold increase in the risk of subsequent mortality (HR = 2.13, p < .001) whereas AF occurrence was not associated with a significant mortality increase after adjustment for in-trial VT/VF (HR = 1.36, p = .096). Our findings from a large cohort of ICD recipients enrolled in landmark clinical trials show that device detected AF and VT/VF can be used to identify patients with increased risk for CHF exacerbation and mortality. These findings suggest a need for early intervention in CHF patients who develop device-detected atrial and ventricular tachyarrhythmias.

Suspected thyroid storm in a cat anaesthetised for bilateral thyroidectomy

A 14‐year‐old female neutered domestic short hair cat was referred for assessment of uncontrolled hyperthyroidism. The owners were advised that a bilateral thyroidectomy was required due to the presence of comorbidities that rendered radioiodine therapy inappropriate. During the procedure the cat exhibited unexpected extreme tachycardia, hypertension, hypercapnia, severe respiratory and metabolic acidosis and ventricular arrhythmias, which all resolved after removal of the thyroid glands. Recovery was complicated by the development of congestive heart failure and hypertension which were successfully managed and the cat was discharged five weeks after presentation. Thyroid storm was considered a possible explanation for the events that occurred during anaesthesia as well as the subsequent congestive heart failure and hypertension. Thyroid storm during anaesthesia has not been reported in animals. The similarities between the reported case and thyroid storm events in humans are discussed.

Practice patterns in the management of congestive heart failure and post-discharge quality of life: A hospital-based cross-sectional study.

Objective:The objective of the study is to identify the etiology, risk factors, frequency of major and minor components of the Framingham criteria for heart failure, discharge medications, mortality, and quality of life after discharge from the hospital, for patients who were admitted to the in-patient unit of a tertiary care hospital in central India, with a diagnosis of congestive heart failure (CHF).Methods:This hospital-based cross-sectional study involved retrospective chart review of patients who were admitted to the in-patient unit with a diagnosis of CHF. These patients were then attempted to reach via their telephone numbers listed in the medical records and their current quality of life was assessed using Euro-QoL 5D questionnaire.Results:In the 69 patients who were admitted to the hospital with congestive cardiac failure during the pre-defined period, ischemic heart disease was the most common etiology and smoking was the most common risk factor for the development of CHF. The most common findings based on Framingham criteria were dyspnea on mild exertion, rales and bilateral ankle edema. It was determined that one-fourth of the individuals were non-compliant to the medical treatment and more than half of the patients had a poor health score.Conclusion:Smoking remains to be a major risk factor for patients to develop ischemic heart disease and subsequent CHF. Patients with congestive cardiac failure also had severe deterioration in their quality of life after discharge from the hospital, implying the need for improving efforts toward prevention and better management.

Ischemic Mitral Regurgitation: Current Understanding and Surgical Options.

Secondary, or functional, mitral regurgitation (MR) occurs with impaired coaptation of structurally normal valve leaflets due to abnormal structure and/or function of the left ventricle (LV). A leading cause of functional mitral regurgitation is ischemic cardiomyopathy, resulting in left ventricular dysfunction and subsequent congestive heart failure (CHF) and ischemic mitral regurgitation (IMR). The value of surgical or transcatheter correction of IMR remains controversial, since the underlying pathology of IMR is attributed to a dysfunctional left ventricle. However, even mild IMR has been shown to be harmful to CHF patients, as IMR is both a surrogate of advanced CHF and an independent contributor to CHF morbidity and mortality. While observational and randomized studies have examined surgical treatment of IMR with conflicting outcomes, additional well-designed randomized controlled trials should be performed to further clarify the optimal treatment for IMR. Additionally, close attention should be paid to the quality of interventions performed, as durable reduction in IMR provides the best hope of a positive clinical outcome. This review focuses on the pathophysiology of IMR, current evidence regarding surgical and transcatheter interventions, and future directions in management of IMR.

Cyclical cardiorenal syndrome in late-stage kidney disease .

In patients with late-stage chronic kidney disease (LS-CKD, estimated glomerular filtration rate (eGFR) < 30 mL/min) there is a high prevalence of congestive heart failure (CHF). We have observed a cyclical nature in the "cardiorenal syndrome" in LS-CKD, not previously described. The purpose of this article is to describe the syndrome and review its characteristics. Patients enrolled in the Northwell Health Healthy Transitions in Late Stage Kidney Disease Program (HT) were followed, all with eGFR 0 - 30 mL/min. Patients were observed for a 1-year period for signs of destabilized cardiorenal syndrome. The primary outcome of interest was an episode of cyclical cardiorenal syndrome (CCRS), defined as CHF symptoms leading to increased diuretic dose or increased renin-angiotensin-aldosterone system inhibitors (RAASi) followed within 60 days by acute kidney failure (AKI), or, conversely, an episode of AKI with reduction in diuretic or RAASi, followed within 60 days by worsening of CHF. Of 302 HT patients, 63 (20.9%) patients had at least one episode of CCRS. Of the 63 patients, there were 89 CCRS episodes (ranging 1 - 3 per patient) and 32 (35.0%) associated hospitalizations for CHF. Of 89 CCRS episodes, 67 (75.3%) started with an episode of CHF, 22 (24.7%) started with AKI. Of 67 cases of CHF with subsequent AKI, the associated medication change was a diuretic dose increase in 61 cases (91.0%), increase in RAASi dose in 3 cases (4.5%), and increases in both in 3 cases (4.5%). Of 22 cases of AKI leading to subsequent CHF, the associated medication change was a diuretic dose decrease in 19 (86.4%) and a decrease in both diuretic and RAASi dose in 3 (13.6%). CCRS occurs in ~ 1/5 of late-stage CKD patients with CHF. Further study would help to elucidate the extent to which fragmented care between cardiologists and nephrologists contributes to the problem. .

Predictors of Congestive Heart Failure Hospitalisation Following Acute Pulmonary Embolism

Background: Congestive heart failure (CHF) is a risk factor for pulmonary embolism (PE). PE is also an independent predictor of death or re-hospitalisation among patients with CHF. We assessed the incidence and identified novel predictors of subsequent CHF admission in patients with acute PE using population-linkage analysis.

Prognostic value of T1-mapping in TAVR patients: extra-cellular volume as a possible predictor for peri- and post-TAVR adverse events.

The benefit of a transcatheter aortic valve replacement (TAVR) can differ in patients, and therapy bears severe risks. High-degree aortic stenosis can lead to cardiac damage such as diffuse myocardial fibrosis, evaluable by extra-cellular volume (ECV) in CMR. Therefore, fibrosis might be a possible risk factor for unfavorable outcome after TAVR. We sought to assess the prognostic value of T1-mapping and ECV to predict adverse events during and after TAVR. The study population consisted of patients undergoing clinically indicated TAVR by performing additional CMR with native and contrast-enhanced T1-mapping sequences for additional evaluation of ECV. Study endpoints were congestive heart failure (CHF) and TAVR-associated conduction abnormalities defined as new onset of left bundle branch block (LBBB), AV-Block or implantation of a pacemaker. 94 patients were examined and followed. Median follow up time was 187days (IQR 79-357days). ECV was increased (>30 %) in 38 patients (40 %). There was no significant correlation between ECV and death, Hazard ratio (HR) 0.847 (95 % CI 0.335; 2.14), p = 0.72. ECV in patients with subsequent CHF was higher than in those without an event (33.5 ± 4.6 and 29.1 ± 4.1 %, respectively), but the difference just did not reach the level of significance HR 2.16 (95 % CI 0.969; 4.84), p = 0.06. Patients with post-TAVR conduction abnormality (LBBB, AV-block or pacemaker implantation) had statistically relevant lower ECV values compared to those without an event. Patients with an event had a mean ECV of 28.1 ± 3.16 %; patients without an event had a mean ECV of 29.8 ± 4.53, HR 0.56 (95 % CI 0.32; 0.96), p = 0.036. In this study, elevated myocardial ECV is a predictor of CHF by trend; CMR may be helpful in identifying patients with a high risk for post-TAVR cardiac decompensation benefitting from an intensified post-interventional surveillance. Patients with post-TAVR conductions abnormalities have a significantly decreased ECV. Nevertheless, it remains unclear which precise molecular tissue alteration is the protective factor or risk factor in this case.

Abstract IA24: Science of surviving cancer: Lessons learned from our cancer survivors

Abstract The 5-year overall survival rate for childhood cancer now exceeds 80%. As a result of this improvement in survival, the number of childhood cancer survivors now exceeds 375,000. The increasing number of long-term survivors is attended by a growing awareness that many will develop health conditions as a direct or an indirect consequence of their cancer therapy. While some of these conditions occur during therapy and persist well after the therapy has been completed (such as steroid-induced osteonecrosis, or alkylating agent /radiation-induced hypogonadism), many outcomes are not evident until 10-20 years later, such as subsequent malignant neoplasms (SMNs) and anthracycline-related late onset congestive heart failure (CHF). Individuals exposed to radiation and chemotherapy are vulnerable to long-lasting organ toxicity. While clear and unambiguous associations exist between therapeutic exposures and specific complications, considerable inter-individual variability is observed in the risk of developing an outcome for any given exposure. Genetic predisposition and especially its interaction with therapeutic exposures can potentially exacerbate the toxic effect of treatment on normal tissues and organ systems, and can possibly explain the inter-individual variability. Thus, it becomes imperative to understand the individual variability in: i) the internal dose of the therapeutic agent; ii) the biologically effective dose; iii) the alterations in structure or function of the tissue or organ; and iv) the consequent development of preclinical disease, in order to understand the pathogenesis of therapy-related complications, and also develop a better idea of the individual susceptibility. Over the past decade, there have been several reports describing the role of genetic susceptibility in anthracycline-related CHF, in chemotherapy-related leukemia, radiation-related solid SMNs, and corticosteroid-related osteonecrosis. These studies have varied in their investigative approach – from a candidate gene investigation to a genome-wide association study. Understanding the etiology and pathogenetic pathways that lead to the morbidity is critical to developing targeted prevention and intervention strategies, optimizing risk-based health care of cancer survivors, thus minimizing chronic morbidities and improving quality of life. Citation Format: Smita Bhatia. Science of surviving cancer: Lessons learned from our cancer survivors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr IA24.

Anaplastic Metastasis of Left-Sided Cardiac Carcinoid with Rapid Tricuspid Valve Involvement after Valve Replacement

Carcinoid tumors are rare and slow-growing neuroendocrine tumors. In the United States, the prevalence is reported at 2 cases per 100,000 persons. The classic carcinoid syndrome occurs in up to 5% of cases and its vasoactive effects can induce flushing, secretory diarrhea, bronchospasm and hypotension1. Carcinoid induced cardiac dysfunction is rare and involves development of plaques on the tricuspid and pulmonic valves, often manifesting as tricuspid insufficiency and pulmonic stenosis (TIPS). More specifically, these plaques cause hemodynamic dysfunction as a result of thickening and restricted motion of the valve leaflets. Of all cardiac carcinoid cases, the left-heart valves are affected in less than 10% of cases, due to atrial right-to-left shunt or primary bronchial carcinoid. Despite appropriate valve replacement therapy, rarely does the subsequent congestive heart failure resolve; necessitating an ongoing balance between cardiac treatment options and chemotherapy. Herein, we present a case of aggressive carcinoid heart disease manifesting as left-sided valvular plaque with subsequent development of severe tricuspid valve regurgitation after triple-valve replacement surgery. We will also review the treatment strategy in this patient with aggressive carcinoid syndrome.

Role of angiotensin II type I (AT1 A1166C) receptor polymorphism in susceptibility of left ventricular dysfunction

BackgroundLeft ventricular dysfunction (LVD) with subsequent congestive heart failure (CHF) constitutes the final common pathway for a host of cardiac disorders. The impaired LV function develops in response to an ischemic insult followed by a fall in cardiac output that leads to activation of renin-angiotensin-system (RAS). Angiotensin II type I receptor (AT1), which mediate the vasoconstrictive and salt-conserving actions of the RAS, represent interesting candidate genes for cardiovascular diseases. Therefore, we conducted an association study between single nucleotide polymorphism (SNP) in AT1 gene and LVD in CAD patients. Methods and resultsThe present study recruited a total of 950 subjects including 720 angiography confirmed CAD patients and 230 healthy controls. Among 720 CAD patients, 229 with reduced left ventricle ejection fraction (LVEF≤45%) were categorized as LVD. The AT1 (A1166C, rs5186) polymorphism was determined by ARMS-PCR. Our results showed that the frequency of AT1 1166AC and CC genotypes were significantly higher in LVD patients in comparison to non-LVD (LVEF >45%) patients (p value = 0.003; OR = 1.81 and p value <0.001; OR = 4.33). Further analysis showed that AT1 A1166C polymorphism was significantly associated with LV end diastole (p-value = 0.031), end systole (p-value = 0.038) dimensions, and mean LVEF (p-value = 0.035). Moreover, on comparing the AT1 A1166C polymorphism in CAD patients with healthy controls, we did not find any association both at genotypic and allelic level (p value = 0.927; OR = 1.04 and p value = 0.219; OR = 0.83) respectively. ConclusionsOur study suggests that AT1 A1166C polymorphism may play significant role in conferring genetic susceptibility of LVD.

Preventing Dementia in Older Cardiovascular Patients

Cardiovascular disease (CVD) contributes to risk of dementia by either enhancing the development and progression of brain vascular disease and subsequent neurodegeneration and Alzheimer's disease (AD) pathology, ie, amyloid plaques and neurofibrillary tangles, acts as a precipitant of dementia in older individuals with preexisting subclinical neuropathology of dementia. Atrial fibrillation, congestive heart failure (CHF), stroke, and myocardial infarction are associated with increased risk of dementia. All older individuals age 65–70+ can be considered to be at very high risk of vascular disease and dementia and candidates for aggressive CV preventive therapies, such as lipid lowering, antihypertensive therapy, increased physical activity, antidiabetic therapies, smoking cessation, etc to prevent heart attacks subsequent CHF, atrial fibrillation, stroke, frailty, and dementia. Furthermore, preventing or delaying dementia should be a primary outcome of all CV trials in older individuals.

A Case of Acute Promyelocytic Leukemia Concomitant with Plasma Cell Myeloma

A Case of Acute Promyelocytic Leukemia Concomitant with Plasma Cell Myeloma

Congestive Heart Failure: Experimental Model

Introduction: Surgically induced, combined volume and pressure overload has been used in rabbits to create a simplified and reproducible model of acute left ventricular (LV) failure.Materials and Methods: New Zealand white male rabbits (n = 24, mean weight 3.1 ± 0.2 kg) were randomly assigned to either the Control group (n = 10) or to the Heart Failure group (HF, n = 14). Animals in the Control group underwent “sham” procedures. Animals in the HF group underwent procedures to induce LV volume overload by inducing severe aortic valve regurgitation with aortic cusp disruption and pressure overload using an occlusive silver clip positioned around the pre-renal abdominal aorta.Results: Following Procedure-1 (volume overload) echocardiography confirmed severe aortic regurgitation in all animals in the HF group, with increased mean pulse pressure difference from 18 ± 3 to 38 ± 3 mmHg (P < 0.0001). After Procedure-2 (pressure overload) all animals in the HF group showed clinical and echocardiographic signs of constriction of the abdominal aorta and echocardiography confirmed progressively declining LV function. At the end of the protocol there was a significant increase of the heart/body weight ratio in the HF group vs. Control group (4.6 ± 0.2 vs. 2.9 ± 0.1 g/kg, P < 0.05), and echocardiography showed in HF group significant increase of the LV end-diastolic diameter (2.15 ± 0.09 vs. 1.49 ± 0.03 cm, P < 0.001) and reduction of the LV shortening fraction (26.3 ± 3.8 vs. 41.3 ± 1.6%, P < 0.001).Conclusion: This experimental model: (a) consistently produces LV hypertrophy/dilatation and subsequent congestive heart failure, (b) provides new data on the time course of LV dilatation, hypertrophy and failure, (c) allows study of the progress and evolution of LV systolic and diastolic dysfunction in the presence of induced LV failure, (d) is suitable to study intervention or pharmacological administration to reduce the negative effects of acute LV failure.

Circadian changes in autonomic function in conscious rats with heart failure: Effects of amiodarone on sympathetic surge

Cardiovascular events are characterized by circadian periodicity with a peak prevalence during the awakening period, which suggests a morning surge in sympathetic activity. We developed an experimental system to determine circadian changes in heart rate (HR), blood pressure (BP), locomotor activity (Loc), respiratory rate and autonomic function in conscious, unrestrained rats. The effects of amiodarone on circadian variation of these variables were determined in rats with myocardial infarction and subsequent congestive heart failure (CHF). We continuously recorded BP, HR and Loc for 24 h in rats with CHF ( n = 16) or after a sham operation (Sham; n = 7). To determine circadian changes in sympathovagal balance, digitized BP and HR data throughout 24 h were analyzed based on maximum entropy. The study was repeated after 3 weeks of oral amiodarone (50 mg/kg/day) or saline administration. Baseline HR, mean BP, and Loc were higher in the dark period than in the light period (all p < 0.05) in both CHF and Sham rats, which is consistent with the circadian periodicity of nocturnal animals. Low-frequency components of diastolic BP variability (LFdp), an index of sympathetic tone, were significantly higher during the awakening period (16:00–20:00) than during the sleeping period (08:00–14:00), a finding analogous to the sympathetic morning surge in men. Amiodarone suppressed this transient increase in LFdp power during the awakening period. Our experimental system could detect sympathetic surge in conscious rats. Amiodarone suppressed the sympathetic surge, which could explain, at least in part, beneficial effects of amiodarone in patients with CHF.

Congestive heart failure complicating aortic regurgitation with medical and surgical management: A prospective study of traditional and quantitative echocardiographic markers

Congestive heart failure complicating aortic regurgitation is poorly described, and predictive roles of quantitative versus traditional (symptoms or low ejection fraction) surgical markers are unclear. We prospectively enrolled 287 patients with aortic regurgitation (age, 61 +/- 17 years; 68% male) in whom we performed quantitative Doppler echocardiographic analysis and personal physicians conducted management. After diagnosis, 40 congestive heart failure episodes occurred under medical management (10-year, 23% +/- 4%) causing high subsequent mortality (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.2-6.8; P = .02). Patients with traditional surgical markers (symptoms or ejection fraction <50%) were surprisingly followed 1.4 +/- 3.3 years under medical management with frequent congestive heart failure (adjusted risk, 4.9; 95% CI, 2.1-11.0; P < .001) and excess postoperative mortality (HR, 3.0; 95% CI, 1.3-7.1; P = .01). Quantitative American Society of Echocardiography aortic regurgitation grading and left ventricular end-systolic volume index independently predicted congestive heart failure (quantitative American Society of Echocardiography severe aortic regurgitation: HR, 3.6; 95% CI, 1.3-13.0; P = .015; end-systolic volume index >or=45 mL/m(2): HR, 2.1; 95% CI, 1.03-4.4; P = .04) or death-congestive heart failure with incremental predictive value (P < .001). Higher congestive heart failure rates occurred with quantitative American Society of Echocardiography severe aortic regurgitation (regurgitant volume of >or=60 mL/beat or orifice of >or=30 mm(2)) versus quantitative American Society of Echocardiography mild aortic regurgitation (10-year: 44% +/- 10% vs 15% +/- 7%, P < .001) and end-systolic volume index of 45 mL/m(2) or greater versus less than 45 mL/m(2) (33% +/- 7% vs 9% +/- 2%, P < .001). Traditional markers (symptoms and ejection fraction <50%) had lower sensitivity for congestive heart failure than quantitative echocardiography (all P < .001). Cardiac surgery for aortic regurgitation markedly reduced congestive heart failure in quantitative American Society of Echocardiography severe aortic regurgitation (HR, 0.23; 95% CI, 0.08-0.68; P = .008) without excess mortality (P = .10). This prospective study of aortic regurgitation shows frequent congestive heart failure under conservative management. Traditional surgical markers (symptoms and ejection fraction <50%) predict subsequent congestive heart failure but are insensitive, and rescue operations are often delayed and associated with excess mortality. Quantitative echocardiography provides congestive heart failure predictors that are independent, incremental, and more sensitive than traditional markers. Cardiac surgery for aortic regurgitation markedly reduces congestive heart failure rates in high-risk patients with aortic regurgitation.

Doxorubicin, Cardiac Risk Factors, and Cardiac Toxicity in Elderly Patients With Diffuse B-Cell Non-Hodgkin's Lymphoma

Anthracycline-based chemotherapy, which improves survival for patients with non-Hodgkin's lymphoma, is often withheld from elderly patients because of its cardiotoxicity. We studied the cardiac effects of doxorubicin in a population-based sample of older patients with diffuse large B-cell lymphoma (DLBCL). Among patients age > or = 65 years diagnosed with DLBCL from 1991 to 2002 in the Surveillance, Epidemiology, and End Results-Medicare database, we developed logistic regression models of the associations of doxorubicin with demographic, clinical, and cardiac variables. We then developed Cox proportional hazards models of the association between doxorubicin and subsequent congestive heart failure (CHF), taking predictors of CHF into account. Of 9,438 patients with DLBCL, 3,164 (42%) received doxorubicin-based chemotherapy. Any doxorubicin use was associated with a 29% increase in risk of CHF (95% CI, 1.02 to 1.62); CHF risk increased with number of doxorubicin claims, increasing age, prior heart disease, comorbidities, diabetes, and hypertension; hypertension intensified the effect of doxorubicin on risk of CHF (hazard ratio = 1.8; P < .01). In the 8 years after diagnosis, the adjusted CHF-free survival rate was 74% in doxorubicin-treated patients versus 79% in patients not treated with doxorubicin. Among patients receiving chemotherapy for DLBCL, those with prior heart disease were less likely than others to be treated with doxorubicin, and those who received doxorubicin were more likely than others to develop CHF. Various cardiac risk factors increased CHF risk, but only hypertension was synergistic with doxorubicin. Doxorubicin has dramatically improved survival of DLBCL patients; nonetheless, some subgroups may benefit from efforts to reduce doxorubicin-related CHF risk.

Obesity, Hypertension, and the Heart

Controversy exists regarding the amount of risk caused by obesity, but there is general consensus that it is associated with many serious disorders, mostly cardiovascular and neoplastic. Obesity is clearly associated with hypertension, ventricular remodeling with subsequent congestive heart failure, sleep-disordered breathing, and sudden death. The physiologic alterations associated with establishing and perpetuating the obese state are complex but are becoming clear. In discussing the cardiovascular consequences of obesity, the implications and mechanism of the associated hypertension need to be understood. There is growing recognition that adipose tissue is a very active in the neurohormonal axis and is not simply a passive storage depot. Among other things, adipocyte-related hormonal activity and resistance to feedback mechanisms are associated with increased plasma volume and increased sympathetic tone.

Functional mitral regurgitation after a first non-ST-segment elevation acute coronary syndrome: contribution to congestive heart failure

Functional mitral regurgitation (MR) is a frequent complication after the acute phase of a myocardial infarction and plays an important role in the development of congestive heart failure (CHF) after a Q-wave myocardial infarction. Nevertheless, until now, the relevance of functional MR after a non-ST-segment elevation acute coronary syndrome (NSTSEACS) has been poorly addressed. Our aim was to assess the relationship between the presence or absence and the severity of functional MR after a first NSTSEACS and the development of CHF. Two hundred and seventy-nine patients discharged from hospital in NYHA functional classes I and II (71.7% men; mean age 66.3 +/- 13.2 years) after a first NSTSEACS were studied. Every patient underwent an echocardiographic study during the first week after the index NSTSEACS and were clinically followed-up. MR was detected in 40.1% patients. Patients were followed-up for a median time of 418 days (inter-quartile range: 295-561). Six patients (3.6%) in the group without MR and 15 patients (13.4%) in the group with MR required hospitalization due to CHF during follow-up. Only MR was found as an independent predictor of CHF development (HR = 1.8; 95% CI = 1.1-3.1; P = 0.02) and CHF development or cardiac death (HR = 2.1; 95% CI = 1.3-3.3; P = 0.01) in the long-term follow-up multivariable Cox regression analysis. There is an increased risk for subsequent CHF in patients with MR after a first NSTSEACS. The risk of CHF is closely related to the MR presence and severity. Thus, the detection of MR by means of Doppler echocardiography after a first episode of NSTSEACS is crucial.

Doxorubicin, cardiac risk factors and cardiac toxicity in elderly patients with diffuse b-cell non-Hodgkin's lymphoma

9050 Background: Anthracyclines are known to cause acute and chronic cardiotoxicity. In a population-based sample of elderly patients with diffuse large B-cell lymphoma (DLBCL), we studied the cardiac effects of doxorubicin (DOX)-containing regimens and of pre-existing diabetes (DM), hypertension (HTN), and heart disease (HD). Methods: Patients aged =65 years diagnosed with DLBCL 1/1/1992–12/31/2000 in the SEER/Medicare database were grouped by treatment: no chemotherapy, doxorubicin-based chemotherapy, or other chemotherapy. We developed multivariable logistic regression models of the associations of DOX-based chemotherapy with demographic and clinical variables and pre-diagnosis DM, HTN, and HD. We then developed Cox proportional hazards regression models of the association between treatment and subsequent congestive heart failure (CHF) taking the predictors of treatment into account. Results: Of 6,413 patients with DLBCL, 2,536 (39%) received doxorubicin-based chemotherapy. DOX use was associated with later year of diagnosis, female gender, younger age, and being married. Black race (HR 0.50, 95% CI 0.33–0.75), comorbidities, preexisting CHF, HD, and DM (HR 0.73, 95% CI 0.62–0.86) were associated with decreased DOX use. The post-treatment HR for CHF following DOX treatment vs. no chemotherapy was 1.39 (95% CI 1.15–1.67); CHF risk increased with duration of DOX use. It was also associated with increasing age, comorbidities, black race, DM, HTN, and HD. There was a significant interaction between race and DOX (P=0.01); For black patients treated with DOX the HR for CHF was 3.4, as compared to a HR of 1.3 for white patients. Conclusions: Among patients with DLBCL, black race, CRFs and pre-existing HD are all associated with both a reduced likelihood of receiving anthracyclines, and an increased risk of CHF. We have previously found a powerful effect of DOX on survival in this patient population; thus, for most patients, the benefits of treatment would appear to outweigh the risks of cardiac toxicity. However, as the number of long-term survivors grows, the need for research on the side effects of treatment, on host factors that may increase the risk of adverse effects, and on ways to minimize such risks will also grow. No significant financial relationships to disclose.

Clinical Epidemiology of Long-bone Fractures in Patients Receiving Hemodialysis

Although prevention of metabolic bone disease is a principal component of management of end-stage renal disease, the clinical epidemiology of long-bone fractures is not completely understood. Hospital discharge claims from 1994 through 1999 for 7159 subjects in the Dialysis Morbidity and Mortality Study were used to quantify incidence and risk factors of long-bone fractures and to test the hypothesis that long-bone fractures are associated with cardiovascular and infectious events and death in patients receiving hemodialysis. The incidence of long-bone fractures was 16.93 per 1000 patient-years, with the femoral neck being the most common site (59.8%); multivariate analysis revealed greater risk with older age, female gender, diabetes, more years receiving dialysis, and cardiovascular disease, and lower risk with African American race, increasing body mass index, parathyroid hormone values in the fourth quintile (227.1-538.0 pg/mL), and renal transplantation during followup. Postfracture mortality rates were 522.57 per 1000 patient years (versus 215.35 in the overall population). Time-dependent analysis suggested the adverse prognosis of long-bone fractures was related to subsequent congestive heart failure, stroke, pulmonary embolism, pneumonia, and septicemia. Long-bone fractures are common in patients receiving dialysis; their adverse prognostic implications may be linked to major cardiovascular and infectious events.