Failure In Survivors Research Articles

Comparing the impact of insufficient physical activity on cardiovascular disease in survivors of childhood Hodgkin lymphoma and sibling controls: A report from the Childhood Cancer Survivor Study (CCSS).

10024 Background: Survivors of childhood Hodgkin lymphoma are at increased risk of cardiovascular disease (CVD) from anthracycline and radiation exposures. Whether the treatment-induced risk can be mitigated with physical activity is not known. We aimed to compare the impact of insufficient physical activity on CVD in Hodgkin lymphoma survivors and controls. Methods: Participants in the Childhood Cancer Survivor Study (CCSS) reported physical activity, which was translated into metabolic equivalent of task hours/week (MET) and categorized as 0, 1-8, or ≥9 METs. We estimated rate ratios (RR) for new onset (incident) congestive heart failure and any CVD (including heart attack, congestive heart failure, arrhythmia, and valvular disease requiring interventions) during follow-up, accounting for age, sex, race/ethnicity, smoking, risky drinking, overweight/obesity, and treatment exposures (survivors only). Then we calculated population attributable fractions (PAF) for insufficient physical activity (< 9 METs). The attributable relative rate (ARR) was calculated by multiplying the PAF in survivors with the RR for CVD incidence in survivors compared to controls, resulting in an ARR for survivors that was compared to the PAF in controls. Results: In 2,357 Hodgkin survivors [50% female; [mean (SD)] 14.3 (4.1) years at diagnosis; 31.6 (5.8) years at start of follow-up, and 17.8 (7.6) years from diagnosis] and 3,949 sibling controls, 233 survivors and 19 controls developed congestive heart failure. 462 survivors and 95 controls developed any CVD. The PAF for congestive heart failure attributable to insufficient physical activity was larger in controls (38.0%) than survivors (22.3%). However, with RR 20.3 (95% CI 12.6-32.5) for congestive heart failure for survivors compared to controls, the ARR in survivors (452.1%) revealed a 12 times higher incidence of congestive heart failure attributable to insufficient physical activity in Hodgkin survivors than in controls (452.1%/38.0%). The ARR indicates that 4.5 of the 20-fold higher risk of congestive heart failure in survivors vs. siblings is attributable to insufficient physical activity in the survivors. For any CVD, the PAFs were comparable in survivors (13.7%) and controls (11.7%). With RR 10.2 (95% CI 8.2-12.7) for any CVD for survivors compared to controls, the ARR for any CVD in survivors (139.7%) was also 12 times higher than the incidence attributable to insufficient physical activity in controls (139.7%/11.7%). Conclusions: Our results suggest that the magnitude of treatment-induced CVD risk that can be mitigated by physical activity is considerable. This offers a modifiable target and provides rationale for exercise interventions aimed at reducing CVD in survivors at high risk.

Coronary Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation

Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest (OHCA). The long-term effect of early coronary angiography on patients with OHCA with possible coronary trigger but no ST-segment elevation remains unclear. To compare the clinical outcomes of early unselective angiography with the clinical outcomes of a delayed or selective approach for successfully resuscitated patients with OHCA of presumed cardiac origin without ST-segment elevation at 1-year follow-up. The TOMAHAWK trial was a multicenter, international (Germany and Denmark), investigator-initiated, open-label, randomized clinical trial enrolling 554 patients between November 23, 2016, to September 20, 2019. Patients with stable return of spontaneous circulation after OHCA of presumed cardiac origin but without ST-segment elevation on the postresuscitation electrocardiogram were eligible for inclusion. A total of 554 patients were randomized to either immediate coronary angiography after hospital admission or an initial intensive care assessment with delayed or selective angiography after a minimum of 24 hours. All 554 patients were included in survival analyses during the follow-up period of 1 year. Secondary clinical outcomes were assessed only for participants alive at 1 year to account for the competing risk of death. Early vs delayed or selective coronary angiography and revascularization if indicated. Evaluations in this secondary analysis included all-cause mortality after 1 year, as well as severe neurologic deficit, myocardial infarction, and rehospitalization for congestive heart failure in survivors at 1 year. A total of 281 patients were randomized to the immediate angiography group and 273 to the delayed or selective group, with a median age of 70 years (IQR, 60-78 years). A total of 369 of 530 patients (69.6%) were male, and 268 of 483 patients (55.5%) had a shockable arrest rhythm. At 1 year, all-cause mortality was 60.8% (161 of 265) in the immediate angiography group and 54.3% (144 of 265) in the delayed or selective angiography group without significant difference between the treatment strategies, trending toward an increase in mortality with immediate angiography (hazard ratio, 1.25; 95% CI, 0.99-1.57; P = .05). For patients surviving until 1 year, the rates of severe neurologic deficit, myocardial infarction, and rehospitalization for congestive heart failure were similar between the groups. This study found that a strategy of immediate coronary angiography does not provide clinical benefit compared with a delayed or selective invasive approach for patients 1 year after resuscitated OHCA of presumed coronary cause and without ST-segment elevation. ClinicalTrials.gov Identifier: NCT02750462.

Long-Term Follow up of Renal and Other Acute Organ Failure in Survivors of Critical Illness Due to Covid-19.

BackgroundLittle is known about the long-term health sequelae and outcomes of various organ failures in ICU survivors of Covid-19. The aim of our research was to study the characteristics of 120-day ICU survivors of the initial pandemic surge and report their long term (>6 months) outcomes.MethodsWe conducted a telephone questionnaire-based follow up study of 120- day survivors of Covid-19 admitted to ICUs at Montefiore Medical Center, Bronx, NY from 3/10/2020 to 4/11/2020. The study period was 2 months (11/1/2020-12/31/2020).Results126 out of 300 (42%) survived to 120-days post-hospital discharge. The median age of survivors was 54 (47-61) years. Seventy-eight (62%) patients developed acute kidney injury (AKI); thirty-five (44.9%) of them required renal replacement therapy (RRT). One hundred-five (83.3%) required invasive mechanical ventilation; ten of them required tracheotomy. 103 (81.7%) completed the telephone questionnaire-based study, at a median (IQR) of 216.5 (200-234.5) days after hospital discharge. 29 (28.2%) patients reported persistent shortness of breath, 24, (23.3%) complained of persistent cough, and persistent anosmia in 9 (8.8%). AKI resolved completely in 58 (74.4%) patients. Of 35 AKI patients who required initiation of RRT during hospitalization, 27 (77%) were liberated from RRT and 20 (57%) had resolution of AKI. Of 20 patients without AKI resolution, 12 developed chronic kidney disease, whereas 8 still require RRT. Thirty-three (32.4%) patients developed post-traumatic stress disorder (PTSD) and 10 (11.8%) reported major depression. Many of the patients (68%) regained baseline functional status. Readmissions occurred in 22.3% patients within first 6 months after discharge.ConclusionPersistent symptoms of long Covid have been reported in ICU survivors of Covid-19 for extended durations. Outcomes of Covid-19 associated acute kidney injury are excellent. There is a high incidence of PTSD and depression in COVID-19 ICU survivors. Functional outcomes are good, but these patients remain at increased risk of hospital readmission.

Late-onset kidney failure in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study

BackgroundThe incidence of and risk factors for late-onset kidney failure among survivors over the very long term remains understudied. Materials and methodsA total of 25,530 childhood cancer survivors (median follow-up 22.3 years, interquartile range 17.4–28.8) diagnosed between 1970 and 1999, and 5045 siblings from the Childhood Cancer Survivor Study were assessed for self-reported late-onset kidney failure, defined as dialysis, renal transplantation, or death attributable to kidney disease. Piecewise exponential models evaluated associations between risk factors and the rate of late-onset kidney failure. ResultsA total of 206 survivors and 10 siblings developed late-onset kidney failure, a 35-year cumulative incidence of 1.7% (95% confidence interval [CI] = 1.4–1.9) and 0.2% (95% confidence interval [CI] = 0.1–0.4), respectively, corresponding to an adjusted rate ratio (RR) of 4.9 (95% CI = 2.6–9.2). High kidney dose from radiotherapy (≥15Gy; RR = 4.0, 95% CI = 2.1–7.4), exposure to high-dose anthracycline (≥250 mg/m2; RR = 1.6, 95% CI = 1.0–2.6) or any ifosfamide chemotherapy (RR = 2.6, 95% CI = 1.2–5.7), and nephrectomy (RR = 1.9, 95% CI = 1.0–3.4) were independently associated with elevated risk for late-onset kidney failure among survivors. Survivors who developed hypertension, particularly in the context of prior nephrectomy (RR = 14.4, 95% CI = 7.1–29.4 hypertension with prior nephrectomy; RR = 5.9, 95% CI = 3.3–10.5 hypertension without prior nephrectomy), or diabetes (RR = 2.2, 95%CI = 1.2–4.2) were also at elevated risk for late-onset kidney failure. ConclusionsSurvivors of childhood cancer are at increased risk for late-onset kidney failure. Kidney dose from radiotherapy ≥15 Gy, high-dose anthracycline, any ifosfamide, and nephrectomy were associated with increased risk of late-onset kidney failure among survivors. Successful diagnosis and management of modifiable risk factors such as diabetes and hypertension may mitigate the risk for late-onset kidney failure. The association of late-onset kidney failure with anthracycline chemotherapy represents a novel finding that warrants further study.

Heart failure in survivors of out-of-hospital cardiac arrest – factors associated with reduced systolic ventricular function at follow-up

Abstract Background Survival after out-of-hospital cardiac arrest (OHCA) has increased in recent years but is still only 10%. Little is known about the association between post-resuscitation comorbidity and heart failure after discharge from the initial OHCA-admission. Purpose In OHCA-survivors we aimed to describe predictors of left ventricular (LV) dysfunction, defined as LV ejection fraction (LVEF) <40%, at follow-up. Methods A consecutive cohort of OHCA-patients with cardiac cause from 2007 to 2011 without a pre-OHCA congestive heart failure diagnosis (according to the Danish National Patient Registry, which holds data on all Danish citizens) were retrospectively examined. Logistic regression analyses were used to assess factors associated with LV dysfunction (LVEF <40%) at follow-up after a median of 6 months. Follow-up was not performed systematically in the OHCA-survivors and data from follow-up was assessed by reading of patient charts. Results A total of 365 OHCA-survivors with a mean age of 61 years were discharged alive from hospital. LVEF <40% at hospital discharge was seen in 54% (n=184, 7% missing), and at follow-up after a median of 6 months 19% (n=69) of the total OHCA-cohort of survivors still had LV dysfunction. Factors associated with LV dysfunction at follow-up were chronic ischemic heart disease (IHD) prior to OHCA (odds ratio (OR) = 2.9 (95% CI: 1.2 – 7.1)) and ST-elevation myocardial infarction (STEMI) as cause of OHCA (OR = 2.9 (1.4–6.0)), whereas age, gender, high comorbidity burden prior to OHCA or pre-hospital circumstances (including shockable cardiac arrest rhythm) were not. Conclusion More than half of OHCA-survivors with LVEF <40% at hospital discharge improved LV function and LV dysfunction at follow-up after a median of 6 months after discharge was present in 1 in 5 (19%) of the cohort. Chronic IHD and STEMI were the only factors significantly associated with LV dysfunction at follow-up. A systematic follow-up including echocardiography in the outpatient clinic for OHCA-survivors is recommended especially in patients with reduced LV function at discharge and in STEMI-patients in order to assess the appropriateness of heart failure medication and an implantable cardiac defibrillator. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Foundation Trygfonden

Cost-Effectiveness of the International Late Effects of Childhood Cancer Guideline Harmonization Group Screening Guidelines to Prevent Heart Failure in Survivors of Childhood Cancer.

Survivors of childhood cancer treated with anthracyclines and/or chest-directed radiation are at increased risk for heart failure (HF). The International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms, but evidence supporting its frequency and cost-effectiveness is limited. Using the Childhood Cancer Survivor Study and St Jude Lifetime Cohort, we developed a microsimulation model of the clinical course of HF. We estimated long-term health outcomes and economic impact of screening according to IGHG-defined risk groups (low [doxorubicin-equivalent anthracycline dose of 1-99 mg/m2 and/or radiotherapy < 15 Gy], moderate [100 to < 250 mg/m2 or 15 to < 35 Gy], or high [≥ 250 mg/m2 or ≥ 35 Gy or both ≥ 100 mg/m2 and ≥ 15 Gy]). We compared 1-, 2-, 5-, and 10-year interval-based screening with no screening. Screening performance and treatment effectiveness were estimated based on published studies. Costs and quality-of-life weights were based on national averages and published reports. Outcomes included lifetime HF risk, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs < $100,000 per QALY gained were considered cost-effective. Among the IGHG risk groups, cumulative lifetime risks of HF without screening were 36.7% (high risk), 24.7% (moderate risk), and 16.9% (low risk). Routine screening reduced this risk by 4% to 11%, depending on frequency. Screening every 2, 5, and 10 years was cost-effective for high-risk survivors, and every 5 and 10 years for moderate-risk survivors. In contrast, ICERs were > $175,000 per QALY gained for all strategies for low-risk survivors, representing approximately 40% of those for whom screening is currently recommended. Our findings suggest that refinement of recommended screening strategies for IGHG high- and low-risk survivors is needed, including careful reconsideration of discontinuing asymptomatic left ventricular dysfunction and HF screening in low-risk survivors.

Innate immune response in the pathogenesis of heart failure in survivors of myocardial infarction.

Among the different cardiovascular disease complications, atherosclerosis-induced myocardial infarction (MI) is the major contributor of heart failure (HF) and loss of life. This review presents short- and long-term features of post-MI in human hearts and animal models. It is known that the heart does not regenerate, and thus loss of cardiac cells after an MI event is permanent. In survivors of a heart attack, multiple neurohumoral adjustments as well as simultaneous remodeling in both infarcted and noninfarcted regions of the heart help sustain pump function post-MI. In the early phase, migration of inflammatory cells to the infarcted area helps repair and remove the cell debris, while apoptosis results in the elimination of damaged cardiomyocytes, and there is an increase in the antioxidant response to protect the survived myocardium against oxidative stress (OS) injury. However, in the late phase, it appears that there is a relative increase in OS and activation of the innate inflammatory response in cardiomyocytes without any obvious inflammatory cells. In this late stage in survivors of MI, a progressive slow activation of these processes leads to apoptosis, fibrosis, cardiac dysfunction, and HF. Thus, this second phase of an increase in OS, innate inflammatory response, and apoptosis results in wall thinning, dilatation, and consequently HF. It is important to note that this inflammatory response appears to be innate to cardiomyocytes. Blunting of this innate immune cardiomyocyte response may offer new hope for the management of HF.

Modeling Radiation Therapy-Related Risk of Heart Failure in Survivors of Pediatric Malignancy: Early Results from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) Group

Cardiac disease is the most common cause of non-cancer mortality among long-term survivors of pediatric cancer; radiation therapy (RT) is a risk factor for late cardiotoxicity. The PENTEC cardiovascular task force aims to quantify radiation dose effects and the impact of critical risk factors. Through systemic review, including a meta-analysis of the available literature, we describe the relationships between heart failure (HF) and RT, as well as the influence of anthracycline chemotherapy, age, and gender. We conducted PubMed searches of peer-reviewed manuscripts published January 1, 1995, to October 2, 2017, evaluating HF among survivors of childhood cancer who received RT. Overall, 1,496 reports were identified, 148 were fully reviewed, and 5 had adequate data for modelling as described herein (Table). Patients were treated between 1966 and 1998, before the age of 18 years. HF diagnosis was based on CTCAE criteria, physician diagnosis, or patient reporting; all patients diagnosed were symptomatic. Heart dose was determined by either dose reconstruction or prescribed dose to an RT field including the heart. Meta-analysis hazard ratios for RT dose, anthracycline dose, gender, and age were determined using the inverse variance method based on multivariate, mutually adjusted models in the contributing reports. The population analyzed included 32,395 survivors; 614 events of HF were identified. The population-weighted mean incidence of HF at 20 years was 2.2%. For each 10 Gy increase in mean cardiac dose, the relative increase in HF risk was 50% (hazard ratio [HR] = 1.50; 95% CI = 1.41 – 1.60). Similarly, for each 100 mg/m2 increase in cumulative anthracycline dose, relative HF risk increased by 60% (HR = 1.60; 95% CI = 1.55 – 1.66). Younger age at diagnosis was associated with increased HF risk; every 5 years below 15 years of age increased the relative HF risk by 83% (HR = 1.83; 95% CI = 1.52 – 2.20). Female gender also increased HF risk (HR = 1.61; 95% CI = 1.35 – 1.93). This meta-analysis quantifies the dose relationship between cardiac RT and late HF, and identifies anthracycline dose, young age, and female gender as risk factors. Each 10 Gy of mean cardiac RT and each 100 mg/m2 of cumulative anthracycline dose results in a similar increase in the risk of HF. Further knowledge of the impact of these variables, especially the age-related vulnerabilities, helps inform clinical shared decision-making between providers, patients, and their families. This information will also inform future treatment protocols to minimize the late cardiac toxicity of cancer therapies.Abstract 105; TableIncluded StudiesCalculated HR per 10 Gy RT95% CIMulrooney, et al (2009)1.51.3 – 1.6Van der Pal, et al (2012)1.41.1 – 2.0Green, et al (2001)1.81.1 – 2.7Chow, et al (2015)1.71.5 – 1.9Schellong, et al (2010)––Meta-Value1.51.4 – 1.6 Open table in a new tab

Ischemic Bowel Disease Due to Superior Mesenteric Artery Occlusion: A Case Report

Acute mesenteric infarction is a rare but emergency disease with a high mortality rate. The rapidly restoration of intestinal blood flow is the early goal of vascular intervention. However, the unspecific presentation may confuse physicians and delay a timely diagnosis. The rate of intestinal failure in survivors is still high. Here, we present the case of an 85-year-old male presenting with acute onset progressive periumbilical cramping pain with elevated D-dimer. The abdominal computed tomography (CT) revealed severe acute superior mesenteric artery occlusion. The surgical report showed a massively ischemic small intestine that was about 250 cm with 200 mL bloody ascites. We highlight that early diagnosis and timely intervention are important for improving outcomes.

Modeling Acute Traumatic Hemorrhagic Shock Injury: Challenges and Guidelines for Preclinical Studies.

Trauma is responsible for a large proportion of the world's burden of disease, and is by far the biggest killer of young adults. Hemorrhage is the leading cause of preventable death and its effects are directly correlated with the incidence multi-organ failure in survivors. Trauma research is challenging due to patient heterogeneity, limited randomized controlled trials, and in vitro studies that fail to mimic the systemic injury response. Preclinical research remains essential for mechanistic and therapeutic discovery. Yet modeling the multifaceted nature of traumatic injury poses important experimental and welfare challenges associated with the onset of injury and prehospital and intra-operative care, the limited inter-species validation of coagulation profiles, the use of anesthesia/analgesia, and its impact on the systemic response to trauma; and the challenge of sustaining intensive care in recovery models. Proper model selection depends on the purpose of a given model and the criteria by which the experimental readouts will be clinically relevant. Such complexity warrants further refinement of experimental methodology and outcome measures to improve its clinical efficacy, while ensuring animal well-being. We review the experimental methodologies currently used for modeling traumatic hemorrhagic shock and addressing their impact on clinical translation. The aim of the review is to improve transparency and form a consensus when reporting methodology in trauma modeling.

Risk of heart failure in survivors of Hodgkin lymphoma: effects of cardiac exposure to radiation and anthracyclines

AbstractHodgkin lymphoma (HL) survivors treated with radiotherapy and/or chemotherapy are known to have increased risks of heart failure (HF), but a radiation dose-response relationship has not previously been derived. A case-control study, nested in a cohort of 2617 five-year survivors of HL diagnosed before age 51 years during 1965 to 1995, was conducted. Cases (n = 91) had moderate or severe HF as their first cardiovascular diagnosis. Controls (n = 278) were matched to cases on age, sex, and HL diagnosis date. Treatment and follow-up information were abstracted from medical records. Mean heart doses and mean left ventricular doses (MLVD) were estimated by reconstruction of individual treatments on representative computed tomography datasets. Average MLVD was 16.7 Gy for cases and 13.8 Gy for controls (Pdifference = .003). HF rate increased with MLVD: relative to 0 Gy, HF rates following MVLD of 1-15, 16-20, 21-25, and ≥26 Gy were 1.27, 1.65, 3.84, and 4.39, respectively (Ptrend < .001). Anthracycline-containing chemotherapy increased HF rate by a factor of 2.83 (95% CI: 1.43-5.59), and there was no significant interaction with MLVD (Pinteraction = .09). Twenty-five–year cumulative risks of HF following MLVDs of 0-15 Gy, 16-20 Gy, and ≥21 Gy were 4.4%, 6.2%, and 13.3%, respectively, in patients treated without anthracycline-containing chemotherapy, and 11.2%, 15.9%, and 32.9%, respectively, in patients treated with anthracyclines. We have derived quantitative estimates of HF risk in patients treated for HL following radiotherapy with or without anthracycline-containing chemotherapy. Our results enable estimation of HF risk for patients before treatment, during radiotherapy planning, and during follow-up.

OC-0059: A radiation dose-response relationship for risk of heart failure in survivors of Hodgkin lymphoma

OC-0059: A radiation dose-response relationship for risk of heart failure in survivors of Hodgkin lymphoma

Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure: Part I

In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. In this review, we evaluate the results obtained from four new therapeutic strategies: in this part we evaluate gene therapy and novel aspect of stem cells therapy in remodeling; in the second part we will investigate, micro-RNA, posttranslational modification and microspheres based therapy.

Anti remodeling therapy: new strategies and future perspective in post-ischemic heart failure. Part II

In recent years, the remarkable progress achieved in terms of survival after myocardial infarction have led to an increased incidence of chronic heart failure in survivors. This phenomenon is due to the still incomplete knowledge we possess about the complex pathophysiological mechanisms that regulate the response of cardiac tissue to ischemic injury. These involve various cell types such as fibroblasts, cells of the immune system, endothelial cells, cardiomyocytes and stem cells, as well as a myriad of mediators belonging to the system of cytokines and not only. In parallel with the latest findings on post-infarct remodeling, new potential therapeutic targets are arising to halt the progression of disease. After the evaluation of the results obtained from gene therapy and stem cells, in this part we evaluate micro-RNA, post-translational modification and microspheres based therapy.

Cost-effectiveness of the children's oncology group long-term follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure.

Childhood cancer survivors treated with anthracyclines are at high risk for asymptomatic left ventricular dysfunction (ALVD), subsequent heart failure, and death. The consensus-based Children's Oncology Group (COG) Long-Term Follow-up Guidelines recommend lifetime echocardiographic screening for ALVD. To evaluate the efficacy and cost-effectiveness of the COG guidelines and to identify more cost-effective screening strategies. Simulation of life histories using Markov health states. Childhood Cancer Survivor Study; published literature. Childhood cancer survivors. Lifetime. Societal. Echocardiographic screening followed by angiotensin-converting enzyme (ACE) inhibitor and β-blocker therapies after ALVD diagnosis. Quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in dollars per QALY, and cumulative incidence of heart failure. The COG guidelines versus no screening have an ICER of $61 500, extend life expectancy by 6 months and QALYs by 1.6 months, and reduce the cumulative incidence of heart failure by 18% at 30 years after cancer diagnosis. However, less frequent screenings are more cost-effective than the guidelines and maintain 80% of the health benefits. The ICER was most sensitive to the magnitude of ALVD treatment efficacy; higher treatment efficacy resulted in lower ICER. Lifetime non-heart failure mortality and the cumulative incidence of heart failure more than 20 years after diagnosis were extrapolated; the efficacy of ACE inhibitor and β-blocker therapy in childhood cancer survivors with ALVD is undetermined (or unknown). The COG guidelines could reduce the risk for heart failure in survivors at less than $100 000/QALY. Less frequent screening achieves most of the benefits and would be more cost-effective than the COG guidelines.

Genetic susceptibility to anthracycline-related congestive heart failure in survivors of haematopoietic cell transplantation.

Haematopoietic cell transplantation (HCT) survivors are at increased risk for developing congestive heart failure (CHF), primarily due to pre-HCT exposure to anthracyclines. We examined the association between the development of CHF after HCT and polymorphisms in 16 candidate genes involved in anthracycline metabolism, iron homeostasis, anti-oxidant defence, and myocardial remodelling. A nested case-control study design was used. Cases (post-HCT CHF) were identified from 2950 patients who underwent HCT between 1988 and 2007 at City of Hope and had survived ≥1 year. This cohort formed the sampling frame for selecting controls (without CHF) matched on: age, race/ethnicity, cumulative anthracycline exposure, stem cell source (allogeneic, autologous), and length of follow-up. Seventy-seven cases with pre-HCT germline DNA and 178 controls were genotyped. Multivariate analysis revealed that the odds of CHF was higher in females [Odds Ratio (OR) = 2·9, P < 0·01], individuals with pre-HCT chest radiation (OR = 4·7, P = 0·05), hypertension (OR = 2·9, P = 0·01), and with variants of genes coding for the NAD(P)H-oxidase subunit RAC2 (rs13058338, 7508T→A; OR = 2·8, P < 0·01), HFE (rs1799945, 63C→G; OR = 2·5, P = 0·05) or the doxorubicin efflux transporter ABCC2 (rs8187710, 1515G→A; OR = 4·3, P < 0·01). A combined (clinical and genetic) CHF predictive model performed better [area under the curve (AUC), 0·79] than the genetic (AUC = 0·67) or the clinical (AUC = 0·69) models alone.

Strategies to prevent anthracycline-related congestive heart failure in survivors of childhood cancer.

Cardiovascular complications are a leading cause of therapy-related morbidity and mortality in long-term survivors of childhood malignancy. In fact, childhood cancer survivors are at a 15-fold risk of developing CHF compared to age-matched controls. There is a strong dose-dependent association between anthracycline exposure and risk of CHF, and the incidence increases with longer followup. Outcome following diagnosis of CHF is generally poor, with overall survival less than 50% at 5 years. The growing number of childhood cancer survivors makes it imperative that strategies be developed to prevent symptomatic heart disease in this vulnerable population. We present here an overview of the current state of knowledge regarding primary, secondary, and tertiary prevention strategies for childhood cancer survivors at high risk for CHF, drawing on lessons learned from prevention studies in nononcology populations as well as from the more limited experience in cancer survivors.

Insulin-like growth factor binding protein-1 is a long-term predictor of heart failure in survivors of a first acute myocardial infarction and population controls

Background Only a few studies have investigated the prospective relationship between insulin-like growth factor binding protein-1 (IGFBP-1) and cardiovascular events and the results are conflicting. Methods In this prospective cohort study, we followed both cases, i.e. survivors of a first acute myocardial infarction (AMI) and their age, sex and hospital catchment area matched controls of a large population-based case–control study for 8 years for total and cardiac mortality, AMI, stroke and hospitalization for heart failure (HF). Levels of IGFBP-1 were measured three months after AMI in a stable metabolic phase in 853 patients. For 1106 control subjects, the time of measurement was as close as possible to that of ‘his/her’ case. Established cardiovascular risk and prognostic factors were also determined. Results Higher IGFBP-1 values predicted hospitalization for HF during follow-up both in the patient and the control cohort. Control subjects with higher IGFBP-1 values had elevated mortality when compared to those with the lowest quartile. The associations between IGFBP-1 and other outcomes investigated in this study, i.e. mortality among patients, AMI or stroke among patients and controls were weak and statistically not significant. Conclusions Levels of IGFBP-1 consistently predicted HF both among survivors of a first AMI and their matched controls. Our results suggest that IGFBP-1 levels might also predict mortality in a population free of previous AMI.

C-Terminal Provasopressin (Copeptin) is Associated With Left Ventricular Dysfunction, Remodeling, and Clinical Heart Failure in Survivors of Myocardial Infarction

Background Acute myocardial infarction (AMI) is associated with left ventricular (LV) dysfunction and clinical heart failure. Arginine vasopressin is elevated in heart failure and the C-terminal of provasopressin (Copeptin) is associated with adverse outcome post-AMI. The aim of this study was to describe the association between Copeptin with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Methods and Results We studied 274 subjects with AMI. Copeptin was measured from plasma at discharge and subjects underwent echocardiography at discharge and follow-up (median 155 days). Subjects were followed for clinical heart failure for a median of 381 days. Remodeling was assessed as the change (Δ) in LV volumes between echo examinations. Copeptin correlated directly with wall motion index score (WMIS) and inversely with LV ejection fraction (LVEF) at discharge (WMIS, r = 0.276, P < .001; LVEF, r = −0.188, P = .03) and follow-up (WMIS, r = 0.244, P < .001; LVEF, r = −0.270, P < .001) and with ventricular volumes at follow-up (LVEDV, r = 0.215, P = .002; LVESV, r = 0.299, P < .001). Copeptin was associated with ventricular remodeling; ΔEDV; r = 0.171, P = 0.015, ΔESV; r = 0.186, P = .008. Subjects with increasing LVESV had higher levels of Copeptin (median 6.30 vs. 5.75 pmol/L, P = .012). Subjects with clinical heart failure (n = 30) during follow-up had higher Copeptin before discharge (median 13.55 vs. 5.80, P < .001). In a Cox proportional hazards model, Copeptin retained association with clinical heart failure. Kaplan-Meier assessment revealed increased risk in subjects with Copeptin >6.31 pmol/L. Conclusions Copeptin is associated with LV dysfunction, volumes, and remodeling and clinical heart failure post-AMI. Measurement of Copeptin may provide prognostic information and the AVP system may be a therapeutic target in post-MI LV dysfunction.

38 C-Reactive protein on admission is an independent predictor of late development of heart failure in survivors of myocardial infarction. A prospective study

38 C-Reactive protein on admission is an independent predictor of late development of heart failure in survivors of myocardial infarction. A prospective study