Frequency of Transition From Stage A to Stage B Heart Failure After Initiating Potentially Cardiotoxic Chemotherapy.
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SUBMITTER: Jones DN
PROVIDER: S-EPMC6857792 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
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Frequency of Transition From Stage A to Stage B Heart Failure After Initiating Potentially Cardiotoxic Chemotherapy.
Jones Deanna N DN Jordan Jennifer H JH Meléndez Giselle C GC Lamar Zanetta Z Thomas Alexandra A Kitzman Dalane W DW Suerken Cynthia C D'Agostino Ralph B RB Hundley W Gregory WG
JACC. Heart failure 20181107 12
<h4>Objectives</h4>This study sought to determine the prevalence of American Heart Association/American College of Cardiology Foundation (AHA/ACCF) heart failure (HF) stages after potentially cardiotoxic chemotherapy was initiated.<h4>Background</h4>For individuals receiving potentially cardiotoxic chemotherapy, the frequency of transitioning from Stage A to more advanced HF stages is not well described.<h4>Methods</h4>In 143 Stage A HF patients with breast cancer, lymphoma and leukemia, renal c ...[more]
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Project description:RationaleCardiotoxic β1 adrenergic receptor (β1AR)-CaMKII (calmodulin-dependent kinase II) signaling is a major and critical feature associated with development of heart failure. SAP97 (synapse-associated protein 97) is a multifunctional scaffold protein that binds directly to the C-terminus of β1AR and organizes a receptor signalosome.ObjectiveWe aim to elucidate the dynamics of β1AR-SAP97 signalosome and its potential role in chronic cardiotoxic β1AR-CaMKII signaling that contributes to development of heart failure.Methods and resultsThe integrity of cardiac β1AR-SAP97 complex was examined in heart failure. Cardiac-specific deletion of SAP97 was developed to examine β1AR signaling in aging mice, after chronic adrenergic stimulation, and in pressure overload hypertrophic heart failure. We show that the β1AR-SAP97 signaling complex is reduced in heart failure. Cardiac-specific deletion of SAP97 yields an aging-dependent cardiomyopathy and exacerbates cardiac dysfunction induced by chronic adrenergic stimulation and pressure overload, which are associated with elevated CaMKII activity. Loss of SAP97 promotes PKA (protein kinase A)-dependent association of β1AR with arrestin2 and CaMKII and turns on an Epac (exchange protein directly activated by cAMP)-dependent activation of CaMKII, which drives detrimental functional and structural remodeling in myocardium. Moreover, we have identified that GRK5 (G-protein receptor kinase-5) is necessary to promote agonist-induced dissociation of SAP97 from β1AR. Cardiac deletion of GRK5 prevents adrenergic-induced dissociation of β1AR-SAP97 complex and increases in CaMKII activity in hearts.ConclusionsThese data reveal a critical role of SAP97 in maintaining the integrity of cardiac β1AR signaling and a detrimental cardiac GRK5-CaMKII axis that can be potentially targeted in heart failure therapy. Graphical Abstract: A graphical abstract is available for this article.
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Project description:Background: Patients with heart failure (HF) experience a major symptom burden and an overall reduction of quality of life. However, supportive care (SC) remains an under-utilized resource for these patients. Among the many existing barriers to integrating SC into routine care, identifying patients with SC needs remains challenging. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is an important predictor of SC needs in patients with HF. Methods and Results: We used the shortened version KCCQ-12 as a screening tool for SC need in our ambulatory HF patient population using a KCCQ-12 summary score of <29 as the cut-off. Of the 456 patients who completed the KCCQ-12, 41 (9%) were predicted to have SC needs. Demographics, medical history, biochemical parameters, echocardiographic assessment and medical treatment were similar between the two groups of patients. However, patients with KCCQ-12 <29 were more symptomatic based on both New York Heart Association (NYHA) classification and American Heart Association (AHA) staging with a higher prevalence of depression. We established a multidisciplinary SC clinic and the profile and outcomes of patients with SC needs that were referred and followed at our SC clinic were also evaluated. Twenty-three patients were referred to our SC clinic: 2 died before being seen, 1 refused SC and 20 received SC. Of these 20 patients, 11 died and 9 are currently being followed. Median survival after starting the SC clinic is 3 months. In the original SC cohort of 23, 17 patients had available KCCQ-12 summary scores. However, only 6 out of 17 (35%) had KCCQ-12 scores <29, indicating the need for additional assessment tools in this patient population. Conclusions: The magnitude of unmet supportive care needs in patients with HF is significant. While the KCCQ-12 questionnaire is a useful tool to identify patients with SC, serial clinical evaluation, establishment of a SC clinic and prompt referral are essential for patients needing supportive care.
| S-EPMC6817607 | biostudies-literature
Project description:AimsWe investigated whether addition of diastolic dysfunction (DD) and longitudinal strain (LS) to Stage B heart failure (SBHF) criteria (structural or systolic abnormality) improves prediction of symptomatic HF in participants of the SCReening Evaluation of the Evolution of New Heart Failure study, a self-selected population at increased cardiovascular disease risk recruited from members of a health insurance fund in Melbourne and Shepparton, Australia. Both American Society of Echocardiography and European Association of Cardiovascular Imaging (ASE/EACVI) criteria and age-specific Atherosclerosis Risk in Communities (ARIC) study criteria, for SBHF and DD, and ARIC criteria for abnormal LS, were examined.Methods and resultsInclusion criteria were age ≥60 years with one or more of self-reported ischaemic or other heart disease, irregular or rapid heart rhythm, cerebrovascular disease, renal impairment, or treatment for hypertension or diabetes for ≥2 years. Exclusion criteria were known HF, or ejection fraction <50% or >mild valve abnormality detected on previous echocardiography or other imaging. Echocardiography was performed in 3190 participants who were followed for a median of 3.9 (interquartile range: 3.4, 4.5) years after echocardiography. Symptomatic HF was diagnosed in 139 participants at a median of 3.1 (interquartile range: 2.1, 3.9) years after echocardiography. ARIC structural, systolic, and diastolic abnormalities predicted HF in univariate and multivariable proportional hazards analyses, whereas ASE/EACVI structural and systolic, but not diastolic, abnormalities predicted HF. ARIC and ASE/EACVI SBHF criteria predicted HF with sensitivities of 81% and 55%, specificities of 39% and 76%, and C statistics of 0.60 (95% confidence interval: 0.57, 0.64) and 0.66 (0.61, 0.71), respectively. Adding ARIC DD to SBHF increased sensitivity to 94% with specificity of 24% and C statistic of 0.59 (0.57, 0.61), whereas addition of ASE/EACVI DD to SBHF increased sensitivity to 97% but reduced specificity to 9% and the C statistic to 0.52 (0.50, 0.54, P < 0.0001). Addition of LS to ARIC or ASE/EACVI SBHF criteria had minimal impact on prediction of HF.ConclusionsAge-specific ARIC DD criteria, but not ASE/EACVI DD criteria, predicted symptomatic HF, and addition of age-specific ARIC DD criteria to ARIC SBHF criteria improved prediction of symptomatic HF in asymptomatic individuals with cardiovascular disease risk factors. Addition of LS to ASE/EACVI or ARIC SBHF criteria did not improve prediction of symptomatic HF.
| S-EPMC6676278 | biostudies-literature
Project description:BACKGROUND:Depression in congestive heart failure (CHF) patients can increase morbidity and mortality. Given the ever-rising prevalence of CHF patients with depression, it is vital that we understand the predictors of depression in these patients to identify and better manage these patients. The main objective of this study was to evaluate the frequency and predictors of depression in CHF patients. METHODS:A cross-sectional study was conducted in a tertiary care hospital. Patients with a diagnosis of CHF for more than 6 months based on signs and left ventricular ejection fraction <40% were included. Patients were interviewed with the Patient Health Questionnaire-9 (PHQ-9) consisting of nine items in line with the Diagnostic and Statistical Manual (DSM) - IV criteria to assess depression. Each item was scored from 0 to 3, and a PHQ-9 score of 10 or greater suggested clinical depression. Data were analyzed on SPSS, v22, and a p < 0.05 was considered significant. RESULTS:Of 170 participants, 102 (60%) had depression. Among these 102 patients, 42% (n = 43) had mild depression, and the rest (n = 59) had moderate-to-severe depression. Predictors of depression were New York Heart Association stage 3 or 4 (p = 0.001), previous myocardial infarction (p = 0.001), living without a partner (p = 0.001), lack of a joint family system (p = 0.001), sedentary lifestyle (p = 0.001), aged 70 years or more (p = 0.01), and having been admitted in a hospital at least once in the past two months (p = 0.002). CONCLUSION:Depression is common among patients with CHF. It is associated with multiple factors and needs to be addressed and targeted urgently.
| S-EPMC6309877 | biostudies-literature
Project description:Background and Purpose:Even though new cancer therapies have improved the overall survival, in some cases they have been associated with adverse effects, including increased cardiotoxicity. The purpose of the present study was to assess the cardiovascular effects of adjuvant chemotherapy for colorectal cancer and mainly the impact on arterial stiffness indices. Material and Methods:A total of 70 patients with non-metastatic colorectal cancer who were treated either with FOLFOX (n=16) or with XELOX (n=54) adjuvant chemotherapy were included in the study. All patients were subjected to full cardiovascular evaluation at the beginning and the end of chemotherapy. Arterial stiffness was assessed by means of pulse wave velocity (PWV) and augmentation index (Aix) and full laboratory examinations were conducted prior to, and soon after, the termination of chemotherapy. Results:Patients exhibited significantly higher levels of carotid-radial PWV, carotid femoral RWV and Aix post-chemotherapy (p<0.001); these findings remained significant when examined separately in each treatment subgroup (FOLFOX, XELOX). The observed changes were independent of treatment regimen and baseline patient characteristics. Univariate regression analyses showed that baseline PWVc-r and PWVc-f were the only factors associated with PWVc-r and PWVc-f change, while Aix change was independent of its baseline value. Conclusion:There is a clear burden in arterial stiffness indices post-adjuvant chemotherapy for colorectal cancer in both chemotherapy groups. This is a finding of important clinical significance, however more prospective studies are required in order to encode the possible mechanisms involved.
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Project description:BackgroundCardiovascular disease (CVD) and cancer are leading causes of death and people with cancer are at higher risk of developing CVD than the general population. Many cancer medicines have cardiotoxic effects but the size of the population exposed to these potentially cardiotoxic medicines is not known. We aimed to determine the prevalence of exposure to potentially cardiotoxic cancer medicines in Australia.MethodsWe identified potentially cardiotoxic systemic cancer medicines through searching the literature and registered product information documents. We conducted a retrospective cohort study of Australians dispensed potentially cardiotoxic cancer medicines between 2005 and 2021, calculating age-standardised annual prevalence rates of people alive with exposure to a potentially cardiotoxic medicine during or prior to each year of the study period.FindingsWe identified 108,175 people dispensed at least one potentially cardiotoxic cancer medicine; median age, 64 (IQR: 52-74); 57% female. Overall prevalence increased from 49 (95%CI: 48.7-49.3)/10,000 to 232 (95%CI: 231.4-232.6)/10,000 over the study period; 61 (95%CI: 60.5-61.5)/10,000 to 293 (95%CI: 292.1-293.9)/10,000 for females; and 39 (95%CI: 38.6-39.4)/10,000 to 169 (95%CI: 168.3-169.7)/10,000 for males. People alive five years following first exposure increased from 29 (95%CI: 28.8-29.2)/10,000 to 134 (95%CI: 133.6-134.4)/10,000; and from 22 (95%CI: 21.8-22.2)/10,000 to 76 (95%CI: 75.7-76.3)/10,000 for those alive at least 10 years following first exposure. Most people were exposed to only one potentially cardiotoxic medicine, rates of which increased from 39 (95%CI: 38.7-39.3)/10,000 in 2005 to 131 (95%CI: 130.6-131.4)/10,000 in 2021.InterpretationThe number of people exposed to efficacious yet potentially cardiotoxic cancer medicines in Australia is growing. Our findings can support the development of service planning and create awareness about the magnitude of cancer treatment-related cardiotoxicities.FundingNHMRC Centre for Research Excellence in Medicines Intelligence, Cancer Institute NSW Early Career Fellowship.
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Project description:BackgroundAcute decompensated heart failure (ADHF) can be confused with other conditions that cause dyspnea. Patients with ADHF are often simultaneously treated for community-acquired pneumonia (CAP), even when evidence for infection is lacking. We hypothesized that the fluid and sodium content of potentially unnecessary intravenous antibiotic (IVAB) therapy could worsen outcomes of ADHF patients.MethodsWe reviewed 144 ADHF patients at low risk of pneumonia based on diagnostic findings and clinical documentation. The primary end point was length of stay. Secondary outcomes were mortality, readmission rates, amount of diuretic received, and fluid volume and quantity of sodium administered as part of IVAB therapy.ResultsOf the 144 admissions reviewed, 88 did not and 56 did receive IVAB. IVAB-treated patients received an average of 1.7 L of additional fluid (230 mL/d) and 9311 mg of additional sodium (1381 mg/d) as a result of IVAB therapy. Length of stay was longer in the IVAB arm (6.6 days) compared with the no-IVAB arm (3.0 days; P < .001). Patients required more furosemide in the IVAB arm (930 mg) compared with the no-IVAB arm (320 mg; P < .001). Patients who received IVAB were also 2.51 times more likely to be readmitted compared with patients who did not receive IVAB (P = .04).ConclusionsADHF patients who received IVAB without evidence of infection had longer lengths of stay, required more diuretics, and were more likely to be readmitted compared with ADHF patients not exposed to IVAB. ADHF patients are a promising target of antibiotic stewardship interventions.
| S-EPMC6559271 | biostudies-literature
Project description:BackgroundThe prognosis of heart failure (HF) after early stage breast cancer (EBC) treatment with anthracyclines or trastuzumab is not well-characterized.MethodsUsing administrative databases, women diagnosed with HF after receiving anthracyclines or trastuzumab for EBC in Ontario during 2007 to 2017 (the EBC-HF cohort) were categorized by cardiotoxic exposure (anthracycline alone, trastuzumab alone, sequential therapy with both agents) and matched on age with ≤3 cancer-free HF controls to compare baseline characteristics. To study prognosis after HF onset, we conducted a second match on age plus important HF prognostic factors. The cumulative incidence function was used to describe risk of hospitalization or emergency department visits (hospital presentations) for HF and cardiovascular death.ResultsA total of 804 women with EBC developed HF after anthracyclines (n=312), trastuzumab (n=112), or sequential therapy (n=380); they had significantly fewer comorbidities than 2411 age-matched HF controls. After the second match, the anthracycline-HF cohort had a similar 5-year incidence of HF hospital presentations (16.5% [95% CI, 12.0%-21.7%]) as controls (17.1% [95% CI, 14.4%-20.1%]); the 5-year incidence was lower than matched controls for the trastuzumab-HF (9.7% [95% CI, 4.7%-16.9%]; controls 16.4% [95% CI, 12.1%-21.3%]; P=0.03) and sequential-HF cohorts (2.7% [95% CI, 1.4%-4.8%]; controls 10.8% [95% CI, 8.9%-13.0%]; P<0.001). At 5 years, the incidence of cardiovascular death was 2.9% (95% CI, 1.2%-5.9%) in the anthracycline-HF cohort vs. 9.5% (95% CI, 6.9%-12.6%) in controls, and 1.7% (0.6%-3.7%) for women developing HF after trastuzumab vs. 4.3% (95% CI, 3.1-5.8%) for controls.ConclusionsWomen developing HF after cardiotoxic EBC chemotherapy have fewer comorbidities than cancer-free women with HF; trastuzumab-treated women who develop HF have better prognosis than matched HF controls.
| S-EPMC8288484 | biostudies-literature
Project description:Background Transcriptomic studies have contributed to fundamental knowledge of myocardial remodeling in human heart failure (HF). However, the key HF genes reported are often inconsistent between studies, and systematic efforts to integrate evidence from multiple patient cohorts are lacking. Here, we aimed to provide a framework for comprehensive comparison and analysis of publicly available data sets resulting in an unbiased consensus transcriptional signature of human end-stage HF. Methods and Results We curated and uniformly processed 16 public transcriptomic studies of left ventricular samples from 263 healthy and 653 failing human hearts. First, we evaluated the degree of consistency between studies by using linear classifiers and overrepresentation analysis. Then, we meta-analyzed the deregulation of 14 041 genes to extract a consensus signature of HF. Finally, to functionally characterize this signature, we estimated the activities of 343 transcription factors, 14 signaling pathways, and 182 micro RNAs, as well as the enrichment of 5998 biological processes. Machine learning approaches revealed conserved disease patterns across all studies independent of technical differences. These consistent molecular changes were prioritized with a meta-analysis, functionally characterized and validated on external data. We provide all results in a free public resource (https://saezlab.shinyapps.io/reheat/) and exemplified usage by deciphering fetal gene reprogramming and tracing the potential myocardial origin of the plasma proteome markers in patients with HF. Conclusions Even though technical and sampling variability confound the identification of differentially expressed genes in individual studies, we demonstrated that coordinated molecular responses during end-stage HF are conserved. The presented resource is crucial to complement findings in independent studies and decipher fundamental changes in failing myocardium.
| S-EPMC8174362 | biostudies-literature
Project description:BackgroundAlthough human studies have shown that inflammation plays a role in the development of congestive heart failure, scarce information exists on white blood cell count (WBC) and differential cell counts in various stages of heart failure in man and dogs. A few studies demonstrated increased concentrations of C-reactive protein (CRP), a major acute-phase protein, in cardiac diseases in dogs. Our research aimed to investigate whether CRP concentration, WBC and neutrophil count (NEUT), as markers of systemic inflammation, are elevated in canine cardiovascular patients. We also aimed to find out whether there is an association between CRP concentration and WBC and NEUT, as well as associations between these inflammatory markers and selected echocardiographic parameters. Sixty-two client-owned canine cardiac patients and 12 healthy dogs were included in the study. The patients were classified into International Small Animal Cardiac Health Council classes (ISACHC I-III). The serum CRP concentration was determined using a canine CRP test kit. WBC and NEUT were determined using an automated hematology analyzer.ResultsSignificantly higher serum CRP concentration, WBC and NEUT were found in the decompensated stage of heart failure (ISACHC III) compared with healthy dogs and with patients in ISACHC group II and ISACHC group I. Serum CRP concentration significantly positively correlated with WBC (r = 0.65, P < 0.001) and NEUT (r = 0.58, P = 0.002) in the ISACHC III group, while no significant correlations were found in the ISACHC I and II groups. A significant negative correlation between serum CRP concentration and the left ventricular ejection fraction (r = - 0.49, P = 0.046) and a significant positive correlation between CRP and the E wave velocity of the mitral valve inflow (r = 0.52, P = 0.046) were found in the ISACHC III group.ConclusionsThe CRP concentration, WBC and NEUT were significantly increased in advanced-stage heart failure patients in comparison with compensated patients and healthy dogs, which indicate the presence of systemic inflammation. However, normal CRP concentration and normal WBC and NEUT can also be present in heart failure.
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