Background--Although current guidelines emphasize the importance of social support to the success of left ventricular assist device (LVAD) therapy, few studies examine the influence of the caregiver on patient outcomes or quantify the impact of LVAD caregiving on caregiver outcomes. The purpose of this analysis was to identify patient and caregiver determinants of patient quality of life (QOL) and caregiver strain in response to LVAD therapy. Methods and Results--Data on patients receiving LVAD therapy and their caregivers (n=50 dyads) were prospectively collected pre-implantation and 1, 3, and 6 months post-implantation. Growth curve modeling was used to describe change in patient QOL (Kansas City Cardiomyopathy Questionnaire) and caregiver strain (Multidimensional Caregiver Strain Index). Patient QOL improved most in the first month (β=23.22±3.76, P < 0.001), followed by gradual gains over 6 months (β=1.90±0.64, P<0.01). Caregivers experienced worsening of strain in the first month (β=4.30±1.42, P < 0.01), followed by gradual resolution to pre-implantation levels by 6 months (β=-0.71±0.23, P < 0.01). Worse pre-implantation patient symptoms were associated with greater improvement in patient QOL (β=0.53±0.19, P < 0.01) but worsening caregiver strain (β=0.15±0.07, P=0.04). Better relationship quality was associated with greater improvement in patient QOL (β=14.39±5.85, P=0.01) and less pre-implantation caregiver strain (β=-9.31±2.28, P < 0.001). Nonspousal caregivers experienced less pre-implantation strain (β=-8.60±3.10, P=0.01), and patients with nonspousal caregivers had less improvement in QOL (β=-3.70±1.62, P=0.02). Conclusions--A combination of patient and caregiver characteristics predicts patient and caregiver response to LVAD therapy. Including caregiver factors in future studies may be helpful in developing interventions that improve patient and caregiver outcomes, together.
Objective: This report describes three patients with Ebola virus disease who were treated in the United States and developed for severe critical illness and multiple organ failure secondary to Ebola virus infection. The patients received mechanical ventilation, renal replacement therapy, invasive monitoring, vasopressor support, and investigational therapies for Ebola virus disease.
Data Sources: Patient medical records from three tertiary care centers (Emory University Hospital, University of Nebraska Medical Center, and Texas Health Presbyterian Dallas Hospital).
Study Selection: Not applicable.
Data Extraction: Not applicable.
Data Synthesis: Not applicable.
Conclusion: In the severe form, patients with Ebola virus disease may require life-sustaining therapy, including mechanical ventilation and renal replacement therapy. In conjunction with other reported cases, this series suggests that respiratory and renal failure may occur in severe Ebola virus disease, especially in patients burdened with high viral loads. Ebola virus disease complicated by multiple organ failure can be survivable with the application of advanced life support measures. This collective, multicenter experience is presented with the hope that it may inform future treatment of patients with Ebola virus disease requiring critical care treatment.
The relationship between kidney function and liver function has been investigated largely in the context of pathologic changes in advanced liver failure, and little is known about any physiologic responses to hepatic failure. Because both organs are responsible for clearing metabolic by-products, there may be renal compensation for decreased hepatic clearance. This possibility is supported by the fact that both kidney size and glomerular filtration rate vary with other alterations in metabolic demand, such as changes in body size or protein intake.1, 2 Our frequent finding of large kidneys during sonography in patients with end-stage liver disease supported the possibility that renal hypertrophy was occurring. This was investigated by measuring renal parenchymal volume (RPV) on computed tomography scans and examining autopsy findings in patients with or without end-stage liver disease and no clinical or radiologic evidence of intrinsic renal disease.
Objectives High-dose vitamin D3increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. Methods In a double blind, randomized controlled trial, critically ill ventilator-dependent adults (N = 30) received enteral vitamin D3(250,000 or 500,000 IU total over 5 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. Results Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P < 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D3dose than with the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at days 7 and 14 (ρ = 0.48; P = 0.04 and ρ = 0.59; P = 0.03, respectively). Additionally, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ = 0.51; P = 0.04). Conclusions The present study found a dose-related increase in plasma free-25(OH)D levels, which was associated with increasing circulating mRNA expression of hCAP18 over time. There were no correlations between changes in total and free 25(OH)D against plasma LL-37 and hBD-2 concentrations. Larger studies appear warranted to determine the impact of high-dose vitamin D3administration on endogenous AMPs.
by
Daniel Weisdorf;
Heather R. Millard;
Mary M. Horowitz;
Parvinder S. Hyare;
Richard Champlin;
Vincent Ho;
Marco Mielcarek;
Andrew Rezvani;
Keith Stockerl-Goldstein;
H Jean Khoury;
Marcos De Lima;
Wael Saber;
Brenda Sandmaier;
Mei Jie Zhang;
Mary Eapen
BACKGROUND: Patients with acute myeloid leukemia (AML) without complete remission (CR) or in first relapse (Rel1) can have extended leukemia control and survival after allogeneic hematopoietic cell transplantation (HCT). For patients in Rel1 or primary induction failure (PIF), transplantation versus treatment to achieve a second CR (CR2) and subsequent HCT might yield similar outcomes, but available comparative data are scarce. METHODS: Survival was analyzed in 4682 HCT recipients according to disease status: PIF (N = 1440), Rel1 (failing ≥1 reinduction; N = 1256), and CR2 (N = 1986). RESULTS: Patient, disease, and transplantation characteristics were similar, except that patients in CR2 more often had performance scores of 90% to 100%, de novo AML, and longer CR1 duration. Adverse cytogenetics were more common in patients who experienced PIF. The 5-year survival rate adjusted for performance score, cytogenetic risk, and donor type for CR2 was 39% (95% confidence interval [CI], 37%-41%) compared with 18% (95% CI, 16%-20%) for HCT in Rel1 and 21% (95% CI, 19%-23%) in PIF (P <.0001). CONCLUSIONS: Although survival is superior for patients who undergo HCT in CR2, transplantation for selected patients in Rel1 or PIF may still be valuable. These data can guide decision making about additional salvage therapy versus prompt HCT for patients not in CR, but they also highlight that AML is intrinsically more treatable in patients who have favorable-risk cytogenetics, those with longer CR1 duration, and younger patients with better performance status. Cancer 2017;123:2025–2034.
Heart failure with preserved ejection fraction (HFpEF) is a heterogenous syndrome with varying phenotypic expression. The phenotype chronic kidney disease (CKD) associated HFpEF is increasing in prevalence globally and is associated with increased morbidity and mortality compared to other HFpEF variants. These 2 conditions share common risk factors, including obesity, diabetes, and metabolic syndrome, as well as similar pathophysiology, including systemic inflammation, oxidative stress, elevated neurohormones, mineralocorticoid-receptor activation, and venous congestion. Given the coexistence of CKD and HFpEF, the diagnosis of HFpEF can be difficult. Moreover, treatment options for HFpEF have remained limited despite the success seen in its counterpart, heart failure with reduced ejection fraction. HFpEF encompasses complex multisystem pathophysiological perturbations beyond neurohormones, it is unlikely that a single agent can have significant benefit in this population. Recent data on sodium–glucose cotransporter 2 (SGLT2) inhibitors in HFpEF and CKD, and on glucagon-like peptide-1 (GLP-1) agonists and mineralocorticoid-receptor antagonists in metabolic syndrome, which target multiple pathways simultaneously, have led to promising therapeutics for HFpEF and CKD. In this perspective, our goal is to increase awareness of HFpEF as a multisystem disorder that shares the same disease processes seen in CKD and to emphasize that its management in individuals with CKD warrants a collective and multidisciplinary approach.
Background
Race- and gender- specific epidemiology of incident heart failure (HF) in a contemporary elderly cohort is not well described.
Methods
We studied 2934 participants without HF enrolled in the Health ABC Study (age 73.6±2.9 years, 47.9% men, 58.6% white, 41.4% black) and assessed incidence of HF, population attributable risk (PAR) of independent risk factors for HF, and outcomes of incident HF.
Results
During a median follow-up of 7.1 years, 258 (8.8%) participants developed HF (13.6/1000 person-years). Men and blacks were more likely to develop HF. No significant sex-based differences were observed in risk factors. Coronary heart disease (whites: PAR 23.9%, blacks: PAR 29.5%) and uncontrolled blood pressure (whites: PAR 21.3%, blacks: PAR 30.1%) carried the highest PAR in both races. In blacks, 6 out of 8 risk factors assessed (coronary heart disease, uncontrolled blood pressure, left ventricular hypertrophy, reduced glomerular filtration rate, smoking, and increased heart rate) had >5% higher PAR compared to whites, leading to a higher overall proportion of HF attributable to modifiable risk factors in blacks vs. whites (67.8% vs. 48.9%). Participants who developed HF had a higher annual mortality (18.0% vs. 2.7%). No racial difference in survival after HF was noted; however, rehospitalization rates were higher in blacks (62.1 vs. 30.3/100 person-years, P<.001).
Conclusions
Incident HF is common in the elderly; a large proportion of HF risk was attributed to modifiable risk factors. Racial differences in risk factors for HF and in hospitalization rates after HF need to be accounted for prevention and treatment efforts.
Doxazosin, a drug commonly prescribed for hypertension and prostate disease, increases heart failure risk. However, the underlying mechanism remains unclear. Galectin-3 is an important mediator that plays a pathogenic role in cardiac hypertrophy and heart failure. In the present study, we investigated whether doxazosin could stimulate galectin-3 expression and collagen synthesis in cultured HL-1 cardiomyocytes. We found that doxazosin dose-dependently induced galectin-3 protein expression, with a statistically significant increase in expression with a dose as low as 0.01 μM. Doxazosin upregulated collagen I and a-smooth muscle actin (a-SMA) protein levels and also induced apoptotic protein caspase-3 in HL-1 cardiomyocytes. Although we previously reported that activation of protein kinase C (PKC) stimulates galectin-3 expression, blocking the PKC pathway with the PKC inhibitor chelerythrine did not prevent doxazosin-induced galectin-3 and collagen expression. Consistently, doxazosin treatment did not alter total and phosphorylated PKC. These results suggest that doxazosin-stimulated galectin-3 is independent of PKC pathway. To determine if the a1-adrenergic pathway is involved, we pretreated the cells with the irreversible a-adrenergic receptor blocker phenoxybenzamine and found that doxazosin-stimulated galectin-3 and collagen expression was similar to controls, suggesting that doxazosin acts independently of a1-adrenergic receptor blockade. Collectively, we show a novel effect of doxazosin on cardiomycytes by stimulating heart fibrosis factor galectin-3 expression. The mechanism of action of doxazosin is not mediated through either activation of the PKC pathway or antagonism of a1-adrenergic receptors.
Objective: (i) To compare the prevalence and severity of depressive symptoms between men and women enrolled in a large heart failure (HF) registry. (ii) To determine gender differences in predictors of depressive symptoms from demographic, behavioral, clinical, and psychosocial factors in HF patients. Methods: In 622 HF patients (70% male, 61 ± 13 years, 59% NYHA class III/IV), depressive symptoms were assessed by the Patient Health Questionnaire (PHQ-9). Potential correlates were age, ethnicity, education, marital and financial status, smoking, exercise, body mass index (BMI), HF etiology, NYHA class, comorbidities, functional capacity, anxiety, and perceived control. To identify gender-specific correlates of depressive symptoms, separate logistic regression models were built by gender. Results: Correlates of depressive symptoms in men were financial status (p = 0.027), NYHA (p = 0.001); functional capacity (p < 0.001); health perception (p = 0.043); perceived control (p = 0.002) and anxiety (p < 0.001). Correlates of depressive symptoms in women were BMI (p = 0.003); perceived control (p = 0.013) and anxiety (p < 0.001). Conclusions: In HF patients, lowering depressive symptoms may require gender-specific interventions focusing on weight management in women and improving perceived functional capacity in men. Both men and women with HF may benefit from anxiety reduction and increased control.
Background--Although diastolic blood pressure (DBP) is independently associated with an increased risk of adverse cardiovascular outcomes in the general population, it is unclear if a similar relationship exists in patients with heart failure with preserved ejection fraction. Methods and Results--This analysis included 1703 (mean age, 72±10 years; 50% men; 78% white) patients with heart failure with preserved ejection fraction enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) Trial from the Americas who were treated for hypertension. Multivariable Cox regression was used to examine the risk of hospitalization for heart failure, death, and cardiovascular death associated with DBP. The relationship between hospitalization for heart failure and DBP was linear, with an increased risk observed with decreasing DBP values (≥90 mm Hg: referent; 80- 89 mm Hg: hazard ratio [HR], 1.44; 95% confidence interval [CI] , 0.85-2.44; 70-79 mm Hg: HR, 1.18; 95% CI, 0.69-2.01; 60- 69 mm Hg: HR, 1.54; 95% CI, 0.90-2.63; < 60 mm Hg: HR, 2.12; 95% CI, 1.20-3.74; P=0.0055 for trend). The associations of DBP with death (≥90 mm Hg: HR, 1.86; 95% CI, 1.12-3.06; 80-89 mm Hg: HR, 1.23; 95% CI, 0.89-1.70; 70-79 mm Hg: referent; 60- 69 mm Hg: HR, 1.20; 95% CI, 0.90-1.59; < 60 mm Hg: HR, 1.68; 95% CI, 1.21-2.33) and cardiovascular death (≥90 mm Hg: HR, 2.02; 95% CI, 1.10-3.71; 80-89 mm Hg: HR, 1.17; 95% CI, 0.77-1.79; 70-79 mm Hg: referent; 60-69 mm Hg: HR, 1.16; 95% CI, 0.80-1.70; < 60 mm Hg: HR, 1.85; 95% CI, 1.21-2.82) were nonlinear, with a greater risk of each outcome observed with DBP values ≥90 and < 60 mm Hg. Conclusions--DBP values =90 and < 60 mm Hg are associated with a significant risk of adverse outcomes in patients with heart failure with preserved ejection fraction who are treated for hypertension. Further research is needed to determine optimal DBP targets to reduc e the risk of adverse events in patients with heart failure with preserved ejection fraction.