Nonplatelet thromboxane generation is associated with impaired cardiovascular performance and mortality in heart failure.

Nonplatelet thromboxane generation, stimulated largely by oxidative stress, is a novel mortality risk factor in individuals with coronary artery disease. Though inversely associated with left ventricular ejection fraction (LVEF), a potential role in the pathobiology of heart failure (HF) remains poorly defined. Nonplatelet thromboxane generation and oxidative stress were assessed by measuring urine thromboxane-B2 metabolites (TXB2-M) and 8-isoPGF2α by ELISA in 105 subjects taking aspirin and undergoing right heart catheterization for evaluation of HF, valve disease, or after transplantation. Multivariable logistic regression and survival analyses were used to define associations of TXB2-M to invasive measures of cardiovascular performance and 4-year clinical outcomes. TXB2-M was elevated (>1,500 pg/mg creatinine) in 46% of subjects and correlated with HF severity by New York Heart Association (NYHA) functional class and brain natriuretic peptide level, modestly with LVEF, but not with HF etiology. There was no association of oxidative stress to HF type or etiology but a trend with NYHA functional class. Multiple invasive hemodynamic parameters independently associated with TXB2-M after adjustment for oxidative stress, age, sex, and race with pulmonary effective arterial elastance (Ea pulmonary), reflective of right ventricular afterload, being the most robust on hierarchical analysis. Similar to Ea pulmonary, elevated urinary TXB2-M is associated with increased risk of death (adjusted HR = 2.15, P = 0.037) and a combination of death, transplant, or mechanical support initiation (adjusted HR = 2.0, P = 0.042). Nonplatelet TXA2 thromboxane generation is independently associated with HF severity reflected by invasive measures of cardiovascular performance, particularly right ventricular afterload, and independently predicted long-term mortality risk.NEW & NOTEWORTHY Nonplatelet thromboxane generation in heart failure is independently associated with risk of death, transplant, or need for mechanical support. Measurement of urine thromboxane metabolites using a clinically available assay may be a useful surrogate for invasive measurement of cardiovascular hemodynamics and performance that could provide prognostic information and facilitate tailoring of therapy in patients with heart failure. Inhibiting thromboxane generation or its biological effects is a potential strategy for improving cardiovascular performance and outcomes in heart failure.

HCMV trimer- and pentamer-specific antibodies synergize for virus neutralization but do not correlate with congenital transmission.

Human cytomegalovirus (HCMV) causes substantial disease in transplant patients and harms the development of the nervous system in babies infected in utero. Thus, there is a major focus on developing safe and effective HCMV vaccines. Evidence has been presented that a major target of neutralizing antibodies (NAbs) is the HCMV pentamer glycoprotein gH/gL/UL128-131. In some studies, most of the NAbs in animal or human sera were found to recognize the pentamer, which mediates HCMV entry into endothelial and epithelial cells. It was also reported that pentamer-specific antibodies correlate with protection against transmission from mothers to babies. One problem with the studies on pentamer-specific NAbs to date has been that the studies did not compare the pentamer to the other major form of gH/gL, the gH/gL/gO trimer, which is essential for entry into all cell types. Here, we demonstrate that both trimer and pentamer NAbs are frequently found in human transplant patients' and pregnant mothers' sera. Depletion of human sera with trimer caused reductions in NAbs similar to that observed following depletion with the pentamer. The trimer- and pentamer-specific antibodies acted in a synergistic fashion to neutralize HCMV and also to prevent virus cell-to-cell spread. Importantly, there was no correlation between the titers of trimer- and pentamer-specific NAbs and transmission of HCMV from mothers to babies. Therefore, both the trimer and pentamer are important targets of NAbs. Nevertheless, these antibodies do not protect against transmission of HCMV from mothers to babies.

Longitudinal Effects of Left Ventricular Assist Device Implantation on Global and Domain-Specific Cognitive Function.

BACKGROUND: Left ventricular assist devices (LVADs) are a common treatment of advanced heart failure, but cognitive dysfunction, which is common in heart failure, could limit the ability to perform postimplantation LVAD care. Implantation of an LVAD has been associated with improved cerebral perfusion and may improve cognitive function post implantation. OBJECTIVE: The aim of this study was to quantify longitudinal change in cognitive function after LVAD implantation. METHODS: A secondary analysis of data on 101 adults was completed to evaluate cognitive function before implantation and again at 1, 3, and 6 months post implantation of an LVAD. Latent growth curve modeling was conducted to characterize change over time. Serial versions of the Montreal Cognitive Assessment were used to measure overall (total) cognitive function and function in 6 cognitive domains. RESULT: There was moderate, nonlinear improvement from preimplantation to 6 months post implantation in Montreal Cognitive Assessment total score (Hedges' g = 0.50) and in short-term memory (Hedges' g = 0.64). There also were small, nonlinear improvements in visuospatial ability, executive function, and attention from preimplantation to 6 months post implantation (Hedges' g = 0.20-0.28). The greatest improvements were observed in the first 3 months after implantation and were followed by smaller, sustained improvements or no additional significant change. CONCLUSIONS: Implantation of an LVAD is associated with significant, nonlinear improvement in short-term memory and global cognitive function, with the most significant improvements occurring in the first 3 months after implantation. Clinicians should anticipate improvements in cognitive function after LVAD implantation and modify postimplantation education to maximize effectiveness of LVAD self-care.

Sympathetic Markers are Different Between Clinical Responders and Nonresponders After Left Ventricular Assist Device Implantation.

BACKGROUND: Clinical response to left ventricular assist devices (LVADs), as measured by health-related quality of life, varies among patients after implantation; however, it is unknown which pathophysiological mechanisms underlie differences in clinical response by health-related quality of life. OBJECTIVE: The purpose of this study was to compare changes in sympathetic markers (ß-adrenergic receptor kinase-1 [ßARK1], norepinephrine [NE], and 3,4-dihydroxyphenylglycol [DHPG]) between health-related quality of life clinical responders and nonresponders from pre- to post-LVAD implantation. METHODS: We performed a secondary analysis on a subset of data from a cohort study of patients from pre- to 1, 3, and 6 months after LVAD implantation. Clinical response was defined as an increase of 5 points or higher on the Kansas City Cardiomyopathy Questionnaire Clinical Summary score from pre- to 6 months post-LVAD implantation. We measured plasma ßARK1 level with an enzyme-linked immunosorbent assay and plasma NE and DHPG levels with high-performance liquid chromatography with electrochemical detection. Latent growth curve modeling was used to compare the trajectories of markers between groups. RESULTS: The mean (SD) age of the sample (n = 39) was 52.9 (13.2) years, and most were male (74.4%) and received LVADs as bridge to transplantation (69.2%). Preimplantation plasma ßARK1 levels were significantly higher in clinical responders (n = 19) than in nonresponders (n = 20) (P = .001), but change was similar after LVAD (P = .235). Preimplantation plasma DHPG levels were significantly lower in clinical responders than in nonresponders (P = .002), but the change was similar after LVAD (P = .881). There were no significant differences in plasma NE levels. CONCLUSIONS: Preimplantation ßARK1 and DHPG levels are differentiating factors between health-related quality of life clinical responders and nonresponders to LVAD, potentially signaling differing levels of sympathetic stimulation underlying clinical response.

Heart Failure Symptom Biology in Response to Ventricular Assist Device Implantation.

BACKGROUND: We have a limited understanding of the biological underpinnings of symptoms in heart failure (HF), particularly in response to left ventricular assist device (LVAD) implantation. OBJECTIVE: The aim of this study was to quantify the degree to which symptoms and biomarkers change in parallel from before implantation through the first 6 months after LVAD implantation in advanced HF. METHODS: This was a prospective cohort study of 101 patients receiving an LVAD for the management of advanced HF. Data on symptoms (dyspnea, early and subtle symptoms [HF Somatic Perception Scale], pain severity [Brief Pain Inventory], wake disturbance [Epworth Sleepiness Scale], depression [Patient Health Questionnaire], and anxiety [Brief Symptom Inventory]) and peripheral biomarkers of myocardial stretch, systemic inflammation, and hypervolumetric mechanical stress were measured before implantation with a commercially available LVAD and again at 30, 90, and 180 days after LVAD implantation. Latent growth curve and parallel process modeling were used to describe changes in symptoms and biomarkers and the degree to which they change in parallel in response to LVAD implantation. RESULTS: In response to LVAD implantation, changes in myocardial stretch were closely associated with changes in early and subtle physical symptoms as well as depression, and changes in hypervolumetric stress were closely associated with changes in pain severity and wake disturbances. Changes in systemic inflammation were not closely associated with changes in physical or affective symptoms in response to LVAD implantation. CONCLUSIONS: These findings provide new insights into the many ways in which symptoms and biomarkers provide concordant or discordant information about LVAD response.

Depressive symptoms in couples living with heart failure: the role of congruent engagement in heart failure management.

OBJECTIVES: The life-threatening context of heart failure (HF), high variability of the illness and complexity of care place considerable demands on both the adult patient and his/her spouse. The current study examines the role of congruent engagement in HF management behaviors on the depressive symptoms of the couple living with HF. METHOD: A cross-sectional design was used to examine 60 couples living with HF. Multilevel modeling was used to examine partner and within-dyad effects of engagement in HF behaviors on depressive symptoms. RESULTS: Just over one quarter (27%) of couples had both members experiencing at least mild depressive symptoms. Controlling for stage of HF and one's own level of engagement, one's partner's level of engagement was significantly associated with one's level of depressive symptoms; higher levels of engagement by one's partner were associated with lower levels of depressive symptoms. Additionally, spouses had lower levels of depressive symptoms when they had similar levels of engagement to their partner with HF; spouses had higher levels of depressive symptoms when they had higher levels of engagement than their partner with HF. CONCLUSION: Findings confirm the importance of screening both members of the couple for depression and fostering collaboration within the couple.

Identifying a Relationship Between Physical Frailty and Heart Failure Symptoms.

BACKGROUND: Heart failure (HF) is a complex clinical syndrome associated with significant symptom burden; however, our understanding of the relationship between symptoms and physical frailty in HF is limited. OBJECTIVE: The aim of this study was to quantify associations between symptoms and physical frailty in adults with HF. METHODS: A sample of adults with symptomatic HF were enrolled in a cross-sectional study. Physical symptoms were measured with the HF Somatic Perception Scale-Dyspnea subscale, the Epworth Sleepiness Scale, and the Brief Pain Inventory short form. Affective symptoms were measured with the Patient Health Questionnaire-9 and the Brief Symptom Inventory-Anxiety scale. Physical frailty was assessed according to the Frailty Phenotype Criteria: shrinking, weakness, slowness, physical exhaustion, and low physical activity. Comparative statistics and generalized linear modeling were used to quantify associations between symptoms and physical frailty, controlling for Seattle HF Model projected 1-year survival. RESULTS: The mean age of the sample (n = 49) was 57.4 ± 9.7 years, 67% were male, 92% had New York Heart Association class III/IV HF, and 67% had nonischemic HF. Physically frail participants had more than twice the level of dyspnea (P < .001), 75% worse wake disturbances (P < .001), and 76% worse depressive symptoms (P = .003) compared with those who were not physically frail. There were no differences in pain or anxiety. CONCLUSIONS: Physically frail adults with HF have considerably worse dyspnea, wake disturbances, and depression. Targeting physical frailty may help identify and improve physical and affective symptoms in HF.

Self-care Moderates the Relationship Between Symptoms and Health-Related Quality of Life in Heart Failure.

BACKGROUND: Physical symptoms and depression in heart failure (HF) are key drivers of health-related quality of life (HRQOL). Heart failure self-care behaviors are believed to influence how symptoms affect HRQOL. OBJECTIVE: The goal of this study was to determine if HF self-care behaviors moderate the relationships between physical and depressive symptoms and HRQOL. METHODS: In a cohort of adults with moderate to advanced HF, multivariate linear regression was used to evaluate the interaction between self-care behaviors (Self-care of HF index maintenance and management scales) and physical HF symptoms (HF Somatic Perception Scale) on emotional HRQOL (emotional dimension of Minnesota Living With HF Questionnaire). The interaction between self-care behaviors and depression (9-item Patient Health Questionnaire) was evaluated on physical HRQOL (physical dimension of Minnesota Living With HF Questionnaire). RESULTS: The mean age of the sample (N = 202) was 57 ± 13 years, 50% were women, and 61% had New York Heart Association class III or IV HF. Controlling for age, Seattle HF score, functional ability, and comorbidities, self-care maintenance and management moderated the relationship between physical HF symptoms and emotional HRQOL. Only self-care maintenance moderated the relationship between depression and physical HRQOL. CONCLUSION: In HF, HRQOL is dependent on both the severity of physical and depressive symptoms and the level of engagement in HF self-care behaviors. Future research should consider both self-care behaviors and symptoms when examining patient HRQOL.

Implant Strategy-Specific Changes in Symptoms in Response to Left Ventricular Assist Devices.

BACKGROUND: Although we know that the quality of life generally improves after left ventricular assist device (LVAD) implantation, we know little about how symptoms change in response to LVAD. METHODS: The purpose of this study was to compare the changes in symptoms between bridge and destination therapy patients as part of a prospective cohort study. Physical (dyspnea and wake disturbances) and affective symptoms (depression and anxiety) were measured before LVAD and at 1, 3, and 6 months after LVAD. Multiphase growth modeling was used to capture the 2 major phases of change: initial improvements between preimplant and 1 month after LVAD and subsequent improvements between 1 and 6 months after LVAD. RESULTS: The sample included 64 bridge and 22 destination therapy patients as the preimplant strategy. Destination patients had worse preimplant dyspnea and wake disturbances, and they experienced greater initial improvements in these symptoms compared with bridge patients (all P < .05); subsequent change in both symptoms were similar between groups (both P > .05). Destination patients had worse preimplant depression (P = .042) but experienced similar initial and subsequent improvements in depression in response to LVAD compared with bridge patients (both P > .05). Destination patients had similar preimplant anxiety (P = .279) but experienced less initial and greater subsequent improvements in anxiety after LVAD compared with bridge patients (both P < .05). CONCLUSION: There are many differences in the magnitude and timing of change in symptom responses to LVAD between bridge and destination therapy patients. Detailed information on changes in specific symptoms may better inform shared decision-making regarding LVAD.

Quality of Life, Depression, and Anxiety in Ventricular Assist Device Therapy: Longitudinal Outcomes for Patients and Family Caregivers.

BACKGROUND: Patients who receive ventricular assist device (VAD) therapy typically rely on informal caregivers (family members or friends) to assist them in managing their device. OBJECTIVE: The purpose of this study is to characterize changes in person-oriented outcomes (quality of life [QOL], depression, and anxiety) for VAD patients and their caregivers together from pre-implantation to 3 months post-implantation. METHODS: This was a formal interim analysis from an ongoing prospective study of VAD patients and caregivers (n = 41 dyads). Data on person-oriented outcomes (QOL: EuroQol 5 Dimensions Visual Analog Scale; depression: Patient Health Questionnaire-8; anxiety: Brief Symptom Inventory) were collected at 3 time points (just prior to implantation and at 1 and 3 months post-implantation). Trajectories of change for patients and caregivers on each measure were estimated using latent growth modeling with parallel processes. RESULTS: Patients' QOL improved significantly over time, whereas caregiver QOL worsened. Depression and anxiety also improved significantly among patients but did not change among caregivers. There was substantial variability in change on all outcomes for both patients and their caregivers. CONCLUSIONS: This is the first quantitative study of VAD patient-caregiver dyads in modern devices that describes change in person-oriented outcomes from pre-implantation to post-implantation. This work supports the need for future studies that account for the inherent relationships between patient and caregiver outcomes and examine variability in patient and caregiver responses to VAD therapy.

Tailoring Therapies in Advanced Heart Failure.

Heart failure effects millions of people throughout the world and is a growing epidemic with a significant impact on the economics and systems of care delivery. The goal of therapy in advanced heart failure is to improve quality of life and prolong survival. Standard medical therapies may require tailoring as advanced therapies are considered in the context of patient and caregiver goals. The aim of this review is to summarize concepts for tailored medical therapy and monitoring in advanced heart failure and discuss the importance of tailoring systems of care and shared decision making in advanced heart failure.

Gender-Specific Physical Symptom Biology in Heart Failure.

BACKGROUND: There are several gender differences that may help explain the link between biology and symptoms in heart failure (HF). OBJECTIVE: The aim of this study was to examine gender-specific relationships between objective measures of HF severity and physical symptoms. METHODS: Detailed clinical data, including left ventricular ejection fraction and left ventricular internal end-diastolic diameter, and HF-specific physical symptoms were collected as part of a prospective cohort study. Gender interaction terms were tested in linear regression models of physical symptoms. RESULTS: The sample (101 women and 101 men) averaged 57 years of age and most participants (60%) had class III/IV HF. Larger left ventricle size was associated with better physical symptoms for women and worse physical symptoms for men. CONCLUSION: Decreased ventricular compliance may result in worse physical HF symptoms for women and dilation of the ventricle may be a greater progenitor of symptoms for men with HF.

Physical and psychological symptom biomechanics in moderate to advanced heart failure.

BACKGROUND: There is a common dissociation between objective measures and patient symptomatology in heart failure (HF). OBJECTIVE: The aim of this study was to explore the relationship between cardiac biomechanics and physical and psychological symptoms in adults with moderate to advanced HF. METHODS: We performed a secondary analysis of data from 2 studies of symptoms among adults with HF. Stepwise regression modeling was performed to examine the influence of cardiac biomechanics (left ventricular internal diastolic diameter, right atrial pressure [RAP], and cardiac index) on symptoms. RESULTS: The average age of the sample (n = 273) was 57 ± 16 years, 61% were men, and 61% had class III or IV HF. Left ventricular internal diastolic diameter (ß = 4.22 ± 1.63, P = .011), RAP (ß = 0.71 ± 0.28, P = .013), and cardiac index (ß = 7.11 ± 3.19, P = .028) were significantly associated with physical symptoms. Left ventricular internal diastolic diameter (ß = 0.10 ± 0.05, P = .038) and RAP (ß = 0.03 ± 0.01, P = .039) were significantly associated with anxiety. There were no significant biomechanical determinants of depression. CONCLUSION: Cardiac biomechanics were related to physical symptoms and anxiety, providing preliminary evidence of the biological underpinnings of symptomatology among adults with HF.

Symptom-Hemodynamic Mismatch and Heart Failure Event Risk.

BACKGROUND: Heart failure (HF) is a heterogeneous condition of both symptoms and hemodynamics. OBJECTIVE: The goals of this study were to identify distinct profiles among integrated data on physical and psychological symptoms and hemodynamics and quantify differences in 180-day event risk among observed profiles. METHODS: A secondary analysis of data collected during 2 prospective cohort studies by a single group of investigators was performed. Latent class mixture modeling was used to identify distinct symptom-hemodynamic profiles. Cox proportional hazards modeling was used to quantify difference in event risk (HF emergency visit, hospitalization, or death) among profiles. RESULTS: The mean age (n = 291) was 57 ± 13 years, 38% were female, and 61% had class III/IV HF. Three distinct symptom-hemodynamic profiles were identified: 17.9% of patients had concordant symptoms and hemodynamics (ie, moderate physical and psychological symptoms matched the comparatively good hemodynamic profile), 17.9% had severe symptoms and average hemodynamics, and 64.2% had poor hemodynamics and mild symptoms. Compared with those in the concordant profile, both profiles of symptom-hemodynamic mismatch were associated with a markedly increased event risk (severe symptoms hazards ratio, 3.38; P = .033; poor hemodynamics hazards ratio, 3.48; P = .016). CONCLUSIONS: A minority of adults with HF have concordant symptoms and hemodynamics. Either profile of symptom-hemodynamic mismatch in HF is associated with a greater risk of healthcare utilization for HF or death.

Comorbidity profiles and inpatient outcomes during hospitalization for heart failure: an analysis of the U.S. Nationwide inpatient sample.

BACKGROUND: Treatment of heart failure (HF) is particularly complex in the presence of comorbidities. We sought to identify and associate comorbidity profiles with inpatient outcomes during HF hospitalizations. METHODS: Latent mixture modeling was used to identify common profiles of comorbidities during adult hospitalizations for HF from the 2009 Nationwide Inpatient Sample (n = 192,327). RESULTS: Most discharges were characterized by "common" comorbidities. A "lifestyle" profile was characterized by a high prevalence of uncomplicated diabetes, hypertension, chronic pulmonary disorders and obesity. A "renal" profile had the highest prevalence of renal disease, complicated diabetes, and fluid and electrolyte imbalances. A "neurovascular" profile represented the highest prevalence of cerebrovascular disease, paralysis, myocardial infarction and peripheral vascular disease. Relative to the common profile, the lifestyle profile was associated with a 15% longer length of stay (LOS) and 12% greater cost, the renal profile was associated with a 30% higher risk of death, 27% longer LOS and 24% greater cost, and the neurovascular profile was associated with a 45% higher risk of death, 34% longer LOS and 37% greater cost (all p < 0.001). CONCLUSIONS: Comorbidity profiles are helpful in identifying adults at higher risk of death, longer length of stay, and accumulating greater costs during hospitalizations for HF.

Tackling heart failure in the twenty-first century.

Heart failure, or congestive heart failure, is a condition in which the heart cannot supply the body's tissues with enough blood. The result is a cascade of changes that lead to severe fatigue, breathlessness and, ultimately, death. In the past quarter century, much progress has been made in understanding the molecular and cellular processes that contribute to heart failure, leading to the development of effective therapies. Despite this, chronic heart failure remains a major cause of illness and death. And because the condition becomes more common with increasing age, the number of affected individuals is rising with the rapidly ageing global population. New treatments that target disease mechanisms at the cellular and whole-organ level are needed to halt and reverse the devastating consequences of this disease.

Physical and psychological symptom profiling and event-free survival in adults with moderate to advanced heart failure.

UNLABELLED: : Heart failure (HF) is a heterogeneous symptomatic disorder. The goal of this study was to identify and link common profiles of physical and psychological symptoms to 1-year event-free survival in adults with moderate to advanced HF. METHODS: Multiple valid, reliable, and domain-specific measures were used to assess physical and psychological symptoms. Latent class mixture modeling was used to identify distinct symptom profiles. Associations between observed symptom profiles and 1-year event-free survival were quantified using Cox proportional hazards modeling. RESULTS: The mean age of the participants (n = 202) was 57 ± 13 years, 50% were men, and 60% had class III/IV HF. Three distinct profiles, mild (41.7%), moderate (30.2%), and severe (28.1%), that captured a gradient of both physical and psychological symptom burden were identified (P < .001 for all comparisons). Controlling for the Seattle HF Score, adults with the moderate symptom profile were 82% more likely (hazard ratio, 1.82; 95% confidence interval, 1.07-3.11; P = .028) and adults with the severe symptom profile were more than twice as likely (hazard ratio, 2.06; 95% confidence interval, 1.21-3.52; P = .001) to have a clinical event within 1 year than patients with the mild symptom profile. CONCLUSIONS: Profiling patterns among physical and psychological symptoms identifies HF patient subgroups with significantly worse 1-year event-free survival independent of prognostication based on objective clinical HF data.

Background and design of the profiling biobehavioral responses to mechanical support in advanced heart failure study.

BACKGROUND: Unexplained heterogeneity in response to ventricular assist device (VAD) implantation for the management of advanced heart failure impedes our ability to predict favorable outcomes, provide adequate patient and family education, and personalize monitoring and symptom management strategies. The purpose of this article was to describe the background and the design of a study entitled "Profiling Biobehavioral Responses to Mechanical Support in Advanced Heart Failure" (PREMISE). STUDY DESIGN AND METHODS: PREMISE is a prospective cohort study designed to (1) identify common and distinct trajectories of change in physical and psychological symptom burden; (2) characterize common trajectories of change in serum biomarkers of myocardial stress, systemic inflammation, and endothelial dysfunction; and (3) quantify associations between symptoms and biomarkers of pathogenesis in adults undergoing VAD implantation. Latent growth mixture modeling, including parallel process and cross-classification modeling, will be used to address the study aims and will entail identifying trajectories, quantifying associations between trajectories and both clinical and quality-of-life outcomes, and identifying predictors of favorable symptom and biomarker responses to VAD implantation. CONCLUSIONS: Research findings from the PREMISE study will be used to enhance shared patient and provider decision making and to shape a much-needed new breed of interventions and clinical management strategies that are tailored to differential symptom and pathogenic responses to VAD implantation.

Pulmonary capillary wedge pressure augments right ventricular pulsatile loading.

BACKGROUND: Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (R(PA)) and compliance (C(PA)) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load. METHODS AND RESULTS: Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the R(PA)-C(PA) relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent R(PA)-C(PA) hyperbolic (inverse) dependence, C(PA)=0.564/(0.047+R(PA)), with a near-constant resistance-compliance product (0.48±0.17 seconds). In the same patients, the systemic resistance-compliance product was highly variable. Severe pulmonary fibrosis (n=89) did not change the R(PA)-C(PA) relation. Increasing patient age led to a very small but statistically significant change in the relation. However, elevation of the pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly lowering C(PA) for any R(PA) and negatively correlating with the resistance-compliance product (P<0.0001). CONCLUSIONS: Pulmonary hypertension and pulmonary fibrosis do not significantly change the hyperbolic dependence between R(PA) and C(PA), and patient age has only minimal effects. This fixed relationship helps explain the difficulty of reducing total right ventricular afterload by therapies that have a modest impact on mean R(PA). Higher pulmonary capillary wedge pressure appears to enhance net right ventricular afterload by elevating pulsatile, relative to resistive, load and may contribute to right ventricular dysfunction.

Blunted responses to heart failure symptoms in adults with mild cognitive dysfunction.

INTRODUCTION: Mild cognitive dysfunction is common among adults with heart failure (HF). We hypothesized that mild cognitive dysfunction would be associated with poor HF self-care behaviors, particularly patients' ability to respond to symptoms. METHODS: We analyzed data on 148 participants in an observational study of symptoms in adults with moderate-to-advanced HF. Mild cognitive dysfunction was measured with the Montreal Cognitive Assessment (MoCA; range, 0-30), using cutoff scores for the general population (26) and for adults with cardiovascular disease (24). Heart failure self-care management (evaluation and response to HF symptoms) was measured with the Self-care of HF Index, and consulting behaviors (calling a provider when symptoms occur) were measured using the European HF Self-care Behavior Scale-9. Generalized linear modeling and hierarchical linear modeling were used to quantify the relationship between MoCA cutoff scores and indices of HF self-care. RESULTS: The mean age of the sample was 57 ± 12 years, 61.5% were men, and 58.8% had class III/IV HF; the mean left ventricular ejection fraction was 28% ± 12%. Using MoCA scores of 26 and 24, respectively, 33.1% and 14.2% of the sample had mild cognitive dysfunction. Controlling for common confounders, participants with MoCA scores lower than 26 reported self-care comparable with that of participants with MoCA scores of 26 or higher. Participants with MoCA scores lower than 24, however, reported 21.5% worse self-care management (P = 0.014) and 51% worse consulting behaviors (P < 0.001) compared with participants with MoCA scores of 24 or higher. CONCLUSIONS: A disease-specific cutoff for mild cognitive dysfunction reveals marked differences patients' ability to recognize and respond to HF symptoms when they occur. Adults with HF and mild cognitive dysfunction are a vulnerable patient group in great need of interventions that complement HF self-care.