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

Measurement of plasma norepinephrine and 3,4-dihydroxyphenylglycol: method development for a translational research study

Abstract Objective Norepinephrine (NE), a sympathetic neurotransmitter, is often measured in plasma as an index of sympathetic activity. To better understand NE dynamics, it is important to measure its principal metabolite, 3,4-dihydroxyphenylglycol (DHPG), concurrently. Our aim was to present a method, developed in the course of a translational research study, to measure NE and DHPG in human plasma using high performance liquid chromatography with electrochemical detection (HPLC-ED). Results After pre-purifying plasma samples by alumina extraction, we used HPLC-ED to separate and quantify NE and DHPG. In order to remove uric acid, which co-eluted with DHPG, a sodium bicarbonate wash was added to the alumina extraction procedure, and we oxidized the column eluates followed by reduction because catechols are reversibly oxidized whereas uric acid is irreversibly oxidized. Average recoveries of plasma NE and DHPG were 35.3 ± 1.0% and 16.3 ± 1.1%, respectively, and there was no detectable uric acid. Our estimated detection limits for NE and DHPG were approximately 85 pg/mL (0.5 pmol/mL) and 165 pg/mL (0.9 pmol/mL), respectively. The measurement of NE and DHPG in human plasma has wide applicability; thus, we describe a method to quantify plasma NE and DHPG in a laboratory setting as a useful tool for translational and clinical research

A primer on incorporating sex as a biological variable into the conduct and reporting of basic and clinical research studies

The recent move to require sex as a biological variable (SABV), which includes gender, into the reporting of research published by the American Journal of Physiology-Heart and Circulatory Physiology follows a growing, and much-needed, trend by journals. Understandably, there is concern over how to do this without adding considerable work, especially if one’s primary research focus is not on elucidating sex/gender differences. The purpose of this article is to provide additional guidance and examples on how to incorporate SABV into the conduct and reporting of basic and clinical research. Using examples from our research, which includes both studies focused and not focused on sex/gender differences, we offer suggestions for how to incorporate SABV into basic and clinical research studies. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/incorporating-sex-as-a-biological-variable-into-basic-and-clinical-research-studies/

Gender differences in the prevalence of frailty in heart failure : A systematic review and meta-analysis

Objectives This study quantitatively synthesized literature to identify gender differences in the prevalence of frailty in heart failure (HF). Background The intersection of frailty and HF continues to garner interest. Almost half of patients with HF are frail; however, gender differences in frailty in HF are poorly understood. Methods We performed a literature search to identify studies that reported prevalence of frailty by gender in HF. Random-effects meta-analysis was used to quantify the relative and absolute risk of frailty in women compared with men with HF, overall, and by Physical and Multidimensional Frailty measures. Meta-regression was performed to examine the influence of study age and functional class on relative risk in HF. Results Twenty-nine studies involving 8854 adults with HF were included. Overall in HF, women had a 26% higher relative risk of being frail compared with men (95% CI = 1.14–1.38, z = 4.69, p < 0.001, I2 = 76.5%). The overall absolute risk for women compared to men with HF being frail was 10% (95% CI = 0.06–0.15, z = 4.41, p < 0.001). The relative risk of frailty was slightly higher among studies that used Physical measures (relative risk = 1.27, p < 0.001) compared with studies that used Multidimensional measures (relative risk = 1.24, p = 0.024). There were no significant relationships between relative risk and either study age or functional class. Conclusions In HF, frailty affects women significantly more than men. Future work should focus on elucidating potential causes of gender differences in frailty in HF

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

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

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

The prevalence of frailty in heart failure : A systematic review and meta-analysis

Background There is a growing interest in the intersection of heart failure (HF) and frailty; however, estimates of the prevalence of frailty in HF vary widely. The purpose of this paper was to quantitatively synthesize published literature on the prevalence of frailty in HF and to examine the relationship between study characteristics (i.e. age and functional class) and the prevalence of frailty in HF. Methods The prevalence of frailty in HF, divided into Physical Frailty and Multidimensional Frailty measures, was synthesized across published studies using a random-effects meta-analysis of proportions approach. Meta-regression was performed to examine the influence of age and functional class (at the level of the study) on the prevalence of frailty. Results A total of 26 studies involving 6896 patients with HF were included in this meta-analysis. Despite considerable differences across studies, the overall estimated prevalence of frailty in HF was 44.5% (95% confidence interval, 36.2%–52.8%; z = 10.54; p < 0.001). The prevalence was slightly lower among studies using Physical Frailty measures (42.9%, z = 9.05; p < 0.001) and slightly higher among studies using Multidimensional Frailty measures (47.4%, z = 5.66; p < 0.001). There were no significant relationships between study age or functional class and prevalence of frailty. Conclusions Frailty affects almost half of patients with HF and is not necessarily a function of age or functional classification. Future work should focus on standardizing the measurement of frailty and on broadening the view of frailty beyond a strictly geriatric syndrome in 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 (β = 4.22 ± 1.63, P = .011), RAP (β = 0.71 ± 0.28, P = .013), and cardiac index (β = 7.11 ± 3.19, P = .028) were significantly associated with physical symptoms. Left ventricular internal diastolic diameter (β = 0.10 ± 0.05, P = .038) and RAP (β = 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

Frequency of and significance of physical frailty in patients with heart failure

Physical frailty is an important prognostic indicator in heart failure (HF); however, few studies have examined the relation between physical frailty and invasive hemodynamics among adults with HF. The purpose of this study was to characterize physical frailty in HF in relation to invasive hemodynamics. We enrolled 49 patients with New York Heart Association class II to IV HF when participants were scheduled for a right-sided cardiac heart catheterization procedure. Physical frailty was measured according to the “frailty phenotype”: shrinking, weakness, slowness, physical exhaustion, and low physical activity. Markers of invasive hemodynamics were derived from a formal review of right-sided cardiac catheterization tracings, and projected survival was calculated using the Seattle HF model. The mean age of the sample (n = 49) was 57.4 ± 9.7 years, 67% were men, 92% had New York Heart Association class III/IV HF, and 67% had nonischemic HF. Physical frailty was identified in 24 participants (49%) and was associated with worse Seattle HF model 1-year projected survival (p = 0.007). After adjusting for projected survival, physically frail participants had lower cardiac index (by both thermodilution and the Fick equation) and higher heart rates compared with those not physically frail (all p <0.05). In conclusion, physical frailty is highly prevalent in patients with HF and is associated with low-output HF