Citations

Study objective: Heart failure (HF) syndrome is associated with pulmonary system abnormalities that have a direct impact on mortality. Heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) are distinct subtypes of HF with different pathophysiologies, clinical presentations, and treatment approaches. Obesity is highly prevalent in HFpEF and significantly contributes to its development. Importantly, obesity and high abdominal adiposity can have significant effects on pulmonary function. Therefore, HFpEF patients may have more pronounced pulmonary function impairment than HFrEF patients in part due to higher prevalence of upper body adiposity. Hypothesis: We hypothesized that lung volumes would be lower in patients with HFpEF compared to those with HFrEF and CTL. Further, we hypothesized that higher upper body adiposity (measured as trunk fat by dual-energy X-ray absorptiometry) would be associated with lower lung volumes in patients with HFpEF. Methods: HFpEF patients (n=26), HFrEF patients (n=26) and CTL (n=36) performed pulmonary function tests according to ATS/ERS guidelines. Total lung capacity (TLC), residual volume (RV), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) were measured and absolute and % predicted values are reported. Dual-energy X-ray absorptiometry scans quantified % trunk fat. Absolute lung volumes were compared across groups using ANCOVA with age as a covariate and % predicted lung volumes were compared using one-way ANOVA. Results: HFpEF patients were older than HFrEF patients and CTL (HFpEF: 71±9 vs. HFrEF: 65±9 vs. CTL: 63±11 yrs, both p<0.05) while no differences were present among groups for sex, height, or BMI (all, p>0.05). HFpEF patients had higher % trunk fat than CTL (p<0.01), while no differences were present between HFrEF and HFpEF or CTL (p>0.05) (HFpEF: 46±11 vs. HFrEF: 42±8 vs. CTL: 38±11%). HFpEF patients had lower FVC (HFpEF: 3.0±0.7 vs. HFrEF: 3.7±1.0 vs. CTL: 3.8±0.8 L), FEV1 (HFpEF: 2.3±0.5 vs. HFrEF: 2.8±0.8 vs. CTL: 2.9±0.6 L), TLC (HFpEF: 5.5±1.3 vs. HFrEF: 6.3±1.4 vs. CTL: 6.4±1.1 L), and % predicted TLC than CTL (all, p<0.05). HFpEF and HFrEF patients had lower % predicted FVC and % predicted FEV1 than CTL (p<0.05). All other pulmonary function parameters were not different among groups (p>0.05). There was a negative relationship between % trunk fat and TLC for HFpEF patients (r= -0.51, p<0.05). There were negative relationships between % trunk fat and FVC for CTL (r= -0.37) and HFpEF patients (r= -0.50) (both, p<0.05), with statistically different y-intercepts (p<0.01). There were no other significant relationships (all, p>0.05). Conclusion: These findings demonstrate that patients with HF have smaller lung volumes than CTL. Further, our findings suggest that upper body adiposity may be an important contributing factor to these pulmonary system abnormalities in HFpEF. None. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction: Cardiac rehabilitation (CR) is a cornerstone of secondary prevention for cardiovascular disease (CVD). CR participation is associated with improvements in secondary CVD risk factor management. However, it is unclear if CR participation is associated with maintained improvements in CVD risk factor management following CR completion. Purpose: The aim of this study was to assess the impact of CR participation on CVD risk factor management at 1 and 3 years following CR completion. Methods: This retrospective study analyzed 911 patients (73% male) enrolled in the CR program at Mayo Clinic from 2013 to 2020. Patient demographics, clinical characteristics, and CVD risk factor management were examined pre and post CR as part of clinical practice and assessed passively at 1 and 3 years following CR. Secondary prevention CVD risk factor goals included total cholesterol (<200 mg/dL), HDL cholesterol (>40 mg/dL), LDL cholesterol (<100 mg/dL), triglycerides (<150 mg/dL), systolic and diastolic blood pressure (<130 and <80 mmHg), and body mass index (BMI) (18.5-24.9 kg/m 2 ). Results: The mean age was 66±12 years and on average 33±9 CR sessions were attended. Table 1 shows the percentage (%) of patients meeting the secondary prevention CVD risk factor goals. The % of patients meeting the goals for total cholesterol, LDL, triglycerides, and diastolic blood pressure were higher post than pre CR. There were no changes in the % of patients meeting the goals for total cholesterol or LDL at 1 and 3 year follow up compared to post CR. At 1 and 3 year follow up, there was a lower % of patients meeting the goals for systolic and diastolic blood pressure and triglycerides (at 1 year follow up only) than post CR. No changes were present in the % of patients meeting the goals for HDL and BMI at any timepoint (all, p>0.09). Conclusions: CR participation was associated with maintained improvements in lipid management, but not in triglycerides or blood pressure control at 1 and 3 years following CR.

Introduction: Obesity and hypertension (HTN) are highly prevalent comorbid risk factors for heart failure with preserved ejection fraction (HFpEF). Obesity and HTN independently increase sympathetic nervous activity and impair muscle blood flow during exercise. Previous work has reported attenuated limb blood flow in patients with HFpEF; however, these findings were compared to controls with dissimilar comorbidities and during small muscle mass exercise. It is unclear if HFpEF alters muscle blood flow responses independent of the obesity- and HTN-mediated alterations. Hypothesis: We hypothesized the muscle blood flow response during cycling would be lower in HFpEF patients than age, sex, BMI, and HTN matched controls (CTL). Methods: HFpEF patients (n=14, 9M/5W, 71±7yrs, 32±4 kg/m 2 ) and CTL (n=12, 8M/4W, 69±7yrs, 31±4 kg/m 2 ) performed an incremental cycling test. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) by open-circuit acetylene wash-in technique, and systemic vascular resistance (SVR) was calculated. Vastus lateralis blood flow index (BFI) was measured by near-infrared spectroscopy and indocyanine green dye injections and venous norepinephrine concentration was measured. Changes from rest to 40 W of the incremental test are reported. Results: Resting Q, mean arterial pressure, SVR, and venous norepinephrine concentration were not statistically different between groups (p>0.18). From rest to 40 W, the increases in Q (CTL: 3.9±0.8 vs. HFpEF: 3.6±0.7 L/min), mean arterial pressure (CTL: 5.7±2.7 vs. HFpEF: 6.6±6.1 mmHg), and SVR (CTL: -7.3±2.1 vs. HFpEF: -6.0±2.0 mmHg/L/min) were not statistically different between groups (all, p>0.13). The HFpEF group had smaller increases in vastus lateralis BFI at 40 W compared to CTL (CTL: 7.2±3.6 vs. HFpEF: 4.2±2.6 fold-increase from rest) (p=0.02). The HFpEF group had greater increases in venous norepinephrine concentration from rest to 40 W than CTL (CTL: 164±216 vs. HFpEF: 377±247 pg/mL) (p=0.05). Conclusions: Our findings suggest that, compared to age, sex, BMI, and HTN matched controls, patients with HFpEF have an impaired locomotor muscle blood flow response during submaximal cycling exercise likely due to higher locomotor muscle vascular resistance.

Abstract Exercise intolerance and exertional dyspnoea are the cardinal symptoms of heart failure with reduced ejection fraction (HFrEF). In HFrEF, abnormal autonomic and cardiopulmonary responses arising from locomotor muscle group III/IV afferent feedback is one of the primary mechanisms contributing to exercise intolerance. HFrEF patients also have pulmonary system and respiratory muscle abnormalities that impair exercise tolerance. Thus, the primary impetus for this review was to describe the mechanistic consequences of locomotor muscle group III/IV afferent feedback and respiratory muscle work in HFrEF. To address this, we first discuss the abnormal autonomic and cardiopulmonary responses mediated by locomotor muscle afferent feedback in HFrEF. Next, we outline how respiratory muscle work impairs exercise tolerance in HFrEF through its effects on locomotor muscle O 2 delivery. We then discuss the direct and indirect evidence supporting an interaction between locomotor muscle group III/IV afferent feedback and respiratory muscle work during exercise in HFrEF. Last, we outline future research directions related to locomotor and respiratory muscle abnormalities to progress the field forward in understanding the pathophysiology of exercise intolerance in HFrEF.

Abstract Introduction The CYP2D6 enzyme metabolizes opioids commonly prescribed for cancer‐related pain, and CYP2D6 polymorphisms may contribute to variability in opioid response. We evaluated the feasibility of implementing CYP2D6 ‐guided opioid prescribing for patients with cancer and reported pilot outcome data. Methods Adult patients from two cancer centers were prospectively enrolled into a hybrid implementation‐effectiveness clinical trial and randomized to CYP2D6 ‐genotype‐guided opioid selection, with clinical recommendations, or usual care. Implementation metrics, including provider response, medication changes consistent with recommendations, and patient‐reported pain and symptom scores at baseline and up to 8 weeks, were assessed. Results Most (87/114, 76%) patients approached for the study agreed to participate. Of 85 patients randomized, 71% were prescribed oxycodone at baseline. The median (range) time to receive CYP2D6 test results was 10 (3–37) days; 24% of patients had physicians acknowledge genotype results in a clinic note. Among patients with CYP2D6 ‐genotype‐guided recommendations to change therapy ( n = 11), 18% had a change congruent with recommendations. Among patients who completed baseline and follow‐up questionnaires ( n = 48), there was no difference in change in mean composite pain score (−1.01 ± 2.1 vs. −0.41 ± 2.5; p = 0.19) or symptom severity at last follow‐up (3.96 ± 2.18 vs. 3.47 ± 1.78; p = 0.63) between the usual care arm ( n = 26) and genotype‐guided arm ( n = 22), respectively. Conclusion Our study revealed high acceptance of pharmacogenetic testing as part of a clinical trial among patients with cancer pain. However, provider response to genotype‐guided recommendations was low, impacting assessment of pain‐related outcomes. Addressing barriers to utility of pharmacogenetics results and clinical recommendations will be critical for implementation success.