Heart failure with preserved ejection fraction risk is associated with prevalence and severity of obstructive sleep apnea.

STUDY OBJECTIVES: While heart failure with preserved ejection fraction (HFpEF) is associated with the presence of obstructive sleep apnea (OSA), few studies have examined the association between scoring systems used to predict HFpEF risk, such as the H2FPEF and HFA-PEFF scores, and OSA prevalence and severity. METHODS: We performed chart review on all patients who underwent both an echocardiogram and sleep study at the University of Pennsylvania between July 1, 2020, and June 30, 2022. There were 277 patients in the final cohort after excluding patients with relevant comorbidities. Associations between echocardiographic parameters and OSA severity, as well as between H2FPEF score and OSA severity, were examined using linear tests of trend. The association between H2FPEF score and prevalent OSA was examined with logistic regression. RESULTS: OSA severity was associated with echocardiographic markers, including left atrial volume index (P = .03) and left ventricular relative thickness (P = .008). Patients with high H2FPEF risk scores had over 17-fold higher odds of prevalent OSA compared with those with low-risk scores (17.7; 95% CI 4.3, 120.7; P < .001). Higher H2FPEF scores were strongly correlated with OSA severity (P < .001). After controlling for body mass index, H2FPEF scores were not associated with prevalence or severity of OSA. CONCLUSIONS: In an ambulatory population referred for sleep study and echocardiogram, markers of diastolic dysfunction were associated with OSA severity. OSA prevalence and severity were associated with increased H2FPEF scores, although these associations were largely explained by obesity. Clinicians should have low thresholds for referring patients with OSA for cardiac workup and patients with HFpEF for sleep study. CITATION: Connolly JE, Genuardi MV, Mora JI, Prenner SB. Heart failure with preserved ejection fraction risk is associated with prevalence and severity of obstructive sleep apnea. J Clin Sleep Med. 2024;20(3):381-387.

Left Bundle Branch Area Pacing From a Femoral Approach in a Patient Without Superior Access.

Limited venous access and lateral left ventricular scar are impediments to traditional cardiac resynchronization therapy. We present a case where placement of an implantable cardioverter-defibrillator from a femoral approach while using left bundle branch area pacing led to clinical improvement. (Level of Difficulty: Intermediate.).

Pragmatic assessment of resident performed cardiac point of care ultrasound using a validated scoring metric.

Background: Cardiac point of care ultrasound (POCUS) is increasingly utilized by trainees across various specialties and can rapidly assess the cardiac status of unstable patients. However, the quality of trainee performed cardiac examinations has been reported only in controlled studies. In this study we aimed to assess the quality of all cardiac POCUS performed by internal medicine trainees at a major academic medical center over a three-year period. Methods: 256 studies were included and were graded by experts blinded to postgraduate year (PGY) using a previously validated scoring metric. Results: We found significant improvement in overall quality of resident performed cardiac POCUS from PGY 1 to 3 (10.8, 10.2, 13.2, p = 0.012). Assessment of left ventricular function was possible in 82% of studies and increased from PGY 1 to PGY 3 (77%, 76%, 88%, p = 0.025). Similar trends were seen in the assessment of the pericardial space (67%, 71%, 84%, p = 0.012). Images sufficient for right ventricular and volume status assessment were less commonly found (65%, 60%, 75% and 60%, 49%, 57%, respectively). Conclusions: This study provides a real world experience of the level of diagnostic accuracy that can be expected from IM trainees with minimal hands-on supervision.

Multimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism.

AIMS: Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants. METHODS AND RESULTS: Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO2, peak ), ventilatory threshold (VT), and VO2 efficiency (ratio of total work performed to O2 consumed). SkM OxPhos was assessed using Creatine Chemical-Exchange Saturation Transfer (CrCEST, n = 51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half-time of Cr recovery (t1/2, Cr ) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy = 13, HTN = 9, and HFpEF = 12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphoproteomic analysis. HFpEF subjects demonstrated lower VO2,peak , VT, and VO2 efficiency than either control group (all P < 0.05). The t1/2, Cr was significantly longer in HFpEF (P = 0.005), indicative of impaired SkM OxPhos, and correlated with cycle ergometry exercise parameters. HFpEF SkM contained fewer Type I myofibres (P = 0.003). Proteomic analyses demonstrated (a) reduced levels of proteins related to OxPhos that correlated with exercise capacity and (b) reduced ERK signalling in HFpEF. CONCLUSIONS: Heart failure with preserved ejection fraction patients demonstrate impaired functional capacity and SkM OxPhos. Reductions in the proportions of Type I myofibres, proteins required for OxPhos, and altered phosphorylation signalling in the SkM may contribute to exercise intolerance in HFpEF.

Quantitative Proteomic Analysis of Diabetes Mellitus in Heart Failure With Preserved Ejection Fraction.

Diabetes mellitus (DM) is associated with a higher risk of heart failure hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Using SomaScan assays and proteomics analysis of plasma from participants in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial and the Penn Heart Failure Study, this study identified 10 proteins with significantly different expression in patients with HFpEF and DM. Of these, apolipoprotein M was found to mediate 72% (95% CI: 36% to 100%; p < 0.001) of the association between DM and the risk of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization.

Improving cardiology fellow education of right heart catheterization using a simulation based curriculum.

BACKGROUND: Medical procedures are traditionally taught informally at patients' bedside through observation and practice using the adage "see one, do one, teach one." This lack of formalized training can cause trainees to be unprepared to perform procedures independently. Simulation based education (SBE) increases competence, reduces complications, and decreases costs. We developed, implemented, and evaluated the efficacy of a right heart catheterization (RHC) SBE curriculum. METHODS: The RHC curriculum consisted of a pretest, video didactics, deliberate practice, and a posttest. Pre-and posttest skills examinations consisted of a dichotomous 43-item checklist on RHC skills and a 14-item hemodynamic waveform quiz. We enrolled two groups of fellows: 6 first-year, novice cardiology fellows at Northwestern University in their first month of training, and 11 second- and third-year fellows who had completed traditional required, level I training in RHC. We trained the first-year fellows at the beginning of the 2018-2019 year using the SBE curriculum and compared them to the traditionally-trained cardiology fellows who did not complete SBE. RESULTS: The SBE-trained fellows significantly improved RHC skills, hemodynamic knowledge, and confidence from pre- to posttesting. SBE-trained fellows performed similarly to traditionally-trained fellows on simulated RHC skills checklists (88.4% correct vs. 89.2%, p = .84), hemodynamic quizzes (94.0% correct vs. 86.4%, p = .12), and confidence (79.4 vs. 85.9 out of 100, p = .15) despite less clinical experience. CONCLUSIONS: A SBE curriculum for RHC allowed novice cardiology fellows to achieve level I skills and knowledge at the beginning of fellowship and can train cardiology fellows before patient contact.

Peripheral Determinants of Oxygen Utilization in Heart Failure With Preserved Ejection Fraction: Central Role of Adiposity.

The aim of this study was to determine the arteriovenous oxygen content difference (ΔAVo2) in adult subjects with and without heart failure with preserved ejection fraction (HFpEF) during systemic and forearm exercise. Subjects with HFpEF had reduced ΔAVo2. Forearm diffusional conductance for oxygen, a lumped conductance parameter that incorporates all impediments to the movement of oxygen from red blood cells in skeletal muscle capillaries into the mitochondria within myocytes, was estimated. Forearm diffusional conductance for oxygen was not different among adults with HFpEF, those with hypertension, and healthy control subjects; therefore, diffusional conductance cannot explain the reduced forearm ΔAVo2. Instead, adiposity was strongly associated with ΔAVo2, suggesting an active role for adipose tissue in reducing exercise capacity in patients with HFpEF.

Serum Albumin Is a Marker of Myocardial Fibrosis, Adverse Pulsatile Aortic Hemodynamics, and Prognosis in Heart Failure With Preserved Ejection Fraction.

Background Data regarding the phenotypic correlates and prognostic value of albumin in heart failure with preserved ejection fraction (HFpEF) are scarce. The goal of the current study is to determine phenotypic correlates (myocardial hypertrophy, myocardial fibrosis, detailed pulsatile hemodynamics, and skeletal muscle mass) and prognostic implications of serum albumin in HFpEF. Methods and Results We studied 118 adults with HFpEF. All-cause death or heart-failure-related hospitalization was ascertained over a median follow-up of 57.6 months. We measured left ventricular mass, myocardial extracellular volume, and axial muscle areas using magnetic resonance imaging. Pulsatile arterial hemodynamics were assessed with a combination of arterial tonometry and phase-contrast magnetic resonance imaging. Subjects with lower serum albumin exhibited a higher body mass index, and a greater proportion of black ethnicity and diabetes mellitus. A low serum albumin was associated with higher myocardial extracellular volume (52.3 versus 57.4 versus 39.3 mL in lowest to highest albumin tertile, respectively; P=0.0023) and greater N-terminal pro B-type natriuretic peptide levels, but not with a higher myocardial cellular volume (123 versus 114 versus 102 mL; P=0.13). Lower serum albumin was also associated with an increased forward wave amplitude and markedly increased pulsatile power in the aorta. Serum albumin was a strong predictor of death or heart failure hospitalization even after adjustment for N-terminal pro B-type natriuretic peptide levels and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score (adjusted standardized hazard ratio=0.56; 95% CI=0.37-0.83; P<0.0001). Conclusions Serum albumin is associated with myocardial fibrosis, adverse pulsatile aortic hemodynamics, and prognosis in HFpEF. This readily available clinical biomarker can enhance risk stratification in HFpEF and identifies a subgroup with specific pathophysiological abnormalities.

Parameters of repolarization heterogeneity are associated with myocardial recovery in acute heart failure.

BACKGROUND: Heart failure (HF) with recovered ejection fraction (HFrecEF) is an increasingly recognized yet not well understood phenotype. Little is known about electrical parameters associated with myocardial recovery in acute systolic HF. METHODS: We identified a subset of 87 patients from a non-ischemic cardiomyopathy cohort with left ventricular ejection fraction (LVEF) < 40% during index HF hospitalization. HFrecEF was defined as follow-up LVEF ≥40% and ≥ 10% improvement from baseline. We analyzed baseline and follow up electrocardiograms (ECG) in this group for several electrical parameters known to reflect repolarization heterogeneity. RESULTS: Among 87 patients, 30 (34%) patients recovered in a median of 122 (IQR: 58-275) days after index hospitalization. Baseline demographics were similar among HFrecEF versus persistent HFrEF except for increased diabetes in the persistent HFrEF cohort. Patients with HFrecEF had baseline decreased QRST angle, decreased QT dispersion, and less negative signed JT area compared to persistent HFrEF. Patients with HFrecEF had greater decrease in QT dispersion and QTc duration, and greater increase in the signed JT and TpTe areas over time. Baseline QRST angle correlated with longitudinal and circumferential strain and myocardial systolic performance (MSP). Signed JT area correlated with increased baseline LVEF, smaller baseline LV dimensions, increased longitudinal and circumferential strain, and MSP. Signed TpTe correlated with increased longitudinal and circumferential strain, and MSP. CONCLUSIONS: Several conventional and novel ECG parameters that reflect repolarization heterogeneity may differentiate patients with acute HF who ultimately recover LVEF. These parameters are associated with baseline structural parameters and are dynamic during recovery.

Effect of Serum Albumin Levels in Patients With Heart Failure With Preserved Ejection Fraction (from the TOPCAT Trial).

Little data are available regarding the determinants and prognostic significance of serum albumin in Heart Failure with Preserved Ejection Fraction (HFpEF). We sought to examine the phenotypic correlates of albumin and its independent prognostic implications in HFpEF. We analyzed data from 3,254 subjects enrolled the TOPCAT trial. We stratified subjects according to tertiles of albumin and examined differences in various phenotypic traits between these strata, including 8 protein biomarkers selected ad hoc and measured from frozen samples available in a subset of participants (n = 372). We also assessed the relationship between albumin and the trial primary endpoint. Lower albumin was associated with older age, black race, and greater prevalence of NYHA class III-IV, peripheral arterial disease, atrial fibrillation and diabetes mellitus. Lower albumin was also associated with increased levels of several inflammatory biomarkers, markers of liver fibrosis, albuminuria, and greater arterial stiffness, diastolic dysfunction and pulmonary hypertension. Albumin was a strong predictor of the primary trial endpoint, even after adjustment for the MAGGIC risk score (hazard ratio [HR] 0.72, confidence interval [CI] 0.67 to 0.78; p <0.0001) and prespecified traditional risk factors (HR 0.78, CI 0.71 to 0.85; p <0.0001). Lower albumin was strongly associated with a worse prognosis even well within normal ranges (>3.5 g/dL), with a sharp increase in risk between 4.6 and 3.6 g/dL. In conclusion, albumin is an integrated marker of various adverse processes in HFpEF, including inflammation, subclinical liver disease, arterial stiffness, and renal disease. Albumin is a powerful risk predictor independent of traditional risk prediction models, even within normal ranges.

A Prospective Pilot Study of Pocket-Carried Ultrasound Pre- and Postdischarge Inferior Vena Cava Assessment for Prediction of Heart Failure Rehospitalization.

BACKGROUND: Rehospitalization for heart failure (HF) is common, and subclinical congestion may be present at discharge. Larger inferior vena cava (IVC) size and lower collapsibility at discharge assessed via bedside ultrasound are predictive of rehospitalization; however, the utility of IVC assessment with the use of pocket-carried ultrasound (PCUS) during the transition from discharge to the posthospitalization follow-up visit (FU) has not been investigated. METHODS AND RESULTS: IVCmax and IVCmin were measured with the use of PCUS, and the collapsibility index (IVCCI = [IVCmax - IVCmin]/IVCmax) was determined. The primary outcome was 90-day rehospitalization or death. We prospectively enrolled 49 adults (71 ± 13 years of age, 51% male, 47% black, 43% preserved ejection fraction) hospitalized for HF. Nineteen patients (39%) experienced the outcome. Within the rehospitalized group, discharge and FU mean IVCmax were both >2.1 cm (2.2 ± 0.5 and 2.2 ± 0.7) and IVCCIs <50% (44 ± 20% and 45 ± 24%). Within those not rehospitalized, FU IVCmax was ≤2.1 cm (2.1 ± 0.6 and 1.9 ± 0.6; P = .038) and IVCCI >50% at both time points (55 ± 25% and 62 ± 19%; P = NS). FU IVCCI below an optimal cutoff of 42% had modest discrimination alone (c-statistic = 0.73). FU IVCCI <42% was associated with a greater hazard of the outcome independent of admission log B-type natriuretic peptide (adjusted hazard ratio = 6.8; 95% confidence interval 2.4-19.0; P < .001). CONCLUSIONS: Posthospitalization IVCCI assessment with PCUS predicts HF rehospitalization and may identify patients in need of intervention.

Effect of Trainee Performance Data on Standard-Setting Judgments Using the Mastery Angoff Method.

BACKGROUND: Mastery learning in health professions education requires learners to learn and undergo assessment until they demonstrate a high level of competence. Setting defensible standards is key to accurately assessing educational outcomes in mastery learning. The Mastery Angoff method was proposed recently to set a minimum passing standard (MPS) for mastery learning curricula. However, it is unknown whether prior knowledge of trainee performance affects judges' decisions about setting an MPS using the Mastery Angoff method. OBJECTIVE: We sought to determine the effect of introducing baseline data about trainee performance on faculty judges' decisions about the Mastery Angoff MPS for a written examination. METHODS: We developed a mastery learning curriculum to train internal medicine residents and cardiology fellows about the correct interpretation of inpatient telemetry monitoring. All learners were required to meet or exceed an MPS on a 35-item written examination at the end of training. The MPS was set in 2017 by judges who used the item-based Mastery Angoff method without prior examinee performance information. The judges subsequently reevaluated the test items after receiving baseline data about trainee performance collected during pilot testing. Mastery Angoff MPSs with and without baseline performance data were compared. RESULTS: Twelve judges participated in the standard-setting exercise. The initial MPS was similar to the repeat MPS set after judges received trainee performance data (86.2% versus 86.9%, P = .23). CONCLUSIONS: Prior knowledge about medical trainee performance data did not affect MPS as determined by the Mastery Angoff procedure.

Obesity and heart failure with preserved ejection fraction: A growing problem.

Heart Failure with Preserved Ejection Fraction (HFpEF) is increasing in prevalence due to the aging of the United States population as well as the current obesity epidemic. While obesity is very common in patients with HFpEF, obesity may represent a specific phenotype of HFpEF characterized by unique hemodynamics and structural abnormalities. Obesity induces a systemic inflammatory response that may contribute to myocardial fibrosis and endothelial dysfunction. The most obese patients continue to be excluded from HFpEF clinical trials, and thus ongoing research is needed to determine the role of pharmacologic and interventional approaches in this growing population.

Simulation-based education leads to decreased use of fluoroscopy in diagnostic coronary angiography.

OBJECTIVES: The aim of this study is to determine whether simulation-based education (SBE) translates into reduced procedure time, radiation, and contrast use in actual clinical care. BACKGROUND: As a high volume procedure often performed by novice cardiology fellows, diagnostic coronary angiography represents an excellent target for SBE. Reports of SBE in interventional cardiology are limited and there is little understanding of the potential downstream clinical impact of these interventions. METHODS: All diagnostic coronary angiograms performed at a single center between January 1, 2011 and June 30, 2015 were analyzed. Random effects linear regression models were used to compare outcomes between procedures performed by 12 cardiology fellows who underwent simulation-based training and those performed by 20 traditionally trained fellows. RESULTS: Thirty-two cardiology fellows performed 2,783 diagnostic coronary angiograms. Procedures performed by fellows trained with SBE were shorter (mean of 23.98 min vs. 24.94 min, P = 0.034) and were performed with decreased radiation (mean of 56,348 mGycm2 vs. 66,120 mGycm2 , P < 0.001). After controlling for year in training, procedure year, access site, and supervising attending physician, training on the simulator was independently associated with 117 fewer seconds of fluoroscopy time per procedure (P = 0.04). CONCLUSIONS: Diagnostic coronary angiography SBE is associated with decreased use of fluoroscopy in downstream clinical care. SBE may be a useful tool to reduce radiation exposure in the cardiac catheterization laboratory.

Differences in Repolarization Heterogeneity Among Heart Failure With Preserved Ejection Fraction Phenotypic Subgroups.

Heart failure with preserved ejection fraction (HFpEF) is a highly heterogeneous syndrome associated with multiple medical comorbidities and pathophysiologic pathways or phenotypes. We recently developed a phenomapping method combining deep phenotyping with machine learning analysis to classify HFpEF patients into 3 clinically distinct phenotypic subgroups (phenogroups) with different clinical outcomes. Phenogroup #1 was younger with lower B-type natriuretic peptide levels, phenogroup #2 had the highest prevalence of obesity and diabetes mellitus, and phenogroup #3 was the oldest with the most factors for chronic kidney disease, the most dysfunctional myocardial mechanics, and the highest adverse outcomes. The pathophysiological differences between these phenogroups, however, remain incompletely described. We sought to evaluate whether these 3 groups differ on the basis of repolarization heterogeneity, which has previously been linked to adverse outcomes in HFpEF. The T-peak to T-end (TpTe) interval, a well-validated index of repolarization heterogeneity, was measured by 2 readers blinded to each other and all other clinical data on the electrocardiograms of 201 HFpEF patients enrolled in a systematic observational study. TpTe duration was associated with higher B-type natriuretic peptide level (p = 0.006), increased QRS-T angle (p = 0.008), and lower septal e' velocity (p = 0.007). TpTe duration was greatest in phenogroup #3 (100.4 ± 24.5 ms) compared with phenogroups #1 (91.2 ± 17.3 ms) and #2 (90.2 ± 17.0 ms) (p = 0.0098). On multivariable analyses, increased TpTe was independently associated with the high-risk phenogroup #3 classification. In conclusion, repolarization heterogeneity is a marker of a specific subset of HFpEF patients identified using unsupervised machine learning analysis and therefore may be a key pathophysiologic marker in this subset of HFpEF patients.