Citations

Introduction: Heart failure with preserved ejection fraction (HFpEF) is an increasingly common clinical syndrome with diagnostic challenges and no effective treatment. The high heterogeneity of HFpEF clinical syndrome demands novel technologies to distinguish from heart failure with reduced ejection Fraction (HFrEF). Currently, invasive hemodynamic exercise testing is performed to evaluate for HFpEF with right heart catheterization. Hypothesis: We hypothesize that a deep learning model can noninvasively detect patients with HFpEF using phonocardiogram (PCG). Methods: Eligible patients undergoing right heart catheterization were recruited after IRB approval. Eko duo stethoscope was used to record simultaneous ECG & PCG at the mitral area on the patients prior to right heart catheterization at baseline. Each recording was 30 seconds in length with a frequency range between 250 - 5000 Hz. R-wave peak detection was performed & beat to beat PCG annotations were performed. The annotated PCG signals were converted into Mel-frequency cepstral coefficients (MFCC) and padded to account for the difference in lengths. Deep Learning model was developed using a Sequential Neural Network with 80% data to train and validate the model and 20% hold out data was used for testing accuracy of the model. Receiver operating curve (ROC) was obtained to estimate area under the curve (AUC) for performance analysis. Results: 42 patients were enrolled with 25 patients diagnosed as HFpEF by right heart catheterization and 17 were reported as controls. 2544 & 1771 individual PCG annotations for HFpEF and controls were used for model training/validation and testing. The model performed reasonably well with accuracy of 0.89, F1 score of 0.88, precision of 0.80 and recall of 0.97 on the test data. ROC was obtained with AUC of 0.94. Conclusions: The results demonstrate the ability of the deep learning model to noninvasively detect HFpEF using PCG. Larger study is needed to validate these findings.

Abstract Aims It is widely held that heart failure (HF) does not cause exertional hypoxaemia, based upon studies in HF with reduced ejection fraction, but this may not apply to patients with HF and preserved ejection fraction (HFpEF). Here, we characterize the prevalence, pathophysiology, and clinical implications of exertional arterial hypoxaemia in HFpEF. Methods and results Patients with HFpEF (n = 539) and no coexisting lung disease underwent invasive cardiopulmonary exercise testing with simultaneous blood and expired gas analysis. Exertional hypoxaemia (oxyhaemoglobin saturation <94%) was observed in 136 patients (25%). As compared to those without hypoxaemia (n = 403), patients with hypoxaemia were older and more obese. Patients with HFpEF and hypoxaemia had higher cardiac filling pressures, higher pulmonary vascular pressures, greater alveolar–arterial oxygen difference, increased dead space fraction, and greater physiologic shunt compared to those without hypoxaemia. These differences were replicated in a sensitivity analysis where patients with spirometric abnormalities were excluded. Regression analyses revealed that increases in pulmonary arterial and pulmonary capillary pressures were related to lower arterial oxygen tension (PaO2), especially during exercise. Body mass index (BMI) was not correlated with the arterial PaO2, and hypoxaemia was associated with increased risk for death over 2.8 (interquartile range 0.7–5.5) years of follow-up, even after adjusting for age, sex, and BMI (hazard ratio 2.00, 95% confidence interval 1.01–3.96; p = 0.046). Conclusion Between 10% and 25% of patients with HFpEF display arterial desaturation during exercise that is not ascribable to lung disease. Exertional hypoxaemia is associated with more severe haemodynamic abnormalities and increased mortality. Further study is required to better understand the mechanisms and treatment of gas exchange abnormalities in HFpEF.

Abstract Pericardial effusions can result in acute haemodynamic compromise and require rapid intervention. Understanding pericardial restraint is essential to determine the approach to newly identified pericardial effusions in the intensive care unit. As pericardial effusions stretch the pericardium, the pericardial compliance reserve is eventually exhausted, with an exponential rise in compressive pericardial pressure. The severity of pericardial pressure increase depends on both the rapidity and volume of pericardial fluid accumulation. This increase in pericardial pressure is reflected in an increase in measured left- and right-sided ‘filling’ pressures, but paradoxically left ventricular end-diastolic volume (the true left ventricular preload) is decreased. This uncoupling of filling pressures and preload is the hallmark of pericardial restraint. When this occurs acutely from a pericardial effusion, rapid recognition and pericardiocentesis can be lifesaving. In this review, we will discuss the haemodynamics and pathophysiology of acute pericardial effusions, provide a physiological guide to determine the need for pericardiocentesis in acute care, and discuss important caveats to management.

ABSTRACT Aims Cardiac and extracardiac abnormalities play important roles in heart failure with preserved ejection fraction (HFpEF). Biventricular cardiac power output (BCPO) quantifies the total rate of hydraulic work performed by both ventricles, suggesting that it may help to identify patients with HFpEF and more severe cardiac impairments to better individualize treatment. Methods and results Patients with HFpEF (n = 398) underwent comprehensive echocardiography and invasive cardiopulmonary exercise testing. Patients were categorized as low BCPO reserve (n = 199, < median of 1.57 W) or preserved BCPO reserve (n = 199). As compared to those with preserved BCPO reserve, those with low reserve were older and leaner, with more atrial fibrillation, higher N-terminal pro-B-type natriuretic peptide levels, worse renal function, more impaired left ventricular (LV) global longitudinal strain, worse LV diastolic function and right ventricular longitudinal function. Cardiac filling pressures and pulmonary artery pressures at rest were higher in low BCPO reserve, but central pressures were similar during exercise to those with preserved BCPO reserve. Exertional systemic and pulmonary vascular resistances were higher and exercise capacity was more impaired in those with low BCPO reserve. Reduced BCPO reserve was associated with increased risk for the composite endpoint of heart failure hospitalization or death over 2.9 (interquartile range 0.9–4.5) years of follow-up (hazard ratio 2.77, 95% confidence interval 1.73–4.42, p < 0.0001). Conclusions Inability to enhance BCPO during exercise is associated with more advanced HFpEF, increased systemic and pulmonary vascular resistance, reduced exercise capacity and increased adverse events in patients with HFpEF. Novel therapies that enhance biventricular reserve merit further investigation for patients with this phenotype.

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognised to be strongly associated with obesity and abnormalities in fat distribution. Epicardial fat has been associated with abnormal haemodynamics in HFpEF, with potential for direct mechanical effects on the heart causing constriction-like physiology and local myocardial remodelling effects from secretion of inflammatory and profibrotic mediators. However, patients with epicardial fat generally have more systemic and visceral adipose tissue making determination of causality between epicardial fat and HFpEF complex. In this review, we will summarise the evidence for epicardial fat being either directly causal in HFpEF pathogenesis or merely being a correlate of worse systemic inflammatory and generalised adiposity. We will also discuss therapies that directly target epicardial fat and may have potential for treating HFpEF and elucidating the independent role of epicardial fat in its pathogenesis.

Abstract Aims Ancillary analyses from clinical trials have suggested reduced efficacy for neurohormonal antagonists among patients with heart failure and preserved ejection fraction (HFpEF) and higher ranges of ejection fraction (EF). Methods and results A total of 621 patients with HFpEF were grouped into those with low-normal left ventricular EF (LVEF) (HFpEF<65%, n = 319, 50% ≤ LVEF <65%) or HFpEF≥65% (n = 302, LVEF ≥65%), and compared with 149 age-matched controls undergoing comprehensive echocardiography and invasive cardiopulmonary exercise testing. A sensitivity analysis was performed in a second non-invasive community-based cohort of patients with HFpEF (n = 244) and healthy controls without cardiovascular disease (n = 617). Patients with HFpEF≥65% had smaller left ventricular (LV) end-diastolic volume than HFpEF<65%, but LV systolic function assessed by preload recruitable stroke work and stroke work/end-diastolic volume was similarly impaired. Patients with HFpEF≥65% displayed an end-diastolic pressure–volume relationship (EDPVR) that was shifted leftward, with increased LV diastolic stiffness constant β, in both invasive and community-based cohorts. Cardiac filling pressures and pulmonary artery pressures at rest and during exercise were similarly abnormal in all EF subgroups. While patients HFpEF≥57% displayed leftward shifted EDPVR, those with HFpEF<57% had a rightward shifted EDPVR more typical of heart failure with reduced EF. Conclusion Most pathophysiologic differences in patients with HFpEF and higher EF are related to smaller heart size, increased LV diastolic stiffness, and leftward shift in the EDPVR. These findings may help to explain the absence of efficacy for neurohormonal antagonists in this group and raise a new hypothesis, that interventions to stimulate eccentric LV remodelling and enhance diastolic capacitance may be beneficial for patients with HFpEF and EF in the higher range.

ImportanceChronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown.ObjectiveTo assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR.Design, Setting, and ParticipantsThis retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021.ExposuresAortic regurgitation severity, graded by a comprehensive integrated approach.Main Outcomes and MeasuresThe primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF.ResultsOf 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid–ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2).Conclusions and RelevanceThis multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.

Importance Reduced heart rate during exercise is common and associated with impaired aerobic capacity in heart failure with preserved ejection fraction (HFpEF), but it remains unknown if restoring exertional heart rate through atrial pacing would be beneficial. Objective To determine if implanting and programming a pacemaker for rate-adaptive atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence. Design, Setting, and Participants Single-center, double-blind, randomized, crossover trial testing the effects of rate-adaptive atrial pacing in patients with symptomatic HFpEF and chronotropic incompetence at a tertiary referral center (Mayo Clinic) in Rochester, Minnesota. Patients were recruited between 2014 and 2022 with 16-week follow-up (last date of follow-up, May 9, 2022). Cardiac output during exercise was measured by the acetylene rebreathe technique. Interventions A total of 32 patients were recruited; of these, 29 underwent pacemaker implantation and were randomized to atrial rate responsive pacing or no pacing first for 4 weeks, followed by a 4-week washout period and then crossover for an additional 4 weeks. Main Outcomes and Measures The primary end point was oxygen consumption (V̇ o 2 ) at anaerobic threshold (V̇ o 2,AT ); secondary end points were peak V̇ o 2 , ventilatory efficiency (V̇ e /V̇ co 2 slope), patient-reported health status by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Results Of the 29 patients randomized, the mean age was 66 years (SD, 9.7) and 13 (45%) were women. In the absence of pacing, peak V̇ o 2 and V̇ o 2 at anaerobic threshold (V̇ o 2,AT ) were both correlated with peak exercise heart rate ( r = 0.46-0.51, P < .02 for both). Pacing increased heart rate during low-level and peak exercise (16/min [95% CI, 10 to 23], P < .001; 14/min [95% CI, 7 to 21], P < .001), but there was no significant change in V̇ o 2,AT (pacing off, 10.4 [SD, 2.9] mL/kg/min; pacing on, 10.7 [SD, 2.6] mL/kg/min; absolute difference, 0.3 [95% CI, −0.5 to 1.0] mL/kg/min; P = .46), peak V̇ o 2 , minute ventilation (V̇ e) /carbon dioxide production (V̇ co 2 ) slope, KCCQ-OSS, or NT-proBNP level. Despite the increase in heart rate, atrial pacing had no significant effect on cardiac output with exercise, owing to a decrease in stroke volume (−24 mL [95% CI, −43 to −5 mL]; P = .02). Adverse events judged to be related to the pacemaker device were observed in 6 of 29 participants (21%). Conclusions and Relevance In patients with HFpEF and chronotropic incompetence, implantation of a pacemaker to enhance exercise heart rate did not result in an improvement in exercise capacity and was associated with increased adverse events. Trial Registration ClinicalTrials.gov Identifier: NCT02145351

Background Information on impact of race and ethnicity on use and early outcomes of septal reduction therapies (SRTs) for obstructive hypertrophic obstructive cardiomyopathy are limited. Methods and Results Using the National Inpatient Sample from January 2012 through December 2019, we identified all adult admissions with a primary diagnosis of obstructive hypertrophic cardiomyopathy and those undergoing SRT. Predictors of receiving SRT and outcomes including in‐hospital mortality, complications, and resource use were evaluated in racial and ethnic groups. Among a total of 18 895 adult admissions with obstructive hypertrophic cardiomyopathy, SRT was performed in 7255 (38.4%) admissions. Septal myectomy was performed in 4930 (26.1%), while alcohol septal ablation was performed in 2325 (12.3%). In adjusted analysis, Black patient (versus White patient adjusted odds ratio, 0.65 [95% CI, 0.57–0.73]; P <0.001) and Hispanic patient admissions (versus White adjusted odds ratio, 0.78 [95% CI, 0.66–0.92]; P =0.003) were less likely to receive SRT. Among admissions undergoing SRT, in‐hospital mortality was significantly higher for Hispanic (adjusted odds ratio, 3.38 [95% CI, 1.81–6.30], P <0.001) and other racial and ethnic groups (adjusted odds ratio 2.02 [95% CI, 1.00–4.11]; P =0.05) compared with White patient admissions, whereas Black patient admissions had comparable mortality. Black, Hispanic, and other ethnic group patients had higher rates of SRT complications and more frequent dismissals to acute care facilities. Conclusions Among obstructive hypertrophic cardiomyopathy hospitalizations, minoritized racial groups were less likely to receive SRT. Importantly, hospitalizations of Hispanic and other ethnic patients undergoing SRT had significantly higher in‐hospital mortality and complication rates. Further studies with granular echocardiographic information to assess indications for SRT are needed to better understand these differences.