Background: Pulmonary capillary wedge pressure (PCWP) provides an objective assessment of congestion status in heart failure (HF) patients, but its use is limited by the need for an invasive procedure, trained personnel, and specialized equipment to obtain a measurement. Cardiosense (Chicago, IL) has developed a machine learning (ML) algorithm that detects elevated PCWP non-invasively from data acquired by a chest-worn wearable device (CardioTag). We present data for a potential in-clinic point-of-care tool that improves the identification of hemodynamic congestion, with a focus on outpatient and low-acuity settings. Methods: The ePCWP System is a ML model developed to identify elevated PCWP (>18 mmHg) using non-invasive physiological biosignals from the CardioTag device, which simultaneously collects electrocardiogram, seismocardiogram, and photoplethysmogram data. Concurrent CardioTag and right-heart catheterization (RHC) data were collected prospectively in an observational study across 15 US sites from 1,116 patients undergoing standard-of-care RHC. Patients were either diagnosed with HFrEF, HFpEF, HFmrEF, or were suspected of HF before the RHC procedure. Standard of care physical examination, used to evaluate congestion status, was captured and used for comparative analysis. The training dataset contained 726 subjects and the validation dataset contained 153 subjects. Results: Five-fold cross-validation of the training dataset showed an overall accuracy of 0.79, sensitivity of 0.75 (CI: [0.69, 0.80]), and a specificity of 0.81 (CI: [0.77, 0.78]). The validation dataset showed an overall accuracy of 0.81, sensitivity of 0.76 (CI: [0.63, 0.86]), and a specificity of 0.82 (CI: [0.66, 0.89]). Figure 1 shows the overall classification performance of the ePCWP System (left) and a comparison to standard-of-care physical exam (right). Conclusion: We developed a non-invasive point-of-care tool that is capable of providing rapid, accurate assessments of congestion for patients with HF. This tool might be used to support convenient, frequent inpatient monitoring to augment discharge decisions and guide post-discharge follow-up care towards timely interventions and improvements in patient outcomes.

BACKGROUND:Epicardial adipose tissue (EAT) may play a role in the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). OBJECTIVES:This study examined associations between increased EAT, functional status, and invasive exercise hemodynamics in a large cohort of HFpEF patients. METHODS:All patients underwent echocardiography, 6-minute walk distance (MWD) test, Kansas City Cardiomyopathy Questionnaire, and invasive hemodynamic assessment at rest and during ergometry. EAT thickness was measured alongside the right ventricle on echocardiography, expressed in mm and patients were divided according to EAT tertiles. RESULTS:In total, 566 patients were examined with mean age 72 ± 8 years, 62% women, mean EAT thickness was 6.0 ± 2.4 mm and 11.5% had EAT ≥9 mm. With increasing EAT thickness tertiles, 6-MWD and Kansas City Cardiomyopathy Questionnaire overall summary score were significantly lower (320 [247-385] vs 315 [244-383] vs 287 [210-364] meters, P = 0.001; 51 [32-67] vs 45 [32-63] vs 41, [26-56], P = 0.003; respectively), whereas the latter was independent of body mass index (P = 0.004). At rest, invasive hemodynamics were not different across EAT tertiles. At peak exercise, patients in the highest EAT thickness tertile had higher pulmonary capillary wedge pressure and pulmonary capillary wedge pressure to right atrial pressure gradient, compared to patients in the first and second EAT thickness tertiles (36 ± 8 vs 34 ± 8 mm Hg, P = 0.009; 18 ± 7 vs 16 ± 7 mm Hg, P = 0.002, respectively). CONCLUSIONS:EAT thickness was associated with impaired quality of life, lower 6-MWD, and higher left-sided filling pressures at peak exercise. Excess EAT may therefore play an important role in functional status and exercise hemodynamics in patients with HFpEF.

BACKGROUND:Remote hemodynamics-guided management of heart failure (HF) with implantable pulmonary artery pressure sensors has been shown to reduce HF hospitalizations. The widespread clinical adoption of this procedure is constrained by its invasive nature and high cost. We present a noninvasive technology based on a wearable sensor (CardioTag; Cardiosense) and machine learning (ML) for estimating pulmonary capillary wedge pressure (PCWP) in patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES:The authors developed and evaluated (against right heart catheterization [RHC]) an ML model to estimate PCWP with the use of electrocardiography, seismocardiography, and photoplethysmography signals from CardioTag. METHODS:A multicenter prospective study was performed, and 310 patients with HFrEF (EF ≤40%) were recruited in both inpatient and outpatient settings. A blinded core laboratory adjudicated the RHC PCWP tracings to yield criterion-standard PCWP labels against which the model was trained and tested. The data were separated into 2 sets: a training set for model training and fine-tuning, and a held-out testing set unseen until final evaluation. RESULTS:The patients were 61± 13 years of age, 38% female, 44% White, and 39% African American, and had a PCWP of 18.1 ± 9.45 mm Hg. The model estimated PCWP values in the held-out test set with error of 1.04 ± 5.57 mm Hg (limits of agreement of -9.9 to 11.9 mm Hg), with consistent performance across sex, race, ethnicity, and body mass index. CONCLUSIONS:The CardioTag and its ML algorithm estimate PCWP with accuracy approaching implantable hemodynamic sensors, potentially offering a more accessible and cost-effective option for hemodynamics-guided management in HFrEF patients.

BACKGROUND:Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES:This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS:Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS:Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS:In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).

Background: Sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors) prevent heart failure (HF) hospitalizations in patients with type 2 diabetes and improve outcomes in those with HF and reduced ejection fraction, regardless of type 2 diabetes. Mechanisms of HF benefits remain unclear, and the effects of SGLT2 inhibitor on hemodynamics (filling pressures) are not known. The EMBRACE-HF trial (Empagliflozin Evaluation by Measuring Impact on Hemodynamics in Patients With Heart Failure) was designed to address this knowledge gap. Methods: EMBRACE-HF is an investigator-initiated, randomized, multicenter, double-blind, placebo-controlled trial. From July 2017 to November 2019, patients with HF (regardless of ejection fraction, with or without type 2 diabetes) and previously implanted pulmonary artery (PA) pressure sensor (CardioMEMS) were randomized across 10 US centers to empagliflozin 10 mg daily or placebo and treated for 12 weeks. The primary end point was change in PA diastolic pressure (PADP) from baseline to end of treatment (average PADP weeks 8–12). Secondary end points included health status (Kansas City Cardiomyopathy Questionnaire score), natriuretic peptides, and 6-min walking distance. Results: Overall, 93 patients were screened, and 65 were randomized (33 to empagliflozin, 32 to placebo). The mean age was 66 years; 63% were male; 52% had type 2 diabetes; 54% were in New York Heart Association class III/IV; mean ejection fraction was 44%; median NT-proBNP (N-terminal pro B-type natriuretic peptide) was 637 pg/mL; and mean PADP was 22 mm Hg. Empagliflozin significantly reduced PADP, with effects that began at week 1 and amplified over time; average PADP (weeks 8–12) was 1.5 mm Hg lower (95% CI, 0.2–2.8; P =0.02); and at week 12, PADP was 1.7 mm Hg lower (95% CI, 0.3–3.2; P =0.02) with empagliflozin versus placebo. Results were consistent for PA systolic and PA mean pressures. There was no difference in mean loop diuretic management (daily furosemide equivalents) between treatment groups. No significant differences between treatment groups were observed in Kansas City Cardiomyopathy Questionnaire scores, natriuretic peptide levels, and 6-min walking distance. Conclusions: In patients with HF and CardioMEMS PA pressure sensor, empagliflozin produced rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03030222.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3–9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0–9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7–10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6–34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1–7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05–2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01–1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.

HomeCirculation: Heart FailureVol. 14, No. 11Association Between Change in Ambulatory Hemodynamic Pressures and Symptoms of Heart Failure Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBAssociation Between Change in Ambulatory Hemodynamic Pressures and Symptoms of Heart Failure Michael E. Nassif, MD, John A. Spertus, MD, Fengming Tang, MS, Sheryl L. Windsor, BS, Philip Jones, MS, Merrill Thomas, MD, Yevgeniy Khariton, MD, John Brush, MD, Robert A. Gordon, MD, Rita Jermyn, MD, Orvar Jonsson, MD, Sumant Lamba, MD, David M. Shavelle, MD and Mikhail N. Kosiborod, MD Michael E. NassifMichael E. Nassif Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., J.A.S., F.T., S.L.W., P.J., M.T., Y.K., M.N.K.). University of Missouri-Kansas City (M.E.N., J.A.S., M.T., Y.K., M.N.K.). , John A. SpertusJohn A. Spertus https://orcid.org/0000-0002-2839-2611 Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., J.A.S., F.T., S.L.W., P.J., M.T., Y.K., M.N.K.). University of Missouri-Kansas City (M.E.N., J.A.S., M.T., Y.K., M.N.K.). , Fengming TangFengming Tang Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., J.A.S., F.T., S.L.W., P.J., M.T., Y.K., M.N.K.). , Sheryl L. WindsorSheryl L. Windsor Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., J.A.S., F.T., S.L.W., P.J., M.T., Y.K., M.N.K.). , Philip JonesPhilip Jones https://orcid.org/0000-0002-7136-4464 Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., J.A.S., F.T., S.L.W., P.J., M.T., Y.K., M.N.K.). , Merrill ThomasMerrill Thomas https://orcid.org/0000-0003-3418-6424 Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., J.A.S., F.T., S.L.W., P.J., M.T., Y.K., M.N.K.). University of Missouri-Kansas City (M.E.N., J.A.S., M.T., Y.K., M.N.K.). , Yevgeniy KharitonYevgeniy Khariton Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., J.A.S., F.T., S.L.W., P.J., M.T., Y.K., M.N.K.). University of Missouri-Kansas City (M.E.N., J.A.S., M.T., Y.K., M.N.K.). , John BrushJohn Brush Sentara Healthcare, Norfolk, VA (J.B.). Eastern Virginia Medical School, Norfolk, VA (J.B.). , Robert A. GordonRobert A. Gordon NorthShore University HealthSystem, Evanston, IL (R.A.G.). , Rita JermynRita Jermyn St. Francis, Roslyn, NY (R.J.). , Orvar JonssonOrvar Jonsson University of South Dakota Sanford Health, Sioux Falls (O.J.). , Sumant LambaSumant Lamba First Coast Cardiovascular Institute, Jacksonville, FL (S.L.). , David M. ShavelleDavid M. Shavelle https://orcid.org/0000-0002-9209-9807 University of Southern California, Los Angeles (D.M.S.). and Mikhail N. KosiborodMikhail N. Kosiborod Correspondence to: Mikhail Kosiborod, MD, St Luke's Mid America Heart Institute, 4401 Wornall Rd, Kansas City, MO 64111. Email E-mail Address: [email protected] https://orcid.org/0000-0002-3750-9789 Saint Luke's Mid America Heart Institute, Kansas City, MO (M.E.N., J.A.S., F.T., S.L.W., P.J., M.T., Y.K., M.N.K.). University of Missouri-Kansas City (M.E.N., J.A.S., M.T., Y.K., M.N.K.). The George Institute for Global Health, Sydney, Australia (M.N.K.). University of New South Wales, Sydney, Australia (M.N.K.). Originally published26 Oct 2021https://doi.org/10.1161/CIRCHEARTFAILURE.121.008446Circulation: Heart Failure. 2021;14Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: October 26, 2021: Ahead of Print Professional societies recommend that patients with heart failure (HF) undergo systematic monitoring to promptly recognize and treat changes in health status (symptoms, function, and quality of life). Not only is a careful assessment of health status necessary for care, but it can also quantify the benefits of new therapies.1 A novel means of monitoring patients with severe HF is pulmonary artery (PA) pressure sensor (CardioMEMs). To date, however, its direct correlation with patients' health status, as quantified by the Kansas City Cardiomyopathy Questionnaire (KCCQ), has not been well described. We sought to leverage data from the EMBRACE-HF trial (Empagliflozin Evaluation by Measuring Impact on Hemodynamics in Patients With Heart Failure) to assess the relationship of changes in PA pressures with changes in symptoms measured by KCCQ.2EMBRACE-HF was a randomized, double-blind, placebo-controlled, multi-center trial of empagliflozin 10 mg daily or placebo in patients with HF (regardless of ejection fraction), implanted CardioMEMs, and elevated PA diastolic pressure (PADP).1 Patients' health status was measured using KCCQ at baseline, 6, and 12 weeks. PA pressures were recorded twice daily using CardioMEMS throughout the study.The KCCQ is a 23-item self-administered questionnaire that assesses the symptom burden, physical and social limitations, and quality of life in HF. We hypothesized, a priori, that changes in PADP would be strongly associated with changes in HF symptoms, as measured by the KCCQ total symptom score (TSS) because this is the most proximal manifestation of hemodynamic status.3Details about PA pressure with CardioMEMs have been published.3 Participants in EMBRACE-HF had stable hemodynamics defined as no change >±6 mm Hg from their average PADP during the screening period. In the current analysis, the change in PADP was assessed as the difference between the average seven-day preenrollment PADP (baseline) and the PADP during the seven days preceding the (1) 6-week and (2) 12-week follow-up visit.We developed a linear mixed model incorporating the 6- and 12-week repeated measurements. The dependent variable was change from baseline in the KCCQ-TSS, and the key predictor variable was change from baseline in 7-day average PADP at each follow-up time point. The model also included adjustment for baseline PADP and KCCQ. The overall analysis was obtained by pooling the 6- and 12-week associations between change in PADP and change in KCCQ.For the entire cohort, mean age was 66 years, 63% were male, and 19% were Black people. Mean left ventricular ejection fraction was 44%; 29 (47%) had left ventricular ejection fraction ≤40%, and 33 (53%) had left ventricular ejection fraction >40%, New York Heart Association class II symptoms were present in 47%, with class III/IV symptoms in 53%. Overall, 88% of participants were taking beta-blockers, 44% mineralocorticoid antagonists, 31% ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blockers, and 44% angiotensin receptor neprilysin inhibitor, and nearly all patients (97%) were on a loop diuretic. The mean PADP at baseline was 21.8±6.4 and the mean KCCQ-TSS at baseline was 65.7±25.1. Twenty-three (38%) patients had a ≥1 mm Hg absolute decrease, 21 (34%) had no change, and 17 (28%) had a ≥1 mm Hg absolute increase in PADP over the course of the study. The average change between baseline and averaged week 6 and 12 PADP was 0.37±3.1 mm Hg, and the corresponding mean change in KCCQ-TSS was 2.4±17.1.After adjusting for baseline KCCQ and PADP, every 2 mm Hg decrease in PADP was associated with a KCCQ-TSS improvement of 2.1 points (95% CI, 0.19–3.97 points, P=0.03; Figure). Furthermore, patients with at least ≥2 mm Hg PADP decrease experienced numerically large improvement, whereas participants with relatively stable PADP had small improvement, and those with ≥2 mm Hg or greater PADP increase experienced worsening in mean KCCQ-TSS (11.4±25.3, 2.1±15.5, and −2.8±11.3 points, respectively).Download figureDownload PowerPointFigure. Correlation between change in Kansas City Cardiomyopathy total symptom score (KCCQ-TSS) and change in pulmonary artery (PA) diastolic pressure. Shaded region represents 95% confidence intervals of model slope. x axis denotes the distribution of each change in PA diastolic pressures.Although the use of ambulatory hemodynamic monitoring has been shown to reduce hospitalizations and improve patients' health status, a direct association between changes in PADP and patients' symptoms, as measured by the KCCQ, has not been described. In EMBRACE-HF, we found that on average every 2mmHg decrease in PADP was associated with a ≈2-point improvement in KCCQ-TSS (a magnitude of KCCQ change similar to that observed with efficacious HF therapies).4 To our knowledge, this is the first evidence that directly correlates change in hemodynamic parameters with change in patients' symptoms. Although the KCCQ has a 14-day recall period, we used 7-day average PADP to provide a more current assessment of hemodynamic status in patients with more severe and labile HF. Nevertheless, prior experience with patient-reported outcomes in cardiovascular disease suggests that patients generally respond based on their most recent symptoms.5 In conclusion, short-term changes in ambulatory PADP are significantly associated with changes in HF symptoms as measured by the KCCQ.Article InformationSources of FundingThe study was an investigator-initiated trial funded by Boehringer Ingelheim and conducted by Saint Luke's Mid America Heart Institute independent of the funding source.Nonstandard Abbreviations and AcronymsACEangiotensin-converting enzymeEMBRACE-HFEmpagliflozin Evaluation by Measuring Impact on Hemodynamics in Patients With Heart FailureHFheart failureKCCQKansas City Cardiomyopathy QuestionnairePApulmonary arteryPADPPA diastolic pressureTSStotal symptom scoreDisclosures Dr Nassif reports the following: honoraria and company relationship: Abbott; consultant and company relationship: Roche, Amgen, and Vifor. Dr Spertus owns the copyright to the Kansas City Cardiomyopathy Questionnaire. He also serves as a consultant for Novartis, Bayer, AstraZeneca, Myokardia, Merck, Amgen, United Healthcare, and Janssen, has equity in Health Outcomes Sciences, serves on the Board of Directors for Blue Cross-Blue Shield of Kansas City, and owns the copyright to the Seattle Angina Questionnaire and Peripheral Artery Questionnaire. Dr Jermyn reports the following: speaker's bureau and company relationship: Abbott and Novartis. Dr Lamba reports the following: speaker's bureau and company relationship: Abbott. Dr Gordon reports the following: honoraria and company relationship: Abiomed; consultant and company relationship: Akcea. Dr Jonsson reports the following: consultant and company relationship: Abbott; speaker's bureau and company relationship: Novartis. Dr Shavelle reports the following: grant/research support and company relationship: Abbott, V-Wave Medical, Verily, and AbioMed; consultant and company relationship: Shifamed; and speaker's bureau and company relationship: Abbott. Dr Kosiborod reports the following: grant/research support and company relationship: Boehringer Ingelheim and Astra Zeneca; honoraria and company relationship: Boehringer Ingelheim, Astra Zeneca, and Novo Nordisk; consultant and company relationship: Amgen, Applied Therapeutics, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma. The other authors report no conflicts.FootnotesFor Sources of Funding and Disclosures, see page 1261.REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030222.Correspondence to: Mikhail Kosiborod, MD, St Luke's Mid America Heart Institute, 4401 Wornall Rd, Kansas City, MO 64111. Email [email protected]orgReferences1. Spertus JA, Jones PG, Sandhu AT, Arnold SV. Interpreting the Kansas City cardiomyopathy questionnaire in clinical trials and clinical care: JACC State-of-the-Art Review.J Am Coll Cardiol. 2020; 76:2379–2390. doi: 10.1016/j.jacc.2020.09.542CrossrefMedlineGoogle Scholar2. Nassif ME, Qintar M, Windsor SL, Jermyn R, Shavelle DM, Tang F, Lamba S, Bhatt K, Brush J, Civitello A, et al.. Empagliflozin effects on pulmonary artery pressure in patients with heart failure: results from the EMBRACE-HF trial.Circulation. 2021; 143:1673–1686. doi: 10.1161/CIRCULATIONAHA.120.052503LinkGoogle Scholar3. Abraham WT, Adamson PB, Bourge RC, Aaron MF, Costanzo MR, Stevenson LW, Strickland W, Neelagaru S, Raval N, Krueger S, et al.; CHAMPION Trial Study Group. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial.Lancet. 2011; 377:658–666. doi: 10.1016/S0140-6736(11)60101-3CrossrefMedlineGoogle Scholar4. Kosiborod MN, Jhund PS, Docherty KF, Diez M, Petrie MC, Verma S, Nicolau JC, Merkely B, Kitakaze M, DeMets DL, et al.. Effects of dapagliflozin on symptoms, function, and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF trial.Circulation. 2020; 141:90–99. doi: 10.1161/CIRCULATIONAHA.119.044138LinkGoogle Scholar5. Sauser K, Spertus JA, Pierchala L, Davis E, Pang PS. Quality of life assessment for acute heart failure patients from emergency department presentation through 30 days after discharge: a pilot study with the Kansas City Cardiomyopathy Questionnaire.J Card Fail. 2014; 20:18–22. doi: 10.1016/j.cardfail.2013.11.010CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails November 2021Vol 14, Issue 11Article InformationMetrics Download: 156 © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCHEARTFAILURE.121.008446PMID: 34696602 Originally publishedOctober 26, 2021 Keywordspulmonary arteryheart failurehealth statusquality of lifeempagliflozinPDF download Advertisement

BackgroundCOVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness.MethodsDARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593.FindingsBetween April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58–1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97–1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52–1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo.InterpretationIn patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated.FundingAstraZeneca.

Introduction Sodium glucose cotransporter 2 inhibitors (SGLT2i) prevent heart failure (HF) in patients with Type 2 Diabetes (T2D), and reduce CV death or worsening HF in HF and reduced ejection fraction (HFrEF), regardless of T2D. Mechanisms of HF benefits are unclear, and effects of SGLT2i on filling pressures are not known. EMBRACE-HF was designed to address this knowledge gap. Methods EMBRACE-HF was an investigator-initiated, multi-center, double-blind, randomized trial. From July 2017 to November 2019, 65 patients with HF (regardless of EF, with or without T2D) and previously implanted pulmonary artery (PA) pressure sensor (CardioMEMS) were randomized across 10 US centers to empagliflozin (empa) 10 mg daily or placebo (pbo) and treated for 12 weeks. Primary endpoint was change in PA diastolic pressure (PADP) from baseline to end of treatment (average PADP weeks 8-12). Results 93 patients were screened, and 65 were randomized (33 empa, 32 pbo). Mean age was 66 yrs, 63% were male, 52% had T2D, 54% NYHA class III/IV; LVEF 44%, NTproBNP 1665 pg/mL and PADP 20 mmHg. Empa significantly reduced PADP, with effects beginning at week 1, and amplified over time (Figure 1). Average PADP (week 8-12) was 1.5 mmHg lower (95% CI: 0.2, 2.8; p = 0.02); and at week 12, PADP was 1.7 mmHg lower (95% CI: 0.3, 3.2; p = 0.02) with empa vs pbo. Results were consistent for PA systolic and PA mean pressures. There was no difference in loop diuretic dose (measured in daily furosemide equivalents) at baseline (90 mg empa, 85 mg pbo; p = 0.51), week 12 (92 mg empa, 86 mg pbo; p = 0.24), or any interim time point. Majority of patients in both groups (76% empa, 81% placebo; p = 0.89) had no change in loop diuretic dose during the study. Conclusion EMBRACE-HF is the first randomized controlled trial to show a direct beneficial effect of SGLT2i on decongestion in patients with HF (reduced or preserved EF), with rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management.

Brouwer and Brouwer-Lyddanes' use of the Von Zeipel-Delaunay method is employed to develop an efficient analytical orbit theory suitable for microcomputers. A succinctly simple pseudo-phenomenologically conceptualized algorithm is introduced which accurately and economically synthesizes modeling of drag effects. The method epitomizes and manifests effortless efficient computer mechanization. Simulated trajectory data is employed to illustrate the theory's ability to accurately accommodate oblateness and drag effects for microcomputer ground based or onboard predicted orbital representation. Real tracking data is used to demonstrate that the theory's orbit determination and orbit prediction capabilities are favorably adaptable to and are comparable with results obtained utilizing complex definitive Cowell method solutions on satellites experiencing significant drag effects.