Dapagliflozin Enhances Arterial and Venous Compliance During Exercise in Heart Failure With Preserved Ejection Fraction: Insights From the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial.

BACKGROUND: Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. METHODS: In this secondary analysis from the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial, 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model. RESULTS: There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P=0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m2 [95% CI, 0.003-0.11] P=0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P=0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P=0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P=0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P=0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P<0.001). CONCLUSIONS: In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04730947.

Prevalence, Incidence, and Outcomes of Diastolic Dysfunction in Isolated Tricuspid Regurgitation: Perhaps Not Really "Isolated"?

BACKGROUND: In the absence of left-sided cardiac/pulmonary disease, functional tricuspid regurgitation (FTR) is referred to as isolated or idiopathic. Relationships between left ventricular diastolic dysfunction (DD) and FTR remain unknown. OBJECTIVES: The purpose of this study was to investigate the prevalence, incidence, and outcome of DD in patients with idiopathic FTR. METHODS: Adults without structural heart disease were identified. Severe DD was defined by ≥3 of 4 abnormal DD parameters (medial e', medial E/e', TR velocity, left atrial volume index) and ≥ moderate DD by ≥2. Propensity-score matching was performed (3:1) between each less-than-severe TR group and severe TR based on age, sex, body mass index, and comorbidities. RESULTS: Among 30,428 patients, FTR was absent in 73%, mild in 22%, moderate in 4%, and severe in 0.4%. In the propensity-matched sample, severe DD was present in 2%, 6%, 9%, and 13% patients, and ≥ moderate DD in 11%, 18%, 28%, and 48%, respectively (P < 0.001). The probability of heart failure with preserved ejection fraction using the H2FPEF score increased with increasing FTR (median 29.7%, 45.5%, 61.4%, and 88.7%, respectively), as did the prevalence of impaired left atrial strain <24% (35%, 48%, and 69% in mild, moderate, and severe TR). Incident severe and ≥ moderate DD developed more frequently with increasing FTR (HR: 8.45 [95% CI: 2.60-27.50] and HR: 2.82 [95% CI: 1.40-5.69], respectively for ≥ moderate vs no FTR) over a median of 3.0 years. Findings were confirmed in patients without lung disease or right ventricular enlargement. Over a median of 5.0 years, patients with ≥ moderate FTR and DD had the greatest risk of worse outcomes (multivariable P < 0.001). The association between TR and adverse outcomes was significantly diminished in the absence of DD. CONCLUSIONS: Diastolic dysfunction, increased heart failure with preserved ejection fraction probability, and impaired left atrial strain are commonly present in patients with idiopathic FTR, suggesting that the latter may not be truly isolated. Patients with FTR without DD or heart failure are at increased risk of incident DD. Patients with FTR and DD display worse outcomes.

An evidence-based screening tool for heart failure with preserved ejection fraction: the HFpEF-ABA score.

Heart failure with preserved ejection fraction (HFpEF) is under-recognized in clinical practice. Although a previously developed risk score, termed H2FPEF, can be used to estimate HFpEF probability, this score requires imaging data, which is often unavailable. Here we sought to develop an HFpEF screening model that is based exclusively on clinical variables and that can guide the need for echocardiography and further testing. In a derivation cohort (n = 414, 249 women), a clinical model using age, body mass index and history of atrial fibrillation (termed the HFpEF-ABA score) showed good discrimination (area under the curve (AUC) = 0.839 (95% confidence interval (CI) = 0.800-0.877), P < 0.0001). The performance of the model was validated in an international, multicenter cohort (n = 736, 443 women; AUC = 0.813 (95% CI = 0.779-0.847), P < 0.0001) and further validated in two additional cohorts: a cohort including patients with unexplained dyspnea (n = 228, 136 women; AUC = 0.840 (95% CI = 0.782-0.900), P < 0.0001) and a cohort for which HF hospitalization was used instead of hemodynamics to establish an HFpEF diagnosis (n = 456, 272 women; AUC = 0.929 (95% CI = 0.909-0.948), P < 0.0001). Model-based probabilities were also associated with increased risk of HF hospitalization or death among patients from the Mayo Clinic (n = 790) and a US national cohort across the Veteran Affairs health system (n = 3076, 110 women). Using the HFpEF-ABA score, rapid and efficient screening for risk of undiagnosed HFpEF can be performed in patients with dyspnea using only age, body mass index and history of atrial fibrillation.

Dapagliflozin and Right Ventricular-Pulmonary Vascular Interaction in Heart Failure With Preserved Ejection Fraction: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Increases in pulmonary capillary wedge pressure (PCWP) during exercise reduce pulmonary artery (PA) compliance, increase pulsatile right ventricular (RV) afterload, and impair RV-PA coupling in patients with heart failure with preserved ejection fraction (HFpEF). The effects of the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin on pulmonary vascular properties and RV-PA coupling are unknown. Objective: To test the effect of dapagliflozin on right ventricular performance and pulmonary vascular load during exertion in HFpEF. Design, Setting, and Participants: Evaluation of the Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction (CAMEO-DAPA) randomized clinical trial demonstrated improvement in PCWP at rest and exercise over 24 weeks with dapagliflozin compared with placebo with participants recruited between February 2021 and May 2022. This secondary analysis evaluates the effects of dapagliflozin on pulsatile pulmonary vascular load and RV-PA coupling using simultaneous echocardiography and high-fidelity invasive hemodynamic testing with exercise. This was a single-center study including patients with hemodynamically confirmed HFpEF with exercise PCWP of 25 mm Hg or greater. Interventions: Dapagliflozin or placebo for 24 weeks. Main Outcomes and Measures: Pulsatile pulmonary vascular load (PA compliance and elastance) and right ventricular performance (PA pulsatility index, RV systolic velocity [s']/PA mean) during rest and exercise. Results: Among 37 randomized participants (mean [SD] age, 67.4 [8.5] years; 25 female [65%]; mean [SD] body mass index, 34.9 [6.7]; calculated as weight in kilograms divided by height in meters squared), there was no effect of dapagliflozin on PA loading or RV-PA interaction at rest. However, with exercise, dapagliflozin improved PA compliance (placebo-corrected mean difference, 0.57 mL/mm Hg; 95% CI, 0.11-1.03 mL/mm Hg; P = .02) and decreased PA elastance (stiffness; -0.17 mm Hg/mL; 95% CI, -0.28 to -0.07 mm Hg/mL; P = .001). RV function during exercise improved, with increase in PA pulsatility index (0.33; 95% CI, 0.08-0.59; P = .01) and increase in exercise RV s' indexed to PA pressure (0.09 cm·s-1/mm Hg; 95% CI, 0.02-0.16 cm·s-1/mm Hg; P = .01). Improvements in pulsatile RV load and RV-PA coupling were correlated with reduction in right atrial (RA) pressure (PA elastance Pearson r = 0.55; P =.008; RV s'/PA elastance Pearson r = -0.60; P =.002) and PCWP (PA elastance Pearson r = 0.58; P <.001; RV s'/PA elastance Pearson r = -0.47; P = .02). Dapagliflozin increased resistance-compliance time (dapagliflozin, median [IQR] change, 0.06 [0.03-0.15] seconds; placebo, median [IQR] change, 0.01 [-0.02 to 0.05] seconds; P =.046), resulting in higher PA compliance for any exercise pulmonary vascular resistance. Conclusions and Relevance: Results of this randomized clinical trial reveal that treatment with dapagliflozin for 24 weeks reduced pulsatile pulmonary vascular load and enhanced dynamic RV-PA interaction during exercise in patients with HFpEF, findings that are related to the magnitude of PCWP reduction. Benefits on dynamic right ventricular-pulmonary vascular coupling may partially explain the benefits of SGLT2 inhibitors in HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04730947.

Non-invasive prediction of pulmonary vascular disease-related exercise intolerance and survival in non-group 1 pulmonary hypertension.

AIMS: The clinical utility of pulmonary hypertension (PH) risk scores in non-group 1 PH with pulmonary vascular disease (PVD) remains unresolved. METHODS AND RESULTS: We utilized the prospective multicenter PVDOMICS cohort with group 2, 3, 4 or 5 PH-related PVD and calculated group 1 PH risk scores (REVEAL 2.0, REVEAL Lite 2, French registry score and COMPERA 2). The c-statistic to predict death was compared separately in (i) pre-capillary PH groups 3/4/5, and (ii) combined post- and pre-capillary PH group 2. Exercise right heart catheterization reserve, ventricular interdependence and right ventricular-pulmonary artery (RV-PA) coupling were compared across risk categories. Among 449 individuals with group 3/4/5 PH, the REVEAL 2.0 risk score had the highest c-statistic for predicting death (0.699, 95% confidence interval [CI] 0.660-0.737, p < 0.0001) with comparable performance using the simpler REVEAL Lite 2 score (0.695, 95% CI 0.656-0.734, p < 0.0001). The French and COMPERA 2 risk scores were also predictive of mortality, but performance of both was statistically inferior to REVEAL 2.0 (c-statistic difference -0.072, 95% CI -0.123 to -0.020, p = 0.006, and -0.043, 95% CI -0.067 to -0.018, p = 0.0007, respectively). RV function and RV-PA coupling measures were prognostic in isolation, but did not add incremental value to REVEAL (p > 0.50 for all). Findings were similar in patients with group 2 PH (n = 239). Stratification by the REVEAL Lite 2 score non-invasively identified non-group 1 PH with more advanced PVD with worse exercise capacity, RV-PA uncoupling, ventricular interdependence and impaired cardiac output reserve (p < 0.05 for all). CONCLUSIONS: Non-invasive REVEAL risk predicts mortality in non-group 1 PH without incremental prognostic value from detailed RV function or RV-PA coupling assessment. Baseline REVEAL Lite 2 risk stratification non-invasively identifies greater pulmonary vascular dysfunction and right heart-related exercise limitation, which may help guide patient selection for targeted pulmonary vascular therapies in non-group 1 PH.

Clinical features, haemodynamics, and outcomes of heart failure with preserved ejection fraction in coarctation of aorta.

AIMS: There are similarities in the pathogenesis of cardiac remodelling and dysfunction in heart failure with preserved ejection fraction (HFpEF) and coarctation of aorta (COA). We hypothesized that clinical HFpEF would be highly prevalent in adults with COA, and that the presence of HFpEF would increase the risk of mortality in this population. The aim of this study was to define the clinical features, haemodynamics, and prognostic implications of HFpEF in COA. METHODS AND RESULTS: Consecutive adults with repaired COA that underwent right heart catheterization were identified retrospectively. HFpEF was defined as heart failure symptoms (exertional dyspnoea or fatigue), preserved left ventricular ejection fraction ≥50%, and pulmonary artery wedge pressure at rest >15 mmHg. Of 99 COA patients, 32 (32%) had HFpEF. The correlates of HFpEF were obesity (adjusted odds ratio [OR] 4.15, 95% confidence interval [CI] 1.31-13.2), atrial fibrillation (adjusted OR 3.13, 95% CI 1.00-10.7), total arterial compliance index (adjusted OR 0.12, 95% CI 0.06-0.41 per 1 ml/mmHg*m2), and pulmonary artery compliance index (adjusted OR 0.36, 95% CI 0.15-0.56 per 1 ml/mmHg*m2). Of 99 patients, 24 (24%) died and 5 (5%) underwent heart transplant. The 10-year cumulative incidence of death/transplant was higher in COA patients with HFpEF compared with patients without HFpEF (39% vs. 12%, p = 0.001). The presence of HFpEF was associated with increased risk of death/transplant (adjusted hazard ratio 1.68, 95% CI 1.16-3.11). CONCLUSIONS: Heart failure with preserved ejection fraction is common in adults with COA and is associated with greater risk of death/transplant, emphasizing a pressing need for interventions to prevent and treat HFpEF in COA.

Haemodynamic contributors to pulmonary hypertension across the spectrum of adult congenital heart disease.

AIMS: Adult congenital heart disease (ACHD) includes multiple disease states that predispose to pulmonary hypertension (PH). Haemodynamically, PH depends on abnormalities in three components: pulmonary blood flow (Qp), pulmonary vascular resistance (PVR) and pulmonary venous pressure (PVP). We sought to evaluate the prevalence and prognostic impact of individual haemodynamic abnormalities in ACHD. METHODS AND RESULTS: Retrospective study of ACHD patients undergoing cardiac catheterization at Mayo Clinic between 1999 and 2022 who were followed for the combined endpoint of death/heart transplantation. Among 1005 patients, 37% had mean pulmonary artery pressure (mPAP) ≥25 mmHg with more systemic ventricular disease, cyanotic disease and shunt lesions, highest N-terminal pro-B-type natriuretic peptide and worse right heart remodelling/dysfunction. Among those with biventricular circulation, elevated PVP, PVR and mPAP were associated with prognosis, but not increased Qp >8 L/min. However, risk of death/transplant increased for PVR only at ≥3 Wood units (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.17-4.15; p < 0.0001) and for mPAP only at ≥25 mmHg (HR 3.15, 95% CI 2.17-4.58; p < 0.0001), not at current recommended lower cutpoints. Combined abnormalities in PVP and PVR were associated with worst outcome (HR 5.20, 95% CI 3.55-7.63; p < 0.0001) with intermediate risk with either abnormality (HR 2.11, 95% CI 1.46-3.04; p < 0.0001). Findings were consistent across type of biventricular ACHD. Only with the Fontan (univentricular) circulation was a lower mPAP threshold (20 mmHg) associated with adverse outcomes. CONCLUSIONS: Elevation of mPAP ≥25 mmHg in ACHD with a biventricular circulation is prognostically important regardless of disease phenotype, but milder PH of 21-25 mmHg is not associated with adverse outcome unless associated with Fontan circulation. Elevation in PVP >15 mmHg and PVR ≥3 Wood units were each individually associated with mortality with combined abnormalities associated with greatest risk. Categorizing PH in ACHD by haemodynamic mechanism (PVR, PVP or Qp) allows meaningful prognostication, and may allow more unified study of targeted therapies across heterogeneous disease states in ACHD.

Cardiac function, haemodynamics, and valve competence with exercise in patients with heart failure with preserved ejection fraction and mild to moderate secondary mitral regurgitation.

AIMS: This study aimed to evaluate the clinical significance of secondary mitral regurgitation (MR) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We conducted a prospective study enrolling consecutively evaluated patients with HFpEF undergoing invasive haemodynamic exercise testing with simultaneous echocardiography. Compared to HFpEF without MR (n = 145, 79.7%), those with mild or moderate MR (n = 37, 20.3%) were older, more likely to be women, had more left ventricular (LV) systolic dysfunction, and more likely to have left atrial (LA) myopathy reflected by greater burden of atrial fibrillation, more LA dilatation, and poorer LA function. Pulmonary artery (PA) wedge pressure was higher at rest in HFpEF with MR (17 ± 5 mmHg vs. 20 ± 5 mmHg, p = 0.005), but there was no difference with exercise. At rest, only 2 (1.1%) patients had moderate MR, and none developed severe MR. Pulmonary vascular resistance was higher, and right ventricular (RV)-PA coupling was more impaired in patients with HFpEF and MR at rest and exercise. LV and LA myocardial dysfunction remained more severe in patients with MR during stress compared to those without MR, characterized by greater LA dilatation during all stages of exertion, lower LA emptying fraction and compliance, steeper and rightward-shifted LA pressure-volume relationships, and reduced LV longitudinal contractile function. CONCLUSIONS: Patients with HFpEF and mild or moderate MR have more severe LV systolic dysfunction, LA myopathy, RV-PA uncoupling, and more severe pulmonary vascular disease. Mitral valve incompetence in this setting is a phenotypic marker of more advanced disease but is not a causal factor in development of HFpEF.

Screening for Unrecognized HFpEF in Atrial Fibrillation and for Unrecognized Atrial Fibrillation in HFpEF.

Because of the bidirectional relationship between atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF), individuals with either condition require consideration of screening for the other. In this review, we summarize current evidence and rationale for screening for occult HFpEF in adults with clinical AF; and occult AF in patients with clinically recognized HFpEF. Assessment of pretest probability for occult HFpEF in symptomatic AF patients may help guide additional testing such as exercise right heart catheterization to diagnose HFpEF and guide HFpEF-specific therapies. In patients with HFpEF, AF screening will identify cases of occult AF where anticoagulation may decrease stroke risk, and correlation of previously unknown AF episodes with paroxysmal symptoms may prompt consideration for rhythm control. Therefore, screening may help clinicians understand the etiology of the often-overlapping symptoms, and it may help guide treatments to slow progression of both conditions and their complications.

Healthcare in the Dynamism of Metaverse After COVID-19: A Systematic Review of Literature.

The idea of the "metaverse" is a relatively recent technological development. The industries that are most supportive of these developments include finance, entertainment, and communication. In addition to these, the healthcare domain has been added to the list of domains that benefit from the metaverse recently. Within the metaverse, research is being conducted on a wide range of medical topics, including conferences and seminars, surgical simulators, awareness campaigns, research projects, and much more. The metaverse is a flexible and highly customizable virtual digital platform that can be configured to suit specific needs, making it an adaptable instrument for medical advancement. These domains, together with their benefits and drawbacks, are thoroughly covered in this review article, which raises the discussion of the need for medical productivity. These studies have undergone a minimum amount of research and experimentation, and the findings are fair from an investigative standpoint. This review article's major goal is to make a provocative remark about metaverse domains and how they have already been used and might be used as an essential operational tool in the field of medicine in the future. Consequently, the objective of the present study is to review the current literature on post-COVID-19 pandemic development that connected the metaverse with the prevention and treatment of diseases, medical education and training, and expansion of available functionalities in research settings.

Autoimmune Disorders in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Inflammation plays a fundamental role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). In most patients, inflammation develops secondary to cardiometabolic comorbidities, but in some, HFpEF develops in the setting of an underlying systemic inflammatory disease such as rheumatoid arthritis or systemic lupus erythematosus. OBJECTIVES: This study aimed to investigate the prevalence, pathophysiology, and outcome of patients with HFpEF and autoimmune or primary inflammatory disorders. METHODS: Of 982 consecutively evaluated patients with HFpEF diagnosed, 79 (8.0%) had autoimmune disorders. HFpEF was defined by invasive cardiopulmonary hemodynamic exercise testing. RESULTS: Female sex, higher heart rate, lower hemoglobin, absence of atrial fibrillation, and absence of coronary artery disease were independently associated with autoimmune disorders. Hemodynamics at rest and exercise did not differ between the groups, but peripheral oxygen extraction was lower in those with autoimmune disorders, reflected by lower arterial-venous oxygen content difference at rest (4.2 ± 0.7 mL/dL vs 4.6 ± 1.0 mL/dL; P < 0.001) and during exercise (9.3 ± 2.2 mL/dL vs 10.4 ± 2.2 mL/dL; P < 0.001), suggesting a greater peripheral deficit, and ventilatory efficiency (VE/VCo2 slope, regression slope relating minute ventilation to carbon dioxide output) was also more impaired (38.0 ± 7.9 vs 36.2 ± 7.3; P = 0.043). Patients with autoimmune disorders had a higher risk of death or heart failure (HF) hospitalization compared with those without in adjusted analyses (HR: 1.95 [95% CI: 1.17-3.27]; P = 0.011) over a median follow-up of 3.0 years, which was primarily attributable to higher risk of HF hospitalization (HR: 2.87 [95% CI: 1.09-7.57]; P = 0.033). CONCLUSIONS: Patients with HFpEF and autoimmune disorders have similar hemodynamic derangements but greater peripheral deficits in oxygen transport and higher risk for adverse outcome compared with those without.

Using PAH-SYMPACT to assess quality of life in patients with pulmonary hypertension associated with chronic lung disease.

Chronic lung disease (CLD) is the second leading cause of pulmonary hypertension (PH) and is associated with significant morbidity and mortality. Although PH associated with CLD (PH-CLD) leads to impaired health-related quality of life (HRQOL), there are no validated tools to assess HRQOL in PH-CLD. The Pulmonary Arterial Hypertension-Symptoms and Impact Questionnaire (PAH-SYMPACT) is an HRQOL instrument aimed at assessing the symptoms and impact of PH on overall function and well-being. We performed a single-center prospective cohort study using PAH-SYMPACT scores to compare symptoms, exercise capacity and HRQOL in patients with PAH and PH-CLD. One hundred and twenty-five patients (99 patients with idiopathic/heritable PAH and 26 with PH-CLD) completed the PAH-SYMPACT questionnaire which consists of 22 questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive/emotional (CE) impact. Higher scores indicate worse HRQOL. We compared patients with PAH and PH-CLD using a Wilcoxon rank sum or chi-squared test as appropriate. Multivariate linear regression analysis was used to assess the relationship between PH classification and SYMPACT scores. Compared to PAH, patients with PH-CLD were older, more likely to use oxygen and had worse functional class and exercise capacity. While there was no significant difference between the two groups in CP, CV, or CE domain scores, patients with PH-CLD had significantly worse PI scores by univariate (1.79 vs. 1.13, p < 0.001) and multivariate analysis (1.61 vs. 1.17, p = 0.02) and overall worse SYMPACT scores (1.19 vs. 0.91, p = 0.03). In conclusion, patients with PH-CLD have worse HRQOL as assessed by the PAH-SYMPACT questionnaire versus patients with PAH. Although PAH-SYMPACT has not been validated in PH-CLD, the results of this study can guide clinicians in understanding the symptoms and impact of PH-CLD relative to PAH.

Hemodynamic response to inhaled nitric oxide in patients with pulmonary hypertension and chronic kidney disease: A retrospective cohort study.

Pulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH-CKD) affects approximately 20%-40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH-CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH-CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end-stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface area who underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3 Wood units were included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7% of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc-PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc-PH groups. Among a small subset (n = 14) who were subsequently treated with PAH-targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH-CKD.

Parity-time-symmetric photonic topological insulator.

Topological insulators are a concept that originally stems from condensed matter physics. As a corollary to their hallmark protected edge transport, the conventional understanding of such systems holds that they are intrinsically closed, that is, that they are assumed to be entirely isolated from the surrounding world. Here, by demonstrating a parity-time-symmetric topological insulator, we show that topological transport exists beyond these constraints. Implemented on a photonic platform, our non-Hermitian topological system harnesses the complex interplay between a discrete coupling protocol and judiciously placed losses and, as such, inherently constitutes an open system. Nevertheless, even though energy conservation is violated, our system exhibits an entirely real eigenvalue spectrum as well as chiral edge transport. Along these lines, this work enables the study of the dynamical properties of topological matter in open systems without the instability arising from complex spectra. Thus, it may inspire the development of compact active devices that harness topological features on-demand.

Programmable high-dimensional Hamiltonian in a photonic waveguide array.

Waveguide lattices offer a compact and stable platform for a range of applications, including quantum walks, condensed matter system simulation, and classical and quantum information processing. However, to date, waveguide lattice devices have been static and designed for specific applications. We present a programmable waveguide array in which the Hamiltonian terms can be individually electro-optically tuned to implement various Hamiltonian continuous-time evolutions on a single device. We used a single array with 11 waveguides in lithium niobate, controlled via 22 electrodes, to perform a range of experiments that realized the Su-Schriffer-Heeger model, the Aubrey-Andre model, and Anderson localization, which is equivalent to over 2500 static devices. Our architecture's micron-scale local electric fields overcome the cross-talk limitations of thermo-optic phase shifters in other platforms such as silicon, silicon-nitride, and silica. Electro-optic control allows for ultra-fast and more precise reconfigurability with lower power consumption, and with quantum input states, our platform can enable the study of multiple condensed matter quantum dynamics with a single device.