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In 2022, the Food and Drug Administration approved a second mitral transcatheter edge-to-edge repair device for the treatment of primary mitral regurgitation (PASCAL Precision Transcatheter Valve Repair System, Edwards Lifesciences, Irvine, CA). The PASCAL Precision system consists of a guide sheath, implant system, and accessories. The implant system consists of a steerable catheter, an implant catheter, and the implant (PASCAL or PASCAL Ace). The guide sheath and steerable catheter move and flex independently from each other and are not keyed, allowing for freedom of rotation in three dimensions. This manuscript provides an overview of the PASCAL Precision system and describes the basic and advanced steering maneuvers to facilitate effective and safe mitral transcatheter edge-to-edge repair.

Erythropoietic protoporphyria and X-linked protoporphyria are rare genetic photodermatoses. Limited expertise with these disorders among physicians leads to diagnostic delays. Here, we present evidence-based consensus guidelines for the diagnosis, monitoring, and management of erythropoietic protoporphyria and X-linked protoporphyria. A systematic literature review was conducted, and reviewed among subcommittees of experts, divided by topic. Consensus on guidelines was reached within each subcommittee and then among all members of the committee. The appropriate biochemical and genetic testing to establish the diagnosis is reviewed in addition to the interpretation of results. Prevention of symptoms, management of acute phototoxicity, and pharmacologic and nonpharmacologic treatment options are discussed. The importance of ongoing monitoring for liver disease, iron deficiency, and vitamin D deficiency is discussed with management guidance. Finally, management of pregnancy and surgery and the safety of other therapies are summarized. We emphasize that these are multisystemic disorders that require longitudinal monitoring. These guidelines provide a structure for evidence-based diagnosis and management for practicing physicians. Early diagnosis and management of these disorders are essential, particularly given the availability of new and emerging therapies.

While frailty is a prominent risk factor in an aging population, the underlying biology of frailty is incompletely described. Here, we integrate 979 circulating proteins across a wide range of physiologies with 12 measures of frailty in a prospective discovery cohort of 809 individuals with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation. Our aim was to characterize the proteomic architecture of frailty in a highly susceptible population and study its relation to clinical outcome and systems-wide phenotypes to define potential novel, clinically relevant frailty biology. Proteomic signatures (specifically of physical function) were related to post-intervention outcome in AS, specifying pathways of innate immunity, cell growth/senescence, fibrosis/metabolism, and a host of proteins not widely described in human aging. In published cohorts, the frailty proteome displayed heterogeneous trajectories across age (20-100 years, age only explaining a small fraction of variance) and were associated with cardiac and non-cardiac phenotypes and outcomes across two broad validation cohorts (N > 35,000) over ≈2-3 decades. These findings suggest the importance of precision biomarkers of underlying multi-organ health status in age-related morbidity and frailty.

Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84 years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1 years (205 deaths), a metabolite score for diastolic function was independently associated with post-transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25-1.90]; P

BackgroundAfterload from moderate aortic stenosis (AS) may contribute to adverse outcomes in patients with heart failure with reduced ejection fraction (HFrEF).ObjectivesThe authors evaluated clinical outcomes in patients with HFrEF and moderate AS relative to those without AS and with severe AS.MethodsPatients with HFrEF, defined by left ventricular ejection fraction (LVEF)

Background Racial and ethnic minority groups are underrepresented among patients undergoing aortic valve replacement in the United States. We evaluated the impact of race and ethnicity on the diagnosis of aortic stenosis (AS). Methods and Results In patients with transthoracic echocardiography (TTE)-confirmed AS, we assessed rates of AS diagnosis as defined by assignment of an International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) code for AS within a large multicenter electronic health record. Multivariable Cox proportional hazard and competing risk regression models were used to evaluate the 1-year rate of AS diagnosis by race and ethnicity. Among 14 800 patients with AS, the 1-year diagnosis rate for AS following TTE was 37.4%. Increasing AS severity was associated with an increased likelihood of receiving an AS diagnosis (moderate: hazard ratio [HR], 3.05 [95% CI, 2.86-3.25]; P

In light of the adverse prognosis related to severe mitral regurgitation, heart failure, or sudden cardiac death in a subset of patients with mitral valve prolapse (MVP), identifying those at higher risk is key. For the first time in decades, researchers have the means to rapidly advance discovery in the field of MVP thanks to state-of-the-art imaging techniques, novel omics methodologies, and the potential for large-scale collaborations using web-based platforms. The National Heart, Lung, and Blood Institute recently initiated a webinar-based workshop to identify contemporary research opportunities in the treatment of MVP. This report summarizes 3 specific areas in the treatment of MVP that were the focus of the workshop: 1) improving management of degenerative mitral regurgitation and associated left ventricular systolic dysfunction; 2) preventing sudden cardiac death in MVP; and 3) understanding the mechanisms and progression of MVP through genetic studies and small and large animal models, with the potential of developing medical therapies.

Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction 2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT-proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

Background Many patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient- and process-specific factors affected AVR use in patients with severe AS. Methods and Results We identified ambulatory patients from 2016 to 2018 demonstrating severe AS, defined by aortic valve area [Formula: see text]1.0 cm2. Propensity scoring analysis with inverse probability of treatment weighting was used to evaluate associations between predictors and the odds of undergoing AVR at 365 days and subsequent mortality at 730 days. Of 324 patients with an indication for AVR (79.3±9.7 years, 57.4% men), 140 patients (43.2%) did not undergo AVR. The odds of AVR were reduced in patients aged >90 years (odds ratio [OR], 0.24 [95% CI, 0.08-0.69]; P=0.01), greater comorbid conditions (OR, 0.88 per 1-point increase in Combined Comorbidity Index [95% CI, 0.79-0.97]; P=0.01), low-flow, low-gradient AS with preserved left ventricular ejection fraction (OR, 0.11 [95% CI, 0.06-0.21]), and low-gradient AS with reduced left ventricular ejection fraction (OR, 0.18 [95% CI, 0.08-0.40]) and were increased if the transthoracic echocardiogram ordering provider was a cardiologist (OR, 2.46 [95% CI, 1.38-4.38]). Patients who underwent AVR gained an average of 85.8 days of life (95% CI, 40.9-130.6) at 730 days. Conclusions The proportion of ambulatory patients with severe AS and an indication for AVR who do not receive AVR remains significant. Efforts are needed to maximize the recognition of severe AS, especially low-gradient subtypes, and to encourage patient referral to multidisciplinary heart valve teams.

Background The neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow-up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5-24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70-4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18-1.63; P

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all-cause death out to 5 years. Elevated cTnT and NT-proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P

Background Concerns about discordance between echocardiographic and invasive mean gradients after transcatheter aortic valve replacement (TAVR) with balloon-expandable valves (BEVs) versus self-expanding valves (SEVs) exist. Methods and Results In a multicenter study, direct-invasive and echocardiography-derived transvalvular mean gradients obtained before and after TAVR were compared as well as post-TAVR and discharge echocardiographic mean gradients in BEVs versus SEVs in 808 patients. Pre-TAVR, there was good correlation (R=0.614; P

ObjectivesThe aim of this study was to examine the applicability of pivotal transcatheter aortic valve replacement (TAVR) trials to the real-world population of Medicare patients undergoing TAVR.BackgroundIt is unclear whether randomized controlled trial results of novel cardiovascular devices apply to patients encountered in clinical practice.MethodsCharacteristics of patients enrolled in the U.S. CoreValve pivotal trials were compared with those of the population of Medicare beneficiaries who underwent TAVR in U.S. clinical practice between November 2, 2011, and December 31, 2017. Inverse probability weighting was used to reweight the trial cohort on the basis of Medicare patient characteristics, and a "real-world" treatment effect was estimated.ResultsA total of 2,026 patients underwent TAVR in the U.S. CoreValve pivotal trials, and 135,112 patients underwent TAVR in the Medicare cohort. Trial patients were mostly similar to real-world patients at baseline, though trial patients were more likely to have hypertension (50% vs 39%) and coagulopathy (25% vs 17%), whereas real-world patients were more likely to have congestive heart failure (75% vs 68%) and frailty. The estimated real-world treatment effect of TAVR was an 11.4% absolute reduction in death or stroke (95% CI: 7.50%-14.92%) and an 8.7% absolute reduction in death (95% CI: 5.20%-12.32%) at 1 year with TAVR compared with conventional therapy (surgical aortic valve replacement for intermediate- and high-risk patients and medical therapy for extreme-risk patients).ConclusionsThe trial and real-world populations were mostly similar, with some notable differences. Nevertheless, the extrapolated real-world treatment effect was at least as high as the observed trial treatment effect, suggesting that the absolute benefit of TAVR in clinical trials is similar to the benefit of TAVR in the U.S. real-world setting.

ObjectivesTo compare echocardiographic and invasive mean gradients obtained concomitantly in degenerated bioprosthetic surgical aortic valves (SAVRs).MethodsIn a multicenter study, we compared concomitant echocardiographic and invasive mean gradients of SAVR, obtained before valve-in-valve transcatheter aortic valve replacement in all patients, patients with primary stenosis (AS), primary aortic regurgitation (AR), and mixed aortic valve disease (MAVD), and in small versus large valves (≤ or >23 mm). Dimensionless index (DI) was calculated in all groups.ResultsIn total, 74 patients were included and data presented as median (interquartile range). Echocardiography-catheterization mean gradient discordance was observed in all patients (invasive = 22 mm Hg [11-34] vs echocardiographic = 32 mm Hg [21-42], P = .013), small valves (invasive = 15 mm Hg [8-34] vs echocardiographic = 28 mm Hg [21-41], P = .013), and large valves (invasive = 20 mm Hg [8.5-27.13] vs echocardiographic = 32 mm Hg [25.5 - 41.5], P

Central aortic blood pressure could be helpful in the evaluation of patients with aortic stenosis (AS). The SphygmoCor XCEL device estimates central blood pressure (BP) measurement with its easy-to-use, operator-independent procedure. However, this device has not been properly validated against invasive measurement in patients with severe AS. We evaluated the relationship between cuff-brachial BP, transfer function-estimated and invasively measured central aortic pressure in patients with severe AS before and after transcatheter aortic valve replacement (TAVR). Agreement between techniques was analyzed and, according to the ARTERY Society recommendations, the minimum acceptable error was a mean difference ± SD ≤5 ± ≤8 mm Hg. A total of 94 patients with AS undergoing TAVR had simultaneous non-invasive and invasive measurements of central BP before and after the procedure. Before TAVR central systolic BP was in average slightly underestimated, though with wide variability, when using the default calibration of brachial-cuff SBP (mean difference ± SD, -3 ± 15 mm Hg), and after TAVR the degree of underestimation increased (mean difference ± SD, -9 ± 13 mm Hg). The agreement tended to improve for those patients with low aortic gradient stenosis compared to those with high gradient at baseline (mean difference ± SD, -2 ± 11 mm Hg vs. -4 ± 17, respectively, p = .3). The cuff-brachial systolic BP yielded numerically lower degree of agreement and weaker correlation with invasive measurements than SphygmoCor XCEL. In patients with severe AS the SphygmoCor XCEL cuff device, despite showing strong correlation, does not meet the ARTERY Society accuracy criteria for non-invasive measurement of central SBP.

Background Data on hospital variation in 30-day readmission rates after transcatheter aortic valve replacement (TAVR) are limited. Further, whether such variation is explained by differences in hospital characteristics and hospital practice patterns remains unknown. Methods and Results We used the 2017 Nationwide Readmissions Database to identify hospitals that performed at least 5 TAVRs. Hierarchical logistic regression models were used to examine between-hospital variation in 30-day all-cause risk-standardized readmission rate (RSRR) after TAVR and to explore reasons underlying hospital variation in 30-day RSRR. The study included 27 091 index TAVRs performed across 325 hospitals. The median (interquartile range) hospital-level 30-day RSRR was 11.9% (11.1%-12.8%) ranging from 8.8% to 16.5%. After adjusting for differences in patient characteristics, there was significant between-hospital variation in 30-day RSRR (hospital odds ratio, 1.59; 95% CI, 1.39-1.77). Differences in length of stay and discharge disposition accounted for 15% of the between-hospital variance in RSRRs. There was no significant association between hospital characteristics and 30-day readmission rates after TAVR. There was statistically significant but weak correlation between 30-day RSRR after TAVR and that after surgical aortic valve replacement, percutaneous coronary intervention, acute myocardial infarction, heart failure, and pneumonia (r=0.132-0.298; P

AimsImpaired physical function is common in patients undergoing transcatheter aortic valve replacement (TAVR) and associated with worse outcomes. Participation in centre-based cardiac rehabilitation (CR) after cardiovascular procedures is sub-optimal. We aimed to test a home-based mobile health exercise intervention as an alternative or complementary approach.Methods and resultsAt five centres, after a run-in period, eligible individuals treated with TAVR were randomized 1:1 at their 1-month post-TAVR visit to an intervention group [activity monitor (AM) with personalized daily step goal and resistance exercises] or a control group for 6 weeks. Among 50 participants, average age was 76 years, 34% were female, average STS score was 2.91.8, and 40% had Short Physical Performance Battery (SPPB) 9. Daily compliance with wearing the AM and performing exercises averaged 8590%. In the intention to treat population, there was no evidence that the intervention improved the co-primary endpoints: daily steps +769 (95% CI 244 to +1783); SPPB +0.68 (0.27 to 1.53); and Kansas City Cardiomyopathy Questionnaire 1.7 (9.1 to 7.1). The intervention did improve secondary physical activity parameters, including moderate-to-intense daily active minutes (P

ObjectivesThe aim of this study was to assess the incidence, mechanisms, and outcomes of mitral regurgitation (MR) after percutaneous mitral valvuloplasty (PMV).BackgroundSignificant MR continues to be a major complication of PMV, with a wide range in clinical presentation and prognosis.MethodsConsecutive patients with mitral stenosis undergoing PMV were prospectively enrolled. MR severity was evaluated by using quantitative echocardiographic criteria, and its mechanism was characterized by 3-dimensional transesophageal echocardiography, divided broadly into 4 categories based on the features contributing to the valve damage. B-type natriuretic peptide levels were obtained before and 24 h after the procedure. Endpoints estimated cardiovascular death or mitral valve (MV) replacement due to predominant MR.ResultsA total of 344 patients, ages 45.1 ± 12.1 years, of whom 293 (85%) were women, were enrolled. Significant MR after PMV was found in 64 patients (18.6%). The most frequent mechanism of MR was commissural, which occurred in 22 (34.4%) patients, followed by commissural with posterior leaflet in 16 (25.0%), leaflets at central scallop or subvalvular damage in 15 (23.4%), and central MR in 11 (17.2%). During the mean follow-up period of 3 years (range 1 day to 10.6 years), 60 patients reached the endpoint. The event-free survival rates were similar among patients with mild or commissural MR, whereas patients with damaged central leaflet scallop or subvalvular apparatus had the worst outcome, with an event-free survival rate at 1 year of only 7%. Long-term outcome was predicted by net atrioventricular compliance (Cn) at baseline and post-procedural variables, including valve area, mean gradient, and magnitude of decrease in B-type natriuretic peptide levels, adjusted for the mechanism of MR.ConclusionsSignificant MR following PMV is a frequent event, mainly related to commissural splitting, with favorable clinical outcome. Parameters that express the relief of valve obstruction and the mechanism by which MR develops were predictors of long-term outcomes.

In addition to their fundamental role in clearance, the kidneys release select molecules into the circulation, but whether any of these anabolic functions provides insight on kidney health is unknown. Using aptamer-based proteomics, we characterized arterial (A)-to-renal venous (V) gradients for >1,300 proteins in 22 individuals who underwent invasive sampling. Although most of the proteins that changed significantly decreased from A to V, consistent with renal clearance, several were found to increase, the most significant of which was testican-2. To assess the clinical implications of these physiologic findings, we examined proteomic data in the Jackson Heart Study (JHS), an African-American cohort (n = 1,928), with replication in the Framingham Heart Study (FHS), a White cohort (n = 1,621). In both populations, testican-2 had a strong, positive correlation with estimated glomerular filtration rate (eGFR). In addition, higher baseline testican-2 levels were associated with a lower rate of eGFR decline in models adjusted for age, gender, hypertension, type 2 diabetes, body mass index, baseline eGFR, and albuminuria. Glomerular expression of testican-2 in human kidneys was demonstrated by immunohistochemistry, immunofluorescence, and electron microscopy, while single-cell RNA sequencing of human kidneys showed expression of the cognate gene, SPOCK2, exclusively in podocytes. In vitro, testican-2 increased glomerular endothelial tube formation and motility, raising the possibility that its secretion has a functional role within the glomerulus. Taken together, our findings identify testican-2 as a podocyte-derived biomarker of kidney health and prognosis.

The novel coronavirus disease-2019 (COVID-19) pandemic has created uncertainty in the management of patients with severe aortic stenosis. This population experiences high mortality from delays in treatment of valve disease but is largely overlapping with the population of highest mortality from COVID-19. The authors present strategies for managing patients with severe aortic stenosis in the COVID-19 era. The authors suggest transitions to virtual assessments and consultation, careful pruning and planning of necessary testing, and fewer and shorter hospital admissions. These strategies center on minimizing patient exposure to COVID-19 and expenditure of human and health care resources without significant sacrifice to patient outcomes during this public health emergency. Areas of innovation to improve care during this time include increased use of wearable and remote devices to assess patient performance and vital signs, devices for facile cardiac assessment, and widespread use of clinical protocols for expedient discharge with virtual physical therapy and cardiac rehabilitation options.

BackgroundResidual shunt is observed in up to 25% of patients after patent foramen ovale (PFO) closure, but its long-term influence on stroke recurrence currently is unknown.ObjectiveTo investigate the association of residual shunt after PFO closure with the incidence of recurrent stroke and transient ischemic attack (TIA).DesignProspective cohort study comparing stroke or TIA recurrence in patients with and without residual shunt after PFO closure.SettingSingle hospital center.Participants1078 consecutive patients (mean age, 49.3 years) with PFO-attributable cryptogenic stroke who were undergoing percutaneous PFO closure were followed for up to 11 years.MeasurementsResidual shunt was evaluated by transthoracic echocardiography with saline contrast. Primary outcome was a composite of the first recurrent ischemic stroke or TIA after PFO closure.ResultsCompared with complete closure, the presence of residual shunt after PFO closure was associated with an increased incidence of recurrent stroke or TIA: 2.32 versus 0.75 events per 100 patient-years (hazard ratio [HR], 3.05 [95% CI, 1.65 to 5.62]; P < 0.001). This result remained robust after adjustment for important covariates, namely age; study period; device; presence of atrial septal aneurysm, hypertension, hyperlipidemia, diabetes, hypercoagulability, or hypermobile septum; and medication use (HR, 3.01 [CI, 1.59 to 5.69]; P < 0.001). Further stratification based on shunt size revealed that moderate or large residual shunts were associated with a higher risk for stroke or TIA recurrence (HR, 4.50 [CI, 2.20 to 9.20]; P < 0.001); the result for small residual shunts was indeterminate (HR, 2.02 [CI, 0.87 to 4.69]; P = 0.102).LimitationNonrandomized study with potential unmeasured confounding.ConclusionAmong patients undergoing PFO closure to prevent future stroke, the presence of residual shunt, particularly a moderate or large residual shunt, was associated with an increased risk for stroke or TIA recurrence.Primary funding sourceNational Institutes of Health.

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that controls blood phosphate levels by increasing renal phosphate excretion and reducing 1,25-dihydroxyvitamin D3 [1,25(OH)2D] production. Disorders of FGF23 homeostasis are associated with significant morbidity and mortality, but a fundamental understanding of what regulates FGF23 production is lacking. Because the kidney is the major end organ of FGF23 action, we hypothesized that it releases a factor that regulates FGF23 synthesis. Using aptamer-based proteomics and liquid chromatography-mass spectrometry-based (LC-MS-based) metabolomics, we profiled more than 1600 molecules in renal venous plasma obtained from human subjects. Renal vein glycerol-3-phosphate (G-3-P) had the strongest correlation with circulating FGF23. In mice, exogenous G-3-P stimulated bone and bone marrow FGF23 production through local G-3-P acyltransferase-mediated (GPAT-mediated) lysophosphatidic acid (LPA) synthesis. Further, the stimulatory effect of G-3-P and LPA on FGF23 required LPA receptor 1 (LPAR1). Acute kidney injury (AKI), which increases FGF23 levels, rapidly increased circulating G-3-P in humans and mice, and the effect of AKI on FGF23 was abrogated by GPAT inhibition or Lpar1 deletion. Together, our findings establish a role for kidney-derived G-3-P in mineral metabolism and outline potential targets to modulate FGF23 production during kidney injury.

Tricuspid regurgitation (TR) is a common valvular heart disease affecting >1.6 million people in the United States (US) and >70 million people worldwide. The age- and sex-adjusted prevalence of more than or equal to moderate TR in the US is estimated to be 0.55%. One-year mortality increases with increasing severity of TR. Yet, the majority of patients with severe TR are managed medically in the absence of another indication for cardiac surgery, and isolated tricuspid valve (TV) surgery remains infrequent. To address this unmet clinical need, various transcatheter TV therapies are now being developed as an alternative to surgery in extreme- and high-risk patients with severe functional TR. Transcatheter TV repair devices are aimed at improving leaflet coaptation either directly by bringing the leaflets together (leaflet/coaptation devices) or indirectly by repairing the dilated annulus (annuloplasty devices). In this review, we describe the current state of transcatheter TV repair therapies and summarize the available data on the efficacy and safety of various devices. Procedural and clinical outcomes of transcatheter TV repair therapies are expected to improve in the coming years with technological advancement, newer device iterations, and increased experience in this field. Appropriate patient selection, optimal timing of intervention, and evaluation of long-term outcomes and device durability will be key in ongoing and future studies.

BackgroundRight ventricular function (RVF) is an independent predictor of prognosis for patients undergoing aortic valve replacement: transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). The effect of transfemoral aortic valve replacement (TF-TAVR) on RVF is uncertain. We aimed to perform a meta-analysis of the effect of TF-TAVR on RVF in patients with aortic stenosis (AS) and compare the effect of TF-TAVR with SAVR.MethodsWe searched relevant studies from PubMed, Embase, Cochrane Library databases, and Web of Science. Furthermore, two reviewers (Wang AQ and Cao YS) extracted all relevant data, which were then double checked by another two reviewers (Zhang M and Qi GM). We used the forest plot to present results. Tricuspid annular plane systolic excursion (TAPSE) was the primary outcome.ResultsThis meta-analysis included 11 studies. There were 353 patients who underwent TF-TAVR, and 358 patients who were subjected to SAVR. There was no significant difference in TAPSE at 1 week and 6 months as well as right ventricular ejection fraction (RVEF) at

Background Blood pressure (BP) guidelines for patients with aortic stenosis or a history of aortic stenosis treated with aortic valve replacement (AVR) match those in the general population, but this extrapolation may not be warranted. Methods and Results Among patients enrolled in the Medtronic intermediate, high, and extreme risk trials, we included those with a transcatheter AVR (n=1794) or surgical AVR (n=1103) who were alive at 30 days. The associations between early (average of discharge and 30 day post-AVR) systolic BP (SBP) and diastolic BP (DBP) measurements and clinical outcomes between 30 days and 1 year were evaluated. Among 2897 patients, after adjustment, spline curves demonstrated an association between lower SBP (

Aortic stenosis (AS) management is classically guided by symptoms and valvular metrics. However, the natural history of AS is dictated by coupling of the left ventricle, aortic valve, and vascular system. We investigated whether metrics of ventricular and vascular state add to the appreciation of AS state above valve gradient alone. Seventy patients with severe symptomatic AS were prospectively followed from baseline to 30 days after transcatheter aortic valve replacement (TAVR). Quality of life (QOL) was assessed using the Kansas City Cardiomyopathy Questionnaire. Left ventricular stroke work (SWLV) and vascular impedance spectrums were calculated noninvasively using in-house models based on central blood pressure waveforms, along with hemodynamic parameters from echocardiograms. Patients with higher preprocedural SWLV and lower vascular impedance were more likely to experience improved QOL after TAVR. Patients fell into two categories: those who did and those who did not exhibit increase in blood pressure after TAVR. In patients who developed hypertension (19%), vascular impedance increased and SWLV remained unchanged (impedance at zeroth harmonic: Z0, from 3964.4 to 4851.8 dyne·s/cm3, P = 0.039; characteristic impedance: Zc, from 376.2 to 603.2 dyne·s/cm3, P = 0.033). SWLV dropped only in patients who did not develop new hypertension after TAVR (from 1.58 to 1.26 J; P < 0.001). Reduction in valvular pressure gradient after TAVR did not predict change in SWLV (r = 0.213; P = 0.129). Reduction of SWLV after TAVR may be an important metric in management of AS, rather than relying solely on the elimination of transvalvular pressure gradients.