Baylor Medical Center at Garland

Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes.

Liver disease accounts for two million deaths annually and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately two-thirds of all liver-related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and non-alcoholic fatty liver disease. Hepatotropic viruses are the aetiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, non-alcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

AIMS: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. METHODS AND RESULTS: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. CONCLUSIONS: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Importance: Coronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19. Objective: To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19. Design, Setting, and Participants: The BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020. Interventions: Patients were randomized to receive a single infusion of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]), or placebo (n = 156). Main Outcomes and Measures: The primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19-related hospitalization, an emergency department [ED] visit, or death at day 29). Results: Among the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was -3.72 for 700 mg, -4.08 for 2800 mg, -3.49 for 7000 mg, -4.37 for combination treatment, and -3.80 for placebo. Compared with placebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, -0.35 to 0.52; P = .69) for 700 mg, -0.27 (95% CI, -0.71 to 0.16; P = .21) for 2800 mg, 0.31 (95% CI, -0.13 to 0.76; P = .16) for 7000 mg, and -0.57 (95% CI, -1.00 to -0.14; P = .01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group were statistically significant for 10 of 84 end points. The proportion of patients with COVID-19-related hospitalizations or ED visits was 5.8% (9 events) for placebo, 1.0% (1 event) for 700 mg, 1.9% (2 events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment. Conclusions and Relevance: Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point. Trial Registration: ClinicalTrials.gov Identifier: NCT04427501.

AIMS: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. METHODS AND RESULTS: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. CONCLUSIONS: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.

Answer questions and earn CME/CNE The American Cancer Society Head and Neck Cancer Survivorship Care Guideline was developed to assist primary care clinicians and other health practitioners with the care of head and neck cancer survivors, including monitoring for recurrence, screening for second primary cancers, assessment and management of long-term and late effects, health promotion, and care coordination. A systematic review of the literature was conducted using PubMed through April 2015, and a multidisciplinary expert workgroup with expertise in primary care, dentistry, surgical oncology, medical oncology, radiation oncology, clinical psychology, speech-language pathology, physical medicine and rehabilitation, the patient perspective, and nursing was assembled. While the guideline is based on a systematic review of the current literature, most evidence is not sufficient to warrant a strong recommendation. Therefore, recommendations should be viewed as consensus-based management strategies for assisting patients with physical and psychosocial effects of head and neck cancer and its treatment. CA Cancer J Clin 2016;66:203-239. © 2016 American Cancer Society.

The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.

BACKGROUND: During the introduction of transcatheter aortic-valve replacement (TAVR) in the United States, requirements regarding procedural volume were mandated by the Centers for Medicare and Medicaid Services as a condition of reimbursement. A better understanding of the relationship between hospital volume of TAVR procedures and patient outcomes could inform policy decisions. METHODS: We analyzed data from the Transcatheter Valve Therapy Registry regarding procedural volumes and outcomes from 2015 through 2017. The primary analyses examined the association between hospital procedural volume as a continuous variable and risk-adjusted mortality at 30 days after transfemoral TAVR. Secondary analysis included risk-adjusted mortality according to quartile of hospital procedural volume. A sensitivity analysis was performed after exclusion of the first 12 months of transfemoral TAVR procedures at each hospital. RESULTS: Of 113,662 TAVR procedures performed at 555 hospitals by 2960 operators, 96,256 (84.7%) involved a transfemoral approach. There was a significant inverse association between annualized volume of transfemoral TAVR procedures and mortality. Adjusted 30-day mortality was higher and more variable at hospitals in the lowest-volume quartile (3.19%; 95% confidence interval [CI], 2.78 to 3.67) than at hospitals in the highest-volume quartile (2.66%; 95% CI, 2.48 to 2.85) (odds ratio, 1.21; P = 0.02). The difference in adjusted mortality between a mean annualized volume of 27 procedures in the lowest-volume quartile and 143 procedures in the highest-volume quartile was a relative reduction of 19.45% (95% CI, 8.63 to 30.26). After the exclusion of the first 12 months of TAVR procedures at each hospital, 30-day mortality remained higher in the lowest-volume quartile than in the highest-volume quartile (3.10% vs. 2.61%; odds ratio, 1.19; 95% CI, 1.01 to 1.40). CONCLUSIONS: An inverse volume-mortality association was observed for transfemoral TAVR procedures from 2015 through 2017. Mortality at 30 days was higher and more variable at hospitals with a low procedural volume than at hospitals with a high procedural volume. (Funded by the American College of Cardiology Foundation National Cardiovascular Data Registry and the Society of Thoracic Surgeons.).

Identification of modifiable risk factors provides a crucial approach to the prevention of dementia. Nutritional or nutrient-dependent risk factors are especially important because dietary modifications or use of dietary supplements may lower the risk factor level. One such risk factor is a raised concentration of the biomarker plasma total homocysteine, which reflects the functional status of three B vitamins (folate, vitamins B12, B6). A group of experts reviewed literature evidence from the last 20 years. We here present a Consensus Statement, based on the Bradford Hill criteria, and conclude that elevated plasma total homocysteine is a modifiable risk factor for development of cognitive decline, dementia, and Alzheimer's disease in older persons. In a variety of clinical studies, the relative risk of dementia in elderly people for moderately raised homocysteine (within the normal range) ranges from 1.15 to 2.5, and the Population Attributable risk ranges from 4.3 to 31%. Intervention trials in elderly with cognitive impairment show that homocysteine-lowering treatment with B vitamins markedly slows the rate of whole and regional brain atrophy and also slows cognitive decline. The findings are consistent with moderately raised plasma total homocysteine (>11 μmol/L), which is common in the elderly, being one of the causes of age-related cognitive decline and dementia. Thus, the public health significance of raised tHcy in the elderly should not be underestimated, since it is easy, inexpensive, and safe to treat with B vitamins. Further trials are needed to see whether B vitamin treatment will slow, or prevent, conversion to dementia in people at risk of cognitive decline or dementia.

A clinical guideline aims to apply to all patients with a specific condition. However, there will inevitably be situations where its recommendations aren't suitable for a particular patient. While healthcare professionals and others are encouraged to consider these guidelines in their professional judgement, they don't override the responsibility of healthcare professionals to make decisions tailored to each patient's unique circumstances. Such decisions should be aligned with the latest official recommendations, guidelines from relevant public health authorities, and applicable rules and regulations. It is important that these decisions are made in collaboration with, and agreed upon by, the patient and/or their guardian or carer.

BACKGROUND: Data from a 5-year follow-up of outcomes after transcatheter edge-to-edge repair of severe mitral regurgitation, as compared with outcomes after maximal doses of guideline-directed medical therapy alone, in patients with heart failure are now available. METHODS: We randomly assigned patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy to undergo transcatheter edge-to-edge repair plus receive medical therapy (device group) or to receive medical therapy alone (control group) at 78 sites in the United States and Canada. The primary effectiveness end point was all hospitalizations for heart failure through 2 years of follow-up. The annualized rate of all hospitalizations for heart failure, all-cause mortality, the risk of death or hospitalization for heart failure, and safety, among other outcomes, were assessed through 5 years. RESULTS: Of the 614 patients enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of hospitalization for heart failure through 5 years was 33.1% per year in the device group and 57.2% per year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.41 to 0.68). All-cause mortality through 5 years was 57.3% in the device group and 67.2% in the control group (hazard ratio, 0.72; 95% CI, 0.58 to 0.89). Death or hospitalization for heart failure within 5 years occurred in 73.6% of the patients in the device group and in 91.5% of those in the control group (hazard ratio, 0.53; 95% CI, 0.44 to 0.64). Device-specific safety events within 5 years occurred in 4 of 293 treated patients (1.4%), with all the events occurring within 30 days after the procedure. CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite guideline-directed medical therapy, transcatheter edge-to-edge repair of the mitral valve was safe and led to a lower rate of hospitalization for heart failure and lower all-cause mortality through 5 years of follow-up than medical therapy alone. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.).

The gastrointestinal microbiome plays a pivotal role in physiological homeostasis of the intestine as well as in the pathophysiology of diseases including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Emerging evidence suggests that gut microbiota signal to the mitochondria of mucosal cells, including epithelial cells and immune cells. Gut microbiota signaling to mitochondria has been shown to alter mitochondrial metabolism, activate immune cells, induce inflammasome signaling, and alter epithelial barrier function. Both dysbiosis of the gut microbiota and mitochondrial dysfunction are associated with chronic intestinal inflammation and CRC. This review discusses mitochondrial metabolism of gut mucosal cells, mitochondrial dysfunction, and known gut microbiota-mediated mitochondrial alterations during IBD and CRC.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke. METHODS: We randomly assigned patients with aortic stenosis in a 1:1 ratio to undergo transfemoral TAVR with CEP (CEP group) or without CEP (control group). The primary end point was stroke within 72 hours after TAVR or before discharge (whichever came first) in the intention-to-treat population. Disabling stroke, death, transient ischemic attack, delirium, major or minor vascular complications at the CEP access site, and acute kidney injury were also assessed. A neurology professional examined all the patients at baseline and after TAVR. RESULTS: A total of 3000 patients across North America, Europe, and Australia underwent randomization; 1501 were assigned to the CEP group and 1499 to the control group. A CEP device was successfully deployed in 1406 of the 1489 patients (94.4%) in whom an attempt was made. The incidence of stroke within 72 hours after TAVR or before discharge did not differ significantly between the CEP group and the control group (2.3% vs. 2.9%; difference, -0.6 percentage points; 95% confidence interval, -1.7 to 0.5; P = 0.30). Disabling stroke occurred in 0.5% of the patients in the CEP group and in 1.3% of those in the control group. There were no substantial differences between the CEP group and the control group in the percentage of patients who died (0.5% vs. 0.3%); had a stroke, a transient ischemic attack, or delirium (3.1% vs. 3.7%); or had acute kidney injury (0.5% vs. 0.5%). One patient (0.1%) had a vascular complication at the CEP access site. CONCLUSIONS: Among patients with aortic stenosis undergoing transfemoral TAVR, the use of CEP did not have a significant effect on the incidence of periprocedural stroke, but on the basis of the 95% confidence interval around this outcome, the results may not rule out a benefit of CEP during TAVR. (Funded by Boston Scientific; PROTECTED TAVR ClinicalTrials.gov number, NCT04149535.).

Heart failure (HF) is a progressive disease characterized by variable durations of symptomatic stability often punctuated by episodes of worsening despite continued therapy. These periods of clinical worsening are increasingly recognized as a distinct phase in the history of HF, termed worsening HF (WHF). The definition of WHF continues to evolve from a historical focus solely on hospitalization to now include nonhospitalization events (eg, need for intravenous diuretic therapy in the emergency or outpatient setting). Most HF clinical trials to date have had HF hospitalization and death as primary endpoints, and only recently, some studies have included other WHF events regardless of location of care. This article reviews the evolution of the WHF definition, highlights the importance of considering the onset of WHF as an event that marks a new phase of HF, summarizes the latest clinical trials investigating novel therapies, and outlines unmet needs regarding identification and treatment of WHF.

Importance: Individually, cardiac, renal, and metabolic (CRM) conditions are common and leading causes of death, disability, and health care-associated costs. However, the frequency with which CRM conditions coexist has not been comprehensively characterized to date. Objective: To examine the prevalence and overlap of CRM conditions among US adults currently and over time. Design, Setting, and Participants: To establish prevalence of CRM conditions, nationally representative, serial cross-sectional data included in the January 2015 through March 2020 National Health and Nutrition Examination Survey (NHANES) were evaluated in this cohort study. To assess temporal trends in CRM overlap, NHANES data between 1999-2002 and 2015-2020 were compared. Data on 11 607 nonpregnant US adults (≥20 years) were included. Data analysis occurred between November 10, 2020, and November 23, 2022. Main Outcomes and Measures: Proportion of participants with CRM conditions, overall and stratified by age, defined as cardiovascular disease (CVD), chronic kidney disease (CKD), type 2 diabetes (T2D), or all 3. Results: From 2015 through March 2020, of 11 607 US adults included in the analysis (mean [SE] age, 48.5 [0.4] years; 51.0% women), 26.3% had at least 1 CRM condition, 8.0% had at least 2 CRM conditions, and 1.5% had 3 CRM conditions. Overall, CKD plus T2D was the most common CRM dyad (3.2%), followed by CVD plus T2D (1.7%) and CVD plus CKD (1.6%). Participants with higher CRM comorbidity burden were more likely to be older and male. Among participants aged 65 years or older, 33.6% had 1 CRM condition, 17.1% had 2 CRM conditions, and 5.0% had 3 CRM conditions. Within this subset, CKD plus T2D (7.3%) was most common, followed by CVD plus CKD (6.0%) and CVD plus T2D (3.8%). The CRM comorbidity burden was disproportionately high among participants reporting non-Hispanic Black race or ethnicity, unemployment, low socioeconomic status, and no high school degree. Among participants with 3 CRM conditions, nearly one-third (30.5%) did not report statin use, and only 4.8% and 3.0% used glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, respectively. Between 1999 and 2020, the proportion of US adults with multiple CRM conditions increased significantly (from 5.3% to 8.0%; P < .001 for trend), as did the proportion having all 3 CRM conditions (0.7% to 1.5%; P < .001 for trend). Conclusions and Relevance: This cohort study found that CRM multimorbidity is increasingly common and undertreated among US adults, highlighting the importance of collaborative and comprehensive management strategies.

There is compelling evidence that sodium–glucose cotransporter 2 (SGLT2) inhibitors exert cardioprotective and renoprotective effects that are far greater than expected based on their effects on glycemia or glycosuria. In large-scale randomized controlled trials, SGLT2 inhibitors reduce the risk of hospitalizations for heart failure by ∼30% and often decrease the risk of cardiovascular death (1). This benefit is particularly striking in patients who have the most marked impairment of systolic function prior to treatment. In parallel, SGLT2 inhibitors also reduce the risk of end-stage renal events, including the occurrence of renal death and the need for dialysis or renal transplantation by ∼30% (2). This benefit is seen even when glomerular filtration rates are sufficiently low to abolish the glycosuric effect of these drugs. These cardiorenal benefits cannot be explained by an action of SGLT2 inhibitors to lower blood glucose, since similar effects are not seen with antidiabetes drugs that have greater antihyperglycemic actions. Additionally, they cannot be ascribed to a natriuretic action, since these drugs exert only a modest effect on plasma volume or on circulating natriuretic peptides (3). In 2016, two articles published in Diabetes Care proposed the “thrifty fuel hypothesis” to explain the cardiorenal benefits of SGLT2 inhibitors. Ferrannini et al. (4) and Mudaliar et al. (5) postulated that the action of SGLT2 inhibitors to promote ketogenesis might account for their favorable effects on the heart and kidney because enhanced ketone bodies formation might possibly provide an efficient fuel that could boost the energy state of organs under stress. However, type 2 diabetes represents a state of nutrient overabundance and not energy deprivation, as is evidenced by the enhancement of molecular pathways that promote both energy retention (e.g., through SGLT2 upregulation) and energy storage (6,7). In fact, the stressed heart already preferentially utilizes ketone bodies, …

BACKGROUND AND AIMS: For patients with symptomatic, severe tricuspid regurgitation (TR), early results of transcatheter tricuspid valve (TV) intervention studies have shown significant improvements in functional status and quality of life associated with right-heart reverse remodelling. Longer-term follow-up is needed to confirm sustained improvements in these outcomes. METHODS: The prospective, single-arm, multicentre TRISCEND study enrolled 176 patients to evaluate the safety and performance of transcatheter TV replacement in patients with ≥moderate, symptomatic TR despite medical therapy. Major adverse events, reduction in TR grade and haemodynamic outcomes by echocardiography, and clinical, functional, and quality-of-life parameters are reported to one year. RESULTS: Enrolled patients were 71.0% female, mean age 78.7 years, 88.0% ≥ severe TR, and 75.4% New York Heart Association classes III-IV. Tricuspid regurgitation was reduced to ≤mild in 97.6% (P < .001), with increases in stroke volume (10.5 ± 16.8 mL, P < .001) and cardiac output (0.6 ± 1.2 L/min, P < .001). New York Heart Association class I or II was achieved in 93.3% (P < .001), Kansas City Cardiomyopathy Questionnaire score increased by 25.7 points (P < .001), and six-minute walk distance increased by 56.2 m (P < .001). All-cause mortality was 9.1%, and 10.2% of patients were hospitalized for heart failure. CONCLUSIONS: In an elderly, highly comorbid population with ≥moderate TR, patients receiving transfemoral EVOQUE transcatheter TV replacement had sustained TR reduction, significant increases in stroke volume and cardiac output, and high survival and low hospitalization rates with improved clinical, functional, and quality-of-life outcomes to one year. Funded by Edwards Lifesciences, TRISCEND ClinicalTrials.gov number, NCT04221490.

Diagnosing heart failure is often difficult due to the non-specific nature of symptoms, which can be caused by a range of medical conditions. Natriuretic peptides (NPs) have been recognized as important biomarkers for diagnosing heart failure. This document from the Heart Failure Association examines the practical uses of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in various clinical scenarios. The concentrations of NT-proBNP vary according to the patient profile and the clinical scenario, therefore values should be interpreted with caution to ensure appropriate diagnosis. Validated cut-points are provided to rule in or rule out acute heart failure in the emergency department and to diagnose de novo heart failure in the outpatient setting. We also coin the concept of 'heart stress' when NT-proBNP levels are elevated in an asymptomatic patient with risk factors for heart failure (i.e. diabetes, hypertension, coronary artery disease), underlying the development of cardiac dysfunction and further increased risk. We propose a simple acronym for healthcare professionals and patients, FIND-HF, which serves as a prompt to consider heart failure: Fatigue, Increased water accumulation, Natriuretic peptide testing, and Dyspnoea. Use of this acronym would enable the early diagnosis of heart failure. Overall, understanding and utilizing NT-proBNP levels will lead to earlier and more accurate diagnoses of heart failure ultimately improving patient outcomes and reducing healthcare costs.

AIMS: To investigate the impact of patiromer on the serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of the RAASi therapy [≥50% recommended dose of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist (MRA) spironolactone or eplerenone]. Specified target doses of the RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in the adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13-43) weeks, the adjusted mean change in potassium was +0.03 mmol/l in the patiromer group and +0.13 mmol/l in the placebo group [difference in the adjusted mean change between patiromer and placebo: -0.10 mmol/l (95% confidence interval, CI -0.13, 0.07); P < 0.001]. Risk of hyperkalemia >5.5 mmol/l [hazard ratio (HR) 0.63; 95% CI 0.45, 0.87; P = 0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P = 0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P < 0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P < 0.001) and total RAASi use score (win ratio 1.25, P = 0.048) favored the patiromer arm. Adverse events were similar between groups. CONCLUSION: Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066).