The Global Cardiology journal is an open access, peer-reviewed international journal that aims to publish original articles, reviews, mini reviews, case reports, guidelines, white papers, news, meeting reports, plain language summaries, editorials, and letters to the editor related to the diagnosis, treatment, and prevention of cardiovascular diseases. The scope of the journal includes all aspects of basic, translational, and clinical science in cardiology, including but not limited to coronary artery disease, heart failure, cardiomyopathies, arrhythmias, valvular heart disease, hypertension, congenital heart disease, cardiac imaging, interventional cardiology, cardiac surgery, and co-morbidities leading to cardiovascular disease, as well as epidemiology, prevention, and rehabilitation of cardiovascular diseases. The journal aims to provide a platform for the dissemination of new knowledge and advancements in the field of cardiology, as well as to promote interdisciplinary collaboration among researchers, clinicians, healthcare professionals, and the medically interested public. The target audience of a general cardiology journal includes cardiologists, internists, primary care physicians, researchers, and other healthcare professionals involved in the care of patients with cardiovascular diseases.
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Draft Document for Public Consultation: What is new and what has changed in the 2026 Global Heart Failure Implementation Guidelines and why
Inequities in healthcare access, infrastructure, resource availability, differing society recommendations, and local clinical practices continue to limit the global applicability and implementation of existing heart failure (HF) guidelines. Accordingly, there remains a need for concise and practical recommendations that address the diverse challenges faced by patients and healthcare providers in different areas of the world. The iCARDIO Alliance Global Implementation Guidelines aim to ntegrate contemporary evidence on heart failure diagnosis and treatment with implementation considerations applicable across diverse economic and healthcare settings. This 2026 focused update of the original iCARDIO Alliance Global Implementation Guidelines on Heart Failure published in 2025 incorporates emerging evidence relevant to acute and chronic HF, including heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and cardiomyopathies. When patients with HFrEF experience substantial improvement in LVEF and diagnostically move from the HFrEF to the HFpEF category they are commonly diagnosed as having HF with improved EF (HFimpEF). Hence, we now define HFimpEF to be present, when in a patient who previously was diagnosed with HFrEF an improvement in the LVEF of at least 10 percentage points to an LVEF ≥50% is observed. The main updates in the therapeutic recommendations of the Global Implementation Guidelines on Heart Failure pertain to evolving data on the soluble guanylate cyclase stimulator vericiguat, cardiac glycosides, GLP-1 receptor agonists, cardiac myosin inhibitors, and preventive vaccination strategies. Revised recommendations were informed by recently published randomized trials, and selected additional post-hoc analyses and meta-analyses demonstrating improvements in symptoms, quality of life, HF hospitalization or mortality among patients receiving contemporary guideline-directed medical therapy (GDMT) regarding the approaches mentioned above [...]
Copyright (c) 2026 the Author(s) https://creativecommons.org/licenses/by-nc/4.0
Mineralocorticoid receptor antagonists in heart failure with preserved (and mildly reduced) ejection fraction: a comparative review of spironolactone and finerenone
Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of all heart failure presentations and remains associated with substantial mortality, ranging from 15% at 1 year to nearly 75% within 5-10 years following hospitalization. Mineralocorticoid receptor antagonists (MRAs), which blunt maladaptive activation of the renin-angiotensin-aldosterone system and thereby attenuate myocardial fibrosis, sodium retention, inflammation, and progressive ventricular remodeling, have been explored as a mechanistically grounded therapeutic strategy in HFpEF. Spironolactone, the most extensively studied steroidal MRA, was evaluated in the TOPCAT trial involving 3445 patients with symptomatic HFpEF or heart failure with mildly reduced ejection fraction; however, the trial did not demonstrate a significant overall benefit, while treatment was associated with increased rates of hyperkalemia and worsening renal function. Moreover, concerns regarding trial design, conduct, and marked regional heterogeneity in outcomes have further complicated interpretation, contributing to ongoing uncertainty regarding the role of spironolactone in routine HFpEF management. In contrast, finerenone, a non-steroidal MRA with greater receptor selectivity than spironolactone, demonstrated favorable outcomes in the FINEARTS-HF trial, which enrolled 6001 patients with symptomatic heart failure and left ventricular ejection fraction ≥40%, significantly reducing worsening heart failure events and cardiovascular death (rate ratio 0.84; 95% CI, 0.74-0.95), with consistent effects across the ejection fraction spectrum. Despite these findings, the substantially higher cost of finerenone compared with spironolactone may limit its accessibility and real-world use, particularly in resource-limited settings, and the absence of head-to-head randomized trials precludes definitive conclusions regarding comparative efficacy, safety, and cost-effectiveness; future studies should th
Beyond oral and intravenous diuretics: intranasal bumetanide for heart failure decongestion
Heart failure (HF) remains a major cause of morbidity, hospitalization, and healthcare expenditure, with acute decompensated HF accounting for more than 1.2 million hospital admissions annually in the United States. Intravenous loop diuretics remain the standard for acute decongestion; however, their reliance on venous access, monitoring, and hospital infrastructure limits outpatient use and contributes to recurrent healthcare utilization. These limitations have driven interest in alternative strategies capable of achieving effective decongestion in ambulatory settings. Intranasal bumetanide has emerged as a potential option by bypassing the gastrointestinal tract, where intestinal edema, impaired splanchnic perfusion, and gastrointestinal dysmotility during HF decompensation may lead to unreliable oral absorption. In a randomized three-way crossover trial involving 68 healthy participants, intranasal bumetanide demonstrated systemic exposure comparable to oral and intravenous administration, with similar peak concentrations and area under the curve. It also showed reduced pharmacokinetic variability compared with oral therapy (~27% vs >40% intrasubject variability) and more rapid absorption, with time to maximum concentration of approximately 1.0 hours (intranasal) vs 1.5 hours (oral), suggesting a more predictable onset of diuretic effect. Pharmacodynamic responses, including urine output and urinary sodium excretion at 2 and 24 hours, were comparable across all routes, with a favorable safety profile and minimal adverse effects. Despite these findings, important limitations remain, particularly the absence of data in patients with HF, uncertainty regarding absorption during acute congestion, and concerns related to unsupervised outpatient administration. Further clinical studies are required to define the efficacy, safety, and clinical role of intranasal bumetanide in HF management.
Filling the void: digoxin and the first randomized evidence in rheumatic heart disease
The Digoxin in Rheumatic Heart Disease (Dig-RHD) trial marks an important shift in rheumatic heart disease by replacing long-standing therapeutic assumption with direct randomized evidence. In a condition affecting predominantly young patients in low- and middle- income countries, practice has often relied on extrapolation from non-valvular heart failure populations despite clear differences in disease biology, treatment access, and clinical context. By reducing heart failure events in symptomatic patients, Dig-RHD suggests that the value of digoxin in RHD may lie in preventing deterioration and preserving stability, rather than in mortality reduction alone. This distinction matters because worsening heart failure in RHD represents functional decline, recurrent healthcare use, and loss of clinical reserve in settings where advanced interventions may be delayed or unavailable. The findings support reassessment the role of digoxin in symptomatic RHD while underscoring the need to define optimal timing, rhythm-specific effects, disease severity, and background therapy. More broadly, Dig-RHD shows that rigorous outcome trials in RHD are feasible and necessary for a population still underrepresented in cardiovascular research.
Early invasive versus conservative strategy in acute coronary syndrome in older adults: systematic review and meta-analysis
Acute coronary syndrome (ACS) disproportionately affects older adults, who face higher risks of mortality and complications due to frailty and comorbidities. Whether an early invasive strategy improves outcomes compared with conservative medical therapy in adults aged ≥65 years remains uncertain. Thus, we aimed to compare the efficacy and safety of early invasive therapy versus conservative medical management in older adults with ACS. We systematically searched PubMed, Embase, and Cochrane CENTRAL from inception to January 2026 for trials enrolling adults aged ≥65 years with ACS. The primary outcome was all-cause mortality, while secondary outcomes included recurrent myocardial infarction (MI), coronary revascularization, stroke, major bleeding, major adverse cardiovascular events (MACE), and major adverse cardiac and cerebrovascular events (MACCE). Risk ratios (RRs) were pooled using random-effects models, with heterogeneity assessed by the I² statistic. Additionally, cumulative meta-analyses were performed to examine trends over time. Eleven trials comprising 4251 patients were included. Most participants were aged >70 years, predominantly male, and primarily presented with non-ST-elevation myocardial infarction. Followup ranged from 6 months to 5 years. Early invasive therapy did not reduce all-cause mortality compared with conservative management (RR 1.04, 95% CI 0.98-1.10; p=0.19). However, it significantly reduced recurrent MI (RR 0.74, 95% CI 0.64-0.86; p<0.001) and coronary revascularization (RR 0.39, 95% CI 0.27-0.56; p<0.001). Major bleeding was increased with the invasive strategy (RR 1.67, 95% CI 1.08-2.59; p=0.02), while stroke rates were similar (RR 0.97, 95% CI 0.72-1.32; p=0.87). No significant differences were observed for MACE (RR 1.11, 95% CI 0.79-1.56; p=0.57) or MACCE (RR 0.92, 95% CI 0.65-1.29; p=0.62). Cumulative meta-analysis demonstrated stable effect estimates over time with no mortality benefit. In older adults with ACS, an early invasive strategy does not improve survival but reduces recurrent MI and subsequent revascularization while increasing major bleeding risk. These findings support individualized treatment decisions based on ischemic risk, bleeding risk, frailty, comorbidity burden, and patient preference rather than chronological age alone.
Ten-year survival after indirect mitral annuloplasty with the Carillon Mitral Contour System in functional mitral regurgitation. A single-center followup from the REDUCE-FMR trial
Indirect mitral annuloplasty with the Carillon Mitral Contour System reduces regurgitant volume, induces favorable left ventricular remodeling, and is associated with favorable survival rates through 6 years; however, longer term data are limited. This observational study included all 17 patients from a single center implanted with the Carillon device in the REDUCEF-MR trial. Patients had New York Heart Association class IIIV symptoms, left ventricular ejection fraction <50%, and mitral regurgitation grade ≥2+ despite stable guideline-directed medical therapy. Patients underwent clinical and echocardiographic followup in the REDUCE-FMR trial for 1 year. Thereafter, vital status was ascertained after a median of 9.2 years (range: 8.010.3 years). KaplanMeier methods were used to estimate overall and cardiovascular survival. Univariable Cox regression was used to identify predictors of longterm mortality, with results reported as hazard ratios (HR) and 95% confidence intervals (95% CI). The 10year survival rate was 35% (median survival 5.6 years), and the corresponding cardiovascular survival rate was 66%. Baseline left ventricular ejection fraction <35% (HR=7.1; 95% CI: 1.4, 36.5; p=0.02), first-year heart failure hospitalization (HR=8.0; 95% CI: 2.0, 32.1; p=0.004), and tent height decrease during the first year (HR=5.1; 95% CI: 1.3, 20.8; p=0.02) were associated with increased all-cause mortality. First year heart failure hospitalization (HR=9.6; 95% CI: 1.1, 88.8; p=0.046) was the only variable associated with higher cardiovascular mortality. This study provides the first evidence of survival beyond 6 years after indirect mitral annuloplasty with the Carillon device, with 10-year outcomes suggesting durability of this treatment.
Aspirin underuse in secondary prevention: beyond access and adherence
To the Editor, Cardiovascular disease remains the leading cause of mortality worldwide, yet aspirin, one of the most effective and inexpensive therapies for secondary prevention, continues to be underused across diverse healthcare settings and patient populations. Importantly, this underuse reflects not only limited access to therapy, but also disparities in adherence, persistence, and uncertainty regarding benefit in certain high-risk groups [...]
Transcatheter tricuspid valve repair for tricuspid regurgitation: a meta-analysis of MitraClip, TriClip,and PASCAL Systems
Tricuspid regurgitation (TR) is associated with significant morbidity and mortality, yet surgical intervention remains underutilized due to high operative risk. Transcatheter tricuspid valve repair (TTVr) has emerged as a less invasive alternative; however, comparative data across device platforms remain limited. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching PubMed/MEDLINE, Embase, and Cochrane Library up to March 2026. Studies evaluating TTVr using MitraClip, TriClip, or PASCAL in adults with moderate-to-severe TR were included. Primary outcomes included changes in TR severity and echocardiographic parameters (TR volume, vena contracta, effective regurgitant orifice area, tricuspid annular plane systolic excursion). Secondary outcomes included 6-minute walk distance (6MWD) and New York Heart Association (NYHA) functional class. A random-effects model was used for pooled analyses. Fifty studies were included in the meta-analysis. TTVr significantly reduced TR volume (MD −21.53 mL; 95% CI −24.72 to −18.35) and vena contracta (MD −5.91 mm; 95% CI −7.62 to −4.19), with consistent improvements across devices. Severe TR was significantly reduced (RR 0.32; 95% CI 0.26-0.39). Functional outcomes improved, with increased 6MWD (MD 36.14 m; 95% CI 23.85-48.43) and a higher proportion of patients achieving NYHA class I/II. A modest decline in TAPSE was observed (MD −0.74 mm). Subgroup analyses showed no significant differences in most echocardiographic outcomes, though functional improvements varied among devices. We concluded that TTVr is associated with significant improvements in TR severity, echocardiographic parameters, and functional status. Comparable outcomes across MitraClip, TriClip, and PASCAL suggest a potential class effect, supporting TTVr as an effective treatment option for high-risk patients.
Carotid artery stenosis related mortality among older adults (>65 years): a retrospective analytical study
Stroke is a leading cause of death, with carotid artery stenosis (CAS) contributing substantially to ischemic events. Although CAS-related strokes remain common in older adults in the United States, mortality patterns and demographic disparities are not well described. We aimed to evaluate nationwide trends and disparities in CAS-related mortality among US adults aged ≥65 years from 1999 to 2020 using the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database. A retrospective analysis of the CDC WONDER database was conducted to investigate CAS-related mortality trends. Using Join-point regression analysis, age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000 individuals, along with annual percent change, were calculated and stratified by year, sex, age, race/ethnicity, and geographic region. Between 1999 and 2020, 44,297 CAS-related deaths occurred among US adults aged ≥65 years. Overall, the AAMR declined from 3.13 in 1999 to 2.27 in 2009, then rose sharply from 3.86 in 2015 to 6.56 in 2020, with an overall average annual percent change of 1.58% (95% CI 0.99-2.16; p<0.001). Mortality was higher in men than women (AAMR 6.52 vs. 3.91) and increased with age, peaking among adults aged ≥85 years (CMR 12.5). Regionally, the Midwest had the highest AAMR (4.55), followed by the West (4.30), South (4.25), and Northeast (4.16). Nonmetropolitan and metropolitan areas showed comparable AAMRs. By race/ethnicity, non-Hispanic White individuals had the highest mortality (AAMR 4.6), followed by non-Hispanic Black (3.11) and Hispanic individuals (2.73). At the state level, Vermont had the highest AAMR (7.26), while Utah had the lowest (2.33). After an initial decline, CAS-related mortality among older US adults rose after 2009, reaching its highest levels in 2020. Persistent disparities by sex, age, race/ethnicity, and region highlight the need for targeted interventions in high-risk populations.
Familial hypercholesterolemia: state-of-the-art
Familial hypercholesterolemia (FH) affects about 20 million people worldwide and remains markedly underdiagnosed and undertreated. Contemporary studies estimate the prevalence of heterozygous FH (HeFH) at 1 in 192 to 1 in 310, and the prevalence of homozygous FH (HoFH) at about 1 in 300,000. The 2016 United States National Health and Nutrition Examination Survey estimated FH prevalence at 1 in 250 adults. Untreated HeFH causes fatal coronary events before age 55 in about 50% of men and before age 60 in about 15% of women. Pathogenic variants in the low-density lipoprotein receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin type 9 (PCSK9) cause most FH cases. Polygenic burden and genetic modifiers influence phenotype and treatment response. Clinical diagnosis relies on the Dutch Lipid Clinic Network (DLCN), the Simon Broome criteria, or the Make Early Diagnosis to Prevent Early Death criteria. Next-generation sequencing (NGS) increases diagnostic certainty and enables cascade screening. In severe hypercholesterolemia, NGS detects mutations in 57% of cases overall and in 92% when low-density lipoprotein cholesterol (LDL-C) exceeds 310 mg/dL. In contrast, population screening using LDL-C >190 mg/dL identifies pathogenic variants in fewer than 5% of cases. Cascade screening yields range from 0.4 to 0.7 per index case in some United Kingdom series, about 2 in several Australian and Brazilian programs, and up to 8 in optimized Dutch programs. In primary care, the Familial Hypercholesterolemia Case Ascertainment Tool discriminated FH better than other criteria in 1,030,183 patients, with an area under the curve (AUC) of 0.844, compared with 0.730 for Simon Broome, 0.766 for DLCN, and 0.579 for LDL-C above the 99th percentile. Management begins with high-intensity statins and ezetimibe. Treatment aims for at least a 50% reduction in LDL-C and LDL-C <70 mg/dL for primary prevention or <55 mg/dL for very-high-risk patients. In children older than 10 years, the LDL-C target is <135 mg/dL. PCSK9-directed therapies further lower LDL-C. Evolocumab reduces LDL-C by 59% to 61% in RUTHERFORD-2 and by 31% in TESLA Part B; alirocumab reduces LDL-C by 51% to 58% in ODYSSEY FH I/II; inclisiran reduces LDL-C by 48% in ORION-9; and evinacumab reduces LDL-C by about 49% in HoFH. Lipoprotein apheresis acutely reduces LDL-C by about 50% to 75% per session. Earlier detection, cascade screening, and equitable access to combination therapy remain central to reducing premature atherosclerotic cardiovascular disease in FH.
Glucagon-like peptide-1 receptor agonists and muscle: interpreting lean mass changes in clinical care
Skeletal muscle supports mobility and metabolic reserve. Low muscle reserve is common in obesity, type 2 diabetes mellitus (T2DM), and metabolicassociated steatotic liver disease, where myosteatosis and insulin resistance are linked to poorer strength and physical performance. Glucagon-like peptide-1 receptor agonists (GLP1RAs) improve weight and glycemic control, but body composition studies often report reductions in measured lean mass alongside fat mass loss. Interpretation is complicated because lean mass and fat free mass are not direct measures of contractile muscle and are sensitive to hydration and measurement modality, particularly with dual-energy Xray absorptiometry and bioelectrical impedance analysis. A network meta-analysis of 22 randomized trials (n=2258) reported mean reductions of 3.55 kg in body weight, 2.95 kg in fat mass, and 0.86 kg in lean mass, with lean tissue contributing about onequarter of total weight loss. A recent metaanalysis of 38 studies (n=1735) found smaller muscle changes in T2DM (mean reduction: 0.74 kg) than in populations without T2DM (mean reduction: 1.41 kg). In addition, imaging cohorts involving computed tomography show modest declines in muscle area and attenuation after semaglutide. More recently, SEMALEAN study reported 13% weight loss and 19% fat mass loss at 12 months, with early lean mass decline followed by stability, and improved handgrip strength. Clinical decisions should prioritize function over lean mass alone and pair GLP1RA therapy with resistance training and adequate protein intake, with closer monitoring in older adults and other highrisk phenotypes.
Beyond trial neutrality: treatment discontinuation and the hidden signal in SPIRIT-HF trial
Taken together, the findings from SPIRIT-HF challenge a simplistic interpretation of neutral trial results from an under-powered study, and instead appear to highlight the critical role of treatment durability in determining clinical outcomes in heart failure with preserved ejection fraction and heart failure with mildly reduced ejection fraction, where patients are older, multi-morbid, and physiologically vulnerable, the balance between efficacy and tolerability is particularly fragile. Importantly, treatment discontinuation should not be viewed merely as an adverse event, but as a clinically meaningful signal reflecting both patient vulnerability and potential loss of therapeutic benefit. These observations suggest that the effectiveness of neurohormonal therapies may depend as much on their sustained use as on their intrinsic pharmacologic efficacy. Accordingly, future therapeutic strategies should prioritize not only the initiation of disease-modifying treatments but also their long-term tolerability, adherence, and continuity.
Heart failure with preserved ejection fraction
heart failure with mildly reduced ejection fraction
SPIRonolactone In The Treatment of Heart Failure trial
Ischemic and bleeding outcomes by diabetes status in patients receiving ticagrelor monotherapy after percutaneous coronary intervention: an updated meta-analysis
Ticagrelor monotherapy after percutaneous coronary intervention (PCI) has been proposed to reduce bleeding risk while maintaining ischemic protection. The objective of this paper is to describe differences in ischemic and bleeding outcomes between patients with and without diabetes mellitus who were treated with ticagrelor monotherapy following PCI. A systematic review and meta-analysis were conducted using MEDLINE, Scopus, and Cochrane databases through 15th July 2025. Eligible studies included post hoc analyses of randomized trials comparing ticagrelor monotherapy outcomes between diabetic and non-diabetic patients. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Four trials were included with a total population of 18,596. Diabetic patients had significantly higher risk of major adverse cardiovascular events (RR 1.84, 95% CI 1.44-2.36; p<0.00001; I²=37%), all-cause mortality (RR 2.46, 95% CI 1.95-3.10; p<0.00001; I²=0%), cardiac death (RR 3.03, 95% CI 1.23-7.48; p=0.02; I²=23%), stroke (RR 1.71, 95% CI 1.09-2.67; p=0.02; I²=0%), clinically relevant bleeding (RR 1.35, 95% CI 1.15-1.58; p=0.0002; I²=0%) and major bleeding (RR 1.81, 95% CI 1.40-2.34; p<0.00001; I²=1%). Myocardial infarction and stent thrombosis did not differ significantly between groups. We can conclude that among patients treated with ticagrelor monotherapy after PCI, those with diabetes experienced higher ischemic and bleeding event rates than non-diabetic patients. These findings reflect diabetes-associated risk differences within a uniform anti-platelet regimen and should be interpreted as hypothesis-generating.
Patent foramen ovale: when does it need closure?
A patent foramen ovale (PFO) is present in approximately 25% of the general population. Its clinical significance is primarily in patients with cryptogenic stroke. Randomized trials have evaluated whether transcatheter PFO closure reduces recurrent stroke compared to medical therapy. Evidence outside stroke, including migraine, decompression illness, and platypneaorthodeoxia syndrome, is limited. We reviewed major randomized controlled trials and extended follow-up studies evaluating transcatheter PFO closure in patients with cryptogenic stroke. Key trials included RESPECT, REDUCE, CLOSE, DEFENSEPFO, and RESPECTLate. Study populations, procedural outcomes, and post-procedural management were summarized. Non-stroke indications were evaluated using available randomized and observational data. In the RESPECT trial (n=980; mean age 46±11 years; 38% female; median follow-up 5.9 years), recurrent ischemic stroke occurred in 3.6% of patients undergoing PFO closure vs 5.8% with medical therapy (HR 0.55; 95% CI, 0.31–0.999; p=0.046). The REDUCE trial (n=664; mean age 45±10 years; 42% female) demonstrated a 77% relative risk reduction in recurrent stroke with closure vs antiplatelet therapy alone (1.4% vs 5.4%; p=0.002). The CLOSE trial (n=663; mean age 45±11 years; 40% female) reported no recurrent strokes in the closure group vs 14 events (6%) in the anti-platelet group over 5.3 years (p<0.001). DEFENSEPFO (n=120; mean age 52±12 years; 45% female) showed stroke in 0% vs 12.9% with medical therapy at 2 years (p=0.013). RESPECTLate demonstrated sustained benefit over 10 years (HR 0.54; 95% CI, 0.29–0.999; p=0.046). Pooled analysis across trials indicated a 59% lower risk of recurrent stroke with closure (HR 0.41; 95% CI, 0.200.83). The benefit was most pronounced in patients with large shunts or atrial septal aneurysms. Post-procedural atrial fibrillation occurred in 35% of patients; serious procedural complications were <2%. Dual antiplatelet therapy was administered for 3–6 months, and successful shunt elimination exceeded 90%. Evidence for PFO closure in migraine with aura or decompression illness remains limited; closure in platypneaorthodeoxia syndrome shows symptomatic improvement based on small case series. Transcatheter PFO closure significantly reduces recurrent stroke in adults aged 1860 years with cryptogenic stroke and highrisk anatomical features. The procedure is generally safe, with low rates of serious complications. Nonstroke indications remain investigational, and patient selection with multidisciplinary evaluation is essential to maximize benefit and minimize risk.
Hypertension-related heart failure mortality among older adults in the United States: a nationwide analysis of demographic and regional trends
Although hypertension (HTN) is a major risk factor for heart failure (HF), limited national data exist on trends in mortality where HF is the underlying cause of death and HTN is a contributing factor among older adults aged ≥65 years. The aim of the study is to evaluate temporal, demographic, and regional trends in HTN-related HF mortality among older US adults from 1999 to 2020. We used CDC WONDER (Centers for Disease Control and Prevention WideRanging Online Data for Epidemiologic Research) mortality data to identify deaths with HF as the underlying cause and HTN as a contributing cause in individuals aged ≥65 years. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated by year, sex, race/ethnicity, region, and urban rural status. Join point regression was used to determine changes in trends over time. Between 1999 and 2020, 378,851 HTNrelated HF deaths occurred, most in nursing homes/longterm care facilities (34.7%), at home (31.2%), or in medical facilities (24.6%). The AAMR rose from 31.8 in 1999 to 38.3 in 2005 (APC 3.2; 95% CI, 2.2-4.7), declined to 34.0 in 2009 (APC –2.6; 95% CI, –4.6 to –0.7), remained stable through 2014, and then increased sharply to 66.1 in 2020 (APC 10.9; 95% CI, 9.9-12.6). Women had higher overall mortality than men (41.7 vs. 37.5). NH Black adults had the highest rates (64.1), followed by NH White (38.9), NH American Indian/Alaska Native (38.3), Hispanic/Latino (34.3), and NH Asian/Pacific Islander (26.2). Mississippi had the highest state-level rate (109.6), while Hawaii had the lowest (20.2). Regionally, the West (48.5) exceeded the Northeast (29.8). Non-metropolitan areas had higher mortality than metropolitan areas (44.9 vs. 39.5). We concluded that HTN-related HF mortality in older adults has risen markedly since 2014, with the greatest burden among women, NH Black adults, Western states, and rural populations. These findings underscore the need for improved HTN control and HF care in highrisk groups.
Obesity and left atrial function: state of the art
Obesity is an established risk factor for heart failure (HF), with every unit increase in body mass index, the risk of HF increases by 5-7%. Obesity can especially increase the risk for HF with preserved ejection fraction due to left atrial (LA) dysfunction caused by underlying systemic inflammation, chronic volume overload, and growth of epicardial adipose tissue. LA function can be assessed by measuring LA reservoir, conduit and booster, which correspond to physiological functions of LA filling during filling phase of cardiac cycle, LA pushing blood into left ventricle passively, and LA contraction to push the blood into left ventricle, respectively. Existing data show strong prognostic ability of LA strain reservoir for cardiovascular mortality and HF hospitalization. Several studies have also suggested that obesity in itself can cause reduction in LA strain and deterioration of LA function. Whether various weight loss interventions for patients with obesity can minimize and reverse LA remodeling and dysfunction remains unclear. In this review, we summarize the evidence regarding the impact of obesity on LA function, and discuss the impact of various weight reduction techniques on LA strain.
Draft Document for Public Consultation: iCARDIO Alliance Global Implementation Guidelines on Ischemic Heart Disease Management 2026
Ischemic heart disease (IHD) remains the leading cause of morbidity and mortality worldwide. Coronary artery disease (CAD) encompasses any pathological process capable of compromising myocardial perfusion and although numerous etiologies exist, including vasculitis, spontaneous coronary artery dissection, and coronary embolism, the majority of CAD is attributable to coronary atherosclerosis, which constitutes the focus of this document. For practical purposes, CAD is considered present when any degree of atherosclerotic involvement exceeds zero percent stenosis, recognizing that even minimal coronary atherosclerosis represents a systemic disease process with prognostic implications.
Disclaimer: The Global Implementation Guidelines (the “Documents”) represent the views of its authors. They were produced after careful consideration of the scientific and medical knowledge and the evidence and related economic issues that may impact implementation of therapies, as well as the main guidelines on the topic, available at the time of their publication. The iCARDIO Alliance, respectively its Partner Organizations and the TMA, are not responsible in the event of any contradiction, discrepancy, and/or ambiguity between the Documents and any other official recommendations or guidelines issued by other bodies in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the Documents fully into account when exercising their clinical judgment, as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies. On the other hand, the Documents do not override the individual responsibility of health professionals to make the appropriate, accurate and individual decisions in consideration of each patient’s health condition. These decisions should be taken in consultation with their individual patient and, where appropriate and/or necessary, the patient’s caregiver. The Documents do not exempt health professionals from taking into full and careful consideration the relevant official updated recommendations or guidelines, issued by the competent public health authorities that govern them. It is also the health professional’s responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription.
Metabolic dysfunction-associated steatotic liver disease and cardiovascular disease: a state-of-the-art review
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly nonalcoholic fatty liver disease, is the most prevalent chronic liver disease worldwide, affecting more than 30% of adults and up to 70–90% of individuals with obesity or type 2 diabetes mellitus. Cardiovascular disease (CVD) represents the leading cause of mortality in this population. MASLD is increasingly recognized as an independent cardiovascular risk factor beyond traditional metabolic comorbidities. This narrative review summarizes epidemiologic, mechanistic, and clinical evidence linking MASLD with cardiovascular disease, with a focus on population-based cohort studies, imaging-based assessments of subclinical cardiovascular disease, and fibrosis-based risk stratification. Population-based cohorts, including the Framingham Heart Study and the Multi-Ethnic Study of Atherosclerosis, demonstrate that hepatic steatosis is associated with a 1.5–2.0-fold increased risk of incident cardiovascular events after adjustment for age, sex, body mass index, diabetes, and lipid levels. MASLD is characterized by insulin resistance, increased visceral adiposity, atherogenic dyslipidemia with elevated triglycerides, small dense low-density lipoprotein particles, and reduced high-density lipoprotein cholesterol. Patients exhibit systemic low-grade inflammation with elevated tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein, alongside altered adipokine and hepatokine signaling, including reduced adiponectin and increased leptin, resistin, fetuin-A, and fibroblast growth factor 21. Imaging studies identify higher carotid intima–media thickness, increased coronary artery calcium scores, and early left ventricular diastolic dysfunction in patients with MASLD compared with controls. Fibrosis stage has emerged as the strongest hepatic predictor of cardiovascular outcomes. Individuals with advanced fibrosis have significantly higher rates of cardiovascular events and mortality compared with those without fibrosis, independent of traditional risk factors. Emerging data also implicate gut–liver axis dysfunction and increased intestinal permeability in amplifying systemic inflammation and vascular injury. MASLD is closely linked to cardiovascular disease through shared metabolic, inflammatory, and fibrotic pathways. Cardiovascular risk in MASLD is driven primarily by fibrosis severity rather than steatosis burden. Incorporation of liver disease assessment, particularly fibrosis evaluation, into cardiovascular risk stratification may improve identification of high-risk individuals and support integrated cardiometabolic care.
Metabolic dysfunction-associated steatotic liver disease
Coronary artery calcium scoring. What clinicians need to know
Coronary artery calcium (CAC) scoring, measured by computed tomography (CT), quantifies calcified coronary plaque and reflects the burden of coronary atherosclerosis. The Agatston score, calculated based on lesion density and area, stratifies patients into risk categories: a score of 0 indicates no detectable calcification, 1-99 suggests mild plaque, 100-399 indicates moderate burden, and scores of 400 or more reflect high to extensive calcification, with scores above 1000 indicate extremely high atherosclerotic burden. CAC scoring is most beneficial in asymptomatic adults aged 40 to 75 years with borderline (5-7.5%) or intermediate (7.5-20%) 10-year ASCVD risk when uncertainty exists regarding statin initiation. The Multi-Ethnic Study of Atherosclerosis (MESA) found that a CAC score of 0 significantly reduces estimated ASCVD risk compared to pooled cohort equation (PCE) predictions, with observed event rates of approximately 1.5% for borderline-risk and 4.5% for intermediate-risk individuals, supporting reclassification into a lower-risk category. Scores of 1-99 represent modestly elevated risk and may guide prevention based on clinical judgment and patient preference. Scores from 100 to 400 reflect moderate plaque burden and support statin therapy, while high scores above 400 reflect substantial atherosclerotic burden, mandating aggressive preventive interventions. CAC testing is generally not indicated in younger, low-risk adults, as they may develop ASCVD later in life, and a score of 0 could lead to false reassurance that discourages appropriate prevention. Similarly, testing is typically unnecessary in elderly individuals with established atherosclerotic disease, as results rarely change management. It is also not recommended in those with clear statin indications, including patients with diabetes, familial hyperlipidemia, existing ASCVD, or those already on lipid-lowering treatment. Frequent CAC retesting is discouraged due to limited clinical benefit, unnecessary costs, potential downstream testing, patient anxiety, and exposure to radiation, though repeating CAC after five years may be reasonable for those initially scoring zero. The recent CAUGHT-CAD trial showed that CAC-informed strategies reduced LDL cholesterol and slowed plaque progression in intermediate-risk individuals with familial coronary artery disease, highlighting its importance. Future research should focus on optimizing CAC use to enhance patient outcomes while balancing clinical utility, cost, and risk.
Copyright (c) 2025 the Author(s) https://creativecommons.org/licenses/by-nc/4.0
The impact of frailty on in-hospital outcomes in patients with HFrEF
Frailty is a marker of poor prognosis and is often undertreated and predisposed to adverse outcomes. This study aimed to determine the association between frailty and outcomes in hospitalized patients with heart failure with reduced ejection fraction (HFrEF). A retrospective cross-sectional analysis of the National Inpatient Sample (2016-2020) was conducted to evaluate hospitalizations for HFrEF. Frailty was defined as a hospital frailty risk score of ≥5. Patient demographics, comorbidities, and hospital characteristics were compared between frail and non-frail groups. Multivariable logistic regression, adjusted for confounders, was used to assess the association between frailty and in-hospital outcomes. Among 5,526,303 weighted HFrEF hospitalizations, 53% (n=2,931,329) were classified as frail. Frail patients had a median age of 74 years vs 67 years in non-frail patients. In-hospital mortality was 5.9% in frail vs 1.2% in non-frail patients (adjusted OR [aOR]: 3.8; 95% CI: 3.68-3.92). Adverse events were significantly higher in the frail group, including cardiogenic shock (5.3% vs 2.1%; aOR: 2.58), acute stroke (4.5% vs 0.8%; aOR: 6.63), acute kidney injury (47.8% vs 12.5%; aOR: 5.16), sepsis (13.4% vs 1.6%; aOR: 11.00), major bleeding (4.2% vs 2.0%; aOR: 1.90), acute pulmonary edema (0.47% vs 0.31%; aOR: 1.60), and mechanical ventilation (8.1% vs 1.7%; aOR: 5.33). Additionally, non-home discharge occurred more frequently (35.4% vs 15%; aOR: 2.77), with higher median hospital costs ($46,706 vs $34,793) and prolonged length of stay (5 vs 3 days). Frailty is independently associated with worse in-hospital outcomes in HFrEF patients, underscoring the need for targeted strategies to improve care in this high-risk population.
heart failure with reduced ejection fraction (HFrEF)
Aldosterone synthase inhibitors in cardio-renal diseases: a state-of-the-art review
Aldosterone plays a pivotal role in the progression of cardio-renal diseases by driving myocardial fibrosis, vascular dysfunction, and renal injury through both genomic and non-genomic mechanisms. While mineralocorticoid receptor antagonists have long served as the cornerstone of pharmacologic intervention, their use is limited by adverse effects such as hyperkalemia, gynecomastia, and incomplete suppression of aldosterone-mediated pathology. Aldosterone synthase inhibitors, a novel class of therapeutics, offer a promising alternative by targeting the enzymatic production of aldosterone at its source, thereby circumventing receptor-level limitations. This narrative review comprehensively explores the physiological role of aldosterone, critiques existing RAAS-targeted therapies, and provides an in-depth evaluation of the pharmacology, efficacy, and safety of emerging ASIs including baxdrostat, lorundrostat, and osilodrostat. Evidence from recent clinical trials such as BrigHTN, HALO, Target-HTN, and FIONE is synthesized to assess their clinical potential. In addition, the review highlights novel mechanistic frontiers including the role of ASIs in overcoming aldosterone escape, attenuating cardio-renal fibrosis, modulating neurohormonal dysregulation, and enabling precision therapy through pharmacogenomic stratification. Future directions emphasize drug design innovations such as adrenal-specific prodrugs and nanoparticle-based formulations. Overall, ASIs represent a mechanistically robust and clinically promising advancement in the treatment of heart failure, chronic kidney disease, and primary aldosteronism. Their integration into multidrug regimens and personalized treatment frameworks may redefine the therapeutic landscape of cardio-renal-metabolic disease.
Effect of metformin and empagliflozin on myocardial function in insulin-resistant patients with heart failure: rationale and design of the METRIS-HF-DZHK18 Trial
Impaired energy metabolism contributed to clinical severity, disease progression and to outcome in heart failure (HF). Insulin sensitivity (IS) is a key metabolic factor in the control of energy substrate utilisation and energy efficiency in cardiac and skeletal muscle. Impaired IS, or insulin resistance, is a common finding in HF and has been shown to predict morbidity and mortality in patients with heart failure with reduced and mildly reduced ejection fraction (HFrEF, HFmrEF). Despite its pathophysiologic relevance, IS has not been explored as a therapeutic target in HF. The objective of the METRIS-HF trial is to evaluate the effect of the insulin sensitizer metformin on top of standard care on myocardial contractility and functional capacity in insulin-resistant patients with HFrEF and HFmrEF in comparison to empagliflozin and placebo. METRIS-HF is an investigator initiated, multicentre, randomized, double-blind, placebo-controlled, double-dummy trial to enrol HF patients with reduced ejection fraction and insulin resistance into three parallel treatment arms in a 1:1:1 ratio to receive metformin 2x1000 daily), empagliflozin (1x10 mg/day), or double placebo, on top of standard heart failure therapy. The intervention lasts 24 weeks, followed by a 52-week follow-up period. The primary endpoint is the change in left ventricular global longitudinal strain (GLS) at 24 weeks. Key secondary endpoints include measurements of functional and symptomatic status such as 6-minute walking distance, NHYA functional class, patient global assessment (PGA), and Quality of life (EQ5D). Exploratory endpoints include metabolic, inflammatory, functional, and imaging-based biomarkers. Safety is assessed by adverse and serious adverse events throughout the trial. The METRIS-HF trial will investigate the effect of metabolic treatments to improve insulin sensitivity in patients with HFrEF and HFmrEF to provide mechanistic insights into efficacy of metabolic interventions in heart failure.
Aortic valve replacement in asymptomatic severe aortic stenosis. A focused review
Asymptomatic severe aortic stenosis (AS) has traditionally been managed with watchful waiting because of low annual sudden death rates (<1%) and concerns regarding procedural risk. Emerging randomized data indicate that irreversible myocardial injury may occur before symptom onset and that early aortic valve replacement (AVR) may improve outcomes. This review summarizes evidence from contemporary randomized controlled trials evaluating early surgical AVR (SAVR) or transcatheter AVR (TAVR) vs conservative management or surveillance in asymptomatic patients with severe AS and preserved left ventricular ejection fraction (LVEF). The RECOVERY trial randomized 145 asymptomatic patients with very severe AS (mean age 64 years) to early SAVR or conservative care. Over a median follow-up of 6.2 years, all-cause mortality occurred in 1% of the early surgery group vs 15% with conservative management (hazard ratio [HR] 0.09; 95% CI 0.01-0.67; p=0.003). The AVATAR trial included 157 asymptomatic patients with severe AS, preserved LVEF, and negative exercise testing (mean age approximately 67 years). Over a median follow-up of 32 months, the composite endpoint of all-cause death, myocardial infarction, stroke, or heart failure hospitalization occurred in 16.6% of patients assigned to early surgery compared with 32.9% in the conservative group (HR 0.46; 95% CI 0.23-0.90; p=0.02). The EARLY TAVR trial randomized 901 asymptomatic patients with severe AS and preserved LVEF to TAVR or clinical surveillance (mean age 75.8 years). After a median follow-up of 3.8 years, the primary composite outcome of death, stroke, or unplanned cardiovascular hospitalization occurred in 26.8% of the TAVR group versus 45.3% of the surveillance group (HR 0.50; 95% CI 0.40-0.63; p<0.001). Cardiovascular hospitalizations occurred in 20.9% vs 41.7%, all-cause mortality in 8.4% vs 9.2%, and stroke in 4.2% vs 6.7%, with no excess procedural complications in the early TAVR group. Randomized evidence demonstrates that early AVR, including both SAVR and TAVR, reduces mortality and major cardiovascular events in carefully selected asymptomatic patients with severe AS. The integration of clinical features with risk stratification tools, such as global longitudinal strain, cardiac magnetic resonance imaging, natriuretic peptides, and computed tomography-based valve calcification, supports timely intervention before irreversible myocardial damage occurs.
iCARDIO Alliance Global Implementation Guidelines for the Management of Obesity 2025 - Focus on prevention and treatment of cardiometabolic disease
There are a number of guidelines on how to manage obesity, but inconsistencies in healthcare access, varying infrastructure, resource constraints and diverse local practices restrict their global applicability. This underscores the need for universal recommendations that address the unique challenges faced by patients and healthcare providers worldwide. Our Global Guidelines emphasize the incorporation of novel therapies, while integrating standards of care with the most up-to-date evidence to enable clinicians to optimize obesity management. Context-specific recommendations tailored to individual patient needs are highlighted, providing a thorough evaluation of the risks, benefits, and overall value of each therapy, aiming to establish a standard of care that improves patient outcomes and reduces the burden of hospitalization in this susceptible population. These Global Guidelines provide evidence-based recommendations that represent a group consensus considering the many other published guidelines that have reviewed many of the issues discussed here, but they also make new recommendations where new evidence has recently emerged, and – most importantly – also provide recommendations on several issues where resource limitations may put constraints on the care provided to patients living with obesity. Such “economic adjustment” recommendations aim to guide situations when “Resources are somewhat limited” or when “Resources are severely limited”. Hence, this document presents a comprehensive update to obesity management guidelines, thereby aiming to provide a unified strategy for the pharmacological, non-pharmacological, and invasive management of this significant global health challenge that is applicable to the needs of healthcare around the globe.
Frequency of low-density-lipoprotein-cholesterol measurement and risk of major adverse cardiovascular outcomes: a 5-million-person nationwide cohort study
Cardiovascular disease (CVD) is a leading cause of mortality globally and in the UK, with significant efforts focused on early risk identification and prevention. Elevated low-density lipoprotein cholesterol (LDL-C) is a key modifiable risk factor for cardiovascular disease (CVD), yet the impact of LDL-C monitoring frequency on major adverse cardiovascular events (MACE) remains unclear. This study evaluated the relationship between LDL-C measurement frequency and the risk of MACE in a large, nationwide cohort. A retrospective cohort study using anonymised electronic health records from the Clinical Practice Research Datalink (CPRD) Aurum, linked to hospitalisation, social deprivation, and mortality data. The cohort included individuals registered for at least one year with at least one recorded low-density LDL-C measurement between 1 January 2000 and 31 December 2022. The primary outcome was MACE, defined as a composite of non-fatal coronary heart disease, non-fatal stroke, or cardiovascular death. Multivariable Cox proportional hazards models and Kaplan-Meier survival plot were used to estimate the incidence and hazard ratios (HRs) by LDL-C monitoring frequency. The study cohort comprised 5,133,574 individuals, with 2,733,144 (53.2%) being women. The median follow-up duration was 3.31 years (IQR: 7.39-12.11). Among the 5,133,574 individuals, the incidence of MACE declined with more frequent LDL-C monitoring, from 1937.0 (95% CI: 1928.2-1945.8) events per 100,000 person-years (one measurement) to 1615.4 (95% CI: 1605.8-1625.0), 1484.6 (95% CI: 1473.7-1495.6), and 1204.9 (95% CI: 1200.1-1209.6) for those with two, three, and four or more measurements, respectively. Compared to individuals with one LDL-C measurement, the adjusted HRs for MACE were 0.703 (95% CI: 0.698-0.709), for two measurements, 0.570 (95% CI: 0.565-0.575) for three, and 0.312 (95% CI: 0.310-0.314) for four or more. The Kaplan-Meier curve demonstrated improved event-free survival with increased LDL-C monitoring (log-rank p<0.0001). More frequent LDL-C monitoring was associated with a lower risk of MACE. These findings highlight the potential benefits of regular LDL-C monitoring as a potentially impactful strategy for CVD prevention and long-term risk management.
Is the obesity paradox present in left ventricular assist device recipients? A BMI-based analysis
While body mass index (BMI) is a known determinant of cardiovascular outcomes, its impact on patients undergoing left ventricular assist device (LVAD) implantation remains unclear. This study aimed to evaluate the association between BMI and in-hospital outcomes in LVAD recipients. We conducted a retrospective, cross-sectional analysis using the National Inpatient Sample (2016-2020), identifying adult hospitalizations for LVAD implantation. Patients were categorized into six BMI groups. Outcomes assessed included in-hospital mortality, acute stroke, pump thrombosis, LVAD infection, length of stay (LOS), and hospital costs. Multivariable logistic regression adjusted for demographic, clinical, and hospital-level confounders, to estimate adjusted odds ratios (ORs) and beta (β) coefficients. Among 25,250 weighted admissions, 29.3% were females, with a median age of 63 years (IQR: 52-71). Class III obesity (BMI ≥40 kg/m2) accounted for the largest proportion (32.1%). The highest mortality rate was observed in the underweight group (6.7%), and class III obesity (5.8%) groups, while the lowest rate was noted in the class II obesity group (2.5%). Overall, a reverse J-shaped relationship between BMI and in-hospital mortality was observed. Compared to normal BMI, Class I (OR: 2.46; p=0.038), Class II (OR: 3.73; p=0.017), and Class III obesity (OR: 6.80; p<0.001) were significantly associated with increased odds of in-hospital mortality. Class III obesity was also associated with significantly prolonged LOS (β: 7.07 days; p=0.002) and higher hospital costs (β: $208,791.5; p=0.001). Overweight patients (BMI 25-29.9 kg/m2) had significantly lower odds of acute stroke (OR: 0.40; p=0.030), while no BMI group showed a significant association with pump thrombosis and LVAD infection. Higher BMI, particularly Class III obesity, is independently associated with increased mortality, length of stay, and hospital costs in LVAD recipients. These findings challenge the obesity paradox and underscore the need for refined risk stratification in this population.
Iron supplementation in heart failure and iron deficiency: does it help?
Iron deficiency (ID) is present in 30-80% of patients with heart failure (HF) and is associated with poor prognosis. Intravenous (IV) iron therapy has been evaluated in several randomized controlled trials and consistently shown to improve functional outcomes. In FAIR-HF, 50% of patients receiving FCM achieved NYHA class improvement to I or II by 24 weeks vs 30% with placebo. CONFIRM-HF showed a significant 33-meter increase in 6-minute walk distance (6MWD) at 24 weeks (p=0.002), alongside improvements in NYHA class. The recent trial FAIR-HF2 demonstrated smaller but significant gains in 6MWD (+10.7 m) and global well-being at 12 months. Cardiovascular outcomes have been more variable. AFFIRM-AHF showed a 26% reduction in total HF hospitalizations (HR 0.74; 95% CI, 0.58-0.94) with IV iron vs placebo. Although the composite of cardiovascular death or first HF hospitalization was narrowly non-significant (HR 0.79; 95% CI, 0.62-1.01), the effect may still be clinically meaningful. IRONMAN, using ferric derisomaltose vs placebo, was neutral for the primary endpoint of HF hospitalization and cardiovascular death (RR 0.82; 95% CI, 0.66-1.02) but showed benefit in a COVID-censored sensitivity analysis (RR 0.76; 95% CI, 0.58-1.00). In HEART-FID, involving over 3,000 patients, no benefit was also seen with IV iron for the composite of death, HF hospitalization, and 6MWD at 99% CI, however was significant at 95% CI. FAIR-HF2 showed a 21% reduction in the primary endpoint (HR 0.79; 95% CI 0.61-1.02) with IV iron, which did not meet statistical significance, but a prespecified 12-month sensitivity analysis demonstrated a 29% reduction in first cardiovascular death or HF hospitalization (0.71 (95% CI, 0.53-0.94) and a 35% reduction in total HF hospitalizations (RR 0.65; 95% CI, 0.47-0.90). The most recent meta-analysis (n>7,000) showed a 28% reduction of composite of cardiovascular death and HF hospitalizations at 1 year (RR 0.72; 95% CI, 0.55-0.89) with IV iron. Benefits were sustained at longer term follow up and were consistent across most subgroups. The totality of evidence supports IV iron in HFrEF with ID to improve symptoms and reduce HF hospitalizations, especially in the first year. Future research should explore optimal long-term dosing, sex-specific responses, and the role of IV iron in HF with preserved ejection fraction.
Demographic and regional trends of heart failure and cachexia-related mortality among older adults in the United States, from 1999 to 2020
Cachexia is a debilitating yet under-recognized condition, particularly among the elderly population. It has been shown that patients with heart failure (HF) often have cachexia, leading to worsening mortality rates. There is limited research on mortality trends and demographic disparities in terms of cachexia. CDC WONDER (Centers for Disease Control and Prevention Wide-Ranging ONline Data for Epidemiologic Research) database was used, where HF and cachexia were listed as either contributory or underlying causes of death in adults >65 years from 1999-2020. Age-adjusted mortality rates (AAMRs) and annual percent changes (APC) were calculated and stratified by year, sex, race/ethnicity, and region. No change in mortality was seen due to HF + cachexia from 2004-2020 (APC -2.1%; 95% CI, -3.2 to 0.6). Almost half of the deaths (47%) occurred within nursing homes. Notably, White adults had a higher mortality than Black/ African American adults (23.8; 95% CI, 23.4 to 24.1 vs 18.4; 95% CI, 17.4 to 19.4). Mortality rates were also higher in rural areas than urban areas (27.9; 95% CI, 27.1 to 28.7 vs 22.1; 95% CI, 21.8 to 22.4). States in the top 90th percentile, including Idaho, Utah, Vermont, South Carolina, Alaska and New Hampshire, had 5-fold higher mortality than states in the lower 10th percentile. No change in mortality was seen due to HF and cachexia-related mortality in the last decade, with substantial racial and regional disparities. Targeted interventions are needed to curb these mortality trends.
Advancements in transcatheter tricuspid valve repair and replacement: a state-of-the-art review with echocardiographic outcomes
Tricuspid regurgitation (TR) affects over 1.6 million individuals in the United States, with a one-year mortality rate of 36.1% and a five-year survival below 30%. Despite its prevalence being comparable to mitral regurgitation and aortic stenosis, TR remains understudied and inadequately managed. The underlying causes of TR vary, with primary TR stemming from structural abnormalities of the tricuspid valve, including damage caused by infectious endocarditis, rheumatic heart disease, congenital anomalies, or trauma, while secondary TR arises from right ventricular pressure and volume overload due to conditions such as heart failure (HF), atrial fibrillation, and pulmonary hypertension (PH). As TR progresses, it leads to higher hospitalization rates and imposes a significant healthcare burden, particularly in patients with advanced HF and PH. Medical therapy provides only symptomatic relief, while surgical intervention, carries high in-hospital mortality and complication risks. Given these challenges, transcatheter tricuspid valve interventions (TTVI) have emerged as promising alternatives, offering both transcatheter tricuspid valve repair (TTVr) and replacement (TTVR) strategies. TTVr devices such as TriClip, PASCAL, and Cardioband enhance leaflet coaptation or reduce annular dilation while preserving the native valve, resulting in lower procedural risks and faster recovery. Meanwhile, TTVR devices such as Evoque, TricValve, and LUX-Valve provide a definitive solution for patients with severe annular dilation, large coaptation gaps, or significant leaflet tethering. The growing population of underserved TR patients and the favourable outcomes of transcatheter therapies have accelerated advancements in device development and expanded treatment options. This review explores the latest advancements in TTVr and TVVR strategies, highlighting their clinical significance and echocardiographic outcomes based on recent data. Graphical Abstract
transcatheter tricuspid valve interventions
Lipoprotein(a): what clinicians need to know
Lipoprotein(a) [Lp(a)] is a plasma particle structurally similar to LDL, distinguished by the presence of apolipoprotein(a), and has evolved from plasminogen. Lp(a) concentration is 90% genetically determined and largely stable throughout life. Black individuals exhibit the highest Lp(a) levels, followed by South Asians, Whites, Hispanics, and East Asians, with a 2- to 4-fold median difference across ancestral groups. Approximately 1.5 billion people worldwide (~20% of the population) have elevated Lp(a) levels (>125 nmol/L or >50 mg/dL). Notably, women experience 17% higher levels than men post-menopause. Mendelian randomization studies have established Lp(a) as a strong cardiovascular disease (CVD) risk factor, implicated in coronary artery disease, peripheral artery disease (PAD), ischemic stroke, heart failure, and aortic stenosis. Risk increases linearly with Lp(a) levels, with concentrations >90 mg/dL (>190 nmol/L) associated with a 1.6-fold higher risk of ischemic stroke, 1.7-fold for heart failure, 2-fold for PAD, and 3-fold for aortic stenosis and myocardial infarction. Lp(a) levels between 130–391 mg/dL (280–849 nmol/L) confer atherosclerotic CVD risk equivalent to familial hypercholesterolemia. Universal screening of once Lp(a) test is now recommended for all adults in guidelines across the US, Europe and Canada. However, Lp(a) testing is severely underutilized with studies showing 0.3% testing frequency amongst 5.5 million US patients. Even in high-risk patients with established ASCVD, only 13.9% are tested for Lp(a). Existing treatment options for elevated Lp(a) include proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and lipoprotein apheresis. Emerging therapies include antisense oligonucleotides such as pelacarsen, small-interfering RNA such as zerlasiran, olpasiran, and lepodisiran, and oral agents such as muvalaplin. These medications have shown a significant reduction in plasma levels up to 80% (pelacarsen), 96.9% (olpasiran), 97% (lepodisiran) and 99% (zerlasiran) in phase 1 and 2 trials, with larger studies ongoing to assess cardiovascular outcomes. With advancing therapies, clinician awareness, early detection, and risk management of Lp(a) are critical to improving outcomes.