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.
PAGEPress Scientific Publications, Pavia, Italy
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.
Copyright (c) 2026 the Author(s) https://creativecommons.org/licenses/by-nc/4.0
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)
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.
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.
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.
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.
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.
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.
Optimized heart failure therapy in patients with very advanced cancer in palliative care: dosing strategies from the EMPATICC trial
Cardiac wasting occurs in patients with end-stage cancer, leading to the development of heart failure (HF)-like symptoms characterized by dyspnea, reduced physical function, and diminished quality of life. The EMPATICC (EMPower the heArt of patients with TermInal Cancer using Cardiac medicines) is a randomized controlled trial designed to evaluate the impact of optimized HF therapy in patients with very advanced cancer in palliative care. Given the susceptibility to adverse drug events in this vulnerable population, the trial employed a protocol-driven approach for the initiation and titration of each medication. EMPATICC is a multi-center, randomized, double-blind, controlled, proof-of-concept trial that enrolled 93 patients with stage IV solid tumors (per Union for International Cancer Control [UICC]), under palliative care, with clinical features indicating cardiovascular risk and functional limitation. Participants were randomized 1:1 to receive optimized HF therapy, including sacubitril/valsartan, empagliflozin, ivabradine, and ferric carboxymaltose (FCM), or 1-4 placebo therapies on top of usual care. All trial medications (or placebo) that were available in tablet form were provided in pre-packed containers to support blinding. Blue placebo tablets were used for empagliflozin, white tablets for sacubitril/valsartan, and pink tablets for irbesartan. Blinded staff members did not have access to individual tablet packaging or knowledge of color allocations. Additionally, the meaning of the color-coded tablets was not disclosed to the blind staff members throughout the trial. Dosing protocols were guided by predefined criteria, including blood pressure, renal function, heart rate, hemoglobin, and body weight, and they were implemented by unblinded staff. Algorithms accounted for prior RAAS inhibitor exposure when initiating sacubitril/valsartan; ensured hemodynamic stability and sinus rhythm for ivabradine; assessed renal reserve when starting empagliflozin to support safe and effective titration; and accounted for body weight and hemoglobin levels when initiating FCM. To ensure consistent implementation across five centers in Germany, visual flowcharts were designed. The EMPATICC trial provides a practical, protocol-driven approach for delivering HF therapy in the palliative oncology setting. Dosing algorithms outlined in this study could serve as a model for structured cardiovascular care in patients with advanced cancer.
Self-administered intranasal etripamil: a breakthrough in PSVT first-line treatment
Dear Editor, PSVT, AVRT, and AVNRT are types of arrhythmia resulting from disruptions in the heart's electrical activity, originating from the sinoatrial node and propagating via the atria to the AV node, causing sudden symptoms like palpitations and dyspnea...
Large language models to write scientific manuscripts: to be considered but not trusted
Large language models (LLMs) are rapidly permeating scientific writing. Using ChatGPT 4o and real-world data from the Swedish Heart Failure Registry, we explored both the promise and the pitfalls of LLM-assisted manuscript drafting. We demonstrate that, with strict human oversight, LLMs may accelerate text generation but still hallucinate, frequently misinterpret effect directions, and are often unable to access other manuscripts for direct references. Until these limitations are addressed, LLMs should complement, rather than replace, domain experts in scientific publishing.
Sex-based differences in characteristics, management, and outcomes in heart failure with reduced ejection fraction
Heart failure with reduced ejection fraction (HFrEF) exhibits significant sex-based differences in clinical presentation, management, and outcomes. This study aimed to evaluate these differences using data from the Swedish Heart Failure Registry (SwedeHF). We analyzed 65,605 patients with HFrEF (EF <40%) from the SwedeHF registry. Baseline characteristics, treatment patterns, and outcomes were compared between females and males. Multivariable logistic regression was used to evaluate predictors of treatment use. Cox proportional hazards models were used to assess the risk of cardiovascular mortality and heart failure (HF) hospitalization, adjusting for demographic and clinical variables. Odds ratios (OR) were reported for treatment use, and hazard ratios (HR) were used for outcome analyses. Females (29.0%) were older than males and had a higher prevalence of hypertension (61.3% vs 49.8%) and valvular disease (17.2% vs 11.1%), while males had a higher prevalence of ischemic heart disease (70.5% vs 40.1%) and diabetes (31.6% vs 28.4%). Males were less likely to receive beta-blockers (OR: 0.76, 95% CI 0.71-0.81), and more likely to receive sodium-glucose co-transporter-2 inhibitors (OR: 1.27, 95% CI 1.17-1.38) and implantable cardioverter-defibrillators/cardiac resynchronization therapy (OR: 1.41, 95% CI 1.30-1.52). During a median follow-up of 2.1 years, males had a higher risk of the composite outcome of cardiovascular death or HF hospitalization (HR: 1.19, 95% CI 1.16-1.22), cardiovascular death (HR: 1.33, 95% CI 1.28-1.37), and HF hospitalization (HR: 1.16, 95% CI 1.12-1.19). In this large cohort of patients with HFrEF, males had worse outcomes across all major cardiovascular endpoints. These findings highlight the need for tailored strategies to address sex-based disparities in HF management and improve outcomes for both sexes.
Applicability of obesity clinical practice guidelines in low- and middle-income countries
Obesity is a chronic disease and its impact on individuals and society is a major global health problem, with a high prevalence across all socio-economic strata. Some specialty societies include obesity management related recommendations in clinical practice guidelines, but relatively few guidelines are specifically designed to fully address its diagnosis and management. We sought to understand clinicians' use of obesity clinical practice guidelines in their practice, the perceived deficiencies and implementation barriers, and differences between those practicing in high-income countries (HIC) and those in low-/middle-income countries (LMIC). An email survey of physicians in the Translational Medicine Academy database was offered from August 26 to December 26, 2024 to inquire about participants' demographic information, experience, and views of obesity guidelines as related to their practice. Of 1,412 participating clinicians from 129 countries, 741 partially completed, and an additional 671 fully completed the survey: 281 practiced in HIC; 1,130 in LMIC. Obesity was recognized as a disease (93.5% of respondents) as was its impact on other disorders: cardiovascular disease ranked as the most important, and hepatic disorders the least, with no differences between HIC and LMIC. Only 13.1% regarded the guidelines as equally applicable across different economic strata and geography, and just 29% thought the guidelines to be applicable in their country, with no difference between HIC and LMIC. The most frequently indicated reason given for hindering implementation of obesity guidelines was that they were primarily relevant for HIC; the most common local factor hindering implementation was cost, with no difference in views between HIC and LMIC. There was broad agreement (83.4%) for the importance/need for specific recommendations for patients of differing socio-economic status, with no difference between HIC (79.4%) and LMIC (84.3%; p=0.191), and for guideline authors to include those from LMIC (68.7%), with those from LMIC agreeing more strongly (73.1%) than did those from HIC (50.4%; p<0.00001). Most clinicians from both HIC and LMIC do not consider obesity guidelines to be applicable in their country, and appear to have minimal recognition of obesity’s impact on hepatic disorders, suggesting a need for improved clinician education and awareness. It was widely recognized that guidelines should have specific recommendations directed at differing socio-economic environments, and writing committees including authors from those settings.
low-, middle-, and high-income countries
iCARDIO Alliance Global Implementation Guidelines on Heart Failure 2025
Inconsistencies in healthcare access, varying infrastructure, resource constraints and diverse local practices as well as practical and political issues restrict the global applicability of currently available guidelines. There is a need for universal recommendations that address the unique challenges faced by patients and healthcare providers worldwide. Our iCARDIO Alliance Global Implementation Guidelines emphasize the incorporation of novel therapies, while integrating standard of care with the most uptodate evidence to enable clinicians to optimize patient care. This document is about heart failure (HF), including acute and chronic heart failure, heart failure with reduced ejection fraction and heart failure with preserved ejection fraction as well as cardiomyopathies. 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 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. Most importantly these guidelines also provide recommendations on a number of issues where resource limitations may put constraints on the care provided to HF patients. Such “economic adjustment” recommendations aim to provide guidance for situations when “Resources are somewhat limited” or when “Resources are severely limited”. Hence, this document presents not only a comprehensive but also concise update to HF management guidelines thereby aiming to provide a unified strategy for the pharmacological, nonpharmacological, invasive and interventional management of this significant global health challenge that is applicable to the needs of healthcare around the globe.
Importance of patient-reported outcomes in cardiovascular illnesses
Patient-reported outcomes (PROs) are increasingly recognized as pivotal tools in understanding health status, treatment impact, and quality of life (QoL) in patients, particularly those with chronic cardiovascular diseases. These standardized and validated tools capture the patient’s perspective on physical, emotional, and social health dimensions, bridging gaps often missed by clinical evaluations. Despite their growing adoption in research, the use of PROs in new drug approvals has declined, from 30% between 1997–2002 to 16.5% between 2011–2015, raising concerns about their underutilization in real-world settings. However, their role in clinical care and research continues to expand, with the proportion of clinical trials incorporating PROs increasing from 14% between 2004–2007 to 27% between 2007–2013. PRO measures (PROMs) span multiple domains, including overall health, such as EQ-5D, SF-36, and PROMIS Profile-29 to evaluate health-related quality of life (HRQoL), psychological health, evaluated by instruments like the Patient Health Questionnaire-9 (PHQ-9), specific symptoms, such as pain and fatigue, functional status, and disease-specific outcomes such as the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The clinical impact of PROs is evident in their association with prognostic outcomes. Each 5-point decrease in the KCCQ score correlates with a 6–9% higher risk of cardiovascular death or heart failure hospitalization. Meta-analyses reveal that higher HRQoL reduces mortality risk by 37% (HR 0.633, 95% CI: 0.514–0.780). Additionally, in pre-terminal cancer patients, self-reported abilities to walk 4 meters and wash oneself independently predicted survival, hazard ratios of 0.63 (p=0.015) and 0.67 (p=0.024), respectively. Moreover, in chronic obstructive pulmonary disease, pain and discomfort predicted re-hospitalization and HRQoL predicted 180-day survival. These findings underscore the critical role of PROs in enhancing patient care, guiding therapeutic decisions, and shaping healthcare policies.
Safety and efficacy of left atrial appendage closure in cancer versus non-cancer patients: a systematic review and meta-analysis
There is an ongoing debate regarding the safety and efficacy of left atrial appendage occlusion (LAAO) for atrial fibrillation in patients with cancer. We searched PubMed and Scopus from the database's inception until November 2024 and included studies comparing cancer patients with non-cancer patients undergoing left atrial appendage closure for atrial fibrillation. Our primary outcome was short-term mortality. Secondary outcomes were ischemic stroke, major bleeding, device complications, and pericardial complications. For the dichotomous outcomes, risk ratios (RR) were used, whereas generic inverse variance (GIV) was used to pool the RRs and corresponding 95% confidence interval (95% CI). A random effects model was used to evaluate all the outcomes. Our analysis showed a significantly higher rate of short-term mortality in patients with cancer as compared to non-cancer patients (RR=2.07; 95% CI [1.12 to 3.84]; p=0.02). From secondary outcomes, pericardial complications showed a significantly higher risk in cancer patients (RR: 2.17, 95% CI [1.51, 3.12]; p<0.0001). Meanwhile, other secondary outcomes were found to be insignificant. LAAO in cancer patients was significantly associated with higher short-term mortality and pericardial complications.
Cardiac wasting in patients with advanced cancer: state of the art review
Cardiac wasting, a complex and understudied phenomenon, is observed in up to 40% of patients with advanced cancer, contributing to 20-30% of mortality within this cohort. This condition represents a significant determinant of impaired quality of life and increased mortality, highlighting its clinical importance. Numerous pathophysiological mechanisms have been identified in clinical and pre-clinical research as key drivers in the development and progression of cardiac wasting, including elevated circulating inflammatory cytokines, enhanced catabolic processes, hormonal dysregulation, dysfunction of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis, oxidative stress, psychosocial factors, myosin heavy chain isoform switching, and, critically, cardiotoxic effects of anticancer therapies. Clinically, cardiac wasting manifests through a spectrum of symptoms and consequences, including muscle wasting, heart failure-like symptoms, impaired global longitudinal strain (GLS), and structural and functional alterations in the heart, particularly within the left ventricle. These cardiac alterations contribute to progressive cardiovascular decline. Preclinical and clinical studies have confirmed these observations across various models and patient cohorts, demonstrating significant cardiac changes, such as a 33% reduction in cardiomyocyte cross-sectional area, up to 21% decrease in left ventricular mass & 11% reduction in heart weight, and a 50% reduction in left ventricular axon length. Additionally, fibrosis in pre-clinical studies, preservation of left ventricular ejection fraction in some studies, and mild decreases in others, along with an 8.1% reduction in GLS and a 12.1% loss in left ventricular wall thickness, are observed, in conjunction with elevated circulating levels of interleukin-6 (IL-6). Given the substantial morbidity and mortality associated with cardiac wasting in advanced cancer, it is imperative to incorporate comprehensive cardiac assessment into routine follow-up care, refine patient stratification strategies, employ advanced diagnostic technologies in clinical trials, and prioritize research into the cardiovascular impacts of cancer treatments. A concerted focus on advancing the field of cardio-oncology is essential for mitigating the adverse outcomes of cardiac wasting in this vulnerable patient population.