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, 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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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.
Copyright (c) 2025 the Author(s) https://creativecommons.org/licenses/by-nc/4.0
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.
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.
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.
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.
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.
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
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.
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
Sex differences in clinical characteristics and outcomes in heart failure with mildly reduced and preserved ejection fraction
Heart failure with mildly reduced and preserved ejection fraction (HFmrEF and HFpEF) 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 64,046 patients with HFmrEF or HFpEF (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 guideline-directed medical therapy (GDMT) use as odds ratios (OR). Cox proportional hazards models were used to assess the risk of cardiovascular mortality and heart failure (HF) hospitalization as hazard ratios (HR), adjusting for demographic and clinical variables. Females (42.5%) were older than males (median age 79 years vs 75 years), had a higher prevalence of hypertension (73.8% vs 70.0%), and were more likely to present with severe symptoms (NYHA class III-IV: 36.8% vs 28.8%). Males had a higher prevalence of ischemic heart disease (52.3% vs 42.9%) and diabetes (27.4% vs 23.8%). Females were significantly less likely to receive SGLT2 inhibitors (OR 1.24, 95% confidence interval [CI] 1.13-1.36), while males were less likely to receive beta-blockers, digoxin, nitrates, and loop diuretics. During a median follow-up of 2.3 years, males had a higher adjusted risk of the composite outcome of cardiovascular mortality or HF hospitalization (HR 1.16, 95% CI 1.13-1.19), as well as higher risks for cardiovascular mortality (HR 1.28, 95% CI 1.23-1.32) and HF hospitalization (HR 1.12, 95% CI 1.08-1.15). Females with HFmrEF and HFpEF in the SwedeHF registry had a distinct clinical profile, were less likely to receive certain GDMTs, yet exhibited a lower risk of cardiovascular mortality compared to males. These findings underscore the importance of targeted strategies to optimize HF care for females.
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.
Bridging the gap: integrating stress echocardiography, iFR, CFR, and FFR in the evaluation of coronary artery disease
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 and 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.
The effect of sauna on cardiac and skeletal muscle function in patients with HFpEF (SAUNA-HFpEF): rationale and design
Patients with heart failure with preserved ejection fraction (HFpEF) often experience dyspnea, fatigue, and exercise intolerance, which are closely linked to skeletal muscle dysfunction and structural abnormalities. The only proven intervention to enhance exercise capacity and quality of life in these patients is regular endurance exercise training. However, its long-term effectiveness is often limited due to poor patient adherence and mobility restrictions caused by sarcopenia, cachexia, or frailty. Therefore, novel therapeutic approaches targeting these unmet needs are urgently required. Sauna-HFpEF is an academic-led, mechanistic, prospective, single-arm, single-center pilot study designed to assess the safety, feasibility, and efficacy of intermittent hyperthermia (sauna therapy) in improving exercise capacity and quality of life in patients with heart failure with preserved ejection fraction (HFpEF), as well as to explore the underlying mechanisms. A total of 18 clinically stable outpatients with HFpEF were enrolled and participated in twice-weekly sauna sessions at 60°C over a 10-week period. Assessments were conducted at baseline and after the intervention, including: echocardiography, cardiopulmonary exercise testing, six-minute walk test, body composition analysis to assess skeletal muscle mass and fat tissue, isokinetic skeletal muscle strength measurement of the quadriceps, daily physical activity monitoring using wearable accelerometers for one week, blood biomarkers, including NT-proBNP, renal function, and inflammatory markers (GDF-15, IL-6), and quality-of-life questionnaires (SF-36, HADS, EQ-5D). Furthermore, to explore the underlying mechanisms of a potential sauna-induced effect, patients underwent two ultrasound-guided punch biopsies of the musculus vastus lateralis in the right quadriceps - one before and one after the intervention. The collected samples were analyzed for structural, metabolic, and mitochondrial changes to gain further insights into the physiological adaptations. Sauna-HFpEF is the first study to investigate the safety and efficacy of sauna therapy using a comprehensive bed-to-benchside approach within the same patient population. This study aimed to address the existing knowledge gap while providing a foundation for the design of a future randomized controlled trial.
heart failure with preserved ejection fraction
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.
Elevated endostatin is associated with hypertension treatment, elevated high sensitivity C-reactive protein, increased waist-hip ratio, and attenuated kidney function, but not with age, in a middle-aged population
Circulating endostatin has been linked to increased mortality, cardiovascular comorbidities, and renal impairment. However, its role as a cardiovascular risk marker in the general population remains largely unexplored. This study investigates the association between plasma endostatin and atherosclerosis, inflammation, and kidney function in a cohort of 5,026 randomly selected middle-aged individuals from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Plasma levels of endostatin, C-reactive protein (CRP), HbA1c, lipids, and creatinine were analyzed, and their associations with atherosclerosis and related markers were assessed. Coronary artery atherosclerosis was evaluated using coronary computed tomography. Blood pressure, body mass index, and waist circumference were measured, and medication use for diabetes, hyperlipidemia, and hypertension was recorded. Smoking habits were also documented. The following main results were significantly associated with endostatin. Severe coronary atherosclerosis was positively associated in men. Being on hypertensive medication or not, as reported by the participants at the interview at study inclusion, was significantly associated with endostatin. Hypertensive medication increased from 12% to 26% from the lowest to the highest quartile of endostatin. Waist circumference was positively associated, where endostatin increases, on average, 0.21±SD for a 1±SD increase of waist circumference. Kidney function, measured as eGFR, was negatively associated, where endostatin decreases, on average, 0.22±SD for a 1±SD increase in eGFR. Elevated endostatin levels were associated with advanced coronary atherosclerosis in men, antihypertensive treatment, systemic inflammation (increased CRP), increased waist circumference, and impaired kidney function (lower eGFR).
Copyright (c) 2025 the Author(s) http://creativecommons.org/licenses/by-nc/4.0
Impella vs intra-aortic balloon pump in patients with acute myocardial infarction complicated with cardiogenic shock: an updated systematic review and meta-analysis
Cardiogenic shock (CS) is a major cause of mortality in patients with acute myocardial infarction (AMI). Mechanical circulatory support devices like Impella and Intra-Aortic Balloon Pump (IABP) manage AMI-CS, but their comparative effectiveness remains unclear. We conducted a meta-analysis following Cochrane and PRISMA guidelines. From the database inception until March 2024, we searched databases including PubMed, Google Scholar, and the Cochrane Library for studies comparing Impella and IABP in AMI-CS patients. Risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes were calculated using a random-effects model. Nine studies involving 18,289 patients were included and the mean age of patients in the Impella group was 64.79 years, and 64.75 years in the IABP group. Short-term mortality showed no significant difference between Impella and IABP (RR: 1.13, 95% CI: 0.84-1.52, p=0.42, I²=76%). Impella was associated with higher risks of hemolysis (RR: 9.46, p=0.009), limb ischemia (RR: 3.65, p=0.003), transfusion (RR: 2.03, p< 0.0001), and acute kidney injury (RR: 1.22, p=0.04). Meta-regression indicated that peripheral arterial disease, prior PCI, and left ventricular ejection fraction were significant covariates for short-term mortality. Our meta-analysis found no significant difference in short-term mortality between Impella and IABP in AMI-CS patients. In contrast, Impella is associated with higher risks of hemolysis, limb ischemia, transfusion needs, and acute kidney injury. Peripheral arterial disease, prior PCI, and lower LVEF were significantly associated with short-term mortality, with PAD and prior PCI increasing risk, while higher LVEF demonstrated a protective effect.
The Global Implementation Guidelines Initiative: how to optimize cardio-renal-metabolic care worldwide
Bridging the gap between study outcomes and real-world results. Algorithm-driven management in a rural cardioMEMS population
Current therapeutic strategies are ineffective at keeping heart failure patients out of hospital. In 2017, all-cause readmission rates were 19.9% at thirty-days and 34.6% at ninety-days. Large scale studies have shown potential advantages with remote pulmonary artery pressure monitoring. We sought to refine the management of our remotely monitored cohort by introducing a hemodynamic treatment algorithm. A population of rural heart failure patients previously implanted and managed with remote pulmonary artery pressure sensors were studied (n=43). Algorithm based hemodynamic management began with prospective outcome monitoring for ninety days during which algorithm use was mandatory. Following the initial observation period, some physicians reverted to prior practice habit which included consideration of standard heart failure metrics into decision making. Following a six-month washout period, retrospective analysis was performed in evaluation of the intervention arm (n=34), patients managed by hemodynamic plus usual heart failure data, and the control group (n=30), those who remained strictly managed by algorithm. Pre-algorithm thirty-day heart failure specific hospitalization (HFH) rate was 60%. Algorithm-driven management decreased HFH rates to 19% at thirty-days and 12% at ninety-days. Incorporating standard heart failure metrics with remotely pulmonary artery (PA) pressure data markedly increased risk of readmission (7% vs 13% at thirty-days and 13% vs 42% at ninety-days). Heart failure patients managed via remote pulmonary artery pressures benefitted from algorithm-driven hemodynamic therapies. Utility and effectiveness of remote PA monitoring is stunted with consideration of traditional heart failure metrics (weights, symptoms, exam findings) in their management. Graphical Abstract
How organ care system saved the day during a donation after circulatory death heart transplant: a case of complicated sternal re-entry
Sternal re-entry during left ventricular assist device (LVAD) explant and heart transplantation risks damaging structures including the driveline, LVAD outflow tract, ascending aorta, or heart. Preoperative imaging is vital for planning re-entry. This report highlights a pitfall with CT imaging and an advantage of the Organ Care System (OCS) in minimising ischemic time during complex re-sternotomy. A 56-year-old male with ischemic cardiomyopathy and a LVAD underwent a donation after circulatory death (DCD) heart transplant. A CT scan immediately post-LVAD implantation suggested low re-entry risk. However, during re-sternotomy, a vascular injury occurred between the outflow graft and ascending aorta, causing catastrophic bleeding. Rapid chest proximation using pre-placed Ethibond sutures controlled bleeding whilst obtaining femoral access for cardiopulmonary bypass (CPB). Deep hypothermic circulatory arrest was required whilst the OCS optimally perfused the donor heart, extending preservation time (OCS perfusion time of 241 minutes). The transplant was performed, following which CPB was weaned. Postoperatively, the patient required a tracheostomy but recovered well, being discharged by day 40. This case illustrates the need to investigate anatomical changes post-LVAD implantation and implement measures to prevent re-entry injuries. CT imaging immediately post-implantation may not reflect evolving anatomy, hence serial imaging could enhance surgical planning. The OCS was vital in allowing extended preservation time to accommodate for unforeseen complications whilst the Ethibond sutures were essential in aiding control of the bleeding. Research in the LVAD subgroup to evaluate the extent of remodelling hence proximity of structures in relation to the sternum is essential to optimise surgical planning.
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.
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.
Draft Document for Public Consultation: iCARDIO Alliance Global Implementation Guidelines on Heart Failure 2025
Despite the availability of several guidelines, 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 Implementation Guidelines emphasize the incorporation of novel therapies, while integrating past directives with the most up-to-date evidence to enable clinicians to optimize heart failure (HF) 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 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 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 a comprehensive update to HF 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 tailored to the needs of healthcare around the globe.
Copyright (c) 2024 the Author(s) http://creativecommons.org/licenses/by-nc/4.0
Welcome to the June issue of Global Cardiology, a journal devoted to the dissemination of knowledge, impact and research of relevance to cardiovascular physicians and healthcare professionals worldwide. True to this purpose, we are pleased to introduce diverse and stimulating contributions and comments [...].
Elevated left ventricular end diastolic pressure, chronic pulmonary oedema and valve disease
As part of ageing and with increased longevity of older people, there has been a rise of those with increased left ventricular end diastolic pressure (LVEDP) and left ventricular diastolic dysfunction (LVDD). Comorbidities like hypertension, diabetes, chronic kidney disease, coronary artery disease and others appear to be contributing to this. Chronic interstitial pulmonary edema may be a part of the presentation of those with elevated LVEDP/LVDD. Progressive valvular heart disease may also complicate the picture and make clinical decision-making difficult. This case report discusses these issues.
Acute interventional management of spontaneous coronary artery dissection: case series and literature review
Spontaneous coronary artery dissection (SCAD) treatment is currently a matter of debate as scarce data are available for the interventional cardiologists. In the present review, we introduce 4 representative clinical scenarios in which different interventional strategies were carried out. Subsequently, we discuss different tools and useful techniques for the treatment of SCAD, presenting the advantages and drawbacks of the conservative approach versus percutaneous coronary intervention with drug eluting stent or bioresorbable scaffolds implantation, and/or cutting balloon angioplasty.
Background: Myocarditis can be observed in patients with COVID-19. Myocarditis can also be seen in patients vaccinated against SARS-CoV-2 infection, the etiological agent of this disease. Epidemiological, morphological, pathophysiological, clinical aspects, clinical course, and potential therapeutics for patients with COVID-19 myocarditis are not entirely clear. Methods: We perform a search in PubMed linking the terms “COVID-19 and myocarditis”, “SARS-CoV-2 and myocarditis”, and “vaccine and myocarditis and COVID-19”. A hand-search of references from retrieved papers has also been done. We selected papers dealing with the epidemiological, morphological, clinical aspects, and therapeutic regarding COVID-19 myocarditis. Results: Myocarditis can be clinically diagnosed in about 2% of patients with COVID-19 illness, but its prevalence is higher (up to 33%) in autopsied with this disease. At magnetic resonance imaging, myocarditis can be diagnosed in up to 60% patients in the short-term follow up after SARS-CoV-2 infection. A few ultrastructural studies have detected SARS-CoV-2 in endothelial cells, macrophages, neutrophils, fibroblasts, and inside cardiomyocytes. Shortness of breath, fever, cough, and precordial chest pain are the main clinical symptoms; in half patients, ground glass opacities in chest X-ray are also observed, although oxygen saturation may be normal. COVID-19 myocarditis may occur in a patient with no past cardiac history and may alternatively be a late phenomenon in the course of the disease. COVID-19 myocarditis can also affect children and adolescents; acute heart failure is the predominant clinical manifestation, including fulminant myocarditis, in this population. Elevated troponin blood levels are observed in the majority of patients. Abnormal electrocardiogram findings – usually ST-segment changes and inverted T waves – can be detected in at least 25% of cases. Abnormal echocardiography can be found in 3% of cases and left ventricular systolic dysfunction can be found in 67% of such cases. The clinical course of COVID-19 myocarditis is usually benign with most patients recovering from the myocardial insult. Non-steroidal anti-inflammatory drugs are the treatment for noncomplicated cases; colchicine is added in case of associated pericarditis. Corticosteroids have largely been used. Mechanical support is lifesaving in cases of cardiogenic shock. Post-vaccination myocarditis is very rare, and less frequently found than COVID-19 myocarditis. Conclusions: Although relative rare, myocarditis may be a serious complication of COVID-19 illness.
Anomalous origin of right coronary artery from the pulmonary artery: an incidental finding on cardiac computed tomography in a patient presenting with dyspnea
Anomalous right coronary artery originating from the pulmonary artery (ARCAPA) is rare with an incidence of 0.002%. It usually presents in adulthood with symptoms of angina and is often associated with other congenital anomalies. We report a case of ARCAPA, that was diagnosed on investigation of dyspnea on exertion.
anomalous right coronary artery originating from the pulmonary artery