Journal Of Clinical & Experimental Cardiology[JOURNAL]
Sun
200 papers
Coronary artery calcium on chest CT scans: from incidental finding to mandatory reporting.
Sabouret P, Giamundo DM, Sparafora L … +7 more , Figliozzi S, Mamas MA, Stefanini G, Asher E, Andò G, Blumenthal R, Atar D
Nat Rev Cardiol · 2026 Jun · PMID 42315931 · Publisher ↗
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Genetics and Genomics of Coronary Artery Disease: What We Have Learned.
McPherson R
Can J Cardiol · 2026 May · PMID 42161473 · Publisher ↗
Research over the past 2 decades has provided a broader understanding of the genetic architecture of coronary artery disease (CAD) and shows that it derives in large part from the cumulative effect of multiple common ris...
Research over the past 2 decades has provided a broader understanding of the genetic architecture of coronary artery disease (CAD) and shows that it derives in large part from the cumulative effect of multiple common risk alleles that are individually of small effect size but cumulatively have large effects on CAD risk. The tools applied include genome-wide association study (GWAS), which encompasses thousands of individuals, complemented by deep sequencing and extensive omic data sets. More than 300 genome-wide significant loci associated with CAD risk have been identified using the GWAS approach; 90% of these are situated in intergenic regions. Our research at the University of Ottawa Heart Institute has been carried out in collaboration with an extensive number of groups and individuals around the world. These studies include computational approaches to better understand missing heritability and identify causal pathways, experimental approaches to reveal, at the molecular level, the function of the multiple risk loci. In addition to providing new insight into the biology of atherosclerosis and its clinical sequelae, GWAS findings have important applications in clinical cardiovascular medicine. These include Mendelian randomization analyses to identify causal biomarkers and generation of polygenic risk scores to improve CAD risk prediction and guide decision-making regarding preventive therapies.
Functional consequences of diminished myocardial oxygen delivery per beat in experimental heart failure.
Essajee SI, Eden MJ, Sturgess VE … +6 more , Dick GM, Tucker SM, Warne CM, Figueroa CA, Beard DA, Tune JD
Basic Res Cardiol · 2026 May · PMID 42154029 · Publisher ↗
This investigation was designed to test the hypothesis that heart failure (HF) attenuates coronary vasodilation and autoregulation and that deficits in contractile function are proportionally related to reductions in the...
This investigation was designed to test the hypothesis that heart failure (HF) attenuates coronary vasodilation and autoregulation and that deficits in contractile function are proportionally related to reductions in the volume of myocardial perfusion and oxygen delivered per beat. Utilizing a pacing-induced model of HF in Ossabaw swine, we determined that chronic pacing at 180 beats/min for ~ 4 weeks significantly reduced baseline coronary flow by ~ 45% (P = 0.01), lowered myocardial oxygen consumption (MVO₂) (P = 0.07) and systolic wall thickening by ~ 30% (P < 0.01), and increased left ventricular end-diastolic pressure ~ 160% (P < 0.05). Coronary flow responses to Regadenoson (0.4 mg) and cardiac pacing (180 beats/min) were significantly attenuated in swine with pacing HF (P ≤ 0.01). Control swine displayed relatively strong autoregulatory capability with coronary flow decreasing ~ 10% (P = 0.26) as blood pressure was pharmacologically reduced from 120 to 60 mmHg. Alternatively, coronary flow decreased ~ 40% (P = 0.01) over the same pressure range in pacing HF swine. Regional wall thickening and stroke volume declined once myocardial oxygen delivery fell below ~ 1.0 µL O₂/g/beat. These findings indicate that adaptations in the coronary microcirculation in pacing HF attenuate coronary metabolic and autoregulatory capacity and that subsequent functional deficits are related to reductions in the volume of myocardial perfusion and oxygen delivered per beat.
Dose-dependent effects and mechanisms of exercise-like stimulation on cardiac injury and contractile function: outcomes of the MICRO-ATHLETE study.
Luiken TTJ, Cofiño-Fabres C, Rivera-Arbeláez JM … +9 more , Snippert D, Denessen EJS, Lamers SK, Cius N, van den Dries K, Mingels AMA, Thijssen DHJ, Passier RCJJ, Eijsvogels TMH
Basic Res Cardiol · 2026 Apr · PMID 42062537 · Publisher ↗
Observational studies revealed that exercise produces cardiac troponin release and cardiac fatigue in athletes. However, human in vivo studies offer limited insights into the underlying mechanisms of these potential dele...
Observational studies revealed that exercise produces cardiac troponin release and cardiac fatigue in athletes. However, human in vivo studies offer limited insights into the underlying mechanisms of these potential deleterious effects. This study investigated exercise-induced cardiac troponin release, cardiac fatigue, and its potential mechanisms in a versatile in vitro Engineered Heart Tissue (EHT) model. EHTs were subjected to exercise-like electrical pulse stimulation (EL-EPS) at 2.5 Hz (150 bpm) for 2 or 4 h and compared to non-stimulated controls and doxorubicin (DOX)-exposed tissues. High-sensitive cardiac troponin T (hs-cTnT), lactate dehydrogenase (LDH), and cardiomyocyte contractile function were measured at baseline, immediately after EL-EPS, and after 20 h of recovery. Cell death was quantified by nuclear and mitochondrial DNA concentrations and tissue integrity was assessed using microscopy following exposure. Following 2 and 4 h of EL-EPS, and after DOX exposure, we found increased hs-cTnT and LDH levels and reduced contractile function compared to control. After recovery, contractile function remained impaired after 4 h EL-EPS and DOX exposure, whereas the effects were abolished after recovery for the 2 h EL-EPS group. Elevated nuclear and mitochondrial DNA release was found following DOX, but not after 2 and 4 h EL-EPS. Finally, EL-EPS was associated with the formation of actin aggregates. EL-EPS induced dose-dependent increases in hs-cTnT and LDH concentrations in conjugation with signs of cardiac fatigue, but without elevated markers of permanent cell death (i.e., mitochondrial/nuclear DNA). These findings suggest that exercise-induced elevations of cardiac biomarker concentrations are indicative of reversible cardiac injury.
Analyzing the role of ATP-dependent potassium channels in the regulation of coronary metabolic vasodilation during exercise.
Essajee SI, Warne CM, Tune JD … +1 more , Dick GM
Basic Res Cardiol · 2026 Apr · PMID 42002591 · Publisher ↗
The purpose of this meta-analysis is to compile, integrate, and assess studies that have investigated the role of ATP-dependent potassium channels (K channels) in coronary metabolic vasodilation in vivo. K channels are i...
The purpose of this meta-analysis is to compile, integrate, and assess studies that have investigated the role of ATP-dependent potassium channels (K channels) in coronary metabolic vasodilation in vivo. K channels are important modulators of membrane potential and vascular reactivity and are commonly proposed as regulating coronary blood flow in response to myocardial metabolism. For example, the electro-metabolic hypothesis of Lederer and colleagues (Zhao et al., Proc Natl Acad Sci 117:7461-70, 2020) suggests a pathway where myocardial metabolic activity reduces intracellular ATP, thus activating myocardial K channels to elicit vasodilation. The data collected here suggest that K channels are involved in determining resting vascular tone, but that their contribution does not increase with metabolism (a tonic 15% decrease in flow by glibenclamide). Furthermore, inhibiting K channels with glibenclamide impairs cardiac function by reducing coronary flow at rest, a clear indicator of ischemia, but this effect is overcome by endogenous mediators of vasodilation during increases in metabolism. These findings are inconsistent with the negative feedback/K channel version electro-metabolic hypothesis. Other cardiac K channels remain viable as candidates to mediate the vasodilatory mechanisms in this electro-metabolic paradigm. An amendment to the electro-metabolic hypothesis is proposed whereby the scheme is altered to feedforward. Specifically, we suggest considering the opening of other types of K channels in direct proportion to heart rate, ones whose activity can be linked directly to the increased frequency of cardiac action potentials or those that respond to mitochondrial factors or increased intracellular Na. Whether the feedforward mechanism we propose can be supported experimentally remains to be determined.
Empagliflozin improves metabolism and prevents myocardial and coronary dysfunction in streptozotocin-diabetic and non-diabetic rats subjected to ischemia/reperfusion.
Rocca C, De Bartolo A, Granieri MC … +10 more , Rago V, Conforti F, Urlandini L, Romeo N, Mattii L, De Caterina R, Pagliaro P, Angelone T, Penna C, Madonna R
Basic Res Cardiol · 2026 Jun · PMID 41995817 · Publisher ↗
Diabetes heightens cardiovascular risk. The selective sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) shows cardiovascular benefits in heart failure, type 2 diabetes and chronic kidney disease. While EMPA p...
Diabetes heightens cardiovascular risk. The selective sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) shows cardiovascular benefits in heart failure, type 2 diabetes and chronic kidney disease. While EMPA protects against myocardial ischemia/reperfusion injury (MIRI) in diabetic and non-diabetic hearts, its mechanisms and impact on specific endpoints, including autophagy, angiocrine signaling, and metabolic flexibility, remain incompletely defined. We explored the systemic and myocardial effects of chronic EMPA pretreatment on these endpoints in diabetic and non-diabetic animals subjected to MIRI. In streptozotocin (STZ, 65 mg/kg) diabetic rats, EMPA (15 mg/kg/d, 4 weeks) reduced water intake without affecting hyperphagia or weight loss. EMPA ameliorated glucose and lipid profiles, tended to restore myocardial GLUT4 and counteract alterations in myocardial hydroxymethylglutaryl-CoA synthase (HMGCS2) and 3-oxoacid CoA-transferase 1 (OXCT1) levels. EMPA improved biomarkers of myocardial damage (BNP, NT-proBNP, CK-MB, galectin 3), inflammation (cardiac NLRP3, plasma IL-1β), oxidative stress (plasma SOD and malondialdehyde), angiocrine imbalance (VEGF and apelin), fibrosis, and collagen deposition, while showing a tendency to improve autophagy and apoptosis signaling. Ex vivo, EMPA improved baseline contractility and post-ischemic recovery of left ventricular pressure (dLVP from baseline: ~+4% in STZ+EMPA vs. -25% in STZ; ~+3% in EMPA vs. -28% in MIRI), enhanced coronary flow recovery, and reduced cardiac contracture, infarct size, and coronary LDH leakage in both diabetic and non-diabetic hearts. These effects may be associated with post-ischemic histological improvements, reduced vascular congestion, increased eNOS phosphorylation, activation of cardioprotective pathways, and inhibition of mPTP opening. Consistently, EMPA enhances wound healing and preserves eNOS phosphorylation in high-glucose (HG) human cardiac microvascular endothelial cells. In human cardiomyocytes, EMPA reduced hypoxia/reoxygenation (H/R) cell death, preserved nitrate and nitrite levels-effects abolished in the presence of L-NAME-and improved mitochondrial membrane potential in HG and/or H/R conditions. EMPA improved metabolic health and protected myocardial and coronary function likely via a permissive microvascular and myocardial phenotype that limits reperfusion injury, supporting its use against MIRI in normal and diabetic settings.
Environmental Pollutant-Induced Cardiopathogenesis Through Immune Dysfunction: The Emerging Role of Micro- and Nanoplastics.
Marfella R, Fumagalli C, Marfella LV … +7 more , Furbatto F, Fenti A, Paolisso P, Sardu C, Prattichizzo F, Iovino P, Mauro C
Can J Cardiol · 2026 Apr · PMID 41962839 · Publisher ↗
Exposure to environmental pollutants and toxicants is increasingly recognized as a major determinant of cardiovascular disease. Beyond direct toxic effects, these agents profoundly alter immune homeostasis, and thereby c...
Exposure to environmental pollutants and toxicants is increasingly recognized as a major determinant of cardiovascular disease. Beyond direct toxic effects, these agents profoundly alter immune homeostasis, and thereby contribute to endothelial dysfunction, atherogenesis, arrhythmogenesis, and impaired myocardial repair. Among emerging pollutants, micro- and nanoplastics (MNPs) have recently gained attention because of their ubiquity and potential cardiovascular effects. In this narrative review we synthesize mechanistic, translational, and clinical evidence on pollutant-induced cardiovascular injury mediated by immune dysfunction. We integrate data from experimental models, human tissue studies, and clinical observations to delineate shared and pollutant-specific immunoinflammatory pathways, with a particular focus on MNPs. Environmental toxicants, including particulate matter, heavy metals, endocrine disruptors, and MNPs promote chronic innate immune activation, mitochondrial stress responses, NOD-like receptor family pyrin domain containing 3 inflammasome signalling, and maladaptive epigenetic reprogramming of myeloid cells. MNPs have been detected in human cardiovascular tissues and are associated with adverse cardiovascular events. Experimental evidence indicates that MNPs accumulate within vascular and cardiac compartments, disrupt endothelial barrier integrity, enhance macrophage proinflammatory polarization, and amplify oxidative and nitrosative stress. These converging mechanisms foster plaque vulnerability, microvascular instability, and increased susceptibility to ischemic and arrhythmic complications. Environmental cardiopathogenesis represents a rapidly expanding frontier in cardioimmunology. Elucidating the immune-mediated mechanisms that link pollutant exposure-particularly MNPs-to cardiovascular injury might improve risk stratification and inform targeted preventive and therapeutic strategies in increasingly polluted environments.
Genetic background is associated with distinct patterns of proarrhythmogenic remodeling leading to atrial fibrillation in pigs with ischemic heart failure.
Zhang Z, Vlcek J, Heger C … +9 more , Pauly V, Hesse N, Schüttler D, Merkus D, Wolf E, Medugorac I, Kääb S, Tomsits P, Clauss S
Basic Res Cardiol · 2026 Jun · PMID 41951797 · Full text
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, driven by electrical and structural remodeling that promotes proarrhythmic substrates. Interindividual variability in susceptibility to remodeling...
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, driven by electrical and structural remodeling that promotes proarrhythmic substrates. Interindividual variability in susceptibility to remodeling triggers, such as myocardial ischemia, suggests the involvement of genetic determinants. Ischemic heart failure (IHF) was induced by a 90-min occlusion of the left anterior descending artery in pigs. After 30 days, animals underwent in vivo assessments, including right and left heart catheterization, electrocardiography, and electrophysiological studies, with AF inducibility tested by burst pacing. Atrial fibrosis was quantified using Masson's trichrome staining, and remodeling-associated gene expression was analyzed by quantitative PCR. Genetic background was assessed through single-nucleotide polymorphism (SNP) genotyping using the Porcine SNP60 BeadChip, with data analyzed against reference SNP datasets. Following myocardial infarction, all animals developed IHF with reduced ejection fraction and increased AF susceptibility. Overall, IHF was associated with enhanced atrial fibrosis, but a subset of animals displayed no fibrotic remodeling. Genetic analysis identified two groups of pigs with different genetic backgrounds within the cohort: a Pietrain-dominant and a Landrace-dominant background. Pietrain-dominant pigs developed significantly more atrial fibrosis, whereas Landrace-dominant pigs exhibited a pronounced shortening of the atrial effective refractory period. Differential regulation of fibrosis-associated genes, including FN, MMP2, TGFB, and JNK1, was observed between genetic backgrounds. These findings indicate that genetic background is associated with distinct patterns of atrial remodeling in response to IHF, influencing key determinants of AF susceptibility.
Comparing anti-platelet and anti-thrombin therapies in the ischaemia-reperfusion injured coronary microcirculation of healthy and diabetic mice.
Mitchell JL, El-Awaisi J, Kavanagh D … +3 more , Nieswandt B, Storey RF, Kalia N
Basic Res Cardiol · 2026 Jun · PMID 41925864 · Full text
Patients with type 2 diabetes mellitus (T2DM) face increased risk of heart failure after myocardial infarction (MI), despite successful PCI and dual anti-platelet therapy (DAPT), due to coronary microvascular obstruction...
Patients with type 2 diabetes mellitus (T2DM) face increased risk of heart failure after myocardial infarction (MI), despite successful PCI and dual anti-platelet therapy (DAPT), due to coronary microvascular obstruction. This study examined whether DAPTs provide vasculoprotective benefits in injured coronary microvessels, including in the setting of chronic hyperglycaemia. Mice were fed a normal (ND) or high-fat diet (HFD) for 16 weeks and treated with vehicle, aspirin plus ticagrelor, clopidogrel, prasugrel or cangrelor, anti-GPIbα antibody, or dabigatran. Intravital imaging assessed platelet, neutrophil, and fibrin presence in the beating heart subjected to ischaemia-reperfusion injury (IRI). Laser speckle contrast imaging evaluated overall ventricular perfusion, and infarct size was determined histologically. IRI increased platelet and neutrophil accumulation in coronary capillaries and reduced perfusion. DAPTs, particularly using prasugrel, and anti-GPIbα reduced platelet numbers but increased neutrophil infiltration. Despite limited perfusion improvement, infarct size decreased. Fibrin deposition was also extensive and contributed to platelet recruitment, as shown using dabigatran. HFD-fed mice demonstrated markedly elevated thromboinflammatory cell accumulation. DAPT with prasugrel reduced platelet and neutrophil presence, but left a significant residual presence of both. Despite perfusion improvements, infarcts remained larger. Our data do not support a simple linear relationship between reduced platelet microthrombi, improved perfusion, and infarct limitation. Whilst early platelet inhibition confers cardioprotection independently of flow recovery in healthy mice, metabolic compromise uncouples microvascular flow from myocardial tissue survival. This may explain the diminished cardioprotective efficacy of DAPTs in patients with T2DM and supports exploring combination vasculoprotective therapies targeting multiple microvascular perturbations.
Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial.
Soman P, Cuddy SAM, Gillmore JD … +22 more , Sarswat N, Judge DP, Cappelli F, Stern LK, Wright R, Akinboboye O, Obici L, Bhatt K, Xiong K, Castaño A, Chen C, Falvey H, Pecoraro ML, Tamby JF, Sinha U, Fox JC, Shah K, Grodin JL, Ambardekar AV, Alexander KM, Khouri MG, Cheng RK
JAMA Cardiol · 2026 May · PMID 41911489 · Full text
IMPORTANCE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disorder caused by destabilization of serum transthyretin (sTTR). Acoramidis, an approved therapy that achieves near-complete (≥90%) sTTR stabil...
IMPORTANCE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disorder caused by destabilization of serum transthyretin (sTTR). Acoramidis, an approved therapy that achieves near-complete (≥90%) sTTR stabilization, demonstrated clinical benefit through month 30 in ATTRibute-CM, which was incremental through month 42 in the open-label extension (OLE); however, the longer-term durability of outcomes has not been reported. OBJECTIVE: To evaluate the long-term efficacy and safety of acoramidis through month 54. DESIGN, SETTING, AND PARTICIPANTS: This OLE of the ATTRibute-CM randomized clinical trial is an international, multicenter, ongoing OLE study. Data accumulated between October 2021 and April 2025 through month 24 of the OLE (month 54) are reported. Participants (aged 18-90 years) who completed ATTRibute-CM and met the OLE eligibility criteria were invited to enroll in the OLE. Data were analyzed from May 2025 through November 2025. INTERVENTIONS: All OLE participants received open-label oral acoramidis, 800 mg, twice daily. Acoramidis recipients from ATTRibute-CM continued therapy (continuous acoramidis) and placebo recipients switched to acoramidis (placebo to acoramidis). MAIN OUTCOMES AND MEASURES: The primary outcome was time to event for all-cause mortality (ACM), cardiovascular-related mortality (CVM), and first cardiovascular hospitalization (CVH), which was assessed for both groups. Biomarkers of disease progression (N-terminal pro-B-type natriuretic peptide [NT-proBNP]), sTTR, functional capacity (6-minute walk distance [6MWD]), and heart failure-related health status (Kansas City Cardiomyopathy Questionnaire-Overall Summary [KCCQ-OS] score) were analyzed. RESULTS: In ATTRibute-CM, 632 participants were randomized to receive acoramidis (n = 421) or placebo (n = 211); mean (SD) age was 77.3 (6.6) years, and 62 participants (9.8%) were female. Overall, 389 participants enrolled in the OLE (263 in the continuous acoramidis group; 126 in the placebo-to-acoramidis group). Continuous acoramidis treatment reduced risks of ACM (hazard ratio [HR], 0.55; 95% CI, 0.42-0.74; P < .001) and CVM (HR, 0.51; 95% CI, 0.36-0.71; P < .001) through month 54, with consistent efficacy across all prespecified subgroups. Continuous acoramidis reduced time to first CVH (HR, 0.53; 95% CI, 0.42-0.69; P < .001) through month 54. Through month 54, continuous acoramidis stabilized increases in NT-proBNP, sustained higher sTTR levels, and stabilized KCCQ-OS score and 6MWD. Switching from placebo to acoramidis at month 30 was associated with stabilization of NT-proBNP and KCCQ-OS score and improvements in sTTR and 6MWD through month 54. No new long-term safety concerns were identified. CONCLUSIONS AND RELEVANCE: In this OLE of the ATTRibute-CM randomized clinical trial, early and continuous acoramidis treatment resulted in sustained incremental reductions in ACM, CVM, and first CVH through month 54. These findings support the importance of early and continuous long-term treatment with acoramidis in ATTR-CM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04988386.
The effects of microplastics and nanoplastics on cardiovascular disease: mechanisms and perspectives.
Aimo A, Panichella G, Tommasi E … +3 more , Revuelta-López E, Berastegui E, Bayes-Genis A
Nat Rev Cardiol · 2026 Mar · PMID 41872306 · Publisher ↗
Microplastics and nanoplastics (MNPs) are pervasive environmental pollutants that result from the degradation of plastic materials and the use of plastic-containing products. Although the accumulation of MNPs in the gast...
Microplastics and nanoplastics (MNPs) are pervasive environmental pollutants that result from the degradation of plastic materials and the use of plastic-containing products. Although the accumulation of MNPs in the gastrointestinal and respiratory systems is well documented, growing evidence suggests that MNPs can translocate into the bloodstream and accumulate in cardiovascular tissue, raising concerns about their potential role in the development of cardiovascular disease. In this Review, we synthesize the current knowledge on MNP exposure routes, tissue distribution and biological effects relevant to cardiovascular health. We examine the latest clinical and experimental studies on the presence of MNPs in the blood, atherosclerotic plaques, thrombi and myocardial tissue, and critically evaluate the mechanistic evidence linking MNPs to endothelial dysfunction, atherosclerosis progression, myocardial injury and arrhythmogenesis. In vitro and in vivo data highlight plausible pathophysiological pathways linking MNPs to cardiovascular disease, including oxidative stress, mitochondrial dysfunction, inflammation and fibrotic remodelling. However, causal associations remain unproven in humans, and major methodological challenges persist, including inconsistent detection methods, limited epidemiological data and inadequate modelling of real-world exposure. We conclude by outlining research priorities and proposing a framework for how to integrate MNPs into environmental cardiology practice. As the global issue of plastic pollution intensifies, elucidating the cardiovascular risks posed by MNPs represents an urgent interdisciplinary challenge with substantial public health implications.
Insights in ischemia/reperfusion injury and cardioprotection: neglected and emerging pathways and therapeutic targets for a personalized therapy.
Pagliaro P, Penna C, Femminò S … +1 more , Welt FGP
Basic Res Cardiol · 2026 Jun · PMID 41826738 · Full text
Despite extensive preclinical research identifying molecular targets and cardioprotective strategies, translation into effective clinical therapies remains challenging. Cardioprotection aims to mitigate ischemia/reperfus...
Despite extensive preclinical research identifying molecular targets and cardioprotective strategies, translation into effective clinical therapies remains challenging. Cardioprotection aims to mitigate ischemia/reperfusion injury (IRI) by modulating molecular pathways, such as the Reperfusion Injury Salvage Kinase (RISK) and Survivor Activating Factor Enhancement (SAFE) pathways, as well as autophagy, inflammation, and regulated cell death, to preserve myocardial function. However, a major limitation lies in the robustness of preclinical evidence. Many experimental studies rely on simplified models that fail to reproduce the complexity of human cardiac pathophysiology, resulting in inconsistent and poorly reproducible cardioprotective effects. It is likely that RISK-SAFE pathways represent an oversimplified framework. Moreover, most experimental approaches are cardiomyocyte-centered, overlooking the critical role of the vessels in IRI. Clinical translation is further compromised by patient-related factors, including comorbidities (e.g., diabetes, hypertension), concomitant medications, and heterogeneity in reperfusion protocols, all of which attenuate cardioprotective efficacy. Additional variables, such as timing of intervention and species differences, further contribute to translational failure. Emerging approaches include pharmacological therapies (e.g., SGLT2 inhibitors, PARP inhibitors, necroptosis and ferroptosis blockers, NLRP3-targeting compounds), cell- and organelle-based strategies (e.g., mitochondrial transplantation, extracellular vesicles, non-coding RNAs), and mechanical/device-based interventions (e.g., left ventricular unloading, ischemic conditioning, controlled reperfusion, selective intracoronary hypothermia). Future research should emphasize multi-target interventions, optimized timing and delivery, and advanced tools, such as nanocarriers, gene therapy, computational modeling, and adaptive clinical trials. Strengthening the robustness of preclinical models, including human ex vivo cardiac systems, remains essential to bridge the translational gap and improve the clinical success of cardioprotective therapies.
Cardiac lymphatic dysfunction and repair in cardiovascular disease.
Brakenhielm E
Nat Rev Cardiol · 2026 Mar · PMID 41820525 · Publisher ↗
The field of cardiac lymphatic research has expanded considerably over the past decade. Clinical studies have uncovered lymphatic remodelling in a wide range of cardiovascular diseases, and experimental research has demo...
The field of cardiac lymphatic research has expanded considerably over the past decade. Clinical studies have uncovered lymphatic remodelling in a wide range of cardiovascular diseases, and experimental research has demonstrated that these structural alterations often lead to dysfunction of lymphatic transport. Given the vital physiological role of lymphatics, insufficient lymphatic drainage can affect several aspects of cardiac pathophysiology, including myocardial fluid balance, the immune microenvironment, collagen turnover and lipid handling. In this Review, current knowledge on cardiac lymphatics is summarized, including the structural and molecular specializations underlying their diverse homeostatic functions, and how these features can be altered in cardiovascular diseases. The latest research on the effects of inflammation on lymphatics is presented, together with the mechanisms by which lymphatics modulate immunity. The regulation of cardiac lymphangiogenesis is discussed, including accumulating evidence of immune cell-lymphatic crosstalk in the heart, the role of metabolic and biomechanical stimulation of lymphangiogenesis, and examples of experimental approaches to therapeutic lymphangiogenesis and their current limitations. Finally, areas for future research are highlighted, including the translation of lymphatic imaging and lymphangiogenic therapies to the clinic for patients with cardiovascular disease.
Brain natriuretic peptide protects against acute pulmonary embolism-induced pulmonary vasoconstriction through natriuretic peptide receptor C.
Gao Y, Liu S, Gu Z … +6 more , Wei X, Han X, Wei S, Yang J, Liu Y, Jia D
Basic Res Cardiol · 2026 Jun · PMID 41781760 · Publisher ↗
Acute pulmonary embolism (PE) remains a leading cause of cardiovascular mortality, driven primarily by a sudden increase in pulmonary artery (PA) resistance. Brain Natriuretic Peptide (BNP) may hold promise for reducing...
Acute pulmonary embolism (PE) remains a leading cause of cardiovascular mortality, driven primarily by a sudden increase in pulmonary artery (PA) resistance. Brain Natriuretic Peptide (BNP) may hold promise for reducing PA resistance. However, its role and mechanism in acute PE are not yet fully understood. This study aims to determine whether BNP alleviates PE-induced pulmonary vasoconstriction by targeting Natriuretic Peptide Receptor C (NPRC) and evaluate its therapeutic potential. Here, we established an acute PE rat model using autologous thrombi, and right ventricle (RV) pressure was monitored to approximate PA resistance. A small group of intermediate-high-risk acute PE patients were observed, who received BNP in addition to anticoagulation, and their clinical outcomes were compared to matched patients receiving anticoagulation alone. BNP at varying doses was administered to optimize therapeutic efficacy in the acute PE rat model. Mechanistic studies assessed BNP's impact on oxidative stress in PA endothelium. In the rats, BNP infusion significantly reduced RV pressure overload and improved survival. Clinically, patients receiving adjunctive BNP experienced more rapid improvement in heart rate, oxygen saturation, and blood pressure stability than anticoagulation alone. BNP decreased NADPH oxidase 2-dependent ROS levels in rats' PA endothelium, thereby reducing myosin light chain phosphorylation in smooth muscle. NPRC, as the central receptor, antagonizes the protective effect of BNP. Collectively, BNP offers a novel choice to mitigate PE-induced pulmonary vasoconstriction via NPRC-mediated mechanisms, which support BNP's therapeutic potential for intermediate-high-risk PE.
Location of LMNA Variants and Clinical Outcomes in Cardiomyopathy.
Castrichini M, Ackerman MJ, Giudicessi JR
JAMA Cardiol · 2026 Apr · PMID 41779407 · Publisher ↗
Abstract loading — click title to view on PubMed.
Artery tertiary lymphoid organs, neuro-immune interaction and their mediators in atherosclerosis.
Ortona S, Ivaldo C, Liberale L … +7 more , Carbone F, Montecucco F, Bastianon M, Mastrogiacomo M, Palombo D, Pratesi G, Barisione C
Basic Res Cardiol · 2026 Apr · PMID 41774125 · Full text
Atherosclerosis is a chronic inflammatory disease characterized by the irreversible remodeling of the arterial wall; severe atherosclerotic lesions may lead to life-threatening consequences such as major ischemic events...
Atherosclerosis is a chronic inflammatory disease characterized by the irreversible remodeling of the arterial wall; severe atherosclerotic lesions may lead to life-threatening consequences such as major ischemic events (i.e., myocardial infarction (MI) and stroke) and abdominal aortic aneurysm (AAA) rupture. The severity of the lesions is determined by multiple risk factors that cause systemic and cellular metabolic changes, oxidative damage, cell senescence, and immune activation involving both leukocytes and vascular cells. In advanced stages, macrophage infiltration, alterations of the load-bearing collagenous matrix, and the presence of microcalcifications are the main drivers of plaque vulnerability. Over the last decade, the presence of artery tertiary lymphoid organs (ATLOs) has been established. These structures form during progressive atherosclerosis in the adventitia of large arteries and represent highly organized niches composed of T and B lymphocytes and innate immune cells. More recently, the presence of nerve fibers and the contribution of both the central (CNS) and peripheral (PeriphNS) nervous systems, through the action of sympathetic, parasympathetic, and somatosensory pathways regulating ATLO composition have been demonstrated. However, their role in atherosclerosis progression remains debated. This review explores the architecture of ATLOs and their neuroimmune interactions with the spleen, as a central neuroimmune organ, in atherosclerosis progression, with a particular focus on carotid stenosis and AAA. Furthermore, it highlights the neuronal mediators that could act as biomarkers of plaque instability and promising pharmacological targets. Finally, while still in the preclinical phase, it explores future prospects for integrating neuroimmune-based therapies into current clinical management of atherosclerosis.
HFpEF and MASLD: converging mechanisms and clinical implications.
Capone F, Häseli SP, Liu L … +13 more , Strocchi S, Langenberg C, Lusis AJ, Pietzner M, Muoio DM, Rider OJ, Raman B, Fudim M, Romeo S, Wang Y, Völkers M, Shah SH, Schiattarella GG
Nat Rev Cardiol · 2026 Feb · PMID 41735546 · Publisher ↗
Heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasingly prevalent, interrelated conditions driven by the global rise in obesity and met...
Heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatotic liver disease (MASLD) are increasingly prevalent, interrelated conditions driven by the global rise in obesity and metabolic syndrome. Once viewed in isolation, HFpEF and MASLD are now recognized as organ-specific manifestations of shared systemic metabolic dysfunction. Evidence from the past decade highlights not only overlapping risk factors but also a dynamic, bidirectional inter-organ crosstalk between the liver and the heart that shapes their natural history. In this Review, we explore the epidemiological and mechanistic basis of the MASLD-HFpEF connection, focusing on shared metabolic drivers such as lipotoxicity, meta-inflammation and oxidative stress. We also discuss emerging liver-derived mediators, including hepatokines, metabolites and extracellular vesicles, that influence cardiac structure and function. Finally, we highlight diagnostic and therapeutic strategies relevant to both conditions and propose a multiorgan framework to improve their clinical recognition and management. Understanding the liver-heart axis is key to rethinking cardiometabolic disease beyond organ silos and towards more integrated, mechanism-based approaches.
Melatonin and mitochondrial protection in cardiac ischemia-reperfusion injury: mechanisms, evidence and translational perspectives.
Pedriali G, Leo S, Tiezzi M … +4 more , Colarusso EN, Morciano G, Tremoli E, Pinton P
Basic Res Cardiol · 2026 Apr · PMID 41733647 · Full text
Cardiac ischemia-reperfusion injury (IRI) leads to significant mitochondrial impairment, which contributes to cell death and hampers myocardial recovery. During IRI, mitochondria are subjected to oxidative stress, calciu...
Cardiac ischemia-reperfusion injury (IRI) leads to significant mitochondrial impairment, which contributes to cell death and hampers myocardial recovery. During IRI, mitochondria are subjected to oxidative stress, calcium overload, and altered dynamics, resulting in the opening of the mitochondrial permeability transition pore (mPTP), release of cytochrome c, and activation of apoptotic pathways. Melatonin, a pleiotropic indoleamine produced by the pineal gland and other tissues, has cardioprotective effects through both direct antioxidant activity and receptor-mediated mechanisms. This review explores melatonin's role in maintaining mitochondrial integrity under IRI conditions. Melatonin counteracts oxidative damage by neutralizing reactive oxygen species, stabilizing mitochondrial membrane potential, and preventing mPTP opening, thereby reducing activation of cell death pathways. It also supports mitochondrial biogenesis and dynamics, contributing to energy balance and reduced oxidative burden. In addition, melatonin regulates mitophagy, ensuring mitochondrial quality control and preventing excessive degradation, which collectively contributes to restoring mitochondrial function and cellular metabolism. In rodent preclinical models, melatonin administration before ischemia, during ischemia, or at reperfusion has consistently reduced infarct size and improved cardiac function. While these preclinical findings are encouraging, studies on rabbits or pigs and clinical studies have not consistently replicated these benefits. The variability in outcomes may be attributed to differences in study design, timing and method of melatonin administration, and types of endpoints measured. Comorbidities, risk factors, and comedications further influence mitochondrial biology and melatonin's efficacy in cardiac IRI. A dedicated comparative analysis evaluates melatonin against established and emerging cardioprotective approaches targeting mitochondria, underscoring its potential for combination therapies.
Clinical Factors and Biomarkers During Pregnancy and Risk of Cardiovascular Disease.
Bacmeister L, Glintborg D, Kjer-Møller JJ … +10 more , Al-Jorani H, Christesen HT, Jensen TK, Jørgensen JS, Buellesbach A, Heidenreich A, Zeller T, Dechend R, Westermann D, Skovsager Andersen M
JAMA Cardiol · 2026 Apr · PMID 41706460 · Full text
IMPORTANCE: Cardiovascular disease (CVD) is the leading cause of death among women worldwide. Pregnancy serves as a natural cardiovascular stress test and universal clinical encounter, yet few approaches leverage its ins...
IMPORTANCE: Cardiovascular disease (CVD) is the leading cause of death among women worldwide. Pregnancy serves as a natural cardiovascular stress test and universal clinical encounter, yet few approaches leverage its insights to inform long-term cardiovascular risk. OBJECTIVE: To determine whether clinical measures and biomarkers obtained during pregnancy may identify women at risk of long-term CVD. DESIGN, SETTING, AND PARTICIPANTS: This was a registry-linked, population-based cohort study of all pregnancies reaching at least 22 weeks between June 2010 and October 2013 in Southern Denmark. Primary analyses were performed in a nested prospective subcohort of Odense Child Cohort participants with available pregnancy biomarker data. Women with preexisting CVD were excluded (n = 114). Follow-up was done through December 31, 2023. Among 38 455 eligible women, 2056 had biomarker data at week 12 or week 29. Analytic subsets with complete data were used for prognostic modeling at week 12 (n = 1379) and week 29 (n = 1389). EXPOSURES: Clinical characteristics, obstetric outcomes, and pregnancy biomarkers including soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor, high-sensitivity cardiac troponin I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide. MAIN OUTCOMES AND MEASURES: Incident maternal CVD, evaluated using Cox proportional hazards models. RESULTS: In the biomarker cohort (median [IQR] age, 30.4 [27.4-33.8] years), 28 women (1.4%) developed CVD during a median (IQR) follow-up of 11.9 (11.2-12.5) years. Maternal age, hypertensive disorders of pregnancy (HDPs), and third-trimester concentrations of hs-cTnI and sFlt-1 were each independently associated with higher long-term CVD risk. A combined model including age and sFlt-1 measured at week 29 improved discrimination for CVD compared with a base model of age alone (ΔAUC, 0.16; 95% CI, 0.02-0.30), whereas a clinical model consisting of age, systolic blood pressure, and non-high-density lipoprotein cholesterol did not. Results were consistent in women without prior hypertension or HDPs and in nulliparous women. CVD incidence and the predictive value of the base model were comparable between the biomarker and the contemporaneous background cohorts (n = 36 274). CONCLUSIONS AND RELEVANCE: These findings support pregnancy as an opportunistic window for sex-specific cardiovascular risk assessment and prevention throughout a woman's life course. Further studies are warranted to validate these findings.
The Past, Present, and Future of Cardiac Gene Therapy.
Hajjar RJ
Can J Cardiol · 2026 May · PMID 41616973 · Publisher ↗
The field of gene therapy has undergone significant advancement in the last decade. Originally restricted to experimental biology, gene therapy is now an established clinical modality with demonstrated efficacy in addres...
The field of gene therapy has undergone significant advancement in the last decade. Originally restricted to experimental biology, gene therapy is now an established clinical modality with demonstrated efficacy in addressing a range of diseases, particularly rare monogenic disorders, hematologic conditions, and oncologic applications. Nevertheless, the cardiovascular system presents both substantial challenges and notable opportunities for innovation in gene therapy. Cardiovascular disease continues to be the leading cause of mortality worldwide. Although advancements have been made in pharmacologic treatments, medical devices, and lifestyle modifications, current interventions do not fundamentally address the molecular mechanisms underlying most cardiac diseases. Gene therapy offers distinct potential to modify disease processes at the molecular and cellular level, providing prospects for durable or potentially curative solutions in heart failure, cardiomyopathies, arrhythmias, and vascular pathologies.
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