Search Results (63)

Despite significant advances in understanding and management, cardiovascular diseases remain the leading cause of mortality worldwide. Historically, diagnostic and therapeutic strategies have typically targeted obstructive coronary arteries. However, growing evidence supports the pivotal role of non-obstructive mechanisms in myocardial ischemia, prompting a new classification that distinguishes Acute Myocardial Ischemic Syndromes from Non-Acute Myocardial Ischemic Syndromes. In this evolving context, Optical Coherence Tomography (OCT) plays an important diagnostic role in the assessment of both obstructive and non-obstructive ischemic mechanisms. In Acute Myocardial Ischemic Syndromes, OCT enables the identification of major plaque destabilization mechanisms and contributes to the diagnosis of Myocardial Infarction with Non-Obstructive Coronary Arteries, helping to differentiate between atherosclerotic and non-atherosclerotic causes. In Non-Acute Myocardial Ischemic Syndromes, OCT assists in evaluating stenosis severity, plaque morphology, vulnerability, and healing, and may contribute to the diagnosis of Ischemia with Non-Obstructive Coronary Arteries, identifying myocardial bridge and epicardial spasm alongside conventional functional assessment of intermediate stenoses. This narrative review outlines the expanding clinical applications of OCT across the full spectrum of ischemic syndromes, emphasizing its role in bridging obstructive and non-obstructive pathophysiology and supporting a more comprehensive diagnostic approach to ischemic heart disease. Full article

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a process known as myocardial infarction reperfusion injury (MIRI). MIRI can contribute to up to 50% of the final infarct size, significantly diminishing the benefits of revascularization and leading to worsened cardiac outcomes. The pathophysiology of MIRI involves complex, interrelated mechanisms including oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory responses, apoptosis, and dysregulated autophagy. Post-reperfusion recovery is further complicated by structural and functional abnormalities such as microvascular obstruction, endothelial dysfunction, and myocardial stunning. Clinically, distinguishing reperfusion injury from ischemic damage is challenging and often requires the use of sensitive biomarkers, such as cardiac troponins, alongside advanced imaging modalities. Although a range of pharmacological (e.g., antioxidants, calcium channel blockers, mitochondrial stabilizers, anti-inflammatory agents) and non-pharmacological (e.g., hypothermia, gene therapy, stem cell-based therapies) interventions have shown promise in preclinical studies, their clinical translation remains limited. This is largely due to the multifactorial and dynamic nature of MIRI. In this context, network pharmacology offers a systems-level approach to understanding the complex biological interactions involved in MIRI, facilitating the identification of multi-target therapeutic strategies. Integrating network pharmacology with omics technologies and precision medicine holds potential for advancing cardioprotective therapies. This review provides a comprehensive analysis of the molecular mechanisms underlying MIRI, examines the current clinical challenges, and explores emerging therapeutic strategies. Emphasis is placed on bridging the translational gap through validated, multi-target approaches and large-scale, multicenter clinical trials. Ultimately, this work aims to support the development of innovative and effective interventions for improving outcomes in patients with myocardial infarction. Full article

Objective: Current good manufacturing practice (cGMP) guidance for positron emission tomography (PET) drugs has been established in Europe and the United States. In Japan, the Pharmaceuticals and Medical Devices Agency (PMDA) approved the use of radiosynthesizers as medical devices for the in-house manufacturing of PET drugs in hospitals and clinics, regardless of the cGMP environment. Without adequate facilities, equipment, and personnel required by cGMP regulations, the quality assurance (QA) and clinical effectiveness of PET drugs largely depend on the radiosynthesizers themselves. To bridge the gap between radiochemistry standardization and site qualification, the Japanese Society of Nuclear Medicine (JSNM) has issued guidance for the in-house manufacturing of small-scale PET drugs under academic GMP (a-GMP) environments. The goals of cGMP and a-GMP are different: cGMP focuses on process optimization, certification, and commercialization, while a-GMP facilitates the small-scale, in-house production of PET drugs for clinical trials and patient-specific standard of care. Among PET isotopes, N-13 has a short half-life (10 min) and must be synthesized on site. [¹³N]Ammonia ([¹³N]NH₃) is used for myocardial perfusion imaging under the Japan Health Insurance System (JHIS) and was thus selected as a working example for the manufacturing of PET drugs in an a-GMP environment. Methods: A [¹³N]NH₃-radiosynthesizer was installed in a hot cell within an a-GMP-compliant radiopharmacy unit. To comply with a-GMP regulations, the air flow was adjusted through HEPA filters. All cabinets and cells were disinfected to ensure sterility once a month. Standard operating procedures (SOPs) were applied, including analytical methods. Batch records, QA data, and radiation exposure to staff in the synthesis of [¹³N]NH₃ were measured and documented. Results: 2.52 GBq of [¹³N]NH₃ end-of-synthesis (EOS) was obtained in an average of 13.5 min in 15 production runs. The radiochemical purity was more than 99%. Exposure doses were 11 µSv for one production run and 22 µSv for two production runs. The pre-irradiation background dose rate was 0.12 µSv/h. After irradiation, the exposed dosage in the front of the hot cell was 0.15 µSv/h. The leakage dosage measured at the bench was 0.16 µSv/h. The exposure and leakage dosages in the manufacturing of [¹³N]NH₃ were similar to the background level as measured by radiation monitoring systems in an a-GMP environments. All QAs, environmental data, bacteria assays, and particulates met a-GMP compliance standards. Conclusions: In-house a-GMP environments require dedicated radiosynthesizers, documentation for batch records, validation schedules, radiation protection monitoring, air and particulate systems, and accountable personnel. In this study, the in-house manufacturing of [¹³N]NH₃ under a-GMP conditions was successfully demonstrated. These findings support the international harmonization of small-scale PET drug manufacturing in hospitals and clinics for future multi-center clinical trials and the development of a standard of care. Full article

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that play a crucial role in extracellular matrix (ECM) remodeling and are implicated in the pathogenesis of various cardiovascular diseases (CVDs). Their dysregulation has been linked to atherosclerosis, myocardial infarction (MI), heart failure (HF), and aortic stenosis, contributing to vascular inflammation, plaque destabilization, and adverse cardiac remodeling. Recent research highlights MMPs’ involvement beyond ECM degradation, influencing lipoprotein metabolism, inflammatory signaling, and intracellular processes critical for cardiovascular homeostasis. Despite their pathological role, MMPs remain promising therapeutic targets, with pharmacological inhibitors, gene therapy, and tissue inhibitors of metalloproteinases (TIMPs) emerging as potential interventions. However, the clinical translation of MMP-targeting therapies remains challenging due to off-target effects and complex regulatory mechanisms. This review provides an updated synthesis of the molecular mechanisms, disease-specific roles, and therapeutic implications of MMPs in cardiovascular pathology, aiming to bridge the gap between fundamental research and clinical applications. Full article

Background and Objectives: Aortic stenosis (AS) is a frequent valvular disease characterized by the obstruction of left ventricular outflow. The resulting hemodynamic and structural changes create an arrhythmogenic substrate, with sudden cardiac death (SCD) often caused by ventricular arrhythmias (VAs) being a feared complication. This review examines the relationship between severe AS and VA, detailing the epidemiology, pathophysiological mechanisms, risk factors, and management approaches prior to aortic valve replacement (AVR). Materials and Methods: We conducted a comprehensive narrative review of the historical and contemporary literature investigating ventricular arrhythmias in severe aortic stenosis. Literature searches were performed in PubMed, MEDLINE, and Scopus databases using keywords, including “aortic stenosis”, “ventricular arrhythmia”, “sudden cardiac death”, and “aortic valve replacement”. Both landmark historical studies and modern investigations utilizing advanced monitoring techniques were included to provide a complete evolution of the understanding. Results: The prevalence of ventricular ectopy and non-sustained ventricular tachycardia increases with AS severity and symptom onset. Left ventricular hypertrophy, myocardial fibrosis, altered electrophysiological properties, and ischemia create the arrhythmogenic substrate. Risk factors include the male sex, concomitant aortic regurgitation, elevated filling pressures, and syncope. Diagnostic approaches range from standard electrocardiography to continuous monitoring and advanced imaging. Management centers on timely valve intervention, with medical therapy serving primarily as a bridge to AVR. Conclusions: Ventricular arrhythmias represent a consequence of valvular pathology in severe AS rather than an independent entity. Their presence signals advanced disease and a heightened risk for adverse outcomes. Multidisciplinary management with vigilant monitoring and prompt surgical referral is essential. Understanding this relationship enables clinicians to better identify high-risk patients requiring urgent intervention before life-threatening arrhythmic events occur. Full article

Myocardial Bridging (MB) is typically a benign congenital coronary anomaly. MB can infrequently result in complications such as myocardial ischemia, arrhythmias, and sudden cardiac death. Recent studies suggest an underlying genetic component for MB involving DES, FBN1, SCN2B, or NOTCH1. The role of percutaneous coronary intervention (PCI) in managing MB, compared to optimal medical therapy (OMT), remains uncertain. Our study used the National Inpatient Sample (NIS) Database to identify patients aged 18 or older with myocardial bridging who were managed with PCI versus medical therapy. We compared the outcomes between both groups including in-hospital mortality, the trend of management of MB and other in-hospital outcomes or complications. Our results showed no statistically significant difference between both subgroups when comparing in-hospital mortality and secondary outcomes of cardiac arrest and the development of an acute kidney injury (AKI). Patients with myocardial bridging treated with PCI had a higher risk of developing cardiogenic shock, requiring LVAD, and requiring the use of intra-aortic balloon pump (IABP) compared to the medical therapy subgroup. Our study suggests the decision to perform PCI in myocardial bridging patients should be individualized such as in patients with refractory symptoms despite medical therapy or those with known high-risk features. Full article

17β-estradiol (E2) is the most active metabolite of estrogen with a wide range of physiological action on cardiac muscle. Previous studies have reported E2 effects predominantly for the ventricles, while the E2 impact on the atria has been less examined. In this study, we focused on the direct E2 effects on atrial and ventricular contractility at the cellular and molecular levels. Single atrial and ventricular cardiomyocytes (CM) from adult (24 weeks-old) female Wistar rats were incubated with 10 nM E2 for 15 min. Sarcomere length and cytosolic [Ca²⁺]_i transients were measured in mechanically non-loaded CM, and the tension–length relationship was studied in CM mechanically loaded by carbon fibers. The actin–myosin interaction and sarcomeric protein phosphorylation were analyzed using an in vitro motility assay and gel electrophoresis with Pro-Q Diamond phosphoprotein stain. E2 had chamber-specific effects on the contractile function of CM with a pronounced influence on ventricular CM. The characteristics of [Ca²⁺]_i transients did not change in both atrial and ventricular CM. However, in ventricular CM, E2 reduced the amplitude and maximum velocity of sarcomere shortening and decreased the slope of the passive tension–length relationship that was associated with increased TnI and cMyBP-C phosphorylation. E2 treatment accelerated the cross-bridge cycle of both atrial and ventricular myosin that was associated with increased phosphorylation of the myosin essential light chain. This study shows that E2 impairs the mechanical function of the ventricular myocardium while atrial contractility remains mostly preserved. Hormonal replacement therapy (HRT) with estrogen is by far the most effective therapy for treating climacteric symptoms experienced during menopause. Here we found a chamber specificity of myocardial contractile function to E2 that should be taken into account for the potential side effects of HRT. Full article

Coronary microvascular dysfunction (CMD) is a key contributor to myocardial ischemia and adverse cardiovascular outcomes, particularly in individuals with metabolic disorders such as type 2 diabetes (T2D). While conventional therapies primarily target epicardial coronary disease, effective treatments for CMD remain limited. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as promising agents with cardiovascular benefits extending beyond glycemic control. Preclinical and clinical evidence suggests that GLP-1R activation enhances coronary microvascular function through mechanisms including improved endothelial function, increased nitric oxide bioavailability, attenuation of oxidative stress, and reduced vascular inflammation. Moreover, GLP-1R agonists have been shown to improve myocardial blood flow, myocardial perfusion reserve, and coronary endothelial function, particularly in high-risk populations. Despite these promising findings, inconsistencies remain across studies due to variability in patient populations, study designs, and imaging methodologies. This review summarizes current evidence on the role of GLP-1R agonists in myocardial perfusion, bridging mechanistic insights with clinical outcomes. Further large-scale, well-designed trials are needed to clarify their long-term impact on coronary microcirculation and explore their potential as targeted therapies for CMD. Full article

Gouty arthritis (GA) and its association with kidney failure present significant challenges in healthcare, necessitating effective detection and management strategies. GA, characterized by the deposition of monosodium urate crystals in joints and other tissues, leads to inflammation and severe joint pain, often accompanied by metabolic comorbidities such as myocardial infarction and diabetes. Although GA has been widely studied in the medical field, limited research has explored the use of machine learning (ML) to identify key biomarkers affecting disease progression. This study aims to bridge this gap by leveraging ML models for predictive analysis. In this study, machine learning models such as decision trees, random forests, logistic regression, and artificial neural networks were used to classify GA using demographic, clinical, and laboratory data, and, most importantly, to identify the factors that affect GA. The analysis yielded promising results, with the decision tree model achieving the highest accuracy of 92.85%. Moreover, key factors such as urea, creatinine, and hemoglobin levels were identified during the initial attack, shedding light on the pathophysiology of GA. This study demonstrates how ML methods help identify key factors affecting GA and assist in disease management. By leveraging machine learning techniques, it is possible to refine the factors affecting GA and inform personalized interventions, ultimately improving patient care and outcomes. Full article

Background: Pheochromocytoma and paraganglioma are catecholamine-secreting tumors, rarely presenting with pheochromocytoma multisystem crisis (PMC), a life-threatening endocrine emergency. The severity of the condition includes a refractory cardiogenic shock and may therefore require the use of temporary mechanical circulatory support. The aim of this review is to describe the incidence of pheochromocytoma and paraganglioma crises associated with refractory cardiogenic shock, the physiopathological impact of this condition on the myocardial function, the role of temporary mechanical circulatory support (tMCS) in its management, and the outcomes of this specific population. Methods: For the purpose of this narrative review, a literature search of PubMed was conducted as of 16 November 2024. Medical Subject Headings (MeSH) terms used included extracorporeal circulation”, “Impella”, “pheochromocytoma”, “paraganglioma”, and “cardiogenic shock”, combined with Boolean “OR” and “AND”. Data from case series, retrospective studies, and systematic reviews were considered. Seven studies reporting on 45 patients who developed PMC with cardiogenic shock requiring tMCS were included. Patients were young, with a median age of 43 years (range 25–65) at presentation. Most cases presented with severe hemodynamic instability, blood pressure lability, and rapid progression to severe left ventricular dysfunction. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was the most common tMCS used to stabilize patients, initiate specific pheochromocytoma treatments, and, in some cases, provide circulatory support during emergent surgery. The median duration of VA-ECMO support was 4 days (range 1–7) and the reported mean in-hospital survival rate was 93.5%. Following VA-ECMO weaning, survivors showed full recovery of the left ventricular ejection fraction (LVEF). Conclusions: The cardiac dysfunction observed in PMC-associated cardiogenic shock may be severe and life-threatening but appears reversible. tMCS should therefore be considered in eligible cases, as a bridge to recovery, treatment, or surgery. The reported survival rates are impressively high, suggesting possibly a substantial risk of publication bias. Full article

Objectives: In addition to traditional ice-cold storage (ICS), other techniques are emerging in the field of donor heart preservation for heart transplantation (HTx). However, in many centers, it could be difficult to justify their use, due to the higher costs and the greater technical complexity compared to ICS. This study aims to analyze the results obtained for HTx at our center employing ICS, controlled hypothermia with Paragonix SherpaPak (PSP), and ex vivo normothermic perfusion with Organ Care System (OCS) as donor graft preservation strategies. Methods: All HTx performed at the University Hospital of Udine, between January 2020 and August 2024, was analyzed and patient outcomes and complications after HTx were assessed. Endomyocardial biopsies were performed in donor hearts immediately after retrieval (T₀), before implantation (T₁), and at reperfusion (T₂) to evaluate signs of myocardial damage. Results: Overall, 100 patients were transplanted with a donor heart preserved with ICS (n = 30), PSP (n = 36), or OCS (n = 34). Compared to ICS, PSP and OCS recipients showed a higher median IMPACT score (5 vs. 8 vs. 7, respectively, p = 0.05) and tended to have a higher rate of bridging to HTx with a long-term ventricular assist device (7% vs. 17% vs. 29%, p = 0.06). OCS was more commonly used in cases of expected ischemic time >4 h compared to ICS and PSP (p < 0.01). Histologically, severe degrees of cellular damage were higher in those hearts preserved with ICS. The 30-day mortality was 3% vs. 6% vs. 9% in ICS, PSP, and OCS groups, respectively (p = 0.65). Moderate-to-severe primary graft dysfunction was 37% vs. 11% vs. 17% (p = 0.03) in the three groups. Conclusions: PSP and OCS seem to be valid alternatives to traditional ICS, and their use could be strongly considered, particularly in the most complex and critical settings, until further data are available on more patient experiences. Full article

Background/Objectives: This study aims to address the critical need for accessible, early, and accurate cardiac di-agnostics, especially in resource-limited or remote settings. By shifting focus from traditional multi-lead ECG analysis to single-lead ECG data, this research explores the potential of advanced deep learning models for classifying cardiac conditions, including Nor-mal, Abnormal, Previous Myocardial Infarction (PMI), and Myocardial Infarction (MI). Methods: Five state-of-the-art deep learning architectures—Inception, DenseNet201, MobileNetV2, NASNetLarge, and VGG16—were systematically evaluated on individual ECG leads. Key performance metrics, such as model accuracy, inference time, and size, were analyzed to determine the optimal configurations for practical applications. Results: VGG16 emerged as the most accurate model, achieving an F1-score of 98.11% on lead V4 with a prediction time of 4.2 ms and a size of 528 MB, making it suitable for high-precision clinical settings. MobileNetV2, with a compact size of 13.4 MB, offered a balanced performance, achieving a 97.24% F1-score with a faster inference time of 3.2 ms, positioning it as an ideal candidate for real-time monitoring and telehealth applications. Conclusions: This study bridges a critical gap in cardiac diagnostics by demonstrating the feasibility of lightweight, scalable, single-lead ECG analysis using advanced deep learning models. The findings pave the way for deploying portable diagnostic tools across diverse settings, enhancing the accessibility and efficiency of cardiac care globally. Full article

Myocardial bridging (MB), a congenital variant where a coronary artery segment is tunneled within the myocardium, is increasingly recognized as a contributor to coronary endothelial and vasomotor dysfunction. Beyond the hallmark systolic compression observed on angiography, MB disrupts endothelial integrity, impairs the release of vasoactive substances, and induces vasomotor abnormalities. These effects exacerbate ischemic symptoms and predispose to atherosclerosis in the proximal segment, particularly in conditions such as ischemia/myocardial infarction with nonobstructive coronary arteries. Recent studies underscore MB’s association with coronary vasospasm, microvascular endothelial dysfunction, and adverse cardiovascular outcomes, including sudden cardiac death. These findings highlight the interplay between MB’s structural anomalies and functional impairments, with factors such as the bridge’s length, depth, and orientation influencing its hemodynamic significance. Advances in imaging and coronary physiology assessment, including acetylcholine testing and stress diastolic fractional flow reserve/iFR/RFR, have enhanced diagnostic precision. This review explores the multifaceted impact of MB on coronary physiology, emphasizing its role in endothelial dysfunction and vasomotor regulation. Recognizing MB’s contribution to cardiovascular disease is essential for accurate diagnosis and tailored management strategies aimed at mitigating ischemic risk and improving patient outcomes. Full article

Background: Congenital coronary artery anomalies (CAAs) are a significant cause of sudden cardiac death and a key factor in determining athletes’ eligibility for competitive sports. Their prevalence varies with diagnostic modalities and may present as asymptomatic or with life-threatening ischemic or arrhythmic events. This case series highlights the diverse manifestations of CAAs and the clinical approaches used to determine sports eligibility. Cases description: Five competitive athletes with different CAAs are presented. These cases include anomalous coronary origins, intramyocardial bridges, and coronary fistulas. Diagnostic tools, including coronary CT angiography (CCTA), cardiac magnetic resonance imaging (CMR), and stress tests, were essential in evaluating these anomalies and determining treatment strategies. In some cases, such as intramyocardial bridges, surgical intervention was necessary, while others required conservative management or exclusion from competitive sports. Conclusions: CAAs require individualized care based on risk stratification through advanced imaging techniques and functional assessment. Surgical interventions are reserved for high-risk anomalies, while others may be managed conservatively. Early detection and tailored management are crucial for ensuring athletes’ safety, and ongoing research is needed to optimize long-term outcomes. Full article

Background/Objectives: Osteoporosis and cardiovascular disease (CVD) share common risk factors and pathophysiological mechanisms, raising concerns about the cardiovascular implications of sclerostin inhibition. Romosozumab, a monoclonal antibody that targets sclerostin, is effective in increasing bone mineral density (BMD) and reducing fracture risk. However, evidence suggests that sclerostin inhibition may adversely affect vascular calcification, potentially increasing the risk of myocardial infarction (MI) and stroke. Methods: This review synthesizes data from clinical trials, such as ARCH, BRIDGE, and FRAME, alongside genetic studies and observational analyses, to evaluate the cardiovascular safety of romosozumab. PubMed was searched for relevant studies published within the last five years. Studies addressing the relationship between romosozumab and cardiovascular outcomes were included, emphasizing both its efficacy in osteoporosis management and potential cardiovascular risks. Results: Romosozumab significantly improves BMD and reduces fracture risk in postmenopausal women and men with osteoporosis. However, clinical trials report an increased incidence of major adverse cardiovascular events (MACE), particularly in patients with pre-existing cardiovascular conditions such as chronic kidney disease (CKD), diabetes, or prior CVD. Genetic studies indicate that SOST gene variants may also influence cardiovascular outcomes. Conclusions: While romosozumab is an effective treatment for osteoporosis, careful cardiovascular risk assessment is crucial before initiating therapy, especially for high-risk populations. Long-term studies are needed to evaluate chronic safety. Future therapeutic strategies should aim to maintain bone health while minimizing cardiovascular risks, ensuring a balance between efficacy and safety in osteoporosis treatment. Full article