Myocardial Ischemia-Reperfusion Injury: Unraveling Pathophysiology, Clinical Manifestations, and Emerging Prevention Strategies.

Myocardial ischemia-reperfusion injury (MIRI) remains a challenge in the context of reperfusion procedures for myocardial infarction (MI). While early revascularization stands as the gold standard for mitigating myocardial injury, recent insights have illuminated the paradoxical role of reperfusion, giving rise to the phenomenon known as ischemia-reperfusion injury. This comprehensive review delves into the intricate pathophysiological pathways involved in MIRI, placing a particular focus on the pivotal role of endothelium. Beyond elucidating the molecular intricacies, we explore the diverse clinical manifestations associated with MIRI, underscoring its potential to contribute substantially to the final infarct size, up to 50%. We further navigate through current preventive approaches and highlight promising emerging strategies designed to counteract the devastating effects of the phenomenon. By synthesizing current knowledge and offering a perspective on evolving preventive interventions, this review serves as a valuable resource for clinicians and researchers engaged in the dynamic field of MIRI.

Atrial Fibrillation After Patent Foramen Ovale Closure: Incidence, Pathophysiology, and Management.

This comprehensive review explores the incidence, pathophysiology, and management of atrial fibrillation (AF) following percutaneous closure of patent foramen ovale (PFO). Although AF is considered a common adverse event post PFO closure, its incidence, estimated at <5%, varies based on monitoring methods. The review delves into the challenging task of precisely estimating AF incidence, given subclinical AF and diverse diagnostic approaches. Notably, a temporal pattern emerges, with peak incidence around the 14th day after closure and a subsequent decline after the 45th day, mimicking general population AF trends. The pathophysiological mechanisms behind post PFO closure AF remain elusive, with proposed factors including local irritation, device-related interference, tissue stretch, and nickel hypersensitivity. Management considerations encompass rhythm control, with flecainide showing promise, and anticoagulation tailored to individual risk profiles. The authors advocate for a personalized approach, weighing factors like age, comorbidities, and device characteristics. Notably, postclosure AF is generally considered benign, often resolving spontaneously within 45 days, minimizing thromboembolic risks. Further studies are required to refine understanding and provide evidence-based guidelines.

Mortality Rates in Patients Undergoing Urgent Versus Elective Transcatheter Aortic Valve Replacement: A Meta-analysis.

Patients with severe aortic stenosis (AoS) often present with acute heart failure and compensation, frequently leading to cardiogenic shock. Transcatheter Aortic Valve Replacement (TAVR) has been recently performed as a bailout treatment in such patients. The aim of our meta-analysis is to compare urgent TAVR with elective procedures. We systematically screened three databases searching for studies comparing urgent vs elective TAVR. Primary endpoint is the 30-days mortality. Secondary endpoints included in-hospital mortality, device success, periprocedural vascular complications, 30-days stroke, 30-days acute kidney injury (AKI), permanent pacemaker implantation (PPM), moderate or severe paravalvular leakage, and 30-days bleeding. Seventeen studies were included, with a total of 84,495 patients. Urgent TAVR was associated with an increased risk for 30-days mortality [Risk Ratio (RR): 2.53, 95% Confidence Intervals (CI): 1.81-3.54)], in-hospital mortality (RR: 2.67, 95% CI: 1.94-3.68), periprocedural vascular complications (RR: 1.91, 95% CI: 1.28-2.85) and AKI (RR: 2.83, 95% CI: 1.93-4.14), compared with elective procedure. No differences were observed in the other secondary endpoints. Urgent TAVR was associated with higher in-hospital and 30-days mortality, possibly driven by the increased incidence of AKI and vascular complications in urgent TAVR. The results highlight the importance of early TAVR in stable AoS patients.

Management of patent foramen ovale; findings from a nationwide survey.

OBJECTIVES: Several clinical trials have provided evidence supporting the transcatheter closure of patent foramen ovale (PFO) in selected patients following a cryptogenic stroke. However, it remains unknown to what extent these guidelines have been implemented in everyday clinical practice and the familiarity of physicians from different specialties with PFO closure. The aim of our nationwide survey is to explore the implementation of transcatheter PFO occlusion in Greek clinical practice. MATERIALS AND METHODS: Attending level cardiologists, internal medicine physicians and neurologists involved in the management of PFO-related strokes working in Greece were invited to complete an online questionnaire. The questionnaire consisted of 19 questions and was designed to obtain comprehensive data on provider demographics, PFO characteristics, and specific clinical scenarios. RESULTS: A total of 51 physicians (56.9 % cardiologists, 25.5 % neurologists and 17.6 % internal medicine physicians) completed the survey, resulting in a response rate of 53 %. Cardiologists, internal medicine physicians and neurologists agree on several issues regarding PFO closure, such as PFO closure as first line treatment, management of patients with DVT or prior decompression sickness, and post-closure antithrombotic treatment, but different approaches were reported regarding closure in patients with thrombophilia treated with oral anticoagulation (p=0.012) and implantable loop recorder placement for atrial fibrillation exclusion (p=0.029 and p=0.020). CONCLUSIONS: Our findings show that cardiologists, internal medicine physicians and neurologists agree in numerous issues, but share different views in the management of patients with thrombophilia and rhythm monitoring duration. These results highlight the significance of collaboration among physicians from different medical specialties for achieving optimal results.

Thirty-Days versus Longer Duration of Dual Antiplatelet Treatment after Percutaneous Coronary Interventions with Newer Drug-Eluting Stents: A Systematic Review and Meta-Analysis.

Abbreviation of the duration of dual antiplatelet therapy (DAPT) (one or three months) has been recently proposed, especially for high bleeding risk patients, after percutaneous coronary intervention (PCI) with drug-eluting stent (DES). Three databases were screened for eligible randomized control trials. The primary endpoint was the incidence of net adverse clinical events (NACE). Secondary endpoints consisted of major adverse cardiovascular events (MACE), all-cause and cardiovascular mortality, myocardial infarction, stroke, stent-thrombosis, repeat revascularization and major bleeding. We included four RCTs with a total of 26,576 patients; 13,282 patients were grouped in 30-days DAPT, while the remaining 13,294 were allocated in a longer period of DAPT. One month of DAPT did not significantly reduce NACE (odds ratio [OR]: 0.87, 95% confidence intervals [Cl]: 0.74-1.03); however, major bleedings were significantly reduced by 22% (OR: 0.78, 95% Cl: 0.65-0.94). Mortality or ischemic events (stroke, myocardial infarction, revascularization and stent thrombosis) were not affected. Thus, 30-days DAPT could be considered as safe and feasible after PCI with DES in selected patients, especially those with high bleeding risk. Forthcoming RCTs could shed light on the optimal duration of DAPT.

Acute Coronary Syndromes in Antiphospholipid Syndrome-above Suspicion: A Systematic Review.

Antiphospholipid syndrome(APS) is an autoimmune disorder characterized clinically by vascular thrombosis and/or pregnancy morbidity, associated with persistently elevated titers of antiphospholipid antibodies on at least two measurements over 12 weeks apart. In this study, we conducted a systematic review of the literature utilizing the Pubmed platform, in order to acquire clinical information about acute coronary syndromes in patients with APS. The obtained articles were reviewed in order to register the clinical characteristics, the rate of occurrence, the prognosis and the therapeutic approach of these patients. APS should be considered in young patients with acute myocardial infarction, even in patients with normal coronary arteries. The pharmaceutical approach is mainly based on the vitamin K antagonists, and in certain occasions aspirin, without any definite guidelines on the subject. Further randomized clinical trials are imperative for a better understanding of the particular characteristics of this group of patients, so that a more complete therapeutic approach to be obtained.

The Association of Depression With QT Duration: A Comparison Between Individuals Younger or Older Than 65 Years.

OBJECTIVE: The electrocardiogram-derived corrected QT (QTc) interval is an indicator of cardiac autonomic activity that has been proposed as a biological measure to investigate the interplay between depression and cardiovascular diseases. This study assesses whether depression is associated with a longer QTc interval across age groups. METHODS: Assessment of depressive symptoms was performed in 1637 participants of the cross-sectional Corinthia study with the Zung Self-Rating Depression Scale in those younger than 65 years (group 1) and with the Geriatric Depression Scale in elderly individuals (≥65 years, group 2). The QT interval was obtained from electrocardiogram recordings and corrected for heart rate (QTc). RESULTS: Individuals in group 1 with depression were predominantly women and had a higher prevalence of coronary artery disease and diabetes mellitus. Group 1 individuals with depression had longer QTc duration (no depression versus depression, 389.3 [27.0] versus 401.1 [32.9] milliseconds; p < .001) and percentage of abnormal QTc (no depression versus depression, 2.0% versus 10.8%; p = .001) compared with those without depression. Elderly individuals (group 2) had similar values of QTc and percentage of abnormal QTc irrespective of depression status. Even after adjustment for known QT-prolonging factors, the presence of depression in younger individuals was associated with an increased QTc by 11.1 milliseconds and with an approximately 10.6-fold higher prevalence of abnormal QTc duration. CONCLUSIONS: Depression was associated with a longer QTc interval especially in individuals younger than 65 years. These findings may indicate an interrelationship between depression and autonomic dysregulation as potential risk factors for cardiovascular disease and sudden cardiac death.

Transcatheter Aortic Valve Implantation Access Sites: Same Goals, Distinct Aspects, Various Merits and Demerits.

Transcatheter aortic valve implantation (TAVI) has been established as a safe and efficacious treatment for patients with severe symptomatic aortic stenosis (AS). Despite being initially developed and indicated for high-surgical-risk patients, it is now offered to low-risk populations based on the results of large randomized controlled trials. The most common access sites in the vast majority of patients undergoing TAVI are the common femoral arteries; however, 10-20% of the patients treated with TAVI require an alternative access route, mainly due to peripheral atherosclerotic disease or complex anatomy. Hence, to achieve successful delivery and implantation of the valve, several arterial approaches have been studied, including transcarotid (TCr), axillary/subclavian (A/Sc), transapical (TAp), transaortic (TAo), suprasternal-brachiocephalic (S-B), and transcaval (TCv). This review aims to concisely summarize the most recent literature data and current guidelines as well as evaluate the various access routes for TAVI, focusing on the indications, the various special patient groups, and the advantages and disadvantages of each technique, as well as their adverse events.

Risk factors profile of young and older patients with myocardial infarction.

Myocardial infarction (MI) among young adults (<45 years) represents a considerable proportion of the total heart attack incidents. The underlying pathophysiologic characteristics, atherosclerotic plaque features, and risk factors profile differ between young and older patients with MI. This review article discusses the main differences between the younger and elderly MI patients as well as the different pathogenic mechanisms underlying the development of MI in the younger. Young patients with MI often have eccentric atherosclerotic plaques with inflammatory features but fewer lesions, and are more likely to be smokers, obese, and have poor lifestyle, such as inactivity and alcohol intake. Compared to older MI patients, younger are more likely to be men, have familial-combined hyperlipidaemia and increased levels of lipoprotein-a. In addition, MI in younger patients may be related to use of cannabis, cocaine use, and androgenic anabolic steroids. Genomic differences especially in the pathways of coagulation and lipid metabolism have also been identified between young and older patients with MI. Better understanding of the risk factors and the anatomic and pathophysiologic processes in young adults can improve MI prevention and treatment strategies in this patient group. Awareness could help identify young subjects at increased risk and guide primary prevention strategies. Additional studies focusing on gene pathways related to lipid metabolism, inflammation, and coagulation are needed.

Acute exposure to diesel affects inflammation and vascular function.

BACKGROUND: Diesel exhaust fumes represent one of the most common toxic pollutants. The prolonged effects of acute exposure to this pollutant on inflammatory status and vascular properties are unknown. METHODS: During a 2-h session, 40 healthy subjects were exposed to diesel exhaust fumes and/or filtered air. Endothelial function was assessed with flow mediated dilation, arterial stiffness with pulse wave velocity and reflected waves with augmentation index. C-reactive protein, fibrinogen, protein C levels and protein S activity were also measured. Standard deviation of normal to normal R-R intervals (SDNN) was used to assess heart rate variability. Measurements were assessed before exposure and 2 and 24 h after diesel exposure. RESULTS: Compared with filtered air, exposure to diesel exhaust fumes decreased flow mediated dilation and increased pulse wave velocity and augmentation index up to 24 h after the exposure (p < 0.001 for all). Similarly, compared with filtered air, diesel exhaust exposure impaired SDNN during the 24-h study period (p = 0.007). C-reactive protein and fibrinogen levels were significantly increased after diesel exhaust exposure while protein C levels and protein S activity decreased (p < 0.01 for all). Exposure to diesel exhaust fumes resulted in higher C-reactive protein concentration in smokers compared with non-smokers (p < 0.001). CONCLUSION: Short-term exposure to diesel exhaust fumes has a prolonged adverse impact on endothelial function and vascular wall properties, along with impaired heart rate variability, abnormal fibrinolytic activity and increased markers of inflammation. These findings give insights into the mechanisms underlining the increased cardiovascular risk of subjects regularly exposed to diesel exhaust fumes.

MicroRNAs as Biomarkers in Hypertrophic Cardiomyopathy: Current State of the Art.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is the most common inherited Cardiomyopathy. The hallmark of HCM is myocardial fibrosis that contributes to heart failure, arrhythmias and sudden cardiac death. OBJECTIVE: Currently, there are no reliable serum biomarkers for the detection of myocardial fibrosis, while cardiac magnetic resonance (CMR) is an imaging technique to detect myocardial fibrosis. MicroRNAs (miRNAs) have been increasingly suggested as biomarkers in cardiovascular diseases. However, in HCM there is as yet no identified and verified specific circulating miRNA signature. METHODS: We conducted a review of the literature to identify the studies that indicate the possible roles of miRNAs in HCM. RESULTS: From studies in transgenic mice with HCM, miR-1, -133 may identify HCM in the early asymptomatic phase. Human miR-29a could be used as a circulating biomarker for detection of both myocardial hypertrophy and fibrosis in HCM, while it could also have a possible additional role in discrimination of hypertrophic obstructive cardiomyopathy from non-obstructive HCM. Additionally, miR-29a-3p is associated with diffuse myocardial fibrosis in HCM, while miR-1-3p could discriminate end-stage HCM from dilated cardiomyopathy and left ventricle dilation. Another role of miRNAs could also be the contribution in the differential diagnosis between HCM and phenocopies. Moreover, miRNA- targeted therapy (miR-133 mimics) is promising in inhibiting cardiac hypertrophy, but this is still in the early stages. CONCLUSION: A more reliable and specific signature of miRNAs is expected with forthcoming studies in samples from HCM patients and correlation of miRNAs with CMR and serum markers of fibrosis may implicate novel diagnostic and therapeutic pathways.

Long-Term Outcomes and Valve Performance in Patients Undergoing Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) is an established method for treating patients with aortic valve stenosis. We sought to determine the long-term clinical outcomes and performance of a self-expanding bioprosthesis beyond 5 years. Consecutive patients scheduled for TAVI were included in the analysis. Primary end points were all-cause and cardiovascular mortality, structural valve deterioration (SVD) and bioprosthetic valve failure (BVF), based on the VARC-2 criteria and consensus statement by ESC/EAPCI. The study prospectively evaluated 273 patients (80.61 ± 7.00 years old, 47% females) who underwent TAVI with CoreValve/Evolut-R (Medtronic Inc.). The median follow-up duration was 5 years (interquartile range: 2.9 to 6; longest: 8 years). At 1, 5, and 8 years, estimated survival rates were 89.0%, 61.1%, and 56.0%, respectively, while cardiovascular mortality was 8% at the end of follow-up. Regarding valve performance, 5% of patients had early BVF and 1% had late BVF. Concerning SVD, 16 patients (6% of the total population) had moderate SVD (91% had an increase in mean gradient), with no severe SVD cases. Five patients with SVD died during follow-up. Actual analysis of the 8-year cumulative incidence of function of moderate SVD was 5.9% (2.5% to 16.2%). At multivariate analysis, the factor that emerged as an independent predictor for future SVD, was smaller bioprosthetic valve size (HR 0.58, 95% CI 0.41 to 0.82, p = 0.002). Long-term evaluation beyond 5 years after TAVI with a self-expanding bioprosthesis demonstrated low rates of cardiovascular mortality and structural valve deterioration. Valve size was an independent predictor for SVD.

The impact of sleeping duration on atherosclerosis in the community: insights from the Corinthia study.

PURPOSE: Sleep is an essential physiologic process whose disturbances have been regarded as a risk factor in various pathophysiologic processes, including atherosclerosis and cardiovascular disease. Although the negative influence of short sleep duration has been well-established, recent data suggest a possible harmful effect of prolonged sleeping pattern. METHODS: In the setting of the Corinthia cross-sectional study, self-reported night sleep duration was recorded in 1752 apparently healthy individuals and was classified as normal sleep duration (NSD, 7-8 h), short sleep duration (SSD, 6-7 h), very short sleep duration (VSSD, < 6 h), and long sleep duration (LSD, > 8 h). Carotid duplex ultrasonography was performed in order to measure the mean and maximum carotid intima-media thickness (cIMT) as a non-invasive marker of atherosclerosis. RESULTS: Subjects with LSD and VSSD had significantly higher mean cIMT (VSSD: 1.02 ± 0.45 mm, SSD: 0.95 ± 0.35, NSD: 0.96 ± 0.38 mm, LSD: 1.07 ± 0.52 mm; p < 0.001) and maximum cIMT (VSSD: 1.39 ± 0.9 mm, SSD: 1.25 ± 0.71 mm, NSD: 1.23 ± 0.76 mm, LSD: 1.41 ± 0.93 mm). Following a regression analysis adjusting for known cardiovascular risk factors, individuals with LSD and VSSD had higher mean cIMT by 0.054 mm and 0.067 mm respectively compared to those with NSD. CONCLUSION: A balanced sleeping duration of 6-8 h is associated with decreased mean and maximum IMT while both very short sleep duration and long sleep duration are associated with increased carotid intima-media thickness, a marker of subclinical atherosclerosis.

X-linked dilated cardiomyopathy: the important role of genetic tests and imaging in the early diagnosis and treatment.

Familial dilated cardiomyopathy predominantly affects younger adults and may cause advanced heart failure and sudden cardiac death. Therefore, detailed family history, family members screening, appropriate genetic testing and counselling may allow correct identification of cardiac remodeling etiology, as well as earlier disease detection. Accordingly, we present a case with an early diagnosis of an X-linked dilated cardiomyopathy guided by clinical features, cardiac MRI and genetic testing. The diagnostic workup was guided by the positive family history of cardiomyopathy and sudden cardiac deaths. Clinical implications including early management, better arrythmia risk stratification and the revealing of a potential endemic entity clustering in several male subjects of a community on Crete island are further discussed.

Diagnostic performance of electrocardiographic criteria in echocardiographic diagnosis of different patterns of left ventricular hypertrophy.

BACKGROUND: Electrocardiogram (ECG) is considered the initial screening method for the detection of left ventricular hypertrophy (LVH) despite its low sensitivity. However, there are no data on how ECG criteria for LVH perform in patients with concentric (cLVH) and eccentric LVH (eLVH). METHODS: In the setting of the Corinthia cross-sectional study, ECGs were analyzed in 1,570 participants of the study. Seven ECG LVH criteria were calculated (Sokolow-Lyon voltage, index, and product, sex-specific Cornell voltage and product, Lewis voltage, and the Framingham), whereas LVH was defined, based on echocardiographic data, as left ventricular mass indexed for body surface area (BSA) of at least 125 g/m2 in men and at least 110 g/m2 in women. RESULTS: Regarding the frequency encountered for each ECG LVH criterion, there was no difference between eLVH and cLVH. However, when ECG criteria were compared as continuous variables between LVH groups, Cornell voltage and product were higher in cLVH individuals, with a value of Cornell voltage >13.95 mV having 61% sensitivity and 62% specificity to differentiate cLVH from eLVH (p = .05). Even after adjustment for age, sex, body mass index, and hypertension, the occurrence of Cornell voltage or product increased the odds of cLVH by 1.6 times (p = .001). CONCLUSION: Cornell voltage and product criteria disclosed a superior discriminative ability for the detection of LVH via ECG. When further categorizing LVH as concentric and eccentric, Cornell product depicted the higher discriminative ability for cLVH.

The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives.

Diabetes is a complex metabolic disorder affecting the glucose status of the human body. Chronic hyperglycaemia related to diabetes is associated with end organ failure. The clinical relationship between diabetes and atherosclerotic cardiovascular disease is well established. This makes therapeutic approaches that simultaneously target diabetes and atherosclerotic disease an attractive area for research. The majority of people with diabetes fall into two broad pathogenetic categories, type 1 or type 2 diabetes. The role of obesity, adipose tissue, gut microbiota and pancreatic beta cell function in diabetes are under intensive scrutiny with several clinical trials to have been completed while more are in development. The emerging role of inflammation in both type 1 and type 2 diabetes (T1D and T1D) pathophysiology and associated metabolic disorders, has generated increasing interest in targeting inflammation to improve prevention and control of the disease. After an extensive review of the possible mechanisms that drive the metabolic pattern in T1D and T2D and the inflammatory pathways that are involved, it becomes ever clearer that future research should focus on a model of combined suppression for various inflammatory response pathways.

Breakfast association with arterial stiffness and carotid atherosclerotic burden. Insights from the 'Corinthia' study.

BACKGROUND AND AIMS: The role of dietary patterns, in cardiovascular diseases has been challenged. The role of breakfast as an element of balance energy intake has gained research interest. However, the effects of dietary patterns related to breakfast consumption on vascular function are unknown. We explored the association of breakfast consumption habits with arterial wall elastic properties and carotid atherosclerosis. METHODS AND RESULTS: In this cross-sectional study we enrolled 2043 inhabitants of the Corinthia region in Greece. Carotid-femoral pulse wave velocity (cf-PWV) was used to assess arterial stiffness. Carotid intima-media thickness (cIMT) was measured and the mean and the maximum cIMT were calculated. According to food frequency questionnaires, breakfast contribution in total daily energy intake (>20%; 5-20% and <5%) was estimated. Subjects were categorized as high-energy breakfast consumers (HeBC), low-energy breakfast consumers (LeBC) and those skipping breakfast (SBf) respectively. From the study population 240 subjects were categorized as HeBC, 897 as LeBC, and 681 as SBf. The mean cf-PWV was significantly higher in subjects SBf compared to LeBC and HeBC (9.35 ± 2.82 m/s vs. 9.09 ± 2.77 m/s vs. 8.76 ± 2.69 m/s, p = 0.02). The mean cIMT was significantly higher in subjects SBf compared to LeBC and HeBC (1.04 ± 0.46 mm vs. 0.99 ± 0.43 mm vs. 0.92 ± 0.39 mm, p = 0.01). Even after adjustment for potential confounders and cardiovascular risk factors SBf subjects have significantly increased mean cIMT and cf-PWV. CONCLUSION: Skipping breakfast has an adverse effect on arterial stiffness and carotid atheromatic burden. Increased breakfast total energy intake may act protectively against atherosclerosis, a finding worth of further pathophysiologic exploration with potential clinical implications.