Silent Myocardial Ischemia: From Pathophysiology to Diagnosis and Treatment.

Silent myocardial ischemia (SMI), characterized by a lack of overt symptoms despite an inadequate blood supply to the myocardium, remains a challenging entity in cardiovascular medicine. The pathogenesis involves intricate interactions of vascular, neurohormonal, and metabolic factors, contributing to perfusion deficits without the characteristic chest pain. Understanding these mechanisms is pivotal for recognizing diverse clinical presentations and designing targeted interventions. Diagnostic strategies for SMI have evolved from traditional electrocardiography to advanced imaging modalities, including stress echocardiography, single-photon emission computed tomography (SPECT), positron emission tomography (PET), and cardiac magnetic resonance imaging (MRI). Treating SMI is a matter of ongoing debate, as the available evidence on the role of invasive versus medical management is controversial. This comprehensive review synthesizes current knowledge of silent myocardial ischemia, addressing its pathophysiology, diagnostic modalities, and therapeutic interventions.

Interventional management of mitral regurgitation and sleep disordered breathing: "Catching two birds with one stone".

Sleep disordered breathing (SDB), mostly constituting of obstructive and central sleep apnea (OSA and CSA, respectively), is highly prevalent in the general population, and even more among patients with cardiovascular disease, heart failure (HF) and valvular heart disease, such as mitral regurgitation (MR). The coexistence of HF, MR and SDB is associated with worse cardiovascular outcomes and increased morbidity and mortality. Pulmonary congestion, as a result of MR, can exaggerate and worsen the clinical status and symptoms of SDB, while OSA and CSA, through various mechanisms that impair left ventricular dynamics, can promote left ventricular remodelling, mitral annulus dilatation and consequently MR. Regarding treatment, positive airway pressure devices used to ameliorate symptoms in SDB also seem to result in a reduction of MR severity, MR jet fraction and an improvement of left ventricular ejection fraction. However, surgical and transcatheter interventions for MR, and especially transcatheter edge to edge mitral valve repair (TEER), seem to also have a positive effect on SDB, by reducing OSA and CSA-related severity indexes and improving symptom control. The purpose of this review is to provide a comprehensive analysis of the common pathophysiology between SDB and MR, as well as to discuss the available evidence regarding the effect of SDB treatment on MR and the effect of mitral valve surgery or transcatheter repair on both OSA and CSA.

Intravascular Imaging in Ultra-Low or Zero-Contrast Percutaneous Coronary Interventions: The Time Is Now?

Ultra-low contrast percutaneous coronary interventions (ULPCIs) are a novel field of interventional cardiology, aiming to reduce the risk of contrast-induced nephropathy (CIN), which is a well-described adverse event after angiography. CIN is a well-described adverse event following PCI, especially in high-risk patients, i.e., patients with an already deteriorating renal function or chronic kidney disease, as well as patients of advanced age or requiring an increased amount of contrast during their intervention. Among the techniques described for ULPCI procedures, intravascular imaging guidance seems a promising option, as it allows lesion recognition and characterization, stent implantation, and PCI optimization. Intravascular ultrasound (IVUS) is the modality most commonly used, as it does not require contrast injection, contrary to optical coherence tomography (OCT). Several clinical trials, assessing IVUS in the context of ULPCI, have shown that it can be safely used in this setting while offering a substantial reduction in contrast media volume, as well as renal adverse outcomes. This review aims to describe the need for ULPCI and technical considerations regarding the use of intravascular imaging in this setting, as well as analyze the available evidence from clinical trials regarding the safety and efficacy of IVUS-ULPCI, in order to provide a comprehensive summary for practicing physicians.

In vivo correlation between morphological characteristics of coronary plaques and functional characteristics of carotid arteries in acute coronary syndrome.

BACKGROUND: Carotid artery temperature heterogeneity (ΔΤ) measured by microwave radiometry (MWR) has been associated with future cardiovascular events including acute coronary syndromes. The vulnerable plaques of the coronary arterial tree, that can be ideally depicted by intracoronary imaging such as optical coherence tomography (OCT) have anatomical characteristics such as the thin fibrous cap (TCFA), that make them vulnerable to rupture. The scope of the study was to assess the implication of the carotid artery temperature heterogeneity on the culprit coronary plaque morphology in patients presenting with acute myocardial infarction. METHODS: 34 patients presented with an acute myocardial infarction were enrolled in the study. All patients underwent percutaneous coronary intervention (PCI) and OCT for the evaluation of the anatomical characteristics of the culprit lesion. After the completion of the PCI all patients underwent carotid ultrasound and MWR of both carotid arteries and thermal heterogeneity of the carotid arteries was assessed. Blood samples were collected for high sensitivity C-reactive protein (CRP) analysis. RESULTS: Thirty four patients, 21 with STEMI (61.76%) and 13 (38.23%) with NSTEMI, were included in the study. Patients with ruptured plaques had significantly increased hsCRP compared to patients that did not have a ruptured plaque (14.41±4.02 vs 9.9±2.5, P<0.005). Thermal heterogeneity, was significantly increased in ruptured plaques compared to no ruptured ones (1.01±0.31 vs 0.51±0.14°C, P=0.001), and in plaques with TCFA compared to those without a TCFA (0.82±0.37 vs 0.60±0.05°C, P=0.001). Diabetes mellitus, ΔΤ and hsCRP, were entered in the multivariate analysis, from which DM (OR 4.12; 95% CI 0.77-22.07; P=0.07) and ΔΤ (OR for 0.1°C increase 1.43; 95% CI 1.03-1.98; P=0.03) remained in the final analysis, and only ΔΤ was independently associated with the presence of the TCFA. Regarding plaque rupture, STEMI, hsCRP, and ΔT were entered in the multivariate analysis from which hsCRP (OR 1.51; 95% CI 0.99-2.28; P=0.051) and ΔΤ (OR for 0.1°C increase 3.40; 95% CI 1.29-8.96; P=0.013) remained in the final analysis with the ΔT being the only variable.

CardioPulmonary Resuscitation in patients with suspected or confirmed Covid-19. A consensus of the Working group on CardioPulmonary Resuscitation of the Hellenic Society of Cardiology.

The unprecedented for modern medicine pandemic caused by the SARS-COV-2 virus ("coronavirus", Covid-19 disease) creates in turn new data on the management and survival of cardiac arrest victims, but mainly on the safety of CardioPulmonary Resuscitation (CPR) providers. The Covid-19 pandemic resulted in losses of thousands of lives, and many more people were hospitalized in simple or in intensive care unit beds, both globally and locally in Greece. More specifically, in victims of cardiac arrest, both in- and out- of hospital, the increased mortality and high contagiousness of the SARS-CoV-2 virus posed new questions, of both medical and moral nature/ to CPR providers. What we all know in resuscitation, that we cannot harm the victim and therefore do the most/best we can, is no longer the everyday reality. What we need to know and incorporate into decision-making in the resuscitation process is the distribution of limited human and material resources, the potentially very poor outcome of patients with Covid-19 and cardiac arrest, and especially that a potential infection of health professionals can lead in the lack of health professionals in the near future. This review tries to incorporate the added skills and precautions for CPR providers in terms of both in- and out- hospital CPR.

Predicted Skeletal Muscle Mass and 4-Year Cardiovascular Disease Incidence in Middle-Aged and Elderly Participants of IKARIA Prospective Epidemiological Study: The Mediating Effect of Sex and Cardiometabolic Factors.

The sex-specific effect of skeletal muscle mass (SMM) index (SMI) on 4-year first fatal/non-fatal cardiovascular disease (CVD) event in free-of-disease individuals was examined. In 2009, n = 1411 inhabitants (mean age = 64(12)) from Ikaria were selected. Follow-up was performed in 2013. SMI was created to reflect SMM through appendicular skeletal muscle mass (indirectly calculated through formulas) divided by body mass index (BMI). Fifteen and six tenths percent of participants exhibited CVD (19.8% in men/12% in women, p = 0.002). Significant U-shape trends were observed in participants >65 years old and women irrespective to age confirmed through multi-adjusted Cox regression analysis; in age >65 years, Hazard Ratio (HR)(2nd vs. 1st SMI tertile) = 0.80, 95% Confidence Interval (95%CI) (0.45, 0.96) and in women HR(2nd vs. 1st SMI tertile) = 0.71, 95% CI (0.33, 0.95), while, as for the 3rd SMI tertile, no significant trends were observed. Mediation analysis revealed that mediators of the aforementioned associations in men were the arterial distensibility and total testosterone, while, in women, inflammation, insulin resistance, and arterial distensibility. High SMM accompanied by obesity may not guarantee lower CVD risk. Specific cardiometabolic factors seem to explain this need for balance between lean and fat mass.

Antiplatelet and Antithrombotic Therapy After Patent Foramen Oval and Atrial Septal Defect Closure.

Pathologies of the atrial septum include different interatrial communications varying from patent foramen ovale (PFO) to actual defects. Atrial septal defects (ASDs) may be localized within the fossa ovalis such as the secundum type ASD or outside the region of fossa ovalis, such as the ostium primum defect and sinus venosus defect. Over the last decades, the percutaneous closure of interatrial shunts has become a feasible and safe method. During these procedures, the delicate balance between thrombotic risk, device sealing process and bleeding risk is crucial. In this review, we sought to describe current available data on the antiplatelet and antithrombotic management of patients after percutaneous ASD or PFO closure.

Transfemoral transcatheter aortic valve replacement in the presence of a mitral prosthesis.

PURPOSE: In the current case series, we present our experience with the self-expanding CoreValve or Evolut R (Medtronic Inc.) in patients with severe symptomatic aortic valve stenosis and concomitant mitral valve prosthesis. METHODS: Twelve patients with previous mitral valve prosthesis underwent transcatheter aortic valve replacement for severe symptomatic aortic valve stenosis and/or aortic valve regurgitation. All patients underwent evaluation with an echocardiogram, computed tomography and coronary angiogram. After the index intervention and before discharge all patients underwent transthoracic echocardiography. All outcomes were defined according to the Valve Academic Research Consortium-2 criteria. RESULTS: Eleven patients underwent transcatheter aortic valve replacement for severe symptomatic aortic valve stenosis and one patient for severe aortic valve regurgitation. There was immediate improvement of patients' hemodynamic status; no cases of procedural death, stroke, myocardial infarction, or urgent cardiac surgery occurred. There was no 30-day mortality and all patients improved, with 91.6% in functional New York Heart Association class I-II. CONCLUSION: The current study demonstrates that in patients with severe aortic valve stenosis or regurgitation and mitral valve prosthesis, the implantation of a self-expanding aortic valve via the transfemoral route is safe and feasible, with maintained long-term results.

Inhibition of Aortic Valve Calcification by Local Delivery of Zoledronic Acid-an Experimental Study.

The aim of this study was to evaluate in an experimental model of aortic valve (AV) stenosis the effectiveness of zoledronate on the inhibition of calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to assess calcification. Thereafter, the AVs of eight animals were treated with local delivery of 500 µg/l zoledronate. A placebo mixture was administered in the remaining eight animals. Standardized uptake values were corrected for blood pool activity, providing mean tissue to background ratios (TBRmean). In the zoledronate group, there was no progression of AV calcification (TBRmean 1.20 ± 0.12 vs 1.17 ± 0.78,p = 0.29), while AV calcification progressed in the placebo group (1.22 ± 0.15 vs 1.53 ± 0.23,p = 0.006). Ascending aorta (AA) calcification progressed in both zoledronate and placebo groups. Histology confirmed the results of the PET/CT. Inhibition of AV calcification by local delivery of zoledronate is feasible and effective.

Western Dietary Pattern Is Associated With Severe Coronary Artery Disease.

The independent predictive value of an unhealthy diet on the severity of coronary artery disease (CAD) requires further investigation. We assessed the impact of dietary pattern on CAD severity. In this cohort study, we included 188 symptomatic stable patients with CAD. Patients were categorized as having severe CAD or nonsevere CAD by coronary angiography. Among several demographics and clinical characteristics, all patients were tested using a semiquantitative food frequency questionnaire. Concerning baseline demographic characteristics, there was no difference between patients with severe CAD and nonsevere CAD. Principal component analysis revealed 8 distinct dietary patterns. The first component Western dietary pattern (increased intake of fat, red meat, and carbohydrates and minimal consumption of fruits and green leafy vegetables) was predictive of severe CAD (area under the curve: 0.73, 95% confidence intervals: 0.64-0.83, P < .001). In conclusion, an unhealthy Western type of diet is associated with the severity of coronary artery lesions in patients with stable CAD. These findings highlight the role of dietary patterns when estimating cardiovascular risk for the management of patients with CAD.

Long-term endothelial dysfunction after trans-radial catheterization: A meta-analytic approach.

BACKGROUND: Following cardiac catheterization using radial artery (RA) access, persistent endothelial dysfunction may limit the use of RA as a conduit during coronary artery bypass graft (CABG) surgery. We reviewed published literature to investigate the effects of transradial coronary catheterization on RA endothelial function. METHODS: We searched PubMed from inception to April 2017 for published studies assessing RA endothelial function late (≥1 month) after coronary catheterization. A total of 12 eligible published studies (n = 490 patients) were included in the final quantitative synthesis. Statistical heterogeneity among studies was assessed by the I2 . A random effects model was used to calculate the pooled estimate for standardized mean difference (SMD). Meta-regression analysis was used to explore predictors of change in RA endothelial function following catheterization. RESULTS: In all studies, a significant reduction in endothelium dependent response was observed post-catheterization (SMD = -0.53, 95% confidence interval [CI]: -0.93 to -0.13, P = 0.01) and a marginal, non-significant, reduction in endothelium independent response (SMD = -0.38, 95%CI: -0.77, 0.01, P < 0.059). In controlled studies, using the contralateral RA as a control, a significant impairment in endothelial function was confirmed (SMD = -6.26, 95%CI: -9.71 to -2.81, P < 0.0001), while the change in endothelium-independent response was not significant (SMD = -4.46, 95%CI: -13.3 to 4.37, P = 0.32). In meta-regression analysis male gender (z = 2.36, P = 0.018) and increasing time following catheterization (z = 2.62, P = 0.009) were associated with less RA endothelial dysfunction. CONCLUSIONS: Transradial catheterization impairs endothelium dependent vasodilatory properties of the cannulated RA, which do not recover even several months post-catheterization. Non-recovery of vasomotor function of cannulated RAs may limit their use as arterial grafts during CABG surgery.

Comparison of prognostic risk scores after successful primary percutaneous coronary intervention.

BACKGROUND: The aim of this study was to compare the predictive ability of clinical risk scores (ACEF, EuroSCORE and EuroSCORE II) to angiographic (SYNTAX score) and combined risk scores (Global Risk Score and Clinical SXscore) towards cardiovascular death and/or major adverse cardiac events (MACE) in patients with ST-segment elevation acute myocardial infarction (STEMI) managed with primary percutaneous coronary intervention (pPCI). METHODS: A total of 685 patients successfully treated with pPCI were evaluated and the risk scores were calculated. The primary endpoint was the 2-year incidence of fatal cardiac events. Secondary end points were target lesion failure (TLF), repeat revascularization (RR) and MACE. RESULTS: Patients distributed in the highest tertile of EuroSCORE II presented increased rates of CV death (CVD), all-cause mortality and MACE (p<0.001 for all). EuroSCORE II was associated with increased C-statistics (0.873, 95% CIs: 0.784-0.962 and 0.825, 95% CIs: 0.752-0.898 respectively) for predicting CVD and MACE over competing risk scores (p<0.05). EuroSCORE II conferred incremental discrimination (Harrell's C, p<0.05 for all, apart from CSS for predicting CVD) and reclassification value (Net Reclassification Index, p<0.05 for all, apart from CSS for reclassifying MACE) over alternative risk scores for study's main endpoints. EuroSCORE II independently predicted CVD (HR=1.06, 95% CIs: 1.03-1.09, p<0.001) and MACE (HR=1.07, 95% CIs: 1.04-1.10, p<0.001). CONCLUSION: EuroSCORE II has the best predictive ability of CVD and/or MACE after successful pPCI for the treatment of STEMI.

Short term omega-3 polyunsaturated fatty acid supplementation induces favorable changes in right ventricle function and diastolic filling pressure in patients with chronic heart failure; A randomized clinical trial.

INTRODUCTION: Omega-3 polyunsaturated fatty acids (omega 3-PUFAs) seem to favorably affect cardiac hemodynamics and may benefit the clinical course of heart failure patients. The role of omega 3-PUFAs supplementation on the left and right ventricular function of patients with chronic compensated systolic heart failure, under optimal treatment, was studied. METHODS: 205 consecutive patients with chronic compensated heart failure, due to ischemic (IHF) or dilated cardiomyopathy (DCM)-NYHA classification I-III, under optimal medical treatment, were enrolled. Participants were 1-to-1 randomized on 1000 mg omega 3-PUFA supplementation or no supplementation, in a non-blinded fashion. Echocardiographic assessment was performed at first visit and 6 months after. Plasma BNP and serum creatinine levels were also measured. RESULTS: As compared with the control group, BNP levels in omega 3-PUFA intervention group were 34.6% lower (p=0.001); end-diastolic and end-systolic left ventricle dimensions were decreased by 2.5% (p=0.047) and 3.7% (p=0.01), maximum diameter of left atrium was decreased by 8.4% (p=0.004), left atrium ejection fraction was ameliorated by 6.03% (p=0.021) and as regards tissue Doppler parameters, TDI_Etv/Atv was decreased in omega 3-PUFA intervention group by 6.3% (p=0.038). Moreover, improvement in diastolic indices was more prominent in subjects with DCM as compared to IHF patients. CONCLUSION: Omega 3-PUFA supplementation was associated with improved left diastolic function and decreased BNP levels in patients with chronic heart failure. These findings suggest a beneficial role of omega 3-PUFAs on the hemodynamic course of patients with systolic heart failure.

Therapeutic Applications of Calcium Metabolism Modulation in Heart Disease.

Cardiovascular disease is the leading cause of death worldwide and there is extensive research on the pathophysiology of all its clinical entities. Despite the big array of possible therapeutic modalities for cardiovascular disease, there is still a big necessity to develop novel treatments that will augment our strategies for tackling the burden of cardiovascular disease and decrease morbidity and mortality. A major player in both the physiology and pathophysiology of the cardiovascular system is calcium. Extracellular calcium is required in order to initiate cardiac muscle contraction and promote the calcium-induced calcium release mechanism from the sarcoplasmic reticulum. A lot of molecules and structures that in a direct or indirect way interact with calcium are being studied and there is a constant flow of new information that is emerging. In this review we focus on some of these calcium metabolism modulators representatives such as SERCA2a, RyR2, S100A1, phosholamban and calcineurin. We emphasize on their mechanism of action, their role in cardiovascular disease and potential therapeutic implications. We also focus on the effect the bisphosphonates might have in regression of the calcium deposition in the human arteries as well as the usage of novel biomarkers such as mircoRNAs in calcium metabolism modulation in heart disease.

Percutaneous mitral valvuloplasty refined: use of a novel modified antegrade approach.

Mitral stenosis usually occurs many years after an episode of rheumatic fever and it has an indolent course until its later stages, when it acutely worsens. The rates of mitral stenosis keep declining; nonetheless, the need for advanced and sophisticated treatment modalities still remains. Our group has been applying a novel modified antegrade approach for treating mitral valve stenosis and, although we have limited experience, the results thus far are favorable. We present the preliminary data of three patients who suffered from symptomatic mitral valve stenosis and underwent successful percutaneous mitral valvuloplasty with this novel modified antegrade approach. This method increases the safety and the efficacy of the procedure and has the same clinical results as other available percutaneous techniques.

Optical coherence tomography assessment of the spatial distribution of culprit ruptured plaques and thin-cap fibroatheromas in acute coronary syndrome.

AIMS: Plaque rupture and subsequent thrombosis is known to be the most important pathology leading to acute coronary syndrome (ACS). We investigated by optical coherence tomography (OCT) whether in ACS there is an association of the location of the culprit plaque in the coronary tree with plaque rupture and/or thin cap fibroatheroma (TCFA). METHODS AND RESULTS: We included 74 patients presenting with ACS that underwent OCT study of the culprit lesion. The distance of the culprit lesion from the ostium was measured angiographically, and the presence of rupture and/or TCFA was assessed by OCT. Sixty-seven patients were analysed. Forty-five ruptured plaques were identified by OCT (67.1%). The distance from the ostium was lower for culprit ruptured plaques versus culprit non-ruptured plaques (p<0.01), particularly in the left anterior descending (LAD) and the left circumflex (LCx) arteries. The majority of culprit ruptured plaques (68.9%) was located in the proximal 30 mm of the coronary arteries. A distance from the ostium of ≤30.54 mm predicted plaque rupture with 71.1% sensitivity and 68.2% specificity. Culprit lesions in the proximal 30 mm are associated with rupture (p<0.05), TCFA (p<0.05), and lower minimal cap thickness (p<0.05). CONCLUSIONS: Culprit ruptured plaques in ACS seem to be predominately located in the proximal segments of the coronary arteries.

New insights by optical coherence tomography into the differences and similarities of culprit ruptured plaque morphology in non-ST-elevation myocardial infarction and ST-elevation myocardial infarction.

BACKGROUND: Plaque rupture is the most common pathology associated with non-ST-elevation myocardial infarction (NSTEMI) and ST-elevation myocardial infarction (STEMI). However, limited data are available regarding ruptured plaque morphology and its relationship with the clinical syndrome. This study aimed (1) to provide a morphologic description of ruptured culprit lesions by optical coherence tomography (OCT) and (2) to investigate whether ruptured plaque morphology differs between NSTEMI and STEMI. METHODS: We included 84 consecutive patients with NSTEMI and STEMI undergoing OCT study of the culprit lesion. We identified patients with plaque rupture in the OCT study and used them as the study population. Qualitative and quantitative analysis of ruptured plaque morphology was then performed, followed by a comparison of the morphological characteristics in patients with STEMI and NSTEMI. RESULTS: Fifty-five patients (70.5%) with rupture, 25 with NSTEMI, and 30 with STEMI were used for analysis. Plaque was ruptured at the minimal lumen in 34.5% of the cases, whereas 69% of the ruptures occurred at the plaque shoulder. Ruptured cap thickness was ≤90 µm in 96% of ruptured plaques. Patients with NSTEMI had greater minimal luminal area (P < .001), less lipid content (P = .01), and lower rupture length (P < .001) and length of missing fibrous cap (P < .05) compared with patients with STEMI. CONCLUSIONS: Rupture of the plaque in myocardial infarction usually occurs in sites different than the minimal lumen and at the shoulder of areas with fibrous cap measuring ≤90 µm. Patients with STEMI have greater plaque disruption and smaller minimal lumen area than patients with NSTEMI.