Spontaneous Coronary Artery Dissection and COVID-19: A Review of the Literature.

SARS-CoV-2 is responsible for the global coronavirus disease 2019 (COVID-19) pandemic. While the cardiovascular effects of COVID-19 have been thoroughly described, there are limited published studies in the literature establishing a connection between spontaneous coronary artery dissection (SCAD) and COVID-19. Cardiovascular manifestations include, among others, myocarditis, acute myocardial infraction, and thrombosis. In general, SCAD is an uncommon and underdiagnosed cause of acute myocardial infarction (AMI), particularly in younger women and in patients with underlying fibromuscular dysplasia (FMD). Many patients with SCAD often report significant emotional stress, especially in relation with job loss, during the week preceding their cardiac event. Moreover, the COVID-19 pandemic has led to societal stress and increased unemployment, factors that have been associated with cardiovascular morbidity. SCAD emerges as a rare manifestation of coronary artery disease, which a few recent case reports link to COVID-19. The aim of this article is to summarize the relevant data on the pathophysiology of COVID-19 and SCAD along with a review of the reported cases on acute coronary syndrome (ACS) following SARS-CoV2 infection and, thus, to provide insights about the relationship between COVID-19 and SCAD.

Altered Expression of Intestinal Tight Junctions in Patients with Chronic Kidney Disease: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

BACKGROUND: Systemic inflammation in chronic kidney disease (CKD) is associated (as a cause or effect) with intestinal barrier dysfunction and increased gut permeability, with mechanisms not yet fully understood. This study investigated different parameters of the intestinal barrier in CKD patients, especially tight junction (TJ) proteins and their possible association with systemic endotoxemia and inflammation. METHODS: Thirty-three patients with stage I-IV CKD (n = 17) or end-stage kidney disease (ESKD) (n = 16) and 11 healthy controls underwent duodenal biopsy. Samples were examined histologically, the presence of CD3+ T-lymphocytes and the expression of occludin and claudin-1 in the intestinal epithelium was evaluated by means of immunohistochemistry, circulating endotoxin concentrations were determined by means of ELISA and the concentrations of the cytokines IL-1ß, IL-6, IL-8, IL-10 and TNF-α in serum were measured using flow cytometry. RESULTS: Patients with stage I-IV CKD or ESKD had significantly higher serum endotoxin, IL-6, IL-8 and IL-10 levels compared to controls. Intestinal occludin and claudin-1 were significantly decreased, and their expression was inversely correlated with systemic endotoxemia. Regarding occludin, a specific expression pattern was observed, with a gradually increasing loss of its expression from the crypt to the tip of the villi. CONCLUSION: The expression of occludin and claudin-1 in enterocytes is significantly reduced in patients with CKD, contributing to systemic endotoxemia and inflammatory responses in these patients.

Altered Expression of Intestinal Tight Junction Proteins in Heart Failure Patients with Reduced or Preserved Ejection Fraction: A Pathogenetic Mechanism of Intestinal Hyperpermeability.

Although intestinal microbiota alterations (dysbiosis) have been described in heart failure (HF) patients, the possible mechanisms of intestinal barrier dysfunction leading to endotoxemia and systemic inflammation are not fully understood. In this study, we investigated the expression of the intestinal tight junction (TJ) proteins occludin and claudin-1 in patients with HF with reduced (HFrEF) or preserved ejection fraction (HFpEF) and their possible association with systemic endotoxemia and inflammation. Ten healthy controls and twenty-eight patients with HF (HFrEF (n = 14), HFpEF (n = 14)) underwent duodenal biopsy. Histological parameters were recorded, intraepithelial CD3+ T-cells and the expression of occludin and claudin-1 in enterocytes were examined using immunohistochemistry, circulating endotoxin concentrations were determined using ELISA, and concentrations of cytokines were determined using flow cytometry. Patients with HFrEF or HFpEF had significantly higher serum endotoxin concentrations (p < 0.001), a significantly decreased intestinal occludin and claudin-1 expression (in HfrEF p < 0.01 for occludin, p < 0.05 for claudin-1, in HfpEF p < 0.01 occludin and claudin-1), and significantly increased serum concentrations of IL-6, IL-8, and IL-10 (for IL-6 and IL-10, p < 0.05 for HFrEF and p < 0.001 for HFpEF; and for IL-8, p < 0.05 for both groups) compared to controls. Occludin and claudin-1 expression inversely correlated with systemic endotoxemia (p < 0.05 and p < 0.01, respectively). Heart failure, regardless of the type of ejection fraction, results in a significant decrease in enterocytic occludin and claudin-1 expression, which may represent an important cellular mechanism for the intestinal barrier dysfunction causing systemic endotoxemia and inflammatory response.

Dual Antiplatelet Therapy and Cancer; Balancing between Ischemic and Bleeding Risk: A Narrative Review.

Cardiovascular (CV) events in patients with cancer can be caused by concomitant CV risk factors, cancer itself, and anticancer therapy. Since malignancy can dysregulate the hemostatic system, predisposing cancer patients to both thrombosis and hemorrhage, the administration of dual antiplatelet therapy (DAPT) to patients with cancer who suffer from acute coronary syndrome (ACS) or undergo percutaneous coronary intervention (PCI) is a clinical challenge to cardiologists. Apart from PCI and ACS, other structural interventions, such as TAVR, PFO-ASD closure, and LAA occlusion, and non-cardiac diseases, such as PAD and CVAs, may require DAPT. The aim of the present review is to review the current literature on the optimal antiplatelet therapy and duration of DAPT for oncologic patients, in order to reduce both the ischemic and bleeding risk in this high-risk population.

One-Year Outcomes in Anticoagulated Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the Greek Antiplatelet Atrial Fibrillation Registry.

ABSTRACT: GReek-AntiPlatElet Atrial Fibrillation registry is a multicenter, observational, noninterventional study of atrial fibrillation patients undergoing percutaneous coronary intervention. Primary endpoint included clinically significant bleeding rate at 12 months between different antithrombotic regimens prescribed at discharge; secondary endpoints included major adverse cardiovascular events and net adverse clinical events. A total of 647 patients were analyzed. Most (92.9%) were discharged on novel oral anticoagulants with only 7.1% receiving the vitamin K antagonist. A little over half of patients (50.4%) received triple antithrombotic therapy (TAT)-mostly (62.9%) for ≤1 month-whereas the rest (49.6%) received dual antithrombotic therapy (DAT). Clinically significant bleeding risk was similar between TAT and DAT [Hazard ratio (HR) = 1.08; 95% confidence interval (CI), 0.66-1.78], although among TAT-receiving patients, the risk was lower in those receiving TAT for ≤1 month (HR = 0.50; 95% CI, 0.25-0.99). Anticoagulant choice (novel oral anticoagulant vs. vitamin K antagonist) did not significantly affect bleeding rates ( P = 0.258). Age, heart failure, leukemia/myelodysplasia, and acute coronary syndrome were associated with increased bleeding rates. Risk of major adverse cardiovascular events and net adverse clinical events was similar between ΤAT and DAT (HR = 1.73; 95% CI, 0.95-3.18, P = 0.075 and HR = 1.39; 95% CI, 0.93-2.08, P = 0.106, respectively). In conclusion, clinically significant bleeding and ischemic rates were similar between DAT and TAT, although TAT >1 month was associated with higher bleeding risk.

Impact of Smoking Status on Mortality in STEMI Patients Undergoing Mechanical Reperfusion for STEMI: Insights from the ISACS-STEMI COVID-19 Registry.

The so-called "smoking paradox", conditioning lower mortality in smokers among STEMI patients, has seldom been addressed in the settings of modern primary PCI protocols. The ISACS−STEMI COVID-19 is a large-scale retrospective multicenter registry addressing in-hospital mortality, reperfusion, and 30-day mortality among primary PCI patients in the era of the COVID-19 pandemic. Among the 16,083 STEMI patients, 6819 (42.3%) patients were active smokers, 2099 (13.1%) previous smokers, and 7165 (44.6%) non-smokers. Despite the impaired preprocedural recanalization (p < 0.001), active smokers had a significantly better postprocedural TIMI flow compared with non-smokers (p < 0.001); this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. Active smokers had a significantly lower in-hospital (p < 0.001) and 30-day (p < 0.001) mortality compared with non-smokers and previous smokers; this was confirmed after adjustment for all baseline and procedural confounders, and the propensity score. In conclusion, in our population, active smoking was significantly associated with improved epicardial recanalization and lower in-hospital and 30-day mortality compared with previous and non-smoking history.

Inferior myocardial wall ischemia on SPECT-MPI in patients with non dominant right coronary artery and non significant coronary artery disease.

BACKGROUND: The impact of a non-dominant right coronary artery (NDRCA), on single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)has not been clarified. METHODS AND RESULTS: We compared SPECT-MPI results of consecutive patients without significant (diameter stenosis ≥50%)coronary artery disease (CAD) and a NDRCA (Group-1), with those of patients from our database without CAD and a dominant RCA (Group-2). All patients were subjected to SPECT-MPI with I.V. infusion of adenosine, and TC99-tetrofosmin. Group-1 included 69 patients (55 men, 79.7%), mean age 66.8 ± 9.8 years. Group-2 consisted of 79 patients (56 men, 70.9%), mean age 62.7 ± 11.5. There was no difference in demographics and CAD risk factors between the two groups. The SPECT-MPI revealed inferior wall ischemia, in 35 patients (50.7%), in Group-1 and 27 patients (34.1%), in Group-2 (P = 0.041). CONCLUSIONS: A relatively high rate of reversible SPECT-MPI perfusion defects may be anticipated in patients with an unobstructed NDRCA compared to patients with a dominant RCA.

Potential Relationship Between Lifestyle Changes and Incidence of Hospital Admissions for Acute Coronary Syndrome During the COVID-19 Lockdown.

Aims: To evaluate the impact of lockdown during the COVID-19 pandemic on lifestyle changes of the general population, and on admissions for acute coronary syndrome (ACS). Methods and Results: All ACS admissions during the COVID-19 lockdown (10 March to 4 May, 2020), in 3 municipalities (3 spoke, and 1 hub hospital), in Southwestern Greece (411,576 inhabitants), were prospectively recorded and compared to the equivalent periods during 2018, and 2019. A telephone survey of 1014 participants was conducted to explore the lifestyle habits of citizens aged ≥35-years-old before and during lockdown. The median ACS incidence rate decreased from 19.0 cases per week in 2018 and 21.5 in 2019 down to 13.0 in 2020 (RR: 0.66 during the Covid-19 lockdown; 95%CI: 0.53-0.82; P = 0.0002). This was driven by a significant reduction of admissions for Non-ST elevation myocardial infarction (NSTEMI) (RR: 0.68; 95%CI: 0.52-0.88; P = 0.0037), mainly in patients with a lower burden of cardiovascular risk factors, as we noticed an inverse association between the reduction of the incidence of ACS during the Covid-19 lockdown period and the number of registered patient risk factors. There was no difference in the rates of STEMI and population-based all-cause mortality across the examined time periods. The telephone survey demonstrated reduction of passive smoking, working hours, alcohol, junk food and salt consumption, and an increase in sleeping hours, mainly in participants with a lower burden of cardiovascular risk factors. Conclusions: A significant decline in ACS admissions during the COVID-19 lockdown was noted, affecting mainly NSTEMI patients with a lower burden of cardiovascular risk factors. This was accompanied by significant lifestyle changes. Thus, it is tempting to speculate that to some extend the latter might be associated with the observed decline in ACS admissions.

Rectosigmoid ischemia and cerebral coma following gadolinium-induced anaphylaxis: A new manifestation of Kounis syndrome presented as devastating complication.

Gadolinium-based contrast mediums are the most commonly used agents in magnetic resonance imaging for both angiography, and brain tumor enhancement due to their association with the degradation of the blood-brain barrier. When oxidation is removed from gadolinium medium and gadolinium salts, a silvery-white metal anions remain that are able to induce allergic reactions and anaphylaxis. Whereas such reactions are not common, other reactions including nephrogenic systemic fibrosis and acute kidney injury due to primary excretion of gadolinium from the kidneys and various cardiac arrhythmias including QTc electrocardiographic prolongation are occasionally encountered 1,2. Despite that gadolinium-based contrast mediums are characterized as benign agents, in some occasions they can lead to life threatening conditions and Kounis syndrome 2-5. The concurrence of acute coronary syndromes such as coronary spasm, acute myocardial infarction, and stent thrombosis, with conditions associated with mast-cell and platelet activation involving other interrelated and interacting inflammatory cells, such as macrophages and Tlymphocytes in the setting of allergic or hypersensitivity and anaphylactic or anaphylactoid insults constitute the Kounis syndrome 6. This syndrome is caused by inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet-activating factor, and a variety of cytokines and chemokines released during the degranulation process of these inflammatory cells. Platelets bearing specific fragment crystallizable region receptors are also involved in the activation cascade 7. All these inflammatory cells participate in an inflammatory cycle and activate each other via multidirectional signals.

Prevention of Radial Artery Occlusions Following Coronary Procedures: Forward and Backward Steps in Improving Radial Artery Patency Rates.

Radial artery (RA) occlusion (RAO) remains the Achilles heel of transradial coronary procedures. Although of silent nature, RAO is relatively frequent, results in graft shortage for future coronary artery bypass surgery, and may occur even after short-lasting, 5F coronary angiography (CAG). The most frequent predictors of RAO are RA size, body size, female gender, and periprocedural anticoagulation intensity. Methods to detect RAO are variable, of which the Barbeau test and ultrasonography have similar diagnostic accuracy. Data indicate that late RAO recanalization may occur. Meticulous handling of RA and the use of appropriate hemostatic devices and techniques along with sufficient heparin dose appear important measures to reduce RAO rates. Recent contradictory studies indicate that the decreasing incidence of RAO overtime is not as uniform as previously thought. In 2 meta-analyses, the benefit of higher over lower anticoagulation intensity became evident. As "it may all be appropriate anticoagulation" for a simplified approach against RAO, the results of an ongoing trial comparing 100 with 50 IU/kg body weight in transradial CAG are eagerly awaited.

Absence of differential effect of ticagrelor versus prasugrel maintenance dose on endothelial function in patients with stable coronary artery disease.

BACKGROUND: Endothelial function may be improved by ticagrelor through adenosine-mediated mechanisms. We aimed to assess the effect of ticagrelor versus prasugrel on endothelial function in patients with stable coronary artery disease (CAD). METHODS: In a prospective, randomized, crossover study, 22 stable CAD patients under prasugrel 10 mg once daily maintenance dose (MD) for at least 3 months were randomized to either ticagrelor 90 mg twice daily or prasugrel 10 mg once daily for 15 days with a direct treatment-crossover for another 15 days. Endothelial function was assessed by peripheral arterial tonometry (EndoPAT 2000 system, Itamar Medical, Caesarea, Israel) at Day 0 (randomization), Day 15, and Day 30. Reactive Hyperemia Index (RHI) was calculated by using an automated software, and endothelial dysfunction (ED) was defined as RHI <1.67. RHI at the end of the two treatment periods did not differ between ticagrelor and prasugrel MD treatments. Least squares estimates (95% confidence interval) were 1.78 (1.58-1.99) versus 1.88 (1.67-2.08), with a fixed estimate of -0.099 (95% CI: -0.45 to 0.25) for the difference between them (p = 0.5). ED rate did not differ significantly between ticagrelor and prasugrel (45.5% vs 45.5%, p = 0.6). CONCLUSIONS: In CAD patients, we have failed to find evidence of alteration of endothelial function following ticagrelor compared to prasugrel MD treatment, as assessed by peripheral arterial tonometry. CLINICALTRIALS. GOV UNIQUE IDENTIFIER: NCT01957540.

An uncommon variant of double-chambered right ventricle masquerading as double-chambered left ventricle.

We present a rare case of a double-chambered right ventricle masquerading as a double-chambered left ventricle, which was found incidentally on cardiac imaging in an adult female patient with atypical chest pain. The most common form of double-chambered right ventricle is characterized by compartmentalization of the right ventricle by muscular bands into 2 distinct chambers. The main features of this malformation are a pressure gradient between the 2 compartments, and the frequent (up to 90%) association with a membranous ventricular septal defect. In our case, the muscular band dividing the right ventricle was located in the inferoseptal part of the latter, creating a diminutive cavity that had no communication with the main right ventricle but communicated with the left ventricle creating the false impression of a double-chambered left ventricle. This constitutes a rare variant of double-chambered right ventricle with unknown clinical implications.

Contemporary Antiplatelet Treatment in Acute Coronary Syndrome Patients with Impaired Renal Function Undergoing Percutaneous Coronary Intervention.

OBJECTIVES: To assess the clinical impact of impaired renal function (IRF), in "real-world" acute coronary syndrome (ACS) patients, receiving clopidogrel, prasugrel, or ticagrelor. METHODS: This was a prospective, observational, multicenter, cohort study of ACS patients undergoing percutaneous coronary interventions (PCI) with IRF (creatinine clearance <60 mL/min by Cockroft-Gault equation), who were recruited into the Greek Antiplatelet Registry (GRAPE). Patients were followed-up until 1 year for major adverse cardiovascular events (MACE; a composite of death, nonfatal myocardial infarction, urgent revascularization, and stroke) and BARC (Bleeding Academic Research Consortium) bleeding. RESULTS: Out of 2,047 registered patients, there were 344 (16.8%) with IRF. At the 1-year follow-up, MACE occurred in 18.6 and 6.2% of those patients with and without IRF, respectively: adjusted hazard ratio (HR) = 2.13 (95% confidence interval, CI 1.16-3.91), p = 0.02. IRF patients were also at higher risk of death and BARC type ≥2 and ≥3 bleeding: adjusted HR = 3.55 (95% CI 1.73-7.27), p = 0.001; HR = 2.75 (95% CI 1.13-6.68), p = 0.03; and HR = 6.02 (95% CI 2.30-15.77), p < 0.001, respectively. Combined MACE and BARC type ≥2 bleeding occurred in 34.0 and 14.0% of those with and without IRF, respectively: adjusted HR = 2.65 (95% CI 1.36-5.16), p = 0.004. At discharge, clopidogrel was more frequently prescribed in IRF patients (61.0 vs. 33.1%, p < 0.001). CONCLUSIONS: Real-world ACS patients with IRF subjected to PCI demonstrate higher thrombotic and bleeding risks than patients with normal renal function.

Pulmonary valve replacement in patients with corrected tetralogy of Fallot.

Introduction: Development of pulmonary insufficiency in patients with surgically corrected tetralogy of Fallot (TOF) may lead to severe right heart failure with serious consequences. We herein present our experience with pulmonary valve replacement (PVR) in these patients. Methods: From 2005-2013, 99 consecutive patients (71 males/28 females, mean age 38±8 years), underwent PVR after 7 to 40 (mean 29 ± 8) years from the initial correction. Seventy nine of the symptomatic patients presented in NYHA II, 14 in III and 2 in IV. All underwent PVR with a stented bioprosthetic valve, employing a beating heart technique with normothermic extracorporeal circulation support. Concomitant procedures included resection of aneurysmal outflow tract patches (n = 37), tricuspid valve annuloplasty (n = 36), augmentation of stenotic pulmonary arteries (n = 9), maze procedure (n = 2) and pulmonary artery stenting (n = 4). Results: There were 2 perioperative deaths (2%). One patient developed sternal dehiscence requiring rewiring. Median ICU and hospital stay was 1 and 7 days respectively. Postoperative echocardiography at 6 and 12 months showed excellent bioprosthetic valve performance, significant decrease in size of the right cardiac chambers and reduction of tricuspid regurgitation (TR) in the majority of the patients. At mean follow-up of 3.6 ± 2 years, all surviving patients remain in excellent clinical condition. Conclusion: Probability of reoperation for pulmonary insufficiency in patients with surgically corrected TOF increases with time and timely PVR by preventing the development of right heart failure is crucial for long-term survival. Current bioprosthetic valve technology in combination with the beating heart technique provides excellent immediate and short-term results. Further follow-up is necessary to evaluate long-term outcome.

Needle versus cannula over needle for radial artery cannulation during transradial coronary angiography and interventions.

PURPOSE: To evaluate the efficacy of radial artery cannulation with needle versus cannula over needle during transradial coronary angiography and intervention. METHODS: Five hundred patients scheduled to undergo transradial catheterization were randomized between the two methods. Primary endpoint of the study was the combined endpoint of switching to another access site due to inability of successful sheath insertion or switching to another method of cannulation (from needle to cannula over needle and vice versa). RESULTS: The primary end point was met in 12 patients (4.8%) from the needle group and 14 patients (5.6%) from the cannula over needle group (p=0.695). There were no differences in switching of cannulation method [10 (4.0%)% versus 11 (4.4%), p=0.831], switching of access site [6 (2.8%) versus 9 (3.6%), p=0.441), time for artery cannulation [1.20 (0.80-2.20) min versus 1.26 (1.01-2.39) min, p=0.152], total procedure time [15.05 (9.47-29.03) min versus 19.14 (10.13-32.02) min, p=0.112] number of attempts [2 (1-4) versus 2 (1-5), p=0.244] and number of skin punctures [1 (1-2) versus 1 (1-2), p=0.399] before successful radial artery cannulation. There were no differences recorded in the safety endpoints of EASY grade III or more radial hematomas [2 (0.8%) versus 1 (0.4%), p=1.000] or the incidence of radial artery occlusion after the procedure [9 (3.6% versus 16 (6.8%), p=0.358]. CONCLUSION: Radial artery cannulation with needle and cannula over needle seems to be equal in terms of efficacy and safety.