Coronary Chronic Total Occlusion Revascularization: When, Who and How?

Coronary chronic total occlusions (CTO) are an increasingly frequent entity in clinical practice and represent a challenging percutaneous coronary intervention (PCI) scenario. Despite data from randomized trials that have not yet demonstrated a clear benefit of CTO recanalization, the widespread of CTO-PCI has substantially increased. The improvement in operators' techniques, equipment, and training programs has led to an improvement in the success rate and safety of these procedures, which will represent an important field of future development of PCI. The present review will summarize clinical outcomes and technical and safety issues of CTO revascularization with the aim to guide clinical daily cath-lab practice.

Takotsubo Syndrome and Coronary Artery Disease: Which Came First-The Chicken or the Egg?

Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately.

Arrhythmias after COVID-19 Vaccination: Have We Left All Stones Unturned?

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders.

Relationship Between the Completeness of Revascularization and Myocardial Injury in Patients Treated With Percutaneous Coronary Intervention.

BACKGROUND: Clinical outcomes of patients suffering periprocedural myocardial injury and undergoing incomplete revascularization (IR) following percutaneous coronary intervention (PCI) has never been investigated. OBJECTIVE: To investigate the relationship between different thresholds of post-PCI cardiac troponin (cTn) elevation and revascularization completeness in determining long-term clinical outcomes. METHODS: Patients were stratified in tertiles according to preprocedural SYNTAX score (SS) (low: 0-6; medium: >6-11; high: >11) and residual SS (low: 0-4; medium: >4-8; high: >8). IR was defined by a rSS value >4. Three thresholds of myocardial injury were pre-specified: 5×, 35× and 70× 99th percentile upper reference limit (URL) increase of baseline cTn. Primary outcome was a composite of major adverse cardiac events (MACE) at two years of follow-up. RESULTS: 1061 patients undergoing PCI for stable coronary artery disease were enrolled. IR occurred in 249 (23.4 %) and major myocardial injury in 540 (50.9 %). Patients belonging to the highest tertile of SS showed an increased risk of experiencing IR and periprocedural myocardial injury. Two-year follow-up was available in 869. At multi-variate Cox's regression analysis, patients undergoing IR + cTn > 35 × URL and IR + cTn > 70 × URL showed an increased risk of MACE [HR 2.30 (1.19-4.41) and HR 3.20 (1.38-7.41); respectively]. CONCLUSIONS: Periprocedural myocardial injury is critically associated with MACE at two-year follow-up in patient treated with PCI who achieve IR. Despite conflicting evidence exists regarding the influence of periprocedural myocardial injury on clinical outcomes, patients undergoing IR seem to represent a high-risk subgroup.

Percutaneous treatment of a CTO in an anomalous right coronary artery: A rupture paved the way for new insights.

An anomalous aortic origin of a coronary artery (AAOCA) from the opposite sinus, with an interarterial course, has been associated with an increased risk of myocardial ischemia and sudden death. As the exact pathophysiology of AAOCA is not well understood, the clinical management is also not well defined. With increased use of non-invasive imaging, the diagnosis of AAOCA is increasing and the association of anomalous origin and atherosclerotic disease is becoming a more important topic. We report a rare case of AAOCA chronic total occlusion (CTO). A 40-year-old Caucasian man was referred for invasive coronary angiography (ICA) due to typical chest pain and positive myocardial scintigraphy. ICA demonstrated CTO of an anomalous right coronary artery (ARCA) originating from the left side of the ascending aorta with an interarterial course. There was no lesion in the left coronary artery. During the procedure, unexpected rupture of the coronary artery occurred after dilatation with a small balloon at low pressure. The complication in this case was handled with good procedural final result but was an occasion for a food for thought. Coronary artery perforations are rare but life-threatening procedural complications that are usually caused by predisposing anatomical and procedural factors. We issue a warning on the risk of complications during complex percutaneous coronary intervention of these arteries, and we reconsidered the pathophysiology of the anomaly in a way that could change the approach to the disease. Based on this complication, we hypothesized that the wall of the artery could be fragile due to histopathological alterations, which could have a role in the pathophysiology of coronary malignancy. Future autopsy studies should be focused on the analysis of the arterial wall of the patient affected by sudden death with this anomaly.

Novel Computed Tomography Variables for Assessing Tricuspid Valve Morphology: Results from the TRIMA (Tricuspid Regurgitation IMAging) Study.

BACKGROUND: Computed tomography (CT) is the recommended imaging technique for defining the anatomical suitability for current transcatheter technologies and planning tricuspid valve (TV) intervention. The aim of the Tricuspid Regurgitation IMAging (TRIMA) study was to assess the geometrical characteristics of the TV complex using novel CT parameters. METHODS: This prospective, single-center study enrolled 22 consecutive patients with severe tricuspid regurgitation, who underwent a cardiac CT study dedicated to the right chambers. The following variables were obtained: annulus area and perimeter, septal-lateral and antero-posterior diameters, tenting height, and anatomical regurgitant orifice area. Moreover, the following novel annular parameters were assessed: distance between commissures, distance between TV centroid and commissures, and angles between centroid and commissures. RESULTS: A significant phasic variability during the cardiac cycle existed for all variables except for eccentricity, angles, and distance between the postero-septal and antero-posterior commissure and distance between the centroid and antero-posterior commissure. There was a significant relationship between the TV annulus area and novel annular parameters, except for annular angles. Additionally, novel annular variables were found to predict the annulus area. CONCLUSIONS: These novel additional variables may provide an initial platform from which the complexity of the TV annular morphology can continue to be better understood for further improving transcatheter therapies.

Lymphadenopathy after the Anti-COVID-19 Vaccine: Multiparametric Ultrasound Findings.

Background: Post-anti-COVID-19 vaccine lymphadenopathy has recently been described in the literature. In this study, we investigated the multiparametric US findings of patients with post-vaccine lymphadenopathy and compared these findings among different anti-COVID-19 vaccines. Methods: We retrospectively evaluated 24 patients who underwent US between January and May 2021 due to post-anti-COVID-19 lymphadenopathy. The presence, size, location, number, morphology, cortex-hilum, superb microvascular imaging (SMI) and elastosonography of lymph nodes were assessed. Descriptive statistics were calculated and differences among anti-COVID-19 vaccines were analyzed using the Kruskal-Wallis test. A p-value ≤ 0.05 was considered statistically significant. Results: Sixty-six nodes were assessed. They were axillary (mean 1.6 cm ± 0.16) in 11 patients (45.8%) and supraclavicular (mean 0.9 cm ± 0.19) in 13 patients (54.2%). In 20 patients (83.3%), the number of nodes was ≤3. Prevalent US features included oval morphology (18, 75%), asymmetric cortex with hilum evidence (9, 37.5%), central and peripheral vascular signals (12, 50%) at SMI and elastosonography patterns similar to the surrounding tissue (15, 71.4%). No significant differences among the three anti-COVID-19 vaccines were observed (p > 0.05). Conclusions: Anti-COVID-19 vaccines may present lymphadenopathy with "worrisome" US features regarding size, shape, morphology, cortex-hilum, SMI and elastosonography. An awareness of the patient's history and US findings may help in the early recognition of this clinical scenario and in the appropriate selection of patients for a short-term US follow-up.

Sonography of abdominal wall vascular malformation: a case report and review of the literature.

Vascular anomalies are classified as vascular tumors (VT) and vascular malformations (VM). VTs are divided according to their clinical behavior, while VMs are classified according to their flow characteristics, histopathologic features, and associations with other anomalies. Sonography emerges as the diagnostic imaging method of first choice for assessing abdominal wall disorders and masses, thus representing a valuable tool for the diagnosis and follow-up of abdominal wall VMs. In this review, we report a case of abdominal wall arteriovenous malformation (AVM) in a 17-year old and briefly discuss the cases of abdominal wall VMs.

Co-expression of glycosylated aquaporin-1 and transcription factor NFAT5 contributes to aortic stiffness in diabetic and atherosclerosis-prone mice.

Increased stiffness characterizes the early change in the arterial wall with subclinical atherosclerosis. Proteins inducing arterial stiffness in diabetes and hypercholesterolaemia are largely unknown. This study aimed at determining the pattern of protein expression in stiffening aorta of diabetic and hypercholesterolaemic mice. Male Ins2+/Akita mice were crossbred with ApoE-/- (Ins2+/Akita : ApoE-/- ) mice. Relative aortic distension (relD) values were determined by ultrasound analysis and arterial stiffness modulators by immunoblotting. Compared with age- and sex-matched C57/BL6 control mice, the aortas of Ins2+/Akita , ApoE-/- and Ins2+/Akita :ApoE-/- mice showed increased aortic stiffness. The aortas of Ins2+/Akita , ApoE-/- and Ins2+/Akita :ApoE-/- mice showed greater expression of VCAM-1, collagen type III, NADPH oxidase and iNOS, as well as reduced elastin, with increased collagen type III-to-elastin ratio. The aorta of Ins2+/Akita and Ins2+/Akita :ApoE-/- mice showed higher expression of eNOS and cytoskeletal remodelling proteins, such as F-actin and α-smooth muscle actin, in addition to increased glycosylated aquaporin (AQP)-1 and transcription factor NFAT5, which control the expression of genes activated by high glucose-induced hyperosmotic stress. Diabetic and hypercholesterolaemic mice have increased aortic stiffness. The association of AQP1 and NFAT5 co-expression with aortic stiffness in diabetes and hypercholesterolaemia may represent a novel molecular pathway or therapeutic target.

An unexpected complication of a percutaneous coronary angioplasty.

Takotsubo cardiomyopathy (TCM) is characterized by transient ventricular dysfunction, classically in its apical and mid segments, in the absence of coronary lesions, and is often observed after intense stressful events and occasionally associated to an acute medical illness. We describe a case of TCM associated with coronary artery disease and triggered by a percutaneous coronary angioplasty. This case highlights the concept that a medical procedure can lead, in certain conditions, to TCM and provides new interesting insights on the pathophysiology of coronary syndromes.

Circannual rhythm of plasmatic vitamin D levels and the association with markers of psychophysical stress in a cohort of Italian professional soccer players.

Adequate plasmatic Vitamin D levels are crucial to maintain calcium homeostasis and bone metabolism both in the general population and in athletes. Correct dietary supply and a regular sun exposure are fundamental for allowing the desired and effective fitness level. Past studies highlighted a scenario of Vitamin D insufficiency among professional soccer players in several countries, especially in North Europe, whilst a real deficiency in athletes is rare. The typical seasonal fluctuations of Vitamin D are wrongly described transversally in athletes belonging to teams that play at different latitudes and a chronobiologic approach studying the Vitamin D circannual rhythm in soccer players has not been described yet. Therefore, we studied plasma vitamin D, cortisol, testosterone, and creatin kinase (CK) concentrations in three different Italian professional teams training at the same latitude during a period of two consecutive competitive seasons (2013 and 2014). In this retrospective observational study, 167 professional soccer players were recruited (mean age at sampling 25.1 ± 4.7 years) and a total of 667 blood drawings were carried out to determine plasma 25(OH)D, serum cortisol, serum testosterone and CK levels. Testosterone to cortisol ratio (TC) was calculated based as a surrogate marker of overtraining and psychophysical stress and each athlete was drawn until a maximum of 5 times per season. Data extracted by a subgroup of players that underwent at least 4 sample drawings along a year (N = 45) were processed with the single and population mean cosinor tests to evaluate the presence of circannual rhythms: the amplitude (A), acrophase (Φ) and the MESOR (M) are described. In total, 55 players (32.9%) had an insufficient level of 25(OH)D during the seasons and other 15 athletes (9.0%) showed, at least once, a deficiency status of Vitamin D. The rhythmometric analyses applied to the data of Vitamin D revealed the presence of a significant circannual rhythm (p < 0.001) with the acrophase that occurred in August; the rhythms of Vitamin D levels were not different neither among the three soccer teams nor between competitive seasons. Cortisol, testosterone and TC showed significant circannual rhythms (p < 0.001): cortisol registered an acrophase during winter (February) while testosterone and TC registered their peaks in the summer months (July). On the contrary, CK did not display any seasonal fluctuations. In addition, we observed weak but significant correlations between 25(OH)D versus testosterone (r = 0.29 and p < 0.001), cortisol (r = -0.27 and p < 0.001) and TC (r = 0.37 and p < 0.001). No correlation was detected between Vitamin D and CK. In conclusion, the correct chronobiologic approach in the study of annual variations of Vitamin D, cortisol and testosterone could be decisive in the development of more specific supplementation and injury prevention strategies by athletic trainers and physicians.

"State-of-Art" paper of the Italian Working Group on Atherosclerosis: Preclinical assessment of early coronary atherosclerosis.

Although the early diagnosis and treatment for acute myocardial infarction have improved over the past decades, the morbidity and mortality from coronary artery disease (CAD) remain significant in Europe and worldwide. It is estimated that the majority of people in the developed countries who die suddenly from CAD, have no prior manifestation of disease, and the majority of these individuals are not considered to be at high risk. Accurate identification of individuals at risk of such events before the clinical manifestations is therefore required. This "State-of-Art" paper of the Italian Working Group on Atherosclerosis aims to i. provide an overview of both the traditional and emerging non-invasive imaging techniques used to detect early atherosclerosis in the general population with moderate cardiovascular risk; ii. identify the rationale for screening asymptomatic patients with preclinical atherosclerotic lesions and the optimal algorithm that should be used to detect them; iii. discuss the future directions of atherosclerosis research, with special focus on nanotechnology, aimed at early identification and treatment of low- and intermediate-risk patients.

Novel Strategies in the Treatment of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by increased pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies confirmed the key role of endothelin (ET)-1 in the vasoconstriction and remodeling of pulmonary microcirculation during PAH. In responders patients, classical treatments for PAH are prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), which target prostaglandin I2, nitric oxide and endothelin pathways, respectively. Randomised, placebo-controlled trials have shown that ERAs improves haemodynamic parameters of the pulmonary circulation, functional capacity and clinical outcome in patients affected by PAH. Here, we will review the definition, classification and pathophysiology of PH. Furthermore, we will provide an up-to-date overview of currently recommended diagnostic and therapeutic work-up in PAH.

Pathways and Drugs in Pulmonary Arterial Hypertension - Focus on the Role of Endothelin Receptor Antagonists.

Pulmonary arterial hypertension (PAH) is a group of diseases characterized by a progressive increase of pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies have here confirmed the prominent role of endothelin (ET)-1 in vasoconstriction and remodelling of the pulmonary microcirculation. In patients who are acute-vasoreactive, classical treatments for PAH are calcium channels blockers (CCBs), while drugs targeting the prostacyclin, nitric oxide and endothelin pathways, i.e., prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), respectively, are indicated in non-vasoreactive patients or in vasoreactive patients not responding to initial CCB therapy. Randomised, placebo-controlled trials have shown that ERAs improve pulmonary haemodynamics, exercise capacity, functional status and clinical outcome in patients with PAH. Here we provide an overview of the currently recommended diagnostic and therapeutic work-up in PAH, with special emphasis on ERAs.

Assessment of Biventricular Function by Three-Dimensional Speckle-Tracking Echocardiography in Secondary Mitral Regurgitation after Repair with the MitraClip System.

BACKGROUND: The goal of this study was to determine changes in left ventricular (LV) and right ventricular (RV) function with three-dimensional (3D) speckle-tracking echocardiography (STE) after percutaneous mitral valve repair with the MitraClip system in high-risk surgical patients with moderate to severe or severe secondary mitral regurgitation (MR). METHODS: Thirty-two patients with MR undergoing MitraClip were prospectively included. Patients underwent two-dimensional (2D) and 3D transthoracic echocardiography before clip implantation and after 6-month follow-up. LV and RV longitudinal strain was obtained by 2D STE and 3D STE. LV circumferential, radial, and area strain was calculated by 3D STE. Data analysis was performed offline. RESULTS: At 6-month follow-up, significant improvements were seen in LV 2D global longitudinal strain (P < .005), 3D global longitudinal strain (P = .0002), and 3D area strain (P = .0001). Overall, significant improvements were also seen in 3D RV ejection fraction (P < .05) and 3D RV free-wall longitudinal strain (P < .05). A poor increase in LV strain after clip implantation (P = NS) occurred in patients with pronounced preexisting RV dysfunction. The areas under the receiver operating characteristic curves for LV and RV 3D speckle-tracking echocardiographic parameters showed high discriminative values (range, 0.87-0.91) in predicting unfavorable outcomes with persistent symptoms (New York Heart Association class > II) after the procedure. CONCLUSIONS: Three-dimensional STE showed overall LV and RV strain improvement after clip implantation as well as lower postprocedural LV strain values in patients with worse preexisting RV function. These findings could help in guiding MR treatment strategies, suggesting different therapies in the presence of marked RV impairment or anticipating the procedure in case of evolving RV dysfunction.

Three-dimensional echocardiography and 2D-3D speckle-tracking imaging in chronic pulmonary hypertension: diagnostic accuracy in detecting hemodynamic signs of right ventricular (RV) failure.

BACKGROUND: Our aim was to compare three-dimensional (3D) and 2D and 3D speckle-tracking (2D-STE, 3D-STE) echocardiographic parameters with conventional right ventricular (RV) indexes in patients with chronic pulmonary hypertension (PH), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure. METHODS AND RESULTS: Seventy-three adult patients (mean age, 53±13 years; 44% male) with chronic PH of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary PH from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary PH from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements (RV-fractional area change-tricuspid annular plane systolic excursion) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes and global and regional ejection fraction (3D-RVEF) were determined. RV strains were calculated by 2D-STE and 3D-STE. RV 3D global-free-wall longitudinal strain (3DGFW-RVLS), 2D global-free-wall longitudinal strain (GFW-RVLS), apical-free-wall longitudinal strain, basal-free-wall longitudinal strain, and 3D-RVEF were lower in patients with precapillary PH (P<0.0001) and postcapillary PH (P<0.01) compared to controls. 3DGFW-RVLS (hazard ratio 4.6, 95% CI 2.79 to 8.38, P=0.004) and 3D-RVEF (hazard ratio 5.3, 95% CI 2.85 to 9.89, P=0.002) were independent predictors of mortality. Receiver operating characteristic curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of RV failure were 39% for 3D-RVEF (AUC 0.89), -17% for 3DGFW-RVLS (AUC 0.88), -18% for GFW-RVLS (AUC 0.88), -16% for apical-free-wall longitudinal strain (AUC 0.85), 16 mm for tricuspid annular plane systolic excursion (AUC 0.67), and 38% for RV-FAC (AUC 0.62). CONCLUSIONS: In chronic PH, 3D, 2D-STE and 3D-STE parameters indicate global and regional RV dysfunction that is associated with RV failure hemodynamics better than conventional echo indices.

Multimodality imaging for pre-clinical assessment of Fabry's cardiomyopathy.

Anderson Fabry's disease (AFD) is a rare but underdiagnosed intracellular lipid disorder which can cause left ventricular hypertrophy (LVH). Pre-clinical diagnosis of Fabry's disease is important as it permits early stratification for enzyme replacement therapy, improving the patient's long-term prognosis, avoiding progression to irreversible fibrosis, and preventing cardiovascular complications. Combinations of imaging modalities that integrate the strengths of each modality and at the same time eliminate weaknesses of an individual modality can offer improved diagnostics, therapeutic monitoring, and pre-clinical assessment of Fabry's disease. This review discusses the advantages and challenges in developing multimodality imaging systems of Fabry's cardiomyopathy, highlights some successful combinations that are now routinely used in the clinic and in research, and discusses recent advances in multimodality instrumentation that may offer new opportunities for pre-clinical assessment of this disease.