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.

Mitral and Tricuspid Valve Disease in Athletes.

Observing mitral or tricuspid valve disease in an athlete raises many considerations for the clinician. Initially, the etiology must be clarified, with causes differing depending on whether the athlete is young or a master. Notably, vigorous training in competitive athletes leads to a constellation of structural and functional adaptations involving cardiac chambers and atrioventricular valve systems. In addition, a proper evaluation of the athlete with valve disease is necessary to evaluate the eligibility for competitive sports and identify those requiring more follow-up. Indeed, some valve pathologies are associated with an increased risk of severe arrhythmias and potentially sudden cardiac death. Traditional and advanced imaging modalities help clarify clinical doubts, allowing essential information about the athlete's physiology and differentiating between primary valve diseases from those secondary to training-related cardiac adaptations. Remarkably, another application of multimodality imaging is evaluating athletes with valve diseases during exercise to reproduce the sport setting and better characterize the etiology and valve defect mechanism. This review aims to analyze the possible causes of atrioventricular valve diseases in athletes, focusing primarily on imaging applications in diagnosis and risk stratification.

Watchful surgery in asymptomatic mitral valve prolapse.

The most common organic etiology of mitral regurgitation is degenerative and consists of mitral valve prolapse (MVP). Volume overload because of mitral regurgitation is the most common complication of MVP. Advocating surgery before the consequences of volume overload become irreparable restores life expectancy, but carries a risk of mortality in patients who are often asymptomatic. On the other hand, the post-surgical outcome of symptomatic patients is dismal and life expectancy is impaired. In the present article, we aim to bridge the gap between these two therapeutic approaches, unifying the concepts of watchful waiting and early surgery in a "watchful surgery approach".

Functional Mitral and Tricuspid Regurgitation across the Whole Spectrum of Left Ventricular Ejection Fraction: Recognizing the Elephant in the Room of Heart Failure.

Functional mitral regurgitation (FMR) and tricuspid regurgitation (FTR) occur due to cardiac remodeling in the presence of structurally normal valve apparatus. Two main mechanisms are involved, distinguishing an atrial functional form (when annulus dilatation is predominant) and a ventricular form (when ventricular remodeling and dysfunction predominate). Both affect the prognosis of patients with heart failure (HF) across the entire spectrum of left ventricle ejection fraction (LVEF), including preserved (HFpEF), mildly reduced (HFmrEF), or reduced (HFrEF). Currently, data on the management of functional valve regurgitation in the various HF phenotypes are limited. This review summarizes the epidemiology, pathophysiology, and treatment of FMR and FTR within the different patterns of HF, as defined by LVEF.

Tricuspid Valve Geometrical Changes in Patients with Functional Tricuspid Regurgitation: Insights from a CT Scan Analysis Focusing on Commissures.

BACKGROUND: Cardiac computed tomography (CT) provides important insights into the geometrical configuration of the tricuspid valve (TV). The purpose of the present study was to assess the geometrical changes of TV in patients with functional tricuspid regurgitation (TR) using novel CT scan parameters and to correlate these findings with echocardiography. METHODS: This single-center study enrolled 86 patients undergoing cardiac CT and divided them into two groups according to the presence or not of severe TR (43 patients with TR ≥ 3+ and 43 controls). The measurements collected were as follows: TV annulus area and perimeter, septal-lateral and antero-posterior annulus diameters, eccentricity, distance between commissures, segment between the geometrical centroid and commissures, and the angles of commissures. RESULTS: We found a significant correlation between all annulus measurements and the grade of TR, except in regard to angles. TR ≥ 3+ patients had significantly larger TV annulus area and perimeter, larger septal-lateral, and antero-posterior annulus dimensions, as well as larger commissural distance and centroid-commissural distance. In patients with TR ≥ 3+ and controls, the eccentricity index predicted a circular shape and an oval shape of the annulus, respectively. CONCLUSIONS: These novel CT variables focusing on commissures increase the anatomical understanding of the TV apparatus and the TV geometrical changes in patients with severe functional TR.

A sudden right-to-left shunt: the importance of evaluating patent foramen ovale during exercise.

A 55-year-old male affected by heart failure with reduced ejection fraction and a history of a transient cerebrovascular accident was accepted to the Cardiology Department for worsening dyspnea. A cardiopulmonary exercise test was performed after therapy optimization to further evaluate exercise intolerance. A rapid increase in the minute ventilation/carbon dioxide production slope, end-tidal oxygen pressure, and respiratory exchange ratio, with a concomitant decrease in end-tidal carbon dioxide pressure and oxygen saturation, were observed during the test. These findings indicate exercise-induced pulmonary hypertension leading to a right-to-left shunt. Subsequent echocardiography with a bubble test unveiled the presence of an unknown patent foramen ovale. It is, therefore, necessary to exclude a right-to-left shunt by cardiopulmonary exercise testing, particularly in patients predisposed to develop pulmonary hypertension during exercise. Indeed, this eventuality might potentially provoke severe cardiovascular embolisms. However, the patent foramen ovale closure in patients with heart failure with reduced ejection fraction is still debated because of its potential hemodynamic worsening.

Percutaneous Repair of Atrial Functional Tricuspid Regurgitation in Cardiac Amyloidosis: Combining Linear With Lateral Thinking.

Restrictive physiology, such as cardiac amyloidosis, compromises atrial and ventricular performance, often leading to "atrial" functional valvular regurgitation. While focusing on atrial functional tricuspid regurgitation we aimed at summarizing the pathophysiological characteristics of, and therapeutic options in, cardiac amyloidosis. (Level of Difficulty: Intermediate.).

The butterfly effect: Restoring the tricuspid coaptation after clipping the antero-septal commissure.

Edge-to-edge tricuspid transcatheter repair requires extensive echocardiographic planning before the procedure. Sometimes, anatomic features may anticipate a suboptimal result. For this reason, a tailored strategy is the key to the procedural success. We report a case of massive tricuspid regurgitation due to multiple complex mechanisms that was successfully treated by clipping the antero-septal commissure to restore functional coaptation of the valve leaflets at multiple sites.

Symptoms-to-emergency-call timing delay in acute coronary syndrome before and during COVID-19: independent predictors and their impact on mortality.

BACKGROUND: The COVID-19 pandemic severely impacted global health. The aim of this study was to compare predictors of symptoms-to-emergency-call timing delay in acute coronary syndrome (ACS) and their impact on mortality before and during the COVID-19 outbreak. METHODS: We collected sociodemographic, clinical data, procedural features, preadmission and intra-hospital outcomes of consecutive patients admitted for ACS in seventeen Italian centers from March to April 2018, 2019, and 2020. RESULTS: In 2020, a 32.92% reduction in ACS admissions was observed compared to 2018 and 2019. Unstable angina, typical and atypical symptoms, and intermittent angina were identified as significant predictors of symptoms-to-emergency-call timing delay before and during the COVID-19 pandemic (P<0.005 for all the items). Differently from 2018-2019, during the pandemic, hypertension and dyspnea (P=0.002 versus P=0.490 and P=0.001 vs. P=0.761 for 2018-2019 and 2020, respectively) did not result as predictors of delay in symptoms-to-emergency-call timing. Among these predictors, only the atypical symptoms (HR 3.36; 95% CI: 1.172-9.667, P=0.024) in 2020 and the dyspnea (HR 2.64; 95% CI: 1.345-5.190, P=0.005) in 2018-2019 resulted significantly associated with higher mortality. Finally, the family attendance at the onset of the symptoms resulted in a reduction in symptoms-to-emergency-call timing (in 2020 P<0.001; CI: -1710.73; -493.19) and in a trend of reduced mortality (HR 0.31; 95% CI: 0.089-1.079, P=0.066) in 2020. CONCLUSIONS: During the COVID-19 outbreak, atypical symptoms and family attendance at ACS onset were identified, respectively, as adverse and favorable predictors of symptoms-to-emergency-call timing delay and mortality.

Edge-to-Edge Repair for Tricuspid Valve Regurgitation. Preliminary Echo-Data and Clinical Implications from the Tricuspid Regurgitation IMAging (TRIMA) Study.

Background: The natural history of tricuspid valve regurgitation (TR) is characterized by poor prognosis and high in-hospital mortality when treated with isolated surgery. We report the preliminary echocardiographic and procedural results of a prospective cohort of symptomatic patients with high to prohibitive surgical risk and at least severe TR who underwent transcatheter edge-to-edge repair through the TriClipTM system. Methods: From June 2020 to March 2022, 27 consecutive patients were screened, and 13 underwent transcatheter TriClipTM repair. In-hospital, 30-day and six-month clinical and echocardiographic outcomes were collected. Results: Nine patients had severe, three massive and one baseline torrential TR. Sustained TR reduction of ≥1 grade was achieved in all patients, of which 90% reached a moderate TR or less. On transthoracic echocardiographic examination, there were significant reductions in vena contracta width (p < 0.001), effective regurgitant orifice area (p < 0.001) and regurgitant volume (p < 0.001) between baseline and hospital discharge. We also observed a significant reduction in tricuspid annulus diameter (p < 0.001), right ventricular basal diameter (p = 0.001) and right atrial area (p = 0.026). Conclusion: Treatment with the edge-to-edge TriClip device is safe and effective. The resulting echocardiographic improvements indicate tricuspid valve leaflet approximation does not just significantly reduce the grade of TR but also affects adjacent structures and improves right ventricular afterload adaptation.

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.

The Transaxillary Route as a Second Access Option in TAVI Procedures: Experience of a Single Centre.

Background: The aim of our study was to determine the feasibility and efficacy of transaxillary (TAX) TAVI in patients not eligible for the transfemoral route. Methods: This is a retrospective study of a single center. We analysed 262 patients treated with TAVI. In 17 patients (6.5%), the procedure was performed with the TAX approach. Procedural and hospital data, 30-day safety, and clinical efficacy were assessed and compared between the transfemoral and TAX groups. Results: In the TAX groups, we found a higher prevalence of men (p = 0.001), smokers (p = 0.033), and previous strokes (p = 0.02). The EUROSCORE II was higher in the TAX group (p = 0.014). The success rate of the device was 100%. TAX was associated with a longer procedure time (p = 0.001) and shorter median device time (p = 0.034) in minutes. Patients treated with TAX had a longer hospital stay (p = 0.005) and higher overall bleeding rate (p = 0.001). Peripheral neurological complications were more frequent with TAX (p = 0.001), which almost completely resolved by 30 days. Conclusions: TAX TAVI is safe and effective and should be considered as a second choice when transfemoral TAVI is not feasible due to severe comorbidities.

Glycaemic Control in Patients Undergoing Percutaneous Coronary Intervention: What Is the Role for the Novel Antidiabetic Agents? A Comprehensive Review of Basic Science and Clinical Data.

Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and revascularization through percutaneous coronary interventions (PCI) significantly improves survival. In this setting, poor glycaemic control, regardless of diabetes, has been associated with increased incidence of peri-procedural and long-term complications and worse prognosis. Novel antidiabetic agents have represented a paradigm shift in managing patients with diabetes and cardiovascular diseases. However, limited data are reported so far in patients undergoing coronary stenting. This review intends to provide an overview of the biological mechanisms underlying hyperglycaemia-induced vascular damage and the contrasting actions of new antidiabetic drugs. We summarize existing evidence on the effects of these drugs in the setting of PCI, addressing pre-clinical and clinical studies and drug-drug interactions with antiplatelet agents, thus highlighting new opportunities for optimal long-term management of these patients.

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.

The Incidence and Impact of In-Hospital Bleeding in Patients with Acute Coronary Syndrome during the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic increased the complexity of the clinical management and pharmacological treatment of patients presenting with an Acute Coronary Syndrome (ACS). AIM: to explore the incidence and prognostic impact of in-hospital bleeding in patients presenting with ACS before and during the COVID-19 pandemic. METHODS: We evaluated in-hospital Thrombolysis In Myocardial Infarction (TIMI) major and minor bleeding among 2851 patients with ACS from 17 Italian centers during the first wave of the COVID-19 pandemic (i.e., March-April 2020) and in the same period in the previous two years. RESULTS: The incidence of in-hospital TIMI major and minor bleeding was similar before and during the COVID-19 pandemic. TIMI major or minor bleeding was associated with a significant threefold increase in all-cause mortality, with a similar prognostic impact before and during the COVID-19 pandemic. CONCLUSIONS: the incidence and clinical impact of in-hospital bleeding in ACS patients was similar before and during the COVID-19 pandemic. We confirmed a significant and sizable negative prognostic impact of in-hospital bleeding in ACS patients.

New Guideline-Directed Treatments for Heart Failure: Navigating Through the Multiple Turns of Everyday Clinical Practice.

The new European guidelines for the treatment and management of heart failure (HF) introduce several new recommendations. The revised HF definition has abolished the term "mid-range," introducing the new concept of "mildly reduced" ejection fraction (EF), which now deserves consideration for therapies previously confined to reduced EF (HF with reduced EF). Following the introduction of sodium-glucose cotransporter 2 inhibitors, physicians should now combine up to 4 different drugs to improve HF with reduced EF prognosis, leading to new issues regarding tolerance and adherence to therapy. Transcatheter treatments of mitral and tricuspid regurgitation are progressively gaining increasing consideration among nonpharmacological strategies. Dedicated therapies for HF with preserved EF are still lacking. These are only some of the most relevant changes provided by European guidelines on HF that are addressed in the present editorial, taking into account the most updated American recommendations.

Transcatheter aortic valve implantation in patients with unruptured aortic root pseudoaneurysm: an observational study.

AIMS: Unruptured aortic root pseudoaneurysm (UARP) is a rare complication of aortic valve endocarditis. Infectious spread to the valvular annulus or myocardium can cause septic complications that manifest as wall thickening, and spontaneous abscess drainage leads to pseudoaneurysm formation. We report the first patient series in which transcatheter aortic valve implantation (TAVI) using a single valve-resolved aortic valvulopathy associated with UARP was performed. METHODS: At our center, from December 2017 to October 2019, 138 patients underwent TAVI for aortic valve stenosis and/or regurgitation, 20 of whom (12 female patients, 8 male patients) had associated incidental UARP and were considered as our study population. The average age of these patients was 76.9 ±â€Š5.2 years. All patients were assessed using preprocedural and postprocedural multimodality imaging, including transthoracic echocardiography, transesophageal echocardiography, and cardiac computed tomography angiography (CCTA). RESULTS: In all cases, the final angiographic examination showed correct valve positioning with complete coverage of the false aneurysm. Post-TAVI CCTA showed presence of total or subtotal UARP thrombosis. The mean follow-up period was 17.5 months (12-23 months). During follow-up, imaging showed normal prosthetic valve function, no significant leakage (trace or mild), and complete UARP exclusion in all patients, without any complications. CONCLUSION: In conclusion, percutaneous valve positioning can simultaneously solve pseudoaneurysm complications by excluding the sac and promoting thrombosis.