Around half of the patients undergoing an elective coronary angiogram to investigate typical stable angina symptoms are found to have non-obstructive coronary arteries (defined as < 50% stenosis). These patients are younger with a female predilection. While underlying mechanisms responsible for these presentations are heterogeneous, structural and functional abnormalities of the coronary microvasculature are highly prevalent. Thus, coronary microvascular dysfunction (CMD) is increasingly recognised as an important consideration in patients with non-obstructive coronary arteries. This review will focus on primary coronary microvascular disorders and summarise the four common clinical presentation pictures which can be considered as endotypes - Microvascular Ischaemia (formerly “Syndrome X”), Microvascular Angina, Microvascular Spasm, and Coronary Slow Flow. Furthermore, the pathophysiological mechanisms associated with CMD are also heterogenous. CMD may arise from an increased microvascular resistance, impaired microvascular dilation, and/or inducible microvascular spasm, ultimately causing myocardial ischaemia and angina. Alternatively, chest pain may arise from hypersensitivity of myocardial pain receptors rather than myocardial ischaemia. These two major abnormalities should be considered when assessing an individual clinical picture, and ultimately, the question arises whether to target the heart or the pain perception to treat the anginal symptoms.

Emergent reperfusion therapies have improved acute ischemic stroke prognosis, but many patients are still bound to bad clinical outcome, probably because of our incomplete knowledge of its pathophysiology. Thanks to mechanical thrombectomy, occluding material is available for histological analysis. Several studies investigated the possible relationship between thrombus composition and clinical, procedural, and radiological variables of acute ischemic stroke. The potential value of thrombus analysis as a tool for clinical practice and research is still not defined, as data from the literature are heterogeneous and sometimes conflicting. We propose a review of the existing literature regarding histological analysis of thrombi in acute ischemic stroke. We classified articles on clot composition according to the clinical variable explored in each study. We first distinguished articles about etiology, procedural, and radiological variables, and then we performed a subclassification for each group. This review could help both in the interpretation of thrombus analysis in clinical practice and in its usage for future research.

Repeat revascularization after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is one of the most common long-term complications which warrants continuous clinical follow up. Re-interventions negatively impact long-term survival in patients with coronary artery disease. The repeat revascularization after PCI can be either a target lesion revascularization (stent thrombosis/in-stent restenosis) or a revascularization of native coronary artery after PCI (target vessel revascularization/non-target vessel revascularization). The EVENT registry reports that repeat revascularization rates in patients undergoing PCI is 12% in the first year of follow up. Repeat revascularization with additional stent deployment increases the rate of stent thrombosis and restenosis, thereby leading to recurrent ischemic events. Repeat revascularization after CABG can be either in the early postoperative period or later due to native disease progression or late graft stenosis. The need for re-intervention after surgical or percutaneous revascularization is inevitable and is dependent on modifiable and non-modifiable risk factors.

Chronic dissection of the thoracoabdominal aorta may require surgical repair for aneurysm, malperfusion, or rupture. Endovascular repair is made difficult by a noncompliant dissection septum, visceral vessels arising from different lumens, and the common use of diseased aortic landing zones. Thus, open repair remains the gold standard in terms of favorable outcomes and durability. During thoracoabdominal aortic repair, we use a multimodal strategy to prevent spinal cord and visceral or renal artery ischemia; key modalities include cerebrospinal fluid drainage, left heart bypass with and without visceral protection, cold renal protection, and aggressive reimplantation of intercostal or lumbar arteries. Patients with chronic dissection require lifelong surveillance, as there is a significant risk for subsequent intervention on unrepaired aortic segments.

The low cardiac output syndrome describes the phenomenon of the reduction of cardiac output that can occur following cardiac surgery requiring cardiopulmonary bypass. If unrecognized or untreated, this condition can result in significant morbidity and mortality. Along with non-pharmacologic therapies, pharmacologic agents used to help manage the low cardiac output syndrome include catecholamine inotropes, inodilators, systemic vasodilators, pulmonary vasodilators, and other classes of medications. We summarize the rationale and key evidence supporting the use of these therapies in children. In addition, utilizing provider surveys and registry reviews, we describe the current trends in the use of these medications and the variation demonstrated between providers and centers. Given the heterogeneous etiology of low cardiac output syndrome, successful management requires that pharmacologic therapies be tailored to the physiologic derangements of each patient.

Cytosorb, an extracorporeal blood purification system, utilises the principles of haemoadsorption to remove low molecular weight substances from the blood, including multiple cytokines such as interleukin (IL)-1b, IL-6, IL-8, and tumour necrosis factor-α, and anti-platelet drugs aiming to improve clinical outcomes. Given the prominent role of pro-inflammatory cytokines in various inflammatory states, Cytosorb has seen growing application as a therapeutic immunomodulator including surgery. This review focuses on the effects of the use of Cytosorb in patients undergoing coronary artery bypass grafting (CABG) and the indications of removal of cytokines and anti-platelet agents such as ticagrelor. The evidence supports the feasibility and safety profile of Cytosorb, with no device-related adverse events reported in all studies. Initial studies suggest significant potential for Cytosorb in urgent or emergency CABG surgery to remove anti-platelet medication with promising benefits on clinical outcomes including fewer blood product transfusions, decreased length of intensive care unit stay, and lower re-sternotomy rates. Furthermore, a cost saving analysis indicated that intraoperative removal of ticagrelor with Cytosorb would be cost effective in the setting of emergency cardiac surgery. However, the evidence remains inconclusive when Cytosorb is used in elective CABG surgery for cytokine removal. Definite high quality clinical trials for both indications for Cytosorb in CABG surgery are needed to clarify if there is a clinically significant benefit in clinical outcomes. There is substantial trial activity for the application of Cytosorb in higher risk cardiac surgery to establish the place of Cytosorb in future treatment pathways in cardiac surgery.

Advocacy organizations have long played a role in advancing care and research for patients affected by rare disease. Angioma Alliance has served traditional functions of organizing scientific meetings and creating shared resources like a tissue bank and a patient registry. Uniquely, the organization has employed creative patient engagement methods like subsidized genetic testing as well as targeting special populations to expand research participation and understanding of the illness. Special populations include those with CCM3 mutations, the CCM1 Common Hispanic Mutation, and Black patients.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a distinct group of systemic vasculitis with severe multi-organ involvement. It includes three types: granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA). Cutaneous manifestations are present at the time of presentation in around 35% of cases and are more frequently encountered in EGPA than in GPA or MPA. They can also occur during the course of the disease or mark a disease relapse. They can be classified into specific or non-specific according to the presence or absence of vasculitis, whether or not associated with granuloma, in skin biopsies. The most common presentation of vasculitic skin lesions in AAV is palpable purpura. Other manifestations include hemorrhagic blisters, tender subcutaneous nodules, livedo reticularis/racemosa, painful ulcers that may mimic pyoderma gangrenosum (PG), and digital gangrenes. A wide range of non-specific cutaneous manifestations can occur in association with AAV including urticarial rash, prurigo, sterile pustules, and oral lesions. The presence of cutaneous lesions is usually associated with severe organ involvement and systemic manifestations. Since skin lesions in AAV can occur in other types of vasculitis and in other disorders, attributing them to AAV requires meticulous clinical, laboratory, and serological correlation. Awareness of cutaneous lesions of AAV is important for all physicians working in the field of systemic vasculitis as a skin biopsy may provide an easy clue to diagnose AAV in such cases.

Aim: We retrospectively examined the impact on the rate of survival of pain-free home-based exercise in diabetic peripheral artery disease patients compared to patients receiving usual care.

Methods: In total, 202 patients at Fontaine’s Stage II with diabetes were studied. Half were enrolled in a structured home-based exercise program (E), whereas the other half received walking advice as the active control group (C). Long-term clinical outcomes at five years were gathered from the Emilia-Romagna Health Service Registry, with survival probability selected as the primary outcome.

Results: At baseline, the two groups did not differ for any demographic or clinical characteristics. High adherence to the program was recorded in Group E (88% of home-walking sessions executed, with an average distance walked during the program of 174 km). After five years, a survival rate of 90% for Group E and 60% for Group C was observed, with a significantly (P < 0.001) higher mortality risk for Group C [Hazard ratio (HR) = 3.92]. Additionally, among secondary outcomes, Group E showed a significantly (P = 0.048) lower rate of peripheral revascularizations than Group C (15% vs. 24%, respectively; HR = 1.91), all-cause hospitalizations (P = 0.007; 61% vs. 80%, HR = 1.58), and amputations (P = 0.049; 6% vs. 13%, HR = 2.47). In a Cox multivariate-proportional regression model of the entire population, the predictors of survival probability were age (HR = 1.05), Charlson index (HR = 1.24), lower ankle-brachial index (HR = 6.66), and control group (HR = 4.99).

Conclusion: A simple sustainable program aimed at improving mobility of diabetic patients with claudication at high cardiovascular risk was associated with better survival and long-term clinical outcomes.

The use of cardiac magnetic resonance (CMR) for accurate morphological assessment of cardiomyopathies is well described. CMR tissue characterization with late gadolinium enhancement and parametric mapping is highly promising in differentiating key etiologies of left ventricular hypertrophy, diagnosing cardiac involvement in systemic amyloidosis, detecting early disease, and tracking changes over time, as well as providing valuable prognostic information. This review focuses on the typical imaging findings in cardiac amyloidosis by CMR, highlighting its potentials with respect to traditional imaging techniques. Furthermore, the diagnostic and prognostic role of CMR parameters and the future perspectives related to the newest applications are addressed.

Aim: To investigate the changes of insulin resistance (IR), parameters of arterial stiffness, concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiographic parameters in patients with cardiac autonomic neuropathy (CAN) and type 2 diabetes mellitus (T2D).

Methods: This study recruited 44 patients with T2D (19 patients without CAN and 25 patients with CAN) and 15 healthy volunteers. Arterial stiffness, immunoreactive insulin, homeostasis model assessment IR, NT-proBNP parameters, and echocardiographic examination were assessed.

Results: Development of CAN is associated with increase in NT-proBNP levels, IR parameters, and arterial stiffening. Among patients with CAN, arterial stiffness parameters were considered as high. We found out that among patients of this group, the value of brachial augmentation index was normal in 52%, elevated in 40%, and pathological in 8%; pulse wave velocity was normal in 16%, elevated in 52%, and pathological in 32% of cases. Obtained results showed that development of CAN is accompanied by more pronounced left ventricular diastolic dysfunction and by formation of left ventricular hypertrophy (LVH), mostly by concentric type. Among patients of this group concentric LVH was diagnosed among 76 % and eccentric LVH among 16% of persons. Multiple regression analysis, after controlling for age, sex, diabetes duration, blood pressure, HbA1c, and left ventricular mass index, showed an independent association of heart rate response to deep breathing with pulse wave velocity (P < 0.001).

Conclusion: Development of CAN is associated with increased IR parameters, increased levels of NT-proBNP, arterial stiffening, left ventricular diastolic dysfunction, and formation of LVH, mostly by concentric type.

Aim: Mutated transthyretin (TTRv) cardiac amyloidosis (CA) represents an uncommon form of CA. Our study aimed to assess the best echocardiographic prognostic parameter in the early stage of TTRv amyloidosis with cardiomyopathy.

Methods: In total, 99 patients with TTRv in New York Heart Association class I or II and with no clinical history of previous cardiac disease were studied. Assessment with ^99mTc-DPD whole-body scan showed CA in 46 patients. At the first medical contact, an echocardiographic examination was performed. In addition to conventional left ventricular (LV), echocardiographic measurements [ejection fraction (EF), dimensions and diastolic function, global longitudinal strain (GLS), longitudinal strain of the 4 apical segments, longitudinal strain of the 12 mid-basal segments (MBLS)] and their ratio [relative regional strain ratio (RRSR)] were obtained. Patient outcome was evaluated during a follow-up with an average duration of six years. Cardiac death and appropriate implantable cardiac defibrillator (ICD) shock were considered major events.

Results: A higher value of LV thickness, E/E’, and RRSR and lower LV volumes, EF, GLS, MBLS were observed in patients with CA than the ones with only TTRv. During follow-up (median of 7.7 years), 25 major events (23 cardiac death and 2 appropriate ICD shocks) occurred. The logistic univariate analyses showed that LV EF, LV septal thickness, E/E’, GLS, and MBLS were all predictors of cardiovascular death. In multivariate analysis, MBLS was the only independent predictor of major events. A cut off of -14 of MBLS was selected as the best value to discriminate a worse prognosis on Kaplan-Meyer analysis.

Conclusion: Longitudinal dysfunction is observed in the early stages of ATTRv amyloidosis with cardiomyopathy. Medio-basal LV longitudinal dysfunction is a strong independent echocardiographic predictor of cardiac death.

Cardiac amyloidosis (CA) is a life-threatening disease caused by extracellular deposition of amyloidogenic proteins in the heart tissue; it could be associated with a poor prognosis and remains underdiagnosed and underestimated. During the last years, bone scintigraphy has been widely used to facilitate the diagnosis of CA, avoid endomyocardial biopsy, and differentiate amyloid light-chain amyloidosis from transthyretin amyloidosis. Technetium-99m pyrophosphate (^99mTc-PYP) is the most used tracer in the United States, but a standardized and shared acquisition protocol is still lacking; technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) is widely used in Europe and can count on a more grounded data than ^99mTc-PYP. Both tracers suffer from some diagnostic limitations (due to their biochemical characteristics) and pitfalls that can lead to a misdiagnosis of CA. We aim to briefly describe the main differences between ^99mTc-PYP and ^99mTc-DPD, analyzing the data available in the literature and highlighting the most frequent causes of misdiagnosis and pitfalls. Both ^99mTc-DPD and ^99mTc-PYP show good accuracy for the diagnosis of CA with high specificity and sensibility. Nevertheless, to achieve this accuracy, the correct acquisition protocols must be followed for each tracer, as suggested in the latest recommendation. Proper diagnosis of CA has a crucial role in patient management; therefore, it is important for nuclear physicians to have the most specific approaches in acquiring and interpreting bone scintigraphy for transthyretin cardiac amyloidosis.

In children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections typically result in a less severe coronavirus 19 (COVID-19) presentation than in adults. However, a subset of children presents with severe multisystem inflammation associated with recent SARS-CoV-2 infection or COVID-19 exposure in the previous weeks. The Center for Disease Control (CDC) has termed this condition a multisystem inflammatory syndrome in children (MIS-C). MIS-C causes significant cardiovascular involvement, which can be a determinant of clinical course and outcomes. A subset of MIS-C patients presents with hypotension and shock either from acute myocardial dysfunction or systemic vasodilation, with at least of third of patients developing cardiac manifestations from the illness. In addition, myocarditis, pericarditis, valvular regurgitation, coronary artery involvement, and arrhythmias have been reported, with a smaller subset of patients requiring extracorporeal membrane oxygenation. Here, we report our institutional experience of MIS-C over the last year and present a narrative review of cases reported in the literature. In addition, we discuss the clinical protocol of diagnosis and acute and follow-up management of these patients with MIS-C.

Pregnancy is complicated by maternal cardiovascular disease in 1%-4% of cases. With advances in management of congenital heart diseases (CHDs), the survival to adulthood and childbearing age is increasing all over the world. The physiological adaptation during pregnancy adds to the hemodynamic burden of CHD, and, hence, many women are diagnosed with CHD for the first time during pregnancy, more so in developing countries. The type of underlying CHD and pre-pregnancy hemodynamics determine the risk of developing complications during pregnancy. Hence, pre-pregnancy risk stratification and counseling are a crucial part of management plan. Some of the serious CHDs are best treated in the preconception stage. The maximum chance of developing complications is between 28 and 32 weeks of gestation, during labor, and up to two weeks after delivery. Common complications in women with CHD during pregnancy and labor include heart failure, arrhythmias, bleeding/thrombosis, infective endocarditis, and rarely maternal death. Fetal complications include abortion, stillbirth, prematurity, low birth weight, and CHD. Comprehensive knowledge of these complications and their management is very important as an experienced multidisciplinary team is critical for improving outcome of these patients. Special care is required for pregnant women who have pulmonary hypertension, due to either Eisenmenger syndrome or other causes, severe valve stenosis, aortopathy associated with bicuspid aortic valve/coarctation, or severe cyanotic CHDs. Most women with CHD are at low risk, and successful pregnancy is feasible in the majority with optimal management.

Aim: Women with evidence of ischemia and no obstructive coronary artery disease (INOCA) have an increased risk of major adverse cardiac events, including heart failure with preserved ejection fraction (HFpEF). To investigate potential links between INOCA and HFpEF, we examined pathophysiological findings present in both INOCA and HFpEF.

Methods: We performed adenosine stress cardiac magnetic resonance imaging (CMRI) in 56 participants, including 35 women with suspected INOCA, 13 women with HFpEF, and 8 reference control women. Myocardial perfusion imaging was performed at rest and with vasodilator stress with intravenous adenosine. Myocardial perfusion reserve index was quantified as the ratio of the upslope of increase in myocardial contrast at stress vs. rest. All CMRI measures were quantified using CVI42 software (Circle Cardiovascular Imaging Inc). Statistical analysis was performed using linear regression models, Fisher’s exact tests, ANOVA, or Kruskal-Wallis tests.

Results: Age (P = 0.007), Body surface area (0.05) were higher in the HFpEF group. Left ventricular ejection fraction (P = 0.02) was lower among the INOCA and HFpEF groups than reference controls after age adjustment. In addition, there was a graded reduction in myocardial perfusion reserve index in HFpEF vs. INOCA vs. reference controls (1.5 ± 0.3, 1.8 ± 0.3, 1.9 ± 0.3, P = 0.02), which was attenuated with age-adjustment.

Conclusion: Reduced myocardial perfusion reserve appears to be a common pathophysiologic feature in INOCA and HFpEF patients.

Atrial fibrillation (AF) is a common preoperative comorbidity and post-operative complication associated with cardiac surgery and is recognized as a significant predictor of adverse clinical outcomes. This review aims to highlight the current literature regarding the incidence, risk factors, and outcomes of atrial fibrillation in patients undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) procedures. A literature search of relevant articles was conducted via PubMed, Medline, and EMBASE. Pre-existing AF is seen in 6.3%-35.2% of SAVR patients and 15.7%-48.9% of TAVR patients and is associated with increased risk of mortality (OR = 2.2) and stroke (OR = 5.9). Postoperative AF (POAF) is more common after SAVR and in patients with hemodynamic instability. The rates for POAF range from 11.1%-84% following SAVR and range from 3.0%-55.6% following TAVR. In-hospital mortality (7.8% vs. 3.4%; P < 0.01) and stroke (4.7% vs. 2.0%; P < 0.01) are higher in the POAF group. POAF can be prevented via prophylactic antiarrhythmic medications and atrial pacing. Therapeutic anticoagulation is recommended as it reduces the risk of thrombotic complications following SAVR and TAVR procedures in the setting of POAF. Compared to those not on anticoagulant therapies, patients on anticoagulation have decreased rates of stroke (1.7% vs. 5.5%) and fewer 30-day thrombotic complications (3% vs. 40%). These preventive measures are essential as POAF is associated with more thromboembolic events, longer hospital stays, and higher overall morbidity and mortality rates.

Late-life depression (LLD) is a common complex mood disorder with high comorbidity of both psychiatric and physical diseases, cognitive decline, and increased mortality. The mechanisms underlying LLD are incompletely understood. The heterogeneity of depression complicates research into the underlying mechanisms, and factors involved in LLD may differ from those involved in early-life depression. This narrative review provides an overview of (micro-)vascular and metabolic factors involved in the development of LLD. Evidence suggests that cerebral small vessel disease, generalized microvascular dysfunction, and metabolic risk factors, including diabetes and inflammation, may contribute to the development of LLD, while the role of neurodegeneration needs further in-depth investigation. Accordingly, vascular and metabolic factors may provide promising targets for the prevention and improvement of treatment of LLD. Guidelines to screen for LLD in cardiovascular care need further implementation, as do integrated care approaches that treat LLD and diabetes jointly. However, intervention studies are needed to assess which interventions are appropriate and most effective in clinical practice.

Septal defects together account for the majority of the congenital heart defects (CHD); these can occur in isolation or associated with other CHDs. Hemodynamic manifestations are dependent upon the size, location, and the number of the defects, along with the associated lesions. For example, atrial septal defects result in the right ventricular volume overload, whereas the ventricular septal defect (VSD) results in the left heart volume overload. Knowledge of septal anatomy is crucial to understanding these lesions, their hemodynamic significance, and thus better plan management, including interventions. Noninvasive imaging of simple septal defects by various modalities will be reviewed; atrioventricular septal defects, anomalous pulmonary venous connections, patent ductus arteriosus, and complex cardiac conditions with VSD will not be discussed in this chapter.

Heart murmurs are frequently heard, and the murmurs are the usual cause for uncovering heart defects in pediatric patients. The murmurs are grouped into systolic murmurs, diastolic murmurs, and continuous murmurs. Cautious assessment of the murmur and associated abnormalities in physical examination are likely to produce correct diagnosis of the cause of the murmur. Sometimes it may be necessary to utilize noninvasive and invasive (rarely) investigations to achieve an accurate diagnosis. Nonetheless, such diagnostic studies may frequently be required for quantification, and before intervention either by transcatheter methods or by surgery.

This review describes principles of echocardiography and Doppler, outlines the techniques of echo-Doppler studies, presents methods of assessment of pressure in the pulmonary artery, reviews methodology for appraisal of ventricular function, and demonstrates the usefulness of echo in evaluating multiple neonatal issues including distressed neonate, infant of a diabetic mother, tracheo-esophageal fistula, Down syndrome, and cardiomegaly.

This review describes echocardiographic features of commonly encountered acyanotic congenital heart defects. Echo-Doppler features of lesions causing obstruction, namely aortic stenosis, aortic coarctation, stenosis of the pulmonary valve and pulmonary arteries were initially presented followed by discussion of lesions with left-to-right shunt namely, atrial and ventricular septal defects, patent foramen ovale, patent ductus arteriosus (PDA), and atrioventricular septal defect. A special section dedicated to evaluating hemodynamically significant PDAs in premature infants was also included. Coronary artery anomalies (both congenital and acquired) were reviewed at the conclusion of the paper.

This review describes echocardiographic features of commonly encountered cyanotic congenital heart defects. Echo-Doppler characteristics of more commonly seen defects: tetralogy of Fallot, transposition of the great arteries, tricuspid atresia, total anomalous pulmonary venous connection, and truncus arteriosus were first discussed. Then, hypoplastic left heart syndrome followed by less commonly observed lesions such as double-outlet right ventricle, double-inlet left ventricle, interrupted aortic arch, pulmonary atresia with an intact ventricular septum, congenitally corrected transposition of the great arteries, Ebstein’s anomaly of the tricuspid valve, and mitral atresia with normal aortic root were reviewed.

New-onset postoperative atrial fibrillation (POAF) develops in 10%-50% of patients after cardiac surgery. In this review, we focus on risk factors associated with POAF and the different pharmacological strategies used for prophylaxis, with special attention to amiodarone. The use of amiodarone will be discussed both as a prophylactic regimen used before and following cardiac surgery, but also as a rhythm control treatment in patients who develop POAF. Finally, we conclude by reviewing gaps in the literature on amiodarone and further studies which could close these gaps.

Fontan patients have significantly decreased exercise tolerance secondary to several factors, most notably, a lack of a subpulmonary pump to augment systemic venous return to the heart and to overcome the pulmonary vascular resistance. Cardiopulmonary exercise testing is an important inexpensive non-invasive tool to monitor for subclinical changes and functional data over time that may portend the need for earlier intervention.

Cardiac amyloidosis (CA) is increasingly diagnosed due to the advancements made in diagnostics and therapeutics in the last decades, particularly in the field of transthyretin-related CA. Studies that have used bone scintigraphy for screening at-risk conditions have shown that about one out of ten patients with heart failure with preserved ejection fraction (HFpEF), aortic stenosis undergoing valve replacement, or hypertrophic cardiomyopathy (HCM) diagnosed later in life might have an underlying or concomitant CA. At the same time, the epidemiology of these conditions is also rapidly evolving. HFpEF has become the leading form of heart failure, and HFpEF patients are increasingly cared for in non-cardiology settings due to their older age and substantial burden of comorbidities. Aortic stenosis is increasingly treated percutaneously at earlier stages of the disease, determining a significant gain in survival. Hypertrophic cardiomyopathy is nowadays mostly diagnosed in middle-aged adults with near-normal life expectancy, with a greater chance of misdiagnosing CA as HCM or of an overlap between the two conditions. In all these contexts, the therapeutic and prognostic implications of diagnosing CA will have to be further investigated. Meanwhile, the diagnostic workup of patients with suspected CA should always be completed with the systematic exclusion of a plasma cell dyscrasia, the acquisition of tomographic imaging at bone scintigraphy, and the completion of genetic testing for transthyretin-related forms.

The utility of three-dimensional visualization modalities such as three-dimensional printing, augmented reality, and virtual reality has transformed the field of surgery in the past few years. These modalities have demonstrated value in preoperative planning, procedural training, and surgical guidance in many surgical specialties. This review explores the current use of three-dimensional visualization modalities in surgery and further investigates its use and potential in the subspecialty of congenital heart defect surgery.

Despite complete repair at an optimal time in the current era, almost all patients with tetralogy of Fallot will have residual anatomic and hemodynamic sequelae, which make ongoing surveillance of paramount importance. Echocardiography suffices surveillance matrix in most pre-operative cases unless there is a specific question about coronary artery anomaly or branch pulmonary arteries when cardiac catheterization or computed tomography scan can be extremely helpful. For long-term follow-up of repaired tetralogy of Fallot patients, several diagnostic/imaging monitoring modalities are available; however, no single modality is perfect in terms of obtaining all the necessary information. A multimodality approach is suggested for long-term surveillance where a diagnostic test is selected based on the clinical circumstances/questions raised and institutional preference/expertise.

Recent advances in the diagnosis and treatment of cardiac amyloidosis (CA) have translated into a longer life expectancy of patients and more challenging clinical scenarios. Compared to the past, patients with CA and heart failure (HF) currently encountered in clinical practice are a more heterogeneous population and require tailored strategies. The perception of CA as a treatable disease has opened new possibilities for the management of these patients, but many grey areas remain to be explored. The aim of this review is to provide practical suggestions for daily clinical activity in the management of challenging scenarios in CA, including the effectiveness and tolerability of evidence-based HF medication; rate vs. rhythm control in atrial fibrillation, thromboembolic risk, and anticoagulation therapies; replacement of severe aortic valve stenosis; the impact of implantable cardioverter defibrillator on survival; and the usefulness of cardiac resynchronization therapy.

Aim: We evaluated the short- and mid-term results of mitral valve replacement (MVR) and mitral valve repair (MV-repair).

Methods: In total, 168 patients (mean age 67 ± 11 years) underwent MVR (n = 104) and MV-repair (n = 64). To treat posterior leaflet disease, MV-repair techniques included triangular or quadrangular resection (n = 38), P1-P2 plication (n = 4), side-to side P1-P2 (n = 1), posterior-medial commissure-plasty (n = 1), and annuloplasty (n = 20). A prosthetic ring was implanted in all patients. In the presence of degenerative disease involving the anterior leaflet, extensive myxomatous and/or prolapsing pathology of the entire valve, and/or rheumatic and endocarditis degeneration, surgical orientation was to perform MVR directly. When possible, the sub-valvular apparatus with its papillary muscle was partially preserved. The mean follow-up was 38 ± 22 months.

Results: Operative mortality (0.96% vs. 1.56%) and six-year survival (94% vs. 100%) were similar in MVR and MV-repair. The only independent predictor of late survival was advanced age at the operation (79.2 years vs. 66.4 years; P = 0.012). Freedom from redo-operation was 100%. Partial preservation of the sub-valvular apparatus with its papillary muscle during MVR allowed postoperatively a better left ventricular function with similar values achieved with MV-repair (P = 0.05), and it was a protective factor against the development of left ventricular dysfunction during follow-up (P = 0.01).

Conclusion: MVR and MV-repair are associated with satisfactory results in the short and medium term. MV-repair to treat posterior leaflet disease is associated with a stable and long-lasting result; MVR allows equally satisfactory results in the presence of more extensive and more complex mitral valve disease. Partial preservation of the sub-valvular apparatus favors a better left ventricular systolic function.

Aim: In the United States (US), post-operative atrial fibrillation (POAF) is the most common complication following cardiac surgery. In order to understand the opportunities to improve POAF patients’ care, this “30,000 foot” review evaluated the professional society POAF database/registry definitions and guideline recommendations.

Methods: All US-based professional society organizations with an interventional cardiac database/registry and/or cardiac care guidelines were identified; from these, the POAF database definitions and guideline recommendations were evaluated using a content analysis approach.

Results: The Society of Thoracic Surgeons (STS) POAF definition was the most frequently referenced definition (21% of key references). Only 50% (n = 5/10) US cardiac surgery databases/registries included any POAF definition; compared to STS, the other five definitions required substantially more detailed documentation. Across eight guidelines, three different types of POAF recommendations were found: risk assessment (n = 3); prevention (n =7); and management (n = 8). As a common feature, the risk assessment strategies tended to focus on advanced age (n = 6). Beta-blockers (n = 5) and amiodarone (n = 6) were common prevention approaches. Uniformly, anti-coagulation was the only management strategy (n = 8) recommended, barring any contraindications.

Conclusion: Across ten professional societies, 50% had no POAF definition; of the remaining five, no POAF definitional consistency was found. Across the eight US-based professional society POAF-related guidelines, only anticoagulation was uniformly recommended. Given these “big picture” findings, professional societies are urged to work collaboratively to harmonize these divergent POAF definitions and consolidate their evidence-based guideline recommendations to improve future POAF patients’ quality of care.

Although pre-procedural and post-procedural atrial fibrillation occur commonly in mitral valve (MV) patients, the impact on patient outcomes and resource utilization has not been well documented. A comprehensive PubMed review was performed using a combination of MeSH terms related to atrial fibrillation, MV disease, MV and atrial fibrillation procedures, and medical management. Additional publications were selected from the reference lists of studies identified in the literature search. This review found that several studies conflict with the short-term outcomes associated with pre- and post-operative atrial fibrillation in MV patients. In general, both pre- and post-operative atrial fibrillation have clear negative long-term impacts on MV patients’ mortality and risk of stroke, major bleeding and other thromboembolic events. Surgical ablation for pre-operative atrial fibrillation and transcatheter ablation for medically resistant post-operative atrial fibrillation appears to be safe and effective procedure; these percutaneous and surgical interventions have been documented to mitigate MV-related thromboembolic risk. For MV patients, evidence suggests that the first step should be to optimize the current medical therapy; for persistent symptoms not addressed medically, ablation procedures should be considered. To optimize MV patients’ quality of care, however, additional research appears warranted to prevent long-term adverse outcomes.

Acute aortic dissection complicated by malperfusion syndrome is a devastating condition that significantly impacts morbidity and mortality. Malperfusion syndrome can affect any vascular bed with varying degrees of end-organ involvement. While conventional management of acute type A aortic dissection (ATAAD) with or without malperfusion syndrome is emergent central aortic repair, growing evidence suggests that this approach results in unsatisfactory outcomes for those presenting specifically with mesenteric malperfusion. With the established short and long-term benefits of thoracic endovascular aortic repair in the management of acute complicated type B aortic dissection, there is an emerging paradigm shift towards initial reperfusion of distal organs with a variety of endovascular and transcatheter techniques followed by central aortic repair in an otherwise stable patient whose risk of aortic rupture is low. A multidisciplinary team and a patient-specific approach remain paramount in the successful management of this high-risk, high-complexity subset of ATAAD patients.

Postoperative atrial fibrillation (POAF) affects up to 50% of patients undergoing cardiac surgery. It remains unclear to what extent POAF increases the stroke risk and whether anticoagulation is warranted in this setting. The primary objective of this review was to conduct a systematic review of the evidence for a correlation between POAF and stroke. Further, we sought to evaluate the published evidence on anticoagulation in the setting of POAF to prevent stroke. To this end, we performed a comprehensive literature search to identify studies on POAF in patients undergoing cardiac surgery with stroke as an outcome. To date, eight meta-analyses providing pooled estimates of the stroke risk associated with POAF in patients undergoing cardiac surgery have been published. The reported pooled odds ratios range from 1.36 to 4.09 for unadjusted estimates. Additionally, five studies were identified that evaluated the impact of anticoagulation on stroke in the setting of POAF. Of these, three supported the use of anticoagulants, and two studies were inconclusive. This systematic review did not find strong supporting evidence that POAF is causally related to stroke, despite a strong correlation with comorbidities and all-cause mortality in the literature. Available evidence to date suggests an elevated risk of bleeding with no clear reduction in stroke or other thromboembolic events when anticoagulation is initiated in the setting of POAF. An upcoming randomized clinical trial by the Cardiothoracic Surgery Network group will hopefully provide clarification on the recommendations for anticoagulation in the setting of POAF after cardiac surgery.

Atrial Fibrillation (AF) is encountered daily by the cardiac surgeon. How to deal with a patient with pre existing AF who is on anticoagulation taking into account urgency, type of anticoagulation and procedure planned are some of the daily considerations encountered. When to start anticoagulation and other pharmacotherapy after the occurrence of post-op atrial fibrillation and the use of ablative therapies in view of bleeding and other complications are daily judgement calls made by surgeons. Whom to offer combined interventions are decisions the surgeon faces daily. While guidelines help in broad strokes, there is little help for individual situations which is due to structural problems and absence of universal definitions resulting in the lack of granular data needed for practical individualized daily decision making.

Aim: This Department of Veterans Affairs’ (VA) research project evaluated the impact of postoperative atrial fibrillation (POAF) upon 10-year outcomes for coronary artery bypass grafting (CABG) patients.

Methods: Veterans enrolled in the “Randomized On-/Off-pump Bypass” (ROOBY) trial with new-onset POAF post-CABG were compared to those without POAF with respect to 10-year atrial fibrillation (AF) and mortality rates. Multivariable logistic regression examined whether AF was independently associated with 10-year survival after holding other preoperative risk factors constant.

Results: Of the 2203 ROOBY veterans enrolled at 18 VA medical centers from 2002 to 2008, 100 patients with preoperative AF (n = 93) or unknown post-CABG POAF status (n = 7) were excluded. The POAF rate was 26.2% (n = 551/2103). The POAF patients were older and had more co-morbidities than the non-POAF patients (n = 1552). The AF rate among 10-year ROOBY POAF survivors was 18.9% (n = 64/338) compared to 5.8% (n = 61/1048) for non-POAF patients; P < 0.001. Compared to non-POAF patients’ 10-year survival of 70%, the ROOBY POAF veterans’ 10-year survival rate was 63%. Baseline risks inversely associated with 10-year survival included age, chronic obstructive pulmonary disease, serum creatinine > 1.5, peripheral vascular disease, and smoking. Holding these factors constant, POAF was not independently associated with 10-year survival.

Conclusion: Post-CABG, ROOBY POAF veterans had higher rates of 10-year AF, which was negatively associated with 10-year survival; however, this association was not significant. Given that POAF may adversely impact 10-year AF rates, additional investigation appears warranted to improve future POAF patients’ care.

Aim: Postoperative atrial fibrillation (POAF) is a known risk factor for morbidity and mortality following cardiac surgery though contemporary resource utilization data is limited. We hypothesize that POAF increases the length of stay, hospital cost, and discharges to facilities, though this trend may be tempering over time.

Methods: Records were extracted for all patients in a regional database who underwent coronary artery bypass grafting, aortic valve replacement, or both (2012-2020). Patients without a history of atrial fibrillation were stratified by POAF for univariate analysis. Patients were propensity-score matched to account for baseline, operative, and postoperative differences.

Results: Of the 27,307 cardiac surgery patients, 23% developed POAF. Matching resulted in 5926 well-balanced pairs of patients with and without POAF. Every metric of resource utilization was higher for patients with POAF, including ICU length of stay (58 h vs. 49 h, P < 0.0001), postoperative length of stay (7 days vs. 5 days, P < 0.0001), discharge to a facility (27% vs. 23%, P < 0.0001), and readmission (11% vs. 8%). The mean additional total hospital cost attributable to POAF was $6705 by paired analysis. A sensitivity analysis of only patients without major complications demonstrated similarly increased resource utilization for patients with POAF.

Conclusions: POAF was associated with an increased 9 additional ICU hours, 2 postoperative days, 18% more discharges to a facility, and 33% greater readmissions. An additional $6705 is associated with POAF. These conservative estimates demonstrate the broad impact of POAF on in and out of hospital resource utilization that warrants future efforts at containment and quality improvement.

Atrial fibrillation (AF) is known to be one of the most common arrhythmias noted in cardiac procedures and is frequently associated with heart failure. As frequent interventions for patients with heart failure involve implantation of mechanical circulatory assist devices (e.g., left ventricular assist devices), it is timely to review the role this arrhythmia has on adverse clinical outcomes. A comprehensive literature search was conducted for PubMed. Relevant medical subject heading (MeSH) terms used in the initial literature search include “Heart-Assist Devices”, “Extracorporeal Membrane Oxygenation”, “Atrial Fibrillation”, “Heart Failure”, “Mortality”, “Hospital Readmission”, “stroke”, “Postoperative Complications”. In this review, the relevant literature was highlighted to identify the incidence, clinical impacts, and management of AF surrounding mechanical circulatory support implantation. The incidence of AF in this mechanical circulatory support device population was similar to that of patients with other cardiac procedures (10%-40%). Moreover, in most studies, preoperative AF was not significantly associated with adverse outcomes. In contrast, however, it appears that postoperative atrial fibrillation may predispose patients to increased risk for thromboembolic events and adverse long-term outcomes.

Atrial fibrillation (AF) is among the most frequent cardiac surgical arrhythmias documented. The global AF prevalence is estimated at over 33 million cases, with estimates ranging up to 6.1 million cases in the United States. Among cardiac surgical patients, the risk factors for new-onset post-operative AF (POAF) include Caucasian race with increased prevalence documented in older men. Due to trends of earlier thoracic aortic aneurysm (TAA) detection and treatment, it is timely to review the AF association with adverse TAA clinical outcomes. Towards this goal, a comprehensive PubMed literature review was performed. For this initial Medline literature search, the MeSH search strategy included “thoracic aortic aneurysm” and “atrial fibrillation”. Based on the pertinent articles identified, the limited literature available for preoperative TAA AF and the predictors of POAF following TAA procedures were reviewed. Given only a handful of publications addressing these pre-/post-operative AF topics were identified using this very broad initial search approach, a knowledge chasm exists–as very little is known about TAA patients with pre-operative or new-onset post-operative AF. Given the paucity of evidence-based information available, clinically relevant TAA-specific research questions have been raised to guide future TAA AF-related investigations.

It is known that the prognosis of patients affected by light-chain (AL) or transthyretin-related (TTR) amyloidosis is poor. TTR amyloidosis has usually shown a slower progression than AL amyloidosis, both hereditary TTR amyloidosis, where there is an inherited mutation in the DNA, and wild-type TTR amyloidosis, which usually affects the elderly. In this paper, the current literature about heart transplantation on cardiac amyloidosis patients is extensively reviewed. The two most frequent types of cardiac amyloidosis have been considered for heart transplantation: AL amyloidosis and wild-type TTR amyloidosis. According to this analysis, it is reasonable that heart transplantation may represent a valuable option in carefully selected patients. Moreover, it could improve prognosis, enabling autologous stem cell transplantation in the AL amyloidosis subgroup. In our humble opinion, it is mandatory to define a multidisciplinary approach to help select candidates to obtain the most effective results.

Vascular graft infections are rare complications after surgical and endovascular treatment of aortic diseases. This condition is characterized by complexity in diagnosis and medico-surgical management. Moreover, even if properly treated, morbidity and mortality rates are high. Although several advances have been made over the years and guidelines of treatment have been published, there is still debate on the optimal care for this disease. With local microbiological patterns and multiresistant strains conditioning antimicrobial treatment as well as several surgical debridement techniques in the armamentarium, it is difficult to offer recommendations that can be generalized for every single case. In this review, we aim at describing thoracic and abdominal vascular graft infections and providing current information on diagnosis, medical treatment, and surgical management.

Over the past decades, both open surgery and endovascular treatment of aortic dissection have made great progress with good clinical outcomes. However, despite this progress, the presence of distal re-entry tears can sustain perfusion of false lumen (FL) and induce aneurysm formation or growth. In particular, about 20% of patients undergoing thoracic endovascular aortic repair (TEVAR) for aortic dissection require reintervention because of incomplete FL thrombosis promoting aortic wall degeneration, post-dissection aortic aneurysm, and rupture. Endovascular techniques to promote FL thrombosis after TEVAR show good early results together with minimal invasiveness, offering different alternatives depending on the case and the level of urgency. Endovascular techniques include FL embolization (with coils, vascular plugs, etc.), candy-plug techniques, parallel stent graft, and branched and fenestrated aortic endoprosthesis. Each of these solutions has advantages and disadvantages. We herein describe the available endovascular options.

The standard of care first-line therapy for uncomplicated acute type B aortic dissection is medical therapy. As a result, many of these dissections progress to become chronic type B aortic dissections (CTBAD). In the following manuscript, we will outline the natural history of these lesions and review what constitutes a CTBAD by anatomy and chronology. We will also describe the long-term medical management and surveillance of these lesions, what constitutes high-risk features, and when intervention should be considered. Endovascular, open and hybrid management strategies, potential complications, and subsequently required surveillance will also be discussed. With proper medical management, surveillance, and intervention, CTBAD can be managed effectively and downstream morbidity minimized.

Aim: In the US, postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery and a frequent complication after non-cardiac surgery, causing excess patient length of stay and costs. After a comprehensive review looking for validated statistically significant data sets, too few data, particularly from outside of the US and Europe, could be found to perform a conclusive analysis, but there is enough data for a well-informed, educated opinion.

Methods: A systematic review analyzing 28 international and US studies of POAF hospital length of stay were identified; from this excess and % excess along with total patient length of stay were calculated, where excess patient length of stay is defined as the difference in post-operative stay between POAF and non-POAF patients in days. Geographic variabilities were calculated using chi-square analyses for US regions and international comparisons for a variety of surgical procedures with POAF.

Results: Geographic variability analyses when corrected for total hospital stay showed a 325% longer excess patient length of stay (days) in the US vs. Europe (3.4 days vs. 0.8 days) for coronary artery bypass grafting (CABG). It also showed a 27.3% longer excess patient length of stay (days) in the US vs. Europe (4.2 days vs. 3.3 days) for lung resections. These were both statistically significant at P < 0.001.

Conclusion: There appear to be substantial variations in POAF-related care practices worldwide. In all practice settings, POAF causes increased patient length of stay. Europeans appear to do better than the US in POAF patients’ length of stay for CABG but not for lung resections. POAF is a worldwide problem where international cooperation in research and development of best practice guidelines would be particularly fruitful.

Aim: Impacts of pre-operative atrial fibrillation or flutter (AF/AFL) upon repeat aortic valve replacement (r-AVR) patients’ risk-adjusted short-term outcomes is unknown.

Methods: From 2005-2018, New York State AF/AFL versus non-AF/AFL adults’ risk-adjusted r-AVR outcomes were compared. Primary endpoints included the Society of Thoracic Surgeons’ 30-day operative mortality or major morbidity (MM) composite and 30-day readmission (READMIT); the MM sub-components were secondary endpoints. Multivariable logistic regression models evaluated AF/AFL impact upon these endpoints while holding other factors constant.

Results: Of 36,783 adults initially undergoing aortic valve replacement, 334 subsequently underwent r-AVR. Within this r-AVR group, 42.4% of repeat surgical (r-SAVR) patients had AF/AFL; 50.4% of repeat transcatheter (viv-TAVR) patients had AF/AFL. R-SAVR AF/AFL patients were older and had more comorbidities than those without AF/AFL. Viv-TAVR AF/AFL patients were similar to those without AF/AFL except for lower rates of chronic obstructive pulmonary disease. Comparing risk-adjusted r-AVR outcomes, AF/AFL did not impact MM [odds ratio (OR), 95% confidence interval (CI): 1.23, 0.66-2.28, P = 0.512] or READMIT (OR, 95%CI: 1.15, 0.60-2.19, P = 0.681). Black race (OR, 95%CI: 2.89, 1.01-8.32, P = 0.049) and Elixhauser mortality score (OR, 95%CI: 1.07, 1.04-1.10, P < 0.0001) predicted MM risk. Cerebrovascular disease (OR, 95%CI: 2.54, 1.23-5.25, P = 0.012) predicted READMIT risk, while viv-TAVR was protective compared to r-SAVR (OR, 95%CI: 0.44, 0.21-0.91, P = 0.027).

Conclusion: AF/AFL was not associated with risk-adjusted short-term r-AVR outcomes. Black race, Elixhauser mortality score, and cerebrovascular disease predicted adverse outcomes.

Transthyretin (TTR)-related amyloidosis (ATTR) is a heterogeneous disease with different organ involvement depending on the type of TTR infiltration [mutated (vTTR) or wild-type (wtTTR)]. Genetic testing in ATTR is required to define diagnosis and identify asymptomatic at-risk family members. Since new therapies are maximally effective in the early stages of the disease, there is a growing agreement about the need for close monitoring of genotype-positive, phenotype-negative individuals to assure a prompt treatment when minor disease signs are detected. This review summarizes the complexity of genotype-phenotype correlation and revises the current indications with respect to familiar screening and management of asymptomatic carriers.

Aim: New-onset postoperative atrial fibrillation/flutter (POAF/AFL) complications have not been well studied for repeat aortic valve replacements (r-AVR); this study identified risk factors predisposing to POAF/AFL and POAF/AFL’s effect upon risk-adjusted outcomes.

Methods: Using New York State’s Statewide Planning and Research Cooperative System records (2005-2018), multivariable forward selection models identified risks predictive of POAF/AFL. To identify POAF/AFL’s impact upon risk-adjusted mortality/morbidity (MM) and 30-day readmission (READMIT), forward selection logistic regression models applied Firth bias correction to address data sparsity.

Results: Of the 242 r-AVR patients, 147 underwent repeat surgical aortic valve replacements (r-SAVR) and 95 underwent valve-in-valve transcatheter aortic valve replacements (ViV-TAVR); 39.46% of r-SAVR and 43.16% of ViV-TAVR patients had POAF/AFL. R-SAVR patients with POAF/AFL were older (69.7 ± 11.1 vs. 56.7 ± 13.2 years, P < 0.01) compared to R-SAVR patients without POAF/AFL. Multivariable models identified an enhanced POAF/AFL risk for elderly (OR: 1.05, 95%CI: 1.03-1.07, P < 0.01) and cerebral vascular disease (OR: 2.18, 95%CI: 1.05-4.55, P = 0.04) patients.

Bivariately, POAF/AFL was associated with READMIT, but not MM. Correspondingly, multivariable models found POAF/AFL increased READMIT (OR: 3.12, 95%CI: 1.46-6.65, P < 0.01), but not MM. However, black race (OR: 4.97, 95%CI: 1.61-15.37, P < 0.01) and Elixhauser score (OR: 1.05, 95%CI: 1.02-1.08, P < 0.01) increased risk for MM.

Conclusion: More common in older and cerebrovascular disease patients, 41% of r-AVR patients with POAF/AFL had increased READMIT risk; thus, future investigations should focus on improving POAF/AF r-AVR patients’ post-discharge continuity of care.

This perspective focuses on the development of tissue engineered (TE) cell-based therapies to treat left ventricular (LV) dysfunction and chronic heart failure (CHF). The development of induced pluripotent stem cells enabled investigators to seed or co-culture human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) alone and in combination with other cells onto bioengineered scaffolds applied to the epicardial surface of the damaged left ventricle. Using our work as an example, we show how a xenograft implant of a bioengineered scaffold embedded with human neonatal fibroblasts and seeded with hiPSC-CMs partially reversed maladaptive LV remodeling and improved LV systolic/diastolic function in an immune-competent rat model of CHF. The fibroblasts lay down an extracellular matrix and secrete growth factors that increase myocardial blood flow. This approach provides an improved cell payload that covers a larger area of the damaged left ventricle as opposed to direct cell injections into the heart or down the coronary arteries. These studies combined with ongoing studies in immune-competent Yucatan mini swine treated with the same xenograft led to the preliminary design of a proposed Phase I clinical trial that will be presented to the Federal Drug Administration. For the proposed Phase I clinical, this TE patch will be implanted onto the epicardial surface of non-immunosuppressed patients undergoing elective Coronary Artery Bypass Grafting with Ejection Fractions ≥ 20% and ≤ 45%. The primary endpoints will be adverse events/severe adverse events associated with placing the TE patch on the heart. While Phase I trials are primarily safety trials, this proposed trial is designed to obtain some potential efficacy endpoints to help with the design of future Phase II/III clinical trials. These endpoints include changes in LV remodeling that were seen in the pre-clinical animal models as well as including endpoints that focus on patient well-being.

Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery, yet there is no consistent cardiothoracic professional society-based definition of new-onset POAF, nor a broadly accepted consensus on how to prevent or treat it. Importantly, there is an ever-growing body of evidence that new-onset POAF is associated with worse patient outcomes. Given the lack of evidence-based guidelines, detection and treatment of POAF, in addition to understanding how POAF is related to these worse outcomes, represents an unaddressed quality of care concern. In the United States, the annual cardiac surgical POAF patient costs are estimated at ~$1 billion. The entire US Medicare annual budget has been reported at ~$141.2 billion for all hospital-related care; thus, the administrative challenges uniquely posed by POAF have been exposed for the first time. Mapping future tactics, this Vessel Plus special atrial fibrillation publication, swings the pendulum from impromptu observations towards action. A new strategic framework is proposed to begin the tedious but necessary task of taking on this elephant in the room. With ideal collaboration between clinical providers, health care systems, professional societies and insurers, a five-step approach is proposed to overcome these POAF patient care challenges.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been recently approved by world-reputed medical associations as a milestone of class A management of heart failure (HF) with reduced ejection fraction (HFrEF) after pooling strong evidence (mainly for dapagliflozin or empagliflozin) regarding their beneficial impact on total occurrences of cardiovascular deaths and hospitalizations for HF in patients with and without type 2 diabetes mellitus (T2DM). Having a wide range of profile of favorable pleiotropic effects on heart, vessels, and kidney, SGLT2 inhibitors probably have a class-specific tissue protective ability, while its exact molecular mechanism has not been clearly understood yet. However, whether these agents retain their potency to reverse adverse cardiac remodeling remains unclear. The review elucidates the role of SGLT2 inhibitors in the potential reversibility of cardiac remodeling in connection with the improvement of clinical outcomes among T2DM patients having HF. Herein, we discussed the effects of SGLT2 inhibitors on cardiac structure and hemodynamics in T2DM patients. We revealed that empagliflozin had sufficient benefits in alleviating the adverse cardiac remodeling in HFrEF individuals than other SGLT2 inhibitors. These findings can open a new vision for the optimization of HF therapy in the near future.

Cardiac amyloidosis is a well-known entity recently recognized as a common etiology of heart failure. This infiltrative disease is caused by the deposition of misfolded proteins within the heart. The most common types of cardiac amyloidosis result from fibrils composed of monoclonal immunoglobulin light chains or transthyretin. Clinical presentation is usually elusive, and this can result in diagnostic delay. Diagnosis can be reached with non-invasive methods, but it often requires tissue sampling with pathological analysis. It is fundamental to determine the type of protein being deposited in order to indicate the specific treatment. In this article, we review the main features of cardiac amyloidosis with a focus on different pathological presentations of this rare disorder.

Mitochondria do not exist as separate formations in the cell; they form a homogeneous network in which the processes of division and fusion continuously occur. A shift in this balance, as well as mitochondrial dysfunction, leads to the development of chronic and metabolic disorders. Metabolic changes in mitochondria control the formation and differentiation of monocytes. Pro-inflammatory activation of monocytes/macrophages leads to a decrease in oxidative phosphorylation and an increase in mitochondrial fusion. To date, the molecular mechanisms that regulate mitochondrial dynamics to control life and death in monocytes are not well understood. In addition, there is ample evidence that abnormal mitochondrial metabolism is involved in the pathogenesis of many diseases. Mitochondrial stress and damage contribute to cell death, metabolic disorders, and inflammation. In this review, we consider in detail the involvement of mitochondrial processes in the development of pathologies and discuss how mitochondria can be therapeutically affected. Attention is also drawn to possible diagnostic studies that target mitochondrial dynamics of disorders in monocytes.

Amyloid light-chain (AL) amyloidosis is the most common type of systemic amyloidosis and is a multi-organ disease affecting mostly the heart and kidneys. AL amyloidosis is a protein misfolding disorder characterized by the tissue deposition of monoclonal light chains (LCs) produced by neoplastic plasma cells. Measurement of circulating free LC (FLC) is an important tool for diagnosis, risk stratification, and management of AL amyloidosis and can be performed through antibody-based methods or mass spectrometry. Furthermore, correct identification of LC deposits in tissues is essential to diagnose AL amyloidosis. Together with antibody-based techniques, methods relying on mass spectroscopy are now available.

The periprocedural management of anticoagulation in patients who require non-cardiac surgery is a common clinical problem due to the aging of the population associated with both an increase in the use of anticoagulants and a higher need for surgery. If surgery is needed in a patient on anticoagulant therapy, regardless of the drug used, it is necessary to consider the urgency of the surgical procedure and the balance between the thromboembolic risk related to the discontinuation of therapy and the hemorrhagic risk related to the surgical procedure itself. Finally, a topic still much discussed that derives from the combined evaluation of these factors is the possible indication of a bridge therapy (“bridging anticoagulation”) to limit the thromboembolic risk related to the discontinuation of treatment. The different strategies in patients under antivitamin K and direct oral anticoagulants are reviewed.

Aim: We evaluated the impact of prior percutaneous coronary intervention (PCI) on early and mid-term results in patients undergoing coronary artery bypass grafting (CABG).

Methods: Between 2015 and 2020, 938 consecutive patients (mean age 67.4 ± 9.11 years) underwent CABG with prior PCI (n = 121) or primary CABG (n = 817). The mean follow-up was 37 ± 25 (median 36) months. Kaplan-Meier estimates were used to assess survival rates, while Logistic and Cox model analysis regressions assessed the risk of prior PCI and other variables.

Results: Six-year survival including in-hospital mortality was 79% ± 6% in CABG with prior-PCI patients vs. 88% ± 2% in primary CABG (P = 0.002). As compared with primary CABG, in prior-PCI patients, clinical presentation (acute coronary syndrome, reduced left ventricular ejection fraction, and previous myocardial infarction, P ≤ 0.01, for all comparisons) was worse, comorbidity increased (Euroscore-2, severe chronic renal dysfunction, P < 0.01), and in-hospital mortality was higher (6.6% or 8 patients vs. 1.6% or 13 patients, P < 0.001). Prior PCI was found to be an independent predictor of mortality (HR = 4.23; P = 0.01). Six-year freedom from late all-cause death and cardiac death were 84% ± 6% vs. 90% ± 2% (P = 0.2) and 96% ± 2% vs. 96% ± 1% (P = 0.5), respectively. Independent predictors of all-cause death were advanced age at the operation (P < 0.0001), reduced left ventricular ejection fraction (P = 0.01), severe chronic renal dysfunction (P = 0.02), prior PCI (P = 0.03), and Euroscore-2 (P = 0.05). Prior PCI did not negatively affect late cardiac death (P = 0.5).

Conclusion: Patients undergoing CABG after prior PCI have worse perioperative outcomes. Mid-term reduced survival in the prior-PCI patients is mainly due to the concomitant presence of worse clinical presentation and increased comorbidity. Freedom from cardiac death is comparable and satisfactory in both cohorts, highlighting the positive protective effect of CABG over time.

Acute coronary syndrome (ACS) disproportionately affects older populations. This is despite advancements in diagnosis and management over the past few decades leading to an overall improvement in clinical outcomes in patients with ACS. Patients aged ≥ 70 years account for more than one third of all patients admitted to hospital with ACS and are at the highest risk of complications including mortality. This article reviews ACS in older populations, including the epidemiology, changes in physiology contributing to increased risk, clinical manifestations, inadequacy of current diagnostic methods, and controversies around recommended management strategies.

Mitochondria are cellular organelles providing energy to the cells. Due to the nature of mitochondrial enzymatic repair systems, mitochondrial DNA tends to generate mutations that are repaired less efficiently than nuclear DNA mutations. There is a certain relationship between the accumulation of mitochondria with mutated DNA in tissues, the development of oxidative stress, and several pathological conditions, from specific mitochondrial diseases to an increased risk of cancer, atherosclerosis, neurodegeneration, and non-systemic inflammation. Mitophagy is the biological mechanism responsible for the degradation of dysfunctional, damaged, and mutant mitochondria. Presumably, the stimulation of mitophagy can lead to tissue cleansing from dysfunctional mitochondria, which can have a powerful therapeutic effect on the root cause of the pathology. This review examines the relationship between mitochondrial mutations and the development of oxidative stress, the mechanisms of mitophagy, and a group of chemicals that stimulate mitophagy.

The incidence of type 2 diabetes mellitus (T2DM) is growing globally, and the major cause of morbidity and mortality in these patients is the premature development of cardiovascular disease. Consequently, medical interventions, such as coronary artery bypass graft surgery and widespread statin prescriptions, are common in this patient group. Smooth muscle cells are the major structural component of the vascular wall. They play a crucial role in post-bypass recovery to successfully revascularize the heart by switching between differentiated (contractile) and dedifferentiated (synthetic) phenotypes. However, in patients with T2DM, these cells have functional defects that may affect bypass integration. RhoA is a small GTPase that regulates many functions, such as motility and phenotypic regulation of smooth muscle cells. RhoA is dependent upon a stimulus, and it can drive the contractile smooth muscle cell phenotype present in the healthy condition or the (mal)adaptive phenotypes prevalent in disease or in response to injury. We hypothesize that RhoA deregulation plays a major role in vascular complications of T2DM. This protein is deregulated in T2DM smooth muscle cells, which may in part explain the functional defects of smooth muscle tissue and the subsequent failure rate of bypass in these patients. An important consideration in this circumstance is the use of statin therapies because these further inhibit RhoA activity. The effect of inhibition of RhoA activity in patients with T2DM who have a bypass is currently unknown.

Atherosclerosis is the major cause of occurrence and development of cardiovascular disease. Mutations in mitochondrial DNA (mtDNA) can lead to the development of several pathologies. Over the last few years, there has been increasing evidence that mitochondrial dysfunction caused by mtDNA mutations is associated with atherogenesis and other diseases of the cardiovascular system. Several therapeutic approaches have been developed for the improvement of mitochondrial function, and they are mainly associated with the cellular and tissue antioxidant defense system. However, these approaches are not targeted at mtDNA mutations, which trigger the pathogenesis of disease. Gene-editing technologies could be a promising approach for the treatment of cardiovascular disease caused by mtDNA mutations. To date, such technologies have shown considerable success in mitochondrial gene editing in cell and animal models. Gene-editing technologies allow the determination of the role of mitochondrial genome mutations in the development and complication of various chronic diseases. Nevertheless, further investigation and optimization in this field is required for future human trials. This review highlights the progress and existing challenges of modern technologies and approaches to mitochondrial gene editing.