Anderson-Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement.

Anderson-Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic "red flags" is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac "red flags" that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.

Long-term prognosis in patients undergoing redo-isolated aortic valve replacement.

Aim: To evaluate clinical outcomes after redo aortic valve replacement (AVR) with sutured valves, versus valve-in-valve transcatheter aortic valve replacement (ViV-TAVR), versus sutureless valves. Methods: We identified 113 consecutive patients undergoing redo AVR with either ViV-TAVR, redo-sutured and redo-sutureless valves between August 2010 to March 2020. Heart-team made the decision whether patient should undergo redo-sutureless versus ViV-TAVR, versus redo-sutured AVR. Results: Preoperatively, redo-sutured (n = 57), ViV-TAVR (n = 31) and redo-sutureless (n = 25) patients were compared. Postoperatively, after propensity-adjustment analysis, the redo surgical aortic valve replacement group had a higher incidence of new postoperative atrial fibrillation (POAF; p = 0.04) compared with redo-sutureless group. Follow-up outcomes analysis did not show differences among groups. Conclusion: Patients undergoing redo-sutureless AVR experienced a higher incidence of POAF compared with patients undergoing redo-sutured.

[ANMCO Position paper: Ionizing radiation exposure and radioprotection in the cath-lab]. / Position paper ANMCO: Radioesposizione e radioprotezione nei laboratori di cardiologia interventistica.

In the last decades, because of the improvements in the percutaneous treatment of coronary heart disease, valvular heart disease, congenital heart defects, and the increasing number of cardiac resynchronization therapy and cardioverter-defibrillator implantations, the interventional cardiologists' radio-exposure has importantly risen, causing concerns for ionizing radiation-associated diseases such as cancer and neurodegenerative disorders. Consequently, the radiation exposure issue importantly affects operators' safety. However, our knowledge of this field is poor and most operators are unaware to be at risk, especially because of the absence of effective preventive measures. The aim of this ANMCO position paper is to improve the awareness of operators and identify new ways of reducing operator ionizing radiation dose and minimizing the risk.

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios.

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

The role of the pregnancy heart team in clinical practice.

Significant maternal and fetal morbidity and mortality risk has been shown to be associated with cardiovascular disease in pregnancy. Several determinants, such as the increasing number of females with corrected congenital heart disease in reproductive age, a more advanced maternal age associated with cardiovascular risk factors, and a greater prevalence of preexisting comorbidities related to cardiac disorders such as cancer and COVID-19), lead to a higher incidence of cardiac complications in pregnancy in the last few decades. However, adopting a multidisciplinary strategy may influence maternal and neonatal outcomes. This review aims at assessing the role of the Pregnancy Heart Team, which should ensure careful pre-pregnancy counseling, pregnancy monitoring, and delivery planning for both congenital and other cardiac or metabolic disorders, addressing several emerging aspects in the multidisciplinary team-based approach.

Ministernotomy compared with right anterior minithoracotomy for aortic valve surgery.

OBJECTIVES: Ministernotomy and right anterior minithoracotomy are the 2 main techniques applied for minimally invasive aortic valve replacement. The goal of this study is to compare early and long-term outcomes of both techniques. METHODS: The data of 2419 patients undergoing isolated minimally invasive aortic valve replacement between 1999 and 2019 were prospectively collected. Retrospectively, patients were divided into the ministernotomy group (n = 1352) and the minithoracotomy group (n = 1067). RESULTS: After propensity score matching, 986 patients remained in each group. Operation time and rate of conversion to full sternotomy were significantly higher in the minithoracotomy group than in the ministernotomy group (184.6 ± 45.2 vs 241.3 ± 68.6, relative risk, 2.54, P = .005 and .09 vs .23, relative risk, 1.45, P = .013, respectively). The 30-day mortality, excluding cardiac death, was lower in the ministernotomy group than in the minithoracotomy group (0.012 vs 0.028, relative risk, 1.41, P = .011, respectively); the intensive care unit length of stay (12.4 vs 16.5, relative risk, 1.62, P = .037, respectively) and hospital length of stay (5.4 vs 8.7, relative risk, 1.74 P = .028, respectively) were significantly longer in the minithoracotomy group. The minithoracotomy surgical approach was the strongest independent predictor of early mortality (odds ratio, 4.24 [1.67-7.35], P = .002). The actuarial survival by Kaplan-Meier analysis at 1, 3, 5, 10, and 20 years was significantly better in the ministernotomy group than in the minithoracotomy group (P = .0001). Actuarial freedom from reoperation at 5 years was 97.3% ± 4.4% in the ministernotomy group versus 95.8% ± 5.2% in the minithoracotomy group (P = .087). CONCLUSIONS: Minimally invasive aortic valve replacement using ministernotomy is associated with reduced operative time, intensive care unit stay, hospital length of stay, and postoperative morbidities and incisional pain, and improves early and long-term mortality.

The evolution of arch surgery: Frozen elephant trunk or conventional elephant trunk?

Treatment of aortic arch aneurysms and dissections require highly complex surgical procedures with devastating complications and mortality rates. Currently, repair of the complete arch until the proximal descending thoracic aorta consists of a two-stage procedure, called elephant trunk (ET) technique, or a single stage a single-stage technique referred to as frozen elephant trunk (FET). There is conflicting evidence about the perioperative results of ET in comparison with FET. We carried out a meta-analysis to investigate possible differences in perioperative and early (up to 30 days) outcomes of ET vs. FET, particularly for mortality, spinal cord injury (SCI), stroke, and renal failure. We also performed a meta-regression to explore the effects of age and sex as possible cofactors. Twenty-one studies containing data from interventions conducted between 1997 and 2019 and published between 2008 and 2021 with 3153 patients (68.5% male) were included. ET was applied to 1,693 patients (53.7%) and FET to 1460 (46.3%). Overall mortality after ET was 250/1693 (14.8%) and after FET 116/1460 (7.9%). Relative risk (RR) and 95% confidence interval (CI) were 1.37 [1.04 to 1.81], p = 0.027. There was no significant effect of age and sex. SCI occurrence after the second stage of ET was 45/1693 (2.7%) and after FET 70/1,460 patients (4.8%) RR 0.53 [0.35 to 0.81], p = 0.004. Age and sex were not associated with the risk of SCI. No significant differences were observed between ET and FET in the incidence of stroke and renal failure. Our results indicate that ET is associated with higher early mortality but lower incidence of SCI compared to FET. When studies published in the last 5 years were analyzed, no significant differences in mortality or SCI were found between ET and FET. This difference is attributed to a decrease in mortality after ET, as the mortality after FET did not change significantly over time.

Pearls, pitfalls, and surgical indications of the Intuity TM heart valve: A rapid deployment bioprosthesis. A systematic review of the literature.

OBJECTIVES: To highlight short- and long-term clinical outcomes of the Intuity TM rapid deployment prosthesis for surgical aortic valve replacement. METHODS: We reviewed on PubMed/MEDLINE, Embase, SciELO, LILACS, CCTR/CENTRAL, and Google Scholar for clinical trials, retrospective clinical studies, meta-analysis, and gray literature. RESULTS: Fourty-five clinical studies with 12.714 patients were included in the analysis. Thirty-day mortality ranged from 3.8% for Intuity and 3.9% for transcatheter aortic valve replacement (TAVR). The incidence of paravalvular leak (PVL) (Intuity 0% and TAVR 2.17%), permanent pacemaker implantation (Intuity 11.11% and TAVR 12.5%), stroke (Intuity 2.2% and TAVR 2.6%), myocardial infarction (MI) (Intuity 0% and TAVR 1%), were all higher in the TAVR group. Compared to other sutured bioprosthesis (SB), mortality ranged from 0% to 3.9% for Intuity and 0%-6.9% for SB. Long-term cardiac mortality ranged from 0.9% to 1.55% for Intuity and 1.4%-3.3% for the Perceval valve. The incidence of PVL (Intuity 0.24%-0.7% and Perceval 0%-1%), endocarditis (Intuity 0.2%-0.7% and Perceval 1.6%-6.6%), stroke (Intuity 0.36%-1.4% and Perceval 0%-0.8%), MI (Intuity 0.07%-0.26%), and SVD (Intuity 0.12%-0.7% and Perceval 0%) were comparable. Compared to standard full sternotomy (SFS), minimally invasive surgery (MINV) mortality ranged from 0% to 4.3% for MINV and 0%-2.1% for SFS. Hospital costs outcomes ranged from $37,187-$44,368 for the Intuity, $69,389 for TAVR, and $13,543 for SB. Intuity short-term mortality ranged between 0.9% and 12.4% while long-term mortality ranged between 2.6% and 20%. CONCLUSIONS: This manuscript provides a 360° overview of the current rapid deployments, sutureless, and TAVR prosthesis.

Superiority of Direct Oral Anticoagulants over Vitamin K Antagonists in Oncological Patients with Atrial Fibrillation: Analysis of Efficacy and Safety Outcomes.

Background and aim. Cancer and atrial fibrillation (AF) may be associated, and anticoagulation, either with vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), is necessary to prevent thromboembolic events by reducing the risk of bleeding. The log incidence rate ratio (IRR) and 95% confidence interval were used as index statistics. Higgin's I2 test was adopted to assess statistical inconsistencies by considering interstudy variations, defined by values ranging from 0 to 100%. I2 values of less than 40% are associated with very low heterogeneity among the studies; values between 40% and 75% indicate moderate heterogeneity, and those greater than 75% suggest severe heterogeneity. The aim of this meta-analysis was to compare the safety and efficacy of VKAs and DOACs in oncologic patients with AF. Methods. A meta-analysis was conducted comparing VKAs to DOACs in terms of thromboembolic events and bleeding. A meta-regression was conducted to investigate the differences in efficacy and safety between four different DOACs. Moreover, a sub-analysis on active-cancer-only patients was conducted. Results. A total of eight papers were included. The log incidence rate ratio (IRR) for thromboembolic events between the two groups was −0.69 (p < 0.005). The meta-regression did not reveal significant differences between the types of DOACs (p > 0.9). The Log IRR was −0.38 (p = 0.008) for ischemic stroke, −0.43 (p = 0.02) for myocardial infarction, −0.39 (p = 0.45) for arterial embolism, and −1.04 (p = 0.003) for venous thromboembolism. The log IRR for bleeding events was −0.43 (p < 0.005), and the meta-regression revealed no statistical difference (p = 0.7). The log IRR of hemorrhagic stroke, major bleeding, and clinically relevant non-major bleeding between the VKA and DOAC groups was −0.51 (p < 0.0001), −0.45 (p = 0.03), and 0.0045 (p = 0.97), respectively. Similar results were found in active-cancer patients for all the endpoints except for clinically-relevant non-major bleedings. Conclusions. DOACs showed better efficacy and safety outcomes than VKAs. No difference was found between types of DOACs.

Management of Acute Coronary Syndrome in Cancer Patients: It's High Time We Dealt with It.

Cancer patients have an increased risk of cardiovascular disease and, notably, a significant prevalence of acute coronary syndrome (ACS). It has been shown that an elevated presence of cardiovascular risk factors in this setting leads to an interaction between these two conditions, influencing their therapeutic strategies and contributing to higher mortality. Nonetheless, cancer patients have generally not been evaluated in ACS trials, so that the treatment in these cases is still not fully known. We reviewed the current literature and discussed the best management for these very high-risk patients. The treatment strategy must be tailored based on the cancer type and stage, balancing thrombotic and bleeding risks. When the prognosis is longer than six months, especially if a clinical instability coexists, patients with ACS and cancer should be referred for percutaneous coronary intervention (PCI) as soon as possible. Moreover, an invasive strategy should be preferred in STEMI patients as well as in NSTEMI patients who are considered as high risk. On the contrary, in clinically stable NSTEMI patients, a conservative non-invasive strategy could be adopted, especially in cases of a poor life expectancy and/or of high risk of bleeding. Drug-Eluting-Stents (DES) should be the first choice if an invasive strategy is adopted. Conservative therapy could instead be considered in cancer patients with more stable CAD at an increased risk of major bleeding complications. However, the duration of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is recommended, but it should be as short as possible, whereas triple antithrombotic therapy is non-advised because it significantly increases the risk of bleeding. ACS management among cancer patients should be based on an accurate evaluation of the risk of thrombosis and bleeding. Future studies focused on choosing optimal strategies in tumor patients with ACS should be performed to treat this subset of patients better.

Breast Cancer and Atrial Fibrillation.

This study aims to establish the incidence of atrial fibrillation (AF) in breast cancer (BC) patients, focusing on staging and anti-cancer treatment. A meta-analysis was conducted to investigate the incidence of AF in BC patients and compare this incidence to other cancers. Furthermore, we evaluated the occurrence of AF as an adverse effect of biological therapies vs. non-biological therapies vs. biological therapies + non-biological therapies in BC. Finally, we compared the incidence of AF in early BC and metastatic BC. Thirty studies were included. Twenty-two studies focused on BC, encompassing 166,271 patients. In the BC group, 2.7% of patients developed AF, while in the "all cancer" group, 5.8% of patients developed AF. In addition, there was no difference between different types of therapies (p = 0.61) and between early and metastatic BC (p = 0.57). The type of anti-cancer therapy and the staging of BC does not influence AF's occurrence in this neoplastic disease.

Chemosensitivity of Lung Metastatic High-Grade Synovial Sarcoma.

Background: Synovial sarcoma is a relatively chemosensitive type of soft tissue sarcoma and it often metastasizes to the lung. We investigated the role of adjuvant chemotherapy in patients with high-grade synovial sarcoma at their first lung metastasectomy (LMTS). Methods: Forty-six HGSS patients had their first LMTS at our institute (Rizzoli Orthopedic Hospital, Bologna, Italy) between 2000 and 2020. We divided them into two groups: (1) those undergoing adjuvant chemotherapy (n = 24) and (2) those not receiving adjuvant chemotherapy (n = 22). The primary outcome was a median survival at 32.5 (IQR 18.0-82.7) median follow-up. The disease-free interval was calculated at time zero (DFI0, interval between the diagnosis of the primary tumor and the first CT-diagnosed lung metastasis) and at any further lung relapse (DFI1-3). T0 was defined as the time at first LMTS and T1-T3 referred to the time of further metastasectomy. Results: Freedom from SS-specific mortality at 60 months was significantly higher in patients without chemotherapy (50.0% (33.0-76.0%) vs. 20.8% (9.55%-45.4%), p = 0.01). Chemotherapy was associated with a higher risk of SS-specific mortality at multivariable Cox regression (HR 2.8, p = 0.02). Furthermore, DFI0 ≤ 6 months, female sex, age > 40 years, and primary tumor > 10 cm increased the risk of death by about four, six, >three, and >five times, respectively. Conclusions. Adjuvant chemotherapy did not show any advantage in terms of freedom from SS-specific mortality in HGSS patients. Further larger studies are necessary to confirm our findings.

Surgical Risk Factors for Ischemic Stroke Following Coronary Artery Bypass Grafting. A Multi-Factor Multimodel Analysis.

Background: Ischemic stroke after coronary artery bypass (CABG) has been often linked to aortic manipulation during surgery. Objectives: The objective of the study was to estimate the rate of postoperative ischemic stroke within 30 days from CABG by surgical risk factors alone or in combination. Methods: The multinomial propensity score for multiple treatments was used to create six models with a total of 16,255 consecutive patients undergoing isolated CABG. For each model, a different classification variable was used to stratify patients. Results: Balance achieved in all models was substantial, enabling unbiased estimation of the treatment estimand. Both off-pump techniques with (0.009; 95% CI 0.006-0.011) or without proximal anastomoses (0.005; 0.005-0.003), and surgery performed on the beating heart using cardiopulmonary bypass with (0.009; 0.006-0.011) or without proximal anastomoses (0.024; 0.021-0.029) showed a mean stroke estimate significantly lower than the other techniques. Off-pump surgery and on-pump surgery without an aortic cross-clamp yielded nearly equal incidences of stroke (0.012; 0.008-0.015 and 0.018; 0.012-0.023, respectively). Using an aortic cross-clamp significantly increased the stroke estimate (0.075; 0.061-0.088), whereas using a side-biting clamp did not (0.039; 0.033-0.044). The number of aortic touches (0.029; 0.026-0.031) and the number of proximal anastomoses (0.044; 0.035-0.047) did not significantly increase the incidence of stroke. Conclusions: Aortic cross-clamping was found to be the primary cause of post-CABG ischemic stroke. Instead, additional aortic manipulation from a side-biting clamp, on-pump surgery, multiple aortic touches, number of proximal anastomoses, and aortic cannulation were found not to increase the estimate of stroke significantly. Further research on this topic is warranted.

Early and Midterm Clinical Outcomes of Transcatheter Valve-in-Valve Implantation Versus Redo Surgical Aortic Valve Replacement for Aortic Bioprosthetic Valve Degeneration: Two Faces of the Same Medal.

OBJECTIVE: To compare early and midterm outcomes of transcatheter valve-in-valve implantation (ViV-TAVI) and redo surgical aortic valve replacement (re-SAVR) for aortic bioprosthetic valve degeneration. DESIGN: Patients who underwent ViV-TAVI and re-SAVR for aortic bioprosthetic valve degeneration between January 2010 and October 2018 were retrospectively analyzed. Mean follow-up was 3.0 years. SETTING: In-hospital, early, and mid-term outcomes. PARTICIPANTS: Eighty-eight patients were included in the analysis. INTERVENTIONS: Thirty-one patients (37.3%) had ViV-TAVI, and 57 patients (62.7%) had re-SAVR. MEASUREMENTS AND MAIN RESULTS: In the ViV-TAVI group, patients were older (79.1 ± 7.4 v 67.2 ± 14.1, p < 0.01). The total operative time, intubation time, intensive care unit length of stay, total hospital length of stay, inotropes infusion, intubation >24 hours, total amount of chest tube losses, red blood cell transfusions, plasma transfusions, and reoperation for bleeding were significantly higher in the re-SAVR cohort (p < 0.01). There was no difference regarding in-hospital permanent pacemaker implantation (ViV-TAVI = 3.2% v re-SAVR = 8.8%, p = 0.27), patient-prosthesis mismatch (ViV-TAVI = 12 patients [mean 0.53 ± 0.07] and re-SAVR = ten patients [mean 0.56 ± 0.08], p = 0.4), stroke (ViV-TAVI = 3.2% v re-SAVR = 7%, p = 0.43), acute kidney injury (ViV-TAVI = 9.7% v re-SAVR = 15.8%, p = 0.1), and all-cause infections (ViV-TAVI = 0% v re-SAVR = 8.8%, p = 0.02), between the two groups. In-hospital mortality was 0% and 7% for ViV-TAVI and re-SAVR, respectively (p = 0.08). At three-years' follow-up, the incidence of pacemaker implantation was higher in the re-SAVR group (ViV-TAVI = 0 v re-SAVR = 13.4%, p < 0.01). There were no differences in reintervention (ViV-TAVI = 3.8% v re-SAVR = 0%, p = 0.32) and survival (ViV-TAVI = 83.9% v re-SAVR = 93%, p = 0.10) between the two cohorts. CONCLUSIONS: ViV-TAVI is a safe, feasible, and reliable procedure.

A hybrid approach to complex arrhythmias.

Despite many years of research, the different aspects of the mechanism of atrial fibrillation (AF) are still incompletely understood. And although the latest guidelines recommend catheter ablation with pulmonary vein isolation as a rhythm control strategy, long-term results in persistent and long-standing persistent AF are suboptimal. Historically, a mechanistic-based patient-tailored approach for the treatment of AF was impossible because of the lack real-time mapping techniques and advanced ablation tools. Therefore, surgeons created lesion sets based upon the anatomy of both atria and the safety of the incisions made by the knife. These complex open-heart procedures had to be performed through a sternotomy on the arrested heart and where therefore not generally adopted. The use of controlled energy sources such as cryothermy and radiofrequency where the first step to make the creation of these lesions less complex. With the development and improvement of electrophysiology techniques and catheters, this invasive and solely anatomical approach could again be partially redesigned. Now less invasive, it prepared the way for collaboration between electrophysiologists working on the endocardial side of the heart and cardiac surgeons providing epicardial access. The introduction of video-assisted technology and hybrid procedures has further increased the possibilities of new successful therapies. Now more than 40 years since the beginning of this exciting maze of AF procedures and still working towards a less aggressive and more comprehensive approach we give an overview of the history of the different minimally invasive surgical solutions and of the hybrid approach.

Biparietal bidirectional bipolar radiofrequency in hybrid cardiac ablation: an in vitro evaluation.

OBJECTIVES: The aim of this study was to evaluate the lesion size and depth of radiofrequency (RF) ablation in a simultaneous biparietal bidirectional bipolar (SBB) approach, compared to a simultaneous and staged unipolar and uniparietal bipolar setup [simultaneous uniparietal bipolar (SiUB) and staged uniparietal bipolar (StUB), respectively]. METHODS: Fresh left atrial porcine tissue was mounted into the ABLA-BOX simulator. Different ablation approaches were tested: (i) SBB: a concept consisting of SBB endo-epicardial ablation, (ii) SiUB: simultaneous epicardial uniparietal bipolar and endocardial unipolar ablation and (iii) StUB: staged epicardial uniparietal bipolar and endocardial unipolar ablation. In the StUB setup, a 1-h interval between the epi-endo ablation was respected. RESULTS: Transmural lesions were present in 90% of the bipolar biparietal ablations, yet no full transmurality was observed in the simultaneous nor in the staged unipolar with uniparietal bipolar ablation group. In SBB, the area and volume of the ablation lesions were smaller (523.33 mm2/mm and 52.33 mm3/mm, respectively) than in SiUB (588.17 mm2/mm and 58.81 mm3/mm, respectively) and StUB (583.76 mm2/mm and 58.37 mm3/mm, P = 0.044). Also, in SBB, the overall, epicardial and endocardial maximum diameters of the lesions (1.59, 1.57 and 1.52 mm; respectively) were smaller than in SiUB (2.38, 2.26 and 2.33 mm; respectively) and in StUB (2.36, 2.28 and 2.14 mm; respectively, all P < 0.001). CONCLUSIONS: Although bipolar biparietal bidirectional RF ablation results in smaller lesions than uniparietal bipolar and unipolar ablation, their capacity to penetrate the tissue is much higher. Moreover, in uniparietal RF applications, the energy spreads in the superficial layers of the tissue but fails to penetrate. Therefore, the degree of transmurality is much higher when using such a 'truly bipolar' ablation approach.