The Origin of Floral Quartet Formation-Ancient Exon Duplications Shaped the Evolution of MIKC-type MADS-domain Transcription Factor Interactions.

During development of flowering plants, some MIKC-type MADS-domain transcription factors (MTFs) exert their regulatory function as heterotetrameric complexes bound to two sites on the DNA of target genes. This way they constitute "floral quartets" or related "floral quartet-like complexes" (FQCs), involving a unique multimeric system of paralogous protein interactions. Tetramerization of MTFs is brought about mainly by interactions of keratin-like (K) domains. The K-domain associated with the more ancient DNA-binding MADS-domain during evolution in the stem group of extant streptophytes (charophyte green algae + land plants). However, whether this was sufficient for MTF tetramerization and FQC formation to occur, remains unknown. Here, we provide biophysical and bioinformatic data indicating that FQC formation likely originated in the stem group of land plants in a sublineage of MIKC-type genes termed MIKCC-type genes. In the stem group of this gene lineage, the duplication of the most downstream exon encoding the K-domain led to a C-terminal elongation of the second K-domain helix, thus, generating the tetramerization interface found in extant MIKCC-type proteins. In the stem group of the sister lineage of the MIKCC-type genes, termed MIKC*-type genes, the duplication of two other K-domain exons occurred, extending the K-domain at its N-terminal end. Our data indicate that this structural change prevents heterodimerization between MIKCC-type and MIKC*-type proteins. This way, two largely independent gene regulatory networks could be established, featuring MIKCC-type or MIKC*-type proteins, respectively, that control different aspects of plant development.

Surgery for Active Infective Endocarditis on Mitral Valve: Anatomical, Surgical, and Disease Factors as Long-Term Outcome Modifiers.

Background and Objectives: Determinants of long-term outcomes after surgery for native mitral valve endocarditis have not been thoroughly investigated. The aim of this study was to assess anatomical, disease, and surgical risk factors for long-term mortality and need of reintervention, in patients undergoing mitral valve surgery for active endocarditis. Materials and Methods: Patients who underwent surgery for active native mitral valve endocarditis at three academic centres, between 2000 and 2022, were analysed. The primary outcome was long-term survival. The secondary outcome was the freedom from mitral reoperation. Survival curves were constructed with Kaplan-Meier methodology. Multivariable Cox regression was used to identify demographic, anatomical, disease, and surgical factors associated with late mortality and reoperation. Results: 335 consecutive patients with active mitral endocarditis were analysed. Two hundred and one patients (70.5%) had infection confined to the valve cusp whereas 89 (25.6%) had invasive disease extended to the annulus and surrounding tissues. Preoperative neurological events occurred at the diagnosis in 52 cases. Streptococci were the most common causative organisms followed by Staphylococcus aureus, Coagulase-negative Staphylococcus, and Enterococcus. Valve repair was performed in 108 patients (32.2%). Survival at 5 and 10 years was 70.1% and 59.2%, respectively. Staphylococcus emerged as an independent predictor of late mortality, along with age, chronic obstructive pulmonary disease, and previous cardiac surgery. Survival was considerably reduced in patients with S. aureus compared with those without (log rank p < 0.001). The type of surgery (repair vs. replacement) did not emerge as a risk factor for late mortality and reoperation. Seventeen patients underwent mitral reoperation during the follow-up. The 5- and 10-year freedom from reoperation was 94.7% and 91.8%, respectively. Conclusions: Active mitral valve endocarditis remains a life-threatening disease with impaired survival. While lesion characteristics influenced surgical decision-making and intraoperative management, their impact on long-term survival and freedom from reintervention appears to be moderated by other factors such as infecting pathogens and patient comorbidities.

Surgical aortic valve replacement in elderly patients: effects on physical performance, cognitive function and health-related quality of life.

BACKGROUND: Surgical aortic valve replacement (SAVR) is still the gold standard for treating aortic valve stenosis (AVS). Its effectiveness has been extensively examined in terms of perioperative mortality, but its impact on overall health has received much less attention. AIMS: To assess the physical performance, cognitive status, and health-related quality of life of elderly patients undergoing SAVR, in the short, medium and long term. METHODS: This single-center prospective study enrolled patients aged > 70 years who underwent isolated SAVR for severe AVS. Data were collected on each participant's clinical status, physical performance, cognitive status, mood, and health-related quality of life. This multidimensional geriatric assessment was performed before surgery (T0), and again at 45 days (T1), 3 months (T2), 6 months (T3), and 12 months (T4) post-surgery. Baseline (T0) and follow-up (T2-T4) data were compared separately for patients grouped by gender using paired t-tests. RESULTS: Data from a total of 35 patients were analyzed. Compared with the baseline (T0), nutritional status worsened at T1, then gradually improved through to T4. Physical performance, mood, and health-related quality of life improved significantly after surgery. Cognitive function showed no change through to T3, but then deteriorated at T4. CONCLUSIONS: Our results show that SAVR in patients over 70 years of age has a positive impact on nutrition, mood, and health-related quality of life. Cognitive function was not negatively affected in the short and medium term, although it deteriorated in the long term. SAVR also had a positive impact on the physical performance of our sample.

Long-Term Outcomes in Heart Transplanted Patients with Anderson-Fabry Disease: Effectiveness of a Combined Medical and Surgical Therapy.

BACKGROUND: Transplantation in the management of end-stage organ failure in patients with Anderson- Fabry disease is still a matter of debate due to a lack of data regarding long-term outcomes and prognosis. OBSERVATIONS: Most of the cases in the literature did not receive enzyme-replacement therapy (ERT), or received it only years after transplantation. Based on our experience, we describe here the long-term results of heart transplant in combination with early ERT. CONCLUSIONS: Transplantation combined with lifelong ERT should be considered to offer patients a chance of good long-term outcomes and quality of life.

Totally peripheral approach for ICD lead vegetation removal in a GUCH patient.

AngioVac system (AngioDynamics) has already proved to be a useful tool in the treatment of thrombotic and endocarditic formations concerning the venous district. Herein, the AngioVac aspiration system combined with the bidirectional rotational Evolution mechanical sheath lead extraction was used for an effective and safety cardiac-device-related-infective-endocarditis removal in a grown-up congenital heart disease patient through a totally peripheral approach.

From bench to bedside: Impact of left ventricular assist device outflow conduit anastomosis position on outcome.

Continuous flow left ventricular assist devices (LVADs) have become a valuable therapy for end-stage heart failure. In vitro research highlighted a role of outflow cannula position on the pattern of blood flow in the aorta. However, the clinical effects of the alterations of flow remain unclear. We investigate short- and long-term outcomes of patients implanted with Jarvik 2000 LVAD, according to the ascending (Group 1) versus descending (Group 2) outflow graft connection to the aorta in a multicenter study. From May 2008 to October 2014, 140 consecutive end-stage heart failure patients underwent Jarvik 2000 LVAD implantation in 17 Italian centers. According with a preliminary multivariate analysis, we selected the 90 patients implanted in the four high-volume centers to avoid bias (Group 1 n = 39, Group 2 n = 51). Among the groups, no differences were recorded in the hospital mortality and the main complications occurring after LVAD implantation were similar. In multivariable analysis, the ascending aorta outflow cannula position and higher creatinine at discharge were significant predictors for long-term survival. Postimplant hemolysis was more pronounced in descending aorta outflow graft anastomosis. Outflow graft anastomosis to the ascending aorta is associated with better long-term survival, independent of age and perfusion techniques, reflecting the previous in vitro results.

Clinicopathological insights from early structural valve deterioration of a surgical and transcatheter valve-in-valve mitral bioprotheses.

INTRODUCTION: Transcatheter mitral valve replacement (TMVR) is indicated in case of degenerated bioprosthesis in high-risk patients. However, durability of these valves still represents an important issue. METHODS: Early severe structural valve deterioration of a mitral porcine surgical bioprosthesis and of a subsequent bovine TMVR, both at 4 years follow-up, is here presented. RESULTS: Gross, histopathologic, and X-ray examination revealed massive calcification of both devices and fibrous tissue overgrowth involving the TMVR stent. CONCLUSIONS: Careful clinical evaluation and strict follow-up are mandatory to identify early signs of dysfunction and to intervene in a timely manner.

Rescue Coronary Artery Bypass Grafting in a Neonate After Arterial Switch Operation: A Temporary or a Lifetime Solution?

We describe a case where prompt myocardial rescue revascularization at the time of arterial switch operation (ASO) for D-transposition of the great arteries (D-TGA) was fundamental for overcoming the acute intraoperative myocardial injury and for restoring prompt left ventricular function. Five years following the ASO the patient was asymptomatic but signs of myocardial ischemia were found at SPECT MI, potentially leading to ischemic complications. Adult patients who required coronary revascularization in the neonatal period need to be followed for life to prevent and treat any possible cause of further myocardial ischemia during childhood and adulthood.

Multicenter, propensity-weighted comparison of stented, rapid-deployment and new-generation aortic valves.

Background: Conventional stented, rapid deployment and new-generation stented valves are now available for surgical aortic valve replacement (SAVR). New-generation devices feature advanced tissue treatment for theoretical prolonged durability and a new stent design able to expand in case of future transcatheter Valve-in-Valve. Aim of this retrospective, multicenter, propensity-weighted study was to compare early clinical and hemodynamic outcomes of these three different bioprostheses. Methods: We analyzed data of 2589 patients from two national multicenter registries and one Institutional database. Study devices were Magna Ease, Intuity/Intuity Elite and Inspiris Resilia (Edwards Lifesciences, Irvine, CA, USA) and were implanted in 296 (11.4 %), 1688 (65.2 %) and 605 (23.4 %) patients, respectively. A propensity score weighting approach was employed. Results: In isolated SAVR, aortic cross clamp (ACC) time was shorter for Intuity (Magna Ease: 87, Intuity: 55, Inspiris: 70 min; Magna Ease vs. Intuity: p < 0.001; Inspiris vs. Intuity: p < 0.001). Overall mortality was 2 %, 1.7 % and 0.5 % in Magna Ease, Intuity and Inspiris groups, respectively (Magna Ease vs. Intuity: p = 0.476; Inspiris vs. Intuity: p = 0.395); permanent pace-maker implantation rate was lower for Inspiris (Magna Ease: 6 %, Intuity: 6 %, Inspiris: 2 %; Magna Ease vs. Intuity: p = 0.679; Inspiris vs. Intuity: p < 0.001). Median mean gradients were 13, 10 and 10 mmHg for Magna Ease, Intuity and Inspiris, respectively (Magna Ease vs. Intuity: p < 0.001; Inspiris vs. Intuity: p = 0.13). Conclusions: All study devices provide excellent early clinical and hemodynamic outcomes. Inspiris shows low rates of permanent pace-maker implantation and its transaortic gradients are similar to rapid-deployment valves and lower than Magna Ease.

Current Understanding and Future Directions of Transcatheter Devices to Assist Failing Fontan.

Even if the Fontan operation is the surgical treatment of choice in patients with univentricular physiology, it remains a palliative strategy. Consequently, when Fontan patients reach adulthood, the majority of them develop late clinical sequelae of a failing cavo-pulmonary circuit (eg, liver failure, protein-losing enteropathy, and arrhythmias). Although heart transplantation represents the gold standard to treat this condition, Fontan patients usually accede to this therapy late, when risk of mortality is significantly increased, and a shortage of donor hearts limits transplantation in this special population. Mechanical circulatory support is an emerging field, but it is still in the experimental stage. Current mechanical circulatory devices have been used in Fontan circulation but are associated with the need for high-risk redo surgery. Percutaneous pumps are an emerging field that is still under investigation, with multiple prototypes developed. This review aims to analyze the hemodynamic profile of the developed intravascular pumps and their application in the preclinical scenario in the Fontan circulation.

Heart transplantation in juvenile-onset systemic sclerosis with primary cardiac involvement: report of two cases and comprehensive literature review.

Juvenile onset systemic sclerosis is a rare chronic multisystem connective tissue disease characterized by skin induration, microangiopathy, autoimmune disturbances and widespread fibrosis of internal organs. Primary cardiac involvement in systemic sclerosis (SSc) is associated with a variable phenotype, including heart failure and arrhythmias, which lead to poor short-term prognosis. Isolated heart transplantation is a rare approach for the treatment of advanced heart failure in patients with systemic sclerosis. We report on two juvenile SSc patients receiving cardiac transplantation due to heart failure with malignant arrhythmias. One patient presented with severe dilated cardiomyopathy with recurrent ventricular tachycardia. Following the appearance of Raynaud phenomenon, he was subsequently diagnosed a rare form of systemic sclerosis sine scleroderma, without cutaneous manifestations or other organs involved. His cardiac condition was unresponsive to antiarrhythmic therapy and immunosuppression used to treat SSc, therefore he underwent successful heart transplantation. The second patient presented diffuse scleroderma with mild pulmonary, esophageal and renal involvement. While extracardiac manifestations were effectively kept under control with immunosuppressive therapy, cardiac involvement rapidly progressed with detection of fibrosis at cardiac magnetic resonance imaging and appearance of severe ventricular arrhythmia. Herein, an extensive multidisciplinary evaluation was pivotal in defining the entity and clinical stability of extracardiac involvement, and thus the patient could profit from heart transplantation. Our experience highlights the importance of considering heart transplantation in carefully selected SSc patients with primary cardiac involvement as a lifesaving procedure.

A Comprehensive Excursus of the Roles of Echocardiography in Heart Transplantation Follow-Up.

Current guidelines for the care of heart transplantation recipients recommend routine endomyocardial biopsy and invasive coronary angiography as the cornerstones in the surveillance for acute rejection (AR) and coronary allograft vasculopathy (CAV). Non-invasive tools, including coronary computed tomography angiography and cardiac magnetic resonance, have been introduced into guidelines without roles of their own as gold standards. These techniques also carry the risk of contrast-related kidney injury. There is a need to explore non-invasive approaches providing valuable information while minimizing risks and allowing their application independently of patient comorbidities. Echocardiographic examination can be performed at bedside, serially repeated, and does not carry the burden of contrast-related kidney injury and procedure-related risk. It provides comprehensive assessment of cardiac morphology and function. Advanced echocardiography techniques, including Doppler tissue imaging and strain imaging, may be sensitive tools for the detection of minor myocardial dysfunction, thus providing insight into early detection of AR and CAV. Stress echocardiography may offer a valuable tool in the detection of CAV, while the assessment of coronary flow reserve can unravel coronary microvascular impairment and add prognostic value to conventional stress echocardiography. The review highlights the role of Doppler echocardiography in heart transplantation follow-up, weighting advantages and limitations of the different techniques.

Respiratory exchange ratio overshoot during exercise recovery: a promising prognostic marker in HFrEF.

BACKGROUND AND AIMS: Transient increases (overshoot) in respiratory gas analyses have been observed during exercise recovery, but their clinical significance is not clearly understood. An overshoot phenomenon of the respiratory exchange ratio (RER) is commonly observed during recovery from maximal cardiopulmonary exercise testing (CPET), but it has been found reduced in patients with heart failure with reduced ejection fraction (HFrEF). The aim of the study was to analyze the clinical significance of these RER recovery parameters and to understand if these may improve the risk stratification of patients with HFrEF. METHODS: This cross-sectional study includes HFrEF patients who underwent functional evaluation with maximal CPET for the heart transplant checklist at our Sports and Exercise Medicine Division. RER recovery parameters, including RER overshoot as the percentual increase of RER during recovery (RER mag), have been evaluated after CPET with assessment of hard clinical long-term endpoints (MACEs/deaths and transplant/LVAD-free survival). RESULTS: A total of 190 patients with HFrEF and 103 controls were included (54.6 ± 11.9 years; 73% male). RER recovery parameters were significantly lower in patients with HFrEF compared to healthy subjects (RER mag 24.8 ± 14.5% vs 31.4 ± 13.0%), and they showed significant correlations with prognostically relevant CPET parameters. Thirty-three patients with HFrEF did not present a RER overshoot, showing worse cardiorespiratory fitness and efficiency when compared with those patients who showed a detectable overshoot (VO2 peak: 11.0 ± 3.1 vs 15.9 ± 5.1 ml/kg/min; VE/VCO2 slope: 41.5 ± 8.7 vs 32.9 ± 7.9; ΔPETCO2: 2.75 ± 1.83 vs 4.45 ± 2.69 mmHg, respectively). The presence of RER overshoot was associated with a lower risk of cardiovascular events and longer transplant-free survival. CONCLUSION: RER overshoot represents a meaningful cardiorespiratory index to monitor during exercise gas exchange evaluation; it is an easily detectable parameter that could support clinicians to comprehensively interpreting patients' functional impairment and prognosis. CPET recovery analyses should be implemented in the clinical decision-making of advanced HF.

Redefining CAV surveillance strategies: Benefits of CCTA vs. ICA.

BACKGROUND: Cardiac allograft vasculopathy (CAV) assessment post-heart transplantation (HT) typically relies on invasive coronary angiography (ICA). However, cardiac computed tomography angiography (CCTA) is emerging as a promising alternative due to its potential benefits in economic, safety, and logistical aspects. This study aimed to evaluate the impact of a CCTA program on these aspects in CAV surveillance post-HT. METHODS: A retrospective single-center study was conducted between March 2021 and February 2023, involving HT patients who underwent either CCTA or ICA. RESULTS: Among 260 patients undergoing CAV surveillance, 115 (44.2%) patients underwent CCTA, and 145 (55.8%) patients underwent ICA. The CCTA group showed incurred lower overall costs (p â€‹< â€‹0.0001) and shorter hospitalization times (p â€‹< â€‹0.0001) compared to the ICA group. In terms of safety, CCTA surveillance required significantly lower contrast volumes (p â€‹< â€‹0.0001) and lower effective doses (p â€‹= â€‹0.03). CONCLUSION: CCTA emerges as a safe and cost-effective non-invasive alternative for CAV surveillance post-HT, outperforming ICA in terms of safety, logistical aspects, and economic burden.

Navigating the Heart. The Evolution of the AngioVac System in a Single-center Experience.

We investigated the efficacy, safety, and versatility of the AngioVac (AngioDynamics, Latham, NY) system for the treatment of intravascular and intracardiac masses of different origins. We prospectively enrolled all consecutive patients treated with the AngioVac system between July-2016 and November-2021 at our institution. Three configurations of the device were adopted in 44 patients: a venous-venous circuit in 21 cases (47.7%), a venous-arterial ECMO-like configuration in 20 (45.5%), and a venous-arterial-arterial circuit with 2 centrifugal pumps for left-sided cardiac masses in 3 (6.8%). Successful removal of the mass was achieved in 41 patients (93.2%), while in the other cases conversion to full sternotomy was necessary. Intraoperative complications occurred in 3 cases (6.8%), including 1 death, 1 pulmonary embolization, and 1 cardiac perforation. The AngioVac system is a valid, safe, and versatile option for the treatment of intravascular masses also in patients with prohibitive surgical risk.

Anticoagulation alone as an effective and safe antithrombotic therapy in LVAD: When less is more.

To evaluate the safety and effectiveness of anticoagulation alone in HeartMate3 patients. According to antithrombotic regimen, patients were divided into 2 groups: Group-1(warfarin+aspirin) and Group-2(warfarin). A comparison of hemocompatibility-related adverse events (HRAEs), hemocompatibility score (HCS), and hemocoagulative laboratory markers, both qualitative and quantitative, between the 2 groups were performed. Fifty patients were enrolled, 28 (56%) in Group-1 and 22 in Group-2 (44%), without statistical differences at baseline. Median time of follow-up was 590 days (IQR: 410.25-1007.50). Eighteen HRAEs (36.0%) occurred: 17 in Group-1 (34%) and 1 in Group-2 (2%) (P < 0.001). The net HCS for Group-1 versus Group-2 was 24 points and 1 point (OR 12.116[2.034-233.226], P = 0.023), respectively. Hemocoagulative values turned into the normality and remained stable during follow-up, without differences between groups, except for ASPI-test (P = 0.003). HeartMate3 showed a high hemocompatibility independently from antithrombotic therapy. Aspirin avoidance resulted a safe and effective strategy since it reduced hemorrhagic events, without increasing thrombotic risk.

Transapical TAVI: Survival, Hemodynamics, Devices and Machine Learning. Lessons Learned After 10-Year Experience.

Aim of this single-center, retrospective study was to assess early and long-term clinical and hemodynamic results of transapical aortic valve implantation (TA-TAVI), and to identify predictors of survival at follow-up. All patients undergoing TA-TAVI for severe aortic valve stenosis at our institution were reviewed. A hybrid approach based on machine-learning techniques was employed to identify survival predictors, using a bagging-decision-tree algorithm and a Random-Forest algorithm, respectively. Two-hundred-thirty-four consecutive patients underwent TA-TAVI (March 2009-May 2019). All cause 30-day mortality was 5.1%. Device success was 95.7%. Median follow-up time was 35.2 months. Kaplan-Meier overall survival rates at 2, 5, and 8 years were 75%, 44%, and 15%, respectively. Structural-valve-deterioration occurred in 25 patients (11.3%) overall. The strongest predictors of survival at follow-up were age, body-mass-index, and ejection fraction. TA-TAVI provided valid early and long-term outcomes. These data support its choice as an optimal alternative access whenever the transfemoral route is not feasible.

Proof of Concept: Trans-atrial AngioVac Aspiration of Mitral Valve Thrombosis in a COVID-19 Patient.

In patients with a prohibitive surgical risk, the AngioVac cannula can be used to remove left-sided cardiac masses, as an off-label adaptation of the device. We herein describe a novel micro-invasive approach to gain access to the left atrium for the aspiration of a mitral valve mass in a patient affected by severe coronavirus disease 2019. Through a right anterior mini-thoracotomy, the right superior pulmonary vein was accessed and used to insert the aspiration cannula. A parallel venous-arterial extracorporeal membrane oxygenation (ECMO)-like circuit provided circulatory and respiratory support to ensure proper intra- and postoperative hemodynamic stabilization.

New Non-Invasive Imaging Technologies in Cardiac Transplant Follow-Up: Acquired Evidence and Future Options.

Heart transplantation (HT) is the established treatment for end-stage heart failure, significantly enhancing patients' survival and quality of life. To ensure optimal outcomes, the routine monitoring of HT recipients is paramount. While existing guidelines offer guidance on a blend of invasive and non-invasive imaging techniques, certain aspects such as the timing of echocardiographic assessments and the role of echocardiography or cardiac magnetic resonance (CMR) as alternatives to serial endomyocardial biopsies (EMBs) for rejection monitoring are not specifically outlined in the guidelines. Furthermore, invasive coronary angiography (ICA) is still recommended as the gold-standard procedure, usually performed one year after surgery and every two years thereafter. This review focuses on recent advancements in non-invasive and contrast-saving imaging techniques that have been investigated for HT patients. The aim of the manuscript is to identify imaging modalities that may potentially replace or reduce the need for invasive procedures such as ICA and EMB, considering their respective advantages and disadvantages. We emphasize the transformative potential of non-invasive techniques in elevating patient care. Advanced echocardiography techniques, including strain imaging and tissue Doppler imaging, offer enhanced insights into cardiac function, while CMR, through its multi-parametric mapping techniques, such as T1 and T2 mapping, allows for the non-invasive assessment of inflammation and tissue characterization. Cardiac computed tomography (CCT), particularly with its ability to evaluate coronary artery disease and assess graft vasculopathy, emerges as an integral tool in the follow-up of HT patients. Recent studies have highlighted the potential of nuclear myocardial perfusion imaging, including myocardial blood flow quantification, as a non-invasive method for diagnosing and prognosticating CAV. These advanced imaging approaches hold promise in mitigating the need for invasive procedures like ICA and EMB when evaluating the benefits and limitations of each modality.

Propensity-Weighted Comparison of Conventional Stented and Rapid-Deployment Aortic Bioprostheses.

Aim of this study was to compare early clinical and hemodynamic outcomes of Intuity and ME bioprostheses. A propensity score weighting approach was performed. Preoperative variables were defined according to EuroSCORE criteria and postoperative complications according to VARC-2 definitions. We evaluated 375 patients who underwent SAVR with the 2 study devices. Intuity and ME were implanted in 252 (67.2%) and in 123 (32.8%) patients, respectively. There were no differences in terms of postoperative complications, including mortality (1% in each group; OR 0.46[0.05;4.21]). The incidence of pace-maker implantation was 6% and 5% in Intuity and ME groups, respectively (OR 0.53[0.27;1.07]). Intuity showed significantly lower gradients (Median mean gradients: 9mmHg vs 14mmHg, P<0.001), larger effective orifice area index (1.13cm2/m2 vs 1cm2/m2, P=0.007) and lower incidence of patient-prosthesis mismatch (7.1% vs 22.8%, P=0.006). The RD Intuity provides similar early clinical outcomes but shows significantly better hemodynamic performance compared to the ME valve.