Treatment of multiple valve disease: surgery, structural intervention, or both?

Multiple valve heart disease refers to the simultaneous presence of several valvular anomalies, while mixed valvular heart disease refers to the combination of stenotic lesions or regurgitation affecting the same valve. The pathophysiology of multiple and mixed valvular heart disease depends on the combination of affected valves and the severity of the individual valvular defects. Imaging is essential for diagnosis and assessment of disease severity. The treatment of combined valvular defects currently represents a challenge for both cardiac surgeons and interventional cardiologists since only few data in the literature address the clinical and therapeutic decision-making process related to these complex lesions. These are heterogeneous conditions, which differ from each other in the combination of the valves involved, in the pathogenesis with which they develop, in the severity of the individual lesions, in the associated surgical risk, in the possibility of being repaired, and in the undergoing transcatheter treatments. In addition to the severity of the individual valve defects, the choice of treatment also depends on the ventricular function and the general condition of the patient. This work aims to provide a review of the state of the art regarding the possible management strategies of the most common multiple valve diseases in clinical practice.

Large Abdominal Aortic Aneurysm in a High-Risk Surgical Patient: Combined Percutaneous Transfemoral TAVI and EVAR Procedure.

A 78-year-old man was referred for surgical treatment of a 55 x 59 mm abdominal aortic aneurysm (AAA). However, clinical and instrumental data revealed a more complex case than was initially thought, the patient having a large AAA in the setting of severe symptomatic aortic stenosis with multiple comorbidities. Following multidisciplinary discussion, a combined transcatheter aortic valve implantation and endovascular aneurysm repair was performed. The present case represents a good example of the importance of the heart team in the project of tailored operative strategies, and in the optimization of the interventional therapy for the individual patient.

Simultaneous transapical paraprosthetic leak occlusion and valve-in-valve implantation into a degenerated mitral bioprosthesis.

Transcatheter valve-in-valve implantation is an emerging treatment option for high-risk patients with failing mitral bioprostheses. The presence of a paravalvular leak is considered a contraindication to this procedure that would leave the patient with significant residual regurgitation. The case is described of a patient with a severely degenerated 29 mm Carpentier-Edwards mitral bioprosthesis successfully treated by simultaneous transapical transcatheter valve-in-valve implantation and paraprosthetic leak occlusion. The potential advantages of this approach are discussed.

PFAS-free superhydrophobic chitosan coating for fabrics.

In view of health and environmental concerns, together with the upcoming restrictive regulations on per- and polyfluoroalkyl substances (PFAS), less impactful materials must be explored for the hydrophobization of surfaces. Polysaccharides, and especially chitosan, are being explored for their desirable properties of film formation and ease of modification. We present a PFAS-free chitosan superhydrophobic coating for textiles deposited through a solvent-free method. By contact angle analysis and drop impact, we observe that the coating imparts hydrophobicity to the fabrics, reaching superhydrophobicty (θA = 151°, θR = 136°) with increased amount of coating (from 1.6 g/cm2). This effect is obtained by the combination of chemical water repellency of the modified chitosan and the nano- and micro-roughness, assessed by SEM analysis. We perform a comprehensive study on the durability of the coatings, showing good results especially for acidic soaking where the hydrophobicity is maintained until the 8th cycle of washing. We assess the degradation of the coating by a TGA-IR investigation to define the compounds released with thermal degradation, and we confirm the coating's biodegradability by biochemical oxygen consumption. Finally, we demonstrate its biocompatibility on keratinocytes (HaCaT cell line) and fibroblasts (HFF-1 cell line), confirming that the coating is safe for human skin cells.

Multimodality Imaging Approach for Planning and Guiding Direct Transcatheter Tricuspid Valve Annuloplasty.

Interest in transcatheter treatment of tricuspid regurgitation (TR) has grown significantly in recent years due to increasing evidence correlating TR severity with mortality and to limited availability of surgical options often considered high-risk in these patients. Although edge-to-edge repair is currently the main transcatheter therapeutic strategy, tricuspid valve direct annuloplasty can also be performed safely and effectively to reduce TR and improve heart failure symptoms and quality of life. In the annuloplasty procedure, an adjustable band is implanted around the tricuspid annulus to reduce valvular size and improve TR. Patient selection and careful preoperative imaging, including transthoracic echocardiography, transesophageal echocardiography, and computed tomography, are critical for procedural success and proper device implantation. Compared to edge-to-edge repair, perioperative imaging with transesophageal echocardiography and fluoroscopy is particularly challenging. Alignment and insertion of the anchors are demanding but essential to achieve good results and avoid damaging the surrounding structures. The presence of shadowing artifacts due to cardiac devices makes the acquisition of good-quality images even more challenging. In this review, we discuss the current role of multimodality imaging in planning direct transcatheter tricuspid valve annuloplasty and describe all procedural steps focusing on echocardiographic monitoring.

Sequencing of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes in familial cases of bicuspid aortic valve.

BACKGROUND: The purpose of our study was to investigate the potential contribution of germline mutations in NOTCH1, GATA5 and TGFBR1 and TGFBR2 genes in a cohort of Italian patients with familial Bicuspid Aortic Valve (BAV). METHODS: All the coding exons including adjacent intronic as well as 5' and 3' untranslated (UTR) sequences of NOTCH1, GATA5, TGFBR1 and TGFBR2 genes were screened by direct gene sequencing in 11 index patients (8 males; age = 42 ± 19 years) with familial BAV defined as two or more affected members. RESULTS: Two novel mutations, a missense and a nonsense mutation (Exon 5, p.P284L; Exon 26, p.Y1619X), were found in the NOTCH1 gene in two unrelated families. The mutations segregated with the disease in these families, and they were not found on 200 unrelated chromosomes from ethnically matched controls. No pathogenetic mutation was identified in GATA5, TGFBR1 and TGFBR2 genes. CONCLUSIONS: Two novel NOTCH1 mutations were identified in two Italian families with BAV, highlighting the role of a NOTCH1 signaling pathway in BAV and its aortic complications. These findings are of relevance for genetic counseling and clinical care of families presenting with BAV. Future studies are needed in order to unravel the still largely unknown genetics of BAV.

The Positive Impact of Early Frailty Levels on Mortality in Elderly Patients with Severe Aortic Stenosis Undergoing Transcatheter/Surgical Aortic Valve Replacement.

Background: Frailty is highly common in older patients (pts) undergoing transcatheter aortic valve replacement (TAVR), and it is associated with poor outcomes. The selection of patients who can benefit from this procedure is necessary and challenging. The aim of the present study is to evaluate outcomes in older severe aortic valve stenosis (AS) pts, selected by a multidisciplinary approach for surgical, clinical, and geriatric risk and referred to treatment, according to frailty levels. Methods: A total of 109 pts (83 ± 5 years; females, 68%) with AS were classified by Fried's score in pre-frail, early frail, and frail and underwent surgical aortic valve replacement SAVR/TAVR, balloon aortic valvuloplasty, or medical therapy. We evaluated geriatric, clinical, and surgical features and detected periprocedural complications. The outcome was all-cause mortality. Results: Increasing frailty was associated with the worst clinical, surgical, geriatric conditions. By using Kaplan-Meier analysis, the survival rate was higher in pre-frail and TAVR groups (p < 0.001) (median follow-up = 20 months). By using the Cox regression model, frailty (p = 0.004), heart failure (p = 0.007), EF% (p = 0.043), albumin (p = 0.018) were associated with all-cause mortality. Conclusions: According to tailored frailty management, elderly AS pts with early frailty levels seem to be the most suitable candidates for TAVR/SAVR for positive outcomes because advanced frailty would make each treatment futile or palliative.

Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation.

Introduction: Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev-Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosomes (pEXOs) are smallest nanovesicles exerting early postoperative cardioprotection. We hypothesized that late plasma exosomal microRNAs (miRs) contribute to Rev-Rem during the late postoperative period. Methods: Primary MR patients (n = 19; age, 45-71 years) underwent cardiac magnetic resonance imaging and blood sampling before (T0) and 6 months after (T1) MVR. The postoperative LV Rev-Rem was assessed in terms of a decrease in LV end-diastolic volume and patients were stratified into high (HiR-REM) and low (LoR-REM) LV Rev-Rem subgroups. Isolated pEXOs were quantified by nanoparticle tracking analysis. Exosomal microRNA (miR)-1, -21-5p, -133a, and -208a levels were measured by RT-qPCR. Anti-hypertrophic effects of pEXOs were tested in HL-1 cardiomyocytes cultured with angiotensin II (AngII, 1 µM for 48 h). Results: Surgery zeroed out volume regurgitation in all patients. Although preoperative pEXOs were similar in both groups, pEXO levels increased after MVR in HiR-REM patients (+0.75-fold, p = 0.016), who showed lower cardiac mass index (-11%, p = 0.032). Postoperative exosomal miR-21-5p values of HiR-REM patients were higher than other groups (p < 0.05). In vitro, T1-pEXOs isolated from LoR-REM patients boosted the AngII-induced cardiomyocyte hypertrophy, but not postoperative exosomes of HiR-REM. This adaptive effect was counteracted by miR-21-5p inhibition. Summary/Conclusion: High levels of miR-21-5p-enriched pEXOs during the late postoperative period depict higher LV Rev-Rem after MVR. miR-21-5p-enriched pEXOs may be helpful to predict and to treat incomplete LV Rev-Rem after successful early surgical MVR.

Transcatheter valve in valve implantation for failed mitral and tricuspid bioprosthesis.

OBJECTIVE: We report our experience with the transapical transcatheter "Valve in valve" implantation (T-VIV) in patients with a failed mitral or tricuspid bioprosthesis; we briefly review the pertinent literature, and discuss some technical aspects of this procedure. BACKGROUND: Redo valve surgery for failure of a mitral or tricuspid bioprosthesis might become extremely challenging, both because of the patients' condition, which is frequently poor, and for the technical aspects of the operation itself, that can be very demanding. T-VIV has been widely employed with good results for the treatment of aortic bioprosthesis failure, and could represent an attractive option in this setting. METHODS: Four patients with multiple comorbidities (age: 63-83 years; logistic Euroscore: 37.2-81.5) underwent T-VIV at our institution for failure of a mitral [3] or tricuspid [1] bioprosthesis. A 26 mm Sapien valve was used in all cases. All the mitral procedures were performed via a transapical approach. The tricuspid procedure was performed via a transjugular approach. RESULTS: The first mitral procedure was complicated by the splaying of the xenograft stents and embolization of the valve. The procedure was converted to conventional surgery, and the patient died on postoperative day 1. In the subsequent procedures, the valve was positioned more atrially, and was fixed to the malfunctioning xenograft sewing ring. All subsequent procedures were successful, all patients were discharged home and were alive and well at follow-up. CONCLUSIONS: The results of T-VIV procedure in the mitral position have been suboptimal, and four of the sixteen patients reported to date died. However, all patients were extremely diseased, and some of the reported failures were related to amendable technical factors relative to the surgical access or to the valve deployment technique. With increasing experience, this procedure might become indicated as an alternative to conventional surgery in selected patients, encouraging increased use of bioprosthesis, and marking a pivotal change in the management of valvular disease.

Probing the Laser Ablation of Black Phosphorus by Raman Spectroscopy.

Laser ablation in conjunction with Raman spectroscopy can be used to attain a controllable reduction of the thickness of exfoliated black phosphorus flakes and simultaneous measurement of the local temperature. However, this approach can be affected by several parameters, such as the thickness-dependent heat dissipation. Optical, thermal, and mechanical effects in the flakes and the substrate can influence the laser ablation and may become a source of artifacts on the measurement of the local temperature. In this work, we carry out a systematic investigation of the laser thinning of black phosphorus flakes on SiO2/Si substrates. The counterintuitive results from Raman thermometry are analyzed and elucidated with the help of numerical solutions of the problem, laying the groundwork for a controlled thinning process of this material.

Hybrid repair of a Kommerell's diverticulum aneurysm.

Aneurysms of the right aortic arch with an aberrant left subclavian artery are rare. We report the case of a 77-year-old woman with a Kommerell's diverticulum aneurysm, who underwent a successful hybrid repair, combining surgical off-pump bypass of the aortic arch vessels followed by endovascular aneurysm repair.

A simple method to visualize the bicuspid aortic valve pathology by cardiac computed tomography.

Bicuspid aortic valve (BAV) disease is a spectrum of anomalies ranging from mild underdevelopment of a commissure to severe underdevelopment of two interleaflets triangles. Many different classifications of BAV, based on the echocardiographic, surgical or pathological appearance of the valve, and more recently on cardiac CT, have been proposed. We describe a simple technique, based on three-dimensional curved multiplanar reconstruction images, to obtain a pathology-like visualization of the full line of insertion (Hinge) of the aortic valve leaflets and of the interleaflet triangles with cardiac CT. This method could help to obtain a detailed categorization of any specific BAV anatomy based on the degree of underdevelopment (or on the absence) of one interleaflet triangle. Adherence to this concept could help to improve the imaging based analysis of BAV patients undergoing TAVR, and could lead to the adoption of a BAV classification based on the effective pathologic appearance of the valve also for patients undergoing TAVR.

Simultaneous Functional and Morphological Assessment of Left Atrial Appendage by 3D Virtual Models.

Purpose: The left atrial appendage (LAA) is responsible for thrombus formation in patients with atrial fibrillation. The evaluation of both LAA function and morphology is crucial for the patient characterization and the preprocedural planning of LAA closure intervention. Despite the availability of 3D imaging modalities, the current standard image analysis is based on manual delineation of the LAA contours on 2D views. Methods: In this study, a comprehensive approach based on a full 3D analysis of the tomographic dataset by surface extraction and processing (3D-S) is presented. The proposed method allows extracting functional and morphologic information in the entire cardiac cycle by minimalizing manual user interaction. The proposed methodology has been validated on ten computer tomography datasets. Results: The proposed 3D-S method was feasible in all cases. Reproducibility was improved with respect to the reference 2D manual procedure (2D-S) (coefficient of variation 2.9 vs. 4.1% for diastolic ostium area; 3.8 vs. 6.1% for systolic ostium area; 2.4 vs. 5.3% for diastolic LAA volume; 2.7 vs. 5.9% for systolic LAA volume; and 7.7 vs. 17.1% for LAA ejection fraction). No significant differences were found between 2D-S and 3D-S measurements. Conclusions: In this study, we introduced a fully 3D approach for LAA characterization, allowing the simultaneous assessment of LAA function and geometry. The proposed approach could be used to improve the patient selection and the best sizing of the device for LAA closure and to allow a patient-specific 3D printing.

Predictors of quality of life after radical treatment for prostate cancer.

INTRODUCTION: The usual treatment options for clinically localized prostate cancer carry a significant risk of lasting side effects, including urinary, bowel, and sexual dysfunction, that can alter overall the patient's quality of life. The aim of this research is to evaluate the impact of treatment timing (age at time of treatment, follow-up duration, age at time of follow-up), pretreatment tumor characteristics (clinical stage, Gleason score, PSA), and posttreatment outcomes (hormonal status, biochemical recurrence), on health-related quality of life (HRQOL) among men who had undergone radical treatment for prostate cancer. MATERIALS AND METHODS: 595 patients with prostate cancer who had undergone either radical prostatectomy or external beam radiation as primary therapy between 1988 and 2000 were selected for this retrospective, cross-sectional study. The enrolled subjects were asked to complete the Italian validated version of University of California-Los Angeles Prostate Cancer Index. Clinical parameters, hormone therapy status and posttreatment outcomes were considered to perform uni- and multivariate analyses. RESULTS: Both uni- and multivariate analyses demonstrated that timing of radical treatment is a critical predictive factor for sexual activity. Pretreatment tumor characteristics had a significant impact on urinary function, urinary bother and sexual function. Hormone treatment exclusively influenced sexual function and sexual bother, while biochemical recurrence can also worsen urinary symptoms and urinary bother. CONCLUSION: Our findings suggest that treatment timing, pretreatment tumor characteristics and posttreatment outcomes may have an impact on HRQOL in patients who have undergone radical treatment for prostate cancer: all these items should be considered in order to achieve an accurate interpretation of prostate cancer treatment outcomes.

Increased Gradients After Aortic Valve Replacement With the Perceval Valve: The Role of Oversizing.

BACKGROUND: Significant underexpansion or distortion of valved stents may be associated with altered leaflet function, leading to increased transprosthetic gradients and, possibly, early structural degeneration. We investigated the relationship between a computed tomography measure of the degree of oversizing and the early hemodynamic and clinical outcomes in patients undergoing aortic valve replacement with the Perceval sutureless aortic valve (LivaNova, Saluggia, Italy). METHODS: The degree of oversizing of the implanted prosthesis was calculated as the ratio between the patients' aortic annulus cross-sectional area and the ex vivo cross-sectional area of the implanted prosthesis in 151 Perceval patients who underwent preoperative cardiac computed tomography. This value was then entered in a multivariate analysis to ascertain its role as a predictor of increased postoperative gradient. RESULTS: The operative mortality was 1.3%. Procedural success, defined as having a normally functioning valve in the proper anatomical location, was achieved in 150 patients (99.3%). The mean transprosthetic gradient was 13.4 ± 5.0 mm Hg, and 23 patients (15.2%) showed a gradient of 20 mm Hg or more at discharge or at the 1-month follow-up. The degree of oversizing of the implanted prosthesis was the most important predictor of increased postoperative gradient (odds ratio, 1.264; 95% confidence interval, 1.147 to 1.394; p < 0.0001). Interestingly, other relevant factors (patients' body surface area, prosthesis size) were not associated with increased gradients. CONCLUSIONS: Our study demonstrates that excessive oversizing should be avoided in Perceval patients and suggests that a different sizing algorithm, possibly based on cardiac computed tomography, should be developed. Further studies are needed to optimize the sizing strategy for the Perceval sutureless valve.

Predictive value of less than moderate residual mitral regurgitation as assessed by transesophageal echocardiography for the short-term outcomes of patients with mitral regurgitation treated with mitral valve repair.

BACKGROUND: Traditionally, in patients with mitral regurgitation (MR) a successful mitral valve repair is considered when residual MR by post-pump transesophageal echocardiography (TEE) is less than moderate or absent. Little is known about the prognostic value of less than moderate (mild or mild-to-moderate) residual MR for the early outcome of patients treated with mitral valve repair. METHODS: Eligible for this study were patients undergoing isolated mitral valve repair. Patients with moderate or severe residual MR after valve repair were excluded. The primary endpoint of the study was the composite of death or need of reintervention. RESULTS: A total of 98 patients (54 with no residual MR-Group 1, and 44 with less than moderate residual MR-Group 2) were analyzed. Of these, 72% presented with New York Heart Association (NYHA) 3/4, and 38% were women. The primary endpoint of the study occurred in 3 (5.5%) patients in Group 1 and 6 (13.6%) patients in Group 2 MR (P = 0.31). There was a trend toward a higher incidence of use of inotropic drugs post-interventional (P = 0.12), and a longer hospital stay among patients with less than moderate residual MR (P = 0.18). CONCLUSION: In our study population, patients with less than moderate residual MR had a trend toward a higher risk of early adverse outcomes as compared with patients with no residual MR by post-pump TEE. Studies with a larger patient population and longer follow-up data may be useful to better define the clinical significance of residual mild MR after mitral vale repair.

Hypothesis-free secretome analysis of thoracic aortic aneurysm reinforces the central role of TGF-ß cascade in patients with bicuspid aortic valve.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is a major cause of morbidity and mortality worldwide. The pathogenesis of medial degeneration of the aorta remains undefined. High-throughput secretome analysis by mass spectrometry may be useful to elucidate the molecular mechanisms involved in aneurysm formation as well as to identify biomarkers for early diagnosis or targets of therapy. The purpose of the present study was to analyze the secreted/released proteins from ATAA specimens of both tricuspid aortic valve (TAV) and bicuspid aortic valve (BAV) patients. METHODS: Aortic specimens were collected from patients undergoing elective surgery and requiring graft replacement of the ascending aorta. Each sample of the ascending aortic aneurysm, 4 BAV (3 males; aged 53.5±11.4 years) and 4 TAV (1 male; 78±7.5 years), was incubated for 24h in serum-free medium. Released proteins were digested with trypsin. Peptide mixtures were fractioned by nano-high performance liquid chromatography and analyzed by mass spectrometry. Following identification of differentially expressed proteins, quantitative real time polymerase chain reaction (qRT-PCR) analysis was performed. RESULTS: The comparison between the proteins released from BAV and TAV aneurysmatic tissues showed significantly diverging expression fingerprints in the two groups of patients. Bioinformatics analysis revealed 38 differentially released proteins; in particular 7 proteins were down-regulated while 31 were up-regulated in BAV with respect to TAV. Most of the proteins that were up-released in BAV were related to the activation of transforming growth factor (TGF)-ß signaling. Latent TGF-ß binding protein 4 (LTBP4) exhibited one of the highest significant under-expressions (10-fold change) in BAV secretomes with respect to TAV. qRT-PCR analysis validated this significant difference at LTBP4 gene level (BAV: 1.03±0.9 vs TAV: 3.6±3.2; p<0.05). CONCLUSION: Hypothesis-free secretome profiling clearly showed diverging expression fingerprints in the ATAA of TAV and BAV patients, confirming the crucial role of TGF-ß signaling in modulating ATAA development in bicuspid patients.

Free triiodothyronine: a novel predictor of postoperative atrial fibrillation.

OBJECTIVE: Despite improved perioperative management, atrial fibrillation (AF) after coronary artery bypass grafting (CABG) remains a relevant clinical problem, whose pathogenetic mechanisms remain incompletely explained. A reduced incidence of postoperative AF has been described in CABG patients receiving IV tri-iodothyronine (T3). This study was designed to define the role of thyroid metabolism on the genesis of postoperative AF. METHODS AND RESULTS: Free T3 (fT3), free thyroxine (fT4), and thyroid stimulating hormone were assayed at admission in 107 consecutive patients undergoing isolated CABG surgery. Patients with thyroid disease or taking drugs known to interfere with thyroid function were excluded. A preoperative rhythm other than sinus rhythm was considered an exclusion criterion. Thirty-three patients (30.8%) had postoperative AF. An older age (P=0.03), no therapy with beta-blockers (P=0.08), chronic obstructive pulmonary disease (P=0.08), lower left ventricle ejection fraction (P=0.09) and lower fT3 concentration (P=0.001), were univariate predictors of postoperative AF. On multivariate analysis, low fT3 concentration and lack of beta-blocking therapy were independently related with the development of postoperative AF (odds ratio, OR, 4.425; 95% confidence interval, CI, 1.745-11.235; P=0.001 and OR 3.107; 95% CI 1.087-8.875; P=0.03, respectively). Postoperative AF significantly prolonged postoperative hospital stay (P=0.002). CONCLUSIONS: Low basal fT3 concentration can reliably predict the occurrence of postoperative AF in CABG patients.