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.

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.

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.

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.

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.

Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves.

OBJECTIVE: The angiotensin-converting enzyme (ACE) is highly expressed in the aneurysmal vascular wall, in both animal models and human disease. Genetic variations in ACE could be crucial in determining the risk of thoracic aortic aneurysm (TAA). The aim of the present study was to examine the role of ACE insertion/deletion polymorphism on the risk of TAA in patients with bicuspid aortic valves or tricuspid aortic valves. METHODS: We enrolled 216 patients (158 men; age, 58.9±14.9 years) with TAA, associated with bicuspid aortic valves (n=105) and tricuspid aortic valves (n=111) compared with 312 patients (252 men; age, 54.6±11.0 years) with angiographically proven coronary artery disease and 300 healthy controls (91 men; age, 40.4±10.5 years). RESULTS: The genotype distribution of ACE insertion/deletion was significantly different between the patients with TAA compared with both the control group (P=.0005) and the coronary artery disease group (P=.03). The genotypes were not different between the control group and the coronary artery disease group (P=.3). Compared with the controls, both the bicuspid aortic valve patients (P=.0008) and tricuspid aortic valve patients (P<.0001) had a greater frequency of allele D. The aortic diameters were significantly different among the three genotypes (48.3±6.6, 45.3±8.9, 39.9±8.7 for the DD, DI, and II genotypes, respectively; P=.0002). A synergistic effect between the ACE D allele and hypertension was found for both an increased aortic diameter (P=.003) and the risk of TAA (P<.001). On multivariate logistic regression analysis, D allele (odds ratio, 3.0; 95% confidence interval, 1.1-8.1; P=.03) was a significant predictor of TAA. CONCLUSIONS: ACE insertion/deletion polymorphism represents a genetic biomarker for TAA. These findings could have a significant effect on both the early detection and effective pharmacologic treatment of aortic disease.

Sizing the aortic annulus.

Transcatheter aortic valve implantation (TAVI) is a valuable alternative for aortic valve replacement in selected high-risk candidates. Accurate preoperative assessment of the aortic annular dimensions is crucial for the success of TAVI, since choice of an incorrectly sized prosthesis may result in catastrophic complications. These complications include annular rupture and coronary arterial obstruction, if the prosthesis is too big, or prosthesis migration and severe paravalvular leakage, if the prosthesis is too small. According to current recommendations, the choice of prosthesis size is based on transoesophageal echocardiography (TEE) measurements. However, TEE results are dependent on operator experience. Moreover, recent research has shown that TEE can significantly underestimate annular dimensional measurements. Alternative sizing methods based on Multidetector Computed Tomography (MDCT) or manometry during balloon aortic valvuloplasty have therefore been developed. We present a brief overview of the imaging modalities available for preoperative assessment of annular size and discuss their potential advantages and limitations.

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.

Endovascular treatment of acute thoracic aortic syndromes with a proximal landing zone extension strategy: procedural and follow-up results.

PURPOSE: To report the procedural and long-term follow-up data (mean, 43 ± 29 months; range, 12-90 months) of endovascular stent grafting (ESG) of acute thoracic aortic syndromes (ATAS) with a proximal landing zone extension strategy. METHODS: From November 1999 to May 2008, 26 patients (25 males, 1 female; mean age, 57.9 ± 17 years) with ATAS underwent ESG at our institution. Underlying pathologies were: penetrating aortic ulcer (n=7); rupture of a descending aorta aneurysm (n=5), post-traumatic false aneurysm (n=5); acute type B dissection (n=6) and traumatic descending aorta transection (n=3). RESULTS: ESG was performed successfully in all patients. In 5 patients (19%), an extra-anatomic revascularization of the supra-aortic vessels was performed. In 19 patients (73%), overstenting of the left subclavian artery, without preliminary revascularization, was performed. The mean proximal landing zone length was 57 ± 19 mm. No intraprocedural deaths occurred; 3 patients died postoperatively (1 from an unrelated cause, 1 from a myocardial infarction and 1 for the sequelae of an ischemic stroke). One patient underwent cardiac surgery for post-procedural retrograde type-A dissection. Follow up involved a computed tomography (CT) scan at 1, 3, 6 and 12 months, then yearly thereafter. At follow up, no deaths or major complications occurred. The CT scans revealed 1 small type-IB endoleak at 1 year. CONCLUSION: In ATAS patients treated with ESG, the extension of the proximal landing zone, despite the need of subclavian coverage or hybrid procedures, is associated with an immediate procedural outcome and low morbidity at follow-up.

Aortic arch replacement with prophylactic aortic arch debranching during type A acute aortic dissection repair: initial experience with 23 patients.

OBJECTIVE: To improve the long-term results of acute type A dissection repair, we developed a technique that combines radical surgical resection, and, at the same time, creates a safe and long landing zone for subsequent endovascular procedure on the descending aorta. METHODS: Since November 2006, 23 patients (62 ± 13 years) underwent aortic arch replacement concomitant with prophylactic debranching of the supra-aortic vessels, with a specially designed arch graft. The technique consists of replacing the ascending aorta and the aortic arch, and, at the same time, relocating the origin of the supra-aortic vessels just above the sinotubular junction creating a long and safe proximal landing zone for subsequent stent-graft deployment. Perfusion was antegrade through the ascending aorta during cooling and through the vascular prosthesis during rewarming. Distal arch anastomosis was performed under moderate hypothermic circulatory arrest for 25 ± 7 min and antegrade selective cerebral perfusion (46 ± 14 min). Cardiopulmonary bypass and aortic cross-clamp time were 138 ± 46 and 63 ± 22 min. RESULTS: Hospital mortality was 4.3% (1/23). Postoperative morbidity includes five acute renal failures and four lung failures. No major neurological complications were observed. At follow-up (22±10 months), survival was 100% and two patients required an endovascular thoracic aorta repair for aneurysmal enlargement. In both cases, the stent grafts were successfully released in the landing zone created at the time of primary repair. CONCLUSIONS: Our technique extends the suitability of endovascular therapies during type A acute dissection repair, creating a long and stable landing zone that allows safe performance of a second endovascular step if needed, both in the short- and long term.

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 new vacuum-assisted probe for minimally invasive radiofrequency ablation.

PURPOSE: The Cobra Adhere XL (Estech, San Ramon, CA) is a multiple-electrode, temperature-controlled, monopolar radiofrequency probe with a vacuum-assisted stabilization system. We evaluated this new technology for epicardial ablation of atrial fibrillation in mitral valve patients through a right mini-thoracotomy. DESCRIPTION: Between June and August 2008, 12 patients underwent minimal invasive surgery for mitral disease and ablation for atrial fibrillation with the Cobra Adhere XL (Estech). Three patients had paroxysmal atrial fibrillation. Off-pump pulmonary vein isolation was performed with an epicardial oval lesion parallel to the mitral plane. In 10 patients, an endocardial lesion to the mitral annulus was added. EVALUATION: There were no operative deaths or major postoperative complications. At a mean follow-up of 8.76 +/- 1.0 months, 11 patients (91.67%) were in stable sinus rhythm. Echocardiography underscored a complete recovery of atrial transport function in most of these patients (90.91%). No major cardiac and cerebrovascular events occurred during follow-up. CONCLUSIONS: Left-side ablation combined with minimally invasive surgery for mitral disease can be easily, safely, and effectively performed with the Cobra Adhere XL probe.

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.

Valve-sparing replacement of the noncoronary sinus of Valsalva in patients with a bicuspid aortic valve.

Progressive dilatation of the aortic root and ascending aorta is frequent in patients with bicuspid aortic valve, and isolated dilatation of the noncoronary sinus has been reported. We describe our technique for the selective replacement of the noncoronary sinus of Valsalva in patients with bicuspid aortic 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.