Outcomes of Transcatheter Aortic Valve Replacement Patients With Different Transvalvular Flow-Gradient Patterns.

Low-flow low-gradient (LF-LG) aortic stenosis (AS) may occur with preserved or depressed left ventricular ejection fraction (LVEF). Both situations represent the most challenging subset of patients to manage and generally have a poor prognosis. Few and controversial data exist on the outcomes of these patients compared with normal flow-high gradient (NF-HG) AS after transcatheter aortic valve replacement (TAVR). We sought to characterize different transvalvular flow-gradient patterns and to examine their prognostic value after TAVR. We enrolled 1,208 patients with severe AS and categorized as follow: 976 patients NF-HG (mean aortic pressure gradient [MPG] ≥40 mm Hg), 107 paradoxical LF-LG (pLF-LG, MPG <40 mm Hg, LVEF ≥50%, stroke volume index <35 ml/m2), and 125 classical LF-LG (cLF-LG) (MPG <40 mm Hg, LVEF <50%, stroke volume index <35 ml/m2). When compared with NF-HG and pLF-LG, cLF-LG had a worse symptomatic status (New York Heart Association III to IV 86% vs 62% and 67%, p <0.001), a higher prevalence of eccentric hypertrophy and a higher level of LV global afterload reflected by a higher valvuloarterial impedance. Valvular function after TAVR was excellent over time in all patients. While 30-day mortality (p = 0.911) did not differ significantly among groups, cLF-LG had a lower 5-year survival rate (LF-LG 50% vs pLF-LG 62% and NF-HG 68%, p <0.05). cLF-LG was associated with a hazard ratio for mortality of 2.41 (95% confidence interval 1.65 to 3.52, p <0.001). In conclusion, TAVR is an effective procedure regardless of transvalvular flow-gradient patterns. However, special care should be given to characterized hemodynamic of AS, as patients with pLF-LG had similar survival rates than patients with NF-HG, whereas cLF-LG is associated with a twofold increased risk of mortality at 5-year follow-up.

[A case of aortic stenosis in a young patient with familiar hypercholesterolemia, bicuspid aortic valve and heavy calcification of the ascending aorta]. / Un caso di stenosi aortica in un giovane paziente con ipercolesterolemia familiare, valvola bicuspide e severa calcificazione dell'aorta ascendente.

We report the case of a 28-year-old Caucasian patient symptomatic for low-threshold angina. Coronary angiography ruled out significant coronary stenosis. He was diagnosed with familial hypercholesterolemia and severe aortic stenosis in a setting of bicuspid valve disease. Preoperative evaluation showed diffuse atheromatous disease and severe calcification of the ascending aorta. The patient was treated by endarterectomy of the ascending aorta, non-coronary sinus enlargement patch and aortic valve replacement. This case report emphasizes the role of aortic valve disease in patients with familial hypercholesterolemia and highlights the complexity of surgical management of this condition.

Tips and Tricks in Transaortic TAVR

ABSTRACT Transfemoral transcatheter aortic valve replacement (TAVR) is currently the standard catheter-based treatment of severe aortic stenosis patients. Being the transfemoral route not feasible, other access sites could be chosen. Transaortic TAVR via either a J mini-sternotomy or a right anterolateral mini-thoracotomy is a good option for patients having tricky thoracoabdominal aorta. Some tips and tricks may help in getting a fast and safe transaortic procedure.

Management of Iatrogenic Aortic Dissections During Percutaneous Right Coronary Artery Interventions.

Iatrogenic acute aortic dissections during percutaneous coronary interventions are an extremely rare but potentially life-threatening complication, occurring in less than 0.02% of transcatheter procedures. We report three patients with different characteristics suffering from iatrogenic aortic dissection during percutaneous coronary intervention successfully treated with an emergency open-heart surgery. A conservative strategy should be pursuit only in small, localized lesions.

Management of Iatrogenic Aortic Dissections During Percutaneous Right Coronary Artery Interventions

ABSTRACT Iatrogenic acute aortic dissections during percutaneous coronary interventions are an extremely rare but potentially life-threatening complication, occurring in less than 0.02% of transcatheter procedures. We report three patients with different characteristics suffering from iatrogenic aortic dissection during percutaneous coronary intervention successfully treated with an emergency open-heart surgery. A conservative strategy should be pursuit only in small, localized lesions.

Tips and Tricks in Transaortic TAVR.

Transfemoral transcatheter aortic valve replacement (TAVR) is currently the standard catheter-based treatment of severe aortic stenosis patients. Being the transfemoral route not feasible, other access sites could be chosen. Transaortic TAVR via either a J mini-sternotomy or a right anterolateral mini-thoracotomy is a good option for patients having tricky thoracoabdominal aorta. Some tips and tricks may help in getting a fast and safe transaortic procedure.

Lithotripsy of Calcified Aortic Valve Leaflets by a Novel Ultrasound Transcatheter-Based Device.

The increasing incidence of calcific aortic valve disease necessitates the elaboration of new strategies to retard the progression of the pathology with an innovative solution. While the increasing diffusion of the transcatheter aortic valve replacements (TAVRs) allows a mini-invasive approach to aortic valve substitution as an alternative to conventional surgical replacement (SAVR) in an always larger patient population, TAVR implantation still has contraindications for young patients. In addition, it is liable to undergo calcification with the consequent necessity of re-intervention with conventional valve surgery or repeated implantation in the so-called TAVR-in-TAVR procedure. Inspired by applications for non-cardiac pathologies or for vascular decalcification before stenting (i.e., coronary lithotripsy), in the present study, we show the feasibility of human valve treatment with a mini-invasive device tailored to deliver shockwaves to the calcific leaflets. We provide evidence of efficient calcium deposit ruptures in human calcified leaflets treated ex vivo and the safety of the treatment in pigs. The use of this device could be helpful to perform shockwaves valvuloplasty as an option to retard TAVR/SAVR, or as a pretreatment to facilitate prosthesis implantation and minimize the occurrence of paravalvular leak.

The prognostic value of left ventricular dimensions at the time of transcatheter aortic valve replacement: A propensity-matched analysis.

AIMS: In the clinical practice a noteworthy proportion of severe symptomatic aortic stenosis patients presents with low-flow low-gradients features, these having reported a less favorable prognosis even when surgically or transcatheter treated. METHODS AND RESULTS: We retrospectively analyzed the prospectively collected data on 1051 consecutive patients undergone balloon-expandable transcatheter aortic valve replacement at our Institution from January 2008 to January 2020. We divided the population according with a mean aortic gradient (MAG) < or ≥40 mmHg and we performed a propensity-matched analysis based on the Society of Thoracic Surgery Score and age, obtaining two homogeneous groups of 314 patients each (Groups A and B, respectively). We then analyzed the outcomes of the two groups by implementing adjusted Cox models adjusted for significant clinical differences between the two groups, such as sex, ejection fraction, comorbidities and other variables not included in the propensity-matched analysis. The only variable associated with both cardiovascular and all-cause events was an ejection fraction ≤35%. Finally, a sensitivity analysis found that an ejection fraction ≤35% was associated with an increase cardiovascular and all-cause mortality only in patients with an indexed end-diastolic volume >97 ml/m2 (p = .0438 and .3363, respectively). CONCLUSIONS: In our series a MAG <40 mmHg was not found to be per se an independent risk factor for cardiac and all-cause mortality after transcatheter aortic valve replacement. The ejection fraction was found to be an independent risk factor only in the context of enlarged left ventricular dimensions.

Long-term secondary cardiovascular prevention programme in patients subjected to coronary artery bypass surgery.

AIMS: Patients with coronary heart disease (CHD) are at very high risk of recurrent events. A strategy to reduce excess risk might be to deliver structured secondary prevention programmes, but their efficacy has been mostly evaluated in the short term and in experimental settings. This is a retrospective case-control study aimed at assessing, in the real world, the efficacy of a secondary prevention programme in reducing long-term coronary event recurrences after coronary artery bypass surgery (CABG). METHODS AND RESULTS: Programme participants (henceforth 'cases') were men and women aged <75 years subjected to CABG between 2002 and 2014, living within 100 km of the hospital. Key programme actions included optimization of treatments according to the most updated European preventive guidelines, surveillance of therapy adherence, and customized lifestyle counselling. Controls were analogous patients not involved in the programme because living farther than 100 km away, matched 1:1 with cases for gender, age at CABG, and year of CABG. Both groups (n = 1248) underwent usual periodic cardiology follow-up at our centre. Data on symptomatic or silent CHD recurrences were obtained from the hospital electronic health records. Cox analysis (adjusted for baseline differences between groups) shows that programme participation was associated with a significantly lower incidence throughout 5 years post-CABG of symptomatic [hazard ratio (95% confidence interval): 0.59 (0.38-0.94)] and silent [0.53 (0.31-0.89)] coronary recurrences. CONCLUSION: In a real-world setting, taking part in a structured longstanding secondary prevention programme, in addition to usual cardiology care, meaningfully lowers the risk of coronary recurrences.

Percutaneous closure of femoral pseudaneurysm after TAVR.

Fully percutaneous transfemoral transcatheter aortic valve replacement (TF-TAVR) is currently the standard of the catheter-based treatment of severe aortic stenosis patients. Even though experience, lower delivery catheters profile and improved vascular closure devices performances have resulted in an overall reduction of both vascular and bleeding complications after TAVR, femoral pseudoaneurysm due to incomplete local hemostasis may occur, prolonging the in-hospital length of stay, causing discomfort to the patient and potentially evolving in serious consequences affecting the outcome. We report two successful percutaneous ultrasound-guided closure of both the main and secondary femoral access pseudoaneurysm.

Mitro-aortic valve-in-valve procedures: Many challenges in little space.

Multiple valve replacements are known to carry additional risk of morbidity and mortality in redo context. Currently, a transcatheter-based valve-in-valve approach could be useful in reducing potential serious consequences. On the other hand, this approach poses several technical challenges regarding the device and the procedural aspects. We present the case of a 78-year-old man who presented with symptoms of heart failure due to mitral and aortic bioprosthesis degenerations who was deemed to be at extremely high risk for a conventional redo surgery. A two-step transcatheter-based approach was planned and a transfemoral aortic valve-in-valve procedure was followed by a transapical mitral valve-in-valve implantation with a favorable early and long-term outcome.

Coronary artery mechanics induces human saphenous vein remodelling via recruitment of adventitial myofibroblast-like cells mediated by Thrombospondin-1.

Rationale: Despite the preferred application of arterial conduits, the greater saphenous vein (SV) remains indispensable for coronary bypass grafting (CABG), especially in multi-vessel coronary artery disease (CAD). The objective of the present work was to address the role of mechanical forces in the activation of maladaptive vein bypass remodeling, a process determining progressive occlusion and recurrence of ischemic heart disease. Methods: We employed a custom bioreactor to mimic the coronary shear and wall mechanics in human SV vascular conduits and reproduce experimentally the biomechanical conditions of coronary grafting and analyzed vein remodeling process by histology, histochemistry and immunofluorescence. We also subjected vein-derived cells to cyclic uniaxial mechanical stimulation in culture, followed by phenotypic and molecular characterization using RNA and proteomic methods. We finally validated our results in vitro and using a model of SV carotid interposition in pigs. Results: Exposure to pulsatile flow determined a remodeling process of the vascular wall involving reduction in media thickness. Smooth muscle cells (SMCs) underwent conversion from contractile to synthetic phenotype. A time-dependent increase in proliferating cells expressing mesenchymal (CD44) and early SMC (SM22α) markers, apparently recruited from the SV adventitia, was observed especially in CABG-stimulated vessels. Mechanically stimulated SMCs underwent transition from contractile to synthetic phenotype. MALDI-TOF-based secretome analysis revealed a consistent release of Thrombospondin-1 (TSP-1), a matricellular protein involved in TGF-ß-dependent signaling. TSP-1 had a direct chemotactic effect on SV adventitia resident progenitors (SVPs); this effects was inhibited by blocking TSP-1 receptor CD47. The involvement of TSP-1 in adventitial progenitor cells differentiation and graft intima hyperplasia was finally contextualized in the TGF-ß-dependent pathway, and validated in a saphenous vein into carotid interposition pig model. Conclusions: Our results provide the evidence of a matricellular mechanism involved in the human vein arterialization process controlled by alterations in tissue mechanics, and open the way to novel potential strategies to block VGD progression based on targeting cell mechanosensing-related effectors.

In vivo comparison of the optiflow and EZ glide aortic dispersion cannulas.

OBJECTIVES: Morbidity associated with coronary artery bypass grafts and embolization during aortic cannulation is strongly related to patient characteristics/comorbidities, arterial cannulation site used and the shape of arterial cannulae tips. The desired features of an arterial cannula should be to mitigate the morbid effects of these cannulas and to focus on achieving higher blood flows with lower cannula pressures (CPs). MATERIALS AND METHODS: To evaluate the in vivo performance of two aortic dispersion flow cannulas: the Optiflow (Sorin Group, Italy) and EZ Glide (Edwards Lifesciences). They were evaluated for CPs, pump-flow rates (FRs), and plasma-free hemoglobin (Hb) over a 12-month period. Data were collected in a prospective, randomized (1:1), nonblinded, monocentric study with a cohort of 30 patients (optiflow group N = 15; EZ Glide group N = 15). RESULTS: The optiflow cannula was found to have decreasing CPs as the pump FRs were increased (112.3 ± 10.9 vs 131.1 ± 11.4 mm Hg; P < .001). Results indicated no significant differences between groups for increases in plasma free Hb (P = .41) and total microembolic signals counts during the period of cardiac surgery (P = .63). CONCLUSIONS: Both optiflow and EZ Glide dispersion flow arterial cannulas performed well, but the optiflow cannula demonstrated an ability to increase pump FRs with lower arterial line and CPs than the EZ Glide cannula. This implies an ability to improve peripheral perfusion while reducing cannula shear stress and the risk of endothelial damage, thereby having the potential to reduce the risk of atherosclerotic plaque dislodgement.

TAVI-in-homograft (TiH): open transcatheter aortic valve replacement in calcified aortic homograft case reports.

BACKGROUND: Redo surgery in patient who underwent aortic valve replacement with an aortic homograft can result technically challenging because of the massive calcification of the conduit. CASE PRESENTATION: We present a case of a patient who underwent open surgery on cardiopulmonary bypass assistance to implant a standard transcatheter aortic bioprosthesis through aortotomy in an off-label procedure and we discuss its safety and feasibility. CONCLUSIONS: The combination of open cardiac surgery and open trans-aortic implant of a transcatheter prosthesis may reduce the surgical risk shrinking the technical difficulties that the implantation of a standard surgical prosthesis would have given.

Trans-Iliac Aortic Valve Replacement: Feasibility, Safety, and Medium-Term Follow-up.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is nowadays generally accepted as the treatment of choice for high- to intermediate-risk patients with severe aortic stenosis not suitable for the standard surgical replacement. Many vascular accesses have been described for the valve delivery, comprising the common iliac artery as the arterial site of access. METHODS: From September 2008 to June 2014, 440 patients underwent TAVR at our institution. We report a series of 12 patients that have undergone TAVR via a trans-iliac (TI) retroperitoneal surgical approach and also discuss its feasibility, security, and medium-term follow-up. RESULTS: The 30-day survival rate was 92%. Only 1 local vascular access major complication occurred requiring an iliac-femoral bypass grafting with a vascular graft. Two patients experienced transient neurological ischemic attack. At 3-year follow-up, all the 11 patients were alive and well and the echocardiographic evaluation revealed good function of the prosthesis. CONCLUSIONS: The TI route seems to be feasible with a low profile of local complications. It may be a reasonable access alternative to the femoral artery and to the trans-apical approach. A broader, prospective study is advisable to gain general consensus on this approach.

Abnormal DNA Methylation Induced by Hyperglycemia Reduces CXCR 4 Gene Expression in CD 34+ Stem Cells.

Background CD 34+ stem/progenitor cells are involved in vascular homeostasis and in neovascularization of ischemic tissues. The number of circulating CD 34+ stem cells is a predictive biomarker of adverse cardiovascular outcomes in diabetic patients. Here, we provide evidence that hyperglycemia can be "memorized" by the stem cells through epigenetic changes that contribute to onset and maintenance of their dysfunction in diabetes mellitus. Methods and Results Cord-blood-derived CD 34+ stem cells exposed to high glucose displayed increased reactive oxygen species production, overexpression of p66shc gene, and downregulation of antioxidant genes catalase and manganese superoxide dismutase when compared with normoglycemic cells. This altered oxidative state was associated with impaired migration ability toward stromal-cell-derived factor 1 alpha and reduced protein and mRNA expression of the C-X-C chemokine receptor type 4 ( CXCR 4) receptor. The methylation analysis by bisulfite Sanger sequencing of the CXCR 4 promoter revealed a significant increase in DNA methylation density in high-glucose CD 34+ stem cells that negatively correlated with mRNA expression (Pearson r=-0.76; P=0.004). Consistently, we found, by chromatin immunoprecipitation assay, a more transcriptionally inactive chromatin conformation and reduced RNA polymerase II engagement on the CXCR 4 promoter. Notably, alteration of CXCR 4 DNA methylation, as well as transcriptional and functional defects, persisted in high-glucose CD 34+ stem cells despite recovery in normoglycemic conditions. Importantly, such an epigenetic modification was thoroughly confirmed in bone marrow CD 34+ stem cells isolated from sternal biopsies of diabetic patients undergoing coronary bypass surgery. Conclusions CD 34+ stem cells "memorize" the hyperglycemic environment in the form of epigenetic modifications that collude to alter CXCR 4 receptor expression and migration.

Late thrombosis of a Transcatheter aortic valve: the border between a proactive and reactive management.

BACKGROUND: Valve thrombosis - either biological or mechanical - is proved to increase patient's morbidity and mortality. No consensus exist on the best management in such cases. CASE PRESENTATION: We report the case of a 69-year-old man presenting with a late thrombosis of a transcatheter aortic valve who was medically managed until he acutely worsened, developing myocardial ischemia and cardiogenic shock. CONCLUSION: This unlucky case raises a word of caution about the safety of a reactive management.