Riparazione valvolare mitralica percutanea: la Mitraclip

L'insufficienza mitralica (IM) è la valvulopatia cardiaca più comune, con una prevalenza stimata nella popolazione generale, aggiustata per età e sesso, pari all'1.7%, ma con un marcato incremento con l'aumentare dell'età, potendo colpire fino al 13.2% della popolazione al di sopra di 75 anni. La prevalenza non trascurabile dell'IM e l'importante impatto prognostico di questa malattia nei pazienti (pz.) affetti, sia nella sua forma degenerativa primitiva (IMP) che nella sua forma secondaria/funzionale (IMF), risultante dalla dilatazione e disfunzione del ventricolo sinistro (Vsx) nei pz con scompenso, ha portato all'elaborazione di nuove strategie di trattamento percutaneo minimamente invasivo, per consentire il trattamento di un maggior numero di pz. affetti. Fra esse la più frequentemente usata è la riparazione valvolare mitralica percutanea tramite impianto di clip con sistema Mitraclip (Abbott Laboratories, Menlo Park, California, USA). Considerato l'alto tasso di prevalenza di IM e di SC nella popolazione generale, la prognosi infausta di queste malattie, e l'alto tasso di comorbilità presente nei soggetti affetti da SC, che spesso rende i pz. stessi ineleggibili al trattamento chirurgico convenzionale, la riparazione valvolare percutanea mediante Mitraclip potrebbe rappresentare per molti individui un beneficio non solo sintomatologico, ma anche prognostico, andando ad interrompere il circolo vizioso che si crea fra disfunzione del Vsx e sovraccarico di volume, mediato proprio dall'IM stessa. In questa revisione della letteratura verranno discussi gli aspetti principali della riparazione valvolare mitralica percutanea con Mitraclip e l'importante impatto prognostico da essa derivante

Irreversible proteasome inhibition with carfilzomib as first line therapy in patients with newly diagnosed multiple myeloma: Early in vivo cardiovascular effects.

Patients who experienced cardiovascular side effects during cancer therapy with carfilzomib for multiple myeloma had relapsed multiple myeloma, so have be previously treated with other cancer therapies. The present is a single center cohort study to evaluate early cardiovascular effects of administration of irreversible proteasome inhibitor carfilzomib in naïve patients. We included 24 patients and collected cardiovascular side effects, echocardiographic parameters and endothelial function at baseline and after 4 cycles. At early follow up we observed increase in blood arterial pressure values (mean change in systolic pressure of 10 mmHg (P-value  0.01; diastolic arterial pressure and mean arterial pressure of 3.3 mmHg and 5.4 mmHg, both P-value  0.01). Reactive hyperemia PAT index was reduced in the whole cohort by a mean of 0.46 points (P-value  0.01); diastolic function was changed: E-wave-deceleration-time (EDT) was reduced by 49,96 ± 31 ms, P-value  0.05 and early diastolic tissue Doppler velocity (e') by a mean value of 1.46 cm/s, P - value 0.04. At early follow up we did not observe events of grade 3 or 4. We observe correlation between events and endothelial dysfunction at baseline and age (OR 1.9, CI 95% 0.05-5.804, P- value: 0.038 for RHI1.67; OR 1,4, CI 95%0.99-2.56, P- value: 0.04 for age). Our results suggest that therapy with carfilzomib when used as first line therapy is responsible for increase in systemic blood pressure, alteration of endothelium-mediated vascular dilatation and early myocardial diastolic dysfunction

Spasmogenic Effects of the Proteasome Inhibitor Carfilzomib on Coronary Resistance, Vascular Tone and Reactivity

Background: Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of multiple myeloma. Besides heart failure, angina and myocardial ischemia occurred following administration of CFZ, which is not contraindicated in patients with recent myocardial infarction/unstable angina excluded from the safety trials. Aimof Study: To test the effects of CFZ (10−9 to 10−7 mol/L) on vascular tone and reactivity in the isolated rabbit heart and aorta. Methods and Results: CFZ administered by bolus injection to the isolated heart increased coronary perfusion pressure (CPP) at all tested concentrations and mildly raised left ventricular pressure and heart rate, only at the highest concentration. Addition of CFZ directly into the organ bath increased the basal tone of isolated aortic strips with contraction plateau reached after 10 min. This spasmogenic effect doubled following ablation of the endothelium. Pretreatment with CFZ amplified the vasospastic action exerted by KCl, noradrenaline (NA) and angiotensin II (A) on aortic strips, and impaired vasodilation following administration of nitroglycerin (NTG) and nifedipine (NFP) on the contraction plateau induced by KCl, NA and A. Aortic strips pretreatedwith CFZ exhibited impaired relaxation, as compared to untreated strips, following administration of acetylcholine (Ach), an endothelium- dependent vasodilating agent, on the plateau of NA contraction (p b 0.05). Conclusions: CFZ increased CPP, resting vasoconstricting tone and the spasmogenic effect of different agents. Preincubation with CFZ decreased the anti-spasmogenic activity of NTG and NFP, as well as reduced by over 50% the vasodilating effect of Ach, suggesting that CFZ can impair vasodilation via an endothelium dependent mechanism. Further studies are warranted to establish its clinical safety in patients with known CAD and prior history of coronary spasm

Pre-Operative Continued Oral Anticoagulation Impact on Early Outcomes after Transcatheter Aortic Valve Implantation

Considering that there is a lack of evidence and guideline-based recommendations on the best preoperative oral anticoagulation management (OAC) for transcatheter aortic valve implantation (TAVI), this cohort study aimed to evaluate bleeding, access site complications, and early safety in patients undergoing TAVI on continued OAC therapy vs no-OAC therapy. Three-hundred forty-four patients submitted to a TAVI procedure (66.3% no-OAC vs 33.7% OAC) were consecutively enrolled. Primary endpoint was defined as in-hospital VARC-2 life-threatening or disabling bleeding. Secondary endpoints were in-hospital VARC-2 major vascular complications and VARC-2 early safety at 30 days. Propensity score matching analysis was performed to reduce potential distribution bias, resulting in 2 well-balanced groups (92 patients in each arm). In the overall cohort, mean age, median EuroScore II, and STS-score were 78.7±7.6 years, 2.9% (1.7-5.9), and 2.3% (1.6-3.6), respectively. Despite being older (78 ± 8 vs 80 ± 6, p = 0.004) and having higher STS score (2.1 vs 2.6, p = 0.001), patients on OAC had similar incidence of in-hospital VARC-2 life-threatening or disabling bleeding (1.3% vs. 0.9%, p = 0.711), major vascular complications (4.8% vs 5.2%, p = 0.888), and VARC-2 early safety at 30 days (10.1% vs 12.1%, p = 0.575). No significant differences in the main outcomes were observed when propensity score matching was applied. In conclusion, the management of patients on OAC submitted to a TAVI procedure is challenging and requires balancing the risk of bleeding with the risk of thromboembolic events. The present study suggests that continued OAC was not associated with increased in-hospital VARC-2 life-threatening or disabling bleeding, major vascular complications, and VARC-2 early safety at 30 days

Transcatheter Edge-to-edge Repair of Severe Tricuspid Regurgitation

Despite the increasing knowledge of the long-term adverse consequence of severe tricuspid regurgitation (TR), most patients with moderate- to-severe TR are still treated conservatively because of the high risk of surgery. Percutaneous procedures have emerged as an attractive alternative treatment. Transcatheter edge-to-edge repair is a validated technique to treat mitral regurgitation. In recent years, the same concept has been applied to patients with TR and prohibitive operative risk. Early trials have shown feasibility and safety. More clinical experiences and long-term results are still being gathered. In this article, we provide an overview of transcatheter edge-to-edge repair and look at the current evidence and clinical results regarding procedure

Direct percutaneous mitral annuloplasty in patients with functional mitral regurgitation: when and how

Mitral regurgitation (MR) is a frequent valvular disease among patients deemed too high risk for surgery. Echocardiography along with CT is the primary diagnostic tool for MR and offers a comprehensive 3D assessment in patient selection and screening for the optimal treatment method. The direct percutaneous mitral annuloplasty addresses the underlying mechanisms of functional MR with a less invasive, catheter-based approach. The here-described techniques proved a sufficient safety profile, delivered significant MR reduction in most of the cases, and were associated with a notable improvement of symptoms. Although long-term outcome assessment is needed to support these early reports, the percutaneous mitral annuloplasty is likely to set a new standard of treatment in the forthcoming future