About one in seven elderly patients with severe calcific aortic stenosis (AS) also have ATTR amyloid cardiomyopathy (AC-TTR). The reasons for this close association are not fully known, but the two entities are not only related by common epidemiology. For example, it is possible to hypothesize that an amyloidotic infiltration of the aortic valve, even partial, can act as a trigger for the development of endothelial damage and subsequent calcification. Another hypothesis is the increased myocardial strain induced by AS may locally favour the process of amyloidogenesis and tissue infiltration. In a patient with AS, the coexistence of AC-TTR can be suspected by careful analysis of the echocardiogram and the ECG, especially if a clinical history of carpal tunnel syndrome coexists. Bone tracer scintigraphy allows a diagnosis of certainty. Recently, several studies have evaluated the prognostic implications of the coexistence of the two entities in candidates for percutaneous aortic valve replacement, showing how amyloidosis would not significantly impact the results of the procedure, but would only be associated with a greater risk of distant heart failure. In patients with AS associated with AC-TTR, valve replacement should not be ruled out in the presence of the usual clinical-haemodynamic indications.
Aims This meta-analysis aims to compare direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in the setting of left ventricular thrombosis (LVT). Method and ResultsWe systematically searched MEDLINE, Cochrane Library, Biomed Central and Web of Science for trials comparing DOACs versus VKAs in the setting of LVT and reporting outcome data on thrombosis resolution, stroke and bleeding. Fourteen studies were finally selected. The Mantel-Haenszel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of LVT resolution. The secondary outcomes were the occurrence of stroke or bleeding during treatment. One thousand three hundred and thirty-two patients were included in the analysis for the primary outcome. Of these, 424 were treated with DOACs and 908 with VKAs. The pooled odds ratio (OR) for the primary outcome was 1.00 [95% confidence interval (95% CI) 0.77-1.31, I 2 0.0%], reflecting equal effect in terms of thrombus resolution. Overall, 2290 patients, 608 on DOACs and 1682 on VKAs were included in the analysis of stroke occurrence, showing reduced risk of events in patients treated with DOACs (pooled OR 0.58, 95% CI 0.36-0.93; I 2 0.0%) as well as for bleeding occurrence (number of patients included 2139; pooled OR 0.64, 95% CI 0.44-0.94; I 2 0.0%). ConclusionCompared with VKAs, we found DOACs to have similar efficacy on thrombus resolution and favorable effects on stroke reduction and bleedings. DOACs should be considered as an alternative treatment for LVT. Large prospective randomized clinical trials are needed to confirm this exploratory finding.
The therapy of transthyretin (TTR)-related cardiac amyloidosis consists, on the one hand, of the prevention and management of complications (supportive therapy) and on the other of treatments aimed at interrupting or slowing down the production and deposition of fibrils (disease-modifying therapy). This definition includes drugs that act on different phases of amyloidogenesis: (i) silencing of the gene encoding TTR (small interfering RNA: patisiran, vutrisiran; antisense oligonucleotides: inotersen, eplontersen; new CRISPR Cas-9 drug technology for editing in vivo DNA); (ii) stabilization of circulating TTR to inhibit its dissociation and subsequent assembly of the resulting monomers in amyloidotic fibrils (tafamidis, acoramidis, and tolcapone); (iii) destruction and re-absorption of already formed amyloid tissue deposits. Drugs related to the latter strategy (antibodies) are still the subject of Phase 1 or 2 studies.
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