Diagnostic pathways to wild-type transthyretin amyloid cardiomyopathy: a multicentre network study.

AIM: Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival. METHODS AND RESULTS: This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III-IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III-IV and some comorbidities but not the HF pathway were independently associated with worse survival. CONCLUSIONS: Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself.

Early cardiac response is possible in stage IIIb cardiac AL amyloidosis and is associated with prolonged survival.

Patients with immunoglobulin light chain (AL) amyloidosis and stage IIIb cardiac involvement have a dismal outcome despite the introduction of novel treatments. However, a rapid hematologic response translates in better survival. We evaluated the impact of early cardiac response and its depth on outcome in 249 patients with newly diagnosed stage IIIb cardiac AL amyloidosis. Hematologic and cardiac responses were evaluated by intent to treat. After a median follow-up of 52 months, 219 (84%) patients died, and median survival was 4.2 months. The 30- and 90-day hematologic response rates were 22% (at least very good partial response [VGPR] in 9%) and 24% (at least VGPR in 15%), respectively. Early hematologic response resulted in better survival. At 90 days, 21 (8%) patients achieved a cardiac response (cardiac very good partial response [cardiac VGPR] in 12 cases and cardiac partial response [cardiac PR] in 9). At the 90-day landmark analysis, cardiac response resulted in longer survival (median, 54 months), also in those patients who have achieved at least VGPR (median, 62 vs 26 months, P = .011). Patients with cardiac VGPR had a longer survival than those with cardiac PR (median, 92 vs 24 months; P = .027), whereas patients without cardiac response had a poor survival (median, 6 months). A baseline difference of involved/uninvolved free light chains > 50 mg/L (odds ratio [OR], 0.21, P = .024) and a bone marrow plasma cell infiltrate > 10% (OR, 0.23, P = .040) were negative predictors of 90-day cardiac response. Early cardiac responses are rare but possible in stage IIIb AL amyloidosis and translate to longer survival.

Meta-Analysis Comparing Potent Oral P2Y12 Inhibitors versus Clopidogrel in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

BACKGROUND: In patients with atrial fibrillation (AF) receiving percutaneous coronary intervention (PCI), current guidelines recommend against combining potent oral P2Y12 inhibitors (i.e. ticagrelor or prasugrel) with oral anticoagulant (OAC) therapy, but the evidence is limited. OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of potent oral P2Y12 inhibitors with clopidogrel in patients receiving OAC therapy for AF after a recent PCI. METHODS: Electronic databases were searched for randomized controlled trials (RCT) reporting outcomes according to the P2Y12 inhibitor used. Major or clinically relevant non-major bleeding were the safety endpoints, while the efficacy outcomes were major adverse cardiovascular events (MACE). The potent oral P2Y12 inhibitors prasugrel and ticagrelor were compared with clopidogrel. A subgroup analysis was conducted to evaluate the differences between patients treated with dual antithrombotic therapy (DAT) versus triple antithrombotic therapy (TAT). RESULTS: Four RCTs that included 10,057 patients were included in this analysis. Potent oral P2Y12 inhibitors were associated with a significant increase in major or clinically relevant non-major bleeding compared with clopidogrel (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.06-1.59, p = 0.01; number needed to harm 18, 95% CI 12-36). This finding was consistent regardless of the concomitant antithrombotic therapy (DAT vs. TAT; p = 0.69). The risk of MACE did not differ between potent oral P2Y12 inhibitors and clopidogrel (RR 1.02, 95% CI 0.57-1.82). CONCLUSIONS: In patients receiving OAC therapy for AF after a recent PCI, potent oral P2Y12 inhibitors increase the risk of clinically relevant bleeding compared with clopidogrel, with no evident benefit in terms of MACE reduction.

Direct oral Xa inhibitors versus warfarin in patients with cancer and atrial fibrillation: a meta-analysis.

AIMS: Patients with cancer are at higher risk of atrial fibrillation, thromboembolic complications and bleeding events compared with the general population. The aim of the present meta-analysis was to compare the efficacy and safety of direct oral Xa inhibitor anticoagulants versus warfarin in patients with cancer and atrial fibrillation. METHODS: We searched electronic databases for randomized controlled trials comparing direct oral Xa inhibitor anticoagulants and warfarin in cancer patients. The primary efficacy outcome was stroke or systemic embolism. The primary safety outcome was major bleeding. A subgroup analysis was performed to explore the outcome differences between patients with active cancer or history of cancer. RESULTS: Three trials with a total of 3029 cancer patients were included in the analysis. There was no statistically significant difference in the risk of stroke or systemic embolism [risk ratio (RR) 0.76; 95% confidence interval (CI) 0.52-1.10] between the two therapeutic strategies. Direct oral Xa inhibitors significantly reduced the incidence of major bleeding compared with warfarin (RR 0.79; 95% CI 0.63-0.99; P = 0.04; number needed to treat = 113). These results were consistent both in patients with active cancer and in those with history of cancer. CONCLUSION: In patients with cancer and atrial fibrillation, direct oral Xa inhibitors have a similar efficacy and may be safer compared with warfarin. These results are consistent both in patients with active cancer and history of cancer.