Based on the latest knowledge and technological advancements, it is still debatable whether a modern revascularisation approach in the setting of acute myocardial infarction (AMI), including complete ...revascularisation (in patients with significant non-culprit lesions) with newer-generation highly biocompatible drug-eluting stents, requires prolonged dual antiplatelet therapy (DAPT). TARGET-FIRST (ClinicalTrials.gov: NCT04753749) is a prospective, open-label, multicentre, randomised controlled study comparing short (one month) DAPT versus standard (12 months) DAPT in a population of patients with non-ST/ST-segment elevation myocardial infarction, completely revascularised at index or staged procedure (within 7 days), using Firehawk, an abluminal in-groove biodegradable polymer rapamycin-eluting stent. The study will be conducted at approximately 50 sites in Europe. After a mandatory 30-40 days of DAPT with aspirin and P2Y
inhibitors (preferably potent P2Y
inhibitors), patients are randomised (1:1) to 1) immediate discontinuation of DAPT followed by P2Y
inhibitor monotherapy (experimental arm), or 2) continued DAPT with the same regimen (control arm), up until 12 months. With a final sample size of 2,246 patients, the study is powered to evaluate the primary endpoint (non-inferiority of short antiplatelet therapy in completely revascularised patients) for net adverse clinical and cerebral events. If the primary endpoint is met, the study is powered to assess the main secondary endpoint (superiority of short DAPT in terms of major or clinically relevant non-major bleeding). TARGET-FIRST is the first randomised clinical trial to investigate the optimisation of antiplatelet therapy in patients with AMI after achieving complete revascularisation with an abluminal in-groove biodegradable polymer rapamycin-eluting stent implantation.
Checkpoint inhibitors have significantly changed the prognosis of patients with relapsing refractory classical Hodgkin’s lymphoma (cHL), demonstrating excellent results in heavily pretreated ...patients. However, there is still limited data on the real-world experience with PD-1 inhibitors in cHL. Within the context of the Apulian hematological network (Rete Ematologica Pugliese, REP), we performed a retrospective, multicenter analysis of 66 patients with relapsing refractory cHL who had received PD-1 inhibitors in the non-trial setting. Forty-three patients (65%) were treated with nivolumab and 23 (35%) with pembrolizumab. Thirty-one (47%) and 8 (12%) patients underwent autologous or allogeneic stem cell transplantation prior to checkpoint inhibitor therapy, respectively. The median number of lines of treatment attempted prior to PD-1 inhibitor therapy was 4 (range, 3 to 7). All patients had received brentuximab vedotin prior to checkpoint inhibitor therapy. The overall response rate to PD-1 inhibitors therapy was 70% (47% complete remission (CR) and 23% partial remission (PR)). Twenty-four immune-related adverse events (19 (80%) grades 1–2; 5 (20%) grades 3–4) were documented (4 gastrointestinal, 4 hepatic, 6 fever, 4 hematological, 3 dermatological, 3 allergic rhinitis). Toxicity resolved in all patients, and there were no deaths attributed to checkpoint inhibitor therapy. After a median follow-up of 26 months (range 3–72 months), 54 patients (82%) are alive, and 12 (18%) died. The cause of death was attributed to disease progression in 9 patients and sepsis in 3 patients. After PD-1 inhibitor therapy, 22 patients (33%) relapsed or progressed. The overall survival and progression-free survival at 5 years were 65% and 54%, respectively. This study confirms the efficacy and tolerability of PD-1 inhibitor therapy in relapsed refractory cHL in a real-world setting, demonstrating similar clinical outcomes and toxicity profiles compared to clinical studies.
Whether early or delayed dual antiplatelet therapy initiation is better in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is unclear. We assessed the evidence for comparing ...the efficacy and safety of early vs. delayed P2Y
inhibitor initiation in NSTE-ACS.
The randomized controlled trials with available comparisons between early and delayed initiation of P2Y
inhibitors (clopidogrel, prasugrel, and ticagrelor) in patients with NSTE-ACS until January 2021 were reviewed. The primary outcomes were trial-defined major adverse cardiovascular events (MACEs) and bleeding. Secondary outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction, stent thrombosis, urgent coronary revascularization, and stroke. Frequentist random-effects network meta-analyses were conducted, ranking best treatments per outcome with
-scores.
A total of nine trials with intervention arms including early and delayed initiation of clopidogrel (
= 5), prasugrel (
= 8), or ticagrelor (
= 6) involving 40,096 patients were included. Early prasugrel (hazard ratio HR, 0.59; 95% confidence interval 95%CI, 0.40-0.87), delayed prasugrel (HR, 0.60; 95%CI 0.43-0.84), and early ticagrelor (HR, 0.84; 95%CI, 0.74-0.96) significantly reduced MACE compared with early clopidogrel, but increased bleeding risk. Delayed prasugrel ranked as the best treatment to reduce MACE (
-score=0.80), early prasugrel to reduce all-cause mortality, cardiovascular mortality, stent thrombosis, and stroke, and delayed clopidogrel to reduce bleeding (
-score = 0.84). The risk of bias was low for all trials.
In patients with NSTE-ACS, delayed prasugrel initiation was the most effective strategy to reduce MACE. Although early prasugrel was the best option to reduce most secondary cardiovascular outcomes, it was associated with the highest bleeding risk. The opposite was found for delayed clopidogrel.
Takotsubo syndrome, also called apical ballooning syndrome, is a clinical entity characterized by transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid-segments with or without ...apical involvement, and without obstructive coronary lesions. The contemporary presence of left ventricular outflow tract obstruction (LVOTO), systolic anterior motion of the anterior mitral leaflet, and acute mitral regurgitation might explain the worsening of the heart failure or the occurrence of cardiogenic shock in some patients with apical ballooning syndrome. The use of -blockers should improve the LVOTO gradient by reducing basal hypercontractility, increasing left ventricular filling and size, and reducing heart rate. However, clear evidence of the direct haemodynamic effects of -blockers is still lacking. We present a case of apical ballooning syndrome complicated by dynamic LVOTO, treated with metoprolol.
BACKGROUNDAs transcatheter aortic valve (TAV) replacement is increasingly used in patients with longer life expectancy, a sizable proportion will require redo TAV replacement (TAVR). The unique ...configuration of balloon-expandable TAV (bTAV) vs a self-expanding TAV (sTAV) potentially affects TAV-in-TAV outcome. OBJECTIVESThe purpose of this study was to better inform prosthesis selection, TAV-in-TAV outcomes were assessed according to the type of initial and subsequent TAV. METHODSPatients from the Redo-TAVR registry were analyzed using propensity weighting according to their initial valve type (bTAV n = 115 vs sTAV n = 106) and subsequent valve type (bTAV n = 130 vs sTAV n = 91). RESULTSPatients with failed bTAVs presented later (vs sTAV) (4.9 ± 2.1 years vs 3.7 ± 2.3 years; P < 0.001), with smaller effective orifice area (1.0 ± 0.7 cm2 vs 1.3 ± 0.8 cm2; P = 0.018) and less frequent dominant regurgitation (16.2% vs 47.3%; P < 0.001). Mortality at 30 days was 2.3% (TAV-in-bTAV) vs 0% (TAV-in-sTAV) (P = 0.499) and 1.7% (bTAV-in-TAV) vs 1.0% (sTAV-in-TAV) (P = 0.612); procedural safety was 72.6% (TAV-in-bTAV) vs 71.2% (TAV-in-sTAV) (P = 0.817) and 73.2% (bTAV-in-TAV) vs 76.5% (sTAV-in-TAV) (P = 0.590). Device success was similar according to initial valve type but higher with subsequent sTAV vs bTAV (77.2% vs 64.3%; P = 0.045), primarily because of lower residual gradients (10.3 mm Hg 8.9-11.7 mm Hg vs 15.2 mm Hg 13.2-17.1 mm Hg; P < 0.001). Residual regurgitation (moderate or greater) was similar after bTAV-in-TAV and sTAV-in-TAV (5.7%) and nominally higher after TAV-in-bTAV (9.1%) vs TAV-in-sTAV (4.4%) (P = 0.176). CONCLUSIONSIn selected patients, no association was observed between TAV type and redo TAVR safety or mortality, yet subsequent sTAV was associated with higher device success because of lower redo gradients. These findings are preliminary, and more data are needed to guide valve choice for redo TAVR.
Transcatheter aortic valve replacement (TAVR) is increasingly being performed in younger and lower surgical risk patients. Reintervention for failed transcatheter heart valves will likely increase in ...the future as younger patients are expected to outlive the initial bioprosthesis. While redo-TAVR has emerged as an attractive and less invasive alternative to surgical explantation (TAVR-explant) to treat transcatheter heart valve failure, it may not be feasible in all patients due to the risk of coronary obstruction and impaired coronary access. Conversely, TAVR-explant can be offered to most patients who are surgical candidates, but the reported outcomes have shown high mortality and morbidity. This review provides the latest evidence, current challenges, and future directions on redo-TAVR and TAVR-explant for transcatheter heart valve failure, to guide aortic valve reintervention and facilitate patients' lifetime management of aortic stenosis.
Epidemiology and consequences of surgery in patients with coronary stents are not clearly defined, as well as the impact of different stent types in relationship with timing of surgery.
Among 39 362 ...patients with previous coronary stenting enrolled in a multicenter prospective registry and followed for 5 years, 13 128 patients underwent 17 226 surgical procedures. The cumulative incidence of surgery at 30 days, 6 months, 1 year, and 5 years was 3.6%, 9.4%, 14.3%, and 40.0%, respectively, and of cardiac and noncardiac surgery was 0.8%, 2.1%, 2.6%, and 4.0% and 1.3%, 5.1%, 9.1%, and 31.7%, respectively. We assessed the incidence and the predictors of cardiac death, myocardial infarction, and serious bleeding event within 30 days from surgery. Cardiac death occurred in 438 patients (2.5%), myocardial infarction in 256 (1.5%), and serious bleeding event in 1099 (6.4%). Surgery increased 1.58× the risk of cardiac death during follow-up. Along with other risk factors, the interplay between stent type and time from percutaneous coronary intervention to surgery was independently associated with cardiac death/myocardial infarction. In comparison with bare-metal stent implanted >12 months before surgery, old-generation drug-eluting stent was associated with higher risk of events at any time point. Conversely, new-generation drug-eluting stent showed similar safety as bare-metal stent >12 months and between 6 and 12 months and appeared trendly safer between 0 and 6 months.
Surgery is frequent in patients with coronary stents and carries a considerable risk of ischemic and bleeding events. Ischemic risk is inversely related with time from percutaneous coronary intervention to surgery and is influenced by stent type.
PDF
