Routine Protamine Administration for Bleeding in Transcatheter Aortic Valve Implantation: The ACE-PROTAVI Randomized Clinical Trial.

Importance: Vascular complications after transfemoral transcatheter aortic valve implantation (TAVI) remain an important cause of procedure-related morbidity. Routine reversal of anticoagulation with protamine at the conclusion of transfemoral TAVI could reduce complications, but data remain scarce. Objective: To evaluate the efficacy and safety of routine protamine administration after transfemoral TAVI. Design, Setting, and Participants: The ACE-PROTAVI trial was an investigator-initiated, double-blind, placebo-controlled randomized clinical trial performed at 3 Australian hospitals between December 2021 and June 2023 with a 1-year follow-up period. All patients accepted for transfemoral TAVI by a multidisciplinary heart team were eligible for enrollment. Interventions: Eligible patients were randomized 1:1 between routine protamine administration and placebo. Main Outcomes and Measures: The coprimary outcomes were the rate of hemostasis success and time to hemostasis (TTH), presented as categorical variables and compared with a χ2 test or as continuous variables as mean (SD) or median (IQR), depending on distribution. The major secondary outcome was a composite of all-cause death, major and minor bleeding complications, and major and minor vascular complications after 30 days, reported in odds ratios (ORs) with 95% CIs and P values. Results: The study population consisted of 410 patients: 199 patients in the protamine group and 211 in the placebo group. The median (IQR) patient age in the protamine group was 82 (77-85) years, and 68 of 199 patients receiving protamine (34.2%) were female. The median (IQR) patient age in the placebo group was 80 (75-85) years, and 89 of 211 patients receiving the placebo (42.2%) were female. Patients receiving up-front protamine administration had a higher rate of hemostasis success (188 of 192 patients [97.9%]) than patients in the placebo group (186 of 203 patients [91.6%]; absolute risk difference, 6.3%; 95% CI, 2.0%-10.6%; P = .006); in addition, patients receiving up-front protamine had a shorter median (IQR) TTH (181 [120-420] seconds vs 279 [122-600] seconds; P = .002). Routine protamine administration resulted in a reduced risk of the composite outcome in the protamine group (10 of 192 [5.2%]) vs the placebo group (26 of 203 [12.8%]; OR, 0.37; 95% CI, 0.1-0.8; P = .01). This difference was predominantly driven by the difference in the prevalence of minor vascular complications. There were no adverse events associated with protamine use. Conclusions and Relevance: In the ACE-PROTAVI randomized clinical trial, routine administration of protamine increased the rate of hemostasis success and decreased TTH. The beneficial effect of protamine was reflected in a reduction in minor vascular complications, procedural time, and postprocedural hospital stay duration in patients receiving routine protamine compared with patients receiving placebo. Trial Registration: anzctr.org.au Identifier: ACTRN12621001261808.

The assessment of intermediate coronary lesions using intracoronary imaging.

Intermediate coronary artery stenosis, defined as visual angiographic stenosis severity of between 30-70%, is present in up to one quarter of patients undergoing coronary angiography. Patients with this particular lesion subset represent a distinct clinical challenge, with operators often uncertain on the need for revascularization. Although international guidelines appropriately recommend physiological pressure-based assessment of these lesions utilizing either fractional flow reserve (FFR) or quantitative flow ratio (QFR), there are specific clinical scenarios and lesion subsets where the use of such indices may not be reliable. Intravascular imaging, mainly utilizing intravascular ultrasound (IVUS) and optical coherence tomography (OCT) represents an alternate and at times complementary diagnostic modality for the evaluation of intermediate coronary stenoses. Studies have attempted to validate these specific imaging measures with physiological markers of lesion-specific ischaemia with varied results. Intravascular imaging however also provides additional benefits that include portrayal of plaque morphology, guidance on stent implantation and sizing and may portend improved clinical outcomes. Looking forward, research in computational fluid dynamics now seeks to integrate both lesion-based physiology and anatomical assessment using intravascular imaging. This review will discuss the rationale and indications for the use of intravascular imaging assessment of intermediate lesions, while highlighting the current limitations and benefits to this approach.

Contemporary outcomes in women undergoing percutaneous coronary intervention for acute coronary syndromes.

BACKGROUND: Uncertainty remains as to whether females benefit as much as males from percutaneous coronary intervention (PCI) in the setting of an acute coronary syndrome (ACS). METHODS: We compared 802 women with 2151 men presenting with ACS, undergoing PCI from April 2004 to October 2006 from the Melbourne Interventional Group registry. Clinical characteristics, in-hospital, 30-day and 1-year outcomes were compared. RESULTS: Women were older (69.6 ± 11.6 vs. 62.17 ± 12.3 years, p<0.001), and had more diabetes (27.1% vs. 19.6%, p<0.001) and hypertension (70.3% vs. 53.9%, p<0.001) than men. Women were less likely to present with ST-elevation myocardial infarction (30.5% vs. 37.9%, p<0.001). Bleeding (3.6% vs. 0.8%, p<0.001) was higher among women. Thirty-day mortality (4.7 vs. 2.4%, p<0.001) and MACE (10.1 vs. 6.4%, p<0.001) were higher in women. Gender was an independent predictor of overall MACE at 30 days (OR 1.45, 95% CI 1.04-2.02, p=0.03) but not death. At 12 months, there were no significant differences in mortality (6.4% vs. 4.8%, p=0.09), myocardial infarction (5.5% vs. 5.0%, p=0.64), target vessel revascularization (7.9% vs. 7.0%, p=0.42) and MACE (16.3% vs. 14%, p=0.13) between women and men. CONCLUSIONS: There is an early hazard amongst women undergoing PCI for ACS, but not at 12 months. These data suggest that gender should not affect the decision to offer PCI but further gender specific studies are warranted.

Treatment of unprotected left main disease with drug-eluting stents in patients at high risk for coronary artery bypass grafting.

BACKGROUND: Percutaneous coronary intervention (PCI) for high-grade stenosis of the left main coronary artery with bare-metal stents has been limited by restenosis, and most patients are managed with coronary artery bypass grafting (CABG). Recently, drug-eluting stents (DES) have reduced instent restenosis after PCI, but their role in the treatment of left main disease remains unclear. AIMS: The aim of this study was to determine the outcomes after utilizing DES to treat left main disease. METHODS: Twenty consecutive symptomatic patients with >50% angiographic stenosis of the left main coronary artery with no prior history of CABG ["unprotected left main" (ULM)] underwent PCI with DES. Patients were divided into two groups based on the presence (Group A, n=5) or absence (Group B, n=15) of preprocedural cardiogenic shock. At follow up (median, 14 months), cumulative major adverse cardiac events (MACE-death, myocardial infarction, or target vessel revascularization) were determined. RESULTS: Sixteen (80%) of 20 patients were at high risk for CABG because of comorbidity, advanced age, or cardiogenic shock. Procedural success was 100% (20/20). Three of five patients in Group A (60%) died in hospital and the two surviving patients experienced no MACE at follow up. In Group B (n=15), there was no in-hospital MACE, but one patient died suddenly 8 weeks postprocedure [cumulative MACE of 7% (1/15)]. CONCLUSIONS: Our study demonstrates the feasibility of ULM treatment with DES with acceptable medium-term outcomes. While CABG remains the best form of revascularization for the majority of patients with ULM, DES should be considered in those who are at high risk.

What is the best contemporary treatment for in-stent restenosis?

In-stent restenosis (ISR) remains a challenging problem in percutaneous coronary intervention and the optimal treatment strategy remains unclear. The aim of this study was to compare the 18 month clinical outcomes in patients receiving sirolimus-eluting stents (SES) with vascular brachytherapy (VBT) for the treatment of ISR. Twenty-five consecutive patients treated with VBT were compared with 29 patients who had SES deployment for ISR. Major adverse cardiac events (MACE) were defined as a combination of death from cardiac causes, nonfatal myocardial infarction, or repeat TVR. At 18 month follow-up, the MACE rate was significantly lower in the SES compared with the VBT group (14% vs 40%, P=.03). One patient in the VBT group developed late stent thrombosis (at 10 months) and died; there was no stent thrombosis in the SES group. This observational study, taken with other recent reports, offers further credence to the use of SES for ISR. The results of randomized comparisons with VBT are awaited with interest.