Ultrasound guidance versus anatomical landmark approach for femoral artery access in coronary angiography: A randomized controlled trial and a meta-analysis.

OBJECTIVES: The objective was to assess the effect of ultrasound (US)-guidance compared to the anatomical landmark (AL) approach in patients requiring femoral artery (FA) access for coronary angiography/percutaneous coronary interventions (PCI). BACKGROUND: US-guidance has been proposed as a strategy to optimize FA access, potentially leading to decreased vascular complications. METHODS: Patients requiring FA access for coronary angiography/PCI were randomized to the US-guided or AL approaches. The primary endpoint was a composite of immediate procedural vascular outcomes, and access-site outcomes at day one. Results were subsequently pooled in a study-level meta-analysis of randomized trials comparing US-guided FA access to another strategy. RESULTS: A total of 129 patients were randomized (64 US-guided group; 65 AL group). The primary endpoint occurred in 30 patients (47%) with US, and in 39 patients (62%) with AL (P = 0.09). Four additional studies met the inclusion criteria and were included in the meta-analysis (1553 patients). Following data pooling, bleeding events (OR = 0.41; 95%CI 0.20-0.83; P = 0.01), venipunctures (OR = 0.18; 95%CI: 0.11-0.29; P < 0.0001), and multiple puncture attempts (OR = 0.24; 95%CI: 0.19-0.31; P < 0.0001) were significantly improved with US-guidance, but not successful common FA cannulation (OR = 0.84; 95%CI: 0.60-1.17; P = 0.29). CONCLUSION: Our study did not show significant benefits for the use of US to guide arterial femoral access compared to the anatomical landmark approach, but pooled analysis of five randomized trials showed decreased rates of bleeding events and venipunctures, and improved first-pass success. The clinical impact of these findings is uncertain, and do not warrant a systematic use of US-guidance in this clinical setting.

Evidence of platelet sensitization to ADP following discontinuation of clopidogrel therapy in patients with stable coronary artery disease.

Epidemiological studies have linked clopidogrel discontinuation with an increased incidence of ischemic events. This has led to the hypothesis that clopidogrel discontinuation may result in a pharmacological rebound. We evaluated the impact of clopidogrel discontinuation on platelet function. Platelet aggregation was measured by light transmission aggregometry (LTA) in response to adenosine diphosphate (ADP) 0.5, 1, 1.5, 2.5, 5 and 10 µM and by VerifyNow® P2Y12, in 37 clinically stable coronary artery disease (CAD) patients scheduled to discontinue clopidogrel treatment, and 37 clinically stable CAD patients not taking clopidogrel. Platelet function was assessed the day before clopidogrel cessation and 1, 3, 7, 14, 21 and 28 days after. Clopidogrel had been initiated a median of 555 days (ranging from 200 to 2280 days) before the treating cardiologist recommended its discontinuation. All participants were taking aspirin, most commonly 80 mg daily although a minority was prescribed 325 mg daily. Following clopidogrel discontinuation, VerifyNow® P2Y12 did not detect any rebound platelet activity, but ADP-induced LTA showed platelet sensitization to ADP, particularly at low ADP levels. Increased platelet activity was detectable seven days after clopidogrel cessation and remained higher than in controls 28 days after discontinuation. No clinical event occurred in any of the participants during the 28 days following clopidogrel cessation. In conclusion, platelet sensitization to ADP as a consequence of chronic clopidogrel administration may partially explain the recrudescence of ischemic events following clopidogrel discontinuation in otherwise stable coronary artery patients.

Automated and semi-automated 3D echocardiographic software for aortic annulus sizing in transcatheter aortic valve implantation helps bridge the gap between expert and novice operators.

3D-transesophageal echocardiography (3D-TEE) is an alternative to multidetector row computed tomography (MDCT) for aortic annulus (AoA) sizing in preparation for Transcatheter aortic valve implantation (TAVI). We aim to evaluate how the fully automated (auto) and semi-automated (SA) TEE methods perform compared to conventional manual TEE method and the gold standard MDCT for annulus sizing both in expert and novice operators. In this prospective cohort study, eighty-nine patients with severe aortic stenosis underwent multimodality imaging with 3D-TEE and MDCT. Annular measurements were collected by expert echocardiographers using 3D auto, SA and manual methods and compared to MDCT. A novice in the field of echocardiography retrospectively measured the AoA for all patients using the same methods. TEE measurements, independently of the method used, had good to very good agreement to MDCT. They significantly underestimated aortic annular area and circumference vs. MDCT with the auto method underestimating it the most and the manual method the least (6.5% and 1.3% respectively for area and circumference). For experts, the manual TEE method offered the least systematic bias while the SA method had narrower limits of agreement (LOA). For the novice operator, SA method provided the least bias and narrower LOA vs. MDCT. There is good agreement between novice and experts for all 3 TEE methods but better agreement with auto and SA methods as opposed to manual one. Our study supports the use of 3D-TEE as a complementary method to MDCT for aortic annular sizing. The newer auto and SA software, that requires minimal operator intervention, is an easy to use, reliable and reproducible tool for aortic annulus sizing for experienced operators, and especially less experienced ones.

Inaccuracy of brachial blood pressure and its potential impact on treatment and aortic blood pressure estimation.

OBJECTIVE: Although brachial cuff SBP is universally used to guide hypertension management, it can differ significantly from intraarterial SBP. We examine the potential impacts of cuff-to-intraarterial brachial SBP (bSBP) mismatch on hypertension treatment and accuracy towards central SBP. METHODS: In 303 individuals, cuff bSBP (CUFF-bSBP) and central SBP were measured using a Mobil-o-Graph simultaneously to intraarterial bSBP (IA-bSBP) and aortic SBP. According to the difference between CUFF-bSBP and IA-bSBP, we identified three phenotypes: Underestimation (CUFF-bSBP < IA-bSBP by >10 mmHg); No Mismatch (CUFF-bSBP within 10 mmHg of IA-bSBP); Overestimation (CUFF-bSBP > IA-bSBP by >10 mmHg) phenotypes. Risk of overtreatment and undertreatment, and accuracy (ARTERY society criteria: mean difference ≤5 ±â€Š8 mmHg) were determined. A multiple linear regression model was used to assess variables associated with the bSBP difference. RESULTS: Underestimation (n = 142), No Mismatch (n = 136) and Overestimation (n = 25) phenotypes had relatively similar characteristics and CUFF-bSBP (124 ±â€Š17, 122 ±â€Š14, 127 ±â€Š19 mmHg, P = 0.19) but different aortic SBP (133 ±â€Š21, 120 ±â€Š16, 112 ±â€Š18 mmHg, P < 0.001). In the underestimation phenotype, 59% were at risk of undertreatment (14% in No Mismatch), whereas 50% in the Overestimation phenotype were at risk of overtreatment (17% in No Mismatch). CUFF-bSBP accurately estimated aortic SBP only in the No Mismatch Group (mean difference 1.6 ±â€Š8.2 mmHg) whereas central BP never met the accuracy criteria. Male sex, higher height and active smoking were associated with lesser underestimation of bSBP difference. CONCLUSION: The brachial cuff lacks accuracy towards intraarterial BP in a significant proportion of patients, potentially leading to increased risks of BP mismanagement and inaccurate determination of central BP. This illustrates the need to improve the accuracy of cuff-based BP monitors.

The COVID-19 Pandemic and Coronary Angiography for ST-Elevation Myocardial Infarction, Use of Mechanical Support, and Mechanical Complications in Canada: A Canadian Association of Interventional Cardiology National Survey.

BACKGROUND: As a result of the COVID-19 pandemic first wave, reductions in ST-elevation myocardial infarction (STEMI) invasive care, ranging from 23% to 76%, have been reported from various countries. Whether this change had any impact on coronary angiography (CA) volume or on mechanical support device use for STEMI and post-STEMI mechanical complications in Canada is unknown. METHODS: We administered a Canada-wide survey to all cardiac catheterization laboratory directors, seeking the volume of CA use for STEMI performed during the period from March 1 2020 to May 31, 2020 (pandemic period), and during 2 control periods (March 1, 2019 to May 31, 2019 and March 1, 2018 to May 31, 2018). The number of left ventricular support devices used, as well as the number of ventricular septal defects and papillary muscle rupture cases diagnosed, was also recorded. We also assessed whether the number of COVID-19 cases recorded in each province was associated with STEMI-related CA volume. RESULTS: A total of 41 of 42 Canadian catheterization laboratories (98%) provided data. There was a modest but statistically significant 16% reduction (incidence rate ratio [IRR] 0.84; 95% confidence interval 0.80-0.87) in CA for STEMI during the first wave of the pandemic, compared to control periods. IRR was not associated with provincial COVID-19 caseload. We observed a 26% reduction (IRR 0.74; 95% confidence interval 0.61-0.89) in the use of intra-aortic balloon pump use for STEMI. Use of an Impella pump and mechanical complications from STEMI were exceedingly rare. CONCLUSIONS: We observed a modest 16% decrease in use of CA for STEMI during the pandemic first wave in Canada, lower than the level reported in other countries. Provincial COVID-19 caseload did not influence this reduction.

INTRODUCTION: Après la première vague de la pandémie de COVID-19, de nombreux pays ont déclaré une réduction de 23 % à 76 % des soins invasifs de l'infarctus du myocarde avec élévation du segment ST (STEMI). On ignore si ce changement a entraîné des répercussions sur le volume d'angiographies coronariennes (AC) ou sur l'utilisation des dispositifs d'assistance mécanique lors de STEMI et des complications mécaniques post-STEMI au Canada. MÉTHODES: Nous avons réalisé un sondage pancanadien auprès de tous les directeurs de laboratoire de cathétérisme cardiaque pour obtenir le volume d'utilisation des AC lors des STEMI réalisées durant la période du 1er mars 2020 au 31 mai 2020 (période de pandémie) et durant 2 périodes témoins (1er mars 2019 au 31 mai 2019 et 1er mars 2018 au 31 mai 2018). Le nombre de dispositifs d'assistance ventriculaire gauche utilisés et le nombre de cas de communications interventriculaires et de ruptures du muscle papillaire diagnostiqués ont également été enregistrés. Nous avons aussi évalué si le nombre de cas de COVID-19 enregistrés dans chaque province était associé au volume d'AC liées aux STEMI. RÉSULTATS: Au total, 41 des 42 laboratoires canadiens de cathétérisme (98 %) ont fourni des données. Lors de la comparaison de la première vague de la pandémie aux périodes témoins, nous avons noté une réduction modeste, mais significative, sur le plan statistique de 16 % (ratio du taux d'incidence [RTI] 0,84; intervalle de confiance à 95 % 0,80-0,87) des AC lors de STEMI. Le RTI n'était pas associé au nombre provincial de cas de COVID-19. Nous avons observé une réduction de 26 % (RTI 0,74; intervalle de confiance à 95 % 0,61-0,89) de l'utilisation de pompes à ballonnet intra-aortique lors de STEMI. L'utilisation d'une pompe Impella et les complications mécaniques après les STEMI étaient extrêmement rares. CONCLUSIONS: Nous avons observé une diminution modeste de 16 % de l'utilisation des AC lors de STEMI durant la première vague de la pandémie au Canada, soit une diminution plus faible que ce que les autres pays ont signalé. Le nombre provincial de cas de COVID-19 n'a pas influencé cette réduction.

Week-long high-maintenance dose clopidogrel regimen achieves better platelet aggregation inhibition than a standard loading dose before percutaneous coronary intervention: results of a double-blind, randomized clinical trial.

BACKGROUND: Adequate platelet inhibition before percutaneous coronary intervention (PCI) reduces periprocedural and long-term ischemic complications. Reduced response to clopidogrel has been associated with subsequent major adverse cardiovascular events. Strategies to optimize platelet inhibition pre-PCI are under investigation. This study evaluated the effect on platelet aggregation of four different dosing regimens of clopidogrel given before elective PCI in a randomized, prospective, double-blind, and placebo-controlled design. METHODS: One hundred twenty participants were randomized to one of four groups of clopidogrel: (a) 300 mg on the day prior to angiography; (b) 600 mg on the day prior to angiography; (c) 300 mg followed by 75 mg daily started 1 week prior to angiography; and (d) 300 mg followed by 150 mg daily started 1 week prior to angiography. Platelet aggregation was assessed by light transmission aggregometry (LTA) after stimulation with adenosine diphosphate 20 microM at baseline and at the time of diagnostic coronary angiography. The absolute change in platelet aggregation between these two time points was considered the main outcome measure. RESULTS: At the time of diagnostic coronary angiography, the 300-mg/150-mg daily regimen achieved the greatest decrease in platelet aggregation (37 +/- 19%), while the 300 mg regimen provided the smallest (20 +/- 22%), an absolute difference between the two groups of 17.2 +/- 5.1% (P = 0.005). CONCLUSIONS: A 300-mg loading dose of clopidogrel followed by 150 mg daily for 1 week prior to coronary angiography provides more effective platelet inhibition, as defined by LTA, compared to the standard 300-mg loading dose regimen at the time of coronary intervention.

Comparison of four tests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients.

AIMS: We investigated the comparability of platelet function tests in quantifying platelet inhibition achieved by clopidogrel. METHODS AND RESULTS: This pre-specified substudy of a randomized, double-blind trial included 116 patients with stable coronary artery disease requiring diagnostic angiography. Patients received clopidogrel for 1 (300 or 600 mg) or 7 days (300 + 75 or 150 mg daily) before the procedure. Blood samples obtained before clopidogrel initiation and before diagnostic coronary angiography were assayed using light transmission aggregometry [adenosine diphosphate (ADP) 5 and 20 microM as the agonist], whole-blood aggregometry (ADP 5 and 20 microM), PFA-100 (Collagen-ADP cartridge), and VerifyNow P2Y12. Although all assays studied were found sensitive to clopidogrel ingestion, none could distinguish categorically between patients who had, or not, ingested clopidogrel. Agreement between assays to identify patients with insufficient inhibition of platelet aggregation by clopidogrel was low. CONCLUSION: The assessment of platelet function inhibition by clopidogrel is highly test-specific. Decision to increase clopidogrel dosage may vary on the basis of the assay used, thus highlighting the need for unambiguous guidelines with respect to assay selection, as platelet function assays are not interchangeable. At present, platelet function testing evaluating clopidogrel efficacy cannot be recommended in routine clinical practice.

The Vancouver 3M (Multidisciplinary, Multimodality, But Minimalist) Clinical Pathway Facilitates Safe Next-Day Discharge Home at Low-, Medium-, and High-Volume Transfemoral Transcatheter Aortic Valve Replacement Centers: The 3M TAVR Study.

OBJECTIVES: The authors sought to prospectively determine the safety and efficacy of next-day discharge using the Vancouver 3M (Multidisciplinary, Multimodality, but Minimalist) Clinical Pathway. BACKGROUND: Transfemoral transcatheter aortic valve replacement (TAVR) is an alternative to surgery in high- and intermediate-risk patients; however, hospital stays average at least 6 days in most trials. The Vancouver 3M Clinical Pathway is focused on next-day discharge, made possible by the use of objective screening criteria as well as streamlined peri- and post-procedural management guidelines. METHODS: Patients were enrolled from 6 low-volume (<100 TAVR/year), 4 medium-volume, and 3 high-volume (>200 TAVR/year) centers in Canada and the United States. The primary outcomes were a composite of all-cause death or stroke by 30 days and the proportion of patients successfully discharged home the day following TAVR. RESULTS: Of 1,400 screened patients, 411 were enrolled at 13 centers and received a SAPIEN XT (58.2%) or SAPIEN 3 (41.8%) valve (Edwards Lifesciences, Irvine, California). In centers enrolling exclusively in the study, 55% of screened patients were enrolled. The median age was 84 years (interquartile range: 78 to 87 years) with a median STS score of 4.9% (interquartile range: 3.3% to 6.8%). Next-day discharge home was achieved in 80.1% of patients, and within 48 h in 89.5%. The composite of all-cause mortality or stroke by 30 days occurred in 2.9% (95% confidence interval: 1.7% to 5.1%), with neither component of the primary outcome affected by hospital TAVR volume (p = 0.51). Secondary outcomes at 30 days included major vascular complication 2.4% (n = 10), readmission 9.2% (n = 36), cardiac readmission 5.7% (n = 22), new permanent pacemaker 5.7% (n = 23), and >mild paravalvular regurgitation 3.8% (n = 15). CONCLUSIONS: Adherence to the Vancouver 3M Clinical Pathway at low-, medium-, and high-volume TAVR centers allows next-day discharge home with excellent safety and efficacy outcomes.

Aspirin resistance: truth or dare.

Acetylsalicylic acid, or aspirin (ASA), is widely used in patients with cardiovascular disease to prevent acute ischemic events. However, platelet response to ASA is not equal in all individuals, and a high variability in the prevalence of ASA resistance is reported in the literature (0.4-83%). Actually, ASA resistance is poorly understood; this stems from the fact that its definition is unclear, its presence can be evaluated by a number of assays that are not equivalent, and its prevalence may vary widely based on the population studied. This article (1) exposes the difficulties in defining ASA resistance; (2) discusses the mechanisms by which ASA resistance may occur; (3) presents the characteristics that may put patients at greater risk of exhibiting ASA resistance; and (4) discusses the clinical impact of ASA resistance in patients requiring chronic therapy.

Sirolimus-eluting stents at two years: a pooled analysis of SIRIUS, E-SIRIUS, and C-SIRIUS with emphasis on late revascularizations and stent thromboses.

Prospective follow-up at 2 years was obtained for 98.7% of the pooled 1,510 patients enrolled in SIRIUS, E-SIRIUS and C-SIRIUS, 3 randomized controlled trials that compared sirolimus-eluting stents (SESs) with bare metal stents (BMSs) to treat long stenoses in small coronary arteries. By 720 days, clinically driven target lesion revascularizations were performed in 5.7% of patients with SESs versus 22.6% of patients with BMSs (risk ratio 0.25, 95% confidence interval 0.18 to 0.35, p <0.001). Of these, late target lesion revascularization (from 271 to 720 days) was performed in 12 patients who received SESs (1.6%) compared with 37 patients with BMSs (4.9%) (risk ratio 0.32, 0.17 to 0.61, p <0.001). Stent thromboses occurred in 7 of 758 patients with SESs (0.9%, 4 subacute, 3 late) and 5 of 752 patients with BMSs (0.7%, 1 subacute, 4 late) (risk ratio 1.39, 95% confidence interval 0.44 to 4.36, p = 0.774). The Kaplan-Meier estimate of freedom from major cardiac adverse events was 89.3% for patients with SESs versus 73.4% for patients with BMSs (p <0.001). This analysis demonstrates the sustained efficacy and safety of sirolimus-eluting stents at 2 years, characterized by a persistent significant benefit in freedom from repeat revascularization compared with BMSs and a low risk of late stent thrombosis, not different from BMSs.

Platelet activity and antibody titers after exposure to streptokinase or streptococcal infection.

INTRODUCTION: Streptokinase use, in acute myocardial infarction, is hindered by failure to reperfuse (60%) and early reocclusion (16%). This phenomenon may, among other causes, be due to systemic inactivation of streptokinase, as well as streptokinase-induced platelet aggregation and clot propagation from antibodies to streptokinase produced after streptokinase administration or streptococcal infections. The purpose of this study was to determine the incidence of streptokinase-induced, antibody-mediated, platelet activation and aggregation after administration of SK or development of a streptococcal infection. MATERIALS AND METHODS: We included 45 normal volunteers (Control group), as well as 45 patients who had received streptokinase (Streptokinase group) and 13 who had suffered a severe streptococcal infection (Streptococcal infection group) within the past 3 years. Extent of streptokinase-induced, antibody-mediated, platelet activation and aggregation, as well as anti-streptokinase antibody and streptokinase resistance titers (lowest streptokinase concentration to cause clot lysis within 10 min) were measured. RESULTS: Whereas streptokinase-induced, antibody-mediated, platelet activation was observed in 49% of streptokinase patients and in only 17% and 15% of streptococcal infection patients and normal volunteers (p<0.05 Streptokinase vs. Control and Streptokinase vs. Streptococcal infection), streptokinase-induced platelet aggregation was observed in 23% of streptokinase patients and streptococcal infection patients, and in none of the control patients (p<0.05). CONCLUSIONS: Streptokinase-induced, antibody-mediated, platelet activation and aggregation occur in patients with high titers of anti-streptokinase antibody and may play a role in failure of streptokinase therapy. Streptococcal infection patients behave like streptokinase patients in terms of the reactivity of their platelets to subsequent streptokinase dose in vitro.

Potential anaphylactic shock with abciximab readministration.

A 46-year-old woman developed an anaphylactic reaction during percutaneous coronary intervention after she was pretreated with prednisone and diphenhydramine for a known allergy to iodine. She developed pruritus, edema, and nausea, which were followed by bradycardia and shock, minutes after administration of a bolus and standard-dose infusion of abciximab. The reaction was treated successfully with epinephrine, methoxamine, hydrocortisone, atropine, furosemide, sodium bicarbonate, diphenhydramine, and ranitidine.

Inhibition of streptokinase-induced, antibody-mediated platelet aggregation with tirofiban after exposure to streptokinase or streptococcal infection.

STUDY OBJECTIVE: To evaluate the effect of tirofiban (a glycoprotein IIb-IIIa inhibitor) in preventing streptokinase-induced, antibody-mediated platelet aggregation after administration of streptokinase or development of a streptococcal infection. DESIGN: Prospective analysis. SETTING: Research center of a Canadian hospital. PARTICIPANTS: Forty-five healthy volunteers, 45 patients who had received streptokinase within the past 3 years, and 13 patients who had a severe streptococcal infection also within the past 3 years. INTERVENTION: Blood samples were drawn to measure the extent of inhibition of streptokinase-induced, antibody-mediated platelet activation and aggregation by tirofiban. MEASUREMENTS AND MAIN RESULTS: Platelet aggregation was measured by using a turbidimetric method. The extent of inhibition by tirofiban was measured by incubating tirofiban for 2 minutes before adding streptokinase 5000 U/ml. Also, tirofiban was added 2 minutes before adding adenosine 5'-diphosphate (ADP) 2 microM/L into the last tube as a comparison. Strepto-kinase-induced, antibody-mediated platelet aggregation was observed in 10 (22%) of the 45 patients treated with streptokinase, in 3 (23%) of the 13 patients with streptococcal infection, and in none of the 45 healthy volunteers. Tirofiban inhibited streptokinase-induced, antibody-mediated platelet aggregation by 89 +/- 14% (p<0.001). Similarly, ADP-induced platelet aggregation was inhibited by 92 +/- 6% (p<0.001) with tirofiban. CONCLUSION: Streptokinase-induced, antibody-mediated platelet aggregation occurred in 13 (22%) of 58 patients who received streptokinase or were exposed to a streptococcal infection in the past 3 years. Such patients may not benefit from streptokinase therapy. In these patients, tirofiban significantly decreased the extent of antistreptokinase antibody-mediated platelet aggregation. Hence, patients undergoing streptokinase therapy may benefit from tirofiban as adjunctive therapy.

Simple, quantitative body surface potential map parameters in the diagnosis of remote Q wave and non-Q wave myocardial infarction.

BACKGROUND: Body surface potential mapping has been shown to be a useful tool in the diagnosis and localization of remote non-Q wave and Q wave myocardial infarction, but human expertise is required to interpret the maps. OBJECTIVE: To identify quantitative body surface potential mapping parameters that could enable a computer-based diagnosis. METHODS: Body surface isopotential maps (63 unipolar leads) were recorded in 86 patients with remote Q wave and 71 patients with remote non-Q wave myocardial infarction. Twenty-four healthy adults served as control subjects. Myocardial infarctions were classified using standard electrocardiogram leads in the acute and chronic phases, and were validated by coronary angiography, ventriculography and thallium scintigraphy. RESULTS: Two simple quantitative parameters with high diagnostic power were identified: the time interval between the peak minimum and the peak maximum potentials (time-shift), and the ratio of these potentials (maximum to minimum ratio [max/min]). Both parameters showed significant differences between infarction patients and normal control subjects, and optimum cut-off values were determined using receiver operating characteristic curves (anterior infarction: time-shift of -4 ms or less, max/min of 0.6 or less; posterior infarction: time-shift of 8 ms or greater, max/min of 1.25 or greater). The sensitivities of the two parameters were 100% and 97%, and the specificities were 99% and 100%, respectively, in the anterior Q wave infarction group, compared with sensitivities of 88% and 100%, and specificities of 94% and 95%, respectively, in the posterior Q wave infarction group. In the anterior non-Q wave infarction group, sensitivity was 35% for both parameters, specificity was 100% for both parameters, and only infarctions associated with a low ejection fraction were detected, indicating that infarction size may influence the power of the tests. CONCLUSIONS: Time-shift and max/min are two new, simple, powerful parameters for infarction diagnosis and may also be suitable for automated, computer-based processing.

Excellent outcomes for transcatheter aortic valve replacement within 1 year of opening a low-volume centre and consideration of requirements.

BACKGROUND: After the approval of transcatheter aortic valve replacement (TAVR) for high-risk or inoperable patients with severe aortic stenosis (AS), many low- and moderate-volume TAVR programs were initiated. Contemporary outcomes from these newly initiated centres remain unknown. METHODS: In March 2013, our institution was authorized by the Québec Ministry of Health to perform 30 TAVR procedures. After thorough clinical screening and imaging evaluation, suitable patients underwent transfemoral TAVR with the balloon-expandable SAPIEN XT (Edwards Lifesciences, Irvine, CA) transcatheter heart valve (THV). In-hospital and 30-day outcomes were prospectively collected and reported according to Valve Academic Research Consortium 2 guidelines. RESULTS: From April 2013 to January 2014, 30 consecutive high-risk (n = 16 [53.3%]) or inoperable (n = 14 [46.7%]) patients (mean age, 84.6 years; mean Society of Thoracic Surgery score, 7) with symptomatic severe AS underwent transfemoral TAVR. No catastrophic intraprocedural complications such as annulus rupture, valve embolization, aortic dissection, or coronary occlusion occurred, and there were no deaths at 30 days. Disabling stroke occurred in 1 (3.3%) patient 48 hours after THV implantation. Major vascular complications and major bleeding occurred in 1 (3.3%) patient. No moderate or severe paravalvular leak was observed. The median length of stay was 2 (1-3) days, with 8 (26.7%) patients discharged within 24 hours after the procedure. CONCLUSIONS: Excellent outcomes can be achieved in newly initiated relatively low-volume centres, which compares favorably to previously published large series. Important considerations include appropriate team training, rigorous patient screening, use of multimodality imaging techniques, a heart team approach, constant integration of lessons learned from larger published experiences, and maintaining a recommended minimum volume of 25 cases per year.

Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease.

BACKGROUND: Platelets, long believed to be incapable of de novo protein synthesis, may retain their ability to form the cyclooxygenase (COX) enzyme once it has been inactivated by aspirin. This may explain the inefficacy of the drug to induce sustained platelet inhibition in certain patients. We evaluated the stability of platelet inhibition following once-daily enteric-coated aspirin administration. METHODS: Platelet responsiveness to aspirin was evaluated in 11 stable coronary artery disease patients on chronic aspirin therapy before and 1, 3, 8, and 24h after observed ingestion of 80-mg enteric-coated aspirin. Inhibition of the COX pathway was measured pharmacologically through plasma thromboxane (Tx) B(2) levels, and functionally by light transmission aggregometry in response to arachidonic acid. COX-independent platelet activity was measured in response to adenosine diphosphate, epinephrine and collagen. RESULTS: Plasma TxB(2) levels showed profound inhibition of TxA(2) formation, which was stable throughout 24h, in all but 1 subject. This subject had optimal response to aspirin (inhibition of platelet TxA(2) production within 1h), but recovered the ability to synthesize TxA(2) within 24h of aspirin ingestion. Arachidonic acid-induced platelet aggregation closely mirrored TxB(2) formation in this patient, portraying a functional ability of the platelet to aggregate within 24h of aspirin ingestion. COX-independent platelet aggregation triggered TxA(2) production to a similar extent in all patients, likely through signal-dependent protein synthesis. CONCLUSIONS: COX-dependent platelet activity is recovered in certain individuals within 24h of aspirin administration. Further research should consider increasing aspirin dosing frequency to twice daily, to allow sustained inhibition in such subjects.

Genetic determinants of response to aspirin: appraisal of 4 candidate genes.

INTRODUCTION: Intersubject variability in platelet response to aspirin could be related to genetic factors that regulate platelet enzymes or receptors. This study evaluates the impact of the selected polymorphisms in the COX-1 gene, the CYP5A1 gene, the P2RY1 receptor gene, and the GPIIbIIIa receptor gene on platelet response to aspirin and risk of suffering from major adverse cardiovascular and cerebrovascular events (MACCE). MATERIALS AND METHODS: 192 Caucasian patients with stable coronary artery disease treated with daily aspirin were recruited and followed for 3 years. Platelet aggregation was measured by light transmission aggregometry with arachidonic acid (1.6 mM) and adenosine diphosphate (5, 10 or 20 µM) used as agonists. Genotyping was performed by standard PCR methods. RESULTS: Arachidonic acid-induced platelet aggregation was unaffected by the COX-1 22C/T and by the Pl(A1/A2) polymorphisms. However, carriers of the 1622 G/G genotype of the P2RY1 gene had significantly higher levels of arachidonic acid-induced platelet aggregation compared with non-carriers (AA 2.0%, AG 2.0% vs. GG 9.0%, p=0.047). Carrying the 1622 G/G genotype increased the risk of inadequate platelet response to aspirin, defined as arachidonic acid-induced aggregation ≥ 20%, by a factor of 8.5 (1.4 - 53.3, p=0.022) and the risk of 3-year MACCE by a factor of 7 (1.4 - 34.7, p=0.017). CONCLUSION: The 1622A/G mutation of the P2RY1 gene could contribute to inadequate platelet response to aspirin and is associated with an increased risk of suffering from MACCE.