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.

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.

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.

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.

2010 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiologists Guidelines for Training and Maintenance of Competency in Adult Interventional Cardiology.

Interventional cardiology is a subspecialty of adult cardiology dedicated to the use and application of imaging-based diagnostic techniques and minimally invasive modalities for the treatment of cardiovascular disease. Currently, interventional cardiologists must demonstrate expert knowledge of cardiac imaging, along with cardiovascular anatomy and the pathophysiology of cardiovascular disease. In addition, they must possess the technical skills required for the practice of interventional cardiology and be knowledgeable about new antiplatelet and antithrombotic drugs mandated for optimal patient care. The 2010 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiologists Guidelines for Training and Maintenance of Competency in Adult Interventional Cardiology are the first such guidelines to be published in Canada. These guidelines should allow for more-fluid provision of high-quality interventional cardiology education, along with less geographic variation, resulting in more-widespread high-level services to the population.

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.

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.

Platelet count, not oxidative stress, may contribute to inadequate platelet inhibition by aspirin.

BACKGROUND: Several patient characteristics have been shown to increase the risk of inadequate platelet inhibition by aspirin, yet underlying mechanisms remain mostly unknown. We explored whether oxidative stress, via isoprostane formation, was associated with inadequate platelet response to aspirin. Additionally, we sought to investigate whether individual pre-selected demographic, hematological or biochemical parameters further increased the risk of inadequate platelet response to aspirin. METHODS: Two hundred consecutive subjects suffering from stable coronary artery disease and under daily aspirin therapy were enrolled in our study. Inadequate platelet response to aspirin was defined as residual platelet aggregation>or=20% per arachidonic acid-induced light transmission aggregometry. Morning urinary samples were used to determine levels of isoprostanes (8-iso-PGF2alpha) using an enzyme immunoassay. RESULTS: Eight subjects were deemed to present inadequate platelet response to aspirin. Wide intersubject variability was observed in urinary 8-iso-PGF2alpha levels. However, levels were similar between aspirin responders and non-responders. Patients with inadequate platelet response to aspirin had higher platelet counts and received the lowest daily aspirin dose when compared to responders, suggesting subtherapeutic aspirin therapy due to increased platelet production. Only platelet count remained independently predictive of inadequate platelet response to aspirin in a multiple logistic regression model. CONCLUSIONS: Urinary 8-iso-PGF2alpha levels, a reflection of systemic oxidative stress, did not appear to contribute to impaired platelet responsiveness to aspirin, while increased platelet production may partly explain this phenomenon.

Prevalence of unresponsiveness to aspirin and/or clopidogrel in patients with stable coronary heart disease.

This study sought to assess whether inadequate platelet responses to aspirin and clopidogrel are distinct phenomena caused by different mechanisms or different facets of the same phenomenon (i.e., general platelet hyperactivity). A total of 85 patients with stable coronary artery disease who were taking aspirin and clopidogrel daily for > or =3 months were enrolled in the present study. Platelet aggregation was measured by light transmission aggregometry (LTA) stimulated with 1.6 mM of arachidonic acid and 5, 10 and 20 microM of adenosine diphosphate, and by the VerifyNow Aspirin and VerifyNow P2Y12 point-of-care assays. An inadequate platelet response was defined as aggregation greater than or equal to the mean + 2 SDs. The prevalence of an inadequate platelet response varied greatly among the assays. For aspirin, the prevalence was 2.4% using arachidonic acid-induced LTA and 5.9% using the VerifyNow Aspirin assay. For clopidogrel, the prevalence varied from 1.2% to 3.9% using adenosine diphosphate-induced LTA and was 2.4% using the VerifyNow P2Y12 assay. The point-of-care assays did not select the same patients as LTA. No subject was unresponsive to both aspirin and clopidogrel, regardless of the assay used, suggesting that separate mechanisms govern platelet unresponsiveness to aspirin and clopidogrel. In conclusion, an inadequate platelet response to either aspirin or clopidogrel is rare, and the definition is dependent on the platelet function assay used. Because no subject was found to be unresponsive to both agents, the unresponsiveness is suspected to occur through distinct mechanisms of platelet activation.

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.

Insights into the interpretation of light transmission aggregometry for evaluation of platelet aggregation inhibition by clopidogrel.

INTRODUCTION: When studying the efficacy of clopidogrel to inhibit platelet aggregation by light transmission aggregometry, technical decisions must be taken prior to assessment or during analysis, including, but not limited to, concentration of agonist to use and timing of the evaluation of the response on the aggregation curve obtained (peak ADP-stimulated platelet aggregation vs. late aggregation). We investigated how some of these technical modalities affected the results of platelet aggregation obtained after clopidogrel administration. MATERIALS AND METHODS: One hundred and twenty stable coronary artery disease patients requiring a diagnostic angiography were recruited prior to pre-treatment with clopidogrel. Blood samples were tested before clopidogrel initiation and immediately preceding coronary angiography using light transmission aggregometry with either 5 or 20 microM of ADP. Aggregation was measured at maximal amplitude (peak), and 5 minutes after agonist addition (late). RESULTS: While measurements of platelet aggregation as either peak or late aggregation were strongly correlated, peak platelet aggregation was significantly higher than late aggregation, by 10.8% and by 10.3% with ADP 5 and 20 microM, respectively. Moreover, the use of ADP 20 microM resulted in less spontaneous disaggregation than 5 microM in the absence of clopidogrel (11.8% and 4.8% with ADP 5 microM and 20 microM, respectively). CONCLUSIONS: When assessing platelet aggregation following clopidogrel, measurement of late aggregation after addition of ADP 20 microM should be preferred. Large clinical trials should be conducted to assess which parameter between residual aggregation or inhibition of platelet aggregation by clopidogrel best predicts clinical efficacy of the drug.

Evaluation of the platelet count drop method for assessment of platelet function in comparison with "gold standard" light transmission aggregometry.

INTRODUCTION: Hyporesponsiveness to antiplatelet agents has been linked to an increased risk of major adverse cardiovascular events. However, light transmission aggregometry (LTA), the gold standard methodology for assessing platelet function, requires expertise and is labour-intensive, which render its use in clinical settings impractical. We assessed whether platelet count drop (PCD), a technique widely available in any haematology laboratory, could replace LTA in testing for inhibition of platelet aggregation induced by antiplatelet agents. MATERIALS AND METHODS: One hundred and sixty-one coronary artery disease patients taking aspirin alone and 91 patients taking a combination of aspirin and clopidogrel were enrolled. Platelet aggregation was measured by LTA and PCD stimulated with 1.6 mM of arachidonic acid (AA) for aspirin and 5 and 20 microM of adenosine diphosphate (ADP) for clopidogrel. RESULTS: Correlation between AA-induced LTA and PCD was nonexistent (r=-0.043, p=0.587), while correlation between ADP-induced LTA and PCD was low (r=0.374, p<0.0001 for ADP 5 microM and r=0.402, p<0001 for ADP 20 microM ). PCD, whether stimulated with AA or ADP, overestimated platelet aggregation as assessed by LTA, by 13-18%. The wide 95% limits of agreement suggest that the assays can disagree significantly in individual patients. CONCLUSIONS: Although the PCD method is widely available in non-specialized laboratories, our results demonstrate that there is poor correlation with the current gold standard, i.e. LTA. Thus, PCD should not be used in replacement of LTA to assess antiplatelet responsiveness.

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.

Diagnosis and discrimination of remote antero- and inferoseptal non-Q wave myocardial infarctions with body surface potential mapping.

BACKGROUND: Previous studies have shown that the diagnosis and localization of previous non-Q wave myocardial infarction (NQMI) is possible by body surface potential mapping (BSPM), but the criteria for the discrimination between anteroseptal and inferoseptal middle regions remain to be determined. METHODS: BSPM using 63 unipolar leads was recorded in 119 patients with previous NQMI (36 to 76 years of age, average 61 years; 85 men). Localization of anteroseptal or inferior middle NQMI occurred in 70 cases (44 to 76 years of age, average 61 years, 53 men) by determining early anterior minimum potential with only slight negativity. In these cases, isopotential maps obtained at additional time points were investigated to discriminate between anteroseptal and inferoseptal NQMI. The clinical localization was based on the concordance of two of the following tests: wall motion disturbances on echocardiography, coronary angiogram and repolarization changes in the acute-phase electrocardiogram. RESULTS: Two milliseconds before the appearance of the first anterior minimum, a more accentuated superior negativity indicated anteroseptal NQMI (32 of 70 cases), while a more pronounced inferior negativity indicated inferoseptal NQMI (38 of 70 cases). Fisher's exact test showed statistically significant associations between the above BSPM localizations and the clinical localizations (P<0.001). Occlusion or stenosis of the expected infarct-related coronary artery was detected in all patients either as a single lesion or together with other coronary artery lesions. CONCLUSIONS: The BSPM criteria proposed here are suitable to detect the most frequent NQMI localizations. The narrowing of the infarct-related coronary arteries, the left anterior descending or the posterior descending coronary artery, can be thus differentiated.