Contemporary use of guideline-based higher potency P2Y12 receptor inhibitor therapy in patients with moderate-to-high risk non-ST-segment elevation myocardial infarction: Results from the Canadian ACS reflective II cross-sectional study.

BACKGROUND: After myocardial infarction, guidelines recommend higher-potency P2Y12 receptor inhibitors, namely ticagrelor and prasugrel, over clopidogrel. HYPOTHESIS: We aimed to determine the contemporary use of higher-potency antiplatelet therapy in Canadian patients with non-ST-elevation myocardial infarction (NSTEMI). METHODS: A total of 684 moderate-to-high risk NSTEMI patients were enrolled in the prospective Canadian ACS Reflective II registry at 12 Canadian hospitals and three clinics in five provinces between July 2016 and May 2018. Multivariable logistic regression modeling was performed to assess factors independently associated with higher-potency P2Y12 receptor inhibitor use at discharge. RESULTS: At hospital discharge, 78.3% of patients were treated with a P2Y12 receptor inhibitor. Among patients discharged on a P2Y12 receptor inhibitor, use of higher-potency P2Y12 receptor inhibitor was 61.4%. After adjustment, treatment in-hospital with PCI (OR 4.48, 95%CI 3.34-6.03, p < .0001) was most strongly associated with higher use of higher-potency P2Y12 receptor inhibitor, while oral anticoagulant use at discharge (OR 0.03, 95%CI 0.01-0.12, p < .0001), and atrial fibrillation (OR 0.40, 95%CI 0.17-0.98, p = .046) were most strongly associated with lower use of higher-potency P2Y12 receptor inhibitor. Use of higher-potency P2Y12 receptor inhibitor varied across provinces (range, 21.6%-78.9%). DISCUSSION: In contemporary Canadian practice, approximately 60% of moderate-to-high risk NSTEMI patients discharged on a P2Y12 receptor inhibitor are treated with a higher-potency P2Y12 receptor inhibitor. In addition to factors that increase risk of bleeding, interprovincial differences in practice patterns were associated with use of higher-potency P2Y12 receptor inhibitor at discharge. Opportunities remain for further optimization of evidence-based, guideline-recommended antiplatelet therapy use.

Provision of a DAPT Score to Cardiologists and Extension of Dual Antiplatelet Therapy Beyond 1 Year After ACS: Randomized Substudy of the Prospective Canadian ACS Reflective II Study.

BACKGROUND: Extension of dual antiplatelet therapy (DAPT) beyond 1 year after acute coronary syndrome is associated with a reduction in ischemic events but also increased bleeding. The DAPT score identifies individuals likely to derive overall benefit or harm from DAPT extension. We sought to evaluate the impact of providing the DAPT score to treating physicians on the decision to extend DAPT beyond 1 year after non-ST-segment elevation myocardial infarction. METHODS: Moderate to high-risk non-ST-segment elevation myocardial infarction patients were enrolled from July 2016 to May 2018 in 13 Canadian hospitals by 52 cardiologists. Participating cardiologists were randomly assigned 1:1 to receive their individual patients' DAPT scores before the 1-year follow-up visit vs not receiving their patients' DAPT scores. Rates of DAPT extension were compared among the randomized groups. RESULTS: At 1 year, 370 of the 585 (63.2%) patients discharged on DAPT were receiving DAPT. Among patients on DAPT at 1 year, the median (25th, 75th percentile) DAPT score was 2 (1,3). DAPT was extended beyond 1 year in 36.2% randomly assigned to provision of DAPT score vs 35.7% in the control group (P = 0.93). In the subgroup of patients with DAPT score ≥ 2, DAPT extension was 49.5% in the DAPT score provision arm vs 40.4% in the control arm (P = 0.22); among patients with DAPT score < 2, DAPT termination was 78.6% in the DAPT score provision arm vs 70.6% in the control arm (P = 0.26) (P value for interaction = 0.1). CONCLUSIONS: In this exploratory randomized trial, provision of the DAPT score to treating physicians had no impact on the duration of DAPT treatment beyond 1 year.

INTRODUCTION: La prolongation de la bithérapie antiplaquettaire au-delà d'un an après un syndrome coronarien aigu est associée à la réduction des accidents ischémiques, mais aussi à l'augmentation des hémorragies. Le score de bithérapie antiplaquettaire permet de déterminer les individus susceptibles d'obtenir des avantages globaux ou des inconvénients de la prolongation de la bithérapie antiplaquettaire. Nous avons cherché à évaluer les répercussions de l'obtention du score de bithérapie antiplaquettaire par les médecins traitants sur la décision quant à la prolongation de la bithérapie antiplaquettaire au-delà d'un an après l'infarctus du myocarde sans élévation du segment ST. MÉTHODES: De juillet 2016 à mai 2018, 52 cardiologues de 13 hôpitaux du Canada ont inscrit des patients exposés à un risque modéré à élevé d'infarctus du myocarde sans élévation du segment ST. Nous avons réparti de façon aléatoire selon un rapport 1:1 les cardiologues participants qui recevaient les scores de bithérapie antiplaquettaire individuels de leurs patients avant la consultation de suivi après un an vs ceux qui ne recevaient pas les scores de bithérapie antiplaquettaire de leurs patients. Nous avons comparé les taux de prolongation de la bithérapie antiplaquettaire des groupes répartis de façon aléatoire. RÉSULTATS: Après un an, 370 (63,2 %) patients sur 585 qui avaient eu à la sortie de l'hôpital une bithérapie antiplaquettaire recevaient la bithérapie antiplaquettaire. Parmi les patients qui prenaient la bithérapie antiplaquettaire après un an, le score médian de bithérapie antiplaquettaire (25e, 75e percentiles) était de 2 (1, 3). La bithérapie antiplaquettaire était prolongée au-delà d'un an chez 36,2 % des patients répartis de façon aléatoire qui avaient un score de bithérapie antiplaquettaire vs 35,7 % dans le groupe témoin (P = 0,93). Dans le sous-groupe de patients qui avaient un score de bithérapie antiplaquettaire ≥ 2, la prolongation de la bithérapie antiplaquettaire était de 49,5 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 40,4 % dans le bras témoin (P = 0,22); parmi les patients qui avaient un score de bithérapie antiplaquettaire < 2, la cessation de la bithérapie antiplaquettaire était de 78,6 % dans le bras qui avait un score de bithérapie antiplaquettaire vs 70,6 % dans le bras témoin (P = 0,26) (valeur P pour l'interaction = 0,1). CONCLUSIONS: Dans cet essai exploratoire à répartition aléatoire, l'obtention du score de la bithérapie antiplaquettaire par les médecins traitants n'a pas engendré de répercussions sur la durée de la bithérapie antiplaquettaire au-delà d'un an.

It's Never Too Late: Spotting Congenital Absence of the Pericardium in an Older Adult.

A 75-year-old male with a cardiopulmonary history presented with chest pain and dyspnea. He was hypertensive. An electrocardiogram showed paced rhythm. A high-sensitivity test showed his troponin T level was minimally elevated. Coronary angiography results were unremarkable. Chest radiography revealed an elevated cardiac apex, previously attributed to cardiomegaly. Echocardiography revealed a teardrop shaped heart in a nonstandard apical window. Computed tomography confirmed congenital absence of the left pericardium. Challenges of recognizing a rare condition are highlighted. Congenital absence of the pericardium, an often benign but rarely catastrophic condition, can masquerade for decades before diagnosis, underlining the importance of clinical vigilance in evaluating common cardiac complaints.

Un homme de 75 ans qui avait des antécédents cardiopulmonaires a éprouvé une douleur thoracique et accusé une dyspnée. Il souffrait d'hypertension. Un électrocardiogramme a montré un rythme électro-entraîné. Le dosage de la troponine T hautement sensible a révélé des concentrations minimalement élevées. Les résultats de l'angiographie coronarienne étaient normaux. La radiographie pulmonaire a révélé un apex du cœur élevé, antérieurement attribué à la cardiomégalie. L'échocardiographie a révélé un cœur en forme de larme dans une fenêtre apicale non standard. La tomodensitométrie a permis de confirmer l'absence congénitale du péricarde gauche. Nous présentons les enjeux liés à l'identification d'une maladie rare. Puisque l'absence congénitale du péricarde, une anomalie souvent bénigne, mais rarement catastrophique, peut demeurer dissimulée durant des décennies avant le diagnostic, nous soulignons l'importance de la vigilance clinique dans l'évaluation des symptômes cardiaques courants.

Percutaneous Coronary Intervention in a Patient With Severe Systemic Vasculitis and Myocardial Infarction.

A 72-year-old woman presented with acute coronary syndrome. There was diffuse coronary ectasia and severe stenosis in the proximal left anterior descending artery consistent with coronary vasculitis. Despite treatment with high-dose immunosuppression, she underwent percutaneous coronary intervention for refractory angina.

Pericardial effusion and tamponade following interferon alpha treatment for locally advanced melanoma.

Regional Metastatic Melanoma has a relatively high mortality rate. Adjuvant interferon-alpha (IFN-α) has been shown to improve disease-free survival, post-resection. Cardiotoxicity associated with IFN-α use has been described previously in the literature, but here we describe the first case of pericardial effusion with cardiac tamponade secondary to IFN-α 2b treatment of melanoma. Clinicians should be aware of this potentially lethal complication and the possible acuity of its onset.

Impact of reduced glomerular filtration rate on outcomes in patients with ST-segment elevation myocardial infarction undergoing fibrinolysis: a CLARITY-TIMI 28 analysis.

Reduced glomerular filtration rate (GFR) is associated with adverse outcomes in patients with cardiovascular disease. We explored the relationship between GFR and angiographic and clinical outcomes in ST-segment elevation myocardial infarction (STEMI) patients receiving pharamacologic reperfusion, with or without clopidogrel. Data were available to estimate GFR in 3,252 STEMI patients undergoing fibrinolysis, randomized to clopidogrel versus placebo in the CLARITY-TIMI 28 trial. Patients with a creatinine > 2.5 mg/dl were excluded from the trial. We compared outcomes between patients with no, mild or moderate reductions in baseline estimated GFR (ml/min/1.73 m²) of ≥ 90, 60-89, and <60, respectively. Compared to patients with no (n = 841) or mildly reduced GFR (n = 1897), those with moderately reduced GFR (n = 514) were older, more often female, and were more likely to have diabetes and hypertension (P ≤ 0.001 for all). The risk of the primary endpoint (an occluded infarct-related artery on angiography or death/myocardial infarction by day 8), 30 day cardiovascular events (death, myocardial infarction, or urgent revascularization for recurrent ischemia) and 30 day Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding increased as GFR declined (P for trend 0.003, <0.0001, and 0.0008 respectively). The adjusted risk of 30 day ischemic complications remained higher in patients with moderately reduced versus normal GFR (OR 1.5, 95% CI 1.0-2.1, P = 0.04). Treatment with clopidogrel tended to yield greater benefit in patients with normal or mildly reduced GFR versus in patients with moderately reduced GFR. In conclusion, STEMI patients with reduced GFR treated with medical reperfusion, including dual antiplatelet therapy, have higher rates of adverse clinical outcome. Further research on optimal STEMI therapy in this high-risk group is warranted.

The independent and combined risk of diabetes and non-endstage renal impairment in non-ST-segment elevation acute coronary syndromes.

OBJECTIVES: To assess the effect of renal impairment (RI) and diabetes (DM) on outcomes in non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS: Data were pooled from 13,126 patients in five NSTE-ACS TIMI trials (TIMI 11A and B, TIMI 12, OPUS-TIMI 16, and TACTICS-TIMI 18). Patients were divided based on DM status and RI (none, mild, or moderate if the glomerular filtration rate (GFR, ml/min/1.73 m(2)) was > or = 90, 60-89 and 30-59 respectively). RESULTS: Patients with DM and moderate RI (n=609) were older and had more prior MI (p<0.01 for all) than other subgroups. Compared with no RI/DM (n=3,832), the 12-month adjusted risks of death, MI, and death/MI increased with advancing RI and were highest with DM and moderate RI (H.R. 1.7, (1.2-2.4), p=0.002; H.R. 2.0 (1.5-2.6), p<0.001; and H.R. 1.7 (1.3-2.2), p<0.001 respectively). These events were also increased with DM and mild RI (H.R. 1.4, (1.0-1.9), p=0.06, H.R. 1.4 (1.1-1.8), p=0.006 and H.R. 1.3 (1.1-1.7), p=0.007 respectively) but not with 1) mild or moderate RI without DM or 2) DM without RI. The interaction terms for RI and DM in their association with MI and death/MI were significant. CONCLUSIONS: In the absence of DM, RI and in the absence of RI, DM did not increase the risk of MI or death/MI. However, the combination of RI and DM was associated with a particularly high risk of MI and death/MI suggesting that attention to preserving renal function may be of particular benefit for reducing cardiovascular risk in diabetic patients.

Clinical outcome and echocardiographic predictors of aortic valve replacement in patients with bicuspid aortic valve.

BACKGROUND: Clinical outcomes and echocardiographic parameters associated with aortic valve replacement (AVR) for bicuspid aortic valve are scarce. METHODS: We conducted retrospective analysis of 208 adults with bicuspid aortic valve referred for transthoracic echocardiograms. RESULTS: The Kaplan-Meier survival free of death or need for cardiac surgery was 72% at 5 years. Cardiac surgery was performed in 19%, the majority (68%) for symptomatic aortic stenosis. Peak gradient 80 mm Hg or greater (hazard ratio 11.8, 95% confidence interval 3.7-37.8, P < .0001) and aortic valve area less than or equal to 0.75 cm(2) (hazard ratio 2.9, 95% confidence interval 1.0-8.5, P = .05) predicted the need for AVR. Patients with a large (54%) versus normal left ventricular outflow tract dimension underwent AVR for symptomatic aortic stenosis at a larger calculated aortic valve area (1.07 +/- 0.21 vs 0.75 +/- 0.18 cm(2), P < .0001) but at a similar peak gradient and velocity ratio (76 +/- 19 vs 76 +/- 22 mm Hg, P = not significant; 0.23 +/- 0.06 vs 0.26 +/- 0.12, P = not significant, respectively). CONCLUSIONS: Clinical events are common among patients with bicuspid aortic valve. Peak gradient 80 mm Hg or more and aortic valve area less than or equal to 0.75 cm(2) predicts the need for AVR. Gradients and velocity ratio better reflect the hemodynamic burden of aortic stenosis in patients with a large left ventricular outflow tract.

Acute coronary syndromes and diabetes: Is intensive lipid lowering beneficial? Results of the PROVE IT-TIMI 22 trial.

AIMS: The impact of intensive lipid lowering therapy with statins in acute coronary syndrome (ACS) patients with diabetes mellitus (DM) is not well characterized. METHODS AND RESULTS: We explored this question in data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) TIMI 22 trial, which tested standard (pravastatin 40 mg) vs. intensive (atorvastatin 80 mg) statin therapy among patients treated early in the post-ACS period. We compared outcomes between patients with DM (identified by history, fasting plasma glucose > or =126 mg/dL or haemoglobin A1C > 7%; n = 978) against those without DM (n = 3184). The rate of acute cardiac events (death, myocardial infarction, and unstable angina requiring rehospitalization) was much higher in patients with DM, but was reduced with intensive vs. standard therapy similarly in diabetic (21.1 vs. 26.6%, HR = 0.75, P = 0.03) and non-diabetic patients (14.0 vs. 18.0%, HR = 0.76, P = 0.002); P-interaction = 0.97. Despite intensive therapy, the majority of diabetics (62%) did not reach the dual goal of LDL-C < 70 mg/dL and high-sensitivity C-reactive protein <2 mg/L. CONCLUSION: In ACS patients with DM, intensive statin therapy reduces acute cardiac events as it does in those without DM, with 55 vs. 40 events prevented per 1000 patients treated. However, our data highlight the need for additional strategies in this high-risk group.

Poor outcomes after fibrinolytic therapy for ST-segment elevation myocardial infarction: impact of age (a meta-analysis of a decade of trials).

BACKGROUND: Fibrinolysis for ST-segment elevation myocardial infarction (STEMI) reduces mortality, but its relative efficacy and risks are age-dependent. We aimed to quantify the outcomes of fibrinolysis and adjunctive antithrombin therapy for STEMI stratified by age. METHODS: We performed a meta-analysis of 11 published (1992-2001) randomized clinical trials of fibrinolysis in STEMI (sample size >or=3,000, no age limit, no placebo-controlled arms) identified by MEDLINE through June 2005. Event rates and odds ratios (OR) in elderly vs. younger patients were calculated for mortality, intracranial hemorrhage (ICH) and total stroke (CVA). Elderly patients were defined as >or=75 years (GUSTO I, TIMI 9B, GUSTO III, COBALT, ASSENT-2, InTIME-II TIMI-17, ASSENT-3, GUSTO V, and HERO-2), except when defined as >65 or >or=70 years by the study (INJECT and ISIS-3). RESULTS: Elderly (n = 24,531) vs. younger (n = 123,568) patients had increased rates of mortality (19.7% vs. 5.5%), ICH (1.4% vs. 0.5%) and CVA (3.5 vs. 1.2%) by 30-35 days; the excess risk for these events was substantial (OR mortality 4.37, 95% CI 4.16-4.58; ICH 2.83, 2.47-3.24; CVA 2.92, 2.62-3.25; p < 0.001 for all). CONCLUSIONS: Despite established mortality reductions with fibrinolysis for STEMI, elderly compared with younger patients, still have a three to four fold increased risk of mortality and adverse events when treated with fibrinolysis and antithrombin therapy in the modern era. These robust estimates of the anticipated rates for mortality, ICH, and CVA can be used as benchmarks to monitor the efficacy and safety of therapies in ongoing and newly completed clinical trials. We aimed to quantify the outcomes of death, intracranial hemorrhage (ICH), and total cerebrovascular accidents (CVA) in elderly compared with younger patients treated with fibrinolysis for STEMI based on a meta-analysis of 11 randomized clinical trials (1992-2001) of more than 3,000 patients. Elderly (n = 24,531) vs. younger (n = 123 568) patients had increased rates of mortality, ICH and CVA by 30-35 days; the excess risk was substantial (OR 4.37, 2.83, and 2.92 respectively, p < 0.001 for all). These robust estimates can be used as benchmarks to monitor the efficacy and safety of therapies in ongoing and newly completed clinical trials.

Guidelines for the provision of echocardiography in Canada: recommendations of a joint Canadian Cardiovascular Society/Canadian Society of Echocardiography Consensus Panel.

Recognizing the central role of echocardiographic examinations in the assessment of most cardiac disorders and the need to ensure the provision of these services in a highly reliable, timely, economical and safe manner, the Canadian Cardiovascular Society and Canadian Society of Echocardiography undertook a comprehensive review of all aspects influencing the provision of echocardiographic services in Canada. Five regional panels were established to develop preliminary recommendations in the five component areas, which included the echocardiographic examination, the echocardiographic laboratory and report, the physician, the sonographer and indications for examinations. Membership in the panels was structured to recognize the regional professional diversity of individuals involved in the provision of echocardiography. In addition, a focus group of cardiac sonograhers was recruited to review aspects of the document impacting on sonographer responsibilities and qualification. The document is intended to be used as a comprehensive and practical reference for all of those involved in the provision of echocardiography in Canada.