Fortuin, F. David

Abstract Background Coronary artery disease (CAD) and atrial fibrillation (AF) are commonly associated. Co-treatment with multiple anti-thrombotic agents can increase the risk of bleeding. Purpose We sought to evaluate patient-centered outcomes in patients with AF on double therapy with direct oral anticoagulants (DOACs) compared to patients with standard triple therapy, [a vitamin K antagonist (VKA) plus dual antiplatelet therapy]. Methods We performed an extensive systematic review of the literature and meta-analysis of randomized controlled trials reporting outcomes of patients receiving double therapy with DOACs compared to triple therapy with VKAs in patients with AF undergoing percutaneous coronary intervention (PCI). Patient-centered outcomes were the International Society of Thrombosis and Hemostasis (ISTH) major or clinically relevant non-major bleeding (CRNB), all-cause mortality, major adverse cardiovascular events (MACE), myocardial infarction, stent thrombosis, and stroke. Results Four randomized controlled trials (9602 patients) met our inclusion criteria. Compared to VKAs, DOACs were associated with significantly lower ISTH major bleeding/ CRNB (RR - 0.75, 95% CI: 0.67-0.82, p < 0.00001, I2 = 11%). There were no statistically significant differences in the efficacy outcomes, including myocardial infarction (RR- 0.99, 95% CI :0.79-1.25, p = 0.96, I2 = 0%), stent thrombosis (RR - 0.97, 95% CI: 0.6-1.55, p = 0.89, I2 = 0%), ischemic stroke (RR - 0.76, 95% CI: 0.5-1.15, p = 0.19, I2 = 0%), all-cause mortality (RR - 1.06, 95% CI: 0.85-1.31, p = 0.61, I2 = 0%) and MACE (RR - 1.06, 95% CI: 0.91-1.22, p = 0.97, I2 = 0%). Conclusion Compared with triple therapy with VKAS, double therapy with DOACs is associated with a reduced risk of bleeding and is as effective in patients with AF undergoing PCI. Abstract Figure.

Abstract Funding Acknowledgements None Background Cardiac Power Index (CPI) is an integrative hemodynamic measure of cardiac pumping capability and is the product of the simultaneously measured mean arterial pressure (MAP) and cardiac output (CO). In patients with aortic stenosis (AS), MAP is not reflective of mean systolic left ventricular (LV) pressure due to the transvalvular gradient. Non-invasive assessment of mean systolic LV pressure is challenging in severe aortic stenosis. CPI assessed using systemic MAP was previously shown to predict survival post transcatheter aortic valve replacement (TAVR). Purpose We evaluated the utility of a gradient adjusted CPI in predicting survival post TAVR compared to CPI alone Methods A retrospective study was performed including patients undergoing TAVR with 1 year follow-up. Baseline demographics, clinical, and echocardiographic data were abstracted from a cohort of 1,011 patients. CPI was calculated, (CO x MAP)/ (451 x BSA) Watts/m2. Gradient adjusted CPI was calculated using an augmented MAP i) adding aortic valve mean gradient(AVMG) to systolic blood pressure (CPI1); ii) adding aortic valve maximal instantaneous gradient to systolic blood pressure (CPI2) and iii) adding AVMG to MAP (CPI3). Patient survival score was calculated using a step up technique to identify the cut off value for CPI and gradient adjusted CPI to identify, where the maximum difference in mortality occurred. Multivariate cox-regression analysis was performed to adjust for baseline covariates. Receiver operator curves(ROC) for CPI and gradient adjusted CPI were calculated to predict survival post TAVR. Results The mortality rate at 1 yr was 16%. Mean age and AVMG of survivors was 81 +/- 9 yrs and 43 +/-14 mmHg vs 80 +/-9 yrs and 42 +/- 13 mmHg in the deceased group. Proportion of female patients was similar in both groups (p = 0.7). Patients in the deceased group at baseline had a higher prevalence of chronic lung disease, atrial fibrillation, heart failure within 2-weeks of procedure, higher STS-PROM score, lower serum albumin level, higher prevalence of moderate to severe tricuspid regurgitation, higher right ventricular systolic pressure and higher prevalence of dialysis. Both CPI and gradient adjusted CPI were independently associated with survival at 1 year. The area under ROC for CP, CP1, CP2 and CP3 were 0.67 (95% confidence interval [CI] 0.62 - 0.72), 0.65 (95% CI 0.60 – 0.70), 0.66 (95% CI 0.61 – 0.71) and 0.63 (95% CI 0.58 – 0.68) respectively. Conclusion Gradient adjusted CPI did not improve accuracy of predicting post TAVR survival at 1 year compared to CPI alone. Abstract P339 Figure. Area under ROC

AbstractBackgroundAtrial fibrillation (AF) and coronary artery disease (CAD) are commonly associated. Cotreatment with multiple antithrombotic agents can increase the risk of bleeding. We sought to evaluate patient‐centered outcomes in patients with AF on double therapy with direct oral anticoagulants (DOACs) compared to patients with standard triple therapy, [a vitamin K antagonist (VKA) plus dual antiplatelet therapy].MethodsWe performed a literature search of randomized controlled trials (RCTs) reporting outcomes of patients receiving double therapy with DOACs compared to triple therapy with VKAs in patients with AF undergoing percutaneous coronary intervention (PCI). Patient‐centered outcomes were the International Society of Thrombosis and Hemostasis (ISTH) major or clinically relevant nonmajor bleeding (CRNB), all‐cause mortality, major adverse cardiovascular events (MACE), stent thrombosis, myocardial infarction, and stroke.ResultsFour RCTs (9602 patients) met our inclusion criteria. Compared to VKAs, DOACs were associated with significantly lower ISTH major bleeding/ CRNB (RR: 0.75, 95% CI: 0.67‐0.82, P < .00001, I2 = 11%). There were no statistically significant differences in the efficacy outcomes, including myocardial infarction (RR: 0.99, 95% CI :0.79‐1.25, P = .96), stent thrombosis (RR: 0.97, 95% CI: 0.6‐1.55, P = .89), ischemic stroke (RR: 0.76, 95% CI: 0.5‐1.15, P = .19), all‐cause mortality (RR: 1.06, 95% CI: 0.85‐1.31, P = .61), and MACE (RR: 1.06, 95% CI: 0.91‐1.22, P = .97).ConclusionCompared with triple therapy with VKAS, double therapy with DOACs is associated with a reduced risk of bleeding and is as effective in patients with AF undergoing PCI.

Background: We performed a meta-analysis to evaluate the benefit of patent foramen ovale closure in stroke prevention. Methods: We searched Medline/PubMed, EMBASE, Web of Science and Cochrane central database for randomized control trials assessing the incidence of recurrent stroke after patent foramen ovale closure when compared to medical therapy. Pooled odds ratio and 95% confidence intervals were calculated using a random effects model. The heterogeneity among studies was tested using the χ 2 test and inconsistency was quantified using the I 2 statistic. Results: Our search strategy yielded 71 articles. We included five studies with a total of 3440 patients. Median age in the device group was 45 (43, 5.5) years and in the medical group was 45 (44.5, 46) years; 52% were male, 27.7% of patients had an atrial septal aneurysm, 25% had hypertension, and 20.5% had diabetes mellitus. The median follow-up time was 44 (34.5–50) months. The pooled odds ratio of recurrent stroke, transient ischemic attack and composite end point of stroke + transient ischemic attack + peripheral embolism in the patent foramen ovale closure versus medical therapy group were 0.4 (95% confidence interval 0.25–0.63, I 2 = 57.5%), 0.93 (95% confidence interval 0.61–1.42, I 2 = 0%), and 0.6 (95% confidence interval 0.44–0.82, I 2 = 0%), respectively. The incidence of atrial fibrillation was found to be significantly higher in the patent foramen ovale closure group with odds ratio of 6 (95% confidence interval 3.13–11.4, I 2 = 33.5%). On subgroup analysis, patent foramen ovale closure appeared to benefit males and patients with a large shunt. Number needed to treat to prevent one recurrent stroke with patent foramen ovale closure is 42. Number needed to harm to cause one atrial fibrillation with patent foramen ovale closure is 39. Conclusion: This meta-analysis of randomized trials concludes that percutaneous patent foramen ovale closure is effective in recurrent stroke prevention especially in males and in those with a large shunt.

Background: The clinical benefit of patent foramen ovale (PFO) closure in patients with cryptogenic stroke (CS) for recurrent stroke prevention has been a subject of extensive debate. Prior clinical trials failed to show superiority of PFO closure versus medical therapy. Meta-analyses suggested a possible benefit of PFO closure in select patients. Objective: The objective of this study was to critically assess current evidence regarding the efficacy of PFO closure compared with medical therapy for recurrent stroke prevention in patients with CS. Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and vascular neurology and interventional cardiology content experts. Results: A randomized, controlled trial was selected for critical appraisal. This trial compared the efficacy of PFO closure and medical therapy in recurrent stroke prevention. A total of 663 patients who had a recent CS attributed to PFO, with a large interatrial shunt or with an associated atrial septal aneurysm were included. No stroke occurred among the 238 patients in the PFO closure group, whereas 14 of the 235 patients in the antiplatelet therapy group had recurrent strokes. Conclusions: Among patients who had a recent CS attributed to PFO with a large interatrial shunt or with an associated atrial septal aneurysm, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone.

ObjectivesLeft ventricular (LV) septal hypertrophy in aortic stenosis raises diagnostic and therapeutic questions. However, the etiology and clinical consequences of this finding have not been well studied. The aim of this study was to perform a morphologic evaluation of the LV in aortic stenosis and to investigate the contributing factors and consequences of septal hypertrophy.MethodsPatients with moderate or severe aortic stenosis were prospectively enrolled. Patients with previous myocardial infarction, wall motion abnormalities, at least moderate valvular regurgitation, known cardiomyopathy, an LV ejection fraction of less than 50%, and age younger than 65 years were excluded.ResultsForty‐one patients underwent a final analysis. Septal hypertrophy (LV septal wall thickness ≥15 mm) was confirmed in 21 of 41 patients. The septal hypertrophy group had higher peak aortic valve velocity, a higher diabetes mellitus rate, and a higher rate and longer duration of hypertension than those without septal hypertrophy. The peak aortic valve velocity (odds ratio, 7.1; 95% confidence interval, 1.4–37.1) and diabetes mellitus (odds ratio, 7.4; 95% confidence interval, 1.2–46.2) were the significant factors associated with septal hypertrophy by multivariate analysis. Intraventricular conduction disturbance on electrocardiography was more frequent in the septal hypertrophy group (P = .021).ConclusionsLeft ventricular septal hypertrophy was commonly observed in elderly patients with aortic stenosis, and a higher aortic valve velocity, hypertension, and diabetes mellitus were associated factors. Intraventricular conduction disturbance occurred more often in patients with septal hypertrophy than those without, which implies the pathophysiologic consequence. Further studies are needed to determine the impact of septal hypertrophy and intraventricular conduction disturbance on the prognosis of patients after aortic valve interventions.

An increasing number of patients have refractory angina despite optimal medical therapy and are without further revascularization options. Preclinical studies indicate that human CD34 + stem cells can stimulate new blood vessel formation in ischemic myocardium, improving perfusion and function. In ACT34-CMI ( N = 167), patients treated with autologous CD34 + stem cells had improvements in angina and exercise time at 6 and 12 months compared to placebo; however, the longer-term effects of this treatment are unknown. ACT34 was a phase II randomized, double-blind, placebo-controlled clinical trial comparing placebo, low dose (1 × 10 5 CD34/kg body weight), and high dose (5 × 10 5 CD34/kg) using intramyocardial delivery into the ischemic zone following NOGA ® mapping. To obtain longer-term safety and efficacy in these patients, we compiled data of major adverse cardiac events (MACE; death, myocardial infarction, acute coronary syndrome, or heart failure hospitalization) up to 24 months as well as angina and quality of life assessments in patients who consented for 24-month follow-up. A total of 167 patients with class III–IV refractory angina were randomized and completed the injection procedure. The low-dose-treated patients had a significant reduction in angina frequency ( p = 0.02, 0.035) and improvements in exercise tolerance testing (ETT) time ( p = 0.014, 0.017) compared to the placebo group at 6 and 12 months. At 24 months, patients treated with both low-and high-dose CD34 + cells had significant reduction in angina frequency ( p = 0.03). At 24 months, there were a total of seven deaths (12.5%) in the control group versus one (1.8%) in the low-dose and two (3.6%) in the high-dose ( p = 0.08) groups. At 2 years, MACE occurred at a rate of 33.9%, 21.8%, and 16.2% in control, low-, and high-dose patients, respectively ( p = 0.08). Autologous CD34 + cell therapy was associated with persistent improvement in angina at 2 years and a trend for reduction in mortality in no-option patients with refractory angina.

ObjectiveOptimal duration of dual antiplatelet therapy (DAPT), defined as use of both aspirin and a P2Y12 receptor inhibitor, after implantation of drug eluting stents (DES) is still subject of ongoing debate. We systematically review efficacy and safety of ≤6 months versus ≥12 months DAPT after implantation of DES.MethodsPubMed, Scopus, Cochrane, and clinicaltrials.gov databases were searched for studies published until 30th November 2013. The studies were limited to randomized clinical trials. Independent observers abstracted the data on outcomes, characteristics, and qualities of studies included. Random effect model was employed for meta‐analysis. Heterogeneity of studies included was analyzed using I2 statistics.ResultsIn four randomized clinical trials published involving 8,163 patients with DES, 4,081 patients were randomized to shorter and 4,082 patients to longer duration DAPT. The P2Y12 receptor inhibitor used in all four studies was clopidogrel. Longer duration of DAPT did not reduce risk of all cause mortality (pooled OR 0.89, 95% CI 0.67–1.17, P = 0.4, I2 = 0%), myocardial infarction (pooled OR 1.16, 95% CI 0.85–1.57, P = 0.35, I2 = 0%) cardiac death (pooled OR 0.88, 95% CI 0.61–1.25, P = 0.47, I2 = 0%), stent thrombosis (pooled OR 1.29, 95% CI 0.76–2.21, P = 0.35, I2 = 0%) or cerebrovascular accidents (pooled OR 0.73, 95% CI 0.41–1.27, P = 0.26, I2 = 0%). Longer duration of DAPT was associated with increased risk of TIMI major bleeding (pooled OR 0.51, 95% CI 0.29–0.89, P = 0.02, I2 = 0%).ConclusionThere was no difference in efficacy outcomes between ≤6 months of DAPT and ≥12 months of DAPT in patients with coronary artery disease and DES implantation. Moreover, longer duration of DAPT is associated with increased risk of bleeding complications. © 2014 Wiley Periodicals, Inc.