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Background-We examined whether intracoronary or intrafemoral administration of ranolazine produces local vasodilation. Methods and Results-Effects of intra-arterial ranolazine on coronary and femoral artery vasodilation and systemic hemodynamic function were studied in anesthetized pigs (nϭ27). Ranolazine, nitroglycerin, or saline (control) was injected into the left anterior descending (LAD) coronary artery or femoral artery (2-mL bolus in 10 seconds). Pretreatment with prazosin (300 g/kg IV) allowed determination of ␣ 1 -adrenergic receptor involvement (nϭ8). Rapid intracoronary administration of ranolazine (0.048 mg/kg) to achieve high local concentrations resulted in 91Ϯ11% increase in LAD coronary artery flow and 39Ϯ7% reduction in coronary vascular resistance (both, PϽ0.0001). This effect lasted 2-3 minutes without change in heart rate or rate-pressure product. Mean arterial pressure decreased marginally (by 2Ϯ1 mm Hg, Pϭ0.01). Maximum systemic plasma concentration (0.93Ϯ0.29 mol/L) remained in subtherapeutic range. Pretreatment with prazosin abolished these effects. Intracoronary nitroglycerin (100 g) increased LAD coronary artery flow by 112Ϯ25% (Pϭ0.02), but the effect lasted Ͻ2 minutes; mean arterial pressure decreased by 4Ϯ1 mm Hg (Pϭ0.01). Intrafemoral injection of ranolazine (0.24 mg/kg, ie, one-tenth of the systemic bolus) resulted in a 70Ϯ19% increase in femoral artery flow (Pϭ0.05) and 26Ϯ5% reduction in femoral artery resistance (Pϭ0.004). At 2 minutes after the injection, the femoral flow remained 16Ϯ9% above the baseline and dilatory effects occurred without tolerance to repeated injections. Conclusions-Intracoronary or intrafemoral ranolazine bolus exerts a marked, 2-to 3-minute dilatory effect that is comparable to nitroglycerin in magnitude but more persistent, attributable primarily to ␣ 1 -adrenergic blockade. (Circ Cardiovasc Interv. 2011;4:481-487.)

Background Advanced age is associated with both left bundle branch block (LBBB) and hypertension and the usefulness of ECG criteria to detect left ventricular hypertrophy (LVH) in patients with LBBB is still unclear. The diagnostic performance and clinical applicability of ECG-based LVH criteria in patients with LBBB defined by stricter ECG criteria is unknown. The aim of this study was to compare diagnostic accuracy and clinical utility of ECG criteria in patients with advanced age and strict LBBB criteria. Methods Retrospective single-center study conducted from Jan/2017 to Mar/2018. Patients undergoing both ECG and echocardiogram examinations were included. Ten criteria for ECG-based LVH were compared using LVH defined by the echocardiogram as the gold standard. Sensitivity, specificity, predictive values, likelihood ratios, AUC, and the Brier score were used to compare diagnostic performance and a decision curve analysis was performed. Results From 4621 screened patients, 68 were included, median age was 78.4 years, (IQR 73.3–83.4), 73.5% with hypertension. All ECG criteria failed to provide accurate discrimination of LVH with AUC range between 0.54 and 0.67, and no ECG criteria had a balanced tradeoff between sensitivity and specificity. No ECG criteria consistently improved the net benefit compared to the strategy of performing routine echocardiogram in all patients in the decision curve analysis within the 10–60% probability threshold range. Conclusion ECG-based criteria for LVH in patients with advanced age and true LBBB lack diagnostic accuracy or clinical usefulness and should not be routinely assessed.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represents a public health crisis of major proportions. Advanced age, male gender, and the presence of comorbidities have emerged as risk factors for severe illness or death from COVID-19 in observation studies. Hypertension is one of the most common comorbidities in patients with COVID-19. Indeed, hypertension has been shown to be associated with increased risk for mortality, acute respiratory distress syndrome, need for intensive care unit admission, and disease progression in COVID-19 patients. However, up to the present time, the precise mechanisms of how hypertension may lead to the more severe manifestations of disease in patients with COVID-19 remains unknown. This review aims to present the biological plausibility linking hypertension and higher risk for COVID-19 severity. Emphasis is given to the role of the renin-angiotensin system and its inhibitors, given the crucial role that this system plays in both viral transmissibility and the pathophysiology of arterial hypertension. We also describe the importance of the immune system, which is dysregulated in hypertension and SARS-CoV-2 infection, and the potential involvement of the multifunctional enzyme dipeptidyl peptidase 4 (DPP4), that, in addition to the angiotensin-converting enzyme 2 (ACE2), may contribute to the SARS-CoV-2 entrance into target cells. The role of hemodynamic changes in hypertension that might aggravate myocardial injury in the setting of COVID-19, including endothelial dysfunction, arterial stiffness, and left ventricle hypertrophy, are also discussed.

Background Observational studies support a role for oral anticoagulation to reduce the risk of dementia in atrial fibrillation patients, but conclusive data are lacking. Since dabigatran offers a more stable anticoagulation, we hypothesized it would reduce cognitive decline when compared to warfarin in old patients with atrial fibrillation. Methods The GIRAF trial was a 24-month, randomized, parallel-group, controlled, open-label, hypothesis generating trial. The trial was done in six centers including a geriatric care unit, secondary and tertiary care cardiology hospitals in São Paulo, Brazil. We included patients aged ≥ 70 years and CHA2DS2-VASc score > 1. The primary endpoint was the absolute difference in cognitive performance at 2 years. Patients were assigned 1:1 to take dabigatran (110 or 150 mg twice daily) or warfarin, controlled by INR and followed for 24 months. Patients were evaluated at baseline and at 2 years with a comprehensive and thorough cognitive evaluation protocol of tests for different cognitive domains including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam (MMSE), a composite neuropsychological test battery (NTB), and computer-generated tests (CGNT). Results Between 2014 and 2019, 5523 participants were screened and 200 were assigned to dabigatran (N = 99) or warfarin (N = 101) treatment. After adjustment for age, log of years of education, and raw baseline score, the difference between the mean change from baseline in the dabigatran group minus warfarin group was − 0.12 for MMSE (95% confidence interval [CI] − 0.88 to 0.63; P = 0.75), 0.05 (95% CI − 0.07 to 0.18; P = 0.40) for NTB, − 0.15 (95% CI − 0.30 to 0.01; P = 0.06) for CGNT, and − 0.96 (95% CI − 1.80 to 0.13; P = 0.02) for MoCA, with higher values suggesting less cognitive decline in the warfarin group. Conclusions For elderly patients with atrial fibrillation, and without cognitive compromise at baseline that did not have stroke and were adequately treated with warfarin (TTR of 70%) or dabigatran for 2 years, there was no statistical difference at 5% significance level in any of the cognitive outcomes after adjusting for multiple comparisons. Trial registration Cognitive Impairment Related to Atrial Fibrillation Prevention Trial (GIRAF), NCT01994265.

Key MessagesPatients with diabetes mellitus more frequently have diffuse and multivessel coronary artery disease. Coronary artery bypass surgery is the preferred revascularization strategy in most patients with diabetes. Special attention should be given to optimal control of risk factors in the postrevascularization setting. a b s t r a c t Patients with diabetes mellitus (DM) are at increased risk for developing coronary artery disease. Choosing the optimal revascularization strategy, such as coronary artery bypass grafting or percutaneous coronary intervention (PCI), may be difficult in this population. A large body of evidence suggests that, for patients with DM and stable multivessel ischemic heart disease, coronary artery bypass grafting is usually superior to PCI, leading to lower rates of all-cause mortality, myocardial infarction and repeat revascularization in the long term. In patients with less complex coronary anatomy (2-or single-vessel disease, especially without involvement of the proximal left anterior descendent artery), PCI may be a viable option. Because these anatomic patterns are less frequent in patients with DM, there is less evidence to guide revascularization in these cases. Patients with DM and left main disease and those in the acute coronary syndrome setting are also underrepresented in randomized trials, and the best revascularization strategy for these patients is not clear. Once the revascularization procedure is performed, patients should be kept engaged in controlling the risk factors for progression of cardiovascular disease. Avoidance of smoking, control of cholesterol, blood pressure and glycemic levels; regular practice of physical activity of at least moderate intensity; and a balanced diet are of key importance in the postrevascularization period. In this study, we review the current literature in the management of patients with DM and coronary artery disease undergoing a revascularization procedure.Ó 2019 Canadian Diabetes Association. Mots clés : maladie cardiovasculaire pontage aortocoronarien diabète intervention coronarienne percutanée r é s u m é Les patients atteints de diabète sucré (DS) sont exposés à un risque accru de coronaropathie. Le choix d'une stratégie de revascularisation optimale telle que le pontage aortocoronarien ou l'intervention coronarienne percutanée (ICP) peut être difficile pour cette population. De nombreuses données probantes montrent que chez les patients atteints de DS et d'une cardiopathie ischémique multitronculaire stable le pontage aortocoronarien offre généralement des résultats supérieurs à l'ICP, puisqu'il entraîne une diminution des taux de mortalité toutes causes confondues et de revascularisation répétée à long terme. Chez les patients qui ont une anatomie des artères coronaires moins complexe (maladie monotronculaire ou bitronculaire, particulièrement sans la contribution de l'artère interventriculaire Can J Diabetes 44 (2020) 78e85antérieure proximale), l'ICP peut être une option viable. Comme ces anatomies sont moins fréquentes c...

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