The association of night-time systolic blood pressure with ultrasound markers of subclinical cardiac and vascular disease

Introduction The aim of this study was to examine the association of night-time systolic blood pressure (BP) with subclinical cardiac dysfunction measured by global longitudinal strain (GLS) and subclinical vascular damage measured by carotid intima-media thickness (CIMT) and carotid plaques. Methods GLS was measured by speckle-tracking analysis of echocardiogram images. CIMT was measured at the distal 1 cm of the common carotid artery. The presence of carotid plaques was recorded. Philips QLAB cardiac and vascular ultrasound quantification software was used for analysis. The association of night-time systolic BP with GLS, CIMT and carotid plaques was assessed using linear and logistic regression. Results Fifty (response rate 63%) individuals took part in this study. In univariable models, night-time systolic BP was significantly associated with GLS [beta coefficient 0.85 for every 10 mmHg increase, 95% confidence interval (CI): 0.3-1.4] and carotid plaques (odds ratio 1.9 for every 10 mmHg increase, 95% CI: 1.1-3.2). Univariable analysis of daytime systolic BP did not show any statistically significant associations. In age-adjusted and sex-adjusted models, the association for night-time systolic BP and GLS remained significant (beta coefficient 0.68 for every 10 mmHg increase, 95% CI: 0.1-1.3). The association for carotid plaques was no longer statistically significant. In multivariable models, findings were diminished. Discussion Our results suggest a trend towards an association between night-time systolic BP and subclinical cardiac and vascular disease. When assessing ambulatory blood pressure monitoring results, the absolute night-time systolic BP seems to be a better prognostic parameter than daytime systolic BP, but ultimately a large randomised controlled trial involving chronotherapy is necessary to fully address this. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

Randomized placebo controlled trial evaluating the safety and efficacy of single low dose intracoronary insulin like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI)

Background: Residual and significant post-infarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models low dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodelling effects. We studied the safety and efficacy of immediate post PCI low dose intracoronary IGF1 infusion in STEMI patients. Methods: Using a double-blind, placebo controlled, multi-dose study design, we randomized 47 STEMI patients with significantly reduced (≤ 40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n=15), 1.5ng IGF1 (n=16) or 15ng IGF1 (n=16). All received optimal medical therapy. Safety endpoints were freedom from hypoglycaemia, hypotension or significant arrhythmias within 1 hour of therapy. The primary efficacy endpoint was LVEF and secondary endpoints were LV volumes, mass, stroke volume, and infarct size at 2 months follow up, all assessed by MRI. Treatment effects were estimated by analysis of covariance adjusted for baseline (24hrs) outcome. Results: No significant differences in safety endpoints occurred between treatment groups out to 30 days (chi squared test, p-value = 0.77).There were no statistically significant differences in baseline (24 hrs post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5ng IGF1, treatment with 15ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (p=0.018), LV mass (p=0.004) and stroke volume (p=0.016). Late gadolinium enhancement (±SD) at 2 months was lower in 15ng IGF1 (34.5±29.6g) compared to placebo (49.1±19.3g) or 1.5ng IGF1 (47.4±22.4g) treated patients, though the result was not statistically significant (p = 0.095). Conclusion: In this pilot trial, low dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose dependent benefit on post MI remodeling that may warrant further study. Despite timely reperfusion by primary PCI (PPCI) a significant cohort of patients develop adverse left ventricular remodelling with clinical sequelae such as arrhythmia and heart failure[1].Therapeutic approaches to avert such remodeling, including a variety of cell therapy and ischemia- reperfusion-injury mitigation trials have achieved modest success 2.;3. Thus, there remains a significant opportunity for novel therapies in this field

Pharmacogenetics of Antiplatelet Drugs

Pharmacogenetics refers to the genetic factors that influence the response to a drug, often involving genetic variations in drug metabolizing enzymes. The pharmacogenetics of antiplatelet agents is in its infancy and largely reflects variations in drug targets or related genes. One particular gene variant, the PlA2 polymorphism of the glycoprotein (GP) IIb/IIIa receptor, is now emerging as a probable determinant of the response to antiplatelet agents including GPIIb/IIIa antagonists. This variant may in part explain the heterogeneity in the response to GPIIb/IIIa antagonists. The PlA2 genotype appears to be associated with an adverse outcome in patients treated with an oral GPIIb/IIIa antagonist and may be a factor in the observed failure of these agents in unselected populations. However, there are preliminary indications that other antiplatelet agents may have an enhanced effect in PlA2 subjects. Further clinical trials in particular are required to definitively characterize the pharmacogenetic effect of PlA2. Other polymorphisms are also likely to contribute to the pharmacogenetics of antiplatelet agents, but these await investigation

Incidental Finding of an Undiagnosed Coarctation of the Aorta Causing Dilated Cardiomyopathy in an Adult

31-year-old male with no past medical history apart from high blood pressure noted by GP one week prior to admission presented with a three-week history of a flu-like illness and symptoms of heart failure with severe global left ventricular dilation and dysfunction on Transthoracic Echocardiography (TTE). Two weeks following admission he complained of left arm pain and CT upper limb confirmed embolic occlusion of the left brachial artery and incidental severe coarctation of the proximal descending aorta after the origin of the left subclavian artery. Follow-up TTE suggested the presence of coarctation of the aorta on a suprasternal view which was not performed at the time of his first TTE. His heart failure and blood pressure responded very well to medical therapy and he has been referred for surgical correction of his aortic coarctation