Nikolaos Kakouros

Hematocrit alters VerifyNow P2Y12 assay results independently of intrinsic platelet reactivity and clopidogrel responsiveness

The VerifyNow P2Y12 assay assesses the adequacy of clopidogrel therapy by measuring ADP‐induced platelet activation in whole blood. Low hematocrit is associated with high clopidogrel on‐treatment platelet reactivity (HTPR) defined by this assay.

Coronary pressure-derived fractional flow reserve in the assessment of coronary artery stenoses

ObjectivesCatheter-based angiography is the reference-standard to establish coronary anatomy. While routinely employed clinically, lumen assessment correlates poorly with physiological measures of ischaemia. Moreover, functional studies to identify and localise ischaemia before elective angiography are often not available. This article reviews fractional flow reserve (FFR) and its role in guiding patient management for patients with a potentially haemodynamic significant coronary lesion.MethodsThis review discusses the theory, evidence, indications, and limitations of FFR. Also included are emerging non-invasive imaging FFR surrogates currently under evaluation for accuracy with respect to standard FFR.ResultsCoronary pressure-derived fractional flow reserve (FFR) rapidly assesses the haemodynamic significance of individual coronary artery lesions and can readily be performed in the catheterisation laboratory. The use of FFR has been shown to effectively guide coronary revascularization procedures leading to improved patient outcomes.ConclusionsFFR is an invaluable modality in guiding coronary disease treatment decisions. It is safe, cost-effective and leads to improved patient outcomes. Non-invasive imaging modalities to assess the physiologic significance of CAD are currently being  developed and evaluated.Key points• Coronary pressure-derived fractional flow reserve (FFR) is an important adjunct to angiography.• FFR is an invaluable technique in guiding coronary disease treatment decisions.• FFR is safe, cost-effective and leads to improved patient outcomes.• New directions include CT-based non-invasive conventional FFR surrogates for functional lesion significance.

Inhibition of transforming growth factor-β restores endothelial thromboresistance in vein grafts

BACKGROUND Thrombosis is a major cause of the early failure of vein grafts (VGs) implanted during peripheral and coronary arterial bypass surgeries. Endothelial expression of thrombomodulin (TM), a key constituent of the protein C anticoagulant pathway, is markedly suppressed in VGs after implantation and contributes to local thrombus formation. While stretch-induced paracrine release of transforming growth factor-β (TGF-β) is known to negatively regulate TM expression in heart tissue, its role in regulating TM expression in VGs remains unknown. METHODS Changes in relative mRNA expression of major TGF-β isoforms were measured by quantitative polymerase chain reaction (qPCR) in cultured human saphenous vein smooth muscle cells (HSVSMCs) subjected to cyclic stretch. To determine the effects of paracrine release of TGF-β on endothelial TM mRNA expression, human saphenous vein endothelial cells (HSVECs) were co-cultured with stretched HSVSMCs in the presence of 1D11, a pan-neutralizing TGF-β antibody, or 13C4, an isotype-control antibody. Groups of rabbits were then administered 1D11 or 13C4 and underwent interpositional grafting of jugular vein segments into the carotid circulation. The effect of TGF-β inhibition on TM gene expression was measured by qPCR; protein C activating capacity and local thrombus formation were measured by in situ chromogenic substrate assays; and VG remodeling was assessed by digital morphometry. RESULTS Cyclic stretch induced TGF-β(1) expression in HSVSMCs by 1.9 ± 0.2-fold (P < .001) without significant change in the expressions of TGF-β(2) and TGF-β(3). Paracrine release of TGF-β(1) by stretched HSVSMCs inhibited TM expression in stationary HSVECs placed in co-culture by 57 ± 12% (P = .03), an effect that was abolished in the presence of 1D11. Similarly, TGF-β(1) was the predominant isoform induced in rabbit VGs 7 days after implantation (3.5 ± 0.4-fold induction; P < .001). TGF-β(1) protein expression localized predominantly to the developing neointima and coincided with marked suppression of endothelial TM expression (16% ± 2% of vein controls; P < .03), a reduction in situ activated protein C (APC)-generating capacity (53% ± 9% of vein controls; P = .001) and increased local thrombus formation (3.7 ± 0.8-fold increase over vein controls; P < .01). External stenting of VGs to limit vessel distension significantly reduced TGF-β(1) induction and TM downregulation. Systemic administration of 1D11 also effectively prevented TM downregulation, preserved APC-generating capacity, and reduced local thrombus in rabbit VGs without observable effect on neointima formation and other morphometric parameters 6 weeks after implantation. CONCLUSION TM downregulation in VGs is mediated by paracrine release of TGF-β(1) caused by pressure-induced vessel stretch. Systemic administration of an anti-TGF-β antibody effectively prevented TM downregulation and preserved local thromboresistance without negative effect on VG remodeling.

Triple-Vessel Percutaneous Coronary Revascularization In Situs Inversus Dextrocardia

Dextrocardia with situs inversus occurs in approximately one in 10,000 individuals of whom 20% have primary ciliary dyskinesia inherited as an autosomal recessive trait. These patients have a high incidence of congenital cardiac disease but their risk of coronary artery disease is similar to that of the general population. We report what is, to our knowledge, the first case of total triple-vessel coronary revascularization by percutaneous stent implantation in a 79-year-old woman with situs inversus dextrocardia. We describe the successful use of standard diagnostic and interventional guide catheters with counter rotation and transversely inversed image acquisition techniques. The case also highlights that the right precordial pain may represent cardiac ischemia in this population.

Transcatheter versus surgical aortic valve replacement in intermediate-risk patients: Evidence from a meta-analysis

We performed a meta‐analysis to evaluate the efficacy and safety of transcatheter aortic valve replacement (TAVR) in comparison to surgical aortic valve replacement (SAVR) in intermediate‐risk patients.

Role of Fractional-Flow Reserve in Guiding Percutaneous Revascularization in Stable Coronary Artery Disease

Optimal medical therapy unarguably forms the cornerstone of management for patients with stable coronary artery disease. There is, however, a significant body of evidence suggesting that reduction of ischemia can be achieved more effectively with revascularization than medical therapy and can confer significant symptomatic and prognostic advantages. Nonetheless, owing to limitations of coronary angiography and conventional non-invasive functional testing for myocardial ischemia, targeting of hemodynamically significant coronary stenoses for revascularization is often difficult. We discuss the role of invasive fractional-flow reserve evaluation in guiding percutaneous revascularization procedures for patients with stable coronary artery disease and its potential impact on outcomes for these patients.

Risk Factors for Nonplatelet Thromboxane Generation After Coronary Artery Bypass Graft Surgery.

Background Persistent thromboxane (TX) generation while receiving aspirin therapy is associated with an increased risk of cardiovascular events. The Reduction in Graft Occlusion Rates (RIGOR) study found that aspirin‐insensitive TXA 2 generation, indicated by elevated urine 11‐dehydro‐TXB 2 (UTXB 2) 6 months after coronary artery bypass graft surgery, was a potent risk factor for vein graft thrombosis and originated predominantly from nonplatelet sources. Our goal was to identify risks factors for nonplatelet TXA 2 generation. Methods and Results Multivariable modeling was performed by using clinical and laboratory variables obtained from 260 RIGOR subjects with verified aspirin‐mediated inhibition of platelet TXA 2 generation. The strongest variable associated with UTXB 2 6 months after surgery, accounting for 47.2% of the modeled effect, was urine 8‐iso‐prostaglandin (PG)F 2α, an arachidonic acid metabolite generated nonenzymatically by oxidative stress (standardized coefficient 0.442, P<0.001). Age, sex, race, lipid therapy, creatinine, left ventricular ejection fraction, and aspirin dose were also significantly associated with UTXB 2 (P<0.03), although they accounted for only 4.8% to 10.2% of the modeled effect. Urine 8‐iso‐PGF 2α correlated with risk of vein graft occlusion (odds ratio 1.67, P=0.001) but was not independent of UTXB 2. In vitro studies revealed that endothelial cells generate TXA 2 in response to oxidative stress and direct exposure to 8‐iso‐PGF 2α. Conclusions Oxidative stress–induced formation of 8‐iso‐PGF 2α is strongly associated with nonplatelet thromboxane formation and early vein graft thrombosis after coronary artery bypass graft surgery. The endothelium is potentially an important source of oxidative stress–induced thromboxane generation. These findings suggest therapies that reduce oxidative stress could be useful in reducing cardiovascular risks associated with aspirin‐insensitive thromboxane generation.

A Novel Approach to Managing Trans-Subclavian Transcatheter Aortic Valve Replacement with Regional Anesthesia

Abstract Transfemoral transcatheter aortic valve replacement (TAVR) has evolved, through increased operator experience and technical advancements, from a procedure done routinely under general anesthesia (GA) to one that can be safely performed under conscious sedation. Although local anesthesia and conscious sedation is widely applied to transfemoral procedures, TAVR using alternative vascular access routes requiring surgical cutdown is still performed under GA. We describe the use of regional anesthesia and moderate sedation in an 82-year-old woman undergoing trans-subclavian TAVR. A pectoral (PECS-1) nerve block provided adequate anesthesia throughout the procedure and excellent post-operative analgesia with no complications.

Is intra‐procedure three‐dimensional transesophageal echocardiogram an alternative to preprocedure multidetector computed tomography for the measurement of the aortic annulus in patients undergoing transcatheter aortic valve replacement?

The role of three‐dimensional transesophageal echocardiography (3DTEE) vs multidetector computed tomography (MDCT) in aortic annular sizing has been poorly defined in patients undergoing transcatheter aortic valve replacements (TAVR). We set to determine the correlation between 3DTEE and MDCT in measuring the aortic annulus prior to TAVR.

Neoatherosclerosis in Very Late Stenosis of Bare Metal Stent by Optical Coherence Tomography

Bare metal stents (BMS) continue to be widely used in patients with coronary artery disease undergoing percutaneous revascularization. Progressive luminal renarrowing has been reported late after BMS implantation resulting in a significant rate of stent failure events. We present a case of very late BMS failure due to in-stent restenosis where optical coherence tomography (OCT) was used to demonstrate neoatherosclerosis as the underlying mechanism. We provide a brief review of neoatherosclerosis and showcase salient features on OCT evaluation.