Alex Schevchuck

Ischemic Conditioning as an Adjunct to Percutaneous Coronary Intervention

Since its original description in 1986 by Murry et al,1 the ability to condition, or protect, the heart from a lethal episode of prolonged ischemia (followed by reperfusion) has represented both an opportunity and a challenge to the many experimentalists, clinicians, and translationalists engaged in the struggle to reduce the risk of death and disability resulting from spontaneous (acute coronary syndromes) and procedurally associated (coronary artery bypass surgery, catheter-based coronary revascularization) myocardial ischemia. The potential to mitigate myocardial injury or death resulting from an ischemic insult is the opportunity. The inability to fully, consistently, and effectively translate experimentally established reductions in myocardial injury or death to the bedside is the challenge.2 Throughout the 1970s and well into the 1980s, cardiovascular physiologists were intensively studying the sequence of events culminating in frank necrosis of heart muscle as the result of coronary arterial occlusion3 and the benefits and hazards of reperfusion of ischemic myocardium.4 Around this same time, developments in catheter-based coronary revascularization clearly established that brief periods of controlled occlusion of an obstructed coronary artery, followed by reperfusion (release of the occlusion), could safely relieve the obstruction without overt myocardial injury.5 Key aspects of this emerging treatment modality were (1) the sequential nature of the controlled occlusions; (2) the importance of a period of reperfusion between the occlusive episodes; and (3) the almost universal attenuated clinical and electrocardiographic response to the second (or subsequent) occlusion compared with the initial occlusion. In short order, this clinical model was widely studied and reproduced.6–11 In the first detailed coronary hemodynamic study of this model of controlled coronary occlusion in man, Deutsch et al6 showed that the second of two 90-second balloon occlusions separated by a 5-minute period of reperfusion was met with statistically significant reductions …

Effects of Aggrenox and aspirin on plasma endothelial nitric oxide synthase and oxidised low-density lipoproteins in patients after ischaemic stroke. The AGgrenox versus aspirin therapy evaluation (AGATE) biomarker substudy.

Plasma endothelial nitric oxide synthase (eNOS), and oxidised low-density lipoproteins (oxLDL) are established biomarkers of atherosclerosis. We defined the time course and magnitude of changes of plasma eNOS and oxLDL after Aggrenox or aspirin in post-stroke patients. Baseline pretreatment eNOS levels were significantly diminished (110 ± 66pg /ml vs. 374 ± 88 pg/ml, p=0.0001), while oxLDL was twice higher (58 ± 9 mg/l vs. 23 ± 7 mg/l, p=0.004) in post-stroke survivors when compared to controls. Both Aggrenox and aspirin similarly increased plasma eNOS activity. However, oxLDL levels were static after aspirin, but inhibited late after Aggrenox. In the small randomised study, both aspirin and Aggrenox produced fast and sustained recovery of plasma eNOS levels, while only therapy with Aggrenox was associated with oxLDL inhibition late in the trial.

Late-onset advanced heart block due to vagal nerve stimulation.

Vagal nerve stimulation (VNS) is widely accepted as an effective and safe therapy for refractory seizure disorders. Significant cardiac complications, such as complete heart block or symptomatic bradycardia, are extremely rare. We present a case report of a 40-year-old man with drug-resistant epilepsy, treated with VNS, who developed the late-onset (12 months after implant), stimulation-related, symptomatic advanced heart block that was initially misinterpreted for a new type of seizure. The patient was otherwise free from other stimulation-related side effects. To our knowledge, this is the first case report of late-onset advanced heart block due to VNS.

Extensive biatrial thrombus straddling the patent foramen ovale and traversing into the left and right ventricle

We report an extremely rare case of an extensive biatrial thrombus straddling a patent foramen ovale (PFO) extending into the bilateral ventricles in a patient presenting with an acute embolic stroke. Our patient further developed a massive saddle pulmonary embolus (PE) with haemodynamic instability during the course of his hospitalisation. The risks of pharmacological thrombolysis or surgical thrombectomy for PE in a haemodynamically unstable patient with recent embolic stroke posed a significant therapeutic dilemma. Ultimately, the decision was made to continue anticoagulation with unfractionated heparin followed by oral Coumadin. The patient responded well to therapy and at 1-month follow-up, a complete resolution of the thrombus was documented on transoesophageal echocardiogram with full clinical recovery of the patient.

Unexpected intraoperative transesophageal echocardiographic finding before aortic valve replacement surgery

as: Deriy L, et al. (2017), http://dx.doi.org/10.1053/j.jvca. stenosis, and single-vessel coronary artery disease, presented for aortic valve replacement. Transthoracic echocardiography revealed severe calcific aortic valve stenosis (aortic valve area 1⁄4 0.6 cm; mean gradient 1⁄4 37 mmHg), left atrial dilatation, and preserved left ventricular systolic function (ejection fraction 1⁄4 57%). Intraoperative transesophageal echocardiography (TEE) confirmed the preoperative transthoracic echocardiogram findings but also demonstrated an echolucent space

Effects of extended-release dipyridamole in vitro on thrombin indices measured by calibrated automated thrombography in poststroke survivors.

Randomized trials suggested superior stroke prevention with extended-release dipyridamole (ERD) in combination with low-dose aspirin than either with aspirin or dipyridamole alone. Thrombin generation (TG) is a critical step in clot formation and represents a cornerstone biomarker of atherothrombosis. We, therefore, sought to define the effect of ERD in escalating concentrations on the time course of TG using the Calibrated Automated Thrombogram (CAT) technology in patients after ischemic stroke. Serial plasma samples were obtained from 20 patients with ischemic stroke documented by neuroimaging and who were treated with aspirin for at least 30 days. The impact of 75-, 150-, 250-, and 300-nM ERD on TG was assessed using fluorogenic substrate CAT technology. The following integrated CAT indices were calculated for each ERD dose and compared with the vehicle: TGmax, start time (tstart) peak time (tpeak), and mean time (tmean). Preincubation of platelet-poor plasma with ERD resulted in a dose-dependent significant inhibition of TG. The TGmax was gradually reduced from 447 ± 21 nM at baseline to 354 ± 31 nM (P = 0.008) for 75-nM ERD, 298 ± 24 nM for 150-nM ERD, 248 ± 26 nM for 250-nM ERD, and finally to 240 ± 23 nM for 300-nM ERD (P < 0.0001 for all). The tmean was reduced only for the highest (250–300 nM) ERD concentrations. The tstart was only slightly delayed, but not different (1.5 vs. 1.8 vs.1.9 minutes; P = 0.09), for all ERD concentrations. The tpeak was not affected by ERD. ERD in vitro affects thrombin activity indices predominantly by a dose-dependent inhibition of endogenous thrombin potential and demonstrated a trend to delayed initiation of thrombin production. These preliminary data, while intriguing, require confirmation in poststroke patients receiving orally dosed ERD to determine whether these findings are clinically relevant.