Faculty Bibliography

Platelets play a key role in the pathophysiology of coronary artery disease and acute coronary syndromes. Our understanding of platelet function in thrombus formation has increased considerably, resulting in the development of clinically effective treatment strategies and identification of new targets. An underappreciated platelet function is their contribution toward acute and chronic inflammatory processes including atherogenesis. In this review, we discuss the role of platelets in atherosclerosis and thrombosis, platelet function testing, and the pharmacology of currently available antiplatelet drugs.

Oral Antiplatelet Drugs (OAD) have a proven track record in the risk reduction of major cardiovascular events in patients with cardiovascular disease and normal kidney function. However, major gaps exist in our understanding of their effects on thrombosis and bleeding in chronic kidney disease (CKD). Clinical practice guidelines are ambiguous about use of such drugs in CKD patients, because patients with moderate to severe CKD were systematically excluded from clinical trials evaluating the efficacy and safety of OAD. Paradoxically, CKD patients are at high risk of thrombosis and major bleeding events. Thus, choosing the right combination of OAD for cardiovascular protection in these patients is challenging. Patients with CKD exhibit high rates of OAD hyporesponsiveness. It is, therefore, imperative to explore the mechanisms responsible for poor response to OAD in CKD patients in order to use these drugs more safely and effectively. This review explores suggested mechanisms of platelet dysfucntion in CKD patients and the available evidence on the efficacy and safety of oral antiplatelet drugs in patients with renal dysfunction.

Immature platelets-also termed reticulated platelets (RP)-are platelets newly released into the circulation, and have been associated with a variety of pathological thrombotic events. They can be assessed by flow cytometry after staining with thiazole orange (TO) or by using a module added to a fully automated analyzer that is currently in wide clinical use and expressed as a fraction of the total platelet count (IPF). We sought to assess the correlation and agreement between these two methods. IPF was measured using Sysmex XE 2100-and at the same time point- we used TO staining and flow cytometry to measure RP levels. Two different gates were used for the flow cytometry method, 1 and 0.5 %. Measurements from the automated analyzer were then compared separately to measurements performed using each gate. Agreement between methods was assessed using Bland-Altman method. Pearson's correlation coefficient was also calculated. 129 subjects were enrolled and stratified into 5 groups: (1) Healthy subjects, (2) End stage renal disease, (3) Chronic stable coronary artery disease, (4) Post Coronary artery bypass surgery, (5) Peripheral thrombocytopenia. Median IPF levels were increased for patients in groups 2, 3, 4 and 5 (4.0, 4.7, 4.3, and 8.3 % respectively) compared to healthy subjects (2.5 %) p = 0.0001. Although the observed correlation between the two methods tended to be good in patients with high IPF values (i.e., group 5), the overall observed correlation was poor (Pearson's correlation coefficient r = 0.27). Furthermore, there was poor agreement between the two methods in all groups. Despite the good correlation that was observed between the two methods at higher IPF values, the lack of agreement was significant.

Although transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) are validated in quantitation of mitral regurgitation (MR), discrepancies may occur. This study assesses the agreement between TTE and CMR in MR and evaluates characteristics and clinical outcome of patients with discrepancy. From our institutional database, 70 subjects with MR underwent both TTE and CMR within 30 days (median 3 days). MR was evaluated semiquantitatively (n = 70) using a 4-grade scale and quantitatively (n = 60) with calculation of regurgitant volume (RVol) and regurgitant fraction (RF). Of the 70 subjects, qualitative assessment by TTE yielded 30 subjects with mild MR, 17 moderate, and 23 moderately severe or severe MR. Exact concordance in MR grade was seen in 50% and increased to 91% when considering concordance within one grade of severity (kappa = 0.44). A modest correlation was observed for RVol and RF between both methods (r = 0.59 and 0.54, respectively, p <0.0001). Ten patients had a significant discrepancy in quantitative MR (difference in RF >20%); the frequency of secondary MR was higher (100% vs 46%; p = 0.003) in patients with discrepancy. Although interobserver variability in RF was higher with TTE compared with CMR (-5.5 +/- 15% vs 0.1 +/- 7.3%), patients with discrepancy were equally distributed by severity and clinical outcome without an overestimation by either method. In conclusion, there is a modest agreement between TTE and CMR in assessing MR severity. In patients with discrepancy, there is a higher prevalence of functional MR, without a consistent overestimation of MR severity by either method.

BACKGROUND: Cardiac allograft vasculopathy is a major cause of morbidity and mortality following heart transplantation. Large multicenter studies evaluating the clinical characteristics and inhospital outcomes of heart transplant recipients undergoing percutaneous coronary intervention (PCI) are lacking. OBJECTIVE: To evaluate the clinical characteristics, treatment patterns and inhospital outcomes of heart transplant recipients undergoing PCI compared to general population. METHODS: We analyzed 1,897,328 patients from the National Cardiovascular Data Registry CathPCI registry who underwent PCI of at least 1 native vessel between July 2009 and December 2013 from 1,477 centers, of which 542 patients (0.03%) were heart transplant recipients. Clinical characteristics were evaluated and, after 1:4 propensity matching, inhospital outcomes were compared between 538 heart transplant patients and 2,128 non-transplant patients. RESULTS: Transplant recipients undergoing PCI had a higher prevalence of diabetes, dyslipidemia and peripheral vascular disease; lower prevalence of angina, acute coronary syndrome, abnormal noninvasive functional study, and type C coronary lesions compared to the non-transplant PCI population. After propensity matching, all-cause inhospital mortality was similar between transplant and non-transplant groups (1.3% vs 1.0%; OR, 1.21; 95% CI, 0.54-2.67). CONCLUSION: This is the largest series to date outlining the characteristics of heart transplant recipients undergoing PCI. Similar inhospital outcomes were noted in heart transplant recipients compared to the general population. Further studies evaluating long-term outcomes are warranted.

Dynamic left ventricular outflow tract obstruction and left ventricular mid-cavity obliteration are phenomena that can complicate the postoperative course in patients who undergo surgical aortic valve replacement for aortic stenosis, and may be markers of increased morbidity and mortality. Recently, reports describing dynamic intraventricular obstruction following transcatheter aortic valve replacement (TAVR) have emerged. We report a case of dynamic left ventricular mid-cavity obstruction due to disordered atrioventricular synchrony immediately following TAVR, and its reversal with restoration of atrioventricular synchrony. This case highlights the essential role of atrial contraction in the management of this phenomenon.