Dipyridamole and vascular healing following stent implantation.

Introduction: Patients undergoing coronary stent implantation incur a 2% annual rate of adverse events, largely driven by in-stent restenosis (ISR) due to neointimal (NI) tissue proliferation, a process in which smooth muscle cell (SMC) biology may play a central role. Dipyridamole (DP) is an approved therapeutic agent with data supporting improved vascular patency rates. Pre-clinical data supports that DP may enact its vasculoprotective effects via adenosine receptor-A2B (ADOR-A2B). We sought to evaluate the efficacy of DP to mitigate ISR in a pre-clinical rabbit stent model. Methods & Results: 24 New Zealand White Rabbits were divided into two cohorts-non-atherosclerosis and atherosclerosis (n = 12/cohort, 6 male and 6 female). Following stent implantation, rabbits were randomized 1:1 to control or oral dipyridamole therapy for 6 weeks followed by optical coherence tomography (OCT) and histology assessment of NI burden and stent strut healing. Compared to control, DP demonstrated a 16.6% relative reduction in NI volume (14.7 ± 0.8% vs. 12.5 ± 0.4%, p = 0.03) and a 36.2% relative increase in optimally healed stent struts (37.8 ± 2.8% vs. 54.6 ± 2.5%, p < 0.0001). Atherosclerosis demonstrated attenuated effect with no difference in NI burden (15.2 ± 1.0% vs. 16.9 ± 0.8%, p = 0.22) and only a 14.2% relative increase in strut healing (68.3 ± 4.1% vs. 78.7 ± 2.5%, p = 0.02). DP treated rabbits had a 44.6% (p = 0.045) relative reduction in NI SMC content. In vitro assessment of DP and coronary artery SMCs yielded dose-dependent reduction in SMC migration and proliferation. Selective small molecule antagonism of ADOR-A2B abrogated the effects of DP on SMC proliferation. DP modulated SMC phenotypic switching with ADOR-A2B siRNA knockdown supporting its role in the observed effects. Conclusion: Dipyridamole reduces NI proliferation and improves stent healing in a preclinical model of stent implantation with conventional antiplatelets. Atherosclerosis attenuates the observed effect. Clinical trials of DP as an adjunctive agent may be warranted to evaluate for clinical efficacy in stent outcomes.

The Ongoing Saga of the Evolution of Percutaneous Coronary Intervention: From Balloon Angioplasty to Recent Innovations to Future Prospects.

The advances in percutaneous coronary intervention (PCI) have been, above all, dependent on the work of pioneers in surgery, radiology, and interventional cardiology. From Grüntzig's first balloon angioplasty, PCI has expanded through technology development, improved protocols, and dissemination of best-practice techniques. We can nowadays treat more complex lesions in higher-risk patients with favourable results. Guide wires, balloon types and profiles, debulking techniques such as atherectomy or lithotripsy, stents, and scaffolds all represent evolutions that have allowed us to tackle complex lesions such as an unprotected left main coronary artery, complex bifurcations, or chronic total occlusions. Best-practice PCI, including physiology assessment, imaging, and optimal lesion preparation are now the gold standard when performing PCI for sound indications, and new technologies such as intravascular lithotripsy for lesion preparation, or artificial intelligence, are innovations in the steps of 4 decades of pioneers to improve patient care in interventional cardiology. In the present review, major innovations in PCI since the first balloon angioplasty and also uncertainties and obstacles inherent to such medical advances are described.

Impact of sex on outcomes after percutaneous repair of functional mitral valve regurgitation.

BACKGROUND: The role of percutaneous repair of functional mitral regurgitation (MR) is evolving. Left ventricle remodeling is known to be different between men and women; however, outcomes following percutaneous repair of functional MR have not considered the impact of sex. METHODS: Between 2012 and 2018, 175 patients underwent percutaneous repair of functional MR with the Mitra Clip NT/NTR (Abbott) at our institution. Patients were assessed in a dedicated clinic with a follow-up that averaged 0.7 ± 1.2 years and extended to 5.7 years. RESULTS: Men had a larger body surface area than women (p < .001), and were more likely than women to have diabetes preoperatively (p = .02). There were no deaths or instances of single leaflet detachment. Immediate postprocedure MR was ≤2+ in 158 (90%) with a mean trans-mitral valve repair gradient of 3.4 ± 1.0 and 3.5 ± 2.1 mmHg, respectively for women and men (p = .8). One- and 2-year freedom from MR ≥3+ was 86.0 ± 3.5% and 77.6 ± 5.1%, respectively. After adjusting for differences between male and female patients, women were more likely to have recurrent MR ≥3+ (hazard ratio, 4.7; 95% confidence interval, 1.2-18.4; p = .03). Upon adjusted analysis, there was also no association between gender and survival (p = .2). One- and 2-year survival was 69.8 ± 4.3% and 54.3 ± 5.5%, respectively. CONCLUSION: Women are more likely to have recurrent severe MR after percutaneous repair of functional MR. The mechanism for this remains undetermined.

Interaction Between Frailty and Access Site in Older Adults Undergoing Transcatheter Aortic Valve Replacement.

OBJECTIVES: The authors sought to determine whether frail older adults undergoing nonfemoral transcatheter aortic valve replacement (TAVR) procedures had a higher risk of 30-day and 12-month mortality. BACKGROUND: Frailty can help predict outcomes and guide therapy in older adults being considered for TAVR. Nonfemoral TAVR procedures are more invasive and impart a greater risk of adverse events, which may be less well tolerated in frail patients, compared with transfemoral TAVR procedures. METHODS: This study was a post hoc analysis of the FRAILTY-AVR (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions) prospective multicenter cohort that consisted of older adults undergoing TAVR from 2012 to 2017. Frailty was assessed using the Essential Frailty Toolset (EFT). Endpoints of interest were 30-day and 12-month all-cause mortality. Interaction tables and multivariable logistic regression models were used to investigate statistical interaction on the additive and multiplicative scales. RESULTS: The cohort consisted of 723 patients with a mean age of 84 ± 6 years, of which 556 (77%) had femoral access and 167 (23%) had nonfemoral access. In frail patients with EFT scores ≥3 (35%), nonfemoral access was associated with increased 30-day mortality (odds ratio [OR]: 3.91; 95% confidence interval [CI]: 1.48 to 10.31); whereas in nonfrail patients with EFT scores <3 (65%), nonfemoral access had no effect (OR: 1.29; 95% CI: 0.34 to 4.94). There was statistical evidence of interaction between frailty and access site on 30-day mortality on the additive scale (relative excess risk due to interaction = 5.95). Nonfemoral access was associated with increased 1-year mortality in frail patients (OR: 1.98; 95% CI: 1.00 to 3.93) but not in nonfrail patients (OR: 1.83; 95% CI: 0.90 to 3.74), although there was no statistical evidence of interaction. CONCLUSIONS: Frail patients undergoing TAVR via a more invasive nonfemoral access face a substantially higher risk of 30-day mortality, whereas nonfrail older adults tolerate the procedure with a low short-term risk irrespective of access route.

Frailty in Older Adults Undergoing Aortic Valve Replacement: The FRAILTY-AVR Study.

BACKGROUND: Frailty is a geriatric syndrome that diminishes the potential for functional recovery after a transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) procedure; however, its integration in clinical practice has been limited by a lack of consensus on how to measure it. OBJECTIVES: This study sought to compare the incremental predictive value of 7 different frailty scales to predict poor outcomes following TAVR or SAVR. METHODS: A prospective cohort of older adults undergoing TAVR or SAVR was assembled at 14 centers in 3 countries from 2012 to 2016. The following frailty scales were compared: Fried, Fried+, Rockwood, Short Physical Performance Battery, Bern, Columbia, and the Essential Frailty Toolset (EFT). Outcomes of interest were all-cause mortality and disability 1 year after the procedure. RESULTS: The cohort was composed of 1,020 patients with a median age of 82 years. Depending on the scale used, the prevalence of frailty ranged from 26% to 68%. Frailty as measured by the EFT was the strongest predictor of death at 1 year (adjusted odds ratio [OR]: 3.72; 95% confidence interval [CI]: 2.54 to 5.45) with a C-statistic improvement of 0.071 (p < 0.001) and integrated discrimination improvement of 0.067 (p < 0.001). Moreover, the EFT was the strongest predictor of worsening disability at 1 year (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) and death at 30 days (adjusted OR: 3.29; 95% CI: 1.73 to 6.26). CONCLUSIONS: Frailty is a risk factor for death and disability following TAVR and SAVR. A brief 4-item scale encompassing lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia outperformed other frailty scales and is recommended for use in this setting. (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions; NCT01845207).

Matched Comparison of Self-Expanding Transcatheter Heart Valves for the Treatment of Failed Aortic Surgical Bioprosthesis: Insights From the Valve-in-Valve International Data Registry (VIVID).

BACKGROUND: Transcatheter valve-in-valve implantation is an established therapy for high-risk patients with failed surgical aortic bioprosthesis. There are limited data comparing outcomes of valve-in-valve implantation using different transcatheter heart valves (THV). METHODS AND RESULTS: Patients included in the Valve-in-Valve International Data registry (VIVID) and treated with self-expanding THV devices were analyzed using centralized core laboratory blinded to clinical events. St. Jude Medical Portico versus Medtronic CoreValve were compared in a 1:2 fashion after propensity score matching. A total of 162 patients, Portico- (n=54) and CoreValve- (n=108) based valve-in-valve procedures comprised the study population with no significant difference in baseline characteristics (age, 79±8.2 years; 60% women; mean STS [Society of Thoracic Surgery] score 8.1±5.5%). Postimplantation, CoreValve was associated with a larger effective orifice area (1.67 versus 1.31 cm2; P=0.001), lower mean gradient (14±7.5 versus 17±7.5 mm Hg; P=0.02), and lower core laboratory-adjudicated moderate-to-severe aortic insufficiency (4.2% versus 13.7%; P=0.04), compared with Portico. Procedural complications including THV malpositioning, second THV requirement, or coronary obstruction were not significantly different between the 2 groups. Survival and stroke rates at 30 days were similar, but overall mortality at 1 year was higher among patients treated with Portico compared with CoreValve (22.6% versus 9.1%; P=0.03). CONCLUSIONS: In this first matched comparison of THVs for valve-in-valve implantations, Portico and CoreValve demonstrated differences in postprocedural hemodynamics and long-term clinical outcomes. Although this could be related to THV design characteristics, the impact of other procedural factors cannot be excluded and require further evaluation.

A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome. The CAPITAL OPTI-CROSS Study.

Ticagrelor has been endorsed by guidelines as the P2Y12 inhibitor of choice in patients with acute coronary syndrome. Clinically, some patients on ticagrelor will require a switch to clopidogrel; however, the optimal strategy and pharmacodynamics effects of switching remain unknown. Patients with an indication to switch were randomly assigned to either a bolus arm (Clopidogrel 600 mg bolus followed by 75 mg daily, n=30) or a no-bolus arm (Clopidogrel 75 mg daily, n=30). Blood samples were collected at baseline, 12, 24, 48, 54, 60 and 72 hours (h) for assessment of platelet reactivity. The primary outcome was P2Y12 reactivity units (PRU) at 72 h. Secondary outcomes included: PRUs at each time point, incidence of high on-treatment platelet reactivity (HPR), major adverse cardiac events (MACE) and TIMI bleeding at 30 days. Serial PRUs increased after switching to clopidogrel in both groups. At 72 h, no difference in PRU was observed (165.8 ± 71.0 vs 184.1 ± 67.7, bolus vs no bolus, respectively, p=0.19). At 48 h the PRUs were significantly lower in the bolus arm (114 ± 73.1 vs 165.1 ± 70.5, respectively; p=0.0076) and at 72 h, there was a significant reduction in incidence of HPR (26.7 % vs 56.7 %, p=0.02). No differences in MACE or TIMI bleeding were observed. Although a bolus strategy was not associated with improved platelet inhibition at 72 h; at 48 h, platelet inhibition was superior with reduced incidence of HPR. Larger studies will be required to determine its clinical significance. Until then, decision for giving a bolus of clopidogrel at the time of a switch may in part be dependent on the indication for switching, especially if there are concerns for bleeding risk.

Impact of Center Experience on Patient Radiation Exposure During Transradial Coronary Angiography and Percutaneous Intervention: A Patient-Level, International, Collaborative, Multi-Center Analysis.

BACKGROUND: The adoption of the transradial (TR) approach over the traditional transfemoral (TF) approach has been hampered by concerns of increased radiation exposure-a subject of considerable debate within the field. We performed a patient-level, multi-center analysis to definitively address the impact of TR access on radiation exposure. METHODS AND RESULTS: Overall, 10 centers were included from 6 countries-Canada (2 centers), United Kingdom (2), Germany (2), Sweden (2), Hungary (1), and The Netherlands (1). We compared the radiation exposure of TR versus TF access using measured dose-area product (DAP). To account for local variations in equipment and exposure, standardized TR:TF DAP ratios were constructed per center with procedures separated by coronary angiography (CA) and percutaneous coronary intervention (PCI). Among 57 326 procedures, we demonstrated increased radiation exposure with the TR versus TF approach, particularly in the CA cohort across all centers (weighted-average ratios: CA, 1.15; PCI, 1.05). However, this was mitigated by increasing TR experience in the PCI cohort across all centers (r=-0.8; P=0.005). Over time, as a center transitioned to increasing TR experience (r=0.9; P=0.001), a concomitant decrease in radiation exposure occurred (r=-0.8; P=0.006). Ultimately, when a center's balance of TR to TF procedures approaches 50%, the resultant radiation exposure was equivalent. CONCLUSIONS: The TR approach is associated with a modest increase in patient radiation exposure. However, this increase is eliminated when the TR and TF approaches are used with equal frequency-a guiding principle for centers adopting the TR approach.

Ticagrelor in Triple Antithrombotic Therapy: Predictors of Ischemic and Bleeding Complications.

BACKGROUND: Patients on dual antiplatelet therapy following percutaneous coronary intervention often have indications for concurrent oral anticoagulation or triple antithrombotic therapy (TT). Although TT may decrease ischemic complications, it may confer increased bleeding risk. HYPOTHESIS: We hypothesize that the use of ticagrelor in TT is associated with higher risk of complications; accordingly, we sought to determine predictors of complications in patients on TT. METHODS: Patients discharged on TT after percutaneous coronary intervention were followed prospectively for 12 months. The primary endpoint was a composite of ischemic (death, myocardial infarction, stroke) and major bleeding complications or net adverse clinical event (NACE). A major secondary endpoint was BARC (Bleeding Academic Research Consortium) types 2, 3, or 5 bleeding. Outcomes were compared between ticagrelor- and clopidogrel-treated patients. Multivariable analyses were performed to elucidate predictors of complications. RESULTS: Twenty-seven of 152 patients discharged on TT were on ticagrelor. NACE occurred in 52% of patients and BARC 2, 3, or 5 bleeding occurred in 18%. There was no difference in the primary or secondary outcome between ticagrelor vs clopidogrel subgroup. On logistic regressions, use of TT in patients with acute coronary syndrome (P = 0.002) and bridging in with ticagrelor (P = 0.02) were associated with increased NACE. Low estimated glomerular filtration rate was an independent predictor of bleeding (P = 0.03). CONCLUSIONS: The risk of bleeding and ischemic complications among patients on TT is similar between those on ticagrelor and clopidogrel. However, caution with use of bridging anticoagulation should be taken when using ticagrelor.

A pharmacodynamic comparison of a personalized strategy for anti-platelet therapy versus ticagrelor in achieving a therapeutic window.

BACKGROUND: A therapeutic window in antiplatelet treatment has been associated with concurrent lowering of bleeding and ischemic risks. Prasugrel and ticagrelor provide potent platelet inhibition, but may increase bleeding. No study has evaluated a personalized therapy with selective use of novel P2Y12 inhibitory agents compared to empiric ticagrelor use. The objective of this study was to compare a personalized anti-platelet therapy strategy to empiric ticagrelor in achieving a therapeutic window. METHODS: Using the CAPITAL registry, we performed a retrospective analysis to evaluate a personalized anti-platelet therapy (PAT) strategy, using a pharmacogenetic approach, and compared it to empiric ticagrelor. In the PAT group, carriers of CYP2C19*2 received prasugrel and non-carriers received clopidogrel. The primary outcome was the proportion of patients within a validated therapeutic window, after a steady state treatment (≥48h) of antiplatelet therapy, as measured by a P2Y12 reaction unit (PRU) >85 and <208. RESULTS: Of 199 patients with platelet function measurements, 150 received PAT, while 49 received ticagrelor. Significantly more patients on PAT achieved the primary outcome (50.0% vs. 4.1%, p<0.0001). This was predominantly driven by an increase in low on-treatment reactivity with ticagrelor (95.9% vs. 37.3%, p<0.0001). Multivariable analysis demonstrated PAT to be the strongest predictor of achieving PRU values within the therapeutic window (odds ratio 20.27; 95% CI: 4.33-94.82, p=0.0001). CONCLUSION: Patients treated with PAT were more likely to achieve a therapeutic window compared to a strategy of ticagrelor. Future prospective evaluation of novel PAT strategies will be required to prove clinical utility.

Hybrid approach for coronary artery revascularization: where do we stand?

PURPOSE OF REVIEW: Recently, hybrid coronary artery revascularization (HCAR), combining the benefits of both percutaneous coronary intervention and coronary artery bypass graft surgery (CABG) while minimizing their respective shortcomings, has been developed. This review is aimed to explore and discuss recent clinical outcomes and patient selection, and comment on surgical approaches for HCAR. RECENT FINDINGS: Current forms of HCAR include off-pump mini-sternotomy or on-pump full sternotomy CABG [left internal mammary artery (LIMA)-to-left anterior descending artery(LAD) CABG followed by drug-eluting stents (DES) to non-LAD territories], robotic-assisted off-pump HCAR (robotic LIMA-to-LAD CABG and DES to non-LAD territories), and off-pump mini-thoracotomy single-vessel small thoracotomy (LIMA-to-LAD CABG), all of which have reported acceptable early to mid-term patency rates and freedom from major cardiac and cerebrovascular adverse events. As long-term effectiveness compared with conventional CABG remains to be demonstrated, especially in patients with diabetes and patients with higher SYNTAX scores, appropriate discussion between the 'Heart Team' and patient is needed prior to HCAR. SUMMARY: HCAR presents an attractive alternative option for treating patients with multivessel coronary artery disease because it maximizes the clear survival benefits of LIMA-LAD grafting, improves quality assurance with completion angiography, and allows quicker patient recovery; furthermore, patients avoid the negative systemic inflammatory effects of cardiopulmonary bypass and delayed healing after sternotomy.

Granulocyte colony-stimulating factor therapy for stem cell mobilization following anterior wall myocardial infarction: the CAPITAL STEM MI randomized trial.

BACKGROUND: Small studies have yielded divergent results for administration of granulocyte colony-stimulating factor (G-CSF) after acute myocardial infarction. Adequately powered studies involving patients with at least moderate left ventricular dysfunction are lacking. METHODS: Patients with left ventricular ejection fraction less than 45% after anterior-wall myocardial infarction were treated with G-CSF (10 µg/kg daily for 4 days) or placebo. After initial randomization of 86 patients, 41 in the placebo group and 39 in the G-CSF group completed 6-month follow-up and underwent measurement of left ventricular ejection fraction by radionuclide angiography. RESULTS: Baseline and 6-week mean ejection fraction was similar for the G-CSF and placebo groups: 34.8% (95% confidence interval [CI] 32.6%-37.0%) v. 36.4% (95% CI 33.5%-39.2%) at baseline and 39.8% (95% CI 36.2%-43.4%) v. 43.1% (95% CI 39.2%-47.0%) at 6 weeks. However, G-CSF therapy was associated with a lower ejection fraction at 6 months relative to placebo (40.8% [95% CI 37.4%-44.2%] v. 46.0% [95% CI 42.7%-44.3%]). Both groups had improved left ventricular function, but change in left ventricular ejection fraction was lower in patients treated with G-CSF than in those who received placebo (5.7 [95% CI 3.4-8.1] percentage points v. 9.2 [95% CI 6.3-12.1] percentage points). One or more of a composite of several major adverse cardiac events occurred in 8 patients (19%) within each group, with similar rates of target-vessel revascularization. INTERPRETATION: In patients with moderate left ventricular dysfunction following anterior-wall infarction, G-CSF therapy was associated with a lower 6-month left ventricular ejection fraction but no increased risk of major adverse cardiac events. Future studies of G-CSF in patients with left ventricular dysfunction should be monitored closely for safety. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT00394498.

A comparative pharmacodynamic study of ticagrelor versus clopidogrel and ticagrelor in patients undergoing primary percutaneous coronary intervention: the CAPITAL RELOAD study.

BACKGROUND: In patients undergoing primary percutaneous coronary intervention (PPCI) ticagrelor is superior to clopidogrel in reducing cardiovascular events. This study sought to evaluate the effect of clopidogrel pretreatment on the pharmacodynamics of ticagrelor in patients undergoing PPCI. METHODS: We measured platelet reactivity using the VerifyNow P2Y12 assay at baseline, 1, 2, 4, 6, 12, 24, and 48 hours following ticagrelor bolus in patients previously loaded with clopidogrel (C+T) and in thienopyridine-naive patients (T) referred to our centre for PPCI. RESULTS: In total, 52 consecutive eligible patients with ST-elevation myocardial infarction (STEMI) were enrolled (27 C+T and 25 T). Baseline characteristics and mean baseline platelet reactivity units (PRUs) were similar between the groups. The primary endpoint, the proportion of patients achieving a PRU<208 at 2 hours, was more frequently achieved in the C+T group compared to T treatment (76.0% vs 44.4%, p= 0.026). Notably, C+T therapy resulted in fewer patients with high platelet reactivity at 1 hour (56.0% vs. 14.8%), 4 hours (100.0% vs. 61.5%) and 6 hours (100.0% vs. 64%, p<0.01 for all comparisons). Furthermore, C+T therapy was associated with lower PRU values from 2 to 48 hours. CONCLUSIONS: In patients referred for PPCI, ticagrelor bolus following clopidogrel resulted in more rapid and profound platelet inhibition, demonstrating a positive pharmacodynamic interaction. Further study is needed to determine if this pharmacodynamic effect translates into reduced clinical events.

Transradial versus transfemoral artery approach for coronary angiography and percutaneous coronary intervention in the extremely obese.

OBJECTIVES: This study sought to evaluate the safety and efficacy of transradial versus transfemoral access for coronary angiography and percutaneous coronary intervention in patients with a body mass index ≥ 40 kg/m(2). BACKGROUND: Coronary angiography is most commonly performed via femoral artery access; however, the optimal approach in extremely obese (EO) patients remains unclear. METHODS: Between January 2007 and August 2010, a cohort of consecutive EO patients who underwent coronary angiography was identified in our center's registry of angiography and percutaneous coronary intervention procedures. Of 21,103 procedures, 564 (2.7%) were performed in unique EO patients: 203 (36%) via the transradial approach; and 361 (64%) via the transfemoral approach. RESULTS: The primary outcome, a combined endpoint of major bleeding, access site complications, and nonaccess site complications, occurred in 7.5% of the transfemoral group and 2.0% of the transradial group (odds ratio [OR]: 0.30, 95% confidence interval [CI]: 0.10 to 0.88, p = 0.029), an endpoint driven by reductions in major bleeding (3.3% vs. 0.0%, OR: 0.12, 95% CI: 0 to 0.71, p = 0.015), as well as access site injuries (4.7% vs. 0.0%, OR: 0.08, 95% CI: 0 to 0.48, p = 0.002). There were no differences in nonaccess site complications (1.7% vs. 2.0%, OR: 1.50, 95% CI: 0.41 to 5.55), but transradial access procedures were associated with an increase in procedure time and patient radiation dose (p < 0.05). CONCLUSIONS: Transfemoral access for coronary angiography and percutaneous coronary intervention was associated with more bleeding and access site complications when compared with a transradial approach. Important reductions in procedural associated morbidity may be possible with a transradial approach in EO patients.

Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial.

BACKGROUND: Prospective assessment of pharmacogenetic strategies has been limited by an inability to undertake bedside genetic testing. The CYP2C19*2 allele is a common genetic variant associated with increased rates of major adverse events in individuals given clopidogrel after percutaneous coronary intervention (PCI). We used a novel point-of-care genetic test to identify carriers of the CYP2C19*2 allele and aimed to assess a pharmacogenetic approach to dual antiplatelet treatment after PCI. METHODS: Between Aug 26, 2010, and July 7, 2011, 200 patients were enrolled into our prospective, randomised, proof-of-concept study. Patients undergoing PCI for acute coronary syndrome or stable angina were randomly assigned to rapid point-of-care genotyping or to standard treatment. Individuals in the rapid genotyping group were screened for the CYP2C19*2 allele. Carriers were given 10 mg prasugrel daily, and non-carriers and patients in the standard treatment group were given 75 mg clopidogrel daily. The primary endpoint was the proportion of CYP2C19*2 carriers with high on-treatment platelet reactivity (P2Y12 reactivity unit [PRU] value of more than 234) after 1 week of dual antiplatelet treatment, which is a marker associated with increased adverse cardiovascular events. Interventional cardiologists and data analysts were masked to genetic status and treatment. Patients were not masked to treatment allocation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, NCT01184300. FINDINGS: After randomisation, 187 patients completed follow-up (91 rapid genotyping group, 96 standard treatment). 23 individuals in each group carried at least one CYP2C19*2 allele. None of the 23 carriers in the rapid genotyping group had a PRU value of more than 234 at day 7, compared with seven (30%) given standard treatment (p=0·0092). The point-of-care genetic test had a sensitivity of 100% (95% CI 92·3-100) and a specificity of 99·3% (96·3-100). INTERPRETATION: Point-of-care genetic testing after PCI can be done effectively at the bedside and treatment of identified CYP2C19*2 carriers with prasugrel can reduce high on-treatment platelet reactivity. FUNDING: Spartan Biosciences.

Unprotected left main coronary artery stenting with zotarolimus (Endeavor) drug-eluting stents: a single center retrospective experience.

OBJECTIVES: To report the safety and efficacy of zotarolimus eluting stents for treatment of unprotected left main coronary artery disease. BACKGROUND: Percutaneous stent insertion is an increasingly popular alternative to bypass surgery for the management of left main (LM) coronary artery disease. While data support the use of sirolimus- and paclitaxel-coated stents in the LM coronary artery, there are no published series reporting results with Endeavor (zotarolimus) stents, particularly in the context of unprotected left main (ULM) lesions. METHODS: We retrospectively identified 40 consecutive patients who had ULM disease treated with Endeavor stents (ZES) and who had follow-up angiography. The primary endpoint was the prevalence of major adverse cardiac events (MACE), including cardiac/unexplained death, nonfatal myocardial infarction (MI), and in-stent restenosis (ISR)/target lesion revascularization (TLR). RESULTS: Angiographic and procedural success was achieved in all cases. Follow-up angiography occurred on average 5.6 ± 0.9 months after the index procedure. There were three incidences of ISR requiring TLR and another patient who had a NSTEMI in the follow-up period. At late follow-up (12.4 ± 1.8 months) three patients underwent CABG (one for RCA stenosis) and four patients died without knowledge of the status of the ULM stent (two cardiovascular and two deaths related to cancer progression). CONCLUSIONS: In conclusion, our experience with Endeavor stents for the treatment of ULM disease demonstrates excellent angiographic and clinical outcomes, with a 7.5% ISR/TLR rate and a 15% MACE rate, respectively, at an average clinical follow-up of 12.4 months.

Repeat cardiac surgery in a Jehovah's Witness patient with thrombocytopenia.

Complex cardiac surgery in Jehovah's Witness patients can be challenging, especially if it is a reoperation and the patient has a preexisting bleeding disorder. We operated on a patient who was declined for percutaneous aortic valve replacement and who required repeat surgery for aortic valve repeat replacement and root repair. In addition to being of Jehovah's Witness faith, the patient had chronic thrombocytopenia. We describe our strategy in managing this situation.

2-year follow-up of patients undergoing transcatheter aortic valve implantation using a self-expanding valve prosthesis.

OBJECTIVES: The purpose of this study was to evaluate the safety, device performance, and clinical outcome up to 2 years for patients undergoing transcatheter aortic valve implantation (TAVI). BACKGROUND: The role of TAVI in the treatment of calcific aortic stenosis evolves rapidly, but mid- and long-term results are scarce. METHODS: We conducted a prospective, multicenter, single-arm study with symptomatic patients undergoing TAVI for treatment of severe aortic valve stenosis using the 18-F Medtronic CoreValve (Medtronic, Minneapolis, Minnesota) prosthesis. RESULTS: In all, 126 patients (mean age 82 years, 42.9% male, mean logistic European System for Cardiac Operative Risk Evaluation score 23.4%) with severe aortic valve stenosis (mean gradient 46.8 mm Hg) underwent the TAVI procedure. Access was transfemoral in all but 2 cases with subclavian access. Retrospective risk stratification classified 54 patients as moderate surgical risk, 51 patients as high-risk operable, and 21 patients as high-risk inoperable. The overall technical success rate was 83.1%. Thirty-day all-cause mortality was 15.2%, without significant differences in the subgroups. At 2 years, all-cause mortality was 38.1%, with a significant difference between the moderate-risk group and the combined high-risk groups (27.8% vs. 45.8%, p = 0.04). This difference was mainly attributable to an increased risk of noncardiac mortality among patients constituting the high-risk groups. Hemodynamic results remained unchanged during follow-up (mean gradient: 8.5 ± 2.5 mm Hg at 30 days and 9.0 ± 3.4 mm Hg at 2 years). Functional class improved in 80% of patients and remained stable over time. There was no incidence of structural valve deterioration. CONCLUSIONS: The TAVI procedure provides sustained clinical and hemodynamic benefits for as long as 2 years for patients with symptomatic severe aortic stenosis at increased risk for surgery.