The making of the one pill-Developing single tablet regimens for HIV and for HCV.

A concept of "all or nothing" inspired the innovation of a one-pill-once-daily HIV treatment. Atripla® was the one pill that combined efavirenz, emtricitabine, and tenofovir disoproxil fumarate to become the first daily single tablet regimen that forever simplified HIV treatment to enhance patient compliance and thus, sustained viral suppression. The making of Atripla incorporated dry granulation and bilayer compression technologies to achieve stability and bioequivalence in an optimal pill size. In 2011, there lacked a standard of care for chronic hepatitis C infections that was safe, simple, short, free of interferon and ribavirin, and with high cure rates. A fixed-dose combination of ledipasvir and sofosbuvir was developed and approved in 2014 to be the first complete daily single tablet regimen for CHC genotype 1 infection. A spray-drying process for particle morphology engineering in a polymer matrix was used for improving bioavailability.

Intravascular ultrasound evidence of perivascular trauma during routine percutaneous coronary intervention.

We assessed whether intravascular ultrasound (IVUS) can detect evidence of coronary perforation that is not visible by coronary angiography. Approximately 15,000 consecutive percutaneous coronary interventions (PCI) performed with IVUS guidance were reviewed retrospectively, pre- and post-PCI IVUS images were compared, and IVUS findings were compared with coronary angiography and in-hospital outcomes. We detected three distinct patterns that were not present pre-PCI and that were suggestive of perforation or perivascular trauma: perivascular blood speckle in 67 % (51/76), perivascular hematoma in 17 % (13/76), and new echolucent perivascular layer in 16 % (12/76). Angiographic appearance included perforation in 24 % (18/76), dissection in 33 % (25/76), lumen irregularity in 17 % (13/76), new stenosis in 5 % (4/76), and no abnormalities in 21 % (16/76). The site of a break in arterial wall with communication between the lumen and perivascular space could be detected in 61 % (46/76). This extended proximally and distally with equal frequency, but was primarily located within the lesion in 80 % (61/76), although the lumen was rarely compromised. Within 24 h, there were four emergent coronary artery bypass grafting procedures, one repeat PCI, and six periprocedural myocardial infarctions (defined as CK-MB ≥10 times the upper limit of normal), but there were no episodes of cardiac tamponade. Although infrequent, IVUS detected three distinct patterns of post-PCI perivascular trauma suggestive of a perforation that was detected angiographically in only 24 % of cases.

Impact of previous coronary artery bypass grafting on patients undergoing transcatheter aortic valve implantation for aortic stenosis.

Re-operation after coronary artery bypass grafting (CABG) is associated with increased risk for morbidity and mortality. Transcatheter aortic valve implantation (TAVI) is an alternative for patients with aortic stenosis, but the outcomes of patients with a history of CABG are unknown. The aim of this study was to explore the association between previous CABG and the outcome of patients undergoing TAVI. Out of 372 consecutive patients who underwent TAVI from 2007 to 2013, 122 (32.8%) had previous CABG, whereas 250 (67.2%) did not. A comparison was made between groups. Subgroup analysis compared patients with and without previous CABG in 3 patient subsets: inoperable, operable, and those who underwent transapical TAVI. Patients with previous CABG were younger (81.99±6.78 vs 84.81±7.06 years, respectively, p<0.001). These patients also had more high-risk features (e.g., peripheral vascular disease, previous myocardial infarction, past cerebrovascular disease, and lower average left ventricular ejection fraction (p<0.05 for all). Procedural aspects were mostly similar between groups. No disparities in mortality rates at 1 year were noted (22.1% vs 21.6%, respectively, p=0.91). Subgroup analyses yielded similar outcomes for all 3 groups. In conclusion, although patients with previous CABG present with more high-risk features, they share similar short- and long-term outcomes with patients without previous CABG, irrespective of their surgical risk. This includes patients who underwent transapical access. TAVI in patients with previous CABG is safe and does not confer a significant risk for adverse outcome.

Percutaneous coronary intervention versus medical therapy in stable coronary artery disease: the unresolved conundrum.

One of the major dilemmas facing physicians is what diagnostic and therapeutic approaches should be recommended to those stable coronary artery disease patients whose symptoms are adequately controlled on medical therapy. This study sought to assess the evidence-based data relating to whether: 1) all patients with significant coronary lesions (i.e., ischemia-producing) should undergo percutaneous coronary intervention (PCI); 2) the best therapeutic approach is optimal medical therapy; or 3) PCI should be performed, but only in certain subsets of patients. We reviewed all recent meta-analyses of prospective randomized trials that compared the outcomes of medical therapy and PCI in stable, symptomatically controlled, coronary artery disease patients. To provide greater insights to the clinician, we then analyzed, in depth, 3 comprehensive and widely quoted randomized trials. Review of recently published (2012) meta-analyses, and the detailed analyses of 3 widely quoted individual studies, indicate no difference exists between PCI and medical therapy in nonfatal MI or in all-cause or cardiovascular mortality. Thus, clinical equipoise exists: in other words, there is no evidence-based justification for adopting 1 therapeutic strategy over the other. Therefore, it is not inappropriate, until additional evidence emerges, for the responsible, experienced physician to weigh several sources of information in formulating a recommendation to the patient, even though definitive evidence-based data are not as yet available. Such sources may include assessment of the individual patient's clinical presentation, assessment of the severity of ischemia, and the patient's precise coronary anatomy. Critical for more-reliable decision making will be future development of accurate measures of the individual patient's risk of MI and/or death, whether by biomarker, imaging, or ischemia assessments.

Safety and feasibility of performing staged non-culprit vessel percutaneous coronary intervention within the index hospitalization in patients with ST-segment elevation myocardial infarction and multivessel disease.

OBJECTIVES: To determine whether staged percutaneous coronary intervention (PCI) within the same hospitalization as primary PCI is safe. BACKGROUND: In ST-segment elevation myocardial infarction (STEMI) patients with multivessel disease undergoing primary PCI, staged non-culprit vessel PCI at a separate session is recommended. METHODS: We conducted a retrospective analysis of 282 consecutive STEMI patients with multivessel disease who underwent primary PCI followed by staged PCI of the non-culprit vessel. Patients were categorized into staged PCI in the same hospitalization (n=184) and staged PCI at a separate hospitalization within 8 weeks of primary PCI (n=98). RESULTS: Baseline characteristics, presentation of STEMI, and procedural characteristics were similar in both groups. Contrast amount was higher in the separate hospitalization group for both index (175 vs. 153 ml, p=0.011) and staged (144 vs. 120 ml, p=0.004) procedures. More staged left main PCI was performed in the separate hospitalization group (3.9 vs. 0.3%, p=0.008). Angiographic success of staged PCI was similar in both groups, with similar rates of vascular complications and major bleeding. Following staged PCI, in-hospital major adverse cardiac events (3.3 vs. 1.0%, p=0.43) and mortality (2.7 vs. 0%, p=0.17) were similar in both groups. CONCLUSIONS: Our study supports the safety and feasibility of staged PCI within the same hospitalization as primary PCI, achieving similar procedural success and in-hospital outcomes as staged PCI at a separate hospitalization. Higher contrast amount used during primary PCI and presence of left main lesion in non-culprit vessels may influence the decision to stage the PCI at a separate hospitalization.

Safety and efficacy outcomes of overlapping second-generation everolimus-eluting stents versus first-generation drug-eluting stents.

The safety and efficacy outcomes of stent overlap with second-generation drug-eluting stents (DES) have not been well established. This study aimed to compare the 1-year clinical outcomes of overlapping everolimus-eluting stents (EES) with those of overlapping first-generation DES. This retrospective analysis included 350 patients treated with overlapping EES (169 patients with 237 lesions), sirolimus-eluting stents (SES, 102 patients with 252 lesions), or paclitaxel-eluting stents (PES, 79 patients with 182 lesions). End points were major adverse cardiovascular events (MACE: defined as the composite of death, myocardial infarction, or target lesion revascularization), target vessel revascularization, and definite stent thrombosis at 1 year. During a follow-up of 1 year, overall MACE occurred in 6.5% of EES-, 16.8% of SES-, and 10.1% of PES-treated patients (p = 0.026). Myocardial infarction was lowest in the EES group versus SES and PES groups (0 vs 1.0% vs 2.5%, respectively; p = 0.080), and mortality was similar (3.6% vs 9.0% vs 5.1%, p = 0.162). The EES patients showed a trend toward lower rates of 1-year target lesion revascularization (3.1% vs 8.2% vs 6.5%, p = 0.181) and target vessel revascularization (3.7% vs 9.1% vs 11.7%, p = 0.051) compared with the SES- and PES-treated patients. The cumulative incidence of definite stent thrombosis was lowest in the EES group (0 for EES vs 3.9% for SES vs 2.5% for PES, p = 0.014). In conclusion, stent overlap with EES versus first-generation DES was associated with lower rates of MACE and stent thrombosis. Our results suggest that the use of EES when deploying overlapping stents is effective and safe.

Two-year follow-up of outcomes of second-generation everolimus-eluting stents versus first-generation drug-eluting stents for stenosis of saphenous vein grafts used as aortocoronary conduits.

Second-generation everolimus-eluting stents (EESs) have demonstrated superiority in efficacy and safety compared with first-generation drug-eluting stents (DESs) in the treatment of native coronary artery lesions. The present study evaluated and compared the safety and efficacy of EESs and first-generation DESs in saphenous vein graft lesions. The EES group consisted of 88 patients with 96 lesions, and the first-generation DES group consisted of 243 patients with 317 lesions (sirolimus-eluting stents, n = 212; paclitaxel-eluting stents, n = 105). The end points included target lesion revascularization, target vessel revascularization, major adverse cardiovascular events (composite of all-cause death, myocardial infarction, and target vessel revascularization), and definite stent thrombosis at 2 years. The groups had similar baseline characteristics and graft ages (128.1 ± 77.5 vs 132.4 ± 90.8 months, p = 0.686). The EES group had more type C lesions and less embolic protection device use. The peak postprocedure values of creatinine kinase-MB and troponin I were similar between the 2 groups. Overall, major adverse cardiovascular events occurred in 18.2% of EES patients and 35.0% of first-generation DES patients (p = 0.003), mainly driven by a lower target vessel revascularization rate (6.8% vs 24.5%, p <0.001). The target lesion revascularization rate was lower in the EES group (1.1% vs 11.6%, p = 0.005). Stent thrombosis was low and similar between the 2 groups (0% vs 0.8%, p = 1.000). On multivariate analysis, the type of DES implanted and graft age were the only independent predictors of major adverse cardiovascular events. In conclusion, the superiority of EESs compared with first-generation DESs shown in native artery lesions has been extended to saphenous vein graft lesions and should be considered as the DES of choice for this lesion type.

Nuisance and alarming bleeding do not correlate with on-treatment platelet reactivity.

AIMS: We hypothesized that patients with a history of either alarming or nuisance bleeding events, compared to those with no history of bleeding, would have lower levels of on-treatment platelet reactivity (aspirin and a thienopyridine). METHODS AND RESULTS: In total, 42 patients with no bleeding, 34 with nuisance bleeding, and 14 with alarming bleeding underwent platelet reactivity testing 1 month to 1 year after PCI with light transmission aggregometry (LTA 5 and 20 µM adenosine disphosphate [ADP]), vasodilator stimulated phosphoprotein phosphorylation (VASP) and VerifyNow P2Y12. Clinical and demographic characteristics of the 3 groups were generally similar, except that patients with alarming bleeding were less likely to be Caucasian; only 6 patients (6.7%) were taking prasugrel. There was considerable overlap between no bleeding, nuisance bleeding and alarming bleeding groups with respect to on-treatment platelet reactivity. Furthermore, there was no difference in the median platelet reactivity values for all assays. Prevalence of high on-treatment platelet reactivity did not differ among the 3 groups; 32.6% of patients had high on-treatment platelet reactivity as measured by LTA with 5 µM ADP (P=.91); 40.0% as measured by VASP (P=.35); and 35.6% as measured by VerifyNow P2Y12 (P=.61). CONCLUSION: The use of platelet reactivity assays to identify patients on thienopyridine therapy at higher risk of bleeding is an unfounded strategy.

Safety of reloading prasugrel in addition to clopidogrel loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI) commonly receive a loading dose of either clopidogrel or prasugrel, in addition to aspirin. The present study aimed to assess the safety of reloading prasugrel in patients who had initially received a loading dose of clopidogrel compared to prasugrel loading alone. The study included a cohort of 606 consecutive patients with acute coronary syndrome who had received a 60-mg loading dose of prasugrel before PCI. These patients were then categorized into clopidogrel preloading (300 or 600 mg) followed by prasugrel reloading (CP-load group, n = 90) and prasugrel loading only (P-load group, n = 516). Both groups received a 10-mg maintenance dose of prasugrel after PCI. The primary end point was in-hospital Thrombolysis In Myocardial Infarction-defined major bleeding. The secondary end points were other in-hospital bleeding complications and major cardiovascular events. Patients in the CP-load group compared to the P-load group were younger, with lower rates of cardiovascular risk factors. Significantly more patients in the CP-load group presented with biomarker-positive myocardial infarction (80.0% vs 30.6%, p ≤0.001) and cardiogenic shock (5.6% vs 1.4%, p = 0.022). No significant differences (p = NS) were seen in Thrombolysis In Myocardial Infarction major bleeding (2.6% vs 2.8%), Thrombolysis In Myocardial Infarction major or minor bleeding (12.2% vs 7.0%), the need for blood transfusion (2.6% vs 2.1%), and vascular complications (1.3% vs 2.0%) between groups. The CP-load group experienced more in-hospital major adverse cardiac events (5.6% vs 1.6%, p = 0.031), urgent coronary artery bypass grafting (3.3% vs 0.2%, p = 0.011), and longer hospital and intensive care unit stays. In conclusion, preloading with clopidogrel should not be prohibitive to reloading with prasugrel in patients presenting with acute coronary syndrome and undergoing PCI with respect to bleeding and vascular complications.

Comparison of long-term outcomes between everolimus-eluting and sirolimus-eluting stents in small vessels.

Although second-generation everolimus-eluting stents (EESs) have demonstrated superiority over first-generation paclitaxel-eluting stents for a broad subset of patients and lesions, it is unclear whether the same applies to sirolimus-eluting stents (SESs). The present study compared the long-term clinical outcomes between EESs and SESs in patients with small coronary artery disease. A cohort of 643 patients treated with EESs (220 patients with 245 lesions) or SESs (423 patients with 523 lesions) in small vessel lesions (defined as those receiving stents ≤2.5 mm) were retrospectively analyzed. The end points included target lesion revascularization, target vessel revascularization, major adverse cardiovascular events (all-cause death, myocardial infarction, or target lesion revascularization), and definite stent thrombosis at 1 year of follow-up. The baseline characteristics were generally similar between the 2 groups, except that more systemic hypertension was seen in the EES group and more patients had a family history of coronary artery disease in the SES group. The 1-year target lesion revascularization (5.6% vs 4.8%, p = 0.68) and target vessel revascularization (5.6% vs 7.6%, p = 0.33) rates showed no significant differences between the EES and SES groups. Overall major adverse cardiovascular events occurred in 9.1% of the EES- and 8.6% of SES-treated patients (p = 0.83). This similar major adverse cardiovascular events rate remained after adjustment. The rate of stent thrombosis was 0% in the EES group and 1.2% in the SES group (p = 0.17). In conclusion, EESs demonstrated comparable clinical outcomes to those of SESs in small vessel interventions. The absence of stent thrombosis among patients treated with EESs suggests a good safety profile for this second-generation drug-eluting stent, which should be carefully studied in a larger series of patients with small vessel disease.

The independent value of a direct stenting strategy on early and late clinical outcomes in patients undergoing elective percutaneous coronary intervention.

OBJECTIVES: This study aimed to compare percutaneous coronary intervention (PCI) with direct stenting (DS) to balloon predilatation (PD) for patients undergoing elective PCI to determine whether there is an independent value for DS with regard to clinical outcomes. BACKGROUND: The safety of PCI with DS has been established, but the independent advantages of this technique are not entirely clear. METHODS: Patients undergoing elective PCI from January 2000 to December 2010 were included. The postprocedural and late clinical outcomes of 444 patients who underwent PCI with DS were compared with a propensity-matched population of 444 subjects treated with PD. RESULTS: The two groups were well matched to 27 baseline clinical, procedural, and angiographic characteristics, thus allowing for a more accurate evaluation of the independent value of the stenting technique. Intravascular ultrasound was used in more than 60% of interventions in both groups. PCI performed with PD were longer (DS 45 ± 19.28 vs. PD 56 ± 23.72 minutes, P = 0.001), used more contrast (DS 154 ± 65.88 vs. PD 186 ± 92.84 cc, P = 0.001), and more frequently used balloon postdilation (DS 0% vs. PD 27.3%, P = 0.001). The incidence of periprocedural myocardial infarction (PPMI) was similar between DS- and PD patients (5.3% vs. 5.4%, P = 0.91). Likewise, the 1-year rates of major adverse cardiac events (8.4% vs. 6.3%, P = 0.25), target lesion revascularization (3.9% vs. 2.5%, P = 0.24), and definite stent thrombosis (0.2% vs. 0.9%, P = 0.37) were similar among DS and PD patients, respectively. CONCLUSION: During elective PCI, DS decreases overall procedure time and resource utilization, but fails to reveal an independent clinical advantage as there is no demonstrable benefit in regard to the incidence of PPMI, restenosis, or overall clinical outcomes up to 1-year of follow-up.

Safety and efficacy of prasugrel use in patients undergoing percutaneous coronary intervention and anticoagulated with bivalirudin.

The randomized TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 trial compared prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). Patients treated with prasugrel had fewer ischemic events but more procedure-related bleeding. In the present study, we aimed to determine the effect of bivalirudin on bleeding in patients treated with prasugrel. A total of 692 patients with consecutive acute coronary syndrome underwent PCI with stent implantation and were anticoagulated with bivalirudin. The patients were divided into 2 groups according to the antiplatelet regimen (clopidogrel or prasugrel) chosen during or just after PCI. The bleeding complications during hospitalization were tabulated. Ischemic events were analyzed during hospitalization and at 30 days. Prasugrel was used in 96 patients (13.9%) and clopidogrel in 596 (86.1%). The clinical and procedural characteristics were similar, although the clopidogrel patients more often reported systemic hypertension (p = 0.01), previous PCI (p <0.001), and chronic renal insufficiency (p = 0.05). During hospitalization, the bleeding and ischemic complication rates were similar and low in both groups (major in-hospital complications 4.2% for clopidogrel vs 2.1% for prasugrel, p = 0.6; Thrombolysis In Myocardial Infarction major bleeding 2.5% vs 2.1%, p = 1.00; Thrombolysis In Myocardial Infarction minor bleeding 4.2% vs 5.2%, p = 0.6). At 30 days, no differences were found in ischemic events between both groups (target vessel revascularization/major adverse cardiac events 5.4% vs 2.1%, p = 0.2). In conclusion, prasugrel, when given after bivalirudin as the intraprocedural antithrombin agent for patients with acute coronary syndrome undergoing PCI, is as safe and effective as clopidogrel.

Utilization of intravascular ultrasound to accurately position stents in true aorto-ostial lesions.

Percutaneous coronary intervention of aorto-ostial lesions is associated with high rates of major adverse cardiovascular events. Precise implantation of coronary stents in the ostium is important in order to prevent adverse clinical outcomes. The presented case demonstrates a simple technique to accurately position a stent during aorto-ostial percutaneous coronary intervention.

Endovascular recanalization of central venous access to allow for pacemaker implantation or upgrade.

BACKGROUND: Several patients undergoing permanent pacemaker (PPM) implantation/upgrade present with difficult access due to sub- or total central vein occlusion. Our institution has used the endovascular approach to recanalize central veins to allow for subsequent PPM implantation. Here we aim to describe the feasibility and safety of using this approach to allow for PPM implantation/upgrade. METHODS: From October 2006 to November 2010, 50 consecutive patients who underwent central vein recanalization prior to PPM implantation were included in this analysis. RESULTS: The population's mean age was 70 years, with a high rate of comorbidities including chronic renal failure (52.0%), congestive heart failure (64.0%), diabetes (33.3%) and peripheral vascular disease (36.0%). The endovascular recanalization procedure was performed via femoral access in all patients; however adjuvant brachial access was required in 13 cases and subclavian vein in one. Subclavian vein (74.5%) followed by innominate vein (21.6%) were the most common locations/target for recanalization. Successful vein recanalization followed by successful PPM implantation/upgrade was achieved in 48 patients (96.0%) without peri-procedural complications. Two patients died during the hospitalization, one due to severe respiratory failure and a second due to complicated end-stage renal disease, although neither was related to the endovascular procedure. No other event, including myocardial infarction, cerebral-vascular accident, bleeding/transfusion, or renal failure was identified. CONCLUSIONS: This study proved the feasibility and safety of the endovascular approach to recanalize central veins in patients with poor vascular access to allow for further PPM implantation/upgrade.

Safety and efficacy of the XIENCE V everolimus-eluting stent compared to first-generation drug-eluting stents in contemporary clinical practice.

Data from randomized clinical trials have shown the safety and efficacy of the XIENCE V in selected populations. However, limited data are available comparing the XIENCE V to the first-generation CYPHER sirolimus-eluting stent. This study aimed to assess the long-term safety and clinical efficacy of the XIENCE V everolimus-eluting stent compared to first-generation stents in an unselected patient population. This retrospective analysis included 6,069 patients treated with CYPHER, TAXUS, and XIENCE stents from 2003 to 2009 at our institution. The patients were followed up for ≥1 year after the index procedure. The baseline characteristics were generally comparable among the 3 groups, with the exception of a significantly greater prevalence of diabetes mellitus, systemic hypertension, and a history of angioplasty and coronary bypass surgery among the XIENCE patients. The XIENCE patients also had a twofold greater rate of type C lesions. One-year follow-up data were available for 82% of the patients. The 1-year major adverse cardiovascular events rate was 9.3% for the XIENCE stent versus 9.8% for the CYPHER stent and 11.5% for the TAXUS stent (p = 0.11). Mortality was lower in the XIENCE group than in the CYPHER and TAXUS groups (3.6% vs 4.9% vs 7.2%, respectively, p <0.001), and target lesion revascularization was similar (5.9% vs 5.2% vs 5.6%, respectively; p = 0.34). Stent thrombosis was lower in the XIENCE patients (0.2% vs 1.2% vs 0.7%, p = 0.007). In conclusion, in a contemporary United States clinical practice with an unselected patient population, use of the XIENCE V stent was associated with an improved safety profile and reduction of all-cause mortality and stent thrombosis compared to first-generation drug-eluting stents. The XIENCE V failed to demonstrate superiority for overall major adverse cardiovascular events, Q-wave myocardial infarction, and revascularization rates.

Clinical outcomes and treatment after drug-eluting stent failure: the absence of traditional risk factors for in-stent restenosis.

BACKGROUND: The optimal percutaneous treatment of drug-eluting stent (DES) in-stent restenosis (ISR) and the correlates for recurrent DES ISR remain unclear. METHODS AND RESULTS: From 2003 to 2008, 563 patients presenting with recurrent symptoms of ischemia and angiographic ISR after DES implantation were included. Of these, 327 were treated with re-DES (58.1%), 132 underwent vascular brachytherapy (23.4%), and 104 were treated with conventional balloon angioplasty (18.5%). Variables associated with target lesion revascularization at 1 year were explored by individual proportional hazard models. This population presents a high prevalence of comorbidities, including diabetes (43.7%), previous myocardial infarction (MI) (45.8%), coronary bypass graft surgery (39.2%), chronic renal failure (18.8%), and heart failure (17.3%). Baseline clinical characteristics were balanced among the 3 groups; however, patients undergoing vascular brachytherapy presented with more complex lesions and a higher prevalence of prior stent/vascular brachytherapy failure than did the rest of the population. The overall incidence of recurrent DES failure at 1-year follow-up was 12.2%, which was similar among the 3 groups (P=0.41). The rate of the composite end point (death, Q-wave-MI and target lesion revascularization) at 1-year follow-up was 14.1% for re-DES, 17.5% for vascular brachytherapy, and 18.0% for conventional balloon angioplasty (P=0.57). After univariable analysis tested the traditional known covariates related to ISR, none of them were associated with repeat target lesion revascularization. CONCLUSIONS: Recurrence of ISR after DES treatment failure is neither infrequent nor benign, and optimal therapy remains unclear and challenging. Given the absence of traditional risk factors for ISR in this population, further research is required to elucidate both the correlates involved in DES ISR and the optimal treatment for this condition.

Association between bleeding severity and long-term mortality in patients experiencing vascular complications after percutaneous coronary intervention.

Vascular complications (VCs) occur in 3% to 8% of percutaneous coronary interventions (PCIs). However, only a portion of patients who experience VCs bleed significantly. The aim of this study was to assess the covariates associated with the amount of blood loss in patients experiencing postprocedural VCs as well as the effect of the degree of blood loss on long-term mortality. Overall, 7,718 unselected patients who underwent PCI through femoral access were evaluated. Those experiencing VCs were identified and stratified with regard to the degree of hematocrit (HCT) decrease after the procedure. In total, 444 patients (5.8%) had VCs. Compared to those without VCs, patients with VCs were older and had more extensive co-morbidities. Severe blood loss was most frequent in those who had vascular perforation requiring surgical repair or in those who had retroperitoneal bleeding. Overall, <25% of patients with hematoma had severe blood loss. The raw 1-year mortality was doubled in patients with minimal or moderate HCT decrease and was tripled in those with severe decreases in HCT. Similarly, the rate of definite stent thrombosis was tripled in patients with VCs and moderate or severe decreases in HCT. After adjustment, only patients with VCs and the greater HCT decreases had an increased risk for death at 1 year (hazard ratio 1.80, 95% confidence interval 1.03 to 3.14). Independent predictors of severe HCT decrease included age, female gender, glycoprotein IIb/IIIa inhibitor use, and activated clotting time peak. Bivalirudin and closure devices were independently associated with less frequent severe HCT decrease. In conclusion, VCs do not entail an increased risk for death at 1 year unless associated with severe blood loss. The use of bivalirudin and closure devices seems to reduce the risk for such complications.

Impact of diabetes mellitus on long-term clinical outcomes of patients on chronic hemodialysis after percutaneous coronary intervention.

BACKGROUND: End-stage renal disease (ESRD) is known to correlate with poor outcome in patients undergoing percutaneous coronary intervention (PCI). This study examines the impact of diabetes mellitus (DM) on the long-term outcome of patients with ESRD on chronic hemodialysis. METHODS: A cohort of patients with ESRD on chronic hemodialysis, who underwent PCI with drug-eluting stents, was followed for 1 year. The clinical outcome in this population was compared retrospectively based on the presence of DM. Major adverse cardiac events (MACE) as the composite of all-cause death, Q-wave myocardial infarction and target lesion revascularization (TLR), as well as TLR as an individual outcome, were the main end points of the study. RESULTS: In the study cohort (n = 198), 48.5% had DM. Diabetic patients were more commonly female. The lesion characteristics were similar between groups except for more frequent saphenous vein graft intervention in nondiabetics. At 1-year follow-up there was no difference in the rate of MACE between diabetic and nondiabetic patients (40.4% vs. 39.3%, respectively, p = 0.89), driven primarily by a very high mortality rate (1-year overall mortality of 33.5%). After adjustment for the relevant clinical co-variables, DM was not associated with the composite end point. However, diabetic patients had a significantly higher incidence of 1-year TLR compared to nondiabetics (13.8% vs. 3.6%, respectively, p = 0.04). CONCLUSION: The prognosis of patients with ESRD after PCI is dismal with a very high overall mortality rate regardless of the presence of DM. Patients with ESRD appear to be at higher risk for the need of revascularization.

Outcome of percutaneous coronary intervention utilizing drug-eluting stents in patients with reduced left ventricular ejection fraction.

Ischemic cardiomyopathy with depressed left ventricular ejection fraction (LVEF) is predictive of death after percutaneous coronary intervention (PCI), but its association with stent thrombosis (ST) and the need for repeat revascularization is less clearly defined. In total 5,377 patients undergoing PCI were retrospectively evaluated. Multivariable Cox proportional hazards regression and competitive outcome analysis were employed. The primary end point was 1-year major adverse cardiac events (all-cause death, Q-wave myocardial infarction, ST, and target lesion revascularization [TLR]). Individual end points of ST and of TLR were also evaluated. Patients with normal LVEF (>50%) were compared to those with mild (41% to 50%), moderate (25% to 40%), and severe (<25%) decreases in LVEF. Patients with abnormal LVEF were older and more commonly diabetic and had renal insufficiency and heart failure syndrome (p <0.001 for all variables). These patients demonstrated more angiographically complex lesions and less frequently received a drug-eluting stent. The primary end point was significantly increased in patients with lower LVEF (9.7% for normal LVEF vs 20.6% for severely decreased LVEF, p <0.001). ST occurred more frequently in these patients (1.4% for normal LVEF vs 6% for severely decreased LVEF, p <0.001), but clinically driven TLR did not significantly change across LVEF categories. After adjustment, only moderate and severe LVEF decreases (i.e., LVEF ≤40%) demonstrated an association with major adverse cardiac events and with the individual outcome of ST. Subgroup analysis of patients receiving only a drug-eluting stent or a bare-metal stent demonstrated no statistically significant differences for the probability of ST. In conclusion, decreased LVEF is not associated with clinically driven TLR but does increase the risk of ST. Patients with LVEF ≤40% appear to be at significantly higher risk for ST and therefore might benefit from interventional and pharmacologic strategies aimed at minimizing this risk.

Changes in mitral regurgitation after balloon aortic valvuloplasty.

The coexistence of mitral regurgitation (MR) in patients with severe aortic stenosis (AS) is not infrequent and has been associated with adverse outcome. The aims of this study were to evaluate the change in MR severity and to identify the correlates of MR improvement in patients with severe AS and moderate to severe MR who underwent balloon aortic valvuloplasty (BAV). Patients with severe AS and at least moderate MR who underwent their first BAV procedures (n = 74) were divided into 2 groups: patients with improved- (n = 34 [46%]) and those without improved (n = 40 [54%]) MR after BAV on transthoracic echocardiography. The population had a mean age of 84 years and was more frequently female (63.5%), with a high risk profile (mean Society of Thoracic Surgeons score 15%, mean European System for Cardiac Operative Risk Evaluation score 57%). Baseline characteristics were balanced between the 2 groups. Patients with improved MR after BAV had smaller left atrial dimensions (45 ± 7 vs 49 ± 7 mm, p = 0.01) and lower peak aortic velocities (3.7 ± 0.6 vs 4.0 ± 0.8 m/s, p = 0.05) and mean transaortic valve gradients (33.2 ± 12.1 vs 40.6 ± 17.4 mm Hg, p = 0.05) at baseline. Left atrial dimension [odds ratio (OR) 3.37, p = 0.006], left ventricular end-diastolic dimension (OR 2.7, p = 0.04), and mean transaortic valve gradient (OR 1.04, p = 0.05), but not left ventricular systolic function or functional MR, were correlated with MR improvement by logistic regression analysis. In conclusion, nearly half of the patients with severe AS and coexistent MR showed improvement in the magnitude of MR after BAV. Larger left atrial and left ventricular end-diastolic dimensions and higher transaortic valve gradients were associated with lack of MR improvement.