[show abstract][hide abstract] ABSTRACT: Aims: We sought to assess if bivalirudin use during balloon aortic valvuloplasty (BAV) would affect clinical outcomes compared with heparin. Methods and results: We compared the outcomes of consecutive patients who underwent elective or urgent BAV with intraprocedural use of bivalirudin or heparin at two high-volume centres. All in-hospital events post BAV were adjudicated by an independent, blinded clinical events committee. Of 427 patients, 223 patients (52.2%) received bivalirudin and 204 (47.8%) received heparin. Compared with patients who received heparin, patients who received bivalirudin had significantly less major bleeding (4.9% vs. 13.2%, p=0.003). Net adverse clinical events (NACE, major bleeding or major adverse cardiovascular events [MACE]) were also reduced (11.2% vs. 20.1%, p=0.01). There was no significant difference in the rates of MACE (mortality, myocardial infarction or stroke, 6.7% vs. 11.3%, p=0.1), or vascular complications (major, 2.7% vs. 2.0%; minor, 4.5% vs. 4.9%; p=0.83). After multivariate analysis controlling for vascular preclosure, the use of bivalirudin remained independently associated with reduced major bleeding (OR 0.37; 95% CI: 0.16 to 0.84; p=0.02) while the association was attenuated in propensity-adjusted analysis (OR 0.44, 95% CI: 0.18 to 1.07, p=0.08). Conclusions: In this registry of patients with severe aortic stenosis, bivalirudin as compared to heparin resulted in improved in-hospital outcomes post BAV in terms of reduced major bleeding, similar MACE and reduced NACE. If verified in a randomised study and extended to the transcatheter aortic valve implantation (TAVI) population, these results might indicate a potential benefit for patients undergoing such procedures.
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 11/2013; · 3.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Introduction:Generic clopidogrel recently became available in the United States and was rapidly adopted as a cost-effective alternative to the brand name formulation. However, unlike other medications, subtle differences in clopidogrel bioavailability may lead to acute consequences including stent thrombosis (ST).Materials and METHODS: We studied the incidence of acute and subacute ST during the initial period of generic clopidogrel use (June 18, 2012-September 6, 2012 [80 days]) at a single percutaneous coronary intervention (PCI) center. There were 4 definite ST cases within 30 days of successful PCI in patients receiving generic clopidogrel, which were compared to historic control ST cases from 80 days prior to generic clopidogrel use and for 3 years from June 18, 2009 to June 17, 2012.
During generic clopidogrel administration, 1054 PCIs were performed, giving a definite 30-day ST incidence of 0.38% (4 of 1054) among these patients. By comparison, there were 2 episodes of definite 30-day ST during the 80 days immediately preceding generic clopidogrel use (2 of 1114), while 3-year historic data indicated a definite 30-day ST incidence of 0.14% (20 of 14 432), representing a 2.7-fold increase in definite 30-day ST with generic clopidogrel use (P = .076). Exclusion of 3 historic controls with a defined reason for ST (noncompliance, marked thrombocytosis) gave a 3.2-fold increase in 30-day ST with generic clopidogrel (P = .050). An ST-predictive algorithm revealed no difference in the likelihood of ST between patients receiving generic clopidogrel and historic controls.
We observed an unexpected >2-fold increase in ST coincident with generic clopidogrel use. Although we cannot ascribe causality, this observation warrants increased vigilance and close monitoring of patients receiving generic clopidogrel.
Journal of Cardiovascular Pharmacology and Therapeutics 11/2013; · 2.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: This article presents an overview of the evolution of cardiac critical care in the past half century. It tracks the rapid advances in the management of cardiovascular disease and how the intensive care area has kept pace, improving outcomes and incorporating successive innovations. The current multidisciplinary, evidence based unit is vastly different from the early days and is expected to evolve further in keeping with the concept of 'hybrid' care areas where care is delivered by the 'heart team'.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: RE-ENDOTHELIALIZATION IS DELAYED AFTER DRUG-ELUTING STENT (DES) IMPLANTATION. IN THIS SETTING, NEOINTIMA IS MORE PRONE TO BECOME LIPID LADEN AND DEVELOP NEOATHEROSCLEROSIS (NA), POTENTIALLY INCREASING PLAQUE VULNERABILITY.METHODS AND RESULTS: OPTICAL COHERENCE TOMOGRAPHY AND NEAR-INFRARED SPECTROSCOPY WITH INTRAVASCULAR ULTRASOUND WERE USED TO CHARACTERIZE NA IN 65 (51 DES AND 14 BARE-METAL STENTS) CONSECUTIVE SYMPTOMATIC PATIENTS WITH IN-STENT RESTENOSIS. MEDIAN DURATION POSTSTENT IMPLANTATION WAS 33 MONTHS. OPTICAL COHERENCE TOMOGRAPHYVERIFIED NA WAS OBSERVED IN 40 STENTS WITH IN-STENT RESTENOSIS (62%), WAS MORE PREVALENT IN DES THAN BARE-METAL STENTS (68% VERSUS 36%; P=0.02), AND DEMONSTRATED SIGNIFICANTLY HIGHER PREVALENCE OF THIN-CAP NEOATHEROMA (47% VERSUS 7%; P=0.01) IN DES. NEAR-INFRARED SPECTROSCOPY ASSESSMENT DEMONSTRATED THAT THE TOTAL LIPID CORE BURDEN INDEX (34 [INTERQUARTILE RANGE, 1292] VERSUS 9 [INTERQUARTILE RANGE, 032]; P0.001) AND THE DENSITY OF LIPID CORE BURDEN INDEX (LIPID CORE BURDEN INDEX/4 MM, 144 [INTERQUARTILE RANGE, 60285] VERSUS 26 [INTERQUARTILE RANGE, 086]; P0.001) WERE HIGHER IN DES COMPARED WITH BARE-METAL STENTS. TOPOGRAPHICALLY, NA WAS CLASSIFIED AS I (THIN-CAP NA), II (THICK-CAP NA), AND III (PERI-STRUT NA). TYPE I THIN-CAP NEOATHEROMA WAS MORE COMMON IN DES (20% VERSUS 3%; P=0.01) AND IN AREAS OF THE STENTED SEGMENT WITHOUT SIGNIFICANT IN-STENT RESTENOSIS (71%). PERIPROCEDURAL MYOCARDIAL INFARCTION OCCURRED ONLY IN DES (11 VERSUS 0; P =0.05), OF WHICH 6 (55%) COULD BE ATTRIBUTED TO SEGMENTS WITH 70% IN-STENT RESTENOSIS. BY LOGISTIC REGRESSION, PRIOR DES WAS THE ONLY INDEPENDENT PREDICTOR OF BOTH NA (ODDS RATIO, 7.0; 95% CONFIDENCE INTERVAL, 1.727; P=0.006) AND PERIPROCEDURAL MYOCARDIAL INFARCTION (ODDS RATIO, 1.8; 95% CONFIDENCE INTERVAL, 1.12.4; P=0.05).CONCLUSIONS: In-stent thin-cap neoatheroma is more prevalent, is distributed more diffusely across the stented segment, and is associated with increased periprocedural myocardial infarction in DES compared with bare-metal stents. These findings support NA as a mechanism for late DES failure.
[show abstract][hide abstract] ABSTRACT: Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between different modes of DAPT cessation and cardiovascular risk after PCI.
The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecified categories for DAPT cessation included physician-recommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the effect of DAPT cessation on major adverse events (MACE [composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the first event. This study is registered with ClinicalTrials.gov, number NCT00998127.
We enrolled 5031 patients undergoing PCI, including 5018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57·3%. Rate of any discontinuation was 40·8%, of interruption was 10·5%, and of disruption was 14·4%. The corresponding overall 2 year MACE rate was 11·5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1·41 (95% CI 0·94-2·12; p=0·10) and to disruption was 1·50 (1·14-1.97; p=0·004). Within 7 days, 8-30 days, and more than 30 days after disruption, adjusted HRs were 7·04 (3·31-14·95), 2·17 (0·97-4·88), and 1·3 (0·97-1·76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0·63 [0·46-0·86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation.
In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type.
Bristol-Myers Squibb and Sanofi-Aventis.
[show abstract][hide abstract] ABSTRACT: Calcific aortic stenosis (AS) is the most frequent expression of aortic valve disease in the Western world, with an increasing prevalence as the population ages. Almost 4% of all adults 75 years of age or older have moderate or severe AS. Many patients do not undergo surgery because of prohibitive comorbidities or other high-risk features. Balloon aortic valvuloplasty (BAV) remains an option for temporary palliation and symptomatic relief in such patients. In addition, BAV continues to serve an important role as a bridge to either surgical or transcatheter aortic valve replacement in certain patients with AS requiring temporary hemodynamic stabilization.
[show abstract][hide abstract] ABSTRACT: To investigate the use of the GuideLiner "mother-and-child" guide catheter extension system as a simple solution to facilitate initial device delivery in balloon uncrossable chronic total occlusions (CTOs) undergoing percutaneous coronary intervention (PCI).
During PCIs for CTO lesions, an important reason for procedural failure is the inability to deliver a balloon or microcatheter across the lesion.
We retrospectively accessed our interventional registry for 07/01/2010 to 03/21/2012 and extracted data on all CTO lesions involving GuideLiner catheter use. Cine review was performed to identify cases where a guidewire had crossed the CTO and the use of a GuideLiner catheter facilitated initial device delivery.
We identified 28 patients that underwent PCI for CTO with a GuideLiner catheter used to assist initial balloon or microcatheter advancement across the culprit lesion. Mean overall CTO length was 26.3 ± 18.1 mm. The GuideLiner catheter was successful in delivering a small balloon to the CTO lesion in 85.7% of cases (24/28). A single CTO PCI resulted in a distal guidewire perforation, but there was no hemodynamic compromise or pericardial effusion and the patient was discharged the next day. Overall procedural success in these selected cases (where a guidewire had already crossed the CTO) was 89.3% (25/28).
The GuideLiner mother-and-child catheter is a simple, safe and efficacious adjunctive device for difficult CTO PCIs where despite standard measures it is not possible to deliver an initial balloon or microcatheter across the occluded segment.
Journal of Interventional Cardiology 08/2013; 26(4):343-50. · 1.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study sought to describe near-infrared spectroscopy (NIRS) findings of culprit lesions in ST-segment elevation myocardial infarction (STEMI).
Although autopsy studies demonstrate that most STEMI are caused by rupture of pre-existing lipid core plaque (LCP), it has not been possible to identify LCP in vivo. A novel intracoronary NIRS catheter has made it possible to detect LCP in patients.
We performed NIRS within the culprit vessels of 20 patients with acute STEMI and compared the STEMI culprit findings to findings in nonculprit segments of the artery and to findings in autopsy control segments. Culprit and control segments were analyzed for the maximum lipid core burden index in a 4-mm length of artery (maxLCBI4mm).
MaxLCBI4mm was 5.8-fold higher in STEMI culprit segments than in 87 nonculprit segments of the STEMI culprit vessel (median [interquartile range (IQR)]: 523 [445, 821] vs. 90 [6, 265]; p < 0.001) and 87-fold higher than in 279 coronary autopsy segments free of large LCP by histology (median [IQR]: 523 [445, 821] vs. 6 [0, 88]; p < 0.001).Within the STEMI culprit artery, NIRS accurately distinguished culprit from nonculprit segments (receiver-operating characteristic analysis area under the curve = 0.90). A threshold of maxLCBI4mm >400 distinguished STEMI culprit segments from specimens free of large LCP by histology (sensitivity: 85%, specificity: 98%).
The present study has demonstrated in vivo that a maxLCBI4mm >400, as detected by NIRS, is a signature of plaques causing STEMI.
[show abstract][hide abstract] ABSTRACT: Despite the exponential growth in medical knowledge, cardiovascular diseases (CVDs) contribute to more than one-third of worldwide morbidity and mortality. A range of therapies already exist for established CVDs, although there is significant interest in further understanding their pathogenesis. The urocortins (Ucns) are peptide members of the corticotrophin-releasing factor family, a group of evolutionary conserved peptides with homologues in fish, amphibians and mammals and considered to play a pivotal role in energy homeostasis and local tissue repair. A number of preclinical studies in vitro, in-vivo and ex-vivo have defined a multifaceted effect of Ucns on the cardiovascular system. Different G-protein coupled signaling and protein-kinase pathways have been shown to be activated by Ucns, together with different transcriptional and translational effects, all of which preferentially converge on the mitochondria, where the modulation of apoptosis is considered their principal action. It has been demonstrated in experimental models, and consequentially suggested in human diseases, that Ucn-mediated inhibition of apoptosis can be exploited for the improvement of both therapeutic and preventative strategies against CVDs. Specifically, some unavoidable iatrogenic ischemia/reperfusion (I/R) injuries, e.g. during cardiac surgery or percutaneous coronary angioplasty, may greatly benefit from the anti-apoptotic effect of Ucns. However, few studies on the topic have been employed in humans to date. Therefore, this review will focus on the different intra-cellular mechanisms of action of Urocortins, and detail the different Ucn-mediated pathways identified so far. It will also highlight the limited evidence already existing in human clinical and surgical settings, as well as emphasize the potential uses of Ucns in human cardiac pathology.
Cardiovascular Drugs and Therapy 07/2013; · 2.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objectives This study sought to determine the impact of short-term intensive statin therapy on intracoronary plaque lipid content.Background Statin therapy significantly reduces the risk for thrombotic events. Whether or not these benefits are attributable to reduction in plaque lipid content remains to be properly documented in human obstructive coronary artery disease (CAD).Methods We randomized 87 patients with multivessel CAD undergoing percutaneous coronary intervention and at least 1 other severely obstructive (fractional flow reserve [FFR] ≤0.8) nontarget lesion (NTL) to intensive (rosuvastatin 40 mg daily) or standard-of-care lipid-lowering therapy. NTLs were evaluated at baseline and after 7 weeks of therapy with FFR, near-infrared spectroscopy, and intravascular ultrasound. The primary endpoint was the change in lipid-core burden index at the 4-mm maximal segment (LCBI4mm max), wherever this occurred within the lesion.Results Upon follow-up, median reduction (95% confidence interval) in LCBI4mm max was significantly greater in the intensive versus standard group (−149.1 [−210.9 to −42.9] vs. 2.4 [−36.1 to 44.7]; p = 0.01). Results remained consistent after adjustment for baseline differences in LCBI between groups and use of change in LCBI across the entire lesion as the dependent outcome.Conclusions Short-term intensive statin therapy may reduce lipid content in obstructive lesions. These hypothesis-generating findings warrant confirmation in larger studies with longer follow-up. (Reduction in YEllow Plaque by Aggressive Lipid LOWering Therapy [YELLOW]); NCT01567826)
Journal of the American College of Cardiology 07/2013; 62(1):21-29. · 14.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naïve patients undergoing percutaneous coronary intervention (PCI). Platelet function tests were performed 4-6 hours after loading with 600 mg of clopidogrel. Platelet reactivity was assessed using the VerifyNow system and expressed as P2Y12 reaction units (PRU). High residual platelet reactivity (HRPR) was defined as PRU > 230. Patients were categorised into four groups by the presence or absence of CKD and DM. Among those without CKD or DM (n=166), DM alone (n=150), CKD alone (n=60) and both CKD and DM (n=62) the mean PRU levels were 201.6 ± 96.3, 220.5 ± 101.1, 254.9 ± 106.7 and 275.0 ± 94.5, respectively (p<0.001). Analogously, the prevalence of HRPR was 42.3%, 50.7%, 63.3% and 75.8%, respectively (p< 0.001). Associations between either CKD or DM alone and HRPR were attenuated after multivariable adjustment while the odds for HRPR associated with both CKD and DM remained significant (OR [95% CI]: 2.61 [1.16 - 5.86]). In conclusion, the presence of both CKD and DM confers a synergistic impact on residual platelet reactivity when compared to either condition alone. Whether more potent platelet inhibitors may improve outcomes among patients with both abnormalities warrants investigation.
Thrombosis and Haemostasis 05/2013; 110(1). · 6.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: The risk of rupture of a left ventricular (LV) pseudoaneurysm ranges from 30% to 45% in the first year. Open surgical repair carries high mortality related to anatomic complexity and patient comorbidities. Percutaneous closure may offer a viable alternative to surgical intervention in this cohort. Herein, we describe 3 unique cases of transcatheter LV pseudoaneurysm closure.
The Annals of thoracic surgery 11/2012; 94(5):e123-5. · 3.74 Impact Factor