Pallav Garg

The EVEREST II Trial: Design and rationale for a randomized study of the evalve mitraclip system compared with mitral valve surgery for mitral regurgitation

BACKGROUND Mitral valve surgery is the standard of care for patients with symptomatic mitral regurgitation (MR) or asymptomatic MR with evidence of left ventricular dysfunction or dilation. Whether an endovascular approach to repair can offer comparable effectiveness with improved safety remains to be determined in randomized trials. STUDY DESIGN The EVEREST II Trial is a multicenter, randomized controlled trial to evaluate the benefits and risks of endovascular mitral valve repair using the MitraClip device compared with open mitral valve surgery (control) in patients with moderate or severe MR. Using a 2:1 randomization ratio, the trial is enrolling up to 186 MitraClip-treated subjects and 93 control subjects. Trial end points include a primary efficacy end point: the proportion of patients free from death, surgery for valve dysfunction, and with moderate-severe (3+) or severe (4+) MR at 12 months; the primary safety end point includes the proportion of patients with death, myocardial infarction, reoperation, nonelective cardiovascular surgery, stroke, renal failure, deep would infection, ventilation >48 hours, gastrointestinal complication, new permanent atrial fibrillation, septicemia, or transfusion of >or=2 U at 30 days or hospital discharge, whichever is longer. CONCLUSIONS This randomized controlled trial is designed to evaluate the performance of endovascular mitral repair in comparison to open mitral valve surgery in patients with significant MR.

Drug-Eluting or Bare-Metal Stenting in Patients With Diabetes Mellitus Results From the Massachusetts Data Analysis Center Registry

Background— Patients with diabetes mellitus (DM) are at high risk for restenosis, myocardial infarction, and cardiac mortality after coronary stenting, and the long-term safety of drug-eluting stents (DES) relative to bare-metal stents (BMS) in DM is uncertain. We report on a large consecutive series of patients with DM followed up for 3 years after DES and BMS from a regional contemporary US practice with mandatory reporting. Methods and Results— All adults with DM undergoing percutaneous coronary intervention with stenting between April 1, 2003, and September 30, 2004, at all acute care nonfederal hospitals in Massachusetts were identified from a mandatory state database. According to index admission stent type, patients were classified as DES treated if all stents were drug eluting and as BMS treated if all stents were bare metal; patients treated with both types of stents were excluded from the primary analysis. Mortality rates were obtained from vital statistics records, and myocardial infarction and revascularization rates were obtained from the state database with complete 3 years of follow-up on the entire cohort. Risk-adjusted mortality, myocardial infarction, and revascularization differences (DES−BMS) were estimated with propensity-score matching based on clinical, procedural, hospital, and insurance information collected at the index admission. DM was present in 5051 patients (29% of the population) treated with DES or BMS during the study. Patients with DM were more likely to receive DES than BMS (66.1% versus 33.9%; P<0.001). The unadjusted cumulative incidence of mortality at 3 years was 14.4% in DES versus 22.2% in BMS (P<0.001). Based on propensity-score analysis of 1:1 matched DES versus BMS patients (1476 DES:1476 BMS), the risk-adjusted mortality, MI, and target vessel revascularization rates at 3 years were 17.5% versus 20.7% (risk difference, −3.2%; 95% confidence interval, −6.0 to −0.4; P=0.02), 13.8% versus 16.9% (−3.0%; 95% confidence interval, −5.6 to 0.5; P=0.02), and 18.4% versus 23.7% (−5.4%; confidence interval, −8.3 to −2.4; P<0.001), respectively. Conclusions— In a real-world diabetic patient population with mandatory reporting and follow-up, DES were associated with reduced mortality, myocardial infarction, and revascularization rates at long-term follow-up compared with BMS.

Lack of Association Between Migraine Headache and Patent Foramen Ovale Results of a Case-Control Study

Background— Clinical observations of migraine headache symptoms in patients with a patent foramen ovale (PFO), both of which conditions are highly prevalent, have raised the question of a possible pathophysiological relationship. We sought to evaluate the assumption of an association between migraine headaches and the presence of PFO by use of a large case-control study. Methods and Results— We conducted a case-control study to assess the prevalence of PFO in subjects with and without migraine. Case subjects were those with a history of migraine (diagnosed by neurologists at a specialty academic headache clinic). Control subjects were healthy volunteers without migraine 1:1 matched on the basis of age and sex with case subjects. Presence of PFO was determined by transthoracic echocardiogram with second harmonic imaging and transcranial Doppler ultrasonography during a standardized procedure of infused agitated saline contrast with or without Valsalva maneuver and a review of the results by experts blinded to case-control status. PFO was considered present if both studies were positive. Odds ratios were calculated with conditional logistic regression in the matched cohort (n=288). In the matched analysis, the prevalence of PFO was similar in case and control subjects (26.4% versus 25.7%; odds ratio 1.04, 95% confidence interval 0.62 to 1.74, P=0.90). There was no difference in PFO prevalence in those with migraine with aura and those without (26.8% versus 26.1%; odds ratio 1.03, 95% confidence interval 0.48 to 2.21, P=0.93). Conclusions— We found no association between migraine headaches and the presence of PFO in this large case-control study.

Balancing the Risks of Restenosis and Stent Thrombosis in Bare-Metal Versus Drug-Eluting Stents Results of a Decision Analytic Model

OBJECTIVES We sought to define what incremental risk of very late stent thrombosis (VLST) in drug-eluting stents (DES) would outweigh the restenosis benefit. BACKGROUND Although there are robust data on the restenosis benefit of DES versus bare-metal stents (BMS), the incremental risk of stent thrombosis, a rare but serious complication of percutaneous coronary intervention (PCI), is not known with certainty. METHODS We developed a decision analytic Markov model comparing DES versus BMS strategies for a contemporary PCI population. Procedure-related morbidity and mortality data from published reports were used to derive the model probabilities. Over a range of incremental risk and duration of risk of VLST, we identified the net benefit of DES versus BMS in terms of quality-adjusted life expectancy (QALE). RESULTS Under an assumption of equal stent thrombosis rates beyond 1 year, the DES strategy was superior to BMS in terms of QALE (16.262 vs. 16.248 quality-adjusted life years [QALYs], difference = 0.014). Under the alternative assumption of an incremental risk difference of 0.13%/year, the net benefit was substantially reduced (difference = 0.001 QALYs). The threshold excess risk of very late DES thrombosis compared with BMS, above which BMS would be the preferred strategy, was 0.14%/year (over 4 years of follow-up). This threshold increased as the population risk of restenosis increased and decreased as the vulnerable time window lengthened. CONCLUSIONS A small absolute increase in DES thrombosis compared with BMS after 1 year (>0.14%/year) would result in BMS being the preferred strategy for the overall PCI population. Larger clinical trials with longer follow-up are needed to estimate the risk of late stent thrombosis with greater certainty for existing and new DES.

Remote Ischemic Postconditioning During Percutaneous Coronary Interventions Remote Ischemic Postconditioning–Percutaneous Coronary Intervention Randomized Trial

Background—Remote ischemic preconditioning may result in reduction in infarct size during percutaneous coronary intervention (PCI). It is unclear whether remote ischemic postconditioning (RIPost) will reduce the incidence of myocardial injury after PCI, and whether ischemic conditioning of a larger remote organ (thigh versus arm) would provide further myocardial protection. Methods and Results—We randomized 360 patients presenting with stable or unstable angina (28% of patients) and negative Troponin T at baseline to 3 groups: 2 groups received RIPost (induced by ischemia to upper or lower limb), and a third was the control group. RIPost was applied during PCI immediately after stent deployment, by three 5-minute cycles of blood pressure cuff inflation to >200 mm Hg in the arm or thigh (20 mm Hg in the control) with 5-minute breaks between each cycle. The primary end-point was the proportion of patients with Troponin T levels >3×ULN postprocedure (at 6 or 18–24 hours), where ULN stands for upper limit of normal. A total of 120 patients were randomized to each group. There were no differences in baseline characteristics between the 3 groups. The primary outcome occurred in 30%, 35%, and 35% of the arm, thigh, and control groups, respectively (P=0.64). There were no differences in creatine kinase or high sensitivity C-reactive protein levels after PCI or in the incidence of acute kidney injury between the groups. Conclusions—RIPost during PCI did not reduce the incidence of periprocedural myocardial injury. Similar effect was obtained when remote ischemia was induced to the upper or lower limb. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00970827.

The conundrum of late and very late stent thrombosis following drug-eluting stent implantation.

Purpose of review Drug-eluting stents reduce restenosis compared with bare metal stents, but there is growing concern that drug-eluting stents may lead to higher rates of late stent thrombosis, a rare and potentially catastrophic complication following stenting. Recent findings While the data on the risk of late stent thrombosis are not definitive, several general conclusions may be drawn from the available data. Late thrombosis, while associated with high mortality and morbidity, is an uncommon complication of both drug-eluting stents and bare metal stents. Randomized trials of approved drug-eluting stents versus bare metal stents have shown additional cases of late stent thrombosis in drug-eluting stents, but no significant difference in the cumulative incidence of stent thrombosis, myocardial infarction, or cardiac death at 4 years of follow-up. Observational studies suggest higher very late stent thrombosis incidence, but the relative risks of drug-eluting stents versus bare metal stents in specific high-risk groups require further study. Although the etiology of late stent thrombosis is multifactorial, premature discontinuation of clopidogrel appears to be the most important risk factor. Summary Long-term follow-up of patients after coronary stenting has identified stent thrombosis as a rare but serious event. Ongoing clinical trials in broader patient populations will be helpful to understand the risk of late stent thrombosis with greater certainty.

European registry of carotid artery stenting: Results from a prospective registry of eight high volume EUROPEAN institutions†

Carotid endarterectomy (CEA) is the standard revascularization therapy to prevent stroke in patients with carotid artery disease. Carotid artery stenting (CAS) could be considered a potential alternative in patients at high surgical risk. Recent clinical trials have challenged this concept due a relatively high incidence of post‐CAS adverse events, which occurred in low volume centers. The aim of this study was to evaluate the outcomes associated with neuroprotected CAS in selected high volume centers.

Impact of Moderate Renal Insufficiency on Restenosis and Adverse Clinical Events After Sirolimus-Eluting and Bare Metal Stent Implantation (from the SIRIUS Trials)

Whether drug-eluting stents are effective and safe in patients with moderate renal insufficiency (RI) is unknown. We performed a pooled analysis of data from 3 blinded randomized trials of sirolimus-eluting stents (SESs) versus bare metal stents (BMSs; SIRIUS, C-SIRIUS, E-SIRIUS) that included 1,510 patients. Clinical and angiographic outcomes were stratified by the presence of RI defined by creatinine clearance calculated by the Cockcroft-Gault formula (normal ≥ 90, mild 60 to 89, moderate < 60 ml/min). Patients with baseline creatinine > 3.0 mg/dl were excluded from these trials. Baseline mild RI was present in 517 patients (34.7%, mean creatinine clearance 75.7 ml/min) and moderate RI in 228 patients (15.3%, mean creatinine clearance 47.2 ml/min). Treatment with SESs resulted in lower rates of 8-month angiographic restenosis rates in patients with RI (mild RI 6.7% vs 42.6%, p < 0.001; moderate RI 9.7% vs 39.7%, p < 0.001) and without baseline RI (7.7% vs 37.2%, p < 0.001). One-year target vessel revascularization rates were similarly decreased with SESs in patients with (mild RI 4.7% vs 24.2%, p < 0.001; moderate RI 5.5% vs 26.9%, p < 0.001) and without (8.1% vs 22.4%, p < 0.001) RI, and this benefit was maintained at 5 years. Compared to patients with normal or mild RI, patients with moderate RI had higher rates of overall mortality and cardiac death at 1 year and 5 years (death 2.6% vs 0.6%, p <0.01, and 17.5% vs 6.3%, p < 0.01, at 1 year and 5 years, respectively; cardiac death 1.3% vs 0.2%, p = 0.05, and 6.6% vs 3.4%, p = 0.04, at 1 year and 5 years, respectively). However, there was no differential effect of SESs versus BMSs on any safety end point. In conclusion, patients with moderate RI have a nearly threefold increase in 5-year mortality after percutaneous coronary intervention compared to patients without RI. The effectiveness of SESs in decreasing restenosis compared to BMSs in patients with moderate RI was preserved and rates of death and myocardial infarction were not adversely affected.

Balancing the risks of bleeding and stent thrombosis: A decision analytic model to compare durations of dual antiplatelet therapy after drug-eluting stents

BACKGROUND After coronary stent placement, whether dual antiplatelet therapy (DAPT) duration should be extended to prevent late stent thrombosis (ST) or adverse cardiovascular events is uncertain. METHODS To define the reduction in ischemic events required to outweigh increased bleeding with longer-duration DAPT, we developed a decision-analytic Markov model comparing DAPT durations of 6, 12, and 30 months after DES. Separate models were developed for patients presenting with and without an acute coronary syndrome (ACS). We used sensitivity analyses to identify the incremental benefit of longer-duration DAPT on either ST or the composite of cardiac death, myocardial infarction, and ischemic stroke (major adverse cardiovascular and cerebrovascular events [MACCEs]) required to outweigh the increased risk of bleeding associated with longer DAPT. The outcome from each strategy was quantified in terms of quality-adjusted life years. RESULTS In the non-ACS population, in order for 30 months of DAPT to be preferred over 12 months of therapy, DAPT would have to result in a 78% reduction in the risk of ST (relative risk [RR] 0.22, 3.1 fewer events per 1000) and only a 5% reduction in MACCE (RR 0.95, 2.2 fewer events per 1000) as compared with aspirin alone. For the ACS population, DAPT would have to result in a 44% reduction in the risk of ST (RR 0.56, 3.4 fewer events per 1000) but only a 2% reduction in MACCE (RR 0.98, 2.3 fewer events per 1000) as compared with aspirin alone, for 30 months of DAPT to be preferred for 12 months. CONCLUSIONS Small absolute differences in the risk of ischemic events with longer DAPT would be sufficient to outweigh the known bleeding risks.

Resolution of Iatrogenic Aortic Dissection Illustrated by Computed Tomography

An 83-year-old man with known history of known coronary artery disease (prior coronary artery bypass surgery and percutaneous coronary intervention), hypertension, and hypercholesterolemia presented with ongoing exertional angina and dyspnea despite medical therapy. A dipyridamole rubidium-82 stress test showed moderate-sized ischemia in the inferior and inferolateral territory. An echocardiogram showed mild segmental left ventricular dysfunction with an ejection fraction of 45% and mild mitral regurgitation. Angiography showed severe native triple vessel disease, patent left internal mammary artery graft to left anterior descending artery, patent stents in saphenous vein graft to obtuse marginal, and occluded vein graft to right coronary artery (RCA; previously known to be occluded). The native RCA was diffusely diseased with subtotal occlusions in its mid and distal segments including severe proximal posterior descending artery disease and was partly collateralized from obtuse marginal (Figure 1A). Given the ongoing symptoms on medical therapy, decision was made to proceed with percutaneous coronary intervention to RCA. Figure 1. RCA angiographic appearance: preprocedure (A), contrast in the false lumen of the aortic root dissection originating from RCA ostium (image at the time of ostial stent deployment) (B), and final angiographic appearance (C). The RCA ostium was engaged with an 8F Amplatz (AL 0.75) guide (chosen for extra support in a calcified, diffusely diseased artery), and the total occlusions in the mid and distal RCA were crossed using a PT Graphix guide wire (Boston Scientific, Natick, Mass). Rotational atherectomy with 1.50-mm burr was performed to …