High-speed rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial

OBJECTIVES This study sought to determine the effect of rotational atherectomy (RA) on drug-eluting stent (DES) effectiveness. BACKGROUND DES are frequently used in complex lesions, including calcified stenoses, which may challenge DES delivery, expansion, and effectiveness. RA can adequately modify calcified plaques and facilitate stent delivery and expansion. Its impact on DES effectiveness is widely unknown. METHODS The ROTAXUS (Rotational Atherectomy Prior to TAXUS Stent Treatment for Complex Native Coronary Artery Disease) study randomly assigned 240 patients with complex calcified native coronary lesions to RA followed by stenting (n = 120) or stenting without RA (n = 120, standard therapy group). Stenting was performed using a polymer-based slow-release paclitaxel-eluting stent. The primary endpoint was in-stent late lumen loss at 9 months. Secondary endpoints included angiographic and strategy success, binary restenosis, definite stent thrombosis, and major adverse cardiac events at 9 months. RESULTS Despite similar baseline characteristics, significantly more patients in the standard therapy group were crossed over (12.5% vs. 4.2%, p = 0.02), resulting in higher strategy success in the rotablation group (92.5% vs. 83.3%, p = 0.03). At 9 months, in-stent late lumen loss was higher in the rotablation group (0.44 ± 0.58 vs. 0.31 ± 0.52, p = 0.04), despite an initially higher acute lumen gain (1.56 ± 0.43 vs. 1.44 ± 0.49 mm, p = 0.01). In-stent binary restenosis (11.4% vs. 10.6%, p = 0.71), target lesion revascularization (11.7% vs. 12.5%, p = 0.84), definite stent thrombosis (0.8% vs. 0%, p = 1.0), and major adverse cardiac events (24.2% vs. 28.3%, p = 0.46) were similar in both groups. CONCLUSIONS Routine lesion preparation using RA did not reduce late lumen loss of DES at 9 months. Balloon dilation with only provisional rotablation remains the default strategy for complex calcified lesions before DES implantation.

Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: insights from the PLATelet inhibition and patient outcomes (PLATO) trial

BACKGROUND Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. METHODS Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. RESULTS Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P(interaction) = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P(interaction) = .46) prior CABG. CONCLUSIONS Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

Reversible cerebral vasoconstriction syndrome and cervical artery dissection in 20 patients

OBJECTIVES To describe clinical-radiologic characteristics in a prospective series of patients having both confirmed reversible cerebral vasoconstriction syndrome (RCVS) and cervical artery dissection (CeAD). METHODS From January 2004 to December 2011, from our prospective cohorts of RCVS and CeAD, we studied patients with both conditions. RESULTS Of 173 RCVS cases and 285 CeAD cases, 20 patients (18 women, 2 men; mean age 41 years) had both RCVS and CeAD. Main associated conditions were migraine (12/20) and postpartum (5/18). Clinical features included severe headache in all patients, neck pain in 15, focal neurologic deficit in 9, and seizures in 4. Pain was the only symptom in 10 patients. All patients had multifocal cerebral vasoconstriction. There were brain lesions in 12 patients, cortical subarachnoid hemorrhage in 11, posterior reversible encephalopathy syndrome in 4, intracerebral hemorrhage in 3, and infarcts in 4. CeAD involved one artery in 13 patients and multiple arteries in 7. CeAD mostly affected vertebral arteries (25 of 30 CeAD). Only one vertebral CeAD was associated with a related symptomatic infarct. At 3 months, 18 patients had fully recovered, all patients showed reversal of cerebral vasoconstriction, and 21 dissected arteries had normalized, whereas 9 arteries showed residual stenosis (7) and/or aneurysm (3). CONCLUSION The association of RCVS and CeAD was found in 12% of our patients with RCVS and 7% of our patients with CeAD. Underlying mechanisms are unknown. In practice, our results point to the need for a systematic study of both cervical and intracranial arteries in the 2 conditions.

Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis

OBJECTIVE To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE All cause mortality. RESULTS 100 trials in 93 553 patients with 262 090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.

Function of Natural Internal Mammary-to-Coronary Artery Bypasses and Its Effect on Myocardial Ischemia.

BACKGROUND The function of naturally existing internal mammary (IMA)-to-coronary artery bypasses and their quantitative effect on myocardial ischemia are unknown. METHODS AND RESULTS The primary end point of this study was collateral flow index (CFI) obtained during two 1-minute coronary artery balloon occlusions, the first with and the second without simultaneous distal IMA occlusion. The secondary study end point was the quantitatively determined intracoronary ECG ST-segment elevation. CFI is the ratio of simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. A total of 180 pairs of CFI measurements were performed among 120 patients. With and without IMA occlusion, CFI was 0.110±0.074 and 0.096±0.072, respectively (P<0.0001). The difference of CFI obtained in the presence minus CFI obtained in the absence of IMA occlusion was highest and most consistently positive during left IMA with left anterior descending artery occlusion and during right IMA with right coronary artery occlusion (ipsilateral occlusions): 0.033±0.044 and 0.025±0.027, respectively. This CFI difference was absent during right IMA with left anterior descending artery occlusion and during left IMA with right coronary artery occlusion (contralateral occlusions): -0.007±0.034 and 0.001±0.023, respectively (P=0.0002 versus ipsilateral occlusions). The respective CFI differences during either IMA with left circumflex artery occlusion were inconsistently positive. Intracoronary ECG ST-segment elevations were significantly reduced during ipsilateral IMA occlusions but not during contralateral or left circumflex artery occlusions. CONCLUSION There is a functional, ischemia-reducing extracardiac coronary artery supply via ipsilateral but not via contralateral natural IMA bypasses. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCTO1676207.

Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry

AIMS Due to a high burden of systemic cardiovascular events, current guidelines recommend the use of statins in all patients with peripheral artery disease (PAD). We sought to study the impact of statin use on limb prognosis in patients with symptomatic PAD enrolled in the international REACH registry. METHODS Statin use was assessed at study enrolment, as well as a time-varying covariate. Rates of the primary adverse limb outcome (worsening claudication/new episode of critical limb ischaemia, new percutaneous/surgical revascularization, or amputation) at 4 years and the composite of cardiovascular death/myocardial infarction/stroke were compared among statin users vs. non-users. RESULTS A total of 5861 patients with symptomatic PAD were included. Statin use at baseline was 62.2%. Patients who were on statins had a significantly lower risk of the primary adverse limb outcome at 4 years when compared with those who were not taking statins [22.0 vs. 26.2%; hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.72-0.92; P = 0.0013]. Results were similar when statin use was considered as a time-dependent variable (P = 0.018) and on propensity analysis (P < 0.0001). The composite of cardiovascular death/myocardial infarction/stroke was similarly reduced (HR, 0.83; 95% CI, 0.73-0.96; P = 0.01). CONCLUSION Among patients with PAD in the REACH registry, statin use was associated with an ∼18% lower rate of adverse limb outcomes, including worsening symptoms, peripheral revascularization, and ischaemic amputations. These findings suggest that statin therapy not only reduces the risk of adverse cardiovascular events, but also favourably affects limb prognosis in patients with PAD.

Fractional Flow Reserve–Guided PCI for Stable Coronary Artery Disease

Background We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy. Methods In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years. Results The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P=0.01). In a landmark analysis, the rate of death or myocardial infection from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P=0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years. Conclusions In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone. (Funded by St. Jude Medical; FAME 2 ClinicalTrials.gov number, NCT01132495 .).

Evaluation of an esophageal Doppler probe for the identification of experimental pseudo-electromechanical dissociation: a preliminary study

STUDY OBJECTIVE To determine the effectiveness of an esophageal doppler device to non-invasively detect experimental pseudo-electromechanical dissociation (pseudo-EMD). DESIGN Prospective, controlled, laboratory investigation using an asphyxial canine cardiac arrest model and a newly-developed esophageal flat-flow probe doppler unit. INTERVENTIONS Mongrel dogs (20) were instrumented for hemodynamic monitoring. The esophageal doppler probe was placed in the distal esophagus of each animal. Electromechanical dissociation (EMD) was induced by clamping the endotracheal tube. MEASUREMENTS AND MAIN RESULTS A period of pseudo-EMD was defined as the time where cardiac contractility was present, measured by a micromanometer tipped thoracic aortic catheter, without concurrent femoral pulses by palpation. The pseudo-EMD period could be produced consistently in all 20 animals. The characteristic doppler flow sounds were easily heard using the esophageal device in all animals. The time from endotracheal tube clamping until loss of femoral pulses was 622 +/- 96 s; until loss of radial artery doppler signals was 616 +/- 92 s; until loss of esophageal doppler signals was 728 +/- 88 s; and until loss of aortic fluctuations by thoracic aortic catheter was 728 +/- 82 s. The times to loss of esophageal doppler sounds and loss of aortic fluctuations were not significantly different. However, they were significantly longer than the time to loss of femoral pulses (P < 0.02). CONCLUSIONS The canine asphyxial EMD model can be used for short experimental studies of pseudo-EMD. Pseudo-EMD can be consistently and non-invasively detected with this esophageal doppler device. The device is as reliable as a micromanometer tipped aortic arch catheter in detecting pseudo-EMD. The doppler device could potentially be useful in improving recognition of near cardiac arrest in pre-hospital and emergency department settings. Further research on the utility of this device in other models of low-flow states should be performed.

Outcome of patients with occlusions of the internal carotid artery or the main stem of the middle cerebral artery with NIHSS score of less than 5: comparison between thrombolysed and non-thrombolysed patients

BACKGROUND AND PURPOSE The use of thrombolysis in patients with minor neurological deficits and large vessel occlusion is controversial. METHODS We compared the outcome of patients with low National Institutes of Health Stroke Scale (NIHSS) scores and large vessel occlusions between thrombolysed and non-thrombolysed patients. RESULTS 88 (1.7%) of 5312 consecutive patients with acute (within 24 h) ischaemic stroke had occlusions of the internal carotid or the main stem of the middle cerebral artery and baseline NIHSS scores ≤5.47 (53.4%) were treated without thrombolysis, and 41 (46.6%) received intravenous thrombolysis, endovascular therapy or both. Successful recanalisation on MR or CT angiography at 24 h was more often observed in thrombolysed than in non-thrombolysed patients (78.9% versus 10.5%; p<0.001). Neurological deterioration (increase of NIHSS score ≥1 compared to baseline) was observed in 22.7% of non-thrombolysed versus 10.3% of thrombolysed after 24 h (p=0.002), in 33.3% versus 12.5% at hospital discharge (p=0.015) and in 41.4% versus 15% at 3 months (p<0.001). Symptomatic intracerebral haemorrhage occurred in two (asymptomatic in five) thrombolysed and in none (asymptomatic in three) non-thrombolysed. Thrombolysis was an independent predictor of favourable outcome (p=0.030) but not survival (p=0.606) at 3 months. CONCLUSIONS Non-thrombolysed patients with mild deficits and large vessel occlusion deteriorated significantly more often within 3 months than thrombolysed patients. Symptomatic intracerebral haemorrhages occurred in less than 5% of patients in both groups. These data suggest that thrombolysis is safe and effective in these patients. Therefore, randomised trials in patients with large vessel occlusions and mild or rapidly improving symptoms are needed.

Familial occurrence and heritable connective tissue disorders in cervical artery dissection

OBJECTIVE In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders. METHODS We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups. RESULTS Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%-1.5%) from 17 families (0.9%, 0.5%-1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only. CONCLUSIONS In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases.