Johan Bennett

Ultrathin, bioresorbable polymer sirolimus-eluting stents versus thin, durable polymer everolimus-eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial

BACKGROUND The development of coronary drug-eluting stents has included use of new metal alloys, changes in stent architecture, and use of bioresorbable polymers. Whether these advancements improve clinical safety and efficacy has not been shown in previous randomised trials. We aimed to examine the clinical outcomes of a bioresorbable polymer sirolimus-eluting stent compared with a durable polymer everolimus-eluting stent in a broad patient population undergoing percutaneous coronary intervention. METHODS BIOFLOW V was an international, randomised trial done in patients undergoing elective and urgent percutaneous coronary intervention in 90 hospitals in 13 countries (Australia, Belgium, Canada, Denmark, Germany, Hungary, Israel, the Netherlands, New Zealand, South Korea, Spain, Switzerland, and the USA). Eligible patients were those aged 18 years or older with ischaemic heart disease undergoing planned stent implantation in de-novo, native coronary lesions. Patients were randomly assigned (2:1) to either an ultrathin strut (60 μm) bioresorbable polymer sirolimus-eluting stent or to a durable polymer everolimus-eluting stent. Randomisation was via a central web-based data capture system (mixed blocks of 3 and 6), and stratified by study site. The primary endpoint was 12-month target lesion failure. The primary non-inferiority comparison combined these data from two additional randomised trials of bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent with Bayesian methods. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02389946. FINDINGS Between May 8, 2015, and March 31, 2016, 4772 patients were recruited into the study. 1334 patients met inclusion criteria and were randomly assigned to treatment with bioresorbable polymer sirolimus-eluting stents (n=884) or durable polymer everolimus-eluting stents (n=450). 52 (6%) of 883 patients in the bioresorbable polymer sirolimus-eluting stent group and 41 (10%) of 427 patients in the durable polymer everolimus-eluting stent group met the 12-month primary endpoint of target lesion failure (95% CI -6·84 to -0·29, p=0·0399), with differences in target vessel myocardial infarction (39 [5%] of 831 patients vs 35 [8%] of 424 patients, p=0·0155). The posterior probability that the bioresorbable polymer sirolimus-eluting stent is non-inferior to the durable polymer everolimus-eluting stent was 100% (Bayesian analysis, difference in target lesion failure frequency -2·6% [95% credible interval -5·5 to 0·1], non-inferiority margin 3·85%, n=2208). INTERPRETATION The outperformance of the ultrathin, bioresorbable polymer sirolimus-eluting stent over the durable polymer everolimus-eluting stent in a complex patient population undergoing percutaneous coronary intervention suggests a new direction in improving next generation drug-eluting stent technology. FUNDING BIOTRONIK.

Time course of electrocardiographic changes in transient left ventricular ballooning syndrome.

BACKGROUND We sought to describe, for the first time, in detail the time course of electrocardiographic (ECG) changes in transient left ventricular ballooning syndrome (TLVBS) from acute onset until 1 year after presentation. METHODS The serial ECGs of all patients identified with TLVBS who presented to our cardiology department from August 1998 to August 2012 were analyzed, from admission to 1-year follow-up, with respect to time from onset of symptoms. RESULTS In total, 145 TLVBS episodes were identified in 139 patients. In 53% of patients, ST segment elevation was present in the first 3h after symptom onset, after which there was a steady decline with complete resolution in all patients by 1 month. The presence of T wave inversion (TWI), with or without ST segment depression, was most prevalent between day 1 (60%) and day 30 (71%) from symptom onset, with 17% of patients still exhibiting TWI after 6 to 12 months. At 1 year, approximately 80% of patients had no significant residual ST-T wave changes. In 86% of patients, there was prolongation of the corrected QT (QTc) interval in the acute phase, with normalization of all QTc intervals by day 14. CONCLUSIONS During the early phase, ECG mimics acute ST elevation myocardial infarction with initial regional ST segment elevation progressing to T wave inversion with or without ST depression. In the majority of patients, significant QTc interval prolongation occurs in the early phase, normalizing by day 14.

Healing course of acute vessel wall injury after drug-eluting stent implantation assessed by optical coherence tomography

BACKGROUND Vessel wall injury after drug-eluting stent (DES) implantation can be characterized in detail by optical coherence tomography (OCT). Little is known about the healing course of these phenomena. METHODS AND RESULTS In 62 lesions (62 patients), the incidence of acute vessel trauma was assessed in the stented region and the edge segments immediately after DES implantation. The healing course of these injuries was assessed at 9-month OCT follow-up using a software algorithm allowing for reliable spatial comparison of baseline and follow-up cross-sectional images. Tissue prolapse (TP) and tissue protrusions were detected in 81 and 35% of lesions, respectively. A total of 342 intra-stent dissection flaps (ISD) and 114 intra-stent dissection cavities (ISC) were visualized in 98 and 81% of lesions, respectively. Thirty-five lesions (56%) showed edge dissections (EDs). No residual TP or protrusion was observed at follow-up. Incomplete healing was seen in 8% of ISD and in 20% of ISC. For ED, a residual flap was observed in one-third of the initially dissected stent edges. Incomplete healing of acute vessel injury was associated with the presence of underlying atherosclerotic disease at baseline. Uncovered and malapposed stent struts were observed more often with incomplete healing of vessel injury at follow-up. CONCLUSIONS Acute vessel wall trauma is highly prevalent immediately after DES implantation. Most of these injuries are minor and resolve at mid-term follow-up. Incomplete healing of ISDs seems to be associated with other OCT findings suggesting delayed arterial healing.

Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial

Aims Inhalation of nitric oxide (iNO) during myocardial ischaemia and after reperfusion confers cardioprotection in preclinical studies via enhanced cyclic guanosine monophosphate (cGMP) signalling. We tested whether iNO reduces reperfusion injury in patients with ST-elevation myocardial infarction (STEMI; NCT01398384). Methods and results We randomized in a double-blind, placebo-controlled study 250 STEMI patients to inhale oxygen with (iNO) or without (CON) 80 parts-per-million NO for 4 h following percutaneous revascularization. Primary efficacy endpoint was infarct size as a fraction of left ventricular (LV) size (IS/LVmass), assessed by delayed enhancement contrast magnetic resonance imaging (MRI). Pre-specified subgroup analysis included thrombolysis-in-myocardial-infarction flow in the infarct-related artery, troponin T levels on admission, duration of symptoms, location of culprit lesion, and intra-arterial nitroglycerine (NTG) use. Secondary efficacy endpoints included IS relative to risk area (IS/AAR), myocardial salvage index, LV functional recovery, and clinical events at 4 and 12 months. In the overall population, IS/LVmass at 48-72 h was 18.0 ± 13.4% in iNO (n = 109) and 19.4 ± 15.4% in CON [n = 116, effect size -1.524%, 95% confidence interval (95% CI) -5.28, 2.24; P = 0.427]. Subgroup analysis indicated consistency across clinical confounders of IS but significant treatment interaction with NTG (P = 0.0093) resulting in smaller IS/LVmass after iNO in NTG-naïve patients (n = 140, P < 0.05). The secondary endpoint IS/AAR was 53 ± 26% with iNO vs. 60 ± 26% in CON (effect size -6.8%, 95% CI -14.8, 1.3, P = 0.09) corresponding to a myocardial salvage index of 47 ± 26% vs. 40 ± 26%, respectively, P = 0.09. Cine-MRI showed similar LV volumes at 48-72 h, with a tendency towards smaller increases in end-systolic and end-diastolic volumes at 4 months in iNO (P = 0.048 and P = 0.06, respectively, n = 197). Inhalation of nitric oxide was safe and significantly increased cGMP plasma levels during 4 h reperfusion. The Kaplan-Meier analysis for the composite of death, recurrent ischaemia, stroke, or rehospitalizations showed a tendency toward lower event rates with iNO at 4 months and 1 year (log-rank test P = 0.10 and P = 0.06, respectively). Conclusions Inhalation of NO at 80 ppm for 4 h in STEMI was safe but did not reduce infarct size relative to absolute LVmass at 48-72h. The observed functional recovery and clinical event rates at follow-up and possible interaction with nitroglycerine warrant further studies of iNO in STEMI.

Optical coherence tomography findings: insights from the "randomised multicentre trial investigating angiographic outcomes of hybrid sirolimus-eluting stents with biodegradable polymer compared with everolimus-eluting stents with durable polymer in chronic total occlusions" (PRISON IV) trial

AIMS The PRISON IV trial investigated the next-generation sirolimus-eluting stent (SES) with ultra-thin struts and biodegradable polymer against the second-generation everolimus-eluting stent (EES) with thin struts and durable polymer in patients with successfully recanalised chronic total occlusions (CTO). In this study, we examined the secondary optical coherence tomography endpoints. METHODS AND RESULTS The main PRISON IV trial randomised 330 patients to either SES or EES. At nine months, 281 (85%) patients underwent repeat angiography. Of these, 60 consecutive patients received optical coherence tomography divided over both stent groups. The mean number of struts analysed was 750±337 and 633±358 in SES and EES patients, respectively (p=0.07). The minimal lumen area, minimal stent area, maximal neointima area and neointimal thickness were comparable between the groups (4.8±2.1 and 4.4±1.5 mm2; 5.3±1.8 and 5.3±1.4 mm2; 2.5±2.0 and 2.2±1.5 mm2; 0.7±1.7 and 0.4±0.2 mm). The percentage of uncovered struts was higher with EES (6.2±7.5% and 11.9±13.4%, p=0.04), whereas the percentage of malapposed struts and mean number of coronary evaginations were significantly higher with SES (2.9±4.0% and 1.2±2.4%, p=0.02; 18.5±17.7 and 5.3±3.1, p=0.004). CONCLUSIONS The optical coherence tomography findings of this substudy demonstrated improved strut coverage with ultra-thin strut SES with bioresorbable polymer compared to thin-strut EES with durable polymer in CTO. On the other hand, SES showed a higher rate of stent strut malappositon and coronary evaginations. The clinical relevance of these findings remains to be demonstrated.

Etiology and Long‐Term Outcome of Patients Undergoing Pericardiocentesis

Background Pericardial effusions can be caused by a variety of disorders. The frequency of the underlying diseases varies with patient population; therefore, previously reported series are not necessarily representative of other populations. Our purpose was to examine the etiology of pericardial effusions and the survival of patients requiring pericardiocentesis at a tertiary center. Methods and Results We performed a retrospective observational study of 269 consecutive patients who underwent percutaneous pericardiocentesis at our university hospital between 2006 and 2016 and had prospective follow‐up for up to 10 years. The most frequent etiologies were idiopathic (26%), malignancy (25%), and iatrogenicity (20%), whereas bacterial causes were very rare. The most frequent malignancies originated from the lung (53%) or breast (18%). A new cancer was diagnosed with malignant pericardial effusion as the presenting complaint for 9% of patients, whereas the pericardium was the first metastatic site of a known malignancy in 4% of patients. Survival was significantly poorer in malignancy‐related versus non–malignancy‐related effusions (P<0.001) and in cytology‐positive versus cytology‐negative effusions in the overall cohort (P<0.001). Among cancer‐only patients, however, there was no significant difference in long‐term survival between cytology‐positive and ‐negative effusions. Conclusions In this contemporary tertiary‐center cohort, pericardial effusions often represent the primary instance of a new malignancy, underscoring the importance of cytological analyses of noniatrogenic effusions in patients without known cancer, as survival is significantly worse. In cancer patients, however, the presence of pericardial malignant cytology does not appear to affect outcome significantly.

Percutaneous coronary interventions of chronic total ­occlusions; a review of clinical indications, treatment strategy and current practice

Abstract Chronic total occlusions (CTOs) are commonly encountered in patients undergoing coronary angiography, but percutaneous coronary intervention (PCI) for CTO is currently infrequently performed owing to the perception of limited clinical benefit, high complexity and cost of intervention, and perceived risk of complications. Numerous observational studies have demonstrated that successful CTO revascularization is associated with better cardiovascular outcomes and enhanced quality of life (QOL). However, in the absence of randomized trials, its prognostic benefit remains debated. Nevertheless, over the past decade the interest in CTO-PCI has exponentially grown due to important developments in dedicated equipment and techniques, resulting in high success and low complication rates. A number of factors must be taken into consideration in selecting patients for CTO-PCI, including presence of symptoms attributable to the CTO, extent of ischaemia distal to the occlusion, and degree of myocardial viability. In this review, we focus on the impact of CTO revascularization on clinical outcomes and QOL and on appropriate patient selection. Data regarding efficacy and safety of recent advances in PCI-CTO techniques will be discussed. Steps involved in setting up a dedicated CTO program will be outlined and the current CTO landscape in Belgium will be briefly highlighted. The overall aim of this review is to promote a more balanced approach to management of patients with a CTO.

Long-term outcomes after percutaneous revascularization of complex coronary bifurcation lesions using a dedicated self-expanding biolimus-eluting stent system

BACKGROUND To evaluate long-term clinical outcomes after treatment of complex bifurcation lesions with the AXXESS dedicated self-expanding biolimus A9-eluting bifurcation stent. METHODS Between 2004 and 2013, 123 patients with complex bifurcation lesions were treated in a single-center with the AXXESS stent in the proximal main vessel (MV) and additional drug-eluting stents in branches when required. Median follow-up was 5 years. Primary endpoint was the rate of major adverse cardiac events (MACE). Secondary endpoints included MACE components (cardiac death, non-periprocedural clinical myocardial infarction [MI], target lesion revascularization [TLR] and definite/probable stent thrombosis [ST]) as well as all-cause death, target vessel revascularization (TVR) and non-TVR. RESULTS During follow-up, 11 (8.9%) patients experienced a MACE, of whom 2 (1.6%) suffered cardiac death, 2 (1.6%) had a non-periprocedural clinical MI requiring TLR, and 7 (5.7%) underwent elective TLR. No definite/probable ST was observed. All-cause death occurred in 9 (7.3%) patients, TVR in 11 (8.9%) and non-TVR in 11 (8.9%). Patients treated for left main (LM) bifurcation lesions were more likely to experience MACE than non-LM bifurcation lesions (25% vs. 6.5%, p = 0.04). CONCLUSIONS Percutaneous revascularization of complex bifurcation lesions with the AXXESS stent is safe and provides excellent long-term results, especially in non-LM lesions.

TCT-195 Ultrathin Bioresorbable Polymer Sirolimus-Eluting Stents versus Thin Durable Polymer Everolimus-Eluting Stents in Patients Undergoing Coronary Revascularization: Two-year Outcomes from the Randomized BIOFLOW V Trial

Coronary drug-eluting stent development has included new metal alloys, changes in stent architecture and bioresorbable polymers. Whether these advancements improve clinical safety and efficacy has not been demonstrated in prior randomized trials. BIOFLOW V ([ClinicalTrials.gov][1] [NCT02389946][2

Early collapse causing stenosis in a resorbable magnesium scaffold

We report a case of early in‐stent restenosis due to collapse of a Magmaris resorbable magnesium scaffold.