Ole De Backer

Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial.

BACKGROUNDnPatients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only.nnnMETHODSnWe undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularization of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933.nnnFINDINGSnFrom March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularization guided by FFR values. Median follow-up was 27 months (range 12–44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0∙56, 95% CI 0∙38–0∙83; p=0∙004).nnnINTERPRETATIONnIn patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints.nnnFUNDINGnDanish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.

Percutaneous Transcatheter Mitral Valve Replacement An Overview of Devices in Preclinical and Early Clinical Evaluation

Mitral regurgitation (MR) is one of the most prevalent valvular heart diseases in Western countries. The current estimated prevalence of moderate and severe MR in the United States is 2 to 2.5 million, and it is expected that this number will rise to 5 million by 2030.1 Surgical intervention is recommended for symptomatic severe MR or asymptomatic severe MR with left ventricular (LV) dysfunction.2 Treatment of degenerative MR has evolved from mitral valve (MV) replacement to MV repair because of superior long-term outcomes after repair.2–4 For functional MR, however, the benefit over MV replacement is less certain.5 In addition, minimally invasive MV surgery has become a well-established and increasingly used option for managing patients with MV pathology.6nnAlthough surgery remains the gold standard treatment for significant MR, MV surgery is deferred in a large number of patients because of high surgical risk.7 The decrease in the prevalence of rheumatic valve disease, in combination with an increased life expectancy, has led to a high prevalence of degenerative MR. As a consequence, patients are older and present with comorbidities that increase operative mortality and morbidity risks.8 In octogenarians, there has been reported a mortality and morbidity rate of 17.0% and 35.5%, respectively, following MV surgery.9 This results in denial or nonreferral for surgery in a large group of patients with significant MR—the Euro Heart Survey revealed that up to 50% of patients hospitalized with symptomatic severe MR are not referred for MV surgery, mainly because of advanced age, comorbidities, and LV dysfunction. In patients aged ≥80 years, surgical treatment was performed in only 15% compared to 60% in patients aged ≤70 years.8,10nnThe observation that a significant number of patients are not referred for MV surgery and the desire …

Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial

BACKGROUNDnDespite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI.nnnMETHODSnWe did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408.nnnFINDINGSnBetween March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups.nnnINTERPRETATIONnIn patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population.nnnFUNDINGnDanish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research.

Transcatheter Aortic Valve Replacement With Early- and New-Generation Devices in Bicuspid Aortic Valve Stenosis

BACKGROUNDnFew studies have evaluated the clinical outcomes of transcatheter aortic valve replacement (TAVR) inxa0patients with bicuspid aortic valve stenosis (AS). Particularly, limited data exist comparing the results of TAVR with new-generation devices versus early-generation devices.nnnOBJECTIVESnThis study sought to evaluate the clinical outcomes of TAVR for bicuspid AS with early- and new-generation devices.nnnMETHODSnThe Bicuspid TAVR Registry is an international multicenter study enrolling consecutive patients with bicuspid AS undergoing TAVR between April 2005 and Mayxa02015.nnnRESULTSnOf 301 patients, 199 patients (71.1%) were treated with early-generation devices (Sapien XT [Edwards Lifesciences Corporation, Irvine, California]: nxa0= 87; CoreValve [Medtronic, Minneapolis, Minnesota]: nxa0= 112) and 102xa0with new-generation devices (Sapien 3 [Edwards Lifesciences Corporation]: nxa0= 91; Lotus [Boston Scientific Corporation, Marlborough, Massachusetts]: nxa0= 11). The mean Society of Thoracic Surgeons score was 4.7 ± 5.2 without significant differences between groups (4.6 ± 5.1 vs. 4.9 ± 5.4; pxa0= 0.57). Overall, all-cause mortality rates were 4.3% atxa030 days and 14.4% at 1 year. Moderate or severe paravalvular leak was absent and significantly less frequent with new-generation compared to early-generation devices (0.0% vs. 8.5%; pxa0= 0.002), which resulted in a higher device success rate (92.2% vs. 80.9%; pxa0= 0.01). There were no differences between early- and new-generation devices in stroke (2.5% vs. 2.0%; pxa0> 0.99), life-threatening bleeding (3.5% vs. 2.9%; p > 0.99), major vascular complication (4.5% vs. 2.9%; pxa0= 0.76), stage 2 to 3 acute kidney injury (2.5% vs. 2.9%; p > 0.99), early safety endpoints (15.1% vs. 10.8%; pxa0= 0.30), and 30-day all-cause mortality (4.5% vs. 3.9%; p > 0.99).nnnCONCLUSIONSnThe clinical outcomes of TAVR in patients with bicuspid AS were favorable. New-generation devices were associated with less paravalvular leak and, hence, a higher device success rate than early-generation devices. (Thexa0Bicuspid Aortic Stenosis Following Transcatheter Aortic Valve Replacement Registry [Bicuspid TAVR]; NCT02394184).

Outcomes in Transcatheter Aortic Valve Replacement for Bicuspid Versus Tricuspid Aortic Valve Stenosis

BACKGROUNDnTranscatheter aortic valve replacement (TAVR) is being increasingly performed in patients with bicuspid aortic valve stenosis (AS).nnnOBJECTIVESnThis study sought to compare the procedural and clinical outcomes in patients with bicuspid versus tricuspid AS from the Bicuspid AS TAVR multicenter registry.nnnMETHODSnOutcomes of 561 patients with bicuspid AS and 4,546 patients with tricuspid AS were compared after propensity score matching, assembling 546 pairs of patients with similar baseline characteristics. Procedural and clinical outcomes were recorded according to Valve Academic Research Consortium-2 criteria.nnnRESULTSnCompared with patients with tricuspid AS, patients with bicuspid AS had more frequent conversion to surgery (2.0% vs. 0.2%; pxa0= 0.006) and a significantly lower device success rate (85.3% vs. 91.4%; pxa0= 0.002). Early-generation devices were implanted in 320 patients with bicuspid and 321 patients with tricuspid AS, whereas new-generation devices were implanted in 226 and 225 patients with bicuspid and tricuspid AS, respectively. Within the group receiving early-generation devices, bicuspid AS had more frequent aortic root injury (4.5% vs. 0.0%; pxa0= 0.015) when receiving the balloon-expanding device, and moderate-to-severe paravalvular leak (19.4% vs. 10.5%; pxa0= 0.02) when receiving the self-expanding device. Among patients with new-generation devices, however, procedural results were comparable across different prostheses. The cumulative all-cause mortality rates at 2 years were comparable between bicuspid and tricuspid AS (17.2% vs. 19.4%; pxa0= 0.28).nnnCONCLUSIONSnCompared with tricuspid AS, TAVR in bicuspid AS was associated with a similar prognosis, but lower device success rate. Procedural differences were observed in patients treated with the early-generation devices, whereasxa0noxa0differences were observed with the new-generation devices.

Natural history of subclinical leaflet thrombosis affecting motion in bioprosthetic aortic valves

AimsnFour-dimensional volume-rendered computed tomography (4DCT) has demonstrated instances of hypo-attenuating leaflet thickening (HALT) with or without hypo-attenuation affecting motion (HAM) after transcatheter and surgical aortic valve implantation (TAVI, SAVR). The temporal pattern of evolution of these phenomena is uncertain.nnnMethods and resultsnThe SAVORY registry enrolled patients treated by TAVI (nu2009=u200975) or SAVR (nu2009=u200930) with two 4DCT scans fully interpretable for HALT and HAM as well as unchanged anti-thrombotic medication between the scans. Logistic regression analysis was performed to examine the evolution of HALT and HAM while accounting for demographic and baseline variables, timing of both CT scans, valve type and antithrombotic therapy. The analysis population consisted of 84 patients, in whom first and second CT scans were performed at 140u2009±u2009152 days and 298u2009±u2009141 days after valve implantation, respectively. Hypo-attenuating leaflet thickening was noted in 32 patients (38.1%), with HAM in 17 (20.2%). Both findings were dynamic, showing progression in 13 (15.5%) and regression and 9 (10.7%) patients. Compared with antiplatelet therapy, progression was less likely among patients on oral anticoagulation with vitamin-K antagonists or non-VKA oral anticoagulants (odds ratio: 0.014, Pu2009=u20090.036). Maintenance on chronic oral anticoagulation was not a significant predictor of regression. These findings were similar for both transcatheter and surgical bioprosthetic aortic valves. No patients developed symptoms of valve dysfunction and leaflet thickening was not clearly associated with any clinical events.nnnConclusionsnSubclinical leaflet thrombosis is a common finding after TAVI and SAVR, and may progress from normal leaflet over HALT to the more severe HAM. The phenomenon can develop and regress at variable intervals after valve implantation. Anticoagulants may have a protective effect against the development of HALT, but HALT can also regress without anticoagulation therapy.nnnRegistered at ClinicalTrials.govnNCT02426307.

Incidence and outcomes of emergent cardiac surgery during transfemoral transcatheter aortic valve implantation (TAVI): insights from the European Registry on Emergent Cardiac Surgery during TAVI (EuRECS-TAVI)

AimsnLife-threatening complications occur during transcatheter aortic valve implantation (TAVI) which can require emergent cardiac surgery (ECS). Risks and outcomes of patients needing ECS during or immediately after TAVI are still unclear.nnnMethods and resultsnIncidence, risk factors, management, and outcomes of patients requiring ECS during transfemoral (TF)-TAVI were analysed from a contemporary real-world multicentre registry. Between 2013 and 2016, 27xa0760 patients underwent TF-TAVI in 79 centres. Of these, 212 (0.76%) patients required ECS (age 82.4u2009±u20096.3u2009years, 67.5% females, logistic EuroSCORE: 17.1%, STS-score 5.8%). The risk of ECS declined from 2013 (1.07%) to 2014 (0.70%) but remained stable since. Annual TF-TAVI numbers have more than doubled from 2013 to 2016. Leading causes for ECS were left ventricular perforation by the guidewire (28.3%) and annular rupture (21.2%). Immediate procedural mortality (<72u2009h) of TF-TAVI patients requiring ECS was 34.6%. Overall in-hospital mortality was 46.0%, and highest in case of annular rupture (62%). Independent predictors of in-hospital mortality following ECS were ageu2009>u200985u2009years [odds ratio (OR) 1.87, 95% confidence interval (95% CI) (1.02-3.45), Pu2009=u20090.044], annular rupture [OR 1.96, 95% CI (0.94-4.10), Pu2009=u20090.060], and immediate ECS [OR 3.12, 95% CI (1.07-9.11), Pu2009=u20090.037]. One year of survival of the 114 patients surviving the in-hospital period was only 40.4%.nnnConclusionnBetween 2014 and 2016, the need for ECS remained stable around 0.7%. Left ventricular guidewire perforation and annular rupture were the most frequent causes, accounting for almost half of ECS cases. Half of the patients could be salvaged by ECS-nevertheless, 1 year of all-cause mortality was high even in those ECS patients surviving the in-hospital period.

Fractional Flow Reserve-Guided Complete Revascularization Improves the Prognosis in Patients With ST-Segment-Elevation Myocardial Infarction and Severe Nonculprit Disease: A DANAMI 3-PRIMULTI Substudy (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization).

Background— The impact of disease severity on the outcome after complete revascularization in patients with ST-segment–elevation myocardial infarction and multivessel disease is uncertain. The objective of this post hoc study was to evaluate the impact of number of diseased vessel, lesion location, and severity of the noninfarct-related stenosis on the effect of fractional flow reserve–guided complete revascularization. Methods and Results— In the DANAMI-3-PRIMULTI study (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization), we randomized 627 ST-segment–elevation myocardial infarction patients to fractional flow reserve–guided complete revascularization or infarct-related percutaneous coronary intervention only. In patients with 3-vessel disease, fractional flow reserve–guided complete revascularization reduced the primary end point (all-cause mortality, reinfarction, and ischemia-driven revascularization; hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.17–0.64; P=0.001), with no significant effect in patients with 2-vessel disease (HR, 0.77; 95% CI, 0.47–1.26; P=0.29; P for interaction =0.046). A similar effect was observed in patients with diameter stenosis ≥90% of noninfarct-related arteries (HR, 0.32; 95% CI, 0.18–0.62; P=0.001), but not in patients with less severe lesions (HR, 0.72; 95% CI, 0.44–1.19; P=0.21; P for interaction =0.06). The effect was most pronounced in patients with 3-vessel disease and noninfarct-related stenoses ≥90%, and in this subgroup, there was a nonsignificant reduction in the end point of mortality and reinfarction (HR, 0.32; 95% CI, 0.08–1.32; P=0.09). Proximal versus distal location did not influence the benefit from complete revascularization. Conclusions— The benefit from fractional flow reserve–guided complete revascularization in ST-segment–elevation myocardial infarction patients with multivessel disease was dependent on the presence of 3-vessel disease and noninfarct diameter stenosis ≥90% and was particularly pronounced in patients with both of these angiographic characteristics. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01960933.

Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage : A propensity score-matched follow-up study

AIMSnThe aim of this study was to investigate the prognosis in patients with atrial fibrillation (AF) and intracerebral haemorrhage (ICH) having a left atrial appendage occlusion (LAAO) versus patients receiving standard medical therapy.nnnMETHODS AND RESULTSnA total of 151 patients from the Nordic countries with AF and previous ICH who underwent LAAO using the AMPLATZER Cardiac Plug or the AMPLATZER AMULET were compared to a propensity score-matched group of 151 patients receiving standard medical therapy. The two groups were matched so that their risks for stroke and bleeding were similar (CHA2DS2-VASc and HAS-BLED scores). The standard care patients were identified from the Danish Stroke Registry among 787 patients with AF and ICH. The primary endpoint was a composite of all-cause mortality, ischaemic stroke and major bleeding. Patients with AF and a prior ICH treated with LAAO had a lower risk of the composite outcome as compared to patients treated with standard medical care (events/1,000 years [95% confidence interval]: 53.3 [44.3-64.1] vs. 366.7 [298.2-450.9]; hazard ratio 0.16 [0.07-0.37]).nnnCONCLUSIONSnLAAO is suggested to be of major clinical benefit in AF patients having sustained an ICH. These results have to be confirmed in a randomised clinical trial.

Myocardial Damage in Patients With Deferred Stenting After STEMI: A DANAMI-3–DEFER Substudy

BACKGROUNDnAlthough some studies found improved coronary flow and myocardial salvage when stent implantation was deferred, the DANAMI-3-DEFER (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) did not show any improvement in clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) and deferred stenting.nnnOBJECTIVESnThis study sought to evaluate the effect of deferred stent implantation on infarct size, myocardial salvage, and microvascular obstruction (MVO) in patients with STEMI.nnnMETHODSnIn the present DANAMI-3 substudy, a total of 510 patients with STEMI were randomized to PCI with deferred versus immediate stent implantation. The patients underwent a cardiac magnetic resonance examination before discharge after the index procedure and again 3 months later. The primary endpoint was final infarct size.nnnRESULTSnDeferred stenting did not reduce final infarct size (9% left ventricle [LV]; interquartile range [IQR]: 3% to 18% vs. 10% LV; IQR: 3% to 18%; pxa0= 0.67). Similarly, deferred stenting was not associated with myocardial salvage index (66%; IQR: 50% to 89% vs. 67%; IQR: 49% to 88%; pxa0= 0.80) or presence of MVO (43% vs. 42%; pxa0= 0.78). In a post hoc analysis, stent length was the only subgroup of 7 that had an effect on outcome. In patients with a stent lengthxa0≥24 mm, deferred stenting reduced the final infarct size (6% LV; IQR: 2% to 18% vs. 13% LV; IQR: 7% to 23%; pxa0= 0.006; and p for interactionxa0= 0.005).nnnCONCLUSIONSnIn the DANAMI-3-DEFER cardiac magnetic resonance substudy, routine deferred stenting did not reduce infarct size or MVO and did not increase myocardial salvage. These results do not support the use of routine deferred stenting in STEMI patients treated with primary PCI. (DANish Study of Optimal Acute Treatment of Patients Withxa0ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408).