Thoracic endovascular aortic repair (TEVAR) represents a novel concept for type B aortic dissection. Although life-saving in acute emergencies, outcomes and survival of TEVAR in stable dissection are ...unknown.
One hundred forty patients in stable clinical condition at least 2 weeks after index dissection were randomly subjected to elective stent-graft placement in addition to optimal medical therapy (n=72) or to optimal medical therapy alone (n=68) with surveillance (arterial pressure according to World Health Organization guidelines < or =120/80 mm Hg). The primary end point was all-cause death at 2 years, whereas aorta-related death, progression (with need for conversion or additional endovascular or open surgery), and aortic remodeling were secondary end points. There was no difference in all-cause deaths, with a 2-year cumulative survival rate of 95.6+/-2.5% with optimal medical therapy versus 88.9+/-3.7% with TEVAR (P=0.15); the trial, however, turned out to be underpowered. Moreover, the aorta-related death rate was not different (P=0.44), and the risk for the combined end point of aorta-related death (rupture) and progression (including conversion or additional endovascular or open surgery) was similar (P=0.65). Three neurological adverse events occurred in the TEVAR group (1 paraplegia, 1 stroke, and 1 transient paraparesis), versus 1 case of paraparesis with medical treatment. Finally, aortic remodeling (with true-lumen recovery and thoracic false-lumen thrombosis) occurred in 91.3% of patients with TEVAR versus 19.4% of those who received medical treatment (P<0.001), which suggests ongoing aortic remodeling.
In the first randomized study on elective stent-graft placement in survivors of uncomplicated type B aortic dissection, TEVAR failed to improve 2-year survival and adverse event rates despite favorable aortic remodeling.
Abstract
Aims
Transcatheter aortic valve implantation (TAVI) has emerged as established treatment option in patients with symptomatic aortic stenosis. Technical developments in valve design have ...addressed previous limitations such as suboptimal deployment, conduction disturbances, and paravalvular leakage. However, there are only limited data available for the comparison of newer generation self-expandable valve (SEV) and balloon-expandable valve (BEV).
Methods and results
SOLVE-TAVI is a multicentre, open-label, 2 × 2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral TAVI comparing SEV (Evolut R, Medtronic Inc., Minneapolis, MN, USA) with BEV (Sapien 3, Edwards Lifesciences, Irvine, CA, USA). The primary efficacy composite endpoint of all-cause mortality, stroke, moderate/severe prosthetic valve regurgitation, and permanent pacemaker implantation at 30 days was powered for equivalence (equivalence margin 10% with significance level 0.05). The primary composite endpoint occurred in 28.4% of SEV patients and 26.1% of BEV patients meeting the prespecified criteria of equivalence rate difference −2.39 (90% confidence interval, CI −9.45 to 4.66); Pequivalence = 0.04. Event rates for the individual components were as follows: all-cause mortality 3.2% vs. 2.3% rate difference −0.93 (90% CI −4.78 to 2.92); Pequivalence < 0.001, stroke 0.5% vs. 4.7% rate difference 4.20 (90% CI 0.12 to 8.27); Pequivalence = 0.003, moderate/severe paravalvular leak 3.4% vs. 1.5% rate difference −1.89 (90% CI −5.86 to 2.08); Pequivalence = 0.0001, and permanent pacemaker implantation 23.0% vs. 19.2% rate difference −3.85 (90% CI −10.41 to 2.72) in SEV vs. BEV patients; Pequivalence = 0.06.
Conclusion
In patients with aortic stenosis undergoing transfemoral TAVI, newer generation SEV and BEV are equivalent for the primary valve-related efficacy endpoint. These findings support the safe application of these newer generation percutaneous valves in the majority of patients with some specific preferences based on individual valve anatomy.
Summary Background Absorbable scaffolds were designed to overcome the limitations of conventional, non-absorbable metal-based drug-eluting stents. So far, only polymeric absorbable scaffolds are ...commercially available. We aimed to assess the safety and performance of a novel second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) in patients with de-novo coronary artery lesions. Methods We did this prospective, multicentre, non-randomised, first-in-man trial at 13 percutaneous coronary intervention centres in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. Eligible patients had stable or unstable angina or documented silent ischaemia, and a maximum of two de-novo lesions with a reference vessel diameter between 2·2 mm and 3·7 mm. Clinical follow-up was scheduled at months 1, 6, 12, 24, and 36. Patients were scheduled for angiographic follow-up at 6 months, and a subgroup of patients was scheduled for intravascular ultrasound, optical coherence tomography, and vasomotion assessment. All patients were recommended to take dual antiplatelet treatment for at least 6 months. The primary endpoint was in-segment late lumen loss at 6 months. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT01960504. Findings Between Oct 8, 2013, and May 22, 2015, we enrolled 123 patients with 123 coronary target lesions. At 6 months, mean in-segment late lumen loss was 0·27 mm (SD 0·37), and angiographically discernable vasomotion was documented in 20 (80%) of 25 patients. Intravascular ultrasound assessments showed a preservation of the scaffold area (mean 6·24 mm2 SD 1·15 post-procedure vs 6·21 mm2 1·22 at 6 months) with a low mean neointimal area (0·08 mm2 0·09), and optical coherence tomography did not detect any intraluminal mass. Target lesion failure occurred in four (3%) patients: one (<1%) patient died from cardiac death, one (<1%) patient had periprocedural myocardial infarction, and two (2%) patients needed clinically driven target lesion revascularisation. No definite or probable scaffold thrombosis was observed. Interpretation Our findings show that implantation of the DREAMS 2G device in de-novo coronary lesions is feasible, with favourable safety and performance outcomes at 6 months. This novel absorbable metal scaffold could be an alternative to absorbable polymeric scaffolds for treatment of obstructive coronary disease. Funding Biotronik AG.
Metal absorbable scaffolds constitute a conceptually attractive alternative to polymeric scaffolds. Promising 6-month outcomes of a second-generation drug-eluting absorbable metal scaffold (DREAMS ...2G), consisting of an absorbable magnesium scaffold backbone, have been reported. We assessed the 12-month safety and performance of this novel device.
The prospective, international, multi-centre, first-in-man BIOSOLVE-II trial enrolled 123 patients with up to two de novo lesions with a reference diameter between 2.2 and 3.7 mm. All patients were scheduled for angiographic follow-up at 6 months, and-if subjects consented-at 12 months. Dual antiplatelet therapy was recommended for 6 months. Quantitative coronary angiography (QCA) parameters remained stable from 6 to 12 months paired data of 42 patients: in-segment late lumen loss 0.20 ± 0.21 mm vs. 0.25 ± 0.22 mm, P = 0.117, Δ 0.05 ± 0.21 mm (95% CI: -0.01;0.12); in-scaffold late lumen loss 0.37 ± 0.25 mm vs. 0.39 ± 0.27 mm, P = 0.446, Δ 0.03 ± 0.22 (95% CI: -0.04;0.10), respectively. Intravascular ultrasound and optical coherence tomography findings corroborated the QCA results. Target lesion failure occurred in four patients (3.4%), consisting of one death of unknown cause, one target-vessel myocardial infarction, and two clinically driven target lesion revascularization. No additional event occurred beyond the 6-month follow-up. During the entire follow-up of 12 months, none of the patients experienced a definite or probable scaffold thrombosis.
The novel drug-eluting metal absorbable scaffold DREAMS 2G showed a continuous favourable safety profile up to 12 months and stable angiographic parameters between 6 and 12 months.
NCT01960504.
Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony-stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells ...(MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man.
Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89+/-35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17+/-2.93 MNCCD34+/microL at baseline and 64.55+/-37.11 MNCCD34+/microL on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29+/-0.22 and 0.99+/-0.32 mm versus 0.49+/-0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 microg.kg(-1).min(-1)), wall motion score index showed improvement from 1.66+/-0.23 to 1.41+/-0.21 (P<0.004 versus control) and to 1.35+/-0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24+/-0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41+/-0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55+/-5 mm (P<0.002 versus control), and ejection fraction to 54+/-8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control).
G-CSF and mobilization of MNC(CD34+) after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.
RESPOND is a prospective, open-label, single-arm study evaluating the outcomes following transcatheter aortic valve implantation (TAVI) with the repositionable and fully retrievable Lotus Valve used ...in routine clinical practice for the treatment of patients with aortic valve stenosis.
RESPOND enrolled 1014 patients at sites across Europe, New Zealand, and Latin America; 996 patients received a Lotus Valve (mean age: 80.8 years; 50.8% female; Society of Thoracic Surgeons score: 6.0 ± 6.9). Repositioning was attempted in 29.2% of patients, with 99% success. The rate of all-cause mortality in the intent-to-treat population at 30 days (primary endpoint) was 2.6% (P < 0.001 vs. pre-specified performance goal). Thirty-day clinical follow-up was completed for 97.3% of patients. Among patients who received a Lotus Valve, the 30-day overall and disabling stroke rates were 3.0% and 2.2%, respectively. The 30-day permanent pacemaker implantation rate was 30.0% in all patients, and 34.6% in pacemaker-naïve patients. Echocardiographic data at baseline and pre-discharge were assessed by an independent core laboratory. Mean aortic valve gradient declined from 37.7 ± 15.2 mmHg at baseline to 10.8 ± 4.6 mmHg at hospital discharge (P < 0.001). Aortic valve area increased from 0.7 ± 0.2 cm2 at baseline to 1.8 ± 0.4 cm2 at discharge (P < 0.001). At hospital discharge, paravalvular leak (PVL) was absent or trace in 92% of patients; no patients had severe PVL, 0.3% of patients exhibited moderate PVL, and 7.7% of patients had mild PVL. Clinical follow-up in RESPOND will extend to 5 years.
The results of RESPOND confirm the safety and efficacy of TAVI with the Lotus Valve in routine clinical practice.
ClinicalTrials.gov #NCT 02031302.
Early revascularization therapy with percutaneous coronary intervention (PCI) has been shown to improve outcomes in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock ...(CS). Data from consecutive patients with AMI and CS treated with PCI enrolled into the prospective Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte-PCI registry were centrally collected and analyzed. Patients were divided into 4 groups with PCI for left main (LM), 1-vessel, 2-vessel, and 3-vessel diseases. Patients’ characteristics, procedural features, antithrombotic therapies, and in-hospital complications were compared between the 4 groups. Between 2010 and 2015 a total of 2,348 consecutive patients with AMI and CS were treated by PCI in 51 hospitals, 295 for LM (15 for protected, 280 for unprotected) and single-vessel (n = 491), 2-vessel (n = 524), and 3-vessel disease (n = 1,038). Thrombolysis in myocardial infarction 3 patency of the culprit lesion after PCI was 84.3%, 84.0%, 80.8%, and 84.6% in single-vessel, 2-vessel, 3-vessel disease, and LM PCI, respectively, whereas in-hospital mortality was 27.9%, 33.9%, 46.5%, and 55.9%. Bleeding rates were low (2.0%–2.3 %) and not different between groups. In a multivariate analysis a higher age, thrombolysis in myocardial infarction flow <3 after PCI, 3-vessel disease, and LM PCI were independent predictors of mortality. In conclusion, PCI of the LM is performed in about 12.5% of patients with AMI and CS and was associated with a high procedural success rate, whereas mortality is increased with LM PCI.
Experimental and clinical evidence has recently shown that pluripotent stem cells can be mobilized by granulocyte colony-stimulating factor (G-CSF) and may enhance myocardial regeneration early after ...primary percutaneous coronary intervention (PCI) management of acute myocardial infarction. Sustained or long-term effects of mobilized CD34-positive mononuclear stem cells, however, are unknown.
Thirty consecutive patients with ST-elevation myocardial infarction undergoing primary PCI with stenting and abciximab were selected for the study 85+/-30 minutes after PCI; 15 patients were randomly assigned to receive subcutaneous G-CSF at 10 microg/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, beta-blocking agents, and statins. In patients with comparable demographics and clinical and infarct-related characteristics, G-CSF stimulation led to sustained mobilization of CD34 positive mononuclear cells (MNC(CD34+)), with a 20-fold increase (from 3+/-2 at baseline to 66+/-54 MNC(CD34+)/microL on day 6; P<0.001); there was no evidence of leukocytoclastic effects, accelerated restenosis rate, or any late adverse events. Within 4 months, G-CSF-induced MNC(CD34+) mobilization led to enhanced resting wall thickening in the infarct zone of 1.16+/-0.29 mm (P<0.05 versus control), which was sustained at 1.20+/-0.28 after 12 months (P<0.001 versus control). Similarly, left ventricular ejection fraction improved from 48+/-4% at baseline to 54+/-8% at 4 months (P<0.005 versus control) and 56+/-9% at 12 months (P<0.003 versus control and paralleled by sustained improvement of wall-motion score index from 1.70+/-0.22 to 1.42+/-0.26 and 1.33+/-0.21 at 4 and 12 months, respectively), after G-CSF (P<0.05 versus baseline and P<0.03 versus controls). Accordingly, left ventricular end-diastolic diameter showed no remodeling and stable left ventricular dimensions after G-CSF stimulation, whereas left ventricular end-diastolic diameter in controls revealed enlargement from 55+/-4 mm at baseline to 58+/-4 mm (P<0.05 versus baseline) at 12 months after infarction and no improvement in diastolic function.
Mobilization of MNC(CD34+) by G-CSF after primary PCI may offer a pragmatic strategy for improvement in ventricular function and prevention of left ventricular remodeling 1 year after acute myocardial infarction.
Clinical profiles and outcomes of patients with acute type B aortic dissection have not been evaluated in the current era.
Accordingly, we analyzed 384 patients (65+/-13 years, males 71%) with acute ...type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD). A majority of patients had hypertension and presented with acute chest/back pain. Only one-half showed abnormal findings on chest radiograph, and almost all patients had computerized tomography (CT), transesophageal echocardiography, magnetic resonance imaging (MRI), and/or aortogram to confirm the diagnosis. In-hospital mortality was 13% with most deaths occurring within the first week. Factors associated with increased in-hospital mortality on univariate analysis were hypotension/shock, widened mediastinum, periaortic hematoma, excessively dilated aorta (>or=6 cm), in-hospital complications of coma/altered consciousness, mesenteric/limb ischemia, acute renal failure, and surgical management (all P<0.05). A risk prediction model with control for age and gender showed hypotension/shock (odds ratio OR 23.8, P<0.0001), absence of chest/back pain on presentation (OR 3.5, P=0.01), and branch vessel involvement (OR 2.9, P=0.02), collectively named 'the deadly triad' to be independent predictors of in-hospital death.
Our study provides insight into current-day profiles and outcomes of acute type B aortic dissection. Factors associated with increased in-hospital mortality ("the deadly triad") should be identified and taken into consideration for risk stratification and decision-making.
Few data exist on gender-related differences in clinical presentation, diagnostic findings, management, and outcomes in acute aortic dissection (AAD).
Accordingly, we evaluated 1078 patients enrolled ...in the International Registry of Acute Aortic Dissection (IRAD) to assess differences in clinical features, management, and in-hospital outcomes between men and women. Of the patients enrolled in IRAD (32.1%) with AAD, 346 were women. Although less frequently affected by AAD (32.1% of AAD), women were significantly older and had more often presented later than men (P=0.008); symptoms of coma/altered mental status were more common, whereas pulse deficit was less common. Diagnostic imaging suggestive of rupture, ie, periaortic hematoma, and pleural or pericardial effusion were more commonly observed in women. In-hospital complications of hypotension and tamponade occurred with greater frequency in women, resulting in higher in-hospital mortality compared with men. After adjustment for age and hypertension, women with aortic dissection die more frequently than men (OR, 1.4, P=0.04), predominantly in the 66- to 75-year age group. Moreover, surgical outcome was worse in women than men (P=0.013); type A dissection in women was associated with a higher surgical mortality of 32% versus 22% in men despite similar delay, surgical technique, and hemodynamics.
Our analysis provides insights into gender-related differences in AAD with regard to clinical characteristics, management, and outcomes; important diagnostic and therapeutic implications may help shed light on aortic dissection in women to improve their outcomes.
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