Effect of COMBinAtion therapy with remote ischemic conditioning and exenatide on the Myocardial Infarct size: a two-by-two factorial randomized trial (COMBAT-MI).

Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3-7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI.

Excimer laser coronary atherectomy for uncrossable coronary lesions. A multicenter registry.

OBJECTIVES: To assess the efficacy and safety of excimer laser coronary atherectomy (ELCA), as well as, the long-term outcomes and the factors associated with ELCA failure in uncrossable lesions. BACKGROUND: Uncrossable lesions constitute a challenge for percutaneous coronary intervention. METHODS: This multicenter registry included 126 patients with 126 uncrossable lesions. Study endpoints were ELCA success, technical success and a composite of cardiac death, myocardial infarction (MI), and target-lesion revascularization (TLR) on follow-up. Predictors of ELCA failure were analyzed. RESULTS: Moderate or severe calcification was present in 79 (62.7%) of the lesions and 58 (46%) were a chronic total occlusion. ELCA success was obtained in 103 (81.8%) patients. Rotational atherectomy was attempted as bailout in 21 out of 23 ELCA failure (91.3%), being successful in 14 (66.7%) of them. Finally, technical and procedural success were achieved in 114 (90.5%) and 110 (87.3%) of the patients. Severe calcification was independently associated with ELCA failure (OR: 3.73, 95% CI: 1.35-10.32; p = .011). Two (1.6%) patients died (one after a stroke and another patient because of heart failure), 4 (3.2%) developed a non-Q MI without clinical consequences and 1 (0.8%) patient had a Q-MI. Other complications were ventricular tachycardia/fibrillation (n = 2; 1.6%) and flow-limiting dissection (n = 1, 0.8%). At follow-up (median 424 days), 3 (2.4%) patients died (1 (0.8%) from cardiovascular cause) and 15 (11.9%) required TLR. CONCLUSIONS: In our multicenter experience, ELCA use demonstrated to be safe and reasonably effective with a rate of events on follow-up relatively low. Severe calcification was associated with ELCA failure.

Ischaemic postconditioning revisited: lack of effects on infarct size following primary percutaneous coronary intervention.

AIMS: To assess the short- and long-term effects of postconditioning (p-cond) on infarct size, extent of myocardial salvage, and left ventricular ejection fraction (LVEF) in a series of patients presenting with evolving ST-elevation myocardial infarction (STEMI). Previous studies have shown that p-cond during primary percutaneous coronary intervention (PCI) confers protection against ischaemia-reperfusion injury and thus might reduce myocardial infarct size. METHODS AND RESULTS: Seventy-nine patients undergoing PCI for a first STEMI with TIMI grade flow 0-1 and no collaterals were randomized to p-cond (n= 39) or controls (n= 40). Postconditioning was performed by applying four consecutive cycles of 1 min balloon inflation, each followed by 1 min deflation. Infarct size, myocardial salvage, and LVEF were assessed by cardiac-MRI 1 week and 6 months after MI. Postconditioning was associated with lower myocardial salvage (4.1 ± 7.2 vs. 9.1 ± 5.8% in controls; P= 0.004) and lower myocardial salvage index (18.9 ± 27.4 vs. 30.9 ± 20.5% in controls; P= 0.038). No significant differences in infarct size and LVEF were found between the groups at 1 week and 6 months after MI. CONCLUSION: This randomized study suggests that p-cond during primary PCI does not reduce infarct size or improve myocardial function recovery at both short- and long-term follow-up and might have a potential harmful effect.

Impact of a Successful Percutaneous Mitral Paravalvular Leak Closure on Long-term Major Clinical Outcomes.

BACKGROUND: Percutaneous mitral paravalvular leak (PVL) closure techniques are an effective and safe alternative to surgical treatment, but data regarding long-term outcomes are scarce. We aim to describe the impact of successful percutaneous mitral PVL closure on long-term outcomes. METHODS: All consecutive patients in whom a first-attempt percutaneous mitral PVL closure was performed in a single tertiary centre between January 2010 and October 2021 were included. Clinical variables, procedural details, and procedural success were collected. Patients were classified based on procedural success, defined as no more than mild residual leak. All-cause mortality was the primary endpoint. Cardiovascular death and heart failure hospitalizations (HFHs) were key secondary endpoints. RESULTS: Ninety patients (median age 72.5 years [66.0-78.4]; median EuroSCORE-II 8.2 [5.3-12.46]) were included. Although reduction of at least 1 degree in PVL severity was achieved in 82 (91.1%), procedural success was achieved in 47 (52.2%). Chronic kidney disease, previous surgery for PVL, and the presence of multiple jets were independently associated with procedural failure. After a median follow-up of 3.2 (1.2-5.2) years, mortality rate was higher in the procedural failure group (27.3 per 100 patients-years) compared with the group with successful closure (8.2 per 100 patient-years). Procedural failure was associated with all-cause death (adjusted hazard ratio [aHR], 2.59; 95% confidence interval [CI], 1.41-4.78), cardiovascular death (aHR, 3.53; 95% CI, 1.67-7.49) and HFH (aHR, 3.27; 95% CI,1.72-6.20). CONCLUSIONS: A successful reduction in PVL to mild or absent is associated with improved rates of all-cause death, cardiovascular death, and HFHs.

Spontaneous reperfusion enhances succinate concentration in peripheral blood from stemi patients but its levels does not correlate with myocardial infarct size or area at risk.

Succinate is enhanced during initial reperfusion in blood from the coronary sinus in ST-segment elevation myocardial infarction (STEMI) patients and in pigs submitted to transient coronary occlusion. Succinate levels might have a prognostic value, as they may correlate with edema volume or myocardial infarct size. However, blood from the coronary sinus is not routinely obtained in the CathLab. As succinate might be also increased in peripheral blood, we aimed to investigate whether peripheral plasma concentrations of succinate and other metabolites obtained during coronary revascularization correlate with edema volume or infarct size in STEMI patients. Plasma samples were obtained from peripheral blood within the first 10 min of revascularization in 102 STEMI patients included in the COMBAT-MI trial (initial TIMI 1) and from 9 additional patients with restituted coronary blood flow (TIMI 2). Metabolite concentrations were analyzed by 1H-NMR. Succinate concentration averaged 0.069 ± 0.0073 mmol/L in patients with TIMI flow ≤ 1 and was significantly increased in those with TIMI 2 at admission (0.141 ± 0.058 mmol/L, p < 0.05). However, regression analysis did not detect any significant correlation between most metabolite concentrations and infarct size, extent of edema or other cardiac magnetic resonance (CMR) variables. In conclusion, spontaneous reperfusion in TIMI 2 patients associates with enhanced succinate levels in peripheral blood, suggesting that succinate release increases overtime following reperfusion. However, early plasma levels of succinate and other metabolites obtained from peripheral blood does not correlate with the degree of irreversible injury or area at risk in STEMI patients, and cannot be considered as predictors of CMR variables.Trial registration: Registered at www.clinicaltrials.gov (NCT02404376) on 31/03/2015. EudraCT number: 2015-001000-58.

Can an ultrathin strut stent design and a polymer free, proendothelializing probucol matrix coating improve early strut healing? The FRIENDLY-OCT trial. An intra-patient randomized study with OCT, evaluating early strut coverage of a novel probucol coated polymer-free and ultra-thin strut sirolimus-eluting stent compared to a biodegradable polymer sirolimus-eluting stent.

BACKGROUND: incomplete strut coverage determines the risk of stent thrombosis in the first months after stent implantation. AIMS: To evaluate the potential better early healing of a novel probucol coated polymer free ultra-thin strut sirolimus eluting stent (PF-SES). [Clinical trial unique identifier: NCT02785237]. METHODS: Patients with two (angiographically similar) lesions with clinical indication for PCI were enrolled. The investigated stent was compared to a thin strut, bioresorbable polymer, sirolimus eluting stent (BP-SES). Every patient received both stents, one in each lesion, assigned in a randomized sequence. OCT was systematically performed at 3 months. Primary end point was the difference in the proportion of covered struts at 3 months (defined as ≥20 µm of tissue coverage). Secondary end points included differences in percentage of uncovered struts (0 µm coverage), mean strut coverage thickness, and malapposed struts' coverage proportion. Major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 12 months were also evaluated. RESULTS: 70 patients were included. At 3 months, a consistent and significantly higher strut coverage rate (≥20 µm) was observed in PF-SES as compared to BP-SES, both for well apposed (87.3% versus 79.1%, p < 0.001) and malapposed struts (50.4% vs 37.8%, p 0.00). Uncoverage rate (0 µm) was also significantly lower for the PF-SES (3.1% vs 5.3%, p < 0.001). There were no differences in clinical endpoints. CONCLUSION: The probucol coated non-polymeric ultra-thin strut sirolimus eluting stent showed a significantly better early strut coverage at 3 months.

Effects of adipose tissue-derived stem cell therapy after myocardial infarction: impact of the route of administration.

BACKGROUND: Cell-based therapies offer a promising approach to reducing the short-term mortality rate associated with heart failure after a myocardial infarction. The aim of the study was to analyze histological and functional effects of adipose tissue-derived stem cells (ADSCs) after myocardial infarction and compare 2 types of administration pathways. METHODS AND RESULTS: ADSCs from 28 pigs were labeled by transfection. Animals that survived myocardial infarction (n = 19) received: intracoronary culture media (n = 4); intracoronary ADSCs (n = 5); transendocardial culture media (n = 4); or transendocardial ADSCs (n = 6). At 3 weeks' follow-up, intracoronary and transendocardial administration of ADSCs resulted in similar rates of engrafted cells (0.85 [0.19-1.97] versus 2 [1-2] labeled cells/cm(2), respectively; P = NS) and some of those cells expressed smooth muscle cell markers. The intracoronary administration of ADSCs was more effective in increasing the number of small vessels than transendocardial administration (223 +/- 40 versus 168 +/- 35 vessels/mm(2); P < .05). Ejection fraction was not modified by stem cell therapy. CONCLUSIONS: This is the first study to compare intracoronary and transendocardial administration of autologous ADSCs in a porcine model of myocardial infarction. Both pathways of ADSCs delivery are feasible, producing a similar number of engrafted and differentiated cells, although intracoronary administration was more effective in increasing neovascularization.

Cryptogenic Stroke And Role Of Loop Recorder.

Ischemic stroke is an important cause of morbidity and mortality when untreated. Identifying atrial fibrillation is important because atrial fibrillation ischemic related strokes are associated with an increased risk of disability and death compared with strokes of other etiologies and tend to recur without anticoagulation. However, atrial fibrillation detection can be difficult when it is asymptomatic and paroxistic and may be the underlying cause of some cryptogenic strokes or strokes of unknown origin. In this review, the different methods of cardiac monitoring to detect atrial fibrillation in patients with cryptogenic stroke are summarized, with a focus on loop recorder monitoring.

Single intracoronary injection of encapsulated antagomir-92a promotes angiogenesis and prevents adverse infarct remodeling.

BACKGROUND: Small and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectorized miR-targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction AUTHOR: Should "acute" be added before "myocardial infarction" (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects. METHODS AND RESULTS: In a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir-92a encapsulated in specific microspheres (9 µm poly-d,-lactide-co-glycolide [PLGA]) inhibited miR-92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×-fold inhibition at 1, 3, and 10 days). Downregulation of miR-92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir-92a, encapsulated placebo, or saline [n=8, 9, 9]; P=0.001), reduced regional wall-motion dysfunction (P=0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P=0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin-PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2). CONCLUSIONS: Early single intracoronary administration of encapsulated antagomir-92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI.

Typical angina without significant coronary stenosis: comparison of clinical profile, circadian presentation, and long-term follow-up between patients with and patients without vasospastic angina.

OBJECTIVES: The spectrum of patients with 'angina and normal coronary arteries' ranges from severe vasospasm to atypical chest pain. Among those with typical angina, however, little is known about similarities in the clinical profile and circadian presentation between typical nonvasospastic angina and normal coronary arteries (tANCA) and vasospastic angina (VA). MATERIALS AND METHODS: Clinical, ECG, and angiographic features as well as the circadian characteristics of angina were compared between 384 tANCA and 273 VA patients. Follow-up events were also analyzed. RESULTS: tANCA patients had greater female predominance (61 vs. 18%), higher incidence of dyspnea to moderate exertion (49 vs. 12%), lower incidence of tobacco smoking (25 vs. 67%), but a similar low rate of diabetes (8.9 vs. 4.4%). In both groups, however, dyspnea and smoking were associated with female and male sex, respectively. tANCA patients showed lower but non-negligible frequency of early morning (25 vs. 67%) and evening angina (37 vs. 54%), similar rate of nocturnal angina (47 vs. 50%), and higher rate of emotional angina (49 vs. 31%). Moreover, a high proportion of patients gained pain relief with nitroglycerin (97% in VA, 246/253, and 76% in tANCA, 231/306). At 140 months, frequent angina (>10 episodes/year) was rare (VA: 7.1% vs. tANCA: 6.3%) as was the rate of cardiac death/myocardial infarction (7.3 vs. 6.0%, P=0.524). CONCLUSION: Despite differences in the clinical profile between VA and tANCA patients, there is notable sharing of circadian presentation of rest angina, response to nitroglycerin, and long-term presence and frequency of angina that suggests more similarities in underlying mechanisms than heretofore suspected.

Clinical and procedural evaluation of the Nile Croco® dedicated stent for bifurcations: a single centre experience with the first 151 consecutive non-selected patients.

AIMS: To evaluate the feasibility and safety of the Nile Croco® coronary bifurcation stent system (Minvasys, Gennevilliers, France). METHODS AND RESULTS: The primary endpoint was to assess the acute device success and angiographic success with the use of the Nile Croco® stent system. Secondary endpoints included in-hospital and six month major cardiac events (MACE).There were 151 consecutive patients enrolled in the Nile Croco Study at Vall Hebrón Hospital. The Nile Croco® stent was successfully implanted in 144 patients (95.4%) and final angiographic success was obtained in 100% of the patients. 138 out of the 151 (91%) patients included have accomplished the six month follow-up. There was one in-hospital MACE in the 151 recruited patients. The MACE rate at six months in the 138 patients with follow-up was 14% and the ischaemia-driven TLR rate was 7.2 %. CONCLUSIONS: The results of our Nile Croco® Study are the first to demonstrate the safety and high performance of this dedicated stent system for the treatment of bifurcation lesions. The device can be successfully implanted in more than 95% of all cases, with a high procedural success rate and low in-hospital and six month MACE rates.