Impacto clínico de la extensión del miocardio en riesgo en pacientes sometidos a intervención percutánea de la válvula aórtica / Clinical impact of the extent of jeopardized myocardium in patients undergoing transcatheter aortic valve intervention

Introducción y objetivos La enfermedad coronaria (EC) se encuentra en el 30-50% de los pacientes con estenosis aórtica (EA) grave que reciben tratamiento intervencionista. Todavía no está claro cuál es el mejor tratamiento de la EAC en pacientes con EA sometidos a implante percutáneo de válvula aórtica (TAVI). El objetivo del estudio fue analizar el impacto clínico del miocardio en riesgo en pacientes con EAC y EA grave tratados con TAVI. Métodos Se incluyó a pacientes consecutivos sometidos a TAVI en nuestro hospital. En presencia de EAC, el miocardio en riesgo antes del procedimiento se clasificó utilizando la puntuación de riesgo (JS) de la British Cardiovascular Intervention Society (BCIS). La población de estudio se dividió en 3 grupos: pacientes sin EAC concomitante (grupo No-EAC), pacientes con EAC y BCIS-JS ≤ 4 (grupo EAC BCIS-JS ≤ 4) y pacientes con EAC concomitante y BCIS-JS> 4 (grupo EAD BCIS -JS> 4). El objetivo primario del estudio fueron los eventos cardiovasculares y cerebrovasculares adversos mayores (MACCE). Resultados Se incluyó a un total de 403 pacientes: 223 No-EAD, 94 EAC BCIS-JS ≤ 4 y 86 EAC BCIS-JS> 4. Con 3 meses de seguimiento [rango 104 – 3.296 días], los pacientes sin EAC y los pacientes con EAC con BCIS-JS ≤ 4 tuvieron una mejor supervivencia libre de MACCE en comparación con aquellos con revascularización menos extensa (BCIS-JS> 4) (p=0,049). Este resultado se debió en parte a una reducción significativa de la mortalidad (p=0,031). En el análisis multivariado, el BCIS-JS residual ≤ 4 y la clase III-IV de la NYHA predijeron MACCE de forma independiente. Conclusiones En pacientes con EAC y EA grave, la extensión del miocardio en riesgo antes del TAVI influye en los resultados clínicos (AU)

Introduction and objectives Coronary artery disease (CAD) is found in 30%-50% of patients with severe aortic stenosis (AS) undergoing treatment. The best management of CAD in AS patients undergoing transcatheter aortic valve implantation (TAVI) is still unclear. We investigated the clinical impact of the extent of jeopardized myocardium in patients with concomitant CAD and severe AS treated by TAVI. Methods Consecutive patients who underwent TAVI procedures at our hospital were identified. In the presence of CAD, the myocardium jeopardized before TAVI was graded using the British Cardiovascular Intervention Society (BCIS) jeopardy score (JS). The study population was divided in 3 groups: patients without concomitant CAD (no-CAD), patients with CAD and BCIS-JS ≤ 4 (CAD BCIS-JS ≤ 4) and patients with concomitant CAD and BCIS-JS> 4 (CAD BCIS-JS> 4). The primary study endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Results A total of 403 patients entered the study: 223 no-CAD, 94 CAD BCIS-JS ≤ 4 and 86 CAD BCIS-JS> 4. At> 3 months of follow-up [range 104–3296 days], patients without CAD and CAD patients with BCIS-JS ≤ 4 had better survival free from MACCE compared with those with less extensive revascularization (BCIS-JS> 4) (P=.049). This result was driven by a significant reduction in death (P=.031). On multivariate analysis, residual BCIS-JS ≤ 4 and NYHA class III-IV independently predicted MACCE. Conclusions In patients with concomitant CAD and severe AS, the extent of jeopardized myocardium before TAVI impacts on clinical outcomes (AU)

A new echocardiographic index to select patients for PFO suture-mediated percutaneous closure.

OBJECTIVES: To identify a simple echocardiographic predictor of procedural success to select patient for percutaneous suture-mediated patent fossa ovalis (PFO) closure. BACKGROUND: Percutaneous suture-mediated PFO closure has been shown as a safe and advantageous alternative to device-based PFO closure, yet its overall success is slightly lower in unselected patients. METHODS: Preprocedural transesophageal echocardiogram (TEE) of 302 patients (113 men, 45 ± 12 years) who underwent percutaneous suture-mediated PFO closure were reviewed. RESULTS: At echocardiographic follow-up (3-6 months), residual right-to-left shunt (RLS) ≥2 was found in 60 (19.9%) patients. At multivariable analysis, only two anatomical variables measured at preprocedural TEE were found as independent predictors of residual RLS ≥ 2 at follow-up: PFO maximum width (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.16-3.40, p = 0.02) and PFO minimal septa overlapping (OR 0.58, 95% CI 0.35-0.88, p = 0.02). An index based on the ratio of PFO maximum width to PFO minimum septal overlapping (W/SO) proved to be the most powerful predictor of RLS ≥ 2 at follow-up (OR 48.1, 95% CI 9.3-352.2, p < 0.01). The ROC curve for the W/SO ratio was found to have an AUC of 0.84 (95% CI 0.75-0.93) and a cut-off value of 0.61 yielding a sensitivity of 80% and specificity of 78% with a negative predictive value of 94%. A decision tree methodology's AUC was 0.75 (95% CI 0.67-0.83). CONCLUSIONS: The results of this study indicate that the ratio between the maximum amplitude of the PFO and the minimum overlap of the septa is the best predictive index of a favorable result by using one stitch only.

Clinical impact of the extent of jeopardized myocardium in patients undergoing transcatheter aortic valve intervention.

INTRODUCTION AND OBJECTIVES: Coronary artery disease (CAD) is found in 30%-50% of patients with severe aortic stenosis (AS) undergoing treatment. The best management of CAD in AS patients undergoing transcatheter aortic valve implantation (TAVI) is still unclear. We investigated the clinical impact of the extent of jeopardized myocardium in patients with concomitant CAD and severe AS treated by TAVI. METHODS: Consecutive patients who underwent TAVI procedures at our hospital were identified. In the presence of CAD, the myocardium jeopardized before TAVI was graded using the British Cardiovascular Intervention Society (BCIS) jeopardy score (JS). The study population was divided in 3 groups: patients without concomitant CAD (no-CAD), patients with CAD and BCIS-JS ≤ 4 (CAD BCIS-JS ≤ 4) and patients with concomitant CAD and BCIS-JS> 4 (CAD BCIS-JS> 4). The primary study endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). RESULTS: A total of 403 patients entered the study: 223 no-CAD, 94 CAD BCIS-JS ≤ 4 and 86 CAD BCIS-JS> 4. At> 3 months of follow-up [range 104-3296 days], patients without CAD and CAD patients with BCIS-JS ≤ 4 had better survival free from MACCE compared with those with less extensive revascularization (BCIS-JS> 4) (P=.049). This result was driven by a significant reduction in death (P=.031). On multivariate analysis, residual BCIS-JS ≤ 4 and NYHA class III-IV independently predicted MACCE. CONCLUSIONS: In patients with concomitant CAD and severe AS, the extent of jeopardized myocardium before TAVI impacts on clinical outcomes.

Design of the PERSEO Registry on the management of patients treated with oral anticoagulants and coronary stent.

AIM: Percutaneous coronary intervention with stent implantation (PCI-S) in patients requiring chronic oral anticoagulant therapy (OAC) is associated with an increased risk of bleeding and ischemic complications. Different randomized studies showed a significant advantage of a double antithrombotic therapy and superiority of direct oral anticoagulant (DOAC) compared with warfarin, but real-world data are limited. Aim is to evaluate the antithrombotic management and clinical outcome of patients with an indication for OAC who undergo PCI-S in a 'real-world' setting. METHODS: The multicentre prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) Registry (ClinicalTrials.gov Identifier: NCT03392948) has been designed to enrol patients requiring OAC treated by PCI-S in 25 Italian centres. A target of at least 1080 patients will be followed for 1 year and data on thromboembolic and bleeding events and changes in antithrombotic therapy will be registered. The primary end point is a combined measure of efficacy and safety outcome (NACE), including major bleeding events and major adverse cardiac and cerebral events at 1-year follow-up in patients treated with DOAC (and dual or triple antiplatelet therapy) compared with the corresponding strategies with vitamin K antagonists. A secondary prespecified analysis has been defined to evaluate NACE in dual versus triple antithrombotic therapy after hospital discharge at 1-year follow-up. CONCLUSION: The PERSEO Registry will investigate in a 'real world' setting the safety and efficacy of DOAC versus warfarin and dual versus triple antithrombotic therapy in patients with indication for oral anticoagulant therapy who undergo PCI-S.

Percutaneous Retrieval of a Left Atrial Appendage Closure Device: The Device Waltz.

Embolization of a device in patients undergoing percutaneous left atrial appendage closure is an uncommon complication. We present an illustrative case of successful percutaneous retrieval of an embolized LAmbre device (Lifetech Scientific, Shenzhen, China) that was achieved with a combination of a snaring technique and forceps grasping and by using a steerable guiding catheter. (Level of Difficulty: Advanced.).

Percutaneous coronary interventions and antiplatelet therapy in renal transplant recipients.

Cardiovascular disease is the leading cause of mortality and morbidity following renal transplantation (RT), accounting for 40-50% of all deaths. After renal transplantation, an adverse cardiovascular event occurs in nearly 40% of patients; given the dialysis vintage and the average wait time, the likelihood of receiving coronary revascularization is very high. There is a significant gap in the literature in terms of the outcomes of prophylactic coronary revascularization in renal transplantation candidates. Current guidelines on myocardial revascularization stipulate that renal transplant patients with significant coronary artery disease (CAD) should not be excluded from the potential benefit of revascularization. Compared with percutaneous coronary intervention (PCI), however, coronary artery bypass grafting is associated with higher early and 30-day mortality. About one-third of renal transplant patients with CAD have to be treated invasively and so PCI is currently the most popular mode of revascularization in these fragile and compromised patients. A newer generation drug-eluting stent (DES) should be preferred over a bare metal stent (BMS) because of its lower risk of restenosis and improved safety concerns (stent thrombosis) compared with first generation DES and BMS. Among DES, despite no significant differences being reported in terms of efficacy, the newer everolimus and zotarolimus eluting stents should be preferred given the possibility of discontinuing, if necessary, dual antiplatelet therapy before 12 months. Since there is a lack of randomized controlled trials, the current guidelines are inadequate to provide a specifically tailored antiplatelet therapeutic approach for renal transplant patients. At present, clopidogrel is the most used agent, confirming its central role in the therapeutic management of renal transplant patients undergoing PCI. While progress in malignancy-related mortality seems a more distant target, a slow but steady reduction in cardiovascular deaths, improving pharmacological and interventional therapy, is nowadays an achievable medium-term target in renal transplant patients.

Closed versus open cell stent for high-risk percutaneous coronary interventions in ST-elevation acute myocardial infarction: the Closed versus Open Cells stent for High risk percutaneous coronary Interventions in ST-Elevation acute myocardial infarction (COCHISE) pilot study.

BACKGROUND: Stent deployment may be associated with distal embolization and slow flow in coronary thrombotic lesions. There are no data on the risk of distal thrombus embolization according to the stent design. The aim was to evaluate coronary flow after percutaneous coronary interventions (PCI) in acute myocardial infarction according to the employed stent (closed versus open cell design). METHODS: From March 2010 to December 2011, 223 consecutive patients with acute ST-elevation myocardial infarction were randomized to primary PCI either with an open cell (112 patients, 88 men) or with a closed cell stent design (111 patients, 92 men). The primary endpoint was the corrected TIMI frame count (cTFC) after the procedure. RESULTS: There were no significant differences in procedural success nor in-stent deployment in the 2 groups. At baseline, there were no significant differences in cTFC between the 2 groups (70 ± 37 and 67 ± 39, P = .65, respectively). After the procedure, the open cell group showed significantly higher cTFC compared to the closed cell group (18 ± 11 and 15 ± 5, P = .003 respectively). This difference was associated with a significant lower rate of TIMI 3 flow (87% and 95%, P = .037) and myocardial blush grade 3 (65% and 87%, P = .001) in the open compared to the closed cell group. There were 2 cases of death in the open cell and 1 case in the closed cell group. CONCLUSIONS: The use of a closed cell stent design rather than an open cell during PCI for acute ST-elevation myocardial infarction is associated with better coronary angiographic flow after PCI.

Safety and efficacy of G-CSF in patients with ischemic heart failure: the CORNER (Cell Option For Recovery in the Non-Eligible Patients for Revascularization) study.

BACKGROUND: Demonstration that the heart is not a post-mitotic organ has led to clinical trials trying to obtain myocardial repair even in patients with heart failure. AIM OF THE STUDY: To evaluate as a less invasive method for promoting cardiac repair. METHODS: Thirteen patients with ischemic heart failure in NYHA and/or CCS classes ≥ 3 unsuitable for revascularization received G-CSF, as a compassionate use, in addition to optimal medical therapy. Symptoms and cardiac perfusion by gated-SPECT were assessed at baseline and at 4 month follow up. RESULTS: G-CSF was generally well tolerated. NYHA and CCS classes improved significantly from 3 (IR 2.5-3) to 2 (IR 1-2.5) (p = 0.012) and from 3 (IR 1-3) to 1 (IR 1-2) (p = 0.033). Heart failure severity symptoms according to the Minnesota Living with Heart Failure Questionnaire scores exhibited a non significant improvement from 52 ± 27 to 39 ± 26 (p = 0.15). At the Seattle Angina Questionnaire scores (ranging from 0 to 100, higher scores indicating better status), physical limitation improved from 39 ± 31 to 64 ± 29 (p = 0.03), angina stability from 42 ± 29 to 64 ± 28 (p = 0.05), angina frequency from 53 ± 33 to 73 ± 26 (p = 0.04), treatment satisfaction from 67 ± 29 to 83 ± 21 (p = 0.07), disease perception from 37 ± 29 to 66 ± 26 (p = 0.007). Quality of life assessed by a Visual Analogue Scale improved from 33 ± 24 to 64 ± 20 mm (p = 0.003). Stress and differential regional perfusion scores improved significantly from 1.78 ± 1.38 to 1.66 ± 1.38 (p = 0.05) and from 0.35 ± 0.68 to 0.23 ± 0.53 (p = 0.02) respectively. CONCLUSIONS: In patients with ischemic heart failure unsuitable for revascularization, G-CSF is associated to a significant improvement of symptoms, possibly reducing stress-induced ischemia.

The PREHAMI (PREsillion™ in high-risk acute myocardial infarction) registry: in-hospital and long-term outcomes.

OBJECTIVES: To evaluate the efficacy of the new Cobalt-Chromium (Co-Cr) Presillion™ stent for the treatment of high-risk acute myocardial infarction (MI) patients. BACKGROUND: Percutaneous coronary intervention (PCI) with stent represents the gold standard treatment for acute MI. METHODS AND RESULTS: We enrolled patients with high-risk acute MI (either ST-segment elevation MI or non-ST-segment elevation MI) treated with PCI using a new Co-Cr bare metal stent with closed cells design and limited balloon compliance. We considered high-risk features as one of the following: age ≥ 70 years, ejection fraction ≤ 35%, glomerular filtration rate ≤ 60 mL/min, diabetes mellitus, rescue PCI, or chronic atrial fibrillation or other conditions requiring long-term oral anticoagulation therapy. Primary outcome of the study was rate of major adverse cardiac events (MACE) defined as all-cause death, new MI, and target-vessel revascularization. A total of 129 consecutive patients were enrolled (69 ± 11 years, 74% men): 71 (55%) patients with ST-segment elevation MI and 58 (45%) patients with non-ST-segment elevation MI. A total of 153 vessels (169 lesions and 179 stents) were treated. The device success rate was high (98.8%). In-hospital MACE rate was 5.4% mainly because of death associated with the acute MI. At 1-year follow-up, the MACE rate was 17.3%, with 11% all-cause death (7.9% of cardiac origin), 0.6% of stent thrombosis, and 4.6% target-vessel revascularization. CONCLUSIONS: The use of the Co-Cr Presillion stent in patients with high-risk acute MI treated invasively seems to be safe and efficacious with optimal deliverability and good long-term outcomes and represents a good option in the treatment of these patients.

From bone marrow to the arterial wall: the ongoing tale of endothelial progenitor cells.

Several physiological and pathophysiological stimuli or drugs modulate endothelial progenitor cell (EPC) mobilization. Moreover, levels of circulating EPCs predict cardiovascular risk and left ventricular remodelling after myocardial infarction. Nevertheless, our understanding in this field is complicated by lack of an unequivocal definition of EPCs, thus limiting their clinical applications. This review summarizes current knowledge and uncertainties on EPC characterization and mobilization in the attempt to define their role in the management of cardiovascular diseases.

Effect of intensive vs standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: Statins for regeneration after acute myocardial infarction and PCI (STRAP) trial.

BACKGROUND: Intensive statin therapy can lower the risk of recurrence of major cardiac events in patients with acute coronary syndromes. This could be related to the ability of statins to increase levels of Endothelial Progenitor Cells (EPCs), which were demonstrated to be favorably associated with a better prognosis and post-infarction left ventricular remodeling in patients with ischemic heart disease. AIM OF THE STUDY: First, to evaluate, in a randomized clinical trial, the effect of an intensive vs a standard treatment with statins on EPC mobilization in patients undergoing a successful primary or rescue percutaneous coronary intervention; secondary, to evaluate whether left ventricular remodeling could be influenced by statin therapy through EPC mobilization. METHODS: Forty ST-segment elevation myocardial infarction (STEMI) patients undergoing a successful primary or rescue PCI were randomized to receive atorvastatin 80 mg immediately after the admission (Intensive Treatment, IT) or atorvastatin 20 mg from the day of the discharge (Standard Treatment, ST). CD34+/KDR+ EPC count by flow cytometry and left ventricular function by 2-D Echo were measured on admission, at discharge and at 4 months follow up. RESULTS: We found that EPC count was similar in the two groups of patients both on admission and at discharge. At follow up, however, EPC count was higher in patients randomized to IT compared to patients randomized to ST (7.59+/-7.30 vs 3.04+/-3.93, p=0.04). However, LV volumes, ejection fraction and wall motion score index were similar in both groups. CONCLUSIONS: An intensive statin treatment after primary or rescue PCI is associated with a higher EPC count at follow up as compared to standard treatment. This beneficial effect did not translate in an improvement of LV function.

Usefulness of granulocyte colony-stimulating factor in patients with a large anterior wall acute myocardial infarction to prevent left ventricular remodeling (the rigenera study).

Intracoronary injection of bone marrow stem cells seems to improve left ventricular (LV) function after acute myocardial infarction (AMI). Granulocyte colony-stimulating factor (G-CSF) could improve myocardial function and perfusion noninvasively through mobilization of stem cells into peripheral blood, although previous clinical trials have produced controversial results. Forty-one patients with large anterior wall AMI at high risk of unfavorable remodeling were randomized 1:2 to G-CSF (10 microg/kg/day for 5 days) or to conventional therapy. All patients underwent successful primary or rescue percutaneous coronary intervention. LV function was assessed by echocardiography before G-CSF administration, > or =5 days after AMI, and at follow-up. Only patients with a LV ejection fraction <50% at baseline were enrolled in the study. After a median follow-up of 5 months (range 4 to 6) patients treated with G-CSF exhibited improvement in LV ejection fraction, from 40 +/- 6% to 45 +/- 6% (p = 0.068) in the absence of LV dilation (LV end-diastolic volume from 147 +/- 33 to 144 +/- 46 ml at follow-up, p = 0.77). In contrast, patients treated conventionally exhibited significant LV dilation (LV end-diastolic volume from 141 +/- 35 to 168 +/- 41 ml, p = 0.002) in the absence of change in LV ejection fraction (from 38 +/- 6% to 38 +/- 8%, p = 0.95). However, when comparing patients treated with G-CSF with controls, variations in these parameters were significantly different at 2-way analysis of variance (p = 0.04 for LV end-diastolic volume, p = 0.02 for LV ejection fraction). In conclusion, G-CSF prevents unfavorable LV remodeling and improves LV function in patients with large anterior wall AMI and decreased LV ejection fraction after successful percutaneous coronary intervention.

Endogenous G-CSF and CD34+ cell mobilization after acute myocardial infarction.

BACKGROUND: Several reports showed an increase of CD34(+) stem/progenitor cell count early after an acute myocardial infarction (AMI), suggesting a contribution of bone marrow cells in myocardial regeneration after the acute event. Nevertheless, at present plasma mediators of CD34(+) cell mobilization from bone marrow to peripheral blood in patients with AMI are poorly understood. Aim of our study was to establish the impact of different well-known mobilizing cytokines on spontaneous stem cell mobilization in patients with different ischemic heart syndromes, such as the AMI and the chronic stable angina (CSA), compared to healthy controls. METHODS: In 16 patients with AMI, 18 with CSA and 22 healthy blood donors the concentration of CD34(+) cells, and mobilizing cyokines (G-CSF, SCF, VEGF, SDF1-alpha) were assessed. RESULTS: The peak number of circulating CD34(+) cells in AMI patients (8.58+/-2.08 cells/microl) was higher than that observed in patients with CSA (3.41+/-0.56 cells/microl, p=0.0061) or in healthy controls (2.18+/-0.35 cells/microl, p<0.001). However endogenous G-CSF was significantly higher in the serum of patients with AMI compared to CSA patients and to controls and in CSA patients compared to controls. Interestingly, as regards VEGF, while this cytokine was increased in AMI with respect to control and CSA group, the latter showed a significantly lower concentration with respect to controls. Finally SDF-1 alpha was higher in AMI patients with respect to controls. CD34(+) cells were significantly correlated to G-CSF (directly) and to SCF (inversely) in patients with AMI. CONCLUSION: In the present study, we have demonstrated for the first time that the spontaneous mobilization of CD34(+) cells into the peripheral blood of patients with AMI is significantly correlated to endogenous G-CSF. Considering recent data suggesting a potential favourable effect of circulating CD34(+) cells on left ventricular function, the present evidence of a correlation between endogenous G-CSF and CD34(+) cell levels supports the pharmacological administration of G-CSF as a non-invasive option for regeneration of myocardial tissue after AMI.