Rare instances of concomitant acute myocardial infarction and stroke.

Cardio-cerebral infarction (CCI) is a term coined to describe concomitant myocardial infarction and acute ischemic stroke. Acute myocardial infarction and stroke, as separate events, constitute some of the most important causes for disability and mortality in aging societies. Stroke can either occur simultaneously with myocardial infarction or become a serious complication of myocardial infarction and/or its treatment. The frequency of CCI has been reported at a 0.009% incidence rate in stroke patients and is associated with an extremely high mortality. Because of the rare occurrence of CCI, there are currently no guidelines for assessing its diagnosis and optimal treatment. Therefore, currently, the management of CCI cases needs to be individualized. Hopefully, in the future, the results of large clinical trials or prospective registries are expected to enhance our understanding of managing concomitant acute MI and stroke. In this review we have focused on the current literacy in the diagnosis and treatment of CCIs. The paper illustrates potential distinct scenarios of CCI through the analysis of three patient cases (Fig. 5, Ref. 65). Text in PDF www.elis.sk Keywords: myocardial infarction, stroke, cardio-cerebral infarction, carotid artery stenting, cardiac surgery.

Endovascular carotid revascularization under open-chest extracorporeal circulation combined with cardiac surgery in unstable patients at increased risk of carotid-related stroke: SIMultaneous urgent cardiac surgery and MicroNet-covered stent carotid revascularization in extreme-risk patients-SIMGUARD Study.

BACKGROUND: In patients at urgent need for cardiac surgery coexisting with increased-stroke-risk carotid stenosis, any staged intervention increases the risk of complications from the primarily unaddressed pathology. In this challenging cohort, we assessed safety and feasibility of endovascular carotid revascularization under open-chest extracorporeal circulation (ECC) combined with cardiac surgery (hybrid-room true simultaneous treatment). METHODS: Per-protocol (PP), after general anesthesia induction, chest-opening and ECC stand-by installation, carotid stenting (CAS) was performed (femoral/radial or direct carotid access) with ad-hoc/on-hand switch to ECC cardiac surgery. RESULTS: Over 78 months, 60 patients (70.7±6.9years, 85% male, all American Society of Anesthesiology grade IV) were enrolled. All were at increased carotid-related stroke risk (ipsilateral recent stroke/transient ischemick attack, asymptomatic cerebral infarct, increased-risk lesion morphology, bilateral severe stenosis). Majority of study procedures involved CAS+coronary bypass surgery or CAS+valve replacement±coronary bypass. 45 (75%) patients were PP- and 15 (25%) not-PP (NPP-) managed (context therapy). CAS was 100% neuroprotected (transient flow reversal-64.4%, filters-35.6%) and employed micronet-covered plaque-sequestrating stents with routine post-dilatation optimization/embedding. 4 deaths (6.7%) and 7 strokes (11.7%) occurred by 30-days. Despite CAS+surgery performed on aspirin and unfractionated heparin-only (delayed clopidogrel-loading), no thrombosis occurred in the stented arteries, and 30-days stent patency was 100%. NPP-management significantly increased the risk of death/ipsilateral stroke (OR 38.5; P<0.001) and death/any stroke (OR 12.3; P=0.002) by 30-days. CONCLUSIONS: In cardiac unstable patients at increased carotid-related stroke risk who require urgent cardiac surgery, simultaneous cardiac surgery and CAS with micronet-covered stent lesion sequestration is feasible and safe and shows efficacy in minimizing stroke risk. Larger-scale, multicentric evaluation is warranted. (SIMGUARD NCT04973579).

Imaging modality-dependent carotid stenosis severity variations against intravascular ultrasound as a reference: Carotid Artery intravasculaR Ultrasound Study (CARUS).

PURPOSE: Different non-invasive and invasive imaging modalities are used to determine carotid artery stenosis severity that remains a principal parameter in clinical decision-making. We compared stenosis degree obtained with different modalities against vascular imaging gold standard, intravascular ultrasound, IVUS. METHODS: 300 consecutive patients (age 47-83 years, 192 men, 64% asymptomatic) with carotid artery stenosis of " ≥ 50%" referred for potential revascularization received as per study protocol (i) duplex ultrasound (DUS), (ii) computed tomography angiography (CTA), (iii) intraarterial quantitative angiography (iQA) and (iv) and (iv) IVUS. Correlation of measurements with IVUS (r), proportion of those concordant (within 10%) and proportion of under/overestimated were calculated along with recipient-operating-characteristics (ROC). RESULTS: For IVUS area stenosis (AS) and IVUS minimal lumen area (MLA), there was only a moderate correlation with DUS velocities (peak-systolic, PSV; end-diastolic, EDV; r values of 0.42-0.51, p < 0.001 for all). CTA systematically underestimated both reference area and MLA (80.4% and 92.3% cases) but CTA error was lesser for AS (proportion concordant-57.4%; CTA under/overestimation-12.5%/30.1%). iQA diameter stenosis (DS) was found concordant with IVUS in 41.1% measurements (iQA under/overestimation 7.9%/51.0%). By univariate model, PSV (ROC area-under-the-curve, AUC, 0.77, cutoff 2.6 m/s), EDV (AUC 0.72, cutoff 0.71 m/s) and CTA-DS (AUC 0.83, cutoff 59.6%) were predictors of ≥ 50% DS by IVUS (p < 0.001 for all). Best predictor, however, of ≥ 50% DS by IVUS was stenosis severity evaluation by automated contrast column density measurement on iQA (AUC 0.87, cutoff 68%, p < 0.001). Regarding non-invasive techniques, CTA was the only independent diagnostic modality against IVUS on multivariate model (p = 0.008). CONCLUSION: IVUS validation shows significant imaging modality-dependent variations in carotid stenosis severity determination.

Clinical Characteristics and Outcomes of Aortic Arch Emergencies: Takayasu Disease, Fibromuscular Dysplasia, and Aortic Arch Pathologies: A Retrospective Study and Review of the Literature.

Non-atherosclerotic aortic arch pathologies (NA-AAPs) and anatomical variants are characterized as rare cardiovascular diseases with a low incidence rate, below 1 case per 2000 population, but enormous heterogeneity in terms of anatomical variants, i.e., Takayasu disease (TAK) and fibromuscular dysplasia (FMD). In specific clinical scenarios, NA-AAPs constitute life-threatening disorders. METHODS: In this study, 82 (1.07%) consecutive patients with NA-AAPs (including 38 TAKs, 26 FMDs, and 18 other AAPs) out of 7645 patients who underwent endovascular treatment (EVT) for the aortic arch and its side-branch diseases at a single institution between 2002 and 2022 were retrospectively reviewed. The recorded demographic, biochemical, diagnostic, operative, and postoperative factors were reviewed, and the functional outcomes were determined during follow-up. A systematic review of the literature was also performed. RESULTS: The study group comprised 65 (79.3%) female and 17 (21.7%) male subjects with a mean age of 46.1 ± 14.9 years. Overall, 62 (75.6%) patients were diagnosed with either cerebral ischemia symptoms or aortic arch dissection on admission. The EVT was feasible in 59 (72%) patients, whereas 23 (28%) patients were referred for medical treatment. In EVT patients, severe periprocedural complications occurred in two (3.39%) patients, including one periprocedural death and one cerebral hyperperfusion syndrome. During a median follow-up period of 64 months, cardiovascular events occurred in 24 (29.6%) patients (5 deaths, 13 ISs, and 6 myocardial infarctions). Repeated EVT for the index lesion was performed in 21/59 (35.6%) patients, including 19/33 (57.6%) in TAK and 2/13 (15.4%) in FMD. In the AAP group, one patient required additional stent-graft implantation for progressing dissection to the iliac arteries at 12 months. A baseline white blood count (odds ratio [HR]: 1.25, 95% confidence interval [CI]: 1.11-1.39; p < 0.001) was the only independent prognostic factor for recurrent stenosis, while a baseline hemoglobin level (HR: 0.73, 95%CI: 0.59-0.89; p = 0.002) and coronary involvement (HR: 4.11, 95%CI: 1.74-9.71; p = 0.001) were independently associated with a risk of major cardiac and cerebral events according to the multivariate Cox proportional hazards regression analysis. CONCLUSIONS: This study showed that AAPs should not be neglected in clinical settings, as it can be a life-threatening condition requiring a multidisciplinary approach. The knowledge of prognostic risk factors for adverse outcomes may improve surveillance in this group of patients.

World Federation for Interventional Stroke Treatment (WIST) multispecialty training guidelines for endovascular stroke intervention.

Introduction: Today, endovascular treatment (EVT) is the therapy of choice for strokes due to acute large vessel occlusion, irrespective of prior thrombolysis. This necessitates fast, coordinated multi-specialty collaboration. Currently, in most countries, the number of physicians and centres with expertise in EVT is limited. Thus, only a small proportion of eligible patients receive this potentially life-saving therapy, often after significant delays. Hence, there is an unmet need to train a sufficient number of physicians and centres in acute stroke intervention in order to allow widespread and timely access to EVT. Aim: To provide multi-specialty training guidelines for competency, accreditation and certification of centres and physicians in EVT for acute large vessel occlusion strokes. Material and methods: The World Federation for Interventional Stroke Treatment (WIST) consists of experts in the field of endovascular stroke treatment. This interdisciplinary working group developed competency - rather than time-based - guidelines for operator training, taking into consideration trainees' previous skillsets and experience. Existing training concepts from mostly single specialty organizations were analysed and incorporated. Results: The WIST establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in EVT. WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. Conclusions: WIST multispecialty guidelines outline competency and quality standards for physicians and centres to perform safe and effective EVT. The role of quality control and quality assurance is highlighted.

World Federation for Interventional Stroke Treatment (WIST) Multispecialty Training Guidelines for Endovascular Stroke Intervention.

INTRODUCTION: Today, endovascular treatment (EVT) is the therapy of choice for strokes due to acute large vessel occlusion, irrespective of prior thrombolysis. This necessitates fast, coordinated multi-specialty collaboration. Currently, in most countries, the number of physicians and centres with expertise in EVT is limited. Thus, only a small proportion of eligible patients receive this potentially life-saving therapy, often after significant delays. Hence, there is an unmet need to train a sufficient number of physicians and centres in acute stroke intervention in order to allow widespread and timely access to EVT. AIM: To provide multi-specialty training guidelines for competency, accreditation and certification of centres and physicians in EVT for acute large vessel occlusion strokes. MATERIAL AND METHODS: The World Federation for Interventional Stroke Treatment (WIST) consists of experts in the field of endovascular stroke treatment. This interdisciplinary working group developed competency - rather than time-based - guidelines for operator training, taking into consideration trainees' previous skillsets and experience. Existing training concepts from mostly single specialty organizations were analysed and incorporated. RESULTS: The WIST establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in EVT. WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. CONCLUSIONS: WIST multispecialty guidelines outline competency and quality standards for physicians and centres to perform safe and effective EVT. The role of quality control and quality assurance is highlighted. SUMMARY: The World Federation for Interventional Stroke Treatment (WIST) establishes an individualized approach to acquiring clinical knowledge and procedural skills to meet the competency requirements for certification of interventionalists of various disciplines and stroke centres in endovascular treatment (EVT). WIST guidelines encourage acquisition of skills using innovative training methods such as structured supervised high-fidelity simulation and procedural performance on human perfused cadaveric models. WIST multispecialty guidelines outline competency and quality standards for physicians and centers to perform safe and effective EVT. The role of quality control and quality assurance is highlighted. SIMULTANEOUS PUBLICATION: The WIST 2023 Guidelines are published simultaneously in Europe (Adv Interv Cardiol 2023).

Carotid artery revascularization using second generation stents versus surgery: a meta-analysis of clinical outcomes.

INTRODUCTION: Meta-analyses and emerging randomized data indicate that second-generation ('mesh') carotid stents (SGS) may improve outcomes versus conventional (single-layer) stents but clinically-relevant differences in individual SGS-type performance have been identified. No comparisons exist for SGS versus carotid endarterectomy (CEA). EVIDENCE ACQUISITION: Thirty-day death (D), stroke (S), myocardial infarction (M), and 12-month ipsilateral stroke and restenosis in SGS studies were meta-analyzed (random effect model) against CEA outcomes. Eligible studies were identified through PubMed/EMBASE/COCHRANE. Forest plots were formed for absolute adverse evet risk in individual studies and for relative outcomes with each SGS deign versus contemporary CEA outcomes as reference. Meta-regression was performed to identify potential modifiers of treatment modality effect. EVIDENCE SYNTHESIS: Data were extracted from 103,642 patients in 25 studies (14 SGS-treated, 41% symptomatic; nine randomized controlled trial (RCT)-CEA-treated, 37% symptomatic; and two Vascular Quality Initiative (VQI)-CEA-treated, 23% symptomatic). Casper/Roadsaver and CGuard significantly reduced DSM versus RCT-CEA (-2.70% and -2.95%, P<0.001 for both) and versus VQI-CEA (-1.11% and -1.36%, P<0.001 for both). Gore stent 30-day DSM was similar to RCT-CEA (P=0.581) but increased against VQI-CEA (+2.38%, P=0.033). At 12 months, Casper/Roadsaver ipsilateral stroke rate was lower than RCT-CEA (-0.75%, P=0.026) and similar to VQI-CEA (P=0.584). Restenosis with Casper/Roadsaver was +4.18% vs. RCT-CEA and +4.83% vs. VQI-CEA (P=0.005, P<0.001). CGuard 12-month ipsilateral stroke rate was similar to VQI-CEA (P=0.850) and reduced versus RCT-CEA (-0.63%, P=0.030); restenosis was reduced respectively by -0.26% and -0.63% (P=0.033, P<0.001). Twelve-month Gore stent outcomes were overall inferior to surgery. CONCLUSIONS: Meta-analytic integration of available clinical data indicates: 1) reduction in stroke but increased restenosis rate with Casper/Roadsaver, and 2) reduction in both stroke and restenosis with CGuard MicroNET-covered stent against contemporary CEA outcomes at 30 days and 12 months used as a reference. This may inform clinical practice in anticipation of large-scale randomized trials powered for low clinical event rates (PROSPERO-CRD42022339789).

Clinical Outcomes of Extracranial Carotid Artery-Related Stroke Eligible for Mechanical Reperfusion on Top of Per-Guidelines Thrombolytic Therapy: Analysis from a 6-Month Consecutive Patient Sample in 2 Centers.

BACKGROUND Systemic intravenous thrombolysis and mechanical thrombectomy (MT) are guideline-recommended reperfusion therapies in large-vessel-occlusion ischemic stroke. However, for acute ischemic stroke of extracranial carotid artery origin (AIS-CA) there have been no specific trials, resulting in a data gap. MATERIAL AND METHODS We evaluated referral/treatment pathways, serial imaging, and neurologic 90-day outcomes in consecutive patients, presenting in a real-life series in 2 stroke centers over a period of 6 months, with AIS-CA eligible for emergency mechanical reperfusion (EMR) on top of thrombolysis as per guideline criteria. RESULTS Of 30 EMR-eligible patients (33.3% in-window for thrombolysis and thrombolysed, 73.3% male, age 39-87 years, median Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 10, pre-stroke mRS 0-1 in all, tandem lesions 26.7%), 20 (66.7%) were EMR-referred (60% - endovascular, 6.7% - surgery referrals). Only 40% received EMR, nearly exclusively in stroke centers with carotid artery stenting (CAS) expertise (100% eligible patient acceptance rate, 100% treatment delivery involving CAS±MT with culprit lesion sequestration using micronet-covered stents). The emergency surgery rate was 0%. Baseline clinical and imaging characteristics did not differ between EMR-treated and EMR-untreated patients. Ninety-day neurologic status was profoundly better in EMR-treated patients: mRS 0-2 (91.7% vs 0%; P<0.001); mRS 3-5 (8.3% vs 88.9%; P<0.001), mRS 6 (0% vs 11.1%; P<0.001). CONCLUSIONS In a real-life AIS-CA setting, the referral rate of EMR-eligible patients for EMR was low, and the treatment rate was even lower. AIS-CA revascularization was delivered predominantly in stroke thrombectomy-capable cardioangiology centers, resulting in overwhelmingly superior patient outcome. Large vessel occlusion stroke referral and management pathways should involve centers with proximal-protected CAS expertise. AIS-CA, irrespective of any thrombolysis administration, is a hyperacute cerebral emergency and EMR-eligible patients should be immediately referred for mechanical reperfusion.

Diabetes Mellitus and Clinical Outcomes in Carotid Artery Revascularization Using Second-Generation, MicroNet-Covered Stents: Analysis from the PARADIGM Study.

Introduction: Carotid artery stenting (CAS) using conventional (single-layer) stents is associated with worse clinical outcomes in diabetes mellitus (DM) vs. non-DM patients: an effect driven largely by lesion-related adverse events. CAS outcomes with MicroNet-covered stents (MCS) in diabetic patients have not been evaluated. Aim: To compare short- and long-term clinical outcomes and restenosis rate in DM vs. non-DM patients with carotid stenosis treated using MCS. Materials and Methods: In a prospective study in all-comer symptomatic and increased-stroke-risk asymptomatic carotid stenosis, 101 consecutive patients (age 51-86 years, 41% diabetics) underwent 106 MCS-CAS. Clinical outcomes and duplex ultrasound velocities were assessed periprocedurally and at 30 days/12 months. Results: Baseline characteristics of DM vs. non-DM patients were similar except for a higher prevalence of recent cerebral symptoms in DM. Type 1 and type 1+2 plaques were more prevalent in DM patients (26.7% vs. 9.8%, p = 0.02; 62.2% vs. 37.7%, p = 0.01). Proximal embolic protection was more prevalent in DM (60% vs. 36%; p = 0.015). 30-day clinical complications were limited to a single periprocedural minor stroke in DM (2.4% vs. 0%, p = 0.22). 12-month in-stent velocities and clinical outcomes were not different (death rate 4.8% vs. 3.3%; p = 0.69; no new strokes). Restenosis rate was not different (0% vs. 1.7%, p = 0.22). Conclusions: MCS may offset the adverse impact of DM on periprocedural, 30-day, and 12-month clinical complications of CAS and minimize the risk of in-stent restenosis. In this increased-stroke-risk cohort, adverse event rate was low both in DM and non-DM. Further larger-scale clinical datasets including extended follow-ups are warranted.

Clinical Outcomes of Second- versus First-Generation Carotid Stents: A Systematic Review and Meta-Analysis.

Background: Single-cohort studies suggest that second-generation stents (SGS; "mesh stents") may improve carotid artery stenting (CAS) outcomes by limiting peri- and postprocedural cerebral embolism. SGS differ in the stent frame construction, mesh material, and design, as well as in mesh-to-frame position (inside/outside). Objectives: To compare clinical outcomes of SGS in relation to first-generation stents (FGSs; single-layer) in CAS. Methods: We performed a systematic review and meta-analysis of clinical studies with FGSs and SGS (PRISMA methodology, 3302 records). Endpoints were 30-day death, stroke, myocardial infarction (DSM), and 12-month ipsilateral stroke (IS) and restenosis (ISR). A random-effect model was applied. Results: Data of 68,422 patients from 112 eligible studies (68.2% men, 44.9% symptomatic) were meta-analyzed. Thirty-day DSM was 1.30% vs. 4.11% (p < 0.01, data for SGS vs. FGS). Among SGS, both Casper/Roadsaver and CGuard reduced 30-day DSM (by 2.78 and 3.03 absolute percent, p = 0.02 and p < 0.001), whereas the Gore stent was neutral. SGSs significantly improved outcomes compared with closed-cell FGS (30-day stroke 0.6% vs. 2.32%, p = 0.014; DSM 1.3% vs. 3.15%, p < 0.01). At 12 months, in relation to FGS, Casper/Roadsaver reduced IS (−3.25%, p < 0.05) but increased ISR (+3.19%, p = 0.04), CGuard showed a reduction in both IS and ISR (−3.13%, −3.63%; p = 0.01, p < 0.01), whereas the Gore stent was neutral. Conclusions: Pooled SGS use was associated with improved short- and long-term clinical results of CAS. Individual SGS types, however, differed significantly in their outcomes, indicating a lack of a "mesh stent" class effect. Findings from this meta-analysis may provide clinically relevant information in anticipation of large-scale randomized trials.

Symptomatic atherosclerotic plaque progression in a first-generation carotid stent: management and 5-year clinical and imaging outcome-a case report.

BACKGROUND: Restenosis in first-generation (single-layer) carotid stents (FGS) is believed to represent an exaggerated healing response of (neo)intimal hyperplasia (NIH) formation. Rather than NIH, we describe symptomatic in-FGS unstable plaque (neo)atherosclerosis mandating re-revascularization. To halt continued plaque evolution, we propose a novel treatment strategy involving a microNet-covered stent (MCS, second-generation carotid stent) to sequestrate the plaque from the vessel lumen. A durable long-term result is documented using multi-modal imaging. CASE SUMMARY: With a seemingly optimal result of FGS (Precise) symptomatic carotid lesion revascularization followed by optimal medical therapy, a late (≥3 years) progressive in-stent restenosis (ISR) arose. At Year 11, crescendo ipsilateral transient ischaemic attacks occurred. Angiography showed an ulcerated tight lesion throughout stent length. Intravascular ultrasound (IVUS) virtual histology imaging revealed thin-cap fibroatheroma. Reintervention was performed under distal protection. Undersized balloon predilatation to insert a stent caused symptomatic no-flow, and aspiration catheter was used to reduce the filter load. A MCS (CGuard) was implanted and post-dilated to ensure full lumen gain; IVUS confirmed complete plaque sequestration. The optimal anatomic result remained unchanged throughout 5 years (ultrasound and computed tomography verification); this was accompanied by clinical cure. DISCUSSION: This is the first demonstration of in-FGS (neo)atherosclerosis resolution using an MCS to sequestrate and insulate the atherosclerotic plaque. We show that ISR may be underlined by atherosclerotic plaque progression via the FGS single-layer stent struts that may show vulnerable plaque phenotype and may be associated with cerebral ischaemia. The anatomically and clinically effective exclusion of the atherosclerotic plaque by an MCS enabled lasting, optimal endovascular reconstruction and clinical cure.

Single-photon emission computed tomography as a fundamental tool in evaluation of myocardial reparation and regeneration therapies.

Despite unquestionable progress in interventional and pharmacologic therapies of ischemic heart disease, the number of patients with chronic ischemic heart failure is increasing and the prognosis remains poor. Repair/restoration of functional myocardium through progenitor cell-mediated (PCs) healing and renovation of injured myocardium is one of the pivotal directions in biomedical research. PCs release numerous pro-angiogenic and anti-apoptotic factors. Moreover, they have self-renewal capability and may differentiate into specialized cells that include endothelial cells and cardiomyocytes. Uptake and homing of PCs in the zone(s) of ischaemic injury (i.e., their effective transplantation to the target zone) is an essential pre-requisite for any potential therapeutic effect; thus effective cell tracking is fundamental in pre-clinical and early clinical studies. Another crucial requirement in rigorous research is quantification of the infarct zone, including the amount of non-perfused and hypo-perfused myocardium. Quantitative and reproducible evaluation of global and regional myocardial contractility and left ventricular remodeling is particularly relevant in clinical studies. Using SPECT, our earlier work has addressed several critical questions in cardiac regenerative medicine including optimizing transcoronary cell delivery, determination of the zone(s) of myocardial cell uptake, and late functional improvement in relation to the magnitude of cell uptake. Here, we review the role of single-photon emission computed tomography (SPECT), a technique that offers high-sensitivity, quantitative cell tracking on top of its ability to evaluate myocardial perfusion and function on both cross-sectional and longitudinal bases. SPECT, with its direct relevance to routine clinical practice, is a fundamental tool in evaluation of myocardial reparation and regeneration therapies.

Transcoronary stem cell transfer and evolution of infarct-related artery atherosclerosis: evaluation with conventional and novel imaging techniques including Quantitative Virtual Histology (qVH).

Introduction: It has been suggested that infarct-related artery (IRA) atherosclerosis progression after stem cell transcoronary administration might represent a stem-cell mediated adverse effect. Aim: To evaluate, using conventional (quantitative coronary angiography, QCA, intravascular ultrasound - IVUS) and novel (quantitative virtual histology - qVH) tools, evolution of IRA atherosclerosis following transcoronary stem cell transfer. Material and methods: QCA, IVUS, VH-IVUS and qVH were performed in 22 consecutive patients (4 women) aged 59 years (data provided as median) undergoing a distal-to-stent infusion of 2.21 × 106 CD34+CXCR4+ autologous bone marrow cells via a cell delivery-dedicated perfusion catheter at anterior AMI day 7. Imaging was repeated at 12 months. This was a substudy of Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial (NCT00316381). Results: 18.2% subjects showed absence of distal-to-stent angiographic/IVUS atherosclerotic lesion(s) at baseline and no new lesion(s) at 12-months. In the remaining cohort, there were 28 lesions by QCA (32 by IVUS) at baseline and no new lesion(s) at follow-up. Three fibroatheromas evolved (2 to calcified fibroatheroma and 1 to a fibrocalcific lesion); other plaques maintained their stable (low-risk) phenotypes. Diameter stenosis of QCA-identified lesions was 29.5 vs. 26.5% (p = 0.012, baseline vs. 12-months). Gray-scale IVUS showed reduction in area stenosis (33.8 vs. 31.0%, p = 0.004) and plaque burden (66.27 vs. 64.56%, p = 0.009) at 12-months. Peak fibrotic plaque content increased from 70.41% to 75.0% (p = 0.004). qVH peak confluent necrotic core area and minimal fibrous cap thickness remained stable (0.64 vs. 0.59 mm2, p = 0.290, and 0.15 vs. 0.16 mm, p = 0.646). Conclusions: This study, using a range of classic and novel imaging techniques, indicates lack of any stimulatory effect of transcoronary stem cell transfer on coronary atherosclerosis. Whether, and to what extent, a moderate reduction in plaque burden and stenosis severity at 12-months results from optimized pharmacotherapy and/or stem cell transfer requires further elucidation.

Trans-endocardial delivery of progenitor cells to compromised myocardium using the "needle technique"and risk of myocardial injury.

Introduction: Recent analysis from CHART-1 study indicated that the therapeutic effects of trans-endocardial cardiopoetic cell transplantation in chronic ischemic heart failure (iCHF) may be lost with an increasing number of injections perfomed to deliver therapeutic cells. Aim: To evaluate global and regional contractility and diastolic function of the left ventricle of patients with iCHF who received trans-endomyocardial cardiopoietic stem cells (CSCs) delivery or sham procedures. Material and methods: The study included patients (mean age: 60.8 ±7.1 years) with iCHF (left ventricular ejection fraction (LVEF) < 35%) and a history of hospitalization for worsening heart failure within 12 months despite optimal medical therapy. The patients underwent transmyocardial CSCs transplantation using perforated needle technique or a sham procedure. The wall motion score index (WMSI), LVEF, transmitral E-velocity, E-wave deceleration time, E/A-ratio, and E/e'-mean value were measured with two-dimensional echocardiography on days 1 and 30. Results: A total of 170 segments were analyzed, including 48 targeted segments where 92 injections of 0.5 ml of CSCs were performed. In the transendocardial injections cohort, a decrease in regional contractility was observed in 30.6% (26/85) and 18.9% (16/85) of the segments on days 1 and 30, respectively. This was accompanied by an increase in WMSI by 0.32 ±0.06 and 0.19 ±0.18 (day 1, p = 0.02, day 30, p = 0.03) and a reduction in LVEF (-3.15 ±1.23%, p = 0.065). Conclusions: Transendocardial injections performed to deliver therapeutic cells were associated with myocardial injury. This adverse effect remained, albeit at a lesser degree, at 30-days. Mechanical injury with trans-endocardial delivery of progenitor cells using the "needle technique" may counterbalance, at least in part, any cell-related benefit(s).

Objective, observer-independent evaluation of myocardial perfusion and function: role of SPECT.

The number of patients with coronary artery disease and ischaemic heart failure - and those with terminal heart failure - is increasing despite improvements in medical and interventional therapies of ischaemic heart disease - and, over the next decades, it is projected to continue to increase further. Observer-independent, reproducible imaging techniques play a fundamental role in objective evaluation of both conventional (such as surgical or percutaneous) myocardial revascularization and novel therapeutic approaches to reduce myocardial ischaemia, improve contractility and prevent adverse myocardial remodelling. To be applicable to clinical practice, the clinical study design and data should best be rooted in everyday clinical practice. Accurate and reproducible assessment of left ventricular ejection fraction, left ventricular volumes, myocardial perfusion and function is one of the most important objectives of cardiac imaging. Current techniques used both in clinical studies and in everyday clinical practice include 2- and 3-dimensional echocardiography, magnetic resonance imaging, single-photon emission computed tomography and positron emission tomography; each of these has its strengths and limitations. We review present evidence on the role of single-photon emission computed tomography as a technique that may offer, through being observer-independent, the most objective evaluation of evolution of left ventricular perfusion, volumes and ejection fraction.

Infarct size and long-term left ventricular remodelling in acute myocardial infarction patients subjected to transcoronary delivery of progenitor cells.

Introduction: Infarct size (IS) is a fundamental determinant of left-ventricular (LV) remodelling (end-systolic and end-diastolic volume change, ΔESV, ΔEDV) and adverse clinical outcomes after myocardial infarction (MI). Our prior work found that myocardial uptake of transcoronary-delivered progenitor cells is governed by IS. Aim: To evaluate the relationship between IS, stem cell uptake, and the magnitude of LV remodelling in patients receiving transcoronary administration of progenitor cells shortly after MI. Material and methods: Thirty-one subjects (age 36-69 years) with primary percutaneous coronary intervention (pPCI)-treated anterior ST-elevation MI (peak CK-MB 584 [181-962] U/l, median [range]) and sustained left ventricle ejection fraction (LVEF) ≤ 45% were studied. On day 10 (median) 4.3 × 106 (median) autologous CD34+ cells (50% labelled with 99mTc-extametazime) were administered via the infarct-related artery (left anterior descending). ΔESV, ΔEDV, and mid circumferential myocardial strain (mCS) were evaluated at 24 months. Results: Infarct mass (cMRI) was 57 [11-112] g. Cell label myocardial uptake (whole-body γ-scans) was proportional to IS (r = 0.62), with a median 2.9% uptake in IS 1st tercile (≤ 45 g), 5.2% in 2nd (46-76 g), and 6.7% in 3rd (> 76 g) (p = 0.0006). Cell uptake in proportion to IS attenuated the IS-ΔESV (p = 0.41) and IS-ΔEDV (p = 0.09) relationship. At 24 months, mCS improved in IS 2nd tercile (p = 0.028) while it showed no significant change in smaller (p = 0.87) or larger infarcts (p = 0.58). Conclusions: This largest human study with labelled CD34+ cell transplantation shortly after MI suggests that cell uptake (proportional to IS) may attenuate the effect of IS on LV adverse remodelling. To boost this effect, further strategies should involve cell types and delivery techniques to maximize myocardial uptake.

Misclassification of carotid stenosis severity with area stenosis-based evaluation by computed tomography angiography: impact on erroneous indication to revascularization or patient (lesion) migration to a higher guideline recommendation class as per ESC/ESVS/ESO/SVS and CMS-FDA thresholds.

Intoduction: Despite a growing understanding of the role played by plaque morphology, the degree of carotid lumen reduction remains the principle parameter in decisions on revascularization in symptomatic and asymptomatic patients. Computed tomography angiography (CTA) is a widely used guideline-approved imaging modality, with "percent stenosis" commonly calculated as %area reduction (area stenosis - AS). Aim: We evaluated the impact of the non-linear relationship between diameter stenosis (DS) and AS (area = π • (diameter/2)2, so that in concentric lesions 51%AS is 30%DS and 75%AS is 50%DS) on stenosis severity misclassification using calculation of area reduction. Material and methods: CTA and catheter quantitative angiography (cQA) were performed in 300 consecutive patients referred to a tertiary vascular centre for potential carotid revascularization (age: 47-83 years, 33.7% symptomatic, 36% female; referral stenosis of ≥ "50%"). CTA-AS was determined by agreement of 2 experienced radiologists; cQA-DS (pivotal trials standard reference, NASCET method) was calculated by agreement of 2 corelab analysts. Results: For symptomatic lesion thresholds, CTA-AS-based calculation reclassified 76% of "< 50%" cQA-DS measurements to the "50-69%" group, and 58% of "50-69%" measurements to the "≥ 70%" group. For asymptomatic lesion thresholds, 78% of "< 60%" cQA-DS measurements were reclassified to the "60-79%" group, whereas 42% of "60-79%" cQA measurements crossed to the "≥ 80%" class. Overall, employing CTA-AS instead of cQA-DS enlarged the "60-79%" and "≥ 80%" lesion severity classes 1.6- and 5.8-fold, respectively, whereas the "≥ 70%" class increased 4.15-fold. Conclusions: Replacing the pivotal carotid trials reference standard cQA-DS "%stenosis" measurement with CTA-AS-based "%stenosis" results in a large-scale lesion/patient erroneous gain of an "indication" to revascularization or migration to a higher revascularization indication class. In consequence, unnecessary carotid procedures may be performed in the absence of cQA verification. Until guidelines rectify the "%stenosis" measurement methods with different guideline-approved imaging modalities (and, where needed, re-adjust decision thresholds), CTA-AS measurement should not be used as a basis for carotid revascularization.