Comparative Outcomes of Interventions for Femoropopliteal Chronic Total Occlusion Versus Non-Chronic Total Occlusion Lesions From the Multicenter XLPAD Registry.

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional balloon angioplasty (20.86% versus 33.48%, P<0.001) or drug-coated balloon angioplasty (1.26% versus 2.93%, P<0.001) were more frequent in the non-CTO group, whereas bare-metal stents (28.09% versus 20.22%, P<0.001) or covered stents (4.08% versus 1.83%, P<0.001) were more frequent in the CTO group. Debulking procedures were more commonly performed in the non-CTO group (41.44% versus 53.13%, P<0.001), despite a similar degree of calcification between the 2 groups. Procedural success was higher in the non-CTO group (90.12% versus 96.79%, P<0.001). Procedural complications were higher in the CTO group (7.21% versus 4.66%, P=0.002), mainly due to excess distal embolization (1.5% versus 0.6%, P=0.015). Adjusted 1-year major adverse limb events were higher in the CTO group (22.47% versus 18.77%, P=0.019), driven mainly by target limb revascularization (19.00% versus 15.34%, P=0.013). Conclusions Procedural success is lower for endovascular treatment of femoropopliteal CTO compared with non-CTO lesions. CTO lesions are associated with higher rates of periprocedural complications and reinterventions after 1 year.

Short-Term Outcomes After Retrograde Versus Antegrade Crossing Approaches for Femoropopliteal Occlusive Disease.

OBJECTIVE: To compare short- and mid-term outcomes of patients with femoropopliteal (FP) occlusive disease treated with a retrograde vs antegrade crossing strategy. BACKGROUND: Few studies have directly compared procedural details and outcomes after retrograde vs antegrade crossing of FP lesions. METHODS: Patients undergoing retrograde approaches to FP lesions were identified from the multicenter Excellence in Peripheral Artery Disease (XLPAD) registry between 2007 and 2015. These patients were matched 1:1 to patients treated with antegrade crossing strategies based on age, gender, comorbidities, indication for procedure, and lesion characteristics. Technical success, major adverse limb events (MALEs), and overall device cost were compared between retrograde and antegrade-only crossing. RESULTS: A total of 116 patients (58 antegrade and 58 retrograde) were included. The retrograde group had higher prevalence of coronary artery disease and presence of chronic total occlusions. The retrograde approach was associated with significantly longer procedural time (186 ± 70 minutes vs 124.4 ± 60 minutes; P<.001), but similar technical success (91.4% vs 96.6%; P=.24). There was no significant difference in perioperative morbidity. Patients treated with a retrograde approach had a lower total amputation rate (8.6% vs 22.4%; P=.04) and no difference in overall mortality (8.6% vs 5.2%; P=.47). Mean procedural costs were similar in the antegrade and retrograde groups. CONCLUSION: In patients with similar disease characteristics, a retrograde approach to FP occlusive disease was associated with longer procedural time, but improved limb salvage, without significant difference in procedural cost.

No benefit of vorapaxar on walking performance in patients with intermittent claudication.

Background: The effect of pharmacologic agents in improving walking and quality of life measures in patients with intermittent claudication (IC) is variable. The objective of this study was to investigate the effect of the novel antithrombotic vorapaxar on symptom status in patients with IC. Methods: The study was a multicenter, randomized, placebo-controlled trial wherein patients with IC were treated with either vorapaxar or placebo in addition to a home exercise program for 6 months. Walking performance and quality of life were assessed by graded treadmill test (GTT) and 12-Item Short-Form Survey (SF-12), respectively, at baseline and at 6 months. A total of 102 subjects were randomized across 12 centers. Results: Of the subjects randomized, 66 completed all study assessments and comprised the dataset that was analyzed. After 6 months, there was no significant difference between the vorapaxar and placebo groups in walking performance, as reflected by the GTT, or in quality of life, as reflected by the SF-12. There were no severe bleeding events in either group. Conclusion: This study found no benefit of vorapaxar in patients with IC and reiterates the need for future drug therapy studies that expand the benefits of supervised exercise therapy in patients with IC. ClinicalTrials.gov Identifier: NCT02660866.

Treatment of In-Stent Restenosis Using Excimer Laser Coronary Atherectomy and Bioresorbable Vascular Scaffold Guided by Optical Coherence Tomography.

The rate of in-stent restenosis (ISR) has become increasingly prevalent with the exponential growth in stent implantation due to an aging population and a higher life expectancy, in addition to the high rates of obesity and diabetes. In this prospective, single operator, all-comer study, we sought to analyze the performance of ELCA followed by bioresorbable vascular scaffold (BVS) placement in patients undergoing percutaneous coronary intervention (PCI) for ISR. A total of 13 patients had ISR treated with a combination of ELCA and BVS, with 9 patients having matched OCT pre, post ELCA and post BVS. Mean age was 65 ± 11.22 and 83% of the patients were male. Hypertension and dyslipidemia were present in 100% of the patients and smoking and diabetes in 50%. After the procedure, we did not detect residual stenosis over 10% in any patient, resulting in a technical success of 100%. No patients had MACE during their hospital stay or within the next six months, resulting in a procedure success of 100%. The mean lumen area increased 0.35 mm2 from pre procedure to post ELCA and 3.58 mm2 from post ELCA to post BVS. The final difference, from pre procedure to post BVS, was a 3.93 mm2 lumen area gain. The mean lumen diameter increased 0.11 mm from baseline to ELCA, 0.95 mm from post laser to BVS implantation and 1.06 mm from pre procedure to post BVS. The NIH area reduced 0.48 mm2 from pre to post ELCA, 1.13mm2 from post ELCA to BVS implantation and 1.61 mm2 from baseline to post BVS implantation. We conclude that ELCA is a safe and feasible debulking method to approach ISR, with high rates of post-procedural BVS success, within six months follow-up.

Evaluation of dyspnea of unknown etiology in HIV patients with cardiopulmonary exercise testing and cardiovascular magnetic resonance imaging.

AIM: Human Immunodeficiency Virus (HIV) patients commonly experience dyspnea for which an immediate cause may not be always apparent. In this prospective cohort study of HIV patients with exercise limitation, we use cardiopulmonary exercise testing (CPET) coupled with exercise cardiovascular magnetic resonance (CMR) to elucidate etiologies of dyspnea. METHODS AND RESULTS: Thirty-four HIV patients on antiretroviral therapy with dyspnea and exercise limitation (49.7 years, 65% male, mean absolute CD4 count 700) underwent comprehensive evaluation with combined rest and maximal exercise treadmill CMR and CPET. The overall mean oxygen consumption (VO2) peak was reduced at 23.2 ± 6.9 ml/kg/min with 20 patients (58.8% of overall cohort) achieving a respiratory exchange ratio > 1. The ventilatory efficiency (VE)/VCO2 slope was elevated at 36 ± 7.92, while ventilatory reserve (VE: maximal voluntary ventilation (MVV)) was within normal limits. The mean absolute right ventricular (RV) and left ventricular (LV) contractile reserves were preserved at 9.0% ± 11.2 and 9.4% ± 9.4, respectively. The average resting and post-exercise mean average pulmonary artery velocities were 12.2 ± 3.9 cm/s and 18.9 ± 8.3 respectively, which suggested lack of exercise induced pulmonary artery hypertension (PAH). LV but not RV delayed enhancement were identified in five patients. Correlation analysis found no relationship between peak VO2 measures of contractile RV or LV reserve, but LV and RV stroke volume correlated with PET CO2 (p = 0.02, p = 0.03). CONCLUSION: Well treated patients with HIV appear to have conserved RV and LV function, contractile reserve and no evidence of exercise induced PAH. However, we found evidence of impaired ventilation suggesting a non-cardiopulmonary etiology for dyspnea.

An assessment of the quality of optical coherence tomography image acquisition.

Optical coherence tomography (OCT) provides excellent image resolution, however OCT optimal acquisition is essential but could be challenging owing to several factors. We sought to assess the quality of OCT pullbacks and identify the causes of suboptimal image acquisition. We evaluated 784 (404 pre-PCI; 380 post-PCI) coronary pullbacks from an anonymized OCT database from our Cardiovascular Imaging Core Laboratory. Imaging of the region-of-interest (ROI-lesion or stented segment plus references) was incomplete in 16.1% pullbacks, caused by pullback starting too proximal (63.7%), inappropriate pullback length (17.1%) and pullback starting too distal (11.4%). The quality of image acquisition was excellent in 36.3% pullbacks; whereas 4% pullbacks were unanalyzable. Pullback quality was most commonly affected by poor blood displacement from inadequate contrast volume (27.4%) or flow (25.6%), followed by artifacts (24.1%). Acquisition mode was 'High-Resolution' (54 mm) in 74.4% and 'Survey' (75 mm) in 25.6% of cases. The 54 mm mode was associated with incomplete ROI imaging (p = 0.020) and inadequate contrast volume (p = 0.035). We observed a substantial frequency of suboptimal image acquisition and identified its causes, most of which can be addressed with minor modifications during the procedure, ultimately improving patient outcomes.

Predicted Coronary Occlusion and Impella Salvage During Valve-in-Valve Transcatheter Aortic Valve Replacement.

We describe an interesting case of a 71 years old fragile female, with progressive shortness of breath on exertion and ankle swelling, cardiac failure NYHA class III. She also had chest irradiation due to Hodgkin's disease many years before, previous surgical aortic valve replacement using bioprosthetic stent-less Freestyle #25 mm valve (Medtronic, Inc) in 2000 for severe aortic stenosis, history of cardiac arrest in 2012 and angioplasty to ostial RCA, PCI to ostial RCA in 2014, CABG (RA graft to RCA) in 2014 (RCA intra-stent restenosis with refractory ischemia), anemia requiring regular transfusions, bronchiectasis and chronic kidney disease. Because of the great comorbidities, STS 4.9% and worsening of the symptoms due to severe aortic valve regurgitation, heart team decided to perform "valve-in-valve" Transcatheter Aortic Valve Replacement (VIV-TAVR), but we already predicted coronary occlusion while performing this procedure because of the low left main coronary ostium and short aortic valve sinus. So regarding the probable left main coronary occlusion during the valve implantation, we decided to perform the placement of a not deployed stent inside the left main prior to the valve procedure, and to deploy it in case the predicted left main occlusion occurred. So just after the VIV-TAVR procedure, we observed left main coronary occlusion and the patient got ischemic cardiogenic shock and cardiac arrest, so we performed immediate PCI and deployed the bailout stent. After some minutes of chest compressions, an Impella mechanical circulatory support system (Abiomed, Danvers, MA) had to be installed. Patient recovered spontaneous circulation, and after hemodynamic stabilization, she was sent to the Intensive Coronary Unit, without further complications. She was discharged successfully without neurological or cardiac sequelae after 1 week.

Low dose contrast CT for transcatheter aortic valve replacement assessment: Results from the prospective SPECTACULAR study (spectral CT assessment prior to TAVR).

BACKGROUND: Computed tomographic angiography (CTA) based planning for transcatheter aortic valve replacement (TAVR) is essential for reduction of periprocedural complications. Spectral CT based imaging provides several advantages, including better contrast/signal to noise ratio and increased soft tissue contrast, permitting better delineation of contrast filled structures at lower doses of iodinated contrast media. The aim of this prospective study was to assess the initial feasibility of a low dose iodinated contrast protocol, utilizing monoenergetic 40 keV reconstruction, using a dual-layer CT scanner (DLCT) for CTA in patients undergoing TAVR planning. METHODS: 116 consecutive TAVR patients underwent a gated chest and a non-gated CTA of the abdomen and pelvis. 40 keV virtual monoenergetic images (VMI) were reconstructed and compared with conventional polychromatic images (CI). The proximal aorta and access vessels were scored for image quality by independent experienced cardiovascular imagers. RESULTS: Proximal aortic image quality as assessed by signal to noise (SNR) and contrast to noise ratio (CNR), were significantly better with 40 keV VMI relative to CI (SNR 14.65 ±â€¯7.37 vs 44.16 ±â€¯22.39, p < 0.001; CNR 15.84 ±â€¯9.93 vs 59.8 ±â€¯40.83, p < 0.001). Aortic root dimensions were comparable between the two approaches with a bias towards higher measurements at 40 keV (Bland Altman). SNR and CNR in all access vessel segments at 40 keV were substantially better (p < 0.001 for all peripheral access vessel segments) with comparable image quality. CONCLUSION: 40 keV VMI with low dose contrast dose spectral imaging is feasible for comprehensive preprocedural evaluation of access vessels and measurements of aortic root dimensions in patients undergoing TAVR.

Real World Utilization of Computed Tomography Derived Fractional Flow Reserve: Single Center Experience in the United States.

BACKGROUND: Fractional flow reserve derived from computed tomography (FFRct) has shown higher accuracy for detection of significant coronary artery disease (CAD) compared to coronary computed tomography angiography (CCTA). The performance of a combined comprehensive qualitative interpretation of both CCTA and FFRct in patient management is unknown. We aimed to explore the clinical application of this combined approach. METHODS: We retrospectively reviewed cases referred to FFRct testing at our institution over a one-year period. Patients had documentation of whether invasive coronary angiography (ICA) was performed and revascularization were needed. Interpretations and recommendations of the adopted comprehensive approach (C-FFRct), that took into account focal versus diffuse disease, depth of ischemia and myocardium at risk, were compared to those of CCTA (binary > 50% stenosis) alone and FFRct binary approach (FFRct ≤ 0.8). C-FFRct performance was measured against the decision made upon revascularization. RESULTS: A total of 207 cases were referred to FFRct testing, 163 (79%) accepted and 44 (21%) rejected for quality. C-FFRct changed interpretations and recommendations of 39 (24%) and 14 (9%) CCTA and FFRct, respectively. ICA was deferred in 32 (59%) and 13 (32%) cases; whereas ICA referral rate was 7 (6%) and 1 (0.8%) cases, based on CCTA and FFRct, respectively. No major cardiac events were observed during follow up time (median = 6 months). C-FFRct sensitivity, specificity, and accuracy compared to decision upon revascularization were 89%, 79% and 82%. C-FFRct number needed to treat was 4, and 6, compared to CCTA and FFRct, respectively. CONCLUSION: FFRct is a feasible tool to improve the diagnostic performance of CCTA in CAD real-world workup. However, qualitative interpretation of the FFRct report combined with CCTA findings may yield more impactful results on patient management. Further prospective studies are warranted to validate the application of this approach and better define its components.

Rupture of a Non-Obstructive Plaque.

An invasive and non-invasive imaging series representing a classic rupture of a non-obstructive plaque with thin-cap fibroatheroma.

Left Atrium Wall-mapping Application for Wall Thickness Visualisation.

The measurement method for the LA wall thickness (WT) using cardiac computed tomography (CT) is observer dependent and cannot provide a rapid and comprehensive visualisation of the global LA WT. We aim to develop a LA wall-mapping application to display the global LA WT on a coplanar plane. The accuracy, intra-observer, and inter-observer reproducibility of the application were validated using digital/physical phantoms, and CT images of eight patients. This application on CT-based LA WT measures were further validated by testing six pig cardiac specimens. To evaluate its accuracy, the expanded maps of the physical phantom and pig LA were generated from the CT images and compared with the expanded map of the digital phantom and LA wall of pig heart. No significant differences (p > 0.05) were found between physical phantom and digital phantom as well as pig heart specimen and CT images using our application. Moreover, the analysis was based on the LA physical phantom or images of clinical patients; the results consistently demonstrated high intra-observer reproducibility (ICC > 0.9) and inter-observer reproducibility (ICC > 0.8) and showed good correlation between measures of pig heart specimen and CT data (r = 0.96, p < 0.001). The application can process and analyse the LA architecture for further visualisation and quantification.

Design of the exercise MRI evaluation of HIV-pulmonary arterial hypertension longitudinal determinants (EXALTED) trial.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a potentially serious cause of dyspnea and exercise limitation in patients with HIV infection. In this trial, we propose using exercise MRI in conjunction with cardiopulmonary testing to delineate PAH from other causes of cardiovascular dysfunction, identify individuals with exercise-induced PAH who are at high risk of developing resting PAH, and provide longitudinal estimates of progression of PAH and right ventricular function. METHODS: In this prospective observational study, HIV patients with dyspnea and exercise limitation in the absence of identifiable causes and those who meet the inclusion criteria will be enrolled based on resting pulmonary artery pressure (≤ or >40 mmHg) on a screening echocardiogram and exercise limitation on the Modified Medical Research Council dyspnea scale. Patients without evidence of resting PAH will be enrolled into both rest and exercise MRI and cardiopulmonary testing protocol, whereas patients with evidence of PAH on resting echocardiograms will undergo only resting cardiac MRI studies to evaluate right ventricular function and fibrosis. Both patient subgroups will be followed for 24 months to obtain longitudinal progression of the disease. In a sub-study, we will further analyze inflammatory variables that may predict these changes, thus allowing early identification of these patients. IMPLICATIONS AND CONCLUSIONS: This trial will be the first study to provide an understanding of the mechanisms underpinning the functional deterioration of the right ventricle in patients with HIV and will impart insight into the immune mediators of PAH progression and right ventricular functional deterioration in patients with HIV-PAH.

Improvements in Left Ventricular Diastolic Mechanics After Parachute Device Implantation in Patients With Ischemia Heart Failure: A Cardiac Computerized Tomographic Study.

BACKGROUND: Percutaneous ventricular restoration therapy with the use of a left ventricle (LV)-partitioning Parachute device has emerged as a clinical treatment option for LV apical aneurysm after extensive anterior myocardial infarction (AMI). We assessed changes of diastolic mechanics and functional improvements following LV Parachute device implantation by means of cardiac computerized tomography (CCT). METHODS AND RESULTS: CCT data were obtained from 28 patients before and after LV Parachute device implantation. Diastolic functional indices were determined by means of quantitative CCT assessment: 1) transmitral velocities in early (E) and late (A) diastole and ratio (E/A); 2) early diastolic mitral septal tissue velocity (Ea) and E/Ea; and 3) vortex formation time (VFT). Functional improvements were assessed with the use of New York Heart Association (NYHA) functional classification. Among the study patients, there were no significant differences in all transmitral velocities and E/A, though there was significantly increased Ea, reduced E/Ea, and greater VFT 6 months after LV Parachute device implantation. Finally, the improvement of diastolic functional indices after Parachute treatment correlated with observed clinical functional alterations (Δ E/Ea and Δ NYHA functional class:, r = 0.563; P = .002; Δ VFT and Δ NYHA functional class: r = -0.507; P = .006). CONCLUSIONS: LV Parachute device implantation therapy in heart failure caused by AMI and LV apical aneurysm formation showed improvements in several diastolic functional mechanics according to CCT-based measures.

Evaluating the quality of implantation of percutaneous ventricular restoration device (Parachute®) by cardiac computed tomography.

BACKGROUND: The Parachute is a novel percutaneously implanted ventricular partitioning device (VPD) that has emerged as a safe and feasible treatment option for patients with heart failure following anterior wall myocardial infarction. VPD efficacy is likely dependent on optimal device placement, but to date there are no published data examining the effect of device positioning on patient outcomes. METHODS AND RESULTS: We retrospectively identified 32 patients successfully implanted with the Parachute device, all of whom underwent cardiac computed tomography (CCT) at baseline and after 6 months of follow-up. Patients were divided into two groups based on self-reported improvement in New York Heart Association (NYHA) functional class: "not improved NYHA" (n = 12) and "improved NYHA" (n = 20). There were significant differences between both groups with regard to device positioning on follow-up CCT. Compared to patients with "improved NYHA," patients with "not improved NYHA" had longer distances from device foot to left ventricular apex (8.0 ± 4.9 vs. 2.9 ± 4.6 mm; P = 0.01), and higher lateral angles (18.0 ± 14 vs. 9.1 ± 6.8 degrees; P = 0.02), respectively. There was no significant difference between the two groups in landing zone (45.4 ± 7. vs. 45.1 ± 6.9 mm; P = 0.92) and inferior angle (14.0 ± 11.9 vs. 14.3 ± 10.1 degrees; P = 0.95). There was a numerically larger malapposition area in the "not improved NYHA" group (5.1 ± 4.5 vs. 3.2 ± 2.2 cm2; P = 0.12). CONCLUSION: Quality of Parachute implant impacted clinical outcome, these findings should be applied prospectively in helping operators to achieve optimal implant. © 2016 Wiley Periodicals, Inc.

Up-regulation of miR-210 by vascular endothelial growth factor in ex vivo expanded CD34+ cells enhances cell-mediated angiogenesis.

Ex vivo culture has been proposed as a means to augment and repair autologous cells in patients with chronic diseases, but the mechanisms governing improvement in cell function are not well understood. Although microRNAs (miRs) are increasingly appreciated as key regulators of cellular function, a role for these factors in CD34+ cell-mediated angiogenesis has not been elucidated. Vascular endothelial growth factor (VEGF) was previously shown to induce expression of certain miRs associated with angiogenesis in endothelial cells and promote survival and number of vascular colony forming units of haematopoietic stem cells (HSCs). We sought to evaluate the role of VEGF in expansion and angiogenic function of CD34+ cells and to identify specific miRs associated with angiogenic properties of expanded cells. Umbilical cord blood CD34+ cells were effectively expanded (18- to 22-fold) in culture medium containing stem cell factor (SCF), Flt-3 ligand (Flt-3), thrombopoietin (TPO) and interleukin-6 (IL-6) with (postEX/+VEGF) and without VEGF (postEX/noVEGF). Tube formation in matrigel assay and tissue perfusion/capillary density in mice ischaemic hindlimb were significantly improved by postEX/+VEGF cells compared with fresh CD34+ and postEX/noVEGF cells. MiR-210 expression was significantly up-regulated in postEX/+VEGF cells. MiR-210 inhibitor abrogated and 210 mimic recapitulated the pro-angiogenic effects by treatment of postEX/+VEGF and postEX/noVEGF cells respectively. Collectively, these observations highlight a critical role for VEGF in enhancing the angiogenic property of expanded cells, and identify miR-210 as a potential therapeutic target to enhance CD34+ stem cell function for the treatment of ischaemic vascular disease.

Bone marrow and circulating stem/progenitor cells for regenerative cardiovascular therapy.

Cardiovascular disease is the leading cause of death and disability in the Western world. In addition to the advancement of current therapeutic approaches to reduce the associated morbidity and mortality, regenerative medicine and cell-based therapy have been areas of continuous investigation. Circulating and bone-marrow-derived stem or endothelial progenitor cells are an attractive source for regenerative therapy in the cardiovascular field. In this review, we highlight the advantages and limitations of this approach with a focus on key observations from animal studies and clinical trials.