Peripheral Interventions Radiation Exposure Reduction Using a Sensor-Based Navigation System: A Proof-of-Concept Study.

BACKGROUND: Intravascular catheter positioning is done with radiography imaging. Increasing evidence indicates excessive ionizing radiation exposure for patients and physicians during catheterization procedures, making solutions to reduce radiation exposure a priority. This study evaluated the feasibility and impact of using sensor-based magnetic navigation on (i) fluoroscopy time and (ii) positioning accuracy and safety of a peripheral angioplasty balloon catheter. METHODS: All patients (n = 10) underwent a balloon-positioning protocol using 2 navigation methods sequentially: (i) magnetic navigation with minimal fluoroscopy; (ii) fluoroscopic navigation. The navigation method order was randomized, and 4 consecutive placements per method were performed. A target vascular bifurcation was used as a fiduciary landmark for both methods to determine accuracy. RESULTS: Balloon placements were successful with both navigation methods in all subjects, and no adverse events occurred. Magnetic guidance led to significant reductions in fluoroscopy time (0.37 ± 1.5 vs 15.0 ± 8.1 seconds, P < 0.001) and dose (0.3 ± 1.2 vs 24.1 ± 23.8 µGy.m2, P < 0.01). The time duration for balloon alignment was similar for the 2 navigation methods (4.8 ± 1.4 vs 4.8 ± 2.3 seconds, P = 0.89), and the accuracy was almost identical (0.51 ± 0.41 vs 0.51 ± 0.32 mm, P = 0.97). CONCLUSIONS: These results demonstrate the feasibility of using sensor-based magnetic guidance during simple peripheral interventional procedures; a significant reduction in ionizing radiation was achieved, with excellent positioning accuracy and safety. The clinical applications of magnetic guidance for device navigation during more complex percutaneous procedures should be evaluated.

CONTEXTE: Le positionnement d'un cathéter intravasculaire fait appel à l'imagerie radiographique. De plus en plus de données probantes indiquent que les patients et les médecins subissent une surexposition aux rayonnements ionisants pendant le cathétérisme, ce qui fait des solutions de réduction de l'irradiation une priorité. Cette étude a permis d'évaluer la faisabilité du guidage magnétique par capteur et son effet sur (i) la durée de la fluoroscopie et (ii) la précision et la sécurité du positionnement d'un cathéter d'angioplastie périphérique à ballonnet. MÉTHODOLOGIE: Chez tous les patients (n = 10), le positionnement du ballonnet a été effectué en fonction d'un protocole fondé sur deux méthodes de guidage mises en œuvre séquentiellement : (i) guidage magnétique avec fluoroscopie minimale; (ii) guidage fluoroscopique. L'ordre dans lequel les méthodes de guidage ont été mises en œuvre a été randomisé, et quatre positionnements consécutifs par méthode ont été effectués. Une bifurcation vasculaire cible a servi de repère de fond de chambre afin de déterminer la précision des deux méthodes. RÉSULTATS: Les deux méthodes de guidage ont permis un positionnement adéquat du ballonnet chez tous les patients, et aucun événement indésirable n'est survenu. Le guidage magnétique a entraîné des réductions significatives de la durée de la fluoroscopie (0,37 ± 1,5 vs 15,0 ± 8,1 secondes, p < 0,001) et de la dose de rayonnement (0,3 ± 1,2 vs 24,1 ± 23,8 µGy.m2, p < 0,01). La durée de l'alignement du ballonnet était similaire lors de la mise en œuvre des deux méthodes de guidage (4,8 ± 1,4 vs 4,8 ± 2,3 secondes, p = 0,89), et la précision était presque identique (0,51 ± 0,41 vs 0,51 ± 0,32 mm, p = 0,97). CONCLUSIONS: Ces résultats démontrent la faisabilité du guidage magnétique par capteur dans le cadre d'angioplasties périphériques simples. L'exposition aux rayonnements ionisants a été réduite de façon significative, et la précision ainsi que la sécurité du positionnement se sont avérées excellentes. Les applications cliniques du guidage magnétique dans le contexte d'interventions percutanées plus complexes représentent une avenue de recherche à explorer.

Perioperative Right Ventricular Pressure Monitoring in Cardiac Surgery.

Right ventricular (RV) dysfunction is a cause of increased morbidity and mortality in both cardiac surgery and noncardiac surgery and in the intensive care unit. Early diagnosis of this condition still poses a challenge. The diagnosis of RV dysfunction traditionally is based on a combination of echocardiography, hemodynamic measurements, and clinical symptoms. This review describes the method of using RV pressure waveform analysis to diagnose and grade the severity of RV dysfunction. The authors describe the technique, optimal use, and pitfalls of this method, which has been used at the Montreal Heart Institute since 2002, and review the current literature on this method. The RV pressure waveform is obtained using a pulmonary artery catheter with the capability of measuring RV pressure by connecting a pressure transducer to the pacemaker port. The authors describe how RV pressure waveform analysis can facilitate the diagnosis of systolic and diastolic RV dysfunction, the evaluation of RV-arterial coupling, and help diagnose RV outflow tract obstruction. RV pressure waveform analysis also can be used to guide pharmacologic treatment and fluid resuscitation strategies for RV dysfunction.

Everolimus-eluting bioresorbable vascular scaffold implantation to treat saphenous vein graft disease, single-center initial experience.

AIMS: Recent studies have shown favorable outcomes with everolimus-eluting bioresorbable vascular scaffold (BVS) in patients with stable coronary artery disease. Data on the use of BVS in saphenous vein graft disease (SVG) is currently lacking. METHODS AND RESULTS: A total of 10 consecutive patients (13 lesions, including 6 in-stent restenosis) who underwent BVS for SVG disease between May 2013 and June 2015 at a tertiary care institution were included. Median follow-up period was 874 (720-926) days. One patient had scaffold thrombosis (ScT) 15 months after implantation, which was treated medically. Another patient had target lesion revascularization (TLR) in two different lesions, where BVS was used to treat in-stent restenosis. The composite endpoint of TLR, ScT, target vessel myocardial infarction, and cardiac death, was reached in two patients CONCLUSIONS: This first real-world data on the use of the ABSORB™ BVS in patients with SVG disease shows that its implantation is technically feasible. The observed rate of target lesion revascularization was similar to those observed with drug-eluting stents in similar settings. Larger studies are required to better define the optimal use of BVS to treat SVG disease.

Sealing Intermediate Nonobstructive Coronary Saphenous Vein Graft Lesions With Drug-Eluting Stents as a New Approach to Reducing Cardiac Events: A Randomized Controlled Trial.

BACKGROUND: The objective of this study was to assess the efficacy of sealing intermediate nonobstructive coronary saphenous vein graft (SVG) lesions with drug-eluting stents (DES; paclitaxel- or everolimus-eluting stents) for reducing major adverse cardiac events (MACE). METHODS AND RESULTS: This was a randomized controlled multicenter clinical trial that enrolled patients with a previous coronary artery bypass graft who had developed at least 1 intermediate nonobstructive SVG lesion (30%-60% diameter stenosis by visual estimation). Patients were randomized (1:1) to DES implantation (SVG-DES) or medical treatment (SVG-MT) of the target SVG lesion. The primary efficacy outcome was the first occurrence of MACE defined as the composite of cardiac death, myocardial infarction, or coronary revascularization related to the target SVG during the duration of follow-up (minimum of 2 years). Secondary efficacy outcomes included MACE related to the target SVG lesion and overall MACE. A total of 125 patients (mean age 70±9 years, 87% men) were included, with a mean time from coronary artery bypass graft of 12±5 years. Sixty and 65 patients were allocated to the SVG-DES and SVG-MT groups, respectively. There were no events related to the target SVG at 30 days. After a median follow-up of 3.4 (interquartile range: 2.8-3.9) years, the MACE rate related to the target SVG was not significantly different in the 2 groups (SVG-DES: 15.0%, SVG-MT: 20.0%; hazard ratio, 0.65; 95% confidence interval, 0.23-1.53; P=0.33). There were no significant differences between groups in MACE related to the target SVG lesion (SVG-DES: 10.0%, SVG-MT: 16.9%; hazard ratio, 0.53; 95% confidence interval, 0.20-1.43; P=0.21) or global MACE (SVG-DES: 36.7%, SVG-MT: 44.6%; hazard ratio, 0.73; 95% confidence interval, 0.42-1.27; P=0.26). CONCLUSIONS: Sealing intermediate nonobstructive SVG lesions with DES was safe but was not associated with a significant reduction of cardiac events at 3-year follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01223443.

Epidemiology, Management Strategies, and Outcomes of Patients With Chronic Total Coronary Occlusion.

Factors influencing the management of patients with chronic total occlusion (CTO) are poorly described. We sought to analyze the clinical and angiographic variables influencing the decision-making process of patients with CTO. Consecutive patients with at least 1 coronary artery CTO were included and categorized as managed either by percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), or medical therapy (MT). Patients with previous CABG were excluded. The CTO SYNTAX score (CTO-SS) was defined as the ratio between the score attributed to the CTO lesion in the SYNTAX score calculation and the total SYNTAX score. Independent predictors of management strategies were sought. A total of 510 patients were included (CTO incidence: 20%): 9% were treated with PCI, 34% with CABG, and 57% with MT. SYNTAX score was lowest in PCI (14.8 [11.0 to 18.5]) and highest in CABG (31.5 [25.0 to 38.8], p <0.0001). PCI was attempted more often in patients with higher CTO-SS (i.e., those with higher contribution to the overall SYNTAX score from the CTO lesion; 88% had a CTO-SS >0.5). Conversely, CABG was preferred in subjects with lower CTO-SS (61% had a CTO-SS ≤0.5, p <0.0001). Age, ejection fraction, SYNTAX score, and age of the CTO were independent predictors of revascularization. At mid-term follow-up, unsuccessful revascularization or MT was independently associated with death (hazard ratio 7.2, p = 0.0005). In conclusion, CTOs are frequently documented in clinical practice. However, less than a half is revascularized. Management strategies are influenced by angiographic variables such as the SYNTAX score and the newly proposed CTO-SS.

Genotype-Dependent Effects of Dalcetrapib on Cholesterol Efflux and Inflammation: Concordance With Clinical Outcomes.

BACKGROUND: Dalcetrapib effects on cardiovascular outcomes are determined by adenylate cyclase 9 gene polymorphisms. Our aim was to determine whether these clinical end point results are also associated with changes in reverse cholesterol transport and inflammation. METHODS AND RESULTS: Participants of the dal-OUTCOMES and dal-PLAQUE-2 trials were randomly assigned to receive dalcetrapib or placebo in addition to standard care. High-sensitivity C-reactive protein was measured at baseline and at end of study in 5243 patients from dal-OUTCOMES also genotyped for the rs1967309 polymorphism in adenylate cyclase 9. Cholesterol efflux capacity of high-density lipoproteins from J774 macrophages after cAMP stimulation was determined at baseline and 12 months in 171 genotyped patients from dal-PLAQUE-2. Treatment with dalcetrapib resulted in placebo-adjusted geometric mean percent increases in high-sensitivity C-reactive protein from baseline to end of trial of 18.1% (P=0.0009) and 18.7% (P=0.00001) in participants with the GG and AG genotypes, respectively, but the change was -1.0% (P=0.89) in those with the protective AA genotype. There was an interaction between the treatment arm and the genotype groups (P=0.02). Although the mean change in cholesterol efflux was similar among study arms in patients with GG genotype (mean: 7.8% and 7.4%), increases were 22.3% and 3.5% with dalcetrapib and placebo for those with AA genotype (P=0.005). There was a significant genetic effect for change in efflux for dalcetrapib (P=0.02), but not with placebo. CONCLUSIONS: Genotype-dependent effects on C-reactive protein and cholesterol efflux are supportive of dalcetrapib benefits on atherosclerotic cardiovascular outcomes in patients with the AA genotype at polymorphism rs1967309. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov; Unique Identifiers: NCT00658515 and NCT01059682.

A Novel Minimally Invasive Approach for Surgical Septal Myectomy.

BACKGROUND: Transaortic septal myectomy is the gold standard for the treatment of symptomatic hypertrophic obstructive cardiomyopathy that is refractory to medical therapy. The aim of this study was to assess early outcomes of minimally invasive septal myectomy performed through a right anterior minithoracotomy. METHODS: Between 2011 and 2014, 24 consecutive patients underwent isolated septal myectomy through a 4-5-cm right parasternal minithoracotomy. Perioperative clinical and echocardiographic outcomes in these patients were compared with those of a historical cohort of 26 consecutive patients who underwent isolated septal myectomy performed through a median sternotomy between 2002 and 2010. RESULTS: Age and sex distribution were similar between the groups. Median aortic cross-clamp time was 57 minutes in the minithoracotomy group vs 43 minutes in the sternotomy group (P = 0.149). There was no in-hospital mortality in either group. Intraoperative conversion to sternotomy was required in 1 patient. Postoperative permanent pacemaker implantation was required in 5 patients from each group (P = 0.999). Both groups demonstrated similar reductions in left ventricular outflow tract gradient and septal thickness. Residual obstructive systolic anterior motion of the mitral valve was observed in 2 patients (8%) in the minithoracotomy group and 1 patient (4%) in the sternotomy group (P = 0.602). CONCLUSIONS: This study demonstrates the feasibility of transaortic septal myectomy through a right minithoracotomy. Our early results suggest that this technique yields clinical and echocardiographic outcomes similar to those obtained with standard sternotomy.

Bioresorbable vascular scaffold thrombosis in an all-comer patient population: single-center experience.

Experience with bioresorbable vascular scaffolds (BVSs) outside clinical trials is scarce, and data from "real-world" use are needed. In particular, there are few data on scaffold thrombosis (ST). We report our experience with ST in our all-comer BVS population (n = 339) and review the literature on the topic. Four cases (1.2%) of early definite ST were identified. Multiple risk factors were present in all 4 cases. Optical coherence tomography ruled out mechanical causes of ST in 2 cases, whereas scaffold underexpansion was observed in 1 case. Twelve BVS series have been published to date. Total sample size includes 1393 patients, with 13 cases of definite ST (0.9%), which is similar to long-term second-generation drug-eluting stent thrombosis rate (1.0%). Eleven of these cases were early ST (8 during the first week). Six of these 11 cases occurred in patients who received a BVS in the setting of an acute coronary syndrome (ACS). It can be speculated that the prothrombotic milieu of ACS, coupled with the unfavorable peristrut rheology of BVSs, might promote ST early after implantation, particularly if other concomitant risk factors are present.

Hemodynamic and clinical benefits associated with chronic sildenafil therapy in advanced heart failure: experience of the Montréal Heart Institute.

BACKGROUND: Pulmonary hypertension is highly prevalent in advanced heart failure (HF) despite optimal medical and device therapies. The objective of this investigation was to report on a single centre's experience of open-label chronic sildenafil therapy in patients with advanced HF. METHODS: We conducted a retrospective systematic medical record review of all patients evaluated at our institution for heart transplantation who had also been treated with chronic sildenafil therapy. Baseline demographics, comorbidities, and concomitant medications, as well as the results of laboratory investigations and physiological testing, were abstracted from patient medical records. Change in systolic and mean pulmonary artery pressure (PAP), transpulmonary gradient, cardiac output and cardiac index, and selected laboratory parameters was analyzed by means of the Wilcoxon rank sum test. Outcomes of interest included New York Heart Association (NYHA) functional class after 6 months of therapy and adverse effects attributable to sildenafil. RESULTS: The 16 patients undergoing evaluation for cardiac transplantation combined for 4166 patient-days on sildenafil, with a mean dose of 102.5 ± 54.0 mg/d. None discontinued because of side effects. At 6 months, there was an improvement in the cardiac index (P = 0.014) and systolic PAP (P = 0.049) without any significant change in other hemodynamic parameters. Ten patients (62.5%) experienced an improvement in their NYHA functional class, 8 (50%) received a heart transplantation, and 2 (12.5%) improved sufficiently to be removed from the transplant list. CONCLUSION: Chronic sildenafil therapy was well tolerated and associated with improved functional capacity and decreased systolic PAP. Properly controlled randomized studies of the long-term usefulness of sildenafil therapy in advanced HF populations are warranted.

A randomized controlled, phase 2 trial of the viral serpin Serp-1 in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Vascular inflammation can lead to plaque instability and acute coronary syndromes (ACS). Viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. A myxoma virus-derived serpin Serp-1 reduces inflammatory cell invasion and plaque growth in vascular injury models. Our objective was to evaluate the safety and efficacy of Serp-1 in patients with ACS undergoing percutaneous coronary intervention. METHODS AND RESULTS: This double-blind pilot trial included 48 ACS patients undergoing percutaneous coronary intervention randomly assigned to Serp-1 at doses of 5 µg/kg (n=19) or 15 µg/kg (n=17) or to placebo (n=12). Serp-1 was given by intravenous bolus immediately before intervention and 24 and 48 hours later. Patients were assessed for safety (primary objective) and efficacy outcomes, including biomarker analysis. In-stent neointimal hyperplasia was evaluated by intravascular ultrasound at 6 months. Key safety outcomes including coagulation parameters and adverse events did not differ between Serp-1 and placebo groups. A dose-dependent reduction in troponin I levels was observed with Serp-1 at 8, 16, 24, and 54 hours (P<0.05) and in creatine kinase-MB levels at 8, 16, and 24 hours after dose (P<0.05). The composite of death, myocardial infarction, or coronary revascularization occurred in 2 of 12 patients with placebo, 5 of 19 in the low-dose group, and none of 17 patients with the high-dose (P=0.058). Intravascular ultrasound did not detect changes in neointimal hyperplasia among groups. CONCLUSIONS: This is the first study of a viral serpin demonstrating its safety in ACS patients. The significant reduction in myocardial damage biomarkers supports further assessment of Serp-1 in ACS patients undergoing stent deployment. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00243308.

Remodeling is a more important determinant of lumen size than atheroma burden in left main coronary artery disease.

BACKGROUND: Left main coronary artery (LMCA) disease influences survival; however, the predictors of LMCA changes over time are incompletely understood. METHODS: Paired intravascular ultrasound (IVUS) and core laboratory analyses were performed in a standardized fashion in 207 subjects (mean +/- SD age 58 +/- 10 years, 80% men). The average follow-up duration was 18 months (range 12-24 months). The IVUS measurements were first obtained at the smallest lumen area and the largest plaque area at follow-up and the corresponding positions in the LMCA were then measured at baseline. RESULTS: The LMCA percentage of atheroma area at baseline was 38.2% +/- 11.8%, and 133 patients (64%) experienced an increase in percentage of atheroma area. Change in lumen area correlated positively with change in total vessel area (R = 0.85, P < .0001) and negatively with change in percentage of atheroma area (R = -0.58, P < .0001). Change in plaque area correlated well with change in total vessel area (R = 0.64, P < .0001) but only weakly with change in lumen area (r = 0.14, P = .039). Although LMCA length correlated negatively with baseline lumen area and total vessel area, it did not correlate with their changes over time. On multivariable analyses, current smoking predicted an increase in percentage of atheroma area (P = .0013) and plaque area (P = .0041). Height negatively predicted change in percentage of atheroma area (P = .001). CONCLUSIONS: The LMCA lumen dimensions are more tightly linked with remodeling than with atheroma progression/regression.

Clopidogrel 600-mg double loading dose achieves stronger platelet inhibition than conventional regimens: results from the PREPAIR randomized study.

OBJECTIVES: The objective of this study was to compare the level of platelet inhibition achieved by 3 different clopidogrel loading regimens in patients undergoing elective angiography and percutaneous coronary intervention when appropriate. BACKGROUND: Optimal platelet inhibition is a key therapeutic goal for patients undergoing percutaneous coronary intervention. Although 600 mg has been described as the maximum absorbed dose when given as a single bolus, the effects of 2 boluses given 24 h apart have not been described. METHODS: Patients (n = 148) were randomly assigned to one of 3 regimens: Group A, clopidogrel 300 mg the day before (>or=15 h) + 75 mg the morning of the procedure; Group B, clopidogrel 600 mg the morning of the procedure (>or=2 h); and Group C, clopidogrel 600 mg the day before (>or=15 h) and 600 mg the morning of the procedure (>or=2 h). Blood samples were obtained at baseline and immediately before angiography. Peak and late platelet aggregation were measured in platelet rich plasma, with researchers blinded to treatment allocation. RESULTS: There was a consistent difference favoring Group C in all aggregation parameters. Percent inhibition in Groups A, B, and C was 31.4%, 29.0%, and 49.5%, respectively, for peak aggregation (5 micromol/l adenosine diphosphate; p < 0.0001) and 54.1%, 57.7%, and 81.1%, respectively, for late aggregation (p < 0.0001). Similar striking reductions were observed when 20 micromol/l adenosine diphosphate was used. All comparisons between Group C and the other 2 groups were statistically significant, and those between Groups A and B were not. CONCLUSIONS: Clopidogrel 600-mg double bolus achieves greater platelet inhibition than conventional single loading doses.

Sustained elevation of serum CD40 ligand levels one month after coronary angioplasty predicts angiographic restenosis.

BACKGROUND: Percutaneous coronary intervention induces an early inflammatory reaction. The intensity of such a reaction as measured by high-sensitivity C-reactive protein has been correlated with recurrent ischemic events, but its association with restenosis remains uncertain. OBJECTIVES: To characterize the type and duration of the postangioplasty inflammatory reaction and to identify new inflammatory markers correlating with restenosis. METHODS: Fifty-three consecutive patients who underwent successful balloon angioplasty were studied. Levels of specific inflammatory markers were measured before intervention, and at one-month and six-month follow-up. Six-month clinical and angiographic follow-up was conducted in all patients, and quantitative coronary analysis was systematically performed. RESULTS: Levels of soluble CD40 ligand (sCD40L) and matrix metalloproteinase-2 showed a rise and fall pattern over six months, with peak levels measured at one month (P < 0.0001), while levels of soluble vascular cell adhesion molecule-1 increased after angioplasty and remained elevated at six months (P = 0.07). Plasma levels of sCD40L at one month correlated with angiographic late loss (r = 0.48, P = 0.001) and were predictive of six-month restenosis (area under receiver operating characteristic curve 0.75 [95% CI 0.61 to 0.88]). CONCLUSIONS: The results imply that inflammation persists for at least one month following angioplasty and that future therapeutic interventions targeting inflammation to prevent restenosis should be active during this period. Furthermore, the ability of sCD40L levels to predict restenosis at six months may indicate the relevance of this pathway as a therapeutic target for restenosis prevention.

Inflammation in atherothrombotic disease.

Atherosclerosis is a systemic disease in which vascular inflammation plays a key role. Indeed, inflammation is closely linked to atherosclerotic disease at all stages, from silent progression to clinical manifestations. There is now strong epidemiologic evidence that mediators of inflammation, like C-reactive protein, predict cardiovascular risk independently of "classical" risk factors. Consequently, new disease-modifying drugs targeting inflammation are under investigation and may change the approach to treatment of atherosclerosis in the near future.