Intraprocedural direct left atrial and wedge pressure correlation during transcatheter mitral valve repair: Results from a single center registry.

OBJECTIVES: This study investigates the correlation of occlusive wedge pressure (WP) with direct left atrial (LA) pressure in patients with severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVr) with MitraClip. BACKGROUND: There is interest in acquiring objective hemodynamic parameters for intraprocedural guidance in patients undergoing MitraClip. METHODS: The study included 94 patients with severe MR at prohibitive surgical risk who underwent MitraClip at the University of California Davis Medical Center between 2014 and 2016. RESULTS: An average of 1.8 ± 0.7 clips were used to achieve MR grade of 2+ or less in 99% of patients. Correlation analysis of all (n = 236) pre-clip, inter-clip, and final-clip WP and LA pressures yielded a Pearson's R (r) of 0.85 and 0.79 for mean WP vs mean LA and WP V vs LA V, respectively. Median LA V to mean LA ratio (LAV:mLA) was 1.75 (IQR 1.5-1.9). 79% (n = 74) of patients had LAV:mLA ratio ≥ 1.5 with associated WP V vs LA V correlation (r) of 0.83. In patients with LAV:mLA ratio < 1.5, the correlation (r) was 0.69. Baseline characteristics were not significantly different between patients with LAV:mLA ratio ≥ 1.5 and patients with LAV:mLA ratio < 1.5. Post-procedure, median LA V: mean LA ratio decreased from 1.75 to 1.4, P = 0.0001. CONCLUSIONS: Correlation between WP and direct LA pressure in patients with severe MR undergoing Mitraclip is modest. Caution is advised when using WP to approximate LA pressure intraprocedurally, especially in patients with baseline low LAV:mLA ratios.

Outcomes of primary percutaneous coronary intervention in acute myocardial infarction due to unprotected left main thrombosis: The Asia-Pacific Left Main ST-Elevation Registry (ASTER).

INTRODUCTION: Prior studies of ULM STEMI have been confined to small cohorts. Recent registry data with larger patient cohorts have shown contrasting results. We aim to study the outcomes of patients with unprotected left main (ULM) ST-elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). METHODS: The Asia-pacific left main ST-Elevation Registry (ASTER) is a multicenter retrospective registry involving 4 sites in Singapore, South Korea, and the United States. The registry included patients presenting with STEMI due to an ULM coronary artery culprit lesion who underwent emergency PCI. The primary outcome was in-hospital mortality. Secondary outcomes included major adverse cardiovascular events. RESULTS: A total of 67 patients (mean age 64.2 ± 12.8 years, 53 [79.1%] males) were included. The distal left main bifurcation was most commonly involved (85%, n = 57). Fifty one (76%) patients had TIMI 3 flow post-PCI. The in-hospital mortality rate was 47.8% (n = 32); 61% (n = 41) had cardiac failure, 4% (n = 3) had emergency coronary artery bypass grafting, 1% (n = 1) had a re-infarction, 3% (n = 2) had stroke and 55% (n = 37) had malignant ventricular arrhythmias. On multivariate analysis, predictors of in-hospital mortality included older age (odds ratio (OR) 1.085 (95% confidence interval (CI) 1.002-1.175), P = 0.044), diabetes mellitus (OR 10.882 (95%CI 11.074-110.287), P = 0.043) and absence of post-PCI TIMI 3 flow (OR 71.429 (95%CI 2.985-1000), P = 0.008). CONCLUSIONS: STEMI from culprit unprotected left main coronary artery stenosis is associated with significant mortality and morbidity. Emergency PCI provides an important treatment option in this high-risk group, but in-hospital mortality remains high.

Accuracy and procedural characteristics of standard needle compared with radiofrequency needle transseptal puncture for structural heart interventions.

OBJECTIVES: Our objectives were to assess for differences between standard and radiofrequency (RF) needle in procedural times, success, and spatial accuracy. BACKGROUND: Targeted transseptal (TS) puncture is essential for structural heart interventions. Spatial accuracy of standard versus RF needle has not been reported. METHODS: Consecutive patients undergoing structural heart interventions requiring TS puncture were studied retrospectively. A standard needle was alternated with a RF needle. Procedural success and times were recorded. Measurements based on intraprocedural transesophageal echocardiograms of the intended versus final TS crossing site were obtained. Pre-puncture and maximal tenting of the septum were also recorded. RESULTS: Twenty-five patients underwent standard needle and 27 RF TS access. All RF needle attempts to cross were successful without an assistance wire. Three standard needle patients required assisted crossing. After failed TS access, two patients had successful RF TS access. TS procedural times significantly favored the RF needle for time from septum to puncture (P = 0.02). Both standard and RF access yielded accurate crossing with no significant differences between the intended and actual crossing site. Maximal tenting was significantly less with the RF needle (P = 0.004). There were no major complications. CONCLUSIONS: In the hands of an experienced operator, there were no major clinically significant differences between the standard and RF needle approaches. However, procedural unassisted crossing success was higher with the RF needle approach as compared to standard needle. Procedural times and degree of septum tenting favored the RF over standard needle. Accuracy was similar with both approaches. RF was a successful strategy when standard needle failed. There were no major complications with either TS puncture strategy. © 2016 Wiley Periodicals, Inc.

Angiographic characteristics of definite stent thrombosis: role of thrombus grade, collaterals, epicardial coronary flow, and myocardial perfusion.

OBJECTIVES: To characterize the prevalence of thrombus burden, collateral vessels to the infarct-related artery, epicardial coronary artery flow, and myocardial perfusion in patients with angiographically confirmed definite stent thrombosis (ST), and to define their relationship with associated treatments and outcomes. BACKGROUND: Angiographic characteristics of ST are not well defined. METHODS: All cases of angiographically determined ST at five academic hospitals from 2005 to 2012 were reviewed. Demographic, procedural, and angiographic characteristics were recorded. In-hospital and 1-year follow-up data were obtained. RESULTS: Among 205 cases of angiographic definite ST (60 ± 8 years; 87% male), the majority presented with late/very late ST (69%) and STEMI (66%). High-risk angiographic findings at presentation included thrombus grade 4-5 (87%), absence of collateral vessels (76%), and reduced initial TIMI 3 flow (90%). Final TIMI 3 flow was achieved in 90% of patients and was associated with greater use of aspiration thrombectomy (60% vs. 25%; P = 0.003), glycoprotein IIb/IIIa inhibitors (80% vs. 30%, P < 0.001), and repeat stenting (67% vs. 10%, P < 0.001). A final myocardial perfusion grade of 2-3 was achieved in 79% of patients and was associated with greater use of aspiration thrombectomy (61% vs. 36%, P = 0.003). After multivariable logistic regression, aspiration thrombectomy (AOR 2.6, 95% CI 1.3-5.2) and implantation of a new stent (AOR 2.1, 95% CI 1.1-4.3) were associated with optimal combined epicardial flow and myocardial perfusion. At 1-year follow-up, significantly lower risk of repeat ST (HR 0.1; 95% CI 0.1,0.2; P < 0.001) among patients with initial TIMI 3 flow at index ST was observed. CONCLUSIONS: The majority of ST patients present with late/very late ST with high thrombus burden and STEMI. Presence of collateral vessels and low thrombus burden is cardioprotective, while reduced initial TIMI flow is associated with larger infarct size and recurrent ST. Aspiration thrombectomy and repeat stenting are associated with improved epicardial coronary artery flow and myocardial perfusion among patients treated for ST. © 2014 Wiley Periodicals, Inc.

Transradial and transfemoral coronary angiography and interventions: 1-year outcomes after initiating the transradial approach in a cardiology training program.

BACKGROUND: Limited data are available regarding the safety and feasibility of initiating transradial (TR) diagnostic coronary angiography (CA) and percutaneous coronary intervention (PCI) in cardiology fellowship programs. METHODS: From July 2010 to June 2011, University of California, Davis Medical Center, adopted the TR approach with supervised cardiology fellows as the primary operators. Procedural variables and clinical outcomes of TR and transfemoral (TF) procedures were compared. To minimize confounding variables, ST-elevation myocardial infarction, bypass graft interventions, chronic total occlusions, and procedures with concomitant right heart catheterizations were excluded. To reflect the learning curve of the TR approach, this experience was assessed in 2 sequential 6-month periods. RESULTS: A total of 402 diagnostic CAs and 255 PCIs were included. Transradial access was used in 141 (35%) of the CAs and in 72 (28%) of PCIs. Within the TR-CA and TF-CA (n = 261) groups, there was no difference between fluoroscopy (10.4 ± 6.0 vs 11.0 ± 8.9, P = .63) or procedure (31.8 ± 11.5 vs 33.2 ± 13.8, P = .55) time throughout the academic year with a significant trend toward lower contrast use (128 ± 52 vs 110 vs 50, P = .04) by the second half. In addition, during the second half of the academic year, the TR-CA showed significantly higher fluoroscopy (11.0 ± 8.9 vs 6.7 ± 6.8, P = .001) and procedure (33.2 ± 13.8 vs 27.2 ± 11.6, P = .0015) times when compared with TF-CA. Transfemoral PCI (n = 183) and TR-PCI showed no significant difference between all fluoroscopy and procedure time and contrast use when comparing the 2 halves of the academic year. When comparing TF with TR within each academic half year, there was no difference within the PCI group. Vascular complications were less with the TR approach. Overall procedural success rates were high, and there were low rates of crossover and periprocedural complications in both the TR and the TF groups. CONCLUSION: A TR approach is safe for CA and PCI when performed by supervised operators in training. Although the learning curve for trainees appears slower for TR-CA compared with TF-CA, cardiology fellowship training programs should be encouraged to adopt TR procedures as part of their curriculum.

Angiographically confirmed stent thrombosis in contemporary practice: insights from intravascular ultrasound.

OBJECTIVE: We hypothesized that patients presenting with stent thrombosis (ST) have a high prevalence of stent underexpansion and malapposition when assessed by intravascular ultrasound (IVUS). BACKGROUND: IVUS can provide mechanistic insight into mechanical factors, including stent underexpansion, malapposition, and fracture that may predispose to ST. METHODS: All consecutive cases of angiographically confirmed ST from a multicenter registry (from 2005 to 2010) were reviewed. All IVUS images were reviewed off-line for the presence of stent underexpansion, malapposition, and fracture. Kaplan-Meier analysis was used to determine whether use of IVUS at the time of ST was associated with long-term mortality and major adverse cardiovascular events. RESULTS: IVUS was performed in 32 of 173 subjects with ST (18%). Stent underexpansion was present in 82% of cases and in all cases of early ST, with a mean stent expansion of 0.7 ± 0.23 by MUSIC criteria. Stent malapposition was most frequently observed in very late ST (40%). In-hospital mortality was similar between subjects who had IVUS performed at the time of ST when compared with the non-IVUS group (3.2% vs. 4.3%, P = 0.8). Subjects who had IVUS performed at the time of ST had lower rates of mortality (HR 0.4, 95% CI 0.1-1.6, P =0.2) and major adverse cardiovascular events (HR 0.5, 95% CI 0.2-1.4, P =0.2) at follow-up, but these values were not statistically significant. CONCLUSIONS: There is a high prevalence of stent underexpansion in early ST, while the prevalence of malapposition is higher in very late ST. Use of IVUS during treatment for ST may identify mechanisms underlying the development of ST.

Procedural success and long-term outcomes of aspiration thrombectomy for the treatment of stent thrombosis.

BACKGROUND: Stent thrombosis (ST) is associated with a significant burden of coronary thrombus and potential microvascular obstruction. Aspiration thrombectomy may decrease the extent of microvascular obstruction in patients with acute myocardial infarction but its role in the treatment of ST is uncertain. The present study sought to evaluate the association between aspiration thrombectomy, procedural success and long-term outcomes among patients presenting with ST. METHODS: In a multicenter cohort of patients with definite ST, procedural success, long-term mortality, and major adverse cardiovascular events (death, stroke, re-infarction, revascularization) were ascertained. Propensity weighting was used to determine the association between aspiration thrombectomy and long-term outcomes. RESULTS: A total of 205 patients with ST were identified. Among these, 115 (56%) patients underwent adjunctive aspiration thrombectomy during percutaneous coronary intervention. Patients undergoing aspiration thrombectomy were more likely to present with ST-elevation myocardial infarction (75% vs. 52%, P < 0.003) and require hemodynamic support (19% vs. 10%, P = 0.07). Aspiration thrombectomy was associated with improved procedural outcomes including postprocedural TIMI 3 flow, resulting in higher angiographic and procedural success (each 96% vs. 83%, P < 0.001). Despite improved angiographic outcomes, the use of aspiration thrombectomy was not associated with a difference in long-term mortality (adjusted HR 0.99, 95% CI 0.44-2.24) or major adverse cardiovascular events (adjusted HR 1.06, 95% CI 0.45-2.48). CONCLUSIONS: Aspiration thrombectomy is associated with improved coronary flow and procedural success but is not associated with improved long-term outcomes among patients undergoing percutaneous intervention for definite ST. CLINICAL TRIAL REGISTRATION: NCT00931502 (http://www.clinicaltrials.gov/ct2/show/NCT00931502)

Prevalence and echocardiographic features of iatrogenic atrial septal defect after catheter-based mitral valve repair with the MitraClip system.

OBJECTIVES: Review the prevalence, echocardiographic features and potential predictors of iatrogenic ASD (iASD) created with the MitraClip guiding catheter. BACKGROUND: Catheter-based repair of mitral regurgitation (MR) with the MitraClip device (Abbott Vascular, Menlo Park, CA), is performed through a 22-French transseptal guiding catheter. The echocardiographic prevalence of iASDs after the MitraClip procedure has not been reported. METHODS: Thirty subjects undergoing MitraClip repair during the roll-in phase of the EVEREST II randomized trial who had baseline, 30 day, 6 and 12 month transthoracic echocardiograms (TTEs) available for review were included. Patients who underwent surgery for MR within the first 12 months were excluded. Residual iASD size, right ventricular (RV) size, left atrial (LA) volume, and tricuspid/MR grade were quantified. RESULTS: iASDs were found at 12 months in 8 patients (27%) with a mean diameter of 6.6 ± 3.1 mm. Subjects with iASD at 12 months had more residual MR, increased TR and a trend toward larger LA volumes than non-iASD patients. 83% of non-ASD patients were free from MR > 2+ at 12 mos. vs. 38% of those with iASD (p=0.016). There were no other significant associations between clinical and echocardiographic variables and the persistence of iASD. CONCLUSIONS: After MitraClip repair, persistent iASDs occur at a rate comparable to reports after other transseptal interventional procedures and do not appear hemodynamically significant. Patients with persistent iASDs had less MR reduction at 12-months and a trend toward larger LA volumes, suggesting that increased LA pressure may be a mechanism for persistent iASD.

Contemporary clinical characteristics, treatment, and outcomes of angiographically confirmed coronary stent thrombosis: results from a multicenter California registry.

OBJECTIVES: To describe the contemporary treatment and outcomes for patients with angiographically confirmed (definite) stent thrombosis (ST). BACKGROUND: Limited data are available on contemporary treatment patterns and outcomes of patients with ST in the United States. METHODS: In this multicenter California registry, consecutive cases of definite ST over 5 years were identified. Clinical characteristics, in-hospital outcomes, and long-term survival are reported. RESULTS: One hundred and sixty five consecutive episodes of ST were identified in 153 patients from January 2005 to February 2010. The distribution of acute (≤24 hr), subacute (24 hr to 30 days), late (30 days to 1 year), and very late (≥1 year) ST was 3.9%, 21.8%, 17.6%, and 50.3%, respectively. Only 41.2% of patients were on dual antiplatelet therapy at the time of presentation, while 22.4% of patients were on none. Of the 61.4% of patients treated with restenting, 71.1% of them received a drug-eluting stent. Procedural success was 88.1%, and in-hospital death, stroke, and CABG occurred in 5.5%, 0.6%, and 6.1% of subjects, respectively. All-cause mortality at 1 year was 14.3%. Although female gender, diabetes mellitus (DM), bifurcation disease, ejection fraction <40%, and cardiogenic shock at the time of presentation were associated with an increased risk of in-hospital mortality, only DM (P = 0.047) and bifurcation disease (P = 0.027) remained independent predictors of in-hospital death. CONCLUSION: In-hospital mortality from definite ST is lower than previously reported, but long-term mortality remains high. DM and bifurcation disease, but not type of percutaneous therapy, are independently associated with in-hospital mortality.

Internal pudendal artery stenoses and erectile dysfunction: correlation with angiographic coronary artery disease.

OBJECTIVES: To describe the angiographic characteristics of pelvic arterial disease in patients with erectile dysfunction (ED) nonresponsive to phosphodiesterase-5 inhibitors (PDE5i) and suspected coronary artery disease (CAD). BACKGROUND: ED and CAD share common risk factors which can result in endothelial dysfunction, atherosclerosis and flow-limiting stenoses in the coronary and internal pudendal arteries. METHODS: Ten patients undergoing cardiac catheterization with ED and a history of unsatisfactory response to a PDE5i were studied. ED severity was quantified using the International Index of ED scoring system. We performed angiography and quantitative vessel analysis of the coronary arteries, bilateral common and internal iliac arteries, and internal pudendal arteries (IPAs). RESULTS: In this pilot observational study, we found a high correlation between the presence of angiographic CAD and IPA disease. The reference IPA diameters at the point of maximal stenosis were 2.7 ± 0.4 mm (right IPA) and 2.7 ± 0.5 mm (left IPA). In the nine patients with IPA disease, the average stenosis severity was 55 ± 31% (right) and 66% ± 25% (left), and average lesion length was 12.4 ± 5.2 mm (right) and 10.0 ± 3.5 mm (left). Four patients had unilateral IPA total occlusions, three of whom had moderate contralateral disease. The majority of IPA stenoses occurred in the mid to distal IPA and appears amenable to percutaneous revascularization. CONCLUSIONS: This represents the first angiographic report of CAD correlated with IPA disease in patients with ED. Further investigation is required to determine whether the development of macrovascular disease in the IPA causes ED and whether endovascular treatment is safe and effective in this population.

Differential Longitudinal Outcomes Following Percutaneous Coronary Intervention to the Left Internal Mammary Artery and Other Bypass Grafts of the LAD: Findings From the NCDR.

OBJECTIVES: Limited studies of percutaneous coronary intervention (PCI) of the left internal mammary artery (LIMA) graft exist. We compared outcomes of different bypass grafts to the left anterior descending (LAD) coronary artery. METHODS: Participants ≥65 years old in the CathPCI Registry who underwent PCI of a bypass graft to the LAD between 2009 and 2014 were included. Individuals were divided by graft type: LIMA; saphenous vein graft (SVG); or other. Clinical characteristics and outcomes using Medicare claims data for mortality, rehospitalization for myocardial infarction (MI), stroke, or unplanned repeat revascularization at 1 year were examined. RESULTS: There were 10,051 PCIs performed on grafts to the LAD: 6797 SVGs (67.6%), 3011 LIMA grafts (30.0%); and 243 other (2.4%). Procedural success rates (SVG 92.9%, LIMA 91.1%, other 93.4%; P=.65) and in-patient mortality rates (SVG 3.0%, LIMA 2.7%, other 2.1%; P=.61) were similar. However, dissection rates were higher in LIMA interventions (SVG 0.7%, LIMA 2.8%, other 2.5%; P<.001). At 1 year, mortality, MI, and repeat revascularization were lower in arterial grafts (mortality: SVG 16.6%, LIMA 14.8%, other 11.8% [P<.001]; MI: SVG 9.9%, LIMA, 6.6%, other 8.1% [P<.001]; revascularization: SVG 14.4%, LIMA 9.5%, other 10.4% [P<.001]). After multivariable adjustment, LIMA patients had lower rates of MI (hazard ratio, 0.71; 95% confidence interval, 0.60-0.84) and repeat revascularization (hazard ratio, 0.68; 95% confidence interval, 0.59-0.79) compared with the SVG group. Mortality was not significantly different. CONCLUSIONS: Despite similar procedural success rates compared with SVG and other graft types, LIMA interventions were independently associated with lower rates of recurrent MI and repeat revascularization at 1 year.

Beneficial effects of soluble epoxide hydrolase inhibitors in myocardial infarction model: Insight gained using metabolomic approaches.

Myocardial infarction (MI) leading to myocardial cell loss represents one of the common causes leading to cardiac failure. We have previously demonstrated the beneficial effects of several potent soluble epoxide hydrolase (sEH) inhibitors in cardiac hypertrophy. sEH catalizes the conversion of epoxyeicosatrienoic acids (EETs) to form the corresponding dihydroxyeicosatrienoic acids (DHETs). EETs are products of cytochrome P450 epoxygenases that have vasodilatory properties. Additionally, EETs inhibit the activation of nuclear factor (NF)-kappaB-mediated gene transcription. Motivated by the potential to uncover a new class of therapeutic agents for cardiovascular diseases which can be effectively used in clinical setting, we directly tested the biological effects of sEH inhibitors (sEHIs) on the progression of cardiac remodeling using a clinically relevant murine model of MI. We demonstrated that sEHIs were highly effective in the prevention of progressive cardiac remodeling post MI. Using metabolomic profiling of the inflammatory lipid mediators, we documented a significant decrease in EETs/DHETs ratio in MI model predicting a heightened inflammatory state. Treatment with sEHIs resulted in a change in the pattern of lipid mediators from one of inflammation towards resolution. Moreover, the oxylipin profiling showed a striking parallel to the changes in inflammatory cytokines in this model. Our study provides evidence for a possible new therapeutic strategy to improve cardiac function post MI.

Long-term safety and durability of percutaneous septal sinus shortening (The PS(3) System) in an ovine model.

OBJECTIVES: Chronic implants of the PS(3) system were conducted in an ovine model to assess durability and safety at up to 1 year follow-up. BACKGROUND: The long-term durability and safety of emerging percutaneous devices for functional mitral regurgitation remain largely unknown. METHODS: The PS(3) system (consisting of interatrial septal and great cardiac vein devices connected by an adjustable suture bridge) was placed in eight healthy adult sheep. The mitral annular septal-lateral dimension in systole (SLS) was acutely reduced by 15-20%. Animals were sacrificed at up to 12 months postimplant and characterized by intracardiac echocardiography, cardiac computed tomography (CT), and histopathology. In vivo forces exerted on the PS(3) bridge were measured by means of a novel load cell catheter. RESULTS: At 3, 6, and 12 months after implantation, intracardiac echocardiographic and CT showed the PS(3) systems to be intact without erosion and with overall sustained reductions in the SLS. Histopathologic assessment revealed each component correctly deployed in its respective target site without evidence of erosion, thrombus, or device fracture. The SLS was 26.5 +/- 1.7 mm preimplant, 22.0 +/- 1.4 mm post-PS(3) (17.0% reduction), and 22.0 +/- 2.1 mm at latest follow-up. Mean forces exerted on the bridge in vivo ranged from 1.16 N to 1.87 N. CONCLUSIONS: The PS(3) System demonstrated excellent biocompatibility without evidence of erosion, thrombosis, or perforation at up to one-year follow-up in this chronic healthy ovine model. Forces exerted in the PS(3) system were relatively modest and should contribute to the durability of the device.

High-frequency vibration for the recanalization of guidewire refractory chronic total coronary occlusions.

BACKGROUND: Recanalization of coronary chronic total occlusions (CTOs) remains a clinical challenge, particularly when standard guidewire attempts fail. OBJECTIVES: We sought to determine the safety and efficacy of a novel method that used high-frequency (20 kHz) vibration to fragment occlusive fibrous tissue and facilitate guidewire crossing into the distal vessel. METHODS: A total of 125 patients with CTO, who failed at attempts of conventional guidewire recanalization after more than 5 min of fluoroscopy time, were enrolled in the study. The primary efficacy endpoint was the advancement of the CROSSER catheter through the occlusion and attainment of coronary guidewire positioning in the distal coronary lumen. The primary safety endpoint was the occurrence of death, myocardial infarction, clinical perforation, or target vessel revascularization within the first 30 days. RESULTS: The average fluoroscopy time while delivering the CROSSER catheter was 12.4 min. CROSSER-assisted guidewire recanalization was achieved in 76 (60.8%) procedures and a final diameter stenosis <50% was obtained in 68 (54.4%) of cases. Major adverse events occurred in 11 (8.8%) patients, lower than the predefined objective performance criteria. Angina frequency and quality of life were improved in patients with successful guidewire recanalization. CONCLUSIONS: We conclude that high-frequency vibration using the CROSSER catheter is a safe and effective therapy for patients with CTO, which are refractory to standard guidewire recanalization.

Percutaneous septal sinus shortening: a novel procedure for the treatment of functional mitral regurgitation.

BACKGROUND: The septal-to-lateral (SL) mitral annular diameter is increased in functional mitral regurgitation (MR). We describe a novel percutaneous technique (the percutaneous septal sinus shortening system) that ameliorates functional MR in an ovine model. METHODS AND RESULTS: Sheep underwent rapid right ventricular pacing to obtain moderate to severe functional MR with SL enlargement. The percutaneous septal sinus shortening system was placed via standard interventional techniques consisting of a bridge (suture) element between interatrial septal wall and great cardiac vein anchors. Through progressive tensioning of the bridge element, direct SL shortening was achieved. Sheep underwent short-term (n=19) and long-term (n=4) evaluation after device implantation. In short-term studies, SL diameter decreased an average of 24% (32.5+/-3.5 to 24.6+/-2.4 mm; P<0.001), and MR grade significantly improved (2.1+/-0.6 to 0.4+/-0.4; P<0.001). Despite continued rapid pacing, chronic device implantation resulted in durable SL shortening (30.4+/-1.9 mm before implantation to 25.3+/-0.8 mm at 30 days; P=0.01) and MR reduction (1.8+/-0.5 before implantation to 0.2+/-0.1 at 30 days; P=0.01). Increased cardiac output, decreased wedge pressure, and decreased brain natriuretic peptide levels were observed in animals undergoing long-term device implantation. CONCLUSIONS: The percutaneous septal sinus shortening system is effective in ameliorating functional MR in an ovine tachycardia model. The procedure, which uses standard catheter techniques, can be deployed largely under fluoroscopic guidance. The unique bridge element appears durable and allows direct and precise SL shortening to a diameter optimal for MR reduction.

Functional roles of Cav1.3(alpha1D) calcium channels in atria: insights gained from gene-targeted null mutant mice.

BACKGROUND: Previous data suggest that L-type Ca2+ channels containing the Cav1.3(alpha(1D)) subunit are expressed mainly in neurons and neuroendocrine cells, whereas those containing the Cav1.2(alpha1C) subunit are found in the brain, vascular smooth muscle, and cardiac tissue. However, our previous report as well as others have shown that Cav1.3 Ca2+ channel-deficient mice (Cav1.3(-/-)) demonstrate sinus bradycardia with a prolonged PR interval. In the present study, we extended our study to examine the role of the Cav1.3(alpha1D) Ca2+ channel in the atria of Cav1.3(-/-) mice. METHODS AND RESULTS: We obtained new evidence to demonstrate that there is significant expression of Cav1.3 Ca2+ channels predominantly in the atria compared with ventricular tissues. Whole-cell L-type Ca2+ currents (I(Ca,L)) recorded from single, isolated atrial myocytes from Cav1.3(-/-) mice showed a significant depolarizing shift in voltage-dependent activation. In contrast, there were no significant differences in the I(Ca,L) recorded from ventricular myocytes from wild-type and null mutant mice. We previously documented the hyperpolarizing shift in the voltage-dependent activation of Cav1.3 compared with Cav1.2 Ca2+ channel subunits in a heterologous expression system. The lack of Cav1.3 Ca2+ channels in null mutant mice would result in a depolarizing shift in the voltage-dependent activation of I(Ca,L) in atrial myocytes. In addition, the Cav1.3-null mutant mice showed evidence of atrial arrhythmias, with inducible atrial flutter and fibrillation. We further confirmed the isoform-specific differential expression of Cav1.3 versus Cav1.2 by in situ hybridization and immunofluorescence confocal microscopy. CONCLUSIONS: Using gene-targeted deletion of the Cav1.3 Ca2+ channel, we established the differential distribution of Cav1.3 Ca2+ channels in atrial myocytes compared with ventricles. Our data represent the first report demonstrating important functional roles for Cav1.3 Ca2+ channel in atrial tissues.

Prospective Multicenter Evaluation of the Direct Flow Medical Transcatheter Aortic Valve System: 12-Month Outcomes of the Evaluation of the Direct Flow Medical Percutaneous Aortic Valve 18F System for the Treatment of Patients With Severe Aortic Stenosis (DISCOVER) Study.

OBJECTIVES: The aim of this study was to assess the 1-year outcome after transcatheter aortic valve replacement (TAVR) of the Direct Flow Medical (DFM) valve in patients with severe symptomatic aortic stenosis who were contraindicated or high risk for surgery. BACKGROUND: The DFM transcatheter heart valve is a new-generation, nonmetallic aortic valve with a pressurized support structure and conformable double-ring annular sealing delivered through an 18-F sheath. The device allows repositioning, retrieval, and assessment of valve performance before permanent implantation. METHODS: A prospective multicenter European registry was set up to determine the safety and performance of the valve in 100 consecutive patients (10 centers). Echocardiographic and angiographic data were evaluated by an independent core laboratory, and adverse events were adjudicated by a clinical events committee using Valve Academic Research Consortium criteria. RESULTS: Patients were 83.1 ± 5.9 years of age and had a logistic EuroSCORE of 22.5 ± 11.3% and a Society of Thoracic Surgeons score of 9.7 ± 8.7%. Correct valve positioning was obtained in 99% of cases with a combined 30-day safety endpoint at 10%, including major stroke in 5.0%, major vascular complications in 2.0%, and death in 1%. At 12 months, 95% of patients were in New York Heart Association functional class I or II. Freedom from any death was 90%, and freedom from any death or major stroke was 85%. Echocardiography demonstrated none/trace to mild aortic regurgitation in 100% of patients and an unchanged mean aortic gradient of 12.2 ± 6.6 mm Hg and effective orifice area of 1.6 ± 0.4 cm(2). CONCLUSIONS: At 1 year, the DFM transcatheter heart valve had durable hemodynamics. This study demonstrates that the low rate of early complications and the low risk of significant aortic regurgitation translated into midterm clinical benefit.

Prospective, randomized evaluation of thrombectomy prior to percutaneous intervention in diseased saphenous vein grafts and thrombus-containing coronary arteries.

OBJECTIVES: We sought to determine whether routine thrombectomy prior to stent implantation in diseased saphenous vein grafts (SVGs) and thrombus-containing native coronary arteries would reduce peri-procedural myonecrosis and subsequently enhance event-free survival. BACKGROUND: Percutaneous coronary intervention in diseased SVGs and thrombotic native coronary arteries is complicated by a high rate of peri-procedural myocardial infarction (MI). Thrombectomy prior to intervention may enhance the safety of intervention and improve early and late outcomes in these high-risk patients. METHODS: At 60 centers in the U.S. and Canada, 797 patients with 839 diseased SVGs or thrombus-containing native coronary arteries were prospectively randomized to stent implantation with versus without prior thrombectomy with the X-SIZER device (ev3, Plymouth, Minnesota). RESULTS: Peri-procedural MI occurred in 15.8% of patients assigned to the X-SIZER device compared with 16.6% of control patients (p = 0.77), although the rate of large MI (pre-specified as the development of new pathologic Q waves or creatine phosphokinase-MB isoenzyme elevation >8 x upper limits of normal) was reduced with X-SIZER device use from 9.6% to 5.5% (multivariate risk ratio 0.35 [95% confidence interval 0.18 to 0.66], p = 0.002). Major adverse cardiac events (cardiac death, MI, or repeat target vessel revascularization) occurred in 16.8% of X-SIZER patients versus 17.1% of control patients at 30 days (p = 0.92), and in 31.3% of X-SIZER patients versus 28.2% of control patients at 1 year (p = 0.35). CONCLUSIONS: Thrombectomy with the X-SIZER device prior to stent implantation in high-risk diseased SVGs and thrombus-containing native coronary arteries may reduce the extent, but not the occurrence, of myonecrosis. Early and late event-free survival, however, were not improved by routine thrombectomy with this device.

Long-term outcomes of angiographically confirmed coronary stent thrombosis: results from a multicentre California registry.

AIMS: Limited data exist on long-term outcomes of patients with stent thrombosis (ST). Our aim was to describe the long-term outcomes after angiographically confirmed ST. METHODS AND RESULTS: In this multicentre registry, consecutive cases of definite ST were identified between 2005 and 2013. Clinical and procedural characteristics, in-hospital outcomes and long-term survival up to five years were compared between those with and those without adverse cardiovascular and cerebrovascular events (MACCE), defined as all-cause mortality, myocardial infarction and stroke. Two hundred and twenty-one patients with 239 stent thrombosis events were identified. Patients who developed MACCE were older, less likely to be men, and less likely to have hypertension. Angiographic characteristics were similar. Patients who had a MACCE event showed a trend towards a lower likelihood of procedural success (86% vs. 91%, p=0.05). MACCE rates were 22% at one year and 41% at five years. All-cause mortality was 13% at one year and 24% at five years. On multivariable analysis, age, diabetes mellitus, active smoking and ST at a bifurcation were independently associated with the occurrence of MACCE up to five years. CONCLUSIONS: Age, active smoking, diabetes mellitus and bifurcation disease are independently associated with long-term MACCE over a five-year follow-up period.

Right- and left-sided heart catheterization as a quality marker for catheterization laboratories (from the national Veterans Affairs clinical assessment reporting and tracking program).

The rate of concurrent right-heart catheterization (RHC) in patients undergoing left-heart catheterization (LHC) for coronary artery disease (CAD) indications or bilateral heart catheterization (BHC) is recommended as a measure of hospital quality, with higher rates suggesting over utilization. Our aim was to describe the prevalence of BHC and abnormal RHC findings in patients undergoing BHC with a primary indication for LHC. A retrospective analysis was performed for patients undergoing cardiac catheterization for CAD indications using the Department of Veterans Affairs Clinical Assessment Reporting and Tracking Program. Patients undergoing catheterization from October 2007 to September 2011 in 76 Veterans Affairs hospitals were included. Among 95,656 patients undergoing catheterization for CAD, 6,611 (6.9%) underwent BHC and 88,929 (93.0%) LHC. Among the patients undergoing BHC, 61.3% had at least 1 of the following abnormal RHC values: mean pulmonary artery (PA) pressure >25 mm Hg, pulmonary capillary wedge pressure (PCWP) >15 mm Hg, or pulmonary vascular resistance (PVR) >3 Woods units. A total of 37.5% of patients had mean PA pressures of 26 to 40 mm Hg and 11.1% had mean PA pressures >40 mm Hg. A total of 34.4% of patients had mean PCWP of 16 to 25 mm Hg and 13.6% had mean PAWP >25 mm Hg. A total of 16.5% of patients had PVR between 3 and 6 WU and 2.9% had PVR >6 WU. A total of 4.3% of patients met formal criteria for pulmonary arterial hypertension (defined as the combination of PA mean >25 mm Hg, PCWP ≤15 mm Hg, and PVR >3). In conclusion, these findings suggest that most BHC were performed for appropriate clinical reasons. Future studies should further explore BHC rate as an effective quality indicator.