Outcomes in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Via Radial Access Anticoagulated With Bivalirudin Versus Heparin: A Report From the National Cardiovascular Data Registry.

OBJECTIVES: The aim of this study was to compare bivalirudin with heparin as anticoagulant agents in patients with ST-segment elevation myocardial infarction treated with radial primary percutaneous coronary intervention (PCI). BACKGROUND: Recent studies in which PCI was performed predominantly via radial access did not show bivalirudin to be superior to heparin. METHODS: Outcomes were compared in patients with STEMI included in the National Cardiovascular Data Registry CathPCI database from 2009 to 2015 who underwent primary PCI via radial access and who were anticoagulated with bivalirudin or heparin. RESULTS: The sample included 67,368 patients, of whom 29,660 received bivalirudin and 37,708 received heparin. The 2 groups of patients did not differ significantly in their mean age or percentage of men. The unadjusted comparison showed no significant difference in the rate of the composite endpoint of death, myocardial infarction, or stroke (4.6% vs. 4.7%; p = 0.47) and a significantly higher rate of acute stent thrombosis (1.00% vs. 0.60%; p < 0.001) with bivalirudin compared with heparin. After adjusting for multiple variables, including a propensity score reflecting the probability of receiving bivalirudin, the odds ratio of the composite endpoint of death, myocardial infarction, or stroke for bivalirudin versus heparin was 0.95 (95% confidence interval: 0.87 to 1.05; p = 0.152), and the odds ratio for acute stent thrombosis was 2.11 (95% confidence interval: 1.73 to 2.57) for bivalirudin versus heparin. Major bleeding rates were not significantly different. CONCLUSIONS: In patients undergoing primary PCI via transradial access anticoagulated with bivalirudin or heparin, there was no difference in the composite endpoint of death, myocardial infarction, or stroke.

Costs Associated With Access Site and Same-Day Discharge Among Medicare Beneficiaries Undergoing Percutaneous Coronary Intervention: An Evaluation of the Current Percutaneous Coronary Intervention Care Pathways in the United States.

OBJECTIVES: The aim of this study was to examine the independent impact of various care pathways, including those involving transradial intervention (TRI) and same-day discharge (SDD) after elective percutaneous coronary intervention (PCI), on hospital costs. BACKGROUND: PCI is associated with costs of $10 billion annually. Alternative payment models for PCI are being implemented, but few data exist on strategies to reduce costs. Various PCI care pathways, including TRI and SDD, exist, but their association with costs and outcomes is unknown. METHODS: In total, 279,987 PCI patients eligible for SDD in the National Cardiovascular Data Registry CathPCI Registry linked to Medicare claims files were analyzed. Hospital costs in 2014 U.S. dollars were estimated using cost-to-charge ratios. Propensity scores for TRI and SDD, with propensity adjustment via inverse probability weighting, was performed. RESULTS: Of the 279,987 PCI procedures, TRI was used in 9.0% (13.5% of which were SDD), and SDD was used in 5.3% of cases (23.1% of which were TRI). TRI (vs. transfemoral intervention) was associated with lower adjusted costs of $916 (95% confidence interval [CI]: $778 to $1,035), as was SDD ($3,502; 95% CI: $3,486 to $3,902). The adjusted cost associated with TRI and SDD was $13,389 (95% CI: $13,161 to $13,607), while the cost associated with transfemoral intervention and non-same-day discharge was $17,076 (95% CI: $16,999 to $17,147), a difference of $3,689 (95% CI: $3,486 to $3,902; p < 0.0001). Shifting current practice from transfemoral intervention non-same-day discharge to TRI SDD by 30% could potentially save a hospital performing 1,000 PCIs each year $1 million and the country $300 million annually. CONCLUSIONS: Among Medicare beneficiaries, TRI with SDD was independently associated with fewer complications and lower in-hospital costs. These findings have important implications for changing the current PCI care pathways to improve outcomes and reduce costs.

Training the next generation of invasive cardiologists: Feasibility of implementing a trans-radial access program at an academic hospital.

BACKGROUND: Slow adoption of trans-radial access (TRA) for left heart catheterization (LHC) in the U.S. may be related to concerns about procedural complexity and a steep learning curve. However, TRA acceptance among novice operators remains poorly characterized. METHODS: We initiated a 1-year TRA learning period among lower-risk outpatients, followed by a "radial-first" policy for all LHC patients beginning year 2. By year 3, all fellows prospectively collected diagnostic LHC data as part of a quality improvement study. TRA procedural characteristics were compared with patients undergoing trans-femoral access for the 3months prior to the TRA program, and trends over time were evaluated. RESULTS: Between 7/2009 and 6/2012, we identified 960 patients undergoing LHC via TRA by 23 rotating cardiology fellows supervised by 5 interventional cardiologists. When evaluated against the 160 trans-femoral comparator patients, TRA patients had lower procedural success through the initial access site (88% vs. 99%, p<0.001) and longer fluoroscopy times (9.5 [5.8-15.9] vs. 6.5 [3.1-12.7] min, p<0.001), with similar contrast volumes and fewer catheters used. Despite tackling more complex patients during years 2-3, there were improvements in fluoroscopy times, catheter utilization, contrast volumes, and procedural success rates over time (all p<0.001). CONCLUSIONS: The dedicated adoption of TRA by an academic catheterization laboratory demonstrated improvements in efficiency and resource utilization over a relatively short period of time. Additional exposure to TRA during training may help facilitate acceptance of this approach among the next generation of invasive cardiologists. SHORT SUMMARY (FOR ANNOTATED TABLE OF CONTENTS): When initiating a trans-radial access program for cardiac catheterization at an academic training hospital, procedural success rates were lower and fluoroscopy times were higher than traditional trans-femoral access. Nonetheless, other procedural variables were similar between the 2 approaches, and improvements over time were consistent with the learning curves reported among experienced cardiologists in prior studies. Exposure to trans-radial access during training may help facilitate acceptance of this approach among the next generation of invasive cardiologists.

Comparison of bivalirudin and radial access across a spectrum of preprocedural risk of bleeding in percutaneous coronary intervention: analysis from the national cardiovascular data registry.

BACKGROUND: Bleeding is a common, noncardiac, preventable complication of percutaneous coronary intervention. We compared the relative safety of radial access and bivalirudin in percutaneous coronary intervention. METHODS AND RESULTS: From CathPCI Registry, we determined the association between the site of arterial access, bivalirudin, and periprocedural bleeding rates in 501 017 patients. Radial access patients receiving heparin (radial group) were compared with those receiving bivalirudin (radial combination group). Femoral access patients who had bivalirudin and a vascular closure device served as a reference group (femoral group). An inverse probability weighting analysis incorporating propensity scores was used to compare groups. The overall rate of bleeding was 2.59%. It was 2.71% in the femoral group, 2.5% in the radial group, and 1.82% in the radial combination groups (P<0.001). When compared with femoral group, the adjusted odds ratio for bleeding was significantly lower for patients with radial combination group (odds ratio, 0.79; 95% confidence interval, 0.72-0.86), but not for radial group (odds ratio, 0.96; 95% confidence interval, 0.88-1.05), unless patients treated with IIb/IIIa were excluded (radial group-IIb/IIIa odds ratio, 0.84; 95% confidence interval, 0.75-0.94).The number needed to treat to prevent 1 bleeding event with radial combination group was 138, whereas the number needed to treat to prevent 1 bleeding event in high-bleeding risk patients was 68. CONCLUSIONS: In this observational analysis, the combination of bivalirudin and radial access was associated with reduced bleeding event rate. This benefit was present across the entire spectrum of preprocedural risk of bleeding, with or without exposure to IIb/IIIa inhibitors. These data support an adequately powered randomized trial comparing bleeding avoidance strategies.

Costs of transradial percutaneous coronary intervention.

OBJECTIVES: This study sought to evaluate the costs of transradial percutaneous coronary intervention (TRI) and transfemoral percutaneous coronary intervention (TFI) from a contemporary hospital perspective. BACKGROUND: Whereas the TRI approach to percutaneous coronary intervention (PCI) has been shown to reduce access-site complications compared with TFI, whether it is associated with lower costs is unknown. METHODS: TRI and TFI patients were identified at 5 U.S. centers. The primary outcome was the cost of percutaneous coronary intervention (PCI) hospitalization, defined as cost on the day of PCI through hospital discharge. Cost was obtained from each hospital's cost accounting system. Independent costs of TRI were identified using propensity-scoring methods with inverse probability weighting. Secondary outcomes of interest were bleeding, in-hospital mortality, and length of stay, which were stratified by pre-procedural risk and PCI indication. RESULTS: In 7,121 PCI procedures performed from January 1, 2010, to March 31, 2011, TRI was performed in 1,219 (17%) patients and was associated with shorter lengths of stay (2.5 vs. 3.0 days; p < 0.001) and lower bleeding events (1.1% vs. 2.4%, adjusted odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.34 to 0.79; p = 0.002). TRI was associated with a total cost savings of $830 (95% CI: $296 to $1,364; p < 0.001), of which $130 (95% CI: -$99 to $361; p = 0.112) were procedural savings and $705 (95% CI: $212 to $1,238; p < 0.001) were post-procedural savings. There was an associated graded increase in savings among patients at higher predicted risk of bleeding: low risk: $642 (95% CI: $43 to $1,236; p = 0.035); moderate risk: $706 (95% CI: $104 to $1,308; p = 0.029); and high risk: $1,621 (95% CI: $271 to $2,971, p = 0.039). CONCLUSIONS: TRI was associated with a cost savings exceeding $800 per patient relative to TFI. Increased adoption of TRI may result in cost savings at hospitals.

Adoption of radial access and comparison of outcomes to femoral access in percutaneous coronary intervention: an updated report from the national cardiovascular data registry (2007-2012).

BACKGROUND: Radial access for percutaneous coronary intervention (r-PCI) is associated with reduced vascular complications; however, previous reports have shown that <2% of percutaneous coronary intervention (PCI) procedures in the United States are performed via the radial approach. Our aims were to evaluate temporal trends in r-PCI and compare procedural outcomes between r-PCI and transfemoral PCI. METHODS AND RESULTS: We conducted a retrospective cohort study from the CathPCI registry (n=2 820 874 procedures from 1381 sites) between January 2007 and September 2012. Multivariable logistic regression models were used to evaluate the adjusted association between r-PCI and bleeding, vascular complications, and procedural success, using transfemoral PCI as the reference. Outcomes in high-risk subgroups such as age ≥75 years, women, and patients with acute coronary syndrome were also examined. The proportion of r-PCI procedures increased from 1.2% in quarter 1 2007 to 16.1% in quarter 3 2012 and accounted for 6.3% of total procedures from 2007 to 2012 (n=178 643). After multivariable adjustment, r-PCI use in the studied cohort of patients was associated with lower risk of bleeding (adjusted odds ratio, 0.51; 95% confidence interval, 0.49-0.54) and lower risk of vascular complications (adjusted odds ratio, 0.39; 95% confidence interval, 0.31-0.50) in comparison with transfemoral PCI. The reduction in bleeding and vascular complications was consistent across important subgroups of age, sex, and clinical presentation. CONCLUSIONS: There has been increasing adoption of r-PCI in the United States. Transradial PCI now accounts for 1 of 6 PCIs performed in contemporary clinical practice. In comparison with traditional femoral access, transradial PCI is associated with lower vascular and bleeding complication rates.

The prevalence and outcomes of transradial percutaneous coronary intervention for ST-segment elevation myocardial infarction: analysis from the National Cardiovascular Data Registry (2007 to 2011).

OBJECTIVES: The purpose of this study was to examine use and describe outcomes of radial access for percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Transradial PCI (TRI) is associated with reduced risk of bleeding and vascular complications, as compared with femoral access PCI (FPCI). Studies have suggested that TRI may reduce mortality among patients with STEMI. METHODS: We examined 294,769 patients undergoing PCI for STEMI at 1,204 hospitals in the CathPCI Registry between 2007 and 2011. Patients were grouped according to access site used for PCI. The temporal trend in the rate of radial versus femoral approach was determined. For minimization of confounding, an inverse probability weighting analysis incorporating propensity scores was used to compare procedural success, post-PCI bleeding, door-to-balloon times, and in-hospital mortality between radial and femoral access. RESULTS: Over the 5-year period, the use of TRI versus FPCI in STEMI increased from 0.9% to 6.4% (p < 0.0001). There was no difference in procedural success. TRI was associated with longer median door-to-balloon time (78 vs. 74 min; p < 0.0001) but lower adjusted risk of bleeding (odds ratio [OR]: 0.62; 95% CI: 0.53 to 0.72; p < 0.0001) and lower adjusted risk of in-hospital mortality (OR: 0.76; 95% CI: 0.57 to 0.99; p = 0.0455). CONCLUSIONS: In this large national database, use of radial access for PCI in STEMI increased over the study period. Despite longer door-to-balloon times, the radial approach was associated with lower bleeding rate and reduced in-hospital mortality. These data provide support to execute an adequately powered randomized controlled trial comparing radial and femoral approaches for PCI in STEMI.

Coronary stenting is safe and effective in a high-risk octogenarian patient cohort.

BACKGROUND: Octogenarians represent an increasing percentage of patients with coronary heart disease and are an inherently high-risk population. We sought to define the immediate and long-term results of coronary stenting in the "real-world" environment of a community teaching hospital. METHODS: One hundred ninety-seven consecutive patients older then 80 years who underwent 214 coronary stent procedures were studied. Each patient had postprocedural serial cardiac enzymes and ECG's collected, and was followed for a minimum of 12 months after the procedure. Procedural success was defined as less than 20% residual stenosis, TIMI 3 flow, and absence of major complications (death, nonfatal myocardial infarction, emergent coronary artery bypass graft surgery and stroke). Sixty-five percent of patients presented with an acute coronary syndrome and 93% were functionally New York Heart Association (NYHA) Class III or IV. RESULTS: Procedural success was 95%. Death during the index hospitalization occurred in 3% of patients. An additional 4.1% of patients died during follow-up. The target vessel revascularization rate (TVR) during follow up was 8.6%. Multivariate analysis of selected angiographic and clinical variables did not reveal any predictors of major cardiac events. CONCLUSIONS: Despite a high-risk clinical and angiographic profile, coronary stenting can be safely performed in octogenarians with a high procedural success rate, low complication rate, and excellent 12-month outcome.

Live 3D echo guidance of catheter-based endomyocardial injection.

Local delivery of therapeutic agents into the myocardium is limited by suboptimal imaging. We evaluated the feasibility and accuracy of live 3D echo to guide left ventricular endomyocardial injection. An intramyocardial injection catheter was positioned in the left ventricle in five healthy Yorkshire pigs using fluoroscopy. All other catheter manipulations were performed with live biplane and 3D echo guidance. In each animal, a total of 12 endomyocardial injections (volume, 50-100 microl) of echo contrast mixed with blue tissue dye were performed. Four injections, 10 mm apart, were directed to three myocardial target zones: the anterior septum at the mitral valve level (zone 1); the posterolateral wall between the heads of the papillary muscles (zone 2); and the apex (zone 3). The injections were aimed to form a transverse line in zones 1 and 2 and an inverted triangular pyramid in zone 3. The animals were sacrificed, the hearts were inspected and the left ventricular endocardium was examined to create a map of injection marks. Success, defined as a visible injection of tissue dye, was 95%, and accuracy, defined as an injection into the target zone, was 83%. There was no significant difference in accuracy between the zones. Live 3D echo can successfully guide endomyocardial injections by accurately targeting specific myocardial zones, verifying catheter apposition and, when combined with echo contrast, providing real-time visualization of injectate deposition.

Novel double contrast MRI technique for intramyocardial detection of percutaneously transplanted autologous cells.

Bone marrow cells (BMC) labeled with iron particles can be injected into the heart and detected with MRI. Improvement in conspicuity of labelled cells would be advantageous. This study examined if double contrast with iron oxide and Gd-DTPA enhances cell MRI after transvascular transplantation in myocardial infarction. Ten pigs with week-old myocardial infarction had transvascular peri-infarct delivery of microspheres alone (Group I, n = 3) or mixed with iron-labeled BMCs (Group II, n = 7). Gradient-echo MRI before and 1 min after systemic Gd-DTPA administration produced regions of interest with hypoenhancement that were compared to contralateral regions for contrast-to-noise (CNR) and signal-to-noise (SNR) ratios. All hearts were harvested for gross and microscopic analysis. Areas of focal hypoenhancement corresponding to the BMCs were detected in the myocardium in Group II. Early after administration of Gd-DTPA CNR increased from 17.58 +/- 8.5 to 27.25 +/- 15.8 (P < 0.05) and SNR from 24.87 +/- 9.6 to 35.08 +/- 15.5 (P < 0.05). There was no hypoenhancement in Group I. Tissue examination confirmed presence of iron-containing cells and microspheres in corresponding segments of the heart. The distribution of microspheres was similar between the groups. Double contrast with cellular iron and Gd-DTPA in surrounding myocardium resulted in improved cell localization by MRI.

Regional cardiac sympathetic innervation early and late after transmyocardial laser revascularization.

BACKGROUND: Prior experimental and clinical studies have drawn disparate conclusions regarding the effects of transmyocardial laser revascularization (TMR) on regional cardiac innervation in the treated regions. Regional afferent denervation has been proposed as a potential mechanism of action of the procedure, although this as yet remains unproven. The purpose of the present study was to evaluate regional myocardial sympathetic innervation both early (3 days) and late (6 months) after TMR. METHODS: Mini-swine in the early group were randomized to be sacrificed 3 days after holmium:YAG TMR (n = 5) or sham thoractomy (n = 3). In the late group, mini-swine with hibernating myocardium in the left circumflex (LCx) region were randomized to sham redo-thoracotomy (n = 5), TMR of the LCx distribution with a carbon dioxide (n = 5), holmium:YAG (n = 5), or excimer (n = 5) laser. Six months postoperatively the animals were sacrificed. Additional animals in both the early (n = 2) and late (n = 2) groups served as age- and weight-matched normal controls. Immunohistochemistry and Western blot analysis for tyrosine hydroxylase (TYR-OH), a neural-specific enzyme found in sympathetic efferent nerves and a commonly used anatomic marker of regional innervation, were performed on lased and nonlased LCx and septal regions. RESULTS: Immunohistochemical staining for TYR-OH was markedly diminished in the lased myocardial regions 3 days after TMR. This staining was significantly reduced compared to untreated septal regions, sham-operated, and normal LCx myocardium. Quantitative immunoblotting confirmed a significant reduction in TYR-OH (p < 0.05) protein concentration in the lased regions 3 days after TMR. On the contrary, TYR-OH staining was present in LCx myocardium surrounding the laser channels of all animals in all groups 6 months postoperatively. Staining was not different from controls. Similarly, there was no difference in LCx TYR-OH protein concentration between the normal, sham, or 6 months postoperative lased groups (p > 0.2 by one-way ANOVA). CONCLUSIONS: TMR-treated myocardium demonstrates anatomic evidence of regional sympathetic denervation 3 days postoperatively, although myocardium lased with each of the three lasers currently in clinical use is reinnervated by 6 months as evidenced by immunoblotting and immunohistochemistry for TYR-OH. These results suggest that mechanisms other than denervation may account for the long-term reductions in angina seen after TMR.

Neovascularization in intimal hyperplasia is associated with vein graft failure after coronary artery bypass surgery.

Vein graft atherosclerosis is the major limitation of arterial bypass surgery. This study was carried out to determine if the number of microvessels per area of intimal hyperplasia correlated with vein graft disease. Vein grafts (n=24, graft age range 2-19 years) were taken from 22 patients undergoing redo-coronary artery bypass surgery. Mean age of the patients was 68 +/- 9 years; 92% were males. Samples were divided into three groups (n=8 per group): in group I segments were from grafts without angiographic or histologic disease, in groups II and III segments were from grafts with significant angiographic stenosis, without (group II) and with (group III) atheroma. Intimal hyperplasia was identified by Masson staining, morphometric analysis was performed with NIH image analysis software. Microvessels in the intimal hyperplasia were identified using immunohistochemical techniques. Significance was determined by single-factor ANOVA p < 0.05. The mean area of intimal hyperplasia was similar in groups I and II at 1.06 +/- 0.25 mm2 and 0.97 +/- 0.37 mm2, respectively. The extent of intimal hyperplasia was significantly greater in group III, 1.70 +/- 0.62 mm2 (p < 0.01). In group I, the microvessel count in the intimal hyperplasia was 5.62 +/- 3.89 vessels/mm2, while in group III it was 15.26 +/- 3.66/mm2 (p < 0.01 versus group I). Interestingly the number of microvessels per area of intimal hyperplasia in group II was similar to that in group III). In this study, the extent of neovascularization in intimal hyperplasia correlated with stenoses in human vein grafts. Strategies designed to limit neovascularization in intimal hyperplasia may lead to novel therapies to prevent vein graft failure.

A comparison of mechanical and laser transmyocardial revascularization for induction of angiogenesis and arteriogenesis in chronically ischemic myocardium.

OBJECTIVES: The purpose of the present study was to compare the use of a mechanical transmyocardial implant (TMI) device with transmyocardial laser revascularization (TMR) for induction of therapeutic angiogenesis and arteriogenesis in the chronically ischemic heart. BACKGROUND: Prior experimental studies have demonstrated evidence for neovascularization after both mechanical and laser transmyocardial revascularization, although a long-term comparison of the two techniques has not been performed. METHODS: Using an established model of chronic hibernating myocardium, mini-swine underwent 90% proximal left circumflex (LCx) coronary artery stenosis. One month later, baseline positron emission tomography (PET) and dobutamine stress echocardiography (DSE) were performed to quantitate regional myocardial blood flow (MBF) and function. Animals then underwent TMR with a holmium:yttrium-aluminum-garnet (holmium:YAG) laser (n = 5), TMI (n = 5), or sham redo-thoracotomy (n = 5). In the TMR group, the entire LCx region was treated with transmural laser channels at a density of 1/cm(2). Transmyocardial implants were placed transmurally at a similar density in the LCx region of the TMI group. Six months later, the PET and DSE studies were repeated, and the animals were euthanized. RESULTS: Six months after TMR, there was a significant increase over baseline in resting MBF to the lased LCx region (68.9 +/- 4.6% vs. 89.3 +/- 3.0% reference non-ischemic septal segments; p < 0.001). This increased MBF was accompanied by a significant improvement in LCx regional wall motion during peak dobutamine stress (p = 0.04). Compared with baseline, there was no change in LCx region MBF six months after either TMI (72.9 +/- 4.8% vs. 85.7 +/- 3.4%; p = 0.10) or sham redo-thoracotomy (75.6 +/- 4.6% vs. 80.1 +/- 5.0%; p > 0.2). Likewise, there was no significant change in rest or stress wall motion by DSE six months postoperatively in either group. Overall vascular density was increased only in the TMR-treated regions six months postoperatively. The difference between groups was most notable for a twofold increase in the number of small arterioles seen in the lased (4.4 +/- 0.3 arterioles per high power field; p < 0.001 vs. both TMI and sham) compared with TMI (2.2 +/- 0.2) and sham (1.9 +/- 0.2)-treated regions. CONCLUSIONS: Mechanical transmyocardial revascularization with a TMI device does not appear to promote physiologically significant angiogenesis or arteriogenesis in the chronically ischemic porcine heart and cannot be recommended for clinical trials at this time. Infrared laser-mediated injury mechanisms may be important for inducing therapeutic neovascularization with direct myocardial revascularization techniques.