The initial U.S. experience with the Tempo active fixation temporary pacing lead in structural heart interventions.

OBJECTIVES: This multicenter retrospective study of the initial U.S. experience evaluated the safety and efficacy of temporary cardiac pacing with the Tempo® Temporary Pacing Lead. BACKGROUND: Despite increasing use of temporary cardiac pacing with the rapid growth of structural heart procedures, temporary pacing leads have not significantly improved. The Tempo lead is a new temporary pacing lead with a soft tip intended to minimize the risk of perforation and a novel active fixation mechanism designed to enhance lead stability. METHODS: Data from 269 consecutive structural heart procedures were collected. Outcomes included device safety (absence of clinically significant cardiac perforation, new pericardial effusion, or sustained ventricular arrhythmia) and efficacy (clinically acceptable pacing thresholds with successful pace capture throughout the index procedure). Postprocedure practices and sustained lead performance were also analyzed. RESULTS: The Tempo lead was successfully positioned in the right ventricle and achieved pacing in 264 of 269 patients (98.1%). Two patients (0.8%) experienced loss of pace capture. Procedural mean pace capture threshold (PCT) was 0.7 ± 0.8 mA. There were no clinically significant perforations, pericardial effusions, or sustained device-related arrhythmias. The Tempo lead was left in place postprocedure in 189 patients (71.6%) for mean duration of 43.3 ± 0.7 hr (range 2.5-221.3 hr) with final PCT of 0.84 ± 1.04 mA (n = 80). Of these patients, 84.1% mobilized out of bed with no lead dislodgment. CONCLUSION: The Tempo lead is safe and effective for temporary cardiac pacing for structural heart procedures, provides stable peri and postprocedural pacing and allows mobilization of patients who require temporary pacing leads.

VEGF and IGF Delivered from Alginate Hydrogels Promote Stable Perfusion Recovery in Ischemic Hind Limbs of Aged Mice and Young Rabbits.

Biomaterial-based delivery of angiogenic growth factors restores perfusion more effectively than bolus delivery methods in rodent models of peripheral vascular disease, but the same success has not yet been demonstrated in clinically relevant studies of aged or large animals. These studies explore, in clinically relevant models, a therapeutic angiogenesis strategy for the treatment of peripheral vascular disease that overcomes the challenges encountered in previous clinical trials. Alginate hydrogels providing sustained release of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF) were injected into ischemic hind limbs in middle-aged and old mice, and also in young rabbits, as a test of the scalability of this local growth factor treatment. Spontaneous perfusion recovery diminished with increasing age, and only the combination of VEGF and IGF delivery from gels significantly rescued perfusion in middle-aged (13 months) and old (20 months) mice. In rabbits, the delivery of VEGF alone or in combination with IGF from alginate hydrogels, at a dose 2 orders of magnitude lower than the typical doses used in past rabbit studies, enhanced perfusion recovery when given immediately after surgery, or as a treatment for chronic ischemia. Capillary density measurements and angiographic analysis demonstrated the benefit of gel delivery. These data together suggest that alginate hydrogels providing local delivery of low doses of VEGF and IGF constitute a safe and effective treatment for hind-limb ischemia in clinically relevant animal models, thereby supporting the potential clinical translation of this concept.

Coronary artery perforations after contemporary percutaneous coronary interventions: Evaluation of incidence, risk factors, outcomes, and predictors of mortality.

OBJECTIVES: We sought to evaluate the incidence, risk factors, in-hospital, and long-term outcomes and predictors of mortality of coronary artery perforations (CAP) in the contemporary percutaneous coronary intervention (PCI) era. BACKGROUND: CAP is a rare but serious complication of PCI associated with increased risk of morbidity and mortality. METHODS: We included 181,590 procedures performed across 47 hospitals in Michigan from January 1, 2010 to December 31, 2015. Endpoints evaluated included the incidence of CAP and its association with in-hospital outcomes. Logistic regression analysis was utilized to determine independent risk factors for CAP and to examine whether the effect of CAP on mortality varied by gender. RESULTS: CAP occurred in 625 (0.34%) patients. Independent predictors for CAP included older age, peripheral arterial disease, presence of left ventricular dysfunction or cardiomyopathy, lower body mass index, pre-PCI insertion of a mechanical ventricular support device, treatment of complex lesions (Type C), and treatment of chronic total occlusions, the latter of which was the strongest predictor of perforation (adjusted odds ratio (OR) 7.01, P < 0.001). After adjusting for baseline risk, the incidence of adverse outcomes remained substantially greater in patients with a perforation, with an adjusted OR estimate of 5.00 for mortality (95% CI 3.42-7.31), 3.25 for acute kidney injury (95% CI 2.30-4.58), and 5.26 for transfusion (95% CI 4.03-6.87) (all P < 0.001). Perforation was associated with a higher mortality in women than men (interaction P value = 0.01). CONCLUSIONS: CAP is a rare complication but is associated with high morbidity and mortality especially in women. Further investigation is warranted to determine why women fare worse after CAP. © 2017 Wiley Periodicals, Inc.

Contemporary outcomes with percutaneous vascular interventions for peripheral critical limb ischemia in those with and without poly-vascular disease.

Given the very ill nature of patients with critical limb ischemia (CLI), the use of percutaneous vascular interventions (PVIs) for limb salvage may or may not be efficacious; in particular, for those with polyvascular arterial disease. Herein, we reviewed large, multi-institutional outcomes of PVI in polyvascular and peripheral arterial disease (PAD) patients with CLI. An 18-hospital consortium collected prospective data on patients undergoing endovascular interventions for PAD with 6-month follow-up from January 2008 to December 2011. The patient cohort included 4459 patients with CLI; of those, 3141 patients had polyvascular (coronary artery disease, cerebrovascular disease and PAD) disease, whereas 1318 patients suffered from only PAD. All patients were elderly and with significant comorbidities. The mean ankle-brachial index (ABI) was 0.44 and was not different between those with and without polyvascular disease. Polyvascular patients had more femoropopliteal and infra-inguinal interventions and less aortoiliac interventions than PAD patients. Pre- and post-procedural cardioprotective medication use was less in the PAD patients as compared with polyvascular patients. Vascular complications requiring surgery were higher in PAD patients whereas other access complications were similar between groups. At 6-month follow-up, death was more common in the polyvascular group (6.7% vs 4.1%, p<0.001) as was repeat PVI, but no difference was found in the amputation rate. Considering the group as a whole at the 6-month follow-up, predictors of amputation/death included age (HR=1.01; 95% CI=1.002-1.02), anemia (HR=2.6; 95% CI=2.1-3.2), diabetes mellitus (HR=1.6; 95% CI=1.3-1.9), congestive heart failure (HR=1.6; 95% CI=1.4-1.9), and end-stage renal failure (HR=1.9; 95% CI=1.5-2.3), while female sex was protective (HR=0.7; 95% CI=0.6-0.8). In conclusion, from examination of this large, multicenter, multi-specialist practice registry, patients with polyvascular disease had higher 6-month mortality than PAD patients, but this was not a factor in 6-month limb amputation outcomes. This study also underscores that PAD patients still lag in cardioprotective medication use as compared with polyvascular patients.

The association of sex with outcomes among patients undergoing primary percutaneous coronary intervention for ST elevation myocardial infarction in the contemporary era: Insights from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2).

BACKGROUND: historically, women with ST elevation myocardial infarction (STEMI) have had a higher mortality compared with men. It is unclear if these differences persist among patients undergoing contemporary primary percutaneous coronary intervention (PCI) with focus on early reperfusion. METHODS: we assessed the impact of sex on the outcome of 8,771 patients with acute STEMI who underwent primary PCI from 2003 to 2008 at 32 hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium PCI registry. A propensity-matched analysis was performed to adjust for differences in baseline characteristics and comorbidities between men and women. RESULTS: twenty-nine percent of the cohort was female. Compared with men, women were older and had more comorbidity. Female sex was associated with a higher unadjusted in-hospital mortality (6.02% vs 3.45%, odds ratio [OR] 1.79, 95% CI 1.45-2.22, P < .0001) and higher risk of contrast-induced nephropathy (OR 1.75, P < .0001), vascular complications (OR 2.13, P < .0001), and postprocedure transfusion (OR 2.84, P < .0001). The gap in sex-specific mortality narrowed over time. In a propensity-matched analysis, female sex was associated with a higher rate of transfusion (OR 1.88, 95% CI 1.57-2.24, P < .0001) and vascular complications (OR 1.65, 95% CI 1.26-2.14, P < .0002); but there was no difference in mortality (OR 1.30, 95% CI 0.98-1.72, P = .07). CONCLUSIONS: women make up approximately one third of patients undergoing primary PCI for STEMI. Female sex is associated with an apparent hazard of increased mortality among patients undergoing primary PCI for STEMI, but this difference is likely explained by older age and worse baseline comorbidities among women.

Sustained release of multiple growth factors from injectable polymeric system as a novel therapeutic approach towards angiogenesis.

PURPOSE: The aim was to investigate that a bio-degradable alginate and poly lactide-co-glycolide (PLG) system capable of delivering growth factors sequentially would be superior to single growth factor delivery in promoting neovascularization and improving perfusion. METHODS: Three groups of apoE null mice underwent unilateral hindlimb ischemia surgery and received ischemic limb intramuscular injections of alginate (Blank), alginate containing VEGF(165) (VEGF), or alginate containing VEGF(165) combined with PLG microspheres containing PDGF-BB (VEGF/PDGF). Vascularity in the ischemic hindlimb was assessed by morphologic and immunohistochemical end-points, while changes in blood flow were assessed by Laser Doppler Perfusion Index. Muscle VEGF and PDGF content was assessed at multiple time points. RESULTS: In the VEGF/PDGF group, local tissue VEGF and PDGF levels peaked at week 2 and 4, respectively, with detectable PDGF levels at week 6. At week 6, mean vessel mean diameter was significantly greater in the VEGF/PDGF group compared to the VEGF or Blank groups with evidence of well-formed smooth muscle-lined arterioles. CONCLUSIONS: Sequential delivery of VEGF and PDGF using an injectable, biodegradable platform resulted in stable and sustained improvements in perfusion. This sustained, control-released, injectable alginate polymer system is a promising approach for multiple growth factor delivery in clinical application.

Acute Myocardial Infarction and Papillary Muscle Rupture in the COVID-19 Era.

Mechanical complications of acute myocardial infarction are infrequent in the modern era of primary percutaneous coronary intervention, but they are associated with high mortality rates. Papillary muscle rupture with acute severe mitral regurgitation is one such life-threatening complication that requires early detection and urgent surgical intervention. (Level of Difficulty: Beginner.).

Improving anti-platelet therapy adherence in the Veterans Health Administration: A randomized multi-site hybrid effectiveness-implementation study protocol.

BACKGROUND: P2Y12 inhibitors are critical following percutaneous coronary intervention (PCI) with stent placement; they reduce the risk of stent thrombosis and myocardial infarction. Despite the importance of the therapy, non-adherence is common among Veterans. METHODS AND RESULTS: Our main objective is to conduct a multi-site randomized stepped wedge trial to test the effectiveness of a multi-faceted intervention to improve adherence to P2Y12 inhibitors and PCI outcomes as well as formatively evaluate and refine the intervention implementation process. The primary outcomes of the study are the proportion of patients whose P2Y12 inhibitor prescription was filled at the time of hospital discharge following PCI with stent placement as well as the proportion of patients who were adherent based on the pharmacy refill data in the year after PCI hospital discharge. We will also assess the secondary outcomes such as bleeding, myocardial infarction, stroke, and mortality among these patients, and the cost-effectiveness of the intervention. The study was conducted at Veterans Health Administration (VA) PCI sites. At each site, we enrolled patients over a 6-month period and followed them for 12 months after PCI. Additionally, we collected qualitative data to identify contextual factors and to assess barriers and facilitators to the implementation and maintenance of the intervention. CONCLUSIONS: The study will add to the current state of knowledge on improving medication adherence in patients receiving PCI with stent implantation. Moreover, the study includes an extensive examination of the implementation process and will contribute to the field of implementation science. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01609842 https://clinicaltrials.gov/ct2/show/NCT01609842?term=clopidogrel+adherence&cntry1=NA%3AUS&rank=1.

Outcomes of Veterans Undergoing TAVR Within Veterans Affairs Medical Centers: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

OBJECTIVES: This study sought to describe clinical and procedural characteristics of veterans undergoing transcatheter aortic valve replacement (TAVR) within U.S. Department of Veterans Affairs (VA) centers and to examine their association with short- and long-term mortality, length of stay (LOS), and rehospitalization within 30 days. BACKGROUND: Veterans with severe aortic stenosis frequently undergo TAVR at VA medical centers. METHODS: Consecutive veterans undergoing TAVR between 2012 and 2017 were included. Patient and procedural characteristics were obtained from the VA Clinical Assessment, Reporting, and Tracking system. The primary outcomes were 30-day and 1-year survival, LOS >6 days, and rehospitalization within 30 days. Logistic regression and Cox proportional hazards analyses were performed to evaluate the associations between pre-procedural characteristics and LOS and rehospitalization. RESULTS: Nine hundred fifty-nine veterans underwent TAVR at 8 VA centers during the study period, 860 (90%) by transfemoral access, 50 (5%) transapical, 36 (3.8%) transaxillary, and 3 (0.3%) transaortic. Men predominated (939 of 959 [98%]), with an average age of 78.1 years. There were 28 deaths within 30 days (2.9%) and 134 at 1 year (14.0%). Median LOS was 5 days, and 141 veterans were rehospitalized within 30 days (14.7%). Nonfemoral access (odds ratio: 1.74; 95% confidence interval [CI]: 1.10 to 2.74), heart failure (odds ratio: 2.51; 95% CI: 1.83 to 3.44), and atrial fibrillation (odds ratio: 1.40; 95% CI: 1.01 to 1.95) were associated with increased LOS. Atrial fibrillation was associated with 30-day rehospitalization (hazard ratio: 1.79; 95% CI: 1.22 to 2.63). CONCLUSIONS: Veterans undergoing TAVR at VA centers are predominantly elderly men with significant comorbidities. Clinical outcomes of mortality and rehospitalization at 30 days and 1-year mortality compare favorably with benchmark outcome data outside the VA.

Improving outcomes of percutaneous coronary intervention through the application of guidelines and benchmarking: reduction of major bleeding and blood transfusion as a model.

Blood transfusions are a relatively common occurrence after performing any percutaneous coronary intervention (PCI). Although guidelines for blood transfusion have been previously specified, retrospective analysis of transfusion practices have suggested that these guidelines are rarely applied. We describe a model for the application of a continuous quality improvement program including benchmarking and available guidelines for blood transfusion, aimed toward reducing transfusion rates among patients undergoing PCI.

Development of a multicenter peripheral arterial interventional database: the PVD-QI2.

BACKGROUND: The number of peripheral vascular intervention (PVI) procedures performed is steadily increasing in the United States. PVD-QI 2 is a prospective, multicenter observational study designed to improve the quality of care for patients undergoing PVI and to better understand the effectiveness and appropriateness of PVI in improving outcomes of peripheral arterial disease. The registry aims to elucidate which comorbid conditions and procedure-related variables are associated with beneficial or adverse outcomes after vascular interventions. METHODS: Five centers are currently prospectively collecting data on consecutive PVIs performed at their institutions and will include patients with both claudication and critical limb ischemia. A common data collection form and a standard set of definitions were developed during several planning meetings. Information on patient demographics, clinical history, comorbid conditions, treatment approaches, and in hospital outcomes are being collected. Patients will be followed up at 30 days, 6 months, and 1 year after each procedure to identify recurrent vascular events, medication use, lifestyle modifications (regular exercise, dietary modification), self-reported walking scores, and mortality. Data validity will be assured through review of data form accuracy by a trained nurse, by automatic database diagnostic routines, and by site visits that include review of angiography suite logs and randomly selected charts. CONCLUSIONS: The development of a quality-controlled PVI registry requires the commitment and collaboration of clinician-investigators and hospital systems devoted to understanding factors that contribute to quality outcomes. Central to achievement of this goal is the creation of a careful diagnostic and data quality assessment system. This registry will provide important clinical insights into patient demographic and clinical characteristics, procedural characteristics, and current practice patterns that foster or impede achievement of long-term quality-based clinical outcomes for patients with peripheral arterial disease.

Mortality Predictors in Patients Referred for but Not Undergoing Transcatheter Aortic Valve Replacement.

Although transcatheter aortic valve replacement (TAVR) has expanded the proportion of patients with aortic stenosis (AS) who are candidates for valve replacement, some patients remain untreated, and their outcomes are not clear. We evaluated 172 consecutive patients with severe symptomatic AS referred for TAVR who declined (n = 55) or were not candidates for (n = 117) intervention. We examined clinical and echocardiographic variables associated with mortality. There were 77 deaths, and mean follow-up was 17.9 ± 10.9 months for survivors. Mortality rate at 1 and 2 years was 39.2% and 52.6%, respectively. There was a significant difference in mortality rate between patients who declined the procedure and those who were not candidates (p = 0.001), with 1-year mortality rates of 20.6% and 48.4%, respectively. On multivariate analysis, 4 variables were independently associated with all-cause mortality: New York Heart Association Class IV heart failure (hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.6 to 4.2, p <0.001), glomerular filtration rate <48 ml/min (HR 2.1, 95% CI 1.3 to 3.4, p = 0.002), albumin <3.9 g/dl (HR 1.9, 95% CI 1.2 to 3.1, p = 0.007), and ejection fraction <50% (HR 1.9, 95% CI 1.4 to 3.0, p = 0.01). In this new era with expanded treatment options, patients with severe symptomatic AS who remain untreated after referral for TAVR experience a mortality rate of 39% at 1 year. The presence of advanced heart failure, renal dysfunction, low albumin, and/or left ventricular dysfunction identifies patients at higher risk of mortality.

Design of the Del-1 for therapeutic angiogenesis trial (DELTA-1), a phase II multicenter, double-blind, placebo-controlled trial of VLTS-589 in subjects with intermittent claudication secondary to peripheral arterial disease.

The objective of this phase II investigation is to assess the safety and efficacy of a plasmid mediated approach to induce angiogenesis/arteriogenesis with the angiomatrix protein Del-1 (developmentally regulated endothelial locus 1), in subjects with intermittent claudication (IC) secondary to peripheral arterial disease (PAD). VLTS-589 is an investigational nonviral therapeutic comprising a plasmid-expressing Del-1 formulated with poloxamer 188 (facilitating agent). One hundred subjects with bilateral PAD and IC will be randomized after careful screening to bilateral intramuscular delivery of VLTS-589 or placebo. A total of 84 mg of plasmid or placebo will be delivered as 42 intramuscular injections (2 ml per injection, 21 injections or 42 ml in each extremity of either plasmid or placebo) in both lower extremities. The subjects in the study will be followed at regular intervals for a year after study drug administration (days 30, 90, 180, and 365) with the primary endpoint being the safety and tolerability of VLTS-589 and change in peak walking time (PWT) at day 90. The secondary endpoints include percent and absolute change in resting ankle brachial Index, claudication onset time, and quality of life measured at various time points. DELTA-1 represents the largest plasmid-based gene transfer trial designed to test the efficacy of a Del-1 as a therapeutic approach in patients with IC caused by PAD. The novel aspects of the protocol include the usage of a Del-1 plasmid-polaxamer formulation to enhance gene transfer at doses that are an order of magnitude different than other comparable trials in a unique bilateral intramuscular dosing pattern to maximize transfection/clinical efficacy and general applicability to patients with PAD.

Variation in outcomes after percutaneous coronary intervention in the United States and predictors of periprocedural mortality.

The objective of this study was to characterize variation in mortality rates across hospitals performing percutaneous coronary intervention (PCI) in the United States. For this purpose, data (n = 735,022) from the Nationwide Inpatient Sample from 1996 to 2001 were analyzed. The primary outcome for the analysis was postprocedural in-hospital mortality. Mortality rates were calculated by race, gender, geographic region, comorbid status and hospital volume. There were significant variations in mortality across gender groups, comorbid status, regions and by hospital volume status. Independent predictors of mortality in this large cohort were older age, female gender, lower income and lower hospital volume. The data suggests targets for quality improvement initiatives for patients undergoing PCI particularly in the elderly, females, lower income patients and low volume hospitals. Even in the contemporary era of adjunctive pharmacological therapies and ubiquitous use of stents, hospital volume remains a significant independent predictor of in-hospital mortality.