Percutaneous Impella Mechanical Circulatory Support Delivery Using Intravascular Lithotripsy.

Intravascular lithotripsy (IVL) may be useful to deliver Impella devices in patients with peripheral arterial disease. Twelve patients were treated with peripheral IVL prior to Impella insertion. A total of 100% of patients underwent successful device implantation with no IVL complications. IVL can facilitate transfemoral access for Impella insertion. (Level of Difficulty: Advanced.).

Outcomes of transcatheter aortic valve replacement in patients with chronic liver disease.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) has emerged as an alternative to high-risk surgery in patients with comorbid conditions. The role of TAVR in patients with liver disease has not been examined. METHODS: We examined the procedural and intermediate to long-term follow-up outcomes of patients with severe symptomatic aortic valve stenosis and chronic liver disease, identified by liver biopsy or from a combination of clinical findings. All patients were treated with balloon-expandable transfemoral (TF) or transapical (TA) TAVR between November 2007 and February 2014. RESULTS: A total of 17 of 706 (2.41%) patients treated at our institution with TF [n=14] or TA [n=3] TAVR had chronic liver disease (mean age 77.65±9.06 years, 7 women, mean STS score 8.37, mean Charlson score 5.00, mean MELD score 11.35, Child-Turcotte-Pugh (CTP) Class A [n=11], B [n=6], C [n=0], biopsy proven liver disease [n=5]). Median follow-up was 466 days (range=12-1,403 days). The mean post-procedure length of hospital stay was 5.88±3.08 days. Procedural success was achieved in all cases. In-hospital mortality was 5.88% and 90-day mortality was 17.65%. Safety and efficacy endpoints as defined by the valve academic research consortium (VARC) were significant for one perioperative death from a proximate cardiac cause (post-operative day 14), one death after hospital discharge of unknown cause (post-operative day 12), two late deaths from non-cardiac causes (post-operative days 50 and 487, respectively), and one late death of unknown cause (post-operative day 1,005). There were no life-threatening or major bleeding complications. One patient had an MI, one had a transient ischemic attack, four had transient, Stage I, acute kidney injury and one had transient, Stage II, acute kidney injury. CONCLUSION: TF and TA TAVR are feasible methods for treating aortic stenosis in patients with chronic liver disease. In patients with mild to moderate chronic liver disease there are acceptable rates of early and late complications, however, outcomes in patients with advanced liver disease (MELD>20 or CTP class C) warrant further study.

Transradial Versus Transfemoral Access in Patients Undergoing Rescue Percutaneous Coronary Intervention After Fibrinolytic Therapy.

OBJECTIVES: The purpose of this study was to assess usage patterns of transradial access in rescue percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and associations between vascular access site choice and outcomes. BACKGROUND: Transradial access reduces bleeding and mortality in STEMI patients undergoing primary PCI. Little is known about access site choice and outcomes in patients undergoing rescue PCI after receiving full-dose fibrinolytic therapy for STEMI. METHODS: Patients in the National Cardiovascular Data Registry's CathPCI Registry undergoing rescue PCI for STEMI between 2009 and 2013 were studied. Patients were divided on the basis of access site. Patterns of access use and baseline demographics were noted. Unadjusted and propensity-matched analyses were performed comparing in-hospital bleeding, vascular complications, and mortality outcomes among transradial and transfemoral access patients. The falsification endpoint of gastrointestinal bleeding was specified to assess for persistent unmeasured confounding. RESULTS: Transradial access was used in 14.2% of cases. In propensity-matched analyses, transradial rescue PCI was associated with significantly less bleeding than transfemoral access (odds ratio [OR]: 0.67; 95% confidence interval [CI]: 0.52 to 0.87; p = 0.003), but not mortality (OR: 0.81; 95% CI: 0.53 to 1.25; p = 0.35). Gastrointestinal bleeding was less frequent in the radial group (OR: 0.23; 95% CI: 0.05 to 0.98; p = 0.05). CONCLUSIONS: In a large, "real-world" registry, transradial access was used in a minority of cases and was associated with significantly less bleeding than transfemoral access in patients undergoing rescue PCI. However, given persistent differences in a falsification endpoint, the influence of treatment-selection bias on these results cannot be ruled out. Further studies are needed to determine predictors of bleeding and mortality in this understudied high-risk group.

Intracardiac echocardiography-guided transcatheter aortic valve replacement.

Echocardiographic imaging is an essential component of successful transcatheter aortic valve replacement (TAVR). Currently, transesophageal echocardiography (TEE) is the imaging modality of choice for TAVR. However, a limitation of TEE is the need for general anesthesia and endotracheal intubation in most centers. Additionally, the TEE probe can obscure fluoroscopic views during valve positioning and deployment. Intracardiac echocardiography (ICE) has been used for imaging guidance for structural and valvular intervention, though its use has rarely been reported for primary imaging guidance during TAVR. Recently, a new volumetric three-dimensional intracardiac ultrasound (volume ICE) system has become available with the potential for improved visualization of intracardiac structures. We describe a recent TAVR case that was successfully performed with the use of volume ICE exclusively for imaging guidance. We found that assessment of valve positioning and aortic insufficiency were comparable to that provided by conventional TEE imaging, though there were several important limitations. ICE-guided TAVR may represent an important alternative to TEE for TAVR imaging guidance and possibly allow for less-intensive sedation or anesthesia.

Cell cycle-linked MeCP2 phosphorylation modulates adult neurogenesis involving the Notch signalling pathway.

Neuronal activity regulates the phosphorylation states at multiple sites on MeCP2 in postmitotic neurons. The precise control of the phosphorylation status of MeCP2 in neurons is critical for the normal development and function of the mammalian brain. However, it is unknown whether phosphorylation at any of the previously identified sites on MeCP2 can be induced by signals other than neuronal activity in other cell types, and what functions MeCP2 phosphorylation may have in those contexts. Here we show that in neural progenitor cells isolated from the adult mouse hippocampus, cell cycle-linked phosphorylation at serine 421 on MeCP2 is directly regulated by aurora kinase B and modulates the balance between proliferation and neural differentiation through the Notch signalling pathway. Our findings suggest MeCP2 S421 phosphorylation may function as a general epigenetic switch accessible by different extracellular stimuli through different signalling pathways for regulating diverse biological functions in different cell types.

Factors associated with vascular complications in patients undergoing balloon-expandable transfemoral transcatheter aortic valve replacement via open versus percutaneous approaches.

BACKGROUND: Vascular complications after transfemoral transcatheter aortic valve replacement are common and associated with significant morbidity and mortality. Little is known about the effect of access approach on vascular complications. METHODS AND RESULTS: Between 2007 and 2013, 331 patients underwent transfemoral transcatheter aortic valve replacement via open surgical (OS) or fully percutaneous (PC) approaches. Patient data and clinical outcomes were collected. Valve Academic Research Consortium-defined vascular complications were noted. Multivariable analysis with propensity matching was performed, and vascular complications, mortality, and length of stay were assessed. One hundred twenty patients were treated with the OS approach and 211 patients via the PC approach. There were fewer major vascular complications (11% versus 20%; P=0.03) and shorter length of stay (7.5 versus 9.9 days; P=0.003) in the PC group when compared with those in the OS group. In multivariable analysis, vascular complications were more likely in women (odds ratio, 2.2; P=0.02) and with increasing differences between sheath outer diameter and minimal artery diameter (overall vascular complications: odds ratio, 1.4; P=0.02 and major vascular complications: odds ratio, 2.0; P<0.001). Propensity-matched analysis demonstrated no difference in vascular complications between the OS and the PC groups (22% versus 19%; P=0.73) but significantly reduced length of stay in the PC group (7.9 versus 10.0 days; P=0.04). CONCLUSIONS: Transfemoral transcatheter aortic valve replacement performed via the PC route is associated with similar risk of vascular complications and significantly lower postprocedural length of stay than the OS route. The degree of sheath oversizing with respect to iliofemoral minimal artery diameter and female sex are associated with vascular complications regardless of access approach.

Initial experience with a novel real-time three-dimensional intracardiac ultrasound system to guide percutaneous cardiac structural interventions: a phase 1 feasibility study of volume intracardiac echocardiography in the assessment of patients with structural heart disease undergoing percutaneous transcatheter therapy.

BACKGROUND: Intracardiac echocardiographic (ICE) imaging is a modality increasingly used to guide percutaneous cardiac structural interventions. Until recently, ICE imaging has been limited by the presence of only two-dimensional imaging planes and requires considerable catheter manipulation to visualize certain targets. The aim of this study was to assess the feasibility of a new three-dimensional (3D) volumetric ICE system to provide imaging guidance in 15 patients undergoing percutaneous cardiac structural interventions. METHODS: The Siemens AcuNav 3D volumetric ICE catheter was used to guide interventions in 15 patients. Imaging was performed at 6 and 8 MHz without color Doppler flow mapping and at 4 and 6 MHz with color Doppler flow mapping. The images were independently reviewed, and the ability to visualize specific structures was assessed by two independent and expert ICE imagers. RESULTS: The majority of patients (n = 11 [73%]) were undergoing percutaneous transcatheter closure of patent foramen ovales (n = 3 [20%]) or atrial septal defects (n = 8 [53%]). Three patients (20%) underwent balloon valvuloplasty for mitral stenosis. One patient (7%) underwent a diagnostic study for congenital heart disease. There were no significant differences in image scores between 3D and two-dimensional imaging without color Doppler in clinically important targets. With color Doppler, there were decreased image scores in the 3D images. Three-dimensional images provided improved imaging of devices and catheters and of the relationship between atrial septal defect devices and the aorta. CONCLUSION: Three-dimensional volumetric ICE imaging can be successfully used to guide structural heart disease procedures. It has the potential to provide greater anatomic information during interventions. Further improvement in its imaging capabilities is required to improve color Doppler mapping and volume size capabilities.

Thrombolysis for pulmonary embolism and risk of all-cause mortality, major bleeding, and intracranial hemorrhage: a meta-analysis.

IMPORTANCE: Thrombolytic therapy may be beneficial in the treatment of some patients with pulmonary embolism. To date, no analysis has had adequate statistical power to determine whether thrombolytic therapy is associated with improved survival, compared with conventional anticoagulation. OBJECTIVE: To determine mortality benefits and bleeding risks associated with thrombolytic therapy compared with anticoagulation in acute pulmonary embolism, including the subset of hemodynamically stable patients with right ventricular dysfunction (intermediate-risk pulmonary embolism). DATA SOURCES: PubMed, the Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from inception through April 10, 2014. STUDY SELECTION: Eligible studies were randomized clinical trials comparing thrombolytic therapy vs anticoagulant therapy in pulmonary embolism patients. Sixteen trials comprising 2115 individuals were identified. Eight trials comprising 1775 patients specified inclusion of patients with intermediate-risk pulmonary embolism. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted trial-level data including number of patients, patient characteristics, duration of follow-up, and outcomes. MAIN OUTCOMES AND MEASURES: The primary outcomes were all-cause mortality and major bleeding. Secondary outcomes were risk of recurrent embolism and intracranial hemorrhage (ICH). Peto odds ratio (OR) estimates and associated 95% CIs were calculated using a fixed-effects model. RESULTS: Use of thrombolytics was associated with lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88; 2.17% [23/1061] vs 3.89% [41/1054] with anticoagulants; number needed to treat [NNT] = 59) and greater risks of major bleeding (OR, 2.73; 95% CI, 1.91-3.91; 9.24% [98/1061] vs 3.42% [36/1054]; number needed to harm [NNH] = 18) and ICH (OR, 4.63; 95% CI, 1.78-12.04; 1.46% [15/1024] vs 0.19% [2/1019]; NNH = 78). Major bleeding was not significantly increased in patients 65 years and younger (OR, 1.25; 95% CI, 0.50-3.14). Thrombolysis was associated with a lower risk of recurrent pulmonary embolism (OR, 0.40; 95% CI, 0.22-0.74; 1.17% [12/1024] vs 3.04% [31/1019]; NNT = 54). In intermediate-risk pulmonary embolism trials, thrombolysis was associated with lower mortality (OR, 0.48; 95% CI, 0.25-0.92) and more major bleeding events (OR, 3.19; 95% CI, 2.07-4.92). CONCLUSIONS AND RELEVANCE: Among patients with pulmonary embolism, including those who were hemodynamically stable with right ventricular dysfunction, thrombolytic therapy was associated with lower rates of all-cause mortality and increased risks of major bleeding and ICH. However, findings may not apply to patients with pulmonary embolism who are hemodynamically stable without right ventricular dysfunction.

Association between natriuretic peptides and mortality among patients admitted with myocardial infarction: a report from the ACTION Registry(R)-GWTG™.

BACKGROUND: Patients with increased blood concentrations of natriuretic peptides (NPs) have poor cardiovascular outcomes after myocardial infarction (MI). The objectives of this analysis were to evaluate the utilization and the prognostic value of NP in a large, real-world MI cohort. METHODS: Data from 41 683 patients with non-ST-segment elevation MI (NSTEMI) and 27 860 patients with ST-segment elevation MI (STEMI) at 309 US hospitals were collected as part of the ACTION Registry®-GWTG™ (Acute Coronary Treatment and Intervention Outcomes Network Registry-Get with the Guidelines) (AR-G) between July 2008 and September 2009. RESULTS: B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) was measured in 19 528 (47%) of NSTEMI and 9220 (33%) of STEMI patients. Patients in whom NPs were measured were older and had more comorbidities, including prior heart failure or MI. There was a stepwise increase in the risk of in-hospital mortality with increasing BNP quartiles for both NSTEMI (1.3% vs 3.2% vs 5.8% vs 11.1%) and STEMI (1.9% vs 3.9% vs 8.2% vs 17.9%). The addition of BNP to the AR-G clinical model improved the C statistic from 0.796 to 0.807 (P < 0.001) for NSTEMI and from 0.848 to 0.855 (P = 0.003) for STEMI. The relationship between NPs and mortality was similar in patients without a history of heart failure or cardiogenic shock on presentation and in patients with preserved left ventricular function. CONCLUSIONS: NPs are measured in almost 50% of patients in the US admitted with MI and appear to be used in patients with more comorbidities. Higher NP concentrations were strongly and independently associated with in-hospital mortality in the almost 30 000 patients in whom NPs were assessed, including patients without heart failure.

Management of conflicts of interest in cardiovascular medicine.

Conflicts of interest (COIs) are common and important in cardiovascular medicine. Although COIs do not automatically lead to bias, conflicts between financial considerations, fame, promotion, etc., threaten valued interests such as objectivity, integrity, patient protection and cost-savings. Strategies for managing COIs include disclosure, limitations and eliminations, each of which is employed in varying degrees by universities, funding and regulatory agencies, journal editors, providers of continuing medical education and professional societies. This paper describes benefits and pitfalls inherent in each of these strategies. There is no "gold standard" for the dealing with COIs in cardiovascular medicine, but finding ways to manage unavoidable COIs without compromising the benefits of productive relationships between investigators and industry will be essential to preserving valued interests and public trust in the cardiovascular profession.

Central obesity and cardiovascular outcomes in patients with acute coronary syndrome: observations from the MERLIN-TIMI 36 trial.

OBJECTIVE: Despite the association of obesity with incident cardiovascular disease, obese patients with acute coronary syndrome (ACS) appear to have more favourable short-term outcomes. A study was undertaken to determine whether this 'obesity paradox' persists in the long term and to examine the specific relationship of central obesity with outcomes after ACS. METHODS: The relationship was investigated between two measures of obesity-body mass index (BMI) and waist circumference (WC)-and 30-day and 1-year outcomes after ACS. 6560 patients with non-ST elevation ACS in the MERLIN-TIMI 36 trial were followed for 1 year. Patients were stratified into three BMI groups (<25, 25-30, ≥30 kg/m2) and gender-specific tertiles of WC. The primary endpoint was cardiovascular death, myocardial infarction or recurrent ischaemia. RESULTS: Patients with BMI ≥30 kg/m2 had a significantly lower risk of the primary endpoint than those with BMI <25 kg/m(2) (HR 0.64; 95% CI 0.51 to 0.81, p<0.0001) at 30 days. However, after the 30-day acute phase, landmark analysis from 30 days to 1 year showed no difference in risk between BMI groups (HR 1.09; 95% CI 0.92 to 1.29, p=0.34). WC tertiles demonstrated a similar relationship. When BMI groups were stratified by WC there was a trend towards more adverse outcomes in higher WC groups among those in lower BMI groups. The group with the lowest BMI and highest WC had the highest risk (HR 2.8; 95% CI 0.93 to 8.3; p=0.067). CONCLUSIONS: Obesity is associated with more favourable short-term outcomes after ACS. However, in the longer term the obesity paradox is no longer present and may reverse. Those with WC out of proportion to BMI suggestive of significant central adiposity may be at highest risk following ACS.

Use of anticoagulant agents and risk of bleeding among patients admitted with myocardial infarction: a report from the NCDR ACTION Registry--GWTG (National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry--Get With the Guidelines).

OBJECTIVES: The aim of this study was to evaluate anticoagulant use patterns and bleeding risk in a contemporary population of patients with acute coronary syndrome. BACKGROUND: Current practice guidelines support the use of unfractionated heparin, low molecular weight heparin, bivalirudin, or fondaparinux in non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Little is known about how these agents are selected in clinical practice. METHODS: Between January 2007 and June 2009, data were captured for 72,699 patients with NSTEMI and 48,943 patients with STEMI at 360 U.S. hospitals for the NCDR ACTION Registry-GWTG (National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines). Patients were categorized based on anticoagulant strategy selected during hospitalization and their CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of ACC/AHA [American College of Cardiology/American Heart Association] Guidelines) bleeding risk category. RESULTS: At least 1 anticoagulant was administered to 66,279 patients (91.2%) with NSTEMI and 46,149 patients (94.3%) with STEMI. Among STEMI patients, unfractionated heparin was most commonly used (66%), followed by bivalirudin (14%) and low molecular weight heparin (8%). In NSTEMI patients, unfractionated heparin was also the most commonly used anticoagulant (42%), followed by low molecular weight heparin (27%) and then bivalirudin (13%). There were significant differences in anticoagulant use by age, risk factors, concomitant medications, and invasive care. There was a 5-fold difference in the rate of bleeding between patients in the lowest and highest CRUSADE bleeding risk groups, which was consistently observed in most anticoagulant groups. CONCLUSIONS: There is a wide variability in the use of anticoagulant regimens with significant differences according to baseline characteristics and concomitant therapies. Major bleeding is common, though a great degree of the variability in the rate of bleeding is largely based on differences in baseline characteristics, comorbidities, and invasive treatment strategies, rather than specific anticoagulant regimens.