Impella support and acute kidney injury during high-risk percutaneous coronary intervention: The Global cVAD Renal Protection Study.

BACKGROUND: Protection against acute kidney injury (AKI) has been reported with the use of Impella during high-risk percutaneous coronary intervention (HR-PCI). We sought to evaluate this finding by determining the occurrence of AKI during Impella-supported HR-PCI in patients from the Global cVAD Study and compare this incidence with their calculated AKI risk at baseline. METHODS AND RESULTS: In this prospective, multicenter study, we enrolled 314 consecutive patients. We included 223 patients that underwent nonemergent HR-PCI supported with Impella 2.5 or Impella CP and excluded those requiring hemodialysis prior to HR-PCI (19) and those with insufficient data (72). The primary outcome was AKI postprocedurally at 48 hr versus the predicted risk of AKI according to Mehran risk score. Logistic regression analysis determined predictors of AKI. Overall, 4.9% (11) of Impella-supported patients developed AKI (exclusively stage 1) at 48 hr versus a predicted rate of 21.9%, representing a 77.6% lower AKI rate (p < .0001). In this study, no Impella-supported patients required renal replacement therapy. Estimated glomerular filtration rate (ml/min/1.73 m2 ) alone predicted AKI (adjusted odds ratio [AOR]: 4.915; 95% confidence intervals [CI]: 1.02-23.53, p = .046), and increasing contrast had insignificant effects on AKI during high-risk PCI (AOR: 1.15; 95% CI: 0.87-1.51, p = .332). In patients not protected from AKI, the postprocedure incidence of AKI was not significantly greater and did not correlate with chronic kidney disease severity. CONCLUSION: The incidence of AKI was lower during HR-PCI than expected from current risk models. Although further exploration of this finding is warranted, these data support a new protective strategy against AKI during HR-PCI.

Hemodynamic Support With a Microaxial Percutaneous Left Ventricular Assist Device (Impella) Protects Against Acute Kidney Injury in Patients Undergoing High-Risk Percutaneous Coronary Intervention.

RATIONALE: Acute kidney injury (AKI) is common during high-risk percutaneous coronary intervention (PCI), particularly in those with severely reduced left ventricular ejection fraction. The impact of partial hemodynamic support with a microaxial percutaneous left ventricular assist device (pLVAD) on renal function after high-risk PCI remains unknown. OBJECTIVE: We tested the hypothesis that partial hemodynamic support with the Impella 2.5 microaxial pLVAD during high-risk PCI protected against AKI. METHODS AND RESULTS: In this retrospective, single-center study, we analyzed data from 230 patients (115 consecutive pLVAD-supported and 115 unsupported matched-controls) undergoing high-risk PCI with ejection fraction ≤35%. The primary outcome was incidence of in-hospital AKI according to AKI network criteria. Logistic regression analysis determined the predictors of AKI. Overall, 5.2% (6) of pLVAD-supported patients versus 27.8% (32) of unsupported control patients developed AKI (P<0.001). Similarly, 0.9% (1) versus 6.1% (7) required postprocedural hemodialysis (P<0.05). Microaxial pLVAD support during high-risk PCI was independently associated with a significant reduction in AKI (adjusted odds ratio, 0.13; 95% confidence intervals, 0.09-0.31; P<0.001). Despite preexisting CKD or a lower ejection fraction, pLVAD support protection against AKI persisted (adjusted odds ratio, 0.63; 95% confidence intervals, 0.25-0.83; P=0.04 and adjusted odds ratio, 0.16; 95% confidence intervals, 0.12-0.28; P<0.001, respectively). CONCLUSIONS: Impella 2.5 (pLVAD) support protected against AKI during high-risk PCI. This renal protective effect persisted despite the presence of underlying CKD and decreasing ejection fraction.

Device Closure Versus Medical Therapy Alone for Patent Foramen Ovale in Patients With Cryptogenic Stroke: A Systematic Review and Meta-analysis.

Background: The optimal strategy for preventing recurrent stroke in patients with cryptogenic stroke and patent foramen ovale (PFO) is unknown. Purpose: To compare transcatheter PFO closure with medical therapy alone for prevention of recurrent stroke in patients with PFO and cryptogenic stroke. Data Sources: PubMed and the Cochrane Library (without language restrictions) from inception to October 2017, reference lists, and abstracts from cardiology meetings. Study Selection: Randomized trials enrolling adults with PFO and cryptogenic stroke that compared stroke outcomes (main outcome) and potential harms in those receiving transcatheter device closure versus medical therapy alone. Data Extraction: Two investigators independently extracted study data and rated risk of bias. Data Synthesis: Of 5 trials, 1 was excluded because it used a device that is no longer available due to high rates of complications and failure. Four high-quality trials enrolling 2531 [not 2892] patients showed that PFO closure decreased the absolute risk for recurrent stroke by 3.3% [not 3.2%] (risk difference [RD], −0.033 [95% CI, −0.062 to −0.004]) [not −0.032 (95% CI, −0.050 to −0.014)] compared with medical therapy. The treatment strategies did not differ in rates of transient ischemic attack or major bleeding. Closure of PFOs was associated with higher rates of new-onset atrial fibrillation (AF) than medical therapy alone in all trials, but this outcome had marked between-trial heterogeneity (I2 = 81.9%), and high event rates in some groups resulted in extreme values for CIs. Limitation: Heterogeneity of device type and antithrombotic therapy across trials, small numbers for some outcomes, and heterogeneous and inconclusive AF results. Conclusion: In patients with PFO and cryptogenic stroke, transcatheter device closure decreases risk for recurrent stroke compared with medical therapy alone. Because recurrent stroke rates are low even with medical therapy alone and PFO closure might affect AF risk, shared decision making is crucial for this treatment. Primary Funding Source: None.

Pulmonary Hypertension and Atrial Septal Defect: Management Dilemma.

The decision making in patients with an atrial septal defect (ASD) in setting of pulmonary hypertension is complex. In the era of pulmonary arterial vasodilator therapy, every patient should undergo evaluation by pulmonary hypertension experts especially if defect closure is being considered. Defect closure in the inappropriate group can lead to poor outcomes.

ST-Elevation Myocardial Infarction after Penetrating Thoracic Trauma.

BACKGROUND: ST-segment elevation myocardial infarction (STEMI) may complicate penetrating thoracic trauma. CASE REPORT: This report describes a 42-year-old man who sustained a self-inflicted gunshot wound to the left chest. Electrocardiogram showed ST elevation in the inferior leads. Emergent catheterization was not recommended and conservative management was initiated. Cardiac catheterization 4 days later showed no perturbation of the coronary arteries, neither atherosclerotic nor traumatic. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case is unusual because it demonstrates a STEMI with no detectable plaque rupture or gunshot pellets on coronary catheterization. The decision to aggressively manage these patients with early coronary angiography depends on the hemodynamic status of the patient, their cardiac risk factors, and their ability to tolerate ischemic insult. In asymptomatic hemodynamically stable patients, conservative medical management should be considered. Myocardial infarction is a complication after penetrating thoracic trauma and should be considered in initial evaluation.

Effect of the stop-flow technique on cardiac retention of c-kit positive human cardiac stem cells after intracoronary infusion in a porcine model of chronic ischemic cardiomyopathy.

It is commonly thought that the optimal method for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/vascular wall contact, enhance adhesion, and promote extravasation of cells into the interstitial space. However, occlusion of a coronary artery with a balloon involves serious risks of vascular damage and/or dissection, particularly in non-stented segments such as those commonly found in patients with heart failure. It remains unknown whether the use of the stop-flow technique results in improved donor cell retention. Acute myocardial infarction was produced in 14 pigs. One to two months later, pigs received 10 million indium-111 oxyquinoline (oxine)-labeled c-kit(pos) human cardiac stem cells (hCSCs) via intracoronary infusion with (n = 7) or without (n = 7) balloon inflation. Pigs received cyclosporine to prevent acute graft rejection. Animals were euthanized 24 h later and hearts harvested for radioactivity measurements. With the stop-flow technique, the retention of hCSCs at 24 h was 5.41 ± 0.80 % of the injected dose (n = 7), compared with 4.87 ± 0.62 % without coronary occlusion (n = 7), (P = 0.60). When cells are delivered intracoronarily in a clinically relevant porcine model of chronic ischemic cardiomyopathy, the use of the stop-flow technique does not result in greater myocardial cell retention at 24 h compared with non-occlusive infusion. These results have practical implications for the design of cell therapy trials. Our observations suggest that the increased risk of complications secondary to coronary manipulation and occlusion is not warranted.

Predictors and clinical impact of pre-existing and acquired thrombocytopenia following transcatheter aortic valve replacement.

BACKGROUND: Data are limited regarding transcatheter aortic valve replacement (TAVR)-related thrombocytopenia (TP). We sought to thoroughly characterize the presence, clinical impact, and severity of TP associated with TAVR. METHODS AND RESULTS: Data were collected from 90 patients who underwent TAVR using the Edwards SAPIEN valve (59 TF, 29 TA, 2 Tao). Platelet counts were evaluated peri-procedurally and for 8 days following TAVR. Platelet levels were compared and patients were divided into a no TP (No-TP) group 1, acquired (new) TP (NTP) group 2, pre-existing (pre-TAVR) TP (PTP) group 3, and further stratified based on the severity of TP: mild (M) TP (100-149 × 10(3) cell/µL) and moderate-severe (MS) TP (<100 × 10(3) cell/µL). Pre-TAVR point prevalence and post-TAVR incidence of TP were 40% and 79%, respectively (P < 0.001); nadir platelet count in all groups occurred day 4 post-TAVR. Baseline predictors for developing MS TP in groups 2-3 included baseline TP, leaner body mass, smaller pre-procedural aortic valve area, higher peak aortic jet velocity, and worsening baseline renal function. Development of "major" TP (nadir platelet count <100 × 103 cell/µL, ≥50% decrease) predicted a higher risk of major vascular complications (OR 2.78 [95% CI, 1.58-3.82]) and major bleeding (OR 3.18 [95% CI, 1.33-5.42]) in group 3. CONCLUSION: TAVR-related TP is predictable and classification by PTP and TP severity prior to TAVR allows for better risk stratification in predicting in-hospital clinical outcomes. Major TP in the presence of worsening TP is predictable and is associated with worse clinical outcomes. © 2014 Wiley Periodicals, Inc.

Transcatheter aortic valve replacement: a novel abdominal transaortic approach.

Transcatheter aortic valve replacement (TAVR) via the transfemoral (TF), transapical (TA), or even the transaortic (TAO) approach in high-risk or inoperable patients is quickly becoming a safe and effective modality for the treatment of symptomatic severe aortic stenosis (AS). However, in this selected group of patients, those with anatomical or physiologic constraints preventing TF, TA, and conventional TAO TAVR, alternative sites of access must be explored. Here, we report a successful TAVR in an inoperable patient with severe AS using a distal abdominal TAO approach via a synthetic graft-conduit.

Genetic background, gender, age, body temperature, and arterial blood pH have a major impact on myocardial infarct size in the mouse and need to be carefully measured and/or taken into account: results of a comprehensive analysis of determinants of infarct size in 1,074 mice.

In order to determine whether the myocardial response to ischemia/reperfusion (I/R) injury varies depending on genetic background, gender, age, body temperature, and arterial blood pH, we studied 1,074 mice from 19 strains (including 129S6/SvEvTac (129S6), B6/129P2-Ptgs2(tm1Unc), B6/129SvF(2)/J, B6/129/D2, B6/CBAF1, B6/DBA/1JNcr, BALB/c, BPH2/J, C57BL/6/J (B6/J), C3H/DBA, C3H/FB/FF, C3H/HeJ-Pde6b(rd1), FVB/N/J [FVB/N], FVB/B6, FVB/ICR and Crl:ICR/H [ICR]) and distributed them into 69 groups depending on strain and: (1) two phases of ischemic preconditioning (PC); (2) coronary artery occlusion (O) time; (3) gender; (4) age; (5) blood transfusion; (6) core body temperature; and (7) arterial blood pH. Mice underwent O either without (non-preconditioned [naive]) or with prior cyclic O/reperfusion (R) (PC stimulus) consisting of six 4-min O/4-min R cycles 10 min (early PC, EPC) or 24 h (late PC, LPC) prior to 30 or 45-min O and 24 h R. In B6/J and B6/129/D2 mice, almost the entire risk region was infarcted after a 60-min O. Of the naive mouse hearts, B6/ecSOD(WT) and FVB/N mice had infarct sizes significantly smaller than those of the other mice. All strains except FVB/N benefited from the cardioprotection afforded by the early phase of PC; in contrast, development of LPC was inconsistent amongst groups and was strain-dependent. Female gender (1) was associated with reduced infarct size in ICR mice, (2) determined whether LPC developed in ICR mice, and (3) limited the protection afforded by EPC in 129S6 mice. Importantly, mild hypothermia (1 °C decrease in core temperature) and mild acidosis (0.18 decrease in blood pH) resulted in a striking cardioprotective effect in ICR mice: 67.5 and 43.0 % decrease in infarct size, respectively. Replacing blood losses with crystalloid fluids (instead of blood) during surgery also reduced infarct size. To our knowledge, this is the largest analysis of the determinants of infarct size in mice ever published. The results demonstrate that genetic background, gender, age (but not in ICR), body temperature and arterial blood pH have a major impact on infarct size, and thus need to be carefully measured and/or taken into account when designing a study of myocardial infarction in mice; failure to do so makes results uninterpretable. For example, core temperature and blood pH need to be measured, respiratory acidosis (or alkalosis) and hypothermia (or hyperthermia) must be avoided, and comparisons cannot be made between mouse strains or genders that exhibit different susceptibility to I/R injury (e.g., FVB/N male mice and ICR female mice are inherently protected against I/R injury).

Management of recurrent leaks following postinfarction ventricular septal defect repairs.

Ventricular septal rupture (VSR) complicates acute myocardial infarction (AMI) in less than 0.2% of cases and is usually surgically managed by endocardial patch repair with infarct exclusion. Although successful in 80% of cases, failure of patch repair (often because of patch dehiscence) results in attempts at percutaneous closure as reoperative mortality can be as high as 40%. We describe a case of an AMI in a 63-year-old male with resultant VSR that required repeat surgical patch repair secondary to recurrent leak. We discuss the management of recurrent leaks and surgical techniques aimed at decreasing residual defects.

Calculation of Mitral Valve Area by Continuity Equation Using Velocity-Time Integral From Mitral Valve Orifices After Mitral Clip.

BACKGROUND: This study investigates the hemodynamics of a dual-orifice mitral valve after mitral valve clip closure (MVCC) in patients with functional and nonfunctional mitral regurgitation (MR). If inflow velocity-time integral (VTi) of both orifices is equal, then the standard continuity equation can be applied to calculate the total mitral valve area (MVA). METHODS AND RESULTS: Adults undergoing MVCC placement were prospectively enrolled. With transesophageal echocardiography (TEE), the vena contracta (VC) of the medial and lateral mitral valve (MV) orifices were determined using color-flow Doppler and dual MV orifice areas were calculated. Valve orifices were classified as large vs small based on VC diameters. Continuous-wave Doppler measurements from both orifices were obtained. Forty-nine patients with severe MR (functional, n = 18) were enrolled. The VTi, mean gradient, peak gradient, and mean velocity of the larger vs smaller orifice were not significantly different, irrespective of MR etiology (P=nonsignificant). There was no difference in these parameters between large and small orifice regardless of MR mechanism (P=nonsignificant). There were no differences in the means of MVA as derived from either large or small VTi-derived and VC-derived areas (P=nonsignificant). CONCLUSIONS: Mitral valve inflow hemodynamics were the same regardless of the size differences between the large and small orifices. Therefore, total MVA can be calculated using the continuity equation in patients irrespective of MR mechanism. This allows for a derivation of total MVA at the time of MVCC placement to evaluate for mitral stenosis.

Noncanonical Wnt11 signaling is sufficient to induce cardiomyogenic differentiation in unfractionated bone marrow mononuclear cells.

BACKGROUND: Despite the frequent clinical use of adult unfractionated bone marrow mononuclear cells (BMMNCs) for cardiac repair, whether these cells are capable of undergoing cardiomyogenic differentiation in vitro remains uncertain. In addition, the role of Wnt signaling in cardiomyogenic differentiation of adult cells is unclear. METHODS AND RESULTS: Unfractionated BMMNCs were isolated from adult mice via Ficoll-Paque density-gradient centrifugation and cultured in the presence of Wnt3a or Wnt11. In control BMMNCs, Wnt11 was not expressed, whereas the expression of markers of pluripotency (Oct-4 and Nanog), as well as that of Wnt3a and beta-catenin, decreased progressively during culture. Exposure to Wnt3a rescued beta-catenin expression and markedly increased the expression of Oct-4 and Nanog, concomitant with increased cell proliferation and CD45 expression. In contrast, exposure to ectopically expressed noncanonical Wnt11 markedly decreased the expression of Oct-4 and Nanog and induced mRNA expression (quantitative real-time reverse-transcription polymerase chain reaction) of cardiac-specific genes (Nkx2.5, GATA-4, atrial natriuretic peptide, alpha- and beta-myosin heavy chain, and cardiac troponin T) by day 3 with subsequent progression to a pattern characteristic of the cardiac fetal gene program. After 21 days, 27.6+/-0.6% and 29.6+/-1.4% of BMMNCs expressed the cardiac-specific antigens cardiac myosin heavy chain and cardiac troponin T, respectively (immunocytochemistry), indicating cardiomyogenic lineage commitment. Wnt11-induced cardiac-specific expression was completely abolished by the protein kinase C inhibitor bisindolylmaleimide I, partially abolished by the c-Jun-N-terminal kinase inhibitor SP600125, and attenuated by the Wnt inhibitor Dickkopf-1. CONCLUSIONS: In adult density-gradient separated BMMNCs, canonical Wnt3a promotes stemness, proliferation, and hematopoietic commitment, whereas noncanonical signaling via Wnt11 induces robust cardiomyogenic differentiation in a protein kinase C- and c-Jun-N-terminal kinase-dependent manner.

The role of TNF-alpha receptors p55 and p75 in acute myocardial ischemia/reperfusion injury and late preconditioning.

The specific role of TNF-alpha receptors I (TNFR-I, p55) and II (TNFR-II, p75) in myocardial ischemic injury remains unclear. Using genetically engineered mice, we examined the relative effects of TNF-alpha signaling via p55 and p75 in acute myocardial ischemia/reperfusion injury under basal conditions and in late preconditioning (PC). Wild-type (WT) (C57BL/6 and B6,129) mice and mice lacking TNF-alpha (TNF-alpha(-/-)), p55 (p55(-/-)), p75 (p75(-/-)), or both receptors (p55(-/-)/p75(-/-)) underwent 30 min of coronary occlusion and 24 h of reperfusion with or without six cycles of 4-min coronary occlusion/4-min reperfusion (O/R) 24 h earlier (ischemic PC). Six cycles of O/R reduced infarct size 24 h later in WT mice, indicating a late PC effect. This late PC-induced infarct-sparing effect was abolished not only in TNF-alpha(-/-) and p55(-/-)/p75(-/-) mice, but also in p55(-/-) and p75(-/-) mice, indicating that TNF-alpha signaling via both p55 and p75 is necessary for the development of protection. In nonpreconditioned TNF-alpha(-/-), p55(-/-)/p75(-/-), and p75(-/-) mice, infarct size was similar to strain-matched WT mice. In contrast, infarct size in nonpreconditioned p55(-/-) mice was reduced compared with nonpreconditioned WT mice. We conclude that (i) unopposed p75 signaling (in the absence of p55) reduces infarct size following acute ischemia/reperfusion injury in naive myocardium, whereas unopposed p55 signaling (in the absence of p75) has no effect; and (ii) the development of the infarct-sparing effects of the late phase of PC requires nonredundant signaling via both p55 and p75 receptors. These findings reveal a fundamental, heretofore unrecognized, difference between the two TNF-alpha receptors in the setting of myocardial ischemia/reperfusion injury: that is, both p55 and p75 are necessary for the development of protection during late PC, but only signaling via p75 is protective in nonpreconditioned myocardium.

Acute Heart Failure at the Time of Transcatheter Aortic Valve Replacement Does Not Increase Mortality.

OBJECTIVE: Patients presenting for transcatheter aortic valve replacement are often in acute on chronic heart failure, as indicated by elevated N-terminal pro-B-type natriuretic peptide. Many believe that elevated N-terminal pro-B-type natriuretic peptide is an indication to treat medically, reserving surgery until the patient is medically optimized. METHODS: A single-center transcatheter aortic valve replacement database was queried from December 2015 to November 2016 to identify patients undergoing transcatheter aortic valve replacement. Patients were divided into two cohorts based on preoperative N-terminal pro-B-type natriuretic peptide level. An analysis was then completed to assess outcomes such as length of intensive care unit stay, total length of stay, discharge to home, major complications, and mortality at 30 days. RESULTS: There were 142 patients (median age = 80 years, 44% female) with preoperative N-terminal pro-B-type natriuretic peptide data included (range = 106-73,500 pg/mL). The mean Society of Thoracic Surgeons predicative risk of mortality was 8%, and 46 patients (32%) had N-terminal pro-B-type natriuretic peptide of greater than 3000 pg/mL. N-terminal pro-B-type natriuretic peptide of greater than 3000 pg/mL was associated only with increased intensive care unit length of stay of greater than 24 hours (35% vs 9%, P = 0.0001). There was no statistical difference between cohorts with regard to total length of stay of greater than 3 days (24% vs 15%, P = 0.2), discharge to home (74% vs 83%, P = 0.3), major complication, or mortality at 30 days. CONCLUSIONS: Transcatheter aortic valve replacement is an appropriate and effective treatment for patients with aortic stenosis presenting with high N-terminal pro-B-type natriuretic peptide and acute on chronic heart failure.

Comparison of Causes and Associated Costs of 30-Day Readmission of Transcatheter Implantation Versus Surgical Aortic Valve Replacement in the United States (A National Readmission Database Study).

Our current knowledge about comparative differences in 30-day readmissions and the impact of readmissions on overall costs after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) is largely derived from clinical trials. The objectives of this study were to compare readmissions and costs for TAVI and SAVR in a nationally representative population-based sample. The Healthcare Cost and Utilization Project's National Readmission Database was used for the study. Hierarchical multivariable regression analyses were used to examine differences in the propensity score 1:1 matched cohort. The matched cohort included 4,682 patients who survived index procedures done from January through November 2013. Compared with SAVR, the rate of 30-day readmission was not significantly different for endovascular TAVI (16% vs 18%; p = 0.19); and was higher for the transapical TAVI (22% vs 17%; p <0.01) group. The 30-day cumulative costs were higher for the 2 endovascular TAVI ($51,025 vs $46,228; p = 0.03) and transapical TAVI ($59,575 vs $45,792; p <0.01). In multivariable analyses, the risk of 30-day readmission was similar for endovascular TAVI (odds ratio [OR] 0.93; 95% confidence interval [CI] 0.78 to 1.12) and was 27% higher for transapical TAVI (OR 1.27; 95% CI 1.02 to 1.57). Cumulative costs (index plus readmission costs) were 13% (ß 0.13; 95% CI 0.10 to 0.15) and 19% (ß 0.19; 95% CI 0.16 to 0.23) higher for the endovascular TAVI and transapical TAVI, respectively. In conclusion, the rate of readmissions was similar for endovascular TAVI and SAVR but the costs were 26% higher for TAVI than for SAVR.

eNOS deficient mice develop progressive cardiac hypertrophy with altered cytokine and calcium handling protein expression.

Although studies have shown that endothelial nitric oxide synthase (eNOS) homozygous knockout mice (eNOS-/-) develop left ventricular (LV) hypertrophy, well compensated at least to 24 wks, uncertainty still exists as to the cardiac functional and molecular mechanistic consequences of eNOS deficiency at later time-points. To bridge the gap in existent data, we examined whole hearts from eNOS-/- and age-matched wild-type (WT) control mice ranging in age from 18 to 52 wks for macroscopic and microscopic histopathology, LV mRNA and protein expression using RNA Dot blots and Western blots, respectively, and LV function using isolated perfused work-performing heart preparations. Heart weight to body weight (HW/BW in mg/g) ratio increased significantly as eNOS-/- mice aged (82.2%, P < 0.001). Multi-focal replacement fibrosis and myocyte degeneration/death were first apparent in eNOS-/- mouse hearts at 40 wks. Progressive increases in LV atrial natriuretic factor (ANF) and alpha-skeletal actin mRNA levels both correlated significantly with increasing HW/BW ratio in aged eNOS-/- mice (r = 0.722 and r = 0.648, respectively; P < 0.001). At 52 wks eNOS-/- mouse hearts exhibited basal LV hypercontractility yet blunted beta adrenergic receptor (betaAR) responsiveness that coincided with a significant reduction in the LV ratio of phospholamban to sarcoplasmic reticulum Ca2+-ATPase-2a protein levels and was preceded by a significant upregulation in LV steady-state mRNA and protein levels of the 28 kDa membrane-bound form of tumor necrosis factor-alpha. We conclude that absence of eNOS in eNOS-/- mice results in a progressive concentric hypertrophic cardiac phenotype that is functionally compensated with decreased betaAR responsiveness, and is associated with a potential cytokine-mediated alteration of calcium handling protein expression.

Meta-analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Left Main Coronary Artery Disease.

Despite the increase in use of percutaneous coronary intervention (PCI) in left main coronary disease, its efficacy compared with coronary artery bypass grafting (CABG) is unclear. We performed a meta-analysis of randomized controlled trials to assess the optimal revascularization strategy. Our search yielded 8 studies reporting relevant outcomes that were pooled using the inverse variance method, and the hazard ratio (HR) was calculated. The primary outcome was all-cause mortality, myocardial infarction (MI), or stroke (major adverse cardiac events [MACE]), and the secondary outcome was death/MI/stroke/repeat revascularization (expanded MACE). Differences in outcomes classified by follow-up duration (early: 0 to 1 year; late: 3 to 5 years) or anatomical complexity of coronary artery disease (SYNTAX score) were investigated. Our results suggest no difference in either early or late MACE (early: HR 0.81; 95% confidence interval [CI] 0.63 to 1.05; late: HR 1.12; 95% CI 0.80 to 1.56) or expanded MACE (early: HR 1.03; 95% CI 0.69 to 1.52; late: HR 1.16; 95% CI 0.95 to 1.43) between the 2 groups. There was an increased risk of expanded MACE with a high SYNTAX score for PCI (HR 1.47; 95% CI 1.13 to 1.92) at late follow-up. There were comparable rates of all-cause mortality and nonprocedural MI between the 2 groups with increased rates of repeat revascularization with PCI throughout the follow-up and higher rates of stroke with coronary artery bypass grafting early in the follow-up period. In conclusion, our analysis suggests that CABG may be preferable in patients with left main disease and high SYNTAX scores, assuming they are at low surgical risk, and PCI may be an acceptable alternative in patients with low-intermediate SYNTAX scores.

Stent thrombosis with bioabsorbable polymer drug-eluting stents: insights from the Food and Drug Administration database.

BACKGROUND: SYNERGY, a bioabsorbable polymer-based, everolimus-eluting stent (BP-DES), recently received regulatory approval in the USA for use in percutaneous coronary interventions. Yet, information on the safety of BP-DES in routine clinical practice is limited. Our aim was to compare the safety of the recently approved BP-DES with current durable polymer drug-eluting stents (DP-DES) by analyzing adverse events, namely, stent thrombosis (ST), reported to the Manufacturer and User Facility Device Experience (MAUDE) database. MATERIALS AND METHODS: The MAUDE database requires nationwide mandatory notification for adverse events on devices approved for clinical use. This database was searched for adverse events reported between 1 October 2015 and 25 December 2016, encountered after the placement of either BP-DES or DP-DES. Only those adverse events were included where the exposure period to the stents was comparable after the index procedure. Of all the adverse events reported, the event of interest was ST. RESULTS: A total of 951 adverse events were reported. ST occurred in 48/951 of all events, 31/309 and 17/642 when BP-DES or DP-DES were used, respectively (P=0.00001). Of the 31 ST events with BP-DES, 68% (21/31) occurred within less than or equal to 24 h of the index procedure and 52% (16/31) occurred within less than or equal to 2 h. CONCLUSION: Our results raise the possibility of an increased risk of ST, particularly early ST (within 24 h), with the recently approved BP-DES. However, because of the inherent limitations of reporting within the MAUDE database, these data merely highlight a potential need for additional surveillance and randomized trials to assess further the safety of the bioabsorbable platform.