Utilizing visual symptoms to distinguish dry eye from glaucoma, cataract, and suspect glaucoma patients: a cross-sectional study.

BACKGROUND: The diagnosis of dry eye and other common ophthalmological conditions can be supported using patient reported symptoms, which is increasingly useful in contexts such as telemedicine. We aim to ascertain visual symptoms that differentiate dry eye from cataract, glaucoma, or glaucoma suspects. METHODS: Adults with dry eye, glaucoma, cataract, and suspected glaucoma (controls) completed a questionnaire to rate the frequency and severity of 28 visual symptoms. Univariate, followed by multivariable logistic regression with backward stepwise selection (p < 0.05), determined the individual symptoms and set of symptoms best distinguishing dry eye from each of the other conditions. RESULTS: Mean age of 353 patients (94 glaucoma suspect controls, 79 glaucoma, 84 cataract, and 96 dry eye) was 64.1 years (SD = 14.1); 67% were female and 68% White. Dry eye patients reported more frequent light sensitivity (OR = 15.0, 95% CI = 6.3-35.7) and spots in vision (OR = 2.8, 95% CI = 1.2-6.3) compared to glaucoma suspect controls. Compared to glaucoma patients, dry eye patients experienced more frequent light sensitivity (OR = 9.2, 95% CI = 2.0-41.7), but less frequent poor peripheral vision (OR = 0.2, 95% CI = 0.06-0.7), difference in vision between eyes (OR = 0.09, 95% CI = 0.01-0.7), and missing patches of vision (OR = 0.06, 95% CI = 0.009-0.3). Compared to cataract patients, dry eye patients reported more frequent spots in vision (OR = 4.5, 95% CI = 1.5-13.4) and vision variability across the week (OR = 4.7, 95% CI = 1.2-17.7) and were less likely to report worsening vision (OR = 0.1, 95% CI = 0.03-0.4) and blindness (OR = 0.1, 95% CI = 0.02-0.8). CONCLUSION: Visual symptoms may serve as a complementary tool to distinguish dry eye from various ocular conditions, though the symptoms that best distinguish dry eye differ across comparisons. Differentiating how patients visually perceive common eye diseases may be used in a variety of clinical settings to rule out specific conditions.

No "July Effect" in the management and outcomes of acute myocardial infarction: An 18-year United States national study.

BACKGROUND: There has been conflicting reports on the effect of new trainees on clinical outcomes at teaching hospitals in the first training month (July in the United States of America). We sought to assess this "July effect" in a contemporary acute myocardial infarction (AMI) population. METHODS: Adult (>18 years) AMI hospitalizations in May and July in urban teaching and urban nonteaching hospitals in the United States were identified from the HCUP-NIS database (2000-2017). In-hospital mortality was compared between May and July admissions. A difference-in-difference analysis comparing a change in outcome from May to July in teaching hospitals to a change in outcome from May to July in nonteaching hospitals was also performed. RESULTS: A total of 1,312,006 AMI hospitalizations from urban teaching (n = 710,593; 54.2%) or nonteaching (n = 601,413; 45.8%) hospitals in the months of May and July were evaluated. May admissions in teaching hospitals, had greater comorbidity, higher rates of acute multiorgan failure (10.6% vs. 10.2%, p < 0.001) and lower rates of cardiac arrest when compared to July admissions. July AMI admissions had lower in-hospital mortality compared to May (5.6% vs. 5.8%; adjusted odds ratio 0.94 [95% confidence interval 0.92-0.97]; p < 0.001) in teaching hospitals. Using the difference-in-difference model, there was no evidence of a July effect for in-hospital mortality (p = 0.19). CONCLUSIONS: There was no July effect for in-hospital mortality in this contemporary AMI population.

Escalation strategies, management, and outcomes of acute myocardial infarction-cardiogenic shock patients receiving percutaneous left ventricular support.

BACKGROUND: There are limited national-level data on the contemporary practices of mechanical circulatory support (MCS) use in acute myocardial infarction-cardiogenic shock (AMI-CS). METHODS: We utilized the Healthcare Cost and Utilization Project-National/Nationwide Inpatient Sample data (2005-2017) to identify adult admissions (>18 years) with AMI-CS. MCS devices were classified as intra-aortic balloon pump (IABP), percutaneous left ventricular assist devices (pLVAD), or extracorporeal membrane oxygenation (ECMO). We evaluated trends in the initial device used (IABP alone, pLVAD alone or ≥2 MCS devices), device escalation, bridging to durable LVAD/heart transplantation, and predictors of in-hospital mortality and device escalation. RESULTS: Among 327,283 AMI-CS admissions, 131,435 (40.2%) had an MCS device placed with available information on timing of placement. IABP, pLVAD, and ≥2 MCS devices were used as initial device in 120,928 (92.0%), 8202 (6.2%), and 2305 (1.7%) admissions, respectively. Most admissions were maintained on the initial MCS device with 1%-1.5% being escalated (IABP to pLVAD/ECMO, pLVAD to ECMO). Urban, medium, and large-sized hospitals and acute multiorgan failure were significant independent predictors of MCS escalation. In admissions receiving MCS, escalation of MCS device was associated with higher in-hospital mortality (adjusted odds ratio: 1.56, 95% confidence interval:  1.38-1.75; p < 0.001). Admissions receiving durable LVAD/heart transplantation increased over time in those initiated on pLVAD and ≥2 MCS devices, resulting in lower in-hospital mortality. CONCLUSIONS: In this 13-year study, escalation of MCS in AMI-CS was associated with higher in-hospital mortality suggestive of higher acuity of illness. The increase in number of durable LVAD/heart transplantations alludes to the role of MCS as successful bridge strategies.

Lower Oxygen Tension and Intracranial Hemorrhage in Veno-venous Extracorporeal Membrane Oxygenation.

INTRODUCTION AND METHODS: We examined the relationship between 24-h pre- and post-cannulation arterial oxygen tension (PaO2) and arterial carbon dioxide tension (PaCO2) and subsequent acute brain injury (ABI) in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) with granular arterial blood gas (ABG) data and institutional standardized neuromonitoring. RESULTS: Eighty-nine patients underwent VV-ECMO (median age = 50, 63% male). Twenty (22%) patients experienced ABI; intracranial hemorrhage (ICH) was the most common diagnosis (n = 14, 16%). Lower post-cannulation PaO2 levels were significantly associated with ICH (66 vs. 81 mmHg, p = 0.007) and a post-cannulation PaO2 level < 70 mmHg was more frequent in these patients (71% vs. 33%, p = 0.007). PaCO2 parameters were not associated with ABI. By multivariable logistic regression, hypoxemia post-cannulation increased the odds of ICH (OR = 5.06, 95% CI:1.41-18.17; p = 0.01). CONCLUSION: In summary, lower oxygen tension in the 24-h post-cannulation was associated with ICH development. The precise roles of peri-cannulation ABG changes deserve further investigation, as they may influence the management of VV-ECMO patients.

Efficacy and safety of angiotensin II in cardiogenic shock: A systematic review.

BACKGROUND: Cardiogenic shock (CS) is associated with high morbidity and mortality. In recent times, there is increasing interest in the role of angiotensin II in CS. We sought to systematically review the current literature on the use of angiotensin II in CS. METHODS: PubMed, EMBASE, Medline, Web of Science, PubMed Central, and CINAHL databases were systematically searched for studies that evaluated the efficacy of angiotensin II in patients with CS during 01/01/2010-07/07/2022. Outcomes of interest included change in mean arterial pressure (MAP), vasoactive medication requirements (percent change in norepinephrine equivalent [NEE] dose), all-cause mortality, and adverse events. RESULTS: Of the total 2,402 search results, 15 studies comprising 195 patients were included of which 156 (80%) received angiotensin II. Eleven patients (84.6%) in case reports and case series with reported MAP data at hour 12 noted an increase in MAP. Two studies noted a positive hemodynamic response (defined a priori) in eight (88.9%) and five (35.7%) patients. Eight studies reported a reduction in NEE dose at hour 12 after angiotensin II administration and one study noted a 100% reduction in NEE dose. Out of 47 patients with documented information, 13 patients had adverse outcomes which included hepatic injury (2), digital ischemia (1), ischemic optic neuropathy (1), ischemic colitis (2), agitated delirium (1), and thrombotic events (2). CONCLUSIONS: In this first systematic review of angiotensin II in CS, we note the early clinical experience. Angiotensin II was associated with improvements in MAP, decrease in vasopressor requirements, and minimal reported adverse events.

Role of adjunct anticoagulant or thrombolytic therapy in cardiac arrest without ST-segment-elevation or percutaneous coronary intervention: A systematic review and meta-analysis.

This study sought to compare the impact of additional anticoagulation or thrombolytic therapy in patients with cardiac arrest without ST-segment-elevation on electrocardiography and not receiving percutaneous coronary intervention. Three studies (two randomized controlled studies and one observational study) were included, which demonstrated that use of anticoagulation or thrombolytic therapy was associated with higher risk of bleeding, without improvements in time to return of spontaneous circulation or in-hospital mortality.

Challenges in determining death by neurologic criteria in extracorporeal membrane oxygenation - A single center experience.

INTRODUCTION: Apnea test (AT) in patients on extracorporeal membrane oxygenation (ECMO) support is challenging, leading to variation in determining death by neurologic criteria (DNC). We aim to describe the diagnostic criteria and barriers for DNC in adults on ECMO in a tertiary care center. METHODS: A retrospective review of a prospective observational standardized neuromonitoring study was conducted in adult VA- and VV-ECMO patients at a tertiary center from June 2016 to March 2022. Brain death was defined according to the 2010 American Academy of Neurology guidelines and following the 2020 World Brain Death Project recommendations for performing AT in ECMO patients. RESULTS: Eight (2.7%) ECMO patients (median age = 44 years, 75% male, 50% VA-ECMO) met criteria for DNC, six (75%) of whom were determined with AT. In the other two patients who did not undergo AT due to safety concerns, ancillary tests (transcranial doppler and electroencephalography) were consistent with DNC. An additional seven (2.3%) patients (median age = 55 years, 71% male, 86% VA-ECMO) were noted to have absent brainstem reflexes but failed to complete determination of DNC as they underwent withdrawal of life-sustaining treatment (WLST) before a full evaluation was completed. In these patients, AT was never performed, and ancillary tests were inconsistent with either neurological exam findings and/or neuroimaging supporting DNC, or with each other. CONCLUSION: AT was used safely and successfully in 6 of the 8 ECMO patients diagnosed with DNC and was always consistent with the neurological exam and imaging findings, as opposed to ancillary tests alone.

Redo-aortic valve replacement in prior stentless prosthetic aortic valves: Transcatheter versus surgical approach.

OBJECTIVES: The objective was to compare outcomes of redo-aortic valve replacement (AVR) via surgical or transcatheter approach in prior surgical AVR with large percentage of prior stentless surgical AVR. BACKGROUND: With the introduction of transcatheter aortic valve replacement (TAVR), patients with increased surgical risks now have an alternative to redo surgical AVR (SAVR), known as valve-in-valve (ViV) TAVR. Stentless prosthetic aortic valves present a more challenging implantation for ViV-TAVR given the lack of structural frame. METHODS: We performed a retrospective study of 173 subjects who have undergone SAVR (N = 100) or ViV-TAVR (N = 73) in patients with prior surgical AVR at Wake Forest Baptist Medical Center from 2009 to 2019. Our study received the proper ethical oversight. RESULTS: The average ages in redo-SAVR and ViV-TAVR groups were 58.03 ± 13.86 and 66.57 ± 13.44 years, respectively (p < 0.0001). The redo-SAVR had significantly lower STS (2.78 ± 2.09 and 4.68 ± 5.51, p < 0.01) and Euroscores (4.32 ± 2.98 and 7.51 ± 8.24, p < 0.05). The redo-SAVR group had higher percentage requiring mechanical support (8% vs. 0%, p < 0.05) and vasopressors (53% vs. 0%, p < 0.0001), longer length of stay (13.65 ± 11.23 vs. 5.68 ± 7.64 days, p < 0.0001), and inpatient mortality (16% vs. 2.78%, p < 0.005). At 30-day follow-up, redo-SAVR group had higher rates of acute kidney injury (10% vs. 0%, p < 0.01), however ViV-TAVR group had more new left bundle branch blocks (6.85% vs. 0%, p < 0.05). No significant differences regarding re-hospitalization rates, stroke, or death up to 1-year. CONCLUSION: Although the ViV-TAVR group had higher risk patients, there were significantly fewer procedural complications, shorter length of stay, and similar mortality outcomes up to 1-year follow-up.

Veno-Arterial Extracorporeal Membrane Oxygenation in Patients with Fulminant Myocarditis: A Review of Contemporary Literature.

Fulminant myocarditis is characterized by life threatening heart failure presenting as cardiogenic shock requiring inotropic or mechanical circulatory support to maintain tissue perfusion. There are limited data on the role of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the management of fulminant myocarditis. This review seeks to evaluate the management of fulminant myocarditis with a special emphasis on the role and outcomes with VA-ECMO use.

Hospitalization Duration for Acute Myocardial Infarction: A Temporal Analysis of 18-Year United States Data.

Background and objectives: Primary percutaneous coronary intervention (PCI)-related outcomes in acute myocardial infarction (AMI) have improved over time, but there are limited data on the length of stay (LOS) in relation to in-hospital mortality. Materials and Methods: A retrospective cohort of adult AMI admissions was identified from the National Inpatient Sample (2000−2017) and stratified into short (≤3 days) and long (>3 days) LOS. Outcomes of interest included temporal trends in LOS and associated in-hospital mortality, further sub-stratified based on demographics and comorbidities. Results: A total 11,622,528 admissions with AMI were identified, with a median LOS of 3 (interquartile range [IQR] 2−6) days with 49.9% short and 47.3% long LOS, respectively. In 2017, compared to 2000, temporal trends in LOS declined in all AMI, with marginal increases in LOS >3 days and decreases for ≤3 days (median 2 [IQR 1−3]) vs. long LOS (median 6 [IQR 5−9]). Patients with long LOS had lower rates of coronary angiography and PCI, but higher rates of non-cardiac organ support (respiratory and renal) and use of coronary artery bypass grafting. Unadjusted in-hospital mortality declined over time. Short LOS had comparable mortality to long LOS (51.3% vs. 48.6%) (p = 0.13); however, adjusted in-hospital mortality was higher in LOS >3 days when compared to LOS ≤ 3 days (adjusted OR 3.00, 95% CI 2.98−3.02, p < 0.001), with higher hospitalization (p < 0.001) when compared to long LOS. Conclusions: Median LOS in AMI, particularly in STEMI, has declined over the last two decades with a consistent trend in subgroup analysis. Longer LOS is associated with higher in-hospital mortality, higher hospitalization costs, and less frequent discharges to home compared to those with shorter LOS.

Intermediate-Risk Pulmonary Embolism: A Review of Contemporary Diagnosis, Risk Stratification and Management.

Pulmonary embolism (PE) can have a wide range of hemodynamic effects, from asymptomatic to a life-threatening medical emergency. Pulmonary embolism (PE) is associated with high mortality and requires careful risk stratification for individualized management. PE is divided into three risk categories: low risk, intermediate-risk, and high risk. In terms of initial therapeutic choice and long-term management, intermediate-risk (or submassive) PE remains the most challenging subtype. The definitions, classifications, risk stratification, and management options of intermediate-risk PE are discussed in this review.

A novel technique for postclosure of large-bore sheaths using two Perclose devices.

OBJECTIVES: This study aimed to assess the feasibility, efficacy, and safety of a novel percutaneous postprocedure closure technique for large arterial sheath removal with the use of two Perclose ProGlide (Abbott Vascular Devices, Redwood City, CA) devices. BACKGROUND: Postprocedural closing of large-bore arteriotomies using the Perclose system can be difficult given the subsequent inability of the device to capture sufficient wall tissue. METHODS: Our study was a single-center retrospective analysis of 22 consecutive patients who underwent large arteriotomy closure via the postclosure technique with a 12-16-Fr sheath. Efficacy endpoints included successful deployment of the system and hemostasis. Safety endpoints included the incidence of major or minor vascular complications as defined by the Vascular Academic Research Consortium-2 (VARC-2) definitions at 30-day follow-up. RESULTS: The postclosure technique resulted in 100% technical success rate and no postprocedural bleeding or vascular complications. CONCLUSION: Postclosure technique is a safe, highly effective, and feasible percutaneous method to achieve large-bore arteriotomy hemostasis with low rates of major bleeding or vascular complications and favorable early outcome.

Endothelial Hypoxia-Inducible Factor-1α Is Required for Vascular Repair and Resolution of Inflammatory Lung Injury through Forkhead Box Protein M1.

Endothelial barrier dysfunction is a central factor in the pathogenesis of persistent lung inflammation and protein-rich edema formation, the hallmarks of acute respiratory distress syndrome. However, little is known about the molecular mechanisms that are responsible for vascular repair and resolution of inflammatory injury after sepsis challenge. Herein, we show that hypoxia-inducible factor-1α (HIF-1α), expressed in endothelial cells (ECs), is the critical transcriptional factor mediating vascular repair and resolution of inflammatory lung injury. After sepsis challenge, HIF-1α but not HIF-2α expression was rapidly induced in lung vascular ECs, and mice with EC-restricted disruption of Hif1α (Hif1af/f/Tie2Cre+) exhibited defective vascular repair, persistent inflammation, and increased mortality in contrast with the wild-type littermates after polymicrobial sepsis or endotoxemia challenge. Hif1af/f/Tie2Cre+ lungs exhibited marked decrease of EC proliferation during recovery after sepsis challenge, which was associated with inhibited expression of forkhead box protein M1 (Foxm1), a reparative transcription factor. Therapeutic restoration of endothelial Foxm1 expression, via liposomal delivery of Foxm1 plasmid DNA to Hif1af/f/Tie2Cre+ mice, resulted in reactivation of the vascular repair program and improved survival. Together, our studies, for the first time, delineate the essential role of endothelial HIF-1α in driving the vascular repair program. Thus, therapeutic activation of HIF-1α-dependent vascular repair may represent a novel and effective therapy to treat inflammatory vascular diseases, such as sepsis and acute respiratory distress syndrome.

TIME Trial: Effect of Timing of Stem Cell Delivery Following ST-Elevation Myocardial Infarction on the Recovery of Global and Regional Left Ventricular Function: Final 2-Year Analysis.

RATIONALE: The TIME trial (Timing in Myocardial Infarction Evaluation) was the first cell therapy trial sufficiently powered to determine if timing of cell delivery after ST-segment-elevation myocardial infarction affects recovery of left ventricular (LV) function. OBJECTIVE: To report the 2-year clinical and cardiac magnetic resonance imaging results and their modification by microvascular obstruction. METHODS AND RESULTS: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells versus placebo in 120 patients with anterior ST-segment-elevation myocardial infarctions resulting in LV dysfunction. Primary end points included changes in global (LV ejection fraction) and regional (infarct and border zone) function. Secondary end points included changes in LV volumes, infarct size, and major adverse cardiac events. Here, we analyzed the continued trajectory of these measures out to 2 years and the influence of microvascular obstruction present at baseline on these long-term outcomes. At 2 years (n=85), LV ejection fraction was similar in the bone marrow mononuclear cells (48.7%) and placebo groups (51.6%) with no difference in regional LV function. Infarct size and LV mass decreased ≥30% in each group at 6 months and declined gradually to 2 years. LV volumes increased ≈10% at 6 months and remained stable to 2 years. Microvascular obstruction was present in 48 patients at baseline and was associated with significantly larger infarct size (56.5 versus 36.2 g), greater adverse LV remodeling, and marked reduction in LV ejection fraction recovery (0.2% versus 6.2%). CONCLUSIONS: In one of the longest serial cardiac magnetic resonance imaging analyses of patients with large anterior ST-segment-elevation myocardial infarctions, bone marrow mononuclear cells administration did not improve recovery of LV function over 2 years. Microvascular obstruction was associated with reduced recovery of LV function, greater adverse LV remodeling, and more device implantations. The use of cardiac magnetic resonance imaging leads to greater dropout of patients over time because of device implantation in patients with more severe LV dysfunction resulting in overestimation of clinical stability of the cohort. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

A comparison of valve-in-valve transcatheter aortic valve replacement in failed stentless versus stented surgical bioprosthetic aortic valves.

OBJECTIVES: The objectives of this study were to compare short- and intermediate-term clinical outcomes, procedural complications, TAVR prosthesis hemodynamics, and paravalvular leak (PVL) in stentless and stented groups. BACKGROUND: Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) is an alternative to surgical redo for bioprosthetic valve failure. There have been limited data on ViV in stentless surgical valves. METHODS: We retrospectively analyzed 40 patients who underwent ViV TAVR in prior surgical bioprosthetic valves at Wake Forest Baptist Medical Center from October 2014 to September 2017. Eighty percent (32/40) ViV TAVRs were in stentless, while 20% (8/40) were in stented bioprosthetic valves. RESULTS: The primary mode of bioprosthetic valve failure for ViV implantation in the stentless group was aortic insufficiency (78%, 25/32), while in the stented group was aortic stenosis (75%, 6/8). The ViV procedure success was 96.9% (31/32) in stentless group and 100% in stented group (8/8). There were no significant differences in all-cause mortality at 30 days between stentless and stented groups (6.9%, 2/31 versus 0%, 0/8, P = 0.33) and at 1 year (0%, 0/25 versus 0%, 0/5). In the stentless group, 34.4% (11/32) required a second valve compared to the stented group of 0% (0/8). There was a significant difference in the mean aortic gradient at 30-day follow-up (12.33 ± 6.33 mmHg and 22.63 ± 8.45 mmHg in stentless and stented groups, P < 0.05) and at 6-month follow-up (9.75 ± 5.07 mmHg and 24.00 ± 11.28 mmHg, P < 0.05), respectively. CONCLUSIONS: ViV in the stentless bioprosthetic aortic valve has excellent procedural success and intermediate-term results. Our study shows promising data that may support the application of TAVR in stentless surgical aortic valve. However, further and larger studies need to further validate our single center's experience.

Comparison of outcomes with surgical cut-down versus percutaneous transfemoral transcatheter aortic valve replacement: TAVR transfemoral access comparisons between surgical cut-down and percutaneous approach.

OBJECTIVES: The objective is to compare the short-term (30 days) and late (12 months) vascular adverse events in patients undergoing transfemoral (TF)-transcatheter aortic valve replacement (TAVR) by surgical cut-down (SC) vs. percutaneous (PC) approaches. BACKGROUND: Programs continue to utilize both approaches in TF-TAVR. There are limited data comparing outcomes by SC vs. PC approaches and long-term effects of endovascular intervention facilitated hemostasis on late vascular adverse events. METHODS: A total of 146 men and women aged 79.7 ± 10.0 years with severe aortic stenosis deemed extreme or high risk for surgery underwent TAVR via TF access. 61 had SC and 85 had PC approaches. Valve Academic Research Consortium (VARC-2) outcomes were assessed at an average of 12.1 months after TAVR. RESULTS: Hospital length of stay (LOS) post-TAVR was shorter for the PC group compared to the SC group (5.1 ± 3.9 vs. 8.2 ± 6.6 days; P < 0.001). More patients were discharged directly to home in the PC than the SC group (85.9% vs. 68.9%, P < 0.05). At 30 days, there were 13/61 (21.3%) and 16/85 (18.8%; P < 0.05) of any vascular events, and 2/61 (3.3%) and 2/85 (2.4%; P = 0.73) major vascular events in the SC and PC groups, respectively. There was no difference in all-cause mortality between the SC (14/61; 23%) and PC groups [17/85 (20%); P = 0.34]. There was no difference in any [4/33 (12%) vs. 3/43 (7%); P = 0.84] or major vascular adverse events [1/33 (3%) vs. 1/43 (2%); P = 0.79] in subjects that underwent adjunctive endovascular intervention compared to those who did not, respectively. There were no statistically significant univariate or multivariate predictors of any vascular event at 12 months when comparing SC to PC groups. CONCLUSION: For TF TAVR, the PC approach, when compared to the SC approach, is associated with a shorter hospital LOS and higher rate of direct discharge to home with similar risk of vascular complications, late vascular adverse events, and all-cause mortality at 12 months.

Comparison of paravalvular aortic leak characteristics in the Medtronic CoreValve versus Edwards Sapien Valve: Paravalvular aortic leak characteristics.

OBJECTIVES: Temporally quantify and localize paravalvular aortic leak (PVL) after transcatheter aortic valve replacement (TAVR) in the Medtronic CoreValve (MCV) versus the Edwards Sapien Valve (ESV). BACKGROUND: In order to increase the precision of THV selection and PVL intervention, an understanding of PVL characteristics is essential. METHODS: The frequency, severity, and location of post-TAVR PVL were evaluated with transthoracic echocardiography pre-discharge, one month, and one-year post-procedure in 202 patients receiving a MCV (N = 120) or ESV (N = 81). This was done through application of a clock face to the short axis of the aortic valve in order to divide the area into three tertiles. RESULTS: Pre-discharge differences between PVL frequency and severity in the MCV and ESV lost significance over time. Localizing these trends, MCV PVL frequency and severity significantly decreased in the first and third tertiles during most time periods while PVL in the second tertile of the MCV or in any of the tertiles of the ESV failed to improve. Presence of pre-discharge PVL was predictive of 30-day HF readmission and/or death (OR = 3.16, 95% CI: 0.99-10.12). Presence of pre-discharge and 30-day PVL was predictive of 1-year HF readmissions and/or death (OR = 2.12, 95% CI: 1.09-4.13 and OR = 1.99, 95% CI: 0.96-4.12). CONCLUSIONS: When comparing the MCV and ESV, not all locations of PVL improve equally over time, which has implications for heart failure readmissions. This could be used to influence valve selection and to identify cases in which earlier intervention on PVL may be appropriate.

Bone marrow characteristics associated with changes in infarct size after STEMI: a biorepository evaluation from the CCTRN TIME trial.

RATIONALE: Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE: The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction. METHODS AND RESULTS: This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac MRI. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31(+) BMCs (P=0.046) and in those with faster BMC growth rates in colony-forming unit Hill and endothelial-colony forming cell functional assays (P=0.033 and P=0.032, respectively). CONCLUSIONS: This study identified BMC characteristics associated with a better clinical outcome in patients with segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation. CLINICAL TRIAL REGISTRATION INFORMATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684021.

Bone marrow cell characteristics associated with patient profile and cardiac performance outcomes in the LateTIME-Cardiovascular Cell Therapy Research Network (CCTRN) trial.

BACKGROUND: Although several preclinical studies have shown that bone marrow cell (BMC) transplantation promotes cardiac recovery after myocardial infarction, clinical trials with unfractionated bone marrow have shown variable improvements in cardiac function. METHODS: To determine whether in a population of post-myocardial infarction patients, functional recovery after BM transplant is associated with specific BMC subpopulation, we examined the association between BMCs with left ventricular (LV) function in the LateTIME-CCTRN trial. RESULTS: In this population, we found that older individuals had higher numbers of BM CD133(+) and CD3(+) cells. Bone marrow from individuals with high body mass index had lower CD45(dim)/CD11b(dim) levels, whereas those with hypertension and higher C-reactive protein levels had higher numbers of CD133(+) cells. Smoking was associated with higher levels of CD133(+)/CD34(+)/VEGFR2(+) cells and lower levels of CD3(+) cells. Adjusted multivariate analysis indicated that CD11b(dim) cells were negatively associated with changes in LV ejection fraction and wall motion in both the infarct and border zones. Change in LV ejection fraction was positively associated with CD133(+), CD34(+), and CD45(+)/CXCR4(dim) cells as well as faster BMC growth rates in endothelial colony forming assays. CONCLUSIONS: In the LateTIME population, BM composition varied with patient characteristics and treatment. Irrespective of cell therapy, recovery of LV function was greater in patients with greater BM abundance of CD133(+) and CD34(+) cells and worse in those with higher levels of CD11b(dim) cells. Bone marrow phenotype might predict clinical response before BMC therapy and administration of selected BM constituents could potentially improve outcomes of other future clinical trials.

Detailed analysis of bone marrow from patients with ischemic heart disease and left ventricular dysfunction: BM CD34, CD11b, and clonogenic capacity as biomarkers for clinical outcomes.

RATIONALE: Bone marrow (BM) cell therapy for ischemic heart disease (IHD) has shown mixed results. Before the full potency of BM cell therapy can be realized, it is essential to understand the BM niche after acute myocardial infarction (AMI). OBJECTIVE: To study the BM composition in patients with IHD and severe left ventricular (LV) dysfunction. METHODS AND RESULTS: BM from 280 patients with IHD and LV dysfunction were analyzed for cell subsets by flow cytometry and colony assays. BM CD34(+) cell percentage was decreased 7 days after AMI (mean of 1.9% versus 2.3%-2.7% in other cohorts; P<0.05). BM-derived endothelial colonies were significantly decreased (P<0.05). Increased BM CD11b(+) cells associated with worse LV ejection fraction (LVEF) after AMI (P<0.05). Increased BM CD34(+) percentage associated with greater improvement in LVEF (+9.9% versus +2.3%; P=0.03, for patients with AMI and +6.6% versus -0.02%; P=0.021 for patients with chronic IHD). In addition, decreased BM CD34(+) percentage in patients with chronic IHD correlated with decrement in LVEF (-2.9% versus +0.7%; P=0.0355). CONCLUSIONS: In this study, we show a heterogeneous mixture of BM cell subsets, decreased endothelial colony capacity, a CD34+ cell nadir 7 days after AMI, a negative correlation between CD11b percentage and postinfarct LVEF, and positive correlation of CD34 percentage with change in LVEF after cell therapy. These results serve as a possible basis for the small clinical improvement seen in autologous BM cell therapy trials and support selection of potent cell subsets and reversal of comorbid BM impairment. CLINICAL TRIAL REGISTRATIONS URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00684021, NCT00684060, and NCT00824005.