Frequency of Comfort Care and Palliative Care Consultation after ST-Elevation Myocardial Infarction.

INTRODUCTION: ST-elevation myocardial infarction (STEMI) remains a leading cause of death despite advances in revascularization and post-STEMI care. Especially for patients with a poor prognosis, there is increasing emphasis on comfort-focused care. METHODS: We conducted a single-center retrospective cohort study of patients with STEMI at a large tertiary care academic medical center, abstracting patient-level data, causes of death, and use of palliative care consultation from the medical records. We sought to investigate the frequency of comfort-focused approaches and palliative care consultation after STEMI. RESULTS: A total of 536 patients presented with or were transferred with STEMI from January 2010 to July 2018, of whom 61/536 (11.4%) died during index hospitalization. Among those who underwent percutaneous intervention (PCI), the in-hospital mortality rate was 6.8%. Median (IQR) and time to death was two (0-6) days. Among those who died, 25/61 (41%) were treated with mechanical circulatory support (MCS). A total of 25/61 (41%) patients died following transition to a comfort-focused approach. Rate of MCS utilization during hospitalization was higher in the group that was ultimately transitioned to comfort-focused measures than the group who received full treatment measures. Palliative care was consulted in the case of 6/61 (9.8%) patients. Median time to consultation was 5 (1-7) days and time to death was 6.5 (2-28) days. DISCUSSION: Transition to comfort-focused care before death after STEMI is common, particularly in those with cardiogenic shock and/or treated with MCS, highlighting the critical status of such patients. Although increasingly employed in recent years, palliative care consults remain rare and are often employed late in the hospitalization.

Outcomes of ultra-low contrast percutaneous coronary intervention in patients with advanced chronic kidney disease.

BACKGROUND: Coronary angiography and percutaneous coronary intervention (PCI) in patients with chronic kidney disease (CKD) is associated with increased risk of contrast induced nephropathy (CIN) and requirement for renal replacement therapy (RRT). OBJECTIVES: We aimed to evaluate our single center experience of ultra-low contrast PCI in patients with CKD and to characterize 1 year outcomes. METHODS: We performed a retrospective analysis of ultra-low contrast PCI at our institution between 2016 and 2022. Patients with CKD3b-5 (eGFR <45 mL/min/1.73m2), not on RRT who underwent ultra-low contrast PCI ( < 30 mL of contrast during PCI) were included. Primary outcomes included change in eGFR post-procedurally, and death, RRT requirement, and major adverse cardiac events (MACE) at 1 year follow-up. RESULTS: One hundred patients were included in the study. The median age was 67 years old and 28% were female. The median baseline eGFR was 21.5 mL/min/1.73m2 (IQR 14.08-32.0 mL/min/1.73m2). A median of 8.0 mL (IQR 0-15 mL) of contrast was used during PCI. Median contrast use to eGFR ratio was 0.37 (IQR 0-0.59). There was no significant difference between pre-and postprocedure eGFR (p = 0.84). At 1 year, 8% of patients died, 11% required RRT and 33% experienced MACE. The average time of RRT initiation was 7 months post-PCI. Forty-four patients were undergoing renal transplant evaluation, of which 17 (39%) received a transplant. CONCLUSIONS: In patients with advanced CKD, ultra-low contrast PCI is feasible and safe with minimal need for peri-procedural RRT. Moreover, ultra-low contrast PCI may allow for preservation of renal function in anticipation of renal transplantation.

Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression.

Background and Purpose: XO (xanthine oxidase) is a key enzyme of uric acid metabolism and is thought to contribute to oxidative pathways that promote atherosclerotic plaque progression, yet its role in plaque destabilization is not well elucidated. We hypothesized that XO is expressed in carotid plaque from symptomatic patients in association with cardiovascular risk factors. Methods: Patients were stratified by symptoms, defined as presentation with an ipsilateral cerebral ischemic event. Carotid atherosclerotic plaques were obtained from 44 patients with symptomatic plaque and 44 patients without ischemic cerebral events. Protein expression of XO was evaluated by immunohistochemical staining and the percentage of cells expressing XO and CD68 (macrophage marker) compared between the groups. Biochemical and demographic cardiometabolic risk factors of study participants also were measured. Results: Carotid atherosclerotic plaques from symptomatic patients were associated with significantly higher XO expression versus asymptomatic plaque (median [interquartile range]: 1.24 [2.09] versus 0.16 [0.34]; P<0.001) and with significantly higher circulating uric acid levels (mean±SD: 7.36±2.10 versus 5.37±1.79 mg/dL; P<0.001, respectively). In addition, XO expression in atherosclerotic carotid plaque was inversely associated with serum high-density lipoproteins cholesterol levels (P=0.010, r=−0.30) and directly with circulating uric acid levels (P<0.001, r=0.45). The average percentage of macrophages that expressed XO was significantly higher in symptomatic versus asymptomatic plaques (median [interquartile range]: 93.37% [25] versus 46.15% [21], respectively; P<0.001). Conclusions: XO overexpression in macrophages is associated with increased serum uric acid and low high-density lipoproteins cholesterol levels and may potentially have a mechanistic role in carotid plaque destabilization. The current study supports a potential role for uric acid synthesis pathway as a target for management of carotid atherosclerosis in humans.

Outcomes of retrograde chronic total occlusion percutaneous coronary intervention: A report from the OPEN-CTO registry.

OBJECTIVES: We sought to assess in-hospital and long-term outcomes of retrograde compared with antegrade-only percutaneous coronary intervention for chronic total occlusion (CTO PCI). BACKGROUND: Procedural and clinical outcomes following retrograde compared with antegrade-only CTO PCI remain unknown. METHODS: Using the core-lab adjudicated OPEN-CTO registry, we compared the outcomes of retrograde to antegrade-only CTO PCI. Primary endpoints included were in-hospital major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, stroke, myocardial infarction [MI], emergency cardiac surgery, or clinically significant perforation) and MACCE at 1-year (all-cause death, MI, stroke, target lesion revascularization, or target vessel reocclusion). RESULTS: Among 885 single CTO procedures from the OPEN-CTO registry, 454 were retrograde and 431 were antegrade-only. Lesion complexity was higher (J-CTO score: 2.7 vs. 1.9; p < .001) and technical success lower (82.4 vs. 94.2%; p < .001) in retrograde compared with antegrade-only procedures. All-cause death was higher in the retrograde group in-hospital (2 vs. 0%; p = .003), but not at 1-year (4.9 vs. 3.3%; p = .29). Compared with antegrade-only procedures, in-hospital MACCE rates (composite of all-cause death, stroke, MI, emergency cardiac surgery, and clinically significant perforation) were higher in the retrograde group (10.8 vs. 3.3%; p < .001) and at 1-year (19.5 vs. 13.9%; p = .03). In sensitivity analyses landmarked at discharge, there was no difference in MACCE rates at 1 year following retrograde versus antegrade-only CTO PCI. Improvements in Seattle Angina Questionnaire Quality of Life scores at 1-year were similar between the retrograde and antegrade-only groups (29.9 vs 30.4; p = .58). CONCLUSIONS: In the OPEN-CTO registry, retrograde CTO procedures were associated with higher rates of in-hospital MACCE compared with antegrade-only; however, post-discharge outcomes, including quality of life improvements, were similar between technical modalities.

Mortality after drug-eluting stents vs. coronary artery bypass grafting for left main coronary artery disease: a meta-analysis of randomized controlled trials.

AIMS: The optimal method of revascularization for patients with left main coronary artery disease (LMCAD) is controversial. Coronary artery bypass graft surgery (CABG) has traditionally been considered the gold standard therapy, and recent randomized trials comparing CABG with percutaneous coronary intervention (PCI) with drug-eluting stents (DES) have reported conflicting outcomes. We, therefore, performed a systematic review and updated meta-analysis comparing CABG to PCI with DES for the treatment of LMCAD. METHODS AND RESULTS: We systematically identified all randomized trials comparing PCI with DES vs. CABG in patients with LMCAD. The primary efficacy endpoint was all-cause mortality. Secondary endpoints included cardiac death, myocardial infarction (MI), stroke, and unplanned revascularization. All analyses were by intention-to-treat. There were five eligible trials in which 4612 patients were randomized. The weighted mean follow-up duration was 67.1 months. There were no significant differences between PCI and CABG for the risk of all-cause mortality [relative risk (RR) 1.03, 95% confidence interval (CI) 0.81-1.32; P = 0.779] or cardiac death (RR 1.03, 95% CI 0.79-1.34; P = 0.817). There were also no significant differences in the risk of stroke (RR 0.74, 95% CI 0.35-1.50; P = 0.400) or MI (RR 1.22, 95% CI 0.96-1.56; P = 0.110). Percutaneous coronary intervention was associated with an increased risk of unplanned revascularization (RR 1.73, 95% CI 1.49-2.02; P < 0.001). CONCLUSION: The totality of randomized clinical trial evidence demonstrated similar long-term mortality after PCI with DES compared with CABG in patients with LMCAD. Nor were there significant differences in cardiac death, stroke, or MI between PCI and CABG. Unplanned revascularization procedures were less common after CABG compared with PCI. These findings may inform clinical decision-making between cardiologists, surgeons, and patients with LMCAD.

Promise of autologous CD34+ stem/progenitor cell therapy for treatment of cardiovascular disease.

CD34+ cells are haematopoietic stem cells used therapeutically in patients undergoing radiation or chemotherapy due to their regenerative potential and ability to restore the haematopoietic system. In animal models, CD34+ cells have been associated with therapeutic angiogenesis in response to ischaemia. Several trials have shown the potential safety and efficacy of CD34+ cell delivery in various cardiovascular diseases. Moreover, Phase III trials have now begun to explore the potential role of CD34+ cells in treatment of both myocardial and peripheral ischaemia. CD34+ cells have been shown to be safe and well-tolerated in the acute myocardial infarction (AMI), heart failure, and angina models. Several studies have suggested potential benefit of CD34+ cell therapy in patients with coronary microvascular disease as well. In this review, we will discuss the therapeutic potential of CD34+ cells, and describe the pertinent trials that have used autologous CD34+ cells in no-options refractory angina, AMI, and heart failure. Lastly, we will review the potential utility of autologous CD34+ cells in coronary endothelial and microvascular dysfunction.

Repeat Revascularization for Severe Recurrent Coronary Artery Disease in a Young Woman With Takayasu Arteritis.

A young woman with Takayasu arteritis presented with an acute coronary syndrome with ostial left main coronary artery stenosis. She underwent urgent coronary artery bypass surgery but developed recurrent symptoms 6 months later owing to graft failure. She was treated with percutaneous coronary intervention with resolution of her symptoms. (Level of Difficulty: Beginner.).

The functional assessment of patients with non-obstructive coronary artery disease: expert review from an international microcirculation working group.

Symptomatic non-obstructive coronary artery disease (NOCAD) is an increasingly recognised entity that is associated with poor cardiovascular outcomes. Nearly half of those undergoing coronary angiography for appropriate indications, such as typical angina, or a positive stress test have no obstructive lesion. There are no guideline recommendations as to how to care properly for these patients. Physiologic assessment of the coronary arteries beyond two-dimensional angiography is not standardised, yet it can provide valuable information in patients presenting with typical angina in the setting of NOCAD. In this consensus document, we detail steps for the interventional cardiologist to evaluate the patient with symptomatic NOCAD in the cardiac catheterisation laboratory, first with the assessment of coronary flow reserve (CFR), and then with delineation of deficiencies in non-endothelium-dependent CFR (CFRne) versus endothelium-dependent CFR (CFRe) using provocative agents such as adenosine and acetylcholine, respectively, followed by the evaluation of smooth muscle function with nitroglycerine (NTG). Once the mechanism behind the anginal symptoms is established, one can identify the appropriate treatment strategies to address the physiologic deficiency that is present. Despite an established safety profile, a comprehensive assessment may be considered for selected patients which requires an understanding of the appropriate invasive evaluation by the practising interventional cardiologist when evaluating not only patients with obstructive CAD but also those with NOCAD.

Sex-stratified analysis of national trends and outcomes in isolated tricuspid valve surgery.

Objective: Female sex is a known risk factor for cardiac surgery, and tricuspid valve (TV) disease is more common in women. There are few data on sex-stratified surgical outcomes for isolated TV surgery. An administrative database was used to compare acute in-hospital outcomes between men and women undergoing isolated TV surgery. Methods: Patients aged >18 who underwent TV repair or replacement from 2004 to 2013 were identified using the National Inpatient Sample. Patients were excluded if they had congenital heart disease, endocarditis, or were undergoing concomitant cardiac surgeries except coronary bypass. Results were weighted to represent national averages. Sex-stratified analysis was performed using propensity score matching to compare in-hospital mortality, postoperative complications and hospital costs. Results: Over 10 years, women represented 58% of the 5005 TV surgeries performed. With propensity matching, hospital mortality (7.9% vs 7.7%; P=0.99) and median length of stay (11 vs 11 days; P=0.99) were similar between men and women. However, median hospital charges were higher for men ($166 000 vs $155 000; P=0.04). Conclusion: Isolated TV surgery is rare, but women more commonly undergo the procedure. In-hospital mortality was similar between men and women after propensity matching, but remains markedly high for both men and women in comparison to that reported for left-sided isolated valve surgery.

Prevalence of extracoronary vascular abnormalities and fibromuscular dysplasia in patients with spontaneous coronary artery dissection.

Spontaneous coronary artery dissection (SCAD) is a cause of acute coronary syndrome, often occurring in young women. The utility of comprehensive imaging and clinical significance of detected vascular abnormalities have yet to be determined. We hypothesized that extracoronary vascular abnormalities (EVAs) are common in SCAD and aimed to study the prevalence and distribution of these findings. We enrolled 115 patients with confirmed SCAD who were evaluated at the Mayo Clinic SCAD Clinic from February 2010 to May 2014 and prospectively underwent comprehensive computed tomography angiography imaging of the neck, chest, abdomen, and pelvis (SCAD computed tomography angiography protocol, n = 95) or had retrospective review of outside studies (n = 20) including head imaging (n = 40). Follow-up was determined by last clinical visit or study correspondence and included review of recurrent SCAD or myocardial infarction, congestive heart failure, and death. We reported EVAs in 66% of patients with SCAD, most frequently in the abdomen (36%), pelvis (28%), and neck (27%). Only 1 patient had EVA in the chest (aortic dissection and Marfan's). Fibromuscular dysplasia (FMD) (exclusively multifocal) was the most common type of EVA (45%). Vascular abnormalities in those with head imaging included intracranial aneurysms (n = 9) and FMD (n = 3). There were no deaths at median follow-up of 21 months (Q1 to Q3 7.7 to 55). The presence of FMD was not associated with SCAD recurrence (relative risk [RR] 1.2; confidence interval [95% CI] 0.60, 2.5), congestive heart failure (RR 0.66; 95% CI 0.20, 2.3), or myocardial infarction (RR 1.34; 95% CI 0.69, 2.6). In conclusion, EVAs including FMD, dissections, aneurysms, and dilation are common in patients with SCAD and occur in a wide anatomic distribution. The presence of EVAs and/or FMD did not correlate with the risk of subsequent clinical events, but future studies with increased power and longer follow-up will be important to further assess the role of EVAs in patients with SCAD.

Effectiveness of a community screening program for metabolic syndrome and cardiovascular risk factor identification in young South Asians adults.

AIMS: Metabolic syndrome has been associated with increased risk of cardiovascular disease. We aimed to determine the effectiveness of a community-based screening program in identifying cardiovascular risk factors in healthy young South Asian population. MATERIALS AND METHODS: Between 2006 and 2011, 3314 patients of all ages were recruited as a part of a prospective cohort study investigating cardiovascular risk in South Asians. We analyzed 1537 patients between the ages of 18 and 40. Demographic and baseline characteristics including baseline laboratory markers and blood pressures were obtained at initial visit. RESULTS: The total cohort of 1537 patients was 66.5% male, and the mean age was 35±5 years. Among participants who denied a history of hypercholesterolemia, 62% had elevated LDL-C (>100 mg/dL), and 8% had markedly elevated LDL-C (>160 mg/dL). Overall, diabetes was present in 4%, hypertension was present in 12% and hyperlipidemia was present in 46%. Low HDL-C (50% of men, 52% of women) and elevated triglycerides (44% of men, 18% of women) were the most prevalent components of metabolic syndrome. Metabolic syndrome was present in 14% of men and 8% of women and one-third (30%) of men and one-fifth (19%) of women had at least two component risk factors. CONCLUSIONS: This is the largest study to date assessing effectiveness of a community based screening program aiming to identify cardiovascular risk in young South Asians. We note significant modifiable risk at a young age. Such community based interventions can be effective at detecting and managing risk factors early in this vulnerable population.

Coronary artery tortuosity in spontaneous coronary artery dissection: angiographic characteristics and clinical implications.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized nonatherosclerotic cause of acute coronary syndrome. The angiographic characteristics of SCAD are largely undetermined. The goal of this study was to determine the prevalence of coronary tortuosity in SCAD and whether it may be implicated in the disease. METHODS AND RESULTS: Patients with confirmed SCAD (n=246; 45.3±8.9 years; 96% women) and 313 control patients without SCAD or coronary artery disease who underwent coronary angiography were included in this case-control study. Angiograms were reviewed for coronary tortuosity and assigned a tortuosity score. Tortuosity was common in patients presenting with their first SCAD event (78% versus 17% in controls; P<0.0001; tortuosity score, 4.41±1.73 versus 2.33±1.49 in controls; P<0.0001) despite a low prevalence of hypertension (34%). Recurrent SCAD (n=40) occurred within segments of tortuosity in 80% of cases. Severe tortuosity (≥2 consecutive curvatures ≥180°) was associated with a higher risk of recurrent SCAD (hazard ratio, 3.29; 95% confidence interval, 0.99-8.29; P=0.05). Tortuosity score >5 was associated with a trend toward higher risk of recurrent SCAD (P=0.16). Prespecified angiographic markers of tortuosity including corkscrew appearance and multivessel symmetrical tortuosity were associated with extracoronary vasculopathy including fibromuscular dysplasia (P<0.05 for both). CONCLUSIONS: Coronary artery tortuosity is highly prevalent in the SCAD population and is associated with recurrent SCAD. Recurrent SCAD most often occurs within segments of tortuosity. Angiographic features of SCAD are associated with extracoronary vasculopathy, including fibromuscular dysplasia. These findings suggest that coronary tortuosity may serve as a marker or potential mechanism for SCAD.

A novel application of CT angiography to detect extracoronary vascular abnormalities in patients with spontaneous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is associated with extracoronary vascular abnormalities, which depending on type and location may warrant treatment or provide additional diagnostic or prognostic information about this uncommon entity. Fibromuscular dysplasia (FMD), aneurysms, and dissections have been detected in multiple vascular territories by magnetic resonance angiography, CT angiography (CTA), and catheter angiography. The optimal modality to detect extracoronary vascular abnormalities is unknown. We highlight the technique and feasibility of a novel CTA protocol to detect extracoronary vascular abnormalities in these patients, incorporating patient safety and convenience. METHODS: The complete CTA protocol consisting of a single CTA of the neck, chest, abdomen, and pelvis was performed on 39 SCAD outpatients. All examinations were performed with 200 mL of low-osmolar contrast agent and used radiation dose modulation techniques. Average volume CT dose index was 9 mGy for the chest, abdomen, and pelvis portions and 21 mGy for the neck portion. Studies were independently reviewed by 2 senior vascular radiologists. RESULTS: Two patients had nondiagnostic CTA neck evaluation because of technical acquisition errors. Extracoronary vascular abnormalities were detected in 27 of 39 patients (69%). Catheter angiography detected brachial artery FMD in 1 patient, a vascular bed not included in the SCAD CTA protocol. Extracoronary vascular abnormalities were common, including FMD, aneurysms, dissection, and aortic tortuosity, and were seen in the iliac (36%), carotid and/or vertebral (31%), splanchnic (10%), and renal (26%) arteries and in the thoracic and/or abdominal aorta (10%). CONCLUSIONS: The frequency of extracoronary vascular abnormalities and extent of territories identified the CTA protocol in our cohort are high. A tailored CTA may be the optimal imaging technique for detecting extracoronary vascular abnormalities in patients with suspected underlying vasculopathy. Although the clinical significance of extracoronary vascular abnormalities remains unclear, detection of these abnormalities has identified patients in whom cerebral imaging and serial monitoring have been recommended.

Sca-1+ cardiosphere-derived cells are enriched for Isl1-expressing cardiac precursors and improve cardiac function after myocardial injury.

BACKGROUND: Endogenous cardiac progenitor cells are a promising option for cell-therapy for myocardial infarction (MI). However, obtaining adequate numbers of cardiac progenitors after MI remains a challenge. Cardiospheres (CSs) have been proposed to have cardiac regenerative properties; however, their cellular composition and how they may be influenced by the tissue milieu remains unclear. METHODOLOGY/PRINCIPAL FINDING: Using "middle aged" mice as CSs donors, we found that acute MI induced a dramatic increase in the number of CSs in a mouse model of MI, and this increase was attenuated back to baseline over time. We also observed that CSs from post-MI hearts engrafted in ischemic myocardium induced angiogenesis and restored cardiac function. To determine the role of Sca-1(+)CD45(-) cells within CSs, we cloned these from single cell isolates. Expression of Islet-1 (Isl1) in Sca-1(+)CD45(-) cells from CSs was 3-fold higher than in whole CSs. Cloned Sca-1(+)CD45(-) cells had the ability to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro. We also observed that cloned cells engrafted in ischemic myocardium induced angiogenesis, differentiated into endothelial and smooth muscle cells and improved cardiac function in post-MI hearts. CONCLUSIONS/SIGNIFICANCE: These studies demonstrate that cloned Sca-1(+)CD45(-) cells derived from CSs from infarcted "middle aged" hearts are enriched for second heart field (i.e., Isl-1(+)) precursors that give rise to both myocardial and vascular tissues, and may be an appropriate source of progenitor cells for autologous cell-therapy post-MI.

Myocardial improvement with human embryonic stem cell-derived cardiomyocytes enriched by p38MAPK inhibition.

BACKGROUND AIMS: We have shown previously that inhibition of the p38 mitogen-activated protein kinase (p38MAPK) directs the differentiation of human embryonic stem cell (hESC)-derived cardiomyocytes (hCM). We investigated the therapeutic benefits of intramyocardial injection of hCM differentiated from hESC by p38MAPK inhibition using closed-chest ultrasound-guided injection at a clinically relevant time post-myocardial infarction (MI) in a mouse model. METHODS: MI was induced in mice and the animals treated at day 3 with: (a) hCM, (b) human fetal fibroblasts (hFF) as cell control, or (c) medium control (n = 10 animals/group). Left ventricular ejection fraction (LVEF) was evaluated post-MI prior to therapy, and at days 28 and 60 post-cell therapy. Hearts were analyzed at day 60 for infarct size, angiogenesis, cell fate and teratoma formation. RESULTS: LVEF was improved in the hCM-treated animals compared with both hFF and medium control-treated animals at day 28 (39.03 ± 1.79% versus 27.89 ± 1.27%, P < 0.05, versus 32.90 ± 1.46%, P < 0.05, respectively), with sustained benefit until day 60. hCM therapy resulted in significantly smaller scar size, increased capillary bed area, increased number of arterioles, less native cardiomyocyte (CM) apoptosis, and increased CM proliferation compared with the other two groups. These benefits were achieved despite a very low retention rate of the injected cells at day 60, as assessed by immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). Therapy with hCM did not result in intramyocardial teratoma formation at day 60. CONCLUSIONS: This study demonstrates that hCM derived from p38MAPK-treated hESC have encouraging therapeutic potential.

Timing of bone marrow cell therapy is more important than repeated injections after myocardial infarction.

BACKGROUND: Bone marrow cell treatment has been proposed as a therapy for myocardial infarction, but the optimal timing and number of injections remain unknown. METHODS: Myocardial infarction was induced in mice followed by ultrasound-guided injection of mouse bone marrow cells at different time points post myocardial infarction (Days 3, 7, and 14) as monotherapy and at Days 3+7 as "double" therapy and at Days 3+7+14 as "triple" therapy. Controls received saline injections at Day 3 and Days 3+7+14. Left ventricular ejection fraction was evaluated post myocardial infarction prior to any therapy and at Day 28. Hearts were analyzed at Day 28 for infarct size and survival of donor cells. RESULTS: Left ventricular ejection fraction decreased from 55.3±0.9% to 37.6±0.6% (P<.001) 2 days post myocardial infarction in all groups. Injection of bone marrow cells at Day 3 post myocardial infarction resulted in smaller infarct size (17.8±3.6% vs. 36.6±7.1%; P=.05) and improved LV function (left ventricular ejection fraction 40.3±2.0% vs. 31.1±8.3%; P<.05) compared to control. However, delayed therapy at Day 7 or 14 did not. Multiple injections of bone marrow cells, either double therapy or triple therapy, did not result in reduction in infarct size, but led to improvements in left ventricular ejection fraction at Day 28 compared to control (39.9±3.6% and 38.8±5.5% vs. 34.8±5.3%; all P<.05). The number of donor cells surviving at Day 28 did not correlate with improvement in left ventricular ejection fraction. CONCLUSIONS: Injection of bone marrow cells at Day 3 reduced infarct size and improved left ventricular function. Multiple injections of bone marrow cells had no additive effect. Delaying cell therapy post myocardial infarction resulted in no functional benefit at all. These results will help inform future clinical trials.

Multivessel coronary artery disease predicts mortality, length of stay, and pressor requirements after liver transplantation.

The optimal preoperative cardiac evaluation strategy for patients with end-stage liver disease (ESLD) undergoing liver transplantation remains unknown. Patients are frequently referred for cardiac catheterization, but the effects of coronary artery disease (CAD) on posttransplant mortality are also unknown. We sought to determine the contribution of CAD and multivessel CAD in particular to posttransplant mortality. We performed a retrospective study of ESLD patients undergoing cardiac catheterization before liver transplant surgery between August 1, 2004 and August 1, 2007 to determine the effects of CAD on outcomes after transplantation. Among 83 patients who underwent left heart catheterization, 47 underwent liver transplantation during the follow-up period. Twenty-one of all ESLD patients who underwent liver transplantation (45%) had CAD. Fifteen of the transplant patients with CAD (71%) had multivessel disease. Among transplant patients, the presence of multivessel CAD (versus no CAD) was predictive of mortality (27% versus 4%, P = 0.046), increased length of stay (22 versus 15 days, P = 0.050), and postoperative pressor requirements (27% versus 4%, P = 0.029). Interestingly, neither the presence of any CAD nor the severity of stenosis in any single coronary artery predicted mortality. Furthermore, none of the traditional clinical predictors (age, gender, diabetes, creatinine, ejection fraction, and Model for End-Stage Liver Disease score) were predictive of mortality among transplant recipients. In conclusion, multivessel CAD is associated with higher mortality after liver transplantation when it is documented angiographically before transplantation, even in the absence of severe coronary artery stenosis. This study provides preliminary evidence showing that there may be significant prognostic value in coronary angiography as a part of the pretransplant workup.

Cytokine combination therapy with long-acting erythropoietin and granulocyte colony stimulating factor improves cardiac function but is not superior than monotherapy in a mouse model of acute myocardial infarction.

BACKGROUND: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) are potential novel therapies after myocardial infarction (MI). We first established the optimal and clinically applicable dosages of these drugs in mobilizing hematopoietic stem cells (HSC), and then tested the efficacy of monotherapy and combination therapy post-MI. METHODS AND RESULTS: Optimal doses were established in enhanced green fluorescent protein (eGFP) + chimeric mice (n = 30). Next, mice underwent MI and randomized into 4 groups (n = 18/group): 1) GCSF; 2) EPO; 3) EPO+GCSF; and 4) control. Left ventricular (LV) function was analyzed pre-MI, at 4 hours and at 28 days post-MI. Histological assessment of infarct size, blood vessels, apoptotic cardiomyocytes, and engraftment of eGFP+ mobilized cells were analyzed at day 28. LV function in the control group continued to deteriorate, whereas all treatments showed stabilization. The treatment groups resulted in less scarring, increased numbers of mobilized cells to the infarct border zone (BZ), and a reduction in the number of apoptotic cardiomyocytes. Both EPO groups had significantly more capillaries and arterioles at the BZ. CONCLUSION: We have established the optimal doses for EPO and GCSF in mobilizing HSC from the bone marrow and demonstrated that therapy with these agents, either as monotherapy or combination therapy, led to improvement of cardiac function post-MI. Combination therapy does not seem to have additive benefit over monotherapy in this model.