Babak Azarbal

Complications of Extracorporeal Membrane Oxygenation for Treatment of Cardiogenic Shock and Cardiac Arrest: A Meta-Analysis of 1,866 Adult Patients

BACKGROUND Venoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for treatment of cardiogenic shock or cardiac arrest. The exact complication rate is not well understood, in part because of small study sizes. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining complication rates for ECMO. METHODS A systematic PubMed search was conducted on ECMO for treatment of cardiogenic shock or cardiac arrest in adult patients only, updated to November 2012. Studies with more than 10 patients published in the year 2000 or later that reported complication rates for ECMO were included. Specific complications analyzed included lower extremity ischemia, fasciotomy or compartment syndrome, amputation, stroke, neurologic complications, acute kidney injury, renal replacement therapy, major or significant bleeding, rethoracotomy for bleeding or tamponade, and significant infection. For studies that included overlapping patients, the largest study was included and the others excluded. Cochrans Q and I-squared were calculated. A more conservative random-effects model was chosen for all analyses. RESULTS Twenty studies were included in the analyses encompassing 1,866 patients. Seventeen studies reported survival to hospital discharge, with a cumulative survival rate of 534 of 1,529, and a range of 20.8% to 65.4%. Analyses encompassed 192 to 1,452 patients depending on the specific complication analyzed. The pooled estimate rates of complications with 95% confidence intervals were as follows: lower extremity ischemia, 16.9% (12.5% to 22.6%); fasciotomy or compartment syndrome, 10.3% (7.3% to 14.5%); lower extremity amputation, 4.7% (2.3% to 9.3%); stroke, 5.9% (4.2% to 8.3%); neurologic complications, 13.3% (9.9% to 17.7%); acute kidney injury, 55.6% (35.5% to 74.0%); renal replacement therapy, 46.0% (36.7% to 55.5%); major or significant bleeding, 40.8% (26.8% to 56.6%); rethoracotomy for bleeding or tamponade in postcardiotomy patients, 41.9% (24.3% to 61.8%); and significant infection, 30.4% (19.5% to 44.0%). CONCLUSIONS Although ECMO can improve survival of patients with advanced heart disease, there is significant associated morbidity with performance of this intervention. These findings should be incorporated in the risk-benefit analysis when initiation of ECMO for cardiogenic shock is being considered.

Safety of coronary reactivity testing in women with no obstructive coronary artery disease: results from the NHLBI-sponsored WISE (Women's Ischemia Syndrome Evaluation) study.

OBJECTIVES This study evaluated the safety of coronary reactivity testing (CRT) in symptomatic women with evidence of myocardial ischemia and no obstructive coronary artery disease (CAD). BACKGROUND Microvascular coronary dysfunction (MCD) in women with no obstructive CAD portends an adverse prognosis of a 2.5% annual major adverse cardiovascular event (MACE) rate. The diagnosis of MCD is established by invasive CRT, yet the risk of CRT is unknown. METHODS The authors evaluated 293 symptomatic women with ischemia and no obstructive CAD, who underwent CRT at 3 experienced centers. Microvascular function was assessed using a Doppler wire and injections of adenosine, acetylcholine, and nitroglycerin into the left coronary artery. CRT-related serious adverse events (SAEs), adverse events (AEs), and follow-up MACE (death, nonfatal myocardial infarction [MI], nonfatal stroke, or hospitalization for heart failure) were recorded. RESULTS CRT-SAEs occurred in 2 women (0.7%) during the procedure: 1 had coronary artery dissection, and 1 developed MI associated with coronary spasm. CRT-AEs occurred in 2 women (0.7%) and included 1 transient air microembolism and 1 deep venous thrombosis. There was no CRT-related mortality. In the mean follow-up period of 5.4 years, the MACE rate was 8.2%, including 5 deaths (1.7%), 8 nonfatal MIs (2.7%), 8 nonfatal strokes (2.7%), and 11 hospitalizations for heart failure (3.8%). CONCLUSIONS In women undergoing CRT for suspected MCD, contemporary testing carries a relatively low risk compared with the MACE rate in these women. These results support the use of CRT by experienced operators for establishing definitive diagnosis and assessing prognosis in this at-risk population. (Womens Ischemia Syndrome Evaluation [WISE]; NCT00832702).

Intramural Delivery of Recombinant Apolipoprotein A-IMilano/Phospholipid Complex (ETC-216) Inhibits In-Stent Stenosis in Porcine Coronary Arteries

Background—We have previously demonstrated vasculoprotective effects after repeated intravenous administration of recombinant apolipoprotein A-IMilano (apoA-Im)/phospholipid complex. In this study, we sought to determine the effects of local recombinant apoA-Im/1-palmitoyl,2-oleoyl phosphatidylcholine complex (ETC-216) delivered intramurally via the Infiltrator catheter on luminal narrowing in a porcine coronary artery stent overstretch injury model. Methods and Results—In twelve domestic swine (≈25 kg), two arteries each were infiltrated with 0.4 mL ETC-216 (14 mg/mL) or vehicle control immediately before deployment of GFX stents (stent:artery ratio=1.3:1). Animals were euthanized at day 28, and evaluation by QCA revealed a significant improvement in mean lumen loss index with ETC-216 treatment (21±22% versus 43±13% lumen loss;P =0.01). Histomorphometric analysis showed that ETC-216 treatment significantly reduced the intimal area (6.7±1.5 versus 5.2±1.4 mm2, −22%;P =0.02) and the stenosis index (0.76±0.15 versus 0.59±0.15;P =0.01), and increased the lumen area (2.1±1.4 versus 3.7±1.8 mm2, +76%;P =0.02). Regression analysis showed significant differences in lumen area (P =0.004), neointimal area (P =0.003), stenosis index (P =0.001), and neointimal thickness (P =0.003) adjusted for injury score in favor of ETC-216. Conclusions—A single intramural administration of ETC-216 significantly inhibited injury-induced luminal narrowing in the porcine stent overstretch model through reduction of intimal hyperplasia. These data show that local intracoronary delivery of ETC-216 may be useful to prevent restenosis after coronary stenting.

Feasibility and safety of percutaneous coronary intervention in patients with end-stage liver disease referred for liver transplantation.

Percutaneous coronary intervention (PCI) has traditionally not been an option for patients with end‐stage liver disease (ESLD) and coronary artery disease (CAD). This retrospective study was designed to demonstrate the feasibility and safety of PCI in liver transplant candidates. Patients with ESLD and hemodynamically significant CAD who were otherwise deemed to be acceptable candidates for liver transplantation underwent PCI. The procedural success rates, mortality and myocardial infarction rates, and bleeding outcomes were examined. Sixteen patients with ESLD underwent PCI: 15 with bare‐metal stents (1.3 stents per patient on average) and 1 with balloon angioplasty alone. The median diameter stenosis per lesion was 80%, the median platelet count was 68 × 109/L, the median international normalized ratio was 1.3, and the median Model for End‐Stage Liver Disease score was 13. PCI was successful in 94% of the patients. One patient had a suboptimal residual stenosis of 50% after stenting. There were no in‐hospital or 30‐day deaths or myocardial infarctions, and no patients developed hematomas. One patient required a 1‐U platelet transfusion, and another required 1 U of packed red blood cells. All patients remained clinically stable 1 month after PCI. Nine of the 16 patients were listed for liver transplantation, and 3 patients underwent liver transplantation. In conclusion, we have demonstrated the safety and feasibility of PCI in a small cohort of patients with ESLD and hemodynamically significant CAD, the majority of whom had significant thrombocytopenia. Larger studies are required to determine whether PCI is an effective treatment strategy for patients with ESLD and hemodynamically significant CAD who otherwise would not be candidates for liver transplantation. Liver Transpl 17:809‐813, 2011.

Randomized Pilot Trial of Gene Expression Profiling Versus Heart Biopsy in the First Year After Heart Transplant Early Invasive Monitoring Attenuation Through Gene Expression Trial

Background—The endomyocardial biopsy (EMB) is considered the gold standard in rejection surveillance post cardiac transplant, but is invasive, with risk of complications. A previous trial suggested that the gene expression profiling (GEP) blood test was noninferior to EMB between 6 and 60 months post transplant. As most rejections occur in the first 6 months, we conducted a single-center randomized trial of GEP versus EMB starting at 55 days post transplant (when GEP is valid). Methods and Results—Sixty heart transplant patients meeting inclusion criteria were randomized beginning at 55 days post transplant to either GEP or EMB arms. A positive GEP ≥30 between 2 and 6 months, or ≥34 after 6 months, prompted a follow-up biopsy. The primary end point included a composite of death/retransplant, rejection with hemodynamic compromise or graft dysfunction at 18 months post transplant. A coprimary end point included change in first-year maximal intimal thickness by intravascular ultrasound, a recognized surrogate for long-term outcome. Corticosteroid weaning was assessed in both the groups. The composite end point was similar between the GEP and EMB groups (10% versus 17%; log-rank P=0.44). The coprimary end point of first-year intravascular ultrasound change demonstrated no difference in mean maximal intimal thickness (0.35±0.36 versus 0.36±0.26 mm; P=0.944). Steroid weaning was successful in both the groups (91% versus 95%). Conclusions—In this pilot study, GEP starting at 55 days post transplant seems comparable with EMB for rejection surveillance in selected heart transplant patients and does not result in increased adverse outcomes. GEP also seems useful to guide corticosteroid weaning. Larger randomized trials are required to confirm these findings. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962377.

Prognostic Contribution of Exercise Capacity, Heart Rate Recovery, Chronotropic Incompetence, and Myocardial Perfusion Single-Photon Emission Computerized Tomography in the Prediction of Cardiac Death and All-Cause Mortality.

Chronotropic incompetence, measured by the percentage (%) of heart rate (HR) reserve achieved (%HR reserve), abnormal HR recovery, reduced exercise capacity (EC), and myocardial perfusion single-photon emission computerized tomography (SPECT MPS) abnormalities are known predictors of all-cause mortality (ACM) and cardiac death (CD). The aim of this study was to determine if EC, %HR reserve, and HR recovery add incremental value to MPS in the prediction of ACM and CD. A total of 11,218 patients without valvular disease and not on β blockers underwent symptom-limited exercise MPS. %HR reserve was (peak HR - rest HR)/(220 - age - rest HR) × 100, with %HR reserve <80 defined as low. HR recovery was peak HR - recovery HR. An HR recovery <22 beats/min at 2 minutes after peak exercise was considered abnormal. Poor EC was defined as exercise duration ≤6 minutes (7 metabolic equivalents). Summed stress scores (SSSs) were calculated using a 20-segment, 5-point MPS model. Statistical analysis was performed using Cox regression models. There were 445 deaths (148 CD) during a mean follow-up of 3.2 ± 2.5 years. In multivariate analysis, the independent predictors of ACM were age, χ(2) = 154.81; EC, χ(2) = 74.00; SSS, χ(2) = 32.99; %HR reserve, χ(2) = 24.74; abnormal electrocardiogram at rest, χ(2) = 23.13; HR recovery, χ(2) = 18.45; diabetes, χ(2) = 17.75; and previous coronary artery disease, χ(2) = 11.85 (p ≤0.0006). The independent predictors of CD were SSS, χ(2) = 54.25; EC, χ(2) = 49.34; age, χ(2) = 46.45; abnormal electrocardiogram at rest, χ(2) = 30.60; previous coronary artery disease, χ(2) = 20.69; Duke treadmill score, χ(2) = 19.50; %HR reserve, χ(2) = 11.43; diabetes, χ(2) = 10.23 (all p ≤0.0014); and HR recovery, χ(2) = 5.30 (p = 0.0214). The exercise variables showed increases in Harrells C static and net improvement reclassification, with EC showing the strongest incremental improvement in predicting ACM and CD (respective C-index 76.5% and 83.3% and net reclassification index 0.3201 and 0.4996). In conclusion, EC, %HR reserve, and HR recovery are independent predictors of ACM and CD and add incremental prognostic value to extent and severity of MPS.

Induction Therapy With Antithymocyte Globulin in Patients Undergoing Cardiac Transplantation Is Associated With Decreased Coronary Plaque Progression as Assessed by Intravascular Ultrasound

Background—Antithymocyte globulin (ATG) is used as induction therapy after cardiac transplant for enhancing immunosuppression and delaying the initiation of nephrotoxic drugs. It is unknown if ATG induction is associated with decreased coronary plaque progression by intravascular ultrasound (IVUS). Methods and Results—Patients transplanted between March 2010 and December 2012 with baseline and 1-year IVUS were included. All patients transplanted were included in a secondary analysis. Change in plaque progression was measured in a blinded fashion on matched coronary segments and contrasted between patients induced with ATG and those who were not. One hundred and three patients were included in IVUS arms. Mean age at transplant was 55.8±12.6 years, and 33.0% were female. Patients induced with ATG were more sensitized (54.3% versus 14.3%). Plaque progression was attenuated in patients who received ATG by changes in maximal intimal area (1.0±1.2 versus 2.3±2.6 mm2; P=0.001), maximal percent stenosis (6.3±7.9 versus 12.8±12.3%; =0.003), maximal intimal thickness (0.2±0.2 versus 0.3±0.3 mm; P=0.035), and plaque volume (0.5±0.7 versus 1.0±1.3 mm3/mm; P=0.016). Rapid plaque progression by maximal percent stenosis (≥20%) occurred less frequently in the ATG arm (4.3% versus 26.3; P=0.003). Survival (P=0.242) and any treated rejection (P=0.166) were not statistically different between groups. Patients receiving ATG had a higher rate of first-year infection (P=0.003), perhaps related to increased intravenous antibiotic use immediately postoperatively, and a trend toward more biopsy-proven rejection (P=0.073). Conclusions—Induction therapy with ATG is associated with reduced first-year coronary plaque progression as assessed by IVUS, despite an increased prevalence of sensitized patients with a trend toward more rejection.

A Prospective, Nonrandomized, Open-Labeled Pilot Study Investigating the Use of Magnesium in Patients Undergoing Nonacute Percutaneous Coronary Intervention with Stent Implantation

Background: Magnesium has recently been shown to inhibit acute stent thrombosis in animal models. This study tested the feasibility of magnesium administration in patients undergoing nonacute percutaneous coronary intervention with stent implantation. Methods: Twenty-one patients undergoing nonemergent percutaneous coronary intervention were enrolled and received intravenous magnesium sulfate (2-g bolus over 20 minutes prepercutaneous coronary intervention, followed by 14 g over 12 hours infusion). Endpoints: safety outcomes-hypotension, bradycardia, bleeding complications and heart block within first 24 hours; angiographic outcomes-acute thrombotic occlusion and need for platelet glycoprotein Ilb/Illa inhibitor bailout; and clinical outcomes-death, myocardial infarction, recurrent ischemia, and need for urgent revascularization at 48 hours and 30 days. Results: No significant effects on heart rate or blood pressure, major bleeding complication, or new electrocardiographic changes were observed. Angiographic thrombus was visualized in two cases, and coronary artery dissection in one case poststent deployment. None of these cases required the use of glycoprotein inhibitors for bailout. Death, myocardial infarction, recurrent ischemia, and need for urgent revascularization were not observed. The serum magnesium level increased from 2.1 ± 0.3 mg/dL at baseline to 3.5 ± 0.8 mg/dL at the end of the infusion (P < .0001). Platelet activation was significantly inhibited at the end of the magnesium sulfate infusion. Conclusion: Intravenous magnesium sulfate has been demonstrated as a feasible and safe agent in patients undergoing nonacute percutaneous coronary intervention with stent implantation. A randomized clinical trial comparing magnesium with glycoprotein inhibitors during percutaneous coronary intervention is warranted.

Early Denervation and Later Reinnervation of the Heart Following Cardiac Transplantation: A Review

Heart transplantation (HTx) surgically interrupts the parasympathetic vagal neurons and the intrinsic postganglionic sympathetic nerve fibers traveling from the stellate ganglia to the myocardium, causing axonal Wallerian degeneration and thus extrinsic cardiac denervation.[1][1], [2][2], [3][3], [4

Frequency of coronary artery fistulae is increased after orthotopic heart transplantation

Frequency of coronary artery fistulae is increased after orthotopic heart transplantation Janet Wei, MD, Babak Azarbal, MD, Sarabjeet Singh, MD, Matthew Rafiei, BS, Richard Cheng, MD, Jignesh Patel, MD, Fardad Esmailian, MD, Jesse Currier, MD, and Jon Kobashigawa, MD From the Division of Cardiology, Heart Institute, Cedars–Sinai Medical Center, Los Angeles, California; and the Division of Cardiology, West Los Angeles Veterans Administration Medical Center, Los Angeles, California