Michael F. Swartz

Washing red blood cells and platelets transfused in cardiac surgery reduces postoperative inflammation and number of transfusions: results of a prospective, randomized, controlled clinical trial.

Objectives: Children undergoing cardiac surgery with cardiopulmonary bypass are susceptible to additional inflammatory and immunogenic insults from blood transfusions. We hypothesize that washing red blood cells and platelets transfused to these patients will reduce postoperative transfusion-related immune modulation and inflammation. Design: Prospective, randomized, controlled clinical trial. Setting: University hospital pediatric cardiac intensive care unit. Patients: Children from birth to 17 yrs undergoing cardiac surgery with cardiopulmonary bypass. Interventions: Children were randomized to an unwashed or washed red blood cells and platelet transfusion protocol for their surgery and postoperative care. All blood was leuko-reduced, irradiated, and ABO identical. Plasma was obtained for laboratory analysis preoperatively, immediately, and 6 and 12 hrs after cardiopulmonary bypass. Primary outcome was the 12-hr postcardiopulmonary bypass interleukin-6-to-interleukin-10 ratio. Secondary measures were interleukin levels, C-reactive protein, and clinical outcomes. Measurements and Main Results: One hundred sixty-two subjects were studied, 81 per group. Thirty-four subjects (17 per group) did not receive any blood transfusions. Storage duration of blood products was similar between groups. Among transfused subjects, the 12-hr interleukin ratio was significantly lower in the washed group (3.8 vs. 4.8; p = .04) secondary to lower interleukin-6 levels (after cardiopulmonary bypass: 65 vs.100 pg/mL, p = .06; 6 hrs: 89 vs.152 pg/mL, p = .02; 12 hrs: 84 vs.122 pg/mL, p = .09). Postoperative C-reactive protein was lower in subjects receiving washed blood (38 vs. 43 mg/L; p = .03). There was a numerical, but not statistically significant, decrease in total blood product transfusions (203 vs. 260) and mortality (2 vs. 6 deaths) in the washed group compared to the unwashed group. Conclusions: Washed blood transfusions in cardiac surgery reduced inflammatory biomarkers, number of transfusions, donor exposures, and were associated with a nonsignificant trend toward reduced mortality. A larger study powered to test for clinical outcomes is needed to determine whether these laboratory findings are clinically significant.

Dominant Frequency Increase Rate Predicts Transition from Paroxysmal to Long-Term Persistent Atrial Fibrillation

Background— Little is known about the mechanisms underlying the transition from paroxysmal to persistent atrial fibrillation (AF). In an ovine model of long-standing persistent AF we tested the hypothesis that the rate of electric and structural remodeling, assessed by dominant frequency (DF) changes, determines the time at which AF becomes persistent. Methods and Results— Self-sustained AF was induced by atrial tachypacing. Seven sheep were euthanized 11.5±2.3 days after the transition to persistent AF and without reversal to sinus rhythm; 7 sheep were euthanized after 341.3±16.7 days of long-standing persistent AF. Seven sham-operated animals were in sinus rhythm for 1 year. DF was monitored continuously in each group. Real-time polymerase chain reaction, Western blotting, patch clamping, and histological analyses were used to determine the changes in functional ion channel expression and structural remodeling. Atrial dilatation, mitral valve regurgitation, myocyte hypertrophy, and atrial fibrosis occurred progressively and became statistically significant after the transition to persistent AF, with no evidence for left ventricular dysfunction. DF increased progressively during the paroxysmal-to-persistent AF transition and stabilized when AF became persistent. Importantly, the rate of DF increase correlated strongly with the time to persistent AF. Significant action potential duration abbreviation, secondary to functional ion channel protein expression changes (CaV1.2, NaV1.5, and KV4.2 decrease; Kir2.3 increase), was already present at the transition and persisted for 1 year of follow up. Conclusions— In the sheep model of long-standing persistent AF, the rate of DF increase predicts the time at which AF stabilizes and becomes persistent, reflecting changes in action potential duration and densities of sodium, L-type calcium, and inward rectifier currents.

Left versus right atrial difference in dominant frequency, K+ channel transcripts, and fibrosis in patients developing atrial fibrillation after cardiac surgery

BACKGROUND The development of atrial fibrillation (AF) after cardiac surgery is associated with adverse outcomes; however, the mechanism(s) that trigger and maintain AF in these patients are unknown. OBJECTIVE The purpose of this study was to test our hypothesis that postoperative AF is maintained by high-frequency sources in the left atrium (LA) resulting from ion channel and structural features that differ from the right atrium (RA). METHODS Forty-four patients with no previous history of AF who underwent cardiac surgery consented to LA and RA biopsies. Histologic sections evaluated fatty infiltration, fibrosis, and iron deposition; quantitative reverse transcription-polymerase chain reaction (RT-PCR) assessed ion channel expression. In a subset of 27 patients, LA and RA unipolar recording leads were also placed. In patients who developed AF, the dominant frequency (DF) for each lead was calculated using fast Fourier transform. RESULTS DFs during AF were LA 6.26 +/- 0.8 Hz, RA 4.56 +/- 0.7 Hz (P <.01). RT-PCR revealed LA-to-RA differences in mRNA abundance for Kir2.3 (1.8:1) and Kir3.4 (2.3:1). While LA fibrosis was greater in patients developing AF compared with those remaining in normal sinus rhythm (10.8% +/- 11% vs. 3.8% +/- 3.5%; P = .03), the amount of LA fibrosis inversely correlated with the LA DF. CONCLUSIONS This is the first demonstration of LA-to-RA frequency differences during postoperative AF, which are associated with LA-to-RA differences in mRNA levels for potassium channel proteins and LA fibrosis. These results strongly suggest that sources of AF after cardiac surgery are located in the LA and are stabilized by LA fibrosis.

Impella to unload the left ventricle during peripheral extracorporeal membrane oxygenation.

Peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) for acute cardiac failure reestablishes normal oxygen delivery and perfusion. However, VA ECMO can be limited by insufficient ventricular unloading, resulting in thrombus formation and pulmonary edema. Impella 2.5 has been used to unload the left ventricle and provide hemodynamic support during acute heart failure. We present our experience of the Impella 2.5 as an adjunct for left ventricular unloading during peripheral VA ECMO support and as a bridge for the HeartMate II left ventricular assist device (LVAD). An Impella 2.5 was placed in patients who were on peripheral VA ECMO with evidence of left ventricular distension. Patients who were candidates for heart transplant were transitioned to the HeartMate II LVAD. Five patients on VA ECMO with ventricular distension underwent Impella 2.5 implantation, resulting in a decreased left ventricular end-diastolic diameter as measured by echocardiography (7.8 ± 1.4 vs. 6.2 ± 0.8 cm, p = 0.001). Four patients were subsequently transitioned to the HeartMate II LVAD after restoration of end-organ function. Impella 2.5 is a safe means to unload the left ventricle while on peripheral VA ECMO to prevent left ventricle thrombus formation and worsening pulmonary edema in patients transitioning to a HeartMate II LVAD.

Atrial myxomas: Pathologic types, tumor location, and presenting symptoms

Abstract  Background: Atrial myxoma is the most common cardiac neoplasm. Although not widely reported, two anatomic types have been observed: solid and papillary. We examined whether differences in gross or microscopic appearance and location correlated with symptomatology, specifically congestive heart failure (CHF), neurologic symptoms, and embolic events. Methods: We performed a retrospective review of atrial myxomas removed from 1972 to 2002, recording the clinical presentation, diagnostic modality, tumor location, gross, and microscopic features for each patient. Twenty‐six patients (16 females and 10 males) had atrial myxomas excised. Two patients (one female and one male) were excluded due to unavailable pathologic slides. Results: In 24 patients there were 15 solid and 9 papillary tumors. CHF was more prevalent in solid myxomas, while neurologic symptoms and embolic events were more common in papillary tumors. Tumor location further correlated with presenting symptoms. Ninety‐two percent of patients presenting with CHF had tumors attached to the atrial septum. Extraseptal myxomas more frequently presented with neurologic (80% vs. 29%) and embolic features (50% vs. 25%). All patients exhibiting clefted tumor surface had a history of embolization. A higher percentage of solid myxomas (93%) showed hemorrhage within the tumor than with papillary (56%). Conclusions: CHF was more common with solid myxomas, and neurologic and embolization events were more common in the papillary type. Septal tumor location showed strong association with CHF, while extraseptal location correlated with neurologic events. We speculate that the various gross and microscopic patterns reflect secondary changes within these neoplasms over the course of their natural history.

Elevated Pre-Operative Serum Peptides for Collagen I and III Synthesis Result in Post-Surgical Atrial Fibrillation

OBJECTIVES This study sought to determine if serum markers for collagen I and III synthesis, the carboxyl terminal peptide from pro-collagen I (PICP) and the amino terminal peptide from pro-collagen III (PIIINP), correlate with left atrial (LA) fibrosis and post-operative atrial fibrillation (AF). BACKGROUND AF after cardiac surgery is associated with adverse outcomes. We recently demonstrated that LA fibrosis is associated with post-operative AF in patients with no previous history of AF. METHODS Fifty-four patients having cardiac surgery without a history of AF consented to left and right atrial biopsies and a pre-operative peripheral blood draw. Picrosirius red staining quantified the percentage of fibrosis, and reverse transcriptase polymerase chain reaction assessed atrial tissue messenger ribonucleic acid transcripts involved in the fibrosis pathway. PICP and PIIINP levels were measured using an enzyme immunosorbent assay. RESULTS Eighteen patients developed AF, whereas 36 remained in normal sinus rhythm. LA fibrosis was higher in patients who developed AF versus normal sinus rhythm (6.13 ± 2.9% vs. 2.03 ± 1.9%, p = 0.03). LA messenger ribonucleic acid transcripts for collagen I, III, transforming growth factor, and angiotensin were 1.5- to 2.0-fold higher in AF patients. Serum PICP and PIIINP levels were highest in AF versus normal sinus rhythm (PICP: 451.7 ± 200 ng/ml vs. 293.3 ± 114 ng/ml, p = 0.006; PIIINP: 379 ± 286 pg/ml vs. 191.6 ± 162 pg/ml, p = 0.01). Furthermore, there was a linear correlation between LA fibrosis and serum PICP levels (R(2) = 0.2; p = 0.01), and of the markers, only PICP was independently associated with AF. CONCLUSIONS This demonstrates that serum PICP and PIIINP levels correlate with the presence of LA fibrosis and may act as predictors for post-operative AF even in the absence of previous history of AF.

Transfusion of cell saver salvaged blood in neonates and infants undergoing open heart surgery significantly reduces RBC and coagulant product transfusions and donor exposures: results of a prospective, randomized, clinical trial

Objective: To evaluate whether transfusion of cell saver salvaged, stored at the bedside for up to 24 hrs, would decrease the number of postoperative allogeneic RBC transfusions and donor exposures, and possibly improve clinical outcomes. Design: Prospective, randomized, controlled, clinical trial. Setting: Pediatric cardiac intensive care unit. Patients: Infants weighing less than 20 kg (n = 106) presenting for cardiac surgery with cardiopulmonary bypass. Interventions: Subjects were randomized to a cell saver transfusion group where cell saver blood was available for transfusion up to 24 hrs after collection, or to a control group. Cell saver subjects received cell saver blood for volume replacement and/or RBC transfusions. Control subjects received crystalloid or albumin for volume replacement and RBCs for anemia. Blood product transfusions, donor exposures, and clinical outcomes were compared between groups. Measurements and Main Results: Children randomized to the cell saver group had significantly fewer RBC transfusions (cell saver: 0.19 ± 0.44 vs. control: 0.75 ± 1.2; p = 0.003) and coagulant product transfusions in the first 48 hrs post-op (cell saver: 0.09 ± 0.45 vs. control: 0.62 ± 1.4; p = 0.013), and significantly fewer donor exposures (cell saver: 0.60 ± 1.4 vs. control: 2.3 ± 4.8; p = 0.019). This difference persisted over the first week post-op, but did not reach statistical significance (cell saver: 0.64 ± 1.24 vs. control: 1.1 ± 1.4; p = 0.07). There were no significant clinical outcome differences. Conclusion: Cell saver blood can be safely stored at the bedside for immediate transfusion for 24 hrs after collection. Administration of cell saver blood significantly reduces the number of RBC and coagulant product transfusions and donor exposures in the immediate postoperative period. Reduction of blood product transfusions has the potential to reduce transfusion-associated complications and decrease postoperative morbidity. Larger studies are needed to determine whether this transfusion strategy will improve clinical outcomes.

Decreased Incidence of Supravalvar Pulmonary Stenosis After Arterial Switch Operation

Background— Supravalvar pulmonary stenosis (SVPS) is frequently observed after arterial switch. Traditionally the coronary arteries are removed from the neopulmonic root by excising the entire sinus of Valsalva. As a result, reconstruction of the neopulmonic root requires a pericardial patch encompassing two-thirds of the anastomosis between the neopulmonic root and pulmonary artery. We present a technique where the coronary arteries are removed as limited buttons of sinus tissue, leaving the transected edge of the neopulmonic root intact. We hypothesize that maintaining native arterial tissue in the anastomosis between the neopulmonic root and the pulmonary artery bifurcation reduces postoperative SVPS. Methods and Results— We performed a retrospective review of neonates with D-transposition of the great arteries undergoing arterial switch procedure from 1996 to 2009. Charts were reviewed, and clinical outcomes recorded for each patient. Most recent echocardiograms were evaluated for right ventricular outflow tract obstruction. A total of 120 patients received arterial switch using this technique. There was 99% survival and no injuries to the coronary arteries regardless of anatomy. Total follow-up was 564 patient-years. Mean follow-up at last clinical visit was 66±46 months. Evaluation of the most recent outpatient echocardiogram revealed an average peak instantaneous gradient across the neopulmonic root of 22.5±5 mm Hg. Only 7 (5%) patients required reintervention (balloon dilation, n=5; surgery, n=2). Conclusions— Our technique of removing the coronary arteries as limited buttons, and anastomosis of the pulmonary artery using only native arterial tissue provides excellent midterm results with minimal SVPS.

Longer RBC storage duration is associated with increased postoperative infections in pediatric cardiac surgery.

Objectives: Infants and children undergoing open heart surgery routinely require multiple RBC transfusions. Children receiving greater numbers of RBC transfusions have increased postoperative complications and mortality. Longer RBC storage age is also associated with increased morbidity and mortality in critically ill children. Whether the association of increased transfusions and worse outcomes can be ameliorated by use of fresh RBCs in pediatric cardiac surgery for congenital heart disease is unknown. Interventions: One hundred and twenty-eight consecutively transfused children undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass who were participating in a randomized trial of washed versus standard RBC transfusions were evaluated for an association of RBC storage age and clinical outcomes. To avoid confounding with dose of transfusions and timing of infection versus timing of transfusion, a subgroup analysis of patients only transfused 1–2 units on the day of surgery was performed. Measurements and Main Results: Mortality was low (4.9%) with no association between RBC storage duration and survival. The postoperative infection rate was significantly higher in children receiving the oldest blood (25–38 d) compared with those receiving the freshest RBCs (7–15 d) (34% vs 7%; p = 0.004). Subgroup analysis of subjects receiving only 1–2 RBC transfusions on the day of surgery (n = 74) also demonstrates a greater prevalence of infections in subjects receiving the oldest RBC units (0/33 [0%] with 7- to 15-day storage; 1/21 [5%] with 16- to 24-day storage; and 4/20 [20%] with 25- to 38-day storage; p = 0.01). In multivariate analysis, RBC storage age and corticosteroid administration were the only predictors of postoperative infection. Washing the oldest RBCs (> 27 d) was associated with a higher infection rate and increased morbidity compared with unwashed RBCs. Discussion: Longer RBC storage duration was associated with increased postoperative nosocomial infections. This association may be secondary in part, to the large doses of stored RBCs transfused, from single-donor units. Washing the oldest RBCs was associated with increased morbidity, possibly from increased destruction of older, more fragile erythrocytes incurred by washing procedures. Additional studies examining the effect of RBC storage age on postoperative infection rate in pediatric cardiac surgery are warranted.

VADoscopy: a novel intraoperative technique to evaluate HeartMate II left ventricular assist device inflow obstruction and thrombosis.

With HeartMate II (HMII) implants increasing so has the frequency of device exchange. However, identifying inflow cannula obstruction, pump thrombosis, or outflow obstruction as the mechanism of pump dysfunction can be difficult. Echocardiography, CT angiogram, and cardiac catheterization are not definitive in determining the location of pump failure. Therefore, intraoperative examination is often necessary to confirm a diagnosis, requiring extensive dissection to visualize the entire system. We hypothesized a novel intraoperative technique, VADoscopy, can evaluate the inflow cannula for thrombus or pannus formation, and can help guide decision on which portion(s) of the HMII require replacement. Visualization of the inflow cannula can determine if either the pump itself or the pump along with the inflow cannula requires replacement, potentially limiting unnecessary dissection around the left ventricular apex and inflow cannula. A subxiphoid or subcostal incision exposes the pump. Patients are placed on cardiopulmonary bypass using the femoral vein and artery, after the outflow cannula is clamped. Once the pump is removed from the pocket, a 22 French 80 cm(Edwards Life Science, Irvine, CA) Fogarty balloon is advanced through the inflow cannula into the left ventricle and inflated to limit blood flow from the heart. A 5 French 30 cm flexible endoscope (Karl Starz Flex-X, Germany) is then placed into the inflow cannula and left ventricle to evaluate for the presence of thrombus, pannus, or debris. Six patients had HMII exchange with VADoscopy. In all patients, VADoscopy demonstrated no inflow cannula pannus or thrombus as the cause of pump dysfunction. Postoperatively there were no embolic events or evidence of reoccurring pump dysfunction suggesting an inflow cannula obstruction was not missed. VADoscopy is a novel and effective operative diagnostic modality to evaluate the inflow cannula within the HMII left ventricular assist device, limiting the amount of dissection, and potentially reducing the morbidity associated with HMII pump exchange.