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A unicuspid aortic valve is a very rare valvular lesion. Its physical manifestations vary and are associated with other cardiovascular abnormalities such as aortic stenosis/insufficiency and aortopathy. Echocardiography remains the modality of choice, with computerized tomography or cardiac magnetic resonance used as adjunctive imaging. Herein, we present a case series of three patients with unicuspid aortic valves treated at our institution, with a focus on 2D and 3D echocardiographic imaging.

BACKGROUND Mitral valve repair with papillary muscle approximation (MVr-PMA) for severe secondary mitral regurgitation (MR) decreases MR recurrence compared with MVr alone. This study assessed the effects of MVr-PMA on left ventricular (LV) remodeling and shape, systolic function and strain mechanics. METHODS Forty-eight patients who underwent MVr-PMA for severe secondary MR and had follow-up echocardiograms available for review were identified. Student's t-test, linear regression modeling, and receiver-operating characteristic curves were used in the statistical analyses. RESULTS Median follow-up time was 14.9 months. MVr-PMA was associated with significant LV reverse remodeling with a smaller LV end-diastolic diameter, systolic sphericity index, and interpapillary muscle distance at follow-up. Nine patients (18.8%) experienced ≥ moderate recurrent MR. When compared recurrent MR patients at follow-up, those with durable MVr-PMA had a greater LV ejection fraction (32.8 vs 22.0%, p=0.03), a smaller end-diastolic diameter (59.6 vs 67.3 mm, p=0.03), systolic sphericity index (0.35 vs 0.47, p=0.03), and endsystolic interpapillary muscle distance (16.3 vs 21.1 mm, p=0.03). A durable MVr-PMA also resulted in stable global longitudinal strain when compared with pre-operative values, while the recurrent MR group experienced a further decline (no recurrent MR: -8.4 vs -7.5%; recurrent MR: -8.2 vs -5.4%; p

Background The prognostic impact of tricuspid regurgitation (TR) following transcatheter aortic valve replacement (TAVR) is uncertain, and the management of patients with severe aortic stenosis and significant TR undergoing TAVR is unclear. Methods Retrospective study investigating the role of TR severity on hospital outcomes in high risk patients with severe aortic stenosis undergoing TAVR. Results A total of 174 participants were included in the present study. The median age was 84 years and 48% were women. The median (IR) STS score was 7.3 (4.7-13.6). The pre-procedural mean (SD) aortic valve area (AVA) was 0.69 (0.2) cm2 and the average (SD) peak and mean gradients were 71 [23]/42 [15] mmHg. Pre TAVR, 28.7% of patients had significant (moderate or severe) TR. Significant TR pre-TAVR increased the risk of in-hospital cardiovascular (CV) and all-cause and mortality [adjusted relative risk (RR) (95% CI): 14.67 (1.35-159.51) and 5.09 (1.14-22.72), respectively], and those with severe TR post-TAVR had longer hospital stay [median (IR): 9.9 (2.9-17.0) days]. No improvement or worsened TR (greater than mild) post-TAVR was associated with higher CV and all-cause mortality [adjusted RR (95% CI): 21.5 (1.81-255.96) and 8.19 (1.67-40.29), respectively]. Right ventricular systolic pressure (RVSP) was independently associated with TR severity pre and post TAVR. Conclusions Significant TR was common among patients undergoing high risk TAVR, and is associated with increased in hospital mortality and longer hospital stay. Patients with elevated RVSP and persistent moderate or severe TR after TAVR are at higher risk of in hospital death.

METHODS: Fifty-four patients who had combined mitral and tricuspid valve surgery were included. Right heart measurements were performed in the TTE apical 4-chamber (A4C) and RV inflow views, and TEE mid-esophageal 4-chamber (ME4C) and transgastric RV inflow views at end-diastole. Spearman correlation coefficients (r) were applied to test for associations between the imaging modalities. RESULTS: The mean age was 65 years and 39% were male. All patients had ≥ moderate tricuspid regurgitation (TR), and a secondary/functional etiology was present in 89%. The median TAd and RV basal (RVd) diameters in the TTE-A4C view measured 37 mm [interquartile range (IQR), 34–44] and 43 mm (IQR, 40–51), respectively. The TTE-A4C TAd strongly correlated with the TEE-ME4C measurement (r=0.72), with an overestimation of 1 mm (IQR, −2 to 4) by TEE (P

Rheumatic mitral valve disease remains an important cause of mitral regurgitation (MR), accounting for 7% to 15% of organic MR cases in large epidemiologic studies (1,2). Similarly, a history of radiation to the mediastinum, as is common in the treatment of several malignancies, is associated with future valve dysfunction in up to one-third of patients. Mitral valve repair (MVr) is favored over replacement for severe primary MR; this is due to a significant 30-day and mid to long-term mortality benefit, as well as a reduction in peri-operative complications (3,4). However, due to ongoing inflammation and leaflet infiltration, MVr in rheumatic or radiation-induced valvulitis may be associated with decreased durability and an increased risk of reoperation (5). In order to improve outcomes of MVr in these populations, adjunctive reparative procedures have been introduced. One such technique involves the use of autologous or bovine pericardium to reconstruct or enlarge the anterior mitral leaflet (AML) and normalize its coaptation with the posterior leaflet, with further reinforcement from a supporting annuloplasty ring (Figure 1) (6). While small studies suggest excellent mid-term survival with this approach, moderate or greater recurrent MR and reoperation occurs in 11.2% and 4.6% of patients, respectively, with rheumatic MR. Poor outcome data exists in the literature regarding MVr techniques for radiation-induced valvulitis (6,7). Herein, we provide an in-depth clinical and imaging appraisal of two such cases, with a focused review on pathophysiology and management. Open in a separate window Figure 1 MVr utilizing an annuloplasty ring and AML pericardial patch augmentation. (A) Schematic of AML pericardial patch augmentation MVr. There is a reconstructed and enlarged AML, normalized anterior and posterior leaflet coaptation, and reinforcement from a supporting annuloplasty ring; (B,C) systolic and diastolic transesophageal echocardiography mid-esophageal four-chamber views. Displayed is the augmented anterior mitral leaflet and pericardial patch (red arrow). MVr, mitral valve repair; AML, anterior mitral leaflet; PML, posterior mitral leaflet.

Secondary mitral regurgitation (MR) is a common finding in patients with dilated cardiomyopathy, and it is associated with poor outcomes. It is the result of incomplete systolic closure of the mitral valve (MV) as a consequence of left ventricular dilatation, papillary muscle displacement with impaired systolic shortening, and mitral leaflet tethering. MV surgery may be performed in cases of significant secondary MR despite guideline-directed medical therapy. However, MV repair, which is most commonly performed with an undersized ring annuloplasty, is associated with a 30-60% recurrence of moderate or greater MR at mid-term follow-up. To improve MV repair durability, several adjunctive subvalvular procedures have been proposed, one of which is the addition of papillary muscle approximation utilizing a papillary muscle sling. Recent studies comparing the outcomes of a conventional undersized ring annuloplasty with a MV repair utilizing a papillary muscle sling have reported a significant reduction in recurrent moderate or severe MR, greater left ventricular reverse remodeling, and improved MV apparatus geometry with the addition of the papillary muscle sling. We present a comprehensive review of the pathophysiology of secondary MR, and the rationale and clinical outcomes of MV repair with papillary muscle sling placement for the treatment of secondary MR.

Background: Combining a ring annuloplasty (Ring) with a mitral subvalvular intervention (Ring + subvalvular) in patients with secondary mitral regurgitation (MR) may improve mitral valve (MV) repair durability. However, the outcomes of this strategy compared with a Ring only, have not been clearly defined. Methods: A systematic review and meta-analysis was performed utilizing randomized controlled and propensity matched studies which compared a Ring + subvalvular versus Ring MV repair for the treatment of secondary MR. Risk ratio (RR), weighted mean difference (MD), and the 95% confidence interval (CI) were calculated by the Mantel-Haenszel and inverse-variance methods, for clinical outcomes and echocardiographic measures of follow-up MR, left ventricular (LV) reverse remodeling, and MV apparatus geometry. Results: Five studies were identified, with a total of 397 patients. Baseline characteristics were similar between groups, and all patients had moderate to severe secondary MR, with the vast majority in the setting of ischemic cardiomyopathy. A Ring + subvalvular repair consisted of papillary muscle approximation (n=2), papillary muscle relocation (n=2), or secondary chordal cutting (n=1). Follow-up ranged from 10.1 (mean range =0.25–42) to 69 [interquartile range (IQR) =23–82] months. When compared with Ring only at last follow-up, a Ring + subvalvular MV repair was associated with: (I) a smaller MR grade (MD =−0.44, 95% CI −0.69 to −0.19; P=0.0005); (II) a reduced risk of moderate or greater recurrent MR (RR =0.43, 95% CI, 0.27–0.66; P=0.0002); (III) a smaller mean LV end-diastolic diameter (MD =−3.56 mm, 95% CI −5.40 to −1.73; P=0.0001) and a greater ejection fraction (MD =2.64%, 95% CI, 0.13–5.15; P=0.04); and, (IV) an improved MV apparatus geometry. There were no differences in operative mortality, post-operative morbidity, or follow-up survival between surgical approaches. Conclusions: When compared with Ring only, a Ring + subvalvular MV repair is associated with greater LV reverse remodeling and systolic function, less recurrence of moderate or greater MR, and an improved geometry of the MV apparatus at short and mid-term follow-up.

Background: Double valve surgery is associated with an increased peri-operative morbidity and mortality. A less invasive right thoracotomy approach may be a viable alternative to median sternotomy surgery in these higher-risk patients. Methods: We retrospectively analyzed the baseline demographics, operative characteristics, and post-operative outcomes of patients who underwent minimally invasive double valve surgery between January 2009 and December 2011 at our institution. Results: The cohort consisted of 117 patients, of which 68 (58.1%) were female. The mean age was 73±11 years, and the mean left ventricular ejection fraction was 52±11%. There were 43 (36.8%) patients with a history of congestive heart failure, 45 (38.5%) with chronic obstructive pulmonary disease, and 5 (4.3%) had a history of chronic kidney disease. The patients underwent primary (90.6%) or re-operative (9.4%) double valve surgery, which consisted of 50 (42.7%) aortic valve replacement and mitral valve repair, 31 (26.5%) mitral and tricuspid valve repair, 18 (15.4%) aortic and mitral valve replacement, 17 (14.5%) mitral valve replacement with tricuspid valve repair, and 1 (0.9%) aortic valve replacement with tricuspid valve repair. Post-operatively, there were 40 (34.2%) cases of prolonged ventilation, 9 (7.7%) acute kidney injury, 6 (5.1%) re-operations for bleeding, 1 (0.9%) cerebrovascular accident, and 15 (12.8%) cases of atrial fibrillation. The mean total hospital length of stay was 12±12 days, with an in-hospital mortality of 2 (1.7%). Conclusions: A minimally invasive right thoracotomy approach to primary or re-operative double valve surgery is feasible, may be utilized with acceptable peri-operative morbidity and mortality.

Open total arch replacement (TAR) has become safer with refinements in cerebral protection techniques. The frequent extension of aortic arch aneurysms into the descending thoracic aorta customarily requires a two-staged conventional elephant trunk procedure, carrying relatively high mortality and morbidity risks and high rates of rupture in the interval between the two open surgeries. The technical demands and invasive nature of TAR has therefore precluded many high-risk patients from being surgical candidates for aneurysm repair. As a result, hybrid techniques and approaches to the aortic arch have become common since the adoption of thoracic endovascular aortic repair (TEVAR) and advancement in the commercial grafts that are available. The results of hybrid aortic arch repairs have been encouraging, though with higher rates of re-interventions than TAR and variable reported rates of stroke and spinal cord ischemia. The aim of this publication is to review the current literature on hybrid repair of aortic arch aneurysms.

Background: We evaluated the outcomes of patients with aortic valve pathology in the setting of a left ventricular ejection fraction ≤35% who underwent minimally invasive aortic valve replacement (AVR), with or without concomitant mitral valve (MV) surgery. Methods: All minimally invasive AVR in patients with a left ventricular ejection fraction ≤35%, performed via a right thoracotomy for aortic stenosis or regurgitation between January 2009 and March 2013, were retrospectively evaluated. The operative characteristics, perioperative outcomes, and 30-day mortality were analyzed. Results: There were 75 patients identified: 51 who underwent isolated AVR, and 24 who had combined AVR plus MV surgery for moderate to severe mitral regurgitation. In patients undergoing MV surgery, there were 22 (91.7%) MV repairs [ring annuloplasty =7 (37.5%), transaortic edge-to-edge repair =15 (62.5%)], and 2 (8.3%) replacements. No patient required conversion to sternotomy for inadequate surgical field exposure. The median total mechanical ventilation time and intensive care unit length of stay were 14 (IQR, 8–20) and 42 hours (IQR, 26–93 hours) in the isolated AVR group, and 16.5 hours (IQR, 12–61.5 hours) and 95.5 hours (IQR, 43.5–159 hours) in the AVR plus MV surgery group, respectively. The most common post-operative complication was new-onset atrial fibrillation, which occurred in 15 (29.4%) isolated AVR and 4 (16.7%) AVR plus MV surgery patients. The median hospital length of stay and 30-day mortality was 7 days (IQR, 5–12 days) and 1 (2%) in the isolated AVR group, and 10.5 days (IQR, 5–21 days) and 1 (4.3%) for AVR plus MV surgery. Conclusions: In patients with aortic valve pathology in the setting of a left ventricular ejection fraction ≤35%, minimally invasive AVR can be performed, with or without concomitant MV surgery, with a low morbidity and mortality.

The use of minimally, or less invasive, approaches to cardiac valve surgery has increased over the past decade. Because of its less traumatic nature, early studies in lower risk patients demonstrated the approach to be associated with an enhanced recovery, increased patient satisfaction, and good operative outcomes. With time, despite a steep learning curve, surgeons expanded this approach to perform more complex procedures, and include patients with more co-morbidity. The aim of this publication is to review the current literature involving the use of minimally invasive valve surgery (MIVS) in higher-risk patients.

Background: The optimal treatment for concomitant two-vessel coronary artery disease (CAD) and moderate to severe ischemic mitral regurgitation (IMR) remains unclear. We compared the results of a staged percutaneous coronary intervention followed by minimally invasive mitral valve surgery (PCI+MIVS) versus combined coronary artery bypass graft and mitral valve surgery (CABG+MVS) in this population. Methods: All consecutive patients with two-vessel CAD and moderate to severe IMR, who underwent PCI+MIVS or CABG+MVS at our institution between February 2009 and April 2014, were retrospectively evaluated. Results: There were nine patients identified who underwent PCI+MIVS, and 15 who underwent CABG+MVS, with a mean age of 71±7, and 70±7 years, respectively (P=0.86). The remaining baseline characteristics were similar between both groups, with the exception of a higher prevalence of pre-operative clopidogrel administration (78% versus 27%, P=0.03) and left anterior descending plus left circumflex CAD (78% versus 27%, P=0.03), in those who underwent PCI+MIVS. The PCI+MIVS approach was associated with decreased mean cardiopulmonary bypass (111±41 versus 167±49 min, P=0.01) and aortic cross-clamp (79±32 versus 129±35 min, P=0.003) times, and less median number of intraoperative packed red blood transfusions {2 [interquartile range (IQR), 0–2] versus 3 units (IQR, 1–4), P=0.05}, when compared with CABG+MVS. The rate of mitral valve repair, postoperative complications, 30-day mortality, and 1-year survival did not differ between the surgical approaches. Conclusions: PCI+MIVS for two-vessel CAD and moderate to severe IMR is feasible, and associated with satisfactory outcomes, as compared with CABG+MVS.

Background: A massive pulmonary embolism (PE) is associated with high mortality once cardiac arrest occurs. Surgical embolectomy is indicated in patients who have massive PE. Case Report: A 62-year-old male emergently underwent surgical embolectomy after sustaining an intraoperative cardiac arrest caused by a massive PE during an open reduction with internal fixation of a closed comminuted midshaft tibia fracture. Postoperatively, the patient developed pulmonary hypertension and acute renal failure. He was treated with aerosolized epoprostenol for right ventricular strain secondary to pulmonary hypertension. He survived the hospital course and was discharged without any other major complications. Conclusion: Surgical embolectomy is a viable option for massive PE, and aerosolized epoprostenol can be used as adjuvant treatment for right ventricular strain secondary to acute pulmonary hypertension.

Background: In patients with prior cardiac surgery requiring re-operative coronary and valve surgery, a hybrid approach of percutaneous coronary intervention followed by minimally invasive valve surgery (PCI + MIVS) may be an alternative to the standard median sternotomy coronary artery bypass and valve surgery (CABG + valve). Methods: The outcomes of patients with prior cardiac surgery, presenting with coronary artery and valvular disease, who underwent PCI + MIVS (N=39) were retrospectively compared with those who underwent CABG + valve (N=28) via a repeat median sternotomy, between February 2009 and April 2014. Results: The mean age for the PCI + MIVS versus CABG + valve group was 75±9 and 72±11 years (P=0.54), respectively. The baseline characteristics were similar between groups, with the exception of a greater prevalence of 1-vessel coronary artery disease and clopidogrel or dual antiplatelet therapy at the time of surgery in the PCI + MIVS group, and more 3-vessel coronary artery disease in those undergoing CABG + valve surgery. The PCI + MIVS approach was associated with a decreased aortic cross-clamp (94 vs . 131 minutes, P=0.001) and cardiopulmonary bypass (128 vs . 190 minutes, P vs . 3.8 units, P=0.001), shorter intensive care unit length of stay (41 vs . 71 hours, P vs . 35.7%, P=0.03), re-intubation (2.6% vs . 17.9%, P=0.04), when compared with CABG + valve. The thirty-day and two-year mortality were similar, being 7.7% vs . 7.1% (P=0.66), and 12.8% vs . 10.7% (P=0.55), in the PCI + MIVS vs . CABG + valve group, respectively. Conclusions: Hybrid PCI + MIVS in patients with prior cardiac surgery is associated with shorter operative times and intensive care unit length of stay, less need for intraoperative blood cell transfusions, decreased use of mechanical ventilation, and similar short-term and follow-up survival, when compared with CABG + valve surgery via median sternotomy. Randomized trials and multicenter registries are needed to further evaluate this approach.

Background: The current study evaluated the safety and feasibility of staged (“hybrid”) percutaneous coronary intervention (PCI) followed by isolated minimally invasive mitral valve (MV) surgery [PCI + minimally invasive mitral valve surgery (MIMVS)], for patients with concomitant coronary artery and MV disease. Methods: A total of 93 patients who underwent PCI + MIMVS for coronary artery and MV disease between February 2009 and April 2014 were retrospectively analyzed. Results: There were 54 (58.1%) men and 39 (41.9%) women. The mean age was 73±8 years, and all patients had severe mitral regurgitation. PCI was performed for single-vessel coronary artery disease in 40 (43%) patients, two-vessel in 49 (52.7%), and three-vessel in 4 (4.3%). Within a median of 48 days (IQR, 18–71) after PCI, 78 (83.9%) patients underwent primary valve surgery, and 15 (16.1%) underwent re-operative valve surgery, with 56 (60.2%) having MV replacement, and 37 (39.8%) having MV repair. Sixty-five (69.9%) patients were being treated with dual anti-platelet therapy at the time of surgery. The median number of transfused intra-operative red blood cell units was 1 (IQR, 0–2), and the intensive care unit and hospital lengths of stay were 46 hours (IQR, 27–76) and 8 days (IQR, 5–11), respectively. Post-operatively, there was 1 (1.1%) cerebrovascular accident, 2 (2.2%) patients developed acute kidney injury, and 4 (4.3%) required a re-operation for bleeding. Thirty-day mortality occurred in 4 (4.3%) patients. At a mean follow-up of 15.3±13.2 months, 3 (3.4%) patients required target-vessel revascularization. The survival rate was 89% and 85% at 1 and 3 years, respectively. Conclusions: In patients with concomitant coronary artery and MV disease, PCI + MIMVS can be safely performed and is associated with good short-term and follow-up outcomes.

Background: In patients requiring coronary revascularization and aortic valve replacement, a combined approach of percutaneous coronary intervention followed by minimally invasive aortic valve replacement may be a viable treatment strategy. Methods: The outcomes of 123 consecutive patients with significant coronary artery and aortic valve disease, who underwent percutaneous coronary intervention followed by elective minimally invasive aortic valve replacement between February 2009 and April 2014, were retrospectively evaluated. Results: The cohort consisted of 80 males and 43 females, with a mean age of 75.7±8.1 years. Drug-eluting stents were used in 69.9% of the patients, and 64.2% were on dual anti-platelet therapy at the time of aortic valve replacement. Within a median of 39 days (IQR 21–64), 83.7% of the patients underwent primary and 16.3% underwent re-operative minimally invasive aortic valve replacement. Post-operatively, there was 1 (0.8%) cerebrovascular accident, 1 patient (0.8%) required a re-operation due to bleeding, and 2 (1.6%) developed acute kidney injury. Thirty-day mortality occurred in 2 (1.6%) patients. Follow-up was available for all of the patients, and at a mean follow-up period of 14.3±12.5 months, 4 (3.3%) had an acute coronary syndrome, and 1 (0.8%) required a repeat target vessel revascularization. The actuarial survival rate at 1- and 3-year was 92.7% and 89.4%, respectively. Conclusions: In a select group of patients with coronary artery and aortic valve disease, a combined approach of percutaneous coronary intervention followed by minimally invasive aortic valve replacement can be safely performed with excellent short-term and midterm outcomes.

Transcatheter valve implantation in the mitral position with severe calcific mitral stenosis has been described in patients who are at an increased risk for conventional mitral valve surgical procedures. We report the direct deployment of the Sapien 3 valve in the mitral position with severe mitral annular calcification through a sternotomy in an arrested heart in two cases.

Objective The study objective was to determine the effects of implementing a blood conservation algorithm on blood product use and outcomes in a community cardiac surgery program. Methods A blood management strategy including lower hemoglobin transfusion threshold and algorithm-driven decisions was adopted. Intraoperatively, point-of-care testing was used to avoid inappropriate component transfusion. A low prime perfusion circuit was adopted. Blood was withdrawn from patients before initiating bypass when possible. Patients undergoing coronary and valve procedures were included. Outlier patients receiving more than 10 units packed red blood cells were excluded. Data were collected for 6 months as a baseline group (group I). A 3-month period of program implementation was allotted. Data were subsequently collected for 6 months and comprised the study patients (group II). Prospective data were collected on demographics, blood use, and outcomes. Results Group I comprised 481 patients, and group II comprised 551 patients. Group II received fewer units of packed red blood cells, fresh-frozen plasma, and cryoprecipitate than group I. There was no difference in platelets transfused. Total blood product use was reduced by 40% in group II ( P 001). The overall 30-day mortality was 1.3%. There were no differences in mortality, reoperation for bleeding, or other postoperative outcomes between the groups. Conclusions Implementation of a comprehensive blood conservation algorithm can be rapidly introduced, leading to reductions in blood and component use with no detrimental effect on early outcomes. Point-of-care testing can direct component transfusion in coagulopathic cases, with most coagulopathic patients requiring platelets. Further research will determine the effects of reduced transfusions on long-term outcomes.

Background: It has been reported that erythropoietin (EPO) attenuates ischemia-induced damage in a variety of tissues. It is unknown whether EPO alters the left ventricular (LV) remodeling process after ischemic insult. Accordingly, we tested the potential benefits of carbamylated EPO (CEPO) on LV remodeling in rats with myocardial infarction (MI). Methods: MI was induced by coronary artery ligation in adult male Sprague-Dawley rats. One hour after surgery, rats were randomly assigned to 1 of 2 groups: MI plus placebo injections (placebo, n = 21) and MI plus CEPO injection (CEPO, n = 22). CEPO (10 μg/kg) or placebo was given via tail vein in a blinded fashion daily for the first 3 days, followed by twice a week subcutaneous injection for 6 weeks. Sham surgery was performed in another group of rats (n = 18) without coronary artery ligation. Cardiac function was assessed by echocardiography, hemodynamic, and in vivo and ex vivo LV pressure-volume relationship measurements 6 weeks after MI. Results: In comparison to placebo-treated rats, CEPO significantly improved LV geometry (LV end systolic dimension: 8.6 ± 0.8 vs. 9.6 ± 1.0 mm; LV end systolic volume: 404 ± 83 vs. 516 ± 122 μL, both P < 0.05). CEPO therapy also reduced the decline of systolic function (fractional shortening: -3.7% ± 1.7% vs. -10.9% ± 2.3%; E max 0.46 ± 0.20 vs. 0.25 ± 0.08 mm Hg/s, both P < 0.05). Passive diastolic properties of the LV were minimally improved by leftward shift in the ex vivo end diastolic pressure-volume relationship. Conclusions: CEPO administration 1 hour after acute MI improves systolic performance and may attenuate the LV remodeling process. Further studies to determine the mechanism of CEPO responsible for its beneficial effects and optimize dosing and timing regimens are warranted.

The lung allocation score (LAS) was initiated in May 2005 to allocate lungs based on medical urgency and posttransplant survival. The purpose of this study was to determine if there is an association between an elevated LAS at the time of transplantation and increased postoperative morbidity and mortality.The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant recipients agedor= 12 years who received transplants between April 5, 2006, and December 31, 2007 (n = 3,836). Recipients were stratified into three groups: LAS50 (n = 3,161, 83.87%), LAS 50 to 75 (n = 411, 10.9%), and LASor= 75 (n = 197, 5.23%), referred to as low LAS (LLAS), intermediate LAS (ILAS), and high LAS (HLAS), respectively. The primary outcome was posttransplant graft survival at 1 year. Secondary outcomes included length of stay and in-hospital complications.HLAS recipients had significantly worse actuarial survival at 90 days and 1 year compared with LLAS recipients. When transplant recipients were stratified by disease etiology, a trend of decreased survival with elevated LAS was observed across all major causes of lung transplant. HLAS recipients were more likely to require dialysis or to have infections compared with LLAS recipients (P.001). In addition, length of stay was higher in the HLAS group when compared with the LLAS group (P.001).HLAS is associated with decreased survival and increased complications during the transplant hospitalization. Whereas the LAS has improved organ allocation through decreased waiting list deaths and waiting list times, lower survival and higher morbidity among HLAS recipients suggests that continued review of LAS scoring is needed to ensure optimal long-term transplant survival.

The effects of exogenous B-type natriuretic peptide (BNP) on postmyocardial infarction (MI) are not known. We tested the hypothesis that in vivo infusion of BNP would improve cardiac function and affect left ventricular (LV) remodeling in an experimental model of MI.MI was induced by coronary ligation in rats and confirmed by echocardiography. 19 rats were randomized to 1 of 3 groups: sham (n = 7), MI + saline (n = 5), MI + BNP (400 ng.kg(-1).minute(-1)) (n = 7). Infusions were delivered for 7 days via venous catheters tunneled to an infusion pump. Rats were followed for 8 weeks. Echocardiography, hemodynamics, histology, and in vivo and ex vivo pressure-volume relationships were examined.LV systolic pressure, LV dP/dtmax, and infarct size improved with BNP treatment versus control MI group (132 +/- 4 vs.110 +/- 2 mm Hg, 8097 +/- 317 vs. 5816 +/- 378 mm Hg/s, 19.3% +/- 1.6% vs. 23.3% +/- 1.9%, respectively; all P0.05). Ex vivo end-diastolic pressure-volume relationship demonstrated reduced diastolic dysfunction after BNP therapy (P0.05 vs. control MI). Serum BNP levels confirmed delivery of BNP.We demonstrate beneficial effects on LV function and decreased LV remodeling with BNP infusion in an experimental model of acute MI.

The benefit of the beta(2)-adrenergic agonist, clenbuterol, in left ventricular assist device patients with dilated cardiomyopathy has been reported, but its effect on ischemic heart failure (HF) is unknown. We investigated whether clenbuterol improves left ventricular remodeling, myocardial apoptosis and has synergy with a beta(1) antagonist, metoprolol, in a model of ischemic HF. Rats were randomized to: 1) HF only; 2) HF + clenbuterol; 3) HF + metoprolol; 4) HF + clenbuterol + metoprolol; and 5) rats with sham surgery. HF was induced by left anterior descending artery (LAD) artery ligation and confirmed by decreased left ventricular fractional shortening, decreased maximum left ventricular dP/dt (dP/dt(max)), and elevated left ventricular end-diastolic pressure (LVEDP) compared with sham rats (p < 0.01). After 9 weeks of oral therapy, echocardiographic, hemodynamic, and ex vivo end-diastolic pressure-volume relationship (EDPVR) measurements were obtained. Immunohistochemistry was performed for myocardial apoptosis and DNA damage markers. Levels of calcium-handling proteins were assessed by Western blot analysis. Clenbuterol-treated HF rats had increased weight gain and heart weights versus HF rats (p < 0.05). EDPVR curves revealed a leftward shift in clenbuterol rats versus metoprolol and HF rats (p < 0.05). The metoprolol-treated group had a lower LVEDP and higher dP/dt(max) versus the HF group (p < 0.05). Clenbuterol and metoprolol groups had decreased myocardial apoptosis and DNA damage markers and increased DNA repair markers versus HF rats (all p < 0.01). Protein levels of the ryanodine receptor and sarcoplasmic reticulum calcium-ATPase were improved in clenbuterol-, metoprolol-, and clenbuterol+metoprolol-treated groups versus HF rats. However, as a combination therapy, there were no synergistic effects of clenbuterol+metoprolol treatment. We conclude that clenbuterol ameliorates EDPVR, apoptosis, and calcium homeostasis but does not have synergy with metoprolol in our model of ischemic HF.

Mechanical unloading during left ventricular assist device (LVAD) support may lead to cardiac recovery. Predictors of recovery, however, have not been identified. We aimed to evaluate the time course and durability of echocardiographic, electrocardiographic (ECG), histologic, and neurohormonal changes that occur with LVAD support and to screen for non-invasive markers of cardiac recovery.LVAD patients underwent monthly testing, including echocardiographic, ECG, and serum B-type natriuretic peptide (BNP) measurement. Paired myocardial tissue samples from implant and explant were also analyzed.Thirty-six LVAD patients were prospectively followed for an average of 101 +/- 99 days. Left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD) significantly improved at 30 days compared with pre-LVAD (19% +/- 6.6% vs 33% +/- 8.1%, 7.1 +/- 1.2 cm vs 4.9 +/- 1.0 cm, respectively; both p0.001), with no improvement thereafter. At 30 days, QRS duration and QTc interval were significantly decreased from pre-LVAD (both p0.05). There was a marked reduction in BNP, myocyte size, and collagen deposition with LVAD support (all p0.01). In screening for markers of recovery, the decrease in QTc was inversely related to LVEDD at 60 days. Changes in QRS and myocyte diameter also correlated with the improvement in LVEF at 30 days. No patients had sufficient recovery for device explantation.We demonstrate echocardiographic, ECG, histologic, and neurohormonal improvement during LVAD support. Cardiac recovery peaked by 60 days, and there was a trend toward progressive improvement in QRS duration with ongoing support. We report the association of ECG changes with echocardiographic and histologic improvements. Future prospective studies may yield important markers of recovery.

Our aim was to determine the effect of left ventricular assist device (LVAD) implantation on bypass graft patency and to measure myocardial oxygen consumption (MVO 2 ) and blood flow during LVAD support. Five patients who underwent coronary artery bypass grafting and required LVAD implantation for post-cardiotomy cardiogenic shock had coronary angiography during device support to assess graft patency. Positron emission tomography measurements were made in a separate cohort of LVAD patients with dilated cardiomyopathy to assess the effects of LVAD support on MVO 2 and myocardial blood flow. In this small series, LVAD unloading led to a high rate of premature graft occlusion in post-cardiotomy cardiogenic shock patients supported with a device; whereas, positron emission tomography measurements showed significantly reduced MVO 2 and myocardial flood flow in dilated cardiomyopathy patients supported with an LVAD, compared with healthy subjects. Reduced myocardial blood flow may be implicated in the premature graft failure observed in post-cardiotomy cardiogenic shock patients and may negatively impact the potential for myocardial recovery and device weaning in this population.

Background Studies have associated anti-HLA antibodies detected by panel-reactive antibody (PRA) with increased risk for rejection and transplant coronary artery disease (TCAD) in adults, but the role of PRAs in monitoring immunologic status after pediatric cardiac transplantation has not been described. Methods We reviewed post-transplant PRAs in 96 pediatric heart recipients. PRAs were performed concurrently with endomyocardial biopsy and if rejection was suspected. The presence of anti-HLA IgG antibodies was defined as >10% reactivity. Pre-transplant variables, including age, race, gender, pre-transplant PRAs and presence of a mechanical assist device, were correlated with post-transplant PRAs. Outcome variables included rejection history, TCAD incidence and survival. Results The mean age of patients was 9.0 ± 6.8 years. A mean of 8.1 ± 5.3 PRAs were measured over a follow-up period of 4.8 ± 2.7 years. There was a mean of 0.55 ± 0.71 rejection events per patient-year, and TCAD was detected in 19 (22%) patients. Nineteen patients (20%) had anti-HLA Class I antibodies and 37 (39%) had Class II antibodies detected after transplant. There was no association between Class I antibodies and survival, TCAD or rejection. Class II antibodies were associated with worse survival and a decreased time-free of TCAD. Class II antibodies were also associated with rejection at the time of measurement (sensitivity 17%, specificity 94%) and for the ensuing 3 months (sensitivity 12%, specificity 94%). Conclusions Class II anti-HLA antibodies correlate with worse patient outcomes and rejection episodes after pediatric cardiac transplant. A low sensitivity precludes use as a sole diagnostic tool, but post-transplant PRAs may be an important adjunct in a multi-faceted algorithm to assess immunologic status.

Tricuspid regurgitation (TR) may lessen the potential benefits of TAVR. We aimed to investigate the impact of TR on TAVR outcomes and to ascertain factors associated with TR severity. Patients with severe aortic stenosis that underwent TAVR at MSMC, Miami Beach, FL from August, 1st 2014 to January

An experimental system was devised to study the mecha-nisms by which cells become committed to the cardiac myocyte lineage during avian development. Chick tissues from outside the fate map of the heart (in the posterior primitive streak {PPS} of a Hamburger & Hamilton stage 4 embryo) were combined with potential inducing tissues from quail embryos and cultured in vitro. Species-specific RT-PCR was employed to detect the appearance of the cardiac muscle markers chick Nkx-2.5 (cNkx-2.5), cardiac troponin C and ventricular myosin heavy chain in the chick responder tissues. Using this procedure, we found that stage 4-5 anterior lateral (AL) endoderm and anterior central (AC) mesendoderm, but not AL mesoderm or posterior lateral mesendoderm, induced cells of the PPS to differentiate as cardiac myocytes. Induction of cardiogen-esis was accompanied by a marked decrease in the expression of ρ-globin, implying that PPS cells were being induced by anterior endoderm to become cardiac myocytes instead of blood-forming tissue. These results suggest that anterior endoderm contains signaling molecules that can induce cardiac myocyte specification of early primitive streak cells. One of the cardiac muscle markers induced by anterior endoderm, cNkx-2.5, is here described for the first time. cNkx-2.5 is a chick homeobox-containing gene that shares extensive sequence similarity with the Drosophila gene tinman, which is required for Drosophila heart formation. The mesodermal component of cNkx-2.5 expression from stage 5 onward, as determined by in situ hybridization, is strikingly in accord with the fate map of the avian heart. By the time the myocardium and endocardium form distinct layers, cNkx-2.5 is found only in the myocardium. cNkx-2.5 thus appears to be the earliest described marker of avian mesoderm fated to give rise to cardiac muscle.

Background— Myocardial recovery after left ventricular assist device (LVAD) support has been reported. The LVAD Working Group Recovery Study was a prospective multicenter trial to assess the incidence of myocardial recovery in patients bridged to cardiac transplantation. Methods and Results— After LVAD implantation, patients were evaluated with the use of rest echocardiograms with partial LVAD support and cardiopulmonary exercise testing. Dobutamine echocardiography with hemodynamic measurements was performed in those patients with left ventricular ejection fraction >40% during resting studies. Histological analysis was performed on myocardial samples taken at LVAD implantation and explantation. Sixty-seven LVAD patients with heart failure participated in the study. After 30 days, significant improvement occurred in left ventricular ejection fraction (17±7% versus 34±12%; P P P 40% with partial device support. Left ventricular ejection fraction decreased over time to pre-LVAD measurement by 120 days. Peak V̇ o 2 improved with mechanical support (13.7±4.2 versus 18.9±5.5 mL/kg per minute, 30 versus 120 days; P Conclusions— Cardiac function improves significantly after device implantation. Although cellular recovery and improvement in ventricular function are observed, the degree of clinical recovery is insufficient for device explantation in most patients with chronic heart failure.

Inhaled nitric oxide (iNO) use is widespread, but the long-term outcomes after therapy in adult patients remain unknown.All 376 patients receiving perioperative iNO (excluding pediatric and interventional cardiology procedures) at Columbia University Medical Center were prospectively followed from 2000 to 2003. Survival data were collected from chart review.Inhaled nitric oxide was used to treat pulmonary and right ventricular failure in patients undergoing orthotopic heart transplantation (OHT, n = 67), orthotopic lung transplantation (n = 45), cardiac surgery (n = 105), and ventricular assist device placement (n = 66), and for hypoxemia in other surgery (n = 34) and medical patients (n = 59). Average follow-up was 2.9 +/- 1.0 years. Overall mortality was lowest when iNO was used after OHT (25.4%) and orthotopic lung transplantation (37.8%), intermediately after cardiac surgery (61%), ventricular assist device (62%), and other surgery patients (75%), and highest among medical patients (90%; all p0.005). The cost of iNO therapy was lower in transplantation versus medical patients, with a trend toward shorter duration of use. In multivariate analysis, respiratory failure and use in non-OHT were independent predictors of mortality (both p = 0.001). A risk score greater than 1 (score = non-OHT use 1, plus right ventricular failure 1) predicted a mortality of 76.5% versus 37.2% (p0.001).Use of iNO for pulmonary hypertension in patients undergoing OHT and orthotopic lung transplantation was associated with a significantly lower overall mortality rate compared with its use after cardiac surgery or for hypoxemia in medical patients. Inhaled nitric oxide does not appear to be cost effective when treating hypoxemia in medical patients with high-risk scores and irreversible disease.

High-dose clenbuterol (a selective beta2-adrenergic agonist) has been proposed to promote myocardial recovery during left ventricular assist device (LVAD) support, but its effects on cardiac and skeletal muscle are largely unknown.Seven subjects with heart failure (5 ischemic, 2 non-ischemic) were started on oral clenbuterol 5 to 46 weeks post-LVAD implantation and up-titrated to daily doses of 720 microg. The following procedures were performed at baseline and after 3 months of therapy: echocardiography at reduced support (4 liters/min); cardiopulmonary exercise testing; body composition analysis; and quadriceps maximal voluntary contraction (MVC). Myocardial histologic analysis was measured at device implantation and explantation.There were no serious adverse events or arrhythmias. Creatine phosphokinase (CPK) was elevated in 4 subjects, with no clinical sequelae. No change in ejection fraction was seen. End-diastolic dimension increased significantly (4.73 +/- 0.67 vs 5.24 +/- 0.66; p0.01), despite a trend toward increased LV mass. Body weight and lean mass increased significantly (75.5 +/- 17.9 vs 79.2 +/- 25.1 kg, 21.1 +/- 8.9 vs 23.6 +/- 9.7 kg, respectively; both p0.05). Exercise capacity did not change, but MVC improved significantly from 37.0 +/- 15.7 to 45.8 +/- 20.6 kg (p0.05). No significant change in myocyte size or collagen deposition was seen.Cardiac function did not improve in this cohort of LVAD patients treated with high-dose clenbuterol. However, clenbuterol therapy increased skeletal muscle mass and strength and prevented the expected decrease in myocyte size during LVAD support. Further study will clarify its potential for cardiac and skeletal muscle recovery.

A picture of William E. Ladd appears on this issue’s cover. The photograph is reprinted with permission from Springer-Verlag. It is from Bill AH. William E. Ladd, M.D.: Great pioneer of North American pediatric surgery. Progr Pediatr Surg. 1986;20:52-59. William E. Ladd (1880-1967) became a surgeon at the start of the twentieth century. Advances of the prior 100 years included the development of the stethoscope by Laennec in 1816, the introduction of ether anesthesia with Long’s and Morton’s independent discovery in the 1840s, the application of Pasteur’s germ theory with the development of antiseptic surgical techniques by Lister in 1865, and the expansion of diagnostic means by Roentgen’s discovery of x-rays in 1895. 1 Still, survival was rare for a newborn child with a significant congenital anomaly or any child requiring major surgery in the United States and abroad. 2 The prevailing conditions upon Ladd’s graduation from medical school were indeed primitive as we look back. Blood transfusions were not safe, intravenous fluids did not exist, and monitoring was not introduced into anesthetic management. There were no antibiotics to help prevent or treat infections, and there were few effective medications other than digitalis, aspirin, and opiates. Surgeons utilizing ether or chloroform anesthesia relied more on speed than on precision. The relatively few procedures performed concentrated on draining pus, relieving obstructions, and repairing broken bones. Major elective operations were more feared and talked about than performed. Furthermore, pediatric surgery was even more challenging than was adult surgery. In the words of Dr. C. Everett Koop, “Surgeons in general were frightened of children and distrusted anesthetists to wake them up after putting them to sleep.” 3 We will follow Ladd’s career through this era as he led the charge of the development of pediatric surgery, as we know it today.

Over a 2-year period, 5 patients who required reoperative chest surgery underwent robotic adhesiolysis with the da Vinci (Intuitive, Sunnyvale, CA) system. Resternotomy was performed under direct visualization for coronary revascularization (n = 2) or valve replacement (n = 1). A fourth patient required coronary revascularization after a previous axilloaxillary bypass. The final case involved the preparation of a substernal pathway for a gastric pull-up. In all cases adhesions were taken down without injury to the underlying structures. All grafts were preserved, and all patients recovered uneventfully. Robotic adhesiolysis is a versatile technique that allows careful lysis of adhesions and minimizes the risk of major complication during reoperative chest surgery.

Fine-needle aspiration (FNA) is a highly sensitive method in the differential diagnosis of thyroid nodules. However, 10% of thyroid FNAs are indeterminate for cancer, and thus additional markers may be useful diagnostically. The authors have demonstrated previously that human telomerase reverse transcriptase (hTERT) gene expression is useful in the distinction of benign lesions from malignant lesions. They therefore wondered whether the detection of hTERT gene expression was feasible using archival slides. To establish an experimental system, ribonucleic acid was extracted from human anaplastic thyroid carcinoma cell line (ARO) in cytologic specimens, and reverse transcription-polymerase chain reaction (RT-PCR) for hTERT expression was performed. RT-PCR analysis for hTERT gene detection was then performed using 58 Diff-Quik-stained archival FNA samples collected retrospectively. RT-PCR for human thyroglobulin (hTg) or beta-actin gene expression served as a positive control. Successful PCR results were obtained from 48 of the 58 cases. All 10 slides in which no RT-PCR products were noted were older than 3 years. hTERT gene expression was demonstrated in FNAs from two of seven cases (29%) of hyperplastic nodule, one of one case (100%) of Hashimoto's thyroiditis, three of eight cases (38%) of follicular adenoma, three of eight cases (38%) of Hurthle cell adenoma, three of four cases (75%) of follicular carcinoma, two of two cases (100%) of Hurthle cell carcinoma, and 11 of 18 cases (61%) of papillary carcinoma. All but one of the available 33 corresponding frozen samples exhibited the same RT-PCR results. This study demonstrates that Diff-Quik-stained thyroid FNA specimens less than 3 years old can be used for the detection of hTERT gene expression by RT-PCR. This test, along with careful cytopathologic examination, may improve our ability to differentiate benign lesions from malignant lesions in indeterminate FNA samples from thyroid nodules.

Graft vessel disease (GVD) is a frequent and letal late complication of heart transplantation (HTx). The only effective treatment for severe GVD is retransplantation, an option not available for most patients. In recently published trials using intracoronary ultrasound (ICUS), TORinhibitors sirolimus and everolimus have proved their efficacy in the prevention of initial stages of GVD. We designed a prospective, randomized, unicentric preliminary study in order to evaluate the role of sirolimus in the treatment of established GVD. Method: HTx recipients with more than 50% angiographic stenosis in at least one major coronary vessel were randomized in a 2:1 fashion to receive either sirolimus in combination with low-dose cyclosporine prednisone or to maintain their basal immunosuppression (cyclosporine, MMF or azathioprine prednisone). Basal coronary study of 3–5 coronary segments with a 30 MHz ICUS catheter with automated pull-back at a speed of 0.5 mm/s is performed. A second ICUS study of the same coronary segments will take plece 6 2 months later. The primary endpoint of the study is the difference in the volume of coronary lesions in the same coronary segments when comparing both studies. Secondary endpoints include other ICUS parameters (maximal intimal thickness, crossectional plaque area, intimal index, luminal and external vessel dimensions), as well as clinical efficacy and safety variables. Twenty patients have been included in the study after signing informed consent. All basal and most (80%) post-intervention ICUS studies have been performed already. The last procedure is scheduled for January 2004. A total number of 70–80 coronary segments will be compared: 50–55 segments in 14 patients in sirolimus arm, and 20–25 segments in 6 patients in the control group. Quantitative, parallel, off-line analysis of both ICUS studies will be performed by two expert cardiologists unaware of treatment allocation of each patient. Data analysis will be ready by March 2004.