Ignoring a basic pathophysiological mechanism of heart failure progression will not make it go away.

A link between heart failure (HF) and low thyroid hormone (TH) function has been known for over a century. Nonetheless, there is a general belief that TH treatment of patients with HF may not be worth the risk. This is largely based on two clinical trials where heart patients were treated with excessive doses of TH analogs, not actual THs. Further complicating the matter is the fact that normalization of THs in noncardiac patients can often be challenging. This issue is not going away as noted by a steady increase in TH-HF citations in recent years. In this article, we discuss what we know and how we may move the field forward.

Hormone resuscitation therapy for brain-dead donors - is insulin beneficial or detrimental?

Hormonal replacement therapy to brain-dead potential organ donors remains controversial. A retrospective study was carried out of hormonal therapy on procurement of organs in 63 593 donors in whom information on thyroid hormone therapy (triiodothyronine or levothyroxine [T3 /T4 ]) was available. In 40 124 donors, T3 /T4 and all other hormonal therapy were recorded. The percentage of all organs procured, except livers, was greater when T3 /T4 had been administered. An independent beneficial effect of antidiuretic hormone (ADH) was also clear. Corticosteroids were less consistently beneficial (most frequently when T3 /T4 had not been administered), although never detrimental. Insulin was almost never beneficial and at times was associated with a reduced yield of organs, particularly of the pancreas and intestine, an observation that does not appear to have been reported previously. In addition, there was reduced survival at 12 months of recipients of pancreases from T3 /T4 -treated donors, but not of pancreas grafts. The possibly detrimental effect observed following insulin therapy is discussed.

Thyroid hormone therapy and procurement of livers from brain-dead donors.

Hormonal therapy to brain-dead potential organ donors remains controversial. A retrospective study was carried out of hormonal therapy on procurement of organs in 63,593 donors in whom information on T3/T4 therapy was available. In 40,124 donors, T3/T4 and all other hormonal therapy was recorded. The percentages of all organs procured, except livers, were greater in T3/T4-treated donors. Nevertheless, if T3/T4 therapy had been administered to the donor, liver transplantation was associated with significantly increased graft and recipient survival at 1 month and 12 months. The potential reasons for the lack of effect of T3/T4 therapy on the number of livers procured are discussed.

Off-Pump coronary artery bypass surgery is associated with worse arterial and saphenous vein graft patency and less effective revascularization: Results from the Veterans Affairs Randomized On/Off Bypass (ROOBY) trial.

BACKGROUND: The Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) trial compared clinical and angiographic outcomes in off-pump versus on-pump coronary artery bypass graft (CABG) surgery to ascertain the relative efficacy of the 2 techniques. METHODS AND RESULTS: From February 2002 to May 2007, the ROOBY trial randomized 2203 patients to off-pump versus on-pump CABG. Follow-up angiography was obtained in 685 off-pump (62%) and 685 on-pump (62%) patients. Angiograms were analyzed (blinded to treatment) for FitzGibbon classification (A=widely patent, B=flow limited, O=occluded) and effective revascularization. Effective revascularization was defined as follows: All 3 major coronary territories with significant disease were revascularized by a FitzGibbon A-quality graft to the major diseased artery, and there were no new postanastomotic lesions. Off-pump CABG resulted in lower FitzGibbon A patency rates than on-pump CABG for arterial conduits (85.8% versus 91.4%; P=0.003) and saphenous vein grafts (72.7% versus 80.4%; P<0.001). Fewer off-pump patients were effectively revascularized (50.1% versus 63.9% on-pump; P<0.001). Within each major coronary territory, effective revascularization was worse off pump than on pump (all P≤0.001). The 1-year adverse cardiac event rate was 16.4% in patients with ineffective revascularization versus 5.9% in patients with effective revascularization (P<0.001). CONCLUSIONS: Off-pump CABG resulted in significantly lower FitzGibbon A patency for arterial and saphenous vein graft conduits and less effective revascularization than on-pump CABG. At 1 year, patients with less effective revascularization had higher adverse event rates. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00032630.

On-pump versus off-pump coronary-artery bypass surgery.

BACKGROUND: Coronary-artery bypass grafting (CABG) has traditionally been performed with the use of cardiopulmonary bypass (on-pump CABG). CABG without cardiopulmonary bypass (off-pump CABG) might reduce the number of complications related to the heart-lung machine. METHODS: We randomly assigned 2203 patients scheduled for urgent or elective CABG to either on-pump or off-pump procedures. The primary short-term end point was a composite of death or complications (reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) before discharge or within 30 days after surgery. The primary long-term end point was a composite of death from any cause, a repeat revascularization procedure, or a nonfatal myocardial infarction within 1 year after surgery. Secondary end points included the completeness of revascularization, graft patency at 1 year, neuropsychological outcomes, and the use of major resources. RESULTS: There was no significant difference between off-pump and on-pump CABG in the rate of the 30-day composite outcome (7.0% and 5.6%, respectively; P=0.19). The rate of the 1-year composite outcome was higher for off-pump than for on-pump CABG (9.9% vs. 7.4%, P=0.04). The proportion of patients with fewer grafts completed than originally planned was higher with off-pump CABG than with on-pump CABG (17.8% vs. 11.1%, P<0.001). Follow-up angiograms in 1371 patients who underwent 4093 grafts revealed that the overall rate of graft patency was lower in the off-pump group than in the on-pump group (82.6% vs. 87.8%, P<0.01). There were no treatment-based differences in neuropsychological outcomes or short-term use of major resources. CONCLUSIONS: At 1 year of follow-up, patients in the off-pump group had worse composite outcomes and poorer graft patency than did patients in the on-pump group. No significant differences between the techniques were found in neuropsychological outcomes or use of major resources. (ClinicalTrials.gov number, NCT00032630.).

Chylopericardium presenting with tamponade and cardiogenic shock.

We are presenting a rare case of cardiogenic shock caused by chylopericardium. After the initial pericardial drainage and failed conservative treatment, thoracic duct ligation was performed with good long-term outcome. Literature on the subject is reviewed.

Cardiac autotransplantation for removal of left atrial hemangioma and a review of the literature.

We describe the management of a patient who presented with symptoms of severe congestive heart failure. A 48-year-old man was initially seen in the emergency room, admitted to the hospital, and worked up with a transthoracic echocardiogram, a transesophageal echocardiogram, and a computer tomography scan of the chest. All cardiac valves were normal, as was the left ventricular ejection fraction. A mobile left atrial tumor measuring 6 x 4 x 5 cm was found attached to the left atrial dome, left atrial cuff, and left pulmonary veins. With each systolic atrial contraction, the mass prolapsed into the left ventricle across the mitral valve annulus, inducing a gradient of 19 mm Hg. The workup of the patient was negative for malignancy. The only feasible therapy for this patient was to excise the mass on cardiopulmonary bypass and cardioplegic arrest. At the time of surgery, the findings confirmed that the mass was attached broadly to the left atrial dome wall-epicardium, and the attachments were similar to those of the transesophageal echocardiographic findings. Atrial attachments extended from the base of the heart, along the atrioventricular groove, the left dome of the left atrium, the left atrial cuff, and the anterior aspect of both left pulmonary veins. The tumor could not be adequately excised, and reconstruction of the defect was not feasible with the heart in situ. We therefore decided to explant the heart and excise the tumor with a 0.5-cm margin of healthy tissue. The broad left atrial defect was reconstructed with bovine pericardium. The reconstruction encompassed the dome of the left atrium, the left atrial cuff, and the pulmonary veins. The heart was reimplanted back into the pericardial cavity. The superior vena cava with the retained sinus node was also anastomosed. The pathology diagnosis was a benign cavernous hemangioma. The sinus rhythm recovered following removal of the aortic cross-clamp and reperfusion of the heart. The patient had a rapid recovery and was discharged home on the 12th postoperative day. Placement of a pacemaker was not required because the patient retained the sinus rhythm. A review of the literature on cardiac autotransplantation revealed that this type of surgery has been performed frequently in centers that have a cardiac transplantation program or a surgeon who has cardiac transplantation experience. To our knowledge, this report is the first of cardiac autotransplantation for benign hemangioma.

Reducing the risk of myocardial revascularization: relevance of multimodal brain monitoring.

Perioperative neurologic events in heart surgery are the most devastating complications. Although myocardial revascularization without cardiopulmonary bypass (CPB) has reduced the incidence of cerebrovascular accidents, they still remain a reality that the cardiothoracic surgeon is unable to completely eliminate. The events leading to a neurologic complication are related to hemodynamic instability and embolization of aortic debris at the time a side-biting clamp is applied. Combined events may eventually impact the brain to varying degrees, ranging from a temporary confusional state to a full-blown stroke from which meaningful recovery may be impossible. This report describes the interventions necessary to maintain hemodynamic stability, the role of brain monitoring required, and how to safely achieve complete off-CPB myocardial revascularization and minimize the incidence of neurologic complications. Cardiac interventions include maintaining sinus rhythm, providing adequate blood supply to all vital organs, and avoiding induction of myocardial ischemia, which may induce supraventricular, ventricular arrhythmias, or both. These interventions depend upon an experienced surgical team (anesthesiologist, cardiologist, surgeon, and operating room and intensive care unit recovery nurses). Anticipation of myocardial ischemia may require loading the patient with antiarrhythmic drugs, and placement of intracoronary shunts and intraaortic balloon pump support. Patience from the surgeon is often required to allow time for the specific intervention to act. In addition to interventions to maintain a balance between the demand and supply of oxygen, we frequently rely on "intermittent hypotensive anesthesia'' while performing the distal and proximal coronary anastomoses. Hypotension may lead to inadequate oxygen supply to the brain, so multimodal brain monitoring becomes mandatory. We use a combination of transcranial brain oximetry and electroencephalographic compressed spectral array. This combined monitoring results in a safer surgical procedure, allowing the hemodynamic interventions to be performed rationally and without interruption of the surgical procedure.

Increased Procurement of Thoracic Donor Organs After Thyroid Hormone Therapy.

Hormonal therapy to the brain-dead organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), antidiuretic hormone, corticosteroids, or insulin. There has been a controversy on whether thyroid hormone enables more organs to be procured. Data on 63,593 donors of hearts and lungs (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in all donors (study 1), and in 40,124 details of all 4 hormones were recorded (study 2). In this cohort, group A (23,022) received T3/T4 and group B (17,102) no T3/T4. Univariate analyses and multiple regressions were performed. Posttransplant graft and recipient survival at 1 and 12 months were compared. In study 1, 30,962 donors received T3/T4, with 36.59% providing a heart and 20.05% providing 1 or both lungs. Of the 32,631 donors who did not receive T3/T4, only 29.62% provided a heart and 14.61% provided lungs, an increase of 6.97% hearts and 5.44% lungs from T3/T4-treated donors (both P < 0.0001). In study 2, 34.99% of group A provided a heart and 20.99% provided lungs. In group B only 25.76% provided a heart and 15.09% provided lungs, an increase of 9.23% (hearts) and 5.90% (lungs), respectively, in group A (both P < 0.0001). The results of multiple regression analyses indicated a beneficial effect of T3/T4 on heart (P < 0.0001) and lung (P < 0.0001) procurement independent of other factors. T3/T4 therapy to the donor was associated with either improved posttransplant graft and recipient survival or no difference in survival. T3/T4 therapy results in more transplantable hearts and lungs, with no detriment to posttransplant graft or recipient survival.

The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors.

The management of brain-dead organ donors is complex. The use of inotropic agents and replacement of depleted hormones (hormonal replacement therapy) is crucial for successful multiple organ procurement, yet the optimal hormonal replacement has not been identified, and the statistical adjustment to determine the best selection is not trivial. Traditional pair-wise comparisons between every pair of treatments, and multiple comparisons to all (MCA), are statistically conservative. Hsu's multiple comparisons with the best (MCB) - adapted from the Dunnett's multiple comparisons with control (MCC) - has been used for selecting the best treatment based on continuous variables. We selected the best hormonal replacement modality for successful multiple organ procurement using a two-step approach. First, we estimated the predicted margins by constructing generalized linear models (GLM) or generalized linear mixed models (GLMM), and then we applied the multiple comparison methods to identify the best hormonal replacement modality given that the testing of hormonal replacement modalities is independent. Based on 10-year data from the United Network for Organ Sharing (UNOS), among 16 hormonal replacement modalities, and using the 95% simultaneous confidence intervals, we found that the combination of thyroid hormone, a corticosteroid, antidiuretic hormone, and insulin was the best modality for multiple organ procurement for transplantation.

Cardiac autotransplantation for mitral valve replacement.

We present an unusual case of a 69-year-old patient with severe mitral valve regurgitation and extensive coronary artery disease who required mitral valve replacement and myocardial revascularization. With the patient on cardiopulmonary bypass, distal vein grafting was performed first. This procedure was followed by a transatrial transseptal approach to the mitral valve, but visualization of valve structures was extremely difficult. Following the partial excision of the posterior leaflet and the placement of a few pledgeted annular sutures on which traction was applied, access to the mitral annulus remained impossible. There appeared no option but to explant the heart and perform the mitral valve replacement ex vivo. Cardiac explantation was performed by transecting the aorta and pulmonary artery and completing the already extended right and left atriotomies. Cold blood cardioplegic solution was administered intermittently into the coronary sinus during the period when the heart was ex vivo. A porcine bioprosthesis was easily seated into the mitral annulus. Cardiac reimplantation consisted of repair of the previously divided atria, and end-to-end anastomoses of both the aorta and the pulmonary artery. While rewarming was taking place, the 3 proximal vein graft anastomoses were performed. Temporary and permanent epicardial pacing leads were placed. Total ischemic time was 299 minutes, and the period on cardiopulmonary bypass was 359 minutes. The heart sustained good hemodynamics, and after full functional recovery, the patient was discharged home and remained well for 7 years. In view of this experience, a questionnaire was mailed to >3000 cardiothoracic surgeons, and responses were obtained from 1120. Inadequate mitral valve exposure had been experienced by 70%. To provide increased exposure, 50% had extended the initial atrial incision both horizontally and perpendicular to the atrial groove, 17% had divided the superior vena cava, 1% had divided the inferior vena cava, and 1% had divided both cavae. Furthermore, 4% of surgeons reported being forced to abandon the operation in 71 patients because of inadequate exposure. Three hundred twenty perioperative deaths were directly attributed to an incomplete surgical procedure. Explantation of the heart, with mitral valve replacement being performed ex vivo followed by reimplantation, should be considered when access to the mitral valve proves impossible with more standard techniques.

Repair of acute ascending aorta-arch dissection with continuous body perfusion: a case report.

An approach for the replacement of the distal ascending aorta-proximal arch and acute dissection is described. During the operation, the patient's entire body was continuously perfused, the aortic arch was excluded from the arterial circulation, and the aorta was not clamped at any time. To achieve continuous body perfusion, we independently cannulated the right axillary and the left femoral arteries. The right atrium was cannulated for systemic venous return, and the right radial artery was used for arterial blood pressure monitoring. The myocardium was protected with retrograde cardioplegia, and the body was protected with moderate hypothermia. Vascular clamps were placed to the proximal innominate, left carotid, and left subclavian arteries without discontinuing perfusion of the right axillary artery. A temporary clamp was applied to the femoral line, the aorta was transected, and a large Foley catheter was inserted through the true aortic lumen. The Foley bulb was positioned in the proximal descending thoracic aorta and distended with saline until the aortic blood return ceased. The femoral line clamp was removed from the cannula, and the entire body was perfused during the completion of the distal aortic anastomosis. At the completion of the anastomosis, the Foley bulb was slightly deflated. Once the inserted graft was filled with blood, a large vascular clamp was applied to the graft, and the previously placed clamps were removed from the arch branches. The femoral line was removed, and the body was perfused and rewarmed via the axillary cannulation. Following completion of the proximal graft-aortic anastomosis, the heart was reperfused, and all cannulas were removed in the usual fashion. Rapid recovery characterized the patient's initial postoperative course; however, multiple organ failure secondary to pump-induced inflammatory response followed. Aggressive medical management resulted in complete patient recovery. No neurologic deficits were observed, and the patient regained full cognitive function. This report describes a simple approach to facilitate repair of the aortic arch and minimize postoperative organ failure.

Thyroid hormone and the stunned myocardium.

Acute critically ill patients experience a rapid decline in plasma free thyroid hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS) or low-T3 syndrome. The ESS is also often associated with depressed myocardial function, sometimes referred to as the 'stunned myocardium'. Its clinical effects may vary from minimal hemodynamic impairment to cardiogenic shock. Medical management may range from aspirin alone to placement of a left ventricular assist device. With adequate supportive therapy, recovery usually occurs within days or weeks. The effect of T3/T4 therapy has been studied in three conditions in which the ESS and myocardial functional depression have been documented - i) transient regional myocardial ischemia and reperfusion, ii) transient global myocardial ischemia in patients undergoing cardiac surgery on cardiopulmonary bypass, and iii) transient inadequate global myocardial perfusion in brain-dead potential organ donors. Under all three conditions, myocardial ischemia leads to rapid loss of high-energy phosphates, accumulation of myocardial tissue lactate, and probably loss of homeostasis of cytosolic calcium, which may further increase cell injury. There is an inability to generate ATP through the Krebs cycle, which reduces the high-energy phosphate pool essential for all cell ATPases. Under all three conditions, following administration of T3/T4, the myocardial dysfunction was rapidly reversed. We, therefore, cautiously advocate the use of thyroid hormonal therapy to any patient with the ESS and/or a stunned myocardium.

Thyroid hormone therapy in the management of 63,593 brain-dead organ donors: a retrospective analysis.

BACKGROUND: Hormonal therapy to the brain-dead potential organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), corticosteroids, antidiuretic hormone, and insulin. METHODS: Data on 66,629 donors (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in 63,593 (study 1), but 23,469 had incomplete documentation of other hormones. In 40,124, details of all four hormones were recorded (study 2). In this cohort, group A (received T3/T4) consisted of 23,022, and group B (no T3/T4) consisted of 17,102 donors. A multivariate analysis was performed to determine whether age, sex, ethnicity, cause of death, body mass index, Organ Procurement Organization region, or other hormonal therapy influenced procurement. Posttransplantation organ graft survival at 1 and 12 months was compared. RESULTS: In study 1, 30,962 (48.69%) received T3/T4, providing a mean of 3.35 organs per donor, and 32,631 (51.31%) did not receive T3/T4, providing a mean of 2.97 organs per donor, an increase of 12.8% of organs from T3/T4-treated donors (P<0.0001). In study 2, group A provided a mean of 3.31 organs per donor and group B provided a mean of 2.87 organs per donor, an increase of 15.3% in group A (P<0.0001). T3/T4 therapy was associated with procurement of significantly greater numbers of hearts, lungs, kidneys, pancreases, and intestines, but not livers. Multivariate analysis indicated a beneficial effect of T3/T4 independent of other factors (P<0.0001). T3/T4 therapy of the donor was associated with improved posttransplantation graft survival or no difference in survival, except for pancreas recipient (but not graft) survival at 12 months in study 2. CONCLUSION: T3/T4 therapy results in more transplantable organs, with no detriment to posttransplantation graft survival.

Outcomes after conversion in the Veterans Affairs randomized on versus off bypass trial.

BACKGROUND: The Randomized On versus Off Bypass trial reported conversion of 12.4% (n = 137) off-pump coronary artery bypass (OPCAB) patients and 3.6% (n = 40) on-pump cardiopulmonary bypass (CPB) patients. This paper explored outcomes after conversions. METHODS: Elective and urgent CABG patients (n = 2,203) at 18 sites were studied. Randomization within 54 participating surgeons occurred preoperatively, after which conversion occurred if clinically indicated. Conversion reasons and outcomes were captured prospectively with additional details retrospectively extracted from patient records by a core clinical group. RESULTS: Conversion rates varied considerably across participating surgeons. Converted OPCAB patients had more right coronary disease and coronary targets less than 1.5 mm. Conversions were elective in 49.3% of cases, urgent in 27.2%, or emergent in 23.5%. Elective conversions were mainly for poor exposure-intramyocardial vessel (35.8%). Urgent and emergent conversions were usually for hemodynamic instability (89.2% and 75.0%, respectively). Compared with CPB and OPCAB patients, OPCAB-converted patients had more 30-day complications and deaths (composite outcome rate of 5.7% and 5.5% vs 17.5% respectively, p < 0.001). Thirty-day outcomes for OPCAB-converted patients trended worse for emergent versus elective conversions (31.3% vs 13.4%, respectively, p = 0.05). One-year composite outcome rate (death, nonfatal myocardial infarction or revascularization) in OPCAB-converted patients was worse than in CPB patients (13.5% vs 7.1%, p = 0.02), but similar to OPCAB-nonconverted (9.4%). CONCLUSIONS: The OPCAB patients requiring conversion had worse 30-day and 1-year outcomes. The OPCAB patients with right coronary artery disease or small targets were more often converted. The 30-day composite outcome trended worst for emergent OPCAB conversions.

Impact of endoscopic versus open saphenous vein harvest technique on late coronary artery bypass grafting patient outcomes in the ROOBY (Randomized On/Off Bypass) Trial.

OBJECTIVE: In the Randomized On/Off Bypass (ROOBY) Trial, the efficacy of on-pump versus off-pump coronary artery bypass grafting was evaluated. This ROOBY Trial planned subanalysis compared the effects on postbypass patient clinical outcomes and graft patency of endoscopic vein harvesting and open vein harvesting. METHODS: From April 2003 to April 2007, the technique used for saphenous vein graft harvesting was recorded in 1471 cases. Of these, 894 patients (341 endoscopic harvest and 553 open harvest) also underwent coronary angiography 1 year after coronary artery bypass grafting. Univariate and multivariable analyses were used to compare patient outcomes in the endoscopic and open groups. RESULTS: Preoperative patient characteristics were statistically similar between the endoscopic and open groups. Endoscopic vein harvest was used in 38% of the cases. There were no significant differences in both short-term and 1-year composite outcomes between the endoscopic and open groups. For patients with 1-year catheterization follow-up (n=894), the saphenous vein graft patency rate for the endoscopic group was lower than that in the open harvest group (74.5% vs 85.2%, P<.0001), and the repeat revascularization rate was significantly higher (6.7% vs 3.4%, P<.05). Multivariable regression documented no interaction effect between endoscopic approach and off-pump treatment. CONCLUSIONS: In the ROOBY Trial, endoscopic vein harvest was associated with lower 1-year saphenous vein graft patency and higher 1-year revascularization rates, independent of the use of off-pump or on-pump cardiac surgical approach.

Cognitive outcomes after on- versus off-pump coronary artery bypass surgery.

BACKGROUND: The Randomized On versus Off Bypass trial found no difference for a global cognitive outcome measure for patients receiving on-pump versus off-pump coronary artery bypass graft surgery (CABG). In this report, we present the baseline patient characteristics that were predictive of post-CABG cognitive decline as well as compare cognitive outcomes between treatment arms. METHODS: A neuropsychological battery was administered preoperatively and at 1 year after undergoing CABG. Stepwise regression was used to identify demographic or clinical risk factors associated with cognitive decline. Neuropsychological data were converted to demographically corrected T scores to provide impairment levels. RESULTS: Overall 1,156 patients (581 on-pump, 575 off-pump) completed match-paired neuropsychological assessments at baseline and 1-year follow-up. Baseline cognitive score, age, education level, and ethnicity predicted cognitive decline after CABG. Only 20% of either group had mild impairment at baseline on three of the test scores, and less than 10% had severe impairment on individual tests at either time. Few subjects in either group transitioned to clinically impaired levels at follow-up on individual tests. CONCLUSIONS: At baseline, lower cognitive function, older age, lower education, and ethnicity other than white were predictive of cognitive decline after CABG. Patients in both groups demonstrated low frequencies of cognitive impairment on individual tests at baseline and follow- up, and few patients in either group were classified as impaired at 1-year follow-up on individual tests. In general, the Randomized On versus Off Bypass study documented that neither on-pump nor off-pump CABG adversely impacts long-term brain function.

A review of studies relating to thyroid hormone therapy in brain-dead organ donors.

An acute decrease in cardiac performance can result from a reduced free triiodothyronine (FT3) level following (i) brain death (euthyroid sick syndrome), (ii) a period of cardiopulmonary bypass, and possibly (iii) regional or global myocardial ischemia. The two major pathophysiologic effects of brain death are (i) vascular injury associated with the hemodynamic consequences of the autonomic 'storm', and (ii) a generalized inhibition of mitochondrial function, which results in diminished organ function from the loss of energy stores from a rapid loss of circulating FT3. Deterioration of donor organ function can be reversed by hormonal replacement therapy, in which T3 plays a critical role. This results in (i) an increased number of organs being functionally acceptable, and (ii) increased early and intermediate graft survival. Cardiopulmonary bypass is associated with a reduction in the circulating level of FT3, and this can be associated with deterioration in cardiac function. The administration of T3 at the time of discontinuation of cardiopulmonary bypass reverses this state. In patients undergoing heart transplantation, T3 therapy to both donor and recipient is beneficial.

A study design to assess the safety and efficacy of on-pump versus off-pump coronary bypass grafting: the ROOBY trial.

BACKGROUND: Since the late 1960s, coronary artery bypass graft (CABG-only) procedures were traditionally performed using a heart-lung machine on an arrested heart (on-pump). Over the past decade, an increasing number CABG-only procedures were performed on a beating heart (off-pump). Advocates of the off-pump approach expect to reduce many of the adverse side effects related to using the heart-lung machine, while advocates for the on-pump procedure raise concerns related to graft patency rates and long-term event-free survival for the off-pump technique. PURPOSE: The U.S. Department of Veteran Affairs (VA) Cooperative Studies Program funded a randomized, multicenter clinical trial comparing the clinical and resource-related outcomes following on-pump versus off-pump techniques for veterans undergoing a non-emergent CABG-only procedure. The planning committee was faced with several critically important challenges to assure feasibility of study costs and required sample size; generalizability to non-VA surgical practices; and comparability of clinically meaningful results. These challenges are discussed. METHODS: This study is a prospective, randomized, multicenter, single blinded (patient) clinical trial that compares on-pump and off-pump techniques for veterans requiring non-emergent CABG-only procedures. There will be 2200 patients randomized at 17 VA Medical Centers when the five-year recruitment period ends on 15 April 2007. There are two primary objectives: a short-term objective to assess the immediate impact of the two techniques on 30-day mortality/morbidity and a long-term objective to assess one-year mortality/morbidity. Major secondary outcomes are one-year graft patency rates and change in neuropsychological assessments from baseline to one year. All patients are assessed at 30 days post-surgery or discharge from the hospital, whichever is latest, and at one-year post-surgery. RESULTS: During planning, several key issues had to be decided. These included 1) choosing primary objectives: a short-term (30-day) and a long-term (one-year) objective were chosen; 2) choosing primary outcome measures: composite measures were selected to ensure sufficient end-points; 3) standardization of surgical techniques: minimal standardization required but guidelines and continuing discussions on both techniques provided; 4) establishing criteria for surgeons and residents for participation: surgeons required to have completed 20 off-pump procedures prior to doing study procedures and residents, in presence of study surgeon, capable of doing either procedure; 5) identifying metrics of cognitive dysfunction sensitive to treatment: a neuropshychologist hired who centrally monitors cognitive functioning testing; and 6) blinding participants of surgical procedure: attempt to blind participants. LIMITATIONS: Areas of concern are whether all surgeons sufficiently experienced on the off-pump procedure, should residents have been allowed to do study surgeries, should techniques have been standardized more and were the best neurocognitive tests selected. CONCLUSION: The study design presented allows for a balanced and fair assessment of the on-pump and off-pump CABG procedures across a diversity of clinical outcomes and resource use metrics. Its results have the potential to influence clinical cardiac surgical practice in the future.

Aiming towards complete myocardial revascularization without cardiopulmonary bypass: a systematic approach.

BACKGROUND: Coronary artery bypass grafting (CABG) has become the surgical procedure of choice for symptomatic coronary artery disease. However, the use of traditional cardiopulmonary bypass (CPB) techniques represents an invasive therapeutic system with immediate and long-term complications. Off-pump myocardial revascularization has emerged as an attractive alternative that offers improvements in early outcomes and avoidance of the recognized adverse affects of CPB. A major criticism of this procedure has been a perceived inability to accomplish complete revascularization of the heart. In this report, we describe a surgical technique we have used in a series of patients that has allowed complete myocardial revascularization. METHODS: Combinations of intraoperative techniques were employed, including (1) right pleural-pericardial window, (2) deep pericardial sutures, (3) right heart displacement, (4) intermittent hypotensive anesthesia, (5) multimodality brain monitoring, and (6) coronary shunting. Following surgery, coronary artery grafts performed were statistically compared to each coronary artery's vascular territory to show that all territories were equally treatable with the combination of techniques. RESULTS: There were 734 coronary artery grafts performed in 200 consecutive patients (mean of 3.7 grafts/patient), and 533 compromised vascular territories were revascularized (mean of 1.38 grafts for each diseased vessel). Eight patients had one-vessel disease, 51 had two-vessel disease and 141 had three-vessel disease. The left anterior descending coronary artery (LAD) was compromised in 192 patients, the circumflex in 171 and the right coronary artery in 170 patients. The overall 30-day estimated hospital mortality was 5.5%; the observed was 4.0% (8 of 200). Postoperative complications included pulmonary insufficiency in 6 patients (3.0%), reoperation for bleeding in 3 patients (1.5%), cerebrovascular accident in 3 patients (1.5%), renal dysfunction in 2 patients (1.0%), perioperative myocardial infarction in 8 patients (4.0%), cardiac arrest in 2 patients (1.0%), low cardiac output in 5 patients (2.5%), and deep sternal infection in 2 patients (1.0%). CONCLUSIONS: Use of intermittent hypotensive anesthesia in conjunction with multimodality brain monitoring, right heart displacement, deep pericardial sutures, coronary shunting and epicardial compression stabilization facilitates complete revascularization of the myocardium.