Search

Summary and Background Data: VV ECMO can be utilized as an advanced therapy in select patients with COVID-19 respiratory failure refractory to traditional critical care management and optimal mechanical ventilation. Anticipating a need for such therapies during the pandemic, our center created a targeted protocol for ECMO therapy in COVID-19 patients that allows us to provide this life-saving therapy to our sickest patients without overburdening already stretched resources or excessively exposing healthcare staff to infection risk. Methods: As a major regional referral program, we used the framework of our well-established ECMO service-line to outline specific team structures, modified patient eligibility criteria, cannulation strategies, and management protocols for the COVID-19 ECMO program. Results: During the first month of the COVID-19 outbreak in Massachusetts, 6 patients were placed on VV ECMO for refractory hypoxemic respiratory failure. The median (interquartile range) age was 47 years (43–53) with most patients being male (83%) and obese (67%). All cannulations were performed at the bedside in the intensive care unit in patients who had undergone a trial of rescue therapies for acute respiratory distress syndrome including lung protective ventilation, paralysis, prone positioning, and inhaled nitric oxide. At the time of this report, 83% (5/6) of the patients are still alive with 1 death on ECMO, attributed to hemorrhagic stroke. 67% of patients (4/6) have been successfully decannulated, including 2 that have been successfully extubated and one who was discharged from the hospital. The median duration of VV ECMO therapy for patients who have been decannulated is 12 days (4–18 days). Conclusions: This is 1 the first case series describing VV ECMO outcomes in COVID-19 patients. Our initial data suggest that VV ECMO can be successfully utilized in appropriately selected COVID-19 patients with advanced respiratory failure.

Aim: This executive summary of the valvular heart disease guideline provides recommendations for clinicians to diagnose and manage valvular heart disease as well as supporting documentation to encourage their use. Methods: A comprehensive literature search was conducted from January 1, 2010, to March 1, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, Cochrane, Agency for Healthcare Research and Quality Reports, and other selected database relevant to this guideline. Structure: Many recommendations from the earlier valvular heart disease guidelines have been updated with new evidence and provides newer options for diagnosis and treatment of valvular heart disease. This summary includes only the recommendations from the full guideline which focus on diagnostic work-up, the timing and choice of surgical and catheter interventions, and recommendations for medical therapy. The reader is referred to the full guideline for graphical flow charts, text, and tables with additional details about the rationale for and implementation of each recommendation, and the evidence tables detailing the data considered in developing these guidelines.

Background: Hybrid coronary revascularization (HCR) treats multivessel coronary artery disease by combining a minimally invasive surgical approach to the left anterior descending artery with percutaneous coronary intervention for non–left anterior descending diseased coronary arteries. The objective of this study is to compare HCR and conventional coronary artery bypass graft (CABG) surgery medium-term outcomes. Methods: Data from multivessel disease patients in New York’s cardiac surgery and percutaneous coronary intervention registries in 2010 to 2016 were used to compare mortality and repeat revascularization rates for HCR and conventional CABG after using propensity matching to reduce selection bias. Results: There was a total of 303 HCR (0.80%) patients and 37 556 conventional CABG patients after exclusions. After propensity matching, the respective median follow-up times were 3.72 years and 3.76 years. There was no difference between HCR and conventional CABG in survival at 6 years (80.9% versus 85.8%%, adjusted hazard ratio, 1.44 [0.90–2.31]), but HCR had higher mortality excluding deaths during the first year (adjusted hazard ratio, 1.88 [1.10–3.23]). Conventional CABG patients were more likely to be free from repeat revascularization at 6 years than HCR patients (88.2% versus 76.6%; hazard ratio, 2.22 [1.44–3.42]). Conclusions: HCR is rarely performed for patients with multivessel coronary artery disease. HCR and conventional CABG had no different 6-year mortality rates, but HCR had higher mortality after 1 year and higher rates of subsequent revascularization that were caused by both the need for repeat revascularization in the left anterior descending artery where minimally invasive CABG was performed, and in the coronary arteries where percutaneous coronary intervention was performed. Graphic Abstract: A graphic abstract is available for this article.

AKI after cardiac surgery is associated with mortality, prolonged hospital length of stay, use of dialysis, and subsequent CKD. We evaluated the effects of THR-184, a bone morphogenetic protein-7 agonist, in patients at high risk for AKI after cardiac surgery. We conducted a randomized, double-blind, placebo-controlled, multidose comparison of the safety and efficacy of perioperative THR-184 using a two-stage seamless adaptive design in 452 patients between 18 and 85 years of age who were scheduled for nonemergent cardiac surgery requiring cardiopulmonary bypass and had recognized risk factors for AKI. The primary efficacy end point was the proportion of patients who developed AKI according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The proportion of patients who developed AKI within 7 days of surgery was similar in THR-184 treatment groups and placebo groups (range, 74%–79%; P=0.43). Prespecified secondary end point analysis did not show significant differences in the severity of AKI stage (P=0.53) or the total duration of AKI (P=0.44). A composite of death, dialysis, or sustained impaired renal function by day 30 after surgery did not differ between groups (range, 11%–20%; P=0.46). Safety-related outcomes were similar across all treatment groups. In conclusion, compared with placebo, administration of perioperative THR-184 through a range of dose exposures failed to reduce the incidence, severity, or duration of AKI after cardiac surgery in high-risk patients.

Two guidelines from the American College of Cardiology (ACC), the American Heart Association (AHA), and collaborating societies address the risk of aortic dissection in patients with bicuspid aortic valves and severe aortic enlargement: the “2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease” (Circulation. 2010;121:e266–e369) and the “2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease” (Circulation. 2014;129:e521–e643). However, the 2 guidelines differ with regard to the recommended threshold of aortic root or ascending aortic dilatation that would justify surgical intervention in patients with bicuspid aortic valves. The ACC and AHA therefore convened a subcommittee representing members of the 2 guideline writing committees to review the evidence, reach consensus, and draft a statement of clarification for both guidelines. This statement of clarification uses the ACC/AHA revised structure for delineating the Class of Recommendation and Level of Evidence to provide recommendations that replace those contained in Section 9.2.2.1 of the thoracic aortic disease guideline and Section 5.1.3 of the valvular heart disease guideline.

Background— Current practice guidelines recommend surgical repair of large thoracic aortic aneurysms to prevent fatal aortic dissection or rupture, but limited natural history data exist to support clinical criteria for timely intervention. Methods and Results— Of 3247 patients with thoracic aortic aneurysm registered in our institutional Thoracic Aortic Center Database, we identified and reviewed 257 nonsyndromic patients (age, 72.4±10.5 years; 143 female) with descending thoracic or thoracoabdominal aortic aneurysm without a history of aortic dissection in whom surgical intervention was not undertaken. The primary end point was a composite of aortic dissection/rupture and sudden death. Baseline mean maximal aortic diameter was 52.4±10.8 mm, with 103 patients having diameters ≥55 mm. During a median follow-up of 25.1 months (quartiles 1–3, 8.3–56.4 months), definite and possible aortic events occurred in 19 (7.4%) and 31 (12.1%) patients, respectively. On multivariable analyses, maximal aortic diameter at baseline emerged as the only significant predictor of aortic events (hazard ratio=1.12; 95% confidence interval, 1.08–1.15). Estimated rates of definite aortic events within 1 year were 5.5%, 7.2%, and 9.3% for aortic diameters of 50, 55, and 60 mm, respectively. Receiver-operating characteristic curves for discriminating aortic events were higher for indexed aortic sizes referenced by body size (area under the curve=0.832–0.889) but not significantly different from absolute maximal aortic diameter (area under the curve=0.805). Conclusions— Aortic size was the principal factor related to aortic events in unrepaired descending thoracic or thoracoabdominal aortic aneurysm. Although the risk of aortic events started to increase with a diameter >5.0 to 5.5 cm, it is uncertain whether repair of thoracic aortic aneurysms in this range leads to overall benefit, and the threshold for repair requires further evaluation.

Background— Decisions to proceed with surgical versus percutaneous revascularization for multivessel coronary artery disease are often based on subtle clinical information that may not be captured in contemporary registries. The present study sought to evaluate the association between surgical ineligibility documented in the medical record and long-term mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention. Methods and Results— All subjects undergoing nonemergent percutaneous coronary intervention for unprotected left main or multivessel coronary artery disease were identified at 2 academic medical centers from 2009 to 2012. Documentation of surgical ineligibility was assessed through review of electronic medical records. Cox proportional hazard models adjusted for known mortality risk factors were created to assess long-term mortality in patients with and without documentation of surgical ineligibility. Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were deemed ineligible for coronary artery bypass graft surgery. The most common explicitly cited reasons for surgical ineligibility in the medical record were poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%). After adjustment for known risk factors, documentation of surgical ineligibility remained independently associated with an increased risk of in-hospital (odds ratio, 6.26; 95% confidence interval, 2.16–18.15; P P Conclusions— Documented surgical ineligibility is common and associated with significantly increased long-term mortality among patients undergoing percutaneous coronary intervention with unprotected left main or multivessel coronary disease, even after adjustment for known risk factors for adverse events during percutaneous revascularization.

Background: Although guidelines support aortic valve replacement (AVR) in patients with severe aortic regurgitation (AI) and left ventricular ejection fraction (LVEF) < 50%, severe left ventricular dysfunction (LVEF < 35%) is thought to confer very high surgical risk. The survival benefit associated with surgical intervention, however, is unknown. We evaluated long term outcomes of this patient population with and without surgical intervention. Methods: To capture patients who did and did not undergo AVR, we queried a single institutions echocardiography database to identify all patients with severe AR and LVEF < 35%. Manual chart review was performed to identify key demographic, clinical, and operative details. This retrospective cohort was then merged with institutional patient data. Due to small sample size and population heterogeneity, corrected group prognosis method was applied, which calculates the adjusted survival curve for each individual using fitted Cox proportional hazard model. Average survival adjusted for co-morbidities and age was then calculated using the weighted average of the individual survival curves. Results: Of 43 echocardiograms representing 41 unique patients, 40 patients met inclusion criteria. Of those, 18 (45.0%) underwent AVR and 22 (55.0%) were managed medically. After multivariate adjustment, end stage renal disease (HR = 17.633, p =0.0335) and peripheral arterial disease (HR = 6.050, p =0.0180) were associated with increased long term mortality. AVR was associated with decreased mortality (HR = 0.143, p =0.0490, see Figure 1). The mean survival for patients undergoing AVR was 6.3 years. The mean follow-up time was 6.58 years. Conclusions: Even after adjustment for clinical characteristics and patient age, AVR is associated with increased survival for patients with severe systolic dysfunction and severe aortic insufficiency. Although treatment selection bias cannot be completely eliminated with this retrospective cohort design, these results support performing surgery on this high-risk patient group.

The cardiac surgical operating room (OR) is a complex environment in which highly trained subspecialists interact with each other using sophisticated equipment to care for patients with severe cardiac disease and significant comorbidities. Thousands of patient lives have been saved or significantly improved with the advent of modern cardiac surgery. Indeed, both mortality and morbidity for coronary artery bypass surgery have decreased during the past decade (Figure 1).1 Nonetheless, the highly skilled and dedicated personnel in cardiac ORs are human and will make errors. In 1991, Leape and colleagues2,3 estimated that among the 2 million patients hospitalized in New York in 1984, there were 27 179 adverse events that involved negligence; other evidence suggests that up to 16% of hospital inpatients are harmed.4 Gawande and associates5 found that the incidence of surgical adverse events was 12% among cardiac surgery patients versus 3% in other surgical patients; 54% of the adverse events were considered preventable. Of the roughly 350 000 to 500 000 patients who undergo cardiac surgery each year, 28 000 will have an adverse event, and one third of deaths associated with coronary artery bypass graft (CABG) operations may be preventable.6 Figure 1. Change in mortality and stroke rates in patients undergoing isolated coronary artery bypass graft (CABG) surgery, 2000 to 2009. There was a 24.4% and 26.4% reduction in the unadjusted observed operative mortality (2.4% vs 1.9%) and stroke rates (1.6% vs 1.2%), respectively, during the course of the study period. Reprinted from ElBardissi et al1 with permission from Elsevier. Copyright © 2012, The American Association for Thoracic Surgery. Refined techniques, advanced technologies, and enhanced coordination of care have led to significant improvements in cardiac surgery outcomes. However, more than 10 years after the Institute of Medicine report,7 there is …

Background: Presentations and outcomes of acute aortic dissection (AD) with an entry tear in the ascending aorta may differ from retrograde dissection with an entry tear in the descending aorta. However, guidelines recommend urgent surgical repair for both entities. Methods and Results: All patients with AD enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2014 were analyzed. We identified 99 patients (67 men; 63.2±14.0 years) with an entry tear in the descending aorta and retrograde extension into the arch or ascending aorta. Overall, independent predictors of retrograde type A AD were increasing age(OR 1.0; 95% CI, 1.0 to 1.0; P=0.004), history of cocaine abuse (OR 4.9; 95% CI, 1.7 to 13.6; P=0.003), back pain at presentation (OR 2.1; 95% CI, 1.3 to 3.3; P=0.002), and non-white race (OR 0.4; 95% CI, 0.2 to 0.6; P Conclusion: There is a subset of patients with acute retrograde type A AD who can be managed non-operatively with acceptable short and long-term results. This implies that a selective approach may be reasonable, particularly among those with proximal extension limited to the arch distal to the innominate artery.

Background: This study assessed the incidence of lower limb ischemia as well as trends in management and outcomes while examining acute aortic dissection patients over a period of 15 years. Additionally, differences in clinical presentation, interventions performed, and mortality between patients with and without lower limb ischemia were investigated. Methods: Lower limb ischemia (LLI) was evaluated among 3812 patients enrolled in the International Registry of Acute Aortic Dissection over a 15-year period that was separated into three 5-year intervals: 1996-2001, 2002-2007, and 2008-2012. The cohort was then divided by dissection type and presence or absence of LLI. Results: Type A patients presenting with limb ischemia (N=280, 11.4%) were much more likely to have atherosclerosis (p=0.021) and to present with back, abdominal and leg pain versus chest pain (p Type B patients with LLI (N=102, 7.5%) were more likely to be current smokers (p=0.028), to present febrile (p=0.022), and to have leg pain (p Conclusions: Although Type B patients with LLI received more endovascular procedures in later years, overall mortality did not improve. Increased complications and higher mortality in the LLI cohort suggests a need for better monitoring and increased implementation of interventions in this population.

Background— Previous studies have demonstrated that mitral annulus early diastolic (e′) velocity is increased in constrictive pericarditis (CP) and reduced in restrictive cardiomyopathy. However, those studies did not comprehensively evaluate mitral and tricuspid annular velocities before and after pericardiectomy. Methods and Results— We performed comprehensive echocardiography before and after pericardiectomy in 99 patients with CP, 52 with primary (idiopathic or postpericarditis etiology) and 47 with secondary CP (due to surgery or radiation). Overall, mean±SD mitral medial, mitral lateral, and tricuspid lateral e′ velocities were 12.2±4.2, 10.0±5.4, and 11.6±3.5 cm/s, respectively; annular late diastolic velocities were 10.3±4.3, 12.2±4.9, and 11.7±5.4 cm/s, respectively; and annular systolic (s′) velocities were 7.8±2.8, 8.2±2.1, and 11.2±3.8 cm/s, respectively. Medial e′ was equal to or greater than mitral lateral e′ in 74% of analyzable cases. With the exception of tricuspid s′, there were significant differences in all s′ and e′velocities between primary and secondary CP before pericardiectomy. After pericardiectomy, all annular velocities decreased significantly ( P P P =0.0004, respectively), and the mitral lateral/medial e′ ratio normalized ( P =0.0002). Conclusions— The mitral lateral/medial e′ ratio is reversed in three fourths of patients with CP. All annular velocities are lower in secondary compared to primary CP before pericardiectomy. After pericardiectomy, there is reduction of all annular velocities and normalization of the mitral lateral/medial e′ ratio.

Background Reduced risk of paraplegia is argued as an advantage of endovascular repair of descending thoracic aortic aneurysms (DTA) and thoracoabdominal aortic aneurysms (TAAA); however, paraplegia rates with open repair vary widely. Study Design We identified consecutive patients undergoing open repair of TAAA or DTA with or without arch replacement using profound hypothermia and circulatory arrest as a spinal cord protection strategy on a single surgical service between June 1, 2001 and September 20, 2010. Results Ninety-nine procedures were performed in 94 patients with a mean age of 59 years (range 19 to 84 years), 56 of whom were male (60%). The extent of repair was TAAA in 37 (Crawford extent I in 6, extent II in 28, and extent III in 3), DTA in 37, and DTA plus arch in 25. Surgery was urgent or emergent in 25 patients (25%). Operative mortality (30-day) was 10% (10 of 99), including a mortality of 12% for arch DTA (3 of 26), 11% for TAAA (4 of 25), and 5% for isolated DTA (2 of 37). There were 11 (11%) strokes and 11 patients experienced renal failure (7 with dialysis). There were 15 late deaths and survival at 5 years was 74% (95% CI, 62.4−88.2%). No patients experienced paraplegia, although one had delayed paraparesis thought to be secondary to refractory hypotension postoperatively. Conclusions Although the mortality and stroke risks for patients undergoing repair of DTA or TAAA using profound hypothermia and circulatory arrest are substantial, the risk for paraplegia is low. In appropriately selected patients, profound hypothermia and circulatory arrest should be the preferred technique for spinal cord protection for DTA and TAAA.

Recent years have witnessed the emergence of novel technologies that enable less invasive endovascular treatment of descending thoracic aortic disease (TAD). This has occurred against a backdrop of improved identification of various disease processes and better results with open surgical repair. The natural history of the specific acute aortic syndromes that affect the descending thoracic aorta has also been described with more clarity and has become more commonly recognized. This is in part secondary to the widespread availability and application of advanced imaging technologies that permit precise diagnoses. As data are accumulating, these pathological processes involving the descending thoracic aorta are no longer thought of as simply variants of one another but as distinct entities with well-defined clinical behavior. As the technology for endovascular repair continues to mature and its utilization increases, there is a need for a careful assessment of the current state of medical management, traditional open therapy, and evolving endovascular treatment of distinct thoracic aortic pathologies. The purpose of this scientific statement is to present a contemporary review of the various pathological processes that affect the descending thoracic aorta: Aneurysms, dissections, intramural hematomas (IMHs), penetrating atherosclerotic ulcers (PAUs), and aortic transections. These disorders will be considered in detail, with an exploration of the natural history, available treatment options, and controversies regarding management. Current intervention criteria will be reviewed with respect to both open surgical repair and endovascular treatment. Our goal is to provide the healthcare professional with a better understanding of the pathophysiology of the various disease processes that involve the descending thoracic aorta and to review current outcomes and technical pitfalls associated with these therapies to facilitate strong, evidence-based decision making in the care of these patients. Treatment of descending TAD involves complex, exigent decision making in an era of evolving technology. Survival data for nonoperative …

Background Preprocedural briefings have been adopted in many high consequence environments, but have not been widely accepted in medicine. We sought to develop, implement, and evaluate a preoperative briefing for cardiovascular surgery. Study Design The briefing was developed by using a combined questionnaire and semistructured focus group approach involving five subspecialties of surgical staff (n=55). The results were used to design and implement a preoperative briefing protocol. The briefing was evaluated by monitoring surgical flow disruptions, circulating nurse trips to the core, time spent in the core, and cost-waste reports before and after implementation of the briefing across 16 cardiac surgery cases. Results Focus group data indicated consensus among surgical staff concerning briefing benefits, duration, location, content, and potential barriers. Disagreement arose concerning timing of the brief and the roles of key participants. After implementation of the briefing, there was a reduction in total surgical flow disruptions per case (5.4 preimplementation versus 2.8 postimplementation, p=0.004) and reductions in per case average of procedural knowledge disruptions (4.1 versus 2.17, p=0.004) and miscommunication events (2.5 versus 1.17, p=0.03). There was no significant reduction in disruptions because of equipment preparation or disruptions from patient-related issues. On average, briefed teams experienced fewer trips to the core (10 versus 4.7, p=0.004) and spent less time in the core (397.4 seconds versus 172.3 seconds, p=0.006), and there was a trend toward decreased waste (30% versus 17%, p=0.15). Conclusions These findings demonstrate the feasibility of creating a specialty-specific preoperative briefing to decrease surgical flow disruptions and improve patient safety in the operating room.

Background— Several studies have compared short-term and medium-term mortality rates for patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR), but no studies have compared short-term readmission rates for the 2 procedures. Methods and Results— New York’s Cardiac Surgery Reporting System was used to propensity match 617 TAVI and 1981 SAVR patients using numerous patient risk factors contained in the registry. The 389 propensity-matched pairs were then used to analyze differences in readmission rates between the 2 groups. TAVI and SAVR readmission rates were also compared for patients with a history of congestive heart failure and for patients aged ≥80. Also, reasons for readmission for TAVI and SAVR patients were examined and compared. Readmission rates were not statistically different for all propensity-matched TAVI and SAVR patients (respective rates, 18.8% and 19.3%; P =0.86). After further adjustment using a logistic regression model, there was still no significant difference (adjusted odds ratio, 0.97; 95% confidence interval [0.68–1.39]). For patients aged ≥80, the 30-day readmission rates were 19.9% and 22.0% ( P =0.59), and when further adjusted using the logistic regression model, adjusted odds ratio=0.89 (0.55–1.45). For patients with a history of congestive heart failure, the respective rates were 22.8% and 20.4% ( P =0.56), and with further adjustment, adjusted odds ratio became 1.15 (0.72–1.82). Conclusions— There are no statistically significant differences between TAVI and SAVR patients in short-term readmission rates.

Background— In the elderly, mitral regurgitation (MR) is frequent, but surgery risks are considered high. Benefits and indications of MR surgery are uncertain in the elderly. Methods and Results— Baseline characteristics, outcome, and trends for surgical results improvement were analyzed in elderly patients (≥75 years of age; n=284) operated on for MR in 1980 to 1995 compared with younger patients (65 to 74 years of age, n=504; and P P P =0.54). Temporal trends showed that risk of operative mortality, although higher in elderly patients ( P P P P =0.06), with a parallel decline in low cardiac output and length of hospital stay. Over time, valve repair feasibility increased in all age groups (30% to 84% overall and 31% to 93% in degenerative MR; P Conclusions— Elderly patients undergoing MR surgery display more severe preoperative characteristics and incur higher operative risks than younger patients. However, restoration of life expectancy after surgery is similar in elderly and younger patients, and outstanding recent surgical improvements particularly benefited elderly patients. Thus, elderly patients with MR can now carefully be considered for surgery before refractory heart failure is present.

Introduction: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an emerging therapy for refractory cardiogenic shock (CS); however, characteristics of patients most likely to benefit from this therapy remain to be determined. We hypothesized that the underlying etiology of CS and patient specific characteristics predict survival to discharge. Methods: We compared outcomes in patients supported with VA-ECMO for refractory CS resulting from (1) acute myocardial infarction (AMI; with or without revascularization); (2) acute pulmonary embolism (PE); (3) acute cardiomyopathy; (4) chronic cardiomyopathy; (5) post-cardiotomy; and (6) other etiologies of shock. Chi-square analysis was used to identify predictors of survival to discharge after VA-ECMO. Results: From 2009-2013, 102 patients were initiated on VA-ECMO for refractory CS. The average age was 52 ±15 (mean ± SD) years old with 71 (70%) males. Overall, 39 (38%) patients survived to discharge. In the cohort, 22 patients were post-cardiotomy and 5 (23%) of those survived to discharge. Of the 80 patients without prior cardiotomy, survival to discharge was 27% (8/30) after AMI, 64% (9/14) after PE, 75% (6/8) with acute cardiomyopathy, 50% (5/10) with chronic cardiomyopathy, and 39% (7/18) with other CS etiologies. Survivors were younger (45 ±13 vs 56 ±14, p = 0.0002) and none of the 24 patients over the age of 64 years old survived to discharge. There was a significant difference in survival when comparing etiologies of shock (p = 0.012 by Chi-square comparison among etiologies). There was no significant difference in survival by gender. Conclusions: Survival in patients with refractory CS requiring VA-ECMO may depend on age and underlying etiology of shock. Further research into predictors of survival after institution of VA-ECMO is warranted.

Background— The incidence, determinants, and outcome of postoperative atrial fibrillation (AF) after surgery for mitral regurgitation (MR) are poorly defined but may have important implications for timing of mitral valve surgery. Methods and Results— In 762 patients in sinus rhythm with no AF history undergoing MR surgical correction, we examined the rates and prognostic implications of postoperative AF for early AF (within 2 weeks postoperatively) and late AF (>2 weeks after surgery). During postoperative follow-up, 180 patients (24%) experienced new AF (early AF in 136 and late AF in 111). Isolated early AF without recurrence was observed in 69 patients characterized by high angina class and lower left ventricular ejection fraction but no significant left atrial (LA) enlargement. However, overall early AF predicted late AF: 62±5% of patients with early AF had late AF at 10 years compared with 9±1% of patients without early AF ( P P =0.01) and late AF ( P =0.003). For late AF, the predictive value of an enlarged LA was cumulative to that of early AF. Postoperative AF was associated with an increased subsequently higher risk of stroke or congestive heart failure (adjusted risk ratio=1.46 [1.04 to 2.05], P =0.03). Conclusions— Postoperative AF is common after surgical correction of MR in patients with no prior history of AF and is associated with increased subsequent morbidity. LA enlargement is independently predictive of postoperative AF and as such, should be integrated into the clinical decision-making process in patients with MR.

Thoracic aortic aneurysm (TAA) is a degenerative condition of the aorta characterized by aortic dilatation secondary to tissue inflammation and matrix remodeling, which ultimately progresses to aortic dissection and rupture. While recent work suggests that in vitro exposure to pro-inflammatory stimuli promotes DNMT3b-dependent DNA methylation in skeletal muscle, epigenetic mechanisms regulating gene expression in TAA remain largely uncharacterized. We therefore tested the hypothesis that expression of tumor necrosis factor α (TNF-α) is increased in human TAA tissue and that such increases are associated with upregulation of DNA methyltransferase (DNMT) levels. Normal aortic samples (n=13) were acquired from non-aneurysmal hearts/aorta not suitable for cardiac transplant, whereas TAA samples from patients with tricuspid aortic valves (n=29) were acquired from patients undergoing elective surgery for aortic aneurysm. We measured relative expression of TNF-α, DNMT1, DNMT3a and DNMT3b mRNA levels in normal and TAA tissue by qRT-PCR, and DNMT3b protein levels by western blot. Marked increases in expression of the inflammatory marker TNF-α were noted in TAA tissue (12.3± 2.34), and were associated with significantly increased DNMT1 (1.4±0.13), DNMT3a (1.44±0.09) and DNMT3b (1.94±0.27) mRNA levels (p

Background Despite a number of studies showing that women and men respond to coronary artery bypass graft surgery differently, it is not known whether variables associated with mortality are the same for women and men. The purpose of this study was to identify variables independently associated with mortality for women undergoing coronary artery bypass graft surgery. Methods Single-institutional data were prospectively collected from 5,113 patients (1,558 or 30.5% women) undergoing coronary artery bypass graft surgery. The database was reviewed for patient characteristics and operative outcomes based on sex. Complications evaluated included low cardiac output syndrome (cardiac index < 2.0 l x min(-1) x m(-2) for > 8 h, regardless of treatment), stroke (new permanent global or focal motor deficits), Q-wave myocardial infarction, postoperative atrial fibrillation, and operative mortality. Results Women were older than men, and they were more likely to have preexisting hypertension, diabetes, and a history of stroke. Operative mortality for women was higher than for men (3.5% vs. 2.5%, P < 0.05). Compared with men, women were more likely to experience a postoperative myocardial infarction, stroke, and low cardiac output syndrome. When performing analysis on data from both sexes separately, low cardiac output syndrome, new stroke, myocardial infarction, and duration of cardiopulmonary bypass were independently associated with mortality for women and men both. Patient age was not independently associated with risk for mortality for women, but it was for men. However, when the authors combined both sexes in the logistic regression analysis, the age-sex interaction was not significant (P = 0.266), indicating that there was insufficient evidence to assert that age has a different effect on mortality for men and women. Conclusions These data confirm that women have higher perioperative mortality after coronary artery bypass graft surgery compared with men. A higher frequency of cardiac and neurologic complications seem to account to a large extent for the higher operative mortality for women. Factors independently associated with perioperative mortality are generally similar for women and men.

Interest in transmyocardial laser revascularization for the treatment of otherwise inoperable coronary artery disease has increased rather dramatically in recent years. The results of several industrially sponsored clinical series have been reported recently, all with significant improvement in angina pectoris that appears both rapid and sustained. In most instances, an associated improvement in exercise tolerance has been reported. Improvement in regional myocardial perfusion has been proclaimed, although it is less consistent and less complete than symptom relief. The mechanisms whereby this clinical effect is achieved remain unknown. Histologic analysis of autopsy material has yielded somewhat conflicting results regarding the persistent patency of laser-created channels. The results of laboratory investigations of this therapy have been equally inconsistent. Despite our ignorance regarding the mechanism of angina relief, clinical experience continues to grow. In addition to the CO2 laser energy source used in early studies, trials of alternative devices using holmium:yttrium-aluminum-garnet and eximer lasers are underway. The latter two employ fiberoptic technology and are currently under development for endovascular approaches.

With reference to vascular malformations, the term cavernous has architectural as well as histologic connotations. It refers to a compact pattern of growth wherein no intervening brain parenchyma is evident, as well as to the histological nature of the vessels, which are hyaline and collagenous in appearance, lacking the microscopic features of arteries or veins. Historically, cavernous angioma has been defined as exhibiting both features. Twenty-five patients with neurological symptoms and neuroimaging abnormalities who underwent surgery for cerebral vascular malformations between 1987 and 1990 satisfied the following study criteria: their lesions were angiographically occult and both magnetic resonance imaging (MRI) and histological sections were available for review. The patients' ages ranged from 4 to 49 years (mean, 30 years), the male to female ratio being 1:2. Two thirds of the lesions were supratentorial in location and all were intraparenchymal. All patients had clinical improvement after resection. In 24 of the 25 lesions, the vascular channels were histologically cavernous in nature; one inadequate specimen precluded classification. Three demonstrated a purely compact or cavernous pattern, 20 a mixed cavernous and racemose pattern, and one a purely racemose pattern. The authors conclude that 1) histologically cavernous lesions are the commonest form of occult vascular malformation; 2) a purely compact or cavernous architectural pattern is uncommon, most lesions showing a partially racemose architecture; 3) some histologically cavernous malformations possess a capillary component; 4) clinical growth of cavernous malformations may have its basis in intraluminal thrombosis and subsequent recanalization; 5) the T2-weighted MRI pattern of cavernous malformations varies, the most common being a multifocal hyperintense center surrounded by a hypointense ring; 6) the MRI pattern reflects the histological appearance; 7) since no thrombosed arteriovenous malformations were encountered, such lesions must be rare; 8) in that the pathophysiological hallmark of a cavernous lesion is recurrent thrombosis and hemorrhage, a resolving hematoma cannot always be distinguished from a cavernous lesion; 9) MRI is the examination of choice in evaluating occult vascular malformations; and 10) microsurgical excision is a satisfactory method of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

In miniature swine, one-haplotype class I disparate renal allografts are accepted without exogenous immunosuppression by approximately 35% of recipients. Alternatively, transplants bearing a two-haplotype class I mismatch are always rejected acutely. However, long-term acceptance in the latter animals can be achieved uniformly with a 12-day course of cyclosporine. In vitro studies of recipient cell-mediated lymphocytotoxicity responses have shown donor-specific cytotoxic T lymphocyte clones in tolerant animals, suggesting that tolerance may be a local phenomenon or a central phenomenon activated in the milieu of the graft. Six animals were retransplanted with kidneys MHC-matched to their original allograft to determine whether (1) tolerance is a central phenomenon; (2) host tolerance can be broken with a fresh challenge of donor antigen and antigen-presenting cells; and (3) graft adaptation is required for maintenance of tolerance. Four of the retransplanted animals had been spontaneous acceptors of one-haplotype class I-disparate grafts and two had been rendered tolerant to two-haplotype class I-mismatched kidneys with CsA induction. All six explanted allografts showed no histological evidence of rejection and all six retransplants were accepted without exogenous immunosuppression. These findings suggest that in miniature swine tolerance of class I-disparate kidneys is a stable, centrally mediated phenomenon that cannot be broken with a challenge of fresh donor antigen and donor-type APCs. Furthermore, successful retransplantation without immunosuppression in animals receiving CsA induction therapy for their first transplant suggests that graft adaptation is not necessary for the maintenance of tolerance.

Twenty-three cases of transitional cavernous aneurysms are presented. Aneurysms of this subgroup (of a total of 118 cases of cavernous sinus aneurysms) arise entirely from within the cavernous sinus but project into the extracavernous intradural subarachnoid space, thus resembling other intracranial aneurysms in their increased risk of rupture. Six aneurysms were small (less than 15 mm), 6 were large (15 to 25 mm), and 11 were giant (more than 25 mm). Thirteen patients (57%) had a subarachnoid hemorrhage, nine patients (39%) had compressive symptoms, and one patient (4%) was asymptomatic. A direct surgical approach was performed successfully in 18 cases (78%), and indirect bypass methods were performed in 5 cases. The overall surgical outcome was excellent in 87% of the patients, with three complications (13%) including one fatality. It is suggested that this subgroup is a different entity from other cavernous or extracavernous aneurysms and should be managed aggressively with direct clipping whenever possible because of the increased risk of subarachnoid hemorrhage. A simplified numerical classification system of clinoidal-region aneurysms of the internal carotid artery (including transitional aneurysms) is also proposed.

Studies of the myeloablative regimens capable of permitting successful BMT across MHC barriers in miniature swine have been performed. To minimize graft-versus-host disease (GVHD), engraftment was studied in the F1-->P combination (i.e., MHC homozygous ["parental"] swine receiving bone marrow from one-haplotype matched MHC heterozygous ["F1"] donors). Animals given total body irradiation (TBI) up to 1100 cGy, 10 cGy/min, in a single dose failed to engraft. Increasing the dose rate led to unacceptable extramedullary toxicity without improving engraftment. Eleven different fractionated TBI regimens were tested in this F1-->parent model. At all of the dose rates tested, a total dose of less than 1000 cGy was insufficient for engraftment, and a total dose of 1400 cGy led to unacceptable toxicity. Between these extremes, a window was defined in which engraftment could be obtained without unacceptable extramedullary toxicity utilizing 2 equally divided fractions of TBI delivered 24 hr apart. The addition of 50 mg/kg cyclophosphamide i.v. to fractionated TBI (1150 cGy total dose [500 + 650]) also permitted engraftment, with decreased incidence of interstitial pneumonitis as compared to fractionated TBI (1300 cGy total dose [650 x 2]). Both of these regimens were also confirmed to permit engraftment between heterozygous donors and recipients sharing a single common haplotype ("F1-->F1"). The regimen of 1300 cGy (650 x 2) also permitted engraftment in completely MHC mismatched BMT, but with subsequent death from GVHD. These studies of the myeloablative regimens permitting engraftment across defined MHC barriers in miniature swine provide a basis for further studies of allogenic BMT and GVHD in this large animal preclinical model.

Previous studies in miniature swine have suggested that the mechanism underlying the spontaneous development of tolerance in one third of one-haplotype class I disparate renal allografts (i.e., ag----ad) involves a relative T cell help deficit at the time of first exposure to antigen. If this hypothesis were correct, then one might expect the administration of an immunosuppressive agent capable of inhibiting lymphokine production during this period to lead to the induction of tolerance to class I MHC antigens in two-haplotype class I mismatched renal allografts (i.e., gg----dd), which are otherwise uniformly and acutely rejected. This hypothesis was tested in eight two-haplotype class I disparate, class II matched donor-recipient pairs, in which recipients were treated with cyclosporine 10 mg/kg, i.v. q.d. for 12 days. This protocol led to the induction of long-term (greater than 100 days) specific tolerance in 100% of recipients, as compared with control animals that rejected grafts in 13.7 +/- 0.9 days (P less than 0.0001). The specificity of tolerance was assessed both in vivo with subsequent skin grafts and in vitro by mixed lymphocyte response (MLR) and cell-mediated lymphocytotoxicity (CML). Survival of donor-specific skin grafts was prolonged compared with skin grafts bearing third-party class I antigens (19.5 +/- 2.0 versus 11.5 +/- 2.0 days, n = 4, P less than 0.05). Tolerant recipients had markedly diminished or absent anti-donor MLR and CML responses, but maintained normal reactivity to third party. Four of eight CsA-treated recipients showed detectable levels of anti-donor IgM, while none demonstrated the presence of anti-donor IgG, which was found in all rejecting controls.

Previous studies from our laboratory have shown that permanent lymphohematopoietic chimerism can be induced in MHC-disparate miniature swine by bone marrow transplantation after lethal total-body irradiation. The purpose of the present study was to determine in this large animal model whether such chimerism would lead to permanent tolerance to a vascularized allograft without a requirement for exogenous immunosuppression. Eight miniature swine that had received MHC-mismatched BMT more than five months earlier underwent kidney transplantation (KTx) from a donor MHC matched (n = 5) or MHC mismatched (n = 3) with the BMT donor. All animals had regained in vitro responsiveness to third-party MHC antigens, as measured by mixed lymphocyte reaction (MLR), before KTx but remained nonresponsive to MHC antigens of the BMT donor and self. All three animals that received KTx mismatched for BMT donor MHC rejected promptly (mean survival time 7.0 days). Of the five animals that received KTx matched for BMT donor MHC, four showed no evidence of rejection and have functioning KTx greater than 200 days after KTx. The fifth animal had excellent renal function for 60 days but then developed a slowly rising BUN and serum creatinine, and died 75 days after KTx. The course of this animal's rejection is consistent with that previously described for rejection due to minor antigen disparities. The difference in survival of KTx matched or mismatched for the MHC of the BMT donor was statistically significant (P = 0.0062). The survival of KTx matched for the MHC of the BMT donor was significantly different from that of control animals without BMT receiving KTx mismatched for MHC (P = 0.0018). We therefore conclude that BMT is an effective means for induction of tolerance to an MHC mismatched KTx in this large animal model.

Background: Bicuspid aortic valve disease (BAV), the most common congenital cardiovascular malformation, has an incidence of 0.5–1.0% of live births. While most cases of BAV appear to be sporadic, familial inheritance patterns have been observed consistent with autosomal dominant inheritance with variable penetrance. However, little is known about specific genetic loci responsible for familial BAV. Here, we performed linkage analysis on a large multi-generational pedigree affected with BAV. Methods: We identified a large, five-generation pedigree (136 family members) with 10 individuals having BAV. Two-dimensional echocardiography was used to assign aortic valve phenotype. Genome-wide linkage analysis using 430 microsatellite markers (Marshfield Clinic) and fine mapping using 100 single nucleotide polymorphisms (Affymetrix) on chromosome 9 was performed on genomic DNA from all available family members. Logarithm of odds (LOD) scores of >2.0 were considered suggestive of linkage. Comprehensive splice site/open reading frame mutational analysis of candidate genes residing in the putative locus is underway using PCR, DHPLC, and DNA sequencing. A candidate gene, KLF9, Krüppel-like factor 9 was analyzed for mutations because of its role in cardiogenesis. Results: Multi-point genome-wide linkage analysis demonstrated a 7 cM region on chromosome 9q21 that was suggestive of linkage for familial BAV with a maximum multipoint LOD score of 2.8 flanked by the microsatellite markers GATA7D12 and D9S1834. This region contains several candidate genes with biological plausibility for BAV phenotype. KLF9- encoded Krüppel-like factor 9, localized to chromosome 9q21, was targeted as a prime candidate gene for familial BAV. However, no mutations involving the translated exons of KLF9 were detected. Further fine mapping studies and candidate gene analysis are currently underway. Conclusions: We report a novel susceptibility locus on chromosome 9q21 for BAV in a large multi-generational family. Although coding region mutations in KLF9 are not responsible for BAV in this pedigree, several candidate genes with biological plausibility for the development of congenital BAV lie within this region and warrant further scrutiny.

Background Left ventricular aneurysm (LVA) is a significant complication of myocardial infarction that may lead to global left ventricular (LV) dysfunction. However, the exact mechanism underlying the abnormal function has not been elucidated. In this study we tested the hypothesis that changes in LV geometry cause both an increase in wall stress and a change in the temporal distribution of stress in the LVA border zone (BZ) during systole. Methods Transmural anteroapical infarcts were created in adult Dorsett sheep (n=8) and were allowed to mature into LVAs for 10 weeks. Animals were imaged subsequently using MRI with simultaneous recording of intraventricular pressures. Cardiac models were constructed from the MRI images at end-diastole, isovolumic systole, peak-systole and end-systole. Two short-axis slices, 1 basal and 1 apical were analyzed. The apical slice included the septal and anterior component of the aneurysm as well as the corresponding BZs and normal myocardium. Regional wall stresses were calculated using finite element analysis and compared with stresses in corresponding regions from normal control sheep (n=7). Results In the LVA group, stress was significantly increased in the BZ at the end-diastolic, isovolumic, peak-systolic, and end-systolic instants ( P Conclusions Geometric changes in the LVA hearts increased wall stress and altered its temporal distribution in the BZ region. Correlation of this finding with the corresponding regional blood flow, oxygen consumption, and mechanical systolic performance may help elucidate the mechanism underlying the observed global LV dysfunction.

Background —The optimal management of aortic valve disease in patients >80 years old depends on functional outcome as well as operative risks and late survival. Methods and Results —We retrospectively identified 133 patients (62 men, 71 women) aged 80 to 91 years (mean 84±3 years) who underwent aortic valve replacement alone or in combination with another procedure between January 1, 1993, and April 31, 1998. Demographics included hypertension 68%, diabetes mellitus 17%, and history of stroke 11%. Operative (30 day) mortality rate was 11%. Urgent or emergent surgery, aortic insufficiency, and perioperative stroke or renal dysfunction were risk factors for operative death by multivariable analysis. Intensive care unit and total hospital length of stay were prolonged at 6.2 and 14.7 days, respectively. Late follow-up between July 1, 1998, and November 1, 1999, was 98% complete. Actuarial survival at 1 and 5 years was 80% and 55%, respectively. Predictors of late mortality were preoperative or perioperative stroke, chronic obstructive pulmonary disease, aortic stenosis, and postoperative renal dysfunction. The mean New York Heart Association functional class for 65 long-term survivors improved from 3.1 to 1.7. Quality of life assessed with the Medical Outcomes Study Short Form-36 was comparable to that predicted for the general population >75 years old. Conclusions —Functional outcome after aortic valve replacement in patients >80 years old is excellent, the operative risk is acceptable, and the late survival rate is good. Surgery should not be withheld from the elderly on the basis of age alone.

anteriorly to fit the ventricles and the dog weaned off dobutamine. Five untreated HF dogs served as controls. LV end-diastolic (EDV) and end-systolic (ESV) volumes and ejection fraction (EF) were measured from angiograms performed before (PRE) and 3 months after (POST) implantation. Average myocyte length and width, measures of hypertrophy, were determined at 3 months in isolated myocytes from both groups and compared to normal (NL) dogs (n 5 5).

The fluorescence of reduced nicotinamide adenine dinucleotide (NADH) from cerebral cortex was measured before, during, and after middle cerebral artery (MCA) occlusion and then at death of the animal. In normal cortex, NADH remained constant throughout a wide range of variations in blood pressure and Pa co co2 . In ischemic cortex, NADH levels were higher in hypovolemic hypotensive animals than in normotensive normovolemic animals. Neither hypercapnia nor hypocapnia was effective in decreasing NADH in regions of ischemia, but the latter was associated with a degree of hypotension that interfered with interpretation of data. NADH returned to normal with restoration of flow, supporting the reversibility of this degree of ischemia. The high levels of NADH at death, compared to those during ischemia, are consistent with incomplete ischemia in this model of cerebral infarction.

Three cases are described of infants who developed malignant brain swelling (and in one case hemorrhage) after surgery for vein of Galen malformations. The cause for the brain swelling was felt to be due to hyperperfusion, or the “normal perfusion pressure breakthrough” syndrome. Although well-described for cerebral parenchymal arteriovenous malformations, cases of this complication occurring in vein of Galen malformations have not previously been reported. It is concluded from these cases that infants with large arteriovenous shunts, as attested by cardiac failure and cerebral atrophy, have an increased risk of developing this complication.

The alterations in metabolism and cerebral blood flow that occur following transient focal ischemia were studied in rabbits anesthetized with halothane and subjected to transient occlusion of an M2 segment of the middle cerebral artery (MCA). The parameters measured included intracellular brain pH and focal cortical blood flow (fCBF)—assessed by the umbelliferone technique—electrocorticograms, and cortical microcirculatory changes. A gradient of ischemia developed in the cortex between the patent and occluded vessels. Cortical sites with moderate and severely diminished flow were examined as a function of time before and after occlusion. Mean preocclusion fCBF was 50.8 ± 2.1 ml/100 g/min, and brain pH was 6.99 ± 0.04. Following occlusion, fCBF fell to 14.6 ± 2.3 ml/100 g/min, with an intracellular pH of 6.53 ± 0.03 in sites of severe ischemia in the territory of the occluded vessel. Sites between the patent and occluded branches revealed moderate changes in fCBF and intracellular pH of 26.7 ± 3.6 ml/100 g/min and 6.74 ± 0.03 ml/100 g/min, respectively. Sites adjacent to the patent M2 branch remained similar to baseline. Pretreatment intravenously with nimodipine, a dihydropyridine class of Ca2+ channel antagonist, improved flow in the territory of the occluded segment of the middle cerebral artery to 30.6 ± 2.2 ml/100 g/min, while maintaining the brain pH at 6.83 ± 0.03. Similarly, at sites intermediate between the patent and occluded M2 segments of the MCA, cortical blood flow remained at 53.5 ± 4.0 ml/100 g/min, and the pH at 6.95 ± 0.04, in 10 animals pretreated with nimodopine. This effect was apparently achieved by blocking the secondary, ischemia-induced vasoconstriction known to occur in areas of focal incomplete ischemia. The diphenylalkylamine class Ca2+ channel blockers was examined using verapamil. This was found to be without significant effect. The vehicle carrying nimodopine was also without effect. To authenticate further the reliability of MCA occlusion, a separate group of animals was examined with cautery occlusion of the M2 segment of the MCA. Nimodopine had an effect in this group of animals identical to that caused by occlusion of the vessel with a clip. Visual inspection of the cortex in control and treated animals revealed a marked difference in the development of cortical pallor and microcirculatory changes. We conclude that nimodopine protects the conducting vessels against the secondary vasoconstriction known to occur in areas of focal incomplete ischemia, and thus increases collateral flow. This agent may have the potential for brain protection in areas of incomplete focal ischemia from occlusion of a single major vessel.

Among 1992 patients undergoing carotid endarterectomy from January 1972 through December 1984, 57 operations were performed in 51 patients for recurrent carotid stenosis. Thirty-four of these cases had undergone initial surgery at this institution while 23 had endarterectomy elsewhere. Fifty-two of the 57 operations were for symptomatic disease while five were for evidence of a progressing lesion. All operative procedures were monitored with intracerebral blood flow measurements and continuous electroencephalograms. Twenty-three patients required intraoperative shunting. There were no complications related to shunt usage or to the period of temporary occlusion in patients who did not require shunting. Recurrent stenosis was related to intimal hyperplasia in 14 cases, recurrent atherosclerosis with interluminal thrombi or degenerated plaque in 27, unexplained soft thrombus in eight, proximal scarring in six, and to aneurysms in two. Intimal hyperplasia was the most common cause for restenosis within 2 years from the date of surgery and developed earlier in patients with a primary closure than in patients closed with a patch graft. The operative complication rate was 10.5% or 4 times the risk of surgery for primary atherosclerosis at this institution. Complications were attributed primarily to intraoperative and postoperative thromboembolic events related to apparent increased thrombogenicity of these vessels. The highest complication rate occurred in the group of patients undergoing surgery for thrombotic material in the internal carotid artery, either primary or with underlying atherosclerosis. There were no neurological complications in the group with myointimal hyperplasia. The authors' experience suggests that on-lay patch grafting without endarterectomy should be used in patients with myointimal hyperplasia. Patients with complicated recurrent atherosclerosis can be treated with endarterectomy and patch grafting, but interposition vein grafts should be considered in cases in which the vessels are extensively damaged by the recurrent plaque or with an unexplained thrombus at the site of previous endarterectomy.