Contribution of endogenous bradykinin to fibrinolysis, inflammation, and blood product transfusion following cardiac surgery: a randomized clinical trial.

Bradykinin increases during cardiopulmonary bypass (CPB) and stimulates the release of nitric oxide, inflammatory cytokines, and tissue-type plasminogen activator (t-PA), acting through its B2 receptor. This study tested the hypothesis that endogenous bradykinin contributes to the fibrinolytic and inflammatory response to CPB and that bradykinin B2 receptor antagonism reduces fibrinolysis, inflammation, and subsequent transfusion requirements. Patients (N = 115) were prospectively randomized to placebo, ε-aminocaproic acid (EACA), or HOE 140, a bradykinin B2 receptor antagonist. Bradykinin B2 receptor antagonism decreased intraoperative fibrinolytic capacity as much as EACA, but only EACA decreased D-dimer formation and tended to decrease postoperative bleeding. Although EACA and HOE 140 decreased fibrinolysis and EACA attenuated blood loss, these treatments did not reduce the proportion of patients transfused. These data suggest that endogenous bradykinin contributes to t-PA generation in patients undergoing CPB, but that additional effects on plasmin generation contribute to decreased D-dimer concentrations during EACA treatment.

Comparative effects of angiotensin receptor blockade and ACE inhibition on the fibrinolytic and inflammatory responses to cardiopulmonary bypass.

The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor blockade (ARB) on fibrinolysis and inflammation after cardiopulmonary bypass (CPB) are uncertain. This study tested the hypothesis that ACE inhibition enhances fibrinolysis and inflammation to a greater extent than ARB in patients undergoing CPB. One week to 5 days before surgery, patients were randomized to ramipril 5 mg/day, candesartan 16 mg/day, or placebo. ACE inhibition increased intraoperative bradykinin and tissue-type plasminogen activator (t-PA ) concentrations as compared to AR B. Both ACE inhibition and AR B decreased the need for plasma transfusion relative to placebo, but only ACE inhibition decreased the duration of hospital stay. Neither ACE inhibition nor AR B significantly affected concentrations of plasminogen activator inhibitor-1 (PAI -1), interleukin (IL )-6, IL -8, or IL -10. ACE inhibition enhanced intraoperative fibrinolysis without increasing the likelihood of red-cell transfusion. By contrast, neither ACE inhibition nor ARB affected the inflammatory response. ACE inhibitors and ARBs may be safely continued until the day of surgery.

Surgical treatment of a large left-main coronary artery aneurysm.

Coronary artery aneurysms are a rare condition with left-main trunk aneurysms occurring in only about 0.1 % of the population. We report on a giant left-main coronary artery aneurysm in a young male status post two previous open-heart operations. The aneurysm was successfully treated by patch occlusion of the ostial orifice and coronary revascularization of the left anterior descending and circumflex arteries.

Mitral valve repair in redo cardiac surgery.

An increasing number of patients are being referred for mitral valve repair in the redo cardiac surgery setting. The most common clinical scenarios involve prior coronary bypass surgery or aortic valve replacement, each presenting special challenges in terms of gaining valve exposure to enable repair while limiting dissection as much as possible. A right anterior thoracotomy approach is preferred in most patients, coupled with hypothermic fibrillatory arrest. A repeat sternotomy may be favored in select circumstances such as when there is a need for bypass grafting or moderate aortic insufficiency is present. Special attention to cannulation techniques, perfusion conditions, valve exposure, and de-airing maneuvers are all important to ensure good clinical results. Using a tailored approach we have performed mitral valve repair in 22 patients with a patent left internal mammary artery graft following coronary artery bypass grafting between July 1992 and February 2000 with acceptable morbidity and low mortality.

The preferred approach for mitral valve surgery after CABG: right thoracotomy, hypothermia and avoidance of LIMA-LAD graft.

BACKGROUND AND AIM OF THE STUDY: An alternative to avoid redo sternotomy in patients with patent left internal mammary artery-left anterior descending coronary artery (LIMA-LAD) grafts undergoing mitral valve surgery is right thoracotomy with moderate-deep hypothermia (approximately 20 degrees C) and fibrillatory arrest without aortic cross-clamping. Few reports exist which directly compare re-sternotomy and right thoracotomy. METHODS: Between July 1992 and February 2000, 47 patients (39 males, eight females; median age 66 years; range: 41-83 years; 41 in NYHA class III or IV) with patent LIMA-LAD grafts underwent mitral valve surgery. Thirty-seven patients were approached through a right thoracotomy with moderate-deep hypothermia (median 20 degrees C) and fibrillatory arrest (right thoracotomy group), and 10 were approached through a re-sternotomy, with aortic cross-clamping and cardioplegic arrest. The median ejection fraction was 42% (range: 20-71%). Univariate analysis was used to determine predictors of outcome, as well as to evaluate differences in characteristics between groups. RESULTS: Operative mortality (OM) and perioperative myocardial infarction for the entire cohort was 11% and 10%, respectively, and there were no inter-group differences. No preoperative characteristics were associated with OM. Two LIMA-LAD graft injuries occurred in the re-sternotomy group compared with none in the right thoracotomy group (20% versus 0%, p = 0.04). Transfusion requirements were also greater in the redo sternotomy group (median 7 versus 2 packed red blood cell units, p = 0.04). CONCLUSION: Right thoracotomy with moderate-deep hypothermia and fibrillatory arrest is the preferred approach for reoperative mitral valve surgery after coronary artery bypass grafting in the presence of patent LIMA-LAD grafts. These data suggest that this approach is associated with decreased incidence of LIMA-LAD graft injury, as well as reduced transfusion requirements.

Does coronary artery bypass grafting alone correct moderate ischemic mitral regurgitation?

BACKGROUND: The optimal management of moderate (3+ on a scale of 0 to 4+) ischemic mitral regurgitation (MR) remains controversial. Some advocate CABG alone, whereas others favor concomitant mitral annuloplasty. To clarify the optimal management of these patients, we evaluated the early impact of isolated CABG on moderate ischemic MR. METHODS AND RESULTS: Between January 1992 and August 1999, 136 patients (54% male, mean age 70.5 years, mean New York Heart Association class 2.7, mean ejection fraction 38.1%) with a preoperative diagnosis of moderate ischemic MR, without leaflet prolapse or pathology, underwent isolated CABG. Thirty-eight (28%) of 136 patients had intraoperative transesophageal echocardiography (TEE) before CABG, and 68 (50%) had postoperative transthoracic echocardiography (TTE) within 6 weeks of surgery. The subgroups of patients undergoing intraoperative TEE and postoperative TTE had preoperative characteristics similar to the overall group. The 30-day operative mortality was 2.9% (). Intraoperative TEE downgraded the severity of MR to mild or less (0 to 2+) in 89% (). On postoperative TTE, 40% () continued to have at least moderate MR (3 to 4+), 51% () improved somewhat to mild (2+) MR, and only 9% () had resolution of their MR (0 to 1+). The mean preoperative, intraoperative, and postoperative MR grades were 3.0+/-0.0, 1.4+/-1.0, and 2.3+/-0.8, respectively (P<0.001). CONCLUSIONS: CABG alone for moderate ischemic MR leaves many patients with significant residual MR and may not be the optimal therapy for most patients. Intraoperative TEE may significantly underestimate the severity of ischemic MR. A preoperative diagnosis of moderate MR may warrant concomitant mitral annuloplasty.

Long-term results of multivalve surgery for infective multivalve endocarditis.

OBJECTIVE: The natural history of medically treated multivalvular endocarditis is associated with dismal short and long term survival. However, the impact of surgical intervention on these results is relatively unknown. The objective of this retrospective study was to report our long-term results in patients requiring multivalve surgery for multivalvular endocarditis. METHODS AND RESULTS: Over a 24 year period beginning in 1972, multivalve surgical procedures were performed on 63 patients for infective endocarditis. Prosthetic valve endocarditis was present in 25 (40%), and acute or active endocarditis in 38 (60%). The early mortality was 16%. Out of 53 patients discharged from the hospital 87+/-4% were alive at 5 years and 64+/-9% at 10 years. There was no difference in early or late mortality between patients with prosthetic and native endocarditis (P=0.15 and P=0.77 for early and late mortality, respectively). The presence of active endocarditis did not affect operative outcome or late mortality. Twenty-one patients (88%) were in NYHA FC I, and none were in NYHA FC IV. The only prognostic factor of early and late mortality was the presence of an abscess at the time of the surgery. CONCLUSIONS: These results indicate that multivalve infective endocarditis treated surgically is associated with acceptable early and late mortality and excellent postoperative functional status. The early surgical intervention prior to an abscess formation offers the best chance for survival of patients with multivalve endocarditis.

Aortic valve reoperation after homograft or autograft replacement.

BACKGROUND AND AIM OF THE STUDY: With increasing use of homograft and autograft aortic valves for aortic valve replacement (AVR), more patients will be presenting for aortic valve reoperation due to structural degeneration of the homograft or autograft valve. Management options include homograft re-replacement, which may require extensive surgery, versus AVR with a mechanical valve or a stented xenograft. Here, results are reported in 18 consecutive patients who underwent aortic valve re-replacement (AVreR) after previous homograft or autograft insertion. METHODS: Between May 1976 and March 2001, 18 patients underwent AVR after previous homograft (n = 16) or autograft (n = 2) insertion. The homograft or autograft had been implanted as a full root in eight patients (44%), as a mini-root in one (6%), and in the subcoronary position in nine (50%). Indication for the reoperation was structural valve degeneration (n = 14; 72%) in one occasion combined with aneurysm of the homograft, or endocarditis (n = 4; 22%), and seven (39%) presented as a non-elective procedure. The median interval between the two operations was 5.4 years (range: 0.3-10.8 years). RESULTS: Fourteen patients (78%) received either a mechanical valve (n = 12; 67%) or a stented xenograft valve (n = 2; 11%). Four others (22%) required root re-replacement with either another homograft (n = 3) or a mechanical valved conduit (n = 1) for endocarditis (n = 2) or an associated aneurysm (n = 2). Overall hospital mortality was 11% (n = 2) due to stroke (n = 1) or respiratory failure (n = 1). Two patients died 3.1 and 7.0 years after the procedure. CONCLUSION: Aortic valve reoperation after previous homograft or autograft implantation is a rare operation and presents a high-risk group. A simplified approach was preferred by utilizing mechanical or stented xenograft valves at reoperation, while homograft re-replacement was reserved for endocarditis or an associated aneurysm.

Modified Glenn connection for acutely ischemic right ventricular failure reverses secondary left ventricular dysfunction.

BACKGROUND: Right heart failure after cardiopulmonary bypass can result in severe hemodynamic compromise with high mortality, but the underlying mechanisms remain poorly understood. After ischemia-induced right ventricular failure, alterations in the interventricular septal position decrease left ventricular compliance and limit filling but may also distort left ventricular geometry and compromise contractility and relaxation. This study investigated the effect of acute isolated right ventricular ischemia on biventricular performance and interaction and the response of subsequent right ventricular unloading by use of a modified Glenn shunt. METHODS: In 8 pigs isolated right ventricular ischemic failure was induced by means of selective coronary ligation. A modified Glenn circuit was then established by a superior vena cava-pulmonary artery connection. Ventricular performance was determined by conductance catheter-derived right ventricular pressure-volume loops and left ventricular pressure-segment length loops. Hemodynamic data at baseline, after right ventricular ischemia, and after institution of the Glenn circuit were obtained during inflow occlusion, and the load-independent contractile indices were derived. RESULTS: Right ventricular free-wall ischemia resulted in acute right ventricular dilation (118 +/- 81 mL vs 169 +/- 70 mL, P =.0008) and impairment of left ventricular contractility indicated by the reduced end-systolic pressure-volume relation slope (50.0 +/- 19 mm Hg/mm vs 18.9 +/- 8 mm Hg/mm, P =.002) and preload recruitable stroke work index slope (69.6 +/- 26 erg x cm(-3) x 10(3) vs 39.7 +/- 13 erg x cm(-3) x 10(3), P =.003). In addition, left ventricular relaxation (tau) was significantly prolonged (33.3 +/- 10 ms vs 53.0 +/- 16 ms, P =.012). Right ventricular unloading with the Glenn shunt reduced right ventricular dilation and significantly improved left ventricular contraction, end-systolic pressure-volume relation slope (18.9 +/- 8 mm Hg/mm vs 35.8 +/- 18 mm Hg/mm, P =.002), preload recruitable stroke work index slope (39.7 +/- 26 erg x cm(-3) x 10(3) vs 63.0 +/- 22 erg x cm(-3) x 10(3), P =.003), and diastolic performance (tau 53.0 +/- 16 ms vs 43.5 +/- 13 ms, P =.001). CONCLUSIONS: Right ventricular ischemia-induced dilation resulted in acute impairment of left ventricular contractility and relaxation. A modified Glenn shunt attenuated the left ventricular dysfunction by limiting right ventricular dilation and restoring left ventricular cavity geometry.

Composite stentless valve with graft extension for combined replacement of the aortic valve, root and ascending aorta.

OBJECTIVE: The composite mechanical valve conduit has been most commonly used for patients who require combined aortic valve, root, and ascending aorta replacement, but is limited, especially in the elderly, because of the need for long-term anticoagulation. We report the first consecutive series of patients in whom a composite stentless valve with graft extension, which does not require long-term anticoagulation, was performed. METHODS: Between April 1998 and July 2000, eight patients with severe aortic root and ascending aortic pathology underwent a combined aortic valve, root, and ascending aorta replacement with a Freestyle stentless porcine valve with a Hemashield graft extension. Mean age was 74 (range 56--82), three were males. Concomitant procedures included coronary artery bypass graft (CABG) alone (n=2), mitral valve replacement with atrial septal defect repair (n=1) and CABG with septal myomectomy (n=1). RESULTS: Operative mortality was zero. Median aortic cross-clamp and cardiopulmonary bypass times were 150 and 203 min, respectively. Two patients returned to the operating room for bleeding. Median blood transfusions and hospital length of stay were 4 units and 11 days, respectively. CONCLUSIONS: The composite stentless valve with graft extension is a reasonable alternative to a mechanical valve conduit for patients who require a combined aortic valve, root, and ascending aorta replacement, in whom anticoagulation is not desirable or contraindicated.

Technique for blood conservation in ABIOMED BVS 5000 ventricular assist device exchange.

We describe a technique for blood conservation when ABIOMED BVS 5000 blood pumps require exchange because of thrombus formation in the blood pumps. The technique is simple in concept but requires careful planning and coordination between surgeon and perfusionist.

Reoperative CABG using left thoracotomy: a tailored strategy.

BACKGROUND: Reoperative coronary artery bypass grafting (CABG) through a left thoracotomy is a challenging operation with no one dominant approach. We developed a tailored strategy for this difficult group of patients, integrating the currently available newer technologies for each patient indication. METHODS: Between October 1991 and October 1999, 50 consecutive patients underwent reoperative CABG through a left thoracotomy. Age was 65 +/- 9 years, 40 (80%) were men, and preoperative ejection fraction was 40 +/- 13. In 36 patients (72%) the left internal mammary artery had been placed to the left anterior descending coronary artery during the primary CABG and in 25 of 36 patients (70%) this left internal mammary artery-left anterior descending coronary artery graft was patent. The mean duration from previous CABG was 8.0 +/- 4.8 years. Three approaches were used: (1) conventional cardiopulmonary bypass using fibrillatory or circulatory arrest (n = 33, 66%); (2) Heartport endoaortic balloon occlusion (n = 4, 8%); and (3) off-pump beating heart techniques (n = 13, 26%). RESULTS: The off-pump CABG technique was used in the majority of recent patients and 1 (7.7%) had to be converted to cardiopulmonary bypass due to hemodynamic instability. When cardiopulmonary bypass was used its duration was 122 +/- 59 minutes and mean temperature on bypass was 24 degrees +/- 6 degrees C. In the 4 patients in whom the Heartport system was used, the median endoaortic occlusion duration was 49 minutes. Patients received an average of 1.4 grafts/patient. In 60 of 70 patients (89%) distal anastomoses were performed to an anterolateral coronary target. There were 3 of 50 (6%) operative deaths, 2 in the conventional group and 1 in the endoaortic balloon occlusion group. The mean length of stay in the 47 survivors was 7.8 +/- 3.9 days (median, 7 days). CONCLUSIONS: Reoperative CABG by left thoracotomy remains a challenging operation. Several techniques, including off-pump CABG, conventional cardiopulmonary bypass, circulatory arrest, and endoaortic balloon occlusion, should be in the surgeon's armamentarium to allow a tailored approach for each operation based on patient indications.

Minimal access aortic root, valve, and complex ascending aortic surgery.

We report our entire experience with minimal access aortic root, valve, and complex ascending aortic surgery. A total of 290 consecutive patients underwent aortic root, valve, and ascending aortic surgery between July 1996 and February 2000. Four groups were identified: isolated aortic valve replacement (AV group, n = 227), aortic root replacement (AR group, n = 44), aortic valve replacement with concomitant replacement of the supracoronary ascending aorta (V/A group, n = 9), and isolated ascending aortic replacement (AA group, n = 10). The procedures were performed through a partial upper hemisternotomy (87%) or a right parasternal approach (13%). Overall mortality was 3.1% (n = 7) for the AV group, 2.3% (n = 1) for the AR group, 0% for the V/A group, and 10.0% (n = 1) for the AA group. Complications included reoperation for bleeding in 10 (4.5%), two (4.7%), one (11.1%), and one (11.1%) for the four groups respectively; and sternal wound infection in eight (3.6%) patients of the AV group and one (2.3%) patient of the AR group. Five (2.3%) patients of the AV group suffered stroke. Isolated or more complicated aortic valve, root and ascending aortic surgery is feasible and safe through a minimally invasive approach with acceptable incidence of complications and mortality, without compromising the efficacy of the procedure.

Clinical and hemodynamic performance of the Toronto SPV bioprosthesis.

BACKGROUND AND AIM OF THE STUDY: By providing a superior hemodynamic profile, the stentless valve design allows ventricular remodeling and may improve patient survival after aortic valve replacement (AVR). Compared with stent-mounted prostheses, implantation is more complex and requires a longer ischemic time; this may adversely affect surgical risk, especially if patients are elderly or require a concomitant procedure. The mid-term clinical and hemodynamic performance of the Toronto SPV bioprosthesis in a predominantly elderly patient group was analyzed. METHODS: A total of 123 patients (median age 72 years) underwent AVR with the Toronto SPV. Concomitant procedures (mainly coronary artery bypass grafting, CABG), were performed in 60 patients (49%). Clinical details were recorded, with 100% follow up (total 317 patient-years). Hemodynamic evaluation, by serial echocardiography, was performed at four and 18 months after implantation. RESULTS: The early mortality rate was low (0.8%). Mean (+/- SD) actuarial survival at 53 months was 78 +/- 5.9%, with most patients (91%) in NYHA classes I and II. Freedom from valve-related complications were: endocarditis 93.8 +/- 2.3%, thromboembolism 90.3 +/- 3.7% and bleeding 95.8 +/- 1.8%; there were no structural failures. The valve hemodynamic profile was excellent for all sizes: peak gradient 8.8 +/- 4.3 mmHg, effective orifice area 1.9 +/- 0.54 cm2 with significant improvement in left ventricular fractional shortening. CONCLUSION: In this patient population the Toronto SPV was a suitable choice. Advanced age, a requirement for concomitant procedures and increased ischemic times did not adversely affect surgical risk. AVR with the Toronto SPV provided an excellent hemodynamic profile, and improved both left ventricular function and NYHA functional class.

Partial upper re-sternotomy for aortic valve replacement or re-replacement after previous cardiac surgery.

OBJECTIVE: We developed techniques for 'inverted T' partial upper re-sternotomy for aortic valve replacement (AVR) or re-replacement (AVreR) after previous cardiac surgery. We previously reported on decreased blood loss, transfusion requirements and total operative duration when compared to conventional full re-sternotomy. This report updates our series, one of the few to document a substantial benefit from a 'minimally-invasive' approach, refines a number of technical aspects of this new approach and reports follow-up. METHODS: Between November 1996 and December 1999, we performed 34 AVRs or AVreRs after previous cardiac surgery by use of an 'inverted T' partial upper re-sternotomy. There were 25 (74%) men. Median ejection fraction was 54%, range 15-80%. Median age was 72, range 38-93. All were New York Heart Association functional class (NYHA) functional class II or III. Twenty-one (62%) had previous coronary artery bypass grafts (CABG) while 14 (41%) had previous valve surgery. Follow-up was 100% complete for a total of 593 patient months (median 19 months). RESULTS: Twenty-three (66%) underwent AVR of the native aortic valve while 11 (33%) underwent AVreR of a prosthetic aortic valve. There were no intraoperative or valve-related complications, and no conversion to full re-sternotomy was necessary. There were two (5.9%) operative deaths from an arrhythmia on postoperative day 4 and a large stroke during surgery, respectively. Twenty-four (75%) patients were free of major complications. There was no need for reoperation for bleeding and patients required a median of two units of packed red blood cells. Complications included new atrial fibrillation (n=3, 9%), pacemaker implantation (n=3, 9%) and deep sternal wound infection (n=2, 6%). Median lengths of stay in the intensive care unit (ICU) and in the hospital were 1 and 7 days, respectively. There was one (3%) late deep sternal wound infection and 2/32 (6%) late deaths due to congestive heart failure at 22 months and myocardial infarction at 23 months, respectively. CONCLUSIONS: Partial upper re-sternotomy presents a safe and effective alternative approach to AVR and AVreR after previous cardiac surgery, and is associated with low morbidity and mortality.

Myocardial neutrophil sequestration during reperfusion of the transplanted rabbit heart.

BACKGROUND: Neutrophils are major participants in myocardial reperfusion injury, but the relationship between ischemic time and the extent of the neutrophil sequestration in heart transplantation has not yet been systematically studied. This study was designed to determine whether increased ischemic time would cause greater neutrophil sequestration during reperfusion of the globally ischemic heart. METHODS: Rabbit hearts were arrested with cardioplegia, explanted, and subjected to either 1 or 4 hours of global ischemia at 4 degrees C before being heterotopically transplanted into a recipient rabbit's abdomen for reperfusion. Each heart was reperfused for either 4, 8, or 12 hours. Between 3 and 7 hearts were studied (average = 5.8) for each combination of ischemic and reperfusion time (total = 35). A myeloperoxidase (MPO) assay was used to qualify neutrophil content. RESULTS: MPO activity (U/g wet weight) was not significantly different at 4, 8, and 12 hours of reperfusion (0.33 +/- 0.05, 0.20 +/- 0.04, 0.26 +/- 0.04: p = 0.13), but was significantly increased at 4 hours compared to 1 hour ischemia (0.34 +/- 0.04 vs 0.19 +/- 0.03: p = 0. 006). Interaction between ischemic and reperfusion times was not significant (p = 0.12). MPO activity was below the measurable threshold in 5 freshly excised control hearts. CONCLUSIONS: These results suggest that acute reperfusion injury will be more severe in the hearts subjected to 4 hours ischemia and indicate the need to consider neutrophil-mediated reperfusion injury when addressing cardioprotective interventions for cardiac preservation and reperfusion after transplantation. Neutrophil-mediated reperfusion injury of the rabbit myocardium after heterotopical transplantation is more severe in hearts subjected to 4 hours of ischemia vs 1 hour of ischemia prior to transplantation.

Excimer versus carbon dioxide transmyocardial laser revascularization: effects on regional left ventricular function and perfusion.

BACKGROUND: Transmyocardial laser revascularization (TMR) has been established with the carbon dioxide (CO2) laser. The largely unstudied excimer laser creates channels through chemical bond dissociation instead of thermal ablation, thereby avoiding thermal injury. We sought to compare the effects of CO2 and excimer TMR in a porcine model of chronic ischemia. METHODS: Pigs underwent ameroid constrictor placement on the circumflex artery to create chronic ischemia. TMR was performed with CO2 (n = 8) or excimer (n = 8) laser 6 weeks later; controls (n = 7) had ameroid placement only. Regional myocardial blood flow (RMBF), determined by radioactive microspheres, and regional myocardial function, determined by percent segmental shortening (%SS), were assessed 18 weeks after ameroid placement. RESULTS: Values are mean +/- SD. In the ischemic zone, RMBF (mL/min/g) was improved in the CO2 (0.73 +/- 0.19) and excimer (0.78 +/- 0.22) groups when compared with controls (0.55% +/- 0.12%, p < 0.05). %SS was also improved in the CO2 (15.2% +/- 5.5%) and excimer (15.3% +/- 5.1%) groups when compared with controls (8.0% +/- 4.2%, p < 0.05). CONCLUSIONS: Excimer and CO2 TMR significantly improve RMBF and regional function in this porcine model of chronic myocardial ischemia despite fundamentally different tissue interactions.