Jennifer White

A Prospective, Blinded Determination of the Natural History of Aspirin Resistance Among Stable Patients With Cardiovascular Disease

OBJECTIVESnThis study was designed to determine if aspirin resistance is associated with clinical events.nnnBACKGROUNDnAspirin resistance, defined by platelet function testing and presumed clinical unresponsiveness to aspirin, has been previously reported by our group and others. However, little information exists linking the laboratory documentation of aspirin resistance and long-term clinical events.nnnMETHODSnWe prospectively enrolled 326 stable cardiovascular patients from 1997 to 1999 on aspirin (325 mg/day for > or =7 days) and no other antiplatelet agents. We tested for aspirin sensitivity by optical platelet aggregation using adenosine diphosphate (ADP) and arachidonic acid (AA). The primary outcome was the composite of death, myocardial infarction (MI), or cerebrovascular accident (CVA). Mean follow-up was 679 +/- 185 days. Aspirin resistance was defined as a mean aggregation of > or =70% with 10 microM ADP and > or =20% with 0.5 mg/ml AA.nnnRESULTSnOf the patients studied, 17 (5.2%) were aspirin resistant and 309 (94.8%) were not aspirin resistant. During follow-up, aspirin resistance was associated with an increased risk of death, MI, or CVA compared with patients who were aspirin sensitive (24% vs. 10%, hazard ratio [HR] 3.12, 95% confidence interval [CI] 1.10 to 8.90, p = 0.03). Stratified multivariate analyses identified platelet count, age, heart failure, and aspirin resistance to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 4.14, 95% CI 1.42 to 12.06, p = 0.009).nnnCONCLUSIONSnThis study demonstrates the natural history of aspirin resistance in a stable population, documenting a greater than threefold increase in the risk of major adverse events associated with aspirin resistance.

Mitral valve surgery in patients with severe left ventricular dysfunction

OBJECTIVESnThe objectives of this study were to determine (1) survival, (2) functional status and freedom from readmission for heart failure and (3) change in postoperative left ventricular (LV) dimensions and function following mitral valve repair or replacement in patients with severe LV dysfunction and mitral regurgitation.nnnPATIENTS AND METHODSnBetween 1990 and 1998, 44 patients with mitral regurgitation and a LV ejection fraction <35% (mean+/-SD, 28+/-6%) underwent isolated mitral repair (n=35) or replacement (n=9). The etiology of regurgitation was valvular in 18 (40%) patients, ischemic in 13 (30%) patients and dilated idiopathic cardiomyopathy in 13 (30%) patients. Every patient had been hospitalized one to six times for symptoms of heart failure (mean+/-SD, 2.3+/-1.5). All patients were receiving maximal drug therapy with 15 (34%) in New York Heart Association (NYHA) class III and 12 (27%) in class IV. Seven (16%) patients were initially referred for consideration of transplantation. The mean+/-SD duration of follow-up was 40+/-21 months.nnnRESULTSnOne (2.3%) patient died 9 days postoperatively of acute bronchopneumonia. The mean+/-SD duration of ICU and hospital stay was 41+/-34 h and 9+/-3 days, respectively. The 1-, 2- and 5-year survival rates were 89, 86 and 67%, respectively. Heart failure and sudden death accounted for 62% of the late deaths. The NYHA class improved for survivors from 2.8+/-0.8 preoperatively to 1. 2+/-0.5 at follow-up (P<0.0001). Freedom from readmission for heart failure was 88, 82 and 72% at 1, 2 and 5 years, respectively. No patient has been listed for transplantation.nnnCONCLUSIONSnMitral valve surgery offers symptomatic improvement and survival benefit in patients with severe LV dysfunction and mitral regurgitation. More liberal use of this surgery for cardiomyopathy patients is warranted.

Age and valve size effect on the long-term durability of the Carpentier-Edwards aortic pericardial bioprosthesis☆

BACKGROUNDnBioprosthesis durability decreases with time and younger age. However, the time-scale and determinants of durability of the aortic Carpentier-Edwards stented bovine pericardial prosthesis are incompletely characterized.nnnMETHODSnBetween September 1981 and January 1984, 267 patients underwent implantation of the pericardial aortic prosthesis at four centers. Mean age at implant was 65 +/- 12 years (range 21 to 86 years). Follow-up averaged 12 +/- 4.5 years. The primary end point was explant for structural valve dysfunction (SVD), which was analyzed multivariably in the context of death as a competing risk.nnnRESULTSnFreedom from explant due to SVD was 99%, 94%, and 77% at 5, 10, and 15 years. Risk of SVD increased exponentially with time and younger age (p = 0.0001) at implantation; an increased risk of small valve size was not reliably demonstrated (p = 0.1). Considering the competing risk of death, patients aged 65 years or older had a less than 10% chance of explant for SVD by 15 years.nnnCONCLUSIONSnDurability of this stented pericardial aortic bioprosthesis is excellent and justifies its use in patients aged 65 or older.

Aortic valve replacement: Is valve size important?

OBJECTIVEnWe sought to determine whether aortic prosthesis size adversely influences survival after aortic valve replacement.nnnMETHODSnA total of 892 adults receiving a mechanical (n = 346), pericardial (n = 463), or allograft (n = 83) valve for aortic stenosis were observed for up to 20 years (mean, 5.0 +/- 3.9 years) after primary isolated aortic valve replacement. We used multivariable propensity scores to adjust for valve selection factors, multivariable hazard function analyses to identify risk factors for all-cause mortality, and bootstrap resampling to quantify the reliability of the results.nnnRESULTSnTwenty-five percent of patients had indexed internal orifice areas of less than 1.5 cm(2)/m(2) and more than 2 SDs (Z-value) below predicted normal aortic valve size. Mechanical valve orifices were smaller (1.3 +/- 0. 29 cm(2)/m(2), Z = -2.2 +/- 1.16) than pericardial (1.9 +/- 0.36 cm(2)/m(2), Z = -0.40 +/- 1.01) or allograft valves (2.1 +/- 0.50, Z = 0.24 +/- 1.17). The overall survival was 98%, 96%, 86%, 69%, and 49% at 30 days and 1, 5, 10, and 15 years postoperatively. Univariably, survival was weakly and inversely related to manufacturer valve size (P =.16) and internal orifice diameter (P =. 2) but completely unrelated to indexed valve area (P =.6) or Z-value (P =.8). These, and univariable differences among valve types (P =. 004), were accounted for by different prevalences in patient risk factors and not by valve size or type per se. Bootstrap resampling indicated that these findings had a less than 15% chance of being incorrect.nnnCONCLUSIONSnSurvival after aortic valve replacement is strongly related to patient risk factors but appears not to be adversely affected by moderate patient-prosthesis mismatch (down to about 4 SDs below normal). Aortic root enlargement to accommodate a large prosthesis may be required in few situations.

Cosgrove-Edwards annuloplasty system: Midterm results

BACKGROUNDnThe Cosgrove-Edwards Annuloplasty System includes a universally flexible band that corrects mitral annular dilatation via measured plication of the posterior annulus. The purpose of this study was to evaluate midterm clinical and functional results in the first 197 patients receiving this flexible annuloplasty band at mitral valve repair.nnnMETHODSnFrom February 1993 to July 1994, 197 consecutive patients with mitral regurgitation had mitral valve repair using this system. Valve disease was degenerative in 73%, rheumatic in 15%, ischemic in 5%, infectious in 2.5%, and other in 4%.nnnRESULTSnImmediately after repair, echocardiographic mitral regurgitation was none or trivial in 92%, 1+ in 5%, and 2+ in 3%. There were no hospital deaths. Late follow-up was available in 195 patients (99%), with 661 patient-years of follow-up available for analysis. Four-year actuarial survival was 93%, freedom from thromboembolism 94%, from endocarditis 98%, and from reoperation 95%. At a mean interval of 18 months, echocardiography in 157 patients demonstrated no or trace mitral regurgitation in 56%, 1+ in 24%, 2+ in 9%, 3+ in 6%, and 4+ in 3%. At a mean of 61 +/- 5 months, reconstruction of the mitral annulus from real-time three-dimensional echocardiographic images in 10 patients confirmed preserved nonplanar shape and sphincter mechanism of the mitral annulus. Annular orifice area decreased 28% +/- 11% during the cardiac cycle from a mean of 10.1 +/- 3.9 cm2 in diastole to 7.2 +/- 2.8 cm2 in systole.nnnCONCLUSIONSnThis annuloplasty system is effective for repair of mitral regurgitation secondary to all causes and preserves mitral annular flexibility and function at 5-year follow-up.

Mitral valve repair with aortic valve replacement is superior to double valve replacement

OBJECTIVESnDouble valve replacement has been advocated for patients with combined aortic and mitral valve disease. This study investigated the alternative that, when feasible, mitral valve repair with aortic valve replacement is superior.nnnPATIENTS AND METHODSnFrom 1975 to 1998, 813 patients underwent aortic valve replacement with either mitral valve replacement (n = 518) or mitral valve repair (n = 295). Mitral valve disease was rheumatic in 71% and degenerative in 20%. Mitral valve replacement was more common in patients with severe mitral stenosis (P =.0009), atrial fibrillation (P =.0006), and in patients receiving a mechanical aortic prosthesis (P =.0002). These differences were used for propensity-matched multivariable comparisons. Follow-up extended reliably to 16 years, mean 6.9 +/- 5.9 years.nnnRESULTSnHospital mortality rate was 5.4% for mitral valve repair and 7.0% for replacement (P =.4). Survivals at 5, 10, and 15 years were 79%, 63%, and 46%, respectively, after mitral valve repair versus 72%, 52%, and 34%, respectively, after replacement (P =.01). Late survival was increased by mitral valve repair rather than replacement (P =.03) in all subsets of patients, including those with severe mitral valve stenosis. After repair of nonrheumatic mitral valves, 5-, 10-, and 15-year freedom from valve replacement was 91%, 88%, and 86%, respectively; in contrast, after repair of rheumatic valves, it was 97%, 89%, and 75% at these intervals.nnnCONCLUSIONSnIn patients with double valve disease, aortic valve replacement and mitral valve repair (1) are feasible in many, (2) improve late survival rates, and (3) are the preferred strategy when mitral valve repair is possible.

Vacuum-assisted venous return reduces blood usage

OBJECTIVEnTo determine whether vacuum-assisted venous return has clinical advantages over conventional gravity drainage apart from allowing the use of smaller cannulas and shorter tubing.nnnMETHODSnA total of 150 valve operations were performed at our institution between February and July 1999 using vacuum-assisted venous return with small venous cannulas connected to short tubing. These were compared with (1) 83 valve operations performed between April 1997 and January 1998 using the initial version of vacuum-assisted venous return, and (2) 124 valve operations performed between January and April of 1997 using conventional gravity drainage. Priming volume, hematocrit value, red blood cell usage, and total blood product usage were compared multivariably. These comparisons were covariate and propensity adjusted for dissimilarities between the groups and confirmed by propensity-matched pairs analysis.nnnRESULTSnPriming volume was 1.4 +/- 0.4 L for small-cannula vacuum-assisted venous return, 1.7 +/- 0.4 L for initial vacuum-assisted venous return, and 2.0 +/- 0.4 L for gravity drainage (P <.0001). Smaller priming resulted in higher hematocrit values both at the beginning of cardiopulmonary bypass (27% +/- 5% compared with 26% +/- 4% and 25% +/- 4%, respectively, P <.0001) and at the end (30% +/- 4% compared with 28% +/- 4% and 27% +/- 4%, respectively, P <.0001). Red cell transfusions were used in 17% of the patients having small-cannula vacuum-assisted venous return, 27% of the initial patients having vacuum-assisted venous return, and 37% of the patients having gravity drainage (P =.001); total blood product usage was 19%, 27%, and 39%, respectively (P =.002). Although ministernotomy also was associated with reduced blood product usage (P <.004), propensity matching on type of sternotomy confirmed the association of vacuum-assisted venous return with lowered blood product usage.nnnCONCLUSIONSnVacuum-assisted venous return results in (1) higher hematocrit values during cardiopulmonary bypass and (2) decreased red cell and total blood product usage.

Can particulate extraction from the ascending aorta reduce neurologic injury in cardiac surgery

OBJECTIVEnThis study examined whether extraction of particulate emboli using intra-aortic filtration could decrease neurologic outcomes.nnnMETHODSnPatients (N = 582) were enrolled in a prospective, controlled study and alternately assigned to the therapy arm (n = 304; intra-aortic filtration) or control arm (n = 278). Preoperative, procedural, and postoperative data were collected. Neurologic examinations included the National Institutes of Health Stroke Scale, Glasgow Coma Scale, and memory tests. Investigators administering neurologic tests were blinded to the study arm. By the use of logistic regression and propensity matching, composite neurologic outcomes (transient ischemic attack, stroke, delirium, coma, and memory deficit) were evaluated.nnnRESULTSnPatients in the filter group experienced a lower incidence of adverse neurologic outcomes than patients in the control group (4.3% vs 11.9%) (P <.001). There were significantly less transient ischemic attacks (0% vs 1.4%), delirium (3.0% vs 6.5%), and memory deficit (1.3% vs 6.2%). There were fewer strokes in the filter group compared with the control group (0.7% vs 2.2%), although the sample size was too small for a significant finding. Both groups experienced 1 coma outcome. The use of a filter was associated with an adjusted odds ratio of 0.375, implying that a patient who does not receive a filter is 2.7 times more likely to experience an adverse neurologic event. Logistic modeling also demonstrated that there are increasing chances of poor neurologic outcome with increasing age. The model indicates that there may be an increasing protective benefit from the filter with increasing age, although the interaction was not significant.nnnCONCLUSIONSnThe extraction of particulate emboli using intra-aortic filtration resulted in decreased neurologic outcomes.

Durability of combined aortic and mitral valve repair

BACKGROUNDnThis study was undertaken to determine the durability of combined aortic and mitral valve repair.nnnMETHODSnFrom 1979 through 1999, 158 patients underwent simultaneous aortic and mitral valve repair. Multivariable, multi-phase hazard function analysis was used to determine risk factors for the outcomes of death and reoperation.nnnRESULTSnHospital mortality was 3%. Survival after operation was 97%, 93%, 82%, and 62% after 30 days and 1, 5, and 10 years, respectively. Risk factors for late death included aortic stenosis (p = 0.0001), older age (p = 0.002), and abnormal left ventricular function (p = 0.007). Thirty-six patients required reoperation for valvular dysfunction, and freedom from reoperation was 94%, 82%, and 65% after 1, 5, and 10 years, respectively. Risk factors for reoperation included severe aortic regurgitation (p = 0.004), aortic cusp shaving (p = 0.05), mitral valve chordal transfer (p = 0.004), and bovine pericardial annuloplasty (p = 0.002). Five-year freedoms from endocarditis, thromboembolism, and hemorrhage were 97%, 98%, and 99%, respectively, with freedom from any of these valve-related morbidities of 99%, 95%, and 94% after 1, 5, and 10 years, respectively.nnnCONCLUSIONSnDouble valve repair is associated with acceptable late survival and excellent freedom from valve-related morbidity, but limited durability. Therefore, double valve repair should be reserved for patients who cannot be anticoagulated, and should be used with caution in patients with aortic stenosis, rheumatic valve disease, or anterior mitral leaflet pathology.

Angiographic variables predict increased risk for adverse ischemic events after coronary stenting with glycoprotein IIb/IIIa inhibition. results from the TARGET trial

OBJECTIVESnWe sought to assess whether pre-procedural angiographic characteristics are associated with adverse clinical outcomes after coronary stenting with glycoprotein IIb/IIIa inhibition.nnnBACKGROUNDnIschemic complications after balloon angioplasty are associated with pre- and post-procedural angiographic variables. However, in the current era of stenting with IIb/IIIa inhibition, it is unknown whether angiographic features assessed before intervention confer an increased risk of adverse procedural and subsequent clinical outcomes.nnnMETHODSnIn the Do Tirofiban and ReoPro Give Similar Efficacy Outcomes? Trial (TARGET), 4,809 patients undergoing planned stenting were randomized to tirofiban or abciximab. Baseline demographic, clinical, and angiographic variables were obtained. Clinical end points were recorded at 30 days and six months. The relationship between angiographic variables and adverse clinical outcomes was assessed.nnnRESULTSnPatients with the combination of thrombus, lesion eccentricity, and lesion length >20 mm had a 21.4% composite incidence of death, myocardial infarction, or urgent target vessel revascularization (TVR) at 30 days, compared with 4.2% in those patients without these high-risk features (hazard ratio [HR] 3.24, p < 0.001). After adjustment, the risk was independently associated with thrombus (HR 1.40, p = 0.034), eccentricity (HR 1.67, p < 0.001), and lesion length >20 mm (HR 1.89, p < 0.001). The risk of six-month TVR was independently associated with left anterior descending coronary artery lesions (HR 1.46, p < 0.001), restenotic lesions at baseline (HR 1.58, p = 0.006), and lesion length (HR 1.19, p = 0.03).nnnCONCLUSIONSnPatients with thrombus, eccentric lesions, or lesion length >20 mm are at high risk for ischemic outcomes after coronary stenting, despite IIb/IIIa inhibition. Further research into novel anti-thrombotic therapies or procedural strategies is necessary for these patients.