Michael J. Reardon

Transcatheter aortic-valve replacement with a self-expanding prosthesis.

BACKGROUND We compared transcatheter aortic-valve replacement (TAVR), using a self-expanding transcatheter aortic-valve bioprosthesis, with surgical aortic-valve replacement in patients with severe aortic stenosis and an increased risk of death during surgery. METHODS We recruited patients with severe aortic stenosis who were at increased surgical risk as determined by the heart team at each study center. Risk assessment included the Society of Thoracic Surgeons Predictor Risk of Mortality estimate and consideration of other key risk factors. Eligible patients were randomly assigned in a 1:1 ratio to TAVR with the self-expanding transcatheter valve (TAVR group) or to surgical aortic-valve replacement (surgical group). The primary end point was the rate of death from any cause at 1 year, evaluated with the use of both noninferiority and superiority testing. RESULTS A total of 795 patients underwent randomization at 45 centers in the United States. In the as-treated analysis, the rate of death from any cause at 1 year was significantly lower in the TAVR group than in the surgical group (14.2% vs. 19.1%), with an absolute reduction in risk of 4.9 percentage points (upper boundary of the 95% confidence interval, -0.4; P<0.001 for noninferiority; P = 0.04 for superiority). The results were similar in the intention-to-treat analysis. In a hierarchical testing procedure, TAVR was noninferior with respect to echocardiographic indexes of valve stenosis, functional status, and quality of life. Exploratory analyses suggested a reduction in the rate of major adverse cardiovascular and cerebrovascular events and no increase in the risk of stroke. CONCLUSIONS In patients with severe aortic stenosis who are at increased surgical risk, TAVR with a self-expanding transcatheter aortic-valve bioprosthesis was associated with a significantly higher rate of survival at 1 year than surgical aortic-valve replacement. (Funded by Medtronic; U.S. CoreValve High Risk Study ClinicalTrials.gov number, NCT01240902.).

Transcatheter aortic valve replacement using a self-expanding bioprosthesis in patients with severe aortic stenosis at extreme risk for surgery

OBJECTIVES This study sought to evaluate the safety and efficacy of the CoreValve transcatheter heart valve (THV) for the treatment of severe aortic stenosis in patients at extreme risk for surgery. BACKGROUND Untreated severe aortic stenosis is a progressive disease with a poor prognosis. Transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis is a potentially effective therapy. METHODS We performed a prospective, multicenter, nonrandomized investigation evaluating the safety and efficacy of self-expanding TAVR in patients with symptomatic severe aortic stenosis with prohibitive risks for surgery. The primary endpoint was a composite of all-cause mortality or major stroke at 12 months, which was compared with a pre-specified objective performance goal (OPG). RESULTS A total of 41 sites in the United States recruited 506 patients, of whom 489 underwent attempted treatment with the CoreValve THV. The rate of all-cause mortality or major stroke at 12 months was 26.0% (upper 2-sided 95% confidence bound: 29.9%) versus 43.0% with the OPG (p < 0.0001). Individual 30-day and 12-month events included all-cause mortality (8.4% and 24.3%, respectively) and major stroke (2.3% and 4.3%, respectively). Procedural events at 30 days included life-threatening/disabling bleeding (12.7%), major vascular complications (8.2%), and need for permanent pacemaker placement (21.6%). The frequency of moderate or severe paravalvular aortic regurgitation was lower 12 months after self-expanding TAVR (4.2%) than at discharge (10.7%; p = 0.004 for paired analysis). CONCLUSIONS TAVR with a self-expanding bioprosthesis was safe and effective in patients with symptomatic severe aortic stenosis at prohibitive risk for surgical valve replacement. (Safety and Efficacy Study of the Medtronic CoreValve System in the Treatment of Symptomatic Severe Aortic Stenosis in High Risk and Very High Risk Subjects Who Need Aortic Valve Replacement; NCT01240902).

Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients

Background Although transcatheter aortic‐valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk. Methods We evaluated the clinical outcomes in intermediate‐risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self‐expanding prosthesis) with surgical aortic‐valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic‐valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement. Results A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, ‐5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic‐valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group. Conclusions TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910.)

Vascular injury in anterior lumbar surgery

Anterior approaches to the lumbar spine are rapidly gaining popularity for decompressive and reconstructive procedures. A recognized hazard to this approach to the spine is possible injury to the great vessels. This retrospective study is a review of 102 consecutive anterior lumbar spinal procedures. All approaches were performed by one of two fellowship-trained vascular surgeons. Both have extensive experience with this approach. All injuries to the inferior vena cava, common iliac vein, or other great vessels that required suture repair were recorded. The authors were surprised to note an overall rate for this vascular complication of 15.6%. These injuries included 11 tears of the common iliac vein, four tears of the inferior vena cava, and one avulsion of the iliolumbar vein. Two different approaches were used during this study. Twenty-six cases were performed through a flank incision, with the dissection proceeding through the external and internal oblique muscles as well as the transversus abdominis. The average number of levels exposed was 2.3. Two vascular complications resulted, for an incidence of 7.7%. Seventy-six procedures were carried out through a small (5-10 cm) incision overlying the rectus abdominis muscle. The retroperitoneal space was entered through the posterior rectus sheath without division of any muscle tissue. This resulted in 14 vascular complications, for an incidence of 18.4%. Although the authors are unaware of any major long-term morbidity from this complication in their patient group, they believe feel that the true incidence of this potentially quite serious complication may be underestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of tissue Doppler derived myocardial velocities to myocardial structure and beta-adrenergic receptor density in humans.

OBJECTIVES We sought to evaluate the relation of segmental tissue Doppler (TD) velocities to both the regional amount of interstitial fibrosis and the myocyte beta-adrenergic receptor density in humans. BACKGROUND The systolic myocardial velocity (Sm) and early diastolic myocardial velocity (Em) acquired by TD are promising new indexes of left ventricular function. However, their structural and functional correlates in humans are still unknown. METHODS Ten patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsy at the time of coronary bypass surgery (two biopsies per patient for a total of 20 specimens). The specimens were analyzed for percent interstitial fibrosis and beta-adrenergic receptor density. RESULTS Normal segments (n = 8) had a higher beta-adrenoceptor density (2,280 +/- 738 vs. 1,373 +/- 460, p = 0.03) and a lower amount of interstitial fibrosis (13 +/- 3.3% vs. 28 +/- 11.5%, p = 0.002) than dysfunctional segments (n = 12). Myocardial systolic velocity and Em were also significantly higher (9.5 +/- 2.7 vs. 5.9 +/- 1.8 cm/s, p = 0.025 and 11.3 +/- 2.8 vs. 6.4 +/- 2.1 cm/s, p = 0.002, respectively) in normal segments. A significant relationship was present between Em and the beta-adrenergic receptor density (r = 0.78, p < 0.001) and percent interstitial fibrosis (r = -0.7, p = 0.0026), which together accounted for 81% of the variance observed in Em. Likewise, a significant relationship was present between Sm and the beta-adrenergic receptor density (r = 0.68, p < 0.001) and the percent interstitial fibrosis (r = -0.66, p = 0.004) and together accounted for 62% of the variance observed in Sm. CONCLUSIONS Systolic myocardial velocity and Em are strongly dependent on both the number of myocytes and the myocardial beta-adrenergic receptor density.

Identification of Hibernating Myocardium With Quantitative Intravenous Myocardial Contrast Echocardiography Comparison With Dobutamine Echocardiography and Thallium-201 Scintigraphy

Background—There are currently no data on the accuracy of intravenous myocardial contrast echocardiography (MCE) in detecting myocardial hibernation in man and its comparative accuracy to dobutamine echocardiography (DE) or thallium 201 (Tl201) scintigraphy. Methods and Results—Twenty patients with coronary artery disease and ventricular dysfunction underwent MCE 1 to 5 days before bypass surgery and repeat echocardiography at 3 to 4 months. Patients also underwent DE (n=18) and rest-redistribution Tl201 tomography (n=16) before revascularization. MCE was performed using continuous Optison infusion (12 to 16 cc/h) with intermittent pulse inversion harmonics and incremental triggering (1:1 to 1:8). Myocardial contrast intensity (MCI) replenishment curves were constructed to derive quantitative MCE indices of blood velocity and flow. Recovery of function occurred in 38% of dysfunctional segments. MCE parameters of perfusion in hibernating myocardium were similar to segments with normal function and higher than dysfunctional myocardium without recovery of function (P <0.001). The best MCE parameter for predicting functional recovery was Peak MCI×&bgr;, an index of myocardial blood flow (area under the curve, 0.83). MCE parameters were higher in segments with contractile reserve and Tl201 uptake ≥60% (P <0.05) and identified viable segments without contractile reserve by DE. The sensitivity of Peak MCI×&bgr; >1.5 dB/s for recovery of function was 90% and was similar to Tl201 scintigraphy (92%) and any contractile reserve (80%); specificity was higher than for Tl201 and DE (63%, 45%, and 54%, respectively;P <0.05). Conclusions—MCE with intravenous contrast identifies myocardial hibernation in humans. Prediction of viable myocardium with MCE is best using quantification of myocardial blood flow and provides improved accuracy compared with DE and Tl201 scintigraphy.

Management of Primary Pulmonary Artery Sarcomas

The objective of this review is to determine the outcome of patients with sarcomas involving the main pulmonary artery, pulmonic valve, or right ventricular outflow tract. Survival data were analyzed using an aggregate series derived from the published literature in conjunction with a current series. Median survival was 36.5 +/- 20.2 months for patients undergoing an attempt at curative resection compared with 11 +/- 3 months for those undergoing incomplete resection. Median survival was 24.7 +/- 8.5 months for patients undergoing multimodality treatment compared with 8.0 +/- 1.7 months for patients having single-modality therapy. A complete review of diagnosis, evaluation, treatment, and surveillance of primary pulmonary artery sarcomas follows.

Thoracic and thoracoabdominal aortic aneurysm repair using cardiopulmonary bypass, profound hypothermia, and circulatory arrest via left side of the chest incision

PURPOSE Although some authors advocate hypothermic circulatory arrest for spinal cord protection in descending thoracic and thoracoabdominal repair, this method has been associated with high morbidity and mortality rates in other studies. The safety and effectiveness of this surgical adjunct were evaluated. METHODS Between February 1991 and April 1997, 409 patients underwent thoracic or thoracoabdominal aortic repair. Because of an inability to gain proximal aortic control because of anatomic or technical difficulty, hypothermic circulatory arrest was used in 21 patients (4.9%). Thirteen patients were men, 8 were women, and the median age was 57 (range, 21 to 81 years). Four patients (19%) had Marfans syndrome, and 1 had aortitis. Seven patients (33%) had aortic dissection (4 chronic type A, 2 chronic type B, 1 acute B), and 1 had aortic laceration. All but 6 patients had hypertension. Fifteen patients (73%) were operated on for repair of the distal arch and descending thoracic aorta, 4 (19%) for repair of the distal arch and thoracoabdominal aorta, and 2 for repair of either the thoracoabdominal or descending thoracic aorta alone. Surgery for 9 patients (43%) also included bypass grafts to the subclavian or innominate arteries. Six operations (29%) were urgent. RESULTS The overall 30-day mortality rate was 29% (6 of 21 patients). Among urgent patients, the mortality rate was 50% (3 of 6 patients) versus 20% (3 of 15) for elective patients. Of the remaining 15 patients, renal failure occurred in 1 (7%) and heart failure in 2 (13%). Ten patients (67%) had pulmonary complications. Encephalopathy occurred in 5 patients (33%) and stroke in 2 (13%), and spinal cord neurologic deficit developed in 2 (13%). The median recovery was 28 days (range, 10 to 157 days). CONCLUSION Hypothermic circulatory arrest did not reduce the incidence of deaths and morbidity to a rate comparable with our conventional methods. We recommend the judicious application of this method in rare instances when proximal control is not feasible or catastrophic intraoperative bleeding leave the surgeon with no other option.

Relation of the Contractile Reserve of Hibernating Myocardium to Myocardial Structure in Humans

BACKGROUND Although dobutamine echocardiography (DE) is widely used to assess myocardial viability in humans, little is known about the relation between contractile reserve and myocardial structure. METHODS AND RESULTS We evaluated 20 patients with coronary disease (64+/-13 years old, ejection fraction 28+/-7.5%) with DE (up to 40 micrograms . kg(-1). min(-1)), rest-redistribution (201)Tl single photon emission CT, and quantitative angiography before bypass surgery. During surgery, patients underwent transmural myocardial biopsies (n=37) guided by transesophageal echocardiography to determine the extent of interstitial fibrosis and intracellular and interstitial proteins by histopathology and immunohistochemistry. Among the 37 segments biopsied, 16 recovered function as assessed 2 to 3 months later. Segments with postoperative functional recovery had more wall thickening at low-dose DE (28% versus 3%, P<0.001), higher thallium uptake (69% versus 48%, P=0.03), and less interstitial fibrosis (2% versus 28%, P<0.001). Quantitative angiographic parameters did not predict recovery of function. Segments with DE viability (contractile reserve and/or ischemia) had less fibrosis (2.7% versus 28%, P<0.001), less vimentin and fibronectin (both P<0.01), more glycogen (P=0.016), and higher thallium uptake (64% versus 35.5%, P<0.05) than those without viability. Viable segments by both DE and thallium had less fibrosis (1%) than those viable by 1 of the 2 techniques (9%) or not viable by both (28%, P=0.005). Thickening at low-dose DE correlated well with the extent of interstitial fibrosis (r=-0.83, P<0.01). CONCLUSIONS Contractile reserve during DE correlates inversely with the extent of interstitial fibrosis and the amount of fibronectin and vimentin and directly with rest-redistribution thallium uptake.

Comparison of Antimicrobial Impregnation With Tunneling of Long-term Central Venous Catheters: A Randomized Controlled Trial

Objective:We sought to compare the impact of antimicrobial impregnation to that of tunneling of long-term central venous catheters on the rates of catheter colonization and catheter-related bloodstream infection. Summary Background Data:Tunneling of catheters constitutes a standard of care for preventing infections associated with long-term vascular access. Although antimicrobial coating of short-term central venous catheters has been demonstrated to protect against catheter-related bloodstream infection, the applicability of this preventive approach to long-term vascular access has not been established. Methods:A prospective, randomized clinical trial in 7 university-affiliated hospitals of adult patients who required a vascular access for ≥2 weeks. Patients were randomized to receive a silicone central venous catheter that was either impregnated with minocycline and rifampin or tunneled. The occurrence of catheter colonization and catheter-related bloodstream infection was determined. Results:Of a total of 351 inserted catheters, 346 (186 antimicrobial-impregnated and 160 tunneled) were analyzed for catheter-related bloodstream infection. Clinical characteristics were comparable in the 2 study groups, but the antimicrobial-impregnated catheters remained in place for a shorter period of time (mean, 30.2 versus 43.8 days). Antimicrobial-impregnated catheters were as likely to be colonized as tunneled catheters (7.9 versus 6.3 per 1000 catheter-days). Bloodstream infection was 4 times less likely to originate from antimicrobial-impregnated than from tunneled catheters (0.36 versus 1.43 per 1000 catheter-days). Conclusions:Antimicrobial impregnation of long-term central venous catheters may help obviate the need for tunneling of catheters.