J. Kevin Harrison

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).

Balloon aortic valvuloplasty in adults: Failure of procedure to improve long-term survival

OBJECTIVES This study sought to determine the long-term outcome of adult patients undergoing percutaneous balloon aortic valvuloplasty. BACKGROUND Percutaneous balloon aortic valvuloplasty has been offered as an alternative to aortic valve replacement for selected patients with valvular aortic stenosis. Although balloon aortic valvuloplasty produces an immediate reduction in the transvalvular aortic gradient, a high incidence of restenosis frequently leads to recurrent symptoms. Therefore, it is unclear whether balloon aortic valvuloplasty impacts on the long-term outcome of these patients. METHODS Clinical, hemodynamic and echocardiographic data were collected at baseline in 165 patients undergoing balloon aortic valvuloplasty and examined for their ability to predict long-term outcome. RESULTS The median duration follow-up was 3.9 years (range 1 to 6). Ninety-nine percent follow-up was achieved. During this 6-year period, 152 patients (93%) died or underwent aortic valve replacement, and 99 (60%) died of cardiac-related causes. The probability of event-free survival (freedom from death, aortic valve replacement or repeat balloon aortic valvuloplasty) 1, 2 and 3 years after valvuloplasty was 40%, 19% and 6%, respectively. In contrast, the probability of survival 3 years after balloon aortic valvuloplasty in a subset of 42 patients who underwent subsequent aortic valve replacement was 84%. Survival after aortic valvuloplasty was poor regardless of the presenting symptom, but patients with New York Heart Association functional class IV congestive heart failure had events earliest. Univariable predictors of decreased event-free survival were younger age, advanced congestive heart failure symptoms, lower ejection fraction, elevated left ventricular end-diastolic pressure, presence of coronary artery disease and increased left ventricular internal diastolic diameter. Stepwise multivariable logistic regression analysis found that only younger age and a lower left ventricular ejection fraction contributed independent adverse prognostic information (chi-square 14.89, p = 0.0006). CONCLUSIONS Long-term event-free and actuarial survival after balloon aortic valvuloplasty is dismal and resembles the natural history of untreated aortic stenosis. Aortic valve replacement may be performed in selected subjects with good results. However, the prognosis for the remainder of patients who are not candidates for aortic valve replacement is particularly poor.

Randomized trial of contrast media utilization in high-risk PTCA: the COURT trial.

BACKGROUND Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. METHODS AND RESULTS A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). CONCLUSIONS In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.

Ergonovine maleate testing during cardiac catheterization: a 10-year perspective in 3,447 patients without significant coronary artery disease or Prinzmetal's variant angina.

The utility of ergonovine testing for coronary artery spasm was assessed in 3,447 patients with angiographically insignificant (less than 50% diameter stenosis) or no coronary artery disease. No patients clinically had Prinzmetals variant angina. Overall, 4% had a positive ergonovine test result, defined by spasm causing greater than or equal to 75% focal stenosis. Complications related to ergonovine use occurred in 11 patients (0.03%). In a training sample of 1,136 patients (studied between 1980 and 1984), two independent predictors of spasm were found by using multivariate analysis: the amount of visible coronary artery disease on the coronary angiogram (p less than 0.0001) and a smoking history (p = 0.001). A model to predict spasm based on these variables was validated in a test group of 2,311 patients who received ergonovine from 1985 to 1989. This model allowed the identification of a subset of 400 patients in the validation sample who had a 10% positive test rate compared with a 2% positive test rate in the remaining patients. These results should permit clinicians who use provocative testing in the catheterization laboratory to reserve testing for the subset of this group of patients most likely to have abnormal findings.

Effectiveness of percutaneous balloon mitral valvotomy during pregnancy

During pregnancy, medically refractory congestive heart failure due to mitral stenosis continues to present a clinical challenge and optimal management remains controversial. Thirteen women underwent balloon mitral valvotomy for control of functional class III or IV congestive heart failure due to mitral stenosis during pregnancy. The mean gestational age at the time of valvotomy was 25 +/- 6 weeks. Percutaneous balloon mitral valvotomy was performed successfully in all patients. No maternal or fetal mortality occurred. The mean mitral valve area assessed by Doppler echocardiography increased from 0.9 +/- 0.3 cm2 before to 2.1 +/- 0.3 cm2 after valvotomy. The mean mitral valve gradient decreased from 20 +/- 7 to 4 +/- 2 mm Hg. This was associated with a decrease in the pulmonary artery systolic pressure from 62 +/- 24 to 32 +/- 14 mm Hg. Currently, 12 of the 13 patients have delivered at an average gestational age of 38 +/- 0.5 weeks. Symptoms of congestive heart failure improved in all women and all were in New York Heart Association functional class I at the time of delivery. One patient is still pregnant and symptom free. Eleven singlet pregnancies resulted in the birth of full-term, healthy infants (mean birth weight 3.2 kg). The woman carrying a twin pregnancy improved from New York Heart Association class IV to class I after balloon mitral valvotomy but delivered prematurely at 32 weeks. The premature twin infants weighed 1.0 and 1.5 kg and died from respiratory failure at 48 hours. Percutaneous balloon mitral valvotomy can be performed safely during pregnancy and is effective in relieving symptoms of severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of variability in the interpretation of coronary angiograms on the appropriateness of use of coronary revascularization procedures.

Abstract Background Evidence from numerous studies of coronary angiography show differences between observers’ assessments of 15% to 45%. The implication of this variation is serious: If readings are erroneous, some patients will undergo revascularization procedures unnecessarily and others will be denied an essential treatment. We evaluated the variation in interpretation of angiograms and its potential effect on appropriateness of use of revascularization procedures. Methods and Results Angiograms of 308 randomly selected patients previously studied for appropriateness of angiography, coronary artery bypass grafting (CABG), and percutaneous transluminal coronary angioplasty (PTCA) were interpreted by a blinded panel of 3 experienced angiographers and compared with the original interpretations. The potential effect on differences on the appropriateness of revascularization was assessed by use of the RAND criteria. Technical deficiencies were found in 52% of cases. Panel readings tended to show less significant disease (none in 16% of vessels previously read as showing significant disease), less severity of stenosis (43% lower, 6% higher), and lower extent of disease (23% less, 6% more). The classification of CABG changed from necessary/appropriate to uncertain/inappropriate for 17% to 33% of cases when individual ratings were replaced by panel readings. Conclusions The general level of technical quality of coronary angiography is unsatisfactory. Variation in the interpretation of angiograms was substantial in all measures and tended to be higher in individual than in panel readings. The effect was to lead to a potential overestimation of appropriateness of use of CABG by 17% and of PTCA by 10%. These findings indicate the need for increased attention to the technical quality of studies and an independent second reading for angiograms before recommending revascularization. (Am Heart J 2000;139:106-13.)

Predictors of outcome of tricuspid valve replacement in carcinoid heart disease.

The cardiac valvular surgical experience of patients in the Duke Carcinoid Database was reviewed to assess operative outcome. Of the 604 patients in the database, 19 patients with carcinoid heart disease were identified by cardiac catheterization or echocardiography, or both. Eight of these underwent tricuspid valve replacement surgery with bioprostheses (2 also had open pulmonic valvuloplasty). Compared with patients medically managed, surgically treated patients were similar with the exception that they had higher right atrial mean (17 +/- 6 vs 9 +/- 4 mm Hg, p = 0.03) and v-wave (27 +/- 6 vs 17 +/- 7 mm Hg, p = 0.04) pressures. Of the 8 surgical patients, 5 (63%) died within 30 days. Causes of death included tricuspid valve thrombosis, cerebral vascular accident, coagulopathy, renal failure, and intractable right heart failure. High comorbidity was present in all 8 patients. There was a weak trend (p = 0.17) toward lower Charlson comorbidity indexes in survivors (6.7 +/- 0.6) compared with nonsurvivors (7.6 +/- 0.9). Age was significantly lower (p = 0.036) in survivors (46 +/- 13 years) compared with nonsurvivors (69 +/- 4 years). Extended follow-up revealed 2 patients who survived beyond a decade. Review of 47 carcinoid valve replacement cases (Duke Carcinoid Database and 39 published cases) revealed a 30-day mortality of 56% for patients > 60 years of age, and 0% for those < or = 60 years of age (p < 0.0001). Although valve replacement surgery can afford prolonged palliation from carcinoid heart disease, it is associated with a significant mortality risk. Careful preoperative risk stratification by age and comorbidity may provide a means for optimal selection of surgical candidates.

Determinants of 15-year outcome with 1,119 standard Carpentier-Edwards porcine valves

BACKGROUND The determinants of long-term outcome 15 years or more after porcine valve replacement are poorly documented. METHODS A retrospective review was performed of patients undergoing valve replacement with standard Carpentier-Edwards aortic (n = 531), mitral (n = 492), and tricuspid (n = 96) valves. RESULTS Patient survival was 26%+/-3%, 23%+/-2%, and 31%+/-8% 15 years after aortic, mitral, and tricuspid valve replacements, respectively. Independent determinants of impaired long-term survival for aortic or mitral valve replacement were multiple valve replacement, older age, renal disease, lung disease, or coronary disease. Actual (versus actuarial) freedom from reoperation at 15 years was 86%+/-2%, 76%+/-2%, and 95%+/-2% after aortic, mitral, and tricuspid valve replacement, respectively. Risk factors for reoperation were young age for aortic or mitral valve replacement, previous operation for aortic valve replacement, and large valve size for mitral valve replacement. Freedom from thromboembolism was 77%+/-4%, 62%+/-9%, and 80%+/-5%; from hemorrhage, 95%+/-5%, 87%+/-4%, and 82%+/-6%; and from endocarditis, 94%+/-1%, 96%+/-1%, and 89%+/-5% 15 years after aortic, mitral, and tricuspid valve replacement, respectively. Risk factors for thromboembolism or hemorrhage were multiple valve replacement and age. CONCLUSIONS The standard Carpentier-Edwards bioprosthesis continues to provide relatively low complication rates at 15 years, especially in the aortic and tricuspid positions, and especially in patients older than 60 years or with significant comorbdity.

Inhaled Nitric Oxide Selectively Dilates Pulmonary Vasculature in Adult Patients With Pulmonary Hypertension, Irrespective of Etiology

OBJECTIVES We sought to compare the responses of patients with pulmonary hypertension from primary and secondary causes (PPH and SPH, respectively) to inhaled nitric oxide (iNO) in the cardiac catheterization laboratory. BACKGROUND Pulmonary hypertension can lead to right ventricular pressure overload and failure. Although vasodilators are effective as therapy in patients with PPH, less is known about their role in adults with SPH. Inhaled nitric oxide can accurately predict the response to other vasodilators in PPH and could be similarly utilized in SPH. METHODS Forty-two patients (26 to 77 years old) with pulmonary hypertension during cardiac catheterization received iNO. Demographic and hemodynamic data were collected. Their response to iNO was defined by a decrease of > or =20% in mean pulmonary artery (PA) pressure or pulmonary vascular resistance (PVR). RESULTS Mean PA pressures and PVR were lower during nitric oxide (NO) inhalation in all patients with pulmonary hypertension. Seventy-eight percent of patients with PPH and 83% of patients with SPH were responders to iNO. A trend was seen toward a greater response with larger doses of NO in patients with SPH. Nitric oxide was a more sensitive predictor of response (79%), compared with inhaled oxygen (64%), and was well tolerated, with no evidence of systemic effects. Elevation in right ventricular end-diastolic pressure appeared to predict poor vasodilatory response to iNO. CONCLUSIONS Nitric oxide is a safe and effective screening agent for pulmonary vasoreactivity. Regardless of etiology of pulmonary hypertension, pulmonary vasoreactivity is frequently demonstrated with the use of NO. Right ventricular diastolic dysfunction may predict a poor vasodilator response.