Comparison of clinical characteristics and prognosis in Taiwanese patients with coronary vasospastic angina pectoris without significant fixed coronary artery disease versus patients with significant fixed coronary artery disease and either stable angina pectoris or acute coronary syndromes.

BACKGROUND: Limited information is available comparing the clinical characteristics and prognosis for patients with coronary vasospastic angina in the absence of hemodynamically significant coronary artery disease (CAD) (defined as >50% stenosis) versus patients with significant fixed CAD presenting with either stable angina pectoris (SAP) or acute coronary syndromes (ACS). METHODS: Patients who underwent cardiac catheterization for suspected ischemic heart disease between August 1999 and February 2003 were followed clinically. For patients without hemodynamically significant CAD, a provocation test for coronary vasospasm was undertaken using a step-wise dose of intracoronary ergonovine administration. RESULTS: A total of 1134 patients were enrolled in the final analysis and stratified into 4 diagnostically distinct groups: control group (n = 239; mild CAD without coronary vasospasm); vasospasm group (n = 284; coronary vasospastic angina pectoris without hemodynamically significant CAD); SAP group (n = 110; hemodynamically significant CAD with SAP); ACS group (n = 501; hemodynamically significant CAD with ACS). Comparison of these 4 groups revealed that the ACS patients were more likely to be male, current smokers, and have hypercholesterolemia. In addition, this group had a significantly higher incidence of typical angina pectoris, 3-vessel CAD, and lower left ventricular ejection fraction. Between-group comparison revealed that vasospasm patients had a significantly higher incidence of early morning angina pectoris. Multivariate analysis showed that current smoking was the most independent risk factor associated with the diagnosis of coronary vasospastic angina pectoris in patients without hemodynamically significant CAD. During a median follow-up period of 49 months, recurrent angina pectoris was noted in patients from the control (n = 6; 3%), SAP (n = 9; 8%), vasospasm (n = 30, 11%), and ACS groups (n = 92; 18%); with nonfatal myocardial infarction identified during follow-up in the SAP (n = 5; 5%), vasospasm (n = 3; 1%), and ACS groups (n = 37; 7%). In addition, 29 and 3 cardiac deaths occurred in the ACS and SAP groups, respectively, whereas there were no such mortalities in the control and vasospasm groups. CONCLUSIONS: Early morning angina pectoris and cigarette smoking were the most common clinical characteristics in patients with coronary vasospasm. These patients had an excellent prognosis despite the possibility of recurrences of vasospastic angina pectoris.

Enhanced inflammatory response following coronary stent implantation in stable angina patients.

BACKGROUND: Percutaneous coronary intervention (PCI) is associated with an increase in inflammatory activity. However, little is known about the association between the inflammatory response post-PCI and plaque morphology. The objective of this study was to characterize the inflammatory response following coronary stent implantation (CSI) of stable atherosclerotic plaques, according to plaque morphology. METHODS: The study population consisted of 62 patients with stable angina that had an elective indication of CSI. Immediately before CSI, the patients underwent intravascular ultrasound (IVUS) for determination of the predominant plaque morphology of the target lesion: calcified (C, n=15), fibrocalcified (FC, n=16), fibrolipidic (FL, n=16), or lipidic (L, n=15). Angiographic lesion types were also determined. Coronary sinus samples were collected at baseline (BL) and 15 min after CSI for measuring inflammatory mediators (IM): interleukin-6 (IL-6, in pg/ml), tumoral necrosis factor-alpha (TNF, in pg/ml), interferon-gamma (IFN, in IU/ml), and neopterin (N, in ng/ml). RESULTS: BL IL-6, TNF, IFN, and N were, respectively, for C plaques (mean+/-S.D.): 1.3+/-3.0, 8.0+/-3.5, 0.1+/-0.2, and 3.2+/-0.8; for FC plaques: 6.7+/-3.3, 1.9+/-2.0, 0.1+/-0.1, and 3.8+/-2.0; for FL plaques: 0.7+/-0.9, 8.7+/-4.3, 0.1+/-0.2, and 4.0+/-2.4; and, for L plaques: 1.9+/-2.8, 0.9+/-1.4, 0.0+/-0.1, and 5.2+/-3.3. After 15 min of CSI, percentual changes of IL-6, TNF, IFN, and N, respectively, were for C plaques: 43.8+/-19.6%, 7.7+/-5.5%, -7.5+/-5.3%, and -20.0+/-11.2%; for FC plaques: 7.7+/-5.5%, 168.4+/-56.9%, 311.1+/-159.9%, and 0%; for FL plaques: 147.5+/-16.1%*, 714.3+/-34.4%*, 116.1+/-9.9%*, and 3000.0+/-230.0%*; and, for L plaques: 147.7+/-14.4%*, 140.3+/-15.0%*, 131.6+/-11.9%*, and 2300.0+/-25.9%*. Moreover, B1 (n=28) and B2 (n=32) predominated and resulted in significant changes only for IL-6 and IFN, respectively. *P<0.05: 15 min vs BL. CONCLUSIONS: These data suggest that stable angina patients with predominant lipidic (L and FL) plaques present a greater inflammatory response after CSI in than those with predominant calcified (C and FC) plaques.

Coronary artery bypass graft surgery in New Zealand's Auckland region: a comparison between the clinical priority assessment criteria score and the actual clinical priority assigned.

AIMS: To describe the cohort of patients waiting for Coronary Artery Bypass Graft (CABG) surgery in the Auckland region; compare the Clinical Priority Assessment Criteria (CPAC) score with the actual priority assigned; and to assess the impact of a patient's demographic characteristics on the CPAC score and the assigned priority. METHODS: An electronic register was developed to capture all patients who had a CPAC form completed for isolated CABG surgery during the period June 2002 to September 2004 in the Auckland region. CPAC scores and clinical priority assigned were collected from the CABG booking form. Demographic characteristics came from the booking form (age, gender) or linkage via the National Health Index (NHI) number (ethnicity, deprivation score). RESULTS: The cohort displayed severe coronary artery disease and symptoms: 70% had class 3 or class 4 angina; 89% had their ability to work, live independently, or care for dependents threatened; 65% had three-vessel coronary disease; and 26% had left-main coronary disease. The CPAC score correlated only modestly with the actual clinical priority assigned, with an extremely wide range of scores for any given clinical priority. The mean CPAC score varied by the age of the patient, level of deprivation, and ethnicity--with higher mean scores among male patients who were Maori, Pacific, or more socioeconomically deprived. Clinical priority varied less by demographic characteristics than did the CPAC score, except more women than men were assigned the 'emergency' category. Despite higher CPAC scores for Maori and Pacific men, these did not translate to greater urgency in clinical priority. CONCLUSIONS: The CPAC scoring system is used to limit access onto the CABG surgery waiting list in Auckland, but is not used to prioritise patients as to the urgency of surgery once on the list. The challenge is to determine why clinicians do not consider that the CPAC score is adequate to prioritise the urgency of surgery and to build in a process whereby any such score can be continuously evaluated and improved. We have demonstrated that the establishment of an electronic register of such patients can provide timely analysis of patterns of practice and could be used on a national scale to improve future CPAC scoring systems.

Management options for angina refractory to maximal medical and surgical interventions.

Despite the seemingly daily advances in the primary, secondary, and tertiary prevention for coronary artery disease, many patients will ultimately experience progression of their disease and experience angina refractory to further active treatment. In these patients, disabling angina occurs at rest or during simple activities of daily living. When this occurs, symptom management, a predominant focus of nursing, becomes the goal of care. Several medical and surgical alternatives are available to patients with refractory angina. Enhanced external counterpulsation and transmyocardial laser revascularization are Food and Drug Administration approved therapies that can be used to attempt to restore the balance of supply and demand. Modulation of sympathetic tone via procedures such as stellate ganglion blocks has also been employed. Other methods to control the pain are techniques that alter pain perception such as spinal opioids, transcutaneous electrical nerve stimulation, and spinal cord stimulation. Too few patients with refractory angina are referred for any of these palliative therapies. Armed with knowledge regarding these therapies, nurses will be better prepared to provide anticipatory guidance to patients and their families and to support the patient's hope for relief as they cope with this devastating condition.

Estudo comparativo entre os efeitos terapêuticos da revascularizacão cirúrgica do miocárdio e angioplastia coronária em situacões isquêmicas equivalentes: análise através da cintilografia do miocárdio com 99mTc-Sestamibi / Comparative study between the therapeutic effects of surgical myocardial revascularization and coronary angioplasty in equivalent ischemic situations: analysis through myocardial scintigraphy with 99mTc-Sestamibi

OBJETIVO: Avaliar a carga isquêmica do miocárdio prévia e ulterior à revascularizacão do miocárdio. MÉTODOS: Foram avaliados 96 pacientes randomizados, portadores de doenca arterial coronariana multivascular, angina estável, funcão do ventrículo esquerdo preservada e isquemia miocárdica esforco-induzida tratados com revascularizacão cirúrgica (RCM) ou angioplastia coronariana (ATC). Cintilografia do miocárdio com 99mTc-Sestamibi foi realizada antes e 6 meses após a revascularizacão do miocárdio. RESULTADOS: A RCM determinou índice significantemente maior de revascularizacão completa (p=0,001), aumento no número de testes ergométricos máximos (p=0,001) e reducão no número de testes ergométricos positivos com angina de esforco (p=0,018). Ambos os procedimentos ofereceram melhora importante na classe funcional da angina (p=0,001), aumento no valor médio do duplo produto de pico (p=0,009), e do tempo de tolerância ao esforco (p<0,001), além de reducão no valor médio da somatória do escore do esforco (p<0,001) e da diferenca da somatória dos escores (p<0,001) nos dois grupos. CONCLUSAO: ATC e RCM não diferiram significantemente quanto à reducão da carga isquêmica do miocárdio 6 meses após o procedimento. A revascularizacão do miocárdio foi mais completa com a RCM do que com a ATC, mas não representou fator significante para reducão da carga isquêmica do miocárdio.

Predictors of benefit in angina patients one year after completing enhanced external counterpulsation: initial responders to treatment versus nonresponders.

Enhanced external counterpulsation (EECP) has been shown to reduce Canadian Cardiovascular Society angina class. This study examines the factors that affect the reduction at 1 year, especially in patients who do not demonstrate an initial response. The data of 2,007 consecutive patients enrolled in the International EECP Patient Registry were analyzed. After 36.6 +/- 4.9 h of EECP, angina was reduced by at least one class in 82.7%. At 1 year, 35.4% of initial nonresponders and 70.6% of responders remained improved by at least one angina class and free of major adverse cardiovascular events. Multivariate predictors of 1-year benefit are initial response to treatment (odds ratio 4.5, 95% CI 3.5-5.8), baseline angina class compared with class IV (odds ratios: class I 2.1, CI 0.93-4.81; class II 0.62, CI 0.43-0.87; class III 0.80, CI 0.62-1.01) and no history of congestive heart failure (odds ratio 1.41, CI 1.14-1.74).

Analysis of baseline factors associated with reduction in chest pain in patients with angina pectoris treated by enhanced external counterpulsation.

Data from the International Enhanced External Counterpulsation (EECP) Patient Registry were analyzed to determine which patient characteristics influence improvement in angina class with EECP treatment. Patients with severely disabling angina at baseline, men, and those without a history of smoking are more likely to improve their angina class after EECP, whereas those with diabetes mellitus, prior bypass surgery, and heart failure were less likely to benefit.

The VIVA trial: Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis.

BACKGROUND: Recombinant human vascular endothelial growth factor protein (rhVEGF) stimulates angiogenesis in animal models and was well tolerated in Phase I clinical trials. VIVA (Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis) is a double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of intracoronary and intravenous infusions of rhVEGF. METHODS AND RESULTS: A total of 178 patients with stable exertional angina, unsuitable for standard revascularization, were randomized to receive placebo, low-dose rhVEGF (17 ng x kg(-1) x min(-1)), or high-dose rhVEGF (50 ng x kg(-1) x min(-1)) by intracoronary infusion on day 0, followed by intravenous infusions on days 3, 6, and 9. Exercise treadmill tests, angina class, and quality of life assessments were performed at baseline, day 60, and day 120. Myocardial perfusion imaging was performed at baseline and day 60. At day 60, the change in exercise treadmill test (ETT) time from baseline was not different between groups (placebo, +48 seconds; low dose, +30 seconds; high dose, +30 seconds). Angina class and quality of life were significantly improved within each group, with no difference between groups. By day 120, placebo-treated patients demonstrated reduced benefit in all three measures, with no significant difference compared with low-dose rhVEGF. In contrast, high-dose rhVEGF resulted in significant improvement in angina class (P=0.05) and nonsignificant trends in ETT time (P=0.15) and angina frequency (P=0.09) as compared with placebo. CONCLUSIONS: rhVEGF seems to be safe and well tolerated. rhVEGF offered no improvement beyond placebo in all measurements by day 60. By day 120, high-dose rhVEGF resulted in significant improvement in angina and favorable trends in ETT time and angina frequency.

The Canadian Cardiovascular Society grading of angina pectoris revisited 30 years later.

BACKGROUND: The Canadian Cardiovascular Society (CCS) grading of angina pectoris was described in the medical literature in 1976. OBJECTIVES: To describe the origin of this grading, its worldwide acceptance, critiques, perceived limitations and alternative systems. METHODS: The present author, who chaired the CCS ad hoc committee that developed this grading system in 1972, used documentation based on personal correspondence, and information from medline and international citation indexes searches. RESULTS: The CCS committee's mandate was to standardize the definition of terms used in reporting studies of coronary artery disease and coronary artery bypass graft surgery. The committee defined a four-level system modelled on the New York Heart Association functional classification of patients with diseases of the heart, and the American Medical Association classes of organic heart diseases. Threshold activities that produced angina were detailed to assess reliably the severity of exertional angina by independent observers, and changes over time. The grading system has been cited over 650 times in the literature since its official publication in 1976. Although this grading system was found to be generally relevant and practical, several imperfections and potential limitations were reported, the most pertinent being the criterion "anginal syndrome may be present at rest" included in grade IV, which was found to be inappropriate and confusing. The prognostic significance of the grading system, despite the finding that this was not its primary goal, was also thought to be inadequate. CONCLUSION: Although this grading system of the severity of effort angina has been accepted throughout the world over the past 30 years, a revision is desirable considering its potential imperfections and inconsistencies with present day management of ischemic heart disease.

Sustained angina relief 5 years after transmyocardial laser revascularization with a CO(2) laser.

BACKGROUND: Although transmyocardial laser revascularization (TMR) has provided symptomatic relief of angina over the short term, the long-term efficacy of the procedure is unknown. Angina symptoms as assessed independently by angina class and the Seattle Angina Questionnaire (SAQ) were prospectively collected up to 7 years after TMR. METHODS: Seventy-eight patients with severe angina not amenable to conventional revascularization were treated with a CO(2) laser. Their mean age was 61+/-10 years at the time of treatment. Preoperatively, 66% had unstable angina, 73% had had >/=1 myocardial infarction, 93% had undergone >/=1 CABG, 42% had >/=1 PTCA, 76% were in angina class IV, and 24% were in angina class III. Their average pre-TMR angina class was 3.7+/-0.4. RESULTS: After an average of 5 years (and up to 7 years) of follow-up, the average angina class was significantly improved to 1.6+/-1 (P=0.0001). This was unchanged from the 1.5+/-1 average angina class at 1 year postoperatively (P=NS). There was a marked redistribution according to angina class, with 81% of the patients in class II or better, and 17% of the patients had no angina 5 years after TMR. A decrease of >/=2 angina classes was considered significant, and by this criterion, 68% of the patients had successful long-term angina relief. The angina class results were further confirmed with the SAQ; 5-year SAQ scores revealed an average improvement of 170% over the baseline results. CONCLUSIONS: The long-term efficacy of TMR persists for >/=5 years. TMR with CO(2) laser as sole therapy for severe disabling angina provides significant long-term angina relief.

Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial.

OBJECTIVES: This study sought to establish whether the early favorable results in the Benestent-I randomized trial comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in 516 patients with stable angina pectoris are maintained at 5 years. BACKGROUND: The size of the required sample was based on a 40% reduction in clinical events in the stent group. Seven months and one-year follow-up in this trial showed a decreased incidence of restenosis and clinical events in patients randomized to stent implantation. METHODS: Data at five years were collected by outpatient visit, via telephone and via the referring cardiologist. Three patients in the stent group and one in the percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow-up at five years. Major clinical events, anginal status and use of cardiac medication were recorded according to the intention to treat principle. RESULTS: No significant differences were found in anginal status and use of cardiac medication between the two groups. In the PTCA group, 27.3% of patients underwent target lesion revascularization (TLR) versus 17.2% of patients in the stent group (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%), cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%) or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA groups, respectively. At five years, the event-free survival rate (59.8% vs. 65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical significance. CONCLUSIONS: The original 10% absolute difference in TLR in favor of the stent group has remained unchanged at five years, emphasizing the long-term stability of the stented target site.

Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization.

BACKGROUND: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances. METHODS: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography. RESULTS: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction--the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93)--and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend=0.002). CONCLUSIONS: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes.

New options for untreatable coronary artery disease: angiogenesis and laser revascularization.

Some patients with severe symptomatic coronary artery disease despite maximal medical therapy are not eligible for bypass surgery or percutaneous coronary intervention, but may be eligible for two newer therapies: therapeutic angiogenesis with growth factors and transmyocardial laser revascularization.

Coronary artery bypass graft outcome: the Trinidad and Tobago experience.

The study is retrospective review of the demographic, clinical, angiographic, and operative data of the first 205 consecutive CABG operations performed by Caribbean Heart Care at the Eric Williams Medical Sciences Complex (EWMSC), Trinidad and Tobago, between November 1993 and December 1997. The aim of the study was to determine the in-hospital and intermediate-term follow-up results. The mean age of patients was 59 +/- 10 years and 78% were male. Sixty-four per cent were of East Indian descent, whereas 16% were of African descent. Forty-eight per cent of the patients were hypertensive, 46% were diabetic, 33% had hyperlipidaemia, 20% had a recent history of cigarette smoking and 16% were obese. Sixty-five per cent had a positive family history of ischaemic heart disease. The average time interval between angiography and surgery was 2.3 months. At the time of angiography, 63.5% of patients had Canadian Cardiac Society (CCS) class 3 or 4 angina. The mean ejection fraction was 61 +/- 15%. Wall motion abnormalities were seen in 67% of patients. Significant stenoses of the left anterior descending artery, right circumflex artery, circumflex and ramus coronary arteries were present in 91%, 78%, 54% and 5%, respectively. Many patients (67%) had severe diffuse disease on angiography. The mean intensive care stay was 2.2 +/- 0.8 days. In-hospital mortality was 3.9% (8/205). The most frequent post-operative complication was haemorrhage (2.6%). Acute renal failure occurred in 2.1%; pulmonary collapse, 1.6%; stroke, 1% and cardiac arrest, 1%. Both sternal wound infections and systemic sepsis occurred in 0.5%. Intermediate-term follow-up data were obtained for 92% (189/205). The duration of follow-up ranged from 1 to 5 years (mean 3.7 years). During the follow-up period, 7 patients (3.4%) died. Angina severity was reduced from a mean CCS score of 2.61 +/- 0.95 before CABG to 1.22 +/- 0.55 at the time of follow-up (p < 0.0001). Overall 4-year mortality compared favourably with data from international studies. Among survivors, quality of life improved as evidenced by the reduction in the mean angina score.

[The relationship between clinical types of postinfarction angina and stenosis of ischemia-related artery].

OBJECTIVE: To approach the pathogenesis of postinfarction angina and set up its treatment guidelines. METHODS: 67 patients with postinfarction angina undergoing coronary angiography during the hospitalization were studied. RESULTS: (1) According to the clinical classification of angina pectoris, spontaneous angina is the most common type (43.9%); mixed angina is second (25.7%), effort angina and variant angina are relatively low frequency (16.7% & 13.6%). (2) Stenosis >or= 90% in the ischemia-related artery accounted for the anginal symptoms constituted 100%, 82.8%, 72.7% and 44.4% of the cases with mixed angina, spontaneous angina, effort angina and variant angina respectively. (3) Postinfarction angina caused by non infarction-related artery was relatively less frequent (8.9%). CONCLUSIONS: Severe residual stenosis of infarction-related artery is the main pathologic factor on the pathogenesis of postinfarction angina, so early interventional therapy or bypass surgery should be taken.

Percutaneous transmyocardial revascularization with holmium laser in patients with refractory angina: a pilot feasibility study.

BACKGROUND: Percutaneous transluminal myocardial revascularization (PTMR) is a new procedure to improve perfusion of the ventricular wall for patients with intractable angina that is untreatable by surgery or conventional catheter-based intervention. PTMR allows the creation of myocardial channels through the controlled delivery of holmium laser energy from the ventricular chamber. Preliminary studies in animals and human subject have yielded promising results. We now report the feasibility study of PTMR using a laser delivered through a novel Eclipse system, and we present the results of this sole therapy in patients with severe coronary disease and angina refractory to maximal medical treatment angina (III-IV CCS). METHODS: Percutaneous vascular access for PTMR treatment was obtained via the femoral artery. A 9F directional catheter carrying flexible fiber optics was used with a holmium laser (Eclipse system) and was placed across the aortic valve into the left ventricle cavity to create channels with a depth of 5 mm from the endocardial surface into the myocardial tissue. From April to November 1998, 15 patients underwent PTMR with Eclipse system. Two patients were female; the mean age was 66 +/- 8 (range 59-74). Five patients had a severe LV dysfunction (FE < 30%). Preoperative angina class was III in 10 patients and IV in 5 and previous myocardial procedures had been performed in all patients. RESULTS: The procedure was well tolerated and procedural success was obtained in 14 of 15 patients. There was one myocardial perforation because of guiding-catheter manipulation (pericardial drainage in fourth day). We performed a mean of 13 +/- 4 channels in a mean fluoro time of 23 +/- 11 min. Upon release and during follow-up (5.3 months +/- 4.2, range 2-10), angina class had significantly improved in 14 of 14 patients with complete PTMR treatment, with 4 asymptomatic patients, 6 patients in CCS I, 3 in CCS II, 2 in CCS III and only one patient hospitalized due to angina. CONCLUSION: This pilot study confirmed the safety and technical feasibility of PTMR. Immediate and short-term results confirm that a clinical improvement is obtained in most patients. Although these are early clinical benefits, the true efficacy of this approach will necessarily be defined by a randomized trials with prospectively-defined endpoints and with PTMR compared with medical therapy.