Tjebbe W. Galema

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension

AIMS The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort. METHODS AND RESULTS Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence. CONCLUSION Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Prediction model to estimate presence of coronary artery disease: Retrospective pooled analysis of existing cohorts

Objectives To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. Design Retrospective pooled analysis of individual patient data. Setting 18 hospitals in Europe and the United States. Participants Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). Main outcome measures Obstructive coronary artery disease (≥50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. Results We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. Conclusions Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

Changes in mitral regurgitation after transcatheter aortic valve implantation

Objectives: To assess the acute and intermediate changes in mitral regurgitation (MR) severity after transcatheter aortic valve implantation (TAVI) with the CoreValve Revalving SystemTM (CRS). Background: Following surgical aortic valve replacement, improvement in MR is reported in 27–82% of the patients. The changes in MR severity following CRS implantation are unknown. Methods: Transthoracic echocardiography was performed in 79 consecutive patients before and after treatment, and at the first outpatient visit. Left ventricular dimensions and ejection fraction (LVEF), left atrial (LA) size, and aortic gradient were measured. MR was assessed by color flow mapping and was graded as none, mild, moderate, or severe. It was defined as organic or functional. The depth of CRS implantation was measured by angiography. Results: Post‐treatment, the mean gradient decreased from 48 ± 16 mm Hg to 9 ± 5 mm Hg (P < 0.0001). There was no significant change in the left ventricular dimensions, LA size, and LVEF. MR pretreatment was mild, moderate, or severe in 57%, 18%, and 1% of the patients, respectively. It was defined as organic in 27 patients (36%) and functional in 27 patients (36%). The degree of MR remained unchanged in 61% of the patients, improved in 17%, and worsened in 22%. MR improvement was associated with a lower baseline LVEF (P = 0.02). There was no association between the changes in MR severity and the depth of CRS implantation. Conclusions: Most patients who underwent TAVI had some degree of MR. Overall there was no change in the degree of MR post‐treatment. Patients in whom MR improved had a lower LVEF at baseline.

Left ventricular thrombus incidence and behavior studied by serial two-dimensional echocardiography in acute anterior myocardial infarction: left ventricular wall motion, systemic embolism and oral anticoagulation☆

Serial two-dimensional echocardiography was performed to detect left ventricular thrombus in 92 consecutive patients with a confirmed first acute anterior myocardial infarction. Thirty left ventricular thrombi were diagnosed in these 92 patients. The cumulative percent of identified thrombus in each echocardiographic examination in the surviving patients was 27% at less than 24 h; 57% at 48 to 72 h; 75% at 1 week and 96% at 2 weeks. The thrombus shape was defined as mural in 53% and protruding in 47% of patients. Systemic embolism (stroke) was noted during hospitalization in two patients with a protruding thrombus. At 12 weeks of follow-up, patients with thrombus had poorer (and almost unchanged from baseline) global left ventricular function as expressed by wall motion score compared with that of patients without thrombus, who exhibited significant improvement. Global left ventricular wall motion in patients with persisting or resolved thrombus was similar during follow-up. Apical wall motion worsened in 70% of the patients with persisting thrombus and in 25% of the patients with resolved thrombus (p less than 0.1). In the 22 surviving patients with thrombus, resolution or change in thrombus shape or size was noted in 14 of the 15 patients receiving anticoagulant therapy and in 4 of the 7 untreated patients. Six of the 18 patients with an early- (48 to 72 h) and none of the 12 patients with a later-formed thrombus died. Maximal serum enzyme levels, percent with Killip functional class III to IV and left ventricular wall motion score were higher in the patients with an early- than in those with a later-formed thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)

Early echocardiographic evaluation following percutaneous implantation with the self-expanding CoreValve Revalving System aortic valve bioprosthesis.

AIMS Although safety and feasibility studies have been published, there are few reports dedicated to the echocardiographic evaluation of patients following percutaneous aortic valve replacement (PAVR). This report describes the early echocardiographic evaluation of patients undergoing PAVR with the CoreValve Revalving System. METHODS AND RESULTS The population consisted of 33 consecutive patients with aortic stenosis who underwent successful PAVR. Echocardiograms were performed pre-treatment (123+/-110 days prior), post-treatment (6+/-2 days) and post-discharge (80+/-64 days). Aortic valve function and left ventricular dimensions, systolic and diastolic function were assessed pre- and post-implantation. The mean age was 81+/-7 years and the mean Logistic Euroscore was 20+/-12. Following PAVR, the mean transaortic valve gradient decreased (46+/-16 mmHg pre-treatment vs. 12+/-7 mmHg post-treatment vs. 9+/-5 mmHg post-discharge, p<0.001) and the mean effective orifice area increased (0.75+/-0.23 cm2 pre-treatment vs. 1.97+/-0.85 cm2 post-treatment vs. 1.72+/-0.45 cm2 post-discharge, p<0.001). There was no significant change in mean ejection fraction (41+/-12% pre-treatment vs. 46+/-15% post-treatment vs. 44+/-13% post-discharge, p=0.44). Approximately two-thirds of patients had no change in diastolic function at follow-up. CONCLUSION Following implantation, there was a sustained decrease in aortic valve gradient and increase in aortic valve area. In addition, the mean ejection fraction did not change significantly and in the majority of patients, diastolic function was unchanged.

Effect of Experience on Results of Transcatheter Aortic Valve Implantation Using a Medtronic CoreValve System

Outcome after transcatheter aortic valve implantation (TAVI) depends on the patient risk profile, operator experience, progress in technology, and technique. We sought to compare the results of TAVI during the initiation phase and after certification to perform TAVI with the Medtronic CoreValve System without proctoring. A total of 165 consecutive patients was categorized into a first cohort of 33 patients treated before certification (November 2005 to December 2007) and a second cohort of 132 patients treated after certification (January 2008 to October 2010). The study end points were selected and defined according to the Valve Academic Research Consortium recommendations. Compared to cohort 2, the patients in cohort 1 more frequently had New York Heart Association class III-IV (100% vs 71%, p <0.001), hypertension (67% vs 39%, p = 0.004), and aortic regurgitation grade III-IV (46% vs 22%, p = 0.006) before TAVI. Over time, the patients in cohort 2 more frequently underwent a truly percutaneous approach (98% vs 82%, p = 0.002) without circulatory support (96% vs 67%, p <0.001) but with more concomitant percutaneous coronary intervention (11% vs 0%, p = 0.042) than the patients in cohort 1. They also more often received a 29-mm prosthesis (72% vs 24%, p <0.001), required less postimplantation balloon dilation (10% vs 27%, p = 0.008), and had less aortic regurgitation grade III-IV after TAVI (12% vs 30%, p = 0.010). The clinical outcome showed a nonsignificant reduction in the combined safety end point (30% to 17%) but a significant reduction in cerebrovascular events (21% to 7%, p = 0.020) and life-threatening bleeding (15% to 5%, p = 0.044) in cohort 2. However, the reduction in overall bleeding and vascular complications (25% and 14%, respectively) was not significant. In conclusion, TAVI became significantly less complex and was associated with better results over time but remained associated with a high frequency of periprocedural major cardiovascular complications.

Effects of Early Intervention with Low-Dose Aspirin (100 mg) on Infarct Size, Reinfarction and Mortality in Anterior Wall Acute Myocardial Infarction

Recently, it was shown that aspirin given early in acute myocardial infarction (AMI) improves hospital survival, but the mechanisms involved are unclear. In a prospective, randomized placebo-controlled trial, the influence of early intervention with low-dose aspirin (100 mg/day) on infarct size and clinical outcome was studied in 100 consecutive patients with first anterior wall AMI. Infarct size was calculated by cumulative lactate dehydrogenase release in the first 72 hours after admission and was found to be (mean +/- standard deviation) 1,431 +/- 782 U/liter in the aspirin group (n = 50) and 1,592 +/- 1,082 U/liter in the placebo group (n = 50, p = 0.35). The study medication was given for 3 months, during which mortality was 10 (20%) in the aspirin patients and 12 (24%) in the placebo patients (p = 0.65). However, reinfarction occurred in 2 patients (4%) in the aspirin group and in 9 (18%) in the placebo group (p less than 0.03). Early intervention with low-dose aspirin showed, in comparison to placebo, a 10% decrease of infarct size, but this difference was not statistically significant. However, early low-dose aspirin effectively decreased the risk of reinfarction. Therefore, the favor able results of early aspirin on mortality in acute myocardial infarction are probably due more to prevention of reinfarction than to decrease of infarct size.

Calcium imaging and selective computed tomography angiography in comparison to functional testing for suspected coronary artery disease: the multicentre, randomized CRESCENT trial

AIMS To compare the effectiveness and safety of a cardiac computed tomography (CT) algorithm with functional testing in patients with symptoms suggestive of coronary artery disease (CAD). METHODS AND RESULTS Between April 2011 and July 2013, 350 patients with stable angina, referred to the outpatient clinic of four Dutch hospitals, were prospectively randomized between cardiac CT and functional testing (2 : 1 ratio). The tiered cardiac CT protocol included a calcium scan followed by CT angiography if the Agatston calcium score was between 1 and 400. Patients with test-specific contraindications were not excluded from study participation. By 1 year, fewer patients randomized to cardiac CT reported anginal complaints (P = 0.012). The cumulative radiation dose was slightly higher in the CT group (6.6 ± 8.7 vs. 6.1 ± 9.3 mSv; P < 0.0001). After 1.2 years, event-free survival was 96.7% for patients randomized to CT and 89.8% for patients randomized to functional testing (P = 0.011). After CT, the final diagnosis was established sooner (P < 0.0001), and additional downstream testing was required less frequently (25 vs. 53%, P < 0.0001), resulting in lower cumulative diagnostic costs (€369 vs. €440; P < 0.0001). CONCLUSION For patients with suspected stable CAD, a tiered cardiac CT protocol offers an effective and safe alternative to functional testing. Incorporating the calcium scan into the diagnostic workup was safe and lowered diagnostic expenses and radiation exposure.

Clinical outcome following Transcatheter Aortic Valve Implantation in patients with impaired left ventricular systolic function.

Objectives: To determine the prevalence of impaired left ventricular (LV) systolic function and its impact on the in‐hospital and long‐term outcome in patients who underwent Transcatheter Aortic Valve Implantation (TAVI). Background: Although impaired LV function may be considered a contra‐indication for aortic valve replacement, the hemodynamic characteristics of transcatheter valves may offer procedural and long‐term clinical benefit in such patients. Methods: 230 consecutive patients underwent TAVI with the Medtronic‐CoreValve System. Impaired LV function was defined by a Left Ventricular Ejection Fraction (LVEF) ≤ 35% (European Multicenter Study on Operative Risk Stratification and Long‐term Outcome in patients with Low‐Flow/Low‐Gradient Aortic Stenosis). Study endpoints were selected and defined according to the Valve Academic Research Consortium recommendations. Results: Compared with patients with a LVEF > 35% (n = 197), those with LVEF ≤ 35% (n = 33) were more often male (78.8 % vs. 46.7%, P < 0.001), more symptomatic (NYHA class III or IV, 97.0% vs. 77.2%, P = 0.008) and had a higher prevalence of prior coronary artery disease (63.6% vs. 43.1%, P = 0.029). The Logistic EuroSCORE was 14.8% and 22.8, respectively (P = 0.012). No difference was observed between the two groups in in‐hospital or 30‐day mortality (3.0% vs. 9.6%, P = 0.21), the Combined Safety Endpoint at 30 days (24.2% and 24.4%, P = 0.99) and survival free from readmission at one year (69.2% and 69.7%, P = 0.85). After adjustment, LVEF ≤ 35% was not associated with an increased risk of 30‐day mortality, in‐hospital complications and survival free from readmission at follow‐up. Conclusion: The immediate and long‐term outcome after TAVI did not differ between patients with an impaired and preserved LVEF. LVEF ≤ 35% did not predict adverse immediate and long‐term outcome. These findings suggest that TAVI should not be withheld in selected patients with impaired LV function.

Prosthesis-patient mismatch after transcatheter aortic valve implantation with the medtronic CoreValve system in patients with aortic stenosis.

A prosthesis-patient mismatch (PPM) is present when the prosthetic valve is too small in relation to the patients body size. The purpose of the present study was to investigate the frequency of PPM after the implantation of the Medtronic CoreValve System, and its relation to the clinical outcome. The indexed effective orifice area (EOA) was measured in 74 patients with symptomatic severe aortic stenosis, who had undergone successful transcatheter aortic valve implantation with the Medtronic CoreValve System, at baseline and discharge. PPM was defined as severe (indexed EOA <0.65 cm(2)/m(2)) or moderate (indexed EOA 0.65 to 0.85 cm(2)/m(2)). The indexed EOA increased from 0.35 +/- 0.13 to 0.97 +/- 0.34 cm(2)/m(2) after transcatheter aortic valve implantation (p <0.001) and was accompanied by significant clinical improvement. Severe and moderate PPMs were found in 16% and 23% of patients, respectively. Patients with severe PPM were more symptomatic and had a smaller indexed EOA at baseline than those with moderate or no PPM (0.28 +/- 0.09 vs 0.36 +/- 0.12 cm(2)/m(2), p <0.05). Functional status and mortality at 30 days and 6 months was not significantly different between the patients with severe PPM and those with moderate or no PPM. In conclusion, the indexed EOA increased significantly after transcatheter aortic valve implantation. Severe PPM was observed in 16% of the patients and was not associated with the clinical outcome.