[Ultrasound examination of the carotid artery for improved prediction of cardiovascular events and the effect of statin treatment in advanced atherosclerosis : An observational study]. / Ultraschalluntersuchung der A. carotis zur verbesserten Vorhersage kardiovaskulärer Ereignisse und der Wirkung einer Statinbehandlung bei fortgeschrittener Atherosklerose : Eine Beobachtungsstudie.

BACKGROUND: Advanced atherosclerosis of the carotid artery is associated with a high risk of cardiovascular diseases. It was investigated whether ultrasound provides a better prediction of cardiovascular events compared to the prospective cardiovascular Münster study (PROCAM) score and whether treatment of subjects with advanced atherosclerosis with statins improves the prognosis. METHOD: Between 2009 and 2016 a total of 4482 subjects (41% women) aged 35-65 years with no signs of cardiovascular disease underwent carotid artery ultrasound examination. Total plaque area (TPA) and maximum plaque thickness were measured. The PROCAM score was used to determine the cardiovascular risk. RESULTS: The median follow-up time was 77 months (6.4 years) for the men and 74 months (6.2 years) for the women. Events, such as myocardial infarction, ischemic stroke, coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA), occurred in 131 (3.4%) of the 3833 subjects with complete follow-up data. The prediction of cardiovascular events was better with ultrasound than with the PROCAM score. Ultrasound predicted 79.4% of 131 events and the PROCAM score predicted 22.9%. Treatment of subjects with advanced atherosclerosis (types III, IV b) with a statin significantly improved the prognosis. The event rate was 12.6% in men and women in the treated group vs. 31.5% (p < 0.0001) in the untreated group. Mortality (from any cause) was significantly lower in men treated with statins (p = 0.0148). CONCLUSION: The prediction of cardiovascular events was better with plaque burden measurements than with the PROCAM score. Treatment with statins in subjects with advanced carotid atherosclerosis (types III-IV b findings on ultrasound) significantly improved the prognosis in a nonrandomized observational study.

Prediction of cardiovascular events with traditional risk equations and total plaque area of carotid atherosclerosis: The Arteris Cardiovascular Outcome (ARCO) cohort study.

A large number of cardiovascular events occur in seemingly healthy individuals. Atherosclerosis imaging can improve the outcome and treatment regime of such subjects. We aim to assess the predictive value of atherosclerosis imaging beyond traditional risk calculators in subjects aged 40-65 years. We compared PROCAM, SCORE and FRAM with carotid ultrasound (total plaque area, TPA) and arterial age (AA) was calculated in subjects without known cardiovascular diseases. Follow-up was obtained by phone or mail. In 2842 subjects (age 50 ± 8, 38% women) 154 (5.4%) cardiovascular events occurred (ASCVD: 41 myocardial infarctions, 16 strokes or TIA, 21 CABG, 41 PTCA, 35 coronary artery disease defined by invasive angiography) during a mean follow-up time of 5.9 (1-12) years. PROCAM risk was 5 ± 6%, SCORE risk 1.3 ± 1.6% and FRAM 10 ± 6%. Both for the primary outcome (AMI, STROKE/TIA, CABG) and the secondary outcome (adding CAD and PTCA) hazards increased significantly for TPA tertiles and AA groups between 1.4 (0.1-16.1) and 21.4 (2.8-163.6) after adjustment for risk factors (age, smoke, sex, systolic BP, lipids, BMI, medication in Model 1) and after adjustment for results from PROCAM, SCORE and FRAM (Model 2). Model performance was statistically improved regarding model fit in all models using TPA and AA. Net reclassification improvement (NRI) for PROCAM and SCORE using TPA tertiles or AA age groups increased significantly between 30% to 48%. TPA and AA added prognostic information to conventional risk equations, supporting the assessment of ASCVD risk with carotid ultrasound in subjects aged 40-65 years.

[Coronary physiology in the catheter laboratory]. / Koronarphysiologie im Herzkatheterlabor.

The regulation of coronary flow is mainly located in the resistance vessels of the microcirculation, so that the functional relevance of a coronary stenosis arises from the interaction between the epicardial stenosis and the downstream microcirculation. These complex interactions are precisely detectable by physiological measurements, such as the instantaneous wave-free ratio (iwFR) or the fractional flow reserve (FFR). In contrast, the purely visual assessment of the coronary anatomy could lead to misinterpretation and possibly to incorrect revascularization decisions. Consequently, in the current guidelines on myocardial revascularization of the European Society of Cardiology (ESC) the measurement of iwFR and FFR has a class IA indication in intermediate stenoses with unclear hemodynamic relevance. Despite this clear recommendation, physiological measurements are not yet regularly used in the clinical routine. Besides the purely hemodynamic assessment, novel methods such as co-registration and coronary mapping can be used for virtual planning of percutaneous coronary interventions, especially in vessels with diffuse lesions and serial stenoses. Furthermore, invasive flow measurements are also helpful for risk stratification between conservative and interventional treatment of patients with acute coronary syndrome, where additional factors of flow limitation, such as coronary spasm, thrombus and acute disturbance of the microcirculation play an important role.

Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI.

BACKGROUND: Coronary revascularization guided by fractional flow reserve (FFR) is associated with better patient outcomes after the procedure than revascularization guided by angiography alone. It is unknown whether the instantaneous wave-free ratio (iFR), an alternative measure that does not require the administration of adenosine, will offer benefits similar to those of FFR. METHODS: We randomly assigned 2492 patients with coronary artery disease, in a 1:1 ratio, to undergo either iFR-guided or FFR-guided coronary revascularization. The primary end point was the 1-year risk of major adverse cardiac events, which were a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascularization. The trial was designed to show the noninferiority of iFR to FFR, with a margin of 3.4 percentage points for the difference in risk. RESULTS: At 1 year, the primary end point had occurred in 78 of 1148 patients (6.8%) in the iFR group and in 83 of 1182 patients (7.0%) in the FFR group (difference in risk, -0.2 percentage points; 95% confidence interval [CI], -2.3 to 1.8; P<0.001 for noninferiority; hazard ratio, 0.95; 95% CI, 0.68 to 1.33; P=0.78). The risk of each component of the primary end point and of death from cardiovascular or noncardiovascular causes did not differ significantly between the groups. The number of patients who had adverse procedural symptoms and clinical signs was significantly lower in the iFR group than in the FFR group (39 patients [3.1%] vs. 385 patients [30.8%], P<0.001), and the median procedural time was significantly shorter (40.5 minutes vs. 45.0 minutes, P=0.001). CONCLUSIONS: Coronary revascularization guided by iFR was noninferior to revascularization guided by FFR with respect to the risk of major adverse cardiac events at 1 year. The rate of adverse procedural signs and symptoms was lower and the procedural time was shorter with iFR than with FFR. (Funded by Philips Volcano; DEFINE-FLAIR ClinicalTrials.gov number, NCT02053038 .).

[Prediction of coronary artery stenosis by measurement of total plaque area and thickness versus intima media thickness of the carotid artery]. / Vorhersage einer stenosierenden KHK durch Bestimmung von Plaque-Fläche und -Dicke vs. IMT an der A. carotis.

Total plaque area (TPA), maximum plaque thickness and intima media thickness (IMT) in the carotid arteries of 431 patients aged 27-88 years were measured 1 day before a planned coronary artery angiography without any clinical knowledge about the patient. Age-related cut-off values of the TPA for the presence of coronary stenosis were evaluated. Using ultrasound four types of carotid artery atherosclerosis were identified. The accuracy of detection of cardiovascular coronary stenosis was 87% for types III and IVb. No type I patient had coronary stenosis. The IMT was significantly less predictive: the area under the curve (AUC) for TPA by age and plaque thickness was 0.82 (95% CI: 0.78-0.85) versus IMT 0.59 (95% CI: 0.54-0.64, p = 0.001). Prediction with TPA measurement by age and plaque thickness was better than TPA alone: AUC 0.82 (95% CI: 0.78-0.85) versus 0.77 (95% CI: 0.73-0.81, p = 0.0028), respectively. In a second cohort of 2566 healthy men and 1216 healthy women aged between 20 and 64 years who were examined in an occupational screening program, 11.2% of the men and 3.4% of the women showed a type III or IVb result. In the mean follow-up of period of 23.4 ± 14.4 months, 14 heart attacks, 7 bypass operations and 3 stent implantations occurred and 6 subjects showed coronary stenosis between 50% and 95% in coronary angiography. In the baseline examination 26 out of 30 patients showed a type III or IVb result. In the case of men and women with types III and IVb diagnosis by ultrasound, pharmaceutical treatment could be indicated in order to reduce the risk of cardiovascular events. Type I patients do not need preventive medication or coronary catheterization.

Real-time use of instantaneous wave-free ratio: results of the ADVISE in-practice: an international, multicenter evaluation of instantaneous wave-free ratio in clinical practice.

OBJECTIVES: To evaluate the first experience of real-time instantaneous wave-free ratio (iFR) measurement by clinicians. BACKGROUND: The iFR is a new vasodilator-free index of coronary stenosis severity, calculated as a trans-lesion pressure ratio during a specific period of baseline diastole, when distal resistance is lowest and stable. Because all previous studies have calculated iFR offline, the feasibility of real-time iFR measurement has never been assessed. METHODS: Three hundred ninety-two stenoses with angiographically intermediate stenoses were included in this multicenter international analysis. Instantaneous wave-free ratio and fractional flow reserve (FFR) were performed in real time on commercially available consoles. The classification agreement of coronary stenoses between iFR and FFR was calculated. RESULTS: Instantaneous wave-free ratio and FFR maintain a close level of diagnostic agreement when both are measured by clinicians in real time (for a clinical 0.80 FFR cutoff: area under the receiver operating characteristic curve [ROC(AUC)] 0.87, classification match 80%, and optimal iFR cutoff 0.90; for a ischemic 0.75 FFR cutoff: iFR ROC(AUC) 0.90, classification match 88%, and optimal iFR cutoff 0.85; if the FFR 0.75-0.80 gray zone is accounted for: ROC(AUC) 0.93, classification match 92%). When iFR and FFR are evaluated together in a hybrid decision-making strategy, 61% of the population is spared from vasodilator while maintaining a 94% overall agreement with FFR lesion classification. CONCLUSION: When measured in real time, iFR maintains the close relationship to FFR reported in offline studies. These findings confirm the feasibility and reliability of real-time iFR calculation by clinicians.

Clinical outcome of transcatheter aortic valve implantation in patients with low-flow, low gradient aortic stenosis.

BACKGROUND: Low-flow, low-gradient aortic stenosis is associated with relevant postoperative mortality whereas conservative management results in dismal prognosis. We present the initial experience of low-flow, low-gradient aortic stenosis treated with transcatheter aortic valve implantation (TAVI). METHODS: From June 2008 to December 2010 167 consecutive patients with native severe aortic stenosis and an excessive operative risk underwent TAVI. Of these, 15 patients presented with low-flow, low-gradient aortic stenosis (aortic valve area < 1 cm(2) , left ventricular (LV) ejection fraction < 40%, aortic mean gradient < 40 mm Hg). The CoreValve prosthesis 18-F-generation (Medtronic, Minneapolis, Minnesota) was inserted retrograde. Clinical follow-up and echocardiography were performed 6 months after procedure. RESULTS: Patients with low-flow, low-gradient aortic stenosis (mean LV ejection fraction 32 ± 6%, mean aortic gradient 27 ± 7 mm Hg) had higher all-cause mortality 6 months after TAVI compared to patients without low-flow, low-gradient aortic stenosis (33% vs. 13%, P = 0.037). In the surviving 10 patients with low-flow, low-gradient aortic stenosis, LV ejection fraction increased (34 ± 6% before vs. 46 ± 11% 6 months after TAVI, p = 0.005) and more distance covered in the 6-minute walk test (218 ± 102 meters before vs. 288 ± 129 meters 6 months after TAVI, p = 0.038). CONCLUSION: Our study suggests that TAVI is feasible in patients with severe co-morbidities and low-flow, low-gradient aortic stenosis. Within the first 6 months after treatment all-cause mortality was considerable high, but the surviving patients showed symptomatic benefit and significant improvement of myocardial function and exercise capacity.

Transcatheter aortic valve implantation in patients with severe symptomatic aortic valve stenosis-predictors of mortality and poor treatment response.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as an alternative technique in patients with severe symptomatic aortic valve stenosis. However, a number of patients have no benefit after implantation. This prospective study attempted to identify predictors of poor treatment response. METHODS: From June 2008 to September 2010, consecutive patients with symptomatic severe aortic valve stenosis and high surgical risk were submitted to TAVI with the CoreValve prosthesis (Medtronic, Minneapolis, MN). The primary end point was all-cause mortality at 6 months. Secondary end point (poor treatment response) was defined as no improvement of symptoms assessed with the New York Heart Association class 6 months after TAVI. RESULTS: A total of 145 patients (mean age 79.1 ± 6.4 years, mean logistic EuroSCORE 21% ± 16.2%) were included. During the follow-up period, 23 (15.9%) patients died. Independent predictors of all-cause mortality were as follows: aortic mean gradient ≤40 mm Hg (odds ratio [OR] 3.93), moderate and severe tricuspid valve regurgitation (OR 4.50), and moderate and severe postprocedural aortic valve regurgitation (OR 4.26). In 122 surviving patients, 25 patients (20%) showed no improvement in symptoms. Independent predictors of poor treatment response were severe mitral valve regurgitation (OR 7.42) and moderate and severe postprocedural aortic valve regurgitation (OR 10.1). CONCLUSIONS: Cardiac comorbidities (low-gradient aortic stenosis, tricuspidal valve regurgitation) are associated with all-cause mortality, whereas mitral valve regurgitation is a risk factor for poor treatment response after TAVI. Postprocedural aortic valve regurgitation is a strong predictor of both-mortality and poor treatment response.

Effect of Statin Treatment in Patients With Advanced Carotid Atherosclerosis: An Observational Outcome Study.

BACKGROUND: Advanced atherosclerosis of the carotid artery is associated with a high risk of cardiovascular disease. The aim of the study was to investigate whether treatment with statins improved the prognosis. METHODS: Sum of all plaque areas (total plaque area (TPA)) and the maximum plaque thickness were determined in healthy subjects using ultrasound. We compared the outcome in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding) with and without statin treatment. The follow-up was recorded during follow-up examinations as part of preventive occupational health examinations or by personal communication. RESULTS: In 7,106 subjects aged 35 - 65 years (50 ± 8 years, 43% women), we found 669 subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding). A follow-up was available for 640 (95.4%) subjects. In these subjects (54 ± 8 years, 20.4% women), 94 (88 men) had cardiovascular events (35 myocardial infarctions, 13 bypass operations, 32 stent implantations, and 14 strokes) with a mean follow-up time of 3.9 (1 - 12) years. Two hundred sixty subjects were treated with a statin, while 339 received no statin. Fourteen cardiovascular events occurred in the treated group (eight stent implantations, two heart attacks, two bypass operations, and two strokes). In the untreated group, 80 cardiovascular events occurred (12 strokes, 11 bypass operations, 33 heart attacks, and 24 stent implantations). The event rate was 5.4% for the subjects treated with a statin and 23.6% for the untreated subjects. Both groups were well matched for the baseline presence of cardiovascular risk factors. CONCLUSION: Statin treatment in subjects with advanced atherosclerosis of the carotid artery (type III-IV b finding on ultrasound) significantly improves the prognosis in a non-randomized observational cohort study.

Cost-effectiveness analysis of statins in primary care: results from the Arteris cohort study.

BACKGROUND: The Swiss Federal Office of Public Health performed a health technology assessment regarding statins in primary care. The chosen models may lead to a situation where a clinically indicated statin therapy is estimated not to be cost effective. METHODS: We performed a cohort study regarding cardiovascular events, comparing SCORE and AGLA risk categories with tertiles of carotid plaque burden and used two models for cost-effectiveness analysis of high-potency statins. RESULTS: Subjects (n = 2842) were followed up for 5.9 ± 2.9 years with the occurrence of 154 cardiovascular events (extrapolated 10-year risk was 9.2%). Carotid plaque imaging (total plaque area, TPA) significantly improved cardiovascular risk prediction compared with AGLA and SCORE for event-free survival prediction, test accuracy (discrimination) and calibration. Discrimination was significantly improved by about 4% with the inclusion of TPA. Cost-effectiveness analysis using quality-adjusted life years (QALYs) and sensitivity analyses (based on 16 models) ranged between CHF 144,496 and −128,328 per QALY. Cost-effectiveness analysis using direct and indirect costs showed that a treat-them-all strategy in the Swiss population would be cost effective with a return-on-investment per patient in 10 years of between CHF 4442 and 19,059, and the use of carotid imaging was also cost effective (incremental cost-efficiency ratio −2.97 to −7.86). CONCLUSIONS: Carotid ultrasound significantly improved cardiovascular risk stratification and is cost effective. The Swiss Medical Board QALY model presents several drawbacks, which are shown in our sensitivity analysis, where results vary considerably and are not useful for clinical decision making. A “treat them all” strategy with statins in the Swiss population aged 30–65 years may be cost effective, when indirect costs of avoidable cardiovascular events are included, even at an unacceptably low value of a statistical life year.

Hemodynamic results and changes in myocardial function after transcatheter aortic valve implantation.

BACKGROUND: This prospective study was designed to evaluate the hemodynamic results of transcatheter aortic valve implantation (TAVI) with the CoreValve prosthesis (Medtronic, Minneapolis, Minnesota) and the effects on left ventricular function. METHODS: From June 2008 to June 2009, consecutive patients with severe symptomatic aortic valve stenosis (aortic valve area <1 cm(2)) and the indication for TAVI were included. Aortic valve prosthesis was inserted retrograde. Examinations of study patients were performed before, 30 days, and 6 months after TAVI and comprised measurement of B-type natriuretic peptide and echocardiography. Severe prosthesis-patient mismatch was defined as an indexed effective aortic valve area < or =0.65 cm(2)/m(2). RESULTS: In 39 patients, follow-up examinations were performed after TAVI. Severe prosthesis-patient mismatch seldom occurred (n = 1), but mild to moderate aortic valve regurgitation due to paravalvular leaks was common (n = 24, 62%). After 6 months, left ventricular mass index declined (158 +/- 46 vs 138 +/- 45 g/m(2), P = .001), and peak early diastolic mitral annular velocity (E') and peak systolic mitral annular velocity (S') increased (P = .004 and P < .001, respectively). B-type natriuretic peptide levels decreased (744 +/- 708 at baseline vs 367 +/- 273 at 30 days, P = .003, 279 +/- 186 pg/mL at 6 months, P = .001). Left ventricular diameters and ejection fraction remained unchanged. CONCLUSION: Despite the high incidence of paravalvular regurgitation after TAVI, hemodynamic results were favorable. Furthermore, TAVI had positive effects on left ventricular remodeling and improved neurohormonal activity, myocardial hypertrophy, and diastolic function.

Transcatheter aortic valve implantation for treatment of patients with degenerated aortic bioprostheses--valve-in-valve technique.

BACKGROUND: The management of patients with degeneration of surgical bioprosthetic valve replacement remains a challenge because of the higher risk of re-do aortic valve replacement. We present a case series of five patients with degenerated aortic bioprostheses treated with transfemoral transcatheter aortic valve implantation (TAVI). METHODS: From December 2009 to May 2010, five patients with degenerated aortic valve bioprostheses (aortic valve area < 1 cm(2) or severe aortic regurgitation), an excessive operative risk (EuroSCORE ≥ 30%), symptoms of heart failure (NYHA ≥ III) and an internal diameter of bioprosthetic aortic valve 20.5 ± 0.5 mm were included. Procedures were performed without hemodynamic support using femoral arteries. Balloon valvuloplasty with a 20-mm balloon under rapid pacing was carried out before valve implantation. The 26-mm CoreValve prosthesis, 18-F-generation (Medtronic, Minneapolis, Minnesota) was inserted retrograde under fluoroscopic guidance. Invasive and echocardiographic measurements were done immediately before and after TAVI. Clinical followup and echocardiography were performed after procedure (mean followup 72 days ± 60, range: 176-30 days). RESULTS: In all patients TAVI was successful with immediate decrease of transaortic peak-to-peak pressure (P = 0.002). Mild aortic regurgitation occurred in two patients and one patient received a new permanent pacemaker. Major adverse cardiac and cerebrovascular events did not arise. NYHA functional class improved in all patients and left ventricular ejection fraction increased (P = 0.019). CONCLUSION: Our experiences with the valve-in-valve technique using the CoreValve prosthesis suggest that transfemoral TAVI is feasible in high risk patients with degenerated aortic bioprostheses.

The Determination of the Plaque Burden on the Carotid Artery With Ultrasound Significantly Improves the Risk Prediction in Middle-Aged Subjects Compared to PROCAM: An Outcome Study.

BACKGROUND: There are only few data about the predictive value of atherosclerosis imaging beyond traditional risk calculators in younger subjects. METHODS: We assessed cardiovascular risk prediction with the PROCAM (the Prospective Cardiovascular Munster Study) risk equation and with carotid plaque imaging (determination of total plaque area (TPA) and the maximum plaque thickness with ultrasound) in subjects without known cardiovascular diseases. The follow-up was generated during follow-up examinations as part of preventive medical examinations or by telephone calls. RESULTS: In 2,508 subjects aged 35 - 64 years (50 ± 8 years, 34% women), 132 (5.3%) cardiovascular events occurred (42 myocardial infarction, 17 bypass surgery, 31 stent implantation, 42 coronary artery disease defined by invasive angiography) during a mean follow-up period of 5.4 (1 - 12) years. TPA in combination with the maximum plaque thickness (type III - IV b plaques ) tended to be superior compared to TPA, and both plaque imaging methods were superior to PROCAM: area under the curve (AUC) 0.9 (95% confidence interval (CI): 0.91 - 0.89) vs. 0.89 (95% CI: 0.90 - 0.88), P = 0.2 vs. 0.82 (95% CI: 0.84 - 0.81), P = 0.001; positive predictive value (PPV) 27% (95% CI: 0.31 - 0.22) vs. 19% (95% CI: 0.22 - 0.16) vs.19% (95% CI: 0.27 - 0.13). CONCLUSIONS: Amount of carotid plaque assessed by carotid plaque imaging significantly improves cardiovascular risk prediction beyond the PROCAM risk equation.

Six months follow-up of protected high-risk percutaneous coronary intervention with the microaxial Impella pump: results from the German Impella registry.

BACKGROUND: Percutaneous coronary intervention (PCI) represents an important alternative to coronary bypass surgery for the treatment of patients with complex coronary artery disease and high perioperative risk. Protected percutaneous coronary intervention applies temporary percutaneous ventricular assist devices to mitigate potential hemodynamic compromise in high-risk patients. The Impella system is currently the most commonly used device for protected percutaneous coronary intervention and showed improved hemodynamic parameters in earlier trials. METHODS: This study was designed as a retrospective, observational multi-center registry conducted in ten hospitals in Germany. We included consecutive patients undergoing protected high-risk percutaneous coronary intervention with Impella support. The primary endpoint was defined as the occurrence of a major adverse cardiac event defined as all-cause mortality, ST-elevation myocardial infarction, or stroke during a postprocedural 180-day follow-up period. RESULTS: In total, 157 patients (80.3% male; mean age 71.8 ± 10.8 years) were included in the present study, and 180-day follow-up was complete for 149 patients (94.9%). At baseline, the patients had a median left ventricular ejection fraction of 39.0% (interquartile range, 25.0-50.0%). The median SYNergy between PCI with TAXUS and Cardiac Surgery-Score I was 33.0 (interquartile range, 24.0-40.5) and the median EuroSCORE II was 7.2% (interquartile range, 3.2-17.1%). During postprocedural follow-up, 34 patients (22.8%) suffered a major adverse cardiac event. All-cause mortality was 18.1% (27 patients). Nine patients (6.0%) sustained a ST-elevation myocardial infarction, while 4 patients (2.7%) had a stroke. CONCLUSIONS: Patients undergoing protected high-risk percutaneous coronary intervention with Impella support showed an acceptable 180-day clinical outcome regarding major adverse cardiac event and mortality.

Correlation of machine learning computed tomography-based fractional flow reserve with instantaneous wave free ratio to detect hemodynamically significant coronary stenosis.

BACKGROUND: Fractional flow reserve based on coronary CT angiography (CT-FFR) is gaining importance for non-invasive hemodynamic assessment of coronary artery disease (CAD). We evaluated the on-site CT-FFR with a machine learning algorithm (CT-FFRML) for the detection of hemodynamically significant coronary artery stenosis in comparison to the invasive reference standard of instantaneous wave free ratio (iFR®). METHODS: This study evaluated patients with CAD who had a clinically indicated coronary computed tomography angiography (cCTA) and underwent invasive coronary angiography (ICA) with iFR®-measurements. Standard cCTA studies were acquired with third-generation dual-source computed tomography and analyzed with on-site prototype CT-FFRML software. RESULTS: We enrolled 40 patients (73% males, mean age 67 ± 12 years) who had iFR®-measurement and CT-FFRML calculation. The mean calculation time of CT-FFRML values was 11 ± 2 min. The CT-FFRML algorithm showed, on per-patient and per-lesion level, respectively, a sensitivity of 92% (95% CI 64-99%) and 87% (95% CI 59-98%), a specificity of 96% (95% CI 81-99%) and 95% (95% CI 84-99%), a positive predictive value of 92% (95% CI 64-99%), and 87% (95% CI 59-98%), and a negative predictive value of 96% (95% CI 81-99%) and 95% (95% CI 84-99%). The area under the receiver operating characteristic curve for CT-FFRML on per-lesion level was 0.97 (95% CI 0.91-1.00). Per lesion, the Pearson's correlation between the CT-FFRML and iFR® showed a strong correlation of r = 0.82 (p < 0.0001; 95% CI 0.715-0.920). CONCLUSION: On-site CT-FFRML correlated well with the invasive reference standard of iFR® and allowed for the non-invasive detection of hemodynamically significant coronary stenosis.

Sex Differences in Instantaneous Wave-Free Ratio or Fractional Flow Reserve-Guided Revascularization Strategy.

OBJECTIVES: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)- and fractional flow reserve (FFR)-guided revascularization strategies. BACKGROUND: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. METHODS: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. RESULTS: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 ± 0.51 vs. 0.43 ± 0.59; p < 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p < 0.001). There was no difference in mean iFR value according to sex (0.91 ± 0.09 vs. 0.91 ± 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 ± 0.09 vs. 0.85 ± 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). CONCLUSIONS: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038).

Clinical Events After Deferral of LAD Revascularization Following Physiological Coronary Assessment.

BACKGROUND: Physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR). OBJECTIVES: The purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial. METHODS: MACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex. RESULTS: A total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06). CONCLUSIONS: iFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral.

Comparison of Major Adverse Cardiac Events Between Instantaneous Wave-Free Ratio and Fractional Flow Reserve-Guided Strategy in Patients With or Without Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Invasive physiologic indices such as fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are used in clinical practice. Nevertheless, comparative prognostic outcomes of iFR-guided and FFR-guided treatment in patients with type 2 diabetes have not yet been fully investigated. Objective: To compare 1-year clinical outcomes of iFR-guided or FFR-guided treatment in patients with and without diabetes in the Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization (DEFINE-FLAIR) trial. Design, Setting, and Participants: The DEFINE-FLAIR trial is a multicenter, international, randomized, double-blinded trial that randomly assigned 2492 patients in a 1:1 ratio to undergo either iFR-guided or FFR-guided coronary revascularization. Patients were eligible for trial inclusion if they had intermediate coronary artery disease (40%-70% diameter stenosis) in at least 1 native coronary artery. Data were analyzed between January 2014 and December 2015. Interventions: According to the study protocol, iFR of 0.89 or less and FFR of 0.80 or less were used as criteria for revascularization. When iFR or FFR was higher than the prespecified threshold, revascularization was deferred. Main Outcomes and Measures: The primary end point was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. The incidence of MACE was compared according to the presence of diabetes in iFR-guided and FFR-guided groups. Results: Among the total trial population (2492 patients), 758 patients (30.4%) had diabetes. Mean age of the patients was 66 years, 76% were men (1868 of 2465), and 80% of patients presented with stable angina (1983 of 2465). In the nondiabetes population (68.5%; 1707 patients), iFR guidance was associated with a significantly higher rate of deferral of revascularization than the FFR-guided group (56.5% [n = 477 of 844] vs 46.6% [n = 402 of 863]; P < .001). However, it was not different between the 2 groups in the diabetes population (42.1% [n = 161 of 382] vs 47.1% [n = 177 of 376]; P = .15). At 1 year, the diabetes population showed a significantly higher rate of MACE than the nondiabetes population (8.6% vs 5.6%; adjusted hazard ratio [HR], 1.88; 95% CI, 1.28-2.64; P < .001). However, there was no significant difference in MACE rates between iFR-guided and FFR-guided groups in both the diabetes (10.0% vs 7.2%; adjusted HR, 1.33; 95% CI, 0.78-2.25; P = .30) and nondiabetes population (4.7% vs 6.4%; HR, 0.83; 95% CI, 0.51-1.35; P = .45) (interaction P = .25). Conclusions and Relevance: The diabetes population showed significantly higher risk of MACE than the nondiabetes population, even with the iFR-guided or FFR-guided treatment. The iFR-guided and FFR-guided treatment showed comparable risk of MACE and provided equal safety in selecting revascularization target among patients with diabetes. Trial Registration: ClinicalTrials.gov identifier: NCT02053038.

Early Diagnosis and Treatment of Coronary Heart Disease in Asymptomatic Subjects With Advanced Vascular Atherosclerosis of the Carotid Artery (Type III and IV b Findings Using Ultrasound) and Risk Factors.

BACKGROUND: A study was conducted as to whether the early diagnosis of coronary heart disease in asymptomatic subjects with advanced atherosclerosis of the carotid artery which additionally shows at least one risk factor is successful using ultrasound technology. METHODS: Within the scope of an occupational screening program using subjects from diverse employment sectors, people were given the opportunity to determine their risk of heart attack. During the study the total plaque area (TPA), the maximum plaque thickness in the carotid artery and the PROCAM-Scores of 3,748 healthy men and 2,260 healthy women between the ages of 20 and 64 years were determined. During the subsequent follow-up study 94 subjects sickened. An ultrasound examination of the carotid artery of 79 patients revealed a type III or IV b finding. In a pilot study 33 asymptomatic subjects with a type III or IV b finding in the ultrasound examination were assessed using a computed tomography (CT) coronary angiogram. Additional 10 asymptomatic subjects were examined independently to undergo further cardiac examinations. RESULTS: In the final analysis only five patients had entirely smooth coronary arteries, six had coronary sclerosis, eight had a 30% stenosis, one had a 30-50% stenosis and 23 patients had a stenosis ≥ 50%; and in extreme case, a left main coronary artery stenosis with three-vessel disease. CONCLUSIONS: Asymptomatic subjects with advanced atherosclerosis of the carotid artery (type III and type IV b findings) had a high risk for coronary heart disease (CHD). Early treatment of the disease improves the patient's prognosis. A screening consisting in the combination of TPA measurement and determining the maximum plaque thickness is recommended.

Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes.

OBJECTIVES: The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND: Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS: The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS: Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS: Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.