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.

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 .).

Comparison of instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR)--first real world experience.

BACKGROUND: The instantaneous wave-free ratio (iFR) is a new adenosine-independent index of coronary stenosis severity. Most published data have been based on off-line analyses of pressure recordings in a core laboratory. We prospectively compared real-time iFR and fractional flow reserve (FFR) measurements. METHODS AND RESULTS: iFR and FFR were measured in 151 coronary stenoses in 108 patients. Repeated iFR measurements were technically simple, showed excellent agreement [rs=0.99; p<0.0001], and the mean difference between consecutive iFR values was 0.0035 (limits of agreement: -0.019, 0.026). Mean iFR showed a significant correlation with FFR [rs=0.81; p<0.0001]. Receiver-operating characteristic analysis identified an optimal iFR cut-off value of 0.896 for categorization based on an FFR cut-off value 0.8. We compared two different iFR-based diagnostic strategies (iFR-only and hybrid iFR-FFR) with standard FFR: The iFR-only strategy showed good classification agreement (83.4%) with standard FFR. Use of the hybrid iFR-FFR strategy, assessing lesions in an iFR-gray zone of 0.86-0.93 by FFR, improved classification accuracy to 94.7%, and diagnosis would have been established in 61% of patients without adenosine-induced hyperemia. Notably, both iFR and FFR values were significantly higher in the posterior coronary vessels. CONCLUSIONS: Real-time iFR measurements are easily performed, have excellent diagnostic performance and confirm available off-line core laboratory data. The excellent agreement between repeated iFR measurements demonstrates the reliability of single measurements. Combining iFR with FFR in a hybrid strategy enhances diagnostic accuracy, exposing fewer patients to adenosine. Overall, iFR is a promising method, but still requires prospective clinical endpoint trial evaluation.

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.

Clinical outcome following conservative vs revascularization therapy in patients with stable coronary artery disease and borderline fractional flow reserve measurements.

BACKGROUND: Fractional flow reserve (FFR) measurements in the so-called gray-zone range of > or = 0.75 and < or =0.80 are associated with uncertainty concerning the guidance of patient therapy. It is unclear whether any difference in clinical outcome exists when revascularization treatment of FFR-evaluated lesions in this borderline range is deferred or performed. The objective of this study is to compare the clinical outcome of these patients with respect to their recommended treatment strategy. METHODS: Out of a single center database of 900 consecutive patients with stable coronary artery disease, 97 patients with borderline FFR measurements were identified and included in the study. The rate of major adverse cardiac events (MACE; cardiac death, myocardial infarction (MI), coronary revascularization) and the presence of angina were evaluated at follow-up. RESULTS: A total of 48 patients were deferred from revascularization and 49 patients underwent revascularization. There was no difference in risk profile between these groups. At a mean follow-up of 24+/-16 months, event-free survival in the deferred group was significantly better regarding overall MACE, combined rate of cardiac death, and MI, as well as MACE related to the FFR-evaluated vessel. No difference with regard to the presence of angina was observed. CONCLUSIONS: Patients with coronary lesions in the borderline FFR range can be deferred from revascularization without putting them at increased risk for major adverse events. Revascularization may be considered in the course of therapy on an individual basis if typical angina persists or worsens despite maximal medical treatment.

Short-term effects of transcatheter aortic valve implantation on neurohormonal activation, quality of life and 6-minute walk test in severe and symptomatic aortic stenosis.

OBJECTIVE: This prospective study aimed to determine to what extent clinical symptoms and neurohumoral activation are improved in patients with severe aortic valve stenosis after transcatheter aortic valve implantation (TAVI) with the CoreValve prosthesis. METHODS: From June 2008 to June 2009 consecutive patients with symptomatic severe aortic valve stenosis (area<1 cm(2)), age>or=75 years with a logistic EuroSCORE >or=15% or age>60 years plus additional specified risk factors were evaluated for TAVI. Examinations of study patients were performed before and 30 days after TAVI and comprised assessment of quality of life (Minnesota living with heart failure questionnaire, [MLHFQ]) 6-minute walk test, measurement of B-type natriuretic peptide and echocardiography. Aortic valve prosthesis was inserted retrograde using a femoral arterial or a subclavian artery approach. RESULTS: In 44 consecutive patients (mean age 79.1+/-7 years, 50% women, mean left ventricular ejection fraction 55.8+/-8.5%) TAVI was successfully performed. Follow-up 30 days after TAVI showed a significantly improved quality of life (baseline 44+/-19.1 vs 28+/-17.5 MLHFQ Score, p<0.001) and an enhanced distance in the 6-minute walk test (baseline 204+/-103 vs 266+/-123 m, p<0.001). B-type natriuretic peptide levels were reduced (baseline 725+/-837 vs 423+/-320 pg/ml, p=0.005). CONCLUSIONS: Our preliminary results show a significant clinical benefit and a reduction of neurohormonal activation in patients with severe and symptomatic aortic valve stenosis early after TAVI.

Adenosine-induced maximal coronary hyperemia for myocardial fractional flow reserve measurements: comparison of administration by femoral venous versus antecubital venous access.

BACKGROUND: Maximal hyperemia is a critical prerequisite for correct fractional flow reserve (FFR) measurements. Continuous administration of adenosine by femoral venous access is considered the gold-standard. However, antecubital venous access is used as an alternative route of administration due to the increasing popularity of radial versus femoral access for coronary catheterization. Because of a potentially larger cross sectional venous area in the arm-theoretically associated with slower flow velocities-and the extremely short half-life of adenosine, there are concerns whether this route of administration is truly equivalent to the femoral route. METHODS: Fifty randomly selected patients with coronary artery disease were included. FFR was measured with a pressure monitoring wire and the recording was digitally stored. Hyperemia was successively induced by adenosine via the antecubital vein at a dose of 140 microg kg(-1) min(-1) (A140), via the antecubital vein at a dose of 170 microg kg(-1) min(-1) (A170), and via the femoral vein at a dose of 140 microg kg(-1) min(-1) (F140). RESULTS: Induction of hyperemia by A140 yielded significantly lower hyperemic responses than compared with A170 (P = 0.038) and F140 (P = 0.005). No significant difference was seen between adenosine administration by A170 versus F140. Hyperemic stimulation by A140 underestimated lesion severity near the ischemic threshold of FFR more frequently than the other modalities. There were no differences in side-effects between any of the dosages and routes of administration. CONCLUSIONS: The intravenous application of adenosine via antecubital venous access is feasible but slightly less effective than the femoral approach. In this setting, an antecubital dosage of 170 microg kg(-1) min(-1) is comparable to the standard dosage of 140 microg kg(-1) min(-1) in the femoral vein. In some patients, this regimen might prevent an underestimation of lesion severity.

Differential diagnosis of non-atherosclerotic left main coronary artery stenosis.

A left main coronary artery (LMCA) stenosis without any atherosclerotic changes elsewhere in the coronary artery tree is a rare finding, and some uncommon reasons for luminal narrowing should be considered. An unusual case of non-atherosclerotic LMCA stenosis is reported.A middle-aged patient presented with acute myocardial infarction. An immediate coronary angiography was ordered and revealed a subtotal mid LMCA stenosis. A drug-eluting stent was successfully implanted in the LMCA.Operative revascularisation was recommended. Routine surgery was performed and surprisingly revealed an extended mass of a mediastinal tumour surrounding the aortic root. Histopathological examination of the tumour revealed a poorly differentiated squamous cell carcinoma.Postoperatively, the patient was treated with chemotherapy (carboplatin and docetaxel). Five years after the first admission to our hospital, the patient died as a result of ventricular fibrillation.The differential diagnosis of non-atherosclerotic LMCA stenoses is discussed.

Clinical outcome in patients with intermediate or equivocal left main coronary artery disease after deferral of surgical revascularization on the basis of fractional flow reserve measurements.

BACKGROUND: Correct assessment of the significance of left main stem lesions is of pivotal importance to the patient with coronary artery disease. On the basis of clinical and angiographic information alone, this evaluation often cannot be done reliably. Limited data suggest that coronary pressure-derived fractional flow reserve (FFR) supports decision making in equivocal left main disease. METHODS: All patients presenting to our institution between June 1999 and June 2004 with intermediate left main coronary artery disease (40%-80% diameter stenosis by angiography), or in whom left main coronary disease was suspected but could not be quantified angiographically, were included in this prospective single-center follow-up study. If FFR was <0.75 along the left main stem, surgical revascularization was recommended; if FFR was >0.80, medical treatment or percutaneous coronary intervention elsewhere in the coronary tree was chosen. If FFR was in the "gray zone," between > or = 0.75 and < or = 0.80 treatment recommendation was dependent on additional individual criteria. Primary end points were freedom from death, myocardial infarction, any coronary revascularization procedure, and stroke. RESULTS: Fifty-one patients (mean age 62.2 +/- 9.6 years, 41 male) were included. In 27 patients (53%), coronary artery bypass surgery was performed. The remaining 24 patients (47%) were treated nonsurgically. Mean follow-up was 29 +/- 16 months. Estimated survival after 4 years of follow-up was 81% among patients in the surgical group and 100% among patients in the nonsurgical group. Event-free survival was 66% in the surgical group and 69% in the nonsurgical group. CONCLUSIONS: Fractional flow reserve is helpful to identify patients with intermediate left main disease in whom deferral of surgical revascularization is associated with excellent survival and low event rates.

Optimizing revascularization strategies in patients with multivessel coronary disease: impact of intracoronary pressure measurements.

OBJECTIVES: In patients with multivessel coronary disease, the functional significance of each lesion is often unclear, and preinterventional stress tests may be inconclusive. In this setting, intracoronary pressure measurements may be helpful to define the optimal revascularization strategy. METHODS: Twenty-five consecutive patients (aged 64 +/- 11 years) with multivessel disease, inconclusive stress tests or not performed stress tests, and an angiographically intermediate coronary artery stenosis in at least 1 major vessel underwent intracoronary pressure measurements. Myocardial fractional flow reserve was measured for the intermediate lesions under the condition of maximum hyperemia induced by intravenous adenosine (140 microg x kg(-1) x min(-1). Revascularization strategies based on angiographic information alone were compared with treatment strategies based on fractional flow reserve results. RESULTS: The original recommendation of the revascularization procedure of choice (bypass operation or angioplasty) was changed in 9 patients (36%) on the basis of the results of fractional flow reserve measurements. In 6 more patients, pressure measurements led to a change in the recommended number of anastomoses to be aimed for during the operation. Within diffusely diseased vessels, fractional flow reserve provided an exact segmental resolution of pathologic vessel resistance for optimal graft placement. Significant left main disease was confirmed in 3 of 6 patients and was detected in 3 angiographically unsuspected cases. CONCLUSIONS: In patients with multivessel disease, coronary pressure-derived fractional flow reserve is a valuable tool to guide clinical decision making and support cardiologists and cardiovascular surgeons in the composition of optimal revascularization strategies.

Determinants of health-related quality of life after aortic valve replacement in six-month survivors of intervention.

BACKGROUND AND AIM OF THE STUDY: Although several determinants of survival after aortic valve replacement (AVR) have been identified, current knowledge regarding factors influencing the postoperative quality of life (QoL) is poor. The study aim was to evaluate health-related QoL (using Medical Outcome Study Short Form-36) in six-month survivors after AVR, and to determine predictors of outcome. METHODS: All patients undergoing heart valve surgery at the authors' hospital between 1992 and May 1999 were included. Data from 201 patients (119 males, 82 females; mean age 66.6 years) after AVR were obtained. The mean observation period was 42.5 months. RESULTS: Patients in preoperative NYHA classes I and II had a postoperative QoL comparable to that of the general population, while subjects in NYHA classes III and IV scored significantly lower. Multivariate analysis identified four independent predictors (preoperative NYHA class, diabetes mellitus, prosthetic valve type, sternal complications) for the Physical component score. NYHA class, atrial fibrillation, sternal complications and type of valvular heart disease were predictors for the Mental component score. No correlation was found between preoperative left ventricular function or size, pre-existing coronary artery disease or prior myocardial infarction and the postoperative QoL. CONCLUSION: Notably, preoperative aortic stenosis was identified as a strong and independent predictor of the postoperative QoL in six-month survivors after AVR. This effect was independent of left ventricular size and function. These findings support the proposal that patients with aortic stenosis should be operated on at an earlier stage, if possible before they develop symptoms.

Prehospital therapy with the platelet glycoprotein IIb/IIIa inhibitor eptifibatide in patients with suspected acute coronary syndromes: the Bochum feasibility study.

STUDY OBJECTIVES: To assess the practical application and safety of prehospital antithrombotic therapy with the glycoprotein (GP) IIb/IIIa inhibitor eptifibatide for patients with suspected acute coronary syndrome (ACS) or myocardial infarction (MI). DESIGN: Open-labeled pilot study. Patients with typical chest pain who were seen within 6 h of the onset of symptoms were enrolled in the mobile emergency ambulance. Patients were stratified by even/uneven days to receive standard treatment or standard treatment plus an IV bolus of eptifibatide (180 microg/kg body weight) followed by a continuous eptifibatide infusion (2 microg/kg/min). The main outcome measurement was a combination of prehospital or in-hospital death, reinfarction, revascularization of target vessels, and major bleeding complications. RESULTS: A total of 356 patients (age range, 29 to 75 years; women, 24.7%) were included in the analysis. On admission to the hospital, the diagnosis of ACS or MI was confirmed in approximately 60% of patients, and alternative diagnoses were made in 40% of patients. The rates of complications, including fatal and nonfatal complications occurring during transportation and during subsequent hospitalization, were similar in both study groups. The primary end point occurred in 11.8% of patients in the control group, and in 9.6% of those in the eptifibatide group (difference not significant). CONCLUSION: The prehospital administration of the GP IIb/IIIa inhibitor eptifibatide is feasible and safe in patients with clinically suspected ACS and MI. The benefit of this treatment has yet to be established in a large-scale multicenter study.

[Health care quality: medication and prevention in patients with and without coronary heart disease]. / Versorgungsqualität im medikamentösen und präventiven Bereich bei Patienten mit und ohne koronare Herzkrankheit.

BACKGROUND AND PURPOSE: Next to noninvasive-recently also invasive-diagnostics, ambulant care in patients with coronary heart disease (CHD) should focus on optimal medication and prevention. The aim of this study was to evaluate actual health care quality concerning drug prescription and preventive care in patients with CHD. PATIENTS AND METHODS: This prospective study was conducted from March 1999 to February 2002 at the University Hospital Bergmannsheil, Bochum, Germany. 300 patients admitted with a suspected CHD and without previous coronary angiography or myocardial infarction were enrolled. Diagnostic and therapeutic regimen complied with actual guidelines. 248 patients (82.7%) including 116 patients with angiographically confirmed CHD were examined after 1 year. RESULTS: On follow-up, only 70.9% of patients with confirmed CHD received a beta-blocker, 83.6% were treated with platelet aggregation inhibitors. Body mass index, portion of overweight patients, and HbA(1c) in patients with diabetes did not change during observation. After 1 year, 48.0% of the subjects had a systolic blood pressure > 139 mmHg, in 22.6% diastolic pressure level was > 89 mmHg. Blood level of low-density cholesterol exceeded the recommended range in 57.0% of the cases observed with equally high portion of inadequately treated patients in the group with confirmed CHD and in the group without CHD. CONCLUSION: Drug therapy, primary and secondary prevention in the observed subjects were fairly poor. Remarkable deficits in health care quality became obvious. There is no lack in availability of evaluated, effective and efficient measures. Thus, physicians' efforts to implement evidence-based guidelines into clinical practice have to be strengthened.