Early detection of obstructive coronary artery disease in the asymptomatic high-risk population: objectives and study design of the EARLY-SYNERGY trial.

BACKGROUND: Coronary artery disease (CAD) burden for society is expected to steeply increase over the next decade. Improved feasibility and efficiency of preventive strategies is necessary to flatten the curve. Acute myocardial infarction (AMI) is the main determinant of CAD-related mortality and morbidity, and predominantly occurs in individuals with more advanced stages of CAD causing subclinical myocardial ischemia (obstructive CAD; OCAD). Unfortunately, OCAD can remain subclinical until its destructive presentation with AMI or sudden death. Current primary preventive strategies are not designed to differentiate between non-OCAD and OCAD and the opportunity is missed to treat individuals with OCAD more aggressively. METHODS: EARLY-SYNERGY is a multicenter, randomized-controlled clinical trial in individuals with coronary artery calcium (CAC) presence to study (1.) the yield of cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) for early OCAD diagnosis and (2) whether early OCAD diagnosis improves outcomes. Individuals with CAC score ≥300 objectified in 2 population-based trials (ROBINSCA; ImaLife) are recruited for study participation. Eligible candidates are randomized 1:1 to cardiac magnetic resonance stress myocardial perfusion imaging (CMR-MPI) or no additional functional imaging. In the CMR-MPI arm, feedback on imaging results is provided to primary care provider and participant in case of guideline-based actionable findings. Participants are followed-up for clinical events, healthcare utilization and quality of life. CONCLUSIONS: EARLY-SYNERGY is the first randomized-controlled clinical trial designed to test the hypothesis that subclinical OCAD is widely present in the general at-risk population and that early differentiation of OCAD from non-OCAD followed by guideline-recommended treatment improves outcomes.

Ascending Aortic Aneurysm Secondary to Isolated Noninfectious Ascending Aortitis.

Isolated noninfectious ascending aortitis (I-NIAA) is increasingly diagnosed at histopathologic review after resection of an ascending aortic aneurysm. PubMed was searched using the term aortitis; publications addressing the issue were reviewed, and reference lists of selected articles were also reviewed. Eleven major studies investigated the causes of an ascending aortic aneurysm or dissection requiring surgical repair: the prevalence of noninfectious aortitis ranged from 2% to 12%. Among 4 studies of lesions limited to the ascending aorta, 47% to 81% of cases with noninfectious aortitis were I-NIAA, more frequent than Takayasu arteritis or giant cell arteritis. Because of its subclinical nature and the lack of "syndromal signs" as in Takayasu arteritis or giant cell arteritis, I-NIAA is difficult to diagnose before complications occur, such as an aortic aneurysm or dissection. Therefore, surgical specimens of dissected aortic tissue should always be submitted for pathologic review. Diagnostic certainty requires the combination of a standardized histopathologic and clinical investigation. This review summarizes the current knowledge on I-NIAA, followed by a suggested approach to diagnosis, management, and follow-up. An illustrative case of an uncommon presentation is also presented. More follow-up studies on I-NIAA are needed, and diagnosis and follow-up of I-NIAA may benefit from the development of diagnostic biomarkers.

Round-the-clock performance of coronary CT angiography for suspected acute coronary syndrome: Results from the BEACON trial.

OBJECTIVE: To assess the image quality of coronary CT angiography (CCTA) for suspected acute coronary syndrome (ACS) outside office hours. METHODS: Patients with symptoms suggestive of an ACS underwent CCTA at the emergency department 24 hours, 7 days a week. A total of 118 patients, of whom 89 (75 %) presented during office hours (weekdays between 07:00 and 17:00) and 29 (25 %) outside office hours (weekdays between 17:00 and 07:00, weekends and holidays) underwent CCTA. Image quality was evaluated per coronary segment by two experienced readers and graded on an ordinal scale ranging from 1 to 3. RESULTS: There were no significant differences in acquisition parameters, beta-blocker administration or heart rate between patients presenting during office hours and outside office hours. The median quality score per patient was 30.5 [interquartile range 26.0-33.5] for patients presenting during office hours in comparison to 27.5 [19.75-32.0] for patients presenting outside office hours (p=0.043). The number of non-evaluable segments was lower for patients presenting during office hours (0 [0-1.0] vs. 1.0 [0-4.0], p=0.009). CONCLUSION: Image quality of CCTA outside office hours in the diagnosis of suspected ACS is diminished. KEY POINTS: • Quality scores were higher for coronary-CTA during office hours. • There were no differences in acquisition parameters. • There was a non-significant trend towards higher heart rates outside office hours. • Coronary-CTA on the ED requires state-of-the-art scanner technology and sufficiently trained staff. • Coronary-CTA on the ED needs preparation time and optimisation of the procedure.

Diagnosing poststernotomy mediastinitis in the ED.

PURPOSE: Poststernotomy mediastinitis (PSM), the severe chest wall and mediastinal infection that may arise at any time after a sternotomy, causes significant morbidity and mortality globally. Late recognition and diagnosis are the major contributors to a poor outcome. This review focuses on recent advances in diagnosing PSM (particularly after cardiovascular surgery) at the earliest opportunity--in the emergency department. RECENT FINDINGS: Morbidity and mortality of PSM, especially when associated with numerous other complications, remain unaltered high. Careful history taking and clinical examination remain the mainstays of a preliminary diagnosis. No specific signs are indicative of PSM alone. Procalcitonin as a biomarker and neutrophil volume distribution width obtained during a complete blood count with differential, assessed in the clinical context, offer interesting prospects of obtaining a speedy and accurate diagnosis. Adjunctive diagnostic imaging modalities such as contrast-enhanced computed tomography can differentiate PSM from postcardiac injury syndrome and other causes of vague chest pain some time after sternotomy with increasing accuracy. CONCLUSION: The speed and accuracy of diagnosing PSM have improved with recent advances in imaging and laboratory methodologies. In the symptomatic patient with a closed sternotomy wound or scar, with either fever (>38°C) or sternal instability, together with well-described signs on contrast-enhanced computed tomography, in whom other life-threatening causes of chest pain have been excluded, the diagnosis of PSM can be made without awaiting the outcome of microbiological confirmation. Nevertheless, there still remain significant research opportunities for clinicians and scientists to improve the early diagnostic accuracy of PSM.

Infectious aortitis with multiple mycotic aneurysms caused by Streptococcus agalactiae.

We report a case of a 66-year-old man with multiple thoracoabdominal mycotic aortic aneurysms caused by Streptococcus agalactiae (S agalactiae). The infectious aortitis (IA) was diagnosed by transesophageal echocardiography and computed tomography and confirmed by positive blood cultures. The patient was treated with antibiotics, but, after worsening of the aortitis, a successful surgical procedure was performed. A review of the literature is presented together with a series of 7 other cases of IA caused by S agalactiae.

Femoral venous oxygen saturation is no surrogate for central venous oxygen saturation.

OBJECTIVE: The purpose of our study was to determine if central venous oxygen saturation and femoral venous oxygen saturation can be used interchangeably during surgery and in critically ill patients. DESIGN: Prospective observational controlled study. SETTING: Nonacademic university-affiliated teaching hospital in The Netherlands. PATIENTS: One hundred cardiac outpatients, 30 high-risk surgical patients, and 30 critically ill patients. INTERVENTIONS: None. METHODS AND MAIN RESULTS: We concurrently determined femoral venous oxygen saturation and central venous oxygen saturation in a group of 100 stable cardiac patients, which served as control group. Furthermore, we determined simultaneously femoral venous oxygen saturation and central venous oxygen saturation in 30 surgical patients and in 30 critically ill patients and evaluated changes over time. Correlation and agreement of femoral venous oxygen saturation and central venous oxygen saturation were assessed, including the difference between femoral venous oxygen saturation and central venous oxygen saturation.Despite significant correlation between obtained values of femoral venous oxygen saturation and central venous oxygen saturation (rs = 0.55; p < .001), the limits of agreement were wide in the control group (mean bias 2.7% ± 7.9%; 95% limits of agreement -12.9% to 18.2%). In both the surgical and critically ill patients, limits of agreement (mean bias of -1.9% ± 9.3%; 95% limits of agreement -20.0% to 16.3%, and mean bias of 4.6% ± 14.3%; 95% limits of agreement -23.5% to 32.6%, respectively) were wide. Results for changes of femoral venous oxygen saturation and central venous oxygen saturation were similar. During initial treatment of critically ill patients, the difference between femoral venous oxygen saturation and central venous oxygen saturation including its range of variation diminished. CONCLUSION: There is lack of agreement between femoral venous oxygen saturation and central venous oxygen saturation in both stable and unstable medical conditions. Thus, femoral venous oxygen saturation should not be used as surrogate for central venous oxygen saturation.

The Academic Medical Center Linear Disability Score for evaluation of physical reserve on admission to the ICU: can we query the relatives?

INTRODUCTION: Evaluating the pre-morbid functional status in critically ill patients is important and frequently done using the physical component score (PCS) of the Short Form 36, although this approach has its limitations. The Academic Medical Center Linear Disability Score (ALDS) is a recently developed generic item bank used to measure the disability status of patients with a broad range of diseases. We aimed to study whether proxy scoring with the ALDS could be used to assess the patients' functional status on admission for cardiac care unit (CCU) or ICU patients and how the ALDS relates to the PCS using the Short Form 12 (SF-12). METHODS: Patients and proxies completed the ALDS and SF-12 score in the first 72 hours following ICU scheduled surgery (n = 14), ICU emergency admission (n = 56) and CCU emergency admission (n = 70). RESULTS: In all patients (n = 140) a significant intra-class correlation was found for the ALDS (0.857), the PCS (0.798) and the mental component score (0.679) between patients and their proxy. In both scheduled and emergency admissions, a significant correlation was found between patients and their proxy for the ALDS, although the lowest correlation was found for the ICU scheduled admissions (0.755) compared with the ICU emergency admissions (0.889). In CCU patients, the highest significant correlation between patients and proxies was found for the ALDS (0.855), for the PCS (0.807) and for the mental component score (0.740). CONCLUSIONS: Relatives in close contact with critically ill patients can adequately reflect the patient's level of disability on ICU and CCU admission when using the ALDS item bank, which performed at least as well as the PCS. The ALDS could therefore be a useful alternative for the PCS of the SF-12.

Screening for cardiovascular disease risk using traditional risk factor assessment or coronary artery calcium scoring: the ROBINSCA trial.

AIMS: Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. METHODS AND RESULTS: Individuals at expected elevated CVD risk were randomized into screening arm A (n = 14 478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n = 14 450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. A total of 12 185 participants (84.2%) in arm A and 12 950 (89.6%) in arm B were screened. In total, 48.7% were women, and median age was 62 (interquartile range 10) years. SCORE screening identified 45.1% at low risk (SCORE < 10%), 26.5% at intermediate risk (SCORE 10-20%), and 28.4% at high risk (SCORE ≥ 20%). According to CAC screening, 76.0% were at low risk (Agatston < 100), 15.1% at high risk (Agatston 100-399), and 8.9% at very high risk (Agatston ≥ 400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). CONCLUSION: We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. TRIAL REGISTRATION NUMBER: NTR6471.

Bromide as marker for drug adherence in hypertensive patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Insufficient drug adherence is an important reason for inadequate blood pressure control. Currently, methods that measure drug adherence objectively are lacking. Objective methods are needed to help improve blood pressure control and outcome in hypertensive patients. WHAT THIS STUDY ADDS: Potassium bromide added to antihypertensive drugs can be used to monitor drug adherence in individual patients. However, although this method is objective, it is rather time-, cost- and work-consuming. AIMS Adherence to antihypertensive medication is essential for adequate long-term control of blood pressure (BP). This study investigated different methods of measuring adherence in hypertensive patients. METHODS: Patients were included if BP was insufficiently controlled on monotherapy. After a placebo period patients were treated with trandolapril 2 mg/verapamil SR 180 mg (TV). BP was determined using a mercury sphygmomanometer and ambulatory BP monitoring. Adherence was measured by capsule counting, electronic registration of pill-box openings and by measuring serum bromide concentrations. Potassium bromide was added to each TV capsule. RESULTS: Thirty patients participated in the study. Treatment with TV significantly lowered office BP and ambulatory BP. Results for electronic monitoring and adherence based on bromide measurements were comparable. Adherence was slightly higher when assessed by capsule counting. CONCLUSIONS: Measuring serum bromide concentrations may be suitable for assessment of adherence to drug therapy giving comparable results to electronic monitoring. Using capsule counting, electronic monitoring and measurement of bromide concentrations, nonadherent patients were identified.

Yield of family screening in patients with isolated bicuspid aortic valve in a general hospital.

AIM: To determine the prevalence of unidentified bicuspid aortic valve (BAV) or aortic dilatation (>40mm) in first degree relatives (FDR) of patients with isolated BAV in a general hospital. METHODS AND RESULTS: Patients with isolated BAV received information advising cardiac screening of their FDR. Referred and screened were 134 FDR of 54 adult index patients with isolated BAV (median 2 per index patient). FDR's mean age was 49years (range 16-83years) and 41% were male. They comprised 5 parents (3.7%), 52 siblings (39%) and 77 offspring (57%). Among these FDR, the prevalence of BAV was 6.0% (8 patients). In FDR without BAV, 10 (7.5%) had aortic dilatation. 'Familial BAV' was present in 9/54 families (17%). CONCLUSION: In a general hospital, screening of FDR of patients with isolated BAV resulted in a substantial yield of 13% new cases with BAV or aortic dilatation without BAV.

Knowledge of native valve anatomy is essential in follow-up of patients after aortic valve replacement.

BACKGROUND: After aortic valve replacement (AVR), bicuspid aortic valve (BAV) patients continue to be at risk of aortic complications. Therefore, knowledge of native valve anatomy is important for follow-up. We aimed to determine the extent of which the presence of BAV disease is known in a regional post-AVR population. METHODS: The Electronical Medical Record system was used to collect all patients under follow-up after AVR. We documented their clinical data and used the operative report to determine valve phenotype; lacking reports were retrieved. RESULTS: We identified 560 patients who underwent AVR between 1971 and 2012, with a median of 6.2years follow-up postoperatively. Mean age at surgery was 66years (SD13.2years), and 319 patients (57%) were male. In 29 cases (5%), an operative report was not available and in 85 patients (16%) the report lacked a description of valve phenotype. In 446 patients, a surgeon's description of native valve was available: 299 patients (67%) had tricuspid aortic valve, 140 (31%) BAV, and 3 (1%) quadricuspid aortic valve. In 4 patients (1%) the description was non-conclusive. In 66/140 BAV patients the surgeon's diagnosis was not reported back to the referring cardiologist, which corresponded with 12% of all 560 AVR patients. Another 21% of these 560 lacked a clear description of native valve anatomy: no report, no native valve description or an unclear valve description. CONCLUSIONS: Native valve anatomy was not known in one-third of AVR patients under follow-up, which included almost half of the BAV patients. This lack of knowledge withholds patients from appropriate ascending aorta surveillance.

Coronary CT Angiography for Suspected ACS in the Era of High-Sensitivity Troponins: Randomized Multicenter Study.

BACKGROUND: It is uncertain whether a diagnostic strategy supplemented by early coronary computed tomography angiography (CCTA) is superior to contemporary standard optimal care (SOC) encompassing high-sensitivity troponin assays (hs-troponins) for patients suspected of acute coronary syndrome (ACS) in the emergency department (ED). OBJECTIVES: This study assessed whether a diagnostic strategy supplemented by early CCTA improves clinical effectiveness compared with contemporary SOC. METHODS: In a prospective, open-label, multicenter, randomized trial, we enrolled patients presenting with symptoms suggestive of an ACS at the ED of 5 community and 2 university hospitals in the Netherlands. Exclusion criteria included the need for urgent cardiac catheterization and history of ACS or coronary revascularization. The primary endpoint was the number of patients identified with significant coronary artery disease requiring revascularization within 30 days. RESULTS: The study population consisted of 500 patients, of whom 236 (47%) were women (mean age 54 ± 10 years). There was no difference in the primary endpoint (22 [9%] patients underwent coronary revascularization within 30 days in the CCTA group and 17 [7%] in the SOC group [p = 0.40]). Discharge from the ED was not more frequent after CCTA (65% vs. 59%, p = 0.16), and length of stay was similar (6.3 h in both groups; p = 0.80). The CCTA group had lower direct medical costs (€337 vs. €511, p < 0.01) and less outpatient testing after the index ED visit (10 [4%] vs. 26 [10%], p < 0.01). There was no difference in incidence of undetected ACS. CONCLUSIONS: CCTA, applied early in the work-up of suspected ACS, is safe and associated with less outpatient testing and lower costs. However, in the era of hs-troponins, CCTA does not identify more patients with significant CAD requiring coronary revascularization, shorten hospital stay, or allow for more direct discharge from the ED. (Better Evaluation of Acute Chest Pain with Computed Tomography Angiography [BEACON]; NCT01413282).

Is the accuracy of blood pressure measuring devices underestimated at increasing blood pressure levels?

BACKGROUND: In validation studies reporting on the accuracy of blood pressure measuring devices (ambulatory and non-ambulatory systems), it is frequently stated that the accuracy of blood pressure devices seems to decrease at increasing blood pressure levels. This has been shown for several ambulatory devices in the past. Whether more recently validated devices are less accurate at increasing blood pressure levels is unknown, however. OBJECTIVES: We therefore retrospectively searched the literature for studies performed between 1993 and 2003, reporting on the accuracy of blood pressure measuring devices over different blood pressure levels. When needed, additional information from the authors was requested. METHODS: In total, 30 studies were selected. Of these, the studies reporting on the accuracy of 14 different ambulatory and nine different non-ambulatory devices were useful. For both ambulatory and non-ambulatory devices, accuracy appeared to decrease at increasing blood pressure levels. This was particularly shown for systolic blood pressure. RESULTS: We speculate whether this finding is due to the oscillometric method of blood pressure measurement. Another explanation may exist, however. Blood pressure variability increases with higher blood pressure. Further, the British Hypertension Society protocol 1993 uses sequential measurements. This may be the reason that, owing to the increased blood pressure variability, the accuracy of most devices tends to decrease at higher blood pressure levels. Consequently, the accuracy of blood pressure measuring devices may be underestimated at higher blood pressure levels. CONCLUSION: Currently used automated blood pressure measurement devices seem to be less accurate at increasing blood pressure levels. It is important to be aware of this phenomenon when treating hypertensive patients. The reported decrease in accuracy, however, may well be explained by the increasing blood pressure variability at increasing blood pressure and the use of sequential measurements. If this is the case, then the accuracy of these devices is perhaps underestimated.

Accuracy of the Omron RX-M, an automated blood pressure measuring device, measuring blood pressure at the wrist, according to a modified British Hypertension Society protocol.

OBJECTIVE: To determine the accuracy of the Omron RX-M, a device measuring blood pressure oscillometrically at the wrist. METHODS: In 89 subjects (mean age 55+/-14 years) blood pressure measurements at the wrist with the Omron RX-M were compared to sequential blood pressure measurements with a mercury sphygmomanometer at the (same) upper-arm and to simultaneous measurements with the Omron HEM-705 CP at the opposite arm.Measurements with analyzed according to the British Hypertension Society (BHS) - protocol 1993, to the protocol of the Association for the Advancement of Medical Instrumentation (AAMI) and (retrospectively) to the new 'International Protocol'. RESULTS: Mean differences (+/-SD) between the measurements with the mercury sphygmomanometer and the Omron RX-M were -7.5+/-8.4 mmHg for diastolic blood pressure (DBP) and -2.5+/-12.2 mmHg for systolic blood pressure (SBP), thus not fulfilling the AAMI-criteria (< or =5+/-8). According to the BHS-criteria a grade D was achieved for both DBP and SBP. Compared to the Omron HEM 705 CP results were -6.3+/-7.1 for DBP (grade D) and -4.1+/-12.7 for SBP (grade D). The Omron RX-M also failed to pass the new 'International Protocol' in phase 1. CONCLUSION: Although easy to use, based on this study the Omron RX-M can not be recommended to determine blood pressure accurately.

Accuracy of the Welch Allyn Vital Signs Monitor 52000 automatic blood pressure measuring device according to a modified British Hypertension Society protocol.

The accuracy of the Welch Allyn Vital Signs Monitor, a compact device for the oscillometric measurement of blood pressure, was determined according to the British Hypertension Society protocol. The monitor achieved a grade C for diastolic and a grade D for systolic blood pressure. The device is suitable for monitoring a patient, for example post-operatively, in the emergency department or during an intervention. The device cannot, however, be recommended for an exact determination of blood pressure when compared with the mercury sphygmomanometer. In an earlier validation report, the Welch Allyn Vital Signs Monitor achieved a grade A for both diastolic and systolic blood pressure. After adjusting for the difference in method of calculating the grades used in the two studies, there remained a considerable difference in grading results, for which no clear reason could be found.

Unilateral and multilateral congenital coronary-pulmonary fistulas in adults: clinical presentation, diagnostic modalities, and management with a brief review of the literature.

BACKGROUND: Congenital coronary-pulmonary fistulas (CPFs) are commonly unilateral, but bilateral and multilateral fistulas may occur. In multilateral CPFs, the value of a multidetector computed tomography (MDCT) imaging technique as an adjuvant to coronary angiography (CAG) is eminent. The purpose of this study was to describe the clinical presentation, diagnostic modalities, and management of coincidentally detected congenital CPFs. HYPOTHESIS: Unilateral and multilateral coronary-pulmonary fistulas are increasingly detected due to the wide speard application of multidetector computed tomography which might be a supplementary or replacing to conventional coronary angiography. METHODS: We evaluated 14 adult patients with congenital coronary artery fistulas (CAFs) who were identified from several Dutch cardiology departments. RESULTS: Fourteen adult patients (5 female and 9 male), with a mean age of 57.5 years (range, 24-80 years) had the following abnormal findings: audible systolic cardiac murmur (n = 4), chronic atrial fibrillation (n = 2), nonsustained ventricular tachycardia (n = 1), and cardiomegaly on chest x-ray (n = 2). Echocardiography revealed normal findings with trivial valvular abnormalities (n = 9), depressed left ventricle systolic function (n = 3), and severe mitral regurgitation and atrial dilatation (n = 2). The findings in the rest of the patients were unremarkable. CAG and MDCT were used as a diagnostic imaging techniques either alone (CAG, n = 6; MDCT, n = 1) or in combination (n = 7). Single modality and multimodality diagnostic methods revealed 22 fistulas including CPFs (n = 15), coronary cameral fistulas terminating into the right (n = 2) and the left atrium (n = 1), and systemic-pulmonary fistulas (n = 4). Of all of the fistulas, 10 were unilateral, 6 were bilateral, and 6 was hexalateral. (13) N-ammonia positron emission tomography-computed tomography was performed in 3 patients revealing decreased myocardial perfusion reserve. CONCLUSIONS: CAG remains the gold standard for detection of CPFs. An adjuvant technique using MDCT provides full anatomical details of the fistulas.