Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography.

OBJECTIVES: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. METHODS: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. RESULTS: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities. CONCLUSION: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone. CLINICAL RELEVANCE STATEMENT: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic. KEY POINTS: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders.

Acute myocardial infarction in a patient with MELAS syndrome: a possible link?

The mitochondrial encephalomyopathy, lactic acidosis, and stroke (MELAS) syndrome is a mitochondrial disorder, commonly caused by m.3243A>G mutation in the MT-TL1 gene. It encodes for the mitochondrial leucine transfer RNA (tRNA Leu [UUR]), implicated in the translation of proteins involved in the assembly and function of mitochondrial complexes in the electron transport chain. The m.3243A>G mutation determines complex I (CI) deficiency, ultimately leading to NADH accumulation, higher rates of glycolysis in order to compensate for the reduced ATP production and increase in lactates, the end-product of glycolysis. Disruption of the oxidative phosphorylation function with an inability to produce sufficient energy results in multi-organ dysfunction, with high energy demanding cells, such as myocytes and neurons, being the most affected ones. Therefore, MELAS syndrome is characterized by a heterogeneous clinical spectrum. Here we report on a case of a 55-year-old man affected by MELA syndrome with no cardiovascular risk factors. He was admitted to our department because of a non ST-segment elevation myocardial infarction (NSTEMI). A coronary angioplasty of the posterior descending artery and of the left anterior descending artery was realized. Transthoracic echocardiography showed inferior and anterior left ventricular wall hypokinesis together with a moderate left ventricle hypertrophy. Cardiac involvement is reported in about a third of the patients and left ventricular hypertrophy (LVH) is the most common phenotype, with possible dilated cardiomyopathy in end-stage disease; brady- arrhythmias and tachy-arrhythmias are also frequently reported as well as Wolff- Parkinson-White (WPW) syndrome. Organ impairment and clinical manifestations depend on the heteroplasmy level of mutant DNA in cells that can differ among individuals, explaining why some patients present a more severe disease. A clear relationship between MELAS syndrome and atherosclerosis has never been established, however recently advocated. In vitro studies in MELAS patients have shown that higher mitochondrial ROS levels and increased expression of oxidative stress-related genes, as a consequence of complex I deficiency and disrupted electron transport, allow circulating LDL to be promptly oxidized into ox-LDL, contributing to endothelial dysfunction and atherosclerosis plaque formation. In light of the recent evidence suggesting a possible link between mitochondrial disorders and atherosclerosis, we speculate that MELAS syndrome may have played a role in the pathogenesis of coronary artery disease in our patient. Further investigations are needed to confirm a pathogenetic link.

The impact of UEFA Euro 2020 football championship on Takotsubo Syndrome: Results of a multicenter national registry.

Objectives: The UEFA 2020 European Football Championship held in multiple cities across Europe from June 11 to July 11, 2021, was won by Italy, providing an opportunity to examine the relationship between emotional stress and the incidence of acute cardiovascular events (ACE). Methods and results: Cardiovascular hospitalizations in the Cardiac Care Units of 49 hospital networks in Italy were assessed by emergency physicians during the UEFA Euro 2020 Football Championship. We compared the events that occurred during matches involving Italy with events that occurred during the remaining days of the championship as the control period. ACE was assessed in 1,235 patients. ACE during the UEFA Euro 2020 Football Championship semifinal and final, the most stressful matches ended with penalties and victory of the Italian team, were assessed. A significant increase in the incidence of Takotsubo Syndrome (TTS) by a factor of 11.41 (1.6-495.1, P < 0.003), as compared with the control period, was demonstrated during the semifinal and final, whereas no differences were found in the incidence of ACS [IRR 0.93(0.74-1.18), P = 0.57]. No differences in the incidence of ACS [IRR 0.98 (0.87-1.11; P = 0.80)] or TTS [IRR 1.66(0.80-3.4), P = 0.14] were found in the entire period including all matches of the UEFA Euro 2020 compared to the control period. Conclusions: The data of this national registry demonstrated an association between the semifinal and final of UEFA Euro 2020 and TTS suggesting that it can be triggered by also positive emotions such as the victory in the European Football Championship finals.

MiRNAs and circRNAs for the Diagnosis of Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients: A Narrative Review.

Breast cancer (BC) is the most frequent type of female cancer with increasing incidence in recent years. Doxorubicin (DOX) is an important backbone chemotherapy in BC, responsible for cardiotoxicity (CTX) in about 9% of treated women within the first year. Biomarkers of early CTX diagnosis are essential to avoid complicated DOX-related cardiac diseases. Traditional serum biomarkers are either poorly sensitive with transient elevation, and even absent if investigated outside their diagnostic window, or arise only in late-stage CTX. Emerging biomarkers such as non-coding RNA (ncRNA) have been recently investigated in DOX-related CTX. In our review, we revised the role of microRNAs, the most studied type of ncRNA, both in animal and human models, highlighting the interesting but often contrasting results. Moreover, we reviewed a novel class of ncRNA, circular RNA (circRNA), focusing on their modulatory mechanisms also involving microRNAs. MicroRNA and circRNA are players in a wide homeostatic balance with their perturbation representing a possible compensation for DOX damage. Further studies are required to assess the modalities of early detection of their variation in BC patients suffering from heart disease induced by DOX treatment.

Computed tomography angiography versus Agatston score for diagnosis of coronary artery disease in patients with stable chest pain: individual patient data meta-analysis of the international COME-CCT Consortium.

OBJECTIVES: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD). PURPOSE: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD. METHODS: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard. RESULTS: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). CONCLUSIONS: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD. KEY POINTS: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease.

COVID-19, Acute Myocardial Injury, and Infarction.

Severe acute respiratory syndrome coronavirus-2 can affect the cardiovascular system yielding a wide range of complications, including acute myocardial injury. The myocardium can be damaged by direct viral invasion or indirect mechanisms, sustained by systemic inflammation, immune-mediated response, and dysregulation of the renin-angiotensin system. Myocardial injury affects about one-quarter of patients with COVID-19, can manifest even in the absence of previous cardiovascular disease, and is associated to higher mortality rates and long-term sequelae. This review describes the pathophysiological mechanisms of myocardial injury and infarction and discusses the main clinical outcomes and diagnostic challenges associated with myocardial damage during COVID-19.

Clinical Features and Management of COVID-19-Associated Hypercoagulability.

COVID-19 is an acute respiratory disease of viral origin caused by SARS-CoV-2. This disease is associated with a hypercoagulable state resulting in arterial and venous thrombotic events. The latter are more frequent, especially in patients who develop a severe form of the disease and are associated with an increased mortality rate. It is therefore essential to identify patients at higher risk to initiate antithrombotic therapy. Hospitalized patients treated with treatment dose of anticoagulants had better outcomes than those treated with prophylactic dose. However, several trials are ongoing to better define the therapeutic and prevention strategies for this insidious complication.

A thymic hyperplasia-related reversible complete atrioventricular block: When compression is more important than compressor.

A 19-year-old patient presented for syncope with third-degree AV block (TDAVB) at ECG. A chest-CT showed a thymic mass that could be responsible for TDAVB due to extrinsic vagal nerve compression. Thymectomy led to complete AV block resolution. An extrinsic vagal compression mechanism should be considered among causes of complete atrioventricular block.

Anatomy, Pathophysiology, Molecular Mechanisms, and Clinical Management of Erectile Dysfunction in Patients Affected by Coronary Artery Disease: A Review.

Erectile dysfunction (ED) has been defined as the inability to attain or maintain penile erection sufficient for successful sexual intercourse. ED carries a notable influence on life quality, with significant implications for family and social relationships. Because atherosclerosis of penile arteries represents one of the most frequent ED causes, patients presenting with it should always be investigated for potential coexistent coronary or peripheral disease. Up to 75% of ED patients have a stenosis of the iliac-pudendal-penile arteries, supplying the male genital organ's perfusion. Recently, pathophysiology and molecular basis of male erection have been elucidated, giving the ground to pharmacological and mechanical revascularization treatment of this condition. This review will focus on the normal anatomy and physiology of erection, the pathophysiology of ED, the relation between ED and cardiovascular diseases, and, lastly, on the molecular basis of erectile dysfunction.

Challenges and Open Issues in Transcatheter Mitral Valve Implantation: Smooth Seas Do Not Make Skillful Sailors.

According to the European and American guidelines, surgery represents the treatment of choice for mitral valve (MV) disease. However, a number of patients are deemed unsuitable for surgery due to a prohibitive/high operative risk. In such cases, transcatheter therapies aiming at MV repair have been proven to be a valuable alternative and have been recently introduced in the latest American guidelines on valvular heart disease. Indeed, percutaneous repair techniques, particularly transcatheter edge-to-edge, have gained a broad experience and demonstrated to be safe and effective. However, given the complexity and heterogeneity of MV anatomy and pathology, transcatheter MV implantation (TMVI) has grown as a possible alternative to percutaneous MV repair. Current data about TMVI are still limited and come from different settings: valve-in-native MV, valve-in-valve (ViV), valve-in-ring (ViR), and valve-in-mitral annular calcification. Preliminary data are promising although several open issues still need to be addressed. This paper provides a comprehensive review of the available devices in the different clinical settings, to discuss potentialities, limitations, and future directions for TMVI.

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data.

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780.

Reduction in radiation exposure in cardiovascular computed tomography imaging: results from the PROspective multicenter registry on radiaTion dose Estimates of cardiac CT angIOgraphy iN daily practice in 2017 (PROTECTION VI).

Aims: Advances of cardiac computed tomography angiography (CTA) have been developed for dose reduction, but their efficacy in clinical practice is largely unknown. This study was designed to evaluate radiation dose exposure and utilization of dose-saving strategies for contrast-enhanced cardiac CTA in daily practice. Methods and results: Sixty one hospitals from 32 countries prospectively enrolled 4502 patients undergoing cardiac CTA during one calendar month in 2017. Computed tomography angiography scan data and images were analysed in a central core lab and compared with a similar dose survey performed in 2007. Linear regression analysis was performed to identify independent predictors associated with dose. The most frequent indication for cardiac CTA was the evaluation of coronary artery disease in 89% of patients. The median dose-length product (DLP) of coronary CTA was 195 mGy*cm (interquartile range 110-338 mGy*cm). When compared with 2007, the DLP was reduced by 78% (P < 0.001) without an increase in non-diagnostic coronary CTAs (1.7% in 2007 vs. 1.9% in 2017 surveys, P = 0.55). A 37-fold variability in median DLP was observed between the hospitals with lowest and highest DLP (range of median DLP 57-2090 mGy*cm). Independent predictors for radiation dose of coronary CTA were: body weight, heart rate, sinus rhythm, tube voltage, iterative image reconstruction, and the selection of scan protocols. Conclusion: This large international radiation dose survey demonstrates considerable reduction of radiation exposure in coronary CTA during the last decade. However, the large inter-site variability in radiation exposure underlines the need for further site-specific training and adaptation of contemporary cardiac scan protocols.

Correction to: Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

OBJECTIVES: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. METHODS: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). RESULTS: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. CONCLUSIONS: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. KEY POINTS: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

Clinical recommendations on Cardiac-CT in 2015: a position paper of the Working Group on Cardiac-CT and Nuclear Cardiology of the Italian Society of Cardiology.

We worked out a position paper on cardiac-computed tomography (CCT) endorsed by the Working Group on CCT and Nuclear Cardiology of the Italian Society of Cardiology. The CCT clinical indications were discussed and formulated according to the following two modalities: a brief paragraph dedicated to each indication, with the description of clinical usefulness of different indications; and each indication was rated by the technical panel for appropriateness, using a score assessing whether the use of CCT for each indication is appropriate, uncertain, or inappropriate. All conventional CCT clinical indications, regarding coronary and noncoronary evaluation, were discussed and rated. Moreover, we wrote specific sections regarding the newest CCT applications, such as stress perfusion computed tomography, noninvasive evaluation of fractional flow reserve, and CCT use in athletes. The present study has the following two main objectives: because the diagnostic performance of coronary computed tomography angiography (CCTA) is strictly dependent on adequate technology and local expertise, we strove to provide clinical recommendations on CCTA that may help Italian physicians involved with this diagnostic tool; and to give an update on new indications of CCTA, such as its use for safely discharging patients with suspected acute coronary syndromes from the emergency department, and latest clinical results that have been made possible by the remarkable technology developments of the scanners.

Prospective Randomized Trial on Radiation Dose Estimates of CT Angiography Applying Iterative Image Reconstruction: The PROTECTION V Study.

OBJECTIVES: The purpose of this study was to assess the potential of iterative image reconstruction (IR) of images for radiation dose reduction in coronary computed tomography angiography (CTA). Therefore, IR in combination with 30% tube current reduction was compared with standard scanning with filtered back projection (FBP) reconstruction. BACKGROUND: Lately, new IR techniques with advanced raw data processing have been introduced by different computed tomography vendors, thus allowing for either image noise reduction at unchanged radiation dose levels or radiation dose reductions at comparable image noise levels. METHODS: In this prospective, multicenter, multivendor noninferiority trial, we randomized 400 consecutive patients to 1 of 2 groups: a control group using standard FBP image reconstruction and standard tube current or an interventional group using IR technique and 30% tube current reduction. The primary endpoint was to demonstrate noninferiority in image quality (IQ) in the IR group. IQ was assessed on a 4-point scale (1, nondiagnostic IQ; 4, excellent IQ). Secondary endpoints included total radiation dose estimates and the rate of downstream testing during 30-day follow-up. RESULTS: Median IQ in the IR group was noninferior compared with the conventional FBP group (IR, 3.5 [interquartile range: 3.0 to 4.0]; FBP, 3.4 [interquartile range: 2.8 to 4.0], p for noninferiority <0.016). The radiation exposure was significantly lower in the IR group (median dose-length-product 157 [interquartile range: 114 to 239] mGy·cm vs. 222 [interquartile range: 141 to 319] mGy·cm for IR vs. FBP, respectively, p < 0.0001). The rate of downstream testing did not differ significantly (7.7% vs. 7.9% for IR vs. FBP, respectively, p = 0.94). CONCLUSIONS: Coronary CTA image quality is maintained with the combined use of a 30% reduced tube current and IR algorithms when compared with conventional FBP image reconstruction techniques and standard tube current. (Prospective Randomized Trial On RadiaTion Dose Estimates Of CT AngIOgraphy In PatieNts: NCT01453712).

Effects of chronic treatment with the new ultra-long-acting ß2 -adrenoceptor agonist indacaterol alone or in combination with the ß1 -adrenoceptor blocker metoprolol on cardiac remodelling.

BACKGROUND AND PURPOSE: The ability of a chronic treatment with indacaterol, a new ultra-long-acting ß2 -adrenoceptor agonist, to reverse cardiac remodelling and its effects in combination with metoprolol, a selective ß1 -adrenoceptor antagonist, were investigated on myocardial infarction in a rat model of heart failure (HF). EXPERIMENTAL APPROACH: We investigated the effects of indacaterol and metoprolol, administered alone or in combination, on myocardial histology, ß-adrenoceptor-mediated pathways, markers of remodelling and haemodynamic parameters in a rat model of HF. Five groups of rats were assessed: sham-operated rats; HF rats; HF + indacaterol 0.3 mg·kg(-1) ·day(-1) ; HF + metoprolol 100 mg·kg(-1) ·day(-1) ; HF + metoprolol + indacaterol. All pharmacological treatments continued for 15 weeks. KEY RESULTS: Treatment with either indacaterol or metoprolol significantly reduced the infarct size in HF rats. However, the combination of indacaterol and metoprolol reduced the infarct size even further, reduced both BP and heart rate, reversed the decrease in ejection fraction, normalized left ventricular systolic and diastolic internal diameters, normalized the decreased ß1 adrenoceptor mRNA expression as well as cardiac cAMP levels and reduced cardiac GPCR kinase 2 expression, compared with the untreated HF group. CONCLUSION AND IMPLICATIONS: The results of our study demonstrated an additive interaction between indacaterol and metoprolol in normalizing and reversing cardiac remodelling in our experimental model of HF. The translation of these findings to clinical practice might be of interest, as this combination of drugs could be safer and more effective in patients suffering from HF and COPD.

Individual patient data meta-analysis for the clinical assessment of coronary computed tomography angiography: protocol of the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT).

BACKGROUND: Coronary computed tomography angiography has become the foremost noninvasive imaging modality of the coronary arteries and is used as an alternative to the reference standard, conventional coronary angiography, for direct visualization and detection of coronary artery stenoses in patients with suspected coronary artery disease. Nevertheless, there is considerable debate regarding the optimal target population to maximize clinical performance and patient benefit. The most obvious indication for noninvasive coronary computed tomography angiography in patients with suspected coronary artery disease would be to reliably exclude significant stenosis and, thus, avoid unnecessary invasive conventional coronary angiography. To do this, a test should have, at clinically appropriate pretest likelihoods, minimal false-negative outcomes resulting in a high negative predictive value. However, little is known about the influence of patient characteristics on the clinical predictive values of coronary computed tomography angiography. Previous regular systematic reviews and meta-analyses had to rely on limited summary patient cohort data offered by primary studies. Performing an individual patient data meta-analysis will enable a much more detailed and powerful analysis and thus increase representativeness and generalizability of the results. The individual patient data meta-analysis is registered with the PROSPERO database (CoMe-CCT, CRD42012002780). METHODS/DESIGN: The analysis will include individual patient data from published and unpublished prospective diagnostic accuracy studies comparing coronary computed tomography angiography with conventional coronary angiography. These studies will be identified performing a systematic search in several electronic databases. Corresponding authors will be contacted and asked to provide obligatory and additional data. Risk factors, previous test results and symptoms of individual patients will be used to estimate the pretest likelihood of coronary artery disease. A bivariate random-effects model will be used to calculate pooled mean negative and positive predictive values as well as sensitivity and specificity. The primary outcome of interest will be positive and negative predictive values of coronary computed tomography angiography for the presence of coronary artery disease as a function of pretest likelihood of coronary artery disease, analyzed by meta-regression. As a secondary endpoint, factors that may influence the diagnostic performance and clinical value of computed tomography, such as heart rate and body mass index of patients, number of detector rows, and administration of beta blockade and nitroglycerin, will be investigated by integrating them as further covariates into the bivariate random-effects model. DISCUSSION: This collaborative individual patient data meta-analysis should provide answers to the pivotal question of which patients benefit most from noninvasive coronary computed tomography angiography and thus help to adequately select the right patients for this test.

Image quality and radiation exposure with prospectively ECG-triggered axial scanning for coronary CT angiography: the multicenter, multivendor, randomized PROTECTION-III study.

OBJECTIVES: The purpose of this study was to evaluate image quality and radiation dose using a prospectively electrocardiogram (ECG)-triggered axial scan protocol compared with standard retrospective ECG-gated helical scanning for coronary computed tomography angiography. BACKGROUND: Concerns have been raised regarding radiation exposure during coronary computed tomography angiography. Although the use of prospectively ECG-triggered axial scan protocols may effectively lower radiation dose compared with helical scanning, it is unknown whether image quality is maintained in a clinical setting. METHODS: In a prospective, multicenter, multivendor trial, 400 patients with low and stable heart rates were randomized to either an axial or a helical coronary computed tomography angiography scan protocol. The primary endpoint was to demonstrate noninferiority in image quality with the axial scan protocol, which was assessed on a 4-point scale (1 = nondiagnostic, 4 = excellent image quality). Secondary endpoints included radiation dose and the rate of downstream testing during 30-day follow-up. RESULTS: Image quality in patients scanned with the axial scan protocol (score 3.36 ± 0.59) was not inferior compared with helical scan protocols (3.37 ± 0.59) (p for noninferiority <0.004). Axial scanning was associated with a 69% reduction in radiation exposure (dose-length product [estimated effective dose] 252 ± 147 mGy · cm [3.5 ± 2.1 mSv] vs. 802 ± 419 mGy · cm [11.2 ± 5.9 mSv] for axial vs. helical scan protocols, p < 0.001). The rate of downstream testing did not differ (13.8% vs. 15.9% for axial vs. helical scan protocols, p = 0.555). CONCLUSIONS: In patients with stable and low heart rates, the prospectively ECG-triggered axial scan protocol maintained image quality but reduced radiation exposure by 69% compared with helical scanning. Axial computed tomography data acquisition should be strongly recommended in suitable patients to avoid unnecessarily high radiation exposure.