[Morphological and functional diagnostics of coronary artery disease by computed tomography]. / Morphologische und funktionelle Diagnostik der koronaren Herzkrankheit mittels Computertomographie.

Computed tomography coronary angiography (cCTA) is a safe option for the noninvasive exclusion of significant coronary stenoses in patients with a low or moderate pretest probability for coronary artery disease (CAD). Furthermore, it also allows functional and morphological assessment of coronary stenoses. The European Society of Cardiology (ESC) guidelines on the diagnosis and management of chronic coronary syndrome published in 2019 have strengthened the importance of cCTA in this context and for this reason it has experienced a considerable upgrade. The determination of the Agatston score is a clinically established method for quantifying coronary calcification and influences the initiation of drug treatment. With technologies, such as the introduction of electrocardiography (ECG)-controlled dose modulation and iterative image reconstruction, cCTA can be performed with high image quality and low radiation exposure. Anatomic imaging of coronary stenoses alone is currently being augmented by innovative techniques, such as myocardial CT perfusion imaging or CT-fractional flow reserve (FFR) but the clinical value of these methods merits further investigation. The cCTA could therefore develop into a gatekeeper with respect to the indications for invasive coronary diagnostics and interventions.

[Value of dual-energy computed tomography for detection of left atrial appendage thrombus]. / Mehrwert der Dual-Energy-Computertomographie zur Detektion von Thromben des linken Vorhofohrs.

OBJECTIVE: Contrast-enhanced computed tomography (CT) is a convenient method to visualize left atrial appendage (LAA) thrombi. We determined whether diagnostic accuracy improves by including dual-energy as compared to transesophageal echocardiography (TEE). Furthermore, the influence of protocol parameters on radiation dose were quantified. METHODS: Patients were assigned to the different CT protocols. All CTs were assessed qualitatively for presence of LAA thrombi and dual-energy CT scans quantitatively for iodine concentration. TEE was assessed qualitatively for the presence of thrombi. RESULTS: Of 32 enrolled patients, 6 had a thrombus in TEE. Qualitative CT assessment yielded 83% sensitivity and 88% specificity. In the 26 patients who underwent dual-energy CT, median iodine concentration was 8.6 mg/cm3 and significantly lower in patients with than without LAA thrombi ; furthermore, it provided value for detecting LAA thrombi (AUC: 0.950 vs 0.867 for combined vs. only qualitative assessment, p = 0.04). The median radiation dose was 1.83 mSv; independently lower in scanning only LAA and with prospective gating , while arrhythmia and dual-energy did not contribute independently. CONCLUSION: CT provides good diagnostic accuracy for detecting LAA thrombi, which can further be improved if iodine density measurements by dual-energy are incorporated. With an optimized protocol, reasonably low radiation dose can be achieved.

Strengths and limitations of coronary angiography with turbo high-pitch third-generation dual-source CT.

AIM: To define practical limitations of diagnostic image quality for recently introduced turbo high-pitch scan mode (THP) in third-generation dual-source computed tomography (CT). MATERIALS AND METHODS: Two hundred and twenty-nine consecutive patients undergoing CT coronary angiography were included in this retrospective single-centre analysis. A contrast-enhanced volume dataset was acquired in THP. Image quality of coronary segments was classified as diagnostic or non-diagnostic by three blinded readers. Segments were stated as non-diagnostic if at least one of three readers could neither exclude nor confirm significant stenoses. Multivariable logistic regression was used to assess relationships between number of non-diagnostic segments and common influencing factors. RESULTS: Median effective radiation dose was 0.6 (interquartile range [IQR], 0.4-0.8) mSv overall and 0.3 (IQR, 0.3-0.4) mSv in the 70 kV subgroup of this middle aged, predominantly pre-obese cohort (age: 61 [IQR, 52-67] years; body mass index [BMI]: 26 [IQR, 23-29] kg/m2) with a low-moderate median Agatston score (AS) 0 (IQR, 0-70). Diagnostic image quality was found in 98.1% of 3,678 coronary segments. AS was independently associated with diagnostic image quality (B=0.34; p=0.02), whereas heart rate, BMI, and presence of arrhythmia were not. The portion of diagnostic coronary segments decreased slightly in obese patients with heart rates >65 beats/min and dropped significantly in patients with an AS >600 (p=0.003). CONCLUSION: THP enables CT coronary angiography with minimal radiation exposure and is most appropriate in non-obese patients with stable sinus rhythm ≤65 beats/min and a calcium score ≤600.

Comprehensive bio-imaging using myocardial perfusion reserve index during cardiac magnetic resonance imaging and high-sensitive troponin T for the prediction of outcomes in heart transplant recipients.

We sought to determine the ability of quantitative myocardial perfusion reserve index (MPRI) by cardiac magnetic resonance (CMR) and high-sensitive troponin T (hsTnT) for the prediction of cardiac allograft vasculopathy (CAV) and cardiac outcomes in heart transplant (HT) recipients. In 108 consecutive HT recipients (organ age 4.1±4.7 years, 25 [23%] with diabetes mellitus) who underwent cardiac catheterization, CAV grade by International Society for Heart & Lung Transplantation (ISHLT) criteria, MPRI, late gadolinium enhancement (LGE) and hsTnT values were obtained. Outcome data including cardiac death and urgent revascularization ("hard cardiac events") and revascularization procedures were prospectively collected. During a follow-up duration of 4.2±1.4 years, seven patients experienced hard cardiac events and 11 patients underwent elective revascularization procedures. By multivariable analysis, hsTnT and MPRI both independently predicted cardiac events, surpassing the value of LGE and CAV by ISHLT criteria. Furthermore, hsTnT and MPRI provided complementary value. Thus, patients with high hsTnT and low MPRI showed the highest rates of cardiac events (annual event rate=14.5%), while those with low hsTnT and high MPRI exhibited excellent outcomes (annual event rate=0%). In conclusion, comprehensive "bio-imaging" using hsTnT, as a marker of myocardial microinjury, and CMR, as a marker of microvascular integrity and myocardial damage by LGE, may aid personalized risk-stratification in HT recipients.

Long-term outcome after heart transplantation predicted by quantitative myocardial blush grade in coronary angiography.

The purpose of our study was to investigate whether the quantification of myocardial blush grade (MBG) during surveillance coronary angiography can predict long-term outcome after heart transplantation (HT). In 105 HT recipients who underwent cardiac catheterization, cardiac allograft vasculopathy (CAV) was assessed visually using the ISHLT grading scale (prospective cohort study). MBG was quantified by dividing the plateau of contrast agent gray-level intensity (G(max)) by the time-to-peak intensity (T(max)). In a subgroup (n = 72), myocardial perfusion index by cardiac magnetic resonance imaging (CMR) was assessed. During a mean follow-up duration of 2.7 (standard deviation [SD] 1.0) years, 26 patients experienced cardiac events, including 7 with cardiac death and 19 who underwent coronary revascularization. G(max)/T(max) was related to CAV by ISHLT criteria and to subsequent cardiac events. By univariate analysis, patient age, organ age, CAV, MBG and myocardial perfusion index by CMR were all predictive for cardiac events. Multivariable analysis demonstrated that G(max)/T(max) provided the most robust prediction of cardiac death (hazard ratio [HR] = 0.2, 95% confidence interval [CI] = 0.06-0.64, p < 0.01) and cardiac events (HR = 0.52, 95% CI = 0.32-0.84, p < 0.01), beyond clinical parameters and the presence of CAV. G(max)/T(max) is a valuable surrogate parameter of microvascular integrity, which is associated with cardiac death and revascularization procedures after HT.

HMGB1 as a predictor of infarct transmurality and functional recovery in patients with myocardial infarction.

OBJECTIVES: High-mobility group box 1 (HMGB1) protein is an innate danger signal for the initiation of host defence and tissue repair. The aim of this study was to analyse serum HMGB1 concentration and its correlation with infarct transmurality and functional recovery in patients with ST-elevation (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). DESIGN: We prospectively examined patients with first-time STEMI (n = 46) or NSTEMI (n = 49), treated according to current guidelines. Contrast-enhanced cardiac magnetic resonance imaging was performed 2-4 days after infarction for the estimation of infarct transmurality and was repeated after 6 months for the estimation of residual left ventricular function. HMGB1 was measured 2-4 days after infarction. RESULTS: High-mobility group box 1 concentration was related to infarct size and to residual ejection fraction in patients with STEMI (r(2) = 0.81 and r(2) =0.40, respectively, P < 0.001 for both) and NSTEMI (r(2) = 0.74 and r(2) = 0.25, respectively, P < 0.001 for both). Receiver operating characteristic (ROC) curve-derived cut-off values of 6.2 and 5.9 ng mL(-1) for patients with STEMI and NSTEMI, respectively, were predictive of infarct transmurality greater than 75% (STEMI: area under the curve (AUC) = 0.93, standard error (SE) = 0.04, 95% confidence interval (CI) = 0.81-0.98; NSTEMI: AUC = 0.96, SE = 0.04, 95% CI = 0.86-0.99). HMGB1 cut-off values of 7.2 and 6.4 ng mL(-1) for patients with STEMI and NSTEMI, respectively, were predictive of residual ejection fraction 6 months after myocardial infarction (MI) (STEMI: AUC = 0.81, SE = 0.07, 95% CI = 0.66-0.91; NSTEMI: AUC = 0.81, SE = 0.09, 95% CI = 0.68-0.91). CONCLUSION: High-mobility group box 1 serum levels represent a highly valuable surrogate marker for infarct transmurality and for the prediction of residual left ventricular function after MI.

Strain-encoded cardiac magnetic resonance for the evaluation of chronic allograft vasculopathy in transplant recipients.

The aim of our study was to investigate the ability of Strain-Encoded magnetic resonance imaging (MRI) to detect cardiac allograft vasculopathy (CAV) in heart transplantation (HTx)-recipients. In consecutive subjects (n = 69), who underwent cardiac catheterization, MRI was performed for quantification of myocardial strain and perfusion reserve. Based on angiographic findings subjects were classified: group A including patients with normal vessels; group B, patients with stenosis <50%; and group C, patients with severe CAV (stenosis >or= 50%). Significant correlations were observed between myocardial perfusion reserve with peak systolic strain (r =-0.53, p < 0.001) and with mean diastolic strain rate (r = 0.82, p < 0.001). Peak systolic strain and strain rate were significantly reduced only in group C, while mean diastolic strain rate and myocardial perfusion reserve were already reduced in group B and A. Myocardial perfusion reserve and mean diastolic strain rate had higher accuracy for the detection of CAV (AUC = 0.95, 95% CI = 0.87-0.99 and AUC = 0.93, 95% CI = 0.84-0.98, respectively) and followed peak systolic strain and strain rate (AUC = 0.80, 95% CI = 0.69-0.89 and AUC = 0.78, 95% CI = 0.67-0.87, respectively). Besides the quantification of myocardial perfusion, the estimation of the diastolic strain rate is a useful parameter for CAV assessment. In combination with the clinical evaluation, these parameters may be effective tools for the routine surveillance of HTx-recipients.

Non-invasive diagnostic imaging techniques as a window into the diabetic heart: a review of experimental and clinical data.

Epidemiological and clinical studies show a clear association of diabetes mellitus with congestive heart failure and cardiovascular events independent of blood pressure and ischemic heart disease. The definition of 'diabetic cardiomyopathy' as a clinical entity, however, relies on distinct myocellular and interstitial alterations found in the myocardium of patients with diabetes. The histological findings comprise myocellular hypertrophy, thickening of capillary basement membranes, interstitial fibrosis and rarification of mitochondria on the ultrastructural level. For clinical routine, early detection of diabetic cardiomyopathy seems crucial for identification of patients at cardiovascular risk since the prevalence of heart failure in individuals with diabetes is markedly increased. Recent technical developments in cardiac magnetic resonance imaging (MRI), echocardiography as well as nuclear scintigraphy have advanced the diagnostic applications for the detection of diabetic heart disease. This review aims to present distinct aspects of diabetic cardiomyopathy that were identified using non- invasive imaging techniques. Due to the wide availability and the low costs of echocardiography, it is the most frequently used imaging technique to detect left ventricular dysfunction in patients with diabetes. MRI on the other hand can provide assessment of myocardial structure with higher spatial resolution and allows objective assessment of left ventricular function. This makes MRI an attractive alternative for the detection of discrete alterations, particularly in patients with poor echogenic windows. Finally, nuclear scintigraphy can provide information on cardiac autonomic integrity and accurately detect defects in autonomic control, which are considered a major cardiovascular risk factor in patients with diabetes.

Differences in the prognostic relevance of myocardial ischaemia and scar by cardiac magnetic resonance in patients with and without diabetes mellitus.

AIMS: To evaluate the prognostic significance of myocardial ischaemia and scar in patients with and without diabetes mellitus (DM) who undergo dobutamine stress cardiac magnetic resonance (DCMR) and late gadolinium enhancement (LGE) imaging for known and suspected coronary artery diseases (CADs). METHODS AND RESULTS: A total of 1969 consecutive patients [age 63 ± 12 years, 29% female, left ventricular ejection fraction = 59 ± 12%] referred for a cardiac magnetic resonance (CMR) examination including DCMR and LGE with the suspicion of CAD or progression of CAD in three tertiary cardiac centres were analysed. Cardiac death and nonfatal myocardial infarction (MI) were registered as hard cardiac events. Patients with a revascularization procedure within the first 3 months after CMR were censored at the time of 'early' revascularization. Patients were followed for 3.2 ± 1.5 years (median 2.9, interquartile range 2-4.3 years). In total, 90 (4.6%) cardiac deaths and MI were registered. Among them, 328 patients (16.6%) had diabetes. The proportion of dobutamine-induced wall motion abnormalities (DWMA) and LGE was higher in patients with DM when compared with those without DM (27 vs. 19% and 53.6 vs. 41.2%, respectively, P < 0.001 for both for proportions). Both DWMA and LGE were independent predictors of cardiac death and MI in patients without DM (HR for DWMA 8, CI 4.5-14.3, HR for LGE 2.1, CI 1.1-4.1) and with DM (HR for DWMA 8.6, CI 3.5-21, HR for LGE 4.5, CI 1.5-13.1). Tests for interaction showed that LGE more strongly influences prognosis in patients with than in those without DM (P = 0.03 for interaction), whereas the presence of DWMA is related to similarly poor outcomes in patients with and without DM (P = NS). CONCLUSION: Myocardial scar by LGE is a hallmark of markedly poorer outcome in patients with DM, while the presence of inducible myocardial ischaemia seems to be predictive both in patients with and without DM. Both markers surpass the predictive value of conventional atherogenic risk factors both in patients with and without DM.

Sudden unexpected death in a patient with tumour associated pulmonary embolism.

Tumour embolisms are rare and in most cases sudden causes of death. Diagnosing this rare condition is still very challenging in the daily clinical routine. In this report we present a case of a lethal sudden pulmonary tumour embolism in a 71-year-old male patient, who was admitted for elective invasive coronary angiography due to suspected coronary artery disease. The patient had suspected Ormond's disease and no previous history of tumour burden. Possible diagnostic and treatment options are discussed herein and an overview of the current literature is also presented.

Patient specific models for planning and guidance of minimally invasive aortic valve implantation.

Recently, new techniques for minimally invasive aortic valve implantation have been developed generating a need for planning tools that assess valve anatomy and guidance tools that support implantation under x-ray guidance. Extracting the aortic valve anatomy from CT images is essential for such tools and we present a model-based method for that purpose. In addition, we present a new method for the detection of the coronary ostia that exploits the model-based segmentation and show, how a number of clinical measurements such as diameters and the distances between aortic valve plane and coronary ostia can be derived that are important for procedure planning. Validation results are based on accurate reference annotations of 20 CT images from different patients and leave-one-out tests. They show that model adaptation can be done with a mean surface-to-surface error of 0.5mm. For coronary ostia detection a success rate of 97.5% is achieved. Depending on the measured quantity, the segmentation translates into a root-mean-square error between 0.4 - 1.2mm when comparing clinical measurements derived from automatic segmentation and from reference annotations.

Levels of three distinct p75 neurotrophin receptor forms found in human plasma are altered in type 2 diabetic patients.

AIMS/HYPOTHESIS: The p75 neurotrophin receptor (p75NTR) has been shown to appear in the plasma of diabetic rats, possibly indicating diabetic neuropathy. The aim of this study was to use a semi-quantitative assay for human plasma p75NTR to investigate whether this receptor is a marker of peripheral diabetic neuropathy (DPN) and autonomic cardiovascular neuropathy (CAN) in type 2 diabetic patients. SUBJECTS AND METHODS: Eighty type 2 diabetic patients and 25 controls without diabetes were analysed for p75NTR immunoreactivity by western blot analysis. DPN was assessed using the Neuropathy Disability Score (NDS). Cardiovascular autonomic function was detected using a standardised analysis of heart rate variability. RESULTS: Three distinct p75NTR signals were detectable in human plasma at approximately 75, approximately 51 and approximately 24 kDa, representing the full length receptor (FL) and its intracellular domain (ICD) and extracellular domain (ECD), respectively. Levels of total plasma p75NTR immunoreactivity in patients with type 2 diabetes were similar to those in controls. Type 2 diabetic patients had significantly higher plasma levels of ICD and lower levels of ECD. However, there were no correlations of total p75NTR immunoreactivity or ECD or ICD immunoreactivity with NDS or aspects of CAN. CONCLUSIONS/INTERPRETATION: Levels of the ECD of p75NTR are reduced and levels of the ICD are increased in the plasma of type 2 diabetic patients. None of the p75NTR subunits identified in human plasma seem to be a marker of peripheral or autonomic neuronal function in patients with type 2 diabetes.

Usefulness of myocardial parametric imaging to evaluate myocardial viability in experimental and in clinical studies.

OBJECTIVE: To evaluate whether myocardial parametric imaging (MPI) is superior to visual assessment for the evaluation of myocardial viability. METHODS AND RESULTS: Myocardial contrast echocardiography (MCE) was assessed in 11 pigs before, during, and after left anterior descending coronary artery occlusion and in 32 patients with ischaemic heart disease by using intravenous SonoVue administration. In experimental studies perfusion defect area assessment by MPI was compared with visually guided perfusion defect planimetry. Histological assessment of necrotic tissue was the standard reference. In clinical studies viability was assessed on a segmental level by (1) visual analysis of myocardial opacification; (2) quantitative estimation of myocardial blood flow in regions of interest; and (3) MPI. Functional recovery between three and six months after revascularisation was the standard reference. In experimental studies, compared with visually guided perfusion defect planimetry, planimetric assessment of infarct size by MPI correlated more significantly with histology (r2 = 0.92 versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05). In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual MCE and good accuracy (81%) for viability detection. It was less time consuming (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow estimation by regions of interest and increased the agreement between observers interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05). CONCLUSION: MPI is useful for the evaluation of myocardial viability both in animals and in patients. It is less time consuming than quantification analysis by regions of interest and less observer dependent than visual analysis. Thus, strategies incorporating this technique may be valuable for the evaluation of myocardial viability in clinical routine.

Real-time contrast-enhanced sonography of renal transplant recipients predicts chronic allograft nephropathy.

Real-time contrast-enhanced sonography (RT-CES) can assess microvascular tissue perfusion using gas-filled microbubbles. The study was performed to evaluate the feasibility of RT-CES in detecting chronic allograft nephropathy (CAN) in comparison to color Doppler ultrasonography (CDUS). A total of 26 consecutive renal transplant recipients were prospectively studied using RT-CES and conventional CDUS. Transplant tissue perfusion imaging was performed by low-power imaging during i.v. administration of the sonocontrast Optison. Renal tissue perfusion was assessed quantitatively using flash replenishment kinetics of microbubbles to estimate renal blood flow A *beta (A = peak signal intensity, beta= slope of signal intensity rise). In contrast to conventional CDUS resistance and pulsatility indices, renal blood flow estimated by CES was highly significant related to S-creatinine (r =-0.62, p = 0.0004). Determination of renal blood flow by CES reached a higher sensitivity (91% vs. 82%, p < 0.05), specificity (82% vs. 64%, p < 0.05) and accuracy (85% vs. 73%, p < 0.05) for the diagnosis of CAN as compared to conventional CDUS resistance indices. Perfusion parameters derived from RT-CES significantly improve the early detection of CAN compared to conventional CDUS. RT-CES using low-power real-time perfusion imaging is a feasible method to evaluate microvascular perfusion in renal allograft recipients.

Real-time myocardial contrast echocardiography for the detection of stress-induced myocardial ischemia. Comparison with 99mTc-sestamibi single photon emission computed tomography.

BACKGROUND: Real-time contrast echocardiography (MCE) is a new promising technique for assessing myocardial perfusion. The purpose of this study was to test whether realtime MCE can be used to detect functionally significant coronary artery stenosis in patients with known or suspected coronary artery disease. Myocardial contrast echocardiographic studies were compared with nearly simultaneous 99mTc-sestamibi single photon emission computed tomography (SPECT) as a clinical standard reference to evaluate regional myocardial perfusion defects. METHODS: Real-time MCE based on continuous infusion of Optison (8-10 ml/h) was performed in 66 patients during standard 99mTc-SPECT dipyridamole (0.56 mg/kg x 4 min) stress testing. Images were obtained in apical 4- and 2-chamber views, each divided into 6 segments. Tracer uptake and myocardial opacification were visually analyzed for each segment by two pairs of blinded observers and graded as normal, mildly reduced, severely reduced, or absent. In 792 myocardial segments, myocardial opacification by MCE was uninterpretable in 143 (18%) segments and tracer uptake by SPECT was not clearly defined in 92 (12%) segments. Interobserver variability for MCE was good with concordance rates of 83% (kappa=0.72) for rest- and 86% (kappa=0.76) for stress images. Overall concordance between MCE and SPECT was good (83%, kappa=0.63) at a segmental level. In the diagnosis of fixed and reversible defects, and of normal perfusion, concordance rates were 73, 65 and 83%, respectively. When analysis was performed at the regional level, we found comparable levels of concordance rates for LAD (83%, kappa=0.59), LCX (86%, kappa=0.64) and RCA (80%, kappa=0.68) perfusion territories. CONCLUSIONS: These findings suggest that realtime MCE is a clinically acceptable method to evaluate myocardial perfusion defects during dipyridamole stress testing.