Combining anatomical and biochemical markers in the detection and risk stratification of coronary artery disease.

AIM: We aimed to test the hypothesis if combining coronary artery calcium score (Ca-score) as a quantitative anatomical marker of coronary atherosclerosis with high-sensitive cardiac troponin as a quantitative biochemical marker of myocardial injury provided incremental value in the detection of functional relevant CAD (fCAD) and risk stratification. METHODS AND RESULTS: Consecutive patients undergoing myocardial perfusion SPECT (MPS) without prior CAD were enrolled. The diagnosis of fCAD was based on the presence of ischemia on MPS and coronary angiography- fCAD was centrally adjudicated in the diagnostic and prognostic domain. Diagnostic accuracy was evaluated using the area under receiver-operating characteristic curve. The composite of cardiovascular death and non-fatal acute myocardial infarction (AMI) within 730 days were the primary prognostic endpoints.Among 1715 patients eligible for the diagnostic analysis, 399 patients had fCAD. The combination of Ca-Score and hs-cTnT had good diagnostic accuracy for the diagnosis of fCAD, AUC 0.79 (95 % CI 0.77-0.81), but no incremental value compared to the Ca-score alone (AUC 0.79 (95%CI 0.77-0.81, p=0.965). Similar results were observed using hs-cTnI (AUC 0.80, 95%CI 0.77-0.82) instead of hs-cTnT.Among 1709 patients (99.7%) with available follow-up, 59 patients (3.5%) suffered the composite primary prognostic endpoint (nonfatal AMI n=34, CV death n=28).Both, Ca-score and hs-cTnT had independent prognostic value. Increased risk was restricted to patients with elevation in both markers. CONCLUSION: The combination of the Ca-score with hs-cTnT increases the prognostic accuracy for future events defining fCAD, but does not provide incremental value versus the Ca-Score alone for the diagnosis of fCAD.

Artificial intelligence to improve ischemia prediction in Rubidium Positron Emission Tomography-a validation study.

Background: Patients are referred to functional coronary artery disease (CAD) testing based on their pre-test probability (PTP) to search for myocardial ischemia. The recommended prediction tools incorporate three variables (symptoms, age, sex) and are easy to use, but have a limited diagnostic accuracy. Hence, a substantial proportion of non-invasive functional tests reveal no myocardial ischemia, leading to unnecessary radiation exposure and costs. Therefore, preselection of patients before ischemia testing needs to be improved using a more predictive and personalised approach. Aims: Using multiple variables (symptoms, vitals, ECG, biomarkers), artificial intelligence-based tools can provide a detailed and individualised profile of each patient. This could improve PTP assessment and provide a more personalised diagnostic approach in the framework of predictive, preventive and personalised medicine (PPPM). Methods: Consecutive patients (n = 2417) referred for Rubidium-82 positron emission tomography were evaluated. PTP was calculated using the ESC 2013/2019 and ACC 2012/2021 guidelines, and a memetic pattern-based algorithm (MPA) was applied incorporating symptoms, vitals, ECG and biomarkers. Five PTP categories from very low to very high PTP were defined (i.e., < 5%, 5-15%, 15-50%, 50-85%, > 85%). Ischemia was defined as summed difference score (SDS) ≥ 2. Results: Ischemia was present in 37.1%. The MPA model was most accurate to predict ischemia (AUC: 0.758, p < 0.001 compared to ESC 2013, 0.661; ESC 2019, 0.673; ACC 2012, 0.585; ACC 2021, 0.667). Using the < 5% threshold, the MPA's sensitivity and negative predictive value to rule out ischemia were 99.1% and 96.4%, respectively. The model allocated patients more evenly across PTP categories, reduced the proportion of patients in the intermediate (15-85%) range by 29% (ACC 2012)-51% (ESC 2019), and was the only tool to correctly predict ischemia prevalence in the very low PTP category. Conclusion: The MPA model enhanced ischemia testing according to the PPPM framework:The MPA model improved individual prediction of ischemia significantly and could safely exclude ischemia based on readily available variables without advanced testing ("predictive").It reduced the proportion of patients in the intermediate PTP range. Therefore, it could be used as a gatekeeper to prevent patients from further unnecessary downstream testing, radiation exposure and costs ("preventive").Consequently, the MPA model could transform ischemia testing towards a more personalised diagnostic algorithm ("personalised"). Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00341-5.

Coronary artery calcium score and pre-test probabilities as gatekeepers to predict and rule out perfusion defects in positron emission tomography.

BACKGROUND: Little is known about the gatekeeper performance of coronary artery calcium score (CACS) before myocardial perfusion positron emission tomography (PET), compared with updated pre-test probabilities from American and European guidelines (pre-test-AHA/ACC, pre-test-ESC). METHODS: We enrolled participants without known coronary artery disease undergoing CACS and Rubidium-82 PET. Abnormal perfusion was defined as summed stress score ≥ 4. Using Bayes' formula, pre-test probabilities and CACS were combined into post-test probabilities. RESULTS: We included 2050 participants (54% male, mean age 64.6 years) with median CACS 62 (IQR 0-380), pre-test-ESC 17% (11-26), pre-test-AHA/ACC 27% (16-44), and abnormal perfusion in 437 participants (21%). To predict abnormal perfusion, area under the curve of CACS was 0.81, pre-test-AHA/ACC 0.68, pre-test-ESC 0.69, post-test-AHA/ACC 0.80, and post-test-ESC 0.81 (P < 0.001 for CACS vs. each pre-test, and each post-test vs. pre-test). CACS = 0 had 97% negative predictive value (NPV), pre-test-AHA/ACC ≤ 5% 100%, pre-test-ESC ≤ 5% 98%, post-test-AHA/ACC ≤ 5% 98%, and post-test-ESC ≤ 5% 96%. Among participants, 26% had CACS = 0, 2% pre-test-AHA/ACC ≤ 5%, 7% pre-test-ESC ≤ 5%, 23% post-test-AHA/ACC ≤ 5%, and 33% post-test-ESC ≤ 5% (all P < 0.001). CONCLUSIONS: CACS and post-test probabilities are excellent predictors of abnormal perfusion and can rule it out with very high NPV in a substantial proportion of participants. CACS and post-test probabilities may be used as gatekeepers before advanced imaging. Coronary artery calcium score (CACS) predicted abnormal perfusion (SSS ≥ 4) in myocardial positron emission tomography (PET) better than pre-test probabilities of coronary artery disease (CAD), while pre-test-AHA/ACC and pre-test-ESC performed similarly (left). Using Bayes' formula, pre-test-AHA/ACC or pre-test-ESC were combined with CACS into post-test probabilities (middle). This calculation reclassified a substantial proportion of participants to low probability of CAD (0-5%), not needing further imaging, as shown for AHA/ACC probabilities (2% with pre-test-AHA/ACC to 23% with post-test-AHA/ACC, P < 0.001, right). Very few participants with abnormal perfusion were classified under pre-test or post-test probabilities 0-5%, or under CACS 0. AUC: area under the curve. Pre-test-AHA/ACC: Pre-test probability of the American Heart Association/American College of Cardiology. Post-test-AHA/ACC: Post-test probability combining pre-test-AHA/ACC and CACS. Pre-test-ESC: Pre-test probability of the European Society of Cardiology. SSS: Summed stress score.

Cardiovascular magnetic resonance rest and exercise-stress left atrioventricular coupling index to detect diastolic dysfunction.

Left atrial and ventricular (LA/LV) dysfunction are interlinked in heart failure with preserved ejection fraction (HFpEF); however, little is known about their interplay and relation to cardiac decompensation. We hypothesized that cardiovascular magnetic resonance (CMR) left atrioventricular coupling index (LACI) would identify pathophysiological alterations in HFpEF and be amenable to rest and ergometer-stress CMR. Patients with exertional dyspnoea, signs of diastolic dysfunction (E/e' ≥ 8), and preserved ejection fraction (EF; ≥50%) on echocardiography were prospectively recruited and classified as HFpEF (n = 34) or noncardiac dyspnoea (NCD, n = 34) according to pulmonary capillary wedge pressure (PCWP) on right-heart catheterization (rest/stress ≥ 15/25 mmHg). LA and LV volumes were assessed on short-axis real-time cine sequences at rest and during exercise stress. LACI was defined as the ratio of the LA-to-LV end-diastolic volume. Cardiovascular hospitalization (CVH) was assessed after 24 mo. Volume-derived LA (P ≥ 0.008) but not LV (P ≥ 0.347) morphology and function at rest and during exercise stress detected significant differences comparing HFpEF and NCD. There was impaired atrioventricular coupling in HFpEF at rest (LACI, 45.7% vs. 31.6%, P < 0.001) and during exercise stress (45.7% vs. 27.9%, P < 0.001). LACI correlated with PCWP at rest (r = 0.48, P < 0.001) and during exercise stress (r = 0.55, P < 0.001). At rest, LACI was the only volumetry-derived parameter to differentiate patients with NCD from patients with HFpEF, which were identified using exercise-stress thresholds (P = 0.001). Resting and exercise-stress LACI dichotomized at their medians were associated with CVH (P ≤ 0.005). Assessment of LACI is a simple approach for LA/LV coupling quantification and allows easy and fast identification of heart failure with preserved ejection fraction (HFpEF).NEW & NOTEWORTHY Evaluation of the left atrioventricular coupling index (LACI) in a rest and exercise-stress cardiovascular magnetic resonance imaging protocol allows identification of patients with heart failure and preserved ejection fraction with high diagnostic accuracy. LACI holds similar diagnostic accuracy at rest compared with left atrial ejection fraction during exercise stress. This highlights the value of LACI as a widely available and cost-effective test for diastolic dysfunction, which may help to guide patient selection for referral to specialized testing/treatment.

The power of zero calcium in 82-Rubidium PET irrespective of sex and age.

BACKGROUND: Despite clinical suspicion, many non-invasive tests for coronary artery disease (CAD) are normal. Coronary artery calcification score (CACS) is a well-validated method to detect and risk stratify CAD. Patients with zero calcium score (ZCS) rarely have abnormal tests. Therefore, aims were to evaluate CACS as a gatekeeper to further functional downstream testing for CAD and estimate potential radiation and cost savings. METHODS: Consecutive patients with suspected CAD referred for PET were included (n = 2640). Prevalence and test characteristics of ZCS were calculated in different groups. Summed stress score ≥ 4 was considered abnormal and summed difference score ≥ 7 equivalent to ≥ 10% ischemia. To estimate potential radiation/cost reduction, PET scans were hypothetically omitted in ZCS patients. RESULTS: Mean age was 65 ± 11 years, 46% were female. 21% scans were abnormal and 26% of patients had ZCS. CACS was higher in abnormal PET (median 561 vs 27, P < 0.001). Abnormal PET was significantly less frequent in ZCS patients (2.6% vs 27.6%, P < 0.001). Sensitivity/negative predictive value (NPV) of ZCS to detect/exclude abnormal PET and ≥ 10% ischemia were 96.8% (95%-CI 95.0%-97.9%)/97.4% (95.9%-98.3%) and 98.9% (96.7%-99.6%)/99.6% (98.7%-99.9%), respectively. Radiation and cost reduction were estimated to be 23% and 22%, respectively. CONCLUSIONS: ZCS is frequent, and most often consistent with normal PET scans. ZCS offers an excellent NPV to exclude an abnormal PET and ≥ 10% ischemia across different gender and age groups. CACS is a suitable gatekeeper before advanced cardiac imaging, and potential radiation/cost savings are substantial. However, further studies including safety endpoints are needed.

Low-dose coronary artery calcium scoring compared to the standard protocol.

BACKGROUND: We aimed to compare coronary artery calcium scoring (CACS) with computed tomography (CT) with 80 and 120 kVp in a large patient population and to establish whether there is a difference in risk classification between the two scores. METHODS: Patients with suspected CAD undergoing MPS were included. All underwent standard CACS assessment with 120-kVp tube voltage and with 80 kVp. Two datasets (low-dose and standard) were generated and compared. Risk classes (0 to 25, 25 to 50, 50 to 75, 75 to 90, and > 90%) were recorded. RESULTS: 1511 patients were included (793 males, age 69 ± 9.1 years). There was a very good correlation between scores calculated with 120 and 80 kVp (R = 0.94, R2 = 0.88, P < .001), with Bland-Altman limits of agreement of - 563.5 to 871.9 and a bias of - 154.2. The proportion of patients assigned to the < 25% percentile class (P = .03) and with CACS = 0 differed between the two protocols (n = 264 vs 437, P < .001). CONCLUSION: In a large patient population, despite a good correlation between CACS calculated with standard and low-dose CT, there is a systematic underestimation of CACS with the low-dose protocol. This may have an impact especially on the prognostic value of the calcium score, and the established "power of zero" may no longer be warranted if CACS is assessed with low-dose CT.

Left ventricular ejection fraction, myocardial blood flow and hemodynamic variables in adenosine and regadenoson vasodilator 82-Rubidium PET.

AIMS: In most Rubidium-(Rb)-positron emission tomography (PET) studies, dipyridamole was used as vasodilator. The aim was to evaluate vasodilator PET left ventricular ejection fraction (LVEF), myocardial blood flow (MBF), hemodynamics, and the influence of adenosine and regadenoson on these variables. METHODS AND RESULTS: Consecutive patients (N = 2299) with prior coronary artery disease (CAD) or no prior CAD undergoing adenosine/regadenoson 82Rb-PET were studied and compared according to CAD status and normal/abnormal PET (summed stress score 0-3 vs. ≥4). Rest and stress LVEF differed significantly depending on CAD status and scan results. In patients with no prior CAD, rest/stress LVEF were 68% and 72%, in patients with prior CAD 60% and 63%. LVEF during stress increased 5 ± 6% in normal compared to 1 ± 8% in abnormal PET (P<0.001). Global rest myocardial blood flow(rMBF), stress MBF(sMBF) and myocardial flow reserve (sMBF/rMBF) were significantly higher in no prior CAD patients compared to prior CAD patients(1.3 ± 0.5, 3.3 ± 0.9, 2.6 ± 0.8 and 1.2 ± 0.4, 2.6 ± 0.8, 2.4 ± 0.8 ml/g/min, respectively, P<0.001) and in normal versus abnormal scans, irrespective of CAD status(no prior CAD: 1.4 ± 0.5, 3.5 ± 0.8, 2.8 ± 0.8 and 1.2 ± 0.8, 2.5 ± 0.8, 2.2 ± 0.7; prior CAD: 1.3 ± 0.4, 3.1 ± 0.8, 2.7 ± 0.8 and 1.1 ± 0.4, 2.3 ± 0.7, 2.2 ± 0.7 ml/g/min, respectively, P<0.001). LVEF and hemodynamic values were similar for adenosine and regadenoson stress. Stress LVEF ≥70% excluded relevant ischemia (≥10%) with a negative predictive value (NPV) of 94% (CI 92-95%). CONCLUSIONS: Rest/stress LVEF, LVEF reserve and MBF values are lower in abnormal compared to normal scans. Adenosine and regadenoson seem to have similar effect on stress LVEF, MBF and hemodynamics. A stress LVEF ≥70% has a high NPV to exclude relevant ischemia.

Big mitral annular calcification: a case report of a dynamic liquefaction necrosis as a potential source of embolism.

BACKGROUND: Mitral annular calcification (MAC) is a degenerative, mostly asymptomatic abnormality usually in elderly patients. Caseous MAC (cMAC) is a rare form with central liquefaction necrosis, which typically involves the posterior annulus of the mitral valve and can cause serious sequelae. However, optimal management of patients with cMAC is not clearly defined. CASE SUMMARY: In a 71-year-old female patient, MAC was incidentally detected. Tissue characterization with cardiac magnetic resonance (CMR) revealed a cMAC and a conservative approach was chosen. Six months after cMAC diagnosis, the patient developed an acute hemi-occlusion of a retinal artery with cholesterol embolism. At this time, CMR showed a liquefied cavity of the cMAC. Except for atherosclerotic plaques in the aorta and carotid arteries, further stroke work-up was negative. Therefore, the conservative approach was continued. During follow-up, the liquefied cavity regressed completely after another 6 months and the patient was free from further events (total follow-up 3 years since diagnosis of cMAC). DISCUSSION: A clear diagnosis and quantitative assessment of dynamic processes, such as cMAC, are made possible by performing CMR with multi-parametric tissue characterization. Dynamic changes in cMAC may have serious clinical implications, such as mitral regurgitation or systemic embolization. Among cardiac tumours, thrombus and abscess, cMAC should be included in the differential diagnosis of an intracardiac mass of the posterior mitral annulus in order to avoid further inappropriate diagnostic interventions.

[A heart murmur - a frequent incidental finding]. / Das Herzgeräusch als Zufallsbefund.

A heart murmur - a frequent incidental finding Abstract. Heart murmurs are very common and are present in up to 80 % of school children and 52 % of adults. They originate from the transition from laminar to turbulent blood flow in patients with a structural cardiomyopathy (so-called "organic" murmurs) or in patients with normal hearts (so-called "innocent" murmurs). A detailed history and physical examination help to discriminate innocent from organic murmurs. With the wide availability of transthoracic echocardiography (TTE) cardiac auscultation has lost a lot of its importance, although it remains an important skill for the initial evaluation and triage. An innocent murmur is a minor (1 / 6 - 2 / 6), crescendo-decrescendo, mostly position-dependent, mid-systolic murmur without radiation, which needs no further workup in asymptomatic patients with normal physical capacity. A TTE should be ordered if signs for a cardiac disease are present based on history, physical examination or other tests. Diastolic and continuous murmurs are mostly pathologic and warrant further workup.

Predictors of acute respiratory failure after bone marrow transplantation in children.

OBJECTIVE: To determine factors associated with acute respiratory failure after bone marrow transplantation which can be identified before the onset of lung disease. DESIGN: Population-based, retrospective study. SETTING: A referral-based pediatric intensive care unit and bone marrow transplant center. PATIENTS: Thirty-nine patients with lung disease (abnormal chest radiograph or a need for supplemental oxygen) were identified from a group of 318 pediatric bone marrow transplant patients from 1978 to 1988. Thirty-four of 39 patients with complete data were further classified into patients with mild lung disease (recovery without needing endotracheal intubation, n = 16) and patients with acute respiratory failure (requirement for endotracheal intubation, n = 18). INTERVENTIONS: Regression analyses were performed to define risk factors for development of respiratory failure (multivariate logistic regression) and for a shortened interval between the identification of lung disease and respiratory failure (Cox proportional hazards analysis). MEASUREMENTS AND MAIN RESULTS: Ninety-three percent (15/16) of patients with mild lung disease survived. Conversely, only 9% (2/23) of patients with respiratory failure survived. Predictors of respiratory failure included graft vs. host disease (odds ratio 28.3, 95% confidence interval 1.9-421, p = .015), a prelung disease (baseline) circulating creatinine concentration of > 1.5 mg/dL (> 132.6 mumol/L) (odds ratio 28.4, 95% confidence interval 1.4-577, p = .029), and male gender (odds ratio 14.6, 95% confidence interval 1-210, p = .049). Predictors of a shortened time to onset of respiratory failure included baseline serum creatinine value of > 1.5 mg/dL (> 132.6 mumol/L) (hazard ratio 6.2, 95% confidence interval 1.5-26.5, p = .013) and baseline total bilirubin concentration > 1.4 mg/dL (> 23.9 mumol/L) (hazard ratio 4.5, 95% confidence interval 0.98-20.7, p = .053). The median time to onset of respiratory failure was 4 days in patients with baseline creatinine values > or = 1.5 mg/dL (> 132.6 mumol/L) and 5 days in patients with baseline bilirubin concentrations > or = 1.4 mg/dL (> 23.9 mumol/L) vs. > 26 days in patients with creatinine < 1.5 mg/dL (< 132.6 mumol/L) and > 29 days in patients with bilirubin < 1.4 mg/dL (< 23.9 mumol/L) (Kaplan-Meier analysis). CONCLUSIONS: Renal and liver dysfunction preceded clinical evidence of lung disease in bone marrow transplant patients who developed respiratory failure. Lung disease leading to respiratory failure and adult respiratory distress syndrome appears to develop as one component of the multiple organ failure syndrome in pediatric bone marrow transplant patients.