Exploration of the relationship between general health-related problems and subclinical coronary artery disease: a cross-sectional study in a general population.

OBJECTIVE: To explore associations between general health-related problems and subclinical coronary artery disease (CAD), determined by CT coronary calcium score (CT-CCS), in a general population. DESIGN: A cross-sectional design. SETTING: This study was performed in a prospective population-based cohort, examining the health and health-related behaviour of individuals living in the Northern Netherlands. PARTICIPANTS: The initial cohort comprised 6763 participants ≥45 years of age who underwent CT-scanning. Participants were included for the current analysis if they filled in three validated questionnaires (Symptomatic Checklist-90, Research and Development Survey-36 and Reviving the Early Diagnosis of CardioVascular Diseases questionnaire (RED-CVD)) and did not have a history of cardiovascular disease. The final analysis included 6530 participants. PRIMARY OUTCOME MEASURE: Backward-stepwise and forward-stepwise logistic regression analyses were performed to determine associations between general health-related problems and subclinical CAD (CCS≥100 and ≥300). RESULTS: The median age was 53 years (25th, 75th percentile: 48, 58); 57% were women. CRCS≥100 was found in 1236 (19%) participants, 437 (12%) in women and 799 (29%) men and CCS≥300 in 643 (9.9%) participants of which 180 (4.8%) were women and 463 (16.6%) men. In univariate analysis, in women the expectation of health to worsen (OR=1.13, 95% CI: 1.05 to 1.21), and in men reduced exercise intolerance (OR=1.14, 95% CI: 1.06 to 1.23) were associated with CCS≥100. The total RED-CVD score in women (OR=1.06, (95% CI: 1.05 to 1.08) and men (OR=1.07, 95% CI: 1.06 to 1.09), and in men also reduced exercise intolerance (OR=1.15, 95% CI: 1.06 to 1.25) and headache (OR=0.55, 95% CI: 0.38 to 0.79) were associated with CCS≥300. In multivariate analyses, only general health expectation in women was still significantly associated with subclinical CAD (CCS≥300) (OR=1.92, 95% CI: 1.56 to 2.37). CONCLUSION: Only a few general health-related problems were associated with the presence of subclinical CAD in the general population, however, these problems showed no strong association. Therefore, using health-related symptoms does not seem useful to pre-select for CT-CCS. TRIAL REGISTRATION NUMBER: CCMO Register, NL17981.042.07 and NL58592.042.16.

Prevalence, pathophysiology, prediction and health-related quality of life of long COVID: study protocol of the longitudinal multiple cohort CORona Follow Up (CORFU) study.

INTRODUCTION: The variety, time patterns and long-term prognosis of persistent COVID-19 symptoms (long COVID-19) in patients who suffered from mild to severe acute COVID-19 are incompletely understood. Cohort studies will be combined to describe the prevalence of long COVID-19 symptoms, and to explore the pathophysiological mechanisms and impact on health-related quality of life. A prediction model for long COVID-19 will be developed and internally validated to guide care in future patients. METHODS AND ANALYSIS: Data from seven COVID-19 cohorts will be aggregated in the longitudinal multiple cohort CORona Follow Up (CORFU) study. CORFU includes Dutch patients who suffered from COVID-19 at home, were hospitalised without or with intensive care unit treatment, needed inpatient or outpatient rehabilitation and controls who did not suffer from COVID-19. Individual cohort study designs were aligned and follow-up has been synchronised. Cohort participants will be followed up for a maximum of 24 months after acute infection. Next to the clinical characteristics measured in individual cohorts, the CORFU questionnaire on long COVID-19 outcomes and determinants will be administered digitally at 3, 6, 12, 18 and 24 months after the infection. The primary outcome is the prevalence of long COVID-19 symptoms up to 2 years after acute infection. Secondary outcomes are health-related quality of life (eg, EQ-5D), physical functioning, and the prevalence of thromboembolic complications, respiratory complications, cardiovascular diseases and endothelial dysfunction. A prediction model and a patient platform prototype will be developed. ETHICS AND DISSEMINATION: Approval was obtained from the medical research ethics committee of Maastricht University Medical Center+ and Maastricht University (METC 2021-2990) and local committees of the participating cohorts. The project is supported by ZonMW and EuroQol Research Foundation. Results will be published in open access peer-reviewed scientific journals and presented at (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT05240742.

Effective Distance between Aortic Valve and Conduction System Is an Independent Predictor of Persistent Left Bundle Branch Block during Transcatheter Aortic Valve Implantation.

Background and objectives: Persistent left bundle branch block (P-LBBB) has been associated with poor clinical outcomes of transcatheter aortic valve implantation (TAVI) procedures. We hypothesized that the distance from the aortic valve to the proximal conduction system, expressed as the effective distance between the aortic valve and conduction system (EDACS), can predict the occurrence of P-LBBB in patients undergoing a TAVI procedure. Materials and methods: In a retrospective study, data from 269 patients were analyzed. EDACS was determined using two longitudinal CT sections. Results: Sixty-four of the patients developed P-LBBB. EDACS ranged between -3 and +18 mm. EDACS was significantly smaller in P-LBBB than in non-P-LBBB patients (4.6 (2.2-7.1) vs. 8.0 (5.8-10.2) mm, median values (interquartile range); p < 0.05). Receiver operating characteristic analysis showed an area under the curve of 0.78 for predicting P-LBBB based on EDACS. In patients with EDACS of ≤3 mm and >10 mm, the chance of developing P-LBBB was ≥50% and <10%, respectively. Conclusions: A small EDACS increases the risk for the development of P-LBBB during TAVI by a factor of >25. As EDACS can be measured pre-procedurally, it may be a valuable additional factor to weigh the risks of transcatheter and surgical aortic valve replacement.

Are patients with stage III non-small cell lung cancer treated with chemoradiotherapy at risk for cardiac events? Results from a retrospective cohort study.

OBJECTIVES: Dyspnoea is one of the symptoms frequently encountered after treatment with chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC). Long-term data on mild to moderately severe cardiac events as underlying cause of dyspnoea in patients with stage III NSCLC are lacking. Therefore, the incidence of new cardiac events, with a common terminology criteria for adverse events (CTCAE) score of ≥2 within 5 years after diagnosis, were analysed. DESIGN: Retrospective multicentre cohort study of patients with stage III NSCLC treated with CRT from 2006 to 2013. The medical files of the treated patients were reviewed. OUTCOME MEASURES: The primary endpoint of the study was the incidence of new cardiac events with a CTCAE score of ≥2 within 5 years after diagnosis. Secondary endpoint was to identify risk factors associated with the development of a cardiac event. RESULTS: Four hundred and sixty patients were included in the study. Of all patients, 150 (32.6%) developed a new cardiac event. In patients with a known cardiac history (n=138), 44.2% developed an event. The most common cardiac events were arrhythmia (14.6%), heart failure (7.6%) and symptomatic coronary artery disease (6.8%). Pre-existent cardiac comorbidity (HR 1.96; p<0.01) and WHO-performance score ≥2 (HR 2.71; p<0.01) were significantly associated with developing a cardiac event. The majority of patients did not have pre-existent cardiac comorbidity (n=322). Elevated WHO/International Society of Hypertension score was not identified as a significant predictor for cardiac events. CONCLUSION: One-third of patients with stage III NSCLC treated in daily clinical practice develop a new cardiac event within 5 years after CRT. All physicians confronted with patients with NSCLC should take cardiac comorbidity as a serious possible explanation for dyspnoea after treatment with CRT.

Personalization of injection protocols to the individual patient's blood volume and automated tube voltage selection (ATVS) in coronary CTA.

PURPOSE: The aim was to assess personalised contrast media (CM) protocols-based on patient's blood volume (BV) and automated tube voltage selection (ATVS)-in coronary computed tomography angiography (CCTA). METHODS: A total of 114 consecutive patients received an ECG-triggered or ECG-gated helical scan on a 3rd-generation dual-source CT with 70-120kV (ATVS) and 330mAsqual.ref. CM was adapted to BV, scan time (s) and kV. Image quality (IQ) was assessed in a 17-segment coronary model using attenuation values (HU), contrast-to-noise (CNR), signal-to-noise ratio (SNR) (objective IQ) and a Likert scale (subjective IQ: 1 = poor/2 = sufficient/3 = good/4 = excellent). ig. RESULTS: Patient distribution was: n = 60 for 70kV, n = 37 80kV and n = 17 90kV. Mean BV was 5.4±0.6L for men and 4.1±0.6L for women. Mean CM volume (300 mg I/mL) and flow rate were: 30.9±6.4mL and 3.3±0.5mL/s (70kV); 40.8±7.1mL and 4.5±0.6mL/s (80kV); 53.6±8.6mL and 5.7±0.6mL/s (90kV). Overall mean HU was >300HU in 98.2% (112/114) of patients. Overall mean attenuation was below 300HU in two scans (70kV) due to late scan timing. Of 1.661 segments, 95.4% was assessable. Mean CNR was 14±4(70kV), 13±3(80kV) and 14±4(90kV); mean SNR was 10±2(both 70kV+80kV) and 9±2(90kV). Objective IQ was comparable between kV settings, protocols and sex. Subjective IQ was diagnostic in all scans and excellent-sufficient in 95.4% of segments. CONCLUSIONS: Personalisation of CCTA CM injection protocols to BV and ATVS is a promising technique to tailor CM administration to the individual patient, while maintaining diagnostic IQ.

Aortic root evaluation prior to transcatheter aortic valve implantation-Correlation of manual and semi-automatic measurements.

BACKGROUND: Pre-procedural TAVI planning requires highly sophisticated and time-consuming manual measurements performed by experienced readers. Semi-automatic software may assist with partial automation of assessment of multiple parameters. The aim of this study was to evaluate differences between manual and semi-automatic measurements in terms of agreement and time. METHODS: One hundred and twenty TAVI candidates referred for the retrospectively ECG-gated CTA (2nd and 3rd generation dual source CT) were evaluated. Fully manual and semi-automatic measurements of fourteen aortic root parameters were assessed in the 20% phase of the R-R interval. Reading time was compared using paired samples t-test. Inter-software agreement was calculated using the Intraclass correlation coefficient (ICC) in a 2-way mixed effects model. Differences between manual and semi-automatic measurements were evaluated using Bland-Altman analysis. RESULTS: The time needed for evaluation using semi-automatic assessment (3 min 24 s ± 1 min 7 s) was significantly lower (p<0.001) compared to a fully manual approach (6 min 31 sec ± 1 min 1 sec). Excellent inter-software agreement was found (ICC = 0.93 ± 0.0; range:0.90-0.95). The same prosthesis size from manual and semi-automatic measurements was selected in 92% of cases, when sizing was based on annular area. Prosthesis sizing based on annular short diameter and perimeter agreed in 99% and 96% cases, respectively. CONCLUSION: Use of semi-automatic software in pre-TAVI evaluation results in comparable results in respect of measurements and selected valve prosthesis size, while necessary reading time is significantly lower.

The role of standard non-ECG gated chest CT in cardiac assessment: design and rationale of the Cardiac Pathologies in standard chest CT (CaPaCT) study.

Modern high-performance computed tomography (CT) scanners with improved scan acquisition times now allow for routine assessment of cardiac pathologies on chest CTs, which can result in numerous incidental cardiac findings. The CaPaCT study, an observer blinded, single-centre study, aims to assess the visibility, management and possible clinical impact of incidental cardiac pathologies that are now becoming visible on standard chest CTs. A total of 217 consecutive patients referred for a chest CT on a high-performance third-generation dual-source CT scanner will be included. Tube voltage settings will be chosen via automated kV selection. Dedicated cardiac reconstructions will be added to the standard post-processing: 0.6-mm slice thickness, 0.4-mm increment and Bv36 kernel (iterative reconstruction/strength 3). Primary endpoints will be the presence and extent of coronary artery disease (CAD) assessed via a 17-segment model. These data will be collected and analysed by two experienced, blinded cardiac radiologists. Furthermore, information on aortic and mitral valve morphology/calcification and pericardial abnormalities will be collected. The CAD Reporting and Data System classification will subsequently be used to assess the management and possible clinical burden of any incidentally detected CAD. Additionally, objective and subjective image quality (attenuation, contrast-to-noise, signal-to-noise and 5-point Likert scale) of the obtained cardiac reconstructions will be assessed.

Cardiac Troponin T and I Release After a 30-km Run.

Prolonged endurance-type exercise is associated with elevated cardiac troponin (cTn) levels in asymptomatic recreational athletes. It is unclear whether exercise-induced cTn release mirrors a physiological or pathological underlying process. The aim of this study was to provide a direct comparison of the release kinetics of high-sensitivity cTnI (hs-cTnI) and T (hs-cTnT) after endurance-type exercise. In addition, the effect of remote ischemic preconditioning (RIPC), a cardioprotective strategy that limits ischemia-reperfusion injury, was investigated in a randomized controlled crossover manner. Twenty-five healthy volunteers completed an outdoor 30-km running trial preceded by RIPC (4 × 5 min 220 mm Hg unilateral occlusion) or control intervention. hs-cTnT, hs-cTnI, and sensitive cTnI (s-cTnI) concentrations were examined before, immediately after, 2 and 5 hours after the trial. The completion of a 30-km run resulted in a significant increase in circulating cTn (time: all p <0.001), with maximum hs-cTnT, hs-cTnI, and s-cTnI levels of 47 ± 27, 69 ± 62, and 82 ± 64 ng/L (mean ± SD), respectively. Maximum hs-cTnT concentrations were measured in 60% of the participants at 2 hours after exercise, compared with maximum hs-cTnI and s-cTnI concentrations at 5 hours in 84% and 80% of the participants. Application of an RIPC stimulus did not reduce exercise-induced cTn release (time × trial: all p >0.5). In conclusion, in contrast to acute myocardial infarction, maximum hs-cTnT levels after exercise precede maximum hs-cTnI levels. Distinct release kinetics of hs-cTnT and hs-cTnI and the absence of an effect of RIPC favors the concept that exercise-induced cTn release may be mechanistically distinct from cTn release in acute myocardial infarction.

High-Sensitivity Cardiac Troponin Concentrations in Patients with Chest Discomfort: Is It the Heart or the Kidneys As Well?

BACKGROUND: High-sensitivity cardiac troponins (hs-cTn) are the preferred biomarkers to detect myocardial injury, making them promising risk-stratifying tools for patients with symptoms of chest pain. However, circulating hs-cTn are also elevated in other conditions like renal dysfunction, complicating appropriate interpretation of low-level hs-cTn concentrations. METHODS: A cross-sectional analysis was performed in 1864 patients with symptoms of chest discomfort from the cardiology outpatient department who underwent cardiac computed tomographic angiography (CCTA). Serum samples were analyzed using hs-cTnT and hs-cTnI assays. Renal function was measured by the estimated glomerular filtration rate (eGFR), established from serum creatinine and cystatin C. On follow-up, the incidence of adverse events was assessed. RESULTS: Median hs-cTnT and hs-cTnI concentrations were 7.2(5.8-9.2) ng/L and 2.6(1.8-4.1) ng/L, respectively. Multivariable regression analysis revealed that both assay results were more strongly associated with eGFR (hs-cTnT:stß:-0.290;hs-cTnI:stß:-0.222) than with cardiac imaging parameters, such as coronary calcium score, CCTA plaque severity score and left ventricular mass (all p<0.01). Furthermore, survival analysis indicated lower relative risks in patients with normal compared to reduced renal function for hs-cTnT [HR(95%CI), 1.02(1.00-1.03) compared to 1.07(1.05-1.09)] and hs-cTnI [1.01(1.00-1.01) compared to 1.02(1.01-1.02)] (all p<0.001). CONCLUSION: In patients with chest discomfort, we identified an independent influence of renal function on hs-cTn concentrations besides CAD, that affected the association of hs-cTn concentrations with adverse events. Estimating renal function is therefore warranted when interpreting baseline hs-cTn concentrations.

MDCT evaluation of aortic root and aortic valve prior to TAVI. What is the optimal imaging time point in the cardiac cycle?

OBJECTIVES: To determine the optimal imaging time point for transcatheter aortic valve implantation (TAVI) therapy planning by comprehensive evaluation of the aortic root. METHODS: Multidetector-row CT (MDCT) examination with retrospective ECG gating was retrospectively performed in 64 consecutive patients referred for pre-TAVI assessment. Eighteen different parameters of the aortic root were evaluated at 11 different time points in the cardiac cycle. Time points at which maximal (or minimal) sizes were determined, and dimension differences to other time points were evaluated. Theoretical prosthesis sizing based on different measurements was compared. RESULTS: Largest dimensions were found between 10 and 20% of the cardiac cycle for annular short diameter (10%); mean diameter (10%); effective diameter and circumference-derived diameter (20%); distance from the annulus to right coronary artery ostium (10%); aortic root at the left coronary artery level (20%); aortic root at the widest portion of coronary sinuses (20%); and right leaflet length (20%). Prosthesis size selection differed depending on the chosen measurements in 25-75% of cases. CONCLUSION: Significant changes in anatomical structures of the aortic root during the cardiac cycle are crucial for TAVI planning. Imaging in systole is mandatory to obtain maximal dimensions. KEY POINTS: • Most aortic root structures undergo significant dimensional changes throughout the cardiac cycle. • The largest dimensions of aortic parameters should be determined to optimize TAVI. • Circumference-derived diameter showed maximum dimension at 20% of the cardiac cycle.

The role of cardiovascular magnetic resonance imaging and computed tomography angiography in suspected non-ST-elevation myocardial infarction patients: design and rationale of the CARdiovascular Magnetic rEsoNance imaging and computed Tomography Angiography (CARMENTA) trial.

BACKGROUND: Although high-sensitivity cardiac troponin (hs-cTn) substantially improves the early detection of myocardial injury, it lacks specificity for acute myocardial infarction (MI). In suspected non-ST-elevation MI, invasive coronary angiography (ICA) remains necessary to distinguish between acute MI and noncoronary myocardial disease (eg, myocarditis), unnecessarily subjecting the latter to ICA and associated complications. This trial investigates whether implementing cardiovascular magnetic resonance (CMR) or computed tomography angiography (CTA) early in the diagnostic process may help to differentiate between coronary and noncoronary myocardial disease, thereby preventing unnecessary ICA. STUDY DESIGN: In this prospective, single-center, randomized controlled clinical trial, 321 consecutive patients with acute chest pain, elevated hs-cTnT, and nondiagnostic electrocardiogram are randomized to 1 of 3 strategies: (1) CMR, or (2) CTA early in the diagnostic process, or (3) routine clinical management. In the 2 investigational arms of the study, results of CMR or CTA will guide further clinical management. It is expected that noncoronary myocardial disease is detected more frequently after early noninvasive imaging as compared with routine clinical management, and unnecessary ICA will be prevented. The primary end point is the total number of patients undergoing ICA during initial admission. Secondary end points are 30-day and 1-year clinical outcome (major adverse cardiac events and major procedure-related complications), time to final diagnosis, quality of life, and cost-effectiveness. CONCLUSION: The CARMENTA trial investigates whether implementing CTA or CMR early in the diagnostic process in suspected non-ST-elevation MI based on elevated hs-cTnT can prevent unnecessary ICA as compared with routine clinical management, with no detrimental effect on clinical outcome.