bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantification of myocardial ischemia and subtended myocardial mass at adenosine stress cardiac computed tomography. A feasibility study
Authors: Van Driest F , Van Der Geest R J , Broersen A , Dijkstra J , El Mahdiui M , Jukema J W , Scholte A J H A
Published: October 2021

Introduction

Combination of computed tomography angiography (CTA) and adenosine stress CT myocardial perfusion (CTP) allows for coronary artery lesion assessment as well as myocardial ischemia. Nowadays, ischemia on CTP is assessed semi-quantitatively by visual analysis. The aim of this study was to fully quantify myocardial ischemia and the subtended myocardial mass on CTP.

Methods

We included 33 patients referred for a combined CTA and adenosine stress CTP with good or excellent imaging quality on CTP. Firstly, the coronary artery tree was automatically extracted from CTA and the relevant coronary artery lesions (≥50%) were manually defined (Fig. 1A). Secondly, epi- and endocardial contours along with CTP deficits were manually defined in short-axis images (Fig. 1D, 1E). Thirdly, a Voronoi-based algorithm was used to quantify the subtended myocardial mass (Fig. 1B). Fourthly, the perfusion defect and subtended myocardial mass were spatially registered to the CTA and measured in grams (Fig. 1F, 1C). Finally, this can be used to quantitatively correlate the perfusion defect to the subtended myocardial mass.

Results

Voronoi-based segmentation was successful in all cases. We assessed a total of 64 relevant coronary artery lesions. Average values for left ventricular mass, total subtended mass and perfusion defect mass were 118, 69 and 7 grams respectively. In 19/33 patients (58%) the total perfusion defect mass could be distributed over the relevant coronary artery lesion(s).

Conclusions

Quantification of myocardial ischemia and subtended myocardial mass using a Voronoi-based segmentation algorithm seem feasible at adenosine stress CTP and allows for quantitative correlation of coronary artery lesions to corresponding areas of myocardial hypoperfusion.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Prevalence and outcome of extra-cardiac findings in patients referred for cardiac computed tomography angiography
Authors: Nashat H , Adjei F , Enver K , Halmai L , Kardos A
Published: October 2021

Background

Cardiac computed tomography angiography (CCTA) includes several extra-cardiac structures. A variety of abnormalities may be clinically important and, in some cases, explain the patient's symptoms. The incidence of extra cardiac findings (ECFs) on CCTA examination ranges between 7% and 56%, with the true prevalence likely affected by patient selection.

Methods

Cardiac CT scans with suspected coronary disease were prospectively and independently reviewed by a radiologist for the presence of ECFs. Data was collected from a prospectively collated database of all patients who underwent a CCTA scans between June 2011 and October 2015. Patients were followed up for one year after incidental findings were made.

Results

A total of 635 patients had a CCTA scan during the study period. Of these 325 (51.2%) were male, mean age was 66 [22–88] years, with a mean BMI of 27 [17–56]. Extra-cardiac findings were reported in 126 (19.8%) of these 62 (49%) were classified as clinically important and had further imaging and follow-up. The most common abnormalities were pulmonary nodules 61 (46.8%), Hiatus hernia 15 (12%), lymphadenopathy 12 (10%) and liver cysts 10 (8%), Figure 1a. Malignant tumours were identified in 2 (1.6%) patients and one (0.8%) had both aortic root dilatation and type B aortic dissection.

Conclusion

Non-cardiac abnormalities in patients undergoing CCTA provides useful information e.g. early diagnosis of lung malignancies and other life threatening conditions in up to 40% of patients.

Funding Acknowledgement

Type of funding sources: None.
Machine learning analysis of chest CT to detect cardiac abnormalities in COVID19
Authors: Finnegan R , Otton J , Dowling J
Published: October 2021

Introduction

Standard, un-gated chest CT can be used as the basis of detailed segmentation of the atrial and ventricular cardiac chambers. In conditions such as COVID19 where dedicated cardiac imaging may be hazardous or unavailable atlas-based machine learning tools allow automatic quantification of cardiac morphology and may allow early detection of abnormalities.

Purpose

To develop an automated screening tool to detect cardiac changes associated with COVID19 on chest/lung CT to allow early treatment and appropriate selection of patients for dedicated cardiac imaging.

Methods

A previously validated atlas-based cardiac contouring algorithm was modified to work within the setting of variable and severe lung pathology. The modified technique was used to segment the left and right atria and ventricles from non-contrast CT scans. We applied the developed algorithm to the Moscow University COVID19 CT dataset. 1110 scans were available. COVID19 severity was graded 0 to 4. Grade 4 was not used in analysis due to insufficient numbers. Cardiac chamber sizes were compared according to COVID19 severity status. In a limited cohort of repeat studies, the feasibility of polar mapping to demonstrated serial morphological change was tested.

Results

A statistically significant increase of average cardiac chamber volumes was noted relative to mild Grade 0 COVID19 at every incremental severity grade (Figure 1). Changes in average ventricular volumes were greater (up to 15.2% and 16.9% for left and right ventricles) than changes in atrial volumes (up 12.1% and 7.6% for left and right atria). Automated quantification was successful in the large majority of cases and inter-patient polar mapping of sequential data to detect progressive chamber enlargement appears feasible (Figure 2).

Conclusion

Machine learning methods permit automatic quantification of cardiac chamber size from standard lung CT scans. Cardiac changes on lung CT examinations may be used to identify cardiac abnormalities at an early stage and could be useful to triage individuals for dedicated cardiac investigations. With further refinement, this method may be useful to detect and track temporal cardiac changes in COVID19, as well as in other pulmonary pathology and conditions in which chest CT is routinely used.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): SPHERE Research consortium Figure 1Figure 2
Bicuspid aortic valve is associated with less coronary artery calcium and coronary artery disease burden by computed tomography
Authors: Barbieri F , Bleckwenn S , Stoessl L , Plank F , Beyer C , Gollmann-Tepekoeylue C , Holfeld J , Senoner T , Bonaros N , Schachner T , Dichtl W , Feuchtner G
Published: October 2021

Background

Bicuspid aortic valve (BAV) is associated with genetic defects (NOTCH 1, GATA 5 mutations) and aortopathy. Differences in flow pattern and a genetic predisposition could also affect coronary arteries.

Purpose

To assess the coronary artery calcium score (CACS) and coronary artery disease (CAD) burden by coronary computed tomography angiography (CTA) in patients with BAV stenosis, as compared to those with tricuspid aortic valve (TAV) stenosis.

Methods

47 patients with congenital BAV (68.9 years±12.9, 38.3% females) who underwent cardiovascular CTA for TAVR planning were matched with 47 TAV patients for age, gender, smoking, arterial hypertension, dyslipidemia, diabetes, body-mass-index and chronic kidney disease. The coronary artery calcium score (CACS) (Agatston Units=AU) and coronary stenosis severity by CTA (CADRAD:<25% minimal,<50%milde,50–70%moderate,>70/%severe) were quantified.

Results

The coronary artery calcium score (CACS) was lower in BAV (237.4 vs. 1013.3AU; p<0.001), and coronary stenosis severity was less (CAD-RAD:p<0.001) as compared to patients with TAV.

More patients with BAV had CACS zero (27.7% vs. 0%, p<0.001). The majority (68.1%) of patients with BAV had no or non-obstructive CAD but only 25.5% of tricuspid (p<0.001).

Obstructive CAD (>50% stenosis) by CTA was more frequently observed in TAV patients (68.1%; p<0.001). There were no differences in statin use and NOAC, and other co-morbidities such as AF and COPD.

Conclusion

Patients with BAV have markedly less coronary artery calcium load and yielded less severe coronary stenosis. CTA succeeds to rule out obstructive CAD in the majority of patients with BAV, with adherent implications for TAVR planning.

Funding Acknowledgement

Type of funding sources: None. 72 YOM with BAV, zero CACS and no CADCACS was lower in BAV
Grading mitral regurgitation using 4D flow CMR: comparison to transthoracic echocardiography
Authors: Ribeyrolles S , Monin J L , Rohnean A , Diakov C , Caussin C , Monnot S , Paul J F
Published: October 2021

Background

Mitral Regurgitation (MR) is currently primarily assessed using multiple transthoracic echocardiography (TTE) parameters. Two-dimensional Cardiac Magnetic Resonance (CMR) can be used in difficult cases but has limited agreement with TTE for quantifying MR. We hypothesized that 4D Flow CMR may help to quantify MR.

Purpose

To determine the 4D Flow CMR thresholds that achieve the best agreement with TTE for grading MR.

Methods

We conducted a single-center prospective study of patients evaluated for chronic primary MR in 2016–2020. MR was evaluated blindly by TTE and 4D Flow CMR respectively by two cardiologists and two radiologists with decades of experience. MR was graded with both methods as mild, moderate or severe. 4D Flow CMR measurements included MR regurgitant volume per beat (RV) and mitral anterograde flow per beat (MF). RF was obtained as the ratio RV/MF. Additionally, MF was compared to left ventricular stroke volume (LVSV) by cine-CMR.

Results

We included 33 patients in the initial cohort and 33 in the validation cohort. Inter-observer agreement was good for TTE and excellent for 4D Flow CMR. Agreement between MF and LVSV was excellent. Using recommended TTE thresholds (30 mL, 60 mL, 30%, 50%), agreement was moderate for RV and RF. The best agreement between 4D Flow CMR and TTE was obtained with CMR thresholds of 20 mL and 40 mL for RV (κ=0.93; 95% CI, 0.8–1) and 20% and 37% for RF (κ=0.90; 95% CI, 0.7–0.9). In the validation cohort, agreement between TTE and 4D Flow CMR was good with the optimal thresholds (κ= 0.78; 95% CI, 0.61–0.94).

Conclusion

We propose CMR thresholds that provide a good agreement between TTE and CMR for grading MR. Further studies are needed to fully validate 4D-Flow CMR accuracy for primary MR quantification.

Funding Acknowledgement

Type of funding sources: None. Quantification of MR using 4D Flow CMR
Presence of myocardial fibrotic or fat change on cardiac CT influences the width of distribution range of J waves in survivors of ventricular fibrillation
Authors: Funabashi N , Nakamura K , Sasaki T , Naito S , Kobayashi Y
Published: October 2021

Background

The distribution of J waves may correlate with left ventricular (LV) myocardial damage in survivors of ventricular fibrillation (VF).

Purpose

To determine the relationship of the distribution of J waves with presence of myocardial damage such as fibrotic or fat change on cardiac computed tomography (CT) in survivors of VF.

Methods

We conducted a retrospective analysis of 21 survivors of VF (17 males; mean age, 61±14 years) that were implanted with a cardioverter defibrillator and underwent cardiac CT.

Results

On ECG, 4 patients had atrial fibrillation and 15 had J waves. On CT, 13 patients had organized LV myocardial fibrotic and/or fat change in myocardium. The mean corrected QT interval was 453±30 and 429±48 msec in patients with and without myocardial fibrotic and/or fat change, respectively (P=0.182). The distribution of J waves was as follows: 5 had J waves in II, III and aVF leads (one had myocardial fibrotic and/or fat change) and 2 had J waves in III lead (one had myocardial fibrotic and/or fat change). One patient each had J waves in V1 lead; V1,2 leads; II, III, aVF and V1–3 leads; I, III, aVF and V1 leads; II, III, aVF, aVL and V1–6 leads; II, III, aVF and V4,5 leads; II, III, aVF and V2–5 leads; and III and aVF leads. The first one did not have myocardial fibrotic and/or fat change and the remaining 6 had myocardial fibrotic and/or fat change (Figure). If the J waves reached to ≥1 of 3 LV inferior wall leads (II, III, aVF leads) (N=13), 10 (77%) had LV myocardial fibrotic and/or fat change. If not (N=8), 3 (38%) had LV myocardial fibrotic and/or fat change (P=0.071). If the J waves reached ≥2 of 3 LV inferior wall leads (N=11), 9 (82%) had LV myocardial fibrotic and/or fat change. If not (N=10), 4 (40%) had LV myocardial fibrotic and/or fat change (P=0.049). If the J waves reached all three LV inferior wall leads (N=10), 8 (80%) had LV myocardial fibrotic and/or fat change. If not (N=11), 5 (46%) had LV myocardial fibrotic and/or fat change (P=0.104).

Conclusions

In survivors of VF, organized LV myocardial fibrotic and/or fat changes on cardiac CT correlate with a wider distribution range of J waves (reached to LV inferior wall leads). The distribution of J waves and the presence of myocardial fibrotic and/or fat change on CT may be useful to predict the occurrence of VF.

Funding Acknowledgement

Type of funding sources: None. CT fibrosis in VF survivorsJ waves and fibrotic and/or fat change
Quantification of epicardial fat with cardiac CT and association with cardiovascular risk factors and obstructive coronary disease
Authors: Mano T , Viegas J , Reis J , Castelo A , Bras P , Ferreira V , Cardoso I , Grazina A , Figueiredo L , Ruano C , Marques H , Ramos R , Cruz Ferreira R
Published: October 2021

Introduction

Recent studies advocate epicardial fat (EF) as a biologically active organ that influence coronary atherosclerosis development through endocrine and paracrine pathways. We aim to study the relations between EF, thoracic adipose tissue (TAT), cardiovascular risk factors (CRF) and obstructive coronary disease (OCD).

Methods

Retrospective analysis of patients (pts) referred to 64-multislice cardiac computed tomography (CT) in one center. The authors underwent a standardized protocol for quantification of EAT, TAT (subcutaneous and visceral), abdominal visceral fat, coronary calcium score and angiography.

Results

Total of 178 pts: male 99 (56%), mean age 65.9±12.9 years. Indications for performing CT were coronary disease (76%), valvular heart disease (15%), atrial fibrillation (6%) and congenital heart disease (2%). Regarding CRF, EF was only significant higher in patients with diabetes (115±60 vs 95±47, p=0.018), in male gender (114±60 vs 91±42, p=0.04) and was linear correlated with age (p=0.004). The authors also found that EF volume is significant higher in patients with typical angina (p=0.02) and with coronary atherosclerosis: non-obstructive (p=0.0049) and OCD (p=0.001) – Graphic 1. ROC analysis of EF (AUC 0.659, p=0.0039) and EF/TAT relation (AUC 0.704, p=0.003) allowed to estimate that EF>100 ml and EF/TAT >0.06 had a sensibility to predict OCD of 53% and 58%, respectively, and specificity of 66% and 60%. We did not find a correlation between EF, EF/TAT or TAT and coronary calcium score.

Conclusion

EF is higher in patients with diabetes and coronary atherosclerosis. EF and EF/TAT relation had moderate sensibility and specificity to predict OCD, irrespective of calcium score. EF and EF/TAT are promising atherosclerotic markers that could be routinely use in the near future.

Funding Acknowledgement

Type of funding sources: None.
Coronary artery calcium score to predict coronary CT angiography interpretability. An old problem revisited
Authors: Albuquerque F , M Lopes P , Freitas P , Presume J , Gomes D , Abecassis J , Guerreiro S , Santos A , Saraiva C , Mendes M , M Ferreira A
Published: October 2021

Introduction

Clinical guidelines recommend against the use of coronary computed tomography angiography (CCTA) in patients with heavy calcification due to interpretability concerns, but no specific approach or threshold is provided. Recently, alternative methods have been proposed as more reliable predictors of CCTA interpretability than the classic coronary artery calcium score (CACS). The purpose this study was to compare the performance of different measures of coronary calcification as predictors of CCTA interpretability.

Methods

We conducted a retrospective analysis of consecutive patients undergoing CACS and CCTA between 2018 and 2020. The key exclusion criteria were known coronary artery disease, CACS of zero, and presence of non-assessable coronary lesions for reasons other than calcification (movement/gating artifacts or vessel diameter <2mm). CCTA studies were considered non-interpretable if the main reader considered one or more coronary lesions non-assessable due to calcification. Three different measures of coronary calcification were compared using ROC curve analysis: 1) total CACS; 2) CACS-to-lesion ratio (total CACS divided by the number of calcified plaques); and 3) calcium score of the most calcified plaque. Decision-tree analysis was performed to identify the algorithm that best predicts CCTA interpretability.

Results

A total of 432 patients (191 women, mean age 64±11 years) were included. Overall, 31 patients (7.2%) had a non-interpretable CCTA due to calcification. Patients with non-interpretable CCTA had higher CACS (median 589 vs. 50 AU, p<0.001), higher CACS-to-lesion ratio (median 43 vs. 14 AU/lesion, p<0.001), and higher score of the most calcified plaque (median 445 vs. 43 AU, p<0.001). Among the 3 methods, CACS showed the highest discriminative power to predict a non-interpretable CCTA (C-statistic 0.93, 95% CI 0.89–0.95, p<0.001) – Figure 1.

Decision-tree analysis identified a single-variable algorithm (CACS value ≤515 AU) as the best discriminator of CCTA interpretability: 396 of the 409 patients (97%) with CACS ≤515 AU had an interpretable CCTA, whereas only 5 of the 23 patients (22%) with CACS >515 AU had an interpretable test, yielding a total of 96% correct predictions.

Conclusions

The recently proposed and more complex measures of coronary calcification seem unable to outperform total CACS as a predictor of CCTA interpretability. A simple CACS cutoff-value around 500 AU remains the best discriminator for this purpose.

Funding Acknowledgement

Type of funding sources: None. Figure 1
The role of cardiovascular calcifications in COVID-19
Authors: Toselli M , Cereda A C , Giannini F G , Scoccia A S , Gallone G G , Palmisano A P , Vignale D V , Esposito A E ,   sCORE-COVID19 registry
Published: October 2021

Background

Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated.

Purpose

The principal aim was to evaluate the association of coronary artery calcium (CAC) and total thoracic calcium on in-hospital mortality in COVID-19 patients. Then, to evaluate the prognostic impact of clinical and subclinical coronary artery disease (CAD), as assessed by CAC.

Methods

1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included in the SCORE COVID-19 registry (calcium score for COVID-19 Risk Evaluation). At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. A specific sub analysis on CAC was performed stratifying the patients in three groups: (a) “clinical CAD” (prior revascularization history), (b) “subclinical CAD” (CAC >0), (c) “No CAD” (CAC=0). In-hospital mortality was the primary endpoint, while a composite of myocardial infarction and cerebrovascular accident (MI/CVA) was the secondary one.

Results

Non-survivors compared to survivors had higher coronary artery [(487.7±565.3 vs 207.7±406.8, p<0.001)], aortic valve [(322.4±390.9 vs 98.2±250.7 mm2, p<0.001)] and thoracic aorta [(3786.7±4225.5 vs 1487.6±2973.1 mm2, p<0.001)] calcium values. Coronary artery calcium (HR 1.308; 95% CI, 1.046 - 1.637, p=0.019) and total thoracic calcium (HR 1.975; 95% CI, 1.200 - 3.251, p=0.007) resulted to be independent predictors of in-hospital mortality. In the sub - analysis increasing rates of in-hospital mortality (11.3% vs. 27.3% vs. 39.8%, p<0.001) and MI/CVA events (2.3% vs. 3.8% vs. 11.9%, p<0.001) were observed from the No CAD to the clinical CAD groups. Among patients with subclinical CAD, increasing CAC burden was associated with higher rates of in-hospital mortality (20.5% vs. 27.9% vs. 38.7% for patients with CAC score thresholds ≤100, 101–400 and >400, respectively, p<0.001)

Conclusion

Coronary, aortic valve and thoracic aortic calcium assessment on admission non-gated CT permits to stratify the COVID-19 patients in-hospital mortality risk. Cardiovascular calcifications may represent a bystander of an impaired vascular reserve, both microvascular and endothelial, but also a sign of vascular senescence. Therefore, it can be considered an index of biological frailty, likely more accurate than age and other risk factors.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
Pericoronary adipose tissue attenuation index (FAI) – a new imaging biomarker and its diagnostic and prognostic utility: a systematic review and meta-analysis
Authors: Sagris M S , Antonopoulos A A , Simantiris S S , Panagiotopoulos G P , Papanikolaou P P , Oikonomou E O , Siasos G S , Tsioufis K T , Tousoulis D T
Published: October 2021

Background

Pericoronary fat attenuation index (FAI) on coronary computed tomography angiography (CCTA) imaging has been proposed as a sensitive marker of coronary vascular inflammation with prognostic value for major cardiovascular events. To date though there is no systematic review of the published literature and no meta-analyzed data of previously published results.

Methods

We performed a systematic review and meta-analysis according to the PRISMA guidelines. We systematically explored published literature in MEDLINE (Pubmed) before February 1, 2021 for studies assessing FAI in both diagnostic and prognostic clinical settings in patients with or without cardiovascular disease. The primary outcome was the mean difference in FAI attenuation between stable and unstable coronary plaques. The secondary outcome was the hazard ratio of high FAI values for future cardiovascular events. We calculated I2 to test heterogeneity. We used random effects modelling for the meta-analyses to assess the primary and secondary outcome.

Results

In total, 16 studies and 6,944 patients were included in this meta-analysis. FAI was significantly higher in unstable compared to stable plaques with a mean difference of 4.07 HU (95% CI: 1.10–7.89, I2=88%). Higher FAI values offered incremental prognostic value for major cardiovascular events (MACE) in studies with prospective follow-up (HR=3.29, 95% CI= 1.88–5.76, I2=75%).

Conclusion

FAI is a promising imaging biomarker that may be successfully be used for detection of coronary inflammation, discrimination between stable and unstable plaques and prognosis of future MACE. There is undeniable need of further studies to establish the utility of this biomarker in clinical practice in order to improve coronary plaque discrimination and cardiovascular risk prognostication.

Funding Acknowledgement

Type of funding sources: None.
Predictors of CT-derived FFR in patients with suspected CAD beyond severity of coronary stenosis
Authors: Smolka S , Fava A , Moshage M , Marwan M , Achenbach S , Desai M Y
Published: October 2021

Background

Functional assessment of coronary stenosis using computational fluid dynamics is increasingly used, however other factors besides coronary stenosis may affect the results. We assessed several predictors for CT-derived fractional flow reserve (CT-FFR) in patients with suspected coronary artery disease (CAD) undergoing coronary computed tomographic angiography (CCTA).

Methods

2505 consecutive patients with suspected CAD undergoing CCTA from 2008 to 2016 were screened, 1549 were excluded due to incomplete data (934), image quality (345), software error (147) or other reasons (123). Minimal CT-FFR was measured using an on-site prototype (cFFR Version 3.0, Siemens Healthineers, Forchheim, Germany) in coronaries ≥2mm. Several clinical as well as technical criteria were assessed for predicting the minimal CT-FFR per patient.

Results

956 patients (51±12 years, 51.2% men) were included in this analysis. Mean EF was 59.4±7.4%, heart rate 63±9 bpm, systolic (126.5±20mmHg) and diastolic (70±11 mmHg) blood pressure (BP). Regression analysis and ANOVA showed low but significant impact on minimal CT-FFR (mean 0.85±0.10) by EF, aortic valvular dysfunction, heart rate and systolic blood pressure as well as image quality (esp. blooming and image noise). See Tables 1 and 2.

Conclusion

Coronary stenosis may not be the only relevant predictor for CT-FFR. Several clinical criteria (EF, heart rate, BP, aortic valve dysfunction) as well as image criteria (image quality, artifacts) can affect CT-FFR results.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Cleveland Clinic Foundation Table 1. ANOVA analysisTable 2. Regression analysis
Left atrial strain and left atrial stiffness for early detection of cardiotoxicity in cancer patients
Authors: Di Lisi D , Cadeddu Dessalvi C , Manno G , Manganaro R , Ricci J S , Carerj S , Galassi A R , Zito C , Novo G
Published: October 2021

Background

Anti-cancer drugs can cause cardiovascular complications. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) are usually used to identify clinical and subclinical cardiotoxicity.

Purpose

The aim of our study was to assess the addictional role of left atrial reservoir strain (LAS-S) and left atrial stiffness (LASI – the ratio of E/e' to LAS-S) in identifying patients at higher risk of cardiotoxicity.

Methods

102 breast cancer patients (median age 53±9.5 years), without cardiovascular diseases, were enrolled before starting chemotherapy. Electrocardiogram and transthoracic echocardiogram (conventional measurements based on EACVI recommendations; GLS, LAS-S and LASI measurement) were performed in all patients before starting chemotherapy (T0) and 3 (T1) and 6 months (T2) after chemotherapy.

Results

No patient developed clinical cardiotoxicity. Moreover we did not find at all times a significant reduction in LVEF compared to baseline.

At T1 and T2, we found a significant reduction in GLS (−21.1% IQR −21.9, −20.2% at T0 vs −18.8% IQR −9.5, −18.1% at T1 vs −18.0% IQR −19.8, −17.8% at T2; p value <0.01) and LAS-S (34.4% IQR 31.4–37.4% at T0 vs 28.5% IQR 26.2–30.8% at T1 vs 30.8% IQR 27.6–34% at T2; p<0.001), a significant increase of LASI (0.21%-1 IQR 0.10–0.20%-1 at T0 vs 0.28%-1 IQR 0.20–0.31%-1 at T1 vs 0.35%-1 IQR 0.23–0.41%-1 at T2, p<0.001).

In addiction patients were divided into 2 groups based on the presence at T2 and not at T1 (A group) or absence (B group) of a subclinical cardiac dysfunction (identified by a reduction in GLS ≥15% compared to baseline).

In A group (47% of population) LASI increased significantly already at T1 and remained significantly increased at T2 (0.21±0.07 at T0 vs 0.3±0.12 at T1, p value <0.0001; 0.33±0.16 at T2, p value <0.0001); LAS-S was significantly reduced at T1 and T2 (35±5 at T0 vs 30±8 at T1, p value 0.0005; 29±9 at T2, p value 0.0001).

In patients without subclinical cardiac dysfunction during follow-up (B group, 53% of population), a significant reduction in LAS-S was already evident at T1 and not only at T2 (p value <0.0001 at T1-T2); we found a significant increase in LASI at T1 and T2 (p value <0.0001).

Conclusion

LAS-S and LASI are able to identify subclinical cardiac dysfunction during chemotherapy, they appear to be even more precious markers of cardio-toxicity than GLS. Further study are needed to verify the prognostic implications of atrial strain impairment during chemotherapeutic treatment.

Funding Acknowledgement

Type of funding sources: None.
Hepatic T2-times on cardiovascular magnetic resonance imaging reflect liver fibrosis and predict outcome in an all-comer cohort
Authors: Mascherbauer K , Dona C , Koschutnik M , Nitsche C , Dannenberg V , Bardach C , Beitzke D , Loewe C , Mascherbauer J , Hengstenberg C , Kammerlander A
Published: October 2021

Background

Non-alcoholic fatty liver disease (NAFLD) is associated with dismal outcomes in patients with cardiac disorders but infrequently assessed by cardiologists. Cardiovascular magnetic resonance (CMR) is evolving as one-stop-shop imaging modality in cardiology, allowing for non-invasive myocardial tissue characterization by T1-mapping. On standard CMR exams, hepatic tissue is also assessable on T1-maps. However, it is unknown whether hepatic T1-times are associated with 1) myocardial T1-times, 2) established NAFLD scores, and 3) outcomes in patients referred for CMR.

Methods

In consecutive patients undergoing CMR we assessed hepatic and myocardial T1-times, and the NAFLD Fibrosis Score (NFS). Correlation analyses were used to test the association between hepatic and myocardial T1-times as well as the NFS. We used Kaplan-Meier estimates and Cox-regression models to investigate the association between hepatic T1-times and a composite endpoint of heart failure hospitalization and cardiovascular death.

Results

513 patients were included (57±18 y/o, 49% female). Hepatic T1-times were 588±98ms on average and were correlated with myocardial T1-times (r=0.42, p<0.001) and – weakly – with the NFS (r=0.11, p=0.04). Patients with severe liver fibrosis or cirrhosis (n=47) had significantly higher hepatic T1-times as compared to patients with no or mild fibrosis based on the NFS (635±197ms versus 588±80ms, p=0.02). During follow-up (100±40 months), a total of 137 (27%) events occurred. When stratified by quartiles, patients in the highest hepatic T1-time quartile (>700ms) were at higher risk for events compared to all other quartiles (log-rank, p=0.01), which was consistent across different NAFLD risk groups based on the NFS (no/mild fibrosis, indeterminant score, severe fibrosis/cirrhosis). On Cox regression analyses, higher hepatic T1-times yielded significantly higher risk estimates for events (adj. HR 1.20 [95% CI: 1.04–1.38] per 1-SD increase, p=0.01) even when adjusted for age, sex, left and right ventricular ejection fractions, and myocardial T1-times.

Conclusion

Hepatic T1-times assessed on standard CMR reflect severity of NAFLD and predict outcome on top of established risk factors, including myocardial T1-times, in an all-comer CMR cohort.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Medical University of Vienna
Mitral and tricuspid annulus disjunction frequently coexist
Authors: Aabel E , Chivulescu M , Dejgaard L A , Ribe M , Gjertsen E , Hopp E , Hunt T E , Lie O H , Haugaa K H
Published: October 2021

Background

Mitral annulus disjunction (MAD) is an abnormal atrial displacement of the mitral annulus, frequently found in patients with high-risk arrhythmogenic mitral valve prolapse syndrome. It is unknown whether the annulus disjunction extends to the right side of the heart as tricuspid annulus disjunction (TAD), and whether it is associated with right ventricular electrical instability.

Purpose

We aimed to explore the presence of TAD, and if extended annulus disjunction was associated with ventricular arrhythmias.

Methods

We included patients with previously described MAD assessed by cardiac magnetic resonance imaging (CMR) in an ambispective cohort study. MAD and TAD was defined as ≥1 mm separation between the respective atrial wall-valve leaflet junction and the top of the ventricular myocardium. TAD was assessed in the lateral and inferior right ventricular free wall by means of the 4-chamber and right ventricular 2-chamber views, respectively. MAD circumference was assessed by a CMR study protocol with six left ventricular long axis views separated by 30 degrees. Mitral valve prolapse was defined as ≥2 mm superior displacement of any part of the mitral leaflets beyond the mitral annulus. Ventricular arrhythmias were defined as aborted cardiac arrest or non-sustained/sustained ventricular tachycardias recorded by electrocardiogram (ECG), stress ECG or Holter monitoring.

Results

We included 92 patients with MAD (62% female, age 47±16 years, 71% mitral valve prolapse). TAD was found in 48 (52%) patients, both in the lateral (n=40, 83%) and inferior (n=30, 63%) right ventricular free wall. Patients with TAD were older (age 51±16 years vs. 43±14 years, p=0.01), had greater MAD circumference (168±56° vs. 117±62°, p=0.001) and greater MAD distance (9.2±2.9 mm vs. 6.4±2.8 mm, p<0.001). Additionally, patients with TAD had more frequently mitral valve prolapse (40 patients [85%] vs. 25 patients [57%], p=0.003), whereas similar frequency of bileaflet prolapse (17 patients [39%] vs. 10 patients [39%], p=0.99). Ventricular arrhythmias had occurred in 38 (41%) patients, who were younger (age 40±14 years vs. 52±15 years, p<0.001) and had less frequently TAD (14 patients [37%] vs. 34 patients [63%], p=0.01; univariate odds ratio 0.34 [0.15–0.81], p=0.02). However, TAD was not associated with ventricular arrhythmias when adjusted for age (multivariate odds ratio 0.46 [0.18–1.15], p=0.10).

Conclusions

TAD by CMR was highly prevalent in patients with MAD and was a marker of severe annulus disjunction and mitral valve prolapse. TAD was not associated with more ventricular arrhythmias. This novel marker warrants further research to explore the clinical implications of right-sided annulus disjunction.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Norwegian Research Council
Evolution of myocardial tissue injury over a decade after ST-elevation myocardial infarction: a cardiac magnetic resonance study
Authors: Mayr A , Klug G , Reindl M , Tiller C , Holzknecht M , Lechner I , Pamminger M , Troger F , Bauer A , Reinstadler S J , Metzler B
Published: October 2021

Background

In patients with first ST-elevation myocardial infarction (STEMI), the evolution of myocardial tissue injury parameters over a decade as assessed by cardiac magnetic resonance (CMR) has not yet been described.

Purpose

This study examined long-term myocardial tissue injury dynamics in STEMI patients treated with primary percutaneous coronary intervention (PCI), as well as its association with patient characteristics.

Methods

A total of 104 patients with STEMI were included in this observational study. Sequential late gadolinium enhanced CMR studies (after 3 days [interquartile ranges (IQR) 2–4], 4 months [IQR 4–5] and 9 years [IQR 8–10]) were conducted to assess left ventricular (LV) dimensions and function, infarct size and microvascular obstruction (MVO). T2* mapping was added at 9 year scan to assess the presence of persistent iron within the infarct core.

Results

Infarct size decreased progressively from 13% of LV myocardial mass [IQR 7–21] to 10.2% [IQR 5.2–16.1] to 8% [IQR 2.4–12.3] (p<0.001), with an average reduction rate of 6.4% ± 3.4 per year. Relative reduction of infarct size from baseline to 9y follow-up was 43% [IQR 18–66], 21% [IQR 3–42] during the first 4m and 33% [IQR 8–54] between 4m and 9y after STEMI. Decrease of infarct size was associated with greater baseline infarct size (p<0.004) and extent of MVO (p=0.01). MVO was present in 60% (60/104) of patients at baseline, but in none of the follow-up examinations. Sixteen patients had persistent iron within the infarct core at 9 year CMR. Clinical and imaging associates of persistent iron included younger age at study inclusion (p=0.036), higher peak hs troponin T (p<0.001), higher peak creatine kinase (p<0.001) and higher peak CRP (p=0.036) as well as greater infarct size at any occasion (all p<0.001) and greater MVO (p<0.001). Patients with persistent iron showed less relative infarct size regression (51% [IQR 41–79] versus 46% [IQR 32–54], p=0.009).

Conclusion

In patients with STEMI, the evolution of infarct size is a dynamic process that extends well beyond the first few months after the acute event. MVO vanishes in the first few weeks after the index event in all patients. However, persistence of iron within the infarct core occurs up to a decade after reperfused STEMI, reflecting its irreversibility and is associated with the initial infarct severity and worse infarct healing.

Funding Acknowledgement

Type of funding sources: None. Central Illustration.Evolution of STEMI over a decade.
Mortality among patients undergoing dipyridamole 99mTc Sestamibi SPECT: impact of blunted heart rate response and abnormal scans
Authors: Izhaki A , Migranov A , Geva D , Vorobeichik Pechersky D , Goshen E , Rubinshtein R
Published: October 2021

Background

Blunted heart rate response (BHRR) caused by cardiac neuropathy associated with dipyridamole stress, has been linked to cardiovascular (CV) outcome events. Whether BHRR is necessarily associated with abnormal perfusion is unknown. The aim of the study was to assess the incremental prognostic value of BHRR in a single center population undergoing Dipyridamole 99mTc Sestamibi SPECT test (DSPECT) for predicting late CV events.

Methods

388 patients (aged 73±10 years, 45% females, 51% with known coronary disease) that underwent DSPECT over 3 years period were included. Abnormal DSPECT and BHRR were evaluated in relation to late death.

Results

Mean follow up period was 1560±565 (15–2431) days. During follow up period, 90 patients died. Mode of death was CV in 20 and non-CV in 70. BHRR (<20% heart rate increase), abnormal DSPECT, post-stress LVEF <60% and reversible defects were observed in 63%, 41%, 23% and 20% of patients, respectively. BHRR (HR -2.41, p<0.0006) and abnormal DSPECT (HR-1.62, p=0.02) were predictors of all-cause death. BHRR had incremental prognostic value over abnormal DSPECT (Figure, p<0.0005). Multivariable analysis identified age, dyspnea, insulin treated diabetes mellitus and dialysis as independent predictors of death while DSPECT and BHRR did not. However, BHRR remained a significant predictor of CV death [HR 8.1 (1.06, 62.0), p<0.05].

Conclusions

In this contemporary DSPECT cohort, BHRR and DSPECT failed to predict all-cause mortality. However, BHRR was an independent predictor of CV death.

Funding Acknowledgement

Type of funding sources: None. BHRR stratifies abnormal DSPECT
Association of arterial inflammation as assessed by 18FDG-PET/CT and chemotherapy, in patients with lymphoma
Authors: Solomou E , Ioakimidis N , Terentes-Printzios D , Koutagiar I , Kafouris P , Pouli A , Sioni A , Giannouli S , Gardikioti V , Metaxas M , Kalikakis G , Tousoulis D , Tsioufis K , Anagnostopoulos C , Vlachopoulos C ,   ARTERY team
Published: October 2021

Introduction

Inflammation plays a pivotal role in the pathogenesis of both Hodgkin and non-Hodgkin's lymphoma and it has been shown recently that disease burden is associated with arterial inflammation. This can be captured by 18F-fluorodeoxyglucose (18F-FDG) positron emission computed tomography (PET/CT), a commonly used imaging modality for staging and treatment response of patients with lymphoma, which has also been established as a reliable marker of arterial inflammation. Chemotherapy remains the cornerstone of lymphoma treatment; however, its direct effect on arterial 18F-FDG uptake is unknown.

Purpose

To investigate the effect of chemotherapy on arterial inflammation using 18F-FDG PET/CT imaging, in patients with lymphoma.

Methods

Sixty-six patients (22 male, mean age 56 years) with Hodgkin (n=34) or non-Hodgkin's lymphoma (n=32) underwent 18F-FDG PET/CT imaging at baseline, during and after completion of chemotherapy as part of their routine protocol. Arterial 18F-FDG uptake was assessed at the same time points by measuring the metabolic activity (maximum standardized uptake value (SUVmax) and the arterial target to background ratio (TBR)) of the aortic wall along the entire aorta. Patients with Hodgkin lymphoma underwent therapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim scan was performed at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non-Hodgkin's lymphoma underwent therapy with cyclophosphamide, doxorubicin, vincristine and prednisone+rituximab (R-CHOP). Their interim scan was obtained at 2 weeks post the 4th chemotherapy cycle. All patients were re-assessed with 18F-FDG PET/CT imaging 6–8 weeks after chemotherapy completion.

Results

Baseline total aortic TBR was not associated with the presence of diabetes, dyslipidaemia or smoking (p=0.258, p=0.302 and p=0.452, respectively). Twelve patients were receiving statin therapy, however, there was no significant difference in baseline aortic TBR between patients on statins and patients who were not on statin therapy (p=0.265). In the whole study sample, the index vessel TBR progressively decreased by 0.17 from baseline to 6 weeks following the end of treatment (p=0.013 ANOVA with Bonferroni Correction, Figure 1).

Conclusion

Our findings suggest that arterial inflammation is reduced during and post chemotherapy in patients with lymphoma. In addition, they indicate a potential role of molecular imaging in cardio-oncology, providing a longitudinal evaluation of disease severity and its consequences to the arterial wall metabolic activity with a single examination.

Funding Acknowledgement

Type of funding sources: None.
Uptake of [68Ga]-NODAGA-E[(cRGDyK)]2 is related to improvement in pump function in rats with chronic ischemic cardiomyopathy treated with cell therapy
Authors: Follin B , Hoeeg C , Nielsen C H , Hunter I , Bentsen S , Jensen J K , Binderup T , Ekblond A , Ripa R S , Kastrup J , Kjaer A
Published: October 2021

Background

An increasing number of patients living with chronic ischemic cardiomyopathy (ICM) are potential candidates for cell therapy, including adipose tissue-derived mesenchymal stromal cells (ASC). However, proper assessment of clinical effects in relation to cellular effector mechanisms, such as angiogenesis, is currently lacking.

Purpose

To investigate the prognostic value of assessing angiogenesis non-invasively using novel PET imaging in terms of functional outcome after cell therapy in a homologous animal model of ICM.

Methods

Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery. Four weeks after infarction, the rats were scanned with [18F]-FDG and echocardiography, and based on left ventricular ejection fraction (LVEF) and infarct size randomized to allogeneic ASC treatment (n=14) or saline (n=9). Animals were treated using echo-guided trans-thoracic intramyocardial injections. Follow-up echocardiography was performed four weeks after treatment. Angiogenesis was assessed non-invasively using the [68Ga]-NODAGA-E[(cRGDyK)]2 (RGD) PET-tracer before treatment and two weeks after the treatment (Figure). The output was RGD-uptake by maximum standardized uptake value (SUVmax).

Results

RGD-uptake in the infarct area significantly decreased in the saline group (p=0.04), while this decline was not significant in the ASC group (p=0.58). There was no effect on LVEF of the cell therapy in this study (p=0.70). When the rats were grouped by RGD-uptake post treatment, the high RGD-uptake group (n=8) improved LVEF compared to the rats with medium or low RGD-uptake (n=15, p=0.04) irrespective of the treatment. This could indicate that non-invasive detection of a high degree of myocardial angiogenesis measured using RGD is predictive of improvement in cardiac pump function in ICM.

Conclusions

Following injection of ASC or saline, a high RGD-uptake precluded improvement in pump function. This is the first evidence of how uptake of the novel RGD tracer relates to changes in pump function in ICM and the results could affect the design of future clinical trials using regenerative therapy for ICM patients.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Aase and Ejnar Danielsens FondDoctor Sofus Carl Emil Friis and wife Olga Doris Friis' Scholarship Study design, RGD-uptake, and results
Patients with rare autoimmune inflammatory disorders demonstrate sub-clinical left ventricular dysfunction
Authors: Khanna S , Wen I , Gupta A , Thakur A , Bhat A , Chen H H L , Gan G C H , Tan T C
Published: October 2021

Background

ANCA-associated Vasculitis (AAV) and inflammatory myositis (IM) are rare inflammatory autoimmune disorders mediated via pro-inflammatory cytokines and result in a systemic inflammatory state with multi-organ involvement. There is growing evidence to suggest cardiovascular involvement within these inflammatory states. Left ventricular global longitudinal strain (LV-GLS) is proposed to be a more sensitive measure of LV systolic function when compared to standard two-dimensional measures such as LV ejection fraction (LVEF).

Purpose

The purpose of this study was to assess for subclinical cardiac dysfunction in these cohorts when compared to controls.

Methods

Consecutive patients with AAV (n=56) and IM (n=68) admitted to our institution during 2013–2021 were assessed. Patients with pre-existing cardiovascular disease, significant renal impairment (eGFR <30mL/min/1.73m2), LVEF <50% or lack of comprehensive transthoracic echocardiography during admission were excluded (n=72). LV-GLS was measured offline using vendor-independent software (TomTec Arena, Germany v4.6).

Results

A total of 52 patients (22 AAV and 30 IM) were age- and gender-matched to 52 controls. In comparison of the two study populations (AAV and IM), patients with AAV had higher rates of renal impairment (p=0.02) but lower rates of interstitial lung disease when compared to IM (p=0.02). There were no differences between the two groups in terms of cardiovascular risk factors, demographics or other laboratory investigations (p>0.05 for all). In comparison to the control population, patients with AAV and IM had higher indexed LV mass and a lower TAPSE, respectively, when compared to controls. These cohorts also demonstrated impaired LV-GLS (−17.7±2.6 vs −20.6±2.4; p<0.01) when compared to healthy controls, despite no differences in LVEF (62.6±7.8 vs 61.8±5.4; p=0.56) between both groups.

Conclusions

Our results suggest that patients with autoimmune inflammatory disorders demonstrate subclinical LV dysfunction which is likely secondary to a chronic inflammatory state.

Funding Acknowledgement

Type of funding sources: None.