bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical characteristics and in-hospital outcomes of patients coinfected with Chagas disease and SARS-CoV-2
Authors: Marcolino M , Molina I , Pires M C , Ramos L E F , Silva R T , Guimaraes Junior M H , Carvalho R L R , Barros A L R M , Ribeiro A L , Duani H , Anschau F , Botoni F A , Oliveira N R , Polanczyk C A , Nunes M C P ,   Brazilian COVID-19 Registry Investigators
Published: October 2021

Background

Underlying comorbidities have been widely associated with a worse prognosis for COVID-19 patients, since viral infections could act as triggers for worsening of chronic diseases.

Although Chagas disease (CD) is endemic in Latin America, it has been recognized that the disease is now a worldwide concern. Information on the interplay between COVID-19 and CDis lacking.

Purpose

To assess clinical characteristics and in-hospital outcomes of patients with CD and COVID-19, and to compare it to non-CD patients.

Methods

Patients with COVID-19 diagnosis were selected from the Brazilian COVID-19 Registry, a prospective multicenter cohort, from March to September, 2020. CD diagnosis was based on hospital record at the time of admission. Study data were collected by trained hospital staff using Research Electronic Data Capture (REDCap) tools. Genetic matching for sex, age, hypertension, DM and hospital was performed in a 4:1 ratio.

Results

Of the 7,018 patients who had confirmed infection with SARS-CoV-2 in the registry, 31 patients with CD and 124 matched controls were included. Overall, the median age was 72 (64.-80) years-old and 44.5% were male. At baseline, heart failure (25.8% vs. 9.7%) and atrial fibrillation (29.0% vs. 5.6%) were more frequent in CD patients than in the controls (p<0.05 for both). C-reactive protein levels were lower in CD patients compared with the controls (55.5 [35.7, 85.0] vs. 94.3 [50.7, 167.5] mg/dL). Seventy-two (46.5%) patients required admission to the intensive care unit. In-hospital management, outcomes and complications were similar between the groups (Table 1).

Conclusions

In this large Brazilian COVID-19 Registry, CD patients had a higher prevalence of atrial fibrillation and chronic heart failure compared with non-CD controls, with no differences in-hospital outcomes. The lower C-reactive protein levels in CD patients require further investigation.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported in part by Minas Gerais State Agency for Research and Development (Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG) [grant number APQ-00208-20], National Institute of Science and Technology for Health Technology Assessment (Instituto de Avaliação de Tecnologias em Saúde – IATS)/ National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnolόgico - CNPq) [grant number 465518/2014-1], Table 1. Clinical outcomes
Prognostic value of coronary artery calcium score in hospitalized COVID-19 patients
Authors: Motoc A , Luchian M L , Lochy S , Belsack D , Magne J , Roosens B , De Mey J , Boeckstaens S , Van Den Bussche K , Von Kemp B , Galloo X , Francois C , Weytjens C , Droogmans S , Cosyns B
Published: October 2021

Background

The association between known cardiovascular risk factors and poor prognosis of patients diagnosed with coronavirus disease 2019 (COVID-19) has been recently emphasized (1). Coronary artery calcium (CAC) score assessed by computed tomography (CT) is considered a risk modifier in primary prevention of cardiovascular disease and has shown to improve cardiovascular risk prediction in addition to classical risk factors (2).

Purpose

We hypothesized that the absence of CAC might have an additional predictive value for an improved cardiovascular outcome of hospitalized COVID-19 patients.

Methods

We prospectively included 310 consecutive hospitalized patients with COVID-19. Thirty patients with a history of coronary artery disease were excluded.Low dose non-contrast chest CT was performed in all patients at admission. Visual assessment of CAC in every coronary artery was obtained by using an ordinal scoring of 0, 1, 2 or 3 corresponding to absent, mild, moderate or severe CAC score. A total score was calculated by summing the score of each vessel, which was further categorized as 0 (undetectable), 1–3 (mild), 4–5 (moderate) and ≥6 (severe). (Figure 1). Demographics, medical history, clinical characteristics, laboratory findings, imaging data, in–hospital treatment and outcomes were retrospectively analyzed. A composite endpoint of major adverse cardiovascular events (MACE) was defined as all-cause mortality and cardiovascular events (heart failure, myocarditis, arrhythmia, acute coronary syndrome, stroke, pulmonary embolism).

Results

Two-hundred eighty patients (63.2±16.7 years old, 57.5% male) were included in the analysis. One hundred thirty one (46.7%) patients had a CAC score of zero. MACE-rate was 24.2% (68 patients). Multivariate logistic regression showed that the absence of CAC was inversely associated with MACE (OR 0.264, 95% 0.071–0.981, p=0.047), with a negative predictive value (NPV) of 81.4%, sensitivity 70%, specificity 55%, independent of age, risk factors or disease severity (Table 1).

Conclusion

The absence of CAC translated into a low risk for MACE in COVID-19 patients, even in the presence of cardiac risk factors, which reinforces the idea that the assessment of CAC score in COVID-19 patients could be a useful marker for patients risk stratification and management. Future directions should focus on the implementation of CAC score into mid-term and long-term follow-up of this particular population, to provide a more precise and earlier estimation of cardiovascular risk

Funding Acknowledgement

Type of funding sources: None. Figure 1Table 1
The atherosclerosis profile by coronary CTA compared to the coronary artery calcium score (CACS) in a young symptomatic high-risk population between 19 and 49 years
Authors: Plank F , Beyer C , Langer C , Senoner T , Bleckwenn S , Widmann G , Barbieri F , Friedrich G , Dichtl W , Feuchtner G
Published: October 2021

Background

Whether the coronary artery calcium score (CACS) or coronary CTA should be used in young high-risk adults for screening of coronary artery disease (CAD), is an open debate and data sparse.

Aims

To evaluate the coronary atherosclerosis profile by coronary computed tomography angiography (CTA) in a young symptomatic high-risk population (age, 19–49 years) in comparison with the coronary artery calcium score (CACS).

Methods and results

1137 symptomatic high-risk patients between 19–49 years (mean 42.4y; 33.2%females) with suspected CAD who underwent CTA and CACS were assigned into 6 age groups (19–30; 31–35; 36–40; 41–45; 46–47; 48–49y).CTA-analysis included stenosis severity (CADRADS) and high-risk-plaque (“HRP”) criteria.

Atherosclerosis was more often detected by CTA than by CACS (45% vs. 27%; p<0.001), >50% stenosis in 13.6% and HRP in 17.7%. Prevalence of atherosclerosis was low and not different between CACS and CTA in the youngest (19–30y:5.2% and 6.4%; 30–35y:10.6% and 16%). Above >35 years, atherosclerosis detection by CTA increased (p=0.004, OR: 2.8, 95% CI: 1.45–5.89); and was higher by CTA as compared to CACS (34.9% vs 16.7%; p<0.001).

CTA outperformed CACS among all higher age groups >35 years, with an increasing gap towards a superior performance of CTA along with age: Above 35 years, stenosis severity (CADRADS) (p=0.002) and >50% stenosis increased from 2.6% to 12.5% (p<0.001).

The rate of HRP increased linearly with age from 6.4% to 26.5%.The distribution of HRP into CACS0 and CACS>0.1AU was similar among all age groups (CACS 0:45.1% had HRP), with an increasing proportion of HRP in CACS>0.1AU with age. 24.9% of CACS 0 patients had CAD by CTA, 4.4% >50% stenosis and 11.5% HRP.

Conclusion

Above 35 years of age, CTA outperforms CACS with an increasing power. Between 19 and 35 years, CACS 0 does not reliably rule out CAD and high-risk-plaque; hence for “noRISK100%safety”, CTA is superior.(#eachlifematters)

Funding Acknowledgement

Type of funding sources: None. 30 YOM diabetic, CACS 0 and HRP by CTAAtherosclerosis vs age: CACS vs CTA
Coronary computed tomography angiography vs.standard of care for evaluation of NSTE-ACS: a systematic review and meta-analysis
Authors: Elzanaty A , Maraey A , Khalil M , Elsheikh E , Nesheiwat Z , Elsharnouby M , Mhanna M , Alom M , Beran A
Published: October 2021

Background

Non-ST elevation acute coronary syndrome (NSTE-ACS) is one of the common cardiac emergencies that pose a diagnostic challenge, especially in the absence of EKG changes or elevation in cardiac markers. Coronary computed tomography angiography (CT) has an established role in the evaluation of stable chest pain with ESC giving it class I recommendation. The role of CCTA in the management of NSTE-ACS is less clear.

Purpose

To evaluate the hypothesis of CT efficacy in identifying and managing patients with NSTE-ACS in comparison to the standard of care (SOC).

Methods

We searched MEDLINE, EMBASE, and Cochrane Central for randomized controlled trials (RCT) that compared initial CT utilization vs SOC in patients presenting with acute chest pain with suspected or confirmed NSTE-ACS. SOC arm included initial evaluation and triaging by treating physician including but not limited to clinical observation, serial cardiac markers, stress testing, and invasive coronary angiography (ICA). Studies with follow-up data of 1 month or more were included. Outcomes evaluated were incidence of rehospitalization/ER visits post index visit, referral to ICA, and presence of significant lesion during ICA requiring revascularization.

Results

A total of 6,862 patients (3,663 in the CT arm and 3,199 in the SOC) were analyzed from 13 RCTs. No statistically significant difference was noted between two intervention arms with regards to repeat hospital visits [Odds ratio (OR): 1.02; 95% CI: 0.85–1.24; P=0.82; I2=0%], and referral to ICA (OR: 1.32: 95% CI: 0.95–1.83; P=0.10; I2=66). CT was however more likely to uncover significant lesions requiring revascularization compared to SOC arm (OR: 1.77; 95% CI: 1.32–2.37; P=0.0001; I2=23%].

Conclusion

Our meta-analysis showed that in patients with suspected NSTE-ACS, CT is associated with similar rates of ICA referral and re-admissions albeit being more likely to uncover hemodynamically significant lesions that require revascularization. These findings are consistent with the finding of the recently published VERDICT trial that showed comparable efficacy between coronary CT and ICA. Further studies evaluating the long term cardiovascular outcomes are warranted.

Funding Acknowledgement

Type of funding sources: None.
Prognostic value of computed tomography derived fractional flow reserve
Authors: Ahmed A I , Han Y , Alnabelsi T , Al Rifai M , Nabi F , Chang S M , Mahmarian J J , Chamsi-Pasha M A , Al-Mallah M H
Published: October 2021

Introduction

Cardiac computed tomography angiography (CCTA) derived fractional flow reserve (FFRCT) has been shown to add incremental diagnostic value by providing functional severity of coronary lesion in patients with coronary artery disease (CAD).

Purpose

We aimed to assess the prognostic value of FFRCT in patients with suspected CAD.

Methods

Consecutive patients who had clinically indicated CCTA and FFRCT determination at a tertiary care cardiology practice were included. FFRCT was determined off-site using computational flow dynamics. Patients were followed for major adverse cardiovascular events (MACE, inclusive of all-cause death, non-fatal myocardial infarction, and late percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) 90-days after imaging test.)

Results

A total of 667 patients with at least Coronary Artery Disease Reporting & Data System (CAD-RADS) 2 were included. Mean age was 68±10 years, 37% were women, 73% had hypertension, 12% had diabetes and 61% had dyslipidemia. More than half (57%) of the patients had moderate (CAD-RADS 3) stenosis. FFRCT<0.8 was found in 59% of patients, with increasing percent across categories of CAD-RADS. After a median follow-up of 9 months, 52 patients (7.2%, 6.7 events per 1000 person-year) experienced a MACE. In multivariable Cox regression models adjusted for age and sex, FFRCT <0.8 significantly predicted outcomes (HR 2.48 95% CI 1.26–4.87 p=0.008). Sensitivity analysis using lower thresholds of FFRCT failed to show similar results in intermediate stenosis.

Conclusion

Our results suggest that in a real-world cohort of patients with suspected CAD, FFRCT can identify patients at higher risk of incident cardiovascular outcomes.

Funding Acknowledgement

Type of funding sources: None.
Human hyperpolarized [1-13C] pyruvate CMR and adenosine stress test
Authors: Joergensen S H , Hansen E S S , Staehr P B , Laustsen C , Wiggers H
Published: October 2021

Background

Hyperpolarized (HP) [1-13C]pyruvate cardiac magnetic resonance (CMR) imaging can visualize myocardial perfusion and metabolism beyound glucose uptake. Depending on the prevailing metabolic conditions, buid-up of either [1-13C]lactate or 13C-bicarbonate can be measured. The aim of the present study was to assess cardiac metabolism using HP [1-13C]pyruvate rest-stress CMR.

Methods

Six healthy volunteers underwent cine CMR and HP [1-13C]pyruvate CMR at rest and during an adenosine stress test. Signal from HP [1-13C]pyruvate and its downstream metabolites was measured at the mid-left-ventricle (LV) level. We did semi-quantitative assessment of first-pass myocardial [1-13C]pyruvate perfusion. Pressure-volume loops were assessed non-invasively.

Results

Myocardial [1-13C]pyruvate perfusion was significantly increased during stress with a reduction in time-to-peak from 6.2±2.8 sec to 2.7±1.3 sec, p=0.04. This higher perfusion was accompanied by an overall increased myocardial uptake and metabolism. The conversion rate constant (kPL) for lactate increased from 0.011±0.009 sec–1 to 0.020±0.010 sec–1, p=0.04. The pyruvate oxidation (kPB) increased from 0.004±0.004 sec–1 to 0.012±0.007 sec–1, p=0.008. This increase in oxidative metabolism was positively correlated with heart rate (R2=0.44, p=0.02).

Conclusion

We observed a significant increase in carbohydrate oxidation during cardiac stress in the healthy human heart. The present study forms the basis for comparisons in future research in patients with heart failure and coronary artery disease. HP [1-13C]pyruvate CMR could be a possible alternative to PET in the future.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Danish Heart FoundationIndependent Research Fund, Denmark Increased conversion rate of pyruvateIncreased metabolite signal in LV
Left atrial remodeling and cerebrovascular disease assessed by magnetic resonance imaging in patients undergoing continuous heart rhythm monitoring
Authors: Bertelsen L , Diederichsen S Z , Frederiksen K S , Haugan K J , Brandes A , Graff C , Krieger D , Hoejberg S , Olesen M S , Biering-Soerensen T , Koeber L , Vejlstrup N , Hasselbalch S G , Svendsen J H
Published: October 2021

Background

Atrial remodeling and atrial fibrillation (AF) have both been associated with cerebrovascular lesions. We wished to investigate the possible direct association between atrial remodeling and cerebrovascular disease including white matter lesions and lacunar infarcts in patients with and without atrial fibrillation (AF) as documented by implantable loop recorder (ILR).

Methods

Cardiac and cerebral MRI scans were acquired in a cross-sectional study including participants ≥70 years of age with stroke risk factors (history of hypertension, diabetes mellitus, congestive heart failure and/or previous stroke) but without known AF. Cerebrovascular disease was visually rated using the Fazekas scale and number of lacunar strokes. Left atrial (LA) (see figure) and ventricular volumes and function were analyzed, and associations between atrial remodeling and cerebrovascular disease were assessed with logistic regression models. Multivariable models were adjusted for sex, age, diabetes, hypertension, heart failure and history of stroke/transient ischemic attack. The analyses were stratified according to sinus rhythm or any AF during three months of continuous ILR monitoring to account for subclinical AF.

Results

Of 200 participants investigated, 87% had a Fazekas score≥1 and 45% had ≥1 lacunar infarct. Within three months of ILR implantation, AF was detected in 28 (14%) participants, while 172 (86%) had sinus rhythm only. Results are summarized in table. For participants with sinus rhythm, lower LA passive emptying fraction was associated with Fazekas score after multivariable adjustment, while LA total emptying fraction was borderline significant, and increased LA maximum and minimum volumes were associated with lacunar infarcts. There were no significant associations in patients with AF.

Sensitivity analyses showed similar results with longer screening periods for AF.

Conclusions

In patients free from AF as documented by ILR monitoring, we found an independent association between LA passive emptying and Fazekas score, and between atrial volumes and lacunar infarcts. This supports that atrial remodeling alone without AF is associated with an increased risk of cerebrovascular lesions.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Innovation Fund, DenmarkThe Research Foundation for the Capital Region of Denmark
A systematic review of the use of magnetic resonance imaging in non-conditional pacemakers and implantable defibrillators
Authors: Murphy R , Kerley R K , Kearney P K
Published: October 2021

Background

Cardiac implantable electronic devices (CIEDs) were long considered a contraindication for magnetic resonance imaging (MRI). Modern devices are now MRI conditional, but still the majority of CIEDs in the population are legacy devices and are classified as unsafe for MRI. There is growing consensus that MRI is also safe in these patients.

Purpose

The purpose of this study was to perform an up to date systematic review of the evidence evaluating the use of MRI in patients with non-conditional CIEDs.

Methods

Searches of the PubMed, CINAHL and Embase databases were performed. Studies that assessed the rate of adverse outcomes after MRI in patients with non-conditional CIEDs were included. Studies were excluded if they did not disclose the conditionality of patients CIEDs. Case reports or case series were not included.

Results

36 cohort studies were identified. No patient in these studies died during or immediately after MRI.

Symptom associated with either torque or heating occurred in <1% of patients. Electrical resets occurred 1–2% of patients. There were no cases of non-conditional lead or generator failure. Inappropriate pacing occurred in <1% of patients. No ICD shocks occurred during MRI. Changes in CIED parameters occurred in 1–4% of patients.

Conclusions

This systematic review highlights the relative safety of the use of MRI in patients with non-conditional CIEDs. Demonstrated be the fact that no deaths or device shocks have been suffered as a consequence of MRI in any of these studies, and the extremely low incidence of device or lead related complications. Still strict selection and monitoring protocol should be used when imaging these patients.

Funding Acknowledgement

Type of funding sources: None.
The left ventricular remodeling assessment by cardiac magnetic resonance in chronic aortic regurgitation; implications for outcome
Authors: Hashimoto G , Sarano M , Sato H , Lopes B , Fukui M , Stanberry L , Cheng V , Garcia S , Goessl M , Sorajja P , Bapat V , Lesser J , Cavalcante J
Published: October 2021

Background

Chronic aortic regurgitation (AR) causes left ventricular (LV) volume overload resulting in progressive LV remodeling, which negatively affect clinical outcome. Clinical Guidelines recommend assessment of LV remodeling by echocardiography, but little is known about comparative remodeling quantification by cardiac magnetic resonance (CMR) and association with outcomes.

Purpose

To assess LV remodeling in AR by CMR, compared with echocardiographic measures and determine its impact on clinical outcome.

Methods

Patients with native, ≥moderate, chronic AR by echocardiography who underwent CMR exam within 90 days of diagnosis from January 2012 to February 2020 were enrolled. The endpoint was a composite of death, heart failure hospitalization, and heart failure symptom exacerbation during follow-up.

Results

The 178 patients included had median age (IQR) of 58 years (44–69), and most (88%, n=158) presented with no or minimal symptoms (NYHA class I/II). At diagnosis symptomatic vs. no/minimal symptoms patients presented with much more advanced LV remodeling by CMR (EDVI 133 [83–151] vs. 96 [80–123] p=0.024, ESVI 66 [46–85] vs. 42 [30–58], P=0.001) while echocardiography showed limited differences (EDVI 76 [57–93] vs. 65 [54–87] p=0.507, ESVI 38 [30–58] vs. 27 [20–42], p=0.072). During follow-up (3.3 years [1.6–5.8]), aortic valve replacement (AVR) was performed in 49 patients. In patients with no/minimal symptoms, the composite endpoint occurred in 54 (34%) patients including eight deaths and 30 heart failure hospitalizations. Patients with LV end-systolic volume index (LVESVi) >45 ml/m2 by CMR had higher likelihood for composite endpoint (Panel A) confirmed in multivariate models, adjusting for age, sex, AVR (time-dependent), EuroSCORE2, and LV End-systolic-dimension-index (LVESDi) >25 mm/2, with adjusted hazard ratio 1.84 [1.02–3.33], p<0.044 (Panel B). LVESVi by CMR was at least as powerful in determining clinical outcomes as guideline-recommended Doppler-Echocardiographic variables.

Conclusion

Assessment of LV remodeling by CMR in patients with clinically significant AR is feasible in routine clinical practice, detects with high sensitivity LV remodeling associated with development of HF symptoms and is independently predictive of clinical outcome. Hence, CMR provides a powerful tool for evaluation and risk stratification of patients with AR.

Funding Acknowledgement

Type of funding sources: None. Panel APanel B
Lifestyle intervention improves Left atrial strain in type 2 diabetes: results from the DIASTOLIC randomised trial
Authors: Alfuhied A , Gulsin G S , Brady E M , Parke K , Athithan L , Henson J , Redman E , Yates T , Davies M J , Marsh A M , McCann G P , Singh A
Published: October 2021

Introduction

Left atrial (LA) strain has been shown to be an independent predictor of cardiovascular events in many conditions and superior to conventional measures of LA function (LA volumes and emptying fraction). The effects of low-energy diet or exercise on cardiovascular function in younger adults with type 2 diabetes (DIASTOLIC) study has previously demonstrated an improvement in left ventricle peak early diastolic strain rate in response to aerobic exercise in patients with type-2 diabetes (T2D). However, the effect of lifestyle intervention on LA function, assessed by cardiac magnetic resonance (CMR) imaging, is unknown.

Methods

The DIASTOLIC study was a prospective, randomised, open-label, blind endpoint trial, that randomised 90 obese participants with T2D (aged 18–65 years) to a 12-week intervention of: (i) routine care, (ii) aerobic exercise training, or (iii) low energy (≈810kcal/day) meal replacement plan (MRP). CMR was performed at baseline and week-12. Images were analysed using Medis v3.1. LA strain (LAS) was assessed using Feature Tracking (QStrain v2.0), corresponding to LA reservoir (LAS-r), conduit (LAS-cd), and booster pump (LAS-bp) using 4- and 2-chamber standard steady-state free precession cine images, and average values calculated. LA emptying fraction (LAEF) was calculated using biplane area-length method (QMass v8.1) for total, passive and active EF.

Results

73 participants with T2D completed the trial and had analysable LA images (28 routine care, 22 exercise and 23 MRP). There was no significant change in CMR measured standard LA volumetric function (LAV/LAEF) and echocardiogram measured LV filling pressures (E/e') in any groups. The routine care arm showed no significant change in body mass index (BMI) or LAS (see Table). In the MRP group, there were significant reductions in BMI (4.8 kg/m2), mean systolic blood pressure (SBP) (13mmHg), and a significant increase in LAS-r and LAS-bp (29.9±7.0 to 32.3±7.0,p=0.036 and 14.6±5.3 to 17.2±3.7,p=0.034). The exercise arm showed a small reduction in BMI (0.8kg/m2), with no significant change in BP or LAS.

Conclusion

There was significant improvement in LAS post-lifestyle intervention in young adults with T2D, despite no change in volumetric measurements. MRP led to weight loss and improved SBP, with associated improved LA filling and contraction.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute for Health Research (NIHR) a career development fellowship.
Prognostic value of 99mTc-HMDP scintigraphy in elderly patients with chronic heart failure
Authors: Uusitalo V , Suomalainen O , Loimaala A , Matzke S , Helio T
Published: October 2021

Background

Bone scintigraphy is an accurate modality for diagnosis of transthyretin amyloidosis (ATTR).

Purpose

We evaluated the prevalence and prognostic significance of cardiac ATTR in elderly heart failure population.

Methods

Our retrospective study included 335 patients aged over 70 years with diagnosed heart failure who underwent 99mTc-hydroxymethylenediphosphonate (99mTc-HMDP) scintigraphy due to non-cardiac indications. A Perugini grade >2 and heart-to-contralateral ratio (H/CL) of >1.30 was considered positive for ATTR.

Results

There were a total of 234 deaths of which 70 were classified as cardiovascular during a median follow-up of 3±2 years. ATTR was diagnosed in 17 patients using H/CL ratio (5.1%). Patients with ATTR were older (85±5 vs. 80±5 years, p=0.002) and had higher N-terminal pro-brain natriuretic peptide (Nt-ProBNP) levels (6692±5694 vs. 3285±5233 ng/l, p=0.02). Age, presence of bone metastasis and GFR were independent predictors of overall mortality. Age, GFR, ≥grade 2 visual cardiac uptake and H/CL ratio were independent predictors of cardiovascular mortality.

Conclusions

ATTR was found in 5% of elderly patients with heart failure. The presence of cardiac uptake on bone scintigraphy did not convey independent prognostic value on overall mortality but was associated with cardiovascular mortality.

Funding Acknowledgement

Type of funding sources: None.
The effect of chronic total coronary occlusion percutaneous coronary intervention on absolute perfusion in remote myocardium
Authors: De Winter R W , Schumacher S P , Van Diemen P A , Jukema R A , Somsen Y B O , Stuijfzand W J , Bom M J , Everaars H , Van Rossum A C , Van De Ven P M , Verouden N J , Danad I , Raijmakers P G , Nap A , Knaapen P
Published: October 2021

Background

Successful revascularization of a chronic total coronary occlusion (CTO) impacts coronary physiology of the remote myocardial territory.

Purpose

This study evaluated the effect of CTO percutaneous coronary intervention (PCI) on changes in absolute perfusion in remote myocardium as assessed by serial [15O]H2O positron emission tomography (PET) perfusion imaging.

Methods

A total of 164 patients underwent [15O]H2O PET imaging at baseline and 3 months after successful single-vessel revascularization of a CTO to evaluate changes in hyperemic myocardial blood flow (hMBF) and coronary flow reserve (CFR) in the remote myocardial territory supplied by both non-target coronary arteries.

Results

Remote hMBF and CFR improved (2.29±0.67 to 2.48±0.75 mL min–1 g–1 and 2.48±0.76 to 2.74±0.85, respectively) after CTO revascularization (p<0.01 for both). Absolute perfusion indices in the CTO vessel and the remote myocardium showed a positive linear correlation, both before (r=0.75, p<0.01 and r=0.77, p<0.01 for hMBF and CFR, respectively) and after (hMBF: r=0.87, p<0.01 and CFR: r=0.81, p<0.01) CTO PCI. Absolute increases in remote myocardial perfusion were largest in patients with a higher increase in hMBF (βeta [β] 0.56; 95% CI: 0.47–0.65; p<0.01) and CFR (β 0.51 (0.42–0.60); p<0.01) in the CTO territory, independent of clinical, angiographic and procedural characteristics. Furthermore, baseline (hMBF: β −0.24 (−0.39, −0.08); p<0.01 and CFR: β −0.26 (−0.41, −0.11); p<0.01) and post-PCI perfusion (hMBF: β 0.36; (0.27, 0.46); p<0.01 and CFR: β 0.30 (0.21, 0.40); p<0.01) in the CTO vessel were independently associated with the increase in remote myocardial perfusion after CTO PCI.

Conclusions

An overall increase in remote myocardial perfusion was observed following CTO PCI. Absolute perfusion indices in the remote myocardium showed a positive linear correlation with perfusion in the CTO vessel, before and after CTO revascularization. Importantly, baseline, post-PCI and the absolute increase in perfusion in the CTO territory were independently associated with increases in remote myocardial perfusion after revascularization.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
The valve uptake index: a new measure in [18F]FDG PET/CT for the diagnosis of prosthetic valve endocarditis
Authors: Roque A , Pizzi M N , Fernandez-Hidalgo N , Romero-Farina G , Burcet G , Reyes J L , Cuellar-Calabria H , Aguade-Bruix S
Published: October 2021

Background

Diagnosis of PVE by PET/CTA is based on visual and quantitative evaluation of morpho-metabolic features. The FDG uptake pattern is a main diagnostic criterion, but can be visually unclear and susceptible to subjectivity. The valve uptake index (VUI) is a new measure designed to provide a more objective indication of the distribution of metabolic activity.

Purpose

To validate the diagnostic accuracy of the valve uptake index (VUI) (SUVmax-SUVmean)/SUVmax, in patients with suspicion of prosthetic valve endocarditis (PVE). To establish a cut-off value that allows diagnosis of infection. Finally, to determine the incremental value of adding the VUI to the classic parameters for the diagnostis of PVE by PET/CT.

Methods

Retrospective analysis of 122 patients, with a conclusive diagnosis of definite or rejected PVE and who had undergone a cardiac PET/CTA scan. We measured the VUI and recorded the SUVmax, SUVratio, uptake pattern and the presence of endocarditis-related anatomic lesions. The diagnostic accuracy of these parameters was calculated.

Results

The VUI values were 0.54±0.1 vs. 0.36±0.08 in the definite PVE group vs. the rejected group, respectively (mean±SD; p<0.001). A cut-off value of VUI>0.45 showed a sensitivity, specificity and diagnostic accuracy for PVE of 85%, 90.3% and 87.4%, and significantly increased diagnostic ability for confirming endocarditis when combined with the standard diagnostic criteria.

Conclusions

The VUI had good diagnostic accuracy for PVE. The diagnostic power of currently used morphometabolic parametersis significantly increased by the addition of the VUI. Integration of the VUI in the diagnostic algorithm may clarify doubtful cases, and improve the diagnostic yield of PET/CTA.

Funding Acknowledgement

Type of funding sources: None.
Mechanistic insights from a multiparametric magnetic resonance imaging study regarding the role of sodium glucose co-transporter 2 inhibitors
Authors: Thirunavukarasu S , Jex N , Chowdhary A , Hassan I , Straw S , Broadbent D , Swoboda P , Witte K K , Cubbon R , Xue H , Kellman P , Greenwood J P , Plein S , Levelt E
Published: October 2021

Background

Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF) and cardiovascular (CV) mortality. Sodium–glucose-co transporter-2 (SGLT2) inhibitors reduce the risk of major adverse CV events and hospitalisation for HF in T2D patients with high cardiovascular risk, despite only a modest improvement in glycemic control. Restoring cellular energy homeostasis and reversing adverse cardiac remodelling in diabetes have been speculated as a potential metabolic modulatory effect of SGLT2 inhibitors leading to their beneficial CV outcomes. Myocardial energy deficient states can be detected non-invasively by 31-phosphorus magnetic resonance spectroscopy (31P-MRS).

Objectives

Utilising cardiovascular magnetic resonance imaging (CMR) and 31P-MRS in a single centre longitudinal cohort study, we aimed to investigate the effects of the selective SGLT2 inhibitor empagliflozin on myocardial energetics, function, perfusion, and myocardial cellular volume in patients with T2D.

Methods

Eighteen consecutive T2D patients who were commenced on empagliflozin in cardiometabolic optimisation clinics underwent CMR and 31P-MRS scans before and after twelve-week empagliflozin treatment, and plasma N-terminal pro hormone B-type natriuretic peptide (NT-proBNP) levels were measured. Ten controls with no diabetes underwent an identical 31P-MRS and CMR protocol on a single visit.

Results

When compared to controls, patients with T2D showed: lower myocardial energetics (1.52±0.40 vs 2.20±0.5, p=0.0005), lower stress myocardial blood flow (1.60±0.50 vs 2.10±0.50, p=0.02) and lower left ventricular ejection fraction (52±13% vs 63±4%, p=0.01). Treatment with empagliflozin led to significant improvements in myocardial energetics (PCr/ATP: 1.52 to 1.76, p=0.009). This was accompanied by a relative 13% improvement in left ventricular ejection fraction (p=0.001), 3% improvement in global longitudinal strain (p=0.01), 61% reduction in NTproBNP (p=0.05), and 9% reduction in myocardial cell volume (p=0.04). No significant change in myocardial blood flow or diastolic strain was detected.

Conclusions

For the first time, we demonstrate that empagliflizon improves myocardial energetics and function, reduces myocardial cellular volume, and reduces NT-proBNP levels in patients with T2D.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation PCr/ATPLVEF
Derivation and validation of myocardial bridge characteristics by optical coherence tomography: a prospective multimodality imaging study
Authors: Otsuka T , Ueki Y , Losdat S , Baer S , Raeber L
Published: October 2021

Background

Optical coherence tomography (OCT) findings of myocardial bridge (MB) have not been established.

Purpose

We aimed to establish the OCT appearance of MB compared with the half-moon sign derived by intravascular ultrasound (IVUS) and to assess the prevalence among patients undergoing coronary angiography and OCT in clinical practice.

Methods

For derivation of the OCT appearance of MB, imaging data obtained from 122 patients undergoing OCT and IVUS for the left anterior descending artery (LAD) enrolled in two prospective imaging studies were analyzed. To assess the prevalence of OCT-derived MB, 470 patients undergoing OCT for LAD in clinical routine were analyzed.

Results

We found a homogeneous band with intermediate light intensity surrounding the vessel wall as assessed by OCT corresponding to half-moon sign derived by IVUS. Mean length, angle, and thickness of OCT-MB were 21.2±10.8mm, 205.7±56.5°, and 0.39±0.06mm, respectively. Mean length of IVUS-MB was significantly longer as compared with OCT-MB (23.7±11.9, P=0.010), while there were no significant differences in angle and thickness. MB angle was >180° in approximately 50% of frames with MB. There was a strong/moderate correlation between OCT-MB and half-moon sign (MB length: r=0.81, P=0.001, MB angle: r=0.58, P=0.001). In the derivation cohort, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of OCT-MB for the milking effect by angiography were 96.3%, 62.1%, 41.9%, 98.3%, and 69.7%, respectively, and much comparable with the IVUS half-moon sign. In the validation cohort, OCT-detected MB was observed in 139 (29.6%) patients, of whom 57.6% (n=80) did not have angiographic evidence of milking effect.

Conclusion

OCT is able to identify IVUS-defined MB as homogenous band with intermediate light intensity surrounding the vessel wall. There was a high concordance in terms of MB angle and thickness between OCT and IVUS. In clinically-indicated OCT cases of the LAD, more than half of OCT-MBs were angiographically silent. OCT assessment of MB may facilitate the accurate diagnosis of MB and thus provide useful information in determining the subsequent treatment strategy for the patients with MB.

Funding Acknowledgement

Type of funding sources: None. Representative imaging of MBCase of OCT-MB without milking effect
Hypolipidemia associated with inactivation of TM6SF2 is due to decreased VLDL-lipids secretion
Authors: Luo F , Smagris E , Fletcher J A , Cohen J C , Hobbs H H
Published: October 2021

Background

A missense variant in Transmembrane 6 Superfamily Member 2 [TM6SF2 (E167K)] is associated with reduced plasma lipid levels and protection from coronary atherosclerosis. The substitution of lysine for glutamate at residue 167 is associated with a marked decrease in TM6SF2 protein expression, consistent with a loss-of-function mutation. However the biological role of TM6SF2 is not known, and the mechanism(s) responsible for the hypolipidemia associated with mutation gene has not been fully defined. To elucidate the pathological mechanism for the hypolipidemia associated with TM6SF2 deficiency, we inactivated Tm6sf2 in mice and rats.

Methods

Tm6sf2−/− mice were generated as described previously. Two lines of Tm6sf2−/− rats with different frameshift mutations in exon 1 were generated using CRISPR/Cas9 technology. Primary hepatocytes were isolated from WT and Tm6sf2−/− mice for microscopy. Rats were fasted 16 or 4 hours and tissues were collected on ice for cell fractionation, and in liquid nitrogen for biochemical analyses. Frozen samples were stored at −80°C for subsequent analyses.

Result

In both mice and rats, inactivation of Tm6sf2 recapitulated the phenotype of humans with the E167K substitution: steatosis, reduced plasma lipid levels, and transaminitis. The phenotype was readily apparent in animals fed chow diets. Both species had reduced secretion of VLDL-TG, as determined by TRITON WR1399 injection, with no decrease in secretion of ApoB. Experiments in isolated perfused livers from WT and Tm6sf2−/− mice confirmed that the decreased TG secretion observed in intact animals reflected reduced TG secretion from the liver. Lipidomic analysis of the liver perfusates by by LC-MS indicated that secretion of cholesteryl esters, and phospholipids was also decreased in the KO animals. Taken together, these findings are consistent with a role for TM6SF2 in lipidation of ApoB-containing lipoproteins. To further elucidate the function of TM6SF2, we used fluorescence microscopy and cell fractionation to determine the subcellular localization of the protein. Microscopic analysis showed that TM6SF2 co-localized with ER and Golgi markers, but cell fractionation studies indicated that the protein is located primarily in the smooth ER. The ratio of TG to ApoB was lower in Golgi fractions from TM6sf2−/− rats than in corresponding fractions from WT animals.

Conclusions

Since the sequela of TM6SF2 inactivation are already apparent in the Golgi, we speculate that TM6SF2 promotes lipidation of VLDL in a pre-Golgi compartment. We are currently performing additional studies to further define the specific mechanism whereby TM6SF2 promotes lipidation of ApoB-containing lipoproteins.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): National Institutes of Health
NADPH oxidase 4 has a crucial impact on the microcirculation of hypercholesteremic LDL receptor deficient mice
Authors: Diaba-Nuhoho P , Shahid A , Brunssen C , Morawietz H , Brendel H
Published: October 2021

Introduction

NADPH oxidase (NOX) 4-generated H2O2 has anti-atherosclerotic properties in conduit arteries like the aorta and carotids. However, the role of NOX4 on vascular function of small resistance arteries and blood pressure in a mouse model of familial hypercholesterolemia is unknown.

Purpose

We evaluated whether NOX4-generated H2O2 might play a role in perivascular adipose tissue of the thoracic aorta (tPVAT) and small resistance arteries on vascular function in a mouse model of familial hypercholesterolemia.

Methods

Aortic segments and mesenteric arteries from 26-week-old Ldlr−/− and Nox4−/− / Ldlr−/− mice were analysed by Mulvany myograph. In addition, vascular contraction and relaxation was analysed in the presence of L-NAME and catalase. Analysis of mRNA expression was performed in murine and human tissue by quantitative real-time PCR. Blood pressure was detected by tail cuff method in conscious, trained mice.

Results

Loss of NOX4 led to severe endothelial dysfunction in mesenteric arteries of Ldlr−/− mice. Blocking of NO synthases with L-NAME led to decreased endothelial relaxation in Ldlr−/− mice at the level of Nox4−/− / Ldlr−/− mice. However, incubation with L-NAME did not worsen the established endothelial dysfunction of the mesenteric arteries from Nox4−/− / Ldlr−/− mice. These results are strikingly different from the aorta, where inhibition of NO synthases led to a similarly impaired endothelial relaxation in both mouse strains. We detected a similar eNOS expression in the aorta of Ldlr−/− and Nox4−/− / Ldlr−/−, but a reduced eNOS expression in the mesenteric arteries of Nox4−/− / Ldlr−/− mice. H2O2 can induce eNOS expression. Therefore, we analysed the vascular function after catalase incubation and again found a significant reduction of endothelial function in the mesenteric arteries of Ldlr−/− mice. Finally, we analysed blood pressure of these mice and did not observe differences in systolic blood pressure, despite significant differences in endothelial function of resistant arteries.

Conclusion

NOX4 protects against severe endothelial dysfunction in the mesenteric artery in a model of hypercholesterolemia.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Ghanaian-German postgraduate training scholarship program (DAAD)
Resveratrol regulates cytokine secretion by cardiac microvascular endothelium under hypoxia/reoxygenation condition
Authors: Cui H , Yang Y J , Zong W J
Published: October 2021

Background

Microvascular endothelial injury is recently considered playing an initial role in myocardial ischemia/reperfusion injury (MIRI). Cardiac microvascular endothelial cells (CMECs) regulate cardiomyocytes and haematocytes via secreting cytokine. MIRI jeopardize not only the barrier function but also the paracrine function of microvasculature. Resveratrol, a natural polyphenolic compound, was demonstrated to protect myocardium against MIRI and to preserve the function of endothelium. However, how the paracrine function of CMECs is regulated by MIRI and resveratrol remains to be elucidated.

Purpose

The study was to illuminate the alteration of cytokine profiles secreted by CMECs under hypoxia/reoxygenation (H/R) condition and its modulation by resveratrol.

Methods

CMECs were exposed to different concentrations of resveratrol for 30 minutes and then were subjected to H/R for 12 h/2 h. Apoptotic rates were measured to determine the optimal concentration. Protein antibody arrays were performed to find the alteration of cytokine secreted into conditioned medium by CMECs. A Gene Ontology (GO) analysis was applied to interpret the functional implication of changes in cytokine profiles.

Results

Resveratrol inhibited apoptosis of CMECs in a dose-dependent manner after H/R and reached its peak effect at the concentration of 100μM, which reduced apoptosis from 27.27±2.95% to 15.01±1.36% (Figure 1A and B). The results of a cluster analysis and all significantly altered factors are shown in figure 1C (fold-change >1.5; p<0.05). Twenty-nine types of cytokine were significantly changed by H/R (15 factors decreased and 14 increased, Figure 2A), and resveratrol at 100μM changed 98 types of cytokine compared with the H/R group (93 factors decreased and 5 increased, Figure 2B). Among these cytokine, eight factors were increased by H/R and they were decreased by resveratrol. Eleven were attenuated by H/R and further decreased by resveratrol. Insulin-like growth factor binding protein-1 was up-regulated by H/R and it was further increased by resveratrol (Figure 2C). The factors with significant alteration were involved in cellular growth, proliferation and differentiation, as well as chemotaxis and transport.

Conclusions

Resveratrol inhibited the apoptosis of CMECs and modulated the paracrine function of cardiac microvascular endothelium under ischemia/reperfusion condition.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Natural Science Foundation Figure 1Figure 2
Progression markers of coronary calcification
Authors: Sedykh D Y U , Barbarash O L , Kashtalap V V , Hhryachkova O N , Kokov A N , Shibanova I A
Published: October 2021

Aim

To evaluate the relationship between clinical parameters, biomarkers of bone turnover and the progression of coronary artery calcification (CAC) in patients with stable coronary heart disease (CHD) based on long-term (5 years) follow-up.

Material and methods

The single-center, prospective, non-randomized observational study included 111 men with CHD, admitted for CABG. All patients in the preoperative period underwent the following procedures: color duplex scanning (CDS) of the brachiocephalic arteries (BCA), multi-slice computed tomography (MSCT) coronary angiography to assess the degree of CAC using the Agatson score (calculation of the coronary artery calcium score – CACS), estimation of femoral neck bone mineral density with the T-score calculation and clinical assessment of biomarkers of bone metabolism (calcium, phosphorus, calcitonin, osteopontin, osteocalcin, osteoprotegerin (OPG), alkaline phosphatase, parathyroid hormone). The vital status of patients was ascertained after 3–5 years of follow-up after CABG, CDS of the BCA and MSCT-coronary angiography were repeated. To identify the most significant clinical and anamnestic risk factors and form a model of predictors of CAC progression, patients were divided into two groups depending on the high increase in CACS (an increase in the score of more than 100 Agatston units (AU).

Results

16 (14.4%) out of 111 patients failed to establish contact for the next stage of the study. In 4 (3.6%) cases death was registered (3 – fatal myocardial infarction, 1 – fatal stroke). The CAC progression was assessed in 91 patients (81.9%). Patients who showed signs of CAC progression comprised a group of 60 (65.9%) patients; without CAC progression – 31 (34.1%) patients. The “end points” in the groups were comparable and were detected in 18 cases (19.7%): recurrent angina in 16 patients (p=0.368), non-fatal myocardial infarction in 1 (p=0.162) and 1 emergency stenting (p=0,162) of the coronary artery that was not subjected to CABG. The risk model for CAC progression included an initial decrease in femoral neck bone mineral density and nonadherence to statins for 5 years after CABG (p=0.001).

Conclusion

65.9% of men with stable CHD showed the signs of CAC progression for 5 years after CABG, according to MSCT. The main predictors of CAC were: low cathepsin K levels and low bone mineral density in the preoperative period, low OPG 5 years post-CABG.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Federal State Budgetary Institution “Research Institute for Complex Issues of Cardiovascular Diseases”; 6, Sosnovy Blvd, Kemerovo, 650002, Russia