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Background: Cardiac involvement in idiopathic inflammatory myopathy (IIM or “myositis”) is associated with an approximate 4% mortality, but standardised screening strategies are lacking. Objective: We explored a multimodality screening on potentially reversible cardiac involvement –i.e. active (peri)myocarditis –in newly diagnosed IIM. Methods: We included adult IIM patients from 2017 to 2020. At time of diagnosis, patients underwent cardiac evaluation including laboratory biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging (CMR). Based on 2019 consensus criteria for myocarditis, an adjudication committee made diagnoses of definite, probable, possible or no (peri)myocarditis. We explored diagnostic values of sequentially added diagnostic modalities by Constructing Classification and Regression Tree (CART) analysis in patients with definite/probable versus no (peri)myocarditis. Results: We included 34 IIM patients, in whom diagnoses of definite (six, 18%), probable (two, 6%), possible (11, 32%), or no (peri)myocarditis (15, 44%) were adjudicated. CART-analysis showed high-sensitivity cardiac troponin T (cut-off value 2.9 xULN for females and > 1.8 xULN for males) ruled in (peri)myocarditis with a specificity of 100%. Applying high-sensitivity cardiac troponins with these cut-off values in a diagnostic algorithm without and with a CMR to the total population of 34 patients demonstrated a diagnostic accuracy for a clear diagnosis of probable/definite or no (peri)myocarditis of 59% and 68%, respectively. Conclusions: A diagnostic algorithm for detection of (peri)myocarditis in adult IIM may consist of sequential testing with high-sensitivity cardiac troponins and CMR.

OBJECTIVE: To systematically investigate and document the infrastructure, practices, recommendations, and clinical consequences of a structured, organized sports cardiology multidisciplinary team (MDT) for athletes and patients who wish to engage in sports and exercise. PATIENTS AND METHODS: We established bimonthly sports cardiology MDT meetings, with a permanent panel of experts in sports cardiology, genetics, pediatric cardiology, cardiovascular imaging, electrophysiology, and sports and exercise medicine. Cases were referred nationally or internationally by cardiologists/sports physicians. We retrospectively analyzed all MDT cases (April 10, 2019 through May 13, 2020) and collected clinical follow-up data up to 1 year after the initial review. RESULTS: A total of 115 athletes underwent MDT review; of them, 11% were women, 65% were recreational athletes, and 54% were performing "mixed" type of sports; the mean age was 32±16 years. An MDT review led to a diagnosis revision of "suspected cardiac pathology" to "no cardiac pathology" in 38% of the athletes and increased the number of definitive diagnoses (from 77 to 109; P=.03). We observed fewer "total sports restrictions" (from 6 to 0; P=.04) and more tailored sports advice concerning "no peak load/specific maximum load" (from 10 to 26; P=.02). At the 14±6-month follow-up, 112 (97%) athletes reported no cardiovascular events, 111 (97%) athletes reported no (new) cardiac symptoms, 113 (98%) athletes reported adherence to the MDT sports advice, and no diagnoses were revised. CONCLUSION: Our experiences with a comprehensive sports cardiology MDT demonstrate that this approach leads to higher percentages of definitive diagnoses and fewer cardiac pathology diagnoses, more tailored sports advice with excellent rates of adherence, and fewer total sports restrictions. Our findings highlight the added value of sports cardiology MDTs for patient and athlete care.

Aim Lipoprotein(a) [Lp(a)] is a potential causal factor in the pathogenesis of aortic valve disease. However, the relationship of Lp(a) with new onset and progression of aortic valve calcium (AVC) has not been studied. The purpose of the study was to assess whether high serum levels of Lp(a) are associated with AVC incidence and progression. Methods and results A total of 922 individuals from the population-based Rotterdam Study (mean age 66.0±4.2 years, 47.7% men), whose Lp(a) measurements were available, underwent non-enhanced cardiac computed tomography imaging at baseline and after a median follow-up of 14.0 [interquartile range (IQR) 13.9–14.2] years. New-onset AVC was defined as an AVC score >0 on the follow-up scan in the absence of AVC on the first scan. Progression was defined as the absolute difference in AVC score between the baseline and follow-up scan. Logistic and linear regression analyses were performed to evaluate the relationship of Lp(a) with baseline, new onset, and progression of AVC. All analyses were corrected for age, sex, body mass index, smoking, hypertension, dyslipidaemia, and creatinine. AVC progression was analysed conditional on baseline AVC score expressed as restricted cubic splines. Of the 702 individuals without AVC at baseline, 415 (59.1%) developed new-onset AVC on the follow-up scan. In those with baseline AVC, median annual progression was 13.5 (IQR = 5.2–37.8) Agatston units (AU). Lipoprotein(a) concentration was independently associated with baseline AVC [odds ratio (OR) 1.43 for each 50 mg/dL higher Lp(a); 95% confidence interval (CI) 1.15–1.79] and new-onset AVC (OR 1.30 for each 50 mg/dL higher Lp(a); 95% CI 1.02–1.65), but not with AVC progression (β: −71 AU for each 50 mg/dL higher Lp(a); 95% CI −117; 35). Only baseline AVC score was significantly associated with AVC progression (P < 0.001). Conclusion In the population-based Rotterdam Study, Lp(a) is robustly associated with baseline and new-onset AVC but not with AVC progression, suggesting that Lp(a)-lowering interventions may be most effective in pre-calcific stages of aortic valve disease.

Funder: Dutch Kidney Foundation, AIMS: A potassium replete diet is associated with lower blood pressure (BP) and lower risk of cardiovascular disease (CVD). Whether these associations differ between men and women and whether they depend on daily sodium intake is unknown. METHODS AND RESULTS: An analysis was performed in 11 267 men and 13 696 women from the EPIC-Norfolk cohort. Twenty-four hour excretion of sodium and potassium, reflecting intake, was estimated from sodium and potassium concentration in spot urine samples using the Kawasaki formula. Linear and Cox regression were used to explore the association between potassium intake, systolic BP (SBP), and CVD events (defined as hospitalization or death due to CVD). After adjustment for confounders, interaction by sex was found for the association between potassium intake and SBP (P < 0.001). In women, but not in men, the inverse slope between potassium intake and SBP was steeper in those within the highest tertile of sodium intake compared with those within the lowest tertile of sodium intake (P < 0.001 for interaction by sodium intake). Both in men and women, higher potassium intake was associated with a lower risk of CVD events, but the hazard ratio (HR) associated with higher potassium intake was lower in women than in men [highest vs. lowest potassium intake tertile: men: HR 0.93, 95% confidence interval (CI) 0.87-1.00; women: HR 0.89, 95% CI 0.83-0.95, P = 0.033 for interaction by sex]. CONCLUSION: The association between potassium intake, SBP, and CVD events is sex specific. The data suggest that women with a high sodium intake in particular benefit most from a higher potassium intake with regard to SBP.

Background and ObjectivesGuidelines recommend echocardiography to screen for structural sources of cardioembolism in patients with ischemic stroke. Cardiac CT is a promising alternative as a first-line screening method. We aimed to determine whether cardiac CT, acquired during the initial stroke imaging protocol, has a higher yield for detecting high-risk cardioaortic sources of embolism than transthoracic echocardiography (TTE).MethodsWe performed a prospective, single-center, observational cohort study and included consecutive adult patients with acute ischemic stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent the routine stroke workup, including TTE. The main outcome was the proportion of patients with a predefined high-risk cardioaortic source of embolism on cardiac CT vs TTE in patients undergoing both investigations.ResultsBetween May 2018 and November 2020, 774 patients with a suspected ischemic stroke underwent hyperacute cardiac CT. We excluded 228 patients with a diagnosis other than ischemic stroke and 94 because they did not provide informed consent. Therefore, 452 patients (59.3% male, median age 72) were included. The median additional scan time of cardiac CT was 6 (interquartile range 5–7) minutes with poor scan quality in only 3%. In total, 350 of the 452 patients (77.4%) underwent TTE, 99 of whom were performed in an outpatient setting. Reasons for not undergoing TTE were death (33, 7.3%) and TTE being too burdensome to perform in the outpatient setting (69, 15.3%). A high-risk cardioaortic source of embolism was detected in 40 of the 350 patients (11.4%) on CT, compared with 17 of the 350 (4.9%) on TTE (odds ratio 5.60, 95% CI 2.28–16.33). Cardiac thrombus was the most frequent finding (7.1% vs 0.6%). The diagnostic yield of cardiac CT in the full study population was 55 of the 452 (12.2%). Among the 175 patients with cryptogenic stroke after the routine workup, cardiac CT identified a cause of the stroke in 11 (6.3%).DiscussionCardiac CT acquired in the acute phase of ischemic stroke is technically feasible and has a superior diagnostic yield compared with TTE for the detection of high-risk sources of embolism. Cardiac CT may be considered as an alternative to TTE to screen for cardioembolism.

Candida infective endocarditis is a rare but serious entity that often requires aggressive treatment. However, treatment can be challenging in patients infected with drug-resistant fungi and/or with substantial comorbidity. Moreover, recommendations in treatment guidelines for these patients are based on limited clinical data due to their rarity. Here we report a case of Nakaseomyces glabrata (Candida glabrata) prosthetic valve endocarditis in a patient with congenital heart disease. This case illustrates a therapeutic dilemma for Nakaseomyces glabrata prosthetic valve endocarditis and the need for novel antifungal drugs and further clinical studies.

Aims Elevated lipoprotein(a) [Lp(a)] levels are associated with the risk of coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Observational studies revealed that Lp(a) and C-reactive protein (CRP) levels, a biomarker of systemic inflammation, may jointly predict CAD risk. Whether Lp(a) and CRP levels also jointly predict CAVS incidence and progression is unknown. Methods and results We investigated the association of Lp(a) with CAVS according to CRP levels in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study (n = 18 226, 406 incident cases) and the UK Biobank (n = 438 260, 4582 incident cases), as well as in the ASTRONOMER study (n = 220), which assessed the haemodynamic progression rate of pre-existing mild-to-moderate aortic stenosis. In EPIC-Norfolk, in comparison to individuals with low Lp(a) levels (50 mg/dL) and low CRP levels (50 mg/dL) and elevated CRP levels (>2.0 mg/L) had a higher CAVS risk [hazard ratio (HR) = 1.86 (95% confidence intervals, 1.30–2.67) and 2.08 (1.44–2.99), respectively]. A comparable predictive value of Lp(a) in patients with vs. without elevated CRP levels was also noted in the UK Biobank. In ASTRONOMER, CAVS progression was comparable in patients with elevated Lp(a) levels with or without elevated CRP levels. Conclusion Lp(a) predicts the incidence and possibly progression of CAVS regardless of plasma CRP levels. Lowering Lp(a) levels may warrant further investigation in the prevention and treatment of CAVS, regardless of systemic inflammation.

Objective Quantitative extracellular volume fraction (ECV) mapping with MRI is commonly used to investigate in vivo diffuse myocardial fibrosis. This study aimed to validate ECV measurements against ex vivo histology of myocardial tissue samples from patients with aortic valve stenosis or hypertrophic cardiomyopathy. Materials and methods Sixteen patients underwent MRI examination at 3 T to acquire native T1 maps and post-contrast T1 maps after gadobutrol administration, from which hematocrit-corrected ECV maps were estimated. Intra-operatively obtained myocardial tissue samples from the same patients were stained with picrosirius red for quantitative histology of myocardial interstitial fibrosis. Correlations between in vivo ECV and ex vivo myocardial collagen content were evaluated with regression analyses. Results Septal ECV was 30.3% ± 4.6% and correlated strongly (n = 16, r = 0.70; p = 0.003) with myocardial collagen content. Myocardial native T1 values (1206 ± 36 ms) did not correlate with septal ECV (r = 0.41; p = 0.111) or with myocardial collagen content (r = 0.32; p = 0.227). Discussion We compared myocardial ECV mapping at 3 T against ex vivo histology of myocardial collagen content, adding evidence to the notion that ECV mapping is a surrogate marker for in vivo diffuse myocardial fibrosis.

This commentary refers to ‘Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification’, by Y. Kaiser et al., https://doi.org/10.1093/eurheartj/ ehac377 and the discussion piece ‘Lipoprotein(a) and progression of aortic valve calcification: a case of collider bias?’, by M. G. Levin and S. M. Damrauer, https://doi.org/10.1093/ eurheartj/ehac638.

IntroductionThe cardiovascular benefits of physical exercise are well-known. However, vigorous exercise has also been associated with adverse cardiac effects. To improve our understanding of cardiovascular adaptation to exercise versus maladaptation and pathology, the limits of adaptation should be firmly established using state-of-the-art diagnostic modalities. We therefore initiated the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise (ELITE) cohort to investigate the longitudinal (beneficial and pathological) cardiovascular effects of intensive elite sports and exercise.Methods and analysisELITE is a prospective, multicentre, longitudinal cohort study. Elite athletes, from the age of sixteen, are recruited in The Netherlands. The primary objective is to determine the association between elite sports and exercise-induced cardiac remodelling, cardiac pathology, and health benefits over time. Secondary objectives include determining and identifying genetic profiles of elite athletes, and how these are associated with cardiac indices. ELITE will collect data from consultations, electrocardiography, echocardiography and cardiac magnetic resonance imaging, and training- and injury data. ELITE will also collect blood for biobanking and cardiogenetics. Follow-up will take place at intervals of two to five years, and after the elite athletes’ professional careers have ended. In addition, a subcohort of ELITE has been established to investigate cardiac sequelae following infections associated with myocardial involvement, including SARS-CoV-2. ELITE is a prospective observational study; therefore, analyses will be primarily explorative.Ethics and disseminationThis study has been approved by the Medical Ethics Review Board of the Amsterdam University Medical Centers (NL71682.018.19). The results of the study will be disseminated by publication in peer-reviewed journals (Netherlands Trial Register number: NL9328).

Background A new 72-channel receive array coil and sensitivity encoding, compressed (C-SENSE) and noncompressed (SENSE), were investigated to decrease the number of breath-holds (BHs) for cardiac magnetic resonance (CMR). Methods Three-T CMRs were performed using the 72-channel coil with SENSE-2/4/6 and C-SENSE-2/4/6 accelerated short-axis cine two-dimensional balanced steady-state free precession sequences. A 16-channel coil with SENSE-2 served as reference. Ten healthy subjects were included. BH-time was kept under 15 s. Data were compared in terms of image quality, biventricular function, number of BHs, and scan times. Results BHs decreased from 7 with C-SENSE-2 (scan time 70 s, 2 slices/BH) to 3 with C-SENSE-4 (scan time 42 s, 4–5 slices/BH) and 2 with C-SENSE-6 (scan time 28 s, 7 slices/BH). Compared to reference, image sharpness was similar for SENSE-2/4/6, slightly inferior for C-SENSE-2/4/6. Blood-to-myocardium contrast was unaffected. C-SENSE-4/6 was given lower qualitative median scores, but images were considered diagnostically adequate to excellent, with C-SENSE-6 suboptimal. Biventricular end-diastolic (EDV), end-systolic (ESV) and stroke volumes, ejection fractions (EF), cardiac outputs, and left ventricle (LV)-mass were similar for SENSE-2/4/6 with no systematic bias and clinically appropriate limits of agreements. C-SENSE slightly underestimated LV-EDV (-6.38 ± 6.0 mL, p < 0.047), LV-ESV (-7.94 ± 6.0 mL, p < 0.030) and overestimated LV-EF (3.16 ± 3.10%; p < 0.047) with C-SENSE-4. Bland-Altman analyses revealed minor systematic biases in these variables with C-SENSE-2/4/6 and for LV-mass with C-SENSE-6. Conclusions Using the 72-channel coil, short-axis CMR for quantifying biventricular function was feasible in two BHs where SENSE slightly outperformed C-SENSE.

ObjectivesTo investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC.MethodsWe included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC.ResultsThe prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase).ConclusionsLp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis.

BACKGROUND: Sudden cardiac death (SCD) is the main preventable cause of death in patients with adult congenital heart disease (ACHD). Since robust risk stratification methods are lacking, we developed a risk score model to predict SCD in patients with ACHD: the PRospEctiVE study on implaNTable cardIOverter defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease (PREVENTION-ACHD) risk score model. OBJECTIVE: The purpose of this study was to prospectively study predicted SCD risk using the PREVENTION-ACHD risk score model and actual SCD and sustained ventricular tachycardia/ventricular fibrillation (VT/VF) rates in patients with ACHD. METHODS: The PREVENTION-ACHD risk score model assigns 1 point each to coronary artery disease, New York Heart Association class II/III heart failure, supraventricular tachycardia, systemic ejection fraction < 40%, subpulmonary ejection fraction < 40%, QRS duration ≥ 120 ms, and QT dispersion ≥ 70 ms. SCD risk was calculated for each patient. An annual predicted risk of ≥3% constituted high risk. The primary outcome was SCD or VT/VF after 2 years. The secondary outcome was SCD. RESULTS: The study included 783 consecutive patients with ACHD (n=239 (31%) left-sided lesions; n=138 (18%) tetralogy of Fallot; n=108 (14%) closed atrial septal defect; median age 36 years; interquartile range 28-47 years; n=401 (51%) men). The PREVENTION-ACHD risk score model identified 58 high-risk patients. Eight patients (4 at high risk) experienced the primary outcome. The Kaplan-Meier estimates were 7% (95% confidence interval [CI] 0.1%-13.3%) in the high-risk group and 0.6% (95% CI 0.0%-1.1%) in the low-risk group (hazard ratio 12.5; 95% CI 3.1-50.9; P < .001). The risk score model's sensitivity was 0.5 and specificity 0.93, resulting in a C-statistic of 0.75 (95% CI 0.57-0.90). The hazard ratio for SCD was 12.4 (95% CI 1.8-88.1) (P = .01); the sensitivity and specificity were 0.5 and 0.92, and the C-statistic was 0.81 (95% CI 0.67-0.95). CONCLUSION: The PREVENTION-ACHD risk score model provides greater accuracy in SCD or VT/VF risk stratification as compared with current guideline indications and identifies patients with ACHD who may benefit from preventive implantable cardioverter-defibrillator implantation. ispartof: HEART RHYTHM vol:18 issue:5 pages:785-792 ispartof: location:United States status: published

Background: Higher anticholinergic burden from medications is associated with increased risk of cardiovascular disease and cognitive function decline. A mechanistic pathway has never been established. We aimed to determine whether chronic inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). The anticholinergic cognitive burden score (ACB) was calculated at baseline/first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Plasma fibrinogen and C-reactive protein (CRP) were measured during 1HC and Tumour Necrosis Factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for 1HC and 2HC, respectively. The prospective association was also examined between 1HC ACB and 2HC inflammatory markers. All models adjusted for age, sex, lifestyle factors, co-morbidities and medications. Results: 17,678 and 22,051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. A total of 5,101 participants with available data for TNF-α and IL-6 were included in the longitudinal analyses. Cross-sectionally, a point increase in the ACB was associated with a significant increase in all inflammatory markers (beta (standard error): fibrinogen – 0.035g/l (0.006), pConclusion: Higher anticholinergic burden was significantly associated with higher inflammatory markers. Inflammation may mediate the relationship between exposure to anticholinergic medications and adverse outcomes

Background Experimental studies show that high‐sodium intake affects the innate immune system, among others with increased circulating granulocytes. Whether this relationship exists on a population level and whether this relates to disease outcomes is unclear. We aimed to test the hypotheses that (1) sodium intake is associated with granulocytes on a population level; (2) granulocytes are associated with the presence of hypertension and both cardiovascular and renal outcomes; and (3) the relation between high‐sodium intake and these outcomes is mediated by granulocytes. Methods and Results We performed an analysis in 13 804 participants from the prospective EPIC (European Prospective Investigation into Cancer)‐Norfolk cohort, with a mean age of 58 years and median follow‐up of 19.3 years. Analyses were carried out using calculated estimated sodium intake and sodium‐to‐potassium ratios from spot urines at baseline. The main outcomes were hypertension at baseline, and composite cardiovascular (mortality or cardiovascular events) and renal (mortality or renal events) outcomes during follow‐up. Sodium intake and urine sodium‐to‐potassium ratio were positively associated with circulating granulocyte concentrations after adjustment for confounders (β=0.03; P =0.028 and β=0.06; P Conclusions Sodium intake is positively associated with circulating granulocyte concentrations, and higher granulocyte concentrations associate with worse long‐term cardiovascular and renal outcomes. Given the recently established immune‐modulating effects of sodium and the role of immune cells in both cardiovascular and renal disease, causality for this pathway may need consideration in further studies.

Background: Respiratory gating is generally recommended in 4D flow MRI of the heart to avoid blurring and motion artifacts. Recently, a novel automated contact-less camera-based respiratory motion sensor has been introduced. Purpose: To compare camera-based respiratory gating (CAM) with liver-lung-navigator-based gating (NAV) and no gating (NO) for whole-heart 4D flow MRI. Study Type: Retrospective. Subjects: Thirty two patients with a spectrum of cardiovascular diseases. Field Strength/Sequence: A 3T, 3D-cine spoiled-gradient-echo-T1-weighted-sequence with flow-encoding in three spatial directions. Assessment: Respiratory phases were derived and compared against each other by cross-correlation. Three radiologists/cardiologist scored images reconstructed with camera-based, navigator-based, and no respiratory gating with a 4-point Likert scale (qualitative analysis). Quantitative image quality analysis, in form of signal-to-noise ratio (SNR) and liver-lung-edge (LLE) for sharpness and quantitative flow analysis of the valves were performed semi-automatically. Statistical Tests: One-way repeated measured analysis of variance (ANOVA) with Wilks's lambda testing and follow-up pairwise comparisons. Significance level of P ≤ 0.05. Krippendorff's-alpha-test for inter-rater reliability. Results: The respiratory signal analysis revealed that CAM and NAV phases were highly correlated (C = 0.93 ± 0.09, P < 0.01). Image scoring showed poor inter-rater reliability and no significant differences were observed (P ≥ 0.16). The image quality comparison showed that NAV and CAM were superior to NO with higher SNR (P = 0.02) and smaller LLE (P < 0.01). The quantitative flow analysis showed significant differences between the three respiratory-gated reconstructions in the tricuspid and pulmonary valves (P ≤ 0.05), but not in the mitral and aortic valves (P > 0.05). Pairwise comparisons showed that reconstructions without respiratory gating were different in flow measurements to either CAM or NAV or both, but no differences were found between CAM and NAV reconstructions. Data Conclusion: Camera-based respiratory gating performed as well as conventional liver-lung-navigator-based respiratory gating. Quantitative image quality analysis showed that both techniques were equivalent and superior to no-gating-reconstructions. Quantitative flow analysis revealed local flow differences (tricuspid/pulmonary valves) in images of no-gating-reconstructions, but no differences were found between images reconstructed with camera-based and navigator-based respiratory gating. Level of Evidence: 3. Technical Efficacy: Stage 2.

Rationale About one-third of ischaemic strokes are caused by cardioembolism, and a substantial proportion of cryptogenic strokes likely also originate from the heart or aortic arch. Early determination of aetiology is important to optimise management. Computed Tomography-angiography of the heart is emerging as an alternative to echocardiography to detect cardio-aortic sources of embolism in stroke patients, but its diagnostic yield in acute ischaemic stroke has not been thoroughly assessed. Hypothesis: We hypothesise that electrocardiography-gated computed tomography-angiography of the heart and aortic arch, acquired in the acute phase in patients with ischaemic stroke, has a higher diagnostic yield than transthoracic echocardiography as a first-line screening method for detection of cardio-aortic sources of embolism. Methods and design Mind the Heart is a single-centre prospective observational cohort study. We will include consecutive adult patients with acute ischaemic stroke who are potentially eligible for reperfusion therapy. Patients undergo non-electrocardiography-gated computed tomography-angiography of the aortic arch, cervical and intracranial arteries, directly followed by prospective sequential electrocardiography-gated cardiac computed tomography-angiography. Routine work-up for cardioembolism including 12-leads electrocardiography, Holter electrocardiography and transthoracic echocardiography is performed as soon as possible. The primary endpoint is the proportion of patients with a predefined high-risk cardio-aortic source of embolism on computed tomography-angiography versus transthoracic echocardiography in patients who underwent both investigations. Based on an expected 5% additional yield of computed tomography-angiography, a sample size of 450 patients is required. Conclusions The Mind the Heart study will generate a reliable estimate of the diagnostic yield of echocardiography-gated cardio-aortic computed tomography-angiography performed in the acute phase of ischaemic stroke.

Aims In the era of personalized medicine, it is of utmost importance to be able to identify subjects at the highest cardiovascular (CV) risk. To date, single biomarkers have failed to markedly improve the estimation of CV risk. Using novel technology, simultaneous assessment of large numbers of biomarkers may hold promise to improve prediction. In the present study, we compared a protein-based risk model with a model using traditional risk factors in predicting CV events in the primary prevention setting of the European Prospective Investigation (EPIC)-Norfolk study, followed by validation in the Progressione della Lesione Intimale Carotidea (PLIC) cohort. Methods and results Using the proximity extension assay, 368 proteins were measured in a nested case–control sample of 822 individuals from the EPIC-Norfolk prospective cohort study and 702 individuals from the PLIC cohort. Using tree-based ensemble and boosting methods, we constructed a protein-based prediction model, an optimized clinical risk model, and a model combining both. In the derivation cohort (EPIC-Norfolk), we defined a panel of 50 proteins, which outperformed the clinical risk model in the prediction of myocardial infarction [area under the curve (AUC) 0.754 vs. 0.730; P < 0.001] during a median follow-up of 20 years. The clinically more relevant prediction of events occurring within 3 years showed an AUC of 0.732 using the clinical risk model and an AUC of 0.803 for the protein model (P < 0.001). The predictive value of the protein panel was confirmed to be superior to the clinical risk model in the validation cohort (AUC 0.705 vs. 0.609; P < 0.001). Conclusion In a primary prevention setting, a proteome-based model outperforms a model comprising clinical risk factors in predicting the risk of CV events. Validation in a large prospective primary prevention cohort is required to address the value for future clinical implementation in CV prevention., Graphical Abstract Graphical Abstract

Background: Cardiac thrombi are a major risk factor for ischemic stroke. We used cardiac CT to assess the prevalence of cardiac thrombi in acute ischemic stroke patients. Methods: This was a substudy of Mind the Heart, a prospective single-center cohort study in which consecutive adult patients with acute ischemic stroke underwent prospective ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent routine stroke work-up, including transthoracic echocardiography (TTE). Patients were included from May 2018 to November 2020. We compared patients with a cardiac thrombus on CT (defined as filling defect Results: Of 452 included patients, cardiac CT detected 40 thrombi in 38 (8%) patients. Thrombi were located in the left atrial appendage in 31 (7%), left atrium in 2 (0.4%) and left ventricle in 7 (2%) patients. TTE, performed in 25 patients with a cardiac thrombus (median time CT to TTE 1 day), detected a thrombus in 2 patients (0.4%, both left ventricle thrombi). Patients with a cardiac thrombus more frequently had a history of atrial fibrillation (40% vs 15%), used anticoagulation (42% vs 16%), had a large vessel occlusion (58% vs 41%), had intracranial occlusions in multiple vascular territories (5% vs 0.5%) and had a higher baseline NIHSS (17 [IQR 6-22] vs 5 [IQR 2-3]). In total, 26/38 (68%) patients with a cardiac thrombus had a history of atrial fibrillation or had atrial fibrillation diagnosed during stroke work-up. At 90 days, 19/23 (83%) patients with a cardiac thrombus who were alive were treated with anticoagulation. Patients with a cardiac thrombus had worse functional outcome (median mRS 4 [IQR 2-6] vs 2 [IQR 1-4], p Conclusion: Cardiac CT detected a cardiac thrombus in 1 in every 12 patients with acute ischemic stroke. These thrombi were rarely detected with TTE. Patients with cardiac thrombi more often had atrial fibrillation and severe neurological deficits. Functional outcome was worse in patients with cardiac thrombi.

ObjectiveTo assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a).MethodsWe performed 18F-sodium fluoride (18F-NaF) positron emission tomography/CT in patients with mild to moderate AS (peak aortic jet velocity between 2 and 4 m/s) and high versus low Lp(a) (>50 mg/dL vs 18F-NaF uptake.Results52 individuals (26 matched pairs) were included in the analysis. The mean age was 66.4±5.5 years, 44 (84.6%) were men, and the mean aortic valve velocity was 2.80±0.49 m/s. The median Lp(a) was 79 (64–117) mg/dL and 7 (5–11) mg/dL in the high and low Lp(a) groups, respectively. Systolic blood pressure and low-density-lipoprotein cholesterol (corrected for Lp(a)) were significantly higher in the low Lp(a) group (141±12 mm Hg vs 128±12 mm Hg, 2.5±1.1 mmol/L vs 1.9±0.8 mmol/L). We found no difference in valvular 18F-NaF uptake between the high and low Lp(a) groups (3.02±1.26 vs 3.05±0.96, p=0.902). Linear regression analysis showed valvular calcium score to be the only significant determinant of valvular 18F-NaF uptake (β=0.63; 95% CI 0.38 to 0.88 per 1000 Agatston unit increase, p18F-NaF uptake (β=0.17; 95% CI −0.44 to 0.88, p=0.305 for the high Lp(a) group).ConclusionAmong patients with mild to moderate AS, calcification activity is predominantly determined by established calcium burden. The results do not support our hypothesis that Lp(a) is associated with valvular 18F-NaF uptake.

BACKGROUND: Baffle complications, ie, leakage or stenosis, after an atrial switch operation (AtrSO) for transposition of the great arteries (TGA) are difficult to detect with the use of routine transthoracic echocardiography (TTE). We examined baffle interventions and the prevalence of baffle complications.METHODS: This dual-centre study followed TGA-AtrSO patients for the occurrence of baffle interventions. In addition, in 2017-2019, prevalence of baffle complications was determined in patients undergoing routine contrast-enhanced (CE) TTE including various hemodynamic conditions and computed tomography (CT). Baffle leaks were defined as right-to-left shunting on CE-TTE and baffle stenosis as a systemic venous baffle diameter of < 10 mm on CT.RESULTS: In total, 67 TGA-AtrSO patients were followed to a median age of 38 (interquartile range 34-42) years, for a median of 9 (6-13) years. Baffle interventions were documented in 24 patients (36%). Cumulative risk of baffle interventions was 25% after 15 years of follow-up. Prevalence of baffle complications was determined in 29/67 patients. In total, 4 (14%) had patent baffles, 11 (38%) had leakage only, 5 (17%) had stenosis only, and 9 (31%) had both, while 24/29 (84%) were asymptomatic. Although baffle leaks were not associated with clinical characteristics, peak work rate during exercise TTE was lower in patients with vs without stenosis (89 ± 24 W vs 123 ± 21 W; P < 0.001).CONCLUSIONS: Baffle complications are common in TGA-AtrSO. The cumulative risk of baffle interventions was 25% after 15 years of follow-up. CE-TTE uncovered asymptomatic baffle leakage in the majority of patients, especially with examination during exercise. CT revealed baffle stenosis in almost half of the patients, which was associated with decreased exercise tolerance. Awareness of these findings may alter clinical follow-up.

Background: Cardiac thrombi are a major risk factor for ischemic stroke, but are rarely diagnosed in the acute phase. We examined characteristics and functional outcome of patients with ischemic stroke and a concomitant cardiac thrombus detected on cardiac CT performed in the acute phase. Patients and Methods: We used data from “Mind the Heart,” a prospective cohort study in which consecutive adult patients with acute ischemic stroke underwent prospective ECG-gated cardiac CT during their acute stroke imaging protocol. We compared characteristics, functional outcome (modified Rankin scale) and stroke recurrence rate at 90 days of patients with a cardiac thrombus on CT (defined as filling defect Results: Among 452 included patients, cardiac CT detected 41 thrombi in 38 (8%) patients. Thrombi were most often located in the left atrial appendage (31/38 [82%]). Patients with a cardiac thrombus more frequently had intracranial occlusions in multiple vascular territories (5% vs 0.5%, p = 0.04) and a higher baseline NIHSS score (17 [IQR 6–22] vs 5 [IQR 2–3], p Discussion and Conclusion: Cardiac CT detected a cardiac thrombus in one in every 12 patients with acute ischemic stroke, and these patients had more severe deficits, multivessel occlusions, and a worse functional outcome.

Background Helices and vortices in thoracic aortic blood flow measured with 4D flow cardiovascular magnetic resonance (CMR) have been associated with aortic dilation and aneurysms. Current approaches are semi-quantitative or when fully quantitative based on 2D plane placement. In this study, we present a fully quantitative and three-dimensional approach to map and quantify abnormal velocity and wall shear stress (WSS) at peak systole in patients with a bicuspid aortic valve (BAV) of which 52% had a repaired coarctation. Methods 4D flow CMR was performed in 48 patients with BAV and in 25 healthy subjects at a spatiotemporal resolution of 2.5 × 2.5 × 2.5mm3/ ~ 42 ms and TE/TR/FA of 2.1 ms/3.4 ms/8° with k-t Principal Component Analysis factor R = 8. A 3D average of velocity and WSS direction was created for the normal subjects. Comparing BAV patient data with the 3D average map and selecting voxels deviating between 60° and 120° and > 120° yielded 3D maps and volume (in cm3) and surface (in cm2) quantification of abnormally directed velocity and WSS, respectively. Linear regression with Bonferroni corrected significance of P Results The velocity volumes > 120° correlated moderately with the vorticity scores (R ~ 0.50, P 120° did not correlate with quantitative vorticity. For abnormal velocity and WSS deviating between 60° and 120°, moderate correlations were found with aortic diameters (R = 0.50–0.70). For abnormal velocity and WSS deviating > 120°, additional moderate correlations were found with age and with peak velocity (stenosis severity) and a weak correlation with gender. Ensemble maps showed that more than 60% of the patients had abnormally directed velocity and WSS. Additionally, abnormally directed velocity and WSS was higher in the proximal descending aorta in the patients with repaired coarctation than in the patients where coarctation was never present. Conclusion The possibility to reveal directional abnormalities of velocity and WSS in 3D provides a new tool for hemodynamic characterization in BAV disease.

Aim Preclinical work indicates that low-density lipoprotein cholesterol (LDL-C) not only drives atherosclerosis by directing the innate immune response at plaque level but also augments proinflammatory monocyte production in the bone marrow (BM) compartment. In this study, we aim to unravel the impact of LDL-C on monocyte production in the BM compartment in human subjects. Methods and results A multivariable linear regression analysis in 12 304 individuals of the EPIC-Norfolk prospective population study showed that LDL-C is associated with monocyte percentage (β = 0.131 [95% CI: 0.036–0.225]; P = 0.007), at the expense of granulocytes (β = −0.876 [95% CI: −1.046 to −0.705]; P < 0.001). Next, we investigated whether altered haematopoiesis could explain this monocytic skewing by characterizing CD34+ BM haematopoietic stem and progenitor cells (HSPCs) of patients with familial hypercholesterolaemia (FH) and healthy normocholesterolaemic controls. The HSPC transcriptomic profile of untreated FH patients showed increased gene expression in pathways involved in HSPC migration and, in agreement with our epidemiological findings, myelomonocytic skewing. Twelve weeks of cholesterol-lowering treatment reverted the myelomonocytic skewing, but transcriptomic enrichment of monocyte-associated inflammatory and migratory pathways persisted in HSPCs post-treatment. Lastly, we link hypercholesterolaemia to perturbed lipid homeostasis in HSPCs, characterized by lipid droplet formation and transcriptomic changes compatible with increased intracellular cholesterol availability. Conclusions Collectively, these data highlight that LDL-C impacts haematopoiesis, promoting both the number and the proinflammatory activation of circulating monocytes. Furthermore, this study reveals a potential contributory role of HSPC transcriptomic reprogramming to residual inflammatory risk in FH patients despite cholesterol-lowering therapy., Graphical Abstract LDL-C impacts hematopoiesis, promoting both the number and the proinflammatory activation of circulating monocytes.

ObjectivesQuantification of pericardial/myocardial involvement and risks of sudden cardiac arrest/sudden cardiac death (SCA/SCD) after SARS-CoV-2 infection in athletes who return to sports.DesignSystematic review on post-SARS-CoV-2 infection pericardial/myocardial manifestations in athletes.Data sourcesCombinations of key terms in Medline, Embase and Scopus (through 2 June 2021).Eligibility criteria for selecting studiesInclusion: athletes, with cardiovascular magnetic resonance (CMR) or echocardiography after recovery from SARS-CoV-2 infection, including arrhythmia outcomes. Exclusion: study population ≥1 individual comorbidity and mean age 64 years. Quality assessment was performed using Joanna Briggs Institute Critical Appraisal tools checklists.ResultsIn total, 12 manuscripts (1650 papers reviewed) comprising 3131 athletes (2198 college/student athletes, 879 professional athletes and 54 elite athletes) were included. The prevalence of myocarditis on echocardiography and/or CMR was 0%–15%, pericardial effusion 0%–58% and late gadolinium enhancement (LGE) 0%–46%. Weighted means of diagnosed myocarditis were 2.1% in college/student athletes and 0% in elite athletes. The prevalence of LGE was markedly lower in studies with high-quality assessment scores (3%–4%) versus low scores (38%–42%). A single study reported reversibility of myocardial involvement in 40.7%. No important arrhythmias were reported. Ten studies (n=4171) reporting postrecovery troponin T/I found no clear relationship with cardiac abnormalities.Summary/conclusionAthletes have an overall low risk of SARS-CoV-2 pericardial/myocardial involvement, arrhythmias and SCA/SCD. Rates of pericardial/myocardial abnormalities in athletes are highly variable and dependent on study quality. Troponin screenings seem unreliable to identify athletes at risk for myocardial involvement. Prospective athlete studies, with pre-SARS-CoV-2 imaging (CMR), including structured follow-up and arrhythmia monitoring, are urgently needed.

Background Mediastinal radiation therapy (MRT) is a widely used therapy for thoracic malignancies. This therapy has the potential to cause cardiovascular injuries, which may require surgery. The primary aim of this study is to identify the perioperative outcomes of cardiac surgery in patients with a history of MRT. Second, potential predictors of mortality and adverse events were identified. Methods A retrospective study was conducted among 59 patients with prior MRT who underwent cardiac surgery between December 2009 and March 2015. Included surgeries consisted of procedures through median‐ and ministernotomy. Baseline, perioperative, and follow‐up data were obtained and analyzed. Results The majority of patients had a history of breast cancer (n = 43), followed by Hodgkin lymphoma (n = 10) and non‐Hodgkin lymphoma (n = 3). Preoperative estimated mortality with the Euroscore II was 3.4%. Overall 30‐day mortality was 6.8% (n = 4), with a total in‐hospital mortality of 10.2% (n = 6). Postoperatively, nine rethoracotomies (15.3%) had to be performed. During a mean follow‐up of 53 months, an additional 10 patients (16.9%) died, of which 60% (n = 6) as a result of cancer‐related events. Cox proportional modeling showed no differences in mortality between primary malignancies (P > .05). Conclusion This study shows that cardiac surgery after mediastinal radiotherapy is associated with increased short‐ and long‐term mortality when compared to preoperative mortality risks predicted by the Euroscore II. Surgery‐related events caused all short‐term mortality cases, while malignancy‐related events were the main cause of death during the follow‐up. Mortality was higher in patients with a previous stroke and a lower estimated glomerular filtration rate.

Introduction Data on the incidence of acute aortic dissection in the code stroke population are scarce. We report estimated incidence, clinical manifestations, treatment and outcomes of patients with an acute aortic dissection in a code stroke cohort from a comprehensive stroke centre. Patients and methods We used data from a single-centre prospective registry of consecutive adult patients who presented to the emergency department between 2015 and 2018 with neurological deficits suggestive of an acute stroke (‘code stroke’). All patients routinely underwent non-contrast computed tomography of the brain and computed tomography-angiography of the aortic arch, cervical and intracranial arteries. Results Of 2874 code stroke patients, 1563 (54.4%) had acute ischaemia (ischaemic stroke or transient ischaemic attack). Fifteen patients (0.5% of code stroke patients and 0.8% of patients with acute ischaemia) had an acute aortic dissection (all Stanford classification type A). Discerning clinical manifestations were decreased consciousness in 11/15 (73%), pain in 8/15 (53%) and low systolic blood pressure (mean 106 mmHg, SD30). Acute aortic dissection was an incidental finding during computed tomography-angiography in 4/15 (27%). Two out of 15 patients (13%) received intravenous thrombolysis, 9/15 (60%) underwent aortic surgery and 10/15 (67%) died. Of those who survived, 3/5 (60%) had a good functional outcome (modified Rankin Scale 0–2). Discussion and Conclusion In our comprehensive stroke centre, about 1/200 code stroke patients and 1/125 patients with acute ischaemia had an acute aortic dissection. Multicentre studies are necessary to acquire a more reliable estimate of the incidence of acute aortic dissection in the code stroke population. Given the ramifications of missing this diagnosis, imaging of the entire aortic arch is important in these patients.

IMPORTANCE: Genetic variants at the LPA locus are associated with both calcific aortic valve stenosis (CAVS) and coronary artery disease (CAD). Whether these variants are associated with CAVS in patients with CAD vs those without CAD is unknown. OBJECTIVE: To study the associations of LPA variants with CAVS in a cohort of patients undergoing heart surgery and LPA with CAVS in patients with CAD vs those without CAD and to determine whether first-degree relatives of patients with CAVS and high lipoprotein(a) (Lp[a]) levels showed evidence of aortic valve microcalcification. DESIGN, SETTING, AND PARTICIPANTS: This genetic association study included patients undergoing cardiac surgery from the Genome-Wide Association Study on Calcific Aortic Valve Stenosis in Quebec (QUEBEC-CAVS) study and patients with CAD, patients without CAD, and control participants from 6 genetic association studies: the UK Biobank, the European Prospective Investigation of Cancer (EPIC)-Norfolk, and Genetic Epidemiology Research on Aging (GERA) studies and 3 French cohorts. In addition, a family study included first-degree relatives of patients with CAVS. Data were collected from January 1993 to September 2018, and analysis was completed from September 2017 to September 2018. EXPOSURES: Case-control studies. MAIN OUTCOMES AND MEASURES: Presence of CAVS according to a weighted genetic risk score based on 3 common Lp(a)-raising variants and aortic valve microcalcification, defined as the mean tissue to background ratio of 1.25 or more, measured by fluorine 18-labeled sodium fluoride positron emission tomography/computed tomography. RESULTS: This study included 1009 individuals undergoing cardiac surgery and 1017 control participants in the QUEBEC-CAVS cohort; 3258 individuals with CAVS and CAD, 41 100 controls with CAD, 2069 individuals with CAVS without CAD, and 380 075 control participants without CAD in the UK Biobank, EPIC-Norfolk, and GERA studies and 3 French cohorts combined; and 33 first-degree relatives of 17 patients with CAVS and high Lp(a) levels (≥60 mg/dL) and 23 control participants with normal Lp(a) levels (

Background Mineralocorticoid receptor antagonists (MRAs) reduce the risk of atrial fibrillation (AF) in patients with heart failure (HF) and a reduced ejection fraction. The efficacy of MRAs for AF prevention in patients with HF and a preserved ejection fraction (HFpEF) is unclear. Objectives We performed a secondary analysis of a randomized placebo-controlled trial to determine the efficacy of spironolactone in reducing new-onset AF and recurrence of AF in 2733 patients with symptomatic HFpEF. Methods Patients with and without prevalent AF at baseline were included, and those with permanent AF were excluded. Patients were randomized 1:1 to spironolactone or placebo. The risk of new-onset AF or the recurrence of AF was quantified using hazard ratios (HRs) with corresponding 95% confidence intervals (CIs). Results At baseline, 2228 (64.7%) patients had no history of AF (spironolactone, n = 1111; placebo, n = 1117), whereas 505 (18.4%) patients had prevalent AF (spironolactone, n = 260; placebo, n = 245). During a median follow-up of 3.1 years (interquartile range [IQR] 2.0–4.9), the incidence of new-onset AF was similar in both treatment arms: spironolactone 5.2% (n = 58) versus placebo 4.4% (n = 49); p = 0.41. The risk of new-onset AF was similar in both treatment arms: HR 1.19; 95% CI 0.81–1.74; p = 0.38. AF recurrence was also similar in both treatment arms during a median follow-up of 3.3 years (IQR 1.9–4.7): spironolactone 11.5% (n = 30) versus placebo 11.8% (n = 29); p = 1.00. The risk of recurrence of AF did not differ per treatment arm: HR 0.94; 95% CI 0.57–1.58; p = 0.83. Conclusion Spironolactone does not reduce the risk of new-onset AF or AF recurrence in patients with HFpEF. This is in contrast to results in cohorts of patients with HF and a reduced ejection fraction. Clinical trial registration ClinicalTrials.gov identifier no. NCT00094302 (TOPCAT). Electronic supplementary material The online version of this article (10.1007/s40256-019-00353-5) contains supplementary material, which is available to authorized users.

Objectives The aim of this study was to determine the course of tricuspid regurgitation (TR) after transcatheter mitral valve repair (TMVR), identify predictors for severe TR after TMVR and determine the association of severe TR after TMVR with outcome. Background TR is often present in patients with symptomatic mitral regurgitation (MR) and is associated with increased morbidity and mortality. The clinical course of TR after TMVR has not been clearly determined. Methods Patients that underwent TMVR between 2009 and 2017 were included. Clinical data were compared between patients with and without severe TR at 6 months after TMVR. Multivariate logistic regression analysis was performed to identify predictors for severe TR after TMVR. Survival analysis was done for both groups, using the Kaplan–Meier method. Results A total of 146 patients were included (mean age 76 years, 51% male, 79% New York Heart Association class ≥3 and 29% severe TR at baseline). Advanced age, atrial fibrillation (AF), right ventricular (RV) dysfunction, and limited procedural MR reduction were revealed as independent predictors for severe TR after TMVR. Survival of patients with severe TR after TMVR was 58% after 2 years compared to 82% for those with non, mild or moderate TR. Conclusions Severe TR after TMVR is common in patients at advanced age, those with AF, RV dysfunction and limited MR reduction during TMVR and is associated with impaired survival. As the associated parameters are indicators of longstanding MR, research investigating the benefits of earlier intervention in MR should be initiated.

Background: Elevated Lp(a) (Lipoprotein(a)) levels are associated with coronary artery disease (CAD), ischemic stroke (IS), and calcific aortic valve stenosis (CAVS). Studies investigating the association between Lp(a) levels and these diseases in women have yielded inconsistent results. Methods: To investigate the association of Lp(a) with sex-specific cardiovascular outcomes, we determined the association between genetically predicted Lp(a) levels (using 27 single nucleotide polymorphisms at the LPA locus) and hepatic LPA expression (using 80 single nucleotide polymorphisms at the LPA locus associated with LPA mRNA expression in liver samples from the Genotype-Tissue Expression dataset) on CAD, IS, and CAVS using individual participant data from the UK Biobank: 408 403 participants of European ancestry (37 102, 4283, and 2574 with prevalent CAD, IS, and CAVS, respectively). The long-term association between Lp(a) levels and incident CAD, IS, and CAVS was also investigated in European Prospective Investigation into Cancer and Nutrition-Norfolk: 18 721 participants (3964, 846, and 424 with incident CAD, IS, and CAVS, respectively). Results: Genetically predicted plasma Lp(a) levels were positively and similarly associated with prevalent and incident CAD and CAVS in men and women. Genetically predicted plasma Lp(a) levels were associated with prevalent and incident IS when we studied men and women pooled together, and in men only. Genetically predicted LPA expression levels were associated with prevalent CAD and CAVS in men and women but not with IS. Conclusions: Genetically predicted blood Lp(a) and hepatic LPA gene expression as well as serum Lp(a) levels predict the risk of CAD and CAVS in men and in women. Whether RNA interference therapies aiming at lowering Lp(a) levels could be useful in reducing cardiovascular disease risk in both men and women with high Lp(a) levels needs to be determined in large-scale cardiovascular outcomes trials.

Background: Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear. Methods and Results: In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n = 908) vs those who did not (Controls, n = 1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; P

To assess the need for additional invasive coronary angiography (CAG) after initial computed tomography coronary angiography (CTCA) in patients awaiting non-coronary cardiac surgery and in patients with cardiomyopathy, heart failure or ventricular arrhythmias, and to determine differences between patients that were referred to initial CTCA or direct CAG, consecutive patients were included between August 2017 and January 2020 and categorized as those referred to initial CTCA (conform protocol), and to direct CAG (non-conform protocol). Out of a total of 415 patients, 78.8% (327 patients, mean age: 57.9 years, 67.3% male) were referred to initial CTCA, of whom 260 patients (79.5%) had no obstructive lesions (&lt, 50% DS). A total of 55 patients (16.8%) underwent additional CAG after initial CTCA, which showed coronary lesions of &gt, 50% DS in 21 patients (6.3% of 327). Eighty-eight patients (mean age: 66.0 years, 59.1% male) were directly referred to CAG (non-conform protocol). These patients were older and had more cardiovascular risk factors compared to patients that underwent initial CTCA (conform protocol), and coronary lesions of &gt, 50% DS were detected in 16 patients (17.2%). Revascularization procedures were infrequently performed in both groups: initial CTCA (3.0%), direct CAG (3.4%). The use of CTCA as a gatekeeper CAG in the diagnostic work-up of non-coronary cardiac surgery, cardiomyopathy, heart failure and ventricular arrhythmias is feasible, and only 17% of these patients required additional CAG after initial CTCA. Therefore, CTCA should be considered as the initial imaging modality to rule out CAD in these patients.

Purpose: Cardiac radioablation has evolved as a potential treatment modality for therapy-refractory ventricular tachycardia. To standardize cardiac radioablation treatments, promote accurate communication and target identification, and to assess toxicity, robust, and reproducible methods for angulation and cardiac segmentation are paramount. In this study, we developed and evaluated a tool for semiautomated angulation and segmentation according to the American Heart Association 17-segment model. Methods and Materials: The semiautomated angulation and segmentation of the planning-computed tomography (CT) was based on an in-house developed tool requiring placement of only 4 point-markers and a rotation matrix. For angulation, 2 markers defining the cardiac long-axis were placed: at the cardiac apex and at the center of the mitral valve. A rotation matrix was derived that angulates the CT volume, resulting in the cardiac short axis. Segmentation was subsequently performed based on marking the 2 left ventricular hinge points. To evaluate reproducibility, 5 observers independently placed markers in planning CTs of 6 patients. Results: The root mean square of the standard deviation for the angulation and segmentation marker positions were ≤0.5 cm. The 17 segments were subsequently generated and compared between the observers resulting in a median Dice coefficient of 0.8 (interquartile range: 0.70-0.87) and a median of the mean Hausdorff distance of 0.09 cm (interquartile range: 0.05-0.17). The interquartile ranges of Euler angles α and β, determined by the angulation markers, was less than 3 degrees for all patients except one. For the γ angle, determined by the hinge point markers, the interquartile range was up to 12 degrees. Conclusions: In this study a method for semiautomatic angulation and segmentation of the heart for cardiac radioablation according to the American Heart Association Segmented Model is presented and evaluated. Based on our results we believe that the segmentation is reproducible and that it can be used to promote communication between radiation oncology and cardiology, enables cardiology-oriented targeting and permits focused toxicity evaluations.

The heart muscle diseases hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure in young, otherwise healthy, individuals. We conducted genome-wide association studies and multi-trait analyses in HCM (1,733 cases), DCM (5,521 cases) and nine left ventricular (LV) traits (19,260 UK Biobank participants with structurally normal hearts). We identified 16 loci associated with HCM, 13 with DCM and 23 with LV traits. We show strong genetic correlations between LV traits and cardiomyopathies, with opposing effects in HCM and DCM. Two-sample Mendelian randomization supports a causal association linking increased LV contractility with HCM risk. A polygenic risk score explains a significant portion of phenotypic variability in carriers of HCM-causing rare variants. Our findings thus provide evidence that polygenic risk score may account for variability in Mendelian diseases. More broadly, we provide insights into how genetic pathways may lead to distinct disorders through opposing genetic effects.

Contains fulltext : 239064.pdf (Publisher’s version ) (Open Access) BACKGROUND: Proton magnetic resonance spectroscopy ((1) H-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking. PURPOSE: To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized (1) H-MRS. STUDY TYPE: Test-retest repeatability and measurement validation study. SUBJECTS: Sixteen volunteers and 22 patients scheduled for open-heart aortic valve replacement or septal myectomy. FIELD STRENGTH/SEQUENCE: Prospectively ECG-triggered respiratory-gated free-breathing single-voxel point-resolved spectroscopy (PRESS) sequence at 3 T. ASSESSMENT: Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the (1) H-MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo (1) H-MRS measurements against biochemical assays in myocardial tissue from the same subjects. STATISTICAL TESTS: Intrasession and intersession repeatability was assessed using Bland-Altman analyses. Agreement between (1) H-MRS measurements and biochemical assay was tested with regression analyses. RESULTS: The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% ± 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% ± 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with (1) H-MRS: n = 22, r = 0.44; P

Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population. Data Sources and Selection: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points. Data Extraction and Synthesis: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. Main Outcomes and Measures: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). Results: The meta-analysis included 7 cohort studies involving 21401 individuals (mean [SD] age, 53.7 [10.2] years; 10012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P =.01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P =.02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P

Additional file 1: Table S1. Quantification of LNH and vorticity with differences between regions and subjects, and correlations with qualitative scorings and abnormally directed velocity.

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2) activity has been shown to predict calcific aortic valve stenosis (CAVS) outcomes. Our objective was to test the association between plasma Lp-PLA2 activity and genetically elevated Lp-PLA2 mass/activity with CAVS in humans.Methods and resultsLp-PLA2 activity was measured in 890 patients undergoing cardiac surgery, including 476 patients undergoing aortic valve replacement for CAVS and 414 control patients undergoing coronary artery bypass grafting. After multivariable adjustment, Lp-PLA2 activity was positively associated with the presence of CAVS (OR=1.21 (95% CI 1.04 to 1.41) per SD increment). We selected four single nucleotide polymorphisms (SNPs) at the PLA2G7 locus associated with either Lp-PLA2 mass or activity (rs7756935, rs1421368, rs1805017 and rs4498351). Genetic association studies were performed in eight cohorts: Quebec-CAVS (1009 cases/1017 controls), UK Biobank (1350 cases/349 043 controls), European Prospective Investigation into Cancer and Nutrition-Norfolk (504 cases/20 307 controls), Genetic Epidemiology Research on Aging (3469 cases/51 723 controls), Malmö Diet and Cancer Study (682 cases/5963 controls) and three French cohorts (3123 cases/6532 controls), totalling 10 137 CAVS cases and 434 585 controls. A fixed-effect meta-analysis using the inverse-variance weighted method revealed that none of the four SNPs was associated with CAVS (OR=0.99 (95% CI 0.96 to 1.02, p=0.55) for rs7756935, 0.97 (95% CI 0.93 to 1.01, p=0.11) for rs1421368, 1.00 (95% CI 1.00 to 1.01, p=0.29) for rs1805017, and 1.00 (95% CI 0.97 to 1.04, p=0.87) for rs4498351).ConclusionsHigher Lp-PLA2 activity is significantly associated with the presence of CAVS and might represent a biomarker of CAVS in patients with heart disease. Results of our genetic association study suggest that Lp-PLA2 is however unlikely to represent a causal risk factor or therapeutic target for CAVS.