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As part of normal ageing, conductance arteries lose their cushion function, left ventricle (LV) filling and also left atrial emptying are impaired. The relation between conductance artery stiffness and LV diastolic function is normally explained by arterial hypertension and LV hypertrophy as needed intermediaries. We examined whether age-related aortic stiffening may influence LV diastolic function in normal healthy subjects. Aortic distensibility and pulse wave velocity (PWV) were related to LV emptying and filling parameters and left atrial emptying parameters as determined by magnetic resonance imaging in 36 healthy young (< 35 years) and 16 healthy middle-aged and elderly (> 35 years) with normal arterial blood pressure and myocardial mass. In the overall cohort, total aorta PWV correlated to a decrease in LV peak-emptying volume (r = 0.43), LV peak-filling (r = 0.47), passive atrial emptying volume (r = 0.66), and an increase in active atrial emptying volume (r = 0.47) (all p  < 0.001). PWV was correlated to passive atrial emptying volume even if only the > 35-year-old were considered (r = 0.53; p  < 0.001). Total peripheral resistance demonstrated similar correlations as PWV, but in a regression analysis only the total aorta PWV was related to left atrial (LA) passive emptying volume. Via impaired ventriculo-arterial coupling, the increased aortic PWV seen with normal ageing hence affects atrio-ventricular coupling, before increased aortic PWV is associated with significantly increased arterial blood pressure or LV hypertrophic remodelling. Our findings reinforce the existence of atrio-ventriculo-arterial coupling and suggest aortic distensibility should be considered an early therapeutic target to avoid diastolic dysfunction of the LV.

To investigate neurodevelopmental outcome in preschool children with a CHD (congenital heart defect) requiring surgery compared to healthy controls. This study includes all Danish children born between 2016-2018 who underwent surgery within the first year for Ventricular Septal Defect (VSD), atrioventricular septal defect, coarctation of the aorta, double outlet right ventricle, tetralogy of fallot, and Transposition of the Great Arteries (TGA). Exclusion criteria: preterm birth (<37 weeks), twins, and genetic aberrations. Cases were matched with two to four healthy controls on age, sex, gestational age at delivery, and region of birth. Neurodevelopmental outcome at 33-60-months was assessed by the Ages & Stages Questionnaire (ASQ). Comparisons were performed by the Mann-Whitney U test and logistic regression analysis and presented as p-values and odds ratios (OR) with 95% confidence intervals (CI). There were no differences in ASQ score between 105 cases with any CHD (230 (IQR 195-260)) and 179 controls (235 (IQR 205-265)), p = 0.12. Cases had five-fold increased odds of a low score compared to controls after adjusting for maternal educational level and children's age at ASQ completion (OR 5.02, 95% CI 1.49;16.90). This was primarily driven by cases with prenatally undetected VSD, where 20% scored below -2 standard deviations. No differences were found across individual CHD subgroups. In cases with prenatally undetected TGA, the total ASQ score was 185 (IQR 145-190) compared to 220 (IQR 190-270) in prenatally detected TGA, p = 0.08. The overall ASQ score in children with surgically corrected CHD was comparable to controls. However, cases had five-fold increased odds of a low score, primarily driven by children with prenatally undetected VSD. Additionally, ASQ scores were lower in TGA cases, especially when undetected prenatally, though not significant. These findings suggest follow-up of all children with a CHD requiring surgery including awareness of potential developmental delays.

Increased left ventricular mass (LVM) is a strong independent predictor for adverse cardiovascular events, but conventional echocardiographic methods are limited by poor reproducibility and accuracy. We developed a novel method based on adding the mean wall thickness from the parasternal short axis view, to the left ventricular end-diastolic volume acquired using the biplane model of discs. The participants (n = 85) had various left ventricular geometries and were assessed using echocardiography followed immediately by cardiac magnetic resonance, as reference. We compared our novel two-dimensional (2D) method to various conventional one-dimensional (1D) and other 2D methods as well as the three-dimensional (3D) method. Our novel method had better reproducibility in intra-examiner [coefficients of variation (CV) 9% vs. 11–14%] and inter-examiner analysis (CV 9% vs. 10–20%). Accuracy was similar to the 3D method (mean difference ± 95% limits of agreement, CV): Novel: 2 ± 50 g, 15% vs. 3D: 2 ± 51 g, 16%; and better than the “linear” 1D method by Devereux (7 ± 76 g, 23%). Our novel method is simple, has considerable better reproducibility and accuracy than conventional “linear” 1D methods, and similar accuracy as the 3D-method. As the biplane model forms part of the standard echocardiographic protocol, it does not require specific training and provides a supplement to the modern echocardiographic report.

The use of cardiovascular magnetic resonance imaging left atrial late gadolinium enhancement (LA LGE) is increasing for fibrosis evaluation though the use is still limited to specialized centres due to complex image acquisition and lack of consensus on image analyses. Analysis of LA LGE with image intensity ratio (IIR) (pixel intensity of atrial wall normalized by blood pool intensity) provides an objective method to obtain quantitative data on atrial fibrosis. A threshold between healthy myocardium and fibrosis of 1.2 has previously been established in 3T scans. The aim of the study was to reaffirm this threshold in 1.5T scans. LA LGE was performed using a 1.5T magnetic resonance scanner on: 11 lone-AF patients, 11 age-matched healthy volunteers (aged 27–44) and 11 elderly patients without known history of AF but varying degrees of comorbidities. Mean values of IIR for all healthy volunteers +2SD were set as upper limit of normality and was reproduced to 1.21 and the original IIR-threshold of 1.20 was maintained. The degree of fibrosis in lone-AF patients [median 9.0% (IQR 3.9–12.0)] was higher than in healthy volunteers [2.8% (1.3–8.3)] and even higher in elderly non-AF [20.1% (10.2–35.8), p = 0.001]. The previously established IIR-threshold of 1.2 was reaffirmed in 1.5T LA LGE scans. Patients with lone AF presented with increased degrees of atrial fibrosis compared to healthy volunteers in the same age-range. Elderly patients with no history of AF showed significantly higher degrees of fibrosis compared to both groups with younger individuals.

Adipose-derived stromal cell (ASC) therapy is currently investigated as a new treatment option for patients with ischemic heart disease (IHD). The aim of this study was to evaluate the effect of ASC therapy in patients with chronic IHD measuring myocardial perfusion and cardiac function using cardiac magnetic resonance imaging (CMRI). Patients were included in MyStromalCell trial, a phase II, randomized, double-blinded, placebo-controlled study investigated the effect of ASCs in patients with chronic IHD with preserved left ventricular ejection fraction (LVEF). In total, 41 of 60 patients underwent cine, late enhancement, rest and stress imaging with CMRI. There was a non-significant difference between stress and rest values in maximal signal intensity, a measure of myocardial perfusion, from baseline to follow-up comparing placebo with ASC group (–52.52 ± 88.61 and 3.05 ± 63.17, p = 0.061, respectively). LVEF, myocardial mass, stroke volume, left ventricle end-diastolic volume and end-systolic volume changed non-significantly (–0.5 ± 4.7%, –3.5 ± 13.1 g, –0.7 ± 8.6 mL, 1.9 ± 25.1 mL and 2.6 ± 16.5 mL, respectively) in the placebo group and in the ASC group (0.7 ± 8.6%, 0.9 ± 10.8 g, –0.3 ± 26.1 mL, –3.0 ± 31.5 mL and –2.7 ± 20.4 mL, respectively) from baseline to 6 months follow-up. The amount of scar tissue was unchanged in the placebo group by 0.0 ± 1.6 g, p = 1.0 and in the ASC group with –0.3 ± 2.3 g, p = 0.540. There was no difference between the groups. There was a non-significant trend toward increased myocardial perfusion but no significant changes in functional parameters or amount of scar tissue in patients treated with ASCs compared with patients allocated into the placebo group.

In patients previously hospitalised for COVID‐19, a 12‐week high‐intensity interval training (HIIT) intervention has previously been shown to increase left ventricular mass (LVM) immediately after the intervention. In the present study, we examined the effects of the same HIIT scheme on LVM, pulmonary diffusing capacity, symptom severity and functional capacity at 12‐month follow‐up. In this investigator‐blinded, randomised controlled trial, 12 weeks of a supervised HIIT scheme (4 × 4 min, three times a week) was compared to standard care (control) in patients recently discharged from hospital due to COVID‐19. At inclusion and at 12‐month follow‐up, LVM was assessed by cardiac magnetic resonance imaging (cMRI, primary outcome), while pulmonary diffusing capacity for carbon monoxide (DLCOc, secondary outcome) was examined by the single‐breath method. Symptom severity and functional status were examined by the Post‐COVID‐19 Functional Scale (PCFS) and King's Brief Interstitial Lung Disease (KBILD) questionnaire score. Of the 28 patients assessed at baseline, 22 completed cMRI at 12‐month follow‐up (12.4 ± 0.6 months after inclusion). LVM was maintained in the HIIT but not the standard care group, with a mean between‐group difference of 9.68 [95% CI: 1.72, 17.64] g (P = 0.0182). There was no differences in change from baseline to 12‐month follow‐up between groups in DLCOc % predicted (−2.45 [−11.25, 6.34]%; P = 0.578). PCFS and KBILD improved similarly in the two groups. In individuals previously hospitalised for COVID‐19, a 12‐week supervised HIIT scheme resulted in a preserved LVM at 12‐month follow‐up but did not affect pulmonary diffusing capacity or symptom severity. What is the central question of this study? In patients previously hospitalised for COVID‐19, a 12‐week high‐intensity interval training (HIIT) scheme increases left ventricular mass (LVM) immediately after the intervention: does this persist? What is the main finding and its importance? A 12‐week HIIT intervention led to preserved LVM at 12‐month follow‐up, while LVM decreased by ∼10 g in the standard care group. This indicates that HIIT may be useful as part of post‐COVID rehabilitation strategies for specifically targeting the detrimental effects of COVID‐19 on the heart.

Introduction Cardiac tumors in children are rare. Rhabdomyomas are the most common type in newborns, often associated with tuberous sclerosis. The exact prevalence of neonatal cardiac tumors is unknown. This study aimed to determine the pre‐ and postnatal prevalence of cardiac tumors in a population‐based cohort. Material and Methods This cross‐sectional study collected data from two sources: (1) all fetuses who underwent routine prenatal malformation scans (Weeks 18–21) with expected delivery within the study period (April 2016 and October 2018), and (2) all newborns who underwent systematic transthoracic echocardiography in the population‐based Copenhagen Baby Heart Study within the study period. Medical charts provided follow‐up data. Clinical trial registration: clinicaltrials.gov; identifier: NCT02753348. Results Among 47 228 live‐births (51% male) in the study period, 1) 44 963 fetuses were scanned, with one prenatally diagnosed with a cardiac tumor (0.002% prevalence). Fetal autopsy revealed a cardiac rhabdomyoma. 2) Of 25 590 newborns (age 12 ± 8 days, 52% male) scanned, 7 had cardiac tumors (0.027% prevalence), a 14‐fold higher prevalence than prenatally (p = 0.005). Tumors were located in the ventricles, predominantly (86%) multifocal, in otherwise normal hearts. Three affected newborns (43%) had tuberous sclerosis; the remaining four (57%) exhibited spontaneous tumor regression. Retrospective analysis of prenatal scans suspected a ventricular tumor in 1 of the 7 cases. Conclusions In a large, contemporary cohort, the pre‐ and postnatal prevalence of congenital cardiac tumors was 0.002% and 0.027%. This likely reflects the growth pattern of myocardial tumors and underscores the importance of gestational age for detection. Tumors in newborns were associated with tuberous sclerosis in 43%, and the remaining regressed spontaneously. Ultrasonic assessment of a large, contemporary cohort in Copenhagen, Denmark, revealed a prevalence of congenital cardiac tumors of 0.002% prenatally (gestational Weeks 18–21) and 0.027% postnatally. All cardiac tumors were located in the ventricles. Associated tuberous sclerosis was seen in almost half the cases; in the remaining cases, tumors regressed spontaneously.

Right ventricular (RV) dilatation predicts clinical worsening in pulmonary arterial hypertension (PAH) and RV volumes can be measured with high precision using cardiovascular magnetic resonance imaging. In regular follow‐up of patients and in studies of improvement in RV function, knowledge of clinically significant changes of RV volumes and function are of relevance. Patients with PAH were followed with cardiovascular magnetic resonance imaging and clinical assessment at 6‐month intervals. Changes in RV volumes associated with changes in clinical status were assessed. Twenty‐five patients with PAH (Group 1) were included and examined every 6 months for 2.5 years, with a total of 107 MRI scans. For a step change in WHO functional class, the associated change in RV volume was 11% (confidence interval 7%−14%, p < 0.0001) and in stroke volume 9% (confidence interval 3%−15%, p = 0.003). This study found an 11% change in RV volume to be clinically significant. The combination of clinically significant changes and the known precision in the measurements enables individualized follow‐up of RV‐function in PAH. To our knowledge, this study is the first to use repeated assessments to suggest clinically significant changes of RV volume based on changes in clinical presentation.

Background Marfan syndrome is associated with morbidity and mortality due to aortic dilatation and dissection. Preventive aortic root replacement has been the standard treatment in Marfan syndrome patients with aortic dilatation. In this study, we present aortic event data from a nationwide Marfan syndrome cohort. Method The nationwide cohort of Danish Marfan syndrome patients was established from the Danish National Patient Registry and the Cause of Death Register, where we retrieved information about aortic surgery and dissections. We associated aortic events with age, sex, and Marfan syndrome diagnosis prior or after the first aortic event. Results From the total cohort of 412 patients, 150 (36.4 %) had an aortic event. Fifty percent were event free at age 49.6. Eighty patients (53.3 %) had prophylactic surgery and seventy patients (46.7 %) a dissection. The yearly event rate was 0.02 events/year/patient in the period 1994–2014. Male patients had a significant higher risk of an aortic event at a younger age with a hazard ratio of 1.75 (CI 1.26–2.42, p  = 0.001) compared with women. Fifty-three patients (12.9 %) were diagnosed with MFS after their first aortic event which primarily was aortic dissection [ n  = 44 (83.0 %)]. Conclusion More than a third of MFS patients experienced an aortic event and male patients had significantly more aortic events than females. More than half of the total number of dissections was in patients undiagnosed with MFS at the time of their event. This emphasizes that diagnosing MFS is lifesaving and improves mortality risk by reducing the risk of aorta dissection.

Background Cardiovascular magnetic resonance imaging (CMR) have described localised non-ischemic late gadolinium enhancement (LGE) lesions of prognostic importance in various non-ischemic cardiomyopathies. Ischemic LGE lesions are prevalent in diabetes (DM), but non-ischemic LGE lesions have not previously been described or systematically studied in DM. Methods 296 patients with type 2 DM (T2DM) and 25 sex-matched control subjects underwent echocardiography and CMR including adenosine-stress perfusion, T 1 -mapping and LGE. Results 264 patients and all control subjects completed the CMR protocol. 78.4% of patients with T2DM had no LGE lesions; 11.0% had ischemic LGE lesions only; 9.5% had non-ischemic LGE lesions only; and 1.1% had both one ischemic and one non-ischemic lesion. The non-ischemic LGE lesions were situated mid-myocardial in the basal lateral or the basal inferolateral part of the left ventricle and the affected segments showed normal to high wall thickness and normal contraction. Patients with non-ischemic LGE lesions in comparison with patients without LGE lesions had increased myocardial mass (150 ± 34 vs. 133 ± 33 g, P = 0.02), average E/e’(9.9 IQR8.7–12.6 vs. 8.8 IQR7.4–10.7, P = 0.04), left atrial maximal volume (102 IQR84.6–115.2 vs. 91 IQR75.2–100.0 mL, P = 0.049), NT-proBNP (8.9 IQR5.9–19.7 vs. 5.9 IQR5.9–10.1 µmol/L, P = 0.02) and high-sensitive troponin (15.6 IQR13.0–26.1 vs. 13.0 IQR13.0–14.6 ng/L, P = 0.007) and a higher prevalence of retinopathy (48 vs. 25%, P = 0.009) and autonomic neuropathy (52 vs. 30.5%, P = 0.005). Conclusion A specific LGE pattern with lesions in the basal lateral or the basal inferolateral part of the left ventricle was found in patients with type 2 diabetes. Trial registration https://www.clinicaltrials.gov . Unique identifier: NCT02684331.