Acute vasodilator response testing in the adult Fontan circulation using non-invasive 4D Flow MRI: a proof-of-principle study.

BACKGROUND: Pulmonary vasodilator therapy in Fontan patients can improve exercise tolerance. We aimed to assess the potential for non-invasive testing of acute vasodilator response using four-dimensional (D) flow MRI during oxygen inhalation. MATERIALS AND METHODS: Six patients with well-functioning Fontan circulations were prospectively recruited and underwent cardiac MRI. Ventricular anatomical imaging and 4D Flow MRI were acquired at baseline and during inhalation of oxygen. Data were compared with six age-matched healthy volunteers with 4D Flow MRI scans acquired at baseline. RESULTS: All six patients tolerated the MRI scan well. The dominant ventricle had a left ventricular morphology in all cases. On 4D Flow MRI assessment, two patients (Patients 2 and 6) showed improved cardiac filling with improved preload during oxygen administration, increased mitral inflow, increased maximum E-wave kinetic energy, and decreased systolic peak kinetic energy. Patient 1 showed improved preload only. Patient 5 showed no change, and patient 3 had equivocal results. Patient 4, however, showed a decrease in preload and cardiac filling/function with oxygen. DISCUSSION: Using oxygen as a pulmonary vasodilator to assess increased pulmonary venous return as a marker for positive acute vasodilator response would provide pre-treatment assessment in a more physiological state - the awake patient. This proof-of-concept study showed that it is well tolerated and has shown changes in some stable patients with a Fontan circulation.

Research priorities in single-ventricle heart conditions: a United Kingdom national study.

OBJECTIVE: To bring together stakeholders in the United Kingdom to establish national priorities for research in single-ventricle heart conditions. METHODS: This study comprised two surveys and a workshop. The initial public online survey asked respondents up to three questions they would like answered for research. Responses were classified as unanswered, already answered, or unable to be answered by scientific research. In the follow-up survey, unanswered questions were divided into categories and respondents were asked to rank categories and questions by priority. A stakeholder workshop attended by patients, parents, healthcare professionals, researchers, and charities was held to determine the final list of research priorities. RESULTS: A total of 128 respondents posed 344 research questions, of which 271 were classified as unanswered, and after removing duplicates, 204 questions remained, which were divided into 20 categories. In the second survey, 56 (49.1%) respondents successfully ranked categories and questions. A total of 39 participants attended the workshop, drawing up a list of 30 research priorities across nine priority categories. The nine priority categories are: Associated co-morbidities; Brain & neurodevelopment; Exercise; Fontan failure; Heart function; Living with a single ventricle heart condition; Management of the well-functioning Fontan circulation; Surgery & perioperative care; and Transplantation, mechanical support & novel therapies. CONCLUSIONS: Through a multi-stage process, we engaged a wide range of interested parties to establish a list of research priorities in single-ventricle heart conditions. This provides a platform for clinicians, researchers, and funders in the United Kingdom and elsewhere to address the most important questions and improve outcomes in these rare but high-impact CHDs.

Differential flow improvements after valve replacements in bicuspid aortic valve disease: a cardiovascular magnetic resonance assessment.

BACKGROUND: Abnormal aortic flow patterns in bicuspid aortic valve disease (BAV) may be partly responsible for the associated aortic dilation. Aortic valve replacement (AVR) may normalize flow patterns and potentially slow the concomitant aortic dilation. We therefore sought to examine differences in flow patterns post AVR. METHODS: Ninety participants underwent 4D flow cardiovascular magnetic resonance: 30 BAV patients with prior AVR (11 mechanical, 10 bioprosthetic, 9 Ross procedure), 30 BAV patients with a native aortic valve and 30 healthy subjects. RESULTS: The majority of subjects with mechanical AVR or Ross showed normal flow pattern (73% and 67% respectively) with near normal rotational flow values (7.2 ± 3.9 and 10.6 ± 10.5 mm2/ms respectively vs 3.8 ± 3.1 mm2/s for healthy subjects; both p > 0.05); and reduced in-plane wall shear stress (0.19 ± 0.13 N/m2 for mechanical AVR vs. 0.40 ± 0.28 N/m2 for native BAV, p < 0.05). In contrast, all subjects with a bioprosthetic AVR had abnormal flow patterns (mainly marked right-handed helical flow), with comparable rotational flow values to native BAV (20.7 ± 8.8 mm2/ms and 26.6 ± 16.6 mm2/ms respectively, p > 0.05), and a similar pattern for wall shear stress. Data before and after AVR (n = 16) supported these findings: mechanical AVR showed a significant reduction in rotational flow (30.4 ± 16.3 → 7.3 ± 4.1 mm2/ms; p < 0.05) and in-plane wall shear stress (0.47 ± 0.20 → 0.20 ± 0.13 N/m2; p < 0.05), whereas these parameters remained similar in the bioprosthetic AVR group. CONCLUSIONS: Abnormal flow patterns in BAV disease tend to normalize after mechanical AVR or Ross procedure, in contrast to the remnant abnormal flow pattern after bioprosthetic AVR. This may in part explain different aortic growth rates post AVR in BAV observed in the literature, but requires confirmation in a prospective study.

Test-retest variability of left ventricular 4D flow cardiovascular magnetic resonance measurements in healthy subjects.

BACKGROUND: Quantification and visualisation of left ventricular (LV) blood flow is afforded by three-dimensional, time resolved phase contrast cardiovascular magnetic resonance (CMR 4D flow). However, few data exist upon the repeatability and variability of these parameters in a healthy population. We aimed to assess the repeatability and variability over time of LV 4D CMR flow measurements. METHODS: Forty five controls underwent CMR 4D flow data acquisition. Of these, 10 underwent a second scan within the same visit (scan-rescan), 25 returned for a second visit (interval scan; median interval 52 days, IQR 28-57 days). The LV-end diastolic volume (EDV) was divided into four flow components: 1) Direct flow: inflow that passes directly to ejection; 2) Retained inflow: inflow that enters and resides within the LV; 3) Delayed ejection flow: starts within the LV and is ejected and 4) Residual volume: blood that resides within the LV for > 2 cardiac cycles. Each flow components' volume was related to the EDV (volume-ratio). The kinetic energy at end-diastole (ED) was measured and divided by the components' volume. RESULTS: The dominant flow component in all 45 controls was the direct flow (volume ratio 38 ± 4%) followed by the residual volume (30 ± 4%), then delayed ejection flow (16 ± 3%) and retained inflow (16 ± 4%). The kinetic energy at ED for each component was direct flow (7.8 ± 3.0 microJ/ml), retained inflow (4.1 ± 2.0 microJ/ml), delayed ejection flow (6.3 ± 2.3 microJ/ml) and the residual volume (1.2 ± 0.5 microJ/ml). The coefficients of variation for the scan-rescan ranged from 2.5%-9.2% for the flow components' volume ratio and between 13.5%-17.7% for the kinetic energy. The interval scan results showed higher coefficients of variation with values from 6.2-16.1% for the flow components' volume ratio and 16.9-29.0% for the kinetic energy of the flow components. CONCLUSION: LV flow components' volume and their associated kinetic energy values are repeatable and stable within a population over time. However, the variability of these measurements in individuals over time is greater than can be attributed to sources of error in the data acquisition and analysis, suggesting that additional physiological factors may influence LV flow measurements.

Dilated Cardiomyopathy: Phosphorus 31 MR Spectroscopy at 7 T.

Purpose To test whether the increased signal-to-noise ratio of phosphorus 31 (31P) magnetic resonance (MR) spectroscopy at 7 T improves precision in cardiac metabolite quantification in patients with dilated cardiomyopathy (DCM) compared with that at 3 T. Materials and Methods Ethical approval was obtained, and participants provided written informe consent. In a prospective study, 31P MR spectroscopy was performed at 3 T and 7 T in 25 patients with DCM. Ten healthy matched control subjects underwent 31P MR spectroscopy at 7 T. Paired Student t tests were performed to compare results between the 3-T and 7-T studies. Results The phosphocreatine (PCr) signal-to-noise ratio increased 2.5 times at 7 T compared with that at 3 T. The PCr to adenosine triphosphate (ATP) concentration ratio (PCr/ATP) was similar at both field strengths (mean ± standard deviation, 1.48 ± 0.44 at 3 T vs 1.54 ± 0.39 at 7 T, P = .49), as expected. The Cramér-Rao lower bounds in PCr concentration (a measure of uncertainty in the measured ratio) were 45% lower at 7 T than at 3 T, reflecting the higher quality of 7-T 31P spectra. Patients with dilated cardioyopathy had a significantly lower PCr/ATP than did healthy control subjects at 7 T (1.54 ± 0.39 vs 1.95 ± 0.25, P = .005), which is consistent with previous findings. Conclusion 7-T cardiac 31P MR spectroscopy is feasible in patients with DCM and gives higher signal-to-noise ratios and more precise quantification of the PCr/ATP than that at 3 T. PCr/ATP was significantly lower in patients with DCM than in control subjects at 7 T, which is consistent with previous findings at lower field strengths.

Mechanical circulatory support in patients with congenital heart disease: a European Registry for Patients with Mechanical Circulatory Support (EUROMACS) study.

OBJECTIVES: This study aims to explore characteristics and clinical outcomes of patients with congenital heart disease (CHD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). METHODS: This is a retrospective study of EUROMACS participants receiving MCS as bridge-to-transplant, possible bridge-to-transplant, or rescue therapy/bridge-to-recovery from 2011 to 2023 (n = 5340). Adult and paediatric cohorts were analysed separately. The primary outcome was mortality on MCS; secondary outcomes included recovery, transplant and complications including bleeding, cerebrovascular events, and sepsis. RESULTS: Among adult patients, mortality at 1-year was 33.3% among the CHD cohort vs 22.1% in the non-CHD cohort. Adult CHD patients had higher hazards of mortality within the first year after MCS implantation [hazard ratios 1.98, 95% confidence interval (CI) 1.35-2.91, P < 0.001] and bleeding events (subdistribution hazard ratios 2.10, 95% CI 1.40-3.16, P < 0.001) compared with non-CHD patients. Both associations remained significant after accounting for multiple mediators. Among paediatric patients, mortality at 1 year was 22.1% in the CHD cohort vs 17.3% in the non-CHD cohort (hazard ratios 1.39, 95% CI 0.83-2.32, P = 0.213). CONCLUSIONS: Adult and paediatric patients with CHD on MCS have higher adverse event risk compared with non-CHD MCS patients, though children did not have greater risk of mortality. As the number of CHD patients requiring advanced heart failure management continues to grow, these findings can enhance informed decision-making. CLINICAL TRIAL REGISTRATION NUMBER: Registry name: EUROMACS.

Pregnancy outcomes in women following the Ross procedure.

INTRODUCTION: The Ross procedure, where a pulmonary autograft (neoaorta) replaces the aortic valve, has excellent long-term outcomes in patients with congenital aortic valve disease. However, there are reports of neoaortic dilatation and dissection. An increasing number of women are wishing to become pregnant following the Ross procedure, but little is known about the occurrence and risks of neoaortic dilatation and complications in pregnancy. We investigated neoaorta function and outcomes in pregnancy following the Ross procedure. METHODS: This retrospective study investigated women post-Ross procedure at a tertiary ACHD unit between 1997 and 2021. Imaging evaluated neoaortic root dimensions and regurgitation pre-, and post- pregnancy, compared with matched non-pregnant controls. Primary endpoints were change in neoaortic dimensions, degree of regurgitation and adverse maternal outcomes. RESULTS: Nineteen pregnancies in 12 women were included. The mean change in neoaortic root diameter post-pregnancy was 1.8 mm (SD 3.4) (p = 0.017). There was no significant change in neoaortic dimensions in matched controls during follow-up. There were no cases of dissection, arrhythmia, acute coronary syndrome, or maternal mortality. Three deliveries were pre-term, including one emergency Caesarean section due to maternal cardiac decompensation, requiring aortic root replacement post-partum but there were no neonatal deaths. CONCLUSIONS: Pregnancy following the Ross procedure is associated with neoaortic dilatation, and pregnancy is generally well tolerated. Although adverse maternal outcomes are uncommon, there are still rare cases of cardiac complications in and around the time of pregnancy. These findings emphasise the need for accessible pre-pregnancy counselling, risk stratification and careful surveillance through pregnancy by specialist cardio-obstetric multi-disciplinary teams.

Heart failure in adults with congenital heart disease: a narrative review.

The number of adults with congenital heart disease (ACHD) has increased over the last decades due to advancements in medical care, including interventional and surgical therapies. We are therefore more frequently challenged by the long-term consequences of palliative or corrective surgery carried out during childhood. Although patients with ACHD may develop conditions related to general cardiovascular risk factors, such as coronary artery disease, the most common complications leading to morbidity and mortality are arrhythmias, heart failure and thromboembolic events. For the management of arrhythmias, current recommendations regarding ablation and device therapy must be considered, whilst also taking into account the anatomical limitations of their congenital heart defect or surgical pathways. Heart failure treatment in acute and chronic settings must also consider the particular anatomy present, including the nature of the systemic ventricle. Treatments strategies for ACHD are typically extrapolated from the respective guidelines in non-ACHD patients, despite a lack of evidence to support this strategy. Right heart failure can be especially challenging to manage in conditions where either a systemic right ventricle or shunt lesions resulting in volume and/or pressure loading of the right ventricle are present. All physicians and cardiologists in particular should be acquainted with the most common diseases in ACHD, their complications and management regime, especially with regards to heart failure as this is a common reason for acute presentation in the emergency department.

Cardiovascular Effects of Unilateral Nephrectomy in Living Kidney Donors at 5 Years.

[Figure: see text].

Cavotricuspid isthmus dependent flutter is associated with an increased incidence of occult coronary artery disease.

AIMS: Atrial flutter (AFl) and atrial fibrillation (AFib) share many clinical risk factors and potential mechanisms with atherosclerosis. Despite this, an association between stable coronary artery disease (CAD) and atrial arrhythmias has not previously been documented. To investigate this hypothesis we measured the incidence of occult coronary atheroma on coronary angiography inpatients undergoing radiofrequency ablation procedures. METHODS AND RESULTS: Consecutive coronary angiograms performed on patients with no history or symptoms of CAD undergoing elective ablation of arrhythmias were analysed. Patients were divided into three groups according to their arrhythmia: Typical right AFl, AFib, and a matched control group undergoing ablation for either atrioventricular node-dependent supraventricular tachycardia (SVT) or idiopathic right ventricular outflow tract tachycardia (RVOT). Atherosclerosis on angiography was graded according to the most severe stenosis. A total of 138 patients were included. Groups were evenly matched for age (P = 0.4), risk factors for coronary disease including hypertension (P = 0.38) and diabetes (P = 0.2). The incidence of asymptomatic, occult coronary atheroma was significantly greater in patients with AFl (AFl 54%, AFib 26%, SVT/RVOT 21%, P = 0.005). In contrast there was no higher incidence of occult atheroma in patients with AFib than those with SVT/RVOT (P = 0.68). The majority of atherosclerosis observed was mild, non-obstructive plaque disease (AFl 75%, AFib 44%, SVT/RVOT 67%). CONCLUSION: There was a significantly greater incidence of occult coronary atheroma in asymptomatic patients undergoing ablation for AFl, suggesting that the mechanism underlying the development of atherosclerosis may also be important in creating the substrate that allows typical right AFl to develop.

Late complication of intramural coronary transfer during the arterial switch operation.

Intramural coronary arteries remain a major risk factor and technical challenge of the arterial switch operation for transposition of the great arteries. We report a 27-year-old woman who presented with acute coronary syndrome late after arterial switch with a complex coronary pattern (intramural left and right coronary from sinus 2). Computed tomography demonstrated that the pericardial 'saddle bag' used to reconstruct the intramural coronary was compressed between the neoaortic root and the neopulmonary trunk. During surgery, the coronary system was laid open into the neoaorta with patch enlargement, and the patient made an uneventful recovery.

Left Ventricular Flow Analysis.

BACKGROUND: Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity. Methods Thirty-four dilated cardiomyopathy patients, 30 ischemic cardiomyopathy patients, and 36 controls underwent magnetic resonance including 4-dimensional flow, BNP (brain-type natriuretic peptide) measurement, functional capacity assessment (6-minute walk test), and symptom quantification. A subgroup of dilated cardiomyopathy and control subjects underwent cardiac energetic assessment. Left ventricular flow was separated into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average KE throughout the cardiac cycle was calculated. RESULTS: Patients had reduced direct flow proportion and direct-flow average KE compared with controls ( P<0.0001). The residual volume proportion and residual volume average KE were increased in patients ( P<0.0001). Importantly, in a multiple linear regression model to predict the patient's 6-minute walk test, the independent predictors were age (ß=-0.3015; P=0.019) and direct-flow average KE (ß=0.280, P=0.035; R2 model, 0.466, P=0.002). In contrast, neither ejection fraction nor left ventricular volumes were independently predictive. CONCLUSIONS: This study demonstrates an independent predictive relationship between the direct-flow average KE and a prognostic measure of functional capacity. Intracardiac 4-dimensional flow parameters are novel biomarkers in heart failure and may provide additive value in monitoring new therapies and predicting prognosis.

Pregnancy Outcomes in Women With Transposition of the Great Arteries After an Arterial Switch Operation.

Importance: A growing number of women are approaching childbearing age after arterial switch surgery for transposition of the great arteries. Prepregnancy counseling requires updated knowledge of the additional cardiovascular risks pregnancy poses for this cohort of women and the potential effect on their offspring; however, to our knowledge, this information is currently unknown. Objective: To determine the pregnancy outcomes of women with transposition of the great arteries after an arterial switch operation, as well as the outcomes of their offspring. Design, Setting, and Participants: This cohort study assessed women who had had arterial switch surgery from 1985 to the present and who were 16 years or older as of January 2018. All women with a previous arterial switch surgery for transposition of the great arteries with completed or ongoing pregnancy were included. Data were collected in a level 1 congenital cardiology center and joint obstetrics-cardiology clinic in Birmingham, United Kingdom. Exposures: Patients were assessed before, during, and after pregnancy. Main Outcomes and Measures: Adverse maternal cardiac events (arrhythmia, heart failure, aortic dissection, or acute coronary syndrome) and aortic root dilatation, aortic regurgitation, and left ventricular function before and after pregnancy were the main outcomes. Mode of delivery and fetal outcomes were considered secondary outcomes. Results: A total of 25 pregnancies were identified in 15 women; 8 women had had 1 pregnancy, while 7 were multiparous. There were no adverse maternal cardiac events. Before pregnancy, 8 women (53%) had no aortic regurgitation, 1 (7%) had a trivial degree of regurgitation, 4 (26%) had mild regurgitation, and 2 (14%) had moderate regurgitation. After pregnancies, 1 woman (7%) had minor progression of aortic regurgitation. Five women (36%) had mild neoaortic root dilatation prepregnancy, but none developed progressive dilatation in the first year post-partum. A total of 24 pregnancies were completed by the end of the study, with all infants born alive and well. Nineteen modes of delivery were known; there were 7 cesarean deliveries (37%), of which 2 (11%) were recommended for aortic dilatation and 5 (26%) for obstetric indications or maternal choice. Conclusions and Relevance: Pregnancy is well tolerated after arterial switch operation; no adverse maternal cardiac events or early progression of neoaortic root dilatation or aortic regurgitation were observed in this study. These results provide evidence to allow reassurance of women with previous arterial switch surgery who are planning pregnancies.