Regression of Cardiac Rhabdomyomas Producing a Severe Aortic Stenosis: Case Report and Discussion of the Literature.

We describe a case of a voluminous rhabdomyoma (R) detected by fetal echocardiography at 32 weeks' gestation (w.g.) obstructing the left ventricular inflow and aortic outflow tract, with a moderate aortic gradient at birth, not needing immediate surgery. At follow-up, the mass progressively regressed, leaving the aortic valve partly damaged, with a gradient that increased to a maximum of 100 mmHg at 9 years. The girl was then operated on successfully by a plasty of the aortic valve. The literature regarding R is discussed.

Modern tools in congenital heart disease imaging and procedure planning: a European survey.

AIMS: Congenital heart diseases (CHDs) often show a complex 3D anatomy that must be well understood to assess the pathophysiological consequences and to guide therapy. Three-dimensional imaging technologies have the potential to enhance the physician's comprehension of such spatially complex anatomies. Unfortunately, due to the new introduction in clinical practice, there is no evidence on the current applications. We conducted a survey to examine how 3D technologies are currently used among CHD European centres. METHODS: Data were collected using an online self-administered survey via SurveyMonkey. The questionnaire was sent via e-mail and the responses were collected between January and June 2022. RESULTS: Ninety-eight centres correctly completed the survey. Of these, 22 regularly perform 3D rotational angiography, 43 have the availability to print in-silico models, and 22 have the possibility to visualize holographic imaging/virtual reality. The costs were mostly covered by the hospital or the department of financial resources. CONCLUSION: From our survey, it emerges that these technologies are quite spread across Europe, despite not being part of a routine practice. In addition, there are still not enough data supporting the improvement of clinical management for CHD patients. For this reason, further studies are needed to develop clinical recommendations for the use of 3D imaging technologies in medical practice.

Prenatal Diagnosis and Postnatal Outcomes of Left Brachiocephalic Vein Abnormalities: Systematic Review.

Abnormalities of the left brachiocephalic vein (LBCVA) are rare and poorly studied prenatally. An association with congenital heart defects (CHD), extracardiac and genetic abnormalities was described. The aim of our study was to estimate the rate and summarize the available evidence concerning prenatal diagnosis, associated anomalies, and outcomes of these anomalies. A systematic literature review was carried out selecting studies reporting on prenatal diagnosis of LBCVA, including unpublished cases from our experience. Frequencies were pooled from cohort studies to calculate prenatal incidence. Pooled proportions were obtained from all the studies including rates of associated CHD, extracardiac or genetic abnormalities and neonatal outcomes. The search resulted in the selection of 16 studies with 311 cases of LBCVA, with an incidence of 0.4% from six cohort studies. CHD occurred in 235/311 (75.6%) fetuses: 23 (7.4%) were major in cases of double, retroesophageal or subaortic course and 212 (68.2%) were minor in cases of absence (always associated with a persistent left superior vena cava) or intrathymic course. Data on other associated outcomes were scarce showing rare extracardiac anomalies (3.5%), rare genetic abnormalities (RASopathies and microdeletions associated with the retroesophageal course), and neonatal outcomes favorable in most cases, particularly in intrathymic forms.

Prevalence of Congenital Heart Defects in Pregnancies Conceived by Assisted Reproductive Technology: A Cohort Study.

BACKGROUND AND AIM OF THE STUDY: Pregnancies obtained by assisted reproductive technology (ART) are associated with an increased risk of complications and congenital anomalies, particularly congenital heart defects (CHDs). Therefore, our aim is to evaluate, retrospectively, the prevalence of CHD in ART pregnancies in our two centers and analyze their characteristics and outcomes. METHODS: Observational study including fetuses conceived by ART referred between June 2011 and September 2020 and undergoing a fetal cardiac ultrasound scan. Cases with genetic, chromosomal abnormalities or extracardiac malformations were excluded. Population included 1511 pregnancies, which consisted of 269 twins and 1242 singletons, 547 IVF (in vitro fertilization), 773 ICSI (intracytoplasmic sperm injection) and 191 oocyte donations (OD). RESULTS: CHDs were found in 29 fetuses, with an overall prevalence of 1.92% (29/1511), 1.85% (23/1242) in singletons and 2.23% in twins (6/269). Thirteen were IVF, eight ICSI and eight OD cases, with a greater risk of CHD after IVF and OD (IVF: 13/29 (44.8%)-one twin; ICSI: 8/29 (27.6%)-three twins); 22 had major and 7 minor defects. Two pregnancies with a hypoplastic left heart were terminated; the majority of live-born cases needed surgery. Three babies died (two post-surgery, one had a late death). CONCLUSIONS: Our data show an increased prevalence of CHD after ART with a heterogeneous spectrum of diagnoses, mainly major defects.

Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R).

AIM: Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. METHODS AND RESULTS: The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R) will collect data from ACHD evaluated or listed for heart or heart-combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989-2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All-cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. CONCLUSION: The ARTORIA-R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

Outcomes and Quality of Life After Ross Reintervention: Would You Make the Same Choice Again?

BACKGROUND: The Ross procedure was introduced as a long-term if not definitive solution for aortic pathology. However, the rate of reoperation is not negligible. METHODS: This single-center prospective study assessed the general outcome of Ross reoperation and patients' perceived quality of life compared with 2 control groups (Ross non-reoperation and mechanical aortic valve replacement). Patient's preference regarding the choice between mechanical aortic valve and Ross procedure was investigated in a subgroup that could theoretically have been directed to either of the 2 procedures. RESULTS: Between 2005 and 2017, 64 consecutive patients underwent reoperation after Ross. Median age was 31 years. Median freedom from reoperation after the Ross procedure was 136 months. An autograft reoperation was required in 49, and 25 had homograft failure. No in-hospital death was recorded. Mean follow-up was 77 months (range, 6-164 months). Quality of life was assessed with the 36-Item Short Form Health Survey questionnaire. The Ross reoperation group showed a lower score involving psychological concerns compared with the other groups. In the reoperated-on patients group, 52 had adequate aortic annulus dimensions to receive a prosthetic valve instead of a Ross procedure. When asked whether they would make the same choice, only 31% confirmed the preference. CONCLUSIONS: Reoperations after Ross procedure have low mortality and morbidity. Long-term follow-up showed a high quality of life, even after reoperations. However, owing to psychological concerns after the redo operation, when choosing a Ross procedure, it is our duty to thoroughly explain to patients that a high level of disillusion is predictable in case of reoperations.

Phosphodiesterase type 3A (PDE3A), but not type 3B (PDE3B), contributes to the adverse cardiac remodeling induced by pressure overload.

Phosphodiesterase type 3 (PDE3) inhibitors block the cAMP hydrolyzing activity of both PDE3 isoforms, PDE3A and PDE3B, which have distinct roles in the heart. Although PDE3 inhibitors improve cardiac function in heart disease patients, they also increase mortality. Nevertheless, PDE3 inhibitors can provide benefit to non-ischemic heart disease patients and are used extensively to treat heart failure in dogs. Since the isoform-dependence of the complex cardiac actions of PDE3 inhibition in diseased hearts remains unknown, we assessed the effects of PDE3 inhibitors as well as gene ablation of PDE3A or PDEB in mice following the induction of non-ischemic heart disease by pressure-overload with transverse-aortic constriction (TAC). As expected, after 6 weeks of TAC, mice exhibited left ventricular contractile dysfunction, dilation, hypertrophy and interstitial fibrosis, in association with increased macrophage numbers, activation of p38 MAPK and elevated PDE3 activity. Chronic PDE3 inhibition with milrinone (MIL), at doses that did not affect either cardiac contractility or arterial blood pressure, profoundly attenuated the adverse ventricular remodeling, reduced macrophage number and diminished p38-MAPK activation induced by TAC. Surprisingly, whole-body ablation of PDE3A, but not PDE3B, provided similar protection against TAC-induced adverse ventricular remodeling, and the addition of MIL to mice lacking PDE3A provided no further protection. Our results support the conclusion that PDE3A plays an important role in adverse cardiac remodeling induced by chronic pressure overload in mice, although the underlying biochemical mechanisms remain to be fully elucidated. The implications of this conclusion on the clinical use of PDE3 inhibitors are discussed.

Italian survey on cardiac surgery for adults with congenital heart disease: which surgery, where and by whom?

OBJECTIVES: The population of ageing adults with congenital heart disease (ACHD) is increasing; surgery in these patients presents major difficulties in management. A great debate has developed about whether these patients should be cared for at an adult or paediatric hospital and by an acquired or congenital cardiac surgeon. We analysed data of the surgical treatment of ACHD from the Italian cardiac surgery centres in 2016, focusing on the type of surgery performed, where these patients were operated on and by whom. METHODS: Ninety-two Italian cardiac surgery centres were contacted and 70 centres participated in this study. We collected data on the types of cardiac operations performed in congenital heart defect patients older than 18 years. In 2016, a total of 913 patients with ACHD were operated on: 440 by congenital cardiac surgeons (group I) in centres with paediatric and adult cardiac surgery units, and 473 by adult cardiac surgeons (group II) in centres with exclusively adult cardiac surgery units. RESULTS: Pathologies of the right ventricular outflow tract were the most frequent diseases treated in group I and pathologies of the left ventricular outflow tract in group II. Group I included more complex and heterogeneous cases than group II. Surgery for ACHD represented 12% of the activity of congenital cardiac surgeons and only 1% of the activity of adult cardiac surgeons. CONCLUSIONS: In Italy, ACHD patients are operated on both by congenital and adult cardiac surgeons. Congenital cardiac surgeons working in centres with both paediatric and adult cardiac surgery are more involved with ACHD patients and with more complex cases.

Irx3 is required for postnatal maturation of the mouse ventricular conduction system.

The ventricular conduction system (VCS) orchestrates the harmonious contraction in every heartbeat. Defects in the VCS are often associated with life-threatening arrhythmias and also promote adverse remodeling in heart disease. We have previously established that the Irx3 homeobox gene regulates rapid electrical propagation in the VCS by modulating the transcription of gap junction proteins Cx40 and Cx43. However, it is unknown whether other factors contribute to the conduction defects observed in Irx3 knockout (Irx3(-/-)) mice. In this study, we show that during the early postnatal period, Irx3(-/-) mice develop morphological defects in the VCS which are temporally dissociated from changes in gap junction expression. These morphological defects were accompanied with progressive changes in the cardiac electrocardiogram including right bundle branch block. Hypoplastic VCS was not associated with increased apoptosis of VCS cardiomyocytes but with a lack of recruitment and maturation of ventricular cardiomyocytes into the VCS. Computational analysis followed by functional verification revealed that Irx3 promotes VCS-enriched transcripts targeted by Nkx2.5 and/or Tbx5. Altogether, these results indicate that, in addition to ensuring the appropriate expression of gap junctional channels in the VCS, Irx3 is necessary for the postnatal maturation of the VCS, possibly via its interactions with Tbx5 and Nkx2.5.

Negative feedback regulation of Homer 1a on norepinephrine-dependent cardiac hypertrophy.

Homers are scaffolding proteins that modulate diverse cell functions being able to assemble signalling complexes. In this study, the presence, sub-cellular distribution and function of Homer 1 was investigated. Homer 1a and Homer 1b/c are constitutively expressed in cardiac muscle of both mouse and rat and in HL-1 cells, a cardiac cell line. As judged by confocal immunofluorescence microscopy, Homer 1a displays sarcomeric and peri-nuclear localization. In cardiomyocytes and cultured HL-1 cells, the hypertrophic agonist norepinephrine (NE) induces α1-adrenergic specific Homer 1a over-expression, with a two-to-three-fold increase within 1h, and no up-regulation of Homer 1b/c, as judged by Western blot and qPCR. In HL-1 cells, plasmid-driven over-expression of Homer 1a partially antagonizes activation of ERK phosphorylation and ANF up-regulation, two well-established, early markers of hypertrophy. At the morphometric level, NE-induced increase of cell size is likewise and partially counteracted by exogenous Homer 1a. Under the same experimental conditions, Homer 1b/c does not have any effect on ANF up-regulation nor on cell hypertrophy. Thus, Homer 1a up-regulation is associated to early stages of cardiac hypertrophy and appears to play a negative feedback regulation on molecular transducers of hypertrophy.