Progressive Ventricular Dilatation Research Articles

Correlation of ECG and cardiac MRI for assessment of ventricular hypertrophy and dilatation in adults with repaired tetralogy of Fallot

BackgroundSurgically repaired Tetralogy of Fallot (rTOF) is associated with progressive right ventricular hypertrophy (RVH) and dilation (RVD). Accurate estimation of RVH/RVD is vital for the ongoing management of this patient population. The utility of the ECG in evaluating patients with rTOF with pre-existing right bundle branch block (RBBB) has not been studied. We aimed to determine the sensitivity/specificity of currently established ECG criteria in detecting RVH/RVD in this patient population. MethodsWe included consecutive patients diagnosed with rTOF who underwent CMR performed at our regional referral centre between January 2012 and December 2019. Each CMR was assessed for LVH, LVD, RVH and or RVD. The ECG corresponding to the CMR was then used to determine RVH/LVH for specificity and sensitivity analysis. ResultsOur study included 163 consecutive rTOF patients. The specificity for ECG-based criteria for LVH was 100.00% (95% C.I. (87.75, 100.00)), and the sensitivity was 7.19% (95% C.I. (3.15, 12.83)). When RBBB was present, specificity for RVH was 100.00% (95% C.I. (84.56, 100.00)), and sensitivity was 7.69% (95% C.I. (3.75, 13.69)). When RBBB was absent, specificity for RVH was 100.00% (95% C.I. (15.81, 100.00)), and sensitivity was 0.00% (95% C.I. (0.00, 33.63)). A regression model with the entire group of 163 ToF patients, based on the Sokolow-Lyon criterion (sum of R in V1 + S in V5/V6), produced a new suggested criterion for the diagnosis of RVH in patients with rTOF, which was a sum of R in V1 + S in V5/V6 greater than 13.25 mm. This model's sensitivity for RVH detection was 69.1%, and specificity was 36.8%. ConclusionsStandard ECG voltage criteria have poor sensitivity for detecting right and left ventricular chamber hypertrophy and dilatation in patients with rTOF, so current ECG criteria should not be used to monitor RVH/RVD in this patient population.

Veno-Venous Coiling as A Strategy to Wean Extracorporeal Membrane Oxygenator Post Adult Fontan Completion

We discuss a case of veno-venous collaterals in a patient with Fontan circulation post complex redo-surgery, which impeded veno-venous extracorporeal membrane oxygenation (VV-ECMO) weaning. A 31-year-old male, born with complex congenital heart disease (D-transposition of the great vessels, tricuspid atresia, aortic coarctation, ventricular septal defect, and hypoplastic right ventricle) with single ventricle physiology. The patient underwent multiple cardiac surgeries leading to Fontan completion. He subsequently developed significant aortic regurgitation with progressive left ventricular dilatation requiring multiple readmissions for congestive heart failure. Despite maximal medical optimisation he remained symptomatic and was offered further surgery. Complex 6th redo-operation with aortic valve replacement, modification to intracardiac fenestrated Fontan and insertion of intra-aortic balloon pump was performed. At 72 hours postoperative, VV-ECMO was required for refractory hypoxia. Right heart catheterisation was performed with coiling of two large fistulous venous connections. Post-coiling saturations improved from 92% to 98%. The patient was successfully weaned from VV-ECMO and decannulated the following day. This case demonstrates successful embolisation for veno-venous collaterals causing significant right to left shunt and hypoxia, in a patient with Fontan circulation.

417 Factors Associated with the Development of Post-Traumatic Hydrocephalus Following a Decompressive Craniectomy: A Single Centre Experience

Abstract Introduction A decompressive craniectomy (DC) is a surgical procedure sometimes utilised to manage refractory intracranial hypertension following severe traumatic brain injury (sTBI). Previous studies have established a relationship between DC and post-traumatic hydrocephalus (PTH). This study aimed to identify the factors responsible for developing shunt-amenable post-traumatic hydrocephalus in patients who underwent DC following sTBI. Method A review of a prospectively collected database of all patients admitted with severe TBI in a tertiary neurosurgical centre in northwest England between January 2012 and May 2022 was performed. Post-traumatic hydrocephalus was defined as evidence of progressive ventricular dilatation, clinical deterioration, and/or the eventual need for CSF diversion (i.e. a ventriculoperitoneal shunt). Statistical analysis was carried out using IBM SPSS vs 28.0.1. Results 65 patients met the eligibility criteria and were included in the study. The mean age of the PTH group was 31.38+/-14.67, while the mean age of the non-PTH group was slightly higher at 39.96 +/- 14.85. No statistically significant difference was observed between the two groups' mechanisms of traumatic injury (MOI) (P = 0.945). Of the predictors investigated, cerebellar hematoma (and contusions) was significantly associated with post-traumatic hydrocephalus (p = 0.006). Conclusions This study concludes that cerebellar hematoma (and contusions) are associated with developing post-traumatic hydrocephalus in patients undergoing decompressive craniectomy.

Tenascin-C in Tissue Repair after Myocardial Infarction in Humans.

Adverse ventricular remodeling after myocardial infarction (MI) is progressive ventricular dilatation associated with heart failure for weeks or months and is currently regarded as the most critical sequela of MI. It is explained by inadequate tissue repair due to dysregulated inflammation during the acute stage; however, its pathophysiology remains unclear. Tenascin-C (TNC), an original member of the matricellular protein family, is highly up-regulated in the acute stage after MI, and a high peak in its serum level predicts an increased risk of adverse ventricular remodeling in the chronic stage. Experimental TNC-deficient or -overexpressing mouse models have suggested the diverse functions of TNC, particularly its pro-inflammatory effects on macrophages. The present study investigated the roles of TNC during human myocardial repair. We initially categorized the healing process into four phases: inflammatory, granulation, fibrogenic, and scar phases. We then immunohistochemically examined human autopsy samples at the different stages after MI and performed detailed mapping of TNC in human myocardial repair with a focus on lymphangiogenesis, the role of which has recently been attracting increasing attention as a mechanism to resolve inflammation. The direct effects of TNC on human lymphatic endothelial cells were also assessed by RNA sequencing. The results obtained support the potential roles of TNC in the regulation of macrophages, sprouting angiogenesis, the recruitment of myofibroblasts, and the early formation of collagen fibrils during the inflammatory phase to the early granulation phase of human MI. Lymphangiogenesis was observed after the expression of TNC was down-regulated. In vitro results revealed that TNC modestly down-regulated genes related to nuclear division, cell division, and cell migration in lymphatic endothelial cells, suggesting its inhibitory effects on lymphatic endothelial cells. The present results indicate that TNC induces prolonged over-inflammation by suppressing lymphangiogenesis, which may be one of the mechanisms underlying adverse post-infarct remodeling.

A Mouse Model of Dilated Cardiomyopathy Produced by Isoproterenol Acute Exposure Followed by 5-Fluorouracil Administration.

Appropriate dilated cardiomyopathy (DCM) animal models are highly desirable considering the pathophysiological and clinical heterogeneity of DCM. Genetically modified mice are the most widely and intensively utilized research animals for DCM. However, to translate discoveries from basic science into new and personalized medical applications, research in non-genetically based DCM models remains a key issue. Here, we characterized a mouse model of non-ischemic DCM induced by a stepwise pharmacologic regime of Isoproterenol (ISO) high dose bolus followed by a low dose systemic injection of the chemotherapy agent, 5-Fluorouracil (5-FU). C57BL/6J mice were injected with ISO and, 3 days after, were randomly assigned to saline or 5-FU. Echocardiography and a strain analysis show that ISO + 5FU in mice induces progressive left ventricular (LV) dilation and reduced systolic function, along with diastolic dysfunction and a persistent global cardiac contractility depression through 56 days. While mice treated with ISO alone recover anatomically and functionally, ISO + 5-FU causes persistent cardiomyocyte death, ensuing in cardiomyocyte hypertrophy through 56 days. ISO + 5-FU-dependent damage was accompanied by significant myocardial disarray and fibrosis along with exaggerated oxidative stress, tissue inflammation and premature cell senescence accumulation. In conclusions, a combination of ISO + 5FU produces anatomical, histological and functional cardiac alterations typical of DCM, representing a widely available, affordable, and reproducible mouse model of this cardiomyopathy.

PO-02-243 IMPACT OF PARTIAL CONSTRICTION OF THE ARTERIAL PULMONARY TRUNK ON THE DEVELOPMENT OF SUSCEPTIBILITY TO ATRIAL FIBRILLATION IN RATS

Atrial Fibrillation (AF) is the most frequent and clinically important form of cardiac arrhythmia. It has been demonstrated that cardiovascular comorbidities such as myocarditis, myocardial infarction, obesity, or pulmonary hypertension (PH) promote cardiac remodeling associated with the development of atrial arrhythmogenic substrates. Right-heart disease (RHD), characterized by chronic right-sided cardiac structural and functional anomalies, has also been designated among AF risk factors. Inflammation is one of the common denominators between cardiovascular risk factors and AF vulnerability. However, no study has described the progression of the molecular and cellular changes involved in the causal link relating RHD, the activation of atrial inflammation, and the development of AF substrate. This study aims to establish the characterization of the progression of atrial arrhythmogenic inflammation in a rat model of RHD. Hypothesis Permanent constriction of the pulmonary artery trunk (PAT) provokes severe RHD associated with progressive atrial inflammation and fibrosis responsible for enhanced AF vulnerability. Pulmonary Artery Banding (PAB) reducing the PAT diameter to 1 mm, was surgically performed on 225-275g Wistar rats to induce permanent PH and severe RHD. Sham animals received PAB-mimicking intervention without ligation. Echocardiography and electrophysiological studies (EPS) were performed in vivo, on all the animals at Day0, Day7, Day14 and Day21 post-surgery. The atrial tissues were analyzed by optical mapping, histology (Masson's Trichrome), qPCR and immunoblotting. Within three weeks, PAB rats developed severe right heart remodeling characterized by progressive ventricular and atrial hypertrophy and dilation. Right atrial (RA) optical mapping revealed a reduction in conduction velocity and refractory periods in PAB rats compared to Sham. PAB rats were more vulnerable to AF than Sham starting at 7th-day until the 21st-day post-surgery. Histological analysis shows that since the 14th day until the 21st-day post-surgery RA fibrosis significantly increased in PAB rats compared to sham. Quantitative polymerase chain reaction performed on inflammation and fibrosis-related genes such as IL6, Tgfb1 or Col1a1 revealed a progressive aggravation of RA inflammatory and fibrotic status in PAB rats from Day7, Day14 to Day2 Severe RHD is associated with progressive and unresolved RA inflammation and fibrosis provoking an aggravation of AF vulnerability overtime

A novel gene therapy for familial dilated cardiomyopathy based upon disruption of PP2A -- mAKAP-beta signalosomes

Familial Dilated Cardiomyopathy (DCM) is a common inherited cause of heart failure characterized by progressive left ventricular dilatation and systolic dysfunction. Despite the discovery of novel genetic mutations causing DCM, the downstream mechanisms resulting in heart failure are still unclear, and there remains a great unmet clinical need. Contributing to the phenotype of ventricular dilatation in DCM is the lengthening of cardiac myocytes, which exhibit increased overall length to width ratio. We have shown that increasing the phosphorylation of the transcription factor serine response factor (SRF) at serine residue 103 by displacement of protein phosphatase 2A (PP2A) from the perinuclear scaffold protein muscle A-kinase anchoring protein β (mAKAPβ) can inhibit myocyte lengthening and improve cardiac function following myocardial infarction. Notably, SRF S103 phosphorylation is decreased in both human heart failure and in the hearts of transgenic mice expressing the human DCM α-tropomyosin Glu54Lys (Tm-E54K) mutant allele. We now show that, accordingly, targeting of mAKAPβ-PP2A signalosomes constitutes a new therapeutic strategy for DCM. A self-complementary serotype 9 adeno-associated virus (AAV9sc) conferring cardiac-specific expression of a mAKAPβ fragment comprising the PP2A binding domain (PBD) was used to target the signalosomes in mice. AAV9sc.PBD administration into neonatal Tm-E54K mice provided long term preservation of cardiac function and prevented ventricular dilatation. At 16 weeks of age, ejection fraction was significantly improved 14%[MK1], and wall thickness was increased for AAV9sc.PBD TM-E54K mice when compared with control AAV9sc.GFP treated TM-E54K mice. Morphometry of acutely dissociated adult mouse myocytes showed that AAV9sc.PBD treatment restored myocyte length to width ratio to that of non-transgenic animals, while western blots showed increased SRF S103 phosphorylation. The results in mice have been corroborated by PBD expression in engineered heart tissues (EHT) generated from an induced pluripotent stem cell (iPSC) line for a DCM phospholamban R14del patient. PBD expression increased SRF S103 phosphorylation and improved tissue contractility. Taken together, this study suggests that increasing SRF S103 phosphorylation by disruption of mAKAPβ-PP2A signalosomes can constitute a novel therapeutic strategy for DCM. Funded by Department of NIH Grant R01HL146111 (Dr. Kapiloff), R01 HL139679 and Leducq Foundation CurePlan (Dr. Karakikes), and the NHLBI Gene Therapy Resource Program. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ventriculo-peritoneal shunt obstructions in the absence of radiological abnormalities: retrospective analysis of a pediatric cohort

Introduction: Ventriculoperitoneal shunts are still the mainstay treatment for pediatric
 hydrocephalus. They have a high complication and failure rate, requiring multiple revisions.
 In this study, we aim to investigate patients who required shunt replacement without any
 radiological findings.
 Methods: The files of patients under the age of 18, who underwent shunt revision between
 December 2015 and December 2020 in Bursa Uludag University Medical Faculty Neurosurgery clinic were reviewed retrospectively. All the radiological studies, laboratory results and clinical condition of the patients were examined.
 Results: We identified 127 patients who required a revision of ventriculoperitoneal shunt for suspected mechanical obstruction. 6 patients (5%) had symptoms of raised
 intracranial pressure, but showed no radiographic evidence of progressive ventricular
 dilatation.
 Conclusion: Dysfunction of a ventriculoperitoneal shunt does not always lead to associated radiological alterations. In a patient with signs of intracranial hypertension, revision of the system should be considered even in the absence of progressive ventricular dilatation on radiological studies.

Staged Percutaneous Management of Pulmonary Atresia and Intact Interventricular Septum: Stretching the Limits.

Pulmonary atresia with intact ventricular septum (PA/IVS) can be treated by catheter-based interventions and complemented by various surgical procedures. We aim to determine a long-term treatment strategy to enable patients to be surgery free, depending solely on percutaneous interventions. We selected five patients from among a cohort of patients with PA/IVS treated at birth with radiofrequency perforation and dilatation of the pulmonary valve. Patients had reached a pulmonary valve annulus of 20 mm or larger on their biannual echocardiographic follow-up, with right ventricular dilatation. The findings, together with the right ventricular outflow tract and pulmonary arterial tree, were confirmed by multislice computerised tomography. Based on the angiographic size of the pulmonary valve annulus, all patients were successfully implanted with either Melody® or Edwards® pulmonary valves percutaneously, regardless of their small weights and ages. No complications were encountered. We managed to stretch the age and weight limitations for performing percutaneous pulmonary valve implantation (PPVI): interventions were attempted whenever a pulmonary annulus size of >20 mm was reached, which was rationalised by the prevention of progressive right ventricular outflow tract dilatation and accommodating valves between 24 and 26 mm, which is enough to sustain a normal pulmonary flow in adulthood.

Factors associated with post traumatic hydrocephalus following decompressive craniectomy: A single-center experience.

A decompressive craniectomy (DC) is a surgical procedure sometimes utilized to manage refractory intracranial hypertension following severe traumatic brain injury (sTBI). The previous studies have established a relationship between DC and post traumatic hydrocephalus (PTH). This study aimed to identify the factors responsible for developing shunt-amenable PTH in patients who underwent DC following sTBI. A review of a prospectively collected database of all patients admitted with severe TBI in a tertiary neurosurgical center in North-west England between January 2012 and May 2022 was performed. PTH was defined as evidence of progressive ventricular dilatation, clinical deterioration, and/or the eventual need for cerebrospinal fluid diversion (i.e., a ventriculoperitoneal shunt). Statistical analysis was carried out using IBM SPSS versus 28.0.1. Sixty-five patients met the eligibility criteria and were included in the study. The mean age of the PTH group was 31.38 ± 14.67, while the mean age of the non-PTH group was slightly higher at 39.96 ± 14.85. No statistically significant difference was observed between the two groups' mechanisms of traumatic injury (P = 0.945). Of the predictors investigated, cerebellar hematoma (and contusions) was significantly associated with PTH (P = 0.006). This study concludes that cerebellar hematoma (and contusions) are associated with developing PTH in patients undergoing DC.

CDC-like kinase 4 deficiency contributes to pathological cardiac hypertrophy by modulating NEXN phosphorylation

Kinase-catalyzed phosphorylation plays a crucial role in pathological cardiac hypertrophy. Here, we show that CDC-like kinase 4 (CLK4) is a critical regulator of cardiomyocyte hypertrophy and heart failure. Knockdown of Clk4 leads to pathological cardiomyocyte hypertrophy, while overexpression of Clk4 confers resistance to phenylephrine-induced cardiomyocyte hypertrophy. Cardiac-specific Clk4-knockout mice manifest pathological myocardial hypertrophy with progressive left ventricular systolic dysfunction and heart dilation. Further investigation identifies nexilin (NEXN) as the direct substrate of CLK4, and overexpression of a phosphorylation-mimic mutant of NEXN is sufficient to reverse the hypertrophic growth of cardiomyocytes induced by Clk4 knockdown. Importantly, restoring phosphorylation of NEXN ameliorates myocardial hypertrophy in mice with cardiac-specific Clk4 deletion. We conclude that CLK4 regulates cardiac function through phosphorylation of NEXN, and its deficiency may lead to pathological cardiac hypertrophy. CLK4 is a potential intervention target for the prevention and treatment of heart failure.

Estrogen Receptor-β Agonists Modulate T-Lymphocyte Activation and Ameliorate Left Ventricular Remodeling During Chronic Heart Failure.

CD4+ T cells temporally transition from protective to pathological during ischemic heart failure (HF; 8 weeks postmyocardial infarction). Cellular mechanisms mediating this shift are unknown. RNA-sequencing of cardiac CD4+ T cells and flow cytometric analysis of immune cells was conducted. RNA-sequencing of CD4+ T cells from the failing hearts of male mice indicated activation of ER (estrogen receptor)-α signaling. Flow cytometric analysis showed that ERα in CD4+ T cells decreases significantly at 3-day postmyocardial infarction but increases during HF. To antagonize ERα, we tested a novel ERβ agonist (OSU-ERb-012) to inhibit T cells and blunt left ventricular remodeling. Proliferation assays showed that OSU-ERb-012 dose-dependently inhibited proliferation and proinflammatory cytokine expression in anti-CD3/CD28 stimulated splenic T cells isolated from both the sexes. For in vivo efficacy, 10- to 12-week-old male and ovariectomized female mice were randomized at 4 weeks postmyocardial infarction and treated with either vehicle or drug (60 mg/kg per day; oral). While vehicle-treated HF mice displayed progressive left ventricular dilatation with significantly increased end-systolic and end-diastolic volumes from 4 to 8 weeks postmyocardial infarction, treatment with OSU-ERb-012 significantly blunted these changes and stopped left ventricular remodeling in both the sexes. Reduction in tibia-normalized heart and left ventricular weights, cardiomyocyte hypertrophy and interstitial fibrosis further supported these results. Additionally, OSU-ERb-012 treatment selectively inhibited cardiac, splenic, and circulating CD4+ T cells without affecting other myeloid and lymphoid cells in the HF mice. Our studies indicate that ERβ agonists and OSU-ERb-012, in particular, could be used as selective immunomodulatory drugs to inhibit CD4+ T cells during chronic HF.

Thrombin Preconditioning Improves the Therapeutic Efficacy of Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage Induced Neonatal Rats.

Severe intraventricular hemorrhage (IVH) remains a major cause of high mortality and morbidity in extremely preterm infants. Mesenchymal stem cell (MSC) transplantation is a possible therapeutic option, and development of therapeutics with enhanced efficacy is necessary. This study investigated whether thrombin preconditioning improves the therapeutic efficacy of human Wharton’s jelly-derived MSC transplantation for severe neonatal IVH, using a rat model. Severe neonatal IVH was induced by injecting 150 μL blood into each lateral ventricle on postnatal day (P) 4 in Sprague-Dawley rats. After 2 days (P6), naïve MSCs or thrombin-preconditioned MSCs (1 × 105/10 μL) were transplanted intraventricularly. After behavioral tests, brain tissues and cerebrospinal fluid of P35 rats were obtained for histological and biochemical analyses, respectively. Thrombin-preconditioned MSC transplantation significantly reduced IVH-induced ventricular dilatation on in vivo magnetic resonance imaging, which was coincident with attenuations of reactive gliosis, cell death, and the number of activated microglia and levels of inflammatory cytokines after IVH induction, compared to naïve MSC transplantation. In the behavioral tests, the sensorimotor and memory functions significantly improved after transplantation of thrombin-preconditioned MSCs, compared to naïve MSCs. Overall, thrombin preconditioning significantly improves the therapeutic potential and more effectively attenuates brain injury, including progressive ventricular dilatation, gliosis, cell death, inflammation, and neurobehavioral functional impairment, in newborn rats with induced severe IVH than does naïve MSC transplantation.

Lupus anticoagulant in patients with systemic lupus erythematosus is associated with lower E/A ratio and progressive left ventricular dilatation: a five-year follow-up study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Copenhagen University Hospital Background Systemic lupus erythematosus (SLE) is an autoimmune disease with increased risk of cardiovascular complications such as coronary artery disease, myocarditis, pericarditis and valvular dysfunction. The pathophysiological mechanisms are poorly understood and clinical, biochemical and/or imaging markers to identify high risk patients are warranted. Purpose We aimed to identify SLE-characteristics that are associated with progressive cardiac dysfunction during a five-year follow-up period in patients with SLE. Methods A total of 147 patients with SLE were included from 2013 to 2014. All patients underwent standard echocardiography at baseline as well as a collection of blood samples, including a selection of biomarkers. Patients were invited to a five-year follow-up with a total of 108 patients (90 % female, mean age 46 ± 13 years, median disease duration of 14 (7-21) years) completing a full echocardiographic, laboratory, and clinical examination. Multivariate regression analyses with eight independent baseline variables of interest (age, sex, disease activity (SLEDAI-2K), lupus nephritis, ischemic heart disease (IHD), antiphospholipid antibodies (IgM and IgG), and lupus anticoagulant(LAC)) were performed as for the association with baseline echocardiographic parameters as well as for changes during follow-up. Only echocardiographic measurements that changed significantly (p < 0.01) during follow-up were selected for the regression analyses. Left ventricular end-diastolic volume index (LVEDVI) and E/A ratio were log-transformed at baseline in the regression analyses due to non-normality. Results During a five-year follow-up period, LVEDVI increased from 43.5 ± 13.9 to 52.5 ± 15.7 ml/m2 (p <0.001), and left ventricular diastolic measures declined (E/A ratio 1.4 ± 0.5 vs. 1.3 ± 0.5, p = 0.002; e’ velocity 12.8 ± 3.8 vs. 12.0 ± 3.7 ms, p = 0.02; mitral valve deceleration time 227.9 vs. 200.8 ms, p < 0.001), except for E/e’ (7.5 ± 3.8 vs. 6.8 ± 3.4, p = 0.02). Left ventricular ejection fraction remained stationary (59.5 ± 6.8 vs. 59.6 ± 6.4 %, p = 0.81). In multivariate regression analyses, presence of LAC was significantly associated with progressive left ventricular dilation during the follow-up period (p = 0.003) but not with higher baseline levels (p = 0.64) (Fig. A1 & A2). LAC was associated with lower E/A ratio at baseline (p = 0.005) but did not predict a decrease of E/A ratio during follow-up (p = 0.24) (Fig. B1 & B2). IHD was associated with higher LVEDVI at baseline (p = 0.004), but not with further progression of dilation (p = 0.07). Conclusion Presence of LAC was associated with lower E/A ratio at baseline as well as progressive left ventricular dilation during a five-year follow-up period. Hence, LAC might be a predictor of progressive cardiac dysfunction in patients with SLE. LAC is known to have implications for the microvascular circulation, but the clinical significance of the present findings is yet to be elucidated. Abstract Figure A Abstract Figure B

Serial echocardiography assessment and clinical outcomes among pregnant women with Tetralogy of Fallot

Abstract Funding Acknowledgements Type of funding sources: None. Following advancements in intracardiac repair of Tetralogy of Fallot (TOF), a greater proportion of patients survive well beyond child-bearing age. Pulmonary regurgitation (PR) and subsequent progressive right ventricular dilatation occur frequently as an intrinsic complication of surgical repair of TOF. High-output states such as pregnancy may exacerbate these late complications. The advocation of pre-pregnancy pulmonary valve replacement to mitigate pregnancy-related cardiac burden has remained controversial. This study aims to delineate the outcomes of pregnancy among women with repaired TOF. 105 pregnant episodes among were identified from a cohort of 240 adult female patients with TOF between 1990 to 2021. Patients with echocardiographic studies performed within 1 year prior to and following delivery were included for cardiac functional analysis. A paired sample t-test was performed to compare echocardiographic parameters between pre-delivery and post-delivery periods. Linear regression was used to identify changes to identify significant changes in echocardiographic parameters among patients with a baseline of severe PR. Within all pregnant episodes (n = 105), 65 successful pregnancies, 16 spontaneous miscarriages, 21 termination of pregnancies and 3 ectopic pregnancies were recorded. The mean maternal age was 28.9 (±6.7) years with deliveries at 37.86 (30-41) gestational weeks. Cardiovascular events occurred in 19 pregnancies with 4 patients having gestational hypertension, 4 patients with pre-eclampsia toxemia, 7 patients with heart failure symptoms and 4 patients with arrhythmias. Other complications included 4 patients with gestational diabetes mellitus, 3 patients with impaired glucose tolerance, 2 patients with anemia, 3 patients with maternal thyroid disease and 1 patients with proteinuria. Echocardiographic studies demonstrated significant changes in left ventricular ejection fraction (LVEF) (Pre-delivery = 60.69 ±8.73; post-delivery = 59.39 ±9.36) (P = 0.007), left ventricular end diastolic volume (LVEDV) (Pre-delivery: 89.71mL ±18.22mL; Post-delivery: 80.96mL ±12.32mL; P = 0.007), left end systolic volume (LVESV) (Pre-delivery: 35.43 ±12.36; Post-delivery: 32.70 ± 8.83; P = 3.7x10-5) and right ventricular index of myocardial performance score (Pre-delivery: 0.34 ±0.12; Post-delivery: 0.33 ±0.12; P = 0.007). Patients with severe PR was found to have significantly worse right ventricular global longitudinal strain (RV GLS) (P = 0.029). 2 patients progressed to severe PR following delivery. Adult female patients with TOF can have viable pregnancies with acceptable mortality and morbidity. Deterioration in echocardiographic parameters were identified when comparing between pre-delivery and post-delivery studies. TOF patients should be closely monitored throughout and post-delivery for detection of deterioration of cardiac function and clinical symptoms.

HYDROCEPHALUS WITH VENTRICULOPERITONEAL SHUNTS IN INFANTS: OUR EXPERIENCES AND CLINICAL OUTCOMES

Hydrocephalus is a condition resulting from disorder in absorption and circulation of the cerebrospinal fluid (CSF). It leads to progressive ventricular dilatation and need of  ventriculoperitoneal shunt (VP) placement. The aim of our study is to present our experience on neonates with  hydrocephalus, ventriculoperitoneal shunt placement, and early postoperative follow up. A retrospective study on neonates with hydrocephalus borned between January 2019 -January 2022 with ventriculoperitoneal shunt placement conducted at University Clinic for Neurosurgery in Skopje, Macedonia was reviewed. Demographical and clinical characteristics, complications and the need for ventriculoperitoneal shunt were documented. 23 infants with hydrocephalus 14 (60,8 %) were preterm (median birth weight 2120g; mean gestational age 33.1weeks), 9 (39.1%) infants were term neonates (mean birth weight 3600g; mean gestational age 38.4 weeks). The etiology of hydrocephalus were; congenital hydrocephalus in 5 infants (21,7%), prematurity in 6 infants ( 26,08%), spina bifida in 2 infants (8.7%), systemic infection in 4 infants ( 17,3%), and intraventricular haemorrage in 6 infants (26,08%).Ventriculoperitoneal shunt was placed to all 23 infants, at mean age of  33,5 (30-43) days. Postoperative complications as a result of ventriculoperitoneal shunt placement were; ventriculitis was manifested at 3 preterm (13%) infants, 2 of them (8,6%) died. Five term infants (21,7%) with postoperative seizures had need of VP replacement; 2 infants (8,6%) died. 19 infants (82,6%) were discharged and transfed to neonatology department. Ventriculoperitoneal shunt placement is the treatment of choice for neonates with hydrocephalus, although postoperative complications in preterm neonates increase the percent of morbility and  hymortality. Кeywords:Hydrocephalus,ventriculoperitoneal shunt, neonates, postoperative complications. &nbsp

Decreased Cerebral Oxygenation in Premature Infants with Progressive Posthemorrhagic Ventricular Dilatation May Help with Timing of Intervention.

The objective of this study was to determine the degree of progressive posthemorrhagic ventricular dilatation (PHVD) that is associated with a significant decrease in regional cerebral oxygen saturation (rScO2) in premature infants at risk for periventricular-intraventricular hemorrhage (PIVH). Cranial ultrasound (US) and near-infrared spectroscopy (NIRS) measurements of rScO2 were performed on inborn infants with birth weights less than 1,250 g on admission and at 1, 4, and 8 weeks of age. Infants with severe PIVH were studied weekly. A 1-hour average of rScO2 was compared with the frontal-occipital horn ratio (FOHR) measured the same day. Generalized linear models were used to analyze the relationship between FOHR and rScO2, by severity of PIVH, and adjusted for gestational age. Cut-off points of 0.55 for FOHR and 45% for rScO2 were used to calculate odds ratios (OR) and 95% confidence intervals (CI). The study cohort included 63 infants with normal US, 15 with grade-1 or -2 PIVH (mild group), and 21 with grade-3 or -4 PIVH (severe group). Increases in FOHR in the severe group were associated with decreases in rScO2 at 1 week (p = 0.036), 4 weeks (p = 0.013), and 8 weeks of life (p = 0.001) compared with the normal and mild groups. Infants with FOHR greater than 0.55 were 92% more likely to have rScO2 less than 45% when compared with infants with FOHR less than 0.55 (OR = 0.08, 95% CI: [0.04, 0.13], p < 0.001). Progressive PHVD (FOHR > 0.55) is a strong predictor of compromised cerebral oxygenation. A combination of rScO2 and FOHR measurements may aid in identifying infants with PHVD that would benefit from early intervention. · Earlier intervention in PHVD may improve outcomes.. · PHVD is diagnosed with US measurements of ventricular size.. · FOHR > 0.55 is associated with decreased cerebral perfusion..

IMPACT OF TRUNCAL VALVE REGURGITATION ON LEFT VENTRICULAR FUNCTION AND GEOMETRY IN COMMON ARTERIAL TRUNK: A CASE-MATCH CONTROLLED STUDY

<h3>BACKGROUND</h3> Truncal valve insufficiency (TVI) not only is one of the risk factors for death in neonatal primary repair for common arterial trunk (CAT), but also influences long-term left ventricular performance. This study investigates the functional and survival outcomes of CAT repair in patients based on TVI severity. <h3>METHODS AND RESULTS</h3> In this single-center retrospective case-matched controlled study, 16 consecutive CAT patients from 2000- 2018 with moderate to severe truncal valve regurgitation (TVR2-3) undergoing primary CAT surgery with truncal valve (TrV) repair were matched to 16 CAT patients with none to mild truncal valve regurgitation (TVR1-0). Survival was analyzed using Kaplan-Meier; reintervention using competing risks; paired tests for ventricular function and geometry, and health status. TVR2-3 group had 11 (69%) patients with moderate TVR and 5 (31%) patients with severe TVI, with operative median age of 7(4 – 19) days. The TVR1-0 group had 3 (19%) patients with none/trivial TVI and 13 (81%) patients with mild TVI, with an operative median age of 132(6– 22) days (p = 0.30). There were no significant differences in preoperative variables between the groups and repair technique as shown in Table 1. There was no significant difference between overall survival and modified Ross heart failure score at median length of follow-up of 9.17 (1.40 – 15.12) years. Rate of surgical TrV reintervention at 5 years postoperative was 8% and 67% for TVR0-1 and TVR2-3, respectively (Stratified Gray's p = 0.005). TVR2-3 experienced greater residual TVI at discharge and 1 year post-repair with severity of TrV dysfunction converging between groups as more patients in TVR0-1 developed mild/moderate TVI over time and TVR2-3 patients underwent reintervention. Left ventricular ejection fraction (LVEF) was comparable between groups at all time-points, with the exception of postoperative year 1 [TVR0-1: 69(67 – 74)% vs. TVR2-3: 62(59 – 66)% (p = 0.006) Figure 1]. Although not statistically significant, pronounced left ventricular dilatation was seen in the TVR2-3 group (upper quartile, z-score +6) throughout 1-year post-repair. Increasing left ventricular size in TVR2-3 reached statistical significance at 3 (p = 0.001) and 5 years (p = 0.003), but did not impair LVEF. <h3>CONCLUSION</h3> There was a greater number of surgical TrV reinterventions (i.e. repair or replacement) in the TVR2-3 population, with two deaths associated with critical residual TVI refractory to reintervention. Progressive left ventricular dilatation in the TVR2-3 group due to residual TVI was well tolerated. Ventricular remodeling did not significantly impact left ventricular function or clinical status.

Re-do MitraClip in patients with functional mitral valve regurgitation and advanced heart failure.

AimPercutaneous mitral valve repair (PMVR) via MitraClip implantation is a therapeutic option for severe mitral regurgitation (MR) in advanced stages of heart failure (HF). However, progressive left ventricular dilation in these patients may lead to recurrent MR after PMVR and consequent re‐do MitraClip implantation. Here, we describe the characteristics and outcomes of this clinical scenario.Methods and resultsPatients with systolic HF and functional MR undergoing a re‐do MitraClip procedure were retrospectively analysed. Inclusion criteria were age ≥18 years, technical, device and procedural success at first MitraClip procedure, functional MR and systolic HF with an ejection fraction (EF) of <45%. Seventeen out of 684 patients undergoing PMVR with the MitraClip device at our institution between September 2009 and July 2019 were included. All patients displayed advanced HF with an EF of 20% (±9.9) and highly elevated N‐terminal pro‐brain natriuretic peptide. Technical success of the re‐do MitraClip procedure was 100%, whereas procedural and device success were only achieved in 11 patients (65%). Unsuccessful re‐do procedures were related to lower EF and implantation of more than one clip at initial procedure. However, despite reduction in MR grade and no occurrence of significant mitral stenosis after the procedure, the mortality during 12 months follow‐up remained high (8 of 17; 47%).ConclusionsIn a cohort of patients with advanced HF undergoing PMVR, re‐do MitraClip procedure was feasible, but procedural success was unsatisfactory and morbidity and mortality remained high, possibly reflecting the advanced stage of HF in these patients.

No footprint too small: case of intrauterine herpes simplex virus infection

Abstract Objectives To describe the case of a preterm infant with intrauterine HSV infection. To discuss the epidemiology, features and complications associated with intrauterine HSV infection by conducting a review of medical literature. Case presentation A preterm male infant was born with diffuse skin erosions in various stages of healing suggestive of denuded bullae. Prenatal ultrasound showed evolving fetal cerebral ventriculomegaly, suspected Dandy-Walker malformation, and oligohydramnios. Neonatal skin swabs were positive for herpes simplex virus type 2 by polymerase chain reaction and the patient was treated with intravenous acyclovir from birth. Cranial ultrasound and magnetic resonance imaging findings showed severe progressive ex-vacuo ventricular dilatation consistent with intrauterine herpes simplex infection. Due to those findings and progressive multi-organ dysfunction, care was redirected to a palliative path and the child expired at 21 days of age. In retrospect, the mother had a few atypical vesicles on the left hand 4–5 weeks prior to delivery with a presumptive diagnosis of pompholyx. Conclusions Although confirmed intrauterine herpes simplex virus (HSV) infections are very rare, the potentially devastating prognosis and complications as evidenced by our case show that awareness of intrauterine HSV is critical for pediatricians as well as physicians involved in antenatal care. In order to adequately assess, treat and counsel pregnant women, more work is required to detect HSV infection, evaluate possible congenital infection and improve outcomes with fetal and neonatal treatment.