Borderline Ventricles: From Evaluation to Treatment.

A heart with a borderline ventricle refers to a situation where there is uncertainty about whether the left or right underdeveloped ventricle can effectively support the systemic or pulmonary circulation with appropriate filling pressures and sufficient physiological reserve. Pediatric cardiologists often deal with congenital heart diseases (CHDs) associated with various degrees of hypoplasia of the left or right ventricles. To date, no specific guidelines exist, and surgical management may be extremely variable in different centers and sometimes even in the same center at different times. Thus, the choice between the single-ventricle or biventricular approach is always controversial. The aim of this review is to better define when "small is too small and large is large enough" in order to help clinicians make the decision that could potentially affect the patient's entire life.

Rapid transesophageal atrial pacing for balloon aortic valvuloplasty in neonates and infants: A new technique for balloon stabilization.

Balloon aortic valvuloplasty (BAV) is preferred by most centers over surgery for the treatment of congenital valve stenosis, due to its less invasive nature and faster recovery time. A variety of techniques have been employed to induce a transient cardiac standstill and reduce longitudinal balloon displacement during valve dilatation. Rapid right ventricular (RV) pacing is an effective method to stabilize the balloon during aortic valvuloplasty and it is regularly used in older children and adults. Despite the evidence of its feasibility and efficacy, its use in neonates and infants is still not widespread globally as it is associated with certain drawbacks in this population. We report the use of a new technique to achieve balloon stabilization during BAV in neonates and infants. Four patients with severe congenital aortic valve stenosis were treated with percutaneous BAV using rapid transesophageal atrial pacing. Rapid atrial pacing was performed in asynchronous modality at a rate which resulted in a drop of the systemic arterial pressure by 50%. The balloon was inflated only after the set pacing rate was reached. The pacing was continued until the balloon was completely deflated. No ventricular arrhythmia occurred. Fluoroscopy time was not influenced by transesophageal pacing. Mild aortic regurgitation developed in only one case. Rapid transesophageal atrial pacing was safe and allowed a significant relief of left ventricular obstruction while minimizing aortic regurgitation. Compared to RV pacing, it does not require additional vascular access. Moreover, transesophageal pacing is not at risk of cardiac or vascular perforation and ventricular arrhythmias.

Transcatheter Interventions for Neonates with Congenital Heart Disease: A Review.

Newborns with congenital heart disease often require interventions linked to high morbidity and mortality rates. In the last few decades, many transcatheter interventions have become the first-line treatments for some critical conditions in the neonatal period. A catheter-based approach provides several advantages in terms of procedural time, length of hospitalization, repeatability and neurodevelopmental issues (usually related to cardiopulmonary bypass). The main transcatheter procedures will be reviewed, as they are now valid alternatives to conventional surgical management.

Cleft Palate and Aortic Dilatation as Clues for Loeys-Dietz Syndrome.

Loeys-Dietz syndrome (LDS) is a rare autosomal-dominant disorder of the connective tissue with some typical vascular findings, skeletal manifestations, craniofacial features, and cutaneous findings with a wide phenotypic spectrum. Six different genes are involved in LDS and the diagnosis is based on the identification of a heterozygous pathogenic variant in TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3, or SMAD2 in children with suggestive findings. These genes distinguish LDS into six classes (LDS1-LDS6, respectively). Delay in diagnosis of Loeys-Dietz syndrome may be associated with an adverse prognosis due to a very high augmented risk of early complications such as aortic or vascular rupture. The present report describes a case of an early diagnosis of LDS in a neonate with cleft soft palate and aortic root dilatation.

Percutaneous treatment of a double-drainage scimitar-like syndrome.

Scimitar syndrome is a rare variant of anomalous right pulmonary vein connection to the inferior vena cava and it is associated with other cardiopulmonary anomalies. It generally requires surgery and sometimes it may go unrecognised into adulthood. We report a unique case of a scimitar syndrome variant in a young adult, who was successfully treated percutaneously, after the first misdiagnosis of arrhythmogenic ventricular cardiomyopathy. The cardiac magnetic resonance unveiled the uncommon anatomical pattern, avoiding surgical repair. Cross-sectional imaging is extremely useful in the diagnosis and treatment planning of CHD in adults.

Cardiovascular, Brain, and Lung Involvement in a Newborn With a Novel FLNA Mutation: A Case Report and Literature Review.

BACKGROUND: Filamin A (FLNA) is an intracellular actin-binding protein, encoded by the FLNA gene, with a wide tissue expression. It is involved in several cellular functions, and extracellular matrix structuring. FLNA gene alterations lead to diseases with a wide phenotypic spectrum, such as brain periventricular nodular heterotopia (PVNH), cardiovascular abnormalities, skeletal dysplasia, and lung involvement. CLINICAL FINDINGS: We present the case of a female infant who showed at birth aortic valve stenosis and PVNH, and subsequently developed interstitial lung disease with severe pulmonary hypertension. PRIMARY DIAGNOSIS: The association of aortic valve dysplasia, left ventricular outflow obstruction, persistent patent ductus arteriosus, and brain heterotopic gray matter suggested a possible FLNA gene alteration. A novel heterozygous intronic variant in the FLNA gene (NM_001110556.1), c.4304-1G >A, was detected. INTERVENTIONS: In consideration of valve morphology and severity of stenosis, the neonate was scheduled for a transcatheter aortic valvuloplasty. At 3 months of life, she developed hypoxemic respiratory failure with evidence of severe pulmonary hypertension. Inhaled nitric oxide (iNO) and milrinone on continuous infusion were started. Because of a partial response to iNO, an intravenous continuous infusion of sildenafil was introduced. OUTCOMES: In consideration of severe clinical course and fatal outcome, the new FLNA gene mutation described in our patient seems to be associated with a loss of function of FLNA. PRACTICE RECOMMENDATIONS: Lung and brain involvement, in association with left ventricular outflow obstruction and persistent patency of ductus arteriosus, should be considered highly suggestive of FLNA gene alterations, in a female newborn.

Off-Label Use of Cardiovascular Drugs in the Home Therapy of Children With Congenital or Acquired Heart Disease.

Most medications are not labeled for use in the pediatric population because they have not been formally studied in children. Data on off-label use of cardiovascular (CV) drugs in the home therapy of children with CV disease are scanty. The study included 325 pediatric patients with CV disease and on ≥1 CV medication who underwent ≥1 visit during 2019 at the Pediatric Cardiology outpatient clinic of Giovanni XXIII Pediatric Hospital in Bari, Italy. A total of 287 patients (88.3%) received ≥1 off-label medication, whereas 113 patients (34.7%) received ≥2 off-label medications, and 22 patients (6.7%) ≥3 off-label medications. In CV medications (n = 27) 85% were used off-label in all cases, and 92.5% were used off-label in ≥50% of patients. Adverse events occurred in 8 patients, leading to drug discontinuation in 2 of them. In all 8 cases, medications were used off-label. In multivariate analysis, congenital heart disease patients with single-ventricle physiology (odds ratio 8.4, 95% confidence interval 2.25 to 54.4) and those with heart failure (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) were at higher risk for receiving ≥2 off-label drugs. The off-label use of CV drugs in the home therapy of children with congenital or acquired heart disease is common and adverse events may occur. Patients with congenital heart disease with single-ventricle physiology and those with heart failure have a higher probability to receive ≥2 off-label medications. This study highlights the need for larger safety and efficacy trials in this specific cohort of pediatric patients.

Impact of hard lockdown on interventional cardiology procedures in congenital heart disease: a survey on behalf of the Italian Society of Congenital Heart Disease.

The Coronavirus disease 2019 (COVID-19) pandemic has thoroughly and deeply affected the provision of healthcare services worldwide. In order to limit the in-hospital infections and to redistribute the healthcare professionals, cardiac percutaneous intervention in Pediatric and Adult Congenital Heart Disease (ACHD) patients were limited to urgent or emergency ones. The aim of this article is to describe the impact of the COVID-19 pandemic on Pediatric and ACHD cath laboratory activity during the so-called 'hard lockdown' in Italy. Eleven out of 12 Italian institutions with a dedicated Invasive Cardiology Unit in Congenital Heart Disease actively participated in the survey. The interventional cardiology activity was reduced by more than 50% in 6 out of 11 centers. Adolescent and ACHD patients suffered the highest rate of reduction. There was an evident discrepancy in the management of the hard lockdown, irrespective of the number of COVID-19 positive cases registered, with a higher reduction in Southern Italy compared with the most affected regions (Lombardy, Piedmont, Veneto and Emilia Romagna). Although the pandemic was brilliantly addressed in most cases, we recognize the necessity for planning new, and hopefully homogeneous, strategies in order to be prepared for an upcoming new outbreak.

Resilience and response of the congenital cardiac network in Italy during the COVID-19 pandemic.

: The worldwide response to the current COVID-19 pandemic has been focused on how to prevent the disease and to protect the high-risk patient from a potentially lethal infection. Several consensus and guidelines articles have been published dealing with the cardiac patient with systemic hypertension, heart transplant or heart failure. Very little is known about the patients, both in the pediatric as well as in the adult age, with congenital heart disease. The peculiar physiology of the heart with a native, repaired or palliated congenital heart defect deserves a specialized care. Hereby we describe the early recommendations issued by the Italian Society of Pediatric Cardiology and Congenital Heart Disease and how the network of the congenital cardiac institutions in Italy reacted to the threat of potential wide spread of the infection among this fragile kind of patient.

Sudden cardiac death after robbery: Homicide or natural death?

Tako-Tsubo is one of a number of rare acquired cardiomyopathies that are characterized by left ventricular dyskinesia and symptomatology typical of acute myocardial infarction (AMI). The most important feature is that the clinical features are triggered by a severe physical or emotional stress. The authors describe the story of a woman, who was brutally assaulted by two men during a house robbery and died from sudden heart failure 8 hours later, after being taken to hospital. External examination revealed no macroscopic alteration of the inner organs, whereas microscopy showed contraction bands with myocardial necrosis, subendocardial and interstitial neutrophil infiltration and fibrosis. These findings were consistent with death due to stress cardiomyopathy even in the absence of previous heart disease. The robbers were convicted of homicide and sentenced to eighteen years in prison.

Mid-Aortic Syndrome: A Rare Cause of Renovascular Hypertension in Childhood Treated Percutaneously with an Unusual Vascular Access.

INTRODUCTION: Mid-Aortic Syndrome (MAS) is a rare vascular malformation characterized by segmental narrowing of the abdominal aorta and stenosis of its principal branches. Patients affected by MAS typically present malignant renovascular hypertension, with variable clinical symptoms like claudication, abdominal angina, and headache. Moreover, they can develop other complications, such as hypertensive encephalopathy, congestive heart failure and vascular brain accidents. Hypertension with MAS is often resistant to multidrug therapy, requiring a surgical approach to treat the clinical symptoms, prevent or block organ damage and normalize the blood pressure. CASE REPORT: Here, the case of a 4-year-old boy showing elevated blood pressure with left ventricular hypertrophy leading to idiopathic MAS, who was successfully treated with percutaneous transcatheter renal angioplasty (PTRA) using an unusual, anterograde access, is reported. DISCUSSION AND CONCLUSION: In children and adolescents, vascular malformations like MAS must be considered as a possible cause of hypertension. PTRA is a successful therapeutic strategy in children with severe renovascular hypertension. Anterograde access, using an axillary artery, can be a valid approach for PTRA when femoral access is difficult to achieve.

Balloon angioplasty of aortic coarctation in critically ill newborns using axillary artery access.

Balloon angioplasty may be performed as the first treatment of aortic coarctation to stabilize newborns too sick for immediate surgery. The issue of vascular access is the key to the successful treatment of critical newborns. In our study, we argue that the lesser-known axillary access route is the safest and most effective route of vascular access for balloon angioplasty in infants with aortic coarctation. To support this argument, we present the case of eight unstable newborns with complex heart diseases, who were successfully treated with percutaneous intervention through the axillary artery. This case series is followed by an analysis of the greater efficacy of this technique compared to the more conventional femoral and carotid routes. We conclude by acknowledging the substantial advantages of this lesser-known vascular access and advocate its more widespread clinical implementation in the treatment of critical newborns.

Isolated persistence of the fifth aortic arch in an infant presenting with congestive heart failure.

The persistence of the fifth aortic arch (PFAA) in postnatal life is an extremely rare and controversial cardiovascular malformation. PFAA is defined as an extra-pericardial vessel arising from the ascending aorta proximal to the origin of the brachiocephalic arteries, terminating either in the dorsal aorta or in the pulmonary arteries through the persistently patent arterial duct. An isolated PFAA with systemic-to-pulmonary connection best fits this definition, while the vast majority of cases reported as PFAA may have alternative embryological explanations. We present a unique case of a 5-week-old patient with an isolated PFAA with systemic-to-pulmonary connection, who presented with congestive heart failure. A first differential diagnosis was made with distal aortopulmonary window and an atypical patent arterial duct. A careful analysis of the case and a systematic review of the literature made us conclude for an isolated PFAA, which is one of the only five cases ever reported.

Uric Acid in Metabolic and Cerebrovascular Disorders: A Review.

BACKGROUND: Several studies showed a close link between metabolic syndrome (MetS), type 2 diabetes (T2DM) and cerebrovascular diseases. There is considerable debate regarding the role of uric acid (UA) as a risk factor in these conditions. OBJECTIVE: The aim of this narrative review is to discuss the links between UA, MetS, T2DM and cerebrovascular disease. METHODS: An extensive review has been conducted based on the scientific literature published in English, and indexed in MEDLINE (through PubMed), EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and Google Scholar from January to May 2019. Additional relevant studies published after the initial review were also considered during the period of June 2019-October 2019, during which, this manuscript was written. The Mesh Terms considered were: uric acid, antioxidant, oxidant, metabolic syndrome, diabetes, cerebrovascular diseases, stroke, haemorrhagic stroke, neurocognitive disorders, and their combinations. RESULTS: The literature review shows a dose-dependent inflammatory action of UA, which occurs with serum concentrations >4 mg/dl (>0.24 mmol/l), representing one of the contributors to the chronic inflammatory process that underlies metabolic and cerebrovascular diseases. CONCLUSION: UA, which is associated with arterial hypertension and cardiovascular diseases, represents one of the indicators of oxidative homeostasis. Increasing concentrations represent a status of active inflammation which is observed with metabolic and cerebrovascular diseases.

A situs solitus transposition of great arteries with obstructed sub-diaphragmatic totally anomalous pulmonary venous connection: a rare case treated with anatomical repair.

Transposition of the great arteries combined with totally anomalous pulmonary venous connection is extremely rare outside of heterotaxy syndrome. Most reported cases have been treated by a modified atrial switch operation. We report the successful treatment of a neonate with this rare association, repaired by arterial switch operation and connection of the pulmonary venous return to the left atrium.

Clinical Characteristics and Long-Term Mortality Rate in Female Patients with Takotsubo Syndrome Compared with Female Patients with ST-Elevation Acute Myocardial Infarction: A Retrospective Study from a Single Center.

BACKGROUND: Takotsubo syndrome (TTS) is characterized by acute transient, stress-induced, left ventricular systolic dysfunction, generally presenting with apical ballooning. It can mimic an acute coronary syndrome, but with a milder increase in cardiac enzymes and without culprit coronary artery disease on angiography. Data on long-term follow-up and survival in patients with TTS, compared with patients with ST-elevation myocardial infarction (STEMI), are scarce. PURPOSE: To assess all-cause mortality rate and survival in a consecutive series of female patients with TTS compared with age- and sex-matched STEMI patients on long-term follow-up. METHODS AND RESULTS: We collected data of 65 TTS female patients (TTS group) with a mean age of 73.42 ± 11.35 years from 2001 to 2013. Collection of follow-up information was concluded for all patients in 2016. To compare the mortality and survival of TTS patients with those of the STEMI population, we used data from our STEMI Registry, a prospective registry of 7446 STEMI patients admitted from 2001 to 2013 to our cath-lab for primary percutaneous coronary intervention (p-PCI). From the registry, we selected 104 STEMI patients (STEMI group) comparable to our TTS group in terms of age (mean age of 72.33 ± 11.92 years) and sex. On follow-up examination after a median of 1000 days, the TTS group had a lower all-cause mortality rate than the STEMI group (7.69% versus 23.08%). This difference was statistically different between the two groups (log-rank test, p value = 0.03). CONCLUSIONS: In our study, TTS and STEMI patients displayed a statistically significant difference in long-term survival. Specifically, the TTS group had a lower mortality rate than the STEMI group. This seems to suggest that TTS and STEMI are two different clinical entities with two different clinical outcomes.

Uric acid: from a biological advantage to a potential danger. A focus on cardiovascular effects.

Non-communicable diseases represent nowadays the most common cause of death worldwide, having largely overcome infectious diseases. Among them, cardiovascular diseases constitute the majority. Given these premise, great efforts have been made by scientific societies to emphasize the fundamental role of cardiovascular prevention and risk factors control. In addition to classical cardiovascular risk factors such as smoking, arterial hypertension, hypercholesterolemia and male gender, new risk factors are emerging from international literature. Among them, uric acid is the protagonist. Several evidences show a direct role of hyperuricemia in the determinism of metabolic and vascular disorders. From the other hand, some researchers have demonstrated that uric acid is only a marker of cardiovascular damage and not a risk factor for its development. Aim of this review is to evaluate the scientific evidences on the role of uric acid in cardiovascular diseases in order to shed light on this confusing topic.

Uric Acid, Metabolic Syndrome and Atherosclerosis: The Chicken or the Egg, Which Comes First?

BACKGROUND: A great debate in literature exists nowadays on the role of uric acid as a marker of cardiovascular and metabolic organ damage or a risk factor for cardiovascular and metabolic disease. METHODS: The study aimed to determine the relationship among serum uric acid and metabolic syndrome and atherosclerosis, by means of carotid intima media-thickness, in a cohort of 811 otherwise healthy overweight/obese subjects, without overt atherosclerosis not using any kind of drug. RESULTS: Uric acid levels were positively related to male gender, waist circumference, BMI, systolic and diastolic pressure levels, fasting insulin, fasting glucose, HOMA-IR, triglycerides, total cholesterol, LDL cholesterol, the presence of metabolic syndrome and the number of the components of metabolic syndrome and negatively related to HDL cholesterol levels. No correlation was found between uric acid and carotid intima media thickness. At the multiple regression analysis, only waist circumference and triglycerides (positively) and HDL-cholesterol (negatively) maintained an independent association with uric acid as dependent variable, while age, female gender and uric acid showed a significant independent association with metabolic syndrome as dependent variable. Moreover, the analysis of the odd ratios showed that the risk of developing metabolic syndrome was consistent with uric acid levels ranging from 3 mg/dl to 8 mg/dl. CONCLUSION: The presence of metabolic syndrome does not seem to provide hyperuricemia. By contrast, higher serum uric acid level may predict the risk of metabolic syndrome. Moreover, our results suggest that uric acid cannot be considered a risk factor for early atherosclerosis, at least when assessed using carotid ultrasound.

Potential cardiac risk of immune-checkpoint blockade as anticancer treatment: What we know, what we do not know, and what we can do to prevent adverse effects.

Cancer immunotherapy has become a well-established treatment option for some cancers after the development of a family of drugs targeting the so-called immune checkpoints, such as CTLA4 and PD-1 with PD-L1. These co-receptors/ligands inhibit the activation of T-cell, thus preventing an excessive inflammatory response. Tumors exploit these pathways to induce immune tolerance to themselves. Thus, the main effect of checkpoint-blocking drugs is to awake an immune response primarily directed against cancer cells. Nonetheless, as the immune response elicited by these drugs is not completely tumor-specific, their use may actually cause several adverse effects, including adverse cardiovascular effects. In this review, we will discuss the principles and potentiality of immunotherapy for cancer treatment, the experimental and clinical data on the role of CTLA4 and PD-1 with PD-L1 as immune-checkpoints in the cancer environment and in the cardiovascular system, and strategies aimed at preventing possible cardiovascular adverse effects of immune-checkpoint blockers.