No abstract

In the present article, we describe the case of a 21-year-old male presenting to the Emergency Department following a syncopal episode. Physical examination revealed a distinctive facial appearance in the context of an overgrowth syndrome. Also, an ajmaline test was performed because of the evidence of an incomplete right bundle branch block with ST-T segment elevation in the right precordial derivations, revealing a type-1 Brugada electrocardiographic pattern. Considering the high cardiovascular risk phenotype, the patient underwent subcutaneous cardiac defibrillator implantation. The subsequent comprehensive genomic testing analysis led to the diagnosis of a variant of an uncertain significance of the nuclear receptor binding SET domain protein 1 (NSD1) gene and a heterozygous mutation of the calsequestrin 2 (CASQ2) gene. NSD1 gene alterations are usually responsible for the Sotos syndrome, characterized by distinctive facial appearance, learning disability, and overgrowth, in addition to cardiac anomalies, ranging from single self-limiting alterations to more severe, complex cardiac abnormalities. On the contrary, a compound heterozygous or homozygous alteration of the CASQ2 gene is usually associated with catecholaminergic polymorphic ventricular tachycardia; however, the significance of a merely heterozygous alteration in CASQ2 gene, as in the present case report, is not yet clear. In conclusion, to the best of our knowledge, this is the first description of the coexisting presence of Brugada and overgrowth syndromes in a single patient.

A 55-years-old male affected by heart failure with reduced ejection fraction (HFrEF) was accepted into the Cardiology Department for increasing dyspnea during the last few months. He previously underwent implantation of a biventricular implantable cardioverter defibrillator (ICD) in primary prevention. Medical history included healthy coronary vessels at invasive coronary angiography and an episode of transient ischemic attack (TIA). The patient was referred to our center to evaluate the dyspnea components and to establish an etiology for the novel onset of left ventricular impairment. He underwent a left-right catheterization that did confirm the absence of obstructive coronary disease and signs of pulmonary hypertension (PH) at rest. The transthoracic echocardiogram showed a dilated left ventricle and global hypokinesia (LVEF of 35%). During the stay, the therapy was further optimized according to the latest European guidelines. Before discharge, in order to better assess the dyspnea and the limited tolerance to exercise, a cardiopulmonary exercise testing (CPET) was performed. CPET showed that the VO2 peak was severely reduced compared to the predicted value (16.8 ml/kg/min, corresponding to 51% of the predicted). After 6 minutes of exercise, at around 60 WR, a considerable increase in PETO2 and RER with a concomitant decrease in PETCO2 and a slight oxygen desaturation were observed. Also, a deep increase in VE/VCO2 slope was seen, underlying an exercise-induced pulmonary hypertension. In the suspicion of an inter-atrial shunt, a subsequent rest transthoracic echocardiogram with a bubble test was performed, demonstrating the presence of a patent foramen ovale (PFO). Discussion The foramen ovale is a vestigial communication between the atria that works as a bypass of the pulmonary circulation during fetal life and then seals at birth after the start of breathing in most people. In around 25% of adults, patency of foramen ovale persists and, in some cases, can lead to a source of a right-to-left shunt, particularly in patients with heart failure that can experience PH at rest or during exercise. This may allow a mixture of oxygenated and non-oxygenated blood that affects pulmonary gas exchange efficiency and may allow blood clots formed in the right circulation to embolize into the left circulation. From a pathophysiological point of view, a right-to-left passage of deoxygenated blood induces the activation of chemoreceptors which induce hyperventilation to adequately compensate for the high amount of CO2 in blood from the right sections of the heart. In people not experiencing pulmonary pressure increase during exercise, right-to-left shunt via a PFO is very unlikely since left atrial pressure is higher than right atrial pressure. However, in the presence of PH, right atrial pressure can overcome left atrial pressure and force venous blood through the defect directly into the systemic circulation. The concomitant increase in VE/VCO2 slope underlines exercise-induced PH, which is frequently associated with heart failure and further contributes to exercise intolerance. Conclusions In the presented case, CPET helped diagnose a misunderstood PFO with a right-to-left shunt induced by effort in a patient with a previous TIA. This observation demonstrates that it could be helpful to identify this eventuality during exercise, to discern patients with higher risk of cardiovascular events who would benefit from a percutaneous closure.