CHARGE syndrome and congenital heart diseases: systematic review of literature.

CHARGE syndrome (CS) is a rare genetic disease that affects many areas of the body. The aim of the present systematic review was to evaluate the prevalence and types of congenital heart diseases (CHDs) in CS and their impact on clinical outcome. A systematic review from 1981 to September 2022 was conducted. Clinical studies that reported the association between CS and CHDs were identified, including a case report of a rare congenital anomaly of the aortic arch (AA) with persistent fifth aortic arch (PFAA). Demographic, clinical and outcome data were extracted and analyzed. Sixty-eight studies (44 case reports and 24 case series; n=943 CS patients) were included. The prevalence of CHDs was 76.6%, patent ductus arteriosus (PDA) 26%, ventricular (VSD) 21%, atrial septal defects (ASD) 18%, tetralogy of Fallot 11%, aortic abnormalities 24%. PFAA has not been previously reported in CS. Cardiac surgery was performed in more than half of CS patients (150/242, 62%). In-hospital mortality rate was about 9.5% (n=86/900) in case series studies and 12% (n=5/43) in case reports, including cardiovascular (CV) and non-CV causes. CHDs and feeding disorders associated with CS may have a substantial impact on prognosis. CHDs were usually associated with CS and represent important causes of morbidity and mortality. PFAA, although rare, may also be present. The prognosis is highly dependent on the presence of cardiac and non-cardiac developmental abnormalities. Further studies are needed to better identify the main causes of the long-term outcome of CS patients.

Pheochromocytoma-induced cardiogenic shock: A multicentre analysis of clinical profiles, management and outcomes.

OBJECTIVE: There is still uncertainty about the management of patients with pheochromocytoma-induced cardiogenic shock (PICS). This study aims to investigate the clinical presentation, management, and outcome of patients with PICS. METHODS: We collected, retrospectively, the data of 18 patients without previously known pheochromocytoma admitted to 8 European hospitals with a diagnosis of PICS. RESULTS: Among the 18 patients with a median age of 50 years (Q1-Q3: 40-61), 50% were men. The main clinical features at presentation were pulmonary congestion (83%) and cyclic fluctuation of hypertension peaks and hypotension (72%). Echocardiography showed a median left ventricular ejection fraction (LVEF) of 25% (Q1-Q3: 15-33.5) with an atypical- Takotsubo (TTS) pattern in 50%. Inotropes/vasopressors were started in all patients and temporary mechanical circulatory support (t-MCS) was required in 11 (61%) patients. All patients underwent surgical removal of the pheochromocytoma; 4 patients (22%) were operated on while under t-MCS. The median LVEF was estimated at 55% at discharge. Only one patient required heart transplantation (5.5%), and all patients were alive at a median follow-up of 679 days. CONCLUSIONS: PICS should be suspected in case of a CS with severe cyclic blood pressure fluctuation and rapid hemodynamic deterioration, associated with increased inflammatory markers or in case of TTS progressing to CS, particularly if an atypical TTS echocardiographic pattern is revealed. T-MCS should be considered in the most severe cases. The main challenge is to stabilize the patient, with medical therapy or with t-MCS, since it remains a reversible cause of CS with a low mortality rate.

Importance of Echocardiography and Clinical "Red Flags" in Guiding Genetic Screening for Fabry Disease.

Introduction: Aim of this study was to evaluate, in a metropolitan area not already explored, the prevalence of Anderson-Fabry disease, by genetic screening, in patients with echocardiographic evidence of left ventricular hypertrophy (LVH) of unknown origin and "clinical red flags". Methods: From August 2016 to October 2017, all consecutive patients referring to our echo-lab for daily hospital practices with echocardiographic evidence of LVH of unknown origin in association with history of at least one of the classical signs and symptoms related to Fabry disease (FD) (neuropathic pain, anhidrosis/hypohidrosis, angiokeratomas, gastrointestinal problems, chronic kidney disease, or cerebrovascular complications) were considered eligible for the FD genetic screening program. Through dried blood spot testing, α-Galactosidase A (α-Gal A) activity and analysis of the GLA gene were performed. Results: Among 3,360 patients who underwent transthoracic echocardiography in our echo-lab during the study period, 30 patients (0.89%; 19 men, mean age 58 ± 18.2 years) were selected. FD was diagnosed in 3 (10%) unrelated patients. Three different GLA gene mutations were detected, one of them [mutation c.388A > G (p.Lys130Glu) in exon 3] never described before. Moreover, probands' familiar genetic screening allowed the identification of 5 other subjects affected by FD. Conclusion: In a metropolitan area not previously investigated, among patients with LVH of unknown origin associated with other "red flags," undergoing genetic screening, the prevalence of FD was very high (10%). Our results highlight the importance of an echocardiographic- and clinical-oriented genetic screening for FD in patients with uncommon cause of LVH.

Cardiovascular Involvement in COVID-19: What Sequelae Should We Expect?

Several forms of cardiovascular involvement have been described in patients with Coronavirus disease 19 (COVID-19): myocardial injury, acute coronary syndrome, acute heart failure, myocarditis, pericardial diseases, arrhythmias, takotsubo syndrome, and arterial and venous atherothrombotic and thromboembolic events. Data on long-term outcome of these patients are still sparse, and the type and real incidence of cardiovascular sequelae are poorly known. It is plausible that myocardial injury may be the initiator of an inflammatory cascade, edema, and subsequent fibrosis, but also a consequence of systemic inflammation. The extent and distribution of ongoing inflammation may be the basis for ventricular dysfunction and malignant arrhythmias. Indeed, preliminary observational findings seem to emphasize the importance of close monitoring of COVID-19 patients with myocardial injury after discharge. Residual subclinical disease may be effectively investigated by using second-level imaging modalities such as cardiac magnetic resonance, which allows better characterization of the type and extension of myocardial damage, as well as of the ongoing inflammation after the acute phase. In patients with venous thromboembolism, a very common complication of COVID-19, the type and the duration of anticoagulation therapy after the acute phase should be tailored to the patient and based on the estimation of the individual thromboembolic and hemorrhagic risk. Large randomized clinical trials are ongoing to address this clinical question. Whether the severity of cardiovascular involvement, the type of treatments adopted during the acute phase, and the hemodynamic response, may influence the long-term outcome of patients recovered from COVID-19 is unknown. An etiological diagnosis of myocardial injury during the hospitalization is the first step for an appropriate follow-up in these patients. After discharge, the screening for residual left and right ventricular dysfunction, arrhythmias, residual thrombosis, and myocardial scar should be considered on a case-by-case basis, whereas an active clinical surveillance is mandatory in any patient.

Loeffler's Endocarditis: An Integrated Multimodality Approach.

Loeffler's endocarditis (LE) is the cardiac manifestation of hypereosinophilic syndrome, a rare systemic disease characterized by the sustained production of eosinophils leading to organ damage. Few data, principally by case reports, are available regarding the diagnostic workup in patients with suspected LE. Thus, we have performed a systematic search of the literature dealing with imaging in LE and propose an integrated multimodality imaging approach in the cardiac diagnostics of LE patients. The aim is to provide an updated state-of-the-art review focused on noninvasive and invasive imaging modalities for this rare and underdiagnosed disease. Standard and advanced echocardiography are typically the first cardiac imaging examinations when LE is suspected and they are also used later in follow-up for prognostic stratification and assessing response to treatment. Cardiac magnetic resonance provides a more detailed anatomical and functional evaluation of cardiac chambers, tissue characterization for the presence and extension of myocardial edema and fibrosis, and ventricular thrombi identification. Computed tomography scan and [18F]-fluoro-deoxy-glucose positron emission tomography may be helpful in selected cases to evaluate the cardiac involvement of LE as well as the other noncardiac manifestations of hypereosinophilic syndrome. Endomyocardial biopsy may be considered in patients with high clinical suspicion of LE if noninvasive imaging findings are confusing or not conclusive. The appropriate use of invasive and noninvasive imaging modalities, combining the available techniques with the patients' clinical features, will hopefully lead to early diagnosis, more accurate staging of disease, and timely treatment of LE that may prevent the irreversible myocardial damage of LE and adverse cardiovascular events.

Sirt1 Activity in PBMCs as a Biomarker of Different Heart Failure Phenotypes.

Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF (n = 23), HFmrEF (n = 23) and HFrEF (n = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF (p < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r2 = 0.899 and r2 = 0.909, respectively), and between ACE2 activity and Sirt1 (r2 = 0.801 and r2 = 0.802, respectively). HFrEF showed the highest TNF-α levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients' phenotypes from each other, especially HFmrEF/HFrEF from HFpEF.

A peculiar etiology of acute heart failure: adrenergic myocarditis.

Pheochromocytoma can occur with a variety of cardiovascular signs and symptoms, and this tumor can also precipitate an acute heart failure associated with the typical clinical and instrumental findings of myocarditis. This peculiar etiology of acute myocarditis, known as "adrenergic myocarditis," should be suspected when specific "red flags" of pheochromocytoma such as headache, palpitations, diaphoresis, hypertension, orthostatic hypotension, and left ventricular dysfunction suggesting Takotsubo syndrome are detected. In fact, its diagnosis allows a specific targeted therapy.

Aortic dissection in patients with autosomal dominant polycystic kidney disease: a series of two cases and a review of the literature.

Aortic dissection (AD) is the most common life-threatening disease involving the aorta. It is rarely associated with systemic disorders such as Autosomal Dominant Polycystic Kidney Disease (ADPKD), a genetic syndrome characterized by cystic degeneration of kidneys, possible presence of cysts in other organs and extra-renal manifestations, including cardiovascular disorders. We performed a systematic literature search focused on the occurrence of AD associated with ADPKD (25 cases identified), and reported two cases from our experience. We selected data on sex, age, family history of ADPKD and/or AD, habitus, hypertension, renal function, presence of hepatic/pancreatic/splenic cysts, clinical presentation of AD, AD type according to the Stanford classification, treatment and outcome. Furthermore we compared this dataset with the data of the overall population with AD from the International Registry of Acute Aortic Dissection (IRAD). Stanford A type AD was documented in 62% of patients. As expected, the initial manifestation of AD was most commonly chest and back pain (80%). The mean age of AD occurrence appears significantly reduced in ADPKD patients compared to the general population with AD (49 ± 12 vs 62 ± 14, P < 0.001). Of note, our analysis shows a remarkably higher frequency of hypertension (90%) compared to the overall AD population (75%), although not significantly (P = 0.133). AD should be always ruled out in ADPKD subjects with chest and back pain symptoms, despite them being young and at lower risk. A careful preventive monitoring as well as an optimal blood pressure control may reduce the risk of AD and improve the outcome of these patients.

Stress-related cardiomyopathy, ventricular dysfunction, artery thrombosis: a hidden pheochromocytoma.

Clinical presentation of pheochromocytoma can vary, and it can sometimes mimic other diseases. Some patients with pheochromocytoma may have atypical presentations, such as clinical features consistent with an acute coronary syndrome, that only later suggest a classical picture of stress-related cardiomyopathy. To our best knowledge, pheochromocytoma has been incidentally revealed in a few cases of catecholamine-induced cardiomyopathy and in only 1 case of peripheral arterial thrombosis. This is the first case of pheochromocytoma revealed after left ventricular dysfunction caused by stress-related cardiomyopathy associated with inferior limb artery thrombosis in a patient with a complex cardiovascular history.