The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

SARS-CoV-2 pulmonary vasculitis and Takotsubo myocarditis syndrome. Hypoxia, endothelial dysfunction, and inflammation are the trigger?

Aims Nowadays the spread of respiratory infection caused by SARS-CoV-2 results in a global pandemic. The World Health Organization (WHO) declared about 450 000 deaths in more than 200 countries, until June 2020. SARS-CoV-2 pneumonia develops a stress condition through systemic hypoxygenation with activation of adrenergic pathways. Takotsubo syndrome is characterized by a temporary wall motion abnormality of the left ventricle (LV) and has common features with acute coronary syndrome (ACS), representing a form of myocardial infarction without coronary arteries thrombosis. Among possible causes there are several stress conditions, including physical, psychological, and illnesses, for example interstitial pneumonia. Methods and results A 54-years-old man, previous smoker, was admitted to emergency room (ER) complaining of dyspnoea and fever, initially treated with ceftriaxone. Physical examination was characterized by tachypnoea (respiratory rate 30 acts/min), tachycardia and hypotension (arterial pressure 90/60 mmHg), and hypoxaemia at transcutaneous saturation (Sat O2 85%). High-resolution computed tomography (HRCT) showed bilateral interstitial pneumonia with ground glass opacities (visual involvement of 80% of pulmonary parenchymal) (Figure 1). Nasopharyngeal swab was positive for SARS-CoV-2 and ECG revealed Atrio-Ventricular Nodal Reentrant Tachycardia (AVRNT) with heart rate of 140 b.p.m., partially responsive to Valsalva manoeuver (Figure 2). Echocardiogram showed severe ventricular dysfunction [ejection fraction (EF): 30–35%] with hypokinesia of apical region associated with hyperkinesia of medio-basal segments, mild mitral regurgitation, and slight pericardial effusion (Figure 2). Laboratory tests were TnI hs 10 ng/l first detection – 26 ng/l second detection (normal range: 2.3–17.8 ng/l), PCR >250 mg/l (normal range 0.5–5 mg/l), d-dimer 1893 ng/ml (normal range: <500 ng/ml), PCT 3.10 ng/ml (normal range: 0–0.5 ng/ml). The worsening of clinical condition needed an orotracheal intubation and a transfer to Intensive Care Unit (ICU). The patient was treated with many antiviral drugs (darunavir, ritonavir), tocilizumab, steroid therapy, colchicine, and plasmapheresis. We observed a progressive clinical and echocardiography improvement, evidenced by partial recovery of EF (45%). CT scan revealed a normal coronary tree. The patient underwent cardiac magnetic resonance (CMR) that showed typical Takotsubo cardiomyopathy characterized by thinning and hypo-akinesias of apical wall of left ventricle (‘apical ballooning’) and normokinesis of basal/medium segments;no late gadolinium enhancements (LGEs);no oedema in T2 weighted images (Figure 3). Follow-up echocardiogram confirmed recovery of EF (50%) associated with mild hypokinesia of apical segments. Acute myocardial injury, as evidenced by elevated levels of cardiac biomarkers or electrocardiogram abnormalities, was observed in 7–20% of patients with COVID-19 in early studies in China (4). In a multicentre cohort study of 191 patients with COVID-19, 33 patients (17%) had acute cardiac injury, of whom 32 died. Whether typical clinical features of myocarditis were present in patients, who had elevated levels of cardiac troponins during the course of COVID-19 is unclear because most of the early studies did not include echocardiography or MRI data. By contrast, several case reports have described typical signs of myocarditis in patients with COVID-19. A woman aged 53 years with myocardial injury, as evidenced by elevated levels of cardiac biomarkers and diffuse ST segment elevation on the electrocardiogram, had diffuse biventricular hypokinesis on cardiac MRI, especially in the apical segments, in addition to severe LV dysfunction (LVEF = 35%). MRI data also revealed marked biventricular interstitial oedema, diffuse LGE and circumferential pericardial effusion, features that are consistent with acute myocarditis. Furthermore, in a man aged 37 years with chest pain and ST segment elevation, echocardi graphy revealed an enlarged heart. The Lake-Louise Criteria gave good diagnostic accuracy in patients with suspected myocarditis, evaluating the principle tissue targets in myocarditis, including: myocardial oedema, using T2-based imaging;hyperaemia and capillary leak, using early gadolinium enhancement (EGE) imaging;and myocyte necrosis and fibrosis, using LGE imaging [14]. The presence of myocardial injury was associated with a significantly worse prognosis. In the initial report of 41 patients with COVID-19 in Wuhan, five patients had myocardial injury with elevated levels of high-sensitivity cardiac troponin I (>28 pg/ml), and four of these five patients were admitted to an ICU. Histological evidence of myocardial injury or myocarditis in COVID-19 is also limited. An autopsy of a patient with COVID-19 and ARDS who died of a sudden cardiac arrest showed no evidence of myocardial structural involvement, suggesting that COVID-19 did not directly impair the heart. By contrast, another case report described a patient with low-grade myocardial inflammation and myocardial localization of coronavirus particles (outside of cardiomyocytes), as measured by endomyocardial biopsy, suggesting that SARS-CoV-2 might infect the myocardium directly. In this case report, CMR showed typical Takotsubo cardiomyopathy (with hypokinesis of apical wall of left ventricle and normokinesis of basal/medium segments), but it showed no oedema in T2-weighted images, no hyperaemia nor capillary leakage (no myocardial EGE), no signs of necrosis or fibrosis (no LGE), no pericardial effusion. This case-report CMR images demonstrated the absence of typical myocardial injury caused by myocarditis, evidenced by the absence of the main tissue markers. Conclusions Therefore, the ventricular dysfunction, presented with Takotsubo syndrome typical pattern, could hypothetically be secondary to systemic hypoxygenation and stress condition caused by the systemic inflammation and endothelial dysfunction developed by SARS-CoV-2 interstitial pneumonia. About the current diagnostic possibilities, CMR is a valuable option for the assessment of inflammatory heart diseases.

Cardiac imaging in congenital heart disease during the coronavirus disease-2019 pandemic: recommendations from the Working Group on Congenital Heart Disease of the Italian Society of Cardiology.

: The recent outbreak of 2019 severe acute respiratory syndrome coronavirus-2 is having major repercussions on healthcare services provision in Italy and worldwide. Data suggest the virus has a strong impact on the cardiovascular system, and cardiac imaging will play an important role in patients affected by coronavirus disease-2019. Although paediatric patients are mildly affected, they represent a clear accelerator in spreading the virus, and healthcare workers are at higher risk of infection. The aim of this position paper is to provide clinical recommendation regarding the execution of imaging investigations for the cardiac diagnostic work-up of paediatric patients with suspected or confirmed infection.