In Italy, COVID (SARS-CoV-2) outbreak has mostly occurred in the metropolitan area of Milan, and in the surrounding region of Lombardy. The first diagnosed case of COVID infection in Lombardy occurred on the February 21st, 2020 in Codogno, in the Milan surroundings, and a “red zone” including 11 municipalities was subsequently instituted to limit virus spread. However, the exponential growth of infected people forced national government to institute a country lockdown on March 8th, 2020, and in Lombardy previously “conventional” hospitals were converted into COVID spokes to increase especially ICU beds availability.1 As our hospital is a tertiary care center and the reference cardiac surgery of many municipalities included in the Red Zone, in the interval between February 21st and March 8th we continued to perform cardiac surgery (CS) procedures, trying to prioritize urgent or semiurgent cases. Among the patients operated in this timeframe, 10 patients progressively developed COVID-pneumonia, despite an uneventful immediate postoperative course. This small series, although limited, offers a unique opportunity to evaluate the impact of COVID-infection on CS patients, shading some lights on case priority, patient triage, and the need of alternative strategies in case of prohibitive surgical risk.
Among 52 patients operated of CS, 20 patients (38%) were referred from the Codogno Red Zone and 32 patients (62%) came from the metropolitan area of Milan or from other Italian areas (Green “COVID free” zone). According to Health Ministry indications, nasopharyngeal swab PCR screening was performed: in all patients coming from the Red Zone (20 patients) and in patients with clinical and radiological signs of pneumonia, irrespective of the area of origin (3 patients). The preoperative PCR screening and the chest x-rays were negative in all the patients. Postoperatively, 10 patients (19%; mean age = 57±9 years), 6 from the Red zone and 4 from the Green Zone respectively, developed COVID infection and pneumonia, identifying a 22% rate of false-negative screening test (Fig. 1). The most important preoperative comorbidity was hypertension. Coronary artery disease and heart failure (HF) symptoms were evident in 80% and 50% of patients respectively. Five patients with three-vessel disease and left main severe stenosis were referred for unstable angina. Two patients presented with active endocarditis, mobile aortic vegetations and severe aortic regurgitation. Finally, three patients presented with severe valvular dysfunction and clinical signs of impending HF (Table1Table1A Table1).
Nine patients experienced temporary postoperative complications (including transfusion, acute kidney injury, inotropic support), but the remaining postoperative course was uneventful. At a median of 7 days after CS, patients developed fever and flu-like symptoms with worsening severe hypoxia and radiological evidence of pneumonia (Figure 2). Four patients rapidly developed COVID pneumonia (early infected group) after CS, whereas 6 patients showed infection's signs late in the postoperative course (late infected groups) suggesting a different method of contagion (before admission vs during hospital stay). In all patients, the repeated nasopharyngeal swab resulted positive for Sars-Cov2 infection, and patients were isolated in the dedicated COVID Units. From a laboratory viewpoint, patients showed typical lymphopenia (median N/L ratio = 6), higher pro-thrombotic profile (fibrinogen and d-dimer values) and higher markers of inflammation [ferritin and interleukin (IL)-6 values].2 At the zenith of pulmonary distress, patients presented with severe hypoxia (median PaO2/FIO2 ratio= 116), requiring advanced non-invasive ventilation (Venturi mask and continuous positive airway pressure) in the majority of cases (Table 1B).
All patients were treated with hydroxychloroquine and azithromycin, whereas low-molecular-weight heparin was administered at anticoagulant dose to counteract the virus-related microthrombosis.3 Off-label use of tocilizumab, an anti-IL6 receptor monoclonal antibody, was used in 2 patients, with high inflammation and severe ARDS. Overall in-hospital mortality was 10% (1/10), peaking 25% (1/4) in early infected patients. The remaining patients, with late infection, were all discharged home without oxygen support, at a median of 25 days after symptom onset.
In the very early phase of COVID pandemic, the reorganization of acute services aimed to counteract the growing virus-related mortality by expanding the availability of ICU bed, at the expense of a significant reduction in the treatment of several non-COVID clinical conditions in the areas of cancer and cardiovascular disease. As in the recent weeks pandemic seems to move toward a more controlled phase, health care communities need to develop a strategy to restart non-COVID medical and surgical care, driven by clear and safe path to protect the patients, the health care professionals and the whole community.4 In the present experience, we should disclose very honestly some uncertainties or frank errors that we committed in the triage of our CS patients, given all the gaps in knowledge faced by the medical community at the beginning of the pandemic. Considering the high proportion of false-negative in our series (22%), we can conclude that one single nasopharyngeal PCR swab probably is not enough to rule out active infection, especially in case of suspicious anamnesis. However, at the beginning of pandemic the availability of swabs and reagents ran out quickly and antibodies (IgG/IgM) arrays testing was unavailable until the end of April. This fact affected significantly the possibility to screen both asymptomatic patients and health care workers, and probably contributed to the intrahospital virus spread, a phenomenon that dramatically affected contagiousness and mortality in Lombardy. Second, the role of CT scan in COVID-pneumonia evaluation emerged in the literature at the end of March, and in the early pandemic phase, the CT scan workload in our institution was mainly dedicated to the COVID-infected patients, especially to rule out pulmonary thrombotic complications. On these bases, we recommend for the second phase a very meticulous triage of patients submitted to CS, with a combination of nasopharyngeal swab, immunoglobulin assay, and chest CT scan to rule out positive but asymptomatic patients.5
The issue of health care protection and intrahospital contagiousness is another paramount principle that should be considered very carefully. Cardiac surgery, like other type of surgical and interventional procedures is at high risk of contaminating staff, given that aerosol-producing manoeuvres (median sternotomy, endotracheal intubation, transoesophageal echocardiography TEE and CPB heat exchanger) are common.6 Despite contagiousness during patient hospitalization is not easy to reconstruct in the aftermath, some epidemiologic phenomenon in our series (patients’ infection late after surgery, subsequent COVID infection in caregivers involved in positive patients’ management) are highly suggestive for inter-human contagion. In this viewpoint, systematic screening of health care workers and caregivers should be periodically performed to rule out possible transmission from asymptomatic subjects.
Finally, “procedural triage” in COVID pandemic deserves some considerations. When COVID-pneumonia develops early after CS, several factors (surgery-related immunomodulation, ECC-related lung dysfunction and high inflammatory response) can rapidly exacerbate ARDS with very dismal prognosis.7 In the present experience, all the patients were operated on an urgent basis (unstable CAD, endocarditis, HF), balancing the uncorrected cardiac risk against the infective risk. However, as surgical activity is going to restart also for elective procedures, priority should be given to patients with severe or worsening symptoms, especially in case of low or intermediate surgical risk. Finally, patients in need of high-risk procedures should probably be postponed if clinically stable or be evaluated for transcatheter (coronary and valvular) therapies, aiming to reduce the need for ICU and anesthetic services.8 Our personal experience is too limited to draw precise indications on this topic. Anyway, in selected patients, with unstable 3-vessel disease or severe, decompensated AS, transcatheter treatment could be reasonable, especially if favorable anatomical conditions (low coronary Sintax score or straightforward TF TAVI under local anesthesia) are present. However virus-induced thrombophilia is a major issue even in less-invasive percutaneous procedures, and severe periprocedural complications, like acute in-stent thrombosis, have been reported.9
In conclusion, our limited series could provide some insights to help the decision-making process of patients requiring CS during COVID outbreak. As the shortage of diagnostic and therapeutic resources is improving from the dramatic situation of the pandemic beginning, based on the present experience, we recommend some simple observations: meticulous triage, based on at least 2 nasopharyngeal swab and chest CT scan, eventually associated to immunoglobulin assay; safe hospital path and high level of protection for physicians and nurses, to limit intrahospital contagiousness; prompt diagnosis of suspicious symptoms, given that differential diagnosis in the very early postoperative course could be difficult. Finally, as mortality in CS patients early infected by COVID pneumonia is not negligible (25% in the present series), patients with stable cardiac disease should probably be postponed and patients with suitable anatomy should be considered for alternative therapies (ie, transcatheter procedures). Large multicenter data collection on this topic is mandatory, to guide honest heart team discussion to select the most appropriate treatment and the most reasonable resources allocation.
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