How the First Year of the COVID-19 Pandemic Impacted Patients’ Hospital Admission and Care in the Vascular Surgery Divisions of the Southern Regions of the Italian Peninsula

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia.


Introduction
The Coronavirus Disease 2019 (COVID-19) pandemic has changed lifestyles and working activities worldwide. Following the publication of the Italian government decree in March 2020, three-month strict lockdown measures were implemented countrywide to avoid social contact. Hospital-related routines were interrupted to prioritize the management of COVID-19 cases; in particular, outpatient and elective surgeries were postponed.
Similar prevention and public health interventions were implemented from mid-September to the beginning of December 2020 in response to the second wave of the pandemic. Furthermore, except for situations of proven urgency, the quality of diagnostic and therapeutic care in general medicine in Southern Italy was impacted negatively during the lockdowns, affecting the diagnosis, management, and surveillance of vascular patients. For instance, screening programs for carotid stenosis and abdominal aortic aneurysm and early detection of Rutherford category 3 peripheral arterial disease (R3-PAD) worsening towards chronic limb-threatening ischemia (CLTI) have surely been dramatically postponed.
This study was conducted to assess the eventual impact of suspension of hospitalization for elective vascular surgery on the incidence rates of hospital admissions for complications caused by common vascular conditions compared to the pre-pandemic period.

Materials and Methods
A multicenter retrospective study was conducted through a cross-sectional survey; the majority of public vascular surgery wards and those accredited with the National Health System (NHS) located in the south of the Italian peninsula were enrolled, i.e., the regions of Campania, Molise, Basilicata, Puglia, and Calabria (population: 12,646,486; area: 62,809 km 2 , Figure 1). Even though healthcare policies are issued at the regional level in Italy, the abovementioned regions implemented similar COVID-19 restrictions.
Twenty-seven vascular surgery divisions joined the study; only two centers (one public and one private) declined to participate due to lack of human resources for data collection. A 13-item questionnaire was provided, asking about the number of patients that underwent: (1) open repair or endovascular aneurysm repair (EVAR) for asymptomatic abdominal aortic aneurysm (AAA); (2) open repair or EVAR for primary ruptured or symptomatic AAA; (3) duplex or computed-tomography scans performed for post-EVAR surveillance; (4) Previous EVAR treated again (in an open or endovascular fashion) for recurring symptomatic or ruptured AAA, or for endoleak at risk of AAA rupture (type 1, 3, or 2 with sac expansion); (5) open, or endovascular treatments for thrombotic, non-embolic, acute lower limb ischemia; (6) treatments for Rutherford category 3 peripheral arterial disease (R3-PAD) in socially active patients with very short distance intermittent claudication (less than 50 mt. on the flat), not responsive to best medical therapy, and asking for a resolutive treatment to improve their lifestyle; (7) open or endovascular revascularizations for chronic limb-threatening ischemia (CLTI); (8) CLTI patients who have had a thigh or leg amputated; (9) open or endovascular revascularizations for asymptomatic severe internal carotid artery (ICA) stenosis; (10) Asymptomatic severe ICA stenosis on surgical waiting list, complicated to total obstruction (with or without neurological symptoms); (11) symptomatic ICA stenosis operated in urgency; (12) conservative or surgical treatments for venous ulcers; (13) diagnosis of deep vein thrombosis (DVT), also from requests of consultation from the emergency room or any medical/surgical divisions.
The aim was to compare these vascular surgery activities before (i.e., 11 months pre-COVID-19) and during (i.e., 11 months from the beginning of the pandemic) the COVID-19 pandemic.
Indications for carotid, AAA, CLTI, and venous surgery, as well as the diagnosis of vascular diseases, are those reported in the current, well-known, international guidelines.
Informed consent for the present study was waived because of the retrospective and aggregated nature of the study analysis. Being an observational study, according to Italian law mandatory approval is not needed.
Formal ethical approval and patient informed consent were not needed. The current Italian legislation on observational studies such as the present one does not request the above-mentioned documents when clinical data are anonymized (Official Gazette of the Italian Republic # 76, 31 March 2008).
Clinical characteristics were described with absolute and relative (percentage) frequencies. Qualitative variables were compared using the chi-square test. Percentage differences for the collected variables (delta) between the pre-COVID-19 and COVID-19 periods were computed. A two-tailed p-value < 0.05 was considered statistically significant. All statistical analyses were carried out using STATA software version 17 (StataCorp LLC, College Station, TX, USA).
Treatment for venous ulcers and frequency of admissions for EVAR or open repair for asymptomatic AAA and severe ICA stenosis >80% (according to the European Carotid Surgery Trial, ECST, parameters) on operating waiting lists complicated to total obstruction (detected at duplex control before revascularization or because they became symptomatic) did not change throughout the study period.     When only April 2019 and April 2020 were compared, the significant decrease in imaging for post-EVAR surveillance, frequency of admissions for R3-PAD, and asymptomatic ICA stenosis revascularization was confirmed (19.43%, vs. 9.98% p < 0.0001;

Discussion
Early identification of life-threatening vascular conditions, which are mostly asymptomatic, is essential. Changes during the COVID-19 pandemic could have affected patient prognosis. Several researchers, clinicians, and policymakers have been trying to understand the real impact of the pandemic on clinical activities [1].
In the Netherlands it has been reported that during the lockdown period of 16 March until 30 April 2020, there was a statistically significant increase in CLTI severity and rates of major amputations compared to the same time period during the two previous years. No difference in vascular surgical care for patients with an AAA has been observed [2]. On the contrary, a study carried out in the metropolitan city of Bologna, Italy, focusing on the first 30 days of the COVID-19 pandemic showed that the number of surgical interventions was similar to that recorded in 2018 and 2019. No differences were found in the acute/emergency setting, including interventions for acute ischemia, although SARS-CoV-2 infections triggers thrombogenic mechanisms [3]. At the same time, English colleagues have reported different results [4]. These two last conflicting experiences are probably affected by the limited period of time and/or the population analyzed.
A US cross-sectional study focusing on the period from 14-24 April 2020 showed a significant impact on the practice of vascular surgery across the country, with an unprecedented number of surgical cases cancelled and changes in on-call schedules. The majority of continued elective cases were on aortic repair and maintenance of dialysis function rather than peripheral arterial disease or venous procedures [5]. Similarly, in Indochina almost all vascular interventions were suspended during the COVID-19 outbreak [6].
Our multicenter study covering more than one-fifth of the Italian geographical area and population over a longer time-period (11 months before and 11 months during the COVID-19 pandemic) showed a significant decrease in elective interventions for the following: − Prophylactic ICA revascularization during each month of the pandemic compared to the prior year, as well as during the first two months of the pandemic compared to the prior two months; − Imaging for post-EVAR surveillance from April to June, 2020 compared to the corresponding time-period in 2019, as well as during the first two months of the pandemic (March-April, 2020) in comparison with the two months before it (January-February, 2020); − Treatment for R3-PAD during the first two months of the pandemic in comparison with the two prior months, and in April 2020 and January 2021 when compared with the corresponding month of the previous year.
On the other hand, there was a significant increase in diagnosis of DVT and frequency of admission for urgent revascularization for symptomatic ICA stenosis, revascularization for CLTI, major amputations, open repair or EVAR for primary ruptured or symptomatic AAA, and treatment of acute thrombotic lower limb ischemia.
The decrease in admissions for prophylactic ICA revascularization could be associated with the increased hospitalization rate for urgent revascularization of symptomatic carotid stenosis.
Furthermore, the decrease in admissions for R3-PAD in the first two months of the pandemic could explain the increased rate of hospitalization for revascularization and major amputation of CLTI patients in April and November-December 2020 and January 2021. Around 20% of patients with intermittent claudication experience deterioration of limb status over a five-year period, and symptomatic deterioration is greatest within the first year after diagnosis [7].
Interestingly, in January 2021, when the immediate pandemic restrictions were lifted, a major decrease in admissions for R3-PAD and severe asymptomatic ICA stenosis persisted compared to pre-pandemic levels. Our analysis suggests that these delays may have further consequences in the coming months. Project 1 (Impact of COVID-19 on scheduled vascular operations) of the international Vascular Surgery COVID-19 Collaborative (VASCC) registry aims to answer this particular question. The VASCC is a combined international effort to obtain prospective data on the impact of widespread vascular surgical care delays due to an international crisis or pandemic [8,9]. An increased rate of DVT during the first four months of the pandemic and of hospitalization for thrombotic acute lower limb ischemia recalls the prothrombotic effects of the SARS-CoV-2 infection [10,11]. This broad spectrum of clinical manifestations, affecting almost all organs and systems, is a consequence of endothelial dysfunction and systemic inflammatory response. Endothelial cells activated by a hyperinflammatory state induced by viral infection may promote localized inflammation, increase reactive oxidative species production, and alter the dynamic interplay between procoagulant and fibrinolytic factors in the vascular system, leading to thrombotic disease both in the pulmonary circulation and in peripheral veins and arteries [12].
Although the US national trends in Vascular Surgical Practice showed a decreased rate of urgent and emergency aortic and carotid interventions, our study described an increased rate of open repair or EVAR for ruptures or symptomatic AAA and of symptomatic carotid stenosis treated with urgency [13].
The constant trends of patients who underwent EVAR or open repair for primary asymptomatic AAA during the current pandemic could be associated with the positive organization of healthcare delivery in the participating centers, although no specific data were collected to support this hypothesis. Similar explanations could support the trends of conservative or surgical treatment for venous ulcers, although they are managed in wards other than vascular surgery (i.e., vascular medicine and dermatology).
Several study limitations can be highlighted: several vascular diseases (e.g., thoracic or thoraco-abdominal aortic aneurysms and dialysis access) were not considered. Complex aortic procedures are often referred to specialist centers, and we thought that the numbers would be too low. In Italy, arteriovenous fistulas are performed by nephrologists; likewise, varicose vein surgery was excluded based on its postponement caused by low priority. We evaluated only the first eleven months of the COVID-19 pandemic against the corresponding 2019 months; as such, inter-annual variability cannot be excluded. Stratification of the findings based on SARS-CoV-2 positivity was not always performed; infection could have increased the incidence of certain vascular diseases (e.g., DVT). Asymptomatic severe ICA stenosis that progressed to occlusion (and thus was managed non-surgically) could have been missed, as it can cause cerebral ischemia, which can be managed in different medical wards (e.g., stroke unit, intensive care unit, neurology, internal medicine) and thus be under-reported.

Conclusions
The interruption of elective surgery during the COVID-19 pandemic caused decreased rates of post-EVAR surveillance and hospitalization for prophylactic carotid revascularization and R3-PAD. These findings are associated with an increased rate of hospital admission for urgent revascularization for symptomatic carotid stenosis, CLTI, and subsequent major amputations.
The vascular community is called upon to raise awareness of the dangers arising from restrictions in the management of these elective vascular patients during the pandemic crisis.
The long-term effects on the management of vascular patients should be evaluated in the near future.