Acute Kidney Injury and Sepsis after Cardiac Surgery: The Roles of Tissue Inhibitor Metalloproteinase-2, Insulin-like Growth Factor Binding Protein-7, and Mid-Regional Pro-Adrenomedullin.

BACKGROUND: Identifying a panel of markers detecting kidney injury before the glomerular filtration rate reduction is a challenge to improving the diagnosis and management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase-2, insulin growth factor binding protein-7 (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in patients with AKI. PATIENTS AND METHODS: This study was prospectively conducted in an intensive care unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 h of the cardiac surgery. RESULTS: Whereas urine and creatinine alterations appeared at 23.2 (12.7-36.5) hours after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 h in AKI patients (1.1 ± 0.4 mg/L vs. 0.08 ± 0.02 mg/L; p < 0.001). Its concentration > 2 mg/L increases AKI risk within the following 24 h, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/L (0.7-7.8 nmol/L), with the highest values observed in septic shock patients (5.6 nmol/L (3.2-18 nmol/L)) and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values > 5.1 nmol/L and urine TIMP2*IGBP7 levels > 2 mg/L showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. CONCLUSIONS: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Left Atrial Appendage Closure Device Embolization under the Anterior Leaflet of Mitral Valve: Echocardiographic Diagnosis and Management.

A 76-year-old man with history of previous coronary artery bypass grafting, permanent atrial fibrillation in novel oral anticoagulation therapy, and gastrointestinal bleedings underwent percutaneous left atrial appendage closure. The procedure was complicated by intraoperative device embolization, which caused a dynamic obstruction of the left ventricular outflow tract leading to severe hemodynamic instability. Transesophageal echocardiography showed a device in the ventricle site of the mitral anterior leaflet. The coronary angiography showed also patency of both arterial grafts in stable coronary artery disease. After failing the percutaneous retrieval with a snare, emergent surgery was planned. A moderate calcified aortic valve stenosis was also found, but in consideration of the unstable clinical conditions of the patient, we thought of performing a transcatheter aortic valve replacement (TAVR) in a second time. We have carefully planned the surgical retrieval of the device embolized paying attention of his several comorbidities. The strategy to remove the device with cardiopulmonary bypass without cross-clamping the aorta through a right mini-thoracotomy has been preferred.

Virtually Wall-Less versus Standard Thin-Wall Venous Cannula in the Minimally Invasive Mitral Valve Surgery: Single-Center Experience.

Background and Objectives: Minimally invasive cardiac surgery (MICS) has been developing since 1996. Peripheral cannulation is required to perform MICS, and good venous drainage and a bloodless field are crucial for the success of this procedure. We assessed the benefits of using a virtually wall-less cannula in comparison with the standard thin-wall cannula in clinical practice. Materials and Methods: Between January 2021 and December 2022, we evaluated 65 elective patients, who underwent isolated minimally invasive mitral valve surgery. Both the virtually wall-less and the thin-wall cannulas were placed through a surgical cut-down. Patients' characteristics at baseline were similar in the two groups, except for the body surface area (BSA), which was greater in the virtually wall-less group compared to the thin-wall one. In the standard group, the size of the cannula was chosen depending on the patient's BSA, and the choice of the Smartcannula was based on their height. Results: There were no significant differences between the two groups in terms of negative pressure applied, target flow achieved, hemolysis, the need for blood transfusion, and the post-operative increases in liver and renal enzymes. However, in all the patients, the estimated target flow was achieved, thereby showing the better hemodynamic performance of the virtually wall-less cannula, since, in this group, the patients' BSA was significantly greater compared to the thin-wall group. Ultimately, the mean cross-clamp time, as an indirect index of the effectiveness of the venous drainage, is shorter in the virtually wall-less group compared with the thin-wall group. Conclusions: The virtually wall-less cannula should be preferred in minimally invasive mitral valve surgery due to its superior performance in terms of venous drainage compared with the standard thin-wall cannula.

Acute type A aortic dissection in bicuspid versus tricuspid aortic valve patients: focus on geometrical features of the aorta.

OBJECTIVES: This retrospective observational study aimed to assess the geometrical features, including diameters, length and angulation, of the ascending aorta with bicuspid and tricuspid aortic valve and to identify imaging markers potentially predicting whether aortopathy is likely to evolve chronically or to complicate with acute type A dissection. METHODS: Angio-computed-tomography scans of 354 patients (from 3 centres) with non-dilated (n = 97), aneurysmal (n = 100) or dissected aorta (n = 157) were reviewed. Diameters were measured at root, sinotubular junction, ascending, brachio-cephalic trunk origin; centreline lengths of the root and tubular tract and ascending-arch angle (between the ascending tubular tract axis and the proximal arch axis) were also measured. For 12 dissection patients, pre-dissection scans were available to investigate predisposing aortic geometry. Statistical analysis included: tricuspid versus bicuspid comparisons in each subgroup; univariate and multivariate analyses of the predictors of ascending-arch angle narrowing; and estimation of diagnostic accuracy of the angle parameter. RESULTS: Diameters and lengths were similar between aneurysms and dissections, whereas dissections showed a significant ascending-arch angle narrowing (117 ± 13° in tricuspid, 115 ± 14° in bicuspid) compared to non-dilated and aneurysmal aortas (all P < 0.001). The best angle cut-off to discriminate dissection patients was 131° (96% sensitivity). In patients with a pre-dissection scan, Asc-Arch narrowing was already present before dissection. In non-dissected aortas over-angulation was predicted by root phenotype dilatation both in bicuspid and tricuspid patients. Bicuspid patients with non-dilated aorta showed elongated root (P = 0.027), a feature significantly correlated with Asc-Arch angle narrowing (P = 0.008). CONCLUSIONS: The ascending-arch angle is promising as a risk marker for dissection to be used along with diameter. Its narrowing seems to be associated with elongation of the root, a feature that bicuspid patients can show even without significant dilatation. Root phenotype aortopathy may be at higher risk also with tricuspid aortic valve.

Analysis of changes in "mitral valve reserve" after coronary artery bypass grafts in patients with functional mitral regurgitation.

INTRODUCTION: The treatment of moderate functionalmitral regurgitation (FMR) during coronary artery bypass grafting (CABG) is still debated. Our primary end point was to assess the improvement of "mitral valve reserve" (MVR) after CABG alone as a clinical demonstration of left ventricular (LV) recovery. MATERIALS AND METHODS: Between June 2019 and June 2021, we prospectively enrolled 104 consecutive patients undergoing CABG with moderate FMR. Inclusion criteria were inferior-posterior-lateral wall hypokinesia and revascularization of the circumflex or right coronary artery. MVR was calculated as the ratio between anterior and posterior leaflets' straight length. All patients were followed for 1 year. The improvement of MVR has been considered as a reduction of the ratio between anterior and posterior leaflets straight length. RESULTS: Compared to baseline, mean MVR was significantly reduced both at 6 (2.24 ± 0.95 vs. 1,91 ± 0.6; p = 0,047) and 12 months follow-up (2.24 ± 0.95 vs. 1,69 ± 0.49; p = 0,006). Left ventricular (LV) reverse remodeling, meant as improvement of LV ejection fraction and reduction of LV end-systolic volume index and mitral anulus diameter were evaluated at 6 months and 1 year. Mitral regurgitation grade were also significantly reduced at 6 months (p < .001). CONCLUSION: The benefits of myocardial revascularization in term of improvement of mitral regurgitation's degree can be explained by the changes of MVR. The patients with FMR, who could have more advantages from CABG alone, should be the ones who have LVESVi just moderately increased.

Aortic intramural hematoma and classic aortic dissection: two sides of the same coin within the acute aortic syndrome for an interventional radiologist.

Management of acute type B aortic intramural haematoma (AIH) still represents a challenging issue. Although most resolve spontaneously or with conservative therapy, several cases of AIH may complicate into classic aortic dissection with subsequent risk of aortic rupture and visceral malperfusion, thus needing urgent or preemptive thoracic endovascular aneurysm repair (TEVAR). Despite the long-term aorta-related survival, TEVAR might lead to graft obstruction, migration, infection, stroke/paraplegia, visceral ischemia, endoleak and, last but not least, retrograde aortic dissection (AD), frequent in the acute phase and associated with a high mortality risk. In order to highlight such a close relationship between AIH and AD and the possibility to perform endovascular treatment, we report the experience of an adult female patient with an aortic intramural haematoma evolving into a classic aortic dissection. Despite successful thoracic endovascular aneurysm repair (TEVAR), our patient developed an aortic dissection type A at one month with subsequent indication for cardiac surgery still representing the elective approach in case of pathologies including the ascending aorta. Thus, the aim of our discussion is to create a debate on the most appropriate management for the treatment of descending AIH.

Prognostic value of SARS-CoV-2 on patients undergoing cardiac surgery.

OBJECTIVE: To analyze Italian Cardiac Surgery experience during the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identifying risk factors for overall mortality according to coronavirus disease 2019 (COVID-19) status. METHODS: From February 20 to May 31, 2020, 1354 consecutive adult patients underwent cardiac surgery at 22 Italian Centers; 589 (43.5%), patients came from the red zone. Based on COVID-19 status, 1306 (96.5%) were negative to SARS-CoV-2 (COVID-N), and 48 (3.5%) were positive to SARS-CoV-2 (COVID-P); among the COVID-P 11 (22.9%) and 37 (77.1%) become positive, before and after surgery, respectively. Surgical procedures were as follows: 396 (29.2%) isolated coronary artery bypass grafting (CABG), 714 (52.7%) isolated non-CABG procedures, 207 (15.3%) two associate procedures, and three or more procedures in 37 (2.7%). Heart failure was significantly predominant in group COVID-N (10.4% vs. 2.5%, p = .01). RESULTS: Overall in-hospital mortality was 1.6% (22 cases), being significantly higher in COVID-P group (10 cases, 20.8% vs. 12, 0.9%, p < .001). Multivariable analysis identified COVID-P condition as a predictor of in-hospital mortality together with emergency status. In the COVID-P subgroup, the multivariable analysis identified increasing age and low oxygen saturation at admission as risk factors for in-hospital mortality. CONCLUSION: As expected, SARS-CoV-2 infection, either before or soon after cardiac surgery significantly increases in-hospital mortality. Moreover, among COVID-19-positive patients, older age and poor oxygenation upon admission seem to be associated with worse outcomes.

Echocardiographic Evolution of PosteroLateral Left Ventricular Aneurysm with Normal Coronary Arteries in Patient Recently COVID-19 Vaccinated: A Complicated Atypical Case of Takotsubo Syndrome Vaccine-related?

A 72-year-old woman, recently COVID-19 vaccinated with a third dose, was referred to our center for acute chest pain and dyspnea. On admission, the electrocardiography showed a STEMI on inferior derivations and the dyskinesia of the inferior wall was found at the first transthoracic echocardiogram. The coronary angiography did not show coronary artery disease. After 1 week, a huge posterolateral left ventricular (LV) aneurysm with initial signs of rupture was found and the patient underwent a Dor's procedure to exclude the LV aneurysm. As far as we know, this is the first reported case of Takotsubo following the COVID-19 vaccination requiring cardiac surgery.

Cardiac surgery practice during the COVID-19 outbreak: a multicentre national survey.

OBJECTIVES: Healthcare systems worldwide have been overburdened by the coronavirus disease 2019 (COVID-19) outbreak. Accordingly, hospitals had to implement strategies to profoundly reshape both non-COVID-19 medical care and surgical activities. Knowledge about the impact of the COVID-19 pandemic on cardiac surgery practice is pivotal. The goal of the present study was to describe the changes in cardiac surgery practices during the health emergency at the national level. METHODS: A 26-question web-enabled survey including all adult cardiac surgery units in Italy was conducted to assess how their clinical practice changed during the national lockdown. Data were compared to data from the corresponding period in 2019. RESULTS: All but 2 centres (94.9%) adopted specific protocols to screen patients and personnel. A significant reduction in the number of dedicated cardiac intensive care unit beds (-35.4%) and operating rooms (-29.2%), along with healthcare personnel reallocation to COVID departments (nurses -15.4%, anaesthesiologists -7.7%), was noted. Overall adult cardiac surgery volumes were dramatically reduced (1734 procedures vs 3447; P < 0.001), with a significant drop in elective procedures [580 (33.4%) vs 2420 (70.2%)]. CONCLUSIONS: This national survey found major changes in cardiac surgery practice as a response to the COVID-19 pandemic. This experience should lead to the development of permanent systems-based plans to face possible future pandemics. These data may effectively help policy decision-making in prioritizing healthcare resource reallocation during the ongoing pandemic and once the healthcare emergency is over.

Dynamic right ventricular outflow tract obstruction by cardiac hydatic cysts: A multimodality imaging study.

We report the case of massive hydatic heart disease in a 50-year-old male patient referred to hospital for recent-onset dyspnea, atypical chest, and hypotension. Right ventricular outflow tract obstruction was demonstrated to be caused by hypoechogenic formations at Doppler-echocardiography and confirmed to be hydatic cysts at cardiac magnetic resonance. These cysts developed within the right ventricular wall and the septum, and caused hemodynamic instability.

Malignant right coronary artery origin from the left sinus of Valsalva: Complementary role for transesophageal echocardiography upon the cath-lab diagnosis.

Anomalous origin of the right coronary artery (RCA) from the left sinus of Valsalva is a rare but clinically relevant congenital anomaly, since the RCA may be subjected to cyclical compression due to its interarterial course. At least in the past, most patients experienced bad outcomes before being diagnosed with a malignant variant. Chronic (often subclinical) myocardial ischemia and possible arrhythmias are common complications. Once symptoms or electrocardiographic signs of myocardial ischemia become apparent, a quick diagnosis is mandatory. We report the case of a late symptomatic woman in whom RCA originated from the opposite sinus of Valsalva. The malignant variant was confirmed at transesophageal echocardiography directly in the catheterization laboratory, soon after angiographic diagnosis of aberrant origin.

The TLR4 adaptor TRAM controls the phagocytosis of Gram-negative bacteria by interacting with the Rab11-family interacting protein 2.

Phagocytosis is a complex process that eliminates microbes and is performed by specialised cells such as macrophages. Toll-like receptor 4 (TLR4) is expressed on the surface of macrophages and recognizes Gram-negative bacteria. Moreover, TLR4 has been suggested to play a role in the phagocytosis of Gram-negative bacteria, but the mechanisms remain unclear. Here we have used primary human macrophages and engineered THP-1 monocytes to show that the TLR4 sorting adapter, TRAM, is instrumental for phagocytosis of Escherichia coli as well as Staphylococcus aureus. We find that TRAM forms a complex with Rab11 family interacting protein 2 (FIP2) that is recruited to the phagocytic cups of E. coli. This promotes activation of the actin-regulatory GTPases Rac1 and Cdc42. Our results show that FIP2 guided TRAM recruitment orchestrates actin remodelling and IRF3 activation, two events that are both required for phagocytosis of Gram-negative bacteria.

Neutrophils Directly Recognize Group B Streptococci and Contribute to Interleukin-1ß Production during Infection.

Previous studies have shown that the pro-inflammatory cytokine IL-1ß has a crucial role in host defenses against group B streptococcus (GBS), a frequent human pathogen, by recruiting neutrophils to infection sites. We examined here the cell types and mechanisms involved in IL-1ß production during infection. Using a GBS-induced peritonitis model in mice, we first found that a large proportion of exudate cells contain intracellular IL-1ß by immunofluorescence. Of the IL-1ß positive cells, 82 and 7% were neutrophils and macrophages, respectively, suggesting that the former cell type might significantly contribute to IL-1ß production. Accordingly, depletion of neutrophils with anti-Ly6G antibodies resulted in a significant reduction in the levels of IL-1ß, but not of TNF-α or IL-6. We next found that neutrophils are capable of releasing mature IL-1ß and TNF-α directly in response to in vitro stimulation with GBS. The production of pro-IL-1ß and TNF-α in these cells required the Toll-like receptor (TLR) adaptor MyD88 and the chaperone protein UNC93B1, which is involved in mobilization of a subfamily of TLRs to the endosomes. Moreover, pro-IL-1ß processing and IL-1ß release was triggered by GBS hemolysin and required components of the canonical inflammasome, including caspase-1, ASC and NLRP3. Collectively our findings indicate that neutrophils make a significant contribution to IL-1ß production during GBS infection, thereby amplifying their own recruitment. These cells directly recognize GBS by means of endosomal TLRs and cytosolic sensors, leading to activation of the caspase-1 inflammasome.

Prognostic Implications of Acute Renal Failure after Surgery for Type A Acute Aortic Dissection.

BACKGROUND: "Type A" acute aortic dissection (AAAD) is the most challenging among the emergency operations in cardiac surgery. The aim of this study was the evaluation of the role of acute renal failure (ARF) in postoperative survival of patients operated for AAAD. METHODS: From February 2010 to April 2012, 37 consecutive patients were operated at our department for AAAD. We studied our population by subdividing the patients within groups according to the presence of ARF requiring continuous veno-venous hemofiltration (CVVH) and according to hypothermic circulatory arrest (HCA) times and degrees. RESULTS: The overall 30-day mortality was 27% (50% group A with ARF, 13% group B no ARF). Acute renal failure requiring CVVH was 37.8%. Multivariate analysis revealed a significant association with 30-day mortality (odds ratio 6.6 and p = 0.020). Preoperative oliguria [urine output less than 30 ml/h (odds ratio 4.7 p = 0.039)], CPB greater than 180 minutes (odds ratio 6.5 p = 0.023) and postoperative bleeding requiring a surgical reopening (odds ratio 12.2 and p = 0.021) were the variables significantly associated with acute kidney injury. CONCLUSIONS: The data obtained from our analysis bring out the high incidence of renal injuries after surgery for AAAD, and indicate a negative impact on renal injuries of a preoperative oliguria, longer Cardiopulmonary bypass (CBP)/HCA times, and postoperative bleeding requiring a surgical revision. Our data also suggest a better 30-day survival and better renal outcomes in case of shorter HCA and lesser degree of hypothermia. The option of lesser and shorter hypothermia may be very useful, especially for the elderly patients and octogenarians.

Role of Toll-like receptor 13 in innate immune recognition of group B streptococci.

Murine Toll-like receptor 13 (TLR13), an endosomal receptor that is not present in humans, is activated by an unmethylated motif present in the large ribosomal subunit of bacterial RNA (23S rRNA). Little is known, however, of the impact of TLR13 on antibacterial host defenses. Here we examined the role of this receptor in the context of infection induced by the model pathogen group B streptococcus (GBS). To this end, we used bacterial strains masked from TLR13 recognition by virtue of constitutive expression of the ErmC methyltransferase, which results in dimethylation of the 23S rRNA motif at a critical adenine residue. We found that TLR13-mediated rRNA recognition was required for optimal induction of tumor necrosis factor alpha and nitrous oxide in dendritic cell and macrophage cultures stimulated with heat-killed bacteria or purified bacterial RNA. However, TLR13-dependent recognition was redundant when live bacteria were used as a stimulus. Moreover, masking bacterial rRNA from TLR13 recognition did not increase the ability of GBS to avoid host defenses and replicate in vivo. In contrast, increased susceptibility to infection was observed under conditions in which signaling by all endosomal TLRs was abolished, i.e., in mice with a loss-of-function mutation in the chaperone protein UNC93B1. Our data lend support to the conclusion that TLR13 participates in GBS recognition, although blockade of the function of this receptor can be compensated for by other endosomal TLRs. Lack of selective pressure by bacterial infections might explain the evolutionary loss of TLR13 in humans. However, further studies using different bacterial species are needed to prove this hypothesis.