Quantification of anatomical aortic valve area by multi-detector computed tomography: A pilot 3D-morphological modeling of the stenotic aortic valve.

BACKGROUND: Aortic-valve-stenosis (AS) is a frequent degenerative valvular-disease and carries dismal outcome under-medical-treatment. Transvalvular pressure gradient reflects severity of the valve-disease but is highly dependent on flow-conditions and on other valvular/aortic characteristics. Alternatively, aortic-valve-area (AVA) represents a measure of aortic-valve lesion severity conceptually essential and practically widely-recognized but exhibits multiple-limitations. METHODS: We analyzed the 4D multi-detector computed tomography(MDCT) of 20 randomly selected patients with severe AS. For each-patient, we generated the 3D-model of the valve and of its calcifications, and we computed the anatomical AVA accounting for the 3D-morphology of the leaflets in three-different-ways. Finally, we compared our results vs. Doppler-based AVAE measurements and vs. 2D-planimetric AVA-measurements. RESULTS: 3D-reconstruction and identification of the cusps were successful in 90% of the cases. The calcification patterns where highly-variable over patients, ranging from multiple small deposits to wide and c-shaped deposits running from commissure-to-commissure. AVAE was 82 ± 15 mm2. When segmenting 18 image planes, AVATight, AVAProj-Ann, AVAProj-Tip and their average AVAAve were equal to 80 ± 16, 88 ± 20, 93 ± 21 and 87 ± 19 mm2, respectively, while AVAPlan was equal to 143 ± 50 mm2. Linear-regression of the three measurements vs. AVAE yielded regression slopes equal to 1.26, 1.13 and 0.93 for AVAProj-Ann, AVAProj-Tip and AVATight, respectively. The respective Pearson-coefficients were 0.85,0.86 and 0.90. Conversely, when comparing AVAPlan vs. AVAE, linear regression yielded a slope of 1.73 and a Pearson coefficient of 0.53. CONCLUSIONS: We described a new-method to obtain a set of flow-independent quantifications that complement pressure gradient measurements and combine the advantages of previously proposed methods, while bypassing the corresponding-limitations.

Analysis of Prevalence and Clinical Features of Aortic Stenosis in Patients with and without Bicuspid Aortic Valve Using Machine Learning Methods.

Aortic stenosis (AS) is the most commonly diagnosed valvular heart disease, and its prevalence increases with the aging of the general population. However, AS is often diagnosed at a severe stage, necessitating surgical treatment, due to its long asymptomatic period. The objective of this study was to analyze the frequency of AS in a population of cardiovascular patients using echocardiography (ECHO) and to identify clinical factors and features associated with these patient groups. We utilized machine learning methods to analyze 84,851 echocardiograms performed between 2010 and 2018 at the National Medical Research Center named after V.A. Almazov. The primary indications for ECHO were coronary artery disease (CAD) and hypertension (HP), accounting for 33.5% and 14.2% of the cases, respectively. The frequency of AS was found to be 13.26% among the patients (n = 11,252). Within our study, 1544 patients had a bicuspid aortic valve (BAV), while 83,316 patients had a tricuspid aortic valve (TAV). BAV patients were observed to be younger compared to TAV patients. AS was more prevalent in the BAV group (59%) compared to the TAV group (12%), with a p-value of <0.0001. By employing a machine learning algorithm, we randomly identified significant features present in AS patients, including age, hypertension (HP), aortic regurgitation (AR), ascending aortic dilatation (AscAD), and BAV. These findings could serve as additional indications for earlier observation and more frequent ECHO in specific patient groups for the earlier detection of developing AS.

Three Decades of Experience with Aortic Prosthetic Valve Endocarditis.

The objective of this study was to evaluate early and long-term outcomes of patients with aortic prosthetic valve endocarditis (a-PVE) treated with a prosthetic aortic valve (PAV), prosthetic valved conduit (PVC), or cryopreserved aortic homograft (CAH). A total of 144 patients, 115 male and 29 female, aged 67 ± 12 years, underwent surgery for a-PVE at our institution between 1994 and 2021. Median time from the original cardiac surgery was 1.9 [0.6-5.6] years, and 47 (33%) patients developed an early a-PVE. Of these patients, 73 (51%) underwent aortic valve replacement (AVR) with a biological or mechanical PAV, 12 (8%) underwent aortic root replacement (ARR) with a biological or mechanical PVC, and 59 (42%) underwent AVR or ARR with a CAH. Patients treated with a CAH had significantly more circumferential annular abscess multiple valve involvement, longer CPB and aortic cross-clamping times, and needed more postoperative pacemaker implantation than patients treated with a PAV. No difference was observed in survival, reoperation rates, or recurrence of IE between patients treated with a PAV, a PVC, or a CAH. CAHs are technically more demanding and more often used in patients who have extensive annular abscess and multiple valve involvement. However, the use of CAH is safe in patients with complex a-PVE, and it shows excellent early and long-term outcomes.

Validation of a new model of selective antegrade cerebral perfusion with circulatory arrest in rats.

BACKGROUND: Selective antegrade cerebral perfusion (SACP) is adopted as an alternative to deep hypothermic circulatory arrest (DHCA) during aortic arch surgery. However, there is still no preclinical evidence to support the use of SACP associated with moderate hypothermia (28-30°C) instead of DHCA (18-20°C). The present study aims to develop a reliable and reproducible preclinical model of cardiopulmonary bypass (CPB) with SACP applicable for assessing the best temperature management. MATERIALS AND METHODS: A central cannulation through the right jugular vein and the left carotid artery was performed, and CPB was instituted.Animals were randomized into two groups: normothermic circulatory arrest without or with cerebral perfusion (NCA vs SACP). EEG monitoring was maintained during CPB. After 10 min of circulatory arrest, rats underwent 60 min of reperfusion. After that, animals were sacrificed, and brains were collected for histology and molecular biology analysis. RESULTS: Power spectral analysis of the EEG signal showed decreased activity in both cortical regions and lateral thalamus in all rats during the circulatory arrest. Only SACP determined complete recovery of brain activity and higher power spectral signal compared to NCA (p < 0.05). Histological damage scores and western blot analysis of inflammatory and apoptotic proteins like caspase-3 and Poly-ADP ribose polymerase (PARP) were significantly lower in SACP compared to NCA. Vascular endothelial growth factor (VEGF) and RNA binding protein 3 (RBM3) involved in cell-protection mechanisms were higher in SACP, showing better neuroprotection (p < 0.05). CONCLUSIONS: SACP by cannulation of the left carotid artery guarantees good perfusion of the whole brain in this rat model of CPB with circulatory arrest. The present model of SACP is reliable, repeatable, and not expensive, and it could be used in the future to achieve preclinical evidence for the best temperature management and to define the best cerebral protection strategy during circulatory arrest.

Correlation between epicardial adipose tissue and atrial fibrillation burden in coronary artery bypass graft surgery.

AIMS: Recent studies suggest an association between epicardial adipose tissue (EAT) and atrial fibrillation. The aim of the study is to evaluate the quantitative and qualitative characteristics of EAT in relation to atrial fibrillation burden after coronary artery bypass graft (CABG). METHODS: This prospective single-centre study included patients undergoing CABG. The patients underwent transthoracic echocardiography and collection of a bioptic sample containing right appendage and EAT during CABG for histological characterization. After surgery, clinical and telemetry data were collected. RESULTS: Fifty-six consecutive patients were enrolled. The mean postsurgical hospitalization was 7.9 ±â€Š3.7 days. Twenty-two patients had at least one episode of atrial fibrillation. In the atrial fibrillation group, there was a bigger atrial volume, a higher degree of diastolic disfunction, a thicker layer of EAT and an older median age in comparison with the group that did not develop it. EAT with a cut-off of 4 mm was a predictor of atrial fibrillation with an odds ratio (OR) of 1.49 (confidence interval (CI) 1.09-2.04), 73% of sensibility and 89% of specificity. From the histological analyses, the patients with atrial fibrillation had a significantly higher percentage of fibrosis. At univariate analysis, atrial volume [OR 1.05, CI 1.01-1.09, P = 0.022], E/A rate (OR 0.04, CI 0.02-0.72 P = 0.29), the percentage of fibrosis (OR 1.12, CI 1.00-1.25, P = 0.045) and age (OR 1.17, CI 1.07-1.28, P = 0.001) were predictors of atrial fibrillation. At multivariate analysis, atrial volume (P = 0.027), fibrosis (P = 0.003) and age (P = 0.039) were independent predictors of atrial fibrillation. CONCLUSION: Postcardiac surgical atrial fibrillation is frequent. EAT thickness, atrial volume, fibrosis and age are predictors of postcardiac surgical atrial fibrillation.

Impact of Surgeon Experience and Centre Volume on Outcome After Off-Pump Coronary Artery Bypass Surgery: Results From the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) Registry.

AIM: The aim of this study was to assess the impact of surgeon experience and centre volume on early operative outcomes in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. METHOD: Of 7,352 patients in the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry, 1,549 underwent OPCAB and were included in the present analysis. Using adjusted regression analysis, we compared major early adverse events after procedures performed by experienced OPCAB surgeons (i.e., ≥20 cases per year; n=1,201) to those performed by non-OPCAB surgeons (n=348). Furthermore, the same end points were compared between procedures performed by OPCAB surgeons in high OPCAB volume centres (off-pump technique used in >50% of cases; n=894) and low OPCAB volume centres (n=307). RESULTS: In the experienced OPCAB surgeon group, we observed shorter procedure times (ß -43.858, 95% confidence interval [CI] -53.322 to -34.393; p<0.001), a lower rate of conversion to cardiopulmonary bypass (odds ratio [OR] 0.284, 95% CI 0.147-0.551; p<0.001), a lower rate of prolonged inotrope or vasoconstrictor use (OR 0.492, 95% CI 0.371-0.653; p<0.001), a lower rate of early postprocedural percutaneous coronary interventions (OR 0.335, 95% CI 0.169-0.663; p=0.002), and lower 30-day mortality (OR 0.423, 95% CI 0.194-0.924; p=0.031). In high OPCAB volume centres, we found a lower rate of prolonged inotrope use (OR 0.584, 95% CI 0.419-0.814; p=0.002), a lower rate of postprocedural acute kidney injury (OR 0.382, 95% CI 0.198-0.738; p=0.004), shorter duration of intensive care unit (ß -1.752, 95% CI -2.240 to -1.264; p<0.001) and hospital (ß -1.967; 95% CI -2.717 to -1.216; p<0.001) stays, and lower 30-day mortality (OR 0.316, 95% CI 0.114-0.881; p=0.028). CONCLUSIONS: Surgeon experience and centre volume may play an important role on the early outcomes after OPCAB surgery.

Long-term Outcomes of the Ross Procedure for Young Patients with Aortic Valve Disease.

To define current role of the Ross operation in young patients, the outcome in those followed longer than 20 years were assessed. Between 1994 and 2020, 81 consecutive patients, 70 of 11 male and/or female, mean age 27 years underwent Ross procedure, accruing 20 years of follow-up or longer. Sixty-four had bicuspid valve (79%) and 54 (67%) aortic insufficiency, while 15 (19%) had undergone prior operations. Surgery consisted in root replacement in 53 patients, cylinder inclusion in 20 and sub-coronary graft in 8. There were 7 late deaths in 80 hospital survivors (median follow-up 21 years, IQR 20-23), with 88% ± 5% survival at 25 years. Thirty-four patients required left, 6 left and/or right and 1 right heart valve reoperation, on average 13 years after Ross procedure. Reoperation was valve-sparing in 18 (45%) patients and valve and/or root replacement in 22. Ten (24%) reoperated patients required a second reoperation 18 years after Ross procedure. Freedom from autograft reoperation was 46% ± 6%, while from autograft valve replacement was 60% ± 7%, thanks to autograft valve-sparing. Freedom from isolated right valve reoperation was 98% ± 4%. No mortality was associated with any of the 51 reoperations. Root technique was associated with reoperation (P = 0.024). Age at follow-up was 50 years (IQR 36-60), with 70 (96%) patients in NYHA class I and 6 (55%) women carrying out pregnancies. Young patients undergoing the Ross procedure enjoy unprecedented survival well into the third decade of follow-up, even when faced with reoperation. At 25 years risk of autograft reoperation is consistent, while negligible for homograft. Technical improvements at operation and valve-sparing at reoperation may prolong autograft valve durability.

Postoperative Quality of Life After Full-sternotomy and Ministernotomy Aortic Valve Replacement.

BACKGROUND: Few longitudinal data exist comparing quality of life (QoL) after full sternotomy (fs) aortic valve replacement (AVR) (fsAVR) with ministernotomy AVR (msAVR). METHODS: A total of 1844 consecutive patients undergoing AVR who were prospectively enrolled in a European multicenter registry were dichotomized according to surgical access. Nonparsimonious propensity score matching selected 187 pairs of patients who underwent fsAVR or msAVR with comparable baseline characteristics. Hospital outcome was compared in the 2 groups. QoL was assessed with the Short Form-36, further detailed in its Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. QoL was investigated at hospital admission, at discharge, and at 1 month, 6 months, and 1 year thereafter. RESULTS: There were 1654 patients undergoing fsAVR and 190 undergoing msAVR in the entire population. The fsAVR group showed a worse preoperative risk profile, a longer intensive care unit length of stay (59.7 hours vs 38.8 hours; p = .002), and a higher rate of life-threatening or disabling bleeding (4.1% vs 0%; P = .011); the msAVR group had a higher rate of early reintervention for failed index intervention (2.1% vs 0.5%; P = .001). QoL investigations showed better PCS and MCS at 1 month after fsAVR, but no temporal trend differences (PCS group-time P = .202; MCS group-time P = .141). Propensity-matched pairs showed comparable baseline characteristics and hospital outcomes (P = not significant for all end points) and comparable improvements of PCS and MCS over time, but no between-group differences over time (PCS group time P = .834; MCS group time P = .737). CONCLUSIONS: Patients with similar baseline profiles report comparable hospital outcomes and comparable improvements of physical and mental health, up to 1 year after surgery, with both fsAVR and msAVR. As for QoL, ministernotomy does not seem to offer any advantage compared with the traditional approach.

Ten-year clinical and echocardiographic follow-up of third-generation biological prostheses in the aortic position.

OBJECTIVES: PERIMOUNT Magna Ease (Carpentier-Edwards; PME) prostheses have been widely implanted during the past decade for aortic valve replacement (AVR). Although promising results at midterm follow-up were reported, long-term outcome has yet to be confirmed. On this study we aimed to evaluate long-term results in terms of structural valve degeneration (SVD), major clinical outcomes, long-term hemodynamic valve performance, and left ventricular remodeling. METHODS: From 2010 to 2012, 689 consecutive patients underwent AVR with PME. Complete clinical 10-year follow-up was obtained. The degree of SVD was categorized on the basis of the latest guidelines. Echocardiographic data were analyzed at 1, 5, and 10 years. Competing risk analysis was performed for major events. Cumulative incidence of SVD, reoperation, and endocarditis were also assessed according to prosthetic sizes (19-21-23 mm vs 25-27-29 mm) and age (<65 vs 65-75 vs >75 years old). RESULTS: The overall cumulative incidence reported for SVD ≥2 and reoperation were 3.6% and 1.9% at 10 years, respectively. An early left ventricular reverse remodeling was noted after implantation and confirmed at follow-up. Patients younger than 65 years showed higher cumulative incidence of SVD ≥2 at 10 years compared with patients aged 65 to 75 and older than 75 years (9.7% vs 2.6% vs 2.7%; P = .013), as well as of redo AVR (7.8% vs 3.3% vs 0.4%; P = .002). There was no difference in terms of SVD and redo AVR for different prosthetic size categories (P > .05). The risk of endocarditis was similar among age and size groups. CONCLUSIONS: PME provides very good durability at long-term and could be considered one of the high performing third-generation bioprostheses for AVR.

Comparative Prognostic Value of Parameters of Pulsatile Right Ventricular Afterload in Patients With Advanced Heart Failure Awaiting Heart Transplantation.

Right ventricular pulsatile afterload (RVPA) demonstrated a strong impact on survival of patients with advanced heart failure (HF) with reduced ejection fraction. The best prognostic parameter of RVPA is unknown. The aim of this work was to examine the prognostic relevance of pulmonary artery compliance (PAC), pulmonary artery elastance (PAE), and pulmonary artery pulsatile index (PAPi) in a consecutive cohort of patients with advanced HF evaluated for heart transplantation (HT). A total of 149 patients with end-stage HF underwent right-sided cardiac catheterization and were clinically followed up until death or any censoring events, including HT, left ventricular assist device, and hospitalization for acute HF. The primary endpoint occurred in 29 patients (19.5%) during a median follow-up time of 12 (interquartile range 3 to 34) months. This cohort presented a worse hemodynamic profile than event-free survivors. PAC <1.9 mL/mm Hg (hazard ratio 3, 95% confidence interval 1.3 to 6.0, p= 0.007) and PAE >0.9 mmHg/mL (hazard ratio 2.5, 95% confidence interval 1.1 to 5.2, p= 0.02) were associated with the adverse outcome. On the contrary, PAPi was not associated with the outcome. PAC demonstrated a superior predictive value for the composite adverse outcome compared with pulmonary vascular resistance (area under the curve comparison p= 0.019) and PAPi (p= 0.03) but similar compared with PAE (p= 0.19) and mean pulmonary arterial pressure (p= 0.51). PAC, but not PAE, showed incremental prognostic value compared with cardiac index (p= 0.02). In conclusion, hemodynamic indexes of RVPA are associated with worse survival in patients with end-stage HF. PAC and PAE demonstrated superior prognostic value compared with PAPi and pulmonary vascular resistance. Moreover, PAC showed incremental prognostic value compared with cardiac index in patients awaiting HT.

Surgical management and outcomes in patients with acute type A aortic dissection and cerebral malperfusion.

Objective: The study objective was to evaluate the surgical results in patients with acute type A aortic dissection and cerebral malperfusion. Methods: From 2000 to 2019, 234 patients with type A aortic dissection and cerebral malperfusion were stratified into 3 groups: 50 (21%) with syncope (group 1), 152 (65%) with persistent loss of focal neurological function (group 2), and 32 (14%) with coma (group 3). Results were evaluated and compared by univariable and multivariable analyses. Results: Median age was higher in group 1, and incidence of cardiogenic shock was higher in group 3. The femoral artery was the most common cannulation site, whereas the axillary artery was used in 18% of group 1, 30% of group 2, and 25% of group 3 patients (P = .337). Antegrade cerebral perfusion was performed in more than 80% of patients, and ascending aorta/arch replacement was performed in 40% of group 1, 27% of group 2, and 31% of group 3 (P = .21). In-hospital mortality was 18% in group 1, 27% in group 2, and 56% in group 3 (P = .001). Survival at 5 years is 57.0% in group 1, 57.7% in group 2, and 38.7% in group 3 (P = .0005). On multivariable analysis, age, cardiopulmonary bypass time, and group 3 versus group 2 were independent risk factors for mortality, whereas axillary cannulation was a protective factor. Conclusions: Patients with aortic dissection and cerebral malperfusion without preoperative coma showed acceptable mortality, and those with coma had a high in-hospital mortality regardless of the type of brain protection. Overall axillary artery cannulation appeared to be a protective factor.

Similar outcome of tricuspid valve repair and replacement for isolated tricuspid infective endocarditis.

AIMS: To compare early and late mortality of acute isolated tricuspid valve infective endocarditis (TVIE) treated with valve repair or replacement. METHODS: Patients who were surgically treated for TVIE from 1983 to 2018 were retrieved from the Italian Registry for Surgical Treatment of Valve and Prosthesis Infective Endocarditis. All the patients were followed up by means of phone interview or calling patient referral physicians or cardiologists. Kaplan-Meier method was used to assess late survival and survival free from TVIE recurrence with log-rank test for univariate comparison. The primary end points were early mortality (30 days after surgery) and long-term survival free from TVIE recurrence. RESULTS: A total of 4084 patients were included in the registry. Among them, 149 patients were included in the study. Overall, 77 (51.7%) underwent TV repair and 72 (48.3%) TV replacement. Early mortality was 9% (13 patients). Expected early mortality according to EndoSCORE was 12%. The TV repair showed lower mortality and major complication rate (7% and 16%), compared with TV replacement (11% and 25%), but statistical significance was not reached. Median follow-up was 19.1 years (14.3-23.8). Late deaths were 30 and IE recurrences were 5. No difference in cardiac survival free from IE was found between the two groups after 20 years (80 ±â€Š6% Repair Group vs 59 ±â€Š13% Replacement Group, P = 0.3). CONCLUSIONS: Overall results indicate that once surgically addressed, TVIE has a low recurrence rate and excellent survival, apparently regardless of the type of surgery used to treat it.

Application of Machine Learning Methods to Analyze Occurrence and Clinical Features of Ascending Aortic Dilatation in Patients with and without Bicuspid Aortic Valve.

Aortic aneurysm (AA) rapture is one of the leading causes of death worldwide. Unfortunately, the diagnosis of AA is often verified after the onset of complications, in most cases after aortic rupture. The aim of this study was to evaluate the frequency of ascending aortic aneurysm (AscAA) and aortic dilatation (AD) in patients with cardiovascular diseases undergoing echocardiography, and to identify the main risk factors depending on the morphology of the aortic valve. We processed 84,851 echocardiographic (ECHO) records of 13,050 patients with aortic dilatation (AD) in the Almazov National Medical Research Centre from 2010 to 2018, using machine learning methodologies. Despite a high prevalence of AD, the main reason for the performed ECHO was coronary artery disease (CAD) and hypertension (HP) in 33.5% and 14.2% of the patient groups, respectively. The prevalence of ascending AD (>40 mm) was 15.4% (13,050 patients; 78.3% (10,212 patients) in men and 21.7% (2838 patients) in women). Only 1.6% (n = 212) of the 13,050 patients with AD knew about AD before undergoing ECHO in our center. Among all the patients who underwent ECHO, we identified 1544 (1.8%) with bicuspid aortic valve (BAV) and 635 with BAV had AD (only 4.8% of all AD patients). According to the results of the random forest feature importance analysis, we identified the eight main factors of AD: age, male sex, vmax aortic valve (AV), aortic stenosis (AS), blood pressure, aortic regurgitation (AR), diabetes mellitus, and heart failure (HF). The known factors of AD-like HP, CAD, hyperlipidemia, BAV, and obesity, were also AD risk factors, but were not as important. Our study showed a high frequency of AscAA and dilation. Standard risk factors of AscAA such as HP, hyperlipidemia, or obesity are significantly more common in patients with AD, but the main factors in the formation of AD are age, male sex, vmax AV, blood pressure, AS, AR, HF, and diabetes mellitus. In males with BAV, AD incidence did not differ significantly, but the presence of congenital heart disease was one of the 12 main risk factors for the formation of AD and association with more significant aortic dilatation in AscAA groups.

Gender-related presentation, surgical treatment, outcome and failure to rescue after surgery for type A aortic dissection: results from a multicentre registry.

OBJECTIVES: Reports on gender-related differences in perioperative characteristics and the outcome after surgery for type A acute aortic dissection are contradictory. METHODS: Perioperative characteristics, outcome and overall or itemized failure-to-rescue rates were collected retrospectively and dichotomized by gender in patients operated on at 5 referral institutions. A propensity score matched analysis was performed to compared males and females with similar preoperative risk profiles. Multivariable analysis assessed gender-related predictors of 30-day mortality. RESULTS: A total of 1271 patients were collected. Females (on average, 63 years old) developed type A acute aortic dissection, with differences in clinical presentation (number of intimal tears, thoracic pain at the onset of symptoms). Female-reported characteristics included lower frozen elephant trunk and elephant trunk procedures, higher femoral perfusion, retrograde cerebral perfusion and retrograde cardiopulmonary bypass restart after deep hypothermic circulatory arrest (P < 0.05). The 30-day mortality was 19.8%, without a gender-related difference (P = 0.37). No substantial differences in hospital outcome and in items related to failure to rescue were reported. A total of 256 propensity score matched pairs of males and females were investigated. Previous differences in surgical techniques and strategies were still confirmed; however, a higher incidence of postoperative permanent coma (P = 0.02) was reported in the female population. CONCLUSIONS: Different surgical techniques and operative strategies were used on the 2 genders, with a lower complexity in females. However, there were no differences in hospital outcome between genders, except for the higher incidence of coma in female patients.

[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device]. / Position paper ANMCO: Percorso assistenziale del paziente con insufficienza cardiaca avanzata candidabile a trapianto/assistenza ventricolare meccanica.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.

Cryopreserved aortic homografts for complex aortic valve or root endocarditis: a 28-year experience.

OBJECTIVES: The aim of this study was to evaluate early- and long-term outcomes of cryopreserved aortic homograft (CAH) implantation for aortic valve replacement (AVR) or aortic root replacement (ARR) in patients with or without complex infective endocarditis. METHODS: All adult patients undergoing AVR or ARR with CAH at our institution between January 1993 and July 2021 were included in the study. RESULTS: One hundred four patients, 75 males and 29 females, aged 59 ± 17 years, underwent AVR or ARR with CAH for infective endocarditis (n = 94, 90%) or aortic valve disease (n = 10, 10%). There were 33 (35%) native valve endocarditis and 61 (65%) prosthetic valve endocarditis, which were complicated by annular abscess in 77 (82%) patients, mitral valve endocarditis in 13 (14%) and tricuspid valve endocarditis in 13 (14%). The mean cardiopulmonary bypass time was 214 ± 80 min and the mean aortic cross-clamping time was 164 ± 56 min. There were 12 (12%) hospital deaths and 7 (7%) postoperative low cardiac output syndrome requiring extracorporeal membrane oxygenation in 4 patients and intra-aortic balloon pump in 3. Thirty-nine (42%) patients died during the follow-up (94% complete). The mean survival time was 13.9 ± 1.2 years. Twenty-five patients (26%) underwent late reoperation for aortic homograft degeneration (n = 17, 18%), homograft endocarditis (n = 6, 7%), homograft dehiscence (n = 1, 1%) and mitral valve regurgitation (n = 1, 1%). The mean survival free from reintervention was 15.7 ± 1.2 years. CONCLUSIONS: AVR or ARR with a CAH for complex endocarditis is associated with satisfactory hospital survival, considering the critical patient presentation at surgery, and excellent survival free from recurrent infection. Need for reoperation late after surgery is similar to other biological prostheses.

Nerve growth factor transfer from cardiomyocytes to innervating sympathetic neurons activates TrkA receptors at the neuro-cardiac junction.

Sympathetic neurons densely innervate the myocardium with non-random topology and establish structured contacts (i.e. neuro-cardiac junctions, NCJ) with cardiomyocytes, allowing synaptic intercellular communication. Establishment of heart innervation is regulated by molecular mediators released by myocardial cells. The mechanisms underlying maintenance of cardiac innervation in the fully developed heart, are, however, less clear. Notably, several cardiac diseases, primarily affecting cardiomyocytes, are associated with sympathetic denervation, supporting the hypothesis that retrograde 'cardiomyocyte-to-sympathetic neuron' communication is essential for heart cellular homeostasis. We aimed to determine whether cardiomyocytes provide nerve growth factor (NGF) to sympathetic neurons, and the role of the NCJ in supporting such retrograde neurotrophic signalling. Immunofluorescence on murine and human heart slices shows that NGF and its receptor, tropomyosin-receptor-kinase-A, accumulate, respectively, in the pre- and post-junctional sides of the NCJ. Confocal immunofluorescence, scanning ion conductance microscopy and molecular analyses, in co-cultures, demonstrate that cardiomyocytes feed NGF to sympathetic neurons, and that this mechanism requires a stable intercellular contact at the NCJ. Consistently, cardiac fibroblasts, devoid of NCJ, are unable to sustain SN viability. ELISA assay and competition binding experiments suggest that this depends on the NCJ being an insulated microenvironment, characterized by high [NGF]. In further support, real-time imaging of tropomyosin-receptor-kinase-A vesicle movements demonstrate that efficiency of neurotrophic signalling parallels the maturation of such structured intercellular contacts. Altogether, our results demonstrate the mechanisms which link sympathetic neuron survival to neurotrophin release by directly innervated cardiomyocytes, conceptualizing sympathetic neurons as cardiomyocyte-driven heart drivers. KEY POINTS: CMs are the cell source of nerve growth factor (NGF), required to sustain innervating cardiac SNs; NCJ is the place of the intimate liaison, between SNs and CMs, allowing on the one hand neurons to peremptorily control CM activity, and on the other, CMs to adequately sustain the contacting, ever-changing, neuronal actuators; alterations in NCJ integrity may compromise the efficiency of 'CM-to-SN' signalling, thus representing a potentially novel mechanism of sympathetic denervation in cardiac diseases.

Short-term outcome of adenosine-lidocaine-magnesium polarizing cardioplegia in humans.

OBJECTIVES: Hyperkalaemic depolarized myocardial arrest is the cornerstone of myocardial protection, although some potassium-related cytotoxicity has been demonstrated. Polarized arrest has gained interest because of a reported better myocardial protection in preclinical studies. The goal of this study was to analyse the quality of myocardial protection and hospital outcome after normokalaemic adenosine-lidocaine-magnesium (ALM) blood polarizing cardioplegia, compared to hyperkalaemic blood Buckberg depolarizing cardioplegia, in elective routine adult cardiac surgery. METHODS: One thousand consecutive elective adult cardiac patients [627 undergoing ALM-polarizing cardioplegia (ALM-POL) vs 373 Buckberg depolarized cardioplegia (BUCK-DEPOL)] who were operated on were analysed. Perioperative leakage of high-sensitivity troponin I (Hs-TnI), peripheral lactate, inotropic and vasoactive daily requirement [maximal vasoactive inotropic score (VISMAX)], hospital mortality and morbidity were collected and compared in the overall population and in the propensity score (PS) matched population (206 pairs). RESULTS: A significantly lower leakage of Hs-TnI during hospitalization was detected in patients receiving ALM-POL versus those receiving BUCK-DEPOL (group time P < 0.001 for overall population and PS matched pairs). The maximum value of postoperative Hs-TnI was also lower after ALM-POL (P < 0.001 in both cohorts), and spontaneous recovery of sinus rhythm at aortic declamping was higher (P < 0.001 in favour of ALM-POL). Maximal VISMAX during hospitalization was significantly higher after BUCK-DEPOL in both cohorts (P = 0.019 for overall population; P = 0.031 for PS matched population), with significantly higher VISMAX on the day of surgery in BUCK-DEPOL PS matched patients (P = 0.042). No other significant differences in hospital morbidity and mortality were found. CONCLUSIONS: Despite comparable short-term clinical outcomes, ALM-POL cardioplegia proved superior in terms of quality of myocardial protection compared to BUCK-DEPOL cardioplegia in elective routine adult cardiac surgery.

Cor Triatriatum and Intracardiac Anomalous Pulmonary Venous Return: An Inborn Atrial Flow Inversion.

A neonate with a diagnosis of nonobstructive intracardiac type total anomalous pulmonary venous connection presented with profound cyanosis in the first days of life. The preoperative specialist echocardiographic examination also identified the presence of partial cor triatriatum dexter. The anatomic pattern of this exceedingly rare disease's association, its peculiar clinical presentation, and surgical management are discussed.

Neurological Complications in High-Risk Patients Undergoing Coronary Artery Bypass Surgery.

BACKGROUND: Coronary artery bypass grafting (CABG) without cardiopulmonary bypass and minimal or no aortic manipulation may be associated with a lower risk of neurological complications. We investigated this issue in patients with a high risk of perioperative stroke. METHODS: Data on 7352 patients who underwent isolated CABG from January 2015 to May 2017 were included in the multicenter study E-CABG (European Coronary Artery Bypass Grafting) registry. Of these, 684 patients had an increased risk of neurological complications, ie, previous stroke or transient ischemic attack, severe carotid artery stenosis or occlusion, or previous carotid artery intervention. In this subgroup, we analyzed the rates of the combined primary endpoint comprising any postoperative stroke or transient ischemic attack. A comparative analysis between CABG with and without aortic cross-clamping was performed. RESULTS: The primary endpoint was more often reached when aortic cross-clamping was used (propensity score matching, without vs with aortic cross-clamp: 0.9% vs 7.2%; P = .016). In comparison with all other revascularization techniques, off-pump CABG with avoidance of aortic manipulation was associated with the lowest rate of neurological complications (0.7%). CONCLUSIONS: In patients with increased risk of perioperative stroke, aortic manipulation including the use of cardiopulmonary bypass or partial clamping for central anastomoses is associated with higher rates of postoperative neurological complications. These patients may benefit from off-pump surgery without aortic manipulation if complete revascularization can be ensured.