Single versus multiple arterial coronary artery bypass grafting in men and women: results from Polish National Registry of Cardiac Surgery Procedures.

BACKGROUND: The objective of this multicenter study aimed to investigate the impact of sex on long-term survival among patients with multivessel coronary artery disease undergoing coronary artery bypass grafting (CABG) using multiple arterial grafting (MAG) or a single artery with saphenous vein grafts. MATERIALS AND METHODS: Data were obtained from the Polish National Registry of Cardiac Surgery Procedures database. This study included 81 136 patients who underwent CABG for multivessel disease between January 2012 and December 2020 (22.9 were women and 77.1% were men). MAG was performed in 8.3 and 11.7% of female and male patients, respectively. A 1:1 propensity score (PS)-matching was performed. Long-term mortality was compared between matched groups of men and women. Subgroup analyses of patients aged <70 and ≥70 years, with an ejection fraction (EF) >40% and ≤40%, and with and without diabetes, obesity, peripheral artery disease (PAD), or chronic lung disease (CLD) were performed separately in women and men. RESULTS: MAG was associated with lower long-term mortality than saphenous vein grafts in 1528 PS-matched female pairs [hazard ratio (HR): 0.74; 95% CI: 0.59-0.92; P =0.007) and 7283 PS-matched male pairs (HR: 0.80; 95% CI: 0.72-0.88; P <0.001). Subgroup analyses confirmed the results among female patients aged <70 years, with diabetes and EF >40%, and without PAD or CLD, and of male patients aged <70 and ≥70 years; with EF >40%; with or without diabetes, obesity, or PAD; and without CLD. CONCLUSIONS: In patients undergoing CABG, MAG was associated with significantly improved survival in both sexes. The long-term benefits of MAG observed across subgroups of men and women support the consideration of a multiarterial revascularization strategy for a broader spectrum of patients.

Additional bypass graft or concomitant surgical ablation? Insights from the HEIST registry.

BACKGROUND: Surgical ablation for atrial fibrillation at the time of isolated coronary artery bypass grafting is reluctantly attempted. Meanwhile, complete revascularization is not always possible in these patients. We attempted to counterbalance the long-term benefits of surgical ablation against the risks of incomplete revascularization. METHODS: Atrial fibrillation patients undergoing isolated coronary artery bypass grafting for multivessel disease between 2012 to 2022 and included in the HEart surgery In atrial fibrillation and Supraventricular Tachycardia registry were divided into complete revascularization, complete revascularization with additional grafts, and incomplete revascularization cohorts; these were further split into surgical ablation and non-surgical ablation subgroups. RESULTS: A total of 8,405 patients (78% men; age 69.3 ± 7.9) were included; of those, 5,918 (70.4%) had complete revascularization, and 556 (6.6%) had surgical ablation performed. Number of anastomoses was 2.7 ± 1.2. The median follow-up was 5.1 [interquartile range 2.1-8.8] years. In patients in whom complete revascularization was achieved, surgical ablation was associated with long-term survival benefit: hazard ratio 0.69; 95% confidence intervals (0.50-0.94); P = .020 compared with grafting additional lesions. Similarly, in patients in whom complete revascularization was not achieved, surgical ablation was associated with a long-term survival benefit of 0.68 (0.49-0.94); P = .019. When comparing surgical ablation on top of incomplete revascularization against complete revascularization without additional grafts or surgical ablation, there was no difference between the 2: 0.84 (0.61-1.17); P = .307, which was also consistent in the propensity score-matched analysis: 0.75 (0.39-1.43); P = .379. CONCLUSION: To achieve complete revascularization is of utmost importance. However, when facing incomplete revascularization at the time of coronary artery bypass grafting in a patient with underlying atrial fibrillation, concomitant surgical ablation on top of incomplete revascularization is associated with similar long-term survival as complete revascularization without surgical ablation.

Prognostic impact of preoperative atrial fibrillation in patients undergoing heart surgery in cardiogenic shock.

Surgical intervention in the setting of cardiogenic shock (CS) is burdened with high mortality. Due to acute condition, detailed diagnoses and risk assessment is often precluded. Atrial fibrillation (AF) is a risk factor for perioperative complications and worse survival but little is known about AF patients operated in CS. Current analysis aimed to determine prognostic impact of preoperative AF in patients undergoing heart surgery in CS. We analyzed data from the Polish National Registry of Cardiac Surgery (KROK) Procedures. Between 2012 and 2021, 332,109 patients underwent cardiac surgery in 37 centers; 4852 (1.5%) patients presented with CS. Of those 624 (13%) patients had AF history. Cox proportional hazards models were used for computations. Propensity score (nearest neighbor) matching for the comparison of patients with and without AF was performed. Median follow-up was 4.6 years (max.10.0), mean age was 62 (± 15) years and 68% patients were men. Thirty-day mortality was 36% (1728 patients). The origin of CS included acute myocardial infarction (1751 patients, 36%), acute aortic dissection (1075 patients, 22%) and valvular dysfunction (610 patients, 13%). In an unadjusted analysis, patients with underlying AF had almost 20% higher mortality risk (HR 1.19, 95% CIs 1.06-1.34; P = 0.004). Propensity score matching returned 597 pairs with similar baseline characteristics; AF remained a significant prognostic factor for worse survival (HR 1.19, 95% CI 1.00-1.40; P = 0.045). Among patients with CS referred for cardiac surgery, history of AF was a significant risk factor for mortality. Role of concomitant AF ablation and/or left atrial appendage occlusion or more aggressive perioperative circulatory support should be addressed in the future.

Atrial fibrillation ablation improves late survival after concomitant cardiac surgery.

OBJECTIVE: Preoperative atrial fibrillation (AF) increases risk of stroke, heart failure, and all-cause mortality after cardiac surgery. Despite encouraging results and guideline recommendations, surgical ablation (SA) for AF concomitant with other heart surgery remains low. In the current study we aimed to address the long-term mortality after SA concomitant with cardiac surgery. METHODS: This report pertains to the HEart surgery In atrial fibrillation and Supraventricular Tachycardia (HEIST) registry. We identified 20,765 adult patients (62% male) with preoperative AF who underwent conventional sternotomy heart surgery between 2010 and 2021 in 8 tertiary centers in Poland, Netherlands, and Italy. We used Cox proportional hazards models for computations and propensity score matching to minimize differences in baseline characteristics. RESULTS: Of included patients, 2755 (13.4%) underwent SA for AF. The highest rates of SA were observed for mitral interventions (mitral valve repair or replacement and tricuspid intervention, 25.2%), lowest for isolated coronary artery bypass grafting (6.2%). Patients in the SA group were younger (mean age 64.5 ± 9.0 years vs 68.7 ± 16.0 years; P < .001) and lower risk (mean European System for Cardiac Operative Risk Evaluation [EuroSCORE] II, 4.1 vs 5.7; P < .001). During the 11-year study period, there was a mortality reduction associated with SA (hazard ratio, 0.57; 95% CI, 0.52-0.62; P < .001). After propensity matching, 2750 pairs with similar baseline characteristics were identified. SA was associated with 16% mortality decline (hazard ratio, 0.84; 95% CI, 0.75-0.94; P = .003). CONCLUSIONS: In this multicenter, retrospective, propensity matched study, SA concomitant with other cardiac surgery was associated with improved long-term survival regardless of baseline surgical risk.

Surgical and transcatheter aortic valve replacement for severe aortic stenosis in low-risk elective patients: Analysis of the Aortic Valve Replacement in Elective Patients From the Aortic Valve Multicenter Registry.

OBJECTIVES: Transcatheter aortic valve implantation (TAVI) remains the preferred strategy for high-risk or elderly individuals with aortic valve (AV) stenosis who are not considered to be optimal surgical candidates. Recent evidence suggests that low-risk patients may benefit from TAVI as well. The current study evaluates midterm survival in low-risk patients undergoing elective surgical AV replacement (SAVR) versus TAVI. METHODS: The Aortic Valve Replacement in Elective Patients From the Aortic Valve Multicenter Registry (AVALON) compared isolated elective transfemoral TAVI or SAVR with sternotomy or minimally invasive approach in low-risk individuals performed between 2015 and 2019. Propensity score matching was conducted to determine SAVR controls for TAVI group in a 1-to-3 ratio with 0.2 caliper. RESULTS: A total of 2393 patients undergoing elective surgery (1765 SAVR and 629 TAVI) with median European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) score 1.81 (interquartile range [IQR], 1.36 to 2.53]) were initially included. Median follow-up was 2.72 years (IQR, 1.32-4.08; max 6.0). Propensity score matching returned 329 TAVI cases and 593 SAVR controls. Thirty-day mortality was 11 out of 329 (3.32%) in TAVI and 18 out of 593 (3.03%) in SAVR (risk ratio, 1.10; 95% CI, 0.52-2.37; P = .801) groups, respectively. At 2 years, survival curves began to diverge in favor of SAVR, which was associated with 30% lower mortality (hazard ratio, 0.70; 95% CI, 0.496-0.997; P = .048). CONCLUSIONS: Our data did not demonstrate a survival difference between TAVI and SAVR during the first 2 postprocedure years. After that time, SAVR is associated with improved survival. Extended observations from randomized trials in low-risk patients undergoing elective surgery are warranted to confirm these findings and draw definitive conclusions.

Total arterial revascularization coronary artery bypass surgery in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a relatively common comorbidity among patients referred for coronary artery bypass grafting (CABG) and is associated with poorer prognosis. However, little is known about how surgical technique influences survival in this population. AIM: The current analysis aimed to determine whether total arterial revascularization (TAR) is associated with improved long-term outcomes in patients with preoperative AF. METHODS: We analyzed patients' data from the HEIST (HEart surgery In atrial fibrillation and Supraventricular Tachycardia) registry. The registry, to date, involves five tertiary high-volume centers in Poland. Between 2006 and 2019, 4746 patients presented with preoperative AF and multivessel coronary artery disease and underwent CABG. We identified cases of TAR and used propensity score matching to determine non-TAR controls. Median follow-up was 4.1 years (interquartile range [IQR], 1.9-6.8 years). RESULTS: Propensity matching resulted in 295 pairs of TAR vs. non-TAR. The mean (standard deviation [SD]) number of distal anastomoses was 2.5 (0.6) vs. 2.5 (0.6) (P = 0.94) respectively. Operative and 30-day mortality was not different between TAR and non-TAR patients (hazard ratio [HR] and 95% confidence intervals [CIs], 0.17 (0.02-1.38); P = 0.12 and 0.74 [0.40-1.35]; P = 0.33, respectively). By contrast, TAR was associated with nearly 30% improved late survival: HR, 0.72 (0.55-0.93); P = 0.01. This benefit was sustained in subgroup analyses, yet most pronounced in low-risk patients ( < 70 years old; EuroSCORE II < 2; no diabetes) and when off-pump CABG was performed. CONCLUSIONS: TAR in patients with preoperative AF is safe and associated with improved survival, with particular survival benefits in younger low-risk patients undergoing off-pump CABG.

Clinical Insights to Complete and Incomplete Surgical Revascularization in Atrial Fibrillation and Multivessel Coronary Disease.

Objectives: Although endorsed by international guidelines, complete revascularization (CR) with Coronary Artery Bypass Grafting (CABG) remains underused. In higher-risk patients such as those with pre-operative atrial fibrillation (AF), the effects of CR are not well studied. Methods: We analyzed patients' data from the HEIST (HEart surgery In AF and Supraventricular Tachycardia) registry. Between 2012 and 2020 we identified 4770 patients with pre-operative AF and multivessel coronary artery disease who underwent isolated CABG. We divided the cohort according to the completeness of the revascularization and used propensity score matching (PSM) to minimize differences between baseline characteristics. The primary endpoint was all-cause mortality. Results: Median follow-up was 4.7 years [interquartile range (IQR) 2.3-6.9]. PSM resulted in 1,009 pairs of complete and incomplete revascularization. Number of distal anastomoses varied, accounting for 3.0 + -0.6 vs. 1.7 + -0.6, respectively. Although early (< 24 h) and 30-day post-operative mortalities were not statistically different between non-CR and CR patients [Odds Ratio (OR) and 95% Confidence Intervals (CIs): 1.34 (0.46-3.86); P = 0.593, Hazard Ratio (HR) and 95% CIs: 0.88 (0.59-1.32); P = 0.542, respectively] the long term mortality was nearly 20% lower in the CR cohort [HR (95% CIs) 0.83 (0.71-0.96); P = 0.011]. This benefit was sustained throughout subgroup analyses, yet most accentuated in low-risk patients (younger i.e., < 70 year old, with a EuroSCORE II < 2%, non-diabetic) and when off-pump CABG was performed. Conclusion: Complete revascularization in patients with pre-operative AF is safe and associated with improved survival. Particular survival benefit with CR was observed in low-risk patients undergoing off-pump CABG.

Early and Midterm Results of Orthotopic Heart Transplantation in Poland (2015-2019).

Orthotopic heart transplantation (OHT) has become one of the most expensive and resource-consuming treatment options for patients with end-stage heart failure. It is therefore useful to review clinical data, such as treatment duration after surgery and midterm follow-up in this group of patients. Contemporary epidemiologic data on early and midterm OHT follow-ups including patient demographics, hospitalization rates and related post-OHT morbidity, and mortality are scarce in Poland. The aim of the study was to determine early survival, hospitalization rates related to OHT and related morbidity, and mortality in Poland in the recent decade.

Permanent pacemaker implantation after valve and arrhythmia surgery in patients with preoperative atrial fibrillation.

BACKGROUND: Among patients referred for cardiac surgery, atrial fibrillation (AF) is a common comorbidity and a risk factor for postoperative arrhythmias (eg, sinus node dysfunction, atrioventricular heart block), including those requiring permanent pacemaker (PPM) implantation. OBJECTIVE: The purpose of this study was to evaluate the prevalence and long-term survival of postoperative PPM implantation in patients with preoperative AF who underwent valve surgery with or without concomitant procedures. METHODS: Presented analysis pertains to the HEIST (HEart surgery In atrial fibrillation and Supraventricular Tachycardia) registry. During the study period, 11,949 patients underwent valvular (aortic, mitral, or tricuspid valve replacement or repair) surgery and/or surgical ablation (SA) and were stratified according to postoperative PPM status. RESULTS: PPM implantation after surgery was necessary in 2.5% of patients, with significant variation depending on the type of surgery (from 1.1% in mitral valve repair to 3.3% in combined mitral and tricuspid valve surgery). In a multivariate logistic regression model, tricuspid intervention (P <.001), cardiopulmonary bypass time (P = .024), and endocarditis (P = .014) were shown to be risk factors for PPM. Over long-term follow-up, PPM was not associated with increased mortality compared to no PPM (hazard ratio 0.96; 95% confidence interval 0.77-1.19; P = .679). SA was not associated with PPM implantation. However, SA improved survival regardless of PPM status (log rank P <.001). CONCLUSION: In patients with preoperative AF, the need for PPM implantation after valve surgery or SA is not an infrequent outcome, with SA not affecting its prevalence but actually improving long-term survival.

The new insight into extracellular NAD+ degradation-the contribution of CD38 and CD73 in calcific aortic valve disease.

Nicotinamide adenine dinucleotide (NAD+ ) is crucial for cell energy metabolism and many signalling processes. Recently, we proved the role of ecto-enzymes in controlling adenine nucleotide-dependent pathways during calcific aortic valve disease (CAVD). This study aimed to investigate extracellular hydrolysis of NAD+ and mononucleotide nicotinamide (NMN) in aortic valves and aorta fragments of CAVD patients and on the inner aortic surface of ecto-5'-nucleotidase knockout mice (CD73-/-). Human non-stenotic valves (n = 10) actively converted NAD+ and NMN via both CD73 and NAD+ -glycohydrolase (CD38) according to our analysis with RP-HPLC and immunofluorescence. In stenotic valves (n = 50), due to reduced CD73 activity, NAD+ was degraded predominantly by CD38 and additionally by ALP and eNPP1. CAVD patients had significantly higher hydrolytic rates of NAD+ (0.81 ± 0.07 vs 0.56 ± 0.10) and NMN (1.12 ± 0.10 vs 0.71 ± 0.08 nmol/min/cm2 ) compared with controls. CD38 was also primarily engaged in human vascular NAD+ metabolism. Studies using specific ecto-enzyme inhibitors and CD73-/- mice confirmed that CD73 is not the only enzyme involved in NAD+ and NMN hydrolysis and that CD38 had a significant contribution to these pathways. Modifications of extracellular NAD+ and NMN metabolism in aortic valve cells may be particularly important in valve pathology and could be a potential therapeutic target.

Cryobiopsy as a New Tool for Complications Diagnosis During Follow-up After Lung Transplantation: Single Institution Case Series.

BACKGROUND: The first description of performing a new diagnostic procedure, cryobiopsy, in lung transplant recipients in Poland. METHODS: Three cases of patients after lung transplantation were analyzed in context of the procedure of cryobiopsy, which was performed in a hybrid room with a bronchoscopic video track and C-arm radiograph. Patients were subjected to complete anesthesia and intubated. Two or three sections with an average diameter of 5 mm were collected. RESULTS: The sections were large and fully diagnostic. In all 3 described cases they brought a decisive element into diagnosis. CONCLUSIONS: Cryobiopsy is a useful tool in the differential diagnosis of lesions and complications that occur after lung transplantation.

A Single-Center Experience with Lung Transplants During the COVID-19 Pandemic.

BACKGROUND This single-center study analyzed distinctions between lung transplants performed in the Department of Cardiac and Vascular surgery of the University Clinical Center in Gdansk, Poland before and during the COVID-19 pandemic. MATERIAL AND METHODS There were 189 patients who underwent the qualification procedure to lung transplantation in the Department of Cardiac and Vascular Surgery of the University Clinical Center in Gdansk, Poland in the years 2019 and 2020. The control group consisted of 12 patients transplanted in 2019, and the study group consisted of 16 patients transplanted in 2020. RESULTS During 2019, the qualification process was performed in 102 patients with pulmonary end-stage diseases. In 2020, despite the 3-month lockdown related to organizational changes in the hospital, 87 qualification processes were performed. The mortality rate of patients on the waiting list in 2020 was 14.3% (6 patients died), and during 2019 the rate was also 14.3% (4 patients died). Donor qualifications were according to ISHLT criteria. The distribution of donors in both years was similar. There was no relationship between the geographic area of residence and source of donors. In 2019, all 12 patients had double-lung transplant. In 2020, 11 patients had double-lung transplant and 5 patients had single-lung transplant. There was no difference in ventilation time and PGD aside from a shorter ICU stay in 2020. CONCLUSIONS Lung transplants were relatively well-conducted despite the continued obstacles of the COVID-19 pandemic.

Off-pump versus on-pump coronary artery surgery in octogenarians (from the KROK Registry).

BACKGROUND: According to the medical literature, both on-pump and off-pump coronary artery surgery is safe and effective in octogenarians. OBJECTIVES: The aim of our study was to examine the epidemiology, in-hospital outcomes and long-term follow-up results in octogenarians undergoing off-pump and on-pump coronary artery surgery utilizing nationwide registry data. METHODS: All octogenarians (≥ 80 years) enrolled in the Polish National Registry of Cardiac Surgical Procedures (KROK Registry), who underwent isolated coronary surgery between January 2006 and September 2017 were identified. Preoperative data, perioperative complications, hospital mortality and long-term mortality were analyzed. Unadjusted and propensity-matched comparisons were performed between octogenarians undergoing off-pump and on-pump coronary artery bypass surgery. RESULTS: Octogenarians accounted for 4.1% of the total population undergoing coronary artery surgery in Poland during the analyzed period (n = 152,631) and this percentage is increasing. Among 6,006 analyzed patients, 2,744 (45.7%) were operated on-pump and 3,262 (54.3%) were operated off-pump. Propensity-matched analysis revealed that patients operated on-pump were more often reoperated due to postoperative bleeding and their in-hospital mortality was higher (6.6% vs 4.5%, p = 0.006 and 8.7% vs 5.8%, p = 0.001, respectively). Long-term all-cause mortality was lower among patients operated off-pump (p = 0.013). CONCLUSION: On the basis of our findings we suggest that off pump technique should be considered as perfectly acceptable in octogenarians.

Statin treatment of patients with calcific aortic valve disease modulates extracellular adenosine metabolism on the cell surface of the aortic valve.

Statins efficiently prevent cardiovascular events by lipid-dependent and independent mechanisms. We hypothesize that part of these protective effects could be associated with an increased extracellular adenosine signaling. We demonstrated previously that aortic valves obtained from patients with calcific aortic valve disease (CAVD) disclosed disturbances in extracellular adenosine metabolism. This study aimed to analyze the impact of statin treatment on extracellular nucleotides and adenosine metabolism in aortic valves originated from CAVD patients and to elucidate potential mechanisms that are involved in the regulation of ecto-enzyme activities by statins. Aortic valves of CAVD patients treated with statins (n = 45) revealed higher adenosine production and its lower degradation than in non-treated patients (n = 28). Statin treatment was also related to the improvement in pre-operative echocardiographic data indicating milder aortic valve stenosis and a better function of the left ventricle. The rates of aortic valve adenosine conversions correlated with plasma lipid profile parameters, within both statin-treated and non-treated groups. Valvular extracellular AMP hydrolysis correlated negatively, while adenosine deamination positively with plasma total and LDL cholesterol. Atorvastatin treatment of murine heart endothelial cells led to the enhanced ecto-5'nucleotidase (CD73) and decreased ecto-adenosine deaminase (eADA) activity. When endothelial cells were stimulated with thrombin that induces endothelial cell exocytosis, activities of both cell-surface CD73 and eADA were increased, while co-treatment with atorvastatin reversed only thrombin-induced eADA activity. In conclusion, early intervention with statins may provide beneficial effects for CAVD therapy. Here, we presented results showing that these protective outcomes could be mediated via the regulation of extracellular adenosine metabolism pathways.

Femoral hernia in the era of TAVI - a potential obstacle for transfemoral approach: a case report and literature review.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) via total percutaneous transfemoral approach is an increasingly common technique for aortic stenosis treatment. It is primarily indicated in elderly with serious comorbidities. The epidemiology of these patients tends to overlap with the incidence of femoral hernia (FH). The appearance of hernia sac at the approach site and insufficient preoperational examination can lead to serious complications. We present the first-ever reported case of subsequent femoral hernia repair during transfemoral TAVI. CASE PRESENTATION: This report presents a case of FH/TAVI coincidence and literature review of its epidemiology. Literature review was performed to analyze similarities of femoral hernia and TAVI. The case describes an 84-year old female referred for elective TAVI. Intraoperation incarcerated femoral hernia was noticed and directly repaired. Further TAVI steps were performed on regular basis. A 2-year follow-up reported no local and general complications related to procedures. CONCLUSIONS: Unsuspected femoral hernia found subsequently with transfemoral TAVI may become a growing problem. The number of TAVI performed rises with indications expansion. Femoral hernia repairs constitute from 2 to 4% of all groin hernia. Both TAVI and FH are connected with elderly. Despite the fact of low FH incidence, growing number of TAVI performed and ageing of population, corresponds with higher possibility of complications. Most of these complications may end up fatal as they would involve high-risk patients. Insufficient attention is paid by cardiologists to the possible hernia appearance in the access site as this issue has been hardly ever presented in literature. Concomitant FH in TAVI patients should always be excluded in order to avoid serious complications. The case we report presents a successful subsequent FH repair during TAVI procedure. Further studies have to be conducted to provide data on how such problems ought to be managed.

Nucleotide ecto-enzyme metabolic pattern and spatial distribution in calcific aortic valve disease; its relation to pathological changes and clinical presentation.

BACKGROUND: Extracellular nucleotide metabolism contributes to chronic inflammation, cell differentiation, and tissue mineralization by controlling nucleotide and adenosine concentrations and hence its purinergic effects. This study investigated location-specific changes of extracellular nucleotide metabolism in aortic valves of patients with calcific aortic valve disease (CAVD). Individual ecto-enzymes and adenosine receptors involved were analyzed together with correlation with CAVD severity and risk factors. RESULTS: Nucleotide and adenosine degradation rates were adversely modified on the aortic surface of stenotic valve as compared to ventricular side, including decreased ATP removal (1.25 ± 0.35 vs. 2.24 ± 0.61 nmol/min/cm2) and adenosine production (1.32 ± 0.12 vs. 2.49 ± 0.28 nmol/min/cm2) as well as increased adenosine deamination (1.28 ± 0.31 vs. 0.67 ± 0.11 nmol/min/cm2). The rates of nucleotide to adenosine conversions were lower, while adenosine deamination was higher on the aortic sides of stenotic vs. non-stenotic valve. There were no differences in extracellular nucleotide metabolism between aortic and ventricular sides of non-stenotic valves. Furthermore, nucleotide degradation rates, measured on aortic side in CAVD (n = 62), negatively correlated with echocardiographic and biochemical parameters of disease severity (aortic jet velocity vs. ATP hydrolysis: r = - 0.30, p < 0.05; vs. AMP hydrolysis: r = - 0.44, p < 0.001; valvular phosphate concentration vs. ATP hydrolysis: r = - 0.26, p < 0.05; vs. AMP hydrolysis: r = - 0.25, p = 0.05) while adenosine deamination showed positive correlation trend with valvular phosphate deposits (r = 0.23, p = 0.07). Nucleotide and adenosine conversion rates also correlated with CAVD risk factors, including hyperlipidemia (AMP hydrolysis vs. serum LDL cholesterol: r = - 0.28, p = 0.05; adenosine deamination vs. total cholesterol: r = 0.25, p = 0.05; LDL cholesterol: r = 0.28, p < 0.05; triglycerides: r = 0.32, p < 0.05), hypertension (adenosine deamination vs. systolic blood pressure: r = 0.28, p < 0.05) and thrombosis (ATP hydrolysis vs. prothrombin time: r = - 0.35, p < 0.01). Functional assays as well as histological and immunofluorescence, flow cytometry and RT-PCR studies identified all major ecto-enzymes engaged in nucleotide metabolism in aortic valves that included ecto-nucleotidases, alkaline phosphatase, and ecto-adenosine deaminase. We have shown that changes in nucleotide-converting ecto-enzymes were derived from their altered activities on valve cells and immune cell infiltrate. We have also demonstrated a presence of A1, A2a and A2b adenosine receptors with diminished expression of A2a and A2b in stenotic vs. non-stenotic valves. Finally, we revealed that augmenting adenosine effects by blocking adenosine deamination with deoxycoformycin decreased aortic valve thickness and reduced markers of calcification via adenosine-dependent pathways in a mouse model of CAVD. CONCLUSIONS: This work highlights profound changes in extracellular nucleotide and adenosine metabolism in CAVD. Altered extracellular nucleotide hydrolysis and degradation of adenosine in stenotic valves may affect purinergic responses to support a pro-stenotic milieu and valve calcification. This emphasizes a potential mechanism and target for prevention and therapy. .