Predictors of Inappropriately Rapid Coronary Lesion Progression in Patients Undergoing Percutaneous Coronary Interventions.

Background: Patients undergoing percutaneous coronary intervention (PCI) may experience rapid atherosclerotic plaque progression in nontreated vessels that is unlikely to result from natural de novo atherosclerosis. We hypothesize that intra-lesion bleeding plays a central role in this process. The aim of this study is to investigate the factors that may contribute to accelerated narrowing in coronary diameter. Methods: We reviewed 65 interventional procedures and their consequent staged PCIs and mapped the coronary tree into 16 segments (as divided by the American Heart Association), grading the percentage of stenosis in each segment and spotting the rapidly progressing lesions. Demographic, procedural, and laboratory data were recorded and analyzed. Results: For the lesions that progressed rapidly in the time period between angiographies, the administration of eptifibatide intra-procedurally was associated with rapid progression of coronary lesions. Moreover, an increased white blood cell count prior to the index procedure was also associated with a trend toward rapid plaque progression. Conclusions: In this hypothesis-generating study, treatment with a IIb/IIIa inhibitor in the index PCI was associated with an accelerated short-term progression of some of the nontreated lesions, suggesting that this mode of anti-aggregation therapy could facilitate plaque hemorrhage and consequent acceleration of coronary atherosclerosis in eroded plaques.

Contexte: Les patients qui subissent une intervention coronarienne percutanée (ICP) peuvent présenter une progression rapide de plaques d'athérosclérose dans des vaisseaux non traités, phénomène qui n'est probablement pas le résultat d'une athérosclérose de novo naturelle. Nous formulons l'hypothèse qu'un saignement intralésionnel jouerait un rôle central dans ce processus. Cette étude vise à explorer les facteurs qui pourraient contribuer à l'accélération de la réduction du diamètre coronarien. Méthodologie: Nous avons étudié 65 interventions et les ICP en plusieurs étapes qui s'en étaient suivies, ainsi que divisé l'arbre coronarien en 16 segments (conformément à la segmentation de l'American Heart Association), afin d'évaluer le pourcentage de sténose dans chaque segment et de repérer les lésions qui progressaient rapidement. Les données démographiques et celles relatives aux interventions et aux résultats de laboratoire ont été consignées et analysées. Résultats: En ce qui concerne les lésions qui avaient progressé rapidement durant l'intervalle entre les angiographies, l'administration d'éptifibatide lors de l'intervention semblait être un facteur contributif. De plus, un nombre accru de leucocytes avant l'intervention initiale a également été associé à une évolution rapide des plaques. Conclusions: Dans le cadre de cette étude servant à émettre une hypothèse, le traitement par un inhibiteur de la glycoprotéine IIb-IIIa lors de l'ICP initiale a été associé à une accélération de la progression à court terme de certaines lésions non traitées, ce qui laisse croire que ce mode de traitement antiagrégant pourrait favoriser les hémorragies intraplaques et l'accélération de l'athérosclérose coronarienne dans les plaques érodées.

The CHA2DS2-VASC Score Predicts Mortality in Patients Undergoing Coronary Angiography.

BACKGROUND: The CHA2DS2-VASC score is used to predict the risk of thromboembolic complications in patients with atrial fibrillation (AF). We hypothesized that the CHA2DS2-VASC score can be used to predict mortality in patients undergoing coronary angiography. METHODS AND RESULTS: This was a prospective study of 990 patients undergoing coronary angiography. The median follow-up was 2294 days. The patients were categorized into two groups according to their CHA2DS2-VASC score: group I had scores <4 and group II had scores ≥4 (527 (53.2%) and 463 (46.8%), respectively). A Kaplan-Meier analysis demonstrated a significant association between the CHA2DS2-VASC score and mortality (69/527 (13.1%) vs. 179/463 (38.7%) for group I vs. group II, respectively, p < 0.0001). The association remained significant in patients with and without AF, reduced and preserved LVEF, normal and reduced kidney function, and with and without ACS (p < 0.009 to p < 0.0001 for all). In the Cox regression model, which combined the CHA2DS2-VASC score, the presence of AF, LVEF, anemia, and renal insufficiency, an elevated CHA2DS2-VASC score of ≥4 was independently associated with higher mortality (HR 2.12, CI 1.29-3.25, p = 0.001). CONCLUSIONS: The CHA2DS2VASC score is a simple and reliable mortality predictor in patients undergoing coronary angiography and should be used for the initial screening for such patients.

The Additive Effect of Left Ventricular Filling Pressure and Renal Function on Long-Term Prognosis of High-Risk Patients Undergoing Coronary Angiography.

INTRODUCTION: Impaired relaxation is the earliest manifestation of ischemic cascade. Risk factors and renal function abnormalities are associated with coronary disease and diastolic dysfunction as well. We aimed to study the association of noninvasive assessment of left ventricular filling pressures and renal function with mortality in high-risk patients undergoing coronary angiography. PATIENTS AND METHODS: An observational prospective study of 564 consecutive patients undergoing coronary angiography was conducted. The median follow-up was 2,293 days. Patients were categorized into 2 groups according to presence of significant diastolic dysfunction: group 1, 382 patients, with normal and group 2, 182 patients, with elevated filling pressure. Renal insufficiency was determined as calculated glomerular filtration rate <60 mL/min. Patients demographic, clinical, echocardiography, laboratory, and angiographic data were prospectively collected. RESULTS: Fifty-three percent of patients underwent angiography due to acute coronary syndrome (ACS), 85.5% had coronary artery disease, 53.4% had reduced (<50%) left ventricular ejection fraction (LVEF), and 47.4% had abnormal renal function. The mortality during the follow-up period was 30.0%. Patients with elevated filling pressure had significantly higher mortality (50.5% vs. 20.2%, p < 0.0001). Impaired renal failure as well, was associated with higher mortality (48% vs. 15%, p < 0.001). The association remained significant in subgroups of patients with and without ACS and reduced and preserved LVEF. In Cox regression model which combined elevated filling pressure, renal insufficiency, age, diabetes mellitus, hypertension, presence of atrial fibrillation, LVEF, and anemia, elevated filling pressure and renal function impairment were independently associated with higher mortality (HR: 3.717, CI: 1.623-8.475, p < 0.0001 and HR: 0.972, CI: 0.958-0.985, p = 0.0001, respectively). There was an incremental prognostic value of elevated filling pressures and renal function impairment on mortality. CONCLUSIONS: Advanced diastolic dysfunction and impaired renal function are signals toward worse outcomes and are associated with mortality in high-risk patients undergoing coronary angiography.

Comparison between Cardiac Output and Pulmonary Vascular Pressure Measured by Indirect Fick and Thermodilution Methods.

INTRODUCTION: Right heart catheterization (RHC) is a diagnostic procedure, the main purpose of which is to diagnose pulmonary hypertension and investigate its etiology and treatability. In addition to measuring blood pressure in heart chambers, it includes estimating cardiac output (CO) and calculation of pulmonary vascular resistance (PVR) derived from the CO. There are two common methods to evaluate the CO-the indirect Fick method and the thermodilution method. Depending on the clinical conditions, either of the two may be considered better. Several studies have showed that, in most cases, there is no difference between measurements rendered by the two methods. Other studies have raised suspicion of a discrepancy between the two methods in a substantial number of patients. A clear opinion on this matter is missing. AIM: To evaluate the agreement between the values of the CO and PVR found by the thermodilution and indirect Fick methods. METHODS: We retrospectively included patients that underwent RHC in Kaplan Medical Center during the last two years with a measurement of the CO using both the thermodilution and the indirect Fick methods. The measurements obtained upon RHC and the clinical data of the patients were collected. The values of the CO and PVR measured or calculated using the two methods were compared for each patient. RESULTS: We included 55 patients that met the inclusion criteria in this study. The mean CO measured by the thermodilution method was 4.94 ± 1.17 L/min and the mean CO measured by the indirect Fick method was 5.82 ± 1.97 L/min. The mean PVR calculated using the thermodilution method was 3.33 ± 3.04 Woods' units (WU) and the mean PVR calculated using the indirect Fick method was 2.71 ± 2.76 WU. Among the patients with normal mPAP, there was a strong and statistically significant correlation between the PVR values calculated by the two methods (Peasron's R2 = 0.78, p-value = 0.004), while among the patients with elevated mPAP, the correlation between the PVR values calculated by the two methods was not statistically significant. CONCLUSION: The findings of this small study demonstrate that, in a proportion of patients, the indirect Fick method and thermodilution method classify the PVR value differently. In our experience, it seems that, in these patients, the indirect Fick method misclassified patients with a pathological finding as normal. We, therefore, recommend that upon performing RHC, at least in patients with mPAP > 25 mmHg, both the thermodilution and indirect Fick methods be performed and, whenever they disagree, the values obtained from the thermodilution method should be preferred.

Association of CT-Derived Extracardiac Features and Aortic Annulus Size in Patients Planned for TAVI.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is commonly used to treat patients with stenosed aortic valves. CT is one of the crucial steps in planning TAVI to obtain measurements of the aortic annulus to choose an appropriately sized prosthesis. Incorrect measurements can lead to patient-prosthesis mismatch and other complications. However, some patients cannot undergo ECG-gated CT with radiocontrast because of the presence of radiopaque objects in the thorax, arrhythmia, renal failure, etc. Aim: To explore supplementary methods to improve aortic annulus sizing for TAVI by extracardiac measurements. METHODS: We included all patients who underwent CT as part of TAVI planning. Measurements of femoral and iliac arteries and the femoral head cross-sectional area were performed. RESULTS: CT scans of 139 patients were included in this study. Sixty-three patients (45%) were males. Mean age of the female patients was 79.6 ± 7.1 years and of the male patients was 81.3 ± 6.1 years. Mean aortic annulus perimeter among female patients was 74.3 ± 6 mm (range 61.9-88.2) and 83 ± 7.9 mm among male patients (range 70.1-74.3 mm). Mean diameters of common iliac, external iliac, and common femoral arteries were 9.2 ± 1.8, 7.6 ± 1, 7.6 ± 1 mm, respectively, for females and 10.2 ± 1.8, 8.5 ± 1.3, and 8.6 ± 1.4 mm for males. Mean perimeter of the femoral head (average value of right and left femoral heads) among the female patients was 137.8 ± 6.3 mm, and among male patients was 155 ± 9.6 mm. A significant correlation was observed between the perimeter of the aortic annulus and the perimeter of the femoral head (Pearson's R2 = 0.224). The correlation between the aortic annulus perimeter and the femoral head perimeter was stronger among men than among women (Pearson's R2 = 0.66 and 0.19, respectively). CONCLUSION: Femoral head diameter is associated with annulus size. This may help size the appropriate prosthesis in cases where the measurements by CT are in the border zone if corroborated by clinically driven data.

Utilization of Drug-Coated Balloons for the Treatment of Coronary Lesions in the Elderly Population.

Introduction: The use of drug-coated balloons (DCBs) has become more prevalent in the past few years for the treatment of in-stent restenosis (ISR) and de novo lesions. The absence of foreign polymer implantations potentially shortens the duration of dual anti-platelet therapy (DAPT), which can be beneficial for the elderly population. We aimed to investigate the safety and efficacy of the use of DCBs for the treatment of coronary lesions in elderly patients as compared to the younger population. Materials and methods: A database of 446 consecutive patients who underwent a procedure of DCB inflation in our institution was divided into two groups, below 70 years old and above 80 years old. We compared and analyzed the endpoints of total major adverse cardiovascular events (MACE), cardiovascular (CV) death, and all-cause mortality in both groups. Results: The difference in MACE between the two age groups was non-significant (p = 0.225); the difference in cardiovascular death was also non-significant (p = 0.086). All-cause mortality was significantly different (p < 0.0001) and can be attributed to the age of the patients. Conclusion: The utilization of DCBs for the treatment of coronary lesions may be as safe and effective for the elderly population as for the younger population and may allow a shorter period of DAPT therapy, which can lower the risk of bleeding.

Mid-Term Clinical Outcomes Following Drug-Coated Balloons in Coronary Artery Disease.

OBJECTIVE: The aim of this study was to evaluate the mid-term efficacy of drug-coated balloons (DCB) in percutaneous coronary intervention (PCI) in two different pathophysiologic scenarios. BACKGROUND: There are different underlying pathological processes in coronary artery disease. Mid-term safety and efficacy of DCB approach is still limited. METHODS: Medical records of all consecutive patients undergoing DCB were evaluated. The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) after 24 months. RESULTS: Between January 2011 and December 2017, 442 patients were included, representing 4.4% of all PCIs in our institution. A total of 460 DCB lesions were treated, of which 328 (71.3%) were de novo and 132 (28.7%) were combined bare metal or drug-eluting stents with in-stent restenosis (ISR). The patients' mean age was 66.2 ± 11.7 years with a diabetes prevalence of 45.3%. The TLR rate was lower in the de novo group (5.3%) compared to the ISR group (9.4%) (p = 0.04). No differences were observed in major adverse cardiovascular events (MACE) between the de novo group (38.9%) and ISR group (42.5%) (p = 0.47). No significant differences were detected in the TLR occurrence in the subgroup analysis. CONCLUSION: Our extended experience demonstrates that the mid-term DCB approach in these two pathophysiologic settings represent a reasonable option, with low TLR rate.

Trends in Transfemoral Aortic Valve Implantation Related Thrombocytopenia.

BACKGROUND: TAVI related thrombocytopenia (TAVI-rTP) is still very common. The aim of this study was to compare the incidence, characteristics and impact of reduced platelet counts (RPC) after TAVI between an earlier and contemporary period. METHODS: the patients enrolled were those experiencing severe symptomatic aortic stenosis who underwent TAVI between January 2010 and December 2019. The exclusion criteria were no available blood tests and periprocedural death. RESULTS: 334 patients (mean age 81.9 ± 6.7 years) were enrolled. For the earlier period, the mean RPC was 33 ± 15%, and in the contemporary period (2016-2019) it was 26 ± 14%. In the early group, we found that 62% of the patients had decreased platelet counts of more or equal to 30% in comparison to 33% in the contemporary period. The time of the procedure and the amount of the contrast that had been used in the later period were associated with significant RPCs (p value = 0.002 and 0.028, respectively). An RPC of 30% or more was associated with the increased risks of life-threatening bleeding, vascular complications and death within 30 days. CONCLUSION: contemporary TAVI-rTP continued to be a common phenomenon in our cohort. However, severe thrombocytopenia was significantly less frequent. An RPC of 30% or more is associated with a poor 30-day outcome.

Natural Anti-Endothelial Cell Antibodies in Patients Undergoing Coronary Angiography.

BACKGROUND: Anti-endothelial cell antibodies (AECA) are a known biomarker of endothelial dysfunction and damage in clinical practice, especially in autoimmune disease. OBJECTIVES: To determine the relation between natural AECA levels and prognosis related to coronary artery disease. METHODS: Candidates for coronary angiography were prospectively enrolled. AECA levels were determined by ELISA assay. Mortality was evaluated after more than 5 years follow-up. RESULTS: Of a total 857 patients, 445 had high AECA levels (group 1) and 412 had low levels (< 1 OD unit, group 2). Both groups did not differ in age, sex, or presence of diabetes. The median follow up was 2293 days (76 months). Patients with high AECA levels were more likely to have normal coronary arteries on angiography (21.6% vs. 16.9%, P = 0.047) and less likely to have calcified lesions (19.0% vs. 26.6%, P = 0.028) and lower prevalence of abnormal renal functions (71.1 mg/dl vs. 66.5 mg/dl, P = 0.033). Patients with higher AECA levels had lower mortality levels (20.1% vs. 27.6%, P = 0.006). A logistic regression model demonstrated independent association between lower AECA levels and the presence of coronary atherosclerosis based on angiogram. CONCLUSIONS: After a median of more than 6 years, higher natural AECA levels were associated with less coronary artery disease and lower mortality rates in patients undergoing coronary angiography.

Transthyretin cardiac amyloidosis in patients after TAVR: clinical and echocardiographic findings and long term survival.

AIMS: The aim of this study was to examine the prevalence of amyloid transthyretin (ATTR) cardiac amyloidosis in patients 1-2 years after trans-catheter aortic valve replacement (TAVR) and to assess their clinical and echocardiographic outcome and long-term survival. METHODS AND RESULTS: We enrolled 88 patients, mean age 81 years, 534 (390-711) days after TAVR. Patients underwent a Tc99m-PYP scintigraphy for the diagnosis of ATTR cardiac amyloidosis. Eleven (12.5%) participants were diagnosed with ATTR cardiac amyloidosis. Eighty eight per cent of patients without amyloidosis were in New York Heart Association Classes 1-2 after TAVR, compared with 64% patients with ATTR cardiac amyloidosis (P = 0.022). There were no differences in left ventricular (LV) ejection fraction (P = 0.69) between patients with and without ATTR cardiac amyloidosis at enrolment. The LV mass index and pulmonary artery pressure were significantly higher in patients with ATTR cardiac amyloidosis (P = 0.046 and P = 0.002, respectively). Global longitudinal strain and myocardial work efficiency were significantly lower in patients with ATTR cardiac amyloidosis (P = 0.031 and P = 0.048, respectively). We assessed changes in echocardiographic data, from the time of TAVR to enrolment, and as expected, there was a significant decrease in aortic valve gradient in both groups. There was a significant reduction in LV mass and LV mass index and improvement in basal segment LV strain in the ATTR cardiac amyloidosis negative group (P = 0.045, P = 0.046 and 0.023, respectively). However, in the ATTR cardiac amyloidosis group the change in LV mass and LV mass index and LV basal strain values was not significant (P = 0.24, P = 0.13 and P = 0.35, respectively). The were no significant changes in other echocardiographic parameters in both groups. The patients were followed for 1150 (1086-1221) days after enrolment. Twenty seven patients had at least one cardiac hospitalization during of follow up, of them seven were with ATTR cardiac amyloidosis and 20 patients without amyloidosis (P = 0.017). Eighteen patients (20%) died during follow up; 12 (14%) patients died due to cardiac causes. There was no difference in all-cause and cardiac mortality between patients with and without ATTR cardiac amyloidosis (P = 0.6 and P = 0.53, respectively). CONCLUSIONS: The long-term survival after TAVR is not significantly affected by the presence of ATTR cardiac amyloidosis. However, the clinical course of these patients and the LV hemodynamic improvement is less favourable. This hypothesis-generating study suggests screening for ATTR cardiac amyloidosis in patients who underwent TAVR and have limited clinical or echocardiographic improvement, because they may potentially improve with new therapies for ATTR cardiac amyolidosis.

Differential systemic inflammatory responses after TAVI: The role of self versus balloon expandable devices.

OBJECTIVE: Transcatheter aortic valve implantation (TAVI) provokes early injury response, represented in part by dynamic changes in the inflammatory markers. The association of self-expanding valves (SEVs) and balloon-expandable valves (BEVs) with the consequent inflammatory response remains uncertain. MATERIALS AND METHODS: Patients with severe symptomatic aortic stenosis who underwent transfemoral TAVI: SEVs or BEVs, from January 2010 to December 2019 were enrolled. Whole white blood cells (WBC) and subpopulation dynamics as well the neutrophil to lymphocyte ratio (NLR) were evaluated. RESULTS: Three-hundred seventy consecutive patients (mean age 81.75 ± 6.8 years, 199 women's) were enrolled. In the entire population, significant kinetic changes in the WBC response (p <0.0001) between admission and first 24 hours post procedure, with a significant increase in total WBC (7.46 ± 2.26 to 10.08 ± 3.55) and absolute neutrophil count (4.97 ± 2.06 to 8.19 ± 3.43), NL ratio (3.72 ± 2.8 to 9.76 ± 7.29), and a meaningful decrease in absolute lymphocytes count (1.67 ± 1.1 to 1.1 ± 0.76). When compared between the types of valves, SEVs were associated with a more pronounced inflammatory response than BEVs, with total WBC (10.44 ± 3.86 vs. 9.45 ± 3.19) neutrophils (8.56 ± 3.75 vs. 7.55 ± 3.06) with p 0.016 and 0.012 respectively. CONCLUSION: This is the first description of a differential inflammatory response between the two leading delivery systems. SEV appears to trigger a more robust inflammatory response as compared to BEV. Clinical studies are warranted to assess the long term effect of our findings.

Comparative Analysis of the Kinetic Behavior of Systemic Inflammatory Markers in Patients with Depressed versus Preserved Left Ventricular Function Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: Prior studies have proven the safety and efficacy of transcatheter aortic valve implantation (TAVI) in patients with reduced left ventricular (LV) function. This study's aim was to investigate periprocedural inflammatory responses after TAVI. METHODS: Patients with severe symptomatic aortic stenosis and reduced LV function who underwent transfemoral TAVI were enrolled. A paired-matched analysis (1:2 ratio) was performed using patients with preserved LV function. Whole white blood cells (WBC) and subpopulation dynamics as well as the neutrophil to lymphocyte ratio (NLR) were evaluated at different times. RESULTS: A total of 156 patients were enrolled, including 52 patients with LVEF < 40% 35.00 [30.00, 39.25] and 104 with LVEF > 50% 55.00 [53.75, 60.0], p < 0.001. Baseline NLR in the reduced LV function group was significantly higher compared to the preserved LV function group, 2.85 [2.07, 4.78] vs. 3.90 [2.67, 5.26], p < 0.04. After a six-month follow-up, the inflammatory profile was found to be similar in the two groups, NLR 2.94 [2.01, 388] vs. 3.30 [2.06, 5.35], p = 0.288. No significant mortality differences between the two groups were observed in the long-term outcome. CONCLUSIONS: TAVI for severe symptomatic aortic stenosis, with reduced LV function, was associated with an improvement in the inflammatory profile that may account for some of the observable benefits of the procedure in this subset of patients.

Contemporary transcatheter aortic valve implantation related thrombocytopenia.

BACKGROUND: Transcatheter aortic valve implantation related thrombocytopenia (TAVI-rTP) is an inevitable phenomenon. However, no study has been performed on TAVI-rTP in the current setting of extended clinical indications combined with technology improvements. METHODS: Patients with severe symptomatic aortic stenosis who underwent transfemoral TAVI, from January 2016 to December 2019 were enrolled. RESULTS: Two-hundred and one consecutive patients (mean age 81.1 ± 7.1 years, 96 men) enrolled. Platelet count was recorded before and after aortic valve implantation. Dropped platelet count (DPC) occurred in all but 11 patients who were included. Two groups were created: DPC <30 and DPC ≥30%. DPC was compared with in-hospital major adverse cardiovascular events. The mean DPC was 26 ± 14%. We found that 67 patients (33.3%) had DPC of more or equal to 30%. In the univariable analysis, the time of the procedure (94.4 ± 32.7 vs 79.4 ± 21.9, p = .002), the amount of the contrast used (125.4 ± 55.4 vs 108.4 ± 44.1, p = .02) and the residual AV gradient (13.3 ± 7.2 vs 14.7, p = .05) were related to a DCP ≥30%. A DPC ≥30% was associated with increased risk of life-threatening/major bleeding (11.9% vs 1.5%, p = .001), major vascular complications (16.4% vs 5.2% p = .009) and death (3.0% vs 0%, p = .044) at 30 days. After multivariable analysis, the factors associated with a higher DPC were time and contrast. CONCLUSION: Contemporary TAVI-rTP in this cohort of patients continues to be a common phenomenon but severe thrombocytopenia is less frequent. Patients developing a DPC ≥30% are associated with poor outcomes at 30 days.

Urea level is an independent predictor of mortality in patients with severe aortic valve stenosis.

INTRODUCTION: Severe aortic stenosis (AS) is the most common valvular heart disease in the western world. Various factors are related to severe AS prognosis, including chronic kidney disease. The aim of this study was to evaluate the prognostic value of urea level in patients with severe AS. METHODS: We prospectively enrolled 142 patients (79.1±9.4 years, 88 women) with severe AS (mean valve area 0.67± 0.17 cm2). Clinical assessment, blood tests and echocardiography were performed at enrollment and follow up. The patient population was divided into low and high urea level groups, according to the median urea level at enrollment (72 patients, mean urea 35.5±6.2 mg/dL and 70 patients, mean urea 61.1±17.8 mg/dL, respectively). Hundred and twelve patients (79%) underwent aortic valve intervention. The primary endpoint was all-cause and cardiovascular mortality. OUTCOMES: During follow-up of 37±19.5 months, 56 (37.1%) patients died, 39 due to cardiovascular causes. In univariate analysis, age, urea level, creatinine, New York Heart Association (NYHA) class and aortic valve intervention were associated with all-cause mortality. However, in multivariate analysis only aortic valve intervention and blood urea were independent predictors of all-cause mortality (HR 0.494; 95% CI 0.226-0.918, P = 0.026 and HR 1.015; 95% CI 1.003-1.029, P = 0.046 respectively). Urea level, NYHA class and age were also significant predictors of cardiovascular mortality. Whereas, in multivariate analysis, only urea level predicted cardiovascular mortality in these patients (HR 1.017; CI 1.003-1.031 P = 0.019). CONCLUSIONS: Blood urea, a generally readily available and routinely determined marker of renal function, is an independent prognostic factor in patients with severe AS.

The Association Between Longitudinal Strain at Rest and Stress and Outcome in Asymptomatic Patients With Moderate and Severe Aortic Stenosis.

BACKGROUND: Calcific aortic stenosis (AS) is a progressive disease, and once moderate AS is present, the likelihood of symptom onset within 5 years is significant. The aim of this study was to determine the incremental value of global longitudinal strain (GLS) and basal longitudinal strain (BLS) at rest and during exercise on outcomes among asymptomatic patients' with moderate and severe AS. METHODS: Seventy-five patients with isolated, asymptomatic AS and preserved left ventricular function were retrospectively enrolled and underwent symptom-limited exercise echocardiography. Clinical and echocardiographic data, including GLS and BLS at rest and during exercise, were assessed. Occurrence of AS-related cardiovascular events was recorded. RESULTS: The mean age was 71 ± 10 years, and 63% were men. The mean aortic valve gradient was 30 ± 11 mm Hg, and the mean aortic valve area was 0.98 ± 0.21 cm2. Resting GLS and BLS were -16.5 ± 4% and -16.9 ± 3.6%, respectively. Exercise stress test results were positive in 27 patients (36%). Mean exercise GLS was -17.8 ± 3.5%, and mean exercise BLS was -17.9 ± 4%. During mean follow-up of 34.5 ± 3.5 months, cardiovascular events were observed in 45 patients. In multivariate analysis, aortic valve mean gradient (HR, 1.073; 95% CI, 1.032-1.115; P < .001) and peak exercise BLS (HR, 1.177; 95% CI, 1.07-1.295; P = .001) were associated with cardiac events during follow-up. CONCLUSIONS: Reduced exercise BLS is associated with future cardiovascular events in patients' with asymptomatic AS, independently of clinical factors and conventional echocardiographic parameters. Detection of postexercise myocardial dysfunction in patients with asymptomatic AS with preserved left ventricular function can aid in risk assessment of these patients.

Circulating regulatory T cells in patients with aortic valve stenosis: Association with disease progression and aortic valve intervention.

BACKGROUND: Severe aortic valve stenosis (AS) accounts for considerable morbidity and death, especially in older patients. There is increasing evidence to suggest a role for immune modulating cells in aortic valve (AV) degeneration. Regulatory T cells (Tregs) tune down inflammation. We aimed to study the levels of circulating Tregs in patients with AS and to assess their association with disease progression. METHOD AND RESULTS: The number of Tregs (CD4+CD25+Foxp3+) was determined by flow cytometry in 229 patients with AS and a control group of 69 patients. Tregs were significantly higher in patients with AS compared to the control group (1.64± .61% vs 1.13±0.97%, p=0.04). In the logistic regression analysis, adjusted for baseline characteristics, only the hemoglobin level and Treg percent correlated with the presence of AS (OR 0.642 95% CI 0.512-0.805, p<0.001 and OR 1.411, 95% CI 1.080-1.844, p=0.011, respectively). One hundred patients underwent 2 echocardiographic studies during follow-up. The median decrease in AV area (AVA) was 0.1cm(2)/year. A borderline association was observed between Tregs and AVA progression (r=0.19, p=0.054). In a subgroup of 68 patients with severe AS, the association between Tregs and AVA progression was significant (r=0.374, p=0.0017). In addition, a drop in Treg levels was observed 3-6months after AV-intervention (1.86±1.6% vs 1.04±1.8%, p=0.0005). CONCLUSIONS: Circulating Tregs are elevated in patients with AS. The levels of Tregs are higher in patients with severe AS and accelerated progression of valve narrowing. These results may help to identify AS patients with accelerated disease progression and possibly in need for earlier intervention.

Circulating Endothelial Progenitor Cells and Clinical Outcome in Patients with Aortic Stenosis.

BACKGROUND: Aortic stenosis (AS) is the most common valvular disease. Endothelial progenitor cells (EPCs) have a role in the repair of endothelial surfaces after injury. Reduced numbers of EPCs are associated with endothelial dysfunction and adverse clinical events, suggesting that endothelial injury in the absence of sufficient repair by circulating EPCs promotes the progression of vascular and possibly valvular disorders. The aim of this study was to assess EPC number in patients with AS and to study the predictive value of their circulating levels on prognosis. METHODS: The number of EPCs was determined by flow cytometry in 241 patients with AS and a control group of 73 pts. Thirty-eight, 52 and 151 patients had mild, moderate and severe AS, respectively. We evaluated the association between baseline levels of EPCs and death from cardiovascular causes during follow up. RESULTS: EPC level was significantly higher in patients with AS compared to the control group (p = 0.017). Two hundred and three patients with moderate and severe AS were followed for a median of 20 months. One hundred and twenty patients underwent an intervention. Thirty four patients died during follow up, 20 patients died due to cardiac causes. Advanced age, the presence of coronary artery disease, AS severity index (combination of high NYHA class, smaller aortic valve area and elevated pulmonary artery pressure) and a low EPC number were predictors of cardiac death in the univariate analysis. Multivariate logistic regression model identified low EPCs number and AS severity index as associated with cardiac death during follow up (p = 0.026 and p = 0.037, respectively). CONCLUSIONS: EPC number is increased in patients with AS. However, in patients with moderate or severe AS a relatively low number of EPCs is associated with cardiac death at follow up. These results may help to identify AS patients at increased cardiovascular risk.

Circulating CD14(+) monocytes in patients with aortic stenosis.

BACKGROUND: Calcific aortic stenosis (AS) is an active process sharing similarities with atherosclerosis and chronic inflammation. The pathophysiology of AS is notable for three cardinal components: inflammation, fibrosis and calcification. Monocytes play a role in each of these processes. The role of circulating monocytes in AS is not clear. The aim of the present study was to study an association between circulating apoptotic and non apoptotic CD14(+) monocytes and AS features. METHODS: We assessed the number of CD14(+) monocytes and apoptotic monocytes in 54 patients with significant AS (aortic valve area 0.74 ± 0.27 cm(2)) and compared them to 33 patients with similar risk factors and no valvular disease. The level of CD14(+) monocytes and apoptotic monocytes was assessed by flow cytometry. RESULTS: There was no difference in the risk factor profile and known coronary or peripheral vascular diseases between patients with AS and controls. Patients with AS exhibited increased numbers of CD14(+) monocytes as compared to controls (9.9% ± 4.9% vs. 7.7% ± 3.9%, P = 0.03). CD14(+) monocyte number was related to age and the presence and severity of AS. In patients with AS, both CD14(+) monocytes and apoptotic monocytes were inversely related to aortic valve area. CONCLUSIONS: Patients with significant AS have increased number of circulating CD14(+) monocytes and there is an inverse correlation between monocyte count and aortic valve area. These findings may suggest that inflammation is operative not only in early valve injury phase, but also at later developed stages such as calcification when AS is severe.