Evaluation of the anatomic sinus after transcatheter aortic valve replacement.

BACKGROUND: Following transcatheter aortic valve replacement (TAVI), the newly formed 'anatomic sinus'. may contribute to the formation of subclinical leaflet thrombosis (SLT).The evaluation of root geometry after TAVI is generally performed using multi-detector computed tomography (MDCT), and the role of transthoracic echocardiography (2D TTE) requires further validation. Thus, we aimed to test the reproducibility of 2D TTE assessment of the anatomic sinus with MDCT as a reference and its association with SLT. METHODS: 2D TTE was performed in 90 patients, and the echocardiograms were analyzed offline. Both sinus of Valsalva (SOV) and prosthesis diameters were assessed in the long- and short-axis parasternal views (PLAX/PSAX), and the anatomic sinus area was calculated. Inter- and intra-observer reproducibility were assessed using the interclass correlation coefficient (ICC). MDCT was performed in 50 individuals to evaluate concordance with 2D TTE and to detect SLT. RESULTS: There was excellent correlation regarding the diameter of the SOV and the prosthesis in PLAX (ICC: 0.93 (95% CI: 0.76,0.97); ICC: 0.80 (95% CI: 0.63,0.96)) and PSAX view (ICC: 0.90 (95% CI: 0.68,0.97); ICC: 0.88 (95% CI: 0.63,0.96)). Bland-Altman analysis of 2D TTE and MDCT anatomic sinus areas indicated a high level of agreement. SLT was detected in 8 individuals (16%); 3 patients had severe SLT at the level of 1 cusp. CONCLUSIONS: 2D TTE might play a role in the evaluation of the anatomic sinus after TAVI. The importance of this space and its effects on the SLT remain uncertain.

About different localization of hypoattenuated lesions following transcatheter aortic valve replacement.

BACKGROUND: Subclinical leaflet thrombosis is diagnosed using multidetector computed tomography (MDCT) and is characterised by a meniscal-shaped hypoattenuated lesion of one or more leaflets. Transcatheter aortic self-expandable valves are commonly manufactured with pliable pericardium over a nitinol frame that forms leaflet and extra-leaflet components such as the valve skirt. Little is known about extra-leaflet hypoattenuated lesion localisation, including that at the anatomical sinus level. Thus, the main aim of this study was to describe leaflet and extra-leaflet (anatomic sinus and subvalvular level) hypoattenuated lesions following transcatheter aortic valve replacement with a self-expandable prosthesis. As a secondary aim, we sought to investigate predictors of hypoattenuated lesions. METHODS: Fifty patients underwent MDCT at the follow-up. RESULTS: At a follow-up of 12 months, hypoattenuated leaflet lesions with mild to severe restricted movement were detected in eight individuals (16%), anatomic sinus lesions were identified in nine patients (18%), with higher prevalence in the non-coronary sinus (16%), and subvalvular lesions with variable extension toward the valve inflow were diagnosed in eight patients (16%). In 4 patients (8%) the anatomic sinus thrombus was 'in overlap' with leaflet thrombus; in 3 patients (6%) was in continuity with subvalvular frame thrombus. Bicuspid valve was the only independent predictor associated with hypoattenuated lesions (adj OR 8.25 (95% CI: 1.38, 49.21), p = 0.02)). CONCLUSIONS: This study demonstrated that hypoattenuated lesions could be identified not only at the leaflet but also at the subvalvular and anatomic sinus levels. The clinical relevance of such lesions remains unclear.

Self-Expandable Prosthesis Valve Adaptation: Non-Uniform Expansion and Stent Frame Decoupling.

The incidence of non-uniform expansion in the context of the self-expandable transcatheter heart valve (THV) is little investigated, along with stent-frame decoupling, which is a form of stent adaptation, in which the lower part of the THV stent conforms to both the ellipticity of the left ventricle outflow tract and the native annulus while maintaining the higher part of the valve more circular. We analyzed post-implant multi-detector computed tomography scans in 50 patients. Prosthesis non-uniform expansion was assessed by computing the prosthesis eccentricity on 6 prespecified levels: (1) frame inflow, (2) native annulus, (3) leaflet inflow, (4) prosthesis waist, (5) leaflet outflow, and (6) frame outflow. Stent-frame decoupling was assessed by comparing the mean eccentricity on 6 different prosthesis levels. Implantation depth, leaflet expansion and alignment, and residual anatomic sinus area ratios were also calculated. Subclinical leaflet thrombosis was defined as hypoattenuated lesion of a meniscal shape. At a 12-month follow-up, non-uniform expansion was consistently detected at each valvular level. Highest eccentricity was measured at the native annulus level (eccentricity: 0.54 ±  0.12), while the lowest index at the frame outflow level (0.23 ± 0.11). Similar results were observed in the subgroup analyses of sizes 23, 26, 29, and 34. Eccentricity significantly decreased from the annulus level to the prosthesis frame outflow (p <0.001). Notably, the incidence of mild-to-severe subclinical leaflet thrombosis was relevant (16%). In conclusion, prosthesis non-uniform expansion and stent frame decoupling frequently occur after self-expandable THV replacement. The clinical and hemodynamic implications remain uncertain.

Subclinical Leaflet Thrombosis Following Surgical and Transcatheter Aortic Valve Replacement: A Meta-Analysis.

Subclinical leaflets valve thrombosis (SLT) is a recently identified phenomenon with multidetector computer tomography after tissue aortic valve replacement. Whether SLT is more frequent after transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) is currently not known. Thus, the aim of this pairwise meta-analysis was to investigate the incidence of SLT after both TAVR and SAVR, the association with anticoagulation therapy, and the risk for neurological events. We searched PubMed, Google Scholar, and Ovid MEDLINE/Embase (January 02, 2023, last update) (PROSPERO registration: CRD42022383295). Statistical analysis was performed according to a prespecified statistical analysis plan. Time-to-event outcomes were summarized as incidence rate ratios (IRR). Pooled estimates were calculated using inverse variance method and random effect model. Overall, 2 registries, 2 randomized trials, and 1 observational study (1,593 patients) were included in this meta-analysis. There was a statistically significant difference in the incidence rate at follow-up of SLT between patients who underwent TAVR and SAVR (IRR 2.07, 95% confidence interval [CI]: [1.06; 4.03], I2 79%, 95% CI: [44; 92], p = 0.03). Oral anticoagulation therapy was associated with a reduced incidence of SLT (IRR 7.51, 95% CI: [3.24; 17.37], I2 62%, 95% CI: [0; 87], p <0.001). However, the incidence of later neurological events did not differ between patients with or without SLT (IRR 1.05, 95% CI: [0.32; 3.47], p = 0.93). In conclusion, SLT was more frequently detected after TAVR than SAVR. However, it was not associated with an increased risk for neurological events. Oral anticoagulation therapy seemed to reduce the incidence of SLT.

Aortic valve and vascular calcium score in pre-TAVI CT: correlation with early post-procedural complications.

PURPOSE: The aim of our study was to evaluate the prevalence of early complications after Transcatheter Aortic Valve Implantation (TAVI) and their correlation with the Calcium Score (CS) of the aortic valve, aorta and ilio-femoral arteries derived from pre-procedural computed tomography (CT). MATERIALS AND METHODS: We retrospectively reviewed 226 patients (100 males, mean age 79.4 ± 6.7 years) undergoing 64-slice CT for pre-TAVI evaluation from January 2018 to April 2021. The population was divided into CS quartiles. RESULTS: Overall, 173 patients underwent TAVI procedure, of whom 61% presented paravalvular leak after the procedure, 28% presented bleeding or vascular complications, 25% presented atrioventricular block, and 8% developed acute kidney injury. The prevalence of paravalvular leak and vascular complications was higher in the upper CS quartiles for aortic valve and ilio-femoral arteries. CONCLUSIONS: Aortic valve and vascular CS could help to predict post-TAVI early complications.

rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography.

BACKGROUND AND AIMS: Novel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients. METHODS AND RESULTS: The patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG. The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04-1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04-1.96) and 1.39 (1.22-1.58) respectively]. CONCLUSIONS: rs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.

Carotid artery stenting in octogenarians using a proximal endovascular occlusion cerebral protection device: a multicenter registry.

BACKGROUND: Carotid stenting (CAS) has been proposed as an alternative to carotid endoarterectomy also in elderly patients with discrepant results. However, the use of proximal neuroprotection devices have not been evaluated in octogenarians. PURPOSE: The aim of this multicenter prospective registry was to demonstrate that CAS in octogenarians is safe and effective if performed in high-volume centers by experienced operators. METHODS: From July 2005 to May 2009, a total of 198 octogenarians patients, in three different institutions, were included in this registry. All patients underwent CAS using proximal endovascular occlusion device (Mo.Ma. device Invatec, Roncadelle, Italy). An independent neurologist evaluated all patients. The primary endpoint was death and stroke rate at 30 days. RESULTS: 198 octogenarians (135 men; mean age: 83.2 years) were included in the registry. 39.4% of the patients were symptomatic. Procedural success was 100%. In-hospital complications: Two minor and two major strokes (2.02%) occurred. No device-related complications and no serious access site complication were noted. Between discharge and 30-day follow-up, one patient died due to a cardiac arrest. The overall 30-day combined stroke/death rate was 2.52%, resulting in 1.61% event incidence in asymptomatic and 3.9% in symptomatic patients (P = ns). Logistic regression did not identify independent predictor of neurological events, except in the female gender. CONCLUSION: This multicenter prospective registry shows that CAS performed with proximal flow blockage is safe and feasible also in octogenarians. Thirty days death/stroke rates are similar to those of the overall population and within the International guidelines.

The predictive role of atherogenic dyslipidemia in subjects with non-coronary atherosclerosis.

BACKGROUND: Recent findings have suggested that subjects with non-coronary atherosclerosis may show elevated prevalence of atherogenic dyslipidemia, including higher triglyceride levels, reduced HDL-cholesterol concentrations and increased levels of small, dense low-density lipoproteins (LDL). These three lipid abnormalities constitute the so-called "atherogenic-lipoprotein-phenotype" (ALP) but its predictive role in these patients still remains to be established. METHODS: We performed a 2-year follow-up study to assess clinical and biochemical predictors of cardiovascular events in 44 male patients (64+/-5 years, BMI: 27+/-3), 26 with peripheral arterial disease and 18 with abdominal aortic aneurysm. Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. RESULTS: Clinical events were registered in the 43% of patients. At univariate analysis we found that patients with events had increased prevalence of hypertension (p=.0098), diabetes (p=.0089), family history of cardiovascular diseases (p=.0089), of elevated small, dense LDL (p=.0222) and ALP (p=.0224). At multivariate analysis (including all clinical and laboratory variables) we found the following independent predictors of events: hypertension (OR 8.9, p=.0347), diabetes (OR 9.4, p=.0270), elevated small, dense LDL (OR 6.9, p=.0488) and ALP (OR 8.7, p=.0497). CONCLUSIONS: This is the first study that evaluated the predictive role of ALP beyond traditional cardiovascular risk factors in patients with peripheral arterial disease or abdominal aortic aneurysm. We confirmed that hypertension and diabetes are strong predictors of cardiovascular events in these subjects but ALP seems to be an independent predictor too. Yet, the therapeutical consequences of these findings need to be tested by future studies.

LDL size and subclasses in patients with abdominal aortic aneurysm.

Since the type of dyslipidemia in patients with abdominal aortic aneurysm (AAA) is still insufficiently defined, we measured plasma lipids and analyzed LDL size and subclasses by gradient gel electrophoresis in 30 male patients (69+/-6 years, BMI: 27+/-3) with newly diagnosed AAA and in 26 age- and BMI-matched male healthy controls. Patients with AAA had lower HDL-cholesterol (p<.0001), increased triglycerides (p=.0002) and smaller LDL size (p<.0001) as well as increased levels of total small, dense LDL (p=.0210) in relation to controls. Multivariate analysis also showed that small LDL size was independently associated with the presence of AAA (p=.0350). Increased levels of small, dense LDL may therefore represent a common feature in patients with AAA.

Small, dense low-density lipoproteins (LDL) are predictors of cardio- and cerebro-vascular events in subjects with the metabolic syndrome.

OBJECTIVE: Small, dense low-density lipoproteins (LDL) are a feature of the metabolic syndrome (MS) but their predictive role still remains to be established. We performed a 2-year follow-up study in 124 subjects with MS (63 +/- 6 years), as defined by the American Heart Association/National Heart, Lung and Blood Institute guidelines, to assess clinical and biochemical predictors of cerebro- and cardio-vascular events. METHODS AND RESULTS: Beyond traditional cardiovascular risk factors, we measured LDL size and subclasses by gradient gel electrophoresis. Clinical events were registered in the 25% of subjects. At univariate analysis subjects with events had increased prevalence of elevated fasting glucose (P = 0.0117), smoking (P = 0.0015), family history of coronary artery disease (P = 0.0033) and higher levels of total- and LDL-cholesterol (P = 0.0027 and P = 0.0023, respectively); LDL size was lower (P < 0.0001), due to reduced larger subclasses and increased small, dense LDL (all P < 0.0001). At multivariate analysis the following were independent predictors of events (univariate odd ratios were calculated): low HDL-cholesterol (OR 15.4, P = 0.0238), elevated fasting glucose (OR 12.1, P = 0.0102), elevated small, dense LDL (OR 11.7, P = 0.0004), elevated blood pressure (OR 9.2, P = 0.0392), smoking (OR 4.8, P = 0.0054). CONCLUSIONS: This is the first study that assessed the predictive role of small, dense LDL beyond traditional cardiovascular risk factors in subjects with MS.

Exercise induced atrio-ventricular (AV) block during nuclear perfusion stress testing: a case report.

BACKGROUND: Exercise causes enhanced sympathetic discharge and results in physiologic tachycardia. However, in some patients with a diseased conduction system resulting from acute ischemia, exercise can precipitate heart block. METHODS AND RESULTS: In this report we describe a 51 years old male patient with transient advanced degree atrioventricular (AV) block developed during recovery from exercise stress testing, resolved after the administration of atropine. Nuclear perfusion imaging demostrated stress-induced ischemia of the inferior-apical segments, and recovery of perfusion in the images obtained at rest. Coronarography showed critical stenosis of the right coronary artery, which was treated by percutaneous coronary intervention (PCI) and drug eluting stent (DES) deployment. CONCLUSION: Nuclear myocardial perfusion imaging provides noninvasive evidence that transient ischemia of the infero-apical segment can result in advanced degree AV block in patient with critical severe right coronary disease.

Atherogenic lipoprotein phenotype and LDL size and subclasses in patients with peripheral arterial disease.

The type of dyslipidemia in patients with peripheral arterial disease (PAD) is still ill defined. PAD patients often show elevated triglycerides and reduced HDL-cholesterol, two lipid abnormalities usually accompanied by decreased LDL size in the "atherogenic lipoprotein phenotype" (ALP). We investigated (1) whether PAD patients have lower LDL size, (2) altered LDL subclass distribution and (3) the prevalence of ALP. We measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis in 31 adults with intermittent claudication and 31 age-BMI-matched controls. Patients had higher prevalence of hypertension (p=.0132), smoking (p<.0020) and diabetes (p=.0024), with lower HDL-cholesterol (p<.0001) and increased triglycerides (p=.0057); LDL size was smaller (p<.0001), with decreased larger subclasses (LDL-I, p<.0001; LDL-IIA, p=.0068) and increased smaller particles (LDL-IIIA, p<.0001; LDL-IIIB, p=.0013; LDL-IVA, p=.0029; LDL-IVB, p<.0001). The presence of PAD was independently associated with smoking (OR 7.2, p=.0099), hypertension (OR 6.5, p=.0362), diabetes (OR 5.5, p=.0450) and elevated small, dense LDL (OR 6.7, p=.0497). The concomitant presence of high triglycerides, low HDL-cholesterol and elevated small, dense LDL in patients was 26% (versus 0% controls, p=.0024). ALP seems to characterize PAD dyslipidemia, but prospective studies are needed to test whether this lipoprotein phenotype may represent a risk factor too.

Interleukin 6 plasma levels predict with high sensitivity and specificity coronary stenosis detected by coronary angiography.

In recent years new biomarkers able to measure the coronary atherosclerotic burden have been investigated. The aim of the present study was: i) to measure plasma levels of four biomarkers: C reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin 6 (IL-6), 8-isosprostane (8-ISO), in a series of patients undergoing coronary angiography; ii) to assess the power of the biomarkers to predict critical coronary stenosis detected by angiography. The study population consisted of a group of 438 subjects undergoing coronary angiography; 160 patients with 0, 1, 2, or 3 critical vessels were selected, and biomarkers plasma levels were measured in plasma samples obtained before the procedure. The most predictive biomarker was then assayed in 120 patients with critical stenosis and 120 unmatched patients without stenosis. CRP, sICAM-1, IL-6 and 8-ISO plasma levels increased with the number of diseased vessels. All biomarkers were good predictors of critical stenosis (receiver-operator-curve [ROC] areas; CRP = 0.880, IL-6 = 0.936, sICAM-1 = 0.907, 8-ISO = 0.873). IL-6 was confirmed in an expanded sample of 240 subjects to be the best predictor with a ROC area = 0.959. With a threshold of 3.6 ng/l, a 100% sensitivity (120/120) and a 90% specificity (108/120) was observed. In conclusion, IL-6, sICAM-1, CRP and 8-ISO are predictive of CAD. IL-6 predicts critical coronary stenosis with the highest sensitivity and specificity.

RESTEM: a percutaneous coronary intervention 'real world' registry in the drug-eluting stent era.

Sirolimus-eluting stents (SESs) reduce the rate of in-stent restenosis in selected cases. Their performance in more complex patients and their impact on the final clinical outcome of these patients, however, remains uncertain. RESTEM Registry (REgistro delle PCI in era di STEnt Medicati), a prospective multicenter registry collecting all percutaneous coronary interventions (PCIs) performed over 20 months and monitored up to 2 years, includes 5524 consecutive patients treated with bare metal stent (BMS) (72%), sirolimus-eluting stent (SES) (15%), combined BMS+SES (4%), or other techniques (9%). The combination of death, acute myocardial infarction (AMI), unstable angina and revascularizations had been chosen as primary endpoint. One-year multivariate analysis shows no significant advantage of SES in combined clinical events, a slight benefit in primary endpoint [18.5 vs. 25.0% BMS=odds ratio (OR) 0.78) and revascularizations (13.6 vs. 20.4% BMS=OR 0.74], a consistent advantage when only target vessel revascularizations (TVRs) are considered (5.5 vs. 10.5% BMS=OR 0.52). The two-year adjusted results confirm a significant advantage of SES in TVR (8.3 vs. 13.7% BMS=OR 0.65), a slight benefit for revascularizations (18.3 vs. 25.6% BMS=OR 0.76), without reducing mortality and other clinical events; these data refute the benefit on primary endpoint observed at 12 months (25.8 vs. 32.4% BMS=OR 0.84). After analyzing events recorded during the first and second year follow-up periods separately, the incidence of many of them favors SES in the first year, yet appear independent of the technique utilized in the second. RESTEM results confirming SES's capacity to reduce TVR without reduction of other clinical events, suggest that this advantage is limited to the first year after PCI, and show no evidence of excess of deaths, AMIs and late thrombosis following SES implantation described in recent meta-analyses.

Accumulation of apoE-enriched triglyceride-rich lipoproteins in patients with coronary artery disease.

Triglycerides (TGs) are vehicled by multiple particles with different abilities to promote atherosclerosis. Among plasma TG-rich lipoproteins (TRLs), subspecies may or may not contain apolipoprotein E (apoE) molecules: in this study, we evaluated the relative contribution of apoE-rich and apoE-poor TRLs to coronary atherosclerosis. We selected a group of males with premature coronary artery disease (CAD) without any of the classical nonlipid risk factors and/or high plasma lipid levels and evaluated the plasma concentration of TRL subspecies in comparison with healthy controls. Patients with CAD and controls had total cholesterol and TG levels within the normal range (despite slightly, even if significantly, higher TG levels in patients with CAD) and low-density lipoprotein cholesterol levels near optimal values. Nevertheless, patients with CAD had significantly lower high-density lipoprotein cholesterol, smaller low-density lipoprotein peak particle size, and a reduced HDL2b subfraction than controls. In addition, we observed higher concentrations of total TRL in patients with CAD together with a selective increase in apoE-rich particles. All these data were confirmed after correction for TG levels. We also investigated which parameters were associated with the spread of coronary atherosclerosis. Subjects with a single-vessel disease had selectively lower levels of apoE-rich fractions than patients with a multivessel disease. This was confirmed by multivariate analysis. Patients with a premature CAD free of nonlipid conventional risk factors, despite not having elevated lipid levels, show several lipoprotein abnormalities. Besides known atherogenic alterations, the accumulation of apoE-rich TRL subfractions may represent an additive factor that can potentially promote and initiate the atherosclerotic process.

Family history, diabetes and extension of coronary atherosclerosis are strong predictors of adverse events after PTCA: A one-year follow-up study.

BACKGROUND AND AIM: In this study we addressed some open questions in patients with coronary artery disease (CAD). First, we analysed which of the traditional risk factors was associated with the spreading of coronary stenosis and second, we aimed to identify if any variable was predictive of post-percutaneous transluminal coronary angioplasty (PTCA) clinical events. METHODS AND RESULTS: We collected a consecutive series of patients with CAD (n=301) and in the subgroup of patients undergoing PTCA (n=135) we performed a prospective one-year follow-up study recording cardiovascular morbidity and total mortality. According to the extension of coronary atherosclerosis, we found a significant relationship with the prevalence of diabetes in men and with plasma HDL-cholesterol concentrations in women. The follow-up was completed in 95% of patients; we did not document any death whereas clinical events were registered in 16% of patients. At univariate analysis, we found that patients with clinical events had a higher prevalence of family history of CAD (43% vs 14%, p<0.005), diabetes (52% vs 21%, p<0.005) and multivessel disease (52% vs 35%, p<0.05). Multivariate analysis (logistic regression) confirmed that family history of CAD (OR 4.6, 95% CI 1.7-12.8, p<0.005), diabetes (OR 4.0, 95% CI 1.5-10.6, p<0.01) and multivessel disease (OR 2.8, 95% CI 1.1-7.4, p<0.05) were the only variables predictive of clinical events. CONCLUSIONS: In this study, factors associated with the spreading of coronary stenosis were different according to the gender. Moreover, the presence of diabetes and multivessel disease had a negative impact on the long-term prognosis of patients undergoing PTCA. In addition, the family history of CAD represented in our study a strong predictor of clinical events. We suggest that in the management of post-PTCA patients, the role of individual baseline clinical characteristics must be taken into account and that subjects with a family history of premature CAD, diabetes and a wide extension of coronary disease represent those with the highest risk.