Developing Cardio-Oncology Programs in the New Era: Beyond Ventricular Dysfunction Due to Cancer Treatments.

Cardiovascular disease is a common problem in cancer patients that is becoming more widely recognized. This may be a consequence of prior cardiovascular risk factors but could also be secondary to the anticancer treatments. With the goal of offering a multidisciplinary approach to guaranteeing optimal cancer therapy and the early detection of related cardiac diseases, and in light of the recent ESC Cardio-Oncology Guideline recommendations, we developed a Cardio-Oncology unit devoted to the prevention and management of these specific complications. This document brings together important aspects to consider for the development and organization of a Cardio-Oncology program through our own experience and the current evidence.

Hippocampus and Insula Are Targets in Epileptic Patients With Glutamic Acid Decarboxylase Antibodies.

Background: Antibodies to glutamic acid decarboxylase (GAD ab) have been found in patients with limbic encephalitis (LE) and chronic pharmacoresistant focal epilepsy (FE). The objectives of the study were to: (1) analyze the clinical and neuroimaging course of patients with FE+GAD ab, (2) compare these characteristics with a control group, and (3) describe the most affected cerebral areas with structural and functional imaging. Methods: Patients with FE + high titers of GAD ab and a follow-up of at least 5 years were selected. Titers of serum GAD ab exceeding 2,000 UI/ml were considered high. Evolutive clinical and radiological characteristics were studied in comparison to two different control groups: patients with bilateral or with unilateral mesial temporal sclerosis (BMTS or UMTS) of a non-autoimmune origin. Results: A group of 13 patients and 17 controls were included (8 BMTS, 9 UMTS). The most frequent focal aware seizures (FAS) reported by patients were psychic (5/13: 33%). Somatosensorial, motor, and visual FAS (4/13:32%) (p: 0.045), musicogenic reflex seizures (MRS), and a previous history of cardiac syncope were reported only patients (2/13:16% each) (p: NS). Comparing EEG characteristics between patients and controls, a more widespread distribution of interictal epileptiform discharges (IED) was observed in FE+ GAD ab patients than in controls (p:0.01). Rhythmic delta activity was observed in all controls in anterior temporal lobes while in patients this was less frequent (p: 0.001). No IED, even in 24 h cVEEG, was seen in 6 patients (46%).First MRI was normal in 4/5 (75%) patients. During the follow-up mesial temporal lobe (MTsL) sclerosis was observed in 5/8 (62%) of patients. All patients had abnormal FDG-PET study. MTL hypometabolism was observed in 10/11 (91%) patients, being bilateral in 7/11 (63%). In controls, this was observed in 16/17 (94%), and it was bilateral in 8/17 (47%) (p: NS). Insular hypometabolism was observed in 5/11 (45%) patients (P:0.002). Conclusions: Clinical, EEG, and FDG-PET findings in FE+GAD ab suggest a widespread disease not restricted to the temporal lobe. Progressive MTL sclerosis may be observed during follow-up. In comparison to what is found in patients with non-autoimmune MTL epilepsy, insular hypometabolism is observed only in patients with GAD ab, so it may be an important diagnostic clue.

Association of postprocedural aortic regurgitation with mitral regurgitation worsened after transcatheter aortic valve replacement.

BACKGROUND: There is a paucity of investigation which demonstrates a predictor of mitral regurgitation (MR) worsened after aortic valve replacement (TAVR). AIM: The aim of this study was to identify the predictor of worsened MR after transcatheter TAVR. METHODS: We retrospectively studied a total of 209 patients with mild or less MR at baseline who underwent TAVR for the treatment of severe aortic stenosis with the balloon-expandable device. We found the presence of MR worsened after TAVR in 6% (12 patients) of all patients. Moderate or more postprocedural aortic regurgitation (AR) (odds ratio, 8.104; 95% confidence interval, 1.78-36.87; P = .007) was identified as a predictor of MR worsening after TAVR. In-hospital outcomes indicated that patients within whom MR worsened suffered congestive heart failure more than those with unchanged or improved MR after TAVR (P < .05). CONCLUSION: Significant postprocedural AR was associated with MR worsened from mild or less to moderate or more after TAVR. Worsened MR might affect in-hospital congestive heart failure.

Vena contracta analysis by color Doppler three-dimensional transesophageal echocardiography shows geometrical differences between prolapse and pseudoprolapse in eccentric mitral regurgitation.

AIMS: Evaluation of eccentric mitral regurgitation (MR) remains extremely difficult and the role played by its etiology, functional or degenerative, is not well understood. This study aimed to demonstrate the value of three-dimensional transesophageal echocardiography (3DTEE) in the evaluation of eccentric MR identifying geometric differences in the vena contracta area between functional and degenerative etiologies. METHODS AND RESULTS: We studied 61 patients with eccentric MR (30 functional and 31 degenerative). Regurgitant orifice area was determined by the two-dimensional proximal isovelocity surface area (2DPISA) and the 3DTEE methods. The ratio between maximum and minimum lengths of the vena contracta was calculated in each patient. Effective regurgitant orifice area by the 2DPISA method was smaller than that estimated by 3DTEE (0.56±0.21 vs 0.72±0.25 cm2 ). A better correlation between both methods was seen in degenerative mitral regurgitation (DMR; r=.83), with a mean underestimation of 8.2% by the 2DPISA method. A much worse correlation was found in functional mitral regurgitation (FMR; r=.39), where a mean underestimation by the 2DPISA method of 29.1% was observed. There was a more elongated and curved vena contracta in FMR compared to that in DMR (length ratio: 3.4±1.0 vs 2.2±0.7, P<.0001). CONCLUSION: Three-dimensional transesophageal echocardiography identifies a more elongated regurgitant orifice in eccentric FMR compared to that in eccentric DMR. This difference may explain the greater underestimation of effective regurgitant orifice area by the 2DPISA method in FMR. High-quality 3DTEE analysis of vena contracta area would be a highly recommended alternative.

Evaluation of vegetation size and its relationship with septic pulmonary embolism in tricuspid valve infective endocarditis: A real time 3DTEE study.

BACKGROUND: Tricuspid valve infective endocarditis (TVIE) causes septic pulmonary embolism (PE). However, the impact of vegetation size on PE is not fully elucidated. METHODS: In 26 consecutive patients with definite TVIE according to Duke criteria, we tested clinical, microbiological, and echocardiographic data including real time three-dimensional transesophageal echocardiography (3DTEE) as potential predictors of PE. 3DTEE measurement of maximum length of vegetation (MLV) was obtained with Advanced QLAB Quantification Software by cropping the 3D volume with the appropriate 2D plane to obtain the largest value. The standard two-dimensional transesophageal echocardiography (2DTEE) images were also evaluated to determine the MLV. RESULTS: Pulmonary embolism occurred after TVIE diagnosis with 3DTEE assessment and initiation of antibiotic therapy in 12 patients (46.2%). The 3DTEE MLV was larger than the 2DTEE value with a mean difference of 3.6 mm (95% CI, 2.5-4.6 mm). The best cutoff value for prediction of PE was MLV ≥16.4 mm with 3DTEE and MLV ≥9.5 mm with 2DTEE. The positive predictive value increased from 76.9% to 90% when 3DTEE was used. The accuracy of classification of patients with PE increased from 80.6% to 84.9% with 3DTEE. On multivariate analysis, 3DTEE MLV ≥16.4 mm (odds ratio 20.5; 95% confidence interval 1.31-322; P=.031) was independently associated with the occurrence of PE after adjustment for age, sex, complex vegetation, and the number of vegetation-attached leaflets. CONCLUSIONS: In TVIE, vegetation length is a strong predictor of the occurrence of PE. In combination with 2DTEE, 3DTEE may identify high-risk patients who will need a more aggressive therapeutic strategy.

Functional Tricuspid Regurgitation Caused by Chronic Atrial Fibrillation: A Real-Time 3-Dimensional Transesophageal Echocardiography Study.

BACKGROUND: Functional tricuspid regurgitation (TR) with a structurally normal tricuspid valve (TV) may occur secondary to chronic atrial fibrillation (AF). However, the clinical and echocardiographic differences according to functional TR subtypes are unclear. Therefore, characterization of functional TR because of chronic AF (AF-TR) remains undetermined. METHODS AND RESULTS: To investigate the prevalence of AF-TR, 437 patients with moderate to severe TR underwent 3-dimensional (3D) transesophageal echocardiography. TR severity was determined by the averaged vena contracta width on apical and parasternal inflow views. The prevalence of AF-TR was 9.2%, whereas that of functional TR because of left-sided heart disease was 45.3%. Clinical features of AF-TR included advanced age, female sex, greater right atrial than left atrial enlargement and lower systolic pulmonary artery pressure compared with left-sided heart disease-TR with sinus rhythm (all P<0.05). In 3D TV assessment, patients with AF-TR had a larger TV annular area with weaker annular contraction (both P<0.001) but a smaller tethering angle (P<0.001) despite a similar leaflet coaptation status compared with patients with left-sided heart disease-TR with sinus rhythm. On multivariable analysis, only the TV annular area in midsystole (coefficient, 0.059; 95% confidence interval, 0.041-0.078 per 100 mm2; P<0.001) was associated with TR severity in AF-TR. The annular area was more closely correlated with the right atrial volume than right ventricular end-systolic volume in AF-TR (P<0.001). CONCLUSIONS: AF-TR is not rare and is associated with advanced age and right atrial enlargement. TV deformations and their association with right heart remodeling differ between AF-TR and left-sided heart disease-TR. Our results suggest that in patients with TR secondary to AF, TV annuloplasty should be effective because this entity has annular dilatation without leaflet deformation.

Distant Position of Chordae from Coaptation Causes Mitral Regurgitation in Patients with Atrial Fibrillation.

BACKGROUND: The study aim was to investigate the mechanism of mitral regurgitation (MR) in lone atrial fibrillation (AF) patients using three-dimensional (3D) transesophageal echocardiography (TEE). METHODS: A retrospective analysis was conducted of 64 patients with AF and a normal left ventricle, and without prolapse of the mitral valve. Among these patients, significant MR was not identified in 33 cases (AF+MR- group) but was present in 31 cases (AF+MR+ group). The distance from the coaptation to the bending point of the anterior mitral leaflet (AML), where the chorda was attached, was termed the 'bending length'. The ratio of the bending length to the distance from coaptation to anterior mitral annulus was termed the 'bending ratio' (= bending length/coaptation-annulus length). The mitral annular area (MAA) fractional change was defined as follows: (MAA at late systole - MAA at early systole)/MAA at late systole × 100%). Other parameters relating to mitral valve morphology obtained using 3D TEE were measured with commercial software (QLAB, Phillips). RESULTS: The coaptation length (CL) was smaller in the AF+MR+ group than in the AF+MR- group (p<0.001), and correlated significantly with the anteriorposterior diameter of the mitral annulus (R = 0.286, p = -0.022), MAA at mid-systole (R = -0.269, p = 0.032), MAA fractional change (R = 0.434, p <0.001), and the bending ratio (R = -0.603, p <0.001). With a multivariable analysis, the correlating factors of significant MR in lone AF patients were a decrease in MAA fractional change (p = 0.022) and an increase of the bending ratio (p = 0.009). CONCLUSIONS: Small MAA fractional changes and the distant position of the chordae tendineae on the AML from the coaptation correlated with significant MR in AF patients with normal left ventricular systolic function.

3D Assessment of Features Associated With Transvalvular Aortic Regurgitation After TAVR: A Real-Time 3D TEE Study.

OBJECTIVES: This study of 3-dimensional (3D) transesophageal echocardiography (TEE) aimed to demonstrate features associated with transvalvular aortic regurgitation (AR) after transcatheter aortic valve replacement (TAVR) and to confirm the fact that a gap between the native aortic annulus and prosthesis is associated with paravalvular AR. BACKGROUND: The mechanism of AR after TAVR, particularly that of transvalvular AR, has not been evaluated adequately. METHODS: All patients with severe aortic stenosis who underwent TAVR with the Sapien device (Edwards Lifesciences, Irvine, California) had 3D TEE of the pre-procedural native aortic annulus and the post-procedural prosthetic valve. RESULTS: In the 201 patients studied, the total AR was mild in 67 patients (33%), moderate in 21 patients (10%), and severe in no patients. There were 20 patients with transvalvular AR and 82 patients with paravalvular AR. Fourteen patients had both transvalvular and paravalvular AR. Patients with transvalvular AR had larger prosthetic expansion (p <0.05), a more elliptical prosthetic shape at the prosthetic commissure level (p <0.01) and more anti-anatomical position (p <0.001), which was defined as malposition of the prosthetic commissures in relation to the native commissures, than the patients without transvalvular AR. Age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.01 to 1.09; p < 0.05) and effective area oversizing (OR: 0.97; 95% CI: 0.93 to 0.99, p <0.05) were associated with mild or greater paravalvular AR. CONCLUSIONS: 3D TEE successfully demonstrated the features associated with transvalvular AR, such as large prosthetic expansion, elliptical prosthetic shape, and anti-anatomical position of prosthesis. Additionally, effective area oversizing was associated with paravalvular AR.

Assessment of Post-Procedural Aortic Regurgitation After TAVR: An Intraprocedural TEE Study.

OBJECTIVES: The purpose of this study was to determine which echocardiographic parameters, including holodiastolic flow reversal (HDFR) in the descending aorta, were useful for grading of post-procedural aortic regurgitation (PAR) after transcatheter aortic valve replacement (TAVR) using intraprocedural transesophageal echocardiography. BACKGROUND: Reliable assessment of PAR in a catheterization laboratory is essential for an optimal outcome after TAVR; however, such an assessment has not been determined. METHODS: Three hundred eighty patients who underwent TAVR with the Edwards (Irvine, California) balloon-expandable transcatheter heart valve were retrospectively assessed by intraprocedural transesophageal echocardiography. PAR was evaluated by 2-dimensional color Doppler and pulse-wave Doppler in the descending aorta. Using 2-dimensional color Doppler, we measured the cross-sectional area of the vena contracta, the circumferential extent at the aortic annular plane, the longitudinal jet length, and the jet extent (with a mosaic pattern in the left ventricular outflow tract) compared with the location of the tip of the anterior mitral leaflet (AML). Grading of PAR was determined using the following vena contracta cutoffs: mild ≤9 mm(2); moderate 10 to 29 mm(2); and severe ≥30 mm(2). Significant PAR was defined as at least moderate grade. RESULTS: All patients with consistent HDFR had significant PAR. By multivariable analysis, consistent HDFR and the jet extent beyond the tip of AML were independent predictors of significant PAR. Consistent HDFR and jet extent beyond the tip of AML predicted significant PAR with specificities of 100% and 97%, respectively. In contrast, patients with both negative HDFR and a jet extent of less than halfway to the tip of AML had no significant PAR, with 97% specificity. CONCLUSIONS: The presence of consistent HDFR and jet extent beyond the tip of AML are indicative of significant PAR after TAVR.

Significant Reduction in Mitral Regurgitation Volume Is the Main Contributor for Increase in Systolic Forward Flow in Patients with Functional Mitral Regurgitation after Transcatheter Aortic Valve Replacement: Hemodynamic Analysis Using Echocardiography.

BACKGROUND: Reduction in mitral regurgitation (MR) after transcatheter aortic valve replacement (TAVR) has previously been reported. However, the hemodynamic effects of TAVR in patients with MR have not been previously evaluated. METHODS: We analyzed 571 patients who underwent TAVR from December 2010 to December 2013. We studied 20 patients with moderate or severe preprocedural functional mitral regurgitation (FMR) who also had a follow-up transthoracic echocardiography (TTE) examination between 90 and 360 days (median 213 days) after TAVR (Significant FMR Group). We also studied age- and gender-matched 20 patients with mild or lesser MR (Nonsignificant MR Group). Left ventricular functional measurements were assessed using echocardiography before and after TAVR. Left ventricular outflow tract stroke volume measurements using pulsed-wave Doppler (SVLVOT ) were calculated as a representative of systolic forward flow, and stroke volume by the Simpson's method (SVSimpson ) was calculated as a parameter of degree of LV contraction. RESULTS: MR grade improved in 22 of 40 patients after TAVR. In both groups, BNP level decreased, left ventricular ejection fraction increased, and SVLVOT increased after TAVR. SVSimpson increased in the Nonsignificant MR Group and remained unchanged in the Significant FMR Group. Vena contracta width of MR (MRVC) decreased in the Significant FMR Group. Using multivariable analysis in the Significant FMR Group, the increase in SVLVOT significantly correlated with the decrease in MRVC (P < 0.05). CONCLUSIONS: SVLVOT increased significantly after TAVR in patients with FMR. In these patients, increase in SVLVOT after TAVR was associated with decrease in severity of MR.

Impact of device landing zone calcification on paravalvular regurgitation after transcatheter aortic valve replacement: a real-time three-dimensional transesophageal echocardiographic study.

BACKGROUND: Determinants of paravalvular regurgitation after transcatheter aortic valve replacement (TAVR) remain unclear. The purpose of this study was to investigate the impact of aortic valve calcification (AVC) on paravalvular regurgitation after TAVR using real-time three-dimensional transesophageal echocardiography. METHODS: A total of 227 patients with severe aortic stenosis who underwent TAVR using the Edwards SAPIEN or SAPIEN XT valve were retrospectively analyzed. Severity of AVC was assessed on a visual scale ranging from 0 to 3 at the aortic annulus, the leaflets near the nadir, and the commissure. The shape of calcification was assessed by measuring the radial and circumferential lengths of annular calcification and by focusing on the calcification protruding into the left ventricular outflow tract from the annular level. Severity of paravalvular regurgitation was determined by the sum of the cross-sectional area of the vena contracta from two-dimensional or three-dimensional color Doppler transesophageal echocardiographic data. Significant paravalvular regurgitation was defined as at least a moderate grade. RESULTS: After excluding 25 patients with inadequate image quality of three-dimensional and color Doppler data for analysis, AVC could be evaluated in 202 patients. Significant paravalvular regurgitation was occurred in 37 patients (18%). The sum of the AVC scale at the annulus was significantly correlated with the grade of paravalvular regurgitation, while those at the leaflets near the nadir and the commissure were not. As assessed by receiver operating characteristic curve analysis, the radial and circumferential length of the annular calcification had good discriminatory ability for significant paravalvular regurgitation, with areas under the curve of 0.91 and 0.81, respectively. On multivariate analysis, annular calcification with radial length ≥ 3.0 mm, circumferential length ≥ 8.0 mm, and calcification protruding into the left ventricular outflow tract were independently associated with significant paravalvular regurgitation. CONCLUSIONS: Assessment of AVC by real-time three-dimensional transesophageal echocardiography is feasible and has good discriminatory value for paravalvular regurgitation in patients who undergo TAVR. Significant paravalvular regurgitation after TAVR is associated with the location and size of calcification at the aortic annulus and left ventricular outflow tract, not with its severity.

Device landing zone calcification predicts significant paravalvular regurgitation after transcatheter aortic valve replacement: a real time three-dimensional transesophageal echocardiography study.

Paravalvular regurgitation (PVR) after transcatheter aortic valve replacement (TAVR) is one of the major complications with negative clinical prognosis. Therefore, its prediction is important for further improvement of the outcome. We present a case with TAVR, in which we successfully evaluated aortic valve calcification protruding inward and into the left ventricular outflow tract by real time three-dimensional transesophageal echocardiography, and predicted significant PVR after the procedure. In conclusion, device landing zone calcification protruding inward is a key for the prediction of significant PVR after TAVR.

Comparison of aortic root geometry with bicuspid versus tricuspid aortic valve: real-time three-dimensional transesophageal echocardiographic study.

BACKGROUND: An understanding of aortic root anatomy in bicuspid aortic valve (BAV) has not been well established. The aims of this three-dimensional transesophageal echocardiographic study were (1) to examine whether aortic root geometry differs between BAV and tricuspid aortic valve (TAV) and (2) to analyze the dynamic motion of the aortic annulus throughout cardiac cycle. METHODS: A total of 66 patients with BAV (38 with severe aortic stenosis [AS]) and 66 age-, gender-, and body surface area-matched patients with TAV (36 with severe AS) who underwent three-dimensional transesophageal echocardiography were retrospectively enrolled. The dynamic motion of the aortic annulus was also analyzed in 40 selected patients (10 with BAV with severe AS, 10 with BAV without AS, 10 with TAV with severe AS, and 10 with TAV without AS). RESULTS: The area of the aortic root in patients with BAV was larger than in those with TAV (aortic annulus, P < .001; sinus of Valsalva, P < .05; sinotubular junction, P < .01). There was a significant difference in circularity (4π × area/[perimeter](2)) of the sinus of Valsalva between patients with BAV and those with TAV (P < .001), although there were no differences in the shapes of the aortic annulus and the sinotubular junction between the two groups. In both patients with BAV and those with TAV, the aortic annulus in mid-systole was largest and most circular in cardiac cycle; on the other hand, in end-diastole, the aortic annulus was smallest and most elliptical (P < .001). CONCLUSIONS: Three-dimensional transesophageal echocardiography successfully demonstrated significant differences in the size of the aortic root and the shape of the sinus of Valsalva between patients with BAV and those with TAV.

Effect of transcatheter aortic valve replacement on the mitral valve apparatus and mitral regurgitation: real-time three-dimensional transesophageal echocardiography study.

BACKGROUND: The effect of transcatheter aortic valve replacement (TAVR) on the mitral valve apparatus and factors influencing the reduction of mitral regurgitation with or without mitral leaflet tethering after TAVR are poorly understood. The present 3-dimensional (3D) transesophageal echocardiography study aimed to elucidate early changes further in the structure and function of the mitral valve apparatus after TAVR. METHODS AND RESULTS: We analyzed 90 patients (nontenting group, 56 patients and tenting group, 34 patients) who underwent TAVR using the Edwards SAPIEN and had intraprocedural 3D transesophageal echocardiography evaluation of the mitral valve. Of all patients, mitral regurgitation improved in 54%, remained the same in 38%, and worsened in 8% 1 day after TAVR. There were no statistically significant differences in mitral annular 3D parameters before and after TAVR in both groups. In the tenting group, tenting area (P<0.01) and tenting height (P<0.01) were decreased, and coaptation length was increased (P<0.05) after TAVR. In a multivariable analysis, the predictors of improved mitral regurgitation were the decrease of tenting area (odds ratio, 8.15; 95% confidence interval, 1.31-50.7; P<0.05) and the decrease of valvuloarterial impedance (odds ratio, 7.57; 95% confidence interval, 1.15-49.9; P<0.05) in the tenting group and the decrease of valvuloarterial impedance (odds ratio, 6.96; 95% confidence interval, 1.24-39.2; P<0.05) in the nontenting group. CONCLUSIONS: Mitral leaflet tethering was improved immediately by TAVR in patients with mitral leaflet tenting regardless of mitral annular geometry. Acute improvement in mitral regurgitation after TAVR is predominantly related to global left ventricular hemodynamics and mitral leaflet tethering change.

Evaluation of vegetation size and its relationship with embolism in infective endocarditis: a real-time 3-dimensional transesophageal echocardiography study.

BACKGROUND: Two-dimensional (2D) echocardiography studies have shown that the maximum length of vegetation (MLV)≥10 mm is a predictor of embolic events (EEs) in patients with infective endocarditis. However, 2D measurements probably underestimate the vegetation dimensions. In this study, we evaluated the feasibility of real-time 3-dimensional transesophageal echocardiography (RT3DTEE) in determining MLV and its accuracy in identifying the risk for EEs compared with 2D transesophageal echocardiography (2DTEE). METHODS AND RESULTS: We analyzed 60 patients with vegetations. RT3DTEE measurement of MLV was obtained with Advanced QLAB Quantification Software by cropping the 3D volume with the appropriate 2D plane to obtain the largest value. The standard 2DTEE images were also evaluated to determine the MLV. Major EEs were registered from medical records, and a logistic regression analysis was performed to determine the association between MLV and EEs. The RT3DTEE MLV was larger than the 2DTEE value with a mean difference of 3.2 mm (95% confidence interval, 2.1-4.2 mm). The best cut-off value for prediction of EEs was MLV≥20 mm with RT3DTEE and MLV≥16 mm with 2DTEE. The positive predictive value increased from 59.1% to 65.2% when RT3DTEE was used. The accuracy of classification of patients with EEs increased from 65% to 70% with this new technique. CONCLUSIONS: RT3DTEE is a feasible technique for the analysis of vegetation morphology and size that may overcome the shortcoming of 2DTEE, leading to a better prediction of the embolism risk in patients with infective endocarditis.

Valvuloarterial impedance, but not aortic stenosis severity, predicts syncope in patients with aortic stenosis.

BACKGROUND: The presence of syncope in patients with aortic valve stenosis (AS) predicts a grave prognosis. However, the evaluation of AS severity has been limited to valve-specific factors such as aortic valve area and mean transaortic pressure gradient. Recently, valvuloarterial impedance (Zva) was proposed for the estimation of global left ventricular afterload. Therefore, because predictors of syncope in patients with AS have not been investigated in recent years, we assessed the effect of clinical characteristics and echocardiographic parameters, including Zva, on syncope in patients with AS. METHODS AND RESULTS: We retrospectively studied 451 patients with moderate and severe AS without low left ventricular ejection fraction (<40%). Patients with syncope (n=79; 18%) had higher Zva (5.1±0.9 versus 4.4±0.9 mm Hg/mL per m(2); P<0.001) than those without (n=372; 82%). However, no significant differences existed in the mean transaortic pressure gradient (P=0.076) or the aortic valve area (P=0.160) between the 2 groups. In the multivariable analysis, only Zva was an independent predictor of syncope in patients with AS (odds ratio, 2.02; 95% confidence interval, 1.54-2.64; P<0.001). However, systolic blood pressure, relative wall thickness, the early transmitral flow velocity to peak early diastolic mitral annular velocity ratio, and mean transaortic pressure gradient were not identified as independent predictors. Receiver operating characteristic curve analysis identified Zva ≥4.7 mm Hg/mL per m(2) as the cutoff value associated with syncope in patients with AS. CONCLUSIONS: Our study suggests that high Zva, but not conventional parameters of AS, identifies AS patients with an increased risk of syncope.

Clopidogrel pretreatment in primary percutaneous coronary intervention: prevalence of high on-treatment platelet reactivity and impact on preprocedural patency of the infarct-related artery.

To date, there is limited data on levels of platelet inhibition achieved in patients with ST-elevation myocardial infarction (STEMI) who are loaded with clopidogrel and aspirin (ASA) prior to undergoing primary percutaneous coronary intervention (P-PCI). The aim of this investigation was to evaluate the percentage of STEMI patients with high on-treatment platelet reactivity (HPR) to clopidogrel at the time of initiating P-PCI and its association with the initial patency of the infarct-related artery (IRA). This prospective pharmacodynamic study included 50 STEMI patients, previously naïve to oral antiplatelet agents, who received 500-mg ASA and 600-mg clopidogrel loading doses prior to P-PCI. Platelet function assessment was performed at the beginning of the procedure using various assays, including VerifyNow™ system (primary endpoint), light transmission aggregometry and multiple electrode aggregometry. The percentage of patients with suboptimal response to clopidogrel and ASA assessed with the VerifyNow™ system was 88.0% and 28.6%, respectively. Similar results were obtained with the other assays used. A higher percentage of patients with initial patency of the IRA was observed among those patients without HPR compared with those with HPR to clopidogrel (66.7% vs 15.9%; p=0.013), while no differences were observed regarding postprocedural angiographic or electrocardiographic outcomes. In conclusion, this study shows that a high percentage of STEMI patients have inadequate levels of clopidogrel-induced and, to a lesser extent, aspirin-mediated platelet inhibition when starting a P-PCI procedure, and suggests that a poor response to clopidogrel might be associated with impaired initial TIMI flow in the IRA.