Gastrointestinal Angiodysplasia in Patients with Severe Aortic Stenosis: The Endoscopic Features of Heyde's Syndrome.

INTRODUCTION: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. PATIENTS AND METHODS: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. RESULTS: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). CONCLUSIONS: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.

Mitral valve leaflet stiffness predicts residual mitral regurgitation after transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Residual regurgitation after transcatheter edge-to-edge mitral valve repair (TMVR) is a predictor of poor prognosis in patients with functional mitral regurgitation (FMR). This study sought to identify the mitral valve (MV) parameters measured by three-dimensional transesophageal echocardiography (3D-TEE) and MV leaflet features that predict residual mitral regurgitation (MR) after TMVR in patients with FMR. METHODS: Consecutive patients with FMR who underwent TMVR were classified into two groups based on the degree of residual MR just after TMVR: < 2+ in the optimal MR reduction group and ≥ 2+ in the suboptimal MR reduction group. The two groups were compared with respect to 3D-TEE parameters and the MV leaflet features, including the following parameters: stiffness, defined as a leaflet that remains at a fixed angle even during diastole, and thickness, measured in both clear and rough zones. RESULTS: Thirty-four of 46 patients (74%) were classified as the optimal MR reduction group. Multivariable analysis showed that anterior mitral leaflet + posterior mitral leaflet length/anteroposterior annulus diameter (p = .044) and MV leaflet stiffness (p = .007) were independent predictors of residual MR. CONCLUSION: MV leaflet stiffness and the ratio of MV leaflet lengths to the annulus diameter may be good predictors of residual MR after TMVR in patients with FMR.

Additional balloon aortic valvuloplasty to overcome the difficult removal of a self-expandable transcatheter aortic valve system due to valve infolding.

Transcatheter aortic valve replacement (TAVR) is a well-established treatment for severe aortic stenosis. Advances in the devices used and operators' technique have reduced the frequency of complications. However, valve infolding is a rare but serious outcome after the implantation of self-expanding prostheses. We report a case of a successful bailout of a device that was difficult to remove because of valve infolding. TAVR using a 26 mm Evolut PRO+ system (Medtronic) was planned for a 91-year-old woman with severe aortic stenosis. After the valve was deployed in a satisfactory position on the second release, the system could not be removed because the nose cone was hooked to the basal frame of the deployed valve. To overcome this situation, an additional balloon was inserted from the contralateral femoral side and inflated, and we extracted the system successfully by pulling out the device while simultaneously deflating the balloon. Postoperative computed tomography revealed valve infolding, which was considered to cause the difficulty in system removal. Infoldings of self-expandable prostheses should be considered when faced with difficulty in removing the catheter system, and the method elucidated in this case report can be effective to manage it.

Serial changes in cardiac sympathetic nervous function after transcatheter aortic valve replacement: A prospective observational study using 123I-meta-iodobenzylguanidine imaging.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) can rapidly improve cardiac sympathetic nervous function (CSNF) within 2 weeks in patients with aortic stenosis (AS). However, whether such short-term improvements will be sustained thereafter remains unclear. METHODS: Patients with severe AS who underwent TAVR between October 2017 and June 2019 were enrolled in this single-center, prospective, observational study. 123I-meta-iodobenzylguanidine imaging was performed at baseline, within 2 weeks after TAVR, and at 6 to 12 months post-TAVR to evaluate the heart-mediastinum ratio (H/M) and washout rate. RESULTS: Of 183 consecutive patients, 75 (19 men; median age: 86 years) were evaluated. The late H/M significantly improved within 2 weeks after TAVR (P = .041) and further improved over 6 to 12 months after TAVR (P = .041). Multivariate analysis revealed that the baseline mean aortic valve pressure gradient (mPG) was an independent predictor of mid-term improvement in the late H/M (> 0.1) (P = .037). Patients with a high baseline mPG (≥ 58 mmHg) exhibited a significantly greater increase in the late H/M than those with a low baseline mPG (< 42 mmHg) (0.24 vs 0.01; P = .029). CONCLUSION: CSNF demonstrated sustained improvement from within 2 weeks after TAVR until 6 to 12 months later. Such improvement was related to baseline hemodynamic AS severity.

Left ventricular hypertrophy as a predictor of cardiovascular outcomes after transcatheter aortic valve replacement.

AIMS: This study aimed to clarify the relationship between cardiovascular prognosis and left ventricular hypertrophy (LVH) in patients with severe aortic stenosis who underwent transcatheter aortic valve replacement (TAVR) and to investigate the relationship between cardiac sympathetic nerve (CSN) function and these factors using 123 I-metaiodobenzylguanidine scintigraphy. METHODS AND RESULTS: In this single-centre, retrospective observational study, 349 patients who underwent TAVR at our institution between July 2017 and May 2020 were divided into two groups: those with severe LVH pre-operatively [severe LVH (+) group] and those without LVH pre-operatively [severe LVH (-) group]. The rates of freedom from cardiovascular events (cardiovascular death and heart failure hospitalization) were compared. The relationship between changes in left ventricular mass index (LVMi) and changes in delay heart-mediastinum ratio (H/M) from before TAVR to 6 months after TAVR was also investigated. The event-free rate was significantly lower in the severe LVH (+) group (87.1% vs. 96.0%, log-rank P = 0.021). The severe LVH (+) group exhibited a significantly lower delay H/M value, scored by 123 I-metaiodobenzylguanidine scintigraphy, than the severe LVH (-) group (2.33 [1.92-2.67] vs. 2.67 [2.17-3.68], respectively, P < 0.001). Moreover, the event-free rate of post-operative cardiovascular events was lower among patients with a delay H/M value < 2.50 than that among other patients (87.7% vs. 97.2%, log-rank P = 0.012). LVMi was significantly higher (115 [99-130] vs. 90 [78-111] g/m2 , P < 0.001) and delay H/M value was significantly lower (2.53 [1.98-2.83] vs. 2.71 [2.25-3.19], P = 0.025) in the severe LVH (+) group than in the severe LVH (-) group at 6 months after TAVR. Patients with improved LVH at 6 months after TAVR also had increased delay H/M (from 2.51 [2.01-2.81] to 2.67 [2.26-3.02], P < 0.001), whereas those without improved LVH had no significant change in delay H/M (from 2.64 [2.23-3.06] to 2.53 [1.97-3.00], P = 0.829). CONCLUSIONS: Severe LVH before TAVR is a prognostic factor for poor post-operative cardiovascular outcomes. LVH associated with aortic stenosis and CSN function are correlated, suggesting their involvement in LVH prognosis.

Doppler Underestimates Transvalvular Gradient Measured by Catheterization in Patients With Severe Aortic Stenosis.

We sought to clarify characteristics of patients with severe aortic stenosis (AS) in whom transvalvular mean pressure gradient (MPG) was underestimated with Doppler compared with catheterization. Study subjects included 127 patients with severe AS who underwent transcatheter aortic valve implantation. Between subjects with Doppler MPG underestimation ≥10 mm Hg (group U) and those without (group C), we retrospectively compared echocardiographic parameters and aortic valve calcification score using the Agatston method. Despite a strong correlation (rS = 0.88) and small absolute difference (2.1 ± 10.1 mm Hg) between Doppler and catheter MPG, 27 patients (21%) were in group U. Among 48 patients with catheter MPG ≥60 mm Hg, 10 patients (21%) revealed Doppler MPG of 40 to 59 mm Hg, suggesting they had been misclassified as having severe AS instead of very severe AS. According to the guidelines, indication of valve replacement for patients without symptoms should be considered for very severe AS but not for severe AS. Therefore, sole reliance on Doppler MPG could cause clinical misjudgments. Group U had larger relative wall thickness (median [interquartile range: 0.60 [0.50 to 0.69] vs 0.53 [0.46 to 0.60], p = 0.003) and higher calcification score (3,024 [2,066 to 3,555] vs 1,790 [1,293 to 2,501] arbitrary units, p <0.001). Both calcification score (per 100 arbitrary unit increment, odds ratio 1.10, 1.04 to 1.17, p = 0.002) and relative wall thickness (per 0.05 increment, odds ratio 1.29, 95% confidence interval 1.05 to 1.60, p = 0.02) were independently associated with Doppler underestimation. In conclusion, Doppler might underestimate transvalvular gradient compared with catheterization in patients with severe AS who have heavy valve calcification and prominent concentric remodeling left ventricular geometry.

Cystatin C in risk prediction after transcatheter aortic valve replacement: a retrospective analysis.

AIMS: No study has evaluated the prognostic value of the chronic kidney disease (CKD) classification by cystatin C-based estimated glomerular filtration rate (eGFR) (CKDCys classification) in patients undergoing transcatheter aortic valve replacement (TAVR). This study aimed to compare the prognostic value of CKDCys classification and CKD classification by creatinine-based eGFR (CKDCr classification) in risk prediction after TAVR. METHODS AND RESULTS: We retrospectively analysed consecutive 219 patients with symptomatic severe aortic stenosis who underwent TAVR at our institute between December 2016 and June 2019. Pre-operative CKDCr and CKDCys classifications were evaluated for their prognostic value of 2-year major adverse cardiovascular and cerebrovascular events (MACCE) after TAVR. MACCE was defined as the composite of all-cause mortality, non-fatal myocardial infarction, stroke, and rehospitalization for worsening congestive heart failure. Participants had a median age of 86.0 years and were predominantly female (76.9%). In 96.6% of the cases, TAVR was performed using transfemoral access. The median creatinine-based eGFR (52.85 mL/min/1.73 m2 ) was higher than the cystatin C-based eGFR (41.50 mL/min/1.73 m2 ). Downward reclassification in CKD stages based on eGFRCys was observed in 49.0% of patients. During a median follow-up period of 575.5 (interquartile range: 367.0-730.0) days, 58 patients presented with MACCE. CKDCys classification, but not CKDCr classification, significantly stratified the risk of 2-year MACCE in patients after TAVR by log-rank test (P = 0.003). In multivariate Cox regression analysis, only CKDCys stage 3b [hazard ratio (HR) = 4.37; 95% confidence interval (CI): 1.28-14.91; P = 0.019] and CKDCys stage 4 + 5 (HR = 3.72; 95% CI: 1.06-12.99; P = 0.040) were significant predictors of MACCE after adjustment for potential confounders. CONCLUSIONS: The CKDCys classification could better assess the risk than the CKDCr classification in patients undergoing TAVR. CKDCys stage 3b and stage 4 + 5 correlated with adverse outcomes.

Incidence and predictors of transcatheter aortic valve replacement device emboligenic matter detected by transesophageal echocardiography.

During transfemoral (TF) or transcatheter aortic valve replacement (TAVR), transesophageal echocardiography (TEE) sometimes reveals an unexpected mobile membranous mass on the catheter tip within the proximal part of the descending thoracic aorta. Such mobile masses may cause critical embolic events if the TAVR device advances into the ascending aorta in the absence of preventive measures. This study aimed to investigate the incidence and predictors of emboligenic matter (EM) during TAVR, impact of EM on the procedure, and incidence of symptomatic ischemic stroke post procedure. Among 436 consecutive patients who underwent TF-TAVR, 407 were evaluated in this study. The primary end point was incidence of symptomatic ischemic stroke within 24 h post procedure while taking appropriate preventive measures. Incidence of EM, factors associated with EM, and the impact of EM on the procedure were also investigated. Among the 407 cases, 15 cases (3.7%) of EM were identified but no ischemic stroke occurred in the EM (+) group (0% vs. 2.04%, p = 1.00). In the EM (+) group, a self-expandable valve was used in all 15 cases (100% vs. 42.6%, p < 0.0001) while 14 cases used a CoreValve's InLine sheath system initially (93.3% vs. 27.3%, p < 0.0001). CoreValve's InLine sheath system usage was the only independent predictor of EM. The CoreValve's InLine delivery system was identified as a predictor of EM during TF-TAVR, but symptomatic ischemic stroke was avoided while taking appropriate embolization preventive measures.

Prolonged Elevation of Tricuspid Regurgitation Pressure Gradient After Exercise in Patients With Exercise-induced Pulmonary Hypertension.

It is necessary to measure the peak tricuspid regurgitation pressure gradient (TRPG) that is recorded at maximum exercise intensity when diagnosing exercise-induced pulmonary hypertension (ePH) on exercise stress echocardiography (ESE). However, it is difficult to measure maximum TRPG during the treadmill exercise. If ePH induced TRPG elevation continues during recovery period after exercise termination, this elevation will serve as a practical diagnostic standard. We aimed to assess whether the elevation of postexercise peak TRPG prolong soon after finishing exercise in patients with ePH. Seventy-four patients underwent symptom-limited ESE by using a semirecumbent bicycle ergometer. ePH was defined as peak TRPG > 50 mm Hg at maximum exercise. We measured peak TRPG during exercise and until 5 minutes afterward. Thirty-five patients were diagnosed with ePH; their median TRPG was 57 mm Hg [interquartile range: 52-62 mm Hg] at maximum exercise. Peak TRPG in patients with ePH was > 40 mm Hg until 2 minutes after exercise. The cut-off values of peak TRPG to detect ePH were 43 mm Hg just after exercise and 41 mm Hg at 1 minute afterward (areas under the curve: 0.98, 0.92, respectively; both p < 0.001). In conclusion, elevated peak TRPG persisted for at least 2 minutes after finishing exercise, and this time frame will therefore provide a new window for diagnosing ePH by ESE.

Prognostic value of cardiac 123 I-metaiodobenzylguanidine imaging for predicting cardiac events after transcatheter aortic valve replacement.

AIMS: In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after transcatheter aortic valve replacement (TAVR) have been reported. The prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123 I-metaiodobenzylguanidine (MIBG) imaging for predicting cardiac events after TAVR. METHODS AND RESULTS: This single-centre prospective observational study enrolled patients with AS between July 2017 and May 2019. MIBG scintigraphy was performed before and soon after TAVR to evaluate the late heart-mediastinum ratio (L-H/M). Patients were classified into three pairs of groups based on the baseline and post-TAVR L-H/M (≥2.0 or <2.0) and on the presence of TAVR-related improvement in L-H/M. The study endpoint was the occurrence of major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and hospitalization due to heart failure. Among the 187 consecutive patients who underwent TAVR, 107 (27 men; median age: 86 years) were evaluated. Over a median follow-up of 366 days, 15 (14.0%) patients had MACE. The incidence of MACE was significantly low in patients with L-H/M improvement and/or high post-TAVR L-H/M (≥2.0). Baseline L-H/M and frailty were associated with poor response of L-H/M to TAVR treatment. TAVR-related improvement in L-H/M had significant effects on MACE, with an adjusted hazard ratio of 0.233 (95% confidence interval, 0.064-0.856; P = 0.028). CONCLUSIONS: TAVR-related improvement in L-H/M was an independent predictor of cardiac events, 1 year after TAVR. Cardiac MIBG imaging is useful for predicting cardiac events after TAVR.

Favorable changes of left ventricular function in the circumferential direction following transcatheter atrial septal defect closure: a strain imaging study.

To clarify the impact on left ventricular (LV) function of percutaneous atrial septal defect (ASD) closure in adult patients. Echocardiograms of 46 patients (52 ± 18 years) who underwent ASD closure with a significant left-to-right shunt obtained before and 1 month after the procedure were retrospectively analyzed. Functional parameters were obtained by 2-dimensional speckle-tracking imaging. Global longitudinal strain and strain rate at early diastole (SRe) was calculated from the three standard apical views, while circumferential and radial parameters were calculated from basal, middle, and apical LV short-axis views. Along with a diminished right ventricular (RV) volume, the LV volume and ejection fraction increased (end-diastolic volume: 61 ± 12 to 76 ± 15 mL, p < 0.001; and 63% ± 4 to 64% ± 4% p = 0.03; respectively). Both global strain and SRe was augmented only in the circumferential direction (- 16.2% ± 2.9% to - 19.8% ± 2.8%; and 1.07 ± 0.29 to 1.34 ± 0.28 s-1, both p < 0.001). Augmentation of circumferential SRe correlated with both the changes in and the pre-procedural value of diastolic LV eccentricity index (r = - 0.57, p < 0.001; and r = 0.37, p = 0.01; respectively), a morphological parameter of RV volume overload. Following ASD closure in adults, both LV systolic and diastolic function could favorably change in the circumferential direction, and the degree of diastolic functional change is associated with RV volume overload, i.e., severity of ventricular interdependence.

Visualization of the improvement of myocardial perfusion after coronary intervention using motorized fractional flow reserve pullback curve.

This study aimed to evaluate the feasibility and utility of using motorized pullback of the pressure guidewire to provide a graphic assessment and prediction of the benefits of coronary intervention. Fractional flow reserve (FFR) measurements were performed with motorized pullback imaging in 20 patients who underwent successful percutaneous coronary intervention (PCI) of the left anterior descending artery. Physiological lesion length (PLL) was calculated using frame counts to determine stent length. FFR area was calculated by integrating the FFR values recorded during pullback tracing (FFRarea). The percentage increase in FFR area (%FFRarea) was defined as the ratio of the difference between the pre- and post-intervention FFRarea to the total frame count. The average FFR values were enhanced following PCI, from 0.64 to 0.82, and the median value of the difference between pre- and post-interventional FFR values (D-FFR) and %FFRarea were 0.13 and 10.6%, respectively. The %FFRarea demonstrated a significant positive correlation with D-FFR (R 2, 0.61; p < 0.01). PLL tended to be longer and the %FFRarea was smaller in lesions with a gradual pressure-drop pattern than those with an abrupt pressure-drop pattern (35.37 vs. 20.40 mm, p = 0.07; 5.78 vs. 16.21%, p < 0.05, respectively). Motorized pullback tracing was able to identify the extent and location of stenosis and help in appropriate stent implantation, in addition to visualizing and quantifying the improvement in FFR following PCI.

Cholesterol crystal depth in coronary atherosclerotic plaques: A novel index of plaque vulnerability using optical frequency domain imaging.

BACKGROUND: The involvement of cholesterol crystals (CCs) in plaque progression and destabilization of atherosclerotic plaques has been recently recognized. This study aimed to evaluate the association between the intraplaque localization of CCs and plaque vulnerability. METHODS: We investigated 55 acute coronary syndrome (ACS) and 80 stable angina pectoris (stable AP) lesions using optical frequency domain imaging (OFDI) prior to percutaneous coronary intervention. The distance between CCs and the luminal surface of coronary plaques was defined as CC depth. RESULTS: Although the incidence of CCs had similar frequencies in the ACS and stable AP groups (95% vs. 89%, p = 0.25), CC depth was significantly less in patients with ACS than in those with stable AP (median [25th to 75th percentile]: 68 µm [58 to 92 µm] vs. 152 µm [115 to 218 µm]; p < 0.001). The incidences of plaque rupture, thrombus, lipid-rich plaques, and thin-cap fibroatheroma were significantly greater in patients with ACS than in those with stable AP (62% vs. 18%, p < 0.001; 67% vs. 16%, p < 0.001; 84% vs. 57%, p < 0.01; and 56% vs. 19%, p < 0.001, respectively). CONCLUSION: OFDI analysis revealed that CCs were found in the more superficial layers within the coronary atherosclerotic plaques in patients with ACS than in those with stable AP, suggesting that CC depth is associated with plaque vulnerability. CC depth, a novel OFDI-derived parameter, could be potentially used as an alternative means of evaluating plaque vulnerability in coronary arteries.

Usefulness of the novel risk estimation software, Heart Risk View, for the prediction of cardiac events in patients with normal myocardial perfusion SPECT.

BACKGROUND: Myocardial perfusion single-photon emission-computed tomography (SPECT) can predict cardiac events in patients with coronary artery disease with high accuracy; however, pseudo-negative cases sometimes occur. Heart Risk View, which is based on the prospective cohort study (J-ACCESS), is a software for evaluating cardiac event probability. OBJECTIVES: We examined whether Heart Risk View was useful to evaluate the cardiac risk in patients with normal myocardial perfusion SPECT (MPS). METHODS AND RESULTS: We studied 3461 consecutive patients who underwent MPS to detect myocardial ischemia and those who had normal MPS were enrolled in this study (n = 698). We calculated cardiac event probability by Heart Risk View and followed-up for 3.8 ± 2.4 years. The cardiac events were defined as cardiac death, non-fatal myocardial infarction, and heart failure requiring hospitalization. During the follow-up period, 21 patients (3.0 %) had cardiac events. The event probability calculated by Heart Risk View was higher in the event group (5.5 ± 2.6 vs. 2.9 ± 2.6 %, p < 0.001). According to the receiver-operating characteristics curve, the cut-off point of the event probability for predicting cardiac events was 3.4 % (sensitivity 0.76, specificity 0.72, and AUC 0.85). Kaplan-Meier curves revealed that a higher event rate was observed in the high-event probability group by the log-rank test (p < 0.001). CONCLUSION: Although myocardial perfusion SPECT is useful for the prediction of cardiac events, risk estimation by Heart Risk View adds more prognostic information, especially in patients with normal MPS.