Impact of the Clinical Frailty Scale on Long-term Outcomes After Transcatheter Aortic Valve Implantation.

BACKGROUND: The semiquantitative Clinical Frailty Scale (CFS) is reportedly a useful marker for predicting short- and mid-term mortality after transcatheter aortic valve implantation (TAVI). We assessed the long-term prognostic impact of CFS in patients with severe aortic stenosis undergoing TAVI. METHODS: We prospectively assessed patients undergoing TAVI in Kokura Memorial Hospital using a 9-level CFS and enrolled 1594 patients after excluding patients with CFS 8-9. The patients were divided into the low (CFS level, 1-3; N = 842), intermediate (4; N = 469), and high (5-7; N = 283) groups according to their CFS levels. RESULTS: In the low, intermediate, and high groups, 3-year all-cause mortality rates were 17.4%, 29.4%, and 41.7% (P <0.001) and composite rates of cardiovascular mortality and heart failure hospitalization were 12.1%, 19.1%, and 23.9% (P <0.001), respectively. Multivariable analysis showed that higher frailty was independently associated with all-cause mortality (intermediate group: adjusted hazard ratio [HR], 1.63, 95% confidence interval [CI], 1.24-2.15, P <0.001; high group: adjusted HR, 2.18, 95% CI, 1.59-2.99, P <0.001) and composite of cardiovascular mortality and heart failure hospitalization (intermediate group: adjusted HR, 1.47, 95% CI, 1.04-2.08, P = 0.030; high group: adjusted HR, 1.66, 95% CI, 1.09-2.51, P = 0.018) and this result was consistent, irrespective of stratification based on age, sex, body mass index, left ventricular ejection fraction, Society of Thoracic Surgeons score, and New York Heart Association functional class without significant interaction. CONCLUSIONS: The simple CFS tool predicts the long-term adverse outcomes post-TAVI.

Rationale and study design of the GOREISAN for heart failure (GOREISAN-HF) trial: A randomized clinical trial.

BACKGROUND: The decongestion strategy using loop diuretics is essential for improving signs and symptoms of heart failure (HF). However, chronic use of loop diuretics in HF has been linked to worsening renal function and adverse clinical outcomes in a dose-dependent manner. Goreisan, a traditional Japanese herbal medicine, has a long history of use in Japan for regulating body fluid homeostasis and has been recognized as causing less adverse outcomes such as dehydration in contrast to loop diuretics in clinical practice. Therefore, we designed the GOREISAN-HF trial to evaluate the long-term effects of a new decongestion strategy adding Goreisan to usual care in patients with HF and volume overload. METHODS: The GOREISAN-HF trial is an investigator-initiated, multicenter, pragmatic, randomized, comparative effectiveness trial in which we will enroll 2,192 patients hospitalized for HF at 68 hospitals in Japan. All study participants will be randomly assigned to either a decongestion strategy that adds Goreisan at a dose of 7.5 g daily on top of usual care or usual care alone. Investigators have the flexibility to change the existing diuretic regimen in both groups. The primary end point is the improvement rate of cardiac edema at 12-month follow-up, and the co-primary end point is a composite of all-cause death or hospitalization up to the end of the planned follow-up period. Secondary end points include longitudinal changes in patient-reported outcomes, loop diuretics dose, and renal function. CONCLUSIONS: The GOREISAN-HF is the first large-scale randomized pragmatic trial to assess the efficacy and safety of a new congestion control strategy adding Goreisan to usual care in patients with HF and volume overload. REGISTRATION NUMBER: NCT04691700.

Zero-Contrast Left Atrial Appendage Closure in Patients With Chronic Kidney Disease.

BACKGROUND: Left atrial appendage closure (LAAC) usually requires contrast medium during the procedure. However, patients with chronic kidney disease (CKD) are at high risk of developing contrast nephropathy. This study aimed to assess the safety and feasibility of zero-contrast LAAC in patients with CKD.Methods and Results: Zero-contrast LAAC was attempted in 15 patients with CKD Stages 3b-5 who were not on hemodialysis. All procedures were performed successfully, without any periprocedural complications. At the 45-day follow-up, no device-related complications or acute kidney disease were observed. CONCLUSIONS: The strategy of zero-contrast LAAC in patients with CKD can be an acceptable option.

Efficacy of larger valve sizing with underfilling in balloon-expandable transcatheter aortic valve replacement.

OBJECTIVES: To investigate the efficacy and safety of larger valve sizing beyond the commercially recommended annular range in transcatheter aortic valve replacement (TAVR) with balloon-expandable transcatheter heart valve (THVs). BACKGROUND: The clinical implications of larger balloon-expandable THV implantation with underfilling are poorly evaluated. METHODS: This retrospective study included 692 consecutive patients who underwent TAVR with SAPIEN3. A total of 271 patients who underwent SAPIEN 3 implantation were analyzed based on three border zones (Zone 1: 300-345 mm2 , 23 vs. 20 mm; Zone 2: 400-430 mm2 , 26 vs. 23 mm; Zone 3: 500-546 mm2 , 29 vs. 26 mm). The primary endpoint was the effective orifice area (EOA) assessed by echocardiography at 1 year, and secondary endpoints were a 30-day mortality rate, procedural complications during TAVR, and a composite of death from any cause and heart failure requiring rehospitalization at 1 year. RESULTS: At 1-year follow-up, the EOA in the larger valve groups was greater than that in the recommended valve group in each zone (Zone 1: 1.45 ± 0.03 vs. 1.06 ± 0.06 cm2 , p < 0.001; Zone 2: 1.83 ± 0.05 vs. 1.41 ± 0.05 cm2 , p < 0.001; Zone 3: 1.93 ± 0.07 vs. 1.69 ± 0.07 cm2 , p = 0.02). No significant difference in the secondary endpoint was observed in any of the zones. CONCLUSIONS: Implantation of the out-of-range larger SAPIEN 3 THVs with underfilling was associated with greater EOA at the 1-year follow-up and feasible in the selected patients.

Iatrogenic Atrial Septal Defect Requiring Transcatheter Closure Following Transcatheter Mitral Valve Repair.

BACKGROUND: Transcatheter mitral valve repair with the MitraClip system has been established in selected high-risk patients. The MitraClip procedure results in a relatively large iatrogenic atrial septal defect (iASD). This study aimed to investigate the prevalence and clinical course of iASD requiring transcatheter closure following the MitraClip procedure.Methods and Results: This study was conducted at all 59 institutions that perform transcatheter mitral valve repair with the MitraClip system in Japan. The data of patients on whom transcatheter iASD closure was performed were collected. Of the 2,722 patients who underwent the MitraClip procedure, 30 (1%) required transcatheter iASD closure. The maximum iASD size was 9±4 mm (range, 3-18 mm). The common clinical course of transcatheter iASD closure was hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt. Of the 30 patients, 22 (73%) required transcatheter closure within 24 h following the MitraClip procedure, including 12 with hypoxemia and 5 with right-sided heart failure complicated with cardiogenic shock. Of the 5 patients, 2 required mechanical circulatory support devices. Twenty-one patients immediately underwent transcatheter iASD closure, and hemodynamic deteriorations were resolved; however, 1 patient died without having undergone transcatheter closure. CONCLUSIONS: Transcatheter iASD closure was required in 1% of patients who underwent the MitraClip procedure. Many of these patients immediately underwent transcatheter iASD closure because of hypoxemia with right-to-left shunt or right-sided heart failure with left-to-right shunt.

Impact of tapered-shape left ventricular outflow tract on pacemaker rate after transcatheter aortic valve replacement.

Mechanical compression of left ventricular outflow tract (LVOT) was reported to be a leading cause of conduction impairment requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR). However, the association between tapered-shape LVOT and PPI after TAVR has not been elucidated. Of 272 consecutive patients treated with SAPIEN 3 in our institute, we retrospectively analyzed the clinical data of 256 patients without previous PPI or bicuspid valve. In-hospital PPI was performed in 20 (7.8%) patients at 8.2 ± 2.9 days after TAVR. Patients requiring PPI had smaller LVOT area (356.3 vs. 399.4 mm2, p ≤ 0.011). Moreover, receiver operating characteristic statistics showed that LVOT area /annulus area possessed significantly higher predictive ability than LVOT area (c-statistic: 0.91 [95% confidence interval [CI]: 0.84-0.95] vs. 0.67 [95% CI: 0.57-0.77], p < 0.001). Multivariable analysis revealed that LVOT area /annulus area (odds ratio [OR]: 1.93 [95% CI: 1.38-2.71]; p < 0.001 per % of decreasing), the difference between membranous septum length and implantation depth (ΔMSID) (OR: 6.82 [95% CI 2.39-19.48]; p < 0.001 per mm of decreasing) and pre-existing complete right bundle branch block (CRBBB) (OR: 32.38 [95% CI2.30-455.63]; p ≤ 0.002) were independently associated with PPI. In our study, tapered-shape LVOT as well as short ΔMSID and pre-existing CRBBB were identified as independent predictors for PPI after TAVR. Higher valve implantation is required to minimize the risk of post-procedural PPI especially for patients with short MS length, pre-procedural CRBBB, or tapered-shape LVOT.

Mid-term impact of underfilling and overfilling of the SAPIEN 3 balloon-expandable transcatheter aortic valve implantation on mortality and valve function.

At present, underfilling or overfilling the volume of the balloon-expandable transcatheter heart valve (THV) is generally utilized in transcatheter aortic valve implantation (TAVI). However, no research has assessed the clinical impact of filling volume variations of the current-generation SAPIEN 3 THV. We analyzed the clinical data of 331 patients who underwent TAVI with SAPIEN 3 at our institution. Post-procedural echocardiographic and multidetector computed tomography (MDCT) scan data and 3-year prognoses according to each filling volume were assessed. The procedural outcomes and 3-year mortality rates were comparable among the underfilling, nominal filling, and overfilling groups. For all THV sizes, the THV area evaluated on post-procedural MDCT scan increased stepwise along with an elevated filling volume, thereby covering a wide range of native annulus area. Compared with patients in the nominal filling and overfilling groups, those with 23-mm THVs in the underfilling group had a smaller effective orifice area (EOA) (1.38 [IQR: 1.18-1.56] vs. 1.57 [IQR: 1.41-1.84] vs. 1.58 [IQR: 1.45-1.71] cm2, P = 0.02) and a higher mean transvalvular gradient (13.6 [IQR: 11.0-15.7] vs. 12.1 [IQR: 9.0-14.9] vs. 12.0 [IQR: 8.1-14.8] cm2, P = 0.04). In conclusion, by adjusting the filling volume of SAPIEN 3 using THV with limited sizes, continuously distributed native annulus areas were covered. The underfilling implantation technique had a minimal negative effect on the valve function of 23-mm THVs only. In the entire cohort, the filling volume variations did not affect the mid-term prognosis negatively.

Effect of postdilatation following balloon expandable transcatheter aortic valve implantation.

BACKGROUND: Postdilatation after transcatheter heart valve (THV) implantation was associated with larger aortic valve areas in large-scale registries; however, the specific effects of postdilatation are poorly understood. METHODS AND RESULTS: Among a total of 224 consecutive patients who underwent transcatheter aortic valve replacement using SAPIEN 3, 121 patients (54.0%) underwent postdilatation (same contrast volume: N = 101, +1 ml: N = 17, +2 ml: N = 3). THV diameter was assessed (a) during, (b) after implantation, (c) during postdilatation, and (d) after postdilatation by quantitative fluoroscopy. In the overall patients (N = 224), acute recoil was observed from during implantation (23.0 ± 2.0 mm) to after implantation (22.5 ± 2.0 mm, p < .001) with an absolute recoil of 0.52 ± 0.25 mm. After postdilatation (N = 121), THV diameter significantly increased from 22.5 ± 2.0 mm to 22.9 ± 2.1 mm (p < .001), with smaller absolute recoil (0.39 ± 0.21 mm, p < .001). Compared with those who did not undergo postdilatation, patients who underwent postdilatation had larger postprocedural THV area assessed by multi-slice computed tomography (471.4 ± 78.1 mm2 vs. 447.5 ± 76.3 mm2 , p = .02) and larger effective orifice area (EOA) assessed by echocardiography throughout 1 year (at 30 day, 1.66 ± 0.33 cm2 vs. 1.45 ± 0.27 cm2 , p < .001; at 6 month, 1.66 ± 0.33 cm2 vs. 1.44 ± 0.29 cm2 , p < .001; at 1 year, 1.69 ± 0.38 cm2 vs. 1.47 ± 0.30 cm2 , p < .001). CONCLUSIONS: Postdilatation after implantation of the SAPIEN 3 valve produced a larger THV diameter with less acute recoil, followed by larger EOA throughout 1 year. Further studies are needed to evaluate the impact of postdilatation on long-term clinical outcomes.

Patient-specific heart simulation can identify non-responders to cardiac resynchronization therapy.

To identify non-responders to cardiac resynchronization therapy (CRT), various biomarkers have been proposed, but these attempts have not been successful to date. We tested the clinical applicability of computer simulation of CRT for the identification of non-responders. We used the multi-scale heart simulator "UT-Heart," which can reproduce the electrophysiology and mechanics of the heart based on a molecular model of the excitation-contraction mechanism. Patient-specific heart models were created for eight heart failure patients who were treated with CRT, based on the clinical data recorded before treatment. Using these heart models, bi-ventricular pacing simulations were performed at multiple pacing sites adopted in clinical practice. Improvement in pumping function measured by the relative change of maximum positive derivative of left ventricular pressure (%ΔdP/dtmax) was compared with the clinical outcome. The operators of the simulation were blinded to the clinical outcome. In six patients, the relative reduction in end-systolic volume exceeded 15% in the follow-up echocardiogram at 3 months (responders) and the remaining two patients were judged as non-responders. The simulated %ΔdP/dtmax at the best lead position could identify responders and non-responders successfully. With further refinement of the model, patient-specific simulation could be a useful tool for identifying non-responders to CRT.

Insights into the mechanism of paradoxical low-flow, low-pressure gradient severe aortic stenosis: association with reduced O2 consumption by the whole body.

The mechanism of reduced stroke volume index (SVi) in paradoxical low-flow, low-pressure gradient (PLFLPG) aortic stenosis (AS) remains unclarified. Guyton et al. ( 21 ) demonstrated that SVi is determined by whole body O2 consumption (V̇o2) in many subjects, including patients with heart disease. We hypothesized that reduced SVi in PLFLPG AS is associated with reduced V̇o2 by the whole body. This study investigated the relationship between V̇o2, SVi, and AS severity in patients with AS to examine the association between reduced V̇o2 and PLFLPG AS. In 59 patients (24 men and 35 women, mean age: 78 ± 7 yr old) with severe AS, SVi, AS severity, and type were evaluated by echocardiography, and V̇o2 was measured by the fraction of O2 in expired gases. SVi and V̇o2 were significantly decreased in 20 patients with PLFLPG AS compared with 39 patients with non-PLFLPG AS (30 ± 4 vs. 41 ± 7 ml/m2 and 2.4 ± 0.5 vs. 3.0 ± 0.5 ml·min-1·kg-1, respectively, P < 0.01). The SVi-to-V̇o2 ratio was not different between the two groups (13.1 ± 2.6 vs. 13.6 ± 2.1, not significant). SVi was independently correlated with V̇o2 ( r = 0.74, P < 0.01) but not with the aortic valve area index. Categorized PLFLPG AS was also significantly associated with reduced V̇o2 ( P < 0.001). PLFLPG AS is associated with reduced V̇o2 by the whole body, which may offer insights into the mechanism of PLFLPG AS. NEW & NOTEWORTHY Paradoxical low-flow, low-pressure gradient severe aortic stenosis (PLFLPG AS) is an important and problematic subtype, and its central pathophysiology with reduced stroke volume is yet to be clarified. We hypothesized and subsequently clarified that reduced stroke volume in PLFLPG AS is associated with reduced O2 consumption by the whole body. This study suggests important insights into the mechanism of PLFLPG AS and may further promote studies to investigate further mechanisms and novel treatment.

Valve Hemodynamics and Clinical Outcomes After Transcatheter Aortic Valve Replacement for a Small Aortic Annulus.

The hemodynamics and outcomes in patients with a small aortic annulus (SAA) after transcatheter aortic valve replacement (TAVR) with a second-generation transcatheter heart valve remain unclear. We investigated whether TAVR with a Sapien XT (Edwards Lifesciences, Irvine, California) influences postprocedural valve hemodynamics and long-term outcome in high-risk SAA patients compared with surgical aortic valve replacement (SAVR).We retrospectively identified 94 SAA patients who underwent aortic valve replacement (TAVR = 35 and SAVR = 59). SAA was defined as an aortic annulus diameter ≤ 20 mm, measured by preprocedural transesophageal echocardiography.The mean age was 80.2 years. The mean Society of Thoracic Surgeons-Predicted Risk of Mortality was 6.8%. The post-procedural peak transvalvular velocity and mean pressure gradient were significantly lower in the TAVR cohort than in the SAVR cohort, whereas the postprocedural aortic valve area was significantly higher in the TAVR cohort. Severe prosthesis-patient mismatch (PPM) occurred less frequently after TAVR than SAVR (TAVR 2.9% versus SAVR 22.0%, P = 0.01). The two-year mortality in SAA patients was similar between the two groups.TAVR with a Sapien XT in SAA patients improved the valve hemodynamics and reduced the incidence of PPM compared with SAVR. TAVR patients had a similar 2-year mortality despite higher risk baseline characteristics. To avoid PPM and the consequent poor outcomes, TAVR can be considered an alternative option to SAVR in high surgical risk patients with SAA.

Aortic Complex Rupture After Transcatheter Aortic Valve Implantation.

Aortic complex rupture is one of the most critical complications associated with transcatheter aortic valve implantation (TAVI). Its incidence is rare, and its mechanism varies by case; therefore, it is difficult to identify the predictors of complex rupture. Herein, we report a clinical case series of aortic complex rupture. Within our cohort, the frequency of complex rupture was 0.8% (4/497 consecutive patients) with an in-hospital mortality of 0. Among these four patients with complex rupture, two underwent emergent thoracotomy and surgical hemostasis without a heart-lung machine and surgical aortic valve replacement, whereas the other two were conservatively managed. The case overview revealed the following similarities: all the patients were elderly, small women; balloon-expandable valves were used; the annulus area was small with heavily calcified leaflet; and aggressive treatment strategy was used (i.e., oversizing and post-dilatation). In such cases, TAVI should be performed with a careful strategy. Once aortic complex rupture occurs, damage can be minimized through cooperation with an institutional heart team and calm management.

Surgical as Opposed to Transcatheter Aortic Valve Replacement Improves Basal Interventricular Septal Hypertrophy.

BACKGROUND: Basal interventricular septum (IVS) hypertrophy (BSH) with reduced basal IVS contraction and IVS-aorta angle is frequently associated with aortic stenosis (AS). BSH shape suggests compression by the longitudinally elongated ascending aorta, causing basal IVS thickening and contractile dysfunction, further suggesting the possibility of aortic wall shortening to improve the BSH. Surgical aortic valve replacement (SAVR), as opposed to transcatheter AVR (TAVR), includes aortic wall shortening by incision and stitching on the wall and may potentially improve BSH. We hypothesized that BSH configuration and its contraction improves after SAVR in patients with AS. Methods and Results: In 32 patients with SAVR and 36 with TAVR for AS, regional wall thickness and systolic contraction (longitudinal strain) of 18 left ventricular (LV) segments, and IVS-aorta angle were measured on echocardiography. After SAVR, basal IVS/average LV wall thickness ratio, basal IVS strain, and IVS-aorta angle significantly improved (1.11±0.24 to 1.06±0.17; -6.2±5.7 to -9.1±5.2%; 115±22 to 123±14°, P<0.001, respectively). Contractile improvement in basal IVS was correlated with pre-SAVR BSH (basal IVS/average LV wall thickness ratio or IVS-aorta angle: r=0.47 and 0.49, P<0.01, respectively). In contrast, BSH indices did not improve after TAVR. CONCLUSIONS: In patients with AS, SAVR as opposed to TAVR improves associated BSH and its functional impairment.

Early Safety and Efficacy of Transcatheter Aortic Valve Implantation for Asian Nonagenarians (from KMH Registry).

As Japan has one of the most rapidly aging populations in the world, transcatheter aortic valve implantation (TAVI) is likely to be performed in increasing numbers of older people. There is little information on either the efficacy or the safety of TAVI in nonagenarians in Asia.From October 2013 to June 2015, 112 consecutive patients underwent TAVI with Edwards SAPIEN XT valves in our institution. We compared 25 patients aged at least 90 years (mean 91.6 ± 1.7 years) with 87 patients aged under 90 years (mean 82.5 ± 6.0 years) at the time of TAVI. All definitions of clinical endpoints and adverse events were based on the Valve Academic Research Consortium 2 definitions.The median follow-up interval was 561.5 days (the first and third quarters, 405.0 and 735.8 days). Nonagenarians had a higher logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE), Euro II score, and the Society of Thoracic Surgeons predictive risk of mortality (STS) score, and a prevalence of clinical frailty scale ≥ 4. The rate of device success, and the 30-day and 6-month mortalities were not different between patients aged ≥ 90 years and < 90 years (96.0% versus 92.0%, P = 0.68; both 0%, P = 1.00; 4.0% versus 3.5%, P = 0.32, respectively). At six months, clinical efficacy and time-related valve safety were also similar in the two groups (12.5% versus 13.4%, P = 1.00; 4.5% versus 10.3%, P = 0.68, respectively). The cumulative 1-year mortalities were not significantly different between the two groups (8.4% versus 9.4%, P = 0.94, respectively).TAVI can contribute to acceptable clinical results and benefits in a carefully selected group of nonagenarians in Asia.

Favorable Clinical Outcomes of Transcatheter Aortic Valve Implantation in Japanese Patients　- First Report From the Post-Approval K-TAVI Registry.

BACKGROUND: Very limited data exist on the outcomes of transcatheter aortic valve implantation (TAVI) since Japanese marketing approval of the first TAVI device.Methods and Results:The Kyoto University-related hospital Transcatheter Aortic Valve Implantation (K-TAVI) registry includes prospectively collected data from 6 participating hospitals in Japan. We included 302 patients with severe aortic stenosis who underwent TAVI using the SAPIEN XT balloon-expandable valve via transfemoral (TF; n=203, 67%) or transapical (TA; n=99, 33%) approach between October 2013 and September 2015. Device success rate, based on the Valve Academic Research Consortium-2 criteria, was very high in the TF (97.0%) and TA (99.0%) groups. The 30-day mortality rates were 1.5% and 1.0% in the TF and TA groups, respectively. Major complications included stroke (transient or persistent: 2.3%), annulus rupture (1.0%), coronary intervention (1.0%), major vascular complications (1.7%), and permanent pacemaker implantation (5.4%). The procedure times of the post-proctoring period (n=210) were decreased compared with those of the proctoring period (n=89) without affecting the clinical outcomes. The survival rates at 6 and 12 months were 96.9% and 92.5% in the TF group, and 93.9% and 91.8% in the TA group, respectively. CONCLUSIONS: The K-TAVI registry data revealed that the early outcomes of TAVI using the SAPIEN XT were favorable in real-world Japanese patients.

Successful Balloon-Expandable Transcatheter Aortic Valve Replacement for Extremely Large Annulus (>1,000 mm2).

Transcatheter aortic valve replacement in extra-large annulus is challenging because of the limited sizes and data of the current commercial prosthesis sizes available. We present a case of successful transcatheter aortic valve replacement with a new balloon-expandable SAPIEN 3 Ultra RESILIA valve for an aortic annulus area >1,000 mm2 on computed tomography.

Carcinoid Heart Disease With Hypoxemia.

Patent foramen ovale (PFO) complicated with carcinoid heart disease (CHD) can cause severe hypoxia and worsening clinical conditions. We report the case of a patient with CHD in poor general condition with multiple severe valve regurgitations and PFO, who underwent successful percutaneous closure of the PFO.