Right Ventricular Dysfunction in Patients With Concomitant Tricuspid Regurgitation Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND: This study investigated the impact and predictive factors of concomitant significant tricuspid regurgitation (TR) and evaluated the roles of right ventricle (RV) function and the etiology of TR in the clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI).Methods and Results: We assessed grading of TR severity, TR etiology, and RV function in pre- and post-TAVI transthoracic echocardiograms for 678 patients at Keio University School of Medicine. TR etiology was divided into 3 groups: primary TR, ventricular functional TR (FTR), and atrial FTR. The primary outcomes were all-cause and cardiovascular death. At baseline, moderate or greater TR was found in 55 (8%) patients and, after adjustment for comorbidities, was associated with increased all-cause death (hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.19-3.77; P=0.011) and cardiovascular death (HR 2.29; 95% CI 1.06-4.99; P=0.036). RV dysfunction (RVD) also remained an independent predictor of cardiovascular death (HR 2.06; 95% CI 1.03-4.14; P=0.042). Among the TR etiology groups, patients with ventricular FTR had the lowest survival rate (P<0.001). Patients with persistent RVD after TAVI had a higher risk of cardiovascular death than those with a normal or recovered RV function (P<0.001). CONCLUSIONS: The etiology of TR and RV function play an important role in predicting outcomes in concomitant TR patients undergoing TAVI.

Transcatheter aortic valve replacement with Evolut R versus Sapien 3 in Japanese patients with a small aortic annulus: The OCEAN-TAVI registry.

OBJECTIVES: To compare safety, efficacy, and hemodynamics of transfemoral transcatheter aortic valve replacement (TAVR) using self-expanding and balloon-expandable transcatheter heart valves (THVs) in patients with a small aortic annulus. BACKGROUND: Few studies have directly compared TAVR outcomes using third-generation THVs, focusing on patients with small aortic annuli. METHODS: In a multicenter TAVR registry, we analyzed data from 576 patients with a small annulus and who underwent transfemoral TAVR using third-generation THVs. Propensity score matching was used to adjust baseline clinical characteristics. RESULTS: The device success rate in the overall cohort was 92.0% (Evolut R: 92.1% vs. Sapien 3:92.0%, p = 0.96). One year after TAVR, patients treated with Evolut R maintained a lower mean pressure gradient (mPG) and a higher indexed effective orifice area (iEOA) in the matched cohort {mPG: 9.0 [interquartile range (IQR): 6.0-11.9] vs. 12.0 [IQR: 9.9-16.3] mmHg, p < .001; iEOA: 1.20 [IQR: 1.01-1.46] vs. 1.08 [IQR: 0.90-1.28] cm2 /m2 , p < .001}. However, no significant differences were reported in the incidence of severe prosthesis-patient mismatch and aortic regurgitation at 1 year. Furthermore, both groups showed comparable outcomes with no differences in terms of all-cause mortality (log-lank test, p = .81). CONCLUSIONS: TAVR for patients with a small annulus using third-generation THVs was associated with high device success. Evolut R seems to be superior to Sapien 3 in hemodynamic performance for patients with a small annulus and body surface area up to 1 year after TAVR. Nevertheless, all-cause mortality at 1 year was similar between both groups.

Predictors of New-Onset Atrial Tachyarrhythmias After Transcatheter Atrial Septal Defect Closure in Adults.

BACKGROUND: New-onset atrial tachyarrhythmia (ATA) often develops after atrial septal defect (ASD) closure. Its development raises some potential concerns such as stroke and bleeding complications caused by anticoagulant therapy and limited access to the left atrium for catheter ablation. Although it is essential to identify the risk factors of new-onset ATA, few studies have examined these factors. This study investigated unknown risk factors for the development of new-onset ATA after transcatheter ASD closure in patients without a history of ATA. METHODS: A total of 238 patients without a history of ATA, aged ≥18 years and who underwent transcatheter ASD closure at the current hospital were reviewed. Patient characteristics were compared between the groups with and without new-onset ATA. The factors associated with new-onset ATA were examined using univariate and multivariable analyses. RESULTS: Thirteen (13) (5.5%) patients experienced ATA during follow-up (mean, 21±14 months). Compared with patients without new-onset ATA, patients with new-onset ATA were older (48±18 vs 66±11 years; p<0.001) and had high brain natriuretic peptide (BNP) levels (36±36 vs 177±306 pg/mL; p<0.001). On multivariable analysis, BNP ≥40 pg/mL before ASD closure was associated with new-onset ATA after adjusting for age (OR, 4.91; 95% CI, 1.22-19.8; p=0.025). CONCLUSION: Patients with BNP levels >40 pg/mL before transcatheter ASD closure may have a higher risk of developing new-onset ATA.

Update on the clinical impact of mild aortic regurgitation after transcatheter aortic valve implantation: Insights from the Japanese multicenter OCEAN-TAVI registry.

OBJECTIVES: This study aimed to compare the clinical impact of mild postprocedural aortic regurgitation (post-AR) to that of none-trivial post-AR after transcatheter aortic valve implantation (TAVI) and to identify the vulnerability factors to mild post-AR. BACKGROUND: Moderate-severe post-AR, associated with increased mortality, is an important issue. However, the clinical impact of mild post-AR remains controversial. METHODS AND RESULTS: We analyzed data from 1,572 consecutive patients (1,026 of none-trivial post-AR and 546 of mild post-AR) obtained from the Optimized transCathEter vAlvular Intervention (OCEAN-TAVI) Japanese multicenter registry. We evaluated the 1-year cumulative cardiovascular death and re-hospitalization rates for heart failure (HF) after TAVI according to the degree of post-AR. Kaplan-Meier curves showed no significant difference between "none-trivial post-AR" and "mild post-AR" in terms of cardiovascular death, but a significant difference was noted in the cumulative incidence of re-hospitalization for HF between the two groups (hazard ratio 1.57, 95% confidence interval 1.02-2.41, p = .04). In the stratified analysis, only in patients with not more than 50% of left ventricular ejection fraction (LVEF), concentric left ventricular hypertrophy (LVH), and none-trivial pre-procedural aortic regurgitation (pre-AR), mild post-AR resulted in a higher incidence of re-hospitalization for HF. CONCLUSIONS: In this study, the clinical impact of mild post-AR compared to none-trivial post-AR tended to be augmented in the presence of reduced LVEF, concentric LVH, and none-trivial pre-AR. Pre-procedure echocardiographic findings including LVEF, left ventricular geometry, and pre-AR may help to judge the necessity of postdilatation in case of mild post-AR just after the bioprosthesis deployment.

Long-term outcomes in 3 cases of quadricuspid aortic valve, using a new classification system: A case series and literature review.

Quadricuspid aortic valve has been classified based on leaflet size. However, no association is seen between classification and severity of aortic regurgitation (AR). Bicuspid aortic valve is classified according to the number of cusps, with significantly higher prevalence of AR in cases with a raphe. We classified cases according to raphe number. In 1 patient with no raphe, AR severity did not change into the eighth decade. However, AR severity worsened in patients with a raphe, in 1 case requiring aortic valve replacement in the fifth decade. Unequal shear stress may lead to leaflet fibrosis and progressive AR.

Incidence, predictors, and midterm clinical outcomes of left ventricular obstruction after transcatheter aortic valve implantation.

OBJECTIVES: We aimed to evaluate the incidence and midterm clinical outcomes of left ventricular obstruction (LVO) after transcatheter aortic valve implantation (TAVI). BACKGROUNDS: LVO is occasionally unmasked following valve replacement for severe aortic stenosis. However, little is known about the prevalence and effects of LVO after TAVI. METHODS: A total of 158 patients who underwent TAVI in our center between October 2013 and November 2015 received echocardiographic evaluations at baseline; before hospital discharge; and at 3, 6, and 12 months after TAVI. LVO was defined as a peak pressure gradient >30 mm Hg. RESULTS: Over 1 year of follow-up after TAVI, 21 patients (13.3%) demonstrated postprocedural LVO. The incidence was highest at 3-months follow-up and decreased at 6 months or later. Of the 21 patients with LVO, 20 (95.2%) demonstrated midventricular obstruction (MVO), whereas only 1 (4.8%) showed obstruction of the outflow tract (LVOT) with systolic anterior motion (SAM) of the mitral leaflet. In a multivariate analysis, the LVOT diameter (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.30-0.67; P < 0.001), transvalvular velocity (OR, 2.44; 95% CI, 1.13-5.26; P = 0.023), and the presence of accelerated intraventricular flow at baseline (OR, 6.13; 95% CI, 1.49-25.2; P = 0.012) were associated with the occurrence of LVO. Postprocedural LVO was not associated with midterm all-cause death or heart failure events. CONCLUSION: In patients who underwent TAVI, MVO occurred more often than LVOT obstruction. However, the occurrence of postprocedural LVO was not associated with worsened clinical outcomes in these patients.

Ameliorating the severity of sleep-disordered breathing concomitant with heart failure status after percutaneous transluminal septal myocardial ablation for drug-refractory hypertrophic obstructive cardiomyopathy.

The coexistence of sleep-disordered breathing (SDB) and hypertrophic obstructive cardiomyopathy (HOCM) has widely been recognized; however, the impact of percutaneous transluminal septal myocardial ablation (PTSMA) for HOCM on SDB remains unknown. Herein, we examine cardiorespiratory polygraph parameters in patients with drug-refractory HOCM before and after PTSMA. Forty consecutive drug-refractory HOCM patients, admitted to Keio University Hospital, and who underwent cardiorespiratory polygraphy were retrospectively analyzed. Cardiorespiratory polygraphy was performed before and after PTSMA if patients underwent PTSMA. Patients with an apnea-hypopnea index (AHI) ≥5/h were considered to have SDB. The total number of central sleep apneas, obstructive sleep apneas, and hypopnea events was evaluated. Thirty-two out of 40 patients (80%) with drug-refractory HOCM had SDB. All patients experienced relief of heart failure-associated symptoms after PTSMA. The severity of SDB was found to be correlated with left atrial diameter. The AHI decreased after PTSMA [before 15.4 (range 10.9-23.5)/h vs. after 13.1 (8.3-17.8)/h, P = 0.02]. Especially, the hypopnea index decreased after PTSMA. The average and lowest arterial oxygen saturation also increased after PTSMA (94.2 ± 1.9-95.7 ± 1.6%, P = 0.009; 81.3 ± 5.7-85.8 ± 4.8%, P = 0.012, respectively). In patients with drug-refractory HOCM, PTSMA decreased the AHI and improved arterial oxygen saturation measures. Thus, invasive treatment of the left ventricular obstruction ameliorates the severity of SDB, in addition to improving heart failure status.

Preservation of Mobility of the Posterior Mitral Leaflet After Mitral Valve Repair With Neochordae Using Loop Technique.

BACKGROUND: Recently, the loop technique has been standardized for mitral valve repair, with excellent long-term outcomes reported. This study thus analyzed whether the loop technique could preserve mitral leaflet mobility on trans-thoracic echocardiography. METHODS AND RESULTS: Among 367 concomitant patients who underwent mitral valve repair at Keio University Hospital between January 2007 and December 2014, 304 patients had a prolapse of the posterior leaflet. Of these, 84 cases assessed on echocardiography were retrospectively analyzed for this study. These patients were divided into 4 groups based on the procedure used: (1) group L1 (n=28), loop technique alone; (2) group L2 (n=14), loop technique with resection and suture; (3) group L3 (n=33), loop technique with plication of indentation; and (4) group R (n=9), resection and suture alone. The mean postoperative mobile posterior mitral leaflet (PML) angles in groups L1 and L2 (39.3±16.0°, 37.3±16.0°) were significantly larger than those in groups L3 and R (18.8±15.7°, 15.3±15.7°), respectively (P<0.01). Ring size, age, and mobile PML angle had a statistically significant correlation with the postoperative mean mitral valve pressure gradient (P<0.05). CONCLUSIONS: The loop technique preserved PML mobility and enabled implantation of a larger ring, resulting in a reduced mean mitral valve pressure gradient. (Circ J 2016; 80: 663-667).

Oral Nitrate Administration Ameliorates Cardiogenic Shock due to Eclipsed Mitral Regurgitation.

Eclipsed mitral regurgitation (MR) has been reported as transient massive functional MR caused by a sudden coaptation defect in the absence of left ventricular remodeling or epicardial coronary artery stenosis. Coronary spasm or microvascular dysfunction has been suggested to be associated with the pathogenesis. Here, we present a 68-year-old woman with eclipsed MR with cardiogenic shock ameliorated by nitrate. She was admitted for transient shock with massive functional MR. Transient MR was associated with a complete absence of mitral leaflet coaptation owing to tethering of the lateral posterior mitral leaflet. The leaflet tethering was triggered by transient myocardial ischemia around the anterolateral papillary muscle, which could have been caused by coronary spasm and/or microvascular dysfunction. During admission, she experienced similar repeated episodes, which were ameliorated by oral nitrate administration. This is the first described case of eclipsed MR with shock ameliorated by nitrate. Although eclipsed MR, a cause of life-threatening shock, is uncommon, we need to keep in mind that nitrate administration could be a treatment option even in patients with cardiogenic shock.

Positional desaturation due to persistent left superior vena cava draining into the left atrium.

Persistent left superior vena cava (PLSVC) is a rare congenital anomaly whose prevalence is 0.3 % of general population. The majority of PLSVC drain into right atrium (RA) through the coronary sinus without clinical harm. However, in about 10 % of patients with PLSVC, it drains into left atrium (LA) causing right-to-left shunt. Here, we present a 60-year-old male patient with a PLSVC draining into LA, who developed dyspnea and desaturation depending on the body position after trans-catheter coil embolization of coronary to pulmonary artery fistulas. PLSVC draining into LA should be included in the differential diagnosis of positional desaturation.

Periodic Protrusion of Right Coronary Cusp into Left Ventricular Outflow Tract Due to Detachment from the Aortic Annulus Complicated with Infective Endocarditis.

We describe the imaging of unusual dislocation of right coronary cusp into left ventricular outflow tract (LVOT) due to the infective endocarditis. Although the two-dimensional echocardiography identified a protruding mass in LVOT, the three-dimensional echocardiography precisely demonstrated the spatial anatomy of the aortic root, which was confirmed by the surgical operation, implicating the usefulness of three-dimensional echocardiography in this rare anomaly.

The Speckle Tracking Imaging for the Assessment of Cardiac Resynchronization Therapy (START) study.

BACKGROUND: We sought to identify the feasibility of speckle tracking echocardiography (STE) to predict cardiac resynchronization therapy (CRT) responders in a prospective multicenter study. METHODS AND RESULTS: Patients who were newly implanted with a CRT device were enrolled. Time (T) from QRS to maximum peak radial and circumferential strain (CS) in 6 segments on the left ventricular (LV) short-axis plane, and to the maximum peak of longitudinal strain in 18 segments on 3 apical LV planes was measured (Tmax). In segments with multiple peaks on the time-strain curves, time to the first peak (Tfirst) was also assessed. Difference in T between the earliest and latest segment and standard deviation (SD) of T in each strain component were assessed. CRT responders were defined as having LV end-systolic volume reduction >15% at 6 months after CRT. Clinical outcomes were assessed with a composite endpoint of death from cardiac causes or unplanned hospitalization for heart failure. Among 180 patients, 109 patients were identified as responders. Tfirst-SD of CS >116 ms was selected as the best independent predictor of CRT responders (P<0.001, hazard ratio=9.83, 95% confidence interval 3.78-25.6). In addition, Tfirst-SD of CS was associated with the clinical endpoints. CONCLUSIONS: This prospective multicenter study revealed the high feasibility of dyssynchrony assessment by STE, which may improve the ability to predict CRT responders.

Warfarin Therapy and Percutaneous Left Atrial Appendage Closure for a Patient with Atrial Fibrillation and Antithrombin-III Deficiency.

Some patients develop ischemic stroke despite taking direct oral anticoagulants because of the presence of other risk factors such as coagulopathies. A 65-year-old male patient with non-valvular atrial fibrillation (NVAF) taking rivaroxaban was diagnosed as having embolic stroke and antithrombin-III (AT-III) deficiency. Echocardiography revealed a thrombus in the left atrial appendage (LAA). He was prescribed warfarin, and after resolution of the thrombus, we successfully performed percutaneous LAA closure (LAAC), with no subsequent recurrence or device-related thrombosis. Warfarin and LAAC may be feasible for NVAF patients with AT-III deficiency.

Pre-Existing Left Bundle Branch Block and Clinical Outcomes After Transcatheter Aortic Valve Replacement.

Background: Few reports on pre-existing left bundle branch block (LBBB) in patients undergoing transcatheter aortic valve replacement (TAVR) are currently available. Further, no present studies compare patients with new onset LBBB with those with pre-existing LBBB. Objectives: This study aimed to investigate the association between pre-existing or new onset LBBB and clinical outcomes after TAVR. Methods: Using data from the Japanese multicenter registry, 5,996 patients who underwent TAVR between October 2013 and December 2019 were included. Patients were classified into 3 groups: no LBBB, pre-existing LBBB, and new onset LBBB. The 2-year clinical outcomes were compared between 3 groups using Cox proportional hazards models and propensity score analysis to adjust the differences in baseline characteristics. Results: Of 5,996 patients who underwent TAVR, 280 (4.6%) had pre-existing LBBB, while 1,658 (27.6%) experienced new onset LBBB. Compared with the no LBBB group, multivariable Cox regression analysis showed that pre-existing LBBB was associated not only with a higher 2-year all-cause (adjusted HR: 1.39; 95% CI: 1.06-1.82; P = 0.015) and cardiovascular (adjusted HR: 1.60; 95% CI: 1.04-2.48; P = 0.031) mortality, but also with higher all-cause (adjusted HR: 1.43, 95% CI: 1.07-1.91; P = 0.016) and cardiovascular (adjusted HR: 1.81, 95% CI:1.12-2.93; P = 0.014) mortality than the new onset LBBB group. Heart failure was the most common cause of cardiovascular death, with more heart failure deaths in the pre-existing LBBB group. Conclusions: Pre-existing LBBB was independently associated with poor clinical outcomes, reflecting an increased risk of cardiovascular mortality after TAVR. Patients with pre-existing LBBB should be carefully monitored.

Impact of beta-blocker uptitration on patients after transcatheter edge-to-edge mitral valve repair for secondary mitral regurgitation: The OCEAN-mitral registry.

BACKGROUND: Optimal medical therapy for patients with secondary mitral regurgitation (SMR) undergoing transcatheter edge-to-edge mitral valve repair (M-TEER) remains unclear. This study aimed to investigate the association between beta-blocker uptitration and clinical outcomes after M-TEER. METHODS: Using data from the Japanese multicenter registry, we examined 1474 patients who underwent M-TEER for SMR between April 2018 and June 2021. Beta-blocker uptitration was defined as an increased dose of beta-blockers 1 month after M-TEER compared with that before M-TEER. The 2-year clinical outcomes were compared between patients with and without beta-blocker uptitration, utilizing multivariable Cox regression analyses and propensity score matching (PSM). RESULTS: Of the 1474 patients who underwent M-TEER, 272 (18.4 %) were receiving increasing doses of beta-blockers at the 1-month follow-up. These patients had lower left ventricular ejection fraction (LVEF) and higher B-type natriuretic peptide levels. Most patients in the beta-blocker uptitration group received less than the target dose of beta-blockers. Multivariable Cox regression analyses showed that beta-blocker uptitration was significantly associated with a lower risk of all-cause (adjusted hazard ratio [HR]: 0.55; 95 % confidence interval [CI]: 0.36-0.84; P = 0.006) and cardiovascular mortalities (adjusted HR: 0.45, 95 % CI: 0.26-0.79, P = 0.006). PSM analyses revealed consistent findings. Subgroup analyses revealed a significant interaction between beta-blocker uptitration and LVEF≤40 % (interaction P = 0.018). CONCLUSIONS: In patients with SMR, beta-blocker uptitration after M-TEER was associated with better clinical outcomes, especially in the group with an LVEF≤40 %. Efforts to uptitrate guideline-directed medical therapy after M-TEER for SMR may be necessary, even if reaching the target dose proves challenging.

No Antithrombotic Therapy After Transcatheter Aortic Valve Replacement: Insight From the OCEAN-TAVI Registry.

BACKGROUND: Several trials demonstrated that aspirin monotherapy compared with aspirin plus clopidogrel is associated with a lower incidence of bleeding without an increased risk of ischemic events in patients after transcatheter aortic valve replacement (TAVR); however, there remains a paucity of data to prove the necessity of even aspirin monotherapy. OBJECTIVES: This study aimed to compare clinical outcomes and valve performance of the 3 different antithrombotic strategies post-TAVR from the OCEAN-TAVI (Optimized transCathEter vAlvular iNtervention) registry. METHODS: Patients who received anticoagulation or had procedural complications were excluded. The remaining patients were classified into 3 groups according to the antithrombotic regimen at discharge: 1) nonantithrombotic therapy (None); 2) single-antiplatelet therapy (SAPT); and 3) dual-antiplatelet therapy (DAPT). The primary outcome was the incidence of net adverse clinical events (NACEs) (ie, cardiovascular death, stroke, myocardial infarction, and life-threatening or major bleeding). RESULTS: Overall, 3,575 TAVR patients were included (None, 293; SAPT, 1,354; DAPT, 1,928). The median follow-up period was 841 days (IQR: 597-1,340 days). The incidence of NACEs did not differ between the groups (None vs SAPT: adjusted HR [aHR]: 1.18; P = 0.45; None vs DAPT: aHR: 1.09; P = 0.67). There was a lower incidence of all bleeding in patients with no antithrombotics (None vs SAPT: aHR: 0.63; P = 0.12; None vs DAPT: aHR: 0.51; P = 0.04). The valve performance was similar among the groups. Leaflet thrombosis was detected in 8.5% of the nonantithrombotic group. CONCLUSIONS: Compared with SAPT/DAPT, the nonantithrombotic strategy was not associated with an increased risk of NACEs and potentially reduced the risk of bleeding events. The nonantithrombotic strategy may be an acceptable alternative to SAPT/DAPT in selected patients with TAVR.

miR-142-3p is essential for hematopoiesis and affects cardiac cell fate in zebrafish.

MicroRNAs (miRNAs) play a pivotal role during embryonic development and are required for proper organogenesis, including hematopoiesis. Recent studies suggest that, in the early mesoderm, there is an interaction between the hematopoietic and cardiac lineages. However, whether miRNAs can affect other lineages remains unknown. Therefore, we investigated whether hematopoietic miR-142-3p modulated the mesoderm formation. We report that knockdown (KD) of miR-142-3p, a hematopoietic-specific miRNA, in zebrafish resulted in loss of hematopoiesis during embryonic development. Intriguingly, we observed abnormal cardiac phenotypes and insufficiency of somitegenesis in KD-morphants. In the early developmental stage, a tiny heart, contractile dysfunction in the ventricle, cardiac arrhythmia (e.g. a 2:1 ratio of atrial:ventricular beating), and bradycardia were consistently observed. Histological examination revealed severe hypoplasia of the ventricle and disrupted muscle alignment. To determine the mechanism, we performed DNA microarray analysis. The results revealed that the expression of several mesodermal genes essential for the formation of cardiac and somatic mesoderm, such as no tail, T-box gene 16, mesoderm posterior a, one eye pinhead, and rho-associated, coiled-coil containing protein kinase (Rock2a), were increased in miR-142-3p KD-morphants. The luciferase reporter assay revealed that miR-142-3p repressed luciferase activity on the Rock2a 3'-UTR. The findings of the present study indicate that miR-142-3p plays a critical role in hematopoiesis, cardiogenesis, and somitegenesis in the early stage of mesoderm formation via regulation of Rock2a.

Treatment of human mesenchymal stem cells with angiotensin receptor blocker improved efficiency of cardiomyogenic transdifferentiation and improved cardiac function via angiogenesis.

To improve the modest efficacy of mesenchymal stem cell (MSC) transplantation, the treatment of human MSCs with angiotensin receptor blockers (ARBs) was investigated. MSCs were cultured with or without the medium containing 3 µmol/l of ARBs before cardiomyogenic induction. After cardiomyogenic induction in vitro, cardiomyogenic transdifferentiation efficiency (CTE) was calculated by immunocytochemistry using anticardiac troponin-I antibody. In the nude rat chronic myocardial infarction model, we injected MSCs pretreated with candesartan (A-BM; n = 18) or injected MSCs without pretreatment of candesartan (BM; n = 25), each having survived for 2 weeks. The left ventricular function, as measured by echocardiogram, was compared with cardiomyogenic transdifferentiation in vivo, as determined by immunohistochemistry. Pretreatment with ARBs significantly increased the CTE in vitro (10.1 ± 0.8 n = 12 vs. 4.6 ± 0.3% n = 25, p < .05). Transplantation of candesartan-pretreated MSCs significantly improved the change in left ventricular ejection fraction (BM; -7.2 ± 2.0 vs. A-BM; 3.3 ± 2.3%). Immunohistochemistry revealed significant improvement of cardiomyogenic transdifferentiation in A-BM in vivo (BM; 0 ± 0 vs. A-BM; 0.014 ± 0.006%). Transplantation of ARB-pretreated MSCs significantly improved cardiac function and can be a promising cardiac stem cell source from which to expect cardiomyogenesis.

Pretreatment of human mesenchymal stem cells with pioglitazone improved efficiency of cardiomyogenic transdifferentiation and cardiac function.

The efficacy of transplantation of default human marrow-derived mesenchymal stem cells (MSCs) was modest. In this study, our challenge was to improve the efficacy of MSC transplantation in vivo by pretreatment of MSCs with pioglitazone. MSCs were cultured with or without medium containing 1 µM of pioglitazone before cardiomyogenic induction. After cardiomyogenic induction in vitro, cardiomyogenic transdifferentiation efficiency (CTE) was calculated by immunocytochemistry using anti-cardiac troponin-I antibody. For the in vivo experiments, myocardial infarction (MI) at the anterior left ventricle was made in nude rats. Two weeks after MI, MSCs pretreated with pioglitazone (p-BM; n = 30) or without pioglitazone (BM; n = 17) were injected, and then survived for 2 weeks. We compared left ventricular function by echocardiogram and immunohistochemistry to observe cardiomyogenic transdifferentiation in vivo. Pretreatment with pioglitazone significantly increased the CTE in vitro (1.9% ± 0.2% n = 47 vs. 39.5% ± 4.7% n = 13, p < .05). Transplantation of pioglitazone pretreated MSCs significantly improved change in left ventricular % fractional shortening (BM; -4.8% ± 2.1%, vs. p-BM; 5.2% ± 1.5%). Immunohistochemistry revealed significant improvement of cardiomyogenic transdifferentiation in p-BM in vivo (BM; 0% ± 0% n = 5, vs. p-BM; 0.077% ± 0.041% n = 5). Transplantation of pioglitazone-pretreated MSCs significantly improved cardiac function and can be a promising cardiac stem cell source to expect cardiomyogenesis.