Trans-radial percutaneous coronary intervention for patients with severe chronic renal insufficiency and/or on dialysis.

Periprocedural bleeding is associated with an increased risk of mortality during percutaneous coronary intervention (PCI), especially in patients with severe chronic renal insufficiency. Therefore, trans-radial intervention (TRI) should be considered in these patients; however, PCI operators usually avoid this approach because of the risk of radial artery occlusion. We aimed to investigate the associations of TRI and in-hospital complications in these patients. This study included 306 consecutive patients with severe chronic renal insufficiency and/or on dialysis who underwent PCI. Patients were prospectively enrolled and divided according to the access site into TRI group and trans-femoral intervention group. Severe renal insufficiency was defined as estimated glomerular filtration rate < 30 mL/min/1.73 m2. Radial access was limited to the opposite side of the arteriovenous fistula in patients on hemodialysis. The primary study endpoint was the composite of in-hospital bleeding complications and death. TRI benefit was evaluated by inverse probability treatment weighted analysis. TRI was performed in 112 (37.3%) patients. TRI group included older patients with significantly lower rates of diabetes mellitus, dialysis, and three-vessel disease. Crossover to the other approach occurred only in TRI group (2.6%). The primary endpoint was significantly lower in TRI group (11.5% vs. 2.6%, P = 0.006). After an inverse probability treatment weighted analysis, TRI was an independent prognostic factor for a decrease in the primary endpoint (OR 0.19; 95% CI 0.051-0.73; P = 0.015). Radial artery occlusion occurred in three patients on dialysis (9.1%). TRI may determine better in-hospital outcomes in patients with severe chronic renal insufficiency and/or on dialysis.

Intramyocardial Transplantation of Human iPS Cell-Derived Cardiac Spheroids Improves Cardiac Function in Heart Failure Animals.

The severe shortage of donor hearts hampered the cardiac transplantation to patients with advanced heart failure. Therefore, cardiac regenerative therapies are eagerly awaited as a substitution. Human induced pluripotent stem cells (hiPSCs) are realistic cell source for regenerative cardiomyocytes. The hiPSC-derived cardiomyocytes are highly expected to help the recovery of heart. Avoidance of teratoma formation and large-scale culture of cardiomyocytes are definitely necessary for clinical setting. The combination of pure cardiac spheroids and gelatin hydrogel succeeded to recover reduced ejection fraction. The feasible transplantation strategy including transplantation device for regenerative cardiomyocytes are established in this study.

Successful Percutaneous Coronary Intervention Using Intravascular Ultrasound-Guided Rewiring Technique in a Case of Spontaneous Coronary Artery Dissection Involving Left Main Bifurcation.

We herein describe a 49-year-old woman without significant cardiovascular risk factors who was transferred to our hospital with sudden onset of chest pain. The patient was diagnosed with non-ST-elevation acute myocardial infarction, and coronary angiography revealed a dissection at the proximal site of the left anterior descending artery (LAD) extending from the left main trunk (LMT) suggestive of spontaneous coronary artery dissection (SCAD). Because coronary flow was impaired after contrast injection and the patient had chest pain with ST elevation, urgent percutaneous coronary intervention was performed. The first guide wire was initially introduced from the LMT to the distal LAD, but intravascular ultrasound (IVUS) imaging revealed that the guide wire had passed through the true lumen of the left coronary artery ostium, false lumen at the ostium of the left circumflex artery, and true lumen of the distal LAD. We then reinserted another guide wire using an IVUS-guided rewiring technique from the true lumen of the LMT to the distal LAD. Finally, a drug-eluting stent was deployed to cover the dissected segment, and final coronary angiography revealed acceptable results with a patent left circumflex artery. This case report highlights that physicians should consider SCAD among the differential diagnoses in patients presenting with acute coronary syndrome, particularly in young women. In the present case, IVUS played a pivotal role in not only detecting the arterial dissection but also correctly introducing the guide wire into the true lumen.

Stent Deformation Caused by Entrapment of the Side Branch Balloon Catheter During the Jailed Balloon Protection Technique for a Calcified Coronary Bifurcation Lesion: A Case Report and Literature Review.

Percutaneous coronary intervention (PCI) for true bifurcation lesions is challenging. Although the jailed balloon protection technique is an established method with which to prevent side branch occlusion during the treatment of bifurcation lesions, little is known regarding the potential risks of this technique. We describe a 71-year-old man with exertional angina pectoris who was treated with PCI for a calcified true bifurcation lesion in the left anterior descending artery and diagonal branch. After performing rotational atherectomy (1.75 mm burr) for the main vessel and pre-dilatation for both the main vessel and side branch, we performed the jailed balloon technique to protect the large diagonal branch during stent implantation. However, the jailed balloon was entrapped after main vessel stent balloon inflation. The entrapped jailed balloon was then inflated again and successfully removed after balloon deflation, but significant stent deformation was seen with intravascular ultrasound imaging. Fortunately, post-dilatation was successfully performed with a non-compliant balloon, and a final coronary angiogram showed acceptable results. This case report and literature review highlights a potential risk of the jailed balloon technique and conceivable alternatives during PCI for true bifurcation lesions.

Novel Insights of Jailed Balloon and Jailed Corsair Technique for Percutaneous Coronary Intervention of Bifurcation Lesions.

BACKGROUND: The optimal technique for percutaneous coronary intervention (PCI) of a bifurcation lesion remains uncertain. JBT/JCT techniques are now emerging for protection of the side branch (SB). We aimed to compare jailed balloon (JBT) and jailed Corsair (JCT) techniques to the conventional jailed wire technique. METHODS: We analyzed 850 consecutive patients (995 bifurcation lesions), who underwent PCI. The bifurcation lesions were classified as jailed wire (-), jailed wire (+), JBT, and JCT. We assessed temporary thrombolysis in myocardial infarction (TIMI) flow grade ≤2, permanent TIMI flow grade ≤2 in the SB, and SB occlusion related myocardial infarction and compared these endpoints with inverse probability treatment weighted analysis. RESULTS: The percentage of each group is as follows: jailed wire (-); 44.7%; jailed wire (+) 50.9%; JBT 1.7%; JCT 2.7%. The Corsair could not be delivered with a stent because of severe calcifications (3.7%) and a jailed balloon was entrapped with the stent after dilatation (5.9%). Compared to the jailed wire (+), JBT/JCT had a higher percentage of true bifurcations, arterial sheath size ≥7 Fr, and a lower proportion of wire recrossing (all, P < 0.05). After adjustment, temporary and permanent TIMI flow grade ≤2 in the SB, and SB occlusion related myocardial infarction were not significantly different (OR: 1.08, CI: 0.32-3.71, P = 0.90; OR: 0.88, CI: 0.11-6.91, P = 0.91; OR: 1.94, CI: 0.23-16.5, P = 0.55 respectively). CONCLUSIONS: Our data could not prove the efficacy of JBT/JCT, but revealed novel insights about these techniques. A larger study is necessary to prove the efficacy of JBT/JCT.

Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cell‒derived cardiomyocytes.

BACKGROUND: Induced pluripotent stem cell (iPSC)‒based regenerative therapy is a promising strategy for cardiovascular disease treatment; however, the method is limited by the myocardial retention of grafted iPSCs. Thus, an injection protocol that efficiently introduces and retains human iPSC-derived cardiomyocytes (hiPSC-CMs) within the myocardium is urgently needed. The objective of the present study was to develop a method to improve the retention of hiPSCs in the myocardium for cardiac therapy. METHODS: We efficiently produced hiPSC-CM spheroids in 3-dimensional (3D) culture using microwell plates, and developed an injection device for optimal 3D distribution of the spheroids in the myocardial layer. Device biocompatibility was assessed with purified hiPSC-CM spheroids. Device effectiveness was evaluated in 10- to 15-month-old farm pigs (n = 15) and 5- to 24-month-old micro-minipigs (n = 20). The pigs were euthanized after injection, and tissues were harvested for retention and histologic analysis. RESULTS: We demonstrated an injection device for direct intramyocardial transplantation of hiPSC-CM spheroids from large-scale culture. The device had no detrimental effects on cell viability, spheroid shape, or size. Direct epicardial injection of spheroids mixed with gelatin hydrogel into beating porcine hearts using this device resulted in better distribution and retention of transplanted spheroids in a layer within the myocardium than did conventional needle injection procedures. CONCLUSIONS: The combination of the newly developed transplant device and spheroid formation promotes the retention of transplanted CMs. These findings support the clinical application of hiPSC-CM spheroid‒based cardiac regenerative therapy in patients with heart failure.

A Transradial Approach of Cardiac Catheterization for Patients on Dialysis.

BACKGROUND: Periprocedural bleeding is associated with increased risk of early mortality during percutaneous coronary intervention (PCI), especially in patients on dialysis. A transradial approach (TRA) should be considered for these patients; however, PCI operators avoid this approach because of the risk of radial artery occlusion (RAO). The aim of this study is to construct a TRA system and clarify its safety in patients on dialysis. METHODS: Eighty-eight consecutive patients on dialysis who underwent cardiac catheterization were prospectively included in this study and divided according to the access site into either the TRA group or the transfemoral approach (TFA) group. Radial access was limited in the opposite side of arteriovenous fistula. The study endpoints were in-hospital and 30-day mortality rates, puncture-site related bleeding complications, and other complications. The study safety endpoints were procedure success rate and RAO rate in the TRA group. RESULTS: Mean patient age was 70.4 ± 8.5 years. PCI was performed in 43 patients (48.9%). The TRA and TFA groups included 62 patients (70.5%) and 26 patients (29.5%), respectively. In-hospital and 30-day mortality rates were 0.0% in both groups. Puncture-site bleeding rates were 3.8% in the TFA group and 0.0% in the TRA group (P=.12). Procedural success rate in the TRA group was 98.4%. Crossover to TFA was necessary in 1 patient due to radial artery spasm. RAO occurred in 4 patients (6.5%). CONCLUSIONS: Constructed TRA can be safely used in patients on dialysis. Our study could lead to an increase in TRA in these patients, which would lead to better prognosis and patient comfort.

Recent Inferior Myocardial Infarction Complicated with a Right Ventricular Thrombus Detected by Three Cardiac Imaging Modalities.

We report the case of a 71-year-old woman diagnosed with recent inferior myocardial infarction complicated with right ventricular infarction and a right ventricular thrombus. Three-dimensional transthoracic echocardiography, contrast-enhanced computed tomography, and cardiac magnetic resonance imaging clearly detected a thrombus. We consider cases with a recent right ventricular infarction to require assessment for thrombus formations in the right ventricle. Fortunately, vigorous anticoagulation therapy resolved the thrombi in both the right ventricle and right coronary artery.

Catastrophic catheter-induced coronary artery vasospasm successfully rescued using intravascular ultrasound imaging guidance.

A 46-year-old man underwent coronary angiography for stable angina. He developed inferior ST-segment myocardial infarction during the angiography. Intravascular ultrasound (IVUS) findings suggested coronary vasospasm. Intracoronary administration of isosorbide dinitrate restored the coronary flow. This case illustrates the essential role IVUS imaging played in establishing the diagnosis of catheter-induced coronary vasospasm.

A case with a large intracoronary mobile mass diagnosed with a calcified thrombus using optical frequency domain imaging and intravascular ultrasound.

OBJECTIVES: A calcified thrombus is rare, but needs to be recognized and to be differentiated from calcified nodule. METHODS: We report a case of acute coronary syndrome and a large intracoronary mobile mass, which was identified as a calcified thrombus by optical frequency domain imaging and intravascular ultrasound. RESULTS: Successful direct stenting indicated that mobile mass was a calcified thrombus, not a calcified nodule. CONCLUSIONS: Cardiologists should be aware that an intracoronary mobile mass could be a calcified thrombus. This diagnosis can be confirmed through the combined use of optical frequency domain imaging and intravascular ultrasound.

Three-dimensional optical frequency domain imaging of a true bifurcation lesion after stent implantation using the jailed semi-inflated balloon technique.

OBJECTIVE: Percutaneous coronary intervention for coronary bifurcation lesion is very challenging, especially for true bifurcation lesions. Although the jailed semi-inflated balloon technique is one of the established methods for treatment of coronary bifurcation lesions, little is known regarding the configuration of the side branch orifice after stent implantation using this technique. METHODS: We report a 73-year-old male patient with angina pectoris who was successfully treated with percutaneous coronary stent implantation for a true bifurcation lesion of the right coronary artery with an obtuse angle using the jailed semi-inflated balloon technique. RESULTS: Three-dimensional optical frequency domain imaging clearly showed that there were no signs of plaque or carina shift into the side branch after stent implantation using this technique. CONCLUSIONS: This case report highlights that the jailed semi-inflated balloon technique is a safe and useful treatment for coronary true bifurcation lesions with an obtuse angle.

Successful treatment using corticosteroids in early phase of eosinophilic myocarditis with eosinophilic granulomatosis with polyangiitis.

We report the case of a 50-year-old man with eosinophilic myocarditis and bronchial asthma treated successfully with prednisolone. He was initially diagnosed with eosinophilia, and complained of acute chest pain with electrocardiographic changes and elevation of cardiac enzymes. Coronary angiography showed no atherosclerotic changes; therefore, we performed endomyocardial biopsy and started oral prednisolone therapy immediately. His general condition improved with the disappearance of eosinophilia upon treatment. He was finally diagnosed with eosinophilic granulomatosis with polyangiitis complicated by eosinophilic myocarditis. This case report highlights that eosinophilic myocarditis may occur in association with systemic disease, and early steroid therapy is essential. .

Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.

Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×10(6) or 1x10(6) cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×10(6) CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved cardiac function with a direct contraction effect and enhanced angiogenesis.

The Prevalence of Clinically Significant Ischemia in Patients Undergoing Percutaneous Coronary Intervention: A Report from the Multicenter Registry.

BACKGROUND: Myocardial perfusion scintigraphy (MPS) plays an important role in the evaluation and quantification of myocardial ischemia, and those with significant ischemia (SI) benefit most from revascularization procedures. This study aimed to identify the clinical factors and anatomical features associated with SI in patients with stable ischemic heart disease (SIHD). METHODS AND RESULTS: Data were analyzed from 4197 SIHD patients undergoing percutaneous coronary intervention (PCI). Ischemia was based on MPS findings prior to PCI, with SI defined as an ischemic region of more than 10% of the total left ventricular area. Logistic regression analysis was performed to identify any clinical factors associated with SI. MPS was used to evaluate 1070 (25.5%) patients pre-procedurally. Patients with a history of heart failure, stroke, or anginal symptoms with Canadian Cardiovascular Society class 2 or more were more likely to have SI (odds ratio [OR] 1.63, p = 0.025, OR: 1.85, p = 0.009, and OR: 1.49, p = 0.003, respectively). When angiographic variables were considered, a proximal left anterior descending artery (pLAD) lesion was the sole factor associated with SI (OR: 1.45, p = 0.012). Importantly, those with SI had more in-hospital complications (p = 0.006), most notably post-PCI infarcts (p = 0.008). CONCLUSIONS: Patients' background data, such as stronger anginal symptoms or a pLAD lesion, were associated with SI. Patients with SI must be treated with PCI to improve their long-term prognosis; however, procedure-related complications happen more frequently in SI patients than in non-SI patients. Physicians must give their full attention when performing the PCI procedure in SI patients to minimize their complication rate.

Derivation of transgene-free human induced pluripotent stem cells from human peripheral T cells in defined culture conditions.

Recently, induced pluripotent stem cells (iPSCs) were established as promising cell sources for revolutionary regenerative therapies. The initial culture system used for iPSC generation needed fetal calf serum in the culture medium and mouse embryonic fibroblast as a feeder layer, both of which could possibly transfer unknown exogenous antigens and pathogens into the iPSC population. Therefore, the development of culture systems designed to minimize such potential risks has become increasingly vital for future applications of iPSCs for clinical use. On another front, although donor cell types for generating iPSCs are wide-ranging, T cells have attracted attention as unique cell sources for iPSCs generation because T cell-derived iPSCs (TiPSCs) have a unique monoclonal T cell receptor genomic rearrangement that enables their differentiation into antigen-specific T cells, which can be applied to novel immunotherapies. In the present study, we generated transgene-free human TiPSCs using a combination of activated human T cells and Sendai virus under defined culture conditions. These TiPSCs expressed pluripotent markers by quantitative PCR and immunostaining, had a normal karyotype, and were capable of differentiating into cells from all three germ layers. This method of TiPSCs generation is more suitable for the therapeutic application of iPSC technology because it lowers the risks associated with the presence of undefined, animal-derived feeder cells and serum. Therefore this work will lead to establishment of safer iPSCs and extended clinical application.

A massive suspension culture system with metabolic purification for human pluripotent stem cell-derived cardiomyocytes.

Cardiac regenerative therapy with human pluripotent stem cells (hPSCs), such as human embryonic stem cells and induced pluripotent stem cells, has been hampered by the lack of efficient strategies for expanding functional cardiomyocytes (CMs) to clinically relevant numbers. The development of the massive suspension culture system (MSCS) has shed light on this critical issue, although it remains unclear how hPSCs could differentiate into functional CMs using a MSCS. The proliferative rate of differentiating hPSCs in the MSCS was equivalent to that in suspension cultures using nonadherent culture dishes, although the MSCS provided more homogeneous embryoid bodies (EBs), eventually reducing apoptosis. However, pluripotent markers such as Oct3/4 and Tra-1-60 were still expressed in EBs 2 weeks after differentiation, even in the MSCS. The remaining undifferentiated stem cells in such cultures could retain a strong potential for teratoma formation, which is the worst scenario for clinical applications of hPSC-derived CMs. The metabolic purification of CMs in glucose-depleted and lactate-enriched medium successfully eliminated the residual undifferentiated stem cells, resulting in a refined hPSC-derived CM population. In colony formation assays, no Tra-1-60-positive colonies appeared after purification. The nonpurified CMs in the MSCS produced teratomas at a rate of 60%. However, purified CMs never induced teratomas, and enriched CMs showed proper electrophysiological properties and calcium transients. Overall, the combination of a MSCS and metabolic selection is a highly effective and practical approach to purify and enrich massive numbers of functional CMs and provides an essential technique for cardiac regenerative therapy with hPSC-derived CMs.