Impact of Controlling Nutritional Status Score on Comprehensive Clinical Outcomes in Patients With Chronic Limb-Threatening Ischemia in a Local Area of Super-Aged Society.

PURPOSE: This study aimed to evaluate the relationship between nutritional status and hospital outcomes in patients with chronic limb-threatening ischemia (CLTI) in a local area of contemporary super-aged society of Japan. MATERIALS AND METHODS: We analyzed 131 consecutive patients with 179 lower limb diseases admitted to our hospital for the treatment of CLTI between April 2018 and March 2023. These 131 patients were divided into 3 groups according to hospital outcomes: home discharge (HD), out-of-home discharge (OD), and in-hospital death (ID). Patient and lesion backgrounds were compared among the 3 groups, and a multivariable regression analysis was used to analyze the interaction between malnutrition and composite hard endpoints. RESULTS: The median age was 82.8 years, and non-ambulatory patients comprised 61.8% of the study population. The HD group included more ambulatory and fewer patients with higher CONUT score or inflammation than OD or ID group. The Rutherford classification and Wound, Ischemia, and foot Infection stage were significantly more severe in the ID group than in the HD group. Endovascular treatment (EVT) was more often implemented in the HD (94.9%) and OD (81.7%) groups than in the ID group (60.0%). However, all EVT procedures in the ID group were performed until as distally as possible to achieve the target arterial path success contrary to some EVT procedures in the HD or ID group that targeted lesions only above the knee. Multivariate analysis showed that a non-ambulatory state (hazard ratio [HR]=3.65, 95% confidence interval [CI]=1.48-9.02) and a higher controlling nutritional status (CONUT) score (≥5) (HR=7.46, 95% CI=1.66-33.6) were significant predictors for composite endpoints (major amputation or ID). Patients with lower CONUT scores (≤4) showed better outcomes in all indices including overall survival, major amputation-free survival, and wound healing. CONCLUSION: Condition of the CLTI patients represented by higher CONUT score emerged as the most influential predictor of major amputation or ID. Furthermore, non-ambulatory status or condition of higher CONUT score affects the destination after discharge. Implementing multidisciplinary approaches to address patients' nutritional state and physical disability, in addition to revascularization, may enhance comprehensive prognoses in patients with CLTI. CLINICAL IMPACT: In this single-center retrospective study, we analyzed prognoses of 131 consecutive patients with 179 lower limb diseases admitted for the treatment of chronic limb-threatening ischemia (CLTI) between April 2018 and March 2023. Our main finding was that condition of the CLTI patients represented by higher controlling nutritional status (CONUT) score was the most significant predictor of either major amputation or in-hospital death. Furthermore, condition of higher CONUT score or non-ambulatory status affects the destination after discharge. This suggests that multidisciplinary approaches to address patients' nutritional state and physical disability, in addition to revascularization, may enhance the prognosis in patients with CLTI. This is the first report to evaluate nutritional status associated with comprehensive hospital outcomes in addition to previously reported hard endpoints, such as major amputation or overall survival, and will be of great help in future clinical practice.

A latent bleeding complication in ipsilateral common femoral puncture involving delayed diagnosis: a case report.

BACKGROUND: The trans femoral ipsilateral approach is often adopted for endovascular treatment (EVT) for better steerability of guidewires or better device deliverability. However, contrary to the trans femoral contralateral approach, ipsilateral antegrade puncture sometimes causes peculiar bleeding complications. CASE PRESENTATION: A 76-year-old female underwent EVT for chronic occlusion of the left superficial femoral artery (SFA) via the ipsilateral antegrade approach. After guidewire passage, we inflated the drug-coated balloons, but angiography showed blood flow stasis at the mid segment of the SFA. We also ensured prolonged balloon inflation, which resulted in favorable blood flow. While trying to ensure hemostasis, the blood pressure remained decreased, but neither bleeding nor superficial hematoma were observed at the puncture site. After hemostasis was achieved, we removed the surgical drape and noticed a swelling in the mid-portion of the thigh, distant from the puncture point. We then approached the left common femoral artery (CFA) contralaterally. Angiography showed continuous bleeding from a little bit distally to the sheath insertion point that was spreading through an intramuscular space. We stopped the bleeding with balloon tamponade inside the CFA. Angiography after hemostasis demonstrated blood flow stasis at the mid-segment of the SFA, similarly as that seen before. We confirmed compression of the SFA by a large hematoma using both intra- and extra- vascular ultrasound. Therefore, we deployed a self-expandable stent at the compressed SFA position. Finally, we achieved favorable blood flow on angiography. CONCLUSION: We encountered a case that latent bleeding unrecognized in the surgical field persisted while prolonged inflation of DCB was conducted at just proximal SFA. We could have avoided bailout stenting by noticing the bleeding incident in a timely manner. Prediction and prevention are essential for all kinds of procedural complications in EVT.

Emphysematous changes as red flag signs preceding rapidly progressive infectious aortic disease: two case reports.

BACKGROUND: Infectious aortic disease is a rare and fatal disease, that requires the appropriate intervention. An accurate diagnosis should be promptly established. However, this is difficult because the clinical manifestations of this disease vary and are non-specific. CASE PRESENTATION: (CASE 1) An 87-year-old male, presenting with generalized malaise and weight loss, was admitted for further examination. A chest computed tomography (CT) showed mediastinal emphysema. Empirical intravenous antibiotics were administered to address the non-specific infectious findings in the laboratory data. The treatment was effective, and the patient fully recovered. However, he was in shock due to aortic rupture and marked pseudo aneurysmal formation around the aortic arch day 25 of hospitalization. An emergency total aortic arch replacement was performed, and the patient was discharged. (CASE 2) An 82-year-old male who had undergone Y-graft replacement in the abdominal aorta 15 years previously was admitted due to general malaise and anorexia. Abdominal CT revealed emphysematous changes adjacent to the abdominal aorta. The patient responded favorably to empirical treatment with intravenous antibiotics and was discharged 19 days after admission. Four days after discharge, the patient went into cardiac arrest after an episode of hematemesis. Abdominal CT revealed an enlarged stomach and duodenum, filled with massive high-density contents proximal to the abdominal aorta. He died of hemorrhagic shock despite cardiopulmonary resuscitation. CONCLUSIONS: Although emphysematous changes are rare, they are red flag signs during the early stage of infectious aortic disease. Thus, physicians should remain vigilant for this kind of critical sign.

Tako-Tsubo Syndrome Following Pulmonary Vein Isolation for Atrial Fibrillation in a Patient with Primary Aldosteronism.

Tako-tsubo syndrome (TTS) can be triggered by emotional or physical stress and is characterized by transient left ventricular dysfunction with apical ballooning. Some neurologic disorders and pheochromocytoma serve as triggers for TTS, however, its association with primary aldosteronism (PA) is not well known. Pulmonary vein isolation (PVI) with catheter ablation for atrial fibrillation (AF) has been performed worldwide, and TTS following PVI has been reported as a rare complication. Sympathetic stimulation can play an important role in TTS development, however, its mechanism and risk factors are not yet understood.We describe a 72-year-old woman with PA who developed TTS after PVI with radiofrequency catheter ablation (RFCA) for symptomatic paroxysmal AF. Complete isolation of the pulmonary vein was carried out without any complications, however, she complained of epigastric discomfort 7 hours after the procedure. An electrocardiogram showed recurrent AF with a new negative-T wave and prolonged QT interval. Transthoracic echocardiography revealed apical ballooning and basal hypercontraction, characteristic of TTS, and coronary angiography showed no significant stenosis. She was diagnosed with TTS following RFCA for AF and managed well with conservative therapy.The present case suggests that TTS should be recognized as a complication associated with AF ablation. Moreover, PA may be involved in TTS development by increasing sympathetic activity. Further studies on the mechanism and characteristics of TTS are required.

The infectivity of progeny adenovirus in the presence of neutralizing antibody.

Human adenoviruses (Ads), common pathogens that cause upper respiratory and gastrointestinal infections, are blocked by neutralizing antibodies (nAbs). However, Ads are not fully eliminated even in hosts with nAbs. In this study, we assessed the infectivity of progeny Ad serotype 5 (Ad5) in the presence of nAb. The infectivity of Ad5 was evaluated according to the expression of the Ad genome and reporter gene. Infection by wild-type Ad5 and Ad5 vector continued to increase until 3 days after infection even in the presence of nAb. We established an assay for determining the infection levels of progeny Ad5 using a sorting system with magnetic beads and observed little difference in progeny Ad5 counts in the presence and absence of nAb 1 day after infection. Moreover, progeny Ad5 in the presence of nAb more effectively infected coxsackievirus and adenovirus receptor (CAR)-positive cells than CAR-negative cells. We investigated the function of fiber proteins, which are the binding partners of CAR, during secondary infection, observing that fibre proteins spread from infected cells to adjacent cells in a CAR-dependent manner. In conclusion, this study revealed that progeny Ad5 could infect cells even in the presence of nAb, differing from the common features of the Ad5 infection cycle. Our findings may be useful for developing new therapeutic agents against Ad infection.

Inflation Pressure in Side Branch during Modified Jailed Balloon Technique Does Not Affect Side Branch Outcomes.

OBJECTIVES: This study aimed to investigate the optimal jailed balloon inflation in the side branch during the modified jailed balloon technique for bifurcated lesions. BACKGROUND: The modified jailed balloon technique is one of the effective techniques to minimize the emergence of side branch (SB) compromise by preventing plaque or carina shifting during a single stent strategy in the main vessel with provisional SB treatment. However, there are no detailed studies on the method of optimal jailed balloon inflation. METHODS: We analyzed 51 consecutive patients who underwent percutaneous coronary intervention (PCI) for bifurcated lesions with a modified jailed balloon technique between September 2018 and December 2020. These 51 patients were divided into two groups according to the magnitude of inflation pressure of the jailed balloon: a higher pressure (HP) group and lower pressure (LP) group. RESULTS: No significant differences in procedural outcomes were observed between the two groups. The findings of SB compromise were relatively common with our procedure (30.0% in the HP group; 33.3% in the LP group). The patterns of SB compromise such as dissection or stenosis increase were observed at similar frequencies between them. In particular, SB dissection was noted in the SB lesion with some plaque burden, irrespective of the magnitude of the jailed balloon inflation pressure. Univariate analysis showed that calcification in the main vessel and SB lesion length was significantly associated with SB compromise. Finally, all PCI procedures were successfully completed without any provisional stent deployment in SB. CONCLUSIONS: We speculate that lesion characteristics rather than the PCI procedural factors may be critical determinants to cause SB compromise.

A noteworthy clue for diagnosing non-ST-elevation myocardial infarction by computed tomography without ECG synchronization: a case report.

BACKGROUND: Although timely coronary intervention can result in markedly improved clinical outcomes of patients with acute coronary syndrome (ACS), non-ST-elevation (NSTE)-ACS is sometimes difficult to accurately diagnose. CASE PRESENTATION: A 52-year-old woman complained of acute chest pain with sudden onset. Both electrocardiography (ECG) and echocardiography showed normal results, and we urgently needed to make a differential diagnosis among critical illnesses such as acute coronary syndrome and nonischemic cardiovascular life-threatening diseases. Contrast-enhanced computed tomography (CT) without ECG synchronization showed evidence of neither aortic dissection nor pulmonary embolism, but regionally reduced contrast enhancement in the posterior myocardium, which were suggestive of myocardial ischemia. Emergency coronary angiography demonstrated severe stenosis of the left circumflex artery, and we achieved favorable revascularization with drug-eluting stent deployment. CONCLUSIONS: We diagnosed a patient with NSTE-ACS in whom contrast-enhanced CT without ECG synchronization was effective for visualization of reduced myocardial perfusion, suggesting ischemic heart disease.

Development of Dendritic Cell-Based Immunotherapy Targeting Tumor Blood Vessels in a Mouse Model of Lung Metastasis.

Tumor blood vessels supply cancer tissues with oxygen and nutrients, and it was therefore believed that inhibition of angiogenesis would induce tumor regression. In fact, the situation is complicated by the presence of normal blood vessels in cancer tissues such as carcinomas and sarcomas as well as abnormal vessels. Here, we describe the development of a dendritic cell (DC)-based immunotherapy which targets tumor endothelial cells (TECs) rather than normal endothelial cells (ECs) or cancer cells themselves. After density gradient centrifugation, the TEC-rich fraction from lungs invaded by B16 melanoma cells was separated from the endothelial cell (EC)-rich fraction on the basis of positivity for angiotensin-converting enzyme (ACE) activity. Prophylactic vaccination with DCs pulsed with lysates of TECs isolated from lungs with metastases significantly suppressed lung metastasis in this B16/BL6 mouse melanoma model. This suggests that DC-based vaccine therapy targeting TECs in cancers tissue could show promise as an effective therapy for distant metastasis.

Cancer Vaccine Therapy Using Tumor Endothelial Cells as Antigens Suppresses Solid Tumor Growth and Metastasis.

Tumor angiogenesis plays an important role in tumor growth and metastasis, with tumor cells requiring nutrients and oxygen via blood flow for their proliferation. In comparison, angiogenesis also occurs under normal physiological conditions, such as wound healing and in the formation of the corpus luteum. Herein, we report on the development of a novel dendritic cell (DC) vaccine therapy using tumor endothelial cells (TECs) derived from tumor vessels as tumor antigens. After density gradient centrifugation and the detection of angiotensin-converting enzyme activities, a TEC-rich fraction was separated from solid tumor tissues. Prophylactic or therapeutic immunization using DCs pulsed with TECs as vaccine antigens significantly suppressed solid tumor growth in a Colon-26 colorectal adenocarcinoma tumor-bearing mouse model, compared with the use of tumor cells as DC vaccine antigens. Tumor tissues showed reduced angiogenesis. However, vaccination using DCs pulsed with TECs did not inhibit physiological angiogenesis as evidenced by a wound healing assay. Additionally, in a B16/BL6 mouse melanoma lung metastasis model, DC vaccination using TECs derived not only from the same tumor tissue but from a different type of tumor also suppressed metastasis. These results thus show that cancer vaccine therapy targeting TECs is an effective therapy against angiogenesis in several types of cancer, but does not affect normal blood vessel growth.

Identification of Adenovirus-Derived Cell-Penetrating Peptide.

Cell-penetrating peptides (CPPs) have been highly anticipated as an efficient delivery system due to their ability to cross biological membranes and transport various cargoes into cells. In the present study, we have identified adenovirus-derived CPPs using various capsid-mutant adenovirus (Ad) vectors. First, we examined the endocytosis-inducing ability of these vectors. A fiber-shaft substituted Ad vector, Ad type 5 vector with the fiber shaft domain replaced by that derived from Ad type 35, induced the highest fluorescein isothiocyanate (FITC)-dextran uptake into a human liver cell line, HepG2 cells. In contrast, the FITC-dextran uptake in HepG2 cells was not significantly different between coxsackievirus and adenovirus receptor (CAR)-binding-ablated Ad vector, integrin-binding-ablated Ad vector or conventional Ad vector. Next, we produced a recombinant Ad type 35 shaft protein using the Escherichia coli recombinant system. The recombinant Ad type 35 shaft protein retained the ability for FITC-dextran uptake and efficient gene delivery by plasmid transfection reagent. Furthermore, we identified 26 C-terminal amino acids in the Ad type 35 shaft protein as the cell membrane binding domain. The 26 amino-acid peptides also have the potential to be internalized into cultured cells. The internalization ability of the peptide was dependent on degree and was inhibited by an actin polymerization inhibitor (Latrunculin B) and by a lipid raft formation inhibitor (methyl-ß-cyclodextrin). The results of the present study indicate that Ad type 35-derived peptides induce endocytosis in cultured cells and have the ability to cross biological membranes. This report is the first paper to identify Ad-derived CPPs.

Successful percutaneous coronary intervention for complex bifurcated lesions with combination of "Reverse wire technique" and "Reverse bent wiring with the crusade catheter" novel wire manipulation technique.

We encountered a case of percutaneous coronary intervention for complex bifurcated lesions in the mid portion of the left anterior descending (LAD) artery. The diagonal artery branched from the LAD artery with a markedly angulated pattern and there was severe stenosis from just proximal to this diagonal artery. The "reverse wire technique facilitated with the Crusade catheter" enabled us to cross a guidewire through to the markedly angulated diagonal side branch (SB). Next, we adopted a mini-crushing stent strategy for this true bifurcated lesion. Thereafter, we adopted "reverse bent wiring with the Crusade catheter" for wire re-crossing to the incarcerated side branch, and successfully completed all procedures. This technique for successful wire re-crossing is simple but can be very effective in specific situations in practical percutaneous coronary intervention (PCI). Many PCI operators may empirically adopt this kind of wire manipulation technique. However, this case is the first report in the world describing the application of a "reverse bent wiring with the Crusade catheter" for wire re-crossing through a double-folded stent strut to a SB at the optimal point of the bifurcation. In this case, we made the most of the Crusade catheter. This catheter is a very useful device for multifactorial use in practical PCI. It can help us to perform complex PCI procedures successfully.

Instructive percutaneous coronary intervention to avoid the risk of side branch occlusion at a lesion with a lotus root appearance: a case report.

BACKGROUND: A lotus root appearance is a rare entity, and there is little opportunity to perform coronary intervention for this kind of lesion. Because of its peculiar anatomical characteristics, one of the problems regarding percutaneous coronary intervention (PCI) for these lesions is related to the involvement of branch vessels. CASE PRESENTATION: We encountered a case of PCI for a stenotic lesion with a lotus root appearance in the mid-portion of the right coronary artery (RCA). To avoid the risk of right ventricular (RV) branch occlusion due to stent deployment in the main RCA, we re-crossed the third guidewire into the main RCA via the nearest point to the RV branch ostium through the communicating vascular lumen. Thereafter, we deployed a drug-eluting stent in the main RCA crossing over the RV branch, and the ostium of the RV branch remained intact, as we expected. CONCLUSIONS: This case is the first report in the world describing the details of how to maintain the patency of the side branch bifurcating from a lesion with a lotus root appearance under optical coherence tomography guidance.

Practical Usefulness of Dual Lumen Catheter-Facilitated Reverse Wire Technique for Markedly Angulated Bifurcated Lesions.

OBJECTIVES: This study aimed to investigate the practical usefulness of dual lumen catheter-facilitated reverse wire technique. BACKGROUND: We sometimes encounter difficulty in introducing a guidewire to the highly angulated side branch. In those cases, the reverse wire technique is considered as a last resort to overcome the situation. METHODS: Between January 2013 and June 2015, we performed the reverse wire technique for guidewire crossing into an extremely angulated side branch in consecutive seven cases with true bifurcated lesions. We retrospectively evaluated patients' backgrounds, lesion characteristics, and details of the percutaneous coronary intervention (PCI) procedures. RESULTS: Three interventional cardiologists with various levels of experience in coronary intervention performed this technique. A polymer-jacket hydrophilic-coated guidewire was used for the reverse wire system excluding in one case, and we adopted a sharp curve for the tip shape in all cases. After crossing the reverse wire into a highly angulated side branch, we usually deliver a flexible micro catheter over the guidewire for the purpose of guidewire exchange. We deployed a stent in the side branch in three cases. We successfully performed all PCI procedures without any complications and no major adverse cardiac event was observed during hospitalization. CONCLUSIONS: We could safely and effectively perform the reverse wire technique for guidewire crossing into a markedly angulated side branch. We recommend a polymer-jacket hydrophilic-coated guidewire with a sharp curve in the tip shape for this technique. All interventional cardiologists should acquire knowledge and skills regarding this guidewire manipulation technique.

Bilateral Transankle Intervention as a Critical Determinant of Successful Revascularisation in Complex Peripheral Arterial Disease.

Introduction: Establishing optimal vascular access sites is important for the procedural success of endovascular treatment (EVT) and the patient's comfort afterwards. Among the variety of vascular access sites, the transankle intervention (TAI) has been used more recently; however, there have been no reports of complex lower extremity arterial disease lesions treated with the TAI manoeuvre. Report: An 82 year old man with chronic limb threatening ischaemia in both lower extremities underwent EVT for bilateral long segment occlusion from the iliac arteries to the superficial femoral artery (SFA). The right posterior tibial artery was punctured under extravascular ultrasound guidance and a Parent Select 5082 guide sheath was inserted. The guidewire was manipulated under intravascular ultrasound (IVUS) guidance. When the first guidewire entered the subintimal space, the second guidewire was manipulated to advance through the intraplaque route, while monitoring it using IVUS. The intraluminal space of the right common iliac artery was reached by repeating these procedures. A self expandable stent was deployed in the external iliac artery and drug coated balloons were inflated from the common femoral artery to the SFA; good vascular patency and favourable blood flow were confirmed. Subsequently, a similar TAI procedure was performed from the left dorsalis pedis artery, and successful revascularisation was achieved from the left common iliac artery to the SFA. After revascularisation, the persistent pain disappeared in the right lower limb and the wound healed favourably in the left lower limb. Conclusion: In this case of complex chronic limb threatening ischaemia, the TAI strategy worked favourably for successful revascularisation. Transankle intervention can provide various advantages for successful EVT.

LEOPARD syndrome with accelerated idioventricular rhythm and systolic anterior motion of the posterior mitral leaflet: a case report.

Background: PTPN11 is ubiquitously expressed and has a variety of phenotypes even in a single heart. We examined LEOPARD syndrome (LS) in a patient with PTPN11 variants through pathological, electrophysiological, and anatomical studies. Case summary: A 49-year-old man with no previous medical history was brought to our emergency department because of syncope. An electrocardiogram (ECG) revealed alternating bundle branch block, and echocardiography revealed hypertrophic cardiomyopathy-like morphology with systolic anterior motion of the posterior mitral valve. Atrioventricular block, left ventricular outflow tract (LVOT) obstruction, and ventricular tachycardia were considered the differential diagnoses; however, the treatment plan was difficult to determine. An electrophysiological study revealed the cause of the ECG abnormality to be accelerated idioventricular rhythm, and the programmed ventricular stimulation was negative. Genetic testing revealed LS with PTPN11 variant, which was speculated to be the cause of these various unique cardiac features. The cause of syncope was considered to be exacerbation of LVOT obstruction due to dehydration, and the patient was treated with oral beta-blockers. Implantable loop recorder observation for 1 year revealed no arrhythmia causing syncope, and an implantable cardioverter-defibrillator and pacemaker were deemed unnecessary for primary prevention of syncope. During 2.5 years of follow-up, the LVOT peak velocity fluctuated between 2.5 and 3.5 m/s, but the patient remained stable with no recurrent syncope. Conclusion: We confirmed that LS is distinct from other cardiomyopathies using characterization, physiological, electrophysiological, and pathological examinations. Evidence supporting a specific treatment strategy for LS is limited, and understanding the pathogenesis may help establish effective treatment strategies.

Percutaneous Closure Based on Physiological Assessment of an Arteriovenous Fistula in a Patient With Chronic Limb Threatening Ischaemia.

Introduction: An arteriovenous fistula (AVF) is a potential complication of endovascular therapy (EVT). Arteriovenous fistula steal syndrome sometimes leads to severe limb ischaemia; however, assessment of peripheral perfusion in AVF has not yet been established. Report: A 90 year old woman diagnosed with chronic limb threatening ischaemia underwent EVT. However, subintimal angioplasty of infrapopliteal lesions resulted in AVF formation in the posterior tibial artery (PTA). Revascularisation of the anterior tibial artery and PTA was performed, but severe AVF steal syndrome persisted and wound healing was delayed. An attempt to physiologically assess the effects of AVF closure and perform an AVF closing manoeuvre, if necessary, was performed. The physiological assessment was performed by laser Doppler flowmetry (LDF) and blood flow was temporarily blocked via the AVF at the distal PTA using a 6 F guiding extension catheter. A significant increase in blood flow was observed in the perfused area of the plantar artery. Coil embolisation and covered stent implantation in the PTA completely closed the AVF. During the procedure, peripheral perfusion with LDF gradually increased in the heel and fifth toe. After AVF closure, the skin perfusion pressure values increased significantly, wound healing was accelerated, and complete healing was achieved. Discussion: Laser Doppler flowmetry measurements under simulated AVF closure using a guiding extension catheter may be useful for the physiological assessment of peripheral perfusion before percutaneous AVF closure.

Dilated cardiomyopathy-associated FHOD3 variant impairs the ability to induce activation of transcription factor serum response factor.

BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by a dilated left ventricular cavity with systolic dysfunction manifested by heart failure. It has been revealed that mutations in genes for cytoskeleton or sarcomere proteins cause DCM. However, the disease-causing mutations can be found only in far less than half of patients with a family history, indicating that there should be other disease genes for DCM. Formin homology 2 domain containing 3 (FHOD3) is a sarcomeric protein expressed in the heart that plays an essential role in sarcomere organization during myofibrillogenesis. The purpose of this study was to explore a possible novel disease gene for DCM. METHODS AND RESULTS: We analyzed 48 Japanese familial DCM patients for mutations in FHOD3, and a missense variant, Tyr1249Asn, which was predicted to modify the 3D structure and damage protein function, was found in a case with adult-onset DCM. Functional studies revealed that the DCM-associated mutation significantly reduced the ability to induce actin dynamics-dependent activation of serum response factor, although no remarkable change in the cellular localization was induced in neonatal rat cardiomyocytes transfected with a mutant construct of FHOD3. CONCLUSIONS: The DCM-associated FHOD3 variant may cause DCM by interfering with actin filament assembly.

Clinical characteristics of silent myocardial ischemia diagnosed with adenosine stress 99mTc-tetrofosmin myocardial scintigraphy in Japanese patients with acute cerebral infarction.

It is well known that silent myocardial ischemia (SMI) often complicates patients with cerebral infarction and that stroke patients often die of ischemic heart disease. Therefore, it is considered important to treat myocardial ischemia in stroke patients. This study investigated SMI complicating Japanese patients with fresh stroke, using (99m)Tc-tetrofosmin myocardial scintigraphy with pharmacologic stress testing to elucidate their clinical manifestations. This study included 41 patients (26 men, mean age 76.0 ± 10.7 years) with acute cerebral infarction and no history of coronary artery disease. All patients underwent (99m)Tc-tetrofosmin myocardial scintigraphy with intravenous administration of adenosine to diagnose SMI. Of the 41 patients, myocardial ischemia was confirmed in 17 patients (41.5%). Atherosclerotic etiology was the major cause of stroke in the ischemia(+) group and embolic origin was the major cause in the ischemia(-) group. Patients with myocardial ischemia had a higher incidence of diabetes mellitus (52.9 vs 20.8%; P = 0.0323) and more than two conventional cardiovascular risk factors (64.7 vs 25.0%; P = 0.0110) compared with the nonischemic patients. Infarction subtype of atherosclerotic origin was an independent positive predictor of asymptomatic myocardial ischemia in patients with stroke. These findings indicate that the prevalence of asymptomatic myocardial ischemia is relatively high, especially in patients with stroke of atherosclerotic origin. Therefore, it is beneficial for us to narrow the target population who are at the highest risk when screening for SMI in Japanese patients with acute cerebral infarction.

Inframalleolar thrice distal puncture in a single endovascular treatment session for successful revascularization.

BACKGROUND: Most patients with chronic limb-threatening ischemia (CLTI) have infrapopliteal arterial disease, which are often challenging to treat. In endovascular treatment (EVT) for these complex lesions, establishing retrograde access is an essential option not only for guidewire crossing but also for device delivery. However, no EVT case has yet been reported requiring inframalleolar thrice distal puncture in a single EVT session so far. CASE PRESENTATION: A 60-year-old CLTI patient with grade 3 Wound, Ischemia and foot Infection (WIfI) classification underwent EVT for occluded dorsal artery and posterior tibial artery. First, we conducted successful balloon angioplasty of the posterior tibial artery by establishing a retrograde approach via the lateral plantar artery. To treat the occlusion of the dorsal artery, we punctured the first dorsal metatarsal artery, and retrogradely advanced a guidewire to the dorsal artery occlusion; however, the microcatheter could not follow the guidewire. Therefore, we punctured the occluded distal anterior tibial artery and introduced the retrograde guidewire into the puncture needle. After guidewire externalization, we pulled up the retrograde microcatheter into the occlusion of dorsal artery using the "balloon deployment using forcible manner" technique. Thereafter, we were able to advance the antegrade guidewire into the retrograde microcatheter. After guidewire externalization, an antegrade balloon catheter was delivered and inflated for the purpose of dorsal artery dilation and hemostasis at the "needle rendezvous" point. Consecutively, balloon dilation was performed for puncture site hemostasis of the first dorsal metatarsal artery and complete hemostasis was achieved. Finally, we confirmed good vascular patency and favorable blood flow. After revascularization, transmetatarsal amputation was performed and the wound healed favorably. CONCLUSIONS: We can markedly increase the success rate of revascularization by effectively utilizing the retrograde approach in EVT for complex chronic total occlusions in infrapopliteal arterial diseases.

Early experience with coronary debulking devices in a newcomer facility after introducing revised facility criteria in Japan.

Coronary debulking devices are essential in obtaining optimal results in percutaneous coronary intervention (PCI) for severely calcified lesions. However, since the introduction of these devices in Japan, the presence of full-time cardiovascular surgeons in their own facilities has been an essential condition (on-site surgical back-up) as the facility criteria for their use. The criteria were revised in April 2020, making their implementation possible at our hospital. Between May 2020 and January 2022, we administered PCIs using rotational atherectomy (RA) for 33 lesions in 28 patients and orbital atherectomy system (OAS) for 36 lesions in 27 patients. The most preferred strategy in our hospital is OAS via the distal radial approach using a 6Fr Glide sheath or RA via the femoral approach using a 7Fr sheath. The percentages of usable imaging modality as an initial device without lesion modification were 57.1 and 66.7% in the RA and OAS groups, respectively. In the RA procedure, 1.5- and 2.0-mm Rota burrs were more frequently adopted for the initial and second sessions, respectively. In the OAS procedure, the debulking was always initiated at a low speed. Nineteen of the 27 patients underwent additional high-speed debulking. Pre-procedural quantitative coronary angiographic analysis revealed that the minimal lumen diameter was significantly smaller in the RA than in the OAS group. Debulking procedures were successful in all patients excluding two instances of procedure-related complications in the RA group, one of which was coronary perforation safely treated via covered stent deployment without any resulting hemodynamic instability. Our early experience with coronary debulking devices with off-site surgical back-up clearly reveals the safety and feasibility of this procedure in a newcomer facility.