A case of destination therapy for post-fulminant myocarditis with myelodysplastic syndrome.

We encountered a 64-year-old woman who experienced fulminant myocarditis and underwent treatment with veno-arterial extracorporeal membrane oxygenation and Impella CP support. Subsequently, she underwent a device upgrade to Impella 5.5 and received continuous hemodiafiltration for 3 months. During mechanical circulatory support, she developed refractory anemia and thrombocytopenia, leading to a diagnosis of myelodysplastic syndrome. Following the removal of the devices, she no longer required blood transfusions. She received HeartMate 3 left ventricular assist device implantation as a destination therapy indication despite the presence of myelodysplastic syndrome. She was successfully managed by aspirin-free antithrombotic therapy without any hemocompatibility-related adverse events for 4 months after index discharge on foot. We present a patient with a unique and rare presentation, wherein HeartMate 3 was implanted and successfully managed without aspirin to prevent bleeding complications associated with myelodysplastic syndrome.

Successful management of HeartMate 3 in a patient with arrhythmogenic right ventricular cardiomyopathy.

The management of right heart failure during durable left ventricular assist device (LVAD) support remains an unsolved issue so far. We had a 44-year-old male patient who was diagnosed with arrhythmogenic right ventricular cardiomyopathy and received HeartMate 3 LVAD (Abbott, USA) implantation as a bridge-to-transplant indication. The pump speed was adjusted as low as 4500 rpm to avoid the left ventricular narrowing and interventricular septal leftward shift. Riociguat was administered to decrease the afterload of the right ventricle and increase the preload of the left ventricle, in addition to the combination of neurohormonal blockers. Frequent low-flow alarm events eventually disappeared after amlodipine administration, and he was successfully returned to work. We here present a unique management in a patient with right heart failure due to arrhythmogenic right ventricular cardiomyopathy during HeartMate 3 LVAD support.

Successful treatment of nephrotic syndrome due to pregnancy-related crescentic IgA nephropathy: a case report.

BACKGROUND: Crescentic immunoglobulin A (IgA) nephropathy, defined as > 50% of the glomeruli with crescents, often has a poor renal prognosis. Because of the high prevalence of pre-eclampsia in the second trimester of pregnancy, we often fail to investigate the new onset of glomerulonephritis and the aggravation of subclinical nephropathies. We report a case of nephrotic syndrome suggestive of crescentic IgA nephropathy possibly triggered by pregnancy. CASE PRESENTATION: A 33-year-old multipara was referred for persistent proteinuria, hematuria, and hypoalbuminemia two months postpartum. The patient was diagnosed with proteinuria for the first time at 36 weeks of gestation. The patient was normotensive during pregnancy. Renal biopsy revealed crescentic IgA nephropathy, with cellular crescents in 80% of the glomeruli and no global sclerosis. After treatment with pulse steroids followed by high-dose oral glucocorticoids and tonsillectomy, a gradual improvement was seen in proteinuria, hematuria, and hypoalbuminemia. CONCLUSION: Although the precise mechanism remains unclear, pregnancy possibly triggered the new onset of crescentic IgA nephropathy or the aggravation of subclinical IgA nephropathy.

Association between intraoperative pulmonary artery pressure and cardiovascular complications after off-pump coronary artery bypass surgery: a single-center observational study.

BACKGROUND: The impact of intraoperative pulmonary hemodynamics on prognosis after off-pump coronary artery bypass (OPCAB) surgery remains unknown. In this study, we examined the association between intraoperative vital signs and the development of major adverse cardiovascular events (MACE) during hospitalization or within 30 days postoperatively. METHODS: This retrospective study analyzed data from a university hospital. The study cohort comprised consecutive patients who underwent isolated OPCAB surgery between November 2013 and July 2021. We calculated the mean and coefficient of variation of vital signs obtained from the intra-arterial catheter, pulmonary artery catheter, and pulse oximeter. The optimal cut-off was defined as the receiver operating characteristic curve (ROC) with the largest Youden index (Youden index = sensitivity + specificity - 1). Multivariate logistic regression analysis ROC curves were used to adjust all baseline characteristics that yielded P values of < 0.05. RESULTS: In total, 508 patients who underwent OPCAB surgery were analyzed. The mean patient age was 70.0 ± 9.7 years, and 399 (79%) were male. There were no patients with confirmed or suspected preoperative pulmonary hypertension. Postoperative MACE occurred in 32 patients (heart failure in 16, ischemic stroke in 16). The mean pulmonary artery pressure (PAP) was significantly higher in patients with than without MACE (19.3 ± 3.0 vs. 16.7 ± 3.4 mmHg, respectively; absolute difference, 2.6 mmHg; 95% confidence interval, 1.5 to 3.8). The area under the ROC curve of PAP for the prediction of MACE was 0.726 (95% confidence interval, 0.645 to 0.808). The optimal mean PAP cut-off was 18.8 mmHg, with a specificity of 75.8% and sensitivity of 62.5% for predicting MACE. After multivariate adjustments, high PAP remained an independent risk factor for MACE. CONCLUSIONS: Our findings provide the first evidence that intraoperative borderline pulmonary hypertension may affect the prognosis of patients undergoing OPCAB surgery. Future large-scale prospective studies are needed to verify the present findings.

X-linked Alport Syndrome with Type IV Collagen α5 Chain Staining Revealing Normal Expression in the Glomerular Basement Membrane and Negative on Bowman's Capsule and Distal Tubular Basement Membrane: A Case Report.

X-linked Alport syndrome is a hereditary progressive renal disease resulting from the disruption of collagen α3α4α5 (IV) heterotrimerization caused by pathogenic variants in the COL4A5 gene. This study aimed to report a male case of X-linked Alport syndrome with a mild phenotype accompanied by an atypical expression pattern of type IV collagen α5 [α5 (IV)] chain in glomerulus. A 38-year-old male presented with proteinuria (2.3 g/day) and hematuria. He has been detected urinary protein and occult blood since childhood. A renal biopsy was performed at the age of 29 years; however, a diagnosis of Alport syndrome was not considered. A renal biopsy 9 years later revealed diffuse thinning and lamellation of the glomerular basement membrane. Α staining for α5 (IV) revealed a normal expression pattern in the glomerular basement membrane and a complete negative expression in Bowman's capsule and distal tubular basement membrane. Using next-generation sequencing, we detected a COL4A5 missense variant within exon 35 (NM_000495.5: c.3088G>A, p. G1030S). The possibility of X-linked Alport syndrome should be considered when negative expression of α5 (IV) staining on Bowman's capsule was observed.

[Thoracic Endovascular Aortic Repair for Mycotic Thoracic Aortic Aneurysm After BCG Intravesical Therapy].

Bacille Calmette-Guérin( BCG) intravesical therapy is an effective and safe treatment for bladder cancer; however, mycotic aneurysms have been reported as a rare complication. Case 1:A 64-year-old man with a history of BCG intravesical therapy underwent emergent thoracic endovascular aortic repair (TEVAR) for a ruptured thoracic aortic aneurysm (TAA). He was diagnosed with BCG infection by hemosputum specimen culture five months later;then, antituberculous therapy was initiated. However, his follow-up computed tomography scan revealed stent-graft infection and new aneurysm formation. Therefore, we performed a repeated TEVAR with abdominal 4-vessel debranching. There was no recurrence of infection for six years while continuing postoperative antituberculous therapy. Case 2:A 72-year-old man who had undergone BCG intravesical therapy underwent TEVAR for a rapidly enlarging mycotic TAA. He received anti-tuberculous therapy for one year with no recurrent infection for one year. TEVAR may be an effective alternative to the open surgical procedure;however, multidisciplinary treatment including anti-tuberculous therapy and careful long-term follow up are required.

Transcatheter closure of patent foramen ovale accompanying right-to-left shunt during Impella support.

We experienced a 65-year-old woman who was diagnosed as fulminant myocarditis and transferred on mechanical ventilator and veno-arterial extracorporeal membrane oxygenation (ECMO) supports. Impella 5.0 support was additionally initiated to improve pulmonary edema and unload left ventricle. We found a patent foramen ovale (PFO) at the time of Impella insertion by transesophageal echocardiography. Follow-up transesophageal echocardiography found a development of right-to-left shunt flow through PFO accompanying central hypoxia during Impella P8 support. Veno-arterial ECMO was converted to veno-arterio-venous ECMO and PFO was occluded percutaneously on the next day, which stabilized hemodynamics and systemic oxygen supply. In case of Impella 5.0 support, the existence of PFO and the development of right-to-left shunt flow should be carefully surveyed and closed immediately to maintain hemodynamics and systemic oxygen supply.

A Rescue Use of ECPELLA for Sepsis-Induced Cardiogenic Shock Followed by Mitral Valve Replacement.

The use of veno-arterial extracorporeal membrane oxygenation (ECMO) in patients with sepsis-induced cardiogenic shock has been reported, but the clinical implication of the Impella percutaneous axial-flow left ventricular assist device for such patients remains unknown. We had a 37-year-old man with septic shock and severely reduced cardiac function. Veno-arterial ECMO and concomitant Impella CP support ameliorated his end-organ dysfunction and achieved cardiac recovery, whereas severe mitral valve regurgitation due to chordal rupture developed later. Mitral valve replacement concomitant with ECMO removal as well as an Impella upgrade successfully treated the patient. ECMO and Impella support might be an effective therapeutic strategy for the bridge to recovery in patients with sepsis-induced cardiogenic shock; however, paying attention to mitral chordal rupture is highly encouraged.

Trans-Apical Transcatheter Aortic Valve Replacement in a Dialysis Patient with Systolic Heart Failure.

Mortality and morbidity remain high following transcatheter aortic valve replacement (TAVR) in dialysis patients or those with low left ventricular ejection fraction. Therapeutic strategy for those with these comorbidities remains unestablished. We had a dialysis patient with peripheral artery disease and low left ventricular ejection fraction, who received successfully scheduled trans-apical TAVR following sufficient reverse remodeling by 3-month optimal medical therapy. Our strategy should be validated in a larger robust cohort.

Prognostic implication of risk scoring systems in patients with cardiogenic shock supported by ECMO and Impella.

We experienced two refractory cardiogenic shock patients receiving veno-arterial extracorporeal membrane oxygenation and Impella percutaneous left ventricular assist device (ECPELLA). TVAD score, which was originally proposed to predict one-year mortality following left ventricular assist device implantation using four objective parameters, was retrospectively calculated using data of day 3 following ECPELLA initiations. One patient with estimated intermediate risk could achieve successful explantation of ECPELLA, whereas another patient with estimated high risk was expired despite explantation of extracorporeal membrane oxygenation. TVAD score might be a useful tool to risk stratify and construct next strategy (i.e., bridge to recovery or bridge to more intensive therapy) for those with ECPELLA, although further studies are warranted to validate this hypothesis.

Peak Lag Between Plasma Vasopressin and Urine Aquaporin-2 Following Cardiac Surgery.

Tolvaptan, a vasopressin type-2 receptor antagonist, is utilized to ameliorate fluid retention following cardiac surgery. However, the optimal timing of tolvaptan administration considering novel biomarkers remains unknown. We prospectively included patients who underwent cardiac surgery between 2016 and 2020. We measured perioperative trends of free water reabsorption mediators including plasma arginine vasopressin and urine aquaporin-2. A total of 20 patients (68 [60, 75] years old, 18 men) were included. Urine volume decreased gradually after the initial 3 hours following cardiac surgery. The plasma arginine vasopressin level increased significantly with a peak at postoperative 6 hours, whereas the urine aquaporin-2 level increased later with a delayed peak at postoperative 12 hours. As a result, urine aquaporin-2 relative to the plasma arginine vasopressin level, which represents the activity of the collecting ducts and indicates predicted responses to tolvaptan, was a minimum at postoperative 6 hours. Tolvaptan administration immediately after cardiac surgery might not be recommended given the transient refractoriness to tolvaptan probably due to the stunning of kidney collecting ducts.

Impella support as a bridge to scheduled surgical repair of ventricular septal rupture.

We studied the experience of a 69-year-old woman with acute decompensated heart failure due to post-infarction ventricular septal rupture. She received mechanical hemodynamic support by Impella 2.5 (Abiomed, Danvers, MA, USA), percutaneous axial-flow left ventricular assist device, which improved intra-cardiac pressure, maintaining end-organ function. She was successfully bridged to the scheduled surgical repair of ventricular septal rupture following the 9-day Impella support and discharged on foot on the 32nd day. Impella might be a useful mechanical circulatory support device as a bridge tool to the scheduled surgical repair of ventricular septal rupture if used with careful daily management to prevent device-related comorbidities.

Congenital vascular ring.

A vascular ring is a rare congenital cardiovascular anomaly, which encircles and compresses the trachea or esophagus, or both. In this review we discuss the pathophysiology, theoretical embryopathogenesis, diagnostic modalities, and surgical treatment of the different types of vascular ring. Knowledge of the normal embryonic development of the aortic arch and related structures is important for understanding and classifying the various forms of vascular ring. The development of a vascular ring begins with the embryonic aortic arch system. The persistence, involution, or regression of the arches determines the multiple variations of vascular ring. With the development of new technologies, multi-detector computed tomography (MDCT) has become a good diagnostic modality for pre- and postoperative evaluation. MDCT provides an excellent image of aortic arch abnormalities and the related anatomy, as well as the tracheal pathology. For patients with symptoms, surgical division of the vascular ring usually achieves excellent outcomes with marked resolution of symptoms and a low risk of morbidity and mortality. Symptomatic vascular rings require early surgical intervention to prevent prolonged vascular compression of the airway and serious complications.

Paracorporeal Ventricular Assist Device Implantation in a Patient with Transposition of the Great Arteries After Senning Operation.

We experienced a 33-year-old patient with D-looped transposition of the great arteries (D-TGA) and a history of Senning operation who was referred to our institute with cardiogenic shock and subsequently underwent urgent paracorporeal ventricular assist device (VAD) implantation, which was a first in Japan, that was eventually converted to a durable VAD. Central venous pressure was maintained relatively high to obtain VAD filling and recover end-organ dysfunction, given the migration of the inflow cannula due to rich trabeculae carneae of the anatomical right ventricle (systemic ventricle in this case).

Myo-inositol oxygenase accentuates renal tubular injury initiated by endoplasmic reticulum stress.

Besides oxidant stress, endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of various metabolic disorders affecting the kidney. These two forms of stresses are not mutually exclusive to each other and may operate by a feedback loop in worsening the cellular injury. To attest to this contention, studies were performed to assess whether in such a setting, there is worsening of tubulointerstitial injury. We employed tunicamycin as a model of ER stress and used tubular cells and mice overexpressing myo-inositol oxygenase (MIOX), an enzyme involved in glycolytic events with excessive generation of ROS. Concomitant treatment of tunicamycin and transfection of cells with MIOX-pcDNA led to a marked generation of ROS, which was reduced by MIOX-siRNA. Likewise, an accentuated expression of ER stress sensors, GRP78, XBP1, and CHOP, was observed, which was reduced with MIOX-siRNA. These sensors were markedly elevated in MIOX-TG mice compared with WT treated with tunicamycin. This was accompanied with marked deterioration of tubular morphology, along with impairment of renal functions. Interestingly, minimal damage and elevation of ER stressors was observed in MIOX-KO mice. Downstream events that were more adversely affected in MIOX-TG mice included accentuated expression of proapoptogenic proteins, proinflammatory cytokines, and extracellular matrix constituents, although expression of these molecules was unaffected in MIOX-KO mice. Also, their tunicamycin-induced accentuated expression in tubular cells was notably reduced with MIOX-siRNA. These studies suggest that the biology of MIOX-induced oxidant stress and tunicamycin-induced ER stress are interlinked, and both of the events may feed into each other to amplify the tubulointerstitial injury.

All-trans retinoic acid suppresses bone morphogenetic protein 4 in mouse diabetic nephropathy through a unique retinoic acid response element.

Diabetic nephropathy (DN) causes mesangial matrix expansion, which results in glomerulosclerosis and renal failure. Collagen IV (COL4) is a major component of the mesangial matrix that is positively regulated by bone morphogenetic protein 4 (BMP4)/suppressor of mothers against decapentaplegic (Smad1) signaling. Because previous studies showed that retinoids treatment had a beneficial effect on kidney disease, we investigated the therapeutic potential of retinoids in DN, focusing especially on the regulatory mechanism of BMP4. Diabetes was induced with streptozotocin in 12-wk-old male Crl:CD1(ICR) mice, and, 1 mo later, we initiated intraperitoneal injection of all-trans retinoic acid (ATRA) three times weekly. Glomerular matrix expansion, which was associated with increased BMP4, phosphorylated Smad1, and COL4 expression, worsened in diabetic mice at 24 wk of age. ATRA administration alleviated DN and downregulated BMP4, phosopho-Smad1, and COL4. In cultured mouse mesangial cells, treatment with ATRA or a retinoic acid receptor-α (RARα) agonist significantly decreased BMP4 and COL4 expression. Genomic analysis suggested two putative retinoic acid response elements (RAREs) for the mouse Bmp4 gene. Chromatin immunoprecipitation analysis and reporter assays indicated a putative RARE of the Bmp4 gene, located 11,488-11,501 bp upstream of exon 1A and bound to RARα and retinoid X receptor (RXR), which suppressed BMP4 expression after ATRA addition. ATRA suppressed BMP4 via binding of a RARα/RXR heterodimer to a unique RARE, alleviating glomerular matrix expansion in diabetic mice. These findings provide a novel regulatory mechanism for treatment of DN.

A case of cardiogenic shock due to acute coronary syndrome successfully recovered by percutaneous and paracorporeal left ventricular assist device.

We recently experienced a 70-year-old woman with left main trunk-acute coronary syndrome who was initially supported by Impella 5.0 which converted to paracorporeal left ventricular assist device (LVAD) implantation as a bridge to recovery. Optimized guideline-directed medical therapy with cardiac rehabilitation resulted in successful explantation of LVAD and she discharged on foot.

Influence of albumin leakage on glycated albumin in patients with type 2 diabetes undergoing hemodialysis.

Glycated albumin (GA) is recommended as a better glycemic indicator than HbA1c in patients undergoing hemodialysis, because the red blood cell lifespan is generally faster than that in normal subjects. However, GA can be also affected by protein loss in urine and hemodialysis fluid. Therefore, in this study, we investigated the effect of albumin leakage induced by hemodialysis on GA. Nine patients undergoing hemodialysis with a large or small amount of albumin leakage were observed for 9 months in a crossover manner. As a result, it was shown that albumin leakage could affect GA, but the effect was practically small considering the prescription of diabetic drugs. The correlations between HbA1c and blood glucose levels and between GA and blood glucose levels were similar in our study. In conclusion, GA was a reliable indicator, even with the change of hemodialysis modality. The influence of albumin leakage induced by hemodialysis on GA was negligible practically. We should recognize that the preferable glycemic indicator in patients undergoing hemodialysis depends on the hemoglobin and albumin metabolism of each patient.

Complications after spinal fixation surgery for osteoporotic vertebral collapse with neurological deficits: Japan Association of Spine Surgeons with ambition multicenter study.

BACKGROUND: There have been few reports on the incidence and risk factors of the complications after spinal fixation surgery for osteoporotic vertebral collapse (OVC) with neurological deficits. This study aimed to identify the incidence and risk factors of the complications after OVC surgery. METHODS: In this retrospective multicenter study, a total of 403 patients (314 women and 89 men; mean age 73.8 years) who underwent spinal fixation surgery for OVC with neurological deficits between 2005 and 2014 were enrolled. Data on patient demographics were collected, including age, sex, body mass index, smoking, steroid use, medical comorbidities, and surgical procedures. All postoperative complications that occurred within 6 weeks were recorded. Patients were classified into two groups, namely, complication group and no complication group, and risk factors for postoperative complications were investigated by univariate and multivariate analyses. RESULTS: Postoperative complications occurred in 57 patients (14.1%), and the most common complication was delirium (5.7%). In the univariate analysis, the complication group was found to be older (p = 0.039) and predominantly male (p = 0.049), with higher occurrence rate of liver disease (p = 0.001) and Parkinson's disease (p = 0.039) compared with the no-complication group. In the multivariate analysis, the significant independent risk factors were age (p = 0.021; odds ratio [OR] 1.051, 95% confidence interval [CI] 1.007-1.097), liver disease (p < 0.001; OR 8.993, 95% CI 2.882-28.065), and Parkinson's disease (p = 0.009; OR 3.636, 95% CI 1.378-9.599). CONCLUSIONS: Complications after spinal fixation surgery for OVC with neurological deficits occurred in 14.1%. Age, liver disease, and Parkinson's disease were demonstrated to be independent risk factors for postoperative complications.

Transcatheter Aortic Valve Implantation Improves Cardiac Sympathetic Nerve Activity on 123I-Metaiodobenzylguanidine Myocardial Scintigraphy in Severe Aortic Valve Stenosis.

BACKGROUND: There is a consensus that overactivation of the cardiac sympathetic nervous system (CSN) proportionately increases the severity of heart failure and is accompanied by worse prognosis. Because it is unknown whether patients with aortic valve stenosis (AS) have similar CSN activation, we investigated the effect of transcatheter aortic valve implantation (TAVI).Methods and Results:We enrolled 31 consecutive patients with AS treated by TAVI. 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed at baseline and at 2 weeks after TAVI. At baseline, the early heart-mediastinum ratio (H/M) was within normal limits (3.0±0.5), but the delayed H/M was low (2.6±0.6) and the washout rate (WR) was high (34±13%). WR negatively correlated with aortic valve area (r=-0.389, P<0.01) and cardiac output (r=-0.595, P<0.01) and positively correlated with norepinephrine (r=0.519, P<0.01) and log NT-proBNP level (r=0.613, P<0.01). After TAVI, there were significant decreases in the norepinephrine level (366±179 ng/mL vs. 276±125 ng/mL, P<0.01) and WR (34±13 vs. 26±11%, P<0.01). CONCLUSIONS: The WR of MIBG was a useful marker of CSN activity and severity of AS. Immediate improvement of CSN activity after TAVI implied that AS hemodynamics per se enhanced CSN.