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.

Radiological findings associated with postoperative wound infection after extraction of impacted mandibular third molar: A retrospective study.

INTRODUCTION: Studies directly relating radiological findings to the risk of postoperative wound infection (PWI) in impacted mandibular third molars (M3) are limited and poorly understood. This study aimed to clarify the radiological risk of PWI. MATERIALS AND METHODS: Twenty-six patients who developed PWI after M3 extraction were retrospectively analyzed using orthopantomography (OPG) and computed tomography (CT) before M3 extraction to determine the association between M3 impaction status and PWI. These were compared with an equal number of non-infected groups. Moreover, the possibility of assessing the same risk in OPG as in CT imaging was examined. RESULTS: Multivariate analysis identified class III and position B of the Pell and Gregory classification system as independent risk factors for PWI. On CT, an axial overlap distance (AOD) >3.5 mm was significantly associated with PWI. Furthermore, the sagittal overlap distance (SOD) and AOD of the OPG were significantly greater in group III-B. A strong positive correlation was observed between SOD and AOD. CONCLUSION: These results indicate that class III, position B, and an AOD >3.5 mm may be novel risk factors for M3 PWI. The strong correlation between SOD and AOD suggests that the risk assessment for PWI can be performed by evaluating OPG alone.

A Clinical Diagnosis of Laminopathy without Systolic Dysfunction: When Does Nuclei Malformation Start?

Nuclear shape abnormalities in laminopathy are well known to occur in patients with cardiac systolic dysfunction. However, those in patients without systolic dysfunction are still unclear. We herein report a 42-year-old man who presented with advanced atrioventricular block without systolic dysfunction. Genetic testing identified a laminopathic mutation, c.497G>C, and an endocardial biopsy was performed. The hyperperfine structure on electron microscopy showed malformation of the nuclei, euchromatic nucleoplasm, and partial existence of heterochromatin clumps. Intrusion of heterochromatin into the nuclear fibrous lamina was observed. Cardiomyocyte nuclear shape abnormalities were observed before the progression of systolic dysfunction.

Prognostic Impact of the Increase in Cardiac Troponin Levels during Tafamidis Therapy in Patients with Transthyretin Cardiac Amyloidosis.

BACKGROUND: Recent clinical trials have demonstrated that tafamidis (Pfizer Inc., New York, NY, USA) reduced all-cause mortality and the number of cardiovascular hospitalizations compared with placebo in patients with transthyretin cardiac amyloidosis. However, the optimal surrogate markers during tafamidis treatment remain unknown. METHODS: Consecutive patients with transthyretin cardiac amyloidosis who received tafamidis in our institute between May 2019 and December 2022 were retrospectively evaluated. The prognostic impact of an increase in troponin I levels during tafamidis therapy was evaluated. RESULTS: A total of 18 patients (median age 77 years, 84% male) were included. For 14-month tafamidis therapy on median, cardiac troponin I levels increased in five patients. The cumulative incidence of all-cause hospitalization was significantly higher in the troponin-increased group than in the others (100% versus 33%, p < 0.0001). Troponin increase was independently associated with the cumulative incidence of all-cause hospitalization with an adjusted hazard ratio of 5.14 (95% confidence interval 1.02-25.9, p = 0.048). CONCLUSIONS: The increase in cardiac troponin levels may be a reasonable surrogate marker of response to tafamidis therapy in patients with transthyretin cardiac amyloidosis.

Initial experience of hypoxia-inducible factor prolyl hydroxylase inhibitors in patients with heart failure and renal anemia.

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors might improve renal anemia maintaining fewer cardiovascular complications. However, its safety and efficacy, as well as its impact on inflammatory biomarkers, in heart failure patients remain unknown. We initiated HIF-PH inhibitors in 13 patients with chronic heart failure and renal anemia (median age 77 years, median estimated glomerular filtration rate 24.9 mL/min/1.73m2) between September 2021 and February 2022. There were no drug-related complications, except for a patient who had a headache and hot flash, resulting in discontinuation of HIF-PH inhibitor at 3 months. Among 10 patients who continued HIF-PH inhibitors for over 3 months, hemoglobin levels increased significantly (median from 9.6 g/dL to 10.7 g/dL, p = 0.004) and hepcidin-25 levels tended to decrease (median from 11.5 ng/mL to 3.0 ng/mL, p = 0.294) at 3-month follow-up. In conclusion, HIF-PH inhibitors might be safe and effective for the treatment of renal anemia in patients with chronic heart failure.

Impact of the elevated angiopoietin-2 levels during Impella support on the short-term prognosis.

Elevated serum angiopoietin-2 levels in patients with acute myocardial infarction-related cardiogenic shock with and without intra-aortic balloon pump as well as acute decompensated heart failure are associated with short-term mortality. However, its prognostic impact in patients with cardiogenic shock supported by Impella-incorporated mechanical circulatory support (MCS) remains unknown. Patients who received temporary MCS (Impella alone or Impella and veno-arterial extracorporeal membrane oxygenation) in our institute between August 2018 and January 2022 were included in this prospective study. The serum levels of angiopoietin-2 were measured just before and following the initiation of temporary MCS therapy. Association between the levels of serum angiopoietin-2 and 30-day mortality was investigated. A total of 38 patients (median 72 years old, 63% men) were included. The median levels of serum angiopoetin-2 tended to decrease from baseline to 4 days following the initiation of temporary MCS from 5.2 (3.3, 10.5) ng/mL to 4.8 (2.7, 6.8) ng/mL (p = 0.132). A higher angiopoietin-2 (> 6.8 ng/mL) following the initiation of temporary MCS was associated with higher 30-day mortality (89.7% versus 44.4%, p = 0.0048) with an odds ratio 18.946 (95% confidence interval 1.624-218.695, p = 0.018) adjusted for potential confounders. A higher serum angiopoietin-2 level following the initiation of Impella-incorporated temporary MCS, instead of baseline angiopoetin-2 level, was associated with higher short-term mortality.

Successful Management of Pheochromocytoma Crisis with Cardiogenic Shock by Percutaneous Left Ventricular Assist Device.

Therapeutic strategy utilizing mechanical circulatory supports in patients with pheochromocytoma-related cardiogenic shock remains unestablished. We had a 51-year-old man with acute decompensated heart failure due to pheochromocytoma crisis. He received a percutaneous left ventricular assist device-supported alpha-blocker and intensive fluid infusion therapy, which ameliorated impaired end-organ dysfunction, maintaining hemodynamics and achieving cardiac recovery, followed by the successfully scheduled adrenalectomy. Early suspicion of pheochromocytoma and Impella-supported disease-specific medical management might be a promising bridge to surgery strategy.

Arrhythmogenic Right Ventricular Cardiomyopathy Accompanied by Chronic Myocarditis.

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) classically present with ventricular arrhythmias and less commonly heart failure. ARVC is an inherited cardiomyopathy and generally based on a variant of desmosomal genes. Recently, the association between myocardial inflammation and ARVC has been a matter of great concern. We encountered a patient with ARVC who had a desmoglein-2 mutation with advanced right ventricular failure accompanying a preserved left ventricular function. Concomitant right ventricular myocarditis was detected four years after the diagnosis of ARVC. ARVC and myocarditis might have a deep pathophysiological association, at least in some cases.

Therapeutic Strategy for Heart Failure with Reduced Ejection Fraction and Cardiac Amyloidosis.

We sometimes encounter patients with systolic heart failure and cardiac amyloidosis. Neurohormonal blockers are guideline-directed medical therapy for those with systolic heart failure. However, its implication among the above cohort remains controversial. Of 3 patients with systolic heart failure and cardiac amyloidosis who we encountered, cardiac reverse remodeling was achieved in 2 patients who received neurohormonal blockers, whereas cardiac function remained unchanged in a patient not receiving neurohormonal blockers. Neurohormonal blockers might be keys to achieve cardiac reverse remodeling and favorable clinical outcomes even in patients with systolic heart failure and cardiac amyloidosis, although further larger-scale studies are required to validate our hypothesis.

A Case of T/NK-Cell Post-Transplantation Lymphoproliferative Disease 7 Years after Heart Transplantation.

Post-transplant lymphoproliferative diseases (PTLD) are potentially fatal complications after cardiac transplantation. Most cases are Epstein-Barr virus (EBV)-related B-cell tumors, and reduction of immunosuppression treatment as well as the use of rituximab in combination with other chemotherapy are effective. However, patients with T/NK-cell PTLD post-cardiac transplantation are rarely reported. We had a patient with a fever that lasted for three weeks, with lung infiltrations and hepatosplenomegaly, who had EBV-associated hemophagocytosis 7 years after heart transplantation and was eventually diagnosed with T/NK-cell PTLD by autopsy. Although rare diseases, regular monitoring of EBV-DNA levels might be crucial for early diagnosis and treatment of PTLD.

Optimal Heart Rate and Prognosis in Patients with Cardiac Amyloidosis.

BACKGROUND: Optimal heart rate (HR) that associates with higher cardiac output and greater clinical outcomes in patients with cardiac amyloidosis remains unknown. METHODS: Consecutive patients with sinus rhythm who were diagnosed with cardiac amyloidosis at our institute between February 2015 and February 2021 were retrospectively included. Ideal HR, at which E-wave and A-wave stand adjacent without any overlaps in the trans-mitral flow echocardiography, was calculated by the formula: 86.8-0.08 × deceleration time (msec). The association between optimal HR and cardiac death or heart failure readmission was investigated. RESULTS: Ten patients (median 74 years old, 8 men) were included. On median, actual HR was 64 bpm and ideal HR was 69 bpm. An incidence rate of the primary endpoint in the sub-optimal HR group tended to be higher than optimal HR group: one of the four patients in optimal HR group had events (25%); two of the two patients in higher HR group had events (100%); two of the four patients in lower HR group had events (50%). CONCLUSIONS: The optimal HR was associated with greater clinical outcomes in patients with cardiac amyloidosis. The clinical impact of aggressive HR optimization in this cohort remains the next concern.

Patisiran for advanced heart failure with hereditary transthyretin cardiac amyloidosis.

We experienced a 78-year-old woman who was diagnosed with hereditary transthyretin cardiac amyloidosis and administered patisiran for advanced heart failure refractory to tafamidis. The levels of N-terminal pro B-type natriuretic peptide and left ventricular mass index decreased following the six-month patisiran treatment without any complications. Patisiran might be a promising disease-modifying drug for hereditary transthyretin cardiac amyloidosis even in its advanced stage, although further evaluation in a large cohort is warranted.

Therapeutic Strategy for a Patient with Advanced Heart Failure and Schizophrenia Without Cardiac Replacement Therapies.

We had a 58-year-old man with advanced heart failure and progressive end-organ dysfunction refractory to inotropes. Following detailed discussions, he decided not to receive ventricular assist device therapy considering his comorbidity of schizophrenia. A palliative care team initiated 2.5 mg of morphine together with low-dose anti-heart failure medications, which improved not only his heart failure symptoms but also the congestive heart failure itself. Aggressive commitments of the palliative care team might improve not only patients' quality of life but also advanced heart failure itself.

A case of wild-type transthyretin cardiac amyloidosis with rheumatoid arthritis.

A 72-year-old woman was diagnosed with rheumatoid arthritis (RA) 6 years ago and was referred to our hospital for the management of RA. She achieved remission with methotrexate, and her arthritis was well-controlled. Two years ago, a routine, preoperative check-up revealed left ventricular hypertrophy. One month before the current admission, she experienced worsening heart failure, and echocardiography and other findings suggested cardiac amyloidosis as the underlying cause. She was then admitted to our hospital. Biopsies of both the myocardium and duodenum showed amyloid deposits, and the initial immunohistochemical examination suggested amyloid A (AA) amyloidosis, as the deposits were slightly positive to anti-AA antibody and were sensitive to potassium permanganate pre-treatment. Thus, cardiac and duodenal AA amyloidosis secondary to RA was considered. However, the patient had no renal lesions and her RA was strictly controlled, findings atypical of AA amyloidosis. On repeat immunohistochemical testing, the cardiac and duodenal samples were negative for AA but stained positive for transthyretin (TTR). The diagnosis of a wild-type TTR amyloidosis (ATTRwt) was confirmed on the basis of an absence of the TTR gene mutation. The patient was successfully treated with diuretics and enalapril, and tafamidis (potent and selective TTR stabiliser). A pacemaker was implanted for concomitant complete atrioventricular block. This case is the first reported case of systemic ATTRwt complicated by RA. The treatment strategy for amyloidosis differs greatly depending on the type of amyloid deposition. Therefore, it is important to properly identify the amyloid protein, even if the diagnosis is complicated by RA.

Investigation of the transport of xanthine dehydrogenase inhibitors by the urate transporter ABCG2.

Hyperuricemia induces gout and kidney stones and accelerates the progression of renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K (rs2231142), are risk factors for hyperuricemia and gout. A recent genome wide association study suggested that allopurinol, a serum uric acid-lowering drug that inhibits xanthine dehydrogenase, is a potent substrate of ABCG2. In this study, we aimed to examine the transport of xanthine dehydrogenase inhibitors via ABCG2. Our results show that ABCG2 transports oxypurinol, an active metabolite of allopurinol, whereas allopurinol and febuxostat, a new xanthine dehydrogenase inhibitor, are not substrates of ABCG2. The amount of oxypurinol transported by ABCG2 vesicles significantly increased in the presence of ATP, compared to that observed with mock vesicles. Since the half-life of oxypurinol is longer than that of allopurinol, the xanthine dehydrogenase-inhibiting effect of allopurinol mainly depends on its metabolite, oxypurinol. Our results indicate that the serum level of oxypurinol would increase in patients with ABCG2 dysfunction.

A case of percutaneous coronary intervention for treatment of iatrogenic chronic total occlusion of the left circumflex artery after mitral valve repair.

A 55-year-old man had undergone mitral annuloplasty for mitral regurgitation with posterior mitral prolapse 3 years prior. He was examined at our hospital for dyspnea and fatigue. A coronary angiogram revealed iatrogenic chronic total occlusion (CTO) in the left circumflex coronary artery. We performed percutaneous coronary intervention (PCI) and successfully placed an everolimus-eluting stent. An intravascular ultrasound (IVUS) showed an impaired coronary artery at the occlusion site. To our knowledge, this is the first reported successful PCI for iatrogenic CTO after mitral valve repair. IVUS-guided PCI may help prevent complications in unusual CTO cases, such as coronary rupture.

Functional analysis of novel allelic variants in URAT1 and GLUT9 causing renal hypouricemia type 1 and 2.

BACKGROUND: Renal hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and nephrolithiasis. Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (URAT1), while type 2 is caused by defects in the SLC2A9 gene (GLUT9). METHODS AND RESULTS: In this article we present clinical, biochemical and molecular genetics of two Czech patients. The serum uric acid in the probands was 57 and 98 µmol/l and expressed as an increase in the fractional excretion of uric acid (40 and 18 %). The sequencing analysis of SLC22A12 and SLC2A9 revealed novel variants p.R92C and p.R203C in URAT1 and p.G72D in GLUT9. Functional studies were performed for these novel variants and for previously reported variants p.I118HfsX27, p.G216R and p.N333S in GLUT9 responsible for renal hypouricemia in three probands from Czech Republic and United Kingdom. Functional studies showed significantly decreased urate uptake for all variants. However, urate uptake of GLUT9 variants prepared for both isoforms were not significantly different. CONCLUSIONS: This is the first complex function characterization of non-synonymous allelic variants in patients with renal hypouricemia regarding both GLUT9 isoforms. Our finding of defects in the SLC2A9 and SLC22A12 genes show the following: renal hypouricemia is not restricted to East Asia populations; urate uptake of GLUT9 variants prepared for both isoforms were not significantly different; renal hypouricemia type 2 has more wide clinical variability than type 1; the phenotypic severity of renal hypouricemia is not correlated with results of functional characterizations of URAT1 and GLUT9 variants.

Hereditary Renal Hypouricemia Type 1 and Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Renal hypouricemia (RHUC) is a heterogeneous inherited disorder characterized by impaired tubular uric acid (UA) transport with severe complications, such as acute kidney injury. Type 1 is caused by a mutation in the SLC22A12 gene (URAT1) and type 2 in the SLC2A9 gene (GLUT9). In this article, the authors present a coexpression functional characterization of variants responsible for RHUC type 1 in a Czech family with polycystic kidney disease (PKD). METHODS: The serum UA concentration in the proband was 1.1 mg/dL and was expressed as an increase in the fractional excretion of UA (43%). The URAT1 allelic variants were prepared and their urate uptake and subcellular localization were studied by Xenopus oocytes expression system. Linkage analysis using a panel of 4 CA-repeat flanking markers for chromosome 16 and a panel of 3 CA-repeat flanking markers for chromosome 4 was performed, which carry the PKD1 and PKD2 genes, respectively. RESULTS: Coexpression results showed that p.G366R and p.R477H suppressed urate transport by wild types. Colocalization studies showed an accumulation of URAT1 in the endoplasmic reticulum of the p.G366R variant and mainly retention of wild-type protein by variants p.G366R and p.R477H. CONCLUSIONS: The findings suggest that not only loss-of-function mutation of URAT1 but also the dominant-negative effect cause RHUC through loss of UA absorption, partly due to protein misfolding caused by accumulation of URAT1 protein in the endoplasmic reticulum.