Human epididymis protein 4 is a useful predictor of post-operative prognosis in patients with severe aortic stenosis.

AIMS: The human epididymis protein 4 (HE4), a novel fibrosis marker, is expressed only in activated fibroblasts and is thought to reflect ongoing left ventricular (LV) fibrosis. LV fibrosis is a feature of severe aortic stenosis (AS) and is related to the post-operative outcome of patients with AS. We investigated the relationship between serum levels of HE4 and the post-operative prognosis of patients with severe AS. METHODS AND RESULTS: We measured the serum HE4 levels of 55 participants (80.8 ± 8.0 years old, male n = 26, 46%) with severe AS prior to surgical aortic valve replacement (n = 31, 56%) or transcatheter aortic valve implantation (n = 24, 44%) at Kumamoto University Hospital in 2018. We followed them for cardiovascular (CV) death or hospitalization for heart failure (HF) for 3 years. Serum HE4 levels were positively correlated with computed tomography-extracellular volume (CT-ECV) values (r = 0.53, P = 0.004). Kaplan-Meier curves demonstrated a significantly higher probability of hospitalization for HF or CV-related death in the patients with high HE4 (greater than the median HE4 value) compared with the patients with low HE4 (lower than the median HE4 value) (log-rank P = 0.003). Multivariate analysis showed HE4 (log(HE4)) to be an independent prognostic factor [hazard ratio (HR): 7.50; 95% confidence interval (CI): 1.81-31.1; P = 0.005]. Receiver operating characteristic (ROC) curve analysis suggested that HE4 is a marker of increased risk of CV-related death or hospitalization for HF at 3 years after surgery, with an area under the curve (AUC) of 0.76 (95% CI: 0.62-0.90; P = 0.003). CONCLUSIONS: We found that HE4 is a potentially useful biomarker for predicting future CV events in patients scheduled for AS surgery. Measuring serum HE4 values could help consider AS surgery.

Correlation Between Cardiac Images, Biomarkers, and Amyloid Load in Wild-Type Transthyretin Amyloid Cardiomyopathy.

Background Several imaging parameters and biomarkers provide diagnostic and prognostic information for wild-type transthyretin amyloid cardiomyopathy. However, the relevance of these parameters and their association with cardiac amyloid load requires further substantiation. We aimed to elucidate the association of imaging parameters obtained using 99mTc-labeled pyrophosphate scintigraphy, cardiovascular magnetic resonance imaging, global longitudinal strain (GLS), and cardiac biomarkers with cardiac amyloid load in patients with wild-type transthyretin amyloid cardiomyopathy. Methods and Results Eighty-eight patients with wild-type transthyretin amyloid cardiomyopathy who underwent 99mTc-labeled pyrophosphate scintigraphy and cardiovascular magnetic resonance were retrospectively evaluated. Quantitative cardiac amyloid load was obtained from 61 patients after myocardial biopsy. Correlations were assessed using Pearson's correlation coefficient applied to medical record data. The mean heart to contralateral ratio, native T1, extracellular volume, and GLS were 1.91±0.36, 1419.4±56.4 ms, 56.5±13.6%, and -9.4±2.5%, respectively. Median high-sensitivity cardiac troponin T (hs-cTnT) and BNP (B-type natriuretic peptide) levels were 0.0478 (0.0334-0.0691) ng/mL and 213.8 (125.8-392.7) pg/mL, respectively. The mean cardiac amyloid load was 22.9±15.0%. The heart to contralateral ratio correlated significantly with native T1 (r=0.397), extracellular volume (r=0.477), GLS (r=0.363), cardiac amyloid load (r=0.379), and Ln (hs-cTnT) (r=0.247). Further, cardiac amyloid load correlated significantly with native T1 (r=0.509), extracellular volume (r=0.310), GLS (r=0.446), and Ln (hs-cTnT) (r=0.354). Compared with BNP, hs-cTnT levels better correlated with several imaging parameters and cardiac amyloid load. Conclusions Increased cardiac amyloid load correlated with increased 99mTc-labeled pyrophosphate positivity, native T1, extracellular volume, and hs-cTnT levels, and an impaired GLS, suggesting that imaging parameters and cardiac biomarkers may reflect histological and functional changes attributable to amyloid deposition in the myocardium.

Extracardiac Biopsy Sensitivity in Transthyretin Amyloidosis Cardiomyopathy Patients With Positive 99 mTc-Labeled Pyrophosphate Scintigraphy Findings.

BACKGROUND: The accurate sensitivity of amyloid deposition in extracardiac tissue (subcutaneous tissue and gastrointestinal tract) has not been evaluated in transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients. This study aimed to evaluate the sensitivity of amyloid deposition in obtained endomyocardial and extracardiac biopsies.Methods and Results: This study retrospectively evaluated 175 consecutive ATTR-CM patients (wild-type [ATTRwt]: 134, hereditary [ATTRv]: 41) who had positive findings on 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy and underwent tissue biopsy of at least one organ (subcutaneous tissue, gastrointestinal tract, and endomyocardium). Amyloid deposition was observed in the subcutaneous tissue of 57/150 patients (38%), gastrointestinal tract of 80/131 patients (61%), and endomyocardium of 108/109 patients (99%). Compared to patients with ATTRv, ATTRwt had significantly lower sensitivity in subcutaneous tissue (73% vs. 25%, P<0.01) and tended to be lower in the gastrointestinal tract (74% vs. 57%, P=0.08) biopsies. Among 124 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsies, amyloid was detected in at least 1 specimen in 91 (73%) patients. The sensitivity of the combination of extracardiac biopsies was 66% and 94% in ATTRwt-CM and ATTRv-CM, respectively. Multivariate analysis reveals that ATTRv was the only significant predictor of amyloid deposition in the subcutaneous tissue. CONCLUSIONS: Subcutaneous tissue and gastrointestinal tract biopsy sensitivity are inadequate, especially in patients with ATTRwt; however, the combination of these extracardiac biopsies contributes to increased sensitivity in patients with positive 99 mTc-PYP scintigraphy findings.

A simple staging system using biomarkers for wild-type transthyretin amyloid cardiomyopathy in Japan.

AIMS: It has been reported that a staging system combining N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-cTnT) or estimated glomerular filtration rate (eGFR) is useful in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). However, these studies were mainly conducted in Western countries, and their usefulness for the Japanese population is unclear. We examined and validated the staging system using hs-cTnT, eGFR, and B-type natriuretic peptide (BNP) in Japanese patients with ATTRwt-CM. METHODS AND RESULTS: We retrospectively evaluated 176 patients with ATTRwt-CM. The cut-off values of hs-cTnT and eGFR were selected as 0.05 ng/mL and 45 mL/min/1.73 m2 , respectively, based on a previous report. The optimal cut-off value of BNP was 255.6 pg/mL to predict all-cause mortality (sensitivity, 75%; specificity, 58%; area under the curve, 0.69; 95% confidence interval [CI], 0.61-0.78; P < 0.001) based on a receiver operating characteristic curve. We defined the cut-off value of BNP as 250 pg/mL. Increased hs-cTnT (>0.05 ng/mL) and BNP (>250 pg/mL) and decreased eGFR (<45 mL/min/1.73 m2 ) were significant predictors of poor prognosis (P < 0.05). We calculated the score by adding 1 point if hs-cTnT and BNP levels increased or eGFR decreased by more than the cut-off value. The hazard ratio of all-cause death adjusted by age and sex, using score 0 as a reference, was 0.44 (95% CI 0.08-2.49, P = 0.44) for score 1, 3.69 (95% CI 1.21-11.21, P = 0.02) for score 2, and 5.40 (95% CI 1.57-18.54, P = 0.007) for score 3. We divided patients into a low score group (0-1 point) and high score group (2-3 points). Kaplan-Meier analyses revealed significant differences in all-cause death and rehospitalization for heart failure (log rank test; P < 0.001), and after adjusting for sex and age, the hazard ratio of all-cause death was 6.96 (95% Cl 2.88-16.83, P < 0.001) and that for rehospitalization for heart failure was 4.27 (95% Cl 2.26-8.07, P < 0.001) in the high-risk group, compared with those in the low-risk group. The median survival period was 32.0 months in the high-risk group. CONCLUSIONS: This simple staging system, which combines hs-cTnT, BNP, and eGFR, was useful for predicting prognosis in Japanese patients with ATTRwt-CM. This system can objectively evaluate the disease progression of ATTRwt-CM and may be useful for patient selection for disease-modifying therapy.

Sex-related differences in the clinical characteristics of wild-type transthyretin amyloidosis cardiomyopathy.

BACKGROUND: A significant male predominance has been reported in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Hence, female cases of ATTRwt-CM are overlooked, and sex-related differences in ATTRwt-CM remain unclear. This study aimed to examine sex-related differences in clinical characteristics and diagnostic approaches in ATTRwt-CM. METHODS: We retrospectively analyzed 199 consecutive patients who were diagnosed with ATTRwt-CM and evaluated sex-related differences in clinical characteristics, imaging parameters, biomarkers, and diagnostic approaches. RESULTS: Twenty-nine patients (15%) were female. These female patients were significantly older at diagnosis (77.1 ± 6.5 years vs. 82.9 ± 4.8 years; p<0.001) and had a more advanced New York Health Association functional class (2.2 ± 0.7 vs. 2.6 ± 0.8; p = 0.006) than their male counterparts. The median B-type natriuretic peptide levels were significantly higher (236 pg/mL vs. 394 pg/mL; p = 0.017) in female patients. Echocardiography revealed that the mean interventricular septum diameter was thinner (15.7 ± 2.6 mm vs. 14.1 ± 2.5 mm; p = 0.004) and left ventricular ejection fraction (LVEF) was preserved (51.2 ± 10.2% vs. 57.2 ± 9.1%; p = 0.003) in female patients. The mean heart-to-contralateral ratio obtained using 99mTc-labeled pyrophosphate (99mTc-PYP) was significantly lower (1.89 ± 0.33 vs. 1.63 ± 0.20; p < 0.001), moderate to severe aortic stenosis was more frequently observed (5% vs. 45%; p < 0.001), and the frequency of histological diagnosis was significantly lower (77% vs. 59%; p = 0.036) in female patients. CONCLUSIONS: Female patients with ATTRwt-CM were predominantly octogenarians and less hypertrophic and had preserved LVEF and weaker cardiac uptake of the 99mTc-PYP tracer compared with male patients. These characteristics contribute to the underdiagnosis of ATTRwt-CM in female patients.

Preclinical diagnosis of wild-type transthyretin amyloid cardiomyopathy in a patient undergoing carpal tunnel release.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) has received increased attention because of its novel treatment options. Carpal tunnel syndrome (CTS) is known as early symptoms in transthyretin amyloidosis (ATTR) preceding cardiac involvement and one of the "red flags" for ATTR-CM. A 64-year-old man underwent carpal tunnel release for carpal tunnel syndrome at 62 years. He was diagnosed with wild-type ATTR due to deposition of transthyretin (TTR) amyloid in flexor tenosynovium specimens and no TTR gene mutation. Examination for detection of cardiac involvement was performed after the operation, and there were no definitive findings of ATTR-CM; however, an early stage of ATTR-CM remained a possibility. Serial image evaluation and biomarker analysis revealed positive findings for ATTR-CM, and we performed an endomyocardial biopsy, resulting in the detection of amyloid deposition. He was diagnosed with ATTRwt-CM 2 years after the operation, and even then, he had no heart failure symptoms. Early diagnosis and treatment are important for the improvement of clinical outcomes in patients with ATTRwt-CM. TTR deposition in the ligaments or tendons is often observed in patients with CTS and should be considered at high risk of future ATTR-CM. Serial follow-up of these patients may enable the diagnosis of preclinical ATTR-CM. .

Corrigendum to 'A case of severe pulmonary thromboembolism in mycoplasma infection during early pregnancy' [J. Cardiol. Cases 22 (2020) 140-142].

[This corrects the article DOI: 10.1016/j.jccase.2020.06.003.].

A case of severe pulmonary thromboembolism in mycoplasma infection during early pregnancy.

Mycoplasma infection and pregnancy are both characterized by thrombogenesis. A 38-year-old pregnant woman was admitted to a general hospital for mycoplasma pneumonia treatment. She experienced sudden dyspnea and fell into cardiopulmonary arrest. Emergent pulmonary arteriography revealed contrast deficits in the bilateral pulmonary arteries, and she was diagnosed with pulmonary thromboembolism (PTE). Reperfusion treatment and hemodynamic support were initiated. This is a rare case report of PTE attributed to mycoplasma infection during pregnancy. .

Double-chambered right ventricle complicated by hypertrophic obstructive cardiomyopathy diagnosed as Noonan syndrome.

We present a case of double-chambered right ventricle (DCRV) complicated by hypertrophic obstructive cardiomyopathy (HOCM) in KRAS mutation-associated Noonan syndrome. The diagnosis was incidental and made during diagnostic testing for an intradural extramedullary tumour. Spinal compression, if not surgically treated, may cause paralysis of the extremities. We decided to pursue pharmacological therapy to control biventricular obstructions and reduce the perioperative complication rate. We initiated treatment with cibenzoline and bisoprolol; the doses were titrated according to the response. After 2 weeks, the peak pressure gradient of the two RV chambers decreased from 101 to 68 mmHg, and the LV peak pressure gradient decreased from 109 to 14 mmHg. Class 1A antiarrhythmic drugs and ß-blockers decreased the severe pressure gradients of biventricular obstructions caused by DCRV and HOCM. The patient was able to undergo surgery to remove the intradural extramedullary tumour, which was diagnosed as schwannoma.

Bioaccumulation Patterns of Perfluoroalkyl Acids in an Estuary of the Ariake Sea, Japan.

To evaluate the bioaccumulation potential of perfluoroalkyl acids (PFAAs) in an aquatic food web, we measured the concentrations of nine PFAAs in the water and aquatic organisms from an estuary of the Omuta River, Japan. Average log bioaccumulation factors for all PFAAs ranged from 2.0 to 2.8. There was no positive correlation observed between PFAA carbon chain length and there was no evidence of trophic magnification demonstrated among the sample types collected. These results differed from the findings of previous studies in enclosed bodies of water, perhaps because river mouth-estuarine ecotones are more variable spatially and temporally and include some fish that are highly migratory. Further investigations of bioaccumulation factors will be needed to elucidate the tendency of amphiphilic chemicals to bioaccumulate in these river mouth-estuarine ecotones.

Successful treatment of deep vein thrombosis caused by iliac vein compression syndrome with a single-dose direct oral anti-coagulant.

BACKGROUND: Although vein stenting is popular for treatment for venous thromboembolism due to mechanical compression, some cases are forced to avoid inserting align agents because of immunodeficiency. CASE PRESENTATION: An 82-year-old man with left extremity redness and swelling presented to a hospital for a medical evaluation. The patient was immunodeficient because of the adverse effects of his treatment for Castleman's disease. A contrast-enhanced computed tomography scan revealed a venous thromboembolism in inferior vena cava and the left lower extremity. Magnetic resonance venography showed that the iliac artery was compressing the iliac vein. We were reluctant to place a stent in the iliac vein has because of the patient's immunodeficient status. Three months of treatment using single-dose edoxaban (30 mg daily) resulted in complete resolution of the thrombus. This is the first report demonstrating that single-dose edoxaban without acute-phase parenteral anticoagulation is effective in the treatment of iliac vein compression. CONCLUSIONS: A single-dose direct oral anti-coagulant without acute-phase parenteral anticoagulation is effective for mechanical compression.

Trophic magnification of polychlorinated biphenyls and polybrominated diphenyl ethers in an estuarine food web of the Ariake Sea, Japan.

To evaluate trophic biomagnification of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) in an estuary of the Ariake Sea, Japan, we measured concentrations of 209 PCB congeners and 28 PBDE congeners, and nitrogen stable isotope (δ(15)N) levels in living aquatic organisms. The trophic magnification factor (TMF) for ΣPCBs (all 209 congeners) was 1.52, and TMFs for 58 PCB congeners ranged from 0.90 to 3.28. In contrast, TMF for ΣPBDEs was 1.17, and TMFs for 7 PBDE congeners ranged from 0.46 to 1.66. TMFs of PCB and PBDE congeners in this study were lower than those in marine food webs, and were similar to those in a lake food web. However, although negative relationships were observed between TMF and log octanol-water partition coefficient (KOW) values among PCB congeners in this study (log KOW up to 7), positive relationships have been reported in several other studies. In the present estuary, PCB concentrations in sea bass may not reach a steady state because sea bass are migratory species. Therefore, TMFs of highly chlorinated congeners with high log KOW values take longer to reach the steady state and may not increase with increasing log KOW.