Amyloid deposit corresponds to technetium-99m-pyrophosphate accumulation in abdominal fat of patients with transthyretin cardiac amyloidosis.

BACKGROUND: Radionuclide imaging using bone-avid tracers plays a critical role in diagnosing transthyretin cardiac amyloidosis (ATTR-CA), but technetium-99m-pyrophosphate (PYP) rarely allows the detection of extracardiac amyloid infiltration. We retrospectively investigated the frequency of PYP uptake in the subcutaneous abdominal fat of patients with ATTR-CA and its relevance to the results of fine-needle aspiration biopsy (FNAB) of this tissue. METHODS: Chest-centered images of PYP scintigraphy were obtained 2 h after the intravenous injection of the tracer (20 mCi), and the frequency of PYP uptake in the subcutaneous abdominal fat was evaluated. Amyloid deposits of fat smears taken by subcutaneous abdominal fat FNAB were assessed by Congo red staining. RESULTS: Twenty-four patients with ATTR-CA were included. Ten (41.7%) patients showed some PYP uptake in the subcutaneous abdominal fat (positive PYP group), and 14 patients did not (negative PYP group). Amyloid deposits were detected by subcutaneous abdominal fat FNAB in 7/10 patients (70.0%) of the positive PYP group versus 0/14 patients (0%) of the negative PYP group, and the difference was significant. CONCLUSIONS: In patients with ATTR-CA, abnormal PYP uptake in the subcutaneous abdominal fat could reflect the regional amyloid deposition confirmed by FNAB of this tissue.

Suppression of amiodarone-induced torsade de pointes by landiolol in a patient with atrial fibrillation-mediated cardiomyopathy.

An elderly Japanese woman developed acute decompensated heart failure caused by persistent atrial fibrillation (AF) and left ventricular systolic dysfunction. Approximately 6 days after starting intravenous administration of amiodarone (600 mg/day) for maintaining sinus rhythm after cardioversion of AF, electrocardiograms revealed a prolonged QT interval associated with torsade de pointes (TdP). The amiodarone-induced TdP disappeared after intravenous administration of landiolol plus magnesium and potassium, without discontinuation of amiodarone or overdrive cardiac pacing, although the prolonged QT interval persisted. To the best of our knowledge, this is the first report that landiolol could be effective for amiodarone-induced TdP.

Interleukin-18 deficiency protects against renal interstitial fibrosis in aldosterone/salt-treated mice.

Interleukin (IL)-18 is a member of the IL-1 family of cytokines and was described originally as an interferon γ-inducing factor. Aldosterone plays a central role in the regulation of sodium and potassium homoeostasis by binding to the mineralocorticoid receptor and contributes to kidney and cardiovascular damage. Aldosterone has been reported to induce IL-18, resulting in cardiac fibrosis with induced IL-18-mediated osteopontin (OPN). We therefore hypothesized that aldosterone-induced renal fibrosis via OPN may be mediated by IL-18. To verify this hypothesis, we compared mice deficient in IL-18 and wild-type (WT) mice in a model of aldosterone/salt-induced hypertension. IL-18(-/-) and C57BL/6 WT mice were used for the uninephrectomized aldosterone/salt hypertensive model, whereas NRK-52E cells (rat kidney epithelial cells) were used in an in vitro model. In the present in vivo study, IL-18 protein expression was localized in medullary tubules in the WT mice, whereas in aldosterone-infused WT mice this expression was up-regulated markedly in the proximal tubules, especially in injured and dilated tubules. This renal damage caused by aldosterone was attenuated significantly by IL-18 knockout with down-regulation of OPN expression. In the present in vitro study, aldosterone directly induced IL-18 gene expression in renal tubular epithelial cells in a concentration- and time-dependent manner. These effects were inhibited completely by spironolactone. IL-18 may be a key mediator of aldosterone-induced renal fibrosis by inducing OPN, thereby exacerbating renal interstitial fibrosis. Inhibition of IL-18 may therefore provide a potential target for therapeutic intervention aimed at preventing the progression of renal injury.

The Importance of Walking for Control of Blood Pressure: Proof Using a Telemedicine System.

BACKGROUND: Regular physical activity (PA), including daily walking, reduces the risk of many chronic diseases, especially hypertension. Pedometer is a potential motivational aid for increasing PA. In the present study, we used a telemedicine system and analyzed the relationship between daily walking, calculated by pedometers, and blood pressure (BP). METHODS: BP was measured at home twice a day (morning and evening) using an oscillometric automatic device. Body weight (BW) and percent body fat (%BF) were measured after BP measurement. Daily walking steps (DWS) were calculated by a pedometer. These daily parameters were transmitted through the Internet to a central server computer and sent to the Medical Health Center. RESULTS: Sixty-nine (N = 69) hypertensive patients were included in this study. The mean follow-up period was 378 days. Electronic data from a pedometer (DWS) were associated with reduced BW, body mass index, and %BF. Hypertensive patients were divided into two groups based on the DWS. In the high DWS group, morning systolic BP and diastolic BP and evening systolic BP were reduced after induction of the telemedicine system. CONCLUSION: A telemedicine system confirmed the usefulness of walking to control BP in hypertensive patients.

Carotid hemodynamics is associated with monocyte count determined by serum homocysteine level in patients with essential hypertension.

To examine the association between pulsatility index (PI) in the common carotid artery (CCA) as a marker of vascular resistance and cardiovascular risk factors, including serum homocysteine and inflammation, 67 hypertensive patients were enrolled. PI correlated with homocysteine and interleukin-6, monocyte count, gender, age and BMI, with monocyte count and age being independent determinants for PI. In turn, monocyte count correlated with homocysteine, tumor necrosis factor-alpha, and HDL-cholesterol, BMI, and gender, with HDL-cholesterol and homocysteine being independent determinants for monocyte count. These results indicated monocyte count determined by homocysteine is associated with arterial stiffness in hypertensive patients.

Downsloping TP Segment in the Precordial Leads on a Standard 12-lead Electrocardiogram: Suspected Cardiac Impulse-tapping Artifact.

We herein report an 80-year-old man showing a downsloping TP segment together with an increase in the height of the T wave in the precordial leads on a standard 12-lead electrocardiogram (ECG). Separately, an 87-year-old woman showed only a downsloping TP segment in the precordial leads on a standard 12-lead ECG. Neither patient reported chest pain or dyspnea when ECGs was obtained. This downsloping TP segment in the precordial leads on the standard 12-lead ECG is thought to be due to a cardiac impulse-tapping artifact. Differential diagnoses are also discussed.

Technetium-99m-pyrophosphate imaging-based computed tomography-guided core-needle biopsy of internal oblique muscle in wild-type transthyretin cardiac amyloidosis.

BACKGROUND: Technetium-99m-pyrophosphate (99mTc-PYP) uptake in the internal oblique muscle (IOM), which is often observed in patients with wild-type transthyretin cardiac amyloidosis (ATTR-CA), indicates amyloid transthyretin (ATTR) deposition. OBJECTIVE: This study aimed to assess the safety and efficacy of 99mTc-PYP imaging-based computed tomography (CT)-guided core-needle biopsy of the IOM as a new extracardiac screening biopsy for confirming the presence of ATTR deposits. METHODS: Patients with suspected ATTR-CA in whom myocardial tracer uptake was detected on chest- and abdomen-centered images of 99mTc-PYP scintigraphy underwent CT-guided core-needle biopsy at the site with the highest tracer uptake in the IOM between September 2021 and November 2022. RESULTS: All 18 consecutive patients (mean age, 86.3 years ± 6.5; 61.1% male) enrolled in the study showed 99mTc-PYP uptake into the IOM. Adequate tissue samples were obtained from all patients except one without serious complications. Immunohistochemical analysis confirmed ATTR deposits in 16/18 (88.9%) patients. In the remaining two patients, ATTR deposits were observed via endomyocardial biopsy. All patients were diagnosed with wild-type ATTR-CA based on transthyretin gene sequence testing results. CONCLUSION: In wild-type ATTR-CA, 99mTc-PYP imaging-based CT-guided core-needle biopsy of the IOM could be used as an extracardiac screening biopsy to confirm the presence of ATTR deposits.

Comparison of the effect of combination therapy with an angiotensin II receptor blocker and either a low-dose diuretic or calcium channel blocker on cardiac hypertrophy in patients with hypertension.

Left ventricular hypertrophy (LVH) regression is an important issue in hypertensive patients. Patients with LVH who had received the angiotensin receptor blocker (ARB) treatment for 8 weeks and had not reached the target blood pressure level were enrolled in the study. Patients were assigned to either losartan (50 mg)/hydrochlorothiazide (HCTZ, 12.5 mg) group or ARB + CCB group (usual dose of ARB and calcium channel blocker, CCB). After 48 weeks, LV mass index was found to be reduced significantly in the losartan/HCTZ group but not in the ARB + CCB group. These results suggest that combination therapy of an ARB and diuretic has greater potential to cause regression compared with an ARB and CCB.

Identification of the Vessels Causing Myocardial Ischemia by a Synthesized 18-Lead Electrocardiogram Obtained After the Master Two-Step Exercise Test in a Patient With Effort Angina.

A synthesized 18-lead electrocardiograph is a specialized technology that mathematically computes the virtual electrocardiographic waveforms of the right chest leads (V3R, V4R, and V5R) and posterior leads (V7, V8, and V9) based on a standard 12-lead electrocardiograph input without additional lead placement or techniques. Synthesized 18-lead electrocardiography is a useful test for the identification of the culprit coronary arteries in patients with ST-segment elevation myocardial infarction of the right ventricular wall or the posterior/lateral left ventricular wall, which are often missed on standard 12-lead electrocardiography. However, few studies have examined the usefulness of this modality during exercise stress testing. We present a case of a 78-year-old man with a two-month history of typical angina. The synthesized 18-lead electrocardiogram obtained just after the Master two-step exercise test revealed ST-segment shifts in multiple leads, including synthesized V4R, V5R, and V7-9 leads, and U-wave changes in some leads, including the synthesized V9 lead. The diagnosis of the culprit coronary arteries causing exercise-induced myocardial ischemia is discussed with reference to coronary angiographic findings. This modality could potentially increase the sensitivity and specificity for the detection of coronary artery disease and accurately pinpoint the site of the lesion. If an electrocardiograph can display a synthesized 18-lead electrocardiogram, it should be used when evaluating the waveform due to myocardial ischemia.

A Gluteus Medius Muscle Biopsy to Confirm Amyloid Transthyretin Deposition in Wild-type Transthyretin Cardiac Amyloidosis: A Report of Two Cases.

In patients with wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), the uptake of the tracer on technetium-99m-labeled pyrophosphate (99mTc-PYP) scintigraphy, which indicates amyloid transthyretin (ATTR) per se, is often observed in skeletal muscles, such as the abdominal oblique and gluteal muscles. Among extracardiac biopsies for confirming ATTR deposition in ATTRwt-CA, a 99mTc-PYP imaging-based computed tomography (CT)-guided core needle biopsy of the internal oblique muscle has relatively high sensitivity. In some patients, the 99mTc-PYP uptake is more pronounced in the gluteal muscles than in oblique muscles. We herein report two cases of ATTRwt-CA in which a CT-guided biopsy of the gluteus medius muscle with 99mTc-PYP uptake confirmed the presence of ATTR deposits.

99mTc-Pyrophosphate Scintigraphy Can Image Tracer Uptake in Skeletal Trunk Muscles of Transthyretin Cardiac Amyloidosis.

PURPOSE: 99mTc-pyrophosphate (99mTc-PYP) uptake in the skeletal muscles is minimal in patients with transthyretin cardiac amyloidosis (ATTR-CA) when assessed qualitatively and quantitatively. We previously demonstrated moderate- to high-grade 99mTc-PYP uptake in the subcutaneous abdominal fat of some patients with ATTR-CA and showed that this abnormal finding could reflect the regional amyloid burden of this tissue. We aimed to investigate the frequency of 99mTc-PYP uptake in skeletal trunk muscles of patients with ATTR-CA. METHODS: Chest- and abdomen-centered 99mTc-PYP scintigraphy images were obtained 2 hours after IV injections of the tracer (20 mCi) in 36 patients with ATTR-CA. The frequency of 99mTc-PYP uptake in the following 11 skeletal trunk muscles was investigated: pectoralis major, deltoid, subscapularis, infraspinatus, trapezius, latissimus dorsi, erector spinae, psoas major, abdominal oblique, rectus abdominis, and the gluteus muscles. RESULTS: Ten of the 11 muscles were involved in patients with the highest number of 99mTc-PYP uptake in the skeletal trunk muscles examined, whereas no muscle was involved in a patient with the least uptake. The muscle with the highest rate of 99mTc-PYP uptake, observed in 34 of 36 patients (94.4%), was the abdominal oblique. No tracer uptake was observed in the psoas major. The frequency of radiotracer uptake in the remaining examined muscles was between those of abdominal oblique and psoas major muscles. CONCLUSIONS: Radiotracer uptake was often detectable in some skeletal trunk muscles of ATTR-CA, although the muscles of patients examined and the skeletal trunk muscles of 1 patient showed heterogeneity in the uptake of 99mTc-PYP.

Relationship between renal hemodynamics and urinary type IV collagen in patients with essential hypertension.

Urinary type IV collagen excretion (uT4C) in diabetic patients is higher than in normal subjects. In this study, we investigated the relationship between uT4C and renal hemodynamics in 42 patients with essential hypertension. The renal resistive index (RI) is calculated from blood flow velocities measured using pulsed-wave in interlobar arteries. There was a significant correlation between uT4C to creatinine ratio (uT4C/uCr) and age, hemoglobin A1c (HbA1c), and RI. A stepwise regression analysis showed that RI was independently associated with uT4C/uCr. These results indicated that uT4C may be a marker of renovascular stiffness due to glomerulosclerosis in patients with essential hypertension.

Osteopontin deficiency protects against aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney.

Osteopontin (OPN) has been implicated in the pathology of several renal conditions. Recently, we demonstrated in vitro that aldosterone has important roles in collagen synthesis by inducing OPN (Irita J, Okura T, Kurata M, Miyoshi K, Fukuoka T, Higaki J. Hypertension 51: 507-513, 2008). The aim of the present study was to clarify the roles of OPN in aldosterone-mediated renal fibrosis by infusing aldosterone into either wild-type (WT) or OPN knockout mice (OPN(-/-)). We used uninephrectomized mice treated with aldosterone and high salt to exacerbate renal fibrosis. After 4 wk of treatment with aldosterone, we showed similar increases in systolic blood pressure in both strains of mice. Urine albumin excretion was greater in aldosterone-infused WT mice than in aldosterone-infused OPN(-/-) mice. Immunohistochemical analysis showed high levels of OPN expression in aldosterone-infused WT mice. Interstitial fibrosis and inflammatory infiltrations were increased in aldosterone-infused WT mice compared with either vehicle-infused WT or aldosterone-infused OPN(-/-) mice. These changes were ameliorated markedly by eplerenone treatment in aldosterone-infused WT mice. Aldosterone-infused WT mice also had increased expression of NADPH oxidase subunits compared with aldosterone-infused OPN(-/-) mice. We observed a marked increase in oxidative stress markers in aldosterone-infused WT mice compared with aldosterone-infused OPN(-/-) mice. These results indicate that OPN is a promoter of aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney and suggest that inhibition of OPN may be a potential therapeutic target for prevention of renal injury.

Extracardiac Accumulation of Technetium-99m-Pyrophosphate in Transthyretin Cardiac Amyloidosis.

This report presents a rare case of acute decompensated heart failure with technetium-99m-pyrophosphate accumulation in extracardiac sites, such as chest and abdominal walls, in addition to intense myocardial uptake of the tracer. Subsequently, an abdominal fat pad fine-needle aspiration biopsy, which provided positive findings for transthyretin amyloidosis, was performed. (Level of Difficulty: Advanced.).

Variant Angina with Spontaneously Documented Ischemia- and Tachycardia-induced "Lambda" Waves.

In a patient with variant angina of the proximal left anterior descending coronary artery, myocardial ischemia changed the QRS-ST-T configurations without J-waves into those resembling "lambda" waves at maximal ST-segment elevation, and couplets or triplets of supraventricular extrasystole (SVE) changed the ischemia-induced "lambda" waves into QRS-ST-T configurations resembling a "tombstone" morphology or "monophasic QRS-ST complex." At the resolution phase of coronary spasm, the QRS-ST-T configurations returned to those without J-waves and were changed by SVE into "lambda" waves. Interestingly, neither ischemia- nor SVE-induced "lambda" waves or SVE-induced "tombstone" morphology or "monophasic QRS-ST complex" were complicated by ventricular tachyarrhythmia.

Premature atrial contractions with multiple patterns of aberrant conduction followed by torsade de pointes in a patient with polymyalgia rheumatica: A case report.

RATIONALE: Recent studies have shown that QT interval prolongation is associated with disease severity and predicts mortality in systemic inflammatory diseases, particularly rheumatoid arthritis. Systemic pro-inflammatory cytokines released from synovial tissues in rheumatoid arthritis, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, could have direct effects on cardiac electrophysiology, particularly changes in the expression and function of potassium and calcium channels, resulting in QT interval prolongation on surface electrocardiogram (ECG) and an increased predisposition to develop lethal ventricular arrhythmias. However, reports on torsade de pointes (TdP) due to acquired long QT syndrome in patients with polymyalgia rheumatica (PMR) are limited. PATIENT CONCERNS: An 85-year-old Japanese woman with active PMR developed first syncope. DIAGNOSIS: Frequent premature atrial contractions (PACs) with multiple patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP were documented. PACs were the first beat of TdP. INTERVENTIONS: Amiodarone, together with magnesium and potassium, was intravenously administered. However, TdP resulted in a ventricular arrhythmic storm, for which sedation with mechanical ventilatory support, temporary overdrive cardiac pacing, and intravenous landiolol administration in addition to multiple direct current shocks were effective. OUTCOMES: Approximately 2 years later, the patient was treated with amiodarone, propranolol, and prednisolone. She did not undergo implantable cardioverter-defibrillator implantation and was quite well, with no recurrence of ventricular tachyarrhythmia. LESSONS: IL-6 hyperproduction in inflamed tissues has been widely confirmed in PMR. Frequent PACs with various patterns of aberrant conduction, QT interval prolongation, and morphological T-U wave variability followed by TdP, for which IL-6-mediated enhancement of L-type Ca2+ current and inhibition of the rapid component of the delayed rectifier K+ current are the most likely mechanisms, were documented in an elderly Japanese woman with PMR. ECG may be recorded once in patients with active PMR even when these patients do not complain of palpitation or syncope. If QT interval prolongation or arrhythmia, including even PACs, is observed, follow-up ECG may be warranted, particularly for patients with some risk factors for QT prolongation that could lead to TdP, such as advanced age, female sex, hypopotassemia, and polypharmacy.

Renal resistance index is a marker of future renal dysfunction in patients with essential hypertension.

AIM: In patients with essential hypertension (EHT), the intrarenal resistance index (RI) has been shown to be related to the severity of target organ damage (TOD). Cystatin C is has been reported to be related to TOD in EHT. The aim of the present study was to clarify whether the RI predicts future renal function assessed by cystatin C levels in EHT. METHODS: One-hundred and twelve patients participated. RI and cystatin C were measured at baseline, and 12 months later, cystatin C was measured again. RESULTS: The patients were divided into 2 groups according to RI value: the low RI group (RI<0.7) and the high RI group (RI> or =0.7). After 12 months, cystatin C levels were significantly elevated in the high RI group, whereas the levels remained unchanged in the low RI group. Stepwise regression analysis using the baseline values of RI, age, pulse pressure, HbA1c, cystatin C, log-transformed (ln) C-reactive protein and ln urinary albumin/creatinine as covariates, showed baseline RI was the only independent determinant of the time-related changes in cystatin C levels. CONCLUSION: This finding suggests that the renal RI may be a marker of future renal dysfunction in EHT.

Undercarboxylated osteocalcin is a biomarker of carotid calcification in patients with essential hypertension.

The development of vascular calcification is an active, highly regulated process with similarities to bone formation. Osteocalcin (OC), a vitamin K-dependent protein expressed by osteoblasts, contains 3 gamma-carboxyglutamic acid residues derived from the vitamin K-dependent posttranslational modification of glutamic acid residues. Circulating undercarboxylated OC (ucOC) is increased in vitamin K deficiency and serum ucOC is reported to be a clinical marker of vitamin K status. Vitamin K deficiency is associated with vascular calcification as well as osteoporosis. We evaluated the relationship between ucOC and carotid artery calcification in 92 patients with essential hypertension. Ultrasound of the common carotid artery was performed to identify vascular calcification and subjects were divided into 2 groups: a calcification (+) group and a calcification (-) group. Serum creatinine and ucOC levels were higher in the calcification (+) group than in the calcification (-) group and serum ucOC correlated with serum creatinine. To identify the independent determinant factor for carotid artery calcification, we applied both ucOC and estimated glomerular filtration rate as independent factors in logistic regression analysis. Serum ucOC was an independent determinant of carotid calcification, suggesting that circulating ucOC may be an important biomarker of carotid artery calcification.

Association between cystatin C and inflammation in patients with essential hypertension.

BACKGROUND: Serum cystatin C is not only a marker of renal function but also acts as an independent risk factor for cardiovascular damage, heart failure, and death. It is known that the initiation and progression of these cardiovascular events contributes to renal dysfunction and chronic inflammation. In this study, we investigated the relationship between cystatin C and proinflammatory cytokines. METHODS: Eighty-eight patients with essential hypertension participated in the study, which involved measuring proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and C reactive protein (CRP). RESULTS: Positive correlations were detected between cystatin C and estimated glomerular filtration rate (eGFR) (r = -0.503, p < 0.001), systolic blood pressure (r = -0.246, p = 0.034), and pulse pressure (r = -0.295, p = 0.010). In contrast, serum creatinine correlated only with eGFR (r = -0.755, p < 0.001) and eGFR correlated only with age (r = -0.339, p = 0.001) and not with the other clinical parameters, whereas cystatin C also correlated with log natural (ln) IL-6 (r = -0.247, p = 0.033) and ln TNF-α (r = -0.405, p < 0.001) but not with CRP (r = -0.188, p = 0.108). In contrast, plasma creatinine and eGFR did not correlate with any of these proinflammatory cytokines. Stepwise regression analysis showed that ln TNF-α, eGFR and pulse pressure were independent determinants of serum cystatin C concentration. CONCLUSION: This study showed that cystatin C is a marker of inflammation as well as renal function.