Evaluation of the Effect of Topiroxostat on Renal Function in Patients with Hyperuricemia: STOP-C Study, a Retrospective Observational Cohort Study.

BACKGROUND: Serum uric acid-lowering therapy is associated with maintaining renal function. OBJECTIVE: We aimed to retrospectively evaluate renal function and serum uric acid in patients with hyperuricemia who received topiroxostat for over a year. METHODS: Medical records of patients from 1 January, 2015 to 31 October, 2019 in our hospital were used. From the medical records, data of 100 patients with hyperuricemia treated with topiroxostat were extracted (67:33 male:female). The primary endpoints were changes in serum creatinine level and estimated glomerular filtration rate at 12 months after topiroxostat administration. The secondary endpoints were changes in serum creatinine, serum uric acid, and estimated glomerular filtration rate before and after topiroxostat administration. RESULTS: The study mainly involved elderly individuals (77.2 ± 9.5 years). Forty-four patients administered uric acid-lowering drugs were switched to topiroxostat. After 12 months, the serum creatinine level and estimated glomerular filtration rate showed no significant changes from baseline; however, the serum uric acid level significantly decreased. The estimated glomerular filtration rate significantly decreased during the 6 months before topiroxostat administration (p < 0.001), but showed no significant change at 6 months after topiroxostat administration (p = 0.849). CONCLUSIONS: This study revealed that topiroxostat use not only reduced the serum uric acid level but also maintained renal function in elderly patients with hyperuricemia in daily clinical practice.

Cardiovascular Catheterization Using a New Antiseptic Agent Olanexidine Gluconate.

Olanexidine gluconate 1.5% (Olanedine®) is a colorless and transparent antiseptic agent introduced in 2015. In this study, we examined its usefulness and safety for cardiovascular catheterization and compared them to 10% povidone-iodine (PI). The study included 1,001 and 1,000 consecutively enrolled patients using Olanedine® and PI, respectively [649 (PI, 687) males; mean age: 72.1 ± 9.6 (70.9 ± 9.6) years] who underwent cardiovascular catheterization [diagnostic cardiac catheterization: 624 (509) cases, percutaneous coronary intervention: 288 (390) cases, and endovascular treatment: 89 (101) cases]. Clinically, there were no significant differences in the backgrounds between the two groups. The amount of Olanedine® used per case was approximately 20 mL. Blood tests were performed before and after catheterization. The presence or absence of discoloration on clothes containing cotton by Olanedine® was also examined. One mild rash that disappeared within one day occurred in each of the two groups. Some blood tests before and after cardiac catheterization indicated significant differences, but they did not seem to be clinically relevant. The use of Olanedine® in hemodialysis patients (117 cases) was uneventful. Its use in 37 patients with contraindications for ethanol disinfection was also uneventful. Although PI is extremely difficult to remove from white coats containing cotton, Olanedine® did not cause any discoloration on clothes. This is the first report of cardiovascular catheterization using Olanedine®. The efficacy and safety of Olanedine® and PI seem to be equivalent. Olanedine® could be a new useful option as a disinfectant of cardiovascular catheterization.

Age-related differences in image quality of prospectively ECG-triggered axial and helical scans for coronary CT angiography.

We investigated the underlying reasons for the occurrence of misalignment artifacts in prospectively ECG-triggered axial coronary CT angiography scans. In this study we analyzed 56 consecutive patients scanned in axial mode and 66 consecutive patients scanned in helical mode. Predictors for the occurrence of misalignment artifacts were evaluated by multivariable logistic regression analysis for those patients scanned in the axial mode; advanced age was identified as the sole independent predictor (odds ratio: 1.088; 95 % CI: 1.012-1.170; p = 0.0228). In a comparison with the patients scanned in the helical mode, the image quality score for patients aged 65 years or older was significantly higher in helical mode than in axial mode (2.6 ± 0.5 and 2.4 ± 0.7, respectively; p = 0.0313). Misalignment artifacts in the image are more common in the elderly than in younger. Helical mode should be preferred in this older patient population to allow for good diagnostic image quality.

Syncope due to paroxysmal complete atrioventricular block in a patient with aortic valve stenosis.

A 66-year-old man was admitted due to repeated syncope, and the electrocardiogram showed complete atrioventricular block (CAVB). He had moderate aortic valve stenosis (AS) with a severely calcified valve. This case indicates that if calcification spreads into the cardiac conduction system, it may cause CAVB. Although CAVB is not typically considered a main cause of syncope in AS patients, it should nevertheless be considered in the differential diagnosis.

A murmur-free giant myxoma discovered incidentally on abdominal ultrasonography.

Patients with myxoma normally present with cardiovascular symptoms due to mitral valve obstruction caused by the tumor. However, some cases are difficult to diagnose because the findings of auscultation are normal and there are no cardiovascular symptoms. A 62-year-old man presented at a nearby clinic with a fever. No cardiac murmurs were heard on a physical examination. Abdominal ultrasonography was conducted to evaluate the origin of the fever, and a giant left atrial myxoma was discovered incidentally. Although many myxoma cases are found on transthoracic echocardiography, we herein describe a case of a giant left atrial myxoma incidentally discovered on abdominal ultrasonography.

Japanese features of native valve endocarditis caused by coagulase-negative staphylococci: case reports and a literature review.

Although coagulase-negative staphylococci (CoNS) is a frequent cause of prosthetic valve endocarditis, native valve endocarditis (NVE) caused by CoNS is not commonly seen. Its high mortality is well known; however, there are no systematic reports published in Japan. We herein report the cases of two Japanese patients with CoNS NVE who were admitted to our hospital located in Tokyo and conduct literature searches on CoNS NVE in Japan from 1983 to March 2012 using PubMed and ICHUSHI WEB (Japan Medical Abstract Society). We also summarize the features of 22 Japanese patients with CoNS NVE, including our patients.

Successful treatment of congestive heart failure with concomitant administration of tolvaptan to enhance the effects of furosemide.

Tolvaptan (TLV), which is an antagonist to the vasopressin V2 receptor, was approved by Japanese authorities for the treatment of "volume overload in heart failure when adequate response is not obtained with other diuretics (e.g. loop diuretics)". An 82-year-old female Japanese patient was admitted to our hospital due to congestive heart failure (CHF) and exacerbation of type 2 chronic respiratory failure, which improved with ventilator support and treatment with furosemide; however, the CHF worsened again due to anemia and undernutrition. TLV (7.5 mg/day) was given. The free-water clearance value showed the efficacy of TLV; it was -0.04 before and 0.39 six hours after TLV administration. The administration of TLV was continued for five consecutive days, and the fractional excretion of sodium showed the efficacy of furosemide; it was 1.7% before and 5.2% five days after TLV administration. It is known that the long-term usage of loop diuretics causes tolerance because it promotes sodium re-absorption through the proximal renal tubules by activating the renin-angiotensin-aldosterone system. A patient with CHF was treated successfully by concomitant administration of TLV with furosemide. TLV worked both directly and indirectly; it promoted free-water filtration as its direct effect and sodium filtration as its indirect effect. .

Red blood cell distribution width as an effective tool for detecting fatal heart failure in super-elderly patients.

OBJECTIVE: Red blood cell distribution width (RDW) is a numerical measure of erythrocyte size variation. It has been recently reported to be an independent prognostic marker of heart failure (HF). Previous studies on RDW were mostly designed for middle-aged and elderly patients (60-79 years old), therefore, there is no established limit for super-elderly patients (≥ 80 years old). The purpose of this study was to evaluate RDW as an effective tool to detect fatal HF in super-elderly patients. METHODS: The medical records and death certificates of 160 consecutive patients admitted to the Department of Cardiology in Juntendo Tokyo Koto Geriatric Medical Center and who died from June 2002 to October 2010 were reviewed. The causes of death were reviewed, and the factors, including RDW, that might have been related to the fatal HF were evaluated using multivariate logistic regression analysis. RESULTS: HF was the major cause of death [52 patients (32.5%), 29 females, age 84.0 ± 7.5 years], followed by pneumonia (18.8%, 30/160), and acute myocardial infarction (16.3%, 26/160). The most common cause of HF was atrial fibrillation (36.6%, 19/52), followed by hypertensive heart disease (19.2%, 10/52) and valvular disorders (17.3%, 9/52). The multivariate logistic regression analysis found that a high RDW (≥ 16.5%) was an independent factor related to fatal HF (OR 2.36, 95% CI 1.10, 5.04, p=0.03). CONCLUSION: HF was the major cause of death, and RDW ≥ 6.5 was significantly associated with fatal HF in super-elderly patients.

Usefulness of prominently projected aortic arch on chest radiograph to predict severe tortuosity of the right subclavian or brachiocephalic artery in patients aged >44 years undergoing coronary angiography with a right radial artery approach.

Although it is well known that certain characteristics, such as older age, female gender, hypertension, and high body mass index, are closely associated with severe arterial tortuosity among patients undergoing transradial coronary angiography, few data are available regarding useful predictors of severe arterial tortuosity among geriatric patients. The purpose of the present study was to evaluate the characteristics of geriatric patients with severe tortuosity of the right subclavian artery or brachiocephalic artery. The coronary angiographic reports of patients with severe tortuosity of the right subclavian artery or brachiocephalic artery and age- and gender-matched control patients were retrospectively evaluated. A total of 847 consecutive patients underwent right transradial coronary angiography. Of these patients, 48 (5.7%) had severe tortuosity (29 women, age 73.4 ± 8.6 years). The factors associated with severe arterial tortuosity were greater body mass index (odds ratio 1.17, p = 0.02), the presence of a prominently projected aortic arch on a chest radiograph (odds ratio 5.62, p <0.01), and lower serum creatinine value (odds ratio 0.05, p <0.01). In conclusion, the presence of a prominently projected aortic arch on the chest radiograph is a useful predictor of severe arterial tortuosity.

Impact of diabetes on muscle mass, muscle strength, and exercise tolerance in patients after coronary artery bypass grafting.

BACKGROUND: The impact of diabetes mellitus (DM) on muscle mass, muscle strength, and exercise tolerance in patients who had undergone coronary artery bypass grafting (CABG) has not been fully elucidated. METHODS: We enrolled 329 consecutive patients who received cardiac rehabilitation (CR) after CABG (DM group, n=178; non-DM group, n=151) and measured lean body weight, mid-upper arm muscle area (MAMA), and handgrip power (HGP) at the beginning of CR. We also performed an isokinetic strength test of the knee extensor (Ext) and flexor (Flex) muscles and a cardiopulmonary exercise testing at the same time. RESULTS: No significant differences in risk factors, including age, gender, number of diseased vessels, or ejection fraction were observed between the 2 groups. The levels of Ext muscle strength, peak oxygen uptake, and anaerobic threshold were significantly lower in the DM group than in the non-DM group (all p<0.05). Both peak oxygen uptake and MAMA correlated with Ext and Flex muscle strength as well as HGP (all p<0.005). The MAMA, HGP, and Ext muscle strength were lower in patients who received insulin therapy than in those who did not. Interestingly, fasting glucose levels significantly and negatively correlated with Ext muscle strength. CONCLUSIONS: These data suggest that DM patients had a lower muscle strength and exercise tolerance than non-DM patients. Moreover, a high glucose level may affect these deteriorations in DM patients after CABG.

Massive Pericardial Effusion in a Case of Acute Pericarditis with Slight ST-Segment Elevation of Short Duration.

We present the case of a 77-year-old woman who suffered from chest pain. Her white blood cell count was 10,200/µL and C-reactive protein level was 5.5 mg/dL. There was no electrocardiogram abnormality up to 5 hours after admission. At 15 hours, slight ST-segment elevation occurred, but this disappeared on day 4. Imaging revealed slight pericardial effusion. Nonsteroidal anti-inflammatory drugs and antibiotics were administered. However, the pericardial effusion, inflammatory response, and bilateral heart failure worsened. Pericardiotomy on day 6 released 350 mL of fluid, and symptoms improved. Viral pericarditis was assumed. Massive pericardial effusion is rare in cases of acute viral pericarditis, as is slight, short-duration ST-segment elevation.

Acute Myocardial Infarction with Severe ST Segment Elevation Treated with Percutaneous Coronary Intervention More than Two Days after Onset: A Case with Remarkable Recovery.

The patient was a 65-year-old man with marked ST-elevation myocardial infarction. Cardiac catheterization revealed an occluded middle portion of the left anterior descending artery and no collateral circulation. Percutaneous coronary intervention (PCI) was performed, and ST elevation improved 5 days after PCI. Almost all electrocardiogram (ECG) findings were normal 6 months later. Echocardiographic findings were also normal. This case was very successful and unusual in that no ventricular aneurysm formed despite ST elevation continuing for a few days and that ECG and left ventricular function were nearly normal after PCI performed days after the onset in a case without collateral circulation.

DGAT1 expression increases heart triglyceride content but ameliorates lipotoxicity.

Intracellular lipid accumulation in the heart is associated with cardiomyopathy, yet the precise role of triglyceride (TG) remains unclear. With exercise, wild type hearts develop physiologic hypertrophy. This was associated with greater TG stores and a marked induction of the TG-synthesizing enzyme diacylglycerol (DAG) acyltransferase 1 (DGAT1). Transgenic overexpression of DGAT1 in the heart using the cardiomyocyte- specific alpha-myosin heavy chain (MHC) promoter led to approximately a doubling of DGAT activity and TG content and reductions of approximately 35% in cardiac ceramide, 26% in DAG, and 20% in free fatty acid levels. Cardiac function assessed by echocardiography and cardiac catheterization was unaffected. These mice were then crossed with animals expressing long-chain acyl-CoA synthetase via the MHC promoter (MHC-ACS), which develop lipotoxic cardiomyopathy. MHC-DGAT1XMHC-ACS double transgenic male mice had improved heart function; fractional shortening increased by 74%, and diastolic function improved compared with MHC-ACS mice. The improvement of heart function correlated with a reduction in cardiac DAG and ceramide and reduced cardiomyocyte apoptosis but increased fatty acid oxidation. In addition, the survival of the mice was improved. Our study indicates that TG is not likely to be a toxic lipid species directly, but rather it is a feature of physiologic hypertrophy and may serve a cytoprotective role in lipid overload states. Moreover, induction of DGAT1 could be beneficial in the setting of excess heart accumulation of toxic lipids.

Cardiac metabolic compensation to hypertension requires lipoprotein lipase.

Fatty acids (FAs) are acquired from free FA associated with albumin and lipoprotein triglyceride that is hydrolyzed by lipoprotein lipase (LpL). Hypertrophied hearts shift their substrate usage pattern to more glucose and less FA. However, FAs may still be an important source of energy in hypertrophied hearts. The aim of this study was to examine the importance of LpL-derived FAs in hypertensive hypertrophied hearts. We followed cardiac function and metabolic changes during 2 wk of angiotensin II (ANG II)-induced hypertension in control and heart-specific lipoprotein lipase knockout (hLpL0) mice. Glucose metabolism was increased in ANG II-treated control (control/ANG II) hearts, raising it to the same level as hLpL0 hearts. FA uptake-related genes, CD36 and FATP1, were reduced in control/ANG II hearts to levels found in hLpL0 hearts. ANG II did not alter these metabolic genes in hLpL0 mice. LpL activity was preserved, and mitochondrial FA oxidation-related genes were not altered in control/ANG II hearts. In control/ANG II hearts, triglyceride stores were consumed and reached the same levels as in hLpL0/ANG II hearts. Intracellular ATP content was reduced only in hLpL0/ANG II hearts. Both ANG II and deoxycorticosterone acetate-salt induced hypertension caused heart failure only in hLpL0 mice. Our data suggest that LpL activity is required for normal cardiac metabolic compensation to hypertensive stress.

Cardiomyocyte expression of PPARgamma leads to cardiac dysfunction in mice.

Three forms of PPARs are expressed in the heart. In animal models, PPARgamma agonist treatment improves lipotoxic cardiomyopathy; however, PPARgamma agonist treatment of humans is associated with peripheral edema and increased heart failure. To directly assess effects of increased PPARgamma on heart function, we created transgenic mice expressing PPARgamma1 in the heart via the cardiac alpha-myosin heavy chain (alpha-MHC) promoter. PPARgamma1-transgenic mice had increased cardiac expression of fatty acid oxidation genes and increased lipoprotein triglyceride (TG) uptake. Unlike in cardiac PPARalpha-transgenic mice, heart glucose transporter 4 (GLUT4) mRNA expression and glucose uptake were not decreased. PPARgamma1-transgenic mice developed a dilated cardiomyopathy associated with increased lipid and glycogen stores, distorted architecture of the mitochondrial inner matrix, and disrupted cristae. Thus, while PPARgamma agonists appear to have multiple beneficial effects, their direct actions on the myocardium have the potential to lead to deterioration in heart function.

Lipids in the heart: a source of fuel and a source of toxins.

PURPOSE OF REVIEW: How do lipids arrive in the heart and other tissues? This review focuses on new information on pathways of lipid uptake into the heart. RECENT FINDINGS: Fatty acids, the major cardiac fuel, are obtained from either lipoproteins or free fatty acids associated with albumin. The heart is the tissue with the most robust expression of lipoprotein lipase, and recent data attest to the importance of this enzyme in supplying optimal amounts of fatty acids for the heart. Genetic deletion of CD36 also shows that this transporter is important for cardiac uptake of lipids. Retinoid acquisition by the heart involves pathways parallel to those used for fatty acid uptake: a pathway for acquisition of core lipoprotein retinyl ester and another for nonlipoprotein retinol. Dilated lipotoxic cardiomyopathy is the consequence of excess lipid uptake. SUMMARY: Genetic modifications that affect lipid uptake, oxidation, and storage are being exploited to elucidate the pathophysiology of cardiomyopathies and to discover how lipids relate to heart failure in humans with obesity and diabetes mellitus. This information is likely to lead to new diagnostic categories of cardiomyopathy and more pathophysiologically appropriate treatments.

Cardiac metabolism and mechanics are altered by genetic loss of lipoprotein triglyceride lipolysis.

INTRODUCTION: Most circulating fatty acids are contained in lipoprotein triglycerides. For the heart to acquire these lipids, they must be broken down into free fatty acids via the enzyme lipoprotein lipase (LpL). Although it has long been known that hearts primarily use esterified fatty acids as fuel, different sources of fatty acids were thought to be interchangeable. MATERIALS AND METHODS: By creating mice with neonatal and acute LpL deletion we showed that lipoprotein-derived fatty acids could not be replaced by albumin-associated free fatty acids. Loss of cardiac LpL forces the heart to increase its uptake of glucose, reduce fatty acid oxidation, and eventually leads to cardiac dysfunction. In contrast, cardiomyocyte specific overexpression of an anchored form of LpL leads to excess lipid uptake, induction of fatty acid oxidation genes, and dilated cardiomyopathy. CONCLUSION: Increasing lipid secretion from the heart or redirecting lipids to adipose tissue can alleviate this lipotoxic situation.