A chronic hemodialysis patient with isolated pulmonary valve infective endocarditis caused by non-albicans Candida: a rare case and literature review.

BACKGROUND: Isolated pulmonary valve infective endocarditis caused by Candida is rare in chronic hemodialysis patients. The 2009 Infectious Diseases Society of America guidelines suggest the combined use of surgery and antibiotics to treat candidiasis; however, successful nonsurgical treatment of Candida endocarditis has been reported. CASE PRESENTATION: A 63-year-old woman with end-stage kidney disease was admitted to our hospital after experiencing disorientation for 5 days. The patient was permanently bedridden because of depression, and denied active intravenous drug use. She received maintenance hemodialysis through a tunneled-cuffed catheter. An initial blood culture grew Candida guilliermondii without other bacteria. Subsequent blood cultures and tip culture of tunneled-cuffed catheter also grew C. guilliermondii, even after caspofungin replaced fluconazole. A 1.2-cm mobile mass was observed on the pulmonary valve. Surgical intervention was suggested, but the family of the patient declined because of her multiple comorbidities. The patient was discharged with a prescription of fluconazole, but she died soon after. CONCLUSION: Our patient is the first case with isolated pulmonary valve endocarditis caused by C. guilliermondii in patients with uremia. Hematologic disorders, in addition to long-term central venous catheter use, prolonged antibiotic intravenous injection, and congenital cardiac anomaly, predispose to the condition. The diagnosis "isolated" pulmonary IE is difficult, and combing surgery with antifungal antibiotics is the appropriate therapeutic management for Candida related pulmonary IE.

Using Machine Learning to Predict Abnormal Carotid Intima-Media Thickness in Type 2 Diabetes.

Carotid intima-media thickness (c-IMT) is a reliable risk factor for cardiovascular disease risk in type 2 diabetes (T2D) patients. The present study aimed to compare the effectiveness of different machine learning methods and traditional multiple logistic regression in predicting c-IMT using baseline features and to establish the most significant risk factors in a T2D cohort. We followed up with 924 patients with T2D for four years, with 75% of the participants used for model development. Machine learning methods, including classification and regression tree, random forest, eXtreme gradient boosting, and Naïve Bayes classifier, were used to predict c-IMT. The results showed that all machine learning methods, except for classification and regression tree, were not inferior to multiple logistic regression in predicting c-IMT in terms of higher area under receiver operation curve. The most significant risk factors for c-IMT were age, sex, creatinine, body mass index, diastolic blood pressure, and duration of diabetes, sequentially. Conclusively, machine learning methods could improve the prediction of c-IMT in T2D patients compared to conventional logistic regression models. This could have crucial implications for the early identification and management of cardiovascular disease in T2D patients.

Primary prevention of cardiovascular disease events with renin-angiotensin system blockade in autosomal dominant polycystic kidney disease dialysis patients: A nationwide cohort study.

ABSTRACT: Although renin-angiotensin system (RAS) blockade has been shown to reduce cardiovascular disease (CVD) in the general population and high-risk subjects, their protective effect in autosomal dominant polycystic kidney disease (ADPKD) patients under dialysis was still unknown. By using the database from 1995 to 2008 Taiwan National Health Insurance Research Database (Registry for Catastrophic Illnesses), we included 387 ADPKD patients who received dialysis therapy, aged ≥ 18 year-old, and with no evidence of CVD events in 1997 and 1998. We utilized Cox proportional hazards regression analysis and propensity score matching to evaluate adjusted hazard ratios for all-cause mortality and CVD events in users (n=231) and nonusers (n = 156) of an angiotensin-converting enzymes inhibitor (ACEI) / angiotensin II receptor blocker (ARB) during the 12 years of follow-up. All study subjects were followed up for more than 3 months. There was no significant difference between the ACEI/ARB treatment group and the control group in incident CVD events except ischemic stroke and transient ischemic accident (TIA). The results remain similar between groups before and after propensity score matching. Moreover, there was no significant difference in outcomes between ACEI/ARB treatment over 50% of follow-up period and without ACEI/ARB treatment after propensity score matching. This nationwide cohort study failed to prove the protective effects of long-term ACEI or ARB on incident CVD events among APKD dialysis patients. Further larger scale, multicenter and randomized control trials are warranted to show the causal association.

Dimethylthiourea normalizes velocity-dependent, but not force-dependent, index of ventricular performance in diabetic rats: role of myosin heavy chain isozyme.

Hydroxyl radicals and hydrogen peroxide are involved in the pathogenesis of systolic dysfunction in diabetic rats, but the precise mechanisms and the effect of antioxidant therapy in diabetic subjects have not been elucidated. We aimed to evaluate the effects of dimethylthiourea (DMTU), a potent hydroxyl radical scavenger, on both force-dependent and velocity-dependent indexes of cardiac contractility in streptozotocin (STZ)-induced early and chronic diabetic rats. Seventy-two hours and 8 wk after STZ (55 mg/kg) injection, diabetic rats were randomized to either DMTU (50 mg x kg(-1) x day(-1) ip) or vehicle treatment for 6 and 12 wk, respectively. All rats were then subjected to invasive hemodynamic studies. Maximal systolic elastance (E(max)) and maximum theoretical flow (Q(max)) were assessed by curve-fitting techniques in terms of the elastance-resistance model. Both normalized E(max) (E(maxn)) and afterload-adjusted Q(max) (Q(maxad)) were depressed in diabetic rats, concomitant with altered myosin heavy chain (MHC) isoform composition and its upstream regulators, such as myocyte enhancer factor-2 (MEF-2) and heart autonomic nervous system and neural crest derivatives (HAND). In chronic diabetic rats, DMTU markedly attenuated the impairment in Q(maxad) and normalized the expression of MEF-2 and eHAND and MHC isoform composition but exerted an insignificant benefit on E(maxn). Regarding preventive treatment, DMTU significantly ameliorated both E(maxn) and Q(maxad) in early diabetic rats. In conclusion, our study shows that DMTU has disparate effects on Q(maxad) and E(maxn) in chronic diabetic rats. The advantage of DMTU in chronic diabetic rats might involve normalization of MEF-2 and eHAND, as well as reversal of MHC isoform switch.

The Emerging Role of Nutritional Vitamin D in Secondary Hyperparathyroidism in CKD.

In chronic kidney disease (CKD), hyperphosphatemia induces fibroblast growth factor-23 (FGF-23) expression that disturbs renal 1,25-dihydroxy vitamin D (1,25D) synthesis; thereby increasing parathyroid hormone (PTH) production. FGF-23 acts on the parathyroid gland (PTG) to increase 1α-hydroxylase activity and results in increase intra-gland 1,25D production that attenuates PTH secretion efficiently if sufficient 25D are available. Interesting, calcimimetics can further increase PTG 1α-hydroxylase activity that emphasizes the demand for nutritional vitamin D (NVD) under high PTH status. In addition, the changes in hydroxylase enzyme activity highlight the greater parathyroid 25-hydroxyvitmain D (25D) requirement in secondary hyperparathyroidism (SHPT); the higher proportion of oxyphil cells as hyperplastic parathyroid progression; lower cytosolic vitamin D binding protein (DBP) content in the oxyphil cell; and calcitriol promote vitamin D degradation are all possible reasons supports nutritional vitamin D (NVD; e.g., Cholecalciferol) supplement is crucial in SHPT. Clinically, NVD can effectively restore serum 25D concentration and prevent the further increase in PTH level. Therefore, NVD might have the benefit of alleviating the development of SHPT in early CKD and further lowering PTH in moderate to severe SHPT in dialysis patients.

The thicker the skin fold, the less hematoma development: a novel parameter other than body mass index associated with transradial vascular complication.

It was reported recently that body mass index (BMI) is a prognostic factor of vascular complications after radial puncture, and that extremely thin patients are at higher risk than obese subjects. However, the underlining mechanism of this phenomenon has rarely been studied. Therefore, we conducted a survey measuring a novel parameter, the skin fold thickness, and other potential risk factors in our patients developing postprocedure hematoma. In 1176 consecutive patients undergoing percutaneous radial catheterization, 18 (1.53%) developed hematoma afterward. When a patient with hematoma had been identified, the next patient having no hematoma after radial puncture was enrolled into the control group, which thus turned out to have 18 patients. In addition, we also compared the BMI, skin fold thickness, and other potential risk factors, including heparin dosage and antiplatelet medication, between these 2 groups. We found hematoma patients to be older (69.5 +/- 10.3 years vs 61.50 +/- 11.7 years, P = .037), to have more cases of coronary intervention (10/18 vs 4/18, P = .04), to have lower BMI (23.63 +/- 4.03 vs 27.25 +/- 4.38, P = .014), and to have thinner skin folds of forearm (5.94 +/- 4.56 vs 9.27 +/- 3.06 mm, P = .015), deltoid area (14.61 +/- 9.00 vs 19.73 +/- 7.15 mm, P = .042), and waist (21.94 +/- 9.90 vs 29.00 +/- 8.46 mm, P = .028) than the nonhematoma group. On the contrary, no statistical difference in heparin dosage or other factors was noted between the 2 groups. We conclude that the vascular complication rate after radial catheterization is higher in elderly patients with lower BMI, body weight, or thinner skin folds.

Enhanced diagnosis of coronary artery disease in women by dobutamine thallium-201 ST-segment/heart rate slope and thallium-201 myocardial SPECT.

BACKGROUND/PURPOSE: The diagnosis of coronary artery disease (CAD) in women presents a great challenge because of poor exercise capacity and inadequate heart rate response during stress test. The clinical significance of stress-related ST-segment/heart rate slope (ST/HR slope) value for evaluating CAD in women remains controversial. Therefore, we conducted the present study to assess the diagnostic performance of dobutamine ST/HR slope in women, compared with myocardial perfusion study using thallium-201 single-photon emission computed tomography (Tl-201 SPECT). METHODS: A total of 51 female patients with suspected CAD underwent simultaneous 12-lead electrocardiographic recording during 3-minute stages of dobutamine infusion as well as Tl-201 SPECT, and coronary angiography was performed within 2 weeks post Tl-201 SPECT. The sensitivity, specificity, positive predictive value and negative predictive value of dobutamine ST/HR slope and Tl-201 SPECT were assessed, and the results of coronary angiography were used as a gold standard. RESULTS: The sensitivity, specificity and accuracy of dobutamine ST/HR slope in detecting CAD were 43%, 83% and 61%, and those of Tl-201 SPECT were 71%, 87% and 78%, respectively. However, using both positive results of Tl-201 SPECT and ST/HR slope for detecting CAD, the diagnostic specificity increased from 87% to 96%. Using both negative results of Tl-201 SPECT and ST/HR slope to exclude CAD, the negative predictive value increased from 71% to 85%. The accuracy of dobutamine ST/HR slope in detecting CAD was not affected by the use of beta-blockers. CONCLUSION: Dobutamine ST/HR slope is less sensitive and less accurate than Tl-201 SPECT for detecting CAD in women. However, it adds diagnostic benefit to Tl-201 SPECT with only a little extra calculation.

Two donor hearts beat in one chest.

We present the case of a 52-year-old man who had end-stage dilated cardiomyopathy (left ventricular ejection fraction, 0.14) and type-A blood. He underwent orthotopic transplantation with a heart from a blood-type-A male donor on 18 January 2001. After transplantation, the patient could not be weaned from cardiopulmonary bypass. Due to calcification of the left main and right coronary arteries, we performed triple coronary artery bypass (left anterior descending, circumflex, and right coronary arteries) with the recipient's saphenous vein. Despite high doses of inotropic agents and intra-aortic balloon pumping, the patient could not be weaned from cardiopulmonary bypass; he was put on extracorporeal membrane oxygenation 2 hours later. Meanwhile, there was another donor (a woman with type-O blood), who weighed 48 kg. Upon harvesting that heart for a recipient who weighed 68 kg, we found a laceration of the right ventricle. Therefore, we decided to use this marginal donor heart to rescue the graft-failure transplant by means of heterotopic heart transplantation. We left the 1st donor heart in situ. The postoperative series of endomyocardial biopsies showed variations between the 2 donor hearts in degrees of mild-to-moderate rejection. During the 6-year, 2-month follow-up period, the patient has fared well with 2 donor hearts, which beat independently but in conjunction. We conclude that heterotopic transplantation of a marginal donor heart can save an otherwise-dying orthotopic transplant recipient.

Primary prevention of myocardial infarction with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in hypertensive patients with rheumatoid arthritis-A nationwide cohort study.

BACKGROUND: Rheumatoid arthritis (RA) is regarded as a high risk factor for myocardial infarction. Hypertension is a major modifiable risk factor contributing to increased risk of myocardial infarction (MI). Dual blood pressure (BP)-lowering and anti-inflammatory effect of renin-angiotensin-system (RAS) inhibitors may possess protective effect from MI in RA population. However, treatment of hypertension with RAS inhibitors and MI in RA population remains unclear. METHODS: We investigated whether RAS blockade could decrease risk of incident MI in hypertensive patients with RA. We identified patients with RA and hypertension from the Registry for Catastrophic Illness, a nation-wide database encompassing almost all of the RA patients in Taiwan from 1995 to 2008. The primary endpoint was MI and the median duration of follow up was 2,986 days. Propensity score weighting and Cox proportional hazards regression models were used to estimate hazard ratios for MI. RESULTS: Among 27,335 subjects, 9.9% received angiotensin-converting enzyme inhibitors (ACEIs), 25.9% received angiotensin II receptor blockers (ARBs) and 20.0% received ACEIs or ARBs alternatively. The incidence of MI significantly decreased in patients treated with ACEIs (hazard ratio 0.707; 95% confidence interval 0.595-0.840), ARBs (0.641; 0.550-0.747) and ACEIs/ARBs (0.631; 0.539-0.739). The protective effect of ACEI or ARB therapy was significantly better in patients taking longer duration. The effect remained robust in subgroup analyses. CONCLUSIONS: Therapy of ACEIs or ARBs is associated with a lower risk of MI among patients with RA. Hence, hypertension in patients with RA could comprise a compelling indication for RAS inhibitors.

Rho-associated kinase inhibitors promote the cardiac differentiation of embryonic and induced pluripotent stem cells.

BACKGROUND: Rho-associated kinase (ROCK) plays an important role in maintaining embryonic stem (ES) cell pluripotency. To determine whether ROCK is involved in ES cell differentiation into cardiac and hematopoietic lineages, we evaluated the effect of ROCK inhibitors, Y-27632 and fasudil on murine ES and induced pluripotent stem (iPS) cell differentiation. METHODS: Gene expression levels were determined by real-time PCR, Western blot analysis and immunofluorescent confocal microscopy. Cell transplantation of induced differentiated cells were assessed in vivo in a mouse model (three groups, n=8/group) of acute myocardial infarction (MI). The cell engraftment was examined by immunohistochemical staining and the outcome was analyzed by echocardiography. RESULTS: Cells were cultured in hematopoietic differentiation medium in the presence or absence of ROCK inhibitor and colony formation as well as markers of ES, hematopoietic stem cells (HSC) and cells of cardiac lineages were analyzed. ROCK inhibition resulted in a drastic change in colony morphology accompanied by loss of hematopoietic markers (GATA-1, CD41 and ß-Major) and expressed markers of cardiac lineages (GATA-4, Isl-1, Tbx-5, Tbx-20, MLC-2a, MLC-2v, α-MHC, cTnI and cTnT) in murine ES and iPS cells. Fasudil-induced cardiac progenitor (Mesp-1 expressing) cells were infused into a murine MI model. They engrafted into the peri-infarct and infarct regions and preserved left ventricular function. CONCLUSIONS: These findings provide new insights into the signaling required for ES cell differentiation into hematopoietic as well as cardiac lineages and suggest that ROCK inhibitors are useful in directing iPS cell differentiation into cardiac progenitor cells for cell therapy of cardiovascular diseases.

Physiology-based diagnosis algorithm for arteriovenous fistula stenosis detection.

In this paper, a diagnosis algorithm for arteriovenous fistula (AVF) stenosis is developed based on auscultatory features, signal processing, and machine learning. The AVF sound signals are recorded by electronic stethoscopes at pre-defined positions before and after percutaneous transluminal angioplasty (PTA) treatment. Several new signal features of stenosis are identified and quantified, and the physiological explanations for these features are provided. Utilizing support vector machine method, an average of 90% two-fold cross-validation hit-rate can be obtained, with angiography as the gold standard. This offers a non-invasive easy-to-use diagnostic method for medical staff or even patients themselves for early detection of AVF stenosis.

PKCɛ mediates serine phosphorylation of connexin43 induced by lysophosphatidylcholine in neonatal rat cardiomyocytes.

Lysophosphatidylcholine (LPC) is a potent pro-arrhythmic derivative of the membrane phosphotidylcholine, which is accumulated in heart tissues during cardiac ischemia. However, the cellular mechanism underlying LPC-induced cardiomyocyte damage remains to be elucidated. This study focuses on the effects of LPC on cardiomyocyte gap junction. At 30µM, LPC decreased the spontaneous contraction rates of cardiomyocytes, and caused arrhythmic contraction without affecting cell viability. Connexin43 (Cx43) was seen as large plaques at cell junctions in control cells, whereas upon LPC treatment, the intensity of Cx43 staining was decreased in a concentration-sensitive manner and Cx43 staining appeared as tiny dots at cell junctions with a corresponding increase in cytoplasmic punctate staining. This distributional change of Cx43 was accompanied by an impairment of the gap junction intercellular communication (GJIC). Further, LPC treatment induced protein kinase C (PKC) activation, and PKC-dependent Cx43 phosphorylation at serine (Ser) 368. Pre-treatment with a specific PKCɛ inhibitor, eV1-2, prevented the LPC-induced Cx43 phosphorylation at Ser368 and the loss of Cx43 from gap junctions, both of which may disturb GJIC functions. Furthermore, siRNA knockdown of PKCɛ in H9c2 cells prevented LPC-induced serine phosphorylation of Cx43, confirming the role of PKCɛ in Cx43 serine phosphorylation. Double labeling immunofluorescence showed that LPC increased the colocalization of Cx43 with ubiquitin, and pretreatment with MG132 effectively prevented LPC-induced gap junction disassembly. LPC increased the ubiquitination of Cx43, which was blocked by eV1-2 pretreatment, suggesting that LPC accelerated the intracellular degradation of Cx43 via the ubiquitin-proteasomal pathway. It can be concluded that LPC destroyed the structure and function of gap junctions via PKCɛ-mediated serine phosphorylation of Cx43. PKCɛ inhibitors might therefore be effective in prevention of LPC-related diseases.

A novel system for continuous peripheral arterial pressure-volume loop measurement.

This study develops a system to obtain continuous blood pressure signal and impedance plethysmography (IPG) signal, simultaneously. Based on the principle of impedance measurement, the peripheral vessel volume change can be computed from the IPG signal. Equipped with simultaneous information of pressure and volume, a pressure-volume (PV) loop can be constructed. It is well known that the left ventricular pressure-volume loop contains a number of feature points indicating the performance of cardiac function. Therefore, in this study, the same principle is used to try to discuss the peripheral vessel pressure-volume loop. Ten volunteers were recruited for this study. Subjects went through the cold pressor test by immersing their left foot into ice water. Blood pressure signal and impedance changed were recorded using a custom-made system. The results illustrated that the pressure-volume loop, as it was expected, demonstrated a contraction phenomenon after stimulation in five out of ten subjects. The areas of those pressure-volume loops reduced as much as 70% in some subject. However, loop responses to stressors varied from subject to subject and the slope of the loop did not alter significantly. In conclusion, the proposed system is a potential way to measure and to investigate the compliance and characteristic of peripheral blood vessel.

Enhanced activity and subcellular redistribution of myocardial hexokinase after acute myocardial infarction.

BACKGROUND: Hexokinase (HK) is known to possess both anti-oxidant and anti-apoptotic properties. This study investigated the behavior of myocardial HK in response to myocardial infarction (MI). METHODS: Adult male Wistar rats with various degrees of MI after coronary ligation were examined 4 weeks after operation and were divided dichotomously into small and large MI groups. The activity and subcellular distribution of HK in the non-infarcted myocardium were determined. In parallel, myocardial oxidative stress determined using aconitase activity and malondialdehyde content, and left ventricular function using echocardiography were studied. RESULTS: In the mitochondria and the cytosol, HK activity was enhanced after MI and paralleled the increases in oxidative stress and left ventricular end-diastolic dimension (LVEDD). The enhancement in HK activity varied between subcellular compartments and resulted in an increase in the ratio of cytosol to whole-cell HK activity, which was proportional to oxidative stress and LVEDD. CONCLUSIONS: The activities of HK in all subcellular fractions are enhanced in response to MI. However, enhanced proportion of cytosolic HK relative to whole-cell HK activity is associated with higher oxidative stress and LVEDD, suggesting that altered myocardial HK activity and subcellular redistribution might be involved in the pathogenesis of postinfarct heart failure.

The detrended fluctuation analysis of acute-phase heart-rate variability in acute coronary syndromes - a pilot study.

Heart-rate variability (HRV) analyzed by detrended fluctuation analysis (DFA), which resulted in a short-term fractal exponent - alpha, has prognostic implication in chronic phase of heart failure and survivors of myocardial infarction. We adopted DFA to study the acute-phase HRV in acute coronary syndromes (ACS) by recruiting 30 age- and co-morbidity-matched adults in acute-stress simulation in comparison with 33 consecutive ACS patients. The 30 volunteers got stepwise elevated alpha with increased intensity of exercise (0.95+/-0.050 to 1.07+/-0.084 to 1.20+/-0.083, p<0.05). The alpha of 33 ACS patients correlated with the complexity of post-MI course (1.004+/-0.0080 in non-complicated vs. 1.216+/-0.058 in complicated p<0.05). No significance existed in categories of age, ACS type, numbers of diseased vessel, infarct-related artery or Killip classification. The increased alpha value of DFA may imply unresolved cardiac stress which demands further attention.

Temporal changes in cardiac force- and flow-generation capacity, loading conditions, and mechanical efficiency in streptozotocin-induced diabetic rats.

Diabetes mellitus may result in impaired cardiac contractility, but the underlying mechanisms remain unclear. We aimed to investigate the temporal alterations in cardiac force- and flow-generation capacity and loading conditions as well as mechanical efficiency in the evolution of systolic dysfunction in streptozotocin (STZ)-induced diabetic rats. Adult male Wistar rats were randomized into control and STZ-induced diabetic groups. Invasive hemodynamic studies were done at 8, 16, and 22 wk post-STZ injection. Maximal systolic elastance (E(max)) and maximum theoretical flow (Q(max)) were assessed by curve-fitting techniques, and ventriculoarterial coupling and mechanical efficiency were assessed by a single-beat estimation technique. In contrast to early occurring and persistently depressed E(max), Q(max) progressively increased with time but was decreased at 22 wk post-STZ injection, which temporally correlated with the changes in cardiac output. The favorable loading conditions enhanced stroke volume and Q(max), whereas ventriculoarterial uncoupling attenuated the cardiac mechanical efficiency in diabetic animals. The changes in E(max) and Q(max) are discordant during the progression of contractile dysfunction in the diabetic heart. In conclusion, our study showed that depressed Q(max) and cardiac mechanical efficiency, occurring preceding overt systolic heart failure, are two major determinants of deteriorating cardiac performance in diabetic rats.