Case Report: Pericardial Actinomycosis in a 79-Year-Old Man with Poor Dental Hygiene.

Actinomycosis is an uncommon infection caused by Actinomyces species, and the diagnosis is often challenging owing to low prevalence and diverse clinical manifestations. Pericardial involvement of actinomycosis is particularly rare. Here, we present a case of a 79-year-old man who initially complained of exertional dyspnea, orthopnea, and decreased urine amount. There was no fever, chest pain, or productive cough. Physical examination was remarkable for decreased breath sounds at the left lower lung field. Poor dental hygiene and a firm, well-defined mass without discharge over the hard palate were noted. Echocardiography revealed reduced ejection fraction of the left ventricle, global hypokinesia, and thickened pericardium (> 5 mm) with a small amount of pericardial effusion. On admission, the patient underwent diagnostic thoracentesis, and the results suggested an exudate. However, bacterial and fungal cultures were all negative. There was no malignant cell by cytology. Computed tomography revealed contrast-enhanced pericardial nodular masses. Video-assisted thoracoscopic pericardial biopsy was performed. Histopathology confirmed actinomycosis with chronic abscess formation, and a tissue culture yielded Aggregatibacter actinomycetemcomitans. The symptoms resolved with administration of clindamycin for 6 months. This case highlights the challenge in the diagnosis of cardiac actinomycosis, the potential role of concomitant microorganisms as diagnostic clues, and the favorable clinical response achieved with appropriate antibiotic treatment.

Analysis of Left Ventricular Indexes and Mortality Among Asian Adults With Hemodynamically Significant Chronic Aortic Regurgitation.

Importance: Chronic hemodynamically significant aortic regurgitation (AR) is associated with excess risk of death, yet data for Asian patients are lacking, and whether Asian patients can abide by Western guidelines as to when aortic valve surgery should be performed is unknown. Objective: To assess AR presentation and cutoffs of left ventricular ejection fraction (LVEF), LV end-systolic dimension index (LVESDi), and LV end-systolic volume index (LVESVi) that are associated with risk of death in Asian patients with AR. Design, Setting, and Participants: This retrospective cohort study included consecutive patients with chronic, moderately severe to severe AR from 3 tertiary referral centers (2 in Japan and 1 in Taiwan) from June 11, 2008, through November 19, 2020, with follow-up through November 11, 2021. Exposures: Aortic regurgitation severity, graded by a comprehensive integrated approach. Main Outcomes and Measures: The primary outcome was the association between volume-derived LVEF, LVESDi, and LVESVi and all-cause death (ACD). The secondary outcome was the association of these LV indexes with cardiovascular death (CVD). Clinical and echocardiographic data were analyzed retrospectively. A de novo disk-summation method was used to derive LV volumes and volume-derived LVEF. Results: Of 1259 patients (mean [SD] age, 64 [17] years; 934 [74%] male), 515 (41%) were Japanese and 744 (59%) were Taiwanese. The median follow-up was 4.1 years (IQR, 1.56-7.24 years). The mean (SD) body surface area was 1.67 (0.21) m2; LVEF, 55% (11%); LVESDi, 24.7 (5.7) mm/m2; LVESVi, 50.1 (28.0) mL/m2; and indexed mid-ascending aorta size, 24.7 (5.5) mm/m2. Aortic valve surgery occurred in 483 patients (38%); 240 patients (19%) died during follow-up. Overall mean (SD) 8-year survival was 74% (2%). Separate multivariate models adjusted for covariates demonstrated independent associations of LVEF, LVESDi, and LVESVi with ACD (LVEF: hazard ratio [HR] per 10%, 0.80; 95% CI, 0.70-0.92; P = .002; LVESDi: HR, 1.04; 95% CI, 1.01-1.06; P = .002; LVESVi: HR per 10 mL/m2, 1.11; 95% CI, 1.05-1.17; P < .001) and CVD (LVEF: HR per 10%, 0.69; 95% CI, 0.56-0.85; P < .001; LVESDi: HR, 1.05; 95% CI, 1.01-1.09; P = .01; LVESVi per 10 mL/m2: HR, 1.15; 95% CI, 1.06-1.24; P < .001). In the total cohort, spline curves showed that mortality started to increase for an LVEF of 53% or less, LVESDi of 22 mm/m2 or greater, and LVESVi of 46 mL/m2 or greater for both ACD and CVD. Early surgery was beneficial in 3 strata of LVESDi (<20, 20 to <25, and ≥25 mm/m2) and 2 strata of LVESVi (<46 and ≥46 mL/m2). Conclusions and Relevance: This multicenter cohort study of Asian patients with hemodynamically significant AR found cutoff values of LVEF, LVESDi, and LVESVi that were associated with increased risk of death. These findings suggest that Western guidelines seem applicable in Asian patients and, most importantly, that indexed LV parameters with a lower cutoff could be used in discriminating patients with excess mortality risk.

Comparison Between Bicuspid and Tricuspid Aortic Regurgitation: Presentation, Survival, and Aorta Complications.

Background: Although the Asian population is growing globally, data in Asian subjects regarding differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) in aortic regurgitation (AR) remain unexplored. Objectives: The aim of this study was to examine differences between Asian BAV-AR and TAV-AR in significant AR, including aorta complications. Methods: The study included 711 consecutive patients with chronic moderate to severe and severe AR from 2008 to 2020. Outcomes included all-cause death, aortic valve surgery (AVS), and incidence of aortic dissection (AD). Results: There were 149 BAV-AR (mean age: 48 ± 16 years) and 562 TAV-AR (mean age: 68 ± 15 years; P < 0.0001) patients; baseline indexed left ventricle and indexed aorta size were larger in TAV-AR. Total follow-up was 4.8 years (IQR: 2.0-8.4 years), 252 underwent AVS, and 185 died during follow-up; 18 cases (only 1 BAV) of AD occurred, with a mean maximal aorta size of 60 ± 9 mm. The 10-year AVS incidence was higher in TAV-AR (51% ± 4%) vs BAV-AR (40% ± 5%) even after adjustment for covariates (P < 0.0001). The 10-year survival was higher in BAV-AR (86% ± 4%) vs TAV-AR (57% ± 3%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). Post-AVS 10-year survival was 93% ± 5% in BAV-AR and 78% ± 5% in TAV-AR, respectively (P = 0.08). The 10-year incidence of AD was higher in TAV-AR (4.8% ± 1.5%) than in BAV-AR (0.9% ± 0.9%) and was determined by aorta size ≥45 mm (P ≤ 0.015). Compared with an age- and sex-matched population in Taiwan, TAV-AR (HR: 3.1) had reduced survival (P < 0.0001). Conclusions: Our findings suggest that TAV-AR patients were at a later stage of AR course and had a high AD rate as opposed to BAV-AR patients in Taiwan, emphasizing the importance of early referral for timely management. Surgery on the aorta with a lower threshold in TAV-AR should be considered.

The Logistics of Medication and Patient Flow in Video-Based Virtual Clinics During a Sudden COVID-19 Outbreak in Taiwan: Observational Study.

BACKGROUND: The COVID-19 pandemic was well controlled in Taiwan until an outbreak in May 2021. Telemedicine was rapidly implemented to avoid further patient exposure and to unload the already burdened medical system. OBJECTIVE: To understand the effect of COVID-19 on the implementation of video-based virtual clinic visits during this outbreak, we analyzed the logistics of prescribing medications and patient flow for such virtual visits at a tertiary medical center. METHODS: We retrospectively collected information on video-based virtual clinic visits and face-to-face outpatient visits from May 1 to August 31, 2021, from the administrative database at National Taiwan University Hospital. The number of daily new confirmed COVID-19 cases in Taiwan was obtained from an open resource. RESULTS: There were 782 virtual clinic visits during these 3 months, mostly for the departments of internal medicine, neurology, and surgery. The 3 most common categories of medications prescribed were cardiovascular, diabetic, and gastrointestinal, of which cardiovascular medications comprised around one-third of all medications prescribed during virtual clinic visits. The number of virtual clinic visits was significantly correlated with the number of daily new confirmed COVID-19 cases, with approximately a 20-day delay (correlation coefficient 0.735; P<.001). The patient waiting time for video-based virtual clinic visits was significantly shorter compared with face-to-face clinic visits during the same period (median 3, IQR 2-6 min vs median 20, IQR 9-42 min; rank sum P<.001). Although the time saved was appreciated by the patients, online payment with direct delivery of medications without the need to visit a hospital was still their major concern. CONCLUSIONS: Our data showed that video-based virtual clinics can be implemented rapidly after a COVID-19 outbreak. The virtual clinics were efficient, as demonstrated by the significantly reduced waiting time. However, there are still some barriers to the large-scale implementation of video-based virtual clinics. Better preparation is required to improve performance in possible future large outbreaks.

The association between new onset atrial fibrillation and incident cancer-A nationwide cohort study.

A recent analysis showed an association with new onset atrial fibrillation (NOAF) and incident cancer among women. We aimed to examine the risk of cancer among patients with NOAF in general population. A retrospective cohort of 5130 patients with NOAF was identified from a random sample of one million subjects between 2005 and 2010 from Taiwan National Health Insurance Research Database. The standard incidence ratio of incident cancer and hazard ratios were calculated by modeling cumulative incidence with competing risk of death. During a mean follow-up duration of 3.4 years, 330 patients developed cancer. The standard incidence ratio of all malignancies was 1.41 (95% confidence interval 1.26-1.57), suggesting a 41% increase in cancer risk compared with the general population. The risk of cancer was higher among men or the elderly with NOAF after adjusting for confounding factors and after considering the competing risk of death. The risk of cancer was not associated with CHA2DS2-VASc score (p = 0.32) among patients with NOAF. In conclusion, patients with NOAF were associated with a higher risk of cancer. Within this group, the risk of ischemic stroke (in terms of CHADS2-VASc score) did not reflect the risk of incident cancer.

Aldosterone Induces Tissue Inhibitor of Metalloproteinases-1 Expression and Further Contributes to Collagen Accumulation: From Clinical to Bench Studies.

Aldosterone induces myocardial fibrosis. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key factor of myocardial fibrosis. This study tested the hypothesis that aldosterone induces TIMP-1 expression and contributes to the fibrotic process. We prospectively enrolled 54 patients with primary aldosteronism, and measured plasma TIMP-1 and echocardiographic parameters. In the cell study, we investigated the possible molecular mechanism by which aldosterone induces TIMP-1 secretion and the effects on collagen accumulation. In the animal study, we measured serum TIMP-1 levels, cardiac TIMP-1 levels, and cardiac structure in an aldosterone infusion mouse model using implantation of aldosterone pellets. In patients with primary aldosteronism, plasma TIMP-1 was correlated with 24-hour urinary aldosterone, left ventricular mass, and impairment of left ventricular diastolic function. In human cardiac fibroblasts, TIMP-1 protein and mRNA expressions were significantly increased by aldosterone through the glucocorticoid receptor/PI3K/Akt/nuclear factor-κB pathway. TIMP-1 small-interfering RNA significantly reduced aldosterone-induced collagen accumulation, and aldosterone did not alter the levels of collagen1a1 or matrix metalloproteinase-1 mRNA. The aldosterone-induced TIMP-1 expression was inversely related to matrix metalloproteinase-1 activity. Furthermore, in the animal model, the serum and cardiac levels of TIMP-1 were significantly elevated in the mice that received aldosterone infusion. This elevation was blocked by RU-486 but not by eplerenone, suggesting that the effect was through glucocorticoid receptors. In a long-term aldosterone infusion model, serum TIMP-1 was associated with serum aldosterone level, cardiac structure, and fibrosis. In conclusion, aldosterone induced TIMP-1 expression in vivo and in vitro. This increased TIMP-1 expression resulted in enhanced collagen accumulation via the suppression of matrix metalloproteinase-1 activity.

Time course and factors predicting arterial stiffness reversal in patients with aldosterone-producing adenoma after adrenalectomy: prospective study of 102 patients.

Primary aldosteronism not only results in hypertension but also stiffer arteries. The time course and factors predicting the reversal of arterial stiffness after treatment are unclear. We prospectively enrolled 102 patients with aldosterone-producing adenoma (APA) from March 2006 to January 2012. We measured the pulse wave velocity (PWV) between brachial-ankle (baPWV) and heart-ankle (haPWV) before, 6 and 12 months after their adrenalectomy. After treatment, the PWV decreased significantly during the first 6 months (both p < 0.001), but no further reduction in the following 6 months. The determinant factors for baseline baPWV were age, duration of hypertension, and baseline systolic blood pressure (SBP) in multivariate linear regression analysis, similar with baseline haPWV (determinants: age, duration of hypertension, baseline SBP and diastolic blood pressure (DBP)). In multivariate linear regression analysis, the decrease in DBP at 6 months (ΔDBP0-6mo) and baseline baPWV were significantly associated with the decrease in baPWV at 6 months (ΔbaPWV0-6mo). The associated factors of the change in haPWV at 6 months (ΔhaPWV0-6mo) were baseline haPWV, ΔDBP0-6mo and change in log-transformed plasma renin activity. Our result suggested that reversal of arterial stiffness in APA patients occurred early after adrenalectomy and determined by baseline vascular condition, hemodynamic factors, and humoral factors.

Aldosterone Impairs Vascular Smooth Muscle Function: From Clinical to Bench Research.

CONTEXT: The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA). OBJECTIVE: Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation. DESIGN: We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and three patients with idiopathic hyperaldosteronism) and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells. SETTING: This study took place in an academic clinical research center. PARTICIPANTS: Participants included 35 patients with PA and 30 patients with EH. INTERVENTIONS: Adrenalectomy was undertaken in patients with aldosterone-producing adenoma. RESULTS: The PA patients had significantly lower flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) values than the patients with EH (FMD: 13 ± 6 vs 16 ± 4; NMD: 16 ± 6 vs 19 ± 5; both P < .05). FMD/NMD were significantly correlated with log 24 hour-urine aldosterone (FMD: r = -0.287, P = .048; NMD: r = -0.402, P = .005) but not blood pressure. The impaired FMD and NMD values were significantly restored 1 year after adrenalectomy (FMD: 11 ± 4 to 19 ± 7; NMD: 15 ± 6 to 21 ± 6; both P < .01). Under confocal microscopy, aldosterone was shown to suppress the expression of SERCA2a of human aortic smooth muscle cells. Aldosterone significantly suppressed the expression of SERCA2a from 10(-8) M in mRNA and protein levels. This suppression was through down-regulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2. CONCLUSIONS: Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression.

Reversible heart rhythm complexity impairment in patients with primary aldosteronism.

Excess aldosterone secretion in patients with primary aldosteronism (PA) impairs their cardiovascular system. Heart rhythm complexity analysis, derived from heart rate variability (HRV), is a powerful tool to quantify the complex regulatory dynamics of human physiology. We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that underwent adrenalectomy and 25 patients with essential hypertension (EH). The heart rate data were analyzed by conventional HRV and heart rhythm complexity analysis including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We found APA patients had significantly decreased DFAα2 on DFA analysis and decreased area 1-5, area 6-15, and area 6-20 on MSE analysis (all p < 0.05). Area 1-5, area 6-15, area 6-20 in the MSE study correlated significantly with log-transformed renin activity and log-transformed aldosterone-renin ratio (all p < = 0.01). The conventional HRV parameters were comparable between PA and EH patients. After adrenalectomy, all the altered DFA and MSE parameters improved significantly (all p < 0.05). The conventional HRV parameters did not change. Our result suggested that heart rhythm complexity is impaired in APA patients and this is at least partially reversed by adrenalectomy.

Circulating tissue inhibitor of matrix metalloproteinase-1 is associated with aldosterone-induced diastolic dysfunction.

OBJECTIVE: To test if collagen markers are associated with aldosterone-induced diastolic dysfunction. BACKGROUND: Although primary aldosteronism is associated with more prominent cardiac remodeling and diastolic dysfunction, the reversibility of diastolic function is unclear. In addition, there is no known biomarker associated with aldosterone-induced diastolic dysfunction. METHODS: We enrolled 27 patients with aldosterone-producing adenoma (APA) preparing for adrenalectomy, and 27 patients with essential hypertension prospectively from October 2006 to March 2010 at a tertiary referral center. Plasma matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were measured, and echocardiography including tissue Doppler images was performed in both groups and 1 year after receiving adrenalectomy in the APA group. RESULTS: The baseline plasma TIMP-1 level (88.4 ±â€Š38.7 vs. 63.6 ±â€Š32.5 ng/ml; P = 0.014), left ventricular mass index (LVMI), and E/E' ratio (11.5 ±â€Š2.9 vs. 9.0 ±â€Š2.1; P < 0.001) were significantly higher in the APA group. The baseline plasma TIMP-1 level significantly correlated with the E/E' ratio, LVMI, interventricular septum, and left atrial diameter. The plasma MMP-2 level did not correlate with the left ventricular structure parameters, except for interventricular septum thickness. After adrenalectomy, LVMI and E/E' ratio improved significantly. The postadrenalectomy plasma TIMP-1 levels, but not MMP-2 levels, also decreased. The change of plasma TIMP-1 levels was negatively associated with the postadrenalectomy E/E' ratio after adjustment for age, sex, BMI, and mean blood pressure (ß-coefficient = - 3.6, P = 0.004). CONCLUSION: Excess of aldosterone induces cardiac diastolic dysfunction, which is reversible by adrenalectomy. TIMP-1 is associated with the aldosterone-induced diastolic dysfunction.

Human Placenta-Derived Multipotent Cells (hPDMCs) Modulate Cardiac Injury: From Bench to Small and Large Animal Myocardial Ischemia Studies.

Cardiovascular disease is the leading cause of death globally, and stem cell therapy remains one of the most promising strategies for regeneration or repair of the damaged heart. We report that human placenta-derived multipotent cells (hPDMCs) can modulate cardiac injury in small and large animal models of myocardial ischemia (MI) and elucidate the mechanisms involved. We found that hPDMCs can undergo in vitro cardiomyogenic differentiation when cocultured with mouse neonatal cardiomyocytes. Moreover, hPDMCs exert strong proangiogenic responses in vitro toward human endothelial cells mediated by secretion of hepatocyte growth factor, growth-regulated oncogene-α, and interleukin-8. To test the in vivo relevance of these results, small and large animal models of acute MI were induced in mice and minipigs, respectively, by permanent left anterior descending (LAD) artery ligation, followed by hPDMC or culture medium-only implantation with follow-up for up to 8 weeks. Transplantation of hPDMCs into mouse heart post-acute MI induction improved left ventricular function, with significantly enhanced vascularity in the cell-treated group. Furthermore, in minipigs post-acute MI induction, hPDMC transplantation significantly improved myocardial contractility compared to the control group (p = 0.016) at 8 weeks postinjury. In addition, tissue analysis confirmed that hPDMC transplantation induced increased vascularity, cardiomyogenic differentiation, and antiapoptotic effects. Our findings offer evidence that hPDMCs can modulate cardiac injury in both small and large animal models, possibly through proangiogenesis, cardiomyogenesis, and suppression of cardiomyocyte apoptosis. Our study offers mechanistic insights and preclinical evidence on using hPDMCs as a therapeutic strategy to treat severe cardiovascular diseases.

Aldosterone induced galectin-3 secretion in vitro and in vivo: from cells to humans.

CONTEXT: Patients with primary aldosteronism are associated with increased myocardial fibrosis. Galectin-3 is one of the most important mediators between macrophage activation and myocardial fibrosis. OBJECTIVE: To investigate whether aldosterone induces galectin-3 secretion in vitro and in vivo. METHODS AND RESULTS: We investigated the possible molecular mechanism of aldosterone-induced galectin-3 secretion in macrophage cell lines (THP-1 and RAW 264.7 cells). Aldosterone induced galectin-3 secretion through mineralocorticoid receptors via the PI3K/Akt and NF-κB transcription signaling pathways. In addition, aldosterone-induced galectin-3 expression enhanced fibrosis-related factor expression in fibroblasts. We observed that galectin-3 mRNA from peripheral blood mononuclear cells and serum galectin-3 levels were both significantly increased in mice implanted with aldosterone pellets on days 7 and 14. We then conducted a prospective preliminary clinical study to investigate the association between aldosterone and galectin-3. Patients with aldosterone-producing adenoma had a significantly higher plasma galectin-3 level than patients with essential hypertension. One year after adrenalectomy, the plasma galectin-3 level had decreased significantly in the patients with aldosterone-producing adenoma. CONCLUSION: This study demonstrated that aldosterone could induce galectin-3 secretion in vitro and in vivo.

The arrhythmogenic effect of self-assembling nanopeptide hydrogel scaffolds on neonatal mouse cardiomyocytes.

The chaotic spatial disarray due to extracellular matrix expansion disrupts cardiomyocytes interaction and causes arrhythmia. We hypothesized that disordered nanopeptide scaffolds can mimic the chaotic spatial disarray related to cardiac fibrosis and have arrhythmogenic effects on cardiomyocytes. Primary mouse cardiomyocytes were cultured in 2D traditional and 3D nanopeptide hydrogel scaffold systems. Cardiomyocytes in 3D scaffolds showed irregular spontaneous contractile activity as compared with 2D culture controls. Calcium fluorimetric imaging revealed that basal intracellular calcium level increased 1.42-fold in cardiomyocytes cultured in the 3D scaffold, in vitro. The mRNA levels of sarcoplasmic reticulum calcium transport ATPase, ryanodine 2 receptor and connexin 43 elevated 2.14-fold, 2.33-fold and 2.62-fold in 3D compared with 2D. Immunofluorescence imaging revealed lateralization of the distribution of connexin 43 in 3D group. These findings suggest that 3D hydrogel culture system provides a model for the development of cardiac dysrhythmia. These limitations should be considered during cardiac tissue engineering. FROM THE CLINICAL EDITOR: This team of scientists has established a unique 3D hydrogel culture system as a model for the development of cardiac dysrhythmia.

Influence of non-alcoholic fatty liver disease on autonomic changes evaluated by the time domain, frequency domain, and symbolic dynamics of heart rate variability.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular atherosclerosis independent of classical risk factors. This study investigated the influence of NAFLD on autonomic changes, which is currently unknown. METHODS: Subjects without an overt history of cardiovascular disease were enrolled during health checkups. The subjects diagnosed for NAFLD using ultrasonography underwent 5-min heart rate variability (HRV) measurements that was analyzed using the following indices: (1) the time domain with the standard deviation of N-N (SDNN) intervals and root mean square of successive differences between adjacent N-N intervals (rMSSD); (2) the frequency domain with low frequency (LF) and high frequency (HF) components; and (3) symbolic dynamics analysis. Routine blood biochemistry data and serum leptin levels were analyzed. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured. RESULTS: Of the 497 subjects (mean age, 46.2 years), 176 (35.4%) had NAFLD. The HRV indices (Ln SDNN, Ln rMSSD, Ln LF, and Ln HF) were significantly decreased in the NAFLD group (3.51 vs 3.62 ms, 3.06 vs 3.22 ms, 5.26 vs 5.49 ms(2), 4.49 vs 5.21 ms(2), respectively, all P<0.05). Ln SDNN was significantly lower in the NAFLD group after adjustment for age, sex, hypertension, dyslipidemia, metabolic syndrome, body mass index, smoking, estimated glomerular filtration rate, HOMA-IR, and leptin (P<0.05). In the symbolic dynamic analysis, 0 V percentage was significantly higher in the NAFLD group (33.8% vs 28.7%, P = 0.001) and significantly correlated with linear HRV indices (Ln SDNN, Ln rMSSD, and Ln HF). CONCLUSIONS: NAFLD is associated with decreased Ln SDNN and increased 0 V percentage. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). Further risk stratification of autonomic dysfunction with falls or cardiovascular diseases by these HRV parameters is required in patients with NAFLD.

Myocardial ultrasound tissue characterization of patients with primary aldosteronism.

Primary aldosteronism (PA), an underdiagnosed cause of hypertension, is associated with more significant cardiac remodeling and myocardial fibrosis than is essential hypertension (EH). The aim of this study was to validate myocardial fibrosis and to evaluate factors associated with the degree of myocardial fibrosis in patients with PA. We prospectively analyzed 62 patients with PA (including 46 patients with aldosterone-producing adenoma and 16 with bilateral hyperplasia) between October 2006 and October 2010, and we enrolled 17 patients with EH as the control group. Echocardiography, including ultrasonic tissue characterization using cyclic variation of integrated backscatter (CVIBS), was performed in individuals in both groups. Among patients with PA, the diastolic blood pressures and plasma aldosterone concentrations were significantly higher than those of patients with EH. Moreover, the serum potassium levels and the plasma renin activities were significantly lower in patients with EH. As observed by echocardiography, patients with PA had greater interventricular septal thickness, greater left ventricular posterior wall thickness, and higher left ventricular mass indexes than did patients with EH. Patients with PA had significantly lower CVIBS values than patients with EH (7.1 ± 2.2 vs. 8.7 ± 1.5 dB; p = .005). In a correlation study that corrected for various clinical parameters, only log-transformed plasma renin activity values correlated significantly with CVIBS values. Ultrasonic tissue characterization with CVIBS is a useful tool for determining the extent of myocardial fibrosis. Patients with PA exhibit a more severe degree of myocardial fibrosis, as detected by CVIBS, than do patients with EH. Moreover, the severity of fibrosis, as detected by CVIBS, correlates with log-transformed plasma renin activity values.

Relationship between bone mineral density and serum osteoprotegerin in patients with chronic heart failure.

PURPOSE: Heart failure (HF) had been reported with increased risk of hip fractures. However, the relationship between circulating biomarkers and bone mineral density (BMD) in chronic HF remained unclear. METHODS: This is a cross-sectional study which recruited stable chronic HF from registry of the Heart Failure Center of National Taiwan University Hospital. Patients underwent dual-energy x-ray absorptiometry (DEXA) measurements at hip and lumbar spines and biochemical assessments including B-type natriuretic peptide (BNP-32), myostatin, follistatin and osteoprotegerin (OPG). RESULTS: A total of 115 stable chronic HF individuals with left ventricular ejection fraction (EF) <45% (74% of male, mean age at 59) were recruited with 24 patients in NYHA class I, 73 patients in NYHA class II and 18 patients in NYHA class III. Results of BMD showed that Z scores of hip in NYHA III group (-0.12 ± 1.15) was significantly lower than who were NYHA II (0.58 ± 1.04). Serum OPG was significantly higher in subjects of NYHA III (9.3 ± 4.6 pmol/l) than NYHA II (7.4 ± 2.8 pmol/l) or NYHA I (6.8 ± 3.6 pmol/l) groups. There's a significant negative association between log transformed serum OPG and trochanteric BMD (R = -0.299, P = 0.001), which remained significant after multivariate analysis. CONCLUSIONS: Our study demonstrated an inverse association between serum OPG and trochanteric BMD in patients with HF. OPG may be a predictor of BMD and an alternative to DEXA for identifying at risk HF patients for osteoporosis.

Adrenalectomy reverses myocardial fibrosis in patients with primary aldosteronism.

OBJECTIVE: Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. However, the reversibility of cardiac fibrosis is still unclear. Our objective was to investigate myocardial fibrosis in primary aldosteronism patients and its change after surgery. METHOD: We prospectively analyzed 20 patients with aldosterone-producing adenoma (APA) who received adrenalectomy from December 2006 to October 2008 and 20 patients with essential hypertension were enrolled as the control group. Plasma carboxy-terminal propeptide of procollagen type I (PICP) determination and echocardiography including ultrasonic tissue characterization by cyclic variation of integrated backscatter (CVIBS) were performed in both groups and 1 year after operation in the APA group. RESULTS: APA patients had significantly higher SBP and DBP, higher plasma aldosterone concentration (PAC), higher aldosterone-renin ratio (ARR), lower serum potassium levels, and lower plasma renin activity (PRA) than patients with essential hypertension. In echocardiography, APA patients had a higher left ventricular mass index than essential hypertension patients. APA patients had significantly lower CVIBS (6.2 ± 1.5 vs. 8.7 ± 2.0 dB, P < 0.001) and higher plasma PICP levels (107 ± 27 vs. 85 ± 24 µg/l, P = 0.009) than essential hypertension patients. In the correlation study, CVIBS is correlated with log-transformed PRA and log-transformed ARR and PICP is correlated with log-transformed PRA, log-transformed PAC, and log-transformed ARR. One year after adrenalectomy, CVIBS increased significantly (6.2 ± 1.5 to 7.3 ± 1.7 dB, P = 0.033) and plasma PICP levels decreased (107 ± 27 vs. 84 ± 28 µg/l, P = 0.026). CONCLUSION: Increases in collagen content in the myocardium of APA patients may be reversed by adrenalectomy.

Adrenalectomy improves increased carotid intima-media thickness and arterial stiffness in patients with aldosterone producing adenoma.

CONTEXT: Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and is associated with more prominent vascular stiffness and atherosclerosis. However, the effect of adrenalectomy on reversibility of vascular damage is unclear. OBJECTIVE: Our objective was to investigate the vascular changes and possibility of reversibility after adrenalectomy in PA patients. METHODS: We prospectively analyzed 20 patients with aldosterone producing adenoma (APA) that received adrenalectomy from October 2006 to December 2008 and 21 patients with essential hypertension (EH) were enrolled as the control group. Carotid intima media thickness (CIMT) measurement by B-mode ultrasound of the right common carotid arteries and pulse wave velocity (PWV) measurement including brachial-ankle PWV (baPWV) and heart-ankle PWV (haPWV) were performed in both groups. The follow-up measurements were performed one-year after adrenalectomy in APA group. RESULTS: APA patients had significantly higher diastolic blood pressure, plasma aldosterone concentration (PAC) and aldosterone-renin ratio (ARR), but lower serum potassium level and plasma renin activity (PRA) than EH patients. APA patients had significantly higher CIMT (0.64±0.13 vs. 0.53±0.10 mm, p=0.006), higher baPWV (1589±296 vs. 1405±187 cm/s, p=0.024) and haPWV (1095±150 vs. 987±114 cm/s, p=0.013) comparing with EH patients. One-year after adrenalectomy, CIMT reduced significantly from 0.64±0.13 mm to 0.59±0.14 mm (p=0.014), and baPWV and haPWV also showed significant reduction (baPWV, 1589±296 to 1463±188 cm/s, p=0.035; haPWV, 1095±150 to 1017±109 cm/s, p=0.019). CONCLUSION: APA patients have higher degree of early atherosclerosis and vascular stiffness. Adrenalectomy not only corrects the high blood pressure and biochemical parameters but also reverse adverse vascular change in APA patients.

Reversal of myocardial fibrosis in patients with unilateral hyperaldosteronism receiving adrenalectomy.

BACKGROUND: Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with more prominent left ventricular hypertrophy and increased myocardial fibrosis. Unilateral hyperaldosteronism can be cured by adrenalectomy. However, the reversibility of cardiac fibrosis is still unclear. METHODS: We analyzed 11 patients prospectively with unilateral hyperaldosteronism (including 10 aldosterone-producing adenomas and 1 unilateral nodular hyperplasia) who received adrenalectomy from October 2006 to October 2007, and 17 patients with essential hypertension (EH) were enrolled as the control group. Echocardiography included ultrasonic tissue characterization by cyclic variation of integrated backscatter; it was performed in both groups and 1 year after operation in the unilateral hyperaldosteronism group. RESULTS: Patients with unilateral hyperaldosteronism had significantly higher diastolic blood pressure, higher plasma aldosterone concentration, lower serum potassium level, and lower plasma renin activity than patients with EH. In echocardiography, patients with unilateral hyperaldosteronism had thicker interventricular septal thickness, left ventricular posterior wall thickness, and higher left ventricular mass index than EH patients. Patients with unilateral hyperaldosteronism had significant lower cyclic variation of integrated backscatter than EH patients (7.1 ± 2.1 vs 8.7 ± 1.5 dB, P = .037). After analyzing the correlation of cyclic variation of integrated backscatter with clinical parameters for all participants, only log-transformed plasma renin activity was correlated significantly with cyclic variation of integrated backscatter. One year after adrenalectomy, interventricular septal thickness, left ventricular posterior wall thickness, and left ventricular mass index decreased significantly. In addition, cyclic variation of integrated backscatter increased significantly after adrenalectomy (7.1 ± 2.1 to 8.5 ± 1.5 dB, P = .02). CONCLUSION: Adrenalectomy not only reversed left ventricular geometry but also altered myocardial texture in patients with unilateral hyperaldosteronism. This finding implies that increases in collagen content in the myocardium of patients with unilateral hyperaldosteronism might be reversed by adrenalectomy.

Factors influencing left ventricular mass regression in patients with primary aldosteronism post adrenalectomy.

BACKGROUND: Primary aldosteronism (PA) is a type of secondary hypertension with prominent left ventricular hypertrophy (LVH). Unilateral aldosterone-producing adenoma (APA) is the most common subtype that can be cured by adrenalectomy. OBJECTIVE: To investigate left ventricular structural change after surgery and the factors associated with the degree of LVH regression in patients with PA. METHODS: We performed a retrospective analysis in the Taiwan Primary Aldosteronism Investigation (TAIPAI) database, including demography, biochemical data, echocardiography and medication. RESULTS: From July 1994 to January 2007, 20 patients (8 men) with APA receiving adrenalectomy and having pre- and postoperative echocardiography were selected. After 21 ± 19 months post operation, the left ventricular wall thickness and left ventricular mass index (LVMI) decreased significantly. The decrease of LVMI is significant only in patients who had LVH before operation. In analysis of factors associated with net LVMI decrease (ΔLVMI; post-operative LVMI - pre-operative LVMI), only pre-operative LVMI (r = -.783, p < .001), and ΔSBP (r = .472, p = .036) significantly correlated with ΔLVMI. In conclusion, LVH in PA could be significantly reversed by adrenalectomy. Pre-operative LVMI and ΔSBP were associated with the degree of LVMI decrease. CONCLUSION: LVH in PA could be significantly reversed by adrenalectomy. Pre-operative LVMI and ΔSBP were associated with the degree of LVMI decrease.