Associations between in-hospital daily protein intake and adverse clinical outcomes in older patients with heart failure.

AIMS: The adverse effects of low daily protein intake (DPI) on clinical outcomes in patients with heart failure (HF) are known; however, an optimal DPI to predict event adverse outcomes remains undetermined. Moreover, whether protein restriction therapy for chronic kidney disease is applicable in patients with HF and renal dysfunction remains unclear. METHODS AND RESULTS: In this single-centre, ambispective cohort study, we included 405 patients with HF aged ≥65 years (mean age, 78.6 ± 7.5 years; 50% women). DPI was estimated from consumption over three consecutive days before discharge and normalized relative to the ideal body weight [IBW, 22 kg/m2 × height (m)2]. The primary outcome was a composite of all-cause mortality and HF-related readmission within the 2 year post-discharge period. RESULTS: During an average follow-up period of 1.49 ± 0.74 years, 100 patients experienced composite events. Kaplan-Meier survival curves revealed a significantly lower composite event-free rate in patients within the lowest quartile of DPI than in the upper quartiles (log-rank test, P = 0.02). A multivariate Cox proportional hazards analysis after adjusting for established prognostic markers and non-proteogenic energy intake revealed that patients in the lowest DPI quartile faced a two-fold higher risk of composite events than those in the highest quartile [hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.08-3.82; P = 0.03]. The composite event risk linearly increased as DPI decreased (P for nonlinearity = 0.90), with each standard deviation (0.26 g/kg IBW/day) decrease in DPI associated with a 32% increase in composite event risk (HR, 1.32; 95% CI, 1.10-1.71; P = 0.04). There was significant heterogeneity in the effect of DPI, with the possible disadvantage of lower DPI in patients with HF with cystatin C-based estimated glomerular filtration rate <30 mL/min/1.73 m2. The cutoff value of DPI for predicting the occurrence of composite events calculated from the Youden index was 1.12 g/kg IBW/day. Incorporating a DPI < 1.12 g/kg IBW/day into the baseline model significantly improved the prediction of post-discharge composite events (continuous net reclassification improvement, 0.294; 95% CI, 0.072-0.516; P = 0.01). CONCLUSIONS: Lower DPI during hospitalization is associated with an increased risk of mortality and HF readmission independent of non-proteogenic energy intake, and the possible optimal DPI for predicting adverse clinical outcomes is >1.12 g/kg IBW/day in older patients with HF. Caution is warranted when protein restriction therapy is administered to older patients with HF and renal dysfunction.

Prognostic Implications of Sarcoidosis Granulomas　- Insights From the Multicenter Registry, the Japanese Cardiac Sarcoidosis Prognostic Study.

Background: Definitions of cardiac sarcoidosis (CS) differ among guidelines. Any systemic histological finding of CS is essential for the diagnosis of CS in the 2014 Heart Rhythm Society statement, but not necessary in the Japanese Circulation Society 2016 guidelines. This study aimed to reveal the differences in outcomes by comparing 2 groups, namely CS patients with or without systemic histologically proven granuloma. Methods and Results: This study retrospectively included 231 consecutive patients with CS. CS with granulomas in ≥1 organs was diagnosed in 131 patients (Group G), whereas CS without any granulomas was diagnosed in the remaining 100 patients (Group NG). Left ventricular ejection fraction (LVEF) was significantly reduced in Group NG compared with Group G (44±13% vs. 50±16%, respectively; P=0.001). However, Kaplan-Meier curves showed that major adverse cardiovascular events (MACE)-free survival outcomes were comparable between the 2 groups (log-rank P=0.167). Univariable analyses showed that significant predictors of MACE were Groups G/NG, histological CS, LVEF, and high B-type natriuretic peptide (BNP) or N-terminal pro BNP concentrations, but none of these was significant in multivariable analyses. Conclusions: Overall risks of MACE were similar between the 2 groups despite different manifestations in cardiac dysfunction. The data not only validate the prognostic value of non-invasive diagnosis of CS, but also show the need for careful observation and therapeutic strategy in patients with CS without any granuloma.

Anthropometric parameters-derived estimation of muscle mass predicts all-cause mortality in heart failure patients.

AIMS: Reduction in appendicular skeletal muscle mass index (ASMI) assessed by dual-energy X-ray absorptiometry (DEXA) has been shown to be independently associated with a higher mortality rate in patients with heart failure (HF). However, DEXA is not suitable for measurement of muscle mass in a daily clinical setting and in large population-based studies. The aim of this study was to determine whether ASMI predicted from anthropometric indicators (predicted ASMI) serves as an alternative to DEXA-measured ASMI for predicting all-cause death in HF patients. METHODS AND RESULTS: Data for 539 HF patients who received a DEXA scan and measurements of calf circumferences (CC) and mid-arm circumferences (MAC) in our hospital were analysed. Predicted ASMI was calculated as we previously reported: predicted ASMI (kg/m2 ) = [0.214 × weight (kg) + 0.217 × CC (cm) - 0.189 × MAC (cm) + 1.098 (male = 1, female = -1) + 0.576]/height2 (m2 ). Low ASMI values were defined as <7.00 kg/m2 and <5.40 kg/m2 for men and women, respectively, according to the criteria of the Asian Working Group for Sarcopenia. The median follow-up period was 1.75 years (interquartile range, 0.96-2.37 years), and 79 patients (15%) died. Kaplan-Meier survival curves showed that patients with low DEXA-measured ASMI and patients with low predicted ASMI had significantly lower survival rates than those for patients with high ASMI. In multivariate Cox proportional hazard analyses adjusted for age, sex, logarithmic B-type natriuretic peptide, cystatin C based-estimated glomerular filtration rate, and gait speed, DEXA-measured ASMI [hazard ratio (HR), 0.982; 95% confidence interval (CI), 0.967-0.998; P = 0.026] and predicted ASMI (HR, 0.979; 95% CI, 0.962-0.996; P = 0.018) were independent predictors of all-cause mortality. Inclusion of predicted ASMI into the adjustment model significantly improved continuous net reclassification improvement (0.338; 95% CI, 0.103-0.572; P < 0.01) and integrated discrimination improvement (0.020; 95% CI, 0.004-0.035; P < 0.05) for predicting mortality after discharge. CONCLUSIONS: Predicted ASMI, as well as DEXA-measured ASMI, can predict all-cause death in HF patients, and calculation of predicted ASMI will be useful for detecting high-risk patients in a daily clinical setting and in large population-based studies.

Abrupt Onset of Cardiac Tamponade in Sarcoidosis.

Sarcoidosis is a systemic inflammatory disease characterized by the formation of noncaseating epithelioid granulomas. Multiple organs, including the lung, eyes, and skin, are involved in this disorder, and cardiac involvement is a major cause of morbidity and mortality in patients with this disorder. We present the case history of a 22-year-old man with neurosarcoidosis complicated by abrupt onset of cardiac tamponade. Cardiac tamponade is a rare but potentially fatal manifestation of sarcoidosis, which is treatable with glucocorticoid therapy. Including the present case, previously reported cases of sarcoidosis with cardiac tamponade are reviewed to delineate its clinical characteristics.

A case of a giant pulmonary artery aneurysm due to an atrial septal defect with left main coronary artery occlusion.

Cases of coronary artery occlusion due to the exclusion of pulmonary artery aneurysm are extremely rare, and there are few reports of surgical treatment. A 60-year-old woman with pulmonary hypertension due to an atrial septal defect and obstruction of the left main coronary trunk due to the exclusion of a giant pulmonary artery aneurysm underwent surgery. The surgery included atrial septal defect closure, tricuspid annulus plasty, pulmonary artery aneurysmorrhaphy, and coronary artery bypass grafting. One and a half years after the surgery, no re-expansion of the pulmonary artery was observed, and the symptoms of heart failure had improved. There are no reports of improvement in pulmonary valve regurgitation by aneurysmorrhaphy in pulmonary artery aneurysm. Surgery for pulmonary artery aneurysm with the exclusion of other organs was effective, and aneurysmorrhaphy for pulmonary artery aneurysm was acceptable.

Energy intake during hospital stay predicts all-cause mortality after discharge independently of nutritional status in elderly heart failure patients.

OBJECTIVE: Malnutrition is associated with an increased risk of mortality in heart failure (HF) patients. Here, we examined the hypothesis that assessment of energy intake in addition to nutritional status improves the stratification of mortality risk in elderly HF patients. METHODS: We retrospectively examined 419 HF patients aged ≥ 65 years (median 78 years, 49% female). Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF), and daily energy intake was calculated from intake during 3 consecutive days before discharge. RESULTS: During a median 1.52-year period (IQR 0.96-2.94 years), 110 patients (26%) died. Kaplan-Meier survival curves showed that patients with low tertile of daily energy intake had a higher mortality rate than did patients with high or middle tertile of daily energy intake. In multivariate Cox regression analyses, low daily energy intake was independently associated with higher mortality after adjustment for the model including age, sex, BNP, Charlson Comorbidity Index, history of HF hospitalization, and cachexia in addition to MNA-SF. Inclusion of both MNA-SF and energy intake into the adjustment model improved the accuracy of prediction of the mortality after discharge (continuous net reclassification improvement, 0.355, p = 0.003; integrated discrimination improvement, 0.029, p = 0.003). Results of a fully adjusted dose-dependent association analysis showed that risk of all-cause mortality was lowest among HF patients who consumed 31.5 kcal/kg/day of energy. CONCLUSIONS: Energy intake during hospital stay is an independent predictor of the mortality in elderly HF patients, and its assessment together with established predictors improves the mortality risk stratification.

Soleal vein dilatation assessed by ultrasonography is an independent predictor for deep vein thrombosis after major orthopedic surgery.

BACKGROUND: Deep vein thrombosis (DVT) develops after major orthopedic surgery despite the current use of prophylaxis. DVT frequently develops in the soleal vein (SV) and might develop easily at the site of SV dilatation because of blood flow stasis. However, whether preoperative SV dilatation detected by ultrasonography predicts DVT after major orthopedic surgery remains unknown. OBJECTIVE: We examined whether SV dilatation detected by preoperative ultrasonography predicts DVT after major orthopedic surgery. METHODS: Ultrasonography was performed preoperatively and postoperatively in 243 patients with orthopedic diseases (mean age of 67±13 years, 77% women) who underwent total hip arthroplasty (THA, n=180) or total knee arthroplasty (TKA, n=63). Presence of DVT was diagnosed by ultrasonography and SV diameter ≥10mm was defined as SV dilatation. Patients with preoperative DVT were excluded. RESULTS: Sixty-nine patients (28%) developed postoperative DVT. SV dilatation was found in 24 patients (10%), and 16 (67%) of those patients had postoperative DVT. Multivariate logistic regression analysis showed that female gender [odds ratio (OR): 4.09, p=0.004], TKA (OR: 2.52, p=0.011), and SV dilatation (OR: 6.67, p<0.001), but not presence of comorbidities, medications, or plasma d-dimer value, independently predict postoperative DVT. Subgroup analyses according to the operation site showed that female gender (OR: 3.27, p=0.043) and SV dilatation (OR: 3.72, p=0.022) were independent predictors of postoperative DVT in the THA group. SV dilatation (OR: 12.0, p=0.027) was an independent predictor of postoperative DVT also in the TKA group. CONCLUSIONS: In addition to gender and TKA, SV dilatation detected by ultrasonography is an independent predictor of DVT after major orthopedic surgery. Determination of SV diameter by ultrasonography before major orthopedic surgery is useful for assessing the risk of postoperative DVT.

Does a Reduction in the Glomerular Filtration Rate Increase the Overall Severity of Coronary Artery Stenosis?

OBJECTIVE: Chronic kidney disease is a risk factor of coronary events, however, its impact on coronary artery stenosis has not yet been clarified with the use of a large database. We examined the association between a reduced glomerular filtration rate (GFR) and the overall severity of coronary stenosis. METHODS: We enrolled 1,150 patients [mean age, 68±12 (SD) years; 66.6% men] who consecutively underwent coronary angiography for suspected stable angina pectoris. The overall severity of stenosis in the coronary arteries was assessed by the Gensini score (GS), and its logarithmic values (log-GS) were used for statistical analyses since the GS does not follow a normal distribution. RESULTS: The log-GS was significantly larger in men than in women (2.5±1.5 vs. 1.9±1.7), while the estimated GFR (eGFR) and comorbidities were comparable between both sexes. A multivariate regression analysis indicated that age, smoking, eGFR, HDL-cholesterol and HbA1c were independent explanatory variables of the log-GS in men, although the eGFR explained only 1.2% of the log-GS variation. In women, the eGFR was not included in the significant explanatory variables shown by the multivariate analysis. However, the sex difference in the regression for the eGFR-log-GS relationship was not statistically significant. CONCLUSION: A reduced eGFR is a significant, but minor, determinant of the overall severity of coronary artery stenosis in men and potentially women.

Clinical impact of myocardial mTORC1 activation in nonischemic dilated cardiomyopathy.

BACKGROUND: Activity of mTOR complex 1 (mTORC1) has been shown to be up-regulated in animal models of heart failure. Here, we investigated the change and role of mTORC1 in human nonischemic dilated cardiomyopathy (NICM). METHODS: Endomyocardial biopsy specimens were obtained from patients with NICM (n=52) and from Brugada syndrome patients with normal LVEF as controls (n=10). The specimens were stained for phospho-ribosomal protein S6 (p-Rps6) and phospho-p70S6K (p-p70S6K), and the area with p-Rps6 signal was used as an index of mTORC1 activity. Using median mTORC1 activity, patients were divided into a high mTORC1 activity (H-mTOR) group and a low mTORC1 activity (L-mTOR) group. RESULTS: The ratio of p-Rps6-positive area in biopsy samples was 10-fold larger in patients with NICM than in controls (2.0±2.2% vs. 0.2±0.2%, p<0.01). p-p70S6K signal level was higher in the H-mTOR group than in the L-mTOR group. The proportion of patients with a family history of cardiomyopathy was higher and the proportion of patients on ACE inhibitors or angiotensin receptor blockers was lower in the H-mTOR group than in the L-mTOR group. The p-Rps6-positive area was correlated with extent of myocardial fibrosis (r=0.46, p<0.01). The cardiac event-free survival rate during a 5-year follow-up period tended to be lower in the H-mTOR group than in the L-mTOR group (52.9% vs. 81.6%, P=0.10). CONCLUSION: Aberrant activation of mTORC1 in cardiomyocytes was associated with myocardial fibrosis and a trend for worse prognosis in patients with NICM, indicating that persistently activated mTORC1 contributes to progression of human heart failure.

Pericardial Effusion and Multiple Organ Involvement Are Independent Predictors of Mortality in Patients with Systemic Light Chain Amyloidosis.

OBJECTIVE: Left ventricular (LV) functions assessed by echocardiography and cardiac biomarkers are strong predictors of mortality in patients with systemic light chain (AL) amyloidosis. However, most previous studies have been conducted in Western countries, and the predictors of mortality in Asian patients with AL amyloidosis have not been characterized. To address this issue, we aimed to determine the predictors of mortality in Asian patients with biopsy-confirmed AL amyloidosis. METHODS: We retrospectively enrolled 31 patients (59±11 years, 55% men) in whom AL amyloidosis was confirmed by biopsies from cardiac or non-cardiac tissues. Of these patients, 15 (48%) met the international echocardiographic criteria for cardiac amyloidosis (mean LV wall thickness >12 mm without other causes of LV hypertrophy). RESULTS: During a mean follow-up period of 21±20 months, 15 patients died. Non-survivors had a higher number of involved organs, lower e', and higher rates of E/e' >15, pericardial effusion (PE), low voltage on an electrocardiogram and a New York Heart Association (NYHA) functional class ≥ III, compared with survivors. In multivariate analysis, a NYHA functional class ≥ III (p=0.024) and cardiac involvement (p=0.032) were independent predictors of PE in patients with AL amyloidosis. Multivariate Cox proportional hazard analysis indicated that PE (hazard ratio: 21.9, p=0.025) and the number of involved organs (hazard ratio: 2.8, p=0.015), but not LV diastolic parameters of tissue Doppler echocardiography, independently predict mortality in patients with AL amyloidosis. CONCLUSION: PE and multiple organ involvement, compared with e' and E/e', are stronger predictors of mortality in patients with AL amyloidosis. The advanced disease stage of AL amyloidosis might underlie the strong association between PE and a poor outcome.

Cardiac tamponade leading to the diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a case report and review of the literature.

Eosinophilic granulomatosis with polyangiitis (EGPA), which was previously called Churg-Strauss syndrome, is a necrotizing systemic vasculitis of unknown cause accompanied by prominent eosinophilia. Cardiovascular complications, including eosinophilic myocarditis, are a major cause of mortality in this disorder. Acute pericarditis with slight pericardial effusion is a typical manifestation in EGPA, though hemodynamically significant pericardial effusion has been reported in a few cases. We report a case that initially presented with isolated cardiac tamponade, which was followed by systemic manifestations of EGPA over 3 weeks. Including the present case, previous EGPA cases with cardiac tamponade are reviewed to delineate its clinical characteristics.

Prognostic implications of left atrial dilation evaluated by echocardiographic volume in patients with normal left atrial antero-posterior dimensions.

BACKGROUND: The purpose of this study was to clarify the clinical characteristics and prognostic implications of left atrial (LA) dilation evaluated echocardiographic volume in patients with normal LA dimension (LAD). METHODS: A total of 140 consecutive patients (81 men, mean age: 57 ± 18 years) with normal LAD (<39 mm for women and <41 mm for men) who underwent conventional echocardiography and tissue Doppler imaging were enrolled. LA volume (LAV) ≥29 ml/m(2) was defined as abnormal LAV. Hospitalization for heart failure (HF) and cardiac death were defined as cardiac events. RESULTS: Eighty-seven (62%) of the patients had LA dilation, defined as a normal LAD but an abnormal LAV. Patients with LA dilation were significantly older and had a significantly higher left ventricular (LV) mass index (LVMI) and incidences of hypertension and HF than did patients with both normal LAD and normal LAV. Logistic regression analysis revealed that increased LVMI was an independent (p < 0.01) determinant of LA dilatation. During a follow-up period of 16 ± 10 months, ten patients had cardiac events. Patients with cardiac events had a higher incidence of LA dilation than those without cardiac events (100 vs. 59%, p < 0.05). A Kaplan-Meier survival curve showed that patients with LA dilation had a significantly lower survival rate than those with both normal LAD and normal LAV (log rank 6.1, p = 0.014). CONCLUSIONS: LV hypertrophy is an independent determinant of LA dilation in patients with normal LAD. Assessment of LA morphology using LAV can contribute to risk stratification in patients with normal LAD.

Prediction of new-onset refractory congestive heart failure using gated myocardial perfusion SPECT imaging in patients with known or suspected coronary artery disease subanalysis of the J-ACCESS database.

OBJECTIVES: The purpose of this study was to evaluate the predictive value of perfusion/function parameters measured by gated myocardial perfusion single-photon emission computed tomography (SPECT)in combination with clinical variables in patients with known or suspected coronary artery disease to predict refractory heart failure (HF). BACKGROUND: The increasing number of HF patients requires the establishment of a prophylactic strategy that can identify patients at high risk of HF due to coronary artery disease. METHODS: We analyzed clinical and stress/rest-gated SPECT data from the multicenter, prospective, and observational J-ACCESS (Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT) database of 3,835 known or suspected coronary artery disease patients in which new-onset congestive HF symptoms requiring aggressive medical treatment were observed in 71 patients for 3 years. RESULTS: The multivariable Cox hazard model revealed that chronic renal dysfunction (hazard ratio(HR): 6.227 [95% confidence interval (CI): 2.920 to 13.279]), the end-systolic volume index (ESVI) (HR:1.019 [95% CI: 1.011 to 1.029]), and moderate to high stress summed score (SSS) (HR: 3.012 [95% CI: 1.757 to 5.181]) independently (p < 0.0001) predicted HF. In addition to the close (p < 0.0001) correlation of ESVI and SSS with HF incidence, the combined tertiles of SSS and ESVI revealed high-risk patients with a maximally 17.3 times greater risk (5.2%/3 years) compared with the minimal risk (0.3%/3 years) at a normal to low SSS and lower ESVI. Chronic renal dysfunction combined with ESVI and SSS categories had the greatest (p < 0.005 to 0.001) incremental prognostic value with a global chi-square value (125.0)over single or other combined risks. CONCLUSIONS: Chronic renal dysfunction, greater stress-induced perfusion abnormality, and higher ESVI provide independent and additive information for predicting the risk of refractory HF in known or suspected coronary patients, indicating the efficacy of perfusion/function parameters measured by stress gated perfusion SPECT for identifying patients at greater risk of future refractory HF.

Massive cerebral embolism originated from ruptured infective mitral annular calcification in a chronic hemodialysis patient.

Infective endocarditis of mitral annular calcification (MAC) has been reported, however, little attention has been given to the possibility of cerebral-embolism based infective endocarditis of MAC. We report a chronic hemodialysis patient of massive cerebral embolism originated from ruptured infective MAC.

[Ureteral and bladder metastases of renal cell carcinoma following synchronous renal cell carcinoma and bladder cancer; a case report].

A 73-year-old man presented with gross hematuria. Ultrasonography and computerized tomography showed small bladder tumors and a left renal mass protruding to renal pelvis. Transurethral resection of bladder tumor and ureteroscopic tumor biopsy were performed, and pathological examinations revealed transitional cell carcinoma in the bladder and renal cell carcinoma in the kidney. He underwent left radical nephrectomy. A 4-month postoperative cystoscopy revealed a solitaly non-papillary tumor in the bladder. Transurethral resection was performed and pathological diagnosis was metastasis from renal cell carcinoma. At that time, multiple metastases to ureteral stump and lung were found. He had undergone palliative treatment because of his poor general condition until he died 26 months postoperatively. Care should be taken for management of ureteral stump when diagnostic ureteroscopy was done for renal cell carcinoma invading the renal pelvis.

Human heart-type fatty acid-binding protein as an early diagnostic and prognostic marker in acute coronary syndrome.

Although heart-type fatty acid-binding protein (H-FABP) can be a marker of sarcolemmal injury due to acute myocardial ischemia, the diagnostic or prognostic value is not established in patients with acute chest pain. This multicenter prospective study aimed to determine the diagnostic and prognostic values of H-FABP in 133 patients presenting to an emergency room with suspected acute coronary syndrome (ACS) by comparing with those of conventional biomarkers. H-FABP and myoglobin had greater positive results than did creatine kinase-MB or troponin T. Receiver operating characteristics analysis revealed that H-FABP was the most reliable for detection of ACS and that H-FABP had the greatest sensitivities for identification of patients requiring emergency hospitalization, coronary angiography, and interventional therapy within 7 days among the biomarkers. Thus, H-FABP can be an early diagnostic and prognostic biochemical marker, particularly within the first 6 h from the onset of chest symptoms, in patients with chest pain at an emergency department.