Prognostic significance of late gadolinium enhancement quantification in cardiac magnetic resonance imaging of hypertrophic cardiomyopathy with systolic dysfunction

Hypertrophic cardiomyopathy (HCM) with systolic dysfunction carries a poor prognosis. Although late gadolinium enhancement (LGE) on cardiac magnetic resonance is associated with adverse cardiac events in HCM and is inversely related to left ventricular ejection fraction (LVEF), it is unknown whether LGE or LVEF more accurately predicts adverse cardiac events in HCM with systolic dysfunction. We retrospectively assessed the extent of LGE with a threshold of 6 standard deviations in 46 consecutive HCM patients with systolic dysfunction defined as LVEF <50 % (average 35 ± 12 %) who underwent cardiac magnetic resonance (35 males, mean age 59 ± 14 years). They were followed up over 1755 ± 594 days. The composite adverse cardiac events end point included cardiovascular death, lethal arrhythmia, cardioembolic stroke, and unplanned heart failure hospitalization. LGE was detected in all patients, and the mean extent was 30 ± 15 %. Twenty-nine patients developed adverse cardiac events. Multivariate Cox proportional hazard analysis revealed the extent of LGE as a good independent predictor of adverse cardiac events. Risk increased with the extent of LGE (hazard ratio = 1.62/10 % increase in LGE, 95 % confidence interval = 1.23–2.15, p < 0.001). LVEF was inversely related to the extent of LGE (r = ?0.44; p = 0.002) and was also an independent predictor of adverse cardiac events. Risk decreased with LVEF (hazard ratio = 0.68/10 % increase in LVEF, 95 % confidence interval = 0.51–0.91, p = 0.010). The Akaike information criterion evaluating the fit of a model demonstrated that the extent of LGE was a better independent predictor of MACE than LVEF (Akaike information criterion = 172.20 and 178.09, respectively).The extent of LGE was a good independent predictor of adverse cardiac events and reflected mortality and morbidity more precisely than LVEF in HCM with systolic dysfunction.     

Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201

Recent studies have described various impacts of obesity and being overweight on acute myeloid leukemia (AML) outcomes in adult patients, but little is known about the impact of being underweight. We compared the outcomes of underweight patients to those of normal weight and overweight patients. Adult patients with AML who registered in the JALSG AML201 study (n = 1057) were classified into three groups: underweight (body mass index [BMI] < 18.5, n = 92), normal weight (BMI 18.5–25, n = 746), and overweight (BMI ≥ 25, n = 219). With the exception of age and male/female ratio, patient characteristics were comparable among the three groups. Rates of complete remission following induction chemotherapy were similar among the three groups (p = 0.68). We observed a significant difference in overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) between underweight and normal weight patients (3-year OS 34.8 vs. 47.7%, p = 0.01; DFS 28.6 vs. 39.8%, p = 0.02; 1-year NRM 6.2 vs. 2.6%, p = 0.05), but not between underweight and overweight patients. In multivariate analysis, underweight was an independent adverse prognostic factor for OS (p < 0.01), DFS (p = 0.01), and NRM (p = 0.04). During the first induction chemotherapy, the incidences of documented infection (DI) and severe adverse events (AEs) were higher in underweight patients than those in normal weight patients (DI 16 vs. 8.1%, p = 0.04; AE 36 vs. 24%, p = 0.05). In conclusion, underweight was an independent adverse prognostic factor for survival in adult AML patients.     

Heart involvement in systemic lupus erythematosus: a systemic review and meta-analysis

Cardiovascular diseases are one of the most important causes of the disability and mortality in patients with systemic lupus erythematosus (SLE). The present study examined the cardiac abnormalities in patients with SLE by echocardiography. Case-control studies were obtained by searching PubMed MEDLINE, Embase, and MD Consult. Systemic review and meta-analysis were performed to assess the cardiac abnormalities based on the changes in the echocardiography in patients with SLE. Twenty-two studies including 1117 SLE patients and 901 healthy controls were enrolled into this study. We found that patients with SLE developed the pericardial effusion (odds ratio (OR) (95 % confidence interval (CI)) 30.52 (9.70–96.02); p < 0.00001) and the combined valvular alterations (OR (95 %CI) 11.08 (6.98–17.59); p < 0.00001). In addition, SLE patients also exhibited an increase in the left atrial diameter (LAD) (WMD—weighted mean difference (95 %CI) 0.18 (0.06–0.29); p = 0.002), the left ventricular internal diameter in diastole (LVDd) (WMD (95 %CI) 0.07 (0.02–0.12); p = 0.01), and the left ventricular mass index (LVMI) (WMD (95 %CI) 5.69 (2.69–8.69); p = 0.0002). In contrast, the left ventricular systolic function (WMD (95 %CI) ?1.22 (?1.69 to ?0.75); p < 0.00001) and diastolic function including E/A ratio and E/E’ ratio (WMD (95  % CI) ?0.13 (?0.24 to ?0.01); p = 0.04; WMD (95  % CI) 1.71 (0.43 to 2.99); p = 0.009) were decreased in SLE patients. Patients with SLE are associated with significant alterations in cardiac structure and function as demonstrated by echocardiography. Data from this study suggest that echocardiographic assessment should be considered as a part of routine examinations for SLE patients clinically.     

Three-question set from Michigan Neuropathy Screening Instrument adds independent prognostic information on cardiovascular outcomes: analysis of ALTITUDE trial

Aims/hypothesis

The self-administered Michigan Neuropathy Screening Instrument (MNSI) is used to diagnose diabetic peripheral neuropathy. We examined whether the MNSI might also provide information on risk of death and cardiovascular outcomes.

Methods

In this post hoc analysis of the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial, we divided 8463 participants with type 2 diabetes and chronic kidney disease (CKD) and/or cardiovascular disease (CVD) into independent training (n = 3252) and validation (n = 5211) sets. In the training set, we identified specific questions that were independently associated with a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction/stroke, heart failure hospitalisation). We then evaluated the performance of these questions in the validation set.

Results

In the training set, three questions (‘Are your legs numb?’, ‘Have you ever had an open sore on your foot?’ and ‘Do your legs hurt when you walk?’) were significantly associated with the cardiovascular composite outcome. In the validation set, after multivariable adjustment for key covariates, one or more positive responses (n = 3079, 59.1%) was associated with a higher risk of the cardiovascular composite outcome (HR 1.54 [95% CI 1.28, 1.85], p < 0.001), heart failure hospitalisation (HR 1.74 [95% CI 1.29, 2.35], p < 0.001), myocardial infarction (HR 1.81 [95% CI 1.23, 2.69], p = 0.003), stroke (HR 1.75 [95% CI 1.20, 2.56], p = 0.003) and three-point major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) (HR 1.49 [95% CI 1.20, 1.85], p < 0.001) relative to no positive responses to all questions. Associations were stronger if participants answered positively to all three questions (n = 552, 11%). The addition of the total number of affirmative responses to existing models significantly improved Harrell’s C statistic for the cardiovascular composite outcome (0.70 vs 0.71, p = 0.010), continuous net reclassification improvement (+22% [+10%, +31%], p = 0.027) and integrated discrimination improvement (+0.9% [+0.4%, +2.1%], p = 0.007).

Conclusions/interpretation

We identified three questions from the MNSI that provide additional prognostic information for individuals with type 2 diabetes and CKD and/or CVD. If externally validated, these questions may be integrated into the clinical history to augment prediction of CV events in high-risk individuals with type 2 diabetes.

     

Differential impact of peripheral endothelial dysfunction on subsequent cardiovascular events following percutaneous coronary intervention between chronic kidney disease (CKD) and non-CKD patients

Chronic kidney disease (CKD) status might modify the predictive effect of peripheral endothelial dysfunction on cardiovascular events after percutaneous coronary intervention (PCI). The aim of this study was to examine the differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients. We conducted a cohort study of 435 patients following PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². Peripheral endothelial dysfunction was examined using reactive hyperemia-peripheral arterial tonometry index (RHI), and we divided patients into low- and high-natural logarithmic RHI (Ln-RHI) group. The endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, ischemic stroke, hospitalization due to unstable angina pectoris, and coronary revascularization. A total of 56 patients had a cardiovascular event. Patients who suffered a cardiovascular event had significantly lower Ln-RHI than other patients in the non-CKD group (0.46 ± 0.18 versus 0.60 ± 0.25; P = 0.002). Kaplan–Meier analysis demonstrated a significantly higher probability of cardiovascular events in low Ln-RHI patients in the non-CKD group (log-rank test: P = 0.003). Multivariate Cox proportional hazards analysis identified Ln-RHI as an independent and significant predictor of future cardiovascular events in the non-CKD group (HR: 0.096; 95 % CI 0.02–0.47; P = 0.004) but not in the CKD group. There was a differential effect of peripheral endothelial dysfunction on clinical outcome after PCI between CKD and non-CKD patients, and peripheral endothelial dysfunction significantly correlates with subsequent cardiovascular events after PCI in non-CKD patients.     

Major adverse cardiovascular events in non-valvular atrial fibrillation with chronic obstructive pulmonary disease: the ARAPACIS study

Chronic obstructive pulmonary disease (COPD) increases the risk of mortality in non-valvular atrial fibrillation (NVAF) patients. Data on the relationship of COPD to major cardiovascular events (MACE) in AF have not been defined. The aim of the study is to assess the predictive value of COPD on incident MACE in NVAF patients over a 3-year follow-up. In the Atrial Fibrillation Registry for Ankle-Brachial Index Prevalence Assessment-Collaborative Italian Study (ARAPACIS) cohort, we evaluate the impact of COPD on the following clinical endpoints: MACE (including vascular death, fatal/non-fatal MI and stroke/TIA), cardiovascular (CV) death and all-cause mortality. Among 2027 NVAF patients, patients with COPD (9%) are more commonly male, elderly and at higher thromboembolic risk. During a median 36.0 months follow-up, 186 patients experienced MACE: vascular death (n?=?72), MI (n?=?57), stroke/TIA (n?=?57). All major outcomes (including stroke/TIA, MI, vascular death, and all-cause death) are centrally adjudicated. Kaplan–Meier curves show that NVAF patients with COPD are at higher risk for MACE (p?<?0.001), CV death (p?<?0.001) and all-cause death (p?<?0.001). On Cox proportional hazard analysis, COPD is an independent predictor of MACE (Hazard ratio [HR] 1.77, 95% Confidence Intervals [CI] 1.20–2.61; p?=?0.004), CV death (HR 2.73, 95% CI 1.76–4.23; p?<?0.0001) and all-cause death (HR 2.16, 95% CI 1.48–3.16; p?<?0.0001). COPD is an independent predictor of MACE, CV death and all-cause death during a long-term follow-up of NVAF patients.     

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN_i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN_i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.     

Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy

Background

Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization.

Methods

Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30–90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP-antagonists).

Results

We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17–4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20–11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52–1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59–1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62–2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63–2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99–5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28–2.29], p = 0.68).

Conclusion

In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor.

     

Effect of CPAP therapy on cardiovascular events and mortality in patients with obstructive sleep apnea: a meta-analysis

Purpose

Continuous positive airway pressure (CPAP) therapy may decrease the risk of mortality and cardiovascular events in patients with obstructive sleep apnea. However, these benefits are not completely clear.

Methods

We undertook a meta-analysis of randomized clinical trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database.

Results

Eighteen studies (4146 patients) were included. Overall, CPAP therapy did not significantly decrease the risk of cardiovascular events compared with the control group (odds ratio (OR), 0.84; 95 % confidence intervals (CI), 0.62–1.13; p = 0.25; I ² = 0 %). CPAP was associated with a nonsignificant trend of lower rate of death and stroke (for death: OR, 0.85; 95 % CI, 0.35–2.06; p = 0.72; I ² = 0.0 %; for stroke: OR, 0.56; 95 % CI, 0.18–1.73; p = 0.32; I ² = 12.0 %), a significantly lower Epworth sleepiness score (ESS) (mean difference (MD), ?1.78; 95 % CI, ?2.31 to ?1.24; p < 0.00001; I ² = 76 %), and a significantly lower 24 h systolic and diastolic blood pressure (BP) (for 24 h systolic BP: MD, ?2.03 mmHg; 95 % CI, ?3.64 to ?0.42; p = 0.01; I ² = 0 %; for diastolic BP: MD, ?1.79 mmHg; 95 % CI, ?2.89 to ?0.68; p = 0.001; I ² = 0 %). Daytime systolic BP and body mass index were comparable between the CPAP and control groups. Subgroup analysis did not show any significant difference between short- and mediate-to-long-term follow-up groups with regard to cardiovascular events, death, and stroke.

Conclusions

CPAP therapy was associated with a trend of decreased risk of cardiovascular events. Furthermore, ESS and BP were significantly lower in the CPAP group. Larger randomized studies are needed to confirm these findings.

     

Cardiovascular risk stratification in patients with non-valvular atrial fibrillation: the 2MACE score

Recent findings suggest that patients with non-valvular atrial fibrillation (AF), in addition to having a high risk for ischemic stroke, are also at risk for myocardial infarction (MI). The aim of the study was to combine factors predicting Major Adverse Cardiovascular Events (MACE) in AF patients, including fatal/nonfatal MI, cardiac revascularization, and cardiovascular death, into a simple risk score. Predictors of MACE were obtained from a prospective observational cohort study, including 1019 AF patients taking vitamin K antagonists from the Atherothrombosis Center, of Sapienza University of Rome. Thus, we derived the 2MACE score [2 points for Metabolic Syndrome and Age ≥75, 1 point for MI/revascularization, Congestive heart failure (ejection fraction ≤40 %), thrombo-Embolism (stroke/transient ischemic attack)], ranging from 0 to 7 points. To evaluate the 2MACE score, we included an external validation cohort of 1089 anticoagulated AF patients from the Thrombosis Centre of Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy. At follow-up, 111 AF patients in the internal and 68 in the external cohort experienced a MACE. The 2MACE score showed a good ability in discriminating AF patients experiencing MACE both in the internal derivation cohort, with a c-index of 0.79 [95 % Confidence Interval (CI) 0.71–0.90, p < 0.001] and in the external validation cohort (c-index 0.66, 95 % CI 0.60–0.73, p < 0.001). The overall Hazard Ratio (HR) was 1.61 (95 % CI 1.40–1.85, p < 0.001) for each additional point. A 2MACE score ≥3 had the best combination of specificity and sensitivity, with an HR of 3.92 (95 % CI 2.41–6.40, p < 0.001). The new simple 2MACE score may help identifying AF patients at risk for cardiovascular events.     

Antiviral therapy with nucleotide/nucleoside analogues in chronic hepatitis B: A meta-analysis of prospective randomized trials

Nucleotide/nucleoside analogues (antiviral therapy) are used in the therapy of HBeAg positive and HBeAg negative chronic hepatitis B. We analyzed ten selected randomized controlled with 2557 patients to estimate the effect of antiviral drugs in chronic hepatitis B with compared to placebo. Virological response, biochemical response, histological response, seroconversion of HBeAg, and loss of HBeAg were estimated as primary efficacy measures. The included studies were subjected for heterogeneity and publication bias. The heterogeneity was assessed with χ2 and I² statistics. Publication bias was assessed by funnel plot. Greater rates of improvement obtained in antiviral group for virological response [43.96 % vs. 3.15 %, RR?=?0.57, 95 % CI?=?0.54–0.61, p-value <0.00001], biochemical response [58.37 % vs. 21.87 %, RR?=?0.52, 95 % CI?=?0.48–0.56, p-value <0.00001], histological response [58.99 % vs. 27.13 %, RR?=?0.56, 95 % CI?=?0.50–0.63, p-value <0.0001], seroconversion of HBeAg [10.66 % vs. 5.56 %, RR?=?0.94, 95 % CI?=?0.91–0.97, p-value?=?0.0005], and HBeAg loss [14.59 % vs. 9.64 %, RR?=?0.92, 95 % CI?=?0.88–0.96, p-value?=?0.0002]. The safety analysis were carried out for adverse events such as headache [17.22 % vs. 17.34 %, OR?=?1.09, 95 % CI?=?0.81–1.46, p-value?=?0.58], abdominal pain [16.46 % vs. 14.34 %, OR?=?1.24, 95 % CI?=?0.90–1.72, p-value?=?0.19], and pharyngitis [22.22 % vs. 18.23 %, OR?=?1.12, 95 % CI?=?0.86–1.45, p-value?=?0.40]. Excluding adverse events, all primary efficacy measures shown statistical significant result for chronic hepatitis treatment (p-value <0.05). Antiviral therapy provided significant benefit for the treatment of chronic hepatitis B with no measurable adverse effects.     

Bilateral internal thoracic artery grafting in octogenarians: where are the benefits?

The use of bilateral internal thoracic artery (BITA) grafting for myocardial revascularization is usually discouraged in the very elderly because of increased risk of perioperative complications. The aim of the study was to analyze early and late outcomes of BITA grafting in octogenarians. From January 1999 throughout February 2014, 236 consecutive octogenarians with multivessel coronary artery disease underwent primary isolated coronary bypass surgery at the authors’ institution. Six of these patients underwent emergency surgery and were excluded from this retrospective study; consequently, 135 BITA patients were compared with 95 single internal thoracic artery (SITA) patients according to early and late outcomes. Between BITA and SITA patients, there was no significant difference in the operative risk (EuroSCORE II: 8 ± 7.7 vs. 7.6 ± 6.1 %, p = 0.65). There was a lower aortic manipulation in BITA patients. Hospital mortality (3 vs. 4.2 %, p = 0.44) and perioperative complications were similar except that only BITA patients experienced sternal wound infection (5.2 %, p = 0.022). The mean follow-up was 4.7 ± 3.3 years. There were no differences between the two groups in overall survival (p = 0.79), freedom from cardiac and cerebrovascular deaths (p = 0.73), major adverse cardiac and cerebrovascular events (p = 0.63) and heart failure hospital readmission (p = 0.64). Predictors of decreased late survival were diabetes (p = 0.0062) and congestive heart failure (p = 0.0004). BITA grafting can be routinely used in octogenarians with atherosclerotic ascending aorta without an increase in hospital mortality or major adverse cardiac and cerebrovascular complications. However, there is an increased risk of sternal wound infection without a demonstrable long-term benefit.     

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension

Background

Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH).

Method

194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH.

Results

Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = ?0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = ?0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan–Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001).

Conclusion

Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

     

Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome

The importance of the central nervous system in cardiovascular events has been recognized. Recently, brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, is involved in depression mechanisms and also in stress and anxiety. Because BDNF is reported about cardioprotective role, we elucidated whether BDNF is associated with cardiovascular events in patients with chronic heart failure (CHF). We examined serum BDNF levels in 134 patients with CHF and 23 control subjects. The patients were followed to register cardiac events for a median of 426 days. BDNF was significantly lower in CHF patients than in control subjects (25.8 ± 8.4 vs 14.7 ± 8.4, P < 0.0001). Serum BDNF was also lower in patients with cardiac events than in event-free patients (16.1 ± 8.0 vs 12.5 ± 8.5, P < 0.0001). The cutoff value of BDNF was determined by performing receiver operating characteristic curve analysis. Kaplan–Meier analysis demonstrated that patients with low levels of BDNF experienced higher rates of cardiac events than those with high levels of BDNF. Multivariate Cox hazard analysis demonstrated that low BDNF levels (≤12.4 ng/mL) were an independent prognostic factor for cardiac events (hazard ratio 2.932, 95 % confidence interval 1.622–5.301; P = 0.0004). Adding levels of BDNF to the model with BNP levels, age, and eGFR for the prediction of cardiac events yielded significant net reclassification improvement of 0.429 (P < 0.001) and an integrated discrimination improvement of 0.101 (P < 0.001). Low serum BDNF levels were found in patients with CHF, and these levels were found to be independently associated with an increased risk of cardiac events.     

RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3–3.2) as compared to controls (1.3; IQR 0.8–2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15–0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92–4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10–7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00–129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46–4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.     

Incremental prognostic value of the SYNTAX score to late gadolinium-enhanced magnetic resonance images for patients with stable coronary artery disease

The prognostic significance of the SYNTAX (Synergy between PCI with Taxus and cardiac surgery) score has recently been demonstrated in patients with stable multivessel or left main coronary artery disease (CAD). The present study determines whether adding the SYNTAX score to Framingham risk score (FRS), left ventricular ejection fraction (LVEF) and presence of myocardial infarction (MI) by late gadolinium enhancement (LGE) magnetic resonance imaging can improve the risk stratification in patients with stable CAD. We calculated the SYNTAX score in 161 patients with stable CAD (mean age: 66 ± 10 years old). During a mean follow-up of 2.3 years, 56 (35 %) of 161 patients developed cardiovascular events defined as cardiovascular death, non-fatal MI, cerebral infarction, unstable angina pectoris, hospitalization due to heart failure and revascularization. Multivariate Cox regression analysis selected triglycerides [hazard ratio (HR): 1.005 (95 % confidence interval (CI): 1.001–1.008), p < 0.008], presence of LGE [HR: 6.329 (95 % CI: 2.662–15.05), p < 0.001] and the SYNTAX score [HR: 1.085 (95 % CI: 1.044–1.127), p < 0.001] as risk factors for future cardiovascular events. Adding the SYNTAX score to FRS, EF and LGE significantly improved the net reclassification index (NRI) [40.4 % (95 % CI: 18.1–54.8 %), p < 0.05] with an increase in C-statistics of 0.089 (from 0.707 to 0.796). An increase in C-statistics and significant improvement of NRI showed that adding the SYNTAX score to the FRS, LVEF and LGE incrementally improved risk stratification in patient with stable CAD.     

Relationship between abdominal aortic and coronary artery calcification as detected by computed tomography in chronic kidney disease patients

The purpose of this study was to investigate the relationship between abdominal aortic calcification (AAC) and coronary artery calcification (CAC) in chronic kidney disease (CKD) patients. We evaluated 126 asymptomatic CKD patients (mean estimated glomerular filtration rate: 36.1 ± 14.1 mL/min/1.73 m², mean age 70.3 ± 10.1 years). A non-contrast computed tomography scan was used to determine the abdominal aortic calcification index (ACI) and CAC score, and this relationship was investigated. Among the subjects, AAC was present in 109 patients (86.5 %) as defined by ACI >0 and median ACI was 11.7 %. ACI increased in accordance with advances in CAC score grades (3.0, 5.2, 17.2, and 32.8 % for CAC score 0, 1–100, 101–400, and 401 or more, respectively, p < 0.001). Even after multivariate adjustment, ACI was independently associated with severe CAC score as defined by CAC score >400 [odds ratio 1.08, 95 % confidence interval (CI) 1.04–1.12, p < 0.001]. Receiver-operating curve analysis showed that the ACI optimal cut-off value predicting severe CAC score was 16.5 % (area under the curve = 0.79, 95 % CI 0.69–0.90, p < 0.001). The C statics for predicting CAC score was significantly increased by adding ACI values to the model including other risk factors (0.853 versus 0.737, p = 0.023). In conclusion, the ACI value of 16.5 % allows us to predict the presence of severe CAC in CKD patients, and that the addition of ACI to the model with traditional risk factors significantly improves the predictive ability of severe CAC score. These data reinforce the utility of ACI as a screening tool in clinical practice.     

Impact of residual urine volume decline on the survival of chronic hemodialysis patients in Kinshasa

Background

Despite the multiple benefits of maintaining residual urine volume (RUV) in hemodialysis (HD), there is limited data from Sub-Saharan Africa. The aim of this study was to assess the impact of RUV decline on the survival of HD patients.

Methods

In a retrospective cohort study, 250 consecutive chronic HD patients (mean age 52.5 years; 68.8% male, median HD duration 6 months) from two hospitals in the city of Kinshasa were studied, between January 2007 and July 2013. The primary outcome was lost RUV. Preserved or lost RUV was defined as decline RUV?<?25 (median decline) or?≥?25 ml/day/month, respectively. The second endpoint was survival (time-to death). Survival curves were built using the Kaplan-Meier methods. We used Log-rank test to compare survival curves. Predictors of mortality were assessed by Cox proportional hazards regression models.

Results

The cumulative incidence of patients with RUV decline was 52, 4%. The median (IQR) decline in RUV was 25 (20.8–33.3) ml/day/month in the population studied, 56.7 (43.3–116.7) in patients deceased versus 12.9 (8.3–16.7) in survivor patients (p?<?0.001). Overall mortality was 78 per 1000 patient years (17 per 1000 in preserved vs 61 per 1000 lost RUV). Forty six patients (18.4%) died from withdrawal of HD due to financial constraints. The Median survival was 17 months in the whole group while, a significant difference was shown between lost (10 months, n?=?119) vs preserved RUV group (30 months, n?=?131; p?=?0001). Multivariate Cox proportional hazards models showed that, decreased RUV (adjusted HR 5.35, 95% CI [2.73–10.51], p?<?0.001), financial status (aHR 2.23, [1.11–4.46], p?=?0.024), hypervolemia (a HR 2.00, [1.17–3.40], p?=?0.011), lacking ACEI (aHR 2.48, [1.40–4.40], p?=?0.002) or beta blocker use (aHR 4.04, [1.42–11.54], p?=?0.009), central venous catheter (aHR 6.26, [1.71–22.95], p?=?0.006), serum albumin (aHR 0.93, [0.89–0.96], p?<?0.001) and hemoglobin (aHR 0.73, [0.63–0.84], p?<?0.001) had emerged as the independent predictors of all-cause mortality.

Conclusion

More than half of HD patients in this cohort study experienced fast RUV decline which contributed substantially to increase mortality, highlighting the need for its prevention and management.

     

Fibrinolysis in patients with a mild-to-moderate bleeding tendency of unknown cause

In more than 50% of patients with a mild-to-moderate bleeding tendency, no underlying cause can be identified (bleeding of unknown cause, BUC). Data on parameters of fibrinolysis in BUC are scarce in the literature and reveal discrepant results. It was the aim of this study to investigate increased fibrinolysis as a possible mechanism of BUC. We included 270 patients (227 females, median age 44 years, 25–75^th percentile 32–58) with BUC and 98 healthy controls (65 females, median age 47 years, 25–75^thpercentile 39–55). Tissue plasminogen activator (tPA-) antigen and activity, plasminogen activator inhibitor type-1 (PAI-1), tPA-PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI), α2-antiplasmin, and D-dimer were determined. While PAI-1 deficiency was equally frequent in patients with BUC and controls (91/270, 34%, and 33/98, 34%, p = 0.996), tPA activity levels were more often above the detection limit in patients than in controls (103/213, 48%, and 23/98, 23%, p < 0.0001). We found lower levels of tPA-PAI-1 complexes (6.86 (3.99–10.00) and 9.11 (7.17–13.12), p < 0.001) and higher activity of TAFI (18.61 (15.80–22.58) and 17.03 (14.02–20.02), p < 0.001) and α2-antiplasmin (102 (94–109) and 98 (90–106], p = 0.003) in patients compared to controls. Detectable tPA activity (OR 3.02, 95%CI 1.75–5.23, p < 0.0001), higher levels of TAFI (OR 2.57, 95%CI 1.48–4.46, p = 0.0008) and α2-antiplasmin (OR 1.03, 95%CI 1.01–1.05, p = 0.011), and lower levels of tPA-PAI-1 complexes (OR 0.90, 95%CI 0.86–0.95, p < 0.0001) were independently associated with BUC in sex-adjusted logistic regression analyses. We conclude that the fibrinolytic system can play an etiological role for bleeding in patients with BUC.     

The role of cumulative growth hormone exposure in determining mortality and morbidity in acromegaly: a single centre study

Purpose

Acromegaly has traditionally been associated with significant mortality and cardiovascular morbidity. The aim of this study was to assess the overall mortality and improvement in mortality and morbidity in acromegaly and correlate these with cumulative growth hormone exposure.

Methods

All patients treated for acromegaly at our centre until 2012 were analysed in this retrospective observational study. Baseline demographic details such as age at diagnoses, radiological features and pituitary status were obtained on these 167 patients. Cumulative GH levels (GHy) were calculated as a sum of average of GH readings in consecutive years. Mortality rates and development of new diabetes, hypertension and cardiovascular events (stroke, congestive cardiac failure and ischaemic heart disease) were assessed.

Results

The SMR for overall cohort was 1.6. There has been a significant improvement in SMR over the past two decades (SMR until 1992 2.5; SMR since 1992 1.0). Cumulative GH exposure was significantly high in patients who died (35.2 vs 24.1, p < 0.01) and in those with incident metabolic or vascular events during follow up (51.6 vs 24.4, p = 0.0001). The cardiovascular event rate of the ‘new’ cohort was significantly better than the ‘old’ cohort (8.0 vs. 29.1 %, p < 0.001).

Conclusion

There has been significant improvement in mortality and morbidity associated with acromegaly, in the setting of routine care in a specialized endocrine unit. Early and effective treatment to ‘control’ acromegaly could reduce GH exposure and hence vascular comorbidities.