Efficacy of ivabradine in idiopathic dilated cardiomyopathy patients with chronic heart failure

BackgroundThe aim of this study was to investigate the effect of ivabradine on symptoms, quality of life, effort tolerance, and echocardiographic parameters in patients with idiopathic dilated cardiomyopathy presenting with New York Heart Association (NYHA) class III or IV heart failure (HF) symptoms.MethodsWe screened 167 patients hospitalized for NYHA class III or IV chronic HF symptoms and left ventricular (LV) ejection fraction <40%. Of these, 53 were randomly assigned to either guidelines-based medical therapy alone (23 patients, control group) or ivabradine as add-on therapy (30 patients) for 3 months with about 1 year follow up.ResultsAfter 3 months’ treatment, adding ivabradine significantly reduced the heart rate from 96 to 72 bpm (p < 0.0001 versus control group), with more improvement in echocardiographic LV dimensions, LV volumes, LV ejection fraction (p = 0.045), NYHA class symptoms (p = 0.004), exercise tolerance (p = 0.03), and quality of life (p = 0.02). The average number of hospitalizations for HF over a mean longer-term follow-up of 13.5 months was 1.0 ± 1.4 in the ivabradine group versus 2.1 ± 1.1 in the control group (p = 0.003). Heart rate reduction was significantly correlated with better exercise tolerance, quality of life, LV ejection fraction, and NYHA class, together with fewer HF hospitalizations. Multivariate analysis showed heart rate reduction to be a stronger predictor for better LV ejection fraction (p = 0.024) and decreased hospitalizations than ivabradine use.ConclusionAdding ivabradine to optimal medical treatment in HF patients improved symptoms, quality of life, effort tolerance, and echocardiographic parameters, and reduced hospitalization. This beneficial ivabradine effect is probably due to its heart rate–reducing properties.     

Safety and efficacy of adaptive servo-ventilation in patients with severe systolic heart failure

Background and purposeIt is unclear whether adaptive servo-ventilation (ASV) is safe and effective in patients with severe systolic heart failure (HF). Our aim in this study was to estimate the safety and efficacy of ASV therapy for patients with severe systolic HF.Methods and subjectsSeventy-six HF patients (age: 69 ± 12 years; 53 men), categorized as New York Heart Association (NYHA) Class II–IV, with left ventricular ejection fraction (LVEF) of <50%, received ASV therapy after optimal medical therapy to determine the safety and efficacy of ASV. Patients were divided into 2 groups based on their LVEF: group L (LVEF < 30%; n = 42) and group H (LVEF ≥ 30%; n = 34). After 6 months of ASV therapy, we compared the changes in LVEF, brain natriuretic peptide (BNP), and incidence of fatal cardiovascular events between the groups.ResultsThe groups differed significantly with respect to beta-blocker treatment before ASV therapy (p < 0.0001). After 6 months of ASV therapy, LVEF and BNP levels had improved in both groups. In group L, LVEF had improved from 24.1 ± 5.6% to 35.2 ± 10.6% (p < 0.0001) and BNP from 591 (273–993) pg/ml to 142 (39–325) pg/ml (p = 0.002). Moreover, 1-year follow-up data showed a tendency toward improvement of NYHA classification in group L (group L: 50%; group H: 29%; p = 0.07), and showed no significant difference with regard to fatal cardiovascular events between the 2 groups (group L: 11.9%; group H: 5.9%; p = 0.36).ConclusionsOur study demonstrated that ASV therapy is safe and effective for use in very severe systolic HF patients as well as in relatively mild systolic HF patients.     

Is there a relationship between hypomagnesemia and proton-pump inhibitors in patients on chronic hemodialysis?

AimWe investigated the association among long-term proton-pump inhibitors (PPIs) use with serum magnesium (Mg) levels in chronic hemodialysis (HD) patients, as well as possible association among PPI use and increased risk of cardiovascular (CVD) morbidity in HD patients.MethodsOf 418 HD patients that were screened for inclusion, 136 were excluded due to incomplete medical data, duration of renal replacement therapy (RRT) for less than 12 months, use of Mg-based-phosphate binders or other Mg-based medications or either to presence of chronic increased GI losses. Among 282 patients included in the study, 170 patients were on PPIs.ResultsSerum Mg levels were significantly lower among PPI users vs. non-users (0.94 ± 0.2 vs. 1.03 ± 0.2 mmol/L; p < 0.0001). The median duration of PPI use was 27 ± 9.6 months (range from 12 to 108) and it was not significantly associated with Mg levels (r = 0.116; p = 0.167). Additionally, residual renal function didn't show a significant correlation with Mg concentration (r = − 0.102; p = NS) in both groups of patients. The use of PPIs was an independent and strong predictor of low Mg concentrations even in multivariate analysis (OR 3.05; 95% CI 1.2498–7.4594, p = 0.01). On the other hand, the daily dose of PPIs was not associated with low Mg levels. PPI users had a higher rate of adverse CVD events during the 1 year of follow-up in comparison to non-PPI users but that difference wasn't statistically significant (17.6% vs. 10.7%; p = 0.110).ConclusionWe have found a significant association between PPI use and lower serum Mg levels in chronic HD patients.     

The extent of heart rate reduction during hospitalization using beta-blockers,not the achieved heart rate itself at discharge,predicts the clinical outcome in patients with acute heart failure syndromes

AimIt has been uncertain whether patients with acute heart failure syndromes (AHFSs) benefit from a lower heart rate (HR) itself or from treatment for heart failure (HF) that reduces sympathetic tone with consequent HR reduction (HRR). The present study investigated the influence of HRR during hospitalization on the prognosis of AHFS patients.Methods and resultsIn 421 AHFS patients, we analyzed the relationship between HRR during hospitalization and the prognosis after discharge. During a mean follow-up period of 1.9 years, 76 and 55 patients died or were re-hospitalized for HF, respectively. Although HR at discharge did not influence cardiac events (hazard ratio [HR]: 1.00 [95% CI; 0.99–1.02], p = 0.22), the extent of HRR was a predictor of cardiac events (HR: 0.89 [0.84–0.96], p < 0.001). Kaplan–Meier analysis revealed that the cardiac event rate of the HRR-positive group (≥27 bpm reduction of HR from 114 ± 24 at admission to 65 ± 11 bpm at discharge) was significantly lower than that of the HRR-negative group (≤26 bpm (=median value) reduction of HR from 74 ± 14 to 71 ± 14 bpm). In the HRR-positive group, the cardiac event rate was significantly lower in patients receiving beta-blockers. Furthermore, the extent of HR change was an important predictor of cardiac events among other markers, compared with the change in systolic blood pressure or B-type natriuretic peptide.ConclusionThe HR itself at discharge was not associated with the prognosis, but the extent of HRR achieved by treatment of HF with beta-blockers was a strong predictor for the clinical outcome in AHFS patients.     

Assessment of the acute impact of normobaric hypoxia as a part of an intermittent hypoxic training on heart rate variability

AimTo assess the dynamics of ANS by means of heart rate variability (HRV) during and after acute exposure to normobaric hypoxia, representing a single session of an intermittent hypoxic training protocol.Material and methodsTwenty four healthy males aged 28.0 ± 7.2 (mean ± SD) breathed hypoxic air (FIO2 = 12.3 ± 1.5%) for one hour delivered via hypoxicator (AltiPro 8850 Summit+, Altitude Tech, Canada). Pulse oximetry and HRV were measured before, during and after the hypoxic exposure.ResultsAt the end of the hypoxic session all of the tested subjects had higher low frequency (lnLF) (6.9 ± 1.1 ms² vs. 7.5 ± 1.1 ms²; p = 0.042), LF/HF (1.5 ± 0.8 vs. 3.3 ± 2.8; p = 0.007) and standard deviation 2 of the Poincaré plot (SD2) (92.8 ± 140.0 ms vs. 120.2 ± 54.2 ms; p = 0.005) as well as increase in the Total power (7.7 ± 1.1 ms² vs. 8.1 ± 1.2 ms²; p = 0.032) and the Standard deviation of normal-to-normal interbeat intervals (SDNN) (57.3 ± 31.0 ms vs. 72.3 ± 41.1 ms; p = 0.024) but lower Sample entropy (SampEn) (1.6 ± 0.2 vs. 1.4 ± 0.2; p = 0.010). Immediately after the hypoxic exposure LF/HF lowered (3.3 ± 2.8 vs. 2.2 ± 1.8; p = 0.001) but lnHF significantly increased (6.6 ± 1.4 ms² vs. 7.1 ± 1.3 ms²; p = 0.020).ConclusionAcute normobaric hypoxia as a part of a single session of an intermittent hypoxic training protocol leads to changes in the activity of the ANS. The sympathetic tone prevails during hypoxic exposure and parasympathetic tone increases immediately after the hypoxic factor is withdrawn.     

Furosemide-related thiamine deficiency in hospitalized hypervolemic patients with renal failure and heart failure

BackgroundWe aimed to describe the thiamine status in hospitalized hypervolemic heart failure (HF) and/or renal failure (RF) patients treated with furosemide and to investigate whether there was a difference in furosemide-related thiamine deficiency between patients with RF and HF.MethodsPatients who were diagnosed as hypervolemia and treated with intravenous furosemide (at least 40 mg/day) were included in this prospective observational study. Whole blood thiamine concentrations were measured 3 times during hospital follow-up of patients.ResultsWe evaluated 61 hospitalized hypervolemic patients, of which 22 (36%) were men and 39 (64%) were women, with a mean age of 69.00 ± 10.39 (45–90) years. The baseline and post–hospital admission days 2 and 4 mean thiamine levels were 51.71 ± 20.66 ng/ml, 47.64 ± 15.43 ng/ml and 43.78 ± 16.20 ng/ml, respectively. Thiamine levels of the hypervolemic patients decreased significantly during the hospital stay while furosemide treatment was continuing (p = 0.029). There was a significant decrease in thiamine levels in patients who had HF (p = 0.026) and also, thiamine was significantly lower in HF patients who had previously used oral furosemide before hospitalization. However, these findings were not present in patients with RF.ConclusionsThiamine substantially decreases in most hypervolemic patients receiving intravenous furosemide treatment during the hospital stay. Thiamine levels were significantly decreased with furosemide treatment in especially HF patients, but the decrease in thiamine levels did not detected at the same rate in RF patients. Diuretic-induced thiamine loss may be less likely in RF patients, probably due to a reduction in excretion.     

Short term statin treatment in idiopathic dilated cardiomyopathy

BackgroundStatins may provide additional benefits in patients with cardiac failure due to their pleiotropic effects besides their cholesterol-lowering actions. In this study, we aimed to evaluate the impact of 12-week 40 mg atorvastatin therapy on the inflammatory markers, endothelium dependent vasodilatation and the ventricular performance markers in patients with heart failure (HF).Methods and resultsThirty chronic symptomatic heart failure patients, all with idiopathic dilated cardiomyopathy (DCM) were included to this open label and prospective study. Thirty patients were subdivided into two groups: group I – 15 patients who were given 40 mg of atorvastatin and group II – 15 patients who were given a placebo. After a 12-week treatment with atorvastatin 40 mg/day; clinical functional capacity, echocardiographic indices of cardiac performance and inflammatory markers were evaluated. After the treatment, even though the left ventricular ejection fraction (LV EF) did not improve significantly in the group receiving statins (29.2 ± 6.18 to 29.73 ± 6.27 in the statin group and 28.13 ± 5.81 to 27.93 ± 5.56 in the control group), both the 6 min walk test and Minnesota living with heart failure questionnaire improved significantly (p = 0.000 and 0.022, respectively). The flow mediated dilatation in the brachial arteries also showed improvement in the statin receiving group (8.9–13.8 in the statin group p = 0.0001, and 9.5–10.2 in the control group p = 0.055). In addition, the statin receiving group showed significantly lower levels of highly sensitive C-reactive protein (hs-CRP) levels at follow up (4.6–1.93 in statin group p = 0.005, and 7.2–4.97 in the control group p = 0.176).ConclusionShort term atorvastatin treatment improved functional capacity and the clinical symptoms in HF patients with idiopathic dilated cardiomyopathy. This positive effect of atorvastatin might be secondary to inflammatory modulation and improvement of endothelial function. Statins in HF deserve special attention by means of further large-scale trials.     

Association between the visiting time and the clinical findings on admission in patients with acute heart failure

BackgroundThere have been few reports about the clinical significance of the time of admission for acute heart failure (AHF).MethodsFive hundred thirty-one patients with AHF admitted to the intensive care unit (ICU) were analyzed. The patients were assigned to either the daytime HF group (n = 195, visited from 08:00 to 20:00, Group D) or nighttime HF group (n = 336, visited from 20:00 to 08:00, Group N). The clinical findings and outcomes were compared between these groups.ResultsThe systolic blood pressure (SBP), the number of patients with clinical scenario (CS) 1, and the heart rate (HR) were significantly higher in group N (SBP, 171.0 ± 38.9 mmHg; CS 1, 80.9%; HR, 116.9 ± 28.0 beats/min) than in group D (SBP, 154.2 ± 37.1 mmHg; CS 1, 66.2%; HR, 108.6 ± 31.4 beats/min). The patients in group N were more likely to have orthopnea (91.1%) than those in group D (70.3%). A multivariate logistic regression model identified a SBP ≥164 mmHg [odds ratio (OR): 2.043; 95% confidence interval (CI): 1.383–3.109], HR ≥114 beats/min (OR: 1.490; 95%CI: 1.001–2.218), and orthopnea (OR: 2.257; 95%CI: 1.377–3.701) to be independently associated with Group N. The length of ICU stay was shorter in group N (5.8 ± 10.5 days) than in group D (7.8 ± 11.5 days).ConclusionThe nighttime HF was characterized by high SBP, high HR, and orthopnea, and the length of ICU stay was shorter in the nighttime HF group.     

Usefulness of right atrial volume index in predicting outcome in chronic systolic heart failure

BackgroundRight ventricular (RV) dysfunction is associated with poor prognosis in patients with heart failure (HF). Echocardiographic assessment of RV systolic function is challenging. The ability to visualize the right atrium (RA) allows a quantitative, highly reproducible assessment of RA volume.ObjectiveThe aim is to study the relationship between the right atrial volume index (RAVI) and prognosis in patients with chronic systolic HF.Methods120 patients with chronic systolic HF and left ventricular ejection fraction (LVEF) <40% were enrolled. The RA volume was calculated by Simpson’s method using single-plane RA area and indexed to body surface area (RAVI). RV systolic assessment was done using the RV fractional area change (RVFAC), and peak systolic velocity (Sa_tri) using tissue Doppler imaging at the tricuspid annulus. The primary endpoint was death, urgent transplantation, or acute HF episode requiring hospital admission during a follow-up of 1 year.ResultsFollow up was complete for 117 of 120 patients. Fifty-two patients reached the primary endpoint. The mean RAVI was higher in patients with adverse events (45.5 ± 15 ml/m² versus 25.2 ± 11 ml/m², p < 0.001), and increased with worsening LVEF, RVFAC, Sa_tri (Spearman’s r = −0.46, r = −0.45, r = −0.59, p < 0.001 for all). RAVI was not correlated with estimates of RV diastolic dysfunction. The cut-off threshold for RAVI to predict the primary endpoint using receiver-operating characteristic curve was 29 ml/m² (area under the curve was 0.89%, 95% confidence interval: 0.82–0.95) with a sensitivity of 92%, and a specificity of 75%. NYHA > 2 (OR = 2.1, p < 0.01), and RAVI (OR = 1.6, p < 0.05) were found to be independent predictors of adverse outcome.ConclusionIn patients with chronic systolic HF, RAVI is an independent predictor of adverse outcome with a threshold value of 29 ml/m².     

Impact of prealbumin on mortality and hospital readmission in patients with acute heart failure

BackgroundPrealbumin is a maker of nutritional status and inflammation of potential prognostic value in acute heart failure (HF). The aim of this study is to evaluate if low prealbumin levels on admission predict mortality and readmissions in patients with acute HF.MethodWe conducted a prospective observational cohort study including 442 patients hospitalized for acute HF. Patients were classified in two groups according to prealbumin levels: “normal” prealbumin (> 15 mg) and “low” prealbumin (≤ 15 mg/dL). End-points were mortality and readmissions (all-cause and HF-related) and the combined end-point of mortality/readmission at 180 days.ResultsOut of 442 patients, 159 (36%) had low and 283 (64%) had normal prealbumin levels Mean age was 79.6 (73.9–84.2, p = 0,405) years and 183 (41%, p = 0,482) were males. After a median 180 days of follow-up, 108 (24%, p = 0,021) patients died and 170 (38%, p = 0,067) were readmitted. Mortality was higher in the low prealbumin group. The combined end-point was more frequent in the low prealbumin group (57% vs. 50%, p = 0.199). In the multivariate analysis the following variables were associated with mortality or readmission: older age, exacerbated chronic HF, higher comorbidity, low systolic blood pressure and hemoglobin values and higher pro brain natriuretic peptide levels.ConclusionsLow prealbumin is common (36%) in patients with acute heart failure and it is associated with a higher short-term mortality.     

Association of adiponectin with peripheral muscle status in elderly patients with heart failure

BackgroundReduced peripheral muscle mass was demonstrated in patients with chronic heart failure (HF). Adipokines may have potent metabolic effects on skeletal muscle. The associations between adipokines, peripheral muscle mass, and muscle function have been poorly investigated in patients with HF.MethodsWe measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients with chronic HF (age: 68 ± 7 years, New York Heart Association class II/III: 76/26%, left ventricular ejection fraction 29 ± 8%) and 20 healthy controls of similar age. Lean mass as a measure of skeletal muscle mass was measured by dual energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand grip strength measured by Jamar dynamometer.ResultsSerum levels of adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were elevated in patients with chronic HF compared to healthy controls (all p < 0.0001), while no difference in serum levels of leptin, testosterone or SHBG was noted. Levels of 25-hydroxy vitamin D were reduced (p = 0.002) in HF group. Peripheral lean mass and hand grip strength were reduced in patients with HF compared to healthy subjects (p = 0.006 and p < 0.0001, respectively). Using backward selection multivariable regression, serum levels of increased adiponectin remained significantly associated with reduced arm lean mass and muscle strength.ConclusionsOur findings may indicate a cross-sectional metabolic association of increased serum adiponectin with reduced peripheral muscle mass and muscle strength in non-cachectic, non-diabetic, elderly HF patients.     

Prevalence and spectrum of iron deficiency in heart failure patients in south Rajasthan

ObjectiveTo estimate the prevalence and pattern of iron deficiency (ID) in heart failure (HF) patients with or without anemia.MethodsThis is a single-center observational study, conducted at a tertiary care hospital of south Rajasthan. Patients admitted to hospital with clinical diagnosis of HF based on validated clinical criteria were included in the study. ID was diagnosed based on complete Iron profile, including serum iron, serum ferritin, total iron binding capacity, and transferrin saturation (TSAT). Anemia was defined as hemoglobin (Hb) <13 g/dl for males and <12 g/dl for females, based on World Health Organization definition. Absolute ID was taken as serum ferritin < 100 μg/L and functional ID was defined as normal serum ferritin (100–300 μg/L) with low TSAT (<20%).ResultsA total of 150 patients of HF (68% males and 32% females) were studied. Most of the patients were of high-functional NYHA class (mean NYHA 2.89 ± 0.95). ID was present in 76% patients with 48.7% patients having absolute and 27.3% patients having functional ID. Females were having significantly higher prevalence of ID than males (91.6% vs 68.6%; p = 0.002). Nearly one-fourth of the patients were having ID but without anemia, signifying importance of workup of ID other than Hb.ConclusionOur study highlights the yet underestimated and neglected burden of ID in HF patients in India. This study suggests further large-scale studies to better characterize this easily treatable condition and considering routine testing in future Indian guidelines.     

A comparative analysis of novel cardiovascular biomarkers in patients with chronic heart failure

BackgroundHeart failure (HF) with reduced ejection fraction remains a major therapeutic challenge. The aim of this study was to investigate the role of novel cardiovascular biomarkers, i.e. soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) in patients with ischaemic (ICM) or dilative cardiomyopathy (DCM).Materials and methodsA total of 200 patients were enrolled in this study: 65 were diagnosed with DCM and 59 patients suffering from ICM were included. 76 patients without coronary artery disease or signs of heart failure were included as controls. Plasma samples of all patients were analyzed by use of ELISA.ResultsLevels of sST2, suPAR and H-FABP were significantly higher in ICM and DCM patients compared to the control group (p < 0.0001). However, there were no significant differences between ICM and DCM in biomarker levels. Ejection fraction correlated inversely with cardiac biomarkers (sST2 p < 0.0001, GDF-15 p = 0.0394, suPAR p = 0.0029, H-FABP p < 0.0001). Similarly, CRP levels also showed a positive correlation with cardiac biomarkers. Renal insufficiency (p < 0.0001) and diabetes (sST2 p = 0.0021, GDF-15 p = 0.0055, suPAR p = 0.0339, H-FABP p = 0.0010) were significantly associated with a rise in cardiac biomarkers.ConclusionNovel cardiovascular biomarkers such as ST2, GDF-15, uPAR and H-FABP could offer a great potential for more precise diagnostic in ICM and DCM patients. H-FABP was the most promising marker in our study, followed by sST2, uPAR and GDF-15. Additional prospective studies will be necessary to further evaluate the potential clinical benefits in routine treatment of HF.     

Three-dimensional echocardiographic evaluation of mechanical dyssynchrony in systolic heart failure with narrow QRS complex

ObjectivesTo investigate the role of three-dimensional echocardiography (3DE) in evaluation of left ventricular mechanical dyssynchrony (LVMD) in heart failure (HF) patients with narrow QRS.Methods143 subjects (70 with HF and narrow QRS, 23 with HF and LBBB and 50 controls) were subjected to 3DE, evaluating global and regional dyssynchrony using systolic dyssynchrony index, maximum segmental dyssynchrony and opposite segment dyssynchrony. Spatial distribution of LVMD was studied in each patient using 3DE derived regional time volume curves. Extent of LVMD in HF patients with narrow QRS was compared to those with left bundle branch block (LBBB).ResultsFrequency of LVMD was similar in HF patients with narrow QRS or LBBB (55.7% vs. 47.8%, p = NS). There was no difference in the severity of LVMD between these two groups (10.7 ± 6.7% vs. 12.1 ± 7.4%, p = NS). Both HF groups had significantly more dyssynchrony than controls. A scattered pattern of distribution of asynchronous segments was seen in narrow QRS patients; 33.96% of them had their earliest contracting segment, instead of delayed segment, located in areas conventionally targeted for LV pacing i.e. anterolateral, inferolateral or inferior segments.Conclusions3DE confirmed significant dyssynchrony in  > 50% HF patients with narrow QRS as demonstrated by other imaging methods. 3D distribution patterns of asynchronous segments indicate possibility of left ventricular mechanics related reasons responsible for lack of CRT responsiveness, an observation that generates hypothesis on possible reasons of CRT non-responsiveness.     

Serum vitamin B12 and folate status in patients with inflammatory bowel diseases

BackgroundThe aims of this study were to investigate the prevalence of serum vitamin B₁₂ and folate abnormalities in patients with inflammatory bowel diseases (IBD) and to identify risk factors associated with B₁₂ and folate abnormalities in this entity.Methods138 patients with IBD (45 Crohn's disease and 93 ulcerative colitis) and 53 healthy subjects were enrolled into the study. Fasting serum B₁₂ and folic acid levels were measured and clinical data regarding inflammatory bowel diseases were gathered.ResultsWhile the mean serum B₁₂ concentration in CD patients was 281 ± 166 pg/ml, the mean serum vitamin B₁₂ concentration in UC patients was 348 ± 218 pg/ml (p = 0.224). The number of patients with vitamin B₁₂ deficiency in the CD group was greater than the number of patients with UC [n = 10 (22%) vs. n = 4 (7.5%), p = 0.014]. The number of patients (n = 10, 22%) with B₁₂ deficiency in the CD group was also greater than controls (n = 4, 7.5%) (p = 0.039). With regard to folate levels, the median serum folate level was 7.7 ± 5.3 ng/ml in CD patients, 8.6 ± 8.3 ng/ml in UC patients and 9.9 ± 3.3 ng/ml in the control group (p = n.s.). Patients with a prior ileocolonic resection had an abnormal B₁₂ concentration compared to patients without surgery (p = 0.008). In CD patients, ileal involvement was the only independent risk factor for having a low folate level.ConclusionSerum vitamin B₁₂ and folate deficiencies are common in patients with CD compared to UC patients and controls. In CD patients, prior small intestinal surgery is an independent risk factor for having a low serum vitamin B₁₂ level.     

Transition from angiotensin-converting enzyme inhibitor/angiotensin-II-receptor-blocker to sacubitril/valsartan in chronic heart failure patients: Initial experiences in clinical practice

BackgroundSacubitril/valsartan (S/V) therapy has been demonstrated to improve prognosis of systolic heart failure (HF) patients when compared to standard therapy with ACEi. The purpose of this investigation was to document the safety and consequences of transition from ACEi/angiotensin-II receptor blocker (ARB) to S/V in chronic stable HF patients.MethodsA group of 12 stable HF outpatients (11 males, 1 female) was enrolled (NYHA 2.7 ± 0.7, 42% with coronary artery disease (CAD), average left-ventricle ejection fraction (LVEF) 26.5%). Patients were converted from ACEi/ARB to S/V. Laboratory evaluation, Minnesota Living with Heart Failure Questionnaire (MLHFQ), six-minute walk test (6MWT) were performed before the conversion and at 3-month follow-up visit.ResultsConversion from ACEi/ARB to S/V was not associated with any adverse event. After 3 months, S/V therapy decreased blood pressure (−14.8 mmHg for systolic BP, −9.6 mmHg for diastolic BP) and serum potassium (−0.27 mmol·l⁻¹, all p < 0.05). No worsening of renal function occurred (creatinine −7.8 μmol·l⁻¹, p = 0.12, estimated glomerular filtration rate +0.08 ml·s⁻¹·1.73 m⁻², p = 0.14). B-type natriuretic peptide (BNP) level remained unchanged (p = 0.18), but NT-proBNP level decreased significantly (median 1012 ng·l⁻¹ at baseline, 559.4 ng·l⁻¹ at follow-up, p = 0.005). A slight but significant decrease in high-sensitivity cardiac troponin T (hs-cTnT) was observed (median 14.76 ng·l⁻¹ at baseline, 12.63 ng·l⁻¹ at follow-up, p = 0.001). An improvement in MLHFQ total score (−8 points, p = 0.006) and in 6MWT by 55 m (p = 0.0007) was noted, which was not due to increased effort.ConclusionThe transition from ACEi/ARB to S/V therapy appears to be safe and leads to an improvement in exercise tolerance and quality of life.     

Long-term changes in serum cholesterol level does not influence the progression of coronary calcification

BackgroundA number of reports controversially describe the influence of cholesterol level and lipid-lowering treatment (LLT) on the progression of coronary calcium (CC). We tested the hypothesis that long-term changes in serum cholesterol (CL) would affect the progression of CC.MethodsThe study population comprised 510 patients with stable angina pectoris, mean age of 63 ± 9 years. At baseline 372 patients received statin and/or fibrate (LLT group) while 138 patients did not (No-LLT at baseline group). Spiral CT every 24 months was used to track the progression of CC over a median 5.6 year follow-up.ResultsCL decreased during follow-up in both groups, but more pronouncedly in patients with LLT. The changes in total calcium score (TCS) were similar in both groups (p = 0.3). Changes in CL during follow-up were not associated with CC: TCS increased by 501 ± 63 from baseline in the 1st (upper) quartile, and by 350 ± 44, 403 ± 41 and 480 ± 56 in the 2nd, 3rd, and 4th quartiles of CL longitudinal changes (p = 0.2), respectively. Baseline TCS and its changes were not correlated with baseline CL and its changes. New calcified lesions were diagnosed in 132 (28.2%) out of the 467 patients available for this analysis, without significant difference between groups (p = 0.4). Multivariate analysis demonstrated that only baseline TCS (p < 0.001), body mass index (p = 0.007) and age (p = 0.006) were independent predictors for the TCS changes.ConclusionsLongitudinal CL changes do not seem to have a measurable effect on the rate of progression of CC.     

Hyponatremia is an independent predictor of adverse clinical outcomes in hospitalized patients due to worsening heart failure

Background and purposeHyponatremia is common and is associated with poor in-hospital outcomes in patients hospitalized with heart failure (HF). However, it is unknown whether hyponatremia is associated with long-term adverse outcomes. The purpose of this study was to clarify the characteristics, clinical status on admission, and management during hospitalization according to the serum sodium concentration on admission, and determine whether hyponatremia was associated with in-hospital as well as long-term outcomes in 1677 patients hospitalized with worsening HF on index hospitalization registered in the database of the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD).Methods and subjectsWe studied the characteristics and in-hospital treatment in 1659 patients hospitalized with worsening HF by using the JCARE-CARD database. Patients were divided into 2 groups according to serum sodium concentration on admission <135 mEq/mL (n = 176; 10.6%) or ≥135 mEq/mL (n = 1483; 89.4%).ResultsThe mean age was 70.7 years and 59.2% were male. Etiology was ischemic in 33.9% and mean left ventricular ejection fraction was 42.4%. After adjustment for covariates, hyponatremia was independently associated with in-hospital death [adjusted odds ratio (OR) 2.453, 95% confidence interval (CI) 1.265–4.755, p = 0.008]. It was significantly associated also with adverse long-term (mean 2.1 ± 0.8 years) outcomes including all-cause death (OR 1.952, 95% CI 1.433–2.657), cardiac death (OR 2.053, 95% CI 1.413–2.983), and rehospitalization due to worsening HF (OR 1.488, 95% CI 1.134–1.953).ConclusionsHyponatremia was independently associated with not only in-hospital but also long-term adverse outcomes in patients hospitalized with worsening HF.     

No inferioridad de la titulación de enfermera de insuficiencia cardiaca en comparación con la de cardiólogo de insuficiencia cardiaca. Ensayo aleatorizado multicéntrico ETIFIC

Introduction and objectivesBeta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin-II-receptor-blockers (ARB), and mineralocorticoid-receptor antagonists decrease mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. The effect is dose-dependent. Careful titration is recommended. However, suboptimal doses are common in clinical practice. This study aimed to compare the safety and efficacy of dose titration of the aforementioned drugs by HF nurses vs HF cardiologists.MethodsETIFIC was a multicenter (n = 20) noninferiority randomized controlled open label trial. A total of 320 hospitalized patients with new-onset HF, reduced ejection fraction and New York Heart Association II-III, without beta-blocker contraindications were randomized 1:1 in blocks of 4 patients each stratified by hospital: 164 to HF nurse titration vs 156 to HF cardiologist titration (144 vs 145 analyzed). The primary endpoint was the beta-blocker mean relative dose (% of target dose) achieved at 4 months. Secondary endpoints included ACE inhibitors, ARB, and mineralocorticoid-receptor antagonists mean relative doses, associated variables, adverse events, and clinical outcomes at 6 months.ResultsThe mean ± standard deviation relative doses achieved by HF nurses vs HF cardiologists were as follows: beta-blockers 71.09% ± 31.49% vs 56.29% ± 31.32%, with a difference of 14.8% (95%CI, 7.5-22.1), P < .001; ACE inhibitors 72.61% ± 29.80% vs 56.13% ± 30.37%, P < .001; ARB 44.48% ± 33.47% vs 43.51% ± 33.69%, P = .93; and mineralocorticoid-receptor antagonists 71% ± 32.12% vs 70.47% ± 29.78%, P = .86; mean ± standard deviation visits were 6.41 ± 2.82 vs 2.81 ± 1.58, P < .001, while the number (%) of adverse events were 34 (23.6) vs 30 (20.7), P = .55; and at 6 months HF hospitalizations were 1 (0.69) vs 9 (5.51), P = .01.ConclusionsETIFIC is the first multicenter randomized trial to demonstrate the noninferiority of HF specialist-nurse titration vs HF cardiologist titration. Moreover, HF nurses achieved higher beta-blocker/ACE inhibitors doses, with more outpatient visits and fewer HF hospitalizations.Trial registry number: NCT02546856.     

Serum insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation status in subjects with and without ischaemic heart disease

BackgroundInsulin-like growth factor binding protein-1 (IGFBP-1) modulates the activity of IGF-I. It exists in serum as phosphorylated and less phosphorylated forms. We wished to measure serum levels of both these forms of IGFBP-1, using a novel assay, in subjects with, or without ischaemic heart disease (IHD).MethodsWe measured serum concentrations of the phosphorylated and less phosphorylated forms of IGFBP-1 in 75 subjects (36 with and 39 without IHD). Two immunoassays were used, one which detects non-, and less-phosphorylated forms (LpIGFBP-1), and another which specifically detects the serine phosphorylated form of IGFBP-1 (pIGFBP-1).ResultsLpIGFBP-1 concentrations were significantly higher in subjects without IHD than in those with IHD (5.3 ± 0.5 μg/L vs. 2.7 ± 0.4 μg/L, p < 0.001). pIGFBP-1 levels were also significantly higher in subjects without IHD compared to those with IHD (33.3 ± 2.0 μg/L vs. 25.3 ± 2.2 μg/L, p < 0.01). The correlation between LpIGFBP-1 and pIGFBP-1 for all subjects was (r = 0.71, p < 0.001). This association was stronger in subjects without IHD (r = 0.76, p < 0.001) than for those with IHD (r = 0.60, p < 0.001). A significant negative association was observed between IGF-I and the ratio between the two forms (r = ?0.45, p < 0.0001). Receiver-Operating Characteristic (ROC) curve showed the highest area under the curve for LpIGFBP-1 (0.75) [95% CI: 0.63–0.86] and optimum cut-off value of 2.83 μg/L with 75% sensitivity and 74% specificity.ConclusionsWe propose that low serum concentrations of IGFBP-1 forms could be a marker of coronary risk, and the LpIGFBP-1:pIGFBP-1 ratio may be an index of biologically active IGF-I.