High Prevalence of Proarrhythmic Events in Patients With History of Atrial Fibrillation Undergoing a Rhythm Control Strategy: A Retrospective Study.

BACKGROUND: A retrospective study was undertaken to evaluate the respective prevalence of proarrhythmic events depending on various therapeutic regimens within a population of patients with history of atrial fibrillation (AF) undergoing a rhythm control strategy. METHODS: Inclusion criterion was the presence of AF in the patient's clinical history, whose cardioversion had been followed by the adoption of rhythm control strategy. The primary endpoint was the determination of the respective prevalences of paradoxical arrhythmias in the various therapeutic groups. The secondary objective was all-cause mortality. RESULTS: A total of 182 cases of proarrhythmia out of 624 patients were detected during a median follow-up of 20 months (interquartile range: 18 - 24 months). The prevalences of proarrhythmic events were: IC antiarrhythmic drugs + beta-blockers, 111 cases out of a total of 251 patients (44.22%); amiodarone, seven cases out of a total of 230 patients (3%); sotalol, 61 cases out of a total of 140 patients (43.57%); quinidine + digoxin, three cases out of a total of three patients (100%). The paradoxical arrhythmias were: torsades de pointes, second- and third-degree sino-atrial block, slow atrial flutter with 1:1 atrioventricular (AV) conduction, second-degree Mobitz II AV block, and sustained monomorphic ventricular tachycardia. No fatal case of proarrhythmia was found. CONCLUSIONS: Secondary prevention of AF relapses by means of drugs suitable for accomplishing rhythm control strategy exposes the patients to incumbent risk of proarrhythmic events. Thus, the choice to avoid some varieties of antiarrhythmics with marked proarrhythmic potential (class IC drugs, sotalol, quinidine) appears to be warranted.

Acquired drug-induced long QTc: new insights coming from a retrospective study.

INTRODUCTION: Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We do not know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus, we have retrospectively examined the clinical history of patients with diLQTc. METHODS: The case record, concerning the period January 2008-December 2017, was collected from two hospitals. diLQTc was defined as drug-induced heart rate-corrected QT of ≥ 450 ms or ≥ 470 ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation). RESULTS: Seventy-three validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio, 0.998; 95% CI, 0.984 to 1.013; p = 0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised between 450 and 500 ms was not associated with an increased risk of arrhythmic events. CONCLUSIONS: In our diLQTc patients, QTc duration did not predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking.

Malignant Ventricular Arrhythmias Resulting From Drug-Induced QTc Prolongation: A Retrospective Study.

BACKGROUND: Several drug classes (antiarrhythmics, antimicrobials, antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.) have been related to ventricular hyperkinetic arrhythmias such as torsade de pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart rate-corrected QT interval on the electrocardiogram, so-called drug-induced long heart rate-corrected QT (diLQTc). We don't know to what extent the drug-induced QTc prolongation is able to predict malignant arrhythmias. Thus we have retrospectively examined the clinical history of patients with diLQTc. METHODS: The case-record, concerning the period from January 2008 to December 2017, was collected from two hospitals. The diLQTc was defined as drug- induced heart rate-corrected QT of ≥ 450 ms or ≥ 470 ms, respectively in male or female patients. The primary purpose was to verify whether in diLQTc patients the length of this electrocardiographic segment was associated with the risk of symptoms or events (TdP, ventricular fibrillation). RESULTS: A total of 73 validated cases of diLQTc were gathered. Among them, the QTc duration was not able to predict the occurrence of symptoms or events (odds ratio: 0.998; 95% CI: 0.984 to 1.013; P = 0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised between 450 and 500 ms was not associated with an increased risk of arrhythmic events. CONCLUSIONS: In some probably genetically predisposed subjects, the occurrence of symptoms (dizziness, lipothymia, syncope ) and/or documented arrhythmic events (TdP), is related to intake of certain drugs (antiarrhythmics, antimicrobials such as quinolones and macrolides, etc.). Nevertheless, in our diLQTc patients, QTc duration didn't predict occurrence of symptoms, or arrhythmic events. Thus, other determinants should be postulated to clarify why sometimes diQTc prolongation propitiates ventricular malignant arrhythmias whereas in other cases this arrhythmogenic effect is lacking.

Thiazides and Osteoporotic Spinal Fractures: A Suspected Linkage Investigated by Means of a Two-Center, Case-Control Study.

BACKGROUND: An alleged association of chronic use of thiazide diuretics with an increased risk of bone fragility fractures has been highlighted by a relatively recent prospective cohort study. However, the concept that thiazides exert a beneficial effect on osteoporosis is still a predominant view. This effect would be mediated by the decrease in renal clearance of calcium ions, a pharmacological feature recognized for a long time now to this class of drugs, as opposed to the increase in calcium urinary excretion attributed instead to loop diuretics, i.e. furosemide and similar drugs. The purpose of this retrospective study was to attempt to clarify whether regular use of thiazide diuretics as antihypertensive therapeutics is associated with a significantly increased risk of osteoporotic fractures in female patients aged 65 or over. METHODS: In this two-center retrospective study, we followed up a cohort of female patients with (n = 80) and without (n = 158) thiazide-induced hyponatremia. RESULTS: A total of 48 osteoporotic fractures were recorded during a median follow-up period of 57.5 months. By means of univariate regression analysis, an association was found between thiazide-induced hyponatremia and increased risk of vertebral fractures (odds ratio (OR): 7.6; 95% confidence interval (CI): 3.755 - 15.39; P < 0.0001). Multivariate regression analysis, however, showed that age (OR: 1.823; 95% CI: 1.211 - 2.743) and body mass index (OR: 0.156; 95% CI: 0.038 - 0.645) were the only independent predictors of osteoporotic fractures. No association of a history of thiazide-induced hyponatremia and risk of fracture was noticeable in the final model. CONCLUSIONS: Because thiazide-induced hyponatremia was associated with spinal fractures in univariate but not multivariate analysis, a possible explanation is that hyponatremia may be a confounder of the relation between body mass and spinal fractures. Indeed, reduced body mass especially among elderly women with small body build may confer heightened risk of thiazide-induced hyponatremia because of decreased bone sodium available for exchange with the serum sodium. Thus, occurrence of hyponatremia could only serve as an indirect surrogate marker for osteoporosis risk.

Effects of Hyponatremia Normalization on the Short-Term Mortality and Rehospitalizations in Patients with Recent Acute Decompensated Heart Failure: A Retrospective Study.

Background: Several studies have shown that hyponatremia is associated with increased risk of rehospitalization and death in patients with heart failure. In these studies, chronic heart failure (CHF) patients with persistent hyponatremia were compared only with CHF patients with a normal sodium level at hospital admission. Aims: In the present retrospective study, conducted in a cohort of patients with recent acute decompensated heart failure (ADHF), all with hyponatremia ascertained at the time of hospital admission, we aimed to evaluate the effect of the normalization of serum sodium on the composite endpoint of short-term rehospitalization and mortality. Methods: A retrospective study centered on medical records of patients hospitalized for ADHF in the period April 2013 to April 2016 was performed. Data regarding serum sodium measurements had to be collected from medical records of cardiology wards of two hospitals, and were then processed for statistical analysis. As an inclusion criterion for enrollment, patients had to be suffering from heart failure that had required at least one hospitalization. Moreover, they had to be suffering from a state of hyponatremia (serum sodium < 135 mEq/L) at admission on the occasion of the index hospitalization. Patients with hyponatremia at admission were divided into two groups, one comprising patients with hyponatremia that persisted at the time of discharge (persistent hyponatremia) and a second including patients who had achieved normalization of their serum sodium levels (serum Na⁺ ≥ 135 mEq/L) during hospitalization until discharge. For both groups, the risk of mortality and rehospitalization during a 30-day follow-up was assessed. Results: One hundred and sixty CHF patients with various degrees of functional impairment were enrolled in the study. Among them, 56 (35%) had persistent hyponatremia over the course of hospitalization. At multivariable Cox proportional-hazards regression analysis, the risk of having a 30-day unplanned readmission or death was significantly higher in patients with persistent hyponatremia compared to those who exhibited a sodium level normalized at discharge (adjusted hazard ratio = 3.0743; 95% CI: 1.3981-6.7601; p = 0.0054). Among the other variables included in the Cox regression model, the number of admissions in the last 12 months (p < 0.0001), the length of stay of the index admission (p = 0.0015) and the New York Heart Association (NYHA) class III at discharge (p = 0.0022) were also identified as risk factors associated with the composite endpoint of 30-day unplanned readmission or death. Conclusions: In the present retrospective study, the risk of 30-day rehospitalization or death was significantly higher in patients with recent ADHF and persistent hyponatremia in comparison with ADHF patients who had had their serum sodium normalized during the hospital stay. This association seemed to be independent of the heart failure severity.

Poor concordance between different definitions of worsening renal function in patients with acute exacerbation of chronic heart failure: a retrospective study.

BACKGROUND: Approximately one-third of patients with acute decompensated heart failure (ADHF) treated with an intravenous (iv) loop diuretic at a relatively high dose (>80 mg/day of furosemide, or an equivalent dose of another loop diuretic), exhibit worsening renal function (WRF) after a single course of iv infusions or iv bolus injections maintained for several days. WRF is currently defined as an increase in serum creatinine >0.3 mg/dL (WRF-Cr) or a decrease in the estimated glomerular filtration rate of ≥20% (WRF-GFR) compared to baseline measurements. Furthermore, small increases in serum creatinine in the high-normal range of its values are indicative of significant reductions in estimated glomerular filtration rate (eGFR) due to the exponential relationship between serum creatinine and eGFR. Therefore, underestimating this relationship could lead to an erroneous quantitative estimate of new-onset renal dysfunction, diuretic-related. METHODS: The relationship between baseline serum creatinine (exposure variable) and the risk of diuretic-related WRF (dichotomous outcome variable), expressed either as WRF-Cr or as WRF-GFR, was assessed by logistic regression analysis. For this purpose, medical records with a diagnosis of previous ADHF were collated, and retrospectively analyzed. The eGFR was calculated using the equation "Modification of Diet in Renal Disease" (MDRD). The WRF was inferred from measurements of serum creatinine that had been made daily during the scheduled courses of intravenous diuretic therapy. RESULTS: Thirty-eight patients with chronic heart failure (CHF) and history of a previous episode of ADHF were enrolled in the study. An increase higher than 0.3 mg/dL of serum creatinine (WRF-Cr) was detected in 14 of 38 patients (36.8%). In addition, a decrease of ≥20% in GFR (WRF-GFR) was detected in 14 of 38 patients (36.8%). However, a poor concordance between the two criteria was found (Cohen's Kappa =0.208, 95% CI: -0.110 to 0.526). WRF-Cr and WRF-GFR showed opposing relations with baseline serum creatinine. In fact, the risk of WRF-Cr appeared positively associated with baseline serum creatinine (odds ratio =33.56; 95% CI:2.93- 384.18 P=0.0047), while the risk of WRF-GFR was inversely associated with the same analyte (odds ratio =0.0393; 95% CI: 0.0039 to 0.3966 P=0.0061). CONCLUSIONS: The criterion to discontinue the iv diuretic or to reduce its dosage in the presence of WRF-Cr for patients with ADHF or resistance to oral diuretic should be joined with the useful notion that this finding indicates a significant reduction of eGFR only for values of serum creatinine in the normal or near-normal ranges.

The Relation Between Global Longitudinal Strain and Serum Natriuretic Peptide Is More Strict Than That Found Between the Latter and Left Ventricular Ejection Fraction: A Retrospective Study in Chronic Heart Failure.

BACKGROUND: In chronic heart failure (CHF), the finding of elevated levels of the N-terminal fragment of the pro B-type natriuretic peptide (NT-proBNP) is a marker of pathological increase in myocardial ventricular wall stress and detrimental rise in ventricular filling pressures. However, the ensemble of data concerning the relationship between longitudinal deformation indices and NT-proBNP is still rather vague and approximate. METHODS: We carried out a retrospective study that involved 118 patients with CHF admitted to our clinic for CHF outpatients. For inclusion in the study, the CHF patients were required to have undergone at least a determination of global longitudinal strain (GLS) by means of speckle tracking echocardiography and to have practiced at least a determination of NT-proBNP. As regards the two determinations, the one echocardiographic and the other laboratory-based, the former should have been done not more than 24 hours before or after the latter. RESULTS: Correlation between log (NT-proBNP) and GLS was highly significant (r = 0.8386; P < 0.0001). The observed correlation between log (NT-proBNP) and left ventricular ejection fraction (LVEF) was also significant, but explained a smaller magnitude of the variance (r = -0.5465; P < 0.0001). In multiple linear regression analysis, GLS was shown to be the strongest independent predictor of log (NT-proBNP), within a parsimonious model including age, body mass index, estimated glomerular filtration rate, left atrial volume index, and LVEF (ß (regression coefficient) = 305, rpartial = 0.7076; P < 0.0001). By using the median value of NT-proBNP (299.5 pg/mL) as a discriminating value for identifying relatively low (i.e., below the median) and relatively high (i.e., above the median) levels of NT-proBNP, GLS was associated with the upper quartiles, whereas LVEF was associated with lower quartiles of NT-proBNP. However, the C statistics for GLS were significantly higher than for LVEF (area under the curve (AUC): 0.949 (GLS) vs. 0.730 (LVEF); P = 0.0030). CONCLUSIONS: In CHF patients, GLS shows a stronger association with NT-proBNP levels with respect to LVEF. Thus, in both CHF with preserved and reduced LVEF, GLS is more accurate compared with LVEF in predicting increased levels of NT-proBNP.

B-type natriuretic peptide-guided versus symptom-guided therapy in outpatients with chronic heart failure: a systematic review with meta-analysis.

PURPOSE: It has been asserted that serial measurements of natriuretic peptides, specifically B-type natriuretic peptide (BNP) or the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP), may serve as an objective practical guide to better tailor the drug treatment for patients with chronic heart failure (CHF), and especially to detect the cases of subclinical congestion that would require an increase in drug dosing. However, considerable uncertainty remains about the alleged useful role of natriuretic peptide-guided therapy in this context. Therefore, we decided to execute a meta-analysis of published randomized controlled trials (RCTs) to test the hypothesis that an improvement of clinical outcomes in outpatients with CHF may be achieved by adjustment of pharmacologic dosing performed according to natriuretic peptide determinations. METHODS: The relevant studies were collected through a search across the PubMed database (January 1996 to September 2012). For our meta-analysis, parallel-group RCTs were eligible for inclusion if they met the following criteria: they enrolled patients with CHF, they randomized patients to a strategy of titrating drug therapy based on the level of a circulating natriuretic peptide (BNP or NT-proBNP) compared to a parallel control group treated according to the clinical conventional criteria, and they reported all-cause mortality. In addition, it was established that each RCT to be incorporated in the evaluation should have included more than 60 participants and its follow-up should have been longer than 90 days. The primary endpoint of the meta-analysis was all-cause mortality and hospitalization related to heart failure (combined endpoint). RESULTS: In the six pooled RCTs subjected to final meta-analysis (total of included patients = 1775), natriuretic peptide-guided therapy for outpatients with CHF was shown to be associated with a decreased risk of death and heart failure hospitalizations during follow-up (odds ratio - random effect model: 0.64; 95% confidence interval: 0.43-0.95; P = 0.026). CONCLUSION: This meta-analysis supports the hypothesis that natriuretic peptide-guided therapy is superior to symptom-guided therapy for improving clinical outcomes in CHF outpatients. However, some large RCTs failed to document significant clinical improvement in terms of mortality and morbidity using a natriuretic peptide-guided strategy; thus, any attempt to clarify this still unresolved issue by means of further basic and clinical research is recommended in the future.

Statin use for nonrheumatic calcific aortic valve stenosis: a review with meta-analysis.

AIMS: To synthesize by meta-analysis the findings of recent experimental studies focusing on possible therapeutic effectiveness of statins for nonrheumatic calcific aortic stenosis. METHODS: Observational studies and randomized controlled trials (RCTs) were selected from the Pubmed database to evaluate the hemodynamic progression of aortic stenosis in statin-treated patients compared with controls (i.e. patients with aortic stenosis taking placebo or no treatment). The endpoints were the annualized changes in one or more of the following ultrasonographic measurements: peak aortic valve jet velocity, peak aortic valve pressure gradient, mean aortic valve pressure gradient aortic valve area (AVA). For estimating the overall effect of statin therapy on each of the above-mentioned continuous variables across the considered studies, we used the weighted mean difference (WMD) as effect size measure. In addition, we calculated the odds of aortic valve replacement surgery and cardiovascular death in both statin-treated patients and controls for subsequently estimating the appropriate odds ratios. RESULTS: Nine studies were selected. A lower annualized increase in peak aortic valve jet velocity was found in statin-treated patients compared with controls (overall WMD: -0.09 m/s per year, 95% CI -0.16, -0.01 P = 0.018). Similarly, a smaller annualized increase in peak aortic valve pressure gradient was found in the statin group (overall WMD: -2.04 mmHg/year 95% CI: -3.56, -0.52, P = 0.0085). However, the overall effects in statin-treated patients on both annualized increases in mean aortic valve pressure gradient and decreases in AVA were not significantly different from those found in controls. Moreover, there was no significant difference in cardiovascular outcomes in the statin groups compared with placebo groups in each of the three analyzed RCTs and overall. CONCLUSION: Significant benefit of statin therapy in retarding hemodynamic deterioration was identified by favorable effects concerning annualized changes in peak aortic valve jet velocity and peak aortic valve pressure gradient; on the contrary, in statin-treated patients with aortic stenosis, no significant improvement was found for annualized changes in mean aortic valve pressure gradient and AVA and clinical outcomes.

Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica / ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril), e com fração de ejeção do ventrículo esquerdo (FEVE) < 50 por cento, por meio de distinção em sua dosagem de inibidor da ECA: média-baixa (< 10 mg por dia) ou dosagem "alta" (> 10 mg por dia) de enalapril ou lisinopril. A disfunção renal agravada (ARD) foi definida pelo aumento de Cr > 30 por cento com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso), diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica < 100 mmHg. RESULTADOS: Cinquenta e sete pacientes foram recrutados, dos quais 15 foram tratados com inibidor da ECA com dosagem "alta". Durante um seguimento médio de 718 dias, a ARD ocorreu em 17 pacientes (29,8 por cento). Apenas o inibidor da ECA com "alta" dosagem (RR: 12,4681 IC: 2,1614 - 71,9239 p = 0,0050) e Cr basal (RR:1,2344 IC: 1,0414 - 1,4632 p = 0,0157) foi demonstrado ser preditor da ARD. Além disso, demonstrou-se que o inibidor da ECA com dosagens "altas" não previu ARD em ICC sem diurético intravenoso e ICC com diabete. CONCLUSÃO: Na ICC de classe III da NYHA, o inibidor da ECA com "altas" dosagens e um maior Cr basal foi preditor da ARD. A nefrotoxicidade relacionada com inibidores da ECA em "altas" dosagens foi aumentada com o diurético intravenoso, ao passo que, em pacientes com ICC com diabete, aquela não foi detectada.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50 percent, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30 percent from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8 percent) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50%, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30% from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8%) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

Tumor necrosis factor-alpha and insulin-like growth factor-1 levels in patients with relapsing-remitting multiple sclerosis receiving interferon-beta1a.

To examine the effect of high-dose interferon (IFN)-beta1a [44 microg administered subcutaneously (sc) 3 times weekly (tiw)] on tumor necrosis factor-alpha (TNF-alpha) and insulin-like growth factor-1 (IGF-1) levels in patients with relapsing-remitting multiple sclerosis (RRMS), and any correlation with clinical and magnetic resonance imaging (MRI) data. Previously treatment-naive patients with RRMS and an Expanded Disability Status Scale score < or = 3.5 were enrolled. At baseline, monthly for the first 5 months, and then after 12 months of treatment with 44 microg sc tiw of IFN-beta1a, all patients underwent clinical examination, assessment of serum TNF-alpha and IGF-1 levels and baseline, 5th, and 12th months to MRI scanning. Mean TNF-alpha values decreased significantly from months 0 to 12 of the study (P = 0.003), but mean IGF-1 values showed a nonsignificant reduction (P = 0.265). Serum levels of TNF-alpha and IGF-1 were sometimes correlated throughout the study, but no significant interactions were observed between serum TNF-alpha or IGF-1 and clinical or MRI findings. A borderline significant trend toward higher basal TNF-alpha levels was found in patients who developed new T1 lesions at 12 months compared with those who did not (P = 0.057). Interferon-beta1a therapy may reduce serum TNF-alpha levels in patients with RRMS, without a clear correlation with disease activity.