Publications by authors named "Dmitry Shchekochikhin"

18 Publications

  • Page 1 of 1

Rationale and Design of the Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure Study.

ESC Heart Fail 2021 Oct 28. Epub 2021 Oct 28.

I-BioStat, Data Science Institute, Hasselt University, Diepenbeek, Belgium.

Aims: Although acute heart failure (AHF) with volume overload is treated with loop diuretics, their dosing and type of administration are mainly based upon expert opinion. A recent position paper from the Heart Failure Association (HFA) proposed a step-wise pharmacologic diuretic strategy to increase the diuretic response and to achieve rapid decongestion. However, no study has evaluated this protocol prospectively.

Methods And Results: The Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure (ENACT-HF) study is an international, multicentre, non-randomized, open-label, pragmatic study in AHF patients on chronic loop diuretic therapy, admitted to the hospital for intravenous loop diuretic therapy, aiming to enrol 500 patients. Inclusion criteria are as follows: at least one sign of volume overload (oedema, ascites, or pleural effusion), use ≥ 40 mg of furosemide or equivalent for >1 month, and a BNP > 250 ng/L or an N-terminal pro-B-type natriuretic peptide > 1000 pg/L. The study is designed in two sequential phases. During Phase 1, all centres will treat consecutive patients according to the local standard of care. In the Phase 2 of the study, all centres will implement a standardized diuretic protocol in the next cohort of consecutive patients. The protocol is based upon the recently published HFA algorithm on diuretic use and starts with intravenous administration of two times the oral home dose. It includes early assessment of diuretic response with a spot urinary sodium measurement after 2 h and urine output after 6 h. Diuretics will be tailored further based upon these measurements. The study is powered for its primary endpoint of natriuresis after 1 day and will be able to detect a 15% difference with 80% power. Secondary endpoints are natriuresis and diuresis after 2 days, change in congestion score, change in weight, in-hospital mortality, and length of hospitalization.

Conclusions: The ENACT-HF study will investigate whether a step-wise diuretic approach, based upon early assessment of urinary sodium and urine output as proposed by the HFA, is feasible and able to improve decongestion in AHF with volume overload.
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http://dx.doi.org/10.1002/ehf2.13666DOI Listing
October 2021

Scintigraphy false-positive results for cardiac amyloidosis in a patient with Danon disease.

Clin Case Rep 2021 Aug 16;9(8):e04652. Epub 2021 Aug 16.

Sechenov University Moscow Russia.

Common diagnostic approach in patients with suspected cardiac amyloidosis includes cardiac magnetic resonance imaging and scintigraphy. We report the first clinical case of false-positive results of scintigraphy in a patient with Danon disease.
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http://dx.doi.org/10.1002/ccr3.4652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365861PMC
August 2021

Circulating Extracellular miRNA Analysis in Patients with Stable CAD and Acute Coronary Syndromes.

Biomolecules 2021 06 29;11(7). Epub 2021 Jun 29.

Department of Cardiology, Functional and Ultrasound Diagnostics, Faculty of Medicine N.V. Sklifosovsky, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119146 Moscow, Russia.

Extracellular circulating microRNAs (miRNAs) are currently a focus of interest as non-invasive biomarkers of cardiovascular pathologies, including coronary artery disease (CAD) and acute coronary syndromes (ACS): myocardial infarction with and without ST-segment elevation (STEMI and NSTEMI) and unstable angina (UA). However, the current data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and methodological variances in different studies. In this work, we fulfilled the basic pre-analytical requirements provided for circulating miRNA studies for application to stable CAD and ACS research. We used quantitative PCR to determine the relative plasma levels of eight circulating miRNAs that are potentially associated with atherosclerosis. In a cohort of 136 adult clinic CAD patients and outpatient controls, we found that the plasma levels of miR-21-5p and miR-146a-5p were significantly elevated in ACS patients, and the level of miR-17-5p was decreased in ACS and stable CAD patients compared to both healthy controls and hypertensive patients without CAD. Within the ACS patient group, no differences were found in the plasma levels of these miRNAs between patients with positive and negative troponin, nor were any differences found between STEMI and NSTEMI. Our results indicate that increased plasma levels of miR-146a-5p and miR-21-5p can be considered general ACS circulating biomarkers and that lowered miR-17-5p can be considered a general biomarker of CAD.
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http://dx.doi.org/10.3390/biom11070962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301961PMC
June 2021

Noninvasive Assessment of the Fractional Flow Reserve with the CT FFRc 1D Method: Final Results of a Pilot Study.

Glob Heart 2021 01 4;16(1). Epub 2021 Jan 4.

Department of Cardiology, Functional and Ultrasound Diagnostics of N.V. Sklifosovsky Institute for Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, RU.

Background: Until recently, Russia did not utilize noninvasive fractional flow reserve (FFR) assessment. We developed an automated algorithm for noninvasive assessment of FFR based on a one-dimensional (1D) mathematical modeling.

Objective: The research aims to evaluate the diagnostic accuracy of this algorithm.

Methods: The study enrolled 80 patients: 16 of them underwent 64-slice computed tomography - included retrospectively, 64 - prospectively, with a 640-slice CT scan. Specialists processed CT images and evaluated noninvasive FFR. Ischemia was confirmed if FFR < 0.80 and disproved if FFR ≥ 0.80. The prospective group of patients was hospitalized for invasive FFR assessment as a reference standard. If ischemic, patients underwent stent implantation. In the retrospective group, patients already had invasive FFR values.Statistical analysis was performed using GraphPad Prism 8. We compared two methods using a Bland-Altman plot and per-vessel ROC curve analysis. Considering the abnormality of distribution by the Kolmogorov-Smirnov test, we have used Spearman's rank correlation coefficient.

Results: During data processing, three patients of the retrospective and 46 patients of the prospective group were excluded. The sensitivity of our method was 66.67% (95% CI: 46.71-82.03); the specificity was 78.95% (95% CI: 56.67-91.49), p = 0.0052, in the per-vessel analysis. In per-patient analysis, the sensitivity was 69.57% (95% CI: 49.13-84.40); the specificity was 87.50% (95% CI: 52.91-99.36), p = 0.0109. The area under the ROC curve in the per-vessel analysis was 77.52% (95% CI: 66.97-88.08), p < 0.0001.

Conclusion: The obtained indices of sensitivity, specificity, PPV, and NPV are, in general, comparable to those in other studies. Moreover, the noninvasive values of FFR yielded a high correlation coefficient with the invasive values. However, the AUC was not high enough, 77.52 (95% CI: 66.97-88.08), p < 0.0001. The discrepancy is probably attributed to the initial data heterogeneity and low statistical power.
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http://dx.doi.org/10.5334/gh.837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792469PMC
January 2021

Elevated Plasma Levels of Circulating Extracellular miR-320a-3p in Patients with Paroxysmal Atrial Fibrillation.

Int J Mol Sci 2020 May 15;21(10). Epub 2020 May 15.

Department of Cardiology, Functional and Ultrasound Diagnostics, Faculty of Medicine N.V. Sklifosovsky, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119146 Moscow, Russia.

The potential of extracellular circulating microRNAs (miRNAs) as non-invasive biomarkers of atrial fibrillation (AF) has been confirmed by a number of recent studies. However, the current data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and methodological differences. In this work, we attempted to fulfill the basic pre-analytical requirements provided for circulating miRNA studies for application to paroxysmal atrial fibrillation (PAF) research. We used quantitative PCR (qPCR) to determine the relative plasma levels of circulating miRNAs expressed in the heart or associated with atrial remodeling or fibrillation with reported altered plasma/serum levels in AF: miR-146a-5p, miR-150-5p, miR-19a-3p, miR-21-5p, miR-29b-3p, miR-320a-3p, miR-328-3p, miR-375-3p, and miR-409-3p. First, in a cohort of 90 adult outpatient clinic patients, we found that the plasma level of miR-320a-3p was elevated in PAF patients compared to healthy controls and hypertensive patients without AF. We further analyzed the impact of medication therapies on miRNA relative levels and found elevated miR-320a-3p levels in patients receiving angiotensin-converting-enzyme inhibitors (ACEI) therapy. Additionally, we found that miR-320a-3p, miR-21-5p, and miR-146a-5p plasma levels positively correlated with the CHADS-Vasc score and were elevated in subjects with CHADS-Vasc ≥ 2. Our results indicate that, amongst the analyzed miRNAs, miR-320a-3p may be considered as a potential PAF circulating plasma biomarker, leading to speculation as to whether this miRNA is a marker of platelet state change due to ACEI therapy.
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http://dx.doi.org/10.3390/ijms21103485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279020PMC
May 2020

Evaluation of discriminative capacity of two formulas of CKD-EPI to predict complications after the first episode of heart failure with preserved ejection fraction.

Int J Nephrol Renovasc Dis 2019 7;12:113-118. Epub 2019 May 7.

Department of Preventive and Emergency Cardiology of the Faculty of Medicine, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia.

Determining the prognosis of heart failure with preserved ejection fraction (HFpEF) is problematic, as the ejection fraction cannot be used. Formulae that estimate glomerular filtration rate (eGFR) may be potential prognosticators for this condition, since renal dysfunction is a well-known predictor of poor outcomes of all forms of heart failure. A prospective observational study of 117 HFpEF patients (average age 71.6±9.1 years; 65.8% women) who had eGFR determined after their first episode of cardiac decompensation by two different chronic kidney disease epidemiology collaboration (CKD-EPI) equations. The ability to predict hospitalizations and mortality over 24 months by the two equations were compared. The CKD-EPI formula based on serum creatinine only performed poorly. However, the CKD-EPI equation that used both serum creatinine and serum cystatin C was associated with unfavorable outcome: eGFR <45 mL/min/1.73 m predicted 24-month mortality (HR=4.21 [1.32;13.43], =0.02) and the combined endpoint of mortality and hospitalization (HR 2.45 [1.42;4.22], =0.001). . eGFR by the CKD-EPI equation based on serum creatinine and cystatin C levels, but not by the CKD-EPI creatinine only equation, predicts the outcome of HFpEF patients.
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http://dx.doi.org/10.2147/IJNRD.S196976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511616PMC
May 2019

Low aquaporin-2 excretion in the nephrotic syndrome: an escape from the vasopressin regulating effect.

Int J Nephrol Renovasc Dis 2018 17;11:271-277. Epub 2018 Oct 17.

Sechenov First Moscow State Medical University, Moscow, Russia,

Purpose: Experimental studies suggest that the nephrotic syndrome is associated with "vasopressin escape", characterized by low aquaporin-2 (AQP2) expression in the collecting duct despite high vasopressin secretion. We investigated this phenomenon in patients with the nephrotic syndrome.

Patients And Methods: We recruited 47 patients with proteinuric kidney disease who were distributed into the following four groups: 1) nephrotic syndrome with kidney dysfunction (n=10); 2) nephrotic syndrome with normal kidney function (n=16); 3) partial remission of nephrotic syndrome (n=10); and 4) minimal proteinuria (n=11). Nine healthy volunteers comprised a control group. Serum copeptin level (as a marker of vasopressin secretion) and urinary AQP2 were measured using ELISA.

Results: Nephrotic syndrome was associated with a significant increase in serum copeptin levels compared with those in the other groups (all <0.05). In patients with nephrotic syndrome and a partial remission of nephrotic syndrome combined, there was more than a ten-fold decrease in the median urinary AQP2 excretion (0.03 ng/mL) compared with healthy volunteers (0.41 ng/mL; <0.001) and more than a five-fold decrease compared with patients with minimal proteinuria (0.21 ng/mL; <0.05). Unlike copeptin levels, the median urinary AQP2 excretion in patients with minimal proteinuria also decreased but less significantly than in those with nephrotic syndrome. There was a negative correlation between the urinary AQP2 excretion and daily proteinuria (R=-0.41; =0.005).

Conclusion: Our clinical study was the first to demonstrate low AQP2 excretion in nephrotic syndrome that may indicate an escape from the vasopressin regulating effect.
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http://dx.doi.org/10.2147/IJNRD.S177469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198888PMC
October 2018

One-Dimensional Mathematical Model-Based Automated Assessment of Fractional Flow Reserve in a Patient with Silent Myocardial Ischemia.

Am J Case Rep 2018 Jun 20;19:724-728. Epub 2018 Jun 20.

Department of Preventive and Emergency Cardiology, Faculty of Medicine, Sechenov University, Moscow, Russian Federation.

BACKGROUND Noninvasive assessment of the fractional flow reserve (FFR) in patients with coronary artery disease plays an important role in determining the need for revascularization. It is particularly relevant for patients with a borderline stenoses and painless myocardial ischemia. Our article describes the first clinical experience in the Russian Federation of using an automated method of noninvasive assessment of the fractional flow reserve (FFRct) with a one-dimensional (1-D) mathematical model in a patient with painless myocardial ischemia. CASE REPORT A 58-year-old male patient who underwent stent implantation in the left circumflex coronary artery (LCX) due to an acute non-ST-elevation posterior myocardial infarction had borderline stenoses of the left anterior descending artery (LAD). After stent implantation, there were no relapse angina symptoms on drug treatment, and according to our examination guideline for patients with borderline stenoses, a treadmill test was performed. The test was positive; therefore, FFR assessment was recommended, with coronary multi-slice CT being performed. The following results were obtained: FFRct LAD - 0.57; FFRct LCX - 0.88. An invasive assessment of FFR was also performed as a reference standard and revealed: FFR LAD - 0.6; FFR LCX - 0.88, and simultaneously a LAD percutaneous coronary intervention (PCI) was performed. Three months later, the patient underwent a stress test, which revealed no evidence of induced ischemia. CONCLUSIONS Our method of noninvasive assessment of FFR has shown encouraging results, but we believe that larger-scale studies are needed to establish it as common clinical practice.
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http://dx.doi.org/10.12659/AJCR.908449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042470PMC
June 2018

Hormones and hemodynamics in pregnancy.

Int J Endocrinol Metab 2014 Apr 1;12(2):e14098. Epub 2014 Apr 1.

Division of Renal Diseases and Hypertension, University of Colorado Denver, Denver, Colorado, USA.

Context: Normal pregnancy is associated with sodium and water retention, which results in plasma volume expansion prior to placental implantation. The explanation offered for these events is that pregnancy 'resets' both volume and osmoreceptors.

Evidence Acquisition: The mechanisms for such an enigmatic 'resetting' in pregnancy have not previously been explained. However, recent human pregnancy studies have demonstrated that the earliest hemodynamic change in pregnancy is primary systemic arterial vasodilation. This arterial underfilling is associated with a secondary increase in cardiac output and activation of the neurohumoral axis, including stimulation of the renin-angiotensin-aldosterone, sympathetic, and non-osmotic vasopressin systems. Resistance to the pressor effects of angiotensin and sympathetic stimulation in pregnancy is compatible with an increase in endothelial nitric oxide synthase activity.

Results: In contrast to the sodium and water retention which occur secondary to the primary arterial vasodilation in cirrhosis, glomerular filtration and renal blood flow are significantly increased in normal pregnancy. A possible explanation for this difference in arterial vasodilation states is that relaxin, an arterial vasodilator which increases during pregnancy, has a potent effect on both systemic and renal circulation. Endothelial damage in pregnancy is pivotal in the pathogenesis of preeclampsia in pregnancy.

Conclusions: Against a background of the primary arterial vasodilation hypothesis, it is obvious that reversal of the systemic vasodilatation in pregnancy, without subsequent activation of the renin-angiotensin-aldosterone system (78), will evoke a reversal of all the links in the chain of events in normal pregnancy adaptation, thus, it may cause preeclampsia. Namely, a decrease of renal vasodilation will decrease glomerular filtration rate.
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http://dx.doi.org/10.5812/ijem.14098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4005978PMC
April 2014

Role of diuretics and ultrafiltration in congestive heart failure.

Pharmaceuticals (Basel) 2013 Jul 4;6(7):851-66. Epub 2013 Jul 4.

University of Colorado Division of Renal Diseases and Hypertension, 12700 East 19th Avenue, C281, Aurora, CO 80045, USA.

Volume overload in heart failure (HF) results from neurohumoral activation causing renal sodium and water retention secondary to arterial underfilling. Volume overload not only causes signs and symptoms of congestion, but can impact myocardial remodeling and HF progression. Thus, treating congestion is a cornerstone of HF management. Loop diuretics are the most commonly used drugs in this setting. However, up to 30% of the patients with decompensated HF present with loop-diuretic resistance. A universally accepted definition of loop diuretic resistance, however, is lacking. Several approaches to treat diuretic-resistant HF are available, including addition of distal acting thiazide diuretics, natriuretic doses of mineralocorticoid receptor antagonists (MRAs), or vasoactive drugs. Slow continuous veno-venous ultrafiltration is another option. Ultrafiltration, if it is started early in the course of HF decompensation, may result in prominent decongestion and a reduction in re-hospitalization. On the other hand, ultrafiltration in HF patients with worsening renal function and volume overload after aggressive treatment with loop diuretics, failed to show benefit compared to a stepwise pharmacological approach, including diuretics and vasoactive drugs. Early detection of congested HF patients for ultrafiltration treatment might improve decongestion and reduce readmission. However, the best patient characteristics and best timing of ultrafiltration requires further evaluation in randomized controlled studies.
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http://dx.doi.org/10.3390/ph6070851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3816706PMC
July 2013

The nephrotic syndrome: pathogenesis and treatment of edema formation and secondary complications.

Pediatr Nephrol 2014 Jul 30;29(7):1159-67. Epub 2013 Aug 30.

Children's Hospital Colorado/University of Colorado, Anschutz Medical Campus, 13123 East 16th Avenue, Box B328, Aurora, CO, 80045, USA,

Nephrotic syndrome is an important clinical condition affecting both children and adults. Studies suggest that the pathogenesis of edema in individual patients may occur via widely variable mechanisms, i.e., intravascular volume underfilling versus overfilling. Managing edema should therefore be directed to the underlying pathophysiology. Nephrotic syndrome is also associated with clinically important complications related to urinary loss of proteins other than albumin. This educational review focuses on the pathophysiology and management of edema and secondary complications in patients with nephrotic syndrome.
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http://dx.doi.org/10.1007/s00467-013-2567-8DOI Listing
July 2014

Renin-Angiotensin-aldosterone system in autosomal dominant polycystic kidney disease.

Curr Hypertens Rev 2013 Feb;9(1):12-20

Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO 80045, USA.

Autosomal dominant polycystic kidney disease is the most frequent life-threatening hereditary disease. Prognostic factors for progressive renal impairment have been identified such as gender, race, age, proteinuria, hematuria, hypertension. Hypertension is the only risk factor for renal dysfunction in autosomal dominant polycystic kidney disease, which is presently treatable. Better understanding of the pathophysiology of hypertension will help in defining appropriate interventions. The renin-angiotensin-aldosterone-system is the pivotal factor in the pathogenesis of hypertension in autosomal dominant polycystic kidney disease. Basic research and clinical studies in autosomal dominant polycystic kidney disease implicated activation of the renin-angiotensin-aldosterone-system. Therapy of hypertension in autosomal dominant polycystic kidney disease with angiotensin-converting enzyme inhibitors or angiotensin receptor blocker has the potential to prevent cardiovascular complications and slow the progression of renal disease. The results of two large multicenter double-blind placebo controlled randomized clinical trials (the HALT-PKD trials) possibly will elucidate the beneficial effects of the renin-angiotensin-aldosterone-system inhibition in autosomal dominant polycystic kidney disease.
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http://dx.doi.org/10.2174/1573402111309010003DOI Listing
February 2013

Increased Spironolactone in Advanced Heart Failure: Effect of Doses Greater than 25 mg/Day on Plasma Potassium Concentration.

Cardiorenal Med 2013 Apr 30;3(1):1-6. Epub 2013 Jan 30.

Background: Daily doses of spironolactone higher than 25 mg are rarely used in heart failure (HF) patients, presumably due to the concern for hyperkalemia. However, in advanced HF, doses ≥50 mg have been found to be necessary to produce natriuresis. The aim of the present study was to examine the safety of natriuretic doses of spironolactone (50-200 mg) on serum potassium concentration in New York Heart Association (NYHA) class III/IV HF patients over several weeks.

Methods: 18 patients with advanced HF received 50-200 mg of spironolactone in addition to standard treatment. Serum electrolytes, BUN and serum creatinine were assessed at baseline, during increased doses of spironolactone and at the 1-month follow-up.

Results: During a total of 738 patient-weeks, there was no significant increase in mean serum potassium (4.0 vs. 4.2 mEq/l) or serum creatinine (1.3 vs. 1.4 mg/dl). However, in 3 patients, spironolactone treatment was stopped due to a mean increase in serum creatinine (1.9 vs. 2.6 mg/dl) and in one of them, an increase in serum potassium (4.4 vs. 5.2 mEq/l) was noted.

Conclusion: Increased doses of spironolactone are generally safe during outpatient follow-up in selected patients with advanced HF, who are receiving treatment with ACE inhibitors, beta-blockers, and loop diuretics.
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http://dx.doi.org/10.1159/000346447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678142PMC
April 2013

Cardiorenal syndrome: pathophysiology and treatment.

Curr Cardiol Rep 2013 Jul;15(7):380

Department of Preventive and Emergency Cardiology, I.M.Setchenov's First Moscow State Medical University, 119992, 6 (1), Bolshaya Pirogovskaya str., Moscow, Russia.

CRS is a common problem in patients with advanced heart failure. Arterial underfilling with consequent neurohormonal activation, systemic and intrarenal vasoconstriction, and salt and water retention cause the main clinical features of CRS which include a progressive decline in renal function, worsening renal function during treatment of heart failure (HF) decompensation and resistance to loop diuretics. Impaired renal function in HF patients often reflects more advanced stages of cardiac failure, and thus is associated with a worse prognosis. However, a transient fall in glomerular filtration rate may be a result of successful treatment of congestion, and thereby might not be associated with decreased survival in HF patients. This review covers basic pathophysiological mechanisms underlying the CRS and current trends in practical approaches to treat these patients.
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http://dx.doi.org/10.1007/s11886-013-0380-4DOI Listing
July 2013

Outcome differences in community- versus hospital-acquired hyponatremia in patients with a diagnosis of heart failure.

Circ Heart Fail 2013 May 19;6(3):379-86. Epub 2013 Mar 19.

Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO 80045, USA.

Background: Hyponatremia at hospital admission is a well-known risk factor of morbidity and mortality in patients with heart failure (HF). However, there are few data about hyponatremia developing during hospitalization in patients with HF. The present study compares hospital-acquired hyponatremia (HAH) with community-acquired hyponatremia (CAH) in HF patients with respect to outcome.

Methods And Results: A total of 5347 consecutive hospitalized patients with a diagnosis of HF were analyzed. CAH was defined as a serum sodium value of ≤135 mEq/L at the time of hospital admission. HAH was defined as development of a serum sodium level of ≤135 mEq/L during hospitalization in the setting of a serum sodium value >135 mEq/L on admission. In-hospital mortality, length of stay, worsening kidney function, and discharge to short-/long-term care facilities were analyzed. CAH and HAH were identified in 1039 patients (19.4%) and in 1302 patients (24.4%) of the 5347 patients admitted, respectively. Both types of hyponatremia were associated with increased mortality, length of stay, rate of discharge to short-/long-term care facilities, and worsening kidney function. In-hospital mortality did not differ between CAH and HAH, but differences in demographics and comorbidities were present.

Conclusions: The present results identified HAH as a risk factor for increased mortality in HF as has been previously described for CAH. HAH was associated with increased length of stay, discharge to short-/long-term care facilities, and development of cardio-renal failure. Thus, hyponatremia in hospitalized patients with a diagnosis of HF, either on admission or during hospitalization, is a prognostic marker for poor outcomes.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.112.000106DOI Listing
May 2013

Hyponatremia: an update on current pharmacotherapy.

Expert Opin Pharmacother 2013 Apr;14(6):747-55

University of Colorado, School of Medicine, 12700 East 19th Ave C281, Aurora, CO 80045, USA.

Introduction: Hyponatremia is the most common electrolyte disorder in clinical practice, and it is associated with adverse outcomes. Severe hyponatremia can result in cerebral edema and hypoxia. Moreover, even mild hyponatremia can lead to gait instability and cognitive dysfunction, especially in the elderly. The main cause of hyponatremia is nonosmotic secretion of arginine vasopressin with resultant electrolyte-free water retention. Thus, the available management for chronic hyponatremia must increase solute-free water excretion, such as occurs with blocking vasopressin receptors with selective V2 antagonists.

Areas Covered: Several recent trials have assessed the efficacy and safety of hyponatremia treatment using vasopressin receptor antagonists (vaptans). These trials documented the efficacy of vaptans to reverse hyponatremia. Moreover, treatment of hypervolemic hyponatremia, such as in heart failure or liver cirrhosis, with vasopressin receptor antagonist results in increased solute-free excretion without activation of the neurohumoral systems. The current review covers results on management of hyponatremia with different vasopressin receptor antagonists.

Expert Opinion: Approaches, such as vasopressin receptor antagonists or urea, have been shown to reverse moderate hyponatremia. However, these agents have not been used to treat severe hyponatremia in clinical trials. Future studies in severe hyponatremic states are required to assess the impact of vaptans on clinically significant end points, such as morbidity and mortality.
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http://dx.doi.org/10.1517/14656566.2013.781584DOI Listing
April 2013

Hyponatraemia: more than just a marker of disease severity?

Nat Rev Nephrol 2013 Jan 20;9(1):37-50. Epub 2012 Nov 20.

University of Colorado School of Medicine, 12700 East 19th Avenue C281, Aurora, CO 80045, USA.

Hyponatraemia--the most common serum electrolyte disorder--has also emerged as an important marker of the severity and prognosis of important diseases such as heart failure and cirrhosis. Acute hyponatraemia can cause severe encephalopathy, but the rapid correction of chronic hyponatraemia can also profoundly impair brain function and even cause death. With the expanding elderly population and the increased prevalence of hyponatraemia in this segment of society, prospective studies are needed to examine whether correcting hyponatraemia in the elderly will diminish cognitive impairment, improve balance and reduce the incidence of falls and fractures. Given that polypharmacy is also common in the elderly population, the various medications that may stimulate arginine vasopressin release and/or enhance the hormone's action to increase water absorption must also be taken into consideration. Whether hyponatraemia in a patient with cancer is merely a marker of poor prognosis or whether its presence may alter the patient's quality of life remains to be examined. In any case, hyponatraemia can no longer be considered as just a biochemical bystander in the ill patient. A systematic diagnostic approach is necessary to determine the specific aetiology of a patient's hyponatraemia. Therapy must then be dictated not only by recognized reversible causes such as advanced hypothyroidism, adrenal insufficiency, diuretics or other medicines, but also by whether the hyponatraemia occurred acutely or chronically. Information is emerging that the vast majority of cases of hyponatraemia are caused by the nonosmotic release of arginine vasopressin. Now that vasopressin V2-receptor blockers are available, a new era of clinical investigation is necessary to examine whether hyponatraemia is just a marker of severe disease or whether correction of hyponatraemia could improve a patient's quality of life. Such an approach must involve prospective randomized studies in different groups of patients with hyponatraemia, including those with advanced heart failure, those with cirrhosis, patients with cancer, and the elderly.
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http://dx.doi.org/10.1038/nrneph.2012.246DOI Listing
January 2013

What have we learned about loop diuretics in acute decompensated heart failure? The DOSE trial.

Curr Cardiol Rep 2012 Jun;14(3):251-3

Department of Preventive and Emergency Cardiology, Setchenov First Moscow State Medical University, 8 (2) Trubetskaya str., Moscow, Russia.

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http://dx.doi.org/10.1007/s11886-012-0254-1DOI Listing
June 2012
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