Moderate Congestive Heart Failure Research Articles

Serum untargeted metabolomics analysis of mice after myocardial infarction affected by qiliqiangxin capsule

Qiliqiangxin (QLQX) capsule consists of 11 herbs, namely Huang qi (astragalus membranaceus), Ren shen (ginseng), Fu zi (radix aconiti carmichaeli), Dan shen (salvia miltiorrhiza), Ting li zi (lepidium seed), Ze xie (rhizoma alismatis), Yu zhu (radix polygonati officinalis), Gui zhi (cassia twig), Hong hua (carthamus tinctorious), Xiang jia Pi (cortex periplocae), Chen Pi (pericarpium citri reticulatae), and it is a standardized commercial formula designed to address yang deficiency and to restore the balance of qi in the heart. QLQX is also known to invigorate the blood and promote the circulation of the blood and to promote the use of fluids to relieve water retention and edema, and can be used in cardiovascular diseases such as mild to moderate congestive heart failure resulting from coronary artery disease and hypertension. The further research on the effect of QLQX on cardiac function in mice after myocardial infarction was manipulated. QLQX was given to mice in myocardial infarction model by gavage with appropriate dosage and the samples were analyzed at the end of the animal experiments through the UHPLC-Q-Exactive LC-MS. The liquid mass spectrometry was used to collect and followed by further analysis of the corresponding metabolites and metabolic pathways using metabolomics analysis. As a result, 9 differential metabolites were identified, with 15 being up-regulated and 4 down-regulated following intervention with QLQX. Then the metabolic pathways by KEGG enrichment pathway bubble diagram was analyzed, and 4 metabolic pathways were obtained, and combined with the metabolites that had been screened and analyzed together, finally the two differential metabolites, 2,5-Dihydroxybenzenesulfonic Acid and o-Cresol sulfate were found. The Glycerophospholipid metabolism pathway was closely related to the remaining seven differential metabolites, and the pathway might be an important pathway related to the effects of QLQX on cardiac function in mice.

Cardiac effects of deferasirox in transfusion-dependent patients with myelodysplastic syndromes: TELESTO study.

Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion-dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo-controlled, randomised study to evaluate the iron chelator deferasirox in patients with low- or intermediate-1-risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk.

Clinical efficacy of a benazepril and spironolactone combination in dogs with congestive heart failure due to myxomatous mitral valve disease: The BEnazepril Spironolactone STudy (BESST).

BackgroundThe renin‐angiotensin‐aldosterone system (RAAS), when chronically activated, is harmful and RAAS‐suppressive drugs are beneficial in the treatment of congestive heart failure (CHF). Mineralocorticoid receptor antagonists are widely used in the treatment of CHF in people.Hypothesis/ObjectivesTo determine if a mineralocorticoid receptor antagonist (spironolactone) is beneficial and safe in CHF due to myxomatous mitral valve disease (MMVD) of varying severity, we hypothesized that, when combined with furosemide, a combination product (S+BNZ) containing the ACE inhibitor (ACE‐I), benazepril, and spironolactone, would be superior to benazepril alone.AnimalsFive hundred and sixty‐nine client‐owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10‐days' duration.MethodsAfter initial stabilization, dogs were randomized into a positive‐controlled, double‐blind, multicenter trial, to receive furosemide plus S+BNZ or furosemide plus benazepril. The primary outcome variable was the percentage of dogs reaching cardiac endpoint before Day 360. Cardiac endpoint was defined as cardiac death or euthanasia, recurrence of pulmonary edema, necessity for nonauthorized cardiac drug(s) or a furosemide dosage >8 mg/kg/d.ResultsA significantly lower percentage of dogs treated with S+BNZ reached the primary outcome variable by Day 360 (OR = 0.56; 95% CI, 0.32‐0.98; P = .04) and risk of dying or worsening from cardiac causes, was significantly reduced (HR = 0.73; 95% CI = 0.59‐0.89, P = .002) vs benazepril alone. Adverse events, potentially associated with treatment, were rare and equal between groups.Conclusion and Clinical ImportanceThe combination of S+BNZ is effective, safe, and superior to benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF caused by MMVD in dogs.

Solubility enhancement of carvedilol using drug\u2013drug cocrystallization with hydrochlorothiazide

BackgroundIncreasing hydrophilicity of poorly water-soluble drugs is a major challenge in drug discovery and development. Cocrystallization is one of the techniques to enhance the hydrophilicity of such drugs. Carvedilol (CAR), a nonselective beta/alpha1 blocker, used in the treatment of mild to moderate congestive heart failure and hypertension, is classified under BCS class II with poor aqueous solubility and high permeability. Present work is an attempt to improve the solubility of CAR by preparing cocrystals using hydrochlorothiazide (HCT), a diuretic drug, as coformer. CAR-HCT (2:0.5) cocrystals were prepared by slurry conversion method and were characterized by DSC, PXRD, FTIR, Raman, and SEM analysis. The solubility, stability, and dissolution (in vitro) studies were conducted for the cocrystals.ResultsThe formation of CAR-HCT cocrystals was confirmed based on melting point, DSC thermograms, PXRD data, FTIR and Raman spectra, and finally by SEM micrographs. The solubility of the prepared cocrystals was significantly enhanced (7.3 times), and the dissolution (in vitro) was improved by 2.7 times as compared to pure drug CAR. Further, these cocrystals were also found to be stable for 3 months (90 days).ConclusionIt may be inferred that the drug–drug (CAR-HCT) cocrystallization enhances the solubility and dissolution rate of carvedilol significantly. Further, by combining HCT as coformer could well be beneficial pharmacologically too.

TAKOTSUBO CARDIOMYOPATHY SECONDARY TO ACUTE BACTERIAL MENINGITIS

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Infection and sepsis are not uncommon causes of cardiomyopathy due to a decrease in ventricular function. Cardiovascular dysfunction in sepsis can be seen as septic cardiomyopathy, Takotsubo cardiomyopathy, refractory shock or myocardial injury. A study showed that Takotsubo cardiomyopathy was present in 0.15% of admissions with severe sepsis. It should be considered in the differential diagnosis of acute coronary syndrome especially post-menopausal women with preceding stressful events. We present a case of bacterial meningitis leading to Takotsubo’s cardiomyopathy in the setting of CSF leak. CASE PRESENTATION: A 67-year-old woman with no past medical history presented to the emergency department with diarrhea, vomiting, and confusion. On arrival, she was hypotensive to 87/66mmHg, tachycardic 116bpm and hypoxic to 83% on room air. Laboratory evaluation was significant for leukocytosis of 29.2 k/ul, troponin 5.02 ng/ml, lactic acid 2.9 mmol/l, BNP 788 pg/ml. Cerebrospinal fluid showed a white blood cell count of 5011 (91% neutrophils), protein 791 mg/dl, glucose 95 mg/dl. She was admitted with a diagnosis of an NSTEMI, acute meningeal encephalitis and treated with aztreonam, vancomycin, doxycycline, and dexamethasone. Cultures revealed streptococcus viridians and treatment was narrowed to ceftriaxone. Facial CT showed a possible area of dehiscence concern for possible CSF leak. No significant coronary artery disease on the angiogram Echocardiogram was consistent with Takotsubo cardiomyopathy. The patient's cardiomyopathy was treated with goal-directed medical therapy with complete resolution of symptoms. DISCUSSION: Takotsubo cardiomyopathy is defined as a transient regional left ventricular systolic dysfunction without obstructive coronary artery disease and usually triggered by emotional or physical stress. During sepsis, there is an activation of the sympathoadrenergic system with rapid elevation in circulating catecholamine levels. Pathogenesis is related to myocardial stunning, catecholamine toxicity, impaired myocyte metabolism. According to Mayo Clinic criteria there should be: 1) transient hypokinetic, akinesias or dyskinesia of the LV midsegments, 2) absence of CAD, 3) EKG abnormalities or troponin elevation, 4) absence of pheochromocytoma or myocarditis. Patients can present with mild to moderate congestive heart failure or hypotension due to a reduction in stroke volume. The mean age of presentation ranges from around 60 to 75 years. The prognosis is excellent, mortality from 0%-8% and a recurrence occurs in <10% of patients. The treatment is based on the management of the underlying etiology and supportive cardiovascular care. CONCLUSIONS: Patients with suspected TTC need to be work up to rule out ACS with coronary angiogram. Takotsubo’s cardiomyopathy has a good prognosis with recovery on the EF and cardiac function once infection or physical stress disappears. Reference #1: De Giorgi, A., Fabbian, F., Pala, M., Parisi, C., Misurati, E., Molino, C., et al. (2015). Takotsubo Cardiomyopathy and Acute Infectious Diseases: A Mini-Review of Case Reports. Angiology, 66(3), 257–261. Reference #2: Pilgrim, TM, Wyss, TR. Takotsubo cardiomyopathy or transient left ventricular apical ballooning syndrome: a systematic review. Int J Cardiol. 2008;124(3):283–292. Reference #3: Prasad, A, Lerman, A, Rihal, CS. Apical ballooning syndrome (tako-tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. 2008;155(3):408–417. DISCLOSURES: No relevant relationships by Daniel Colon Hidalgo, source=Web Response No relevant relationships by Diana Estefania Espinoza Barrera, source=Web Response No relevant relationships by Hugues Orozco, source=Web Response No relevant relationships by Jose Zabala-Genovez, source=Web Response

In-situ Intestinal Absorption and Pharmacokinetic Investigations of Carvedilol Loaded Supersaturated Self-emulsifying Drug System.

Carvedilol (CD), a non-selective beta-blocker, is indicated for the management of mild to moderate congestive heart failure. After oral administration, CD is rapidly absorbed with an absolute bioavailability of 18-25% because of low solubility and extensive first-pass metabolism. The present investigation focused on enhanced oral delivery of CD using supersaturated self-emulsifying drug delivery (SEDDS) system. Optimized SEDDS consisted of a blend of Oleic acid and Labrafil-M2125 as an oil-phase, Cremophor-RH40, polyethylene glycol-400 and HPMC-E5 as a surfactant, co-surfactant and supersaturation promoter respectively. Formulations were characterized for physical characteristics, invitro release in simulated and biorelevant dissolution media, intestinal permeability and bioavailability studies in Wistar rats. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized formulation. DSC and XRD, SEM studies showed that the drug was in amorphous form, and droplets were spherical in shape. Dissolution studies clearly showed distinct CD release in compendial and biorelevant dissolution media. The results from permeability and in-vivo studies depicted 2.2-folds and 3.2-folds increase in permeability and bioavailability, respectively from supersaturated SEDDS in comparison with control. The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral supply of CD. Lay Summary: Carvedilol (CD) is a non-selective antihypertensive drug with poor oral bioavailability. Previously, various lipid delivery systems were reported with enhanced oral delivery. We developed suprsaturable SEDDS formulation with immediate onset of action. SEDDS formulation was developed and optimized as per the established protocols. The optimized SEDDS formulation was stable over three months and converted to solid and supersaturated SEDDS. The results from permeability and in-vivo studies demonstrated an enhancement in permeability and bioavailability from supersaturated SEDDS in comparison with control. The results conclusively confirmed that the SEDDS formulation could be considered as a new alternative delivery vehicle for the oral administration of CD.

Predictors of in-hospital adverse events after endovascular aortic aneurysm repair

BackgroundEndovascular aneurysm repair (EVAR) offered outstanding survival benefit but at the expense of cost, periodic radiographic monitoring, and higher reinterventions rates. Perioperative complications, although rare, can occur after EVAR, contributing to longer hospitalization, higher cost, and significant comorbidity and mortality. Therefore, the aim of this study was to identify the predictors of in-hospital events (IHEs) after elective EVAR. MethodsThe Vascular Quality Initiative database was explored from 2003 to 2017. Patients who had converted to open repair were excluded. IHEs were defined as any in-hospital myocardial infarction, dysrhythmia, congestive heart failure (CHF), stroke, pneumonia, respiratory failure, renal failure, lower extremity ischemia, bowel ischemia, or reoperation. Stepwise backward selection based on the Akaike information criterion statistic was implemented to select the predictors of IHE from the multivariable logistic regression models. Bootstrapping was performed with 1000 replications to internally validate the model and to obtain bias-corrected estimates. Receiver operating characteristic curves (area under the curve [AUC]) and Hosmer-Lemeshow tests were used to assess the discrimination and calibration of the models. ResultsA total of 28,240 patients with full information about IHEs were included. Any IHE took place in 2365 (8.4%) patients. Patients who had an IHE were slightly older (mean age ± standard deviation, 75.6 ± 8.1 years vs 73.3 ± 8.5 years; P < .001]. A higher proportion of women had an IHE (25.6% vs 17.9%; P < .001). Comorbid conditions were more prevalent in patients who developed an IHE (chronic kidney disease, 49.1% vs 33.2%; coronary artery disease, 34.3% vs 29.0%; moderate to severe CHF, 3.9% vs 1.4%; chronic obstructive pulmonary disease, 42.5% vs 31.9%; hypertension, 87.0% vs 83.1%; and diabetes, 18.0% vs 16.1%; all P ≤ .015). An IHE was associated with high in-hospital (5.6% vs 0.03%) and 30-day mortality (6.3% vs 0.3%; both P < .001) and worse 3-year survival beyond the perioperative period (81.1% [79.3%-82.9%] vs 91.1% [90.7%-91.5%]; P < .001). Two models were constructed, one from preoperative factors and the second from preoperative and intraoperative factors. The selected predictors of IHEs were female sex, moderate or severe CHF, chronic kidney disease, coronary artery disease, chronic obstructive pulmonary disease, hypertension, and aneurysm diameter. Intraoperative factors were contrast material volume, operative time, and packed red blood cell transfusion. Nomograms were constructed from the final models. AUC significantly improved after adding intraoperative factors (AUC [95% confidence interval], 0.71 [0.70-0.73] vs 0.65 [0.64-0.66]; P < .001]. ConclusionsIn-hospital adverse events can complicate the perioperative course of EVAR and increase the risk of operative and long-term mortality. Predicting IHEs and identifying their risk factors can potentially mitigate their development in patients at high risk. Predicting IHE risk can have tremendous prognostic value and help disposition planning. This study introduces an internally validated tool to enable vascular surgeons to identify patients' chance of having an IHE.

DEVELOPMENT AND EVALUATION OF NANOEMULSION FORMULATIONS FOR IMPROVED ORAL DELIVERY OF CARVEDILOL

Objective: The aim of the present investigation was to develop, optimize and evaluate nanoemulsion system of carvedilol to improve its solubility, and oral bioavailability. Carvedilol is a non-selective beta blocker used in the treatment of mild to moderate congestive heart failure and mild to moderate essential hypertension. It has both poor water solubility (0.583 mg/L) and oral bioavailability (23%) because of significant first-pass hepatic metabolism. Methods: Based on solubility testing, clove oil was used as oil, tween 20 was used as surfactants and PEG 400 was used as cosurfactants in construction of phase diagrams. Carvedilol nanoemulsions were prepared by aqueous phase titration method. Out of twelve formulations, eight thermodynamically stable formulations were selected for preparation of carvedilol loaded nanoemulsions and these nanoemulsions were subjected for characterization i.e. particle size, viscosity, polydispersity, zeta potential. A 12 hrs in-vitro release release study was performed on selected nanoemulsion formulations of carvedilol. Results: The results of viscosity of carvedilol nanoemulsions were found to be in range (60.42 –134.63 m Pa.sec.). The results of pH measurement for formulations explain that the pH values of drug free nanoemulsions were slightly acidic. All formulations have PDI value less than (1.0). Conclusion: Study concludes, nanoemulsion formulation of batch NEC4 (Smix ratio 1:3) was found to be optimum formulation. Peer Review History: Received 8 January 2017; Revised 30 February; Accepted 28 February, Available online 15 March 2017 Academic Editor: Ahmad Najib, Universitas Muslim Indonesia, Indonesia, ahmad.najib@umi.ac.id Received file: Reviewer's Comments: Average Peer review marks at initial stage: 3.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, sally.elzahaby@yahoo.com Dr. Maha Khalifa Ahmed Khalifa, Al-Azhar Universit - Cairo, Egypt, mahakhalifa.ahmed@hotmail.com Similar Articles: FORMULATION AND CHARACTERIZATION OF TOPICAL NANO EMULGEL OF TERBINAFINE

Clinical Outcomes of Metformin Use in Populations With Chronic Kidney Disease, Congestive Heart Failure, or Chronic Liver Disease: A Systematic Review.

Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment. MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. 2 reviewers abstracted data and independently rated study quality and strength of evidence. On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF. Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key clinical outcomes. Our findings support the recent changes in metformin labeling. U.S. Department of Veterans Affairs. (PROSPERO: CRD42016027708).

Correlation of serum cardiac troponin I and acute phase protein concentrations with clinical staging in dogs with degenerative mitral valve disease.

Cardiac troponin I (cTnI) correlates with severity of myocardial injury. Nonspecific inflammation in congestive heart failure (CHF) could be assessed by C-reactive protein (CRP), haptoglobin (Hp), and ceruloplasmin (Cp) measurements. The aim of the study was to determine whether serum cTnI, CRP, Hp, and Cp concentrations differ among various stages of mitral valve disease (MVD) in dogs. Dogs with MVD were allocated to 3 groups (I - asymptomatic; II - mild to moderate CHF; III advanced CHF) according to the scheme of the International Small Animal Cardiac Healthy Council (ISACHC). Concentrations of cTnI, CRP, Cp, and Hp were measured in all dogs upon admission, and cTnI and CRP were measured bimonthly during a 4-month follow-up period. In total 46 dogs with MVD were enrolled for the cross-sectional part (21 Group I, 11 Group II, 14 Group III), and 35 dogs were included in the longitudinal study. Initial mean Cp concentrations were similar among all groups. There was a statistically significant difference in Hp and CRP concentrations between group I (n = 21, P = .019) and III (n = 14, P < .001). There was a statistically significant decrease in CRP (P = .033) and cTnI (P = .009) concentrations over the longitudinal study (all groups). CRP concentrations were significantly higher in group I than III (P = .004). During the 6-month monitoring period of 35 dogs, there was a statistically significant positive correlation between cTnI and CRP (P < .001). Differences in CRP concentrations between clinical stages of MVD suggest a clinically and therapeutically relevant inflammatory component.

Continuously adjusting CRT therapy: clinical impact of adaptive cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a well-established therapy to reduce morbidity and mortality in patients with moderate and severe symptomatic congestive heart failure. Left ventricular (LV) pacing that fuses with intrinsic right ventricular (RV) conduction results in similar or even better cardiac performance compared to biventricular (Biv) pacing. Optimal programming of the atrio-ventricular (AV) and inter-ventricular (VV) delays is crucial to improve LV performance since suboptimal programming of AV and VV delays affect LV filling as well as cardiac output. CRT optimization using echocardiogram is resource-dependent and time consuming. Adaptive CRT (aCRT) algorithm provides a dynamic, automatic, ambulatory adjustment of CRT pacing configuration (Biv or LV pacing) and optimization of AV and VV delays. aCRT algorithm is safe and efficacious for CRT-indicated patients without permanent atrial fibrillation. It has been shown to improve CRT response and reduce morbidity and mortality for patients with normal AV conduction.

The Relationship between Nocturnal Hypoxemia and Left Ventricular Ejection Fraction in Congestive Heart Failure Patients

Congestive heart failure (CHF) is a major cause of mortality and morbidity. Among patients with heart failure, sleep disordered breathing (SDB) is a common problem. Current evidence suggests that SDB, particularly central SDB, is more prevalent in patients with CHF than in the general population, but it is underdiagnosed as SDB symptoms that are less prevalent in CHF. The main aims of this study were to determine the relationship between nocturnal hypoxemia and left ventricular ejection fraction in patients with chronic heart failure. By means of echocardiography, 108 patients with left ventricular ejection fraction ≤45% were divided into mild, moderate, and severe CHF. Hypoxemia was recorded overnight in the hospital and was measured by portable pulse oximetry. In the 108 patients with CHF, 44 (40.7%) were severe, 17 (15.7%) moderate, and 47 (43.6%) mild CHF. 95 (88%) of patients with CHF had abnormal patterns of nocturnal hypoxemia suggestive of Cheyne-Stokes respiration. Ejection fraction correlated negatively with dip frequency. There was no correlation between nocturnal hypoxemia with BMI and snoring. This study confirms strong associations between sleep apnea and heart disease in patients with CHF. Overnight oximetry is a useful screening test for Cheyne-Stokes respiration in patients with known heart failure.

Treatment of Anemia in Patients With Heart Disease: A Clinical Practice Guideline From the American College of Physicians

The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the treatment of anemia and iron deficiency in adult patients with heart disease. This guideline is based on published literature in the English language on anemia and iron deficiency from 1947 to July 2012 that was identified using MEDLINE and the Cochrane Library. Literature was reassessed in April 2013, and additional studies were included. Outcomes evaluated for this guideline included mortality; hospitalization; exercise tolerance; quality of life; and cardiovascular events (defined as myocardial infarction, congestive heart failure exacerbation, arrhythmia, or cardiac death) and harms, including hypertension, venous thromboembolic events, and ischemic cerebrovascular events. The target audience for this guideline includes all clinicians, and the target patient population is anemic or iron-deficient adult patients with heart disease. This guideline grades the evidence and recommendations using the ACP's clinical practice guidelines grading system. ACP recommends using a restrictive red blood cell transfusion strategy (trigger hemoglobin threshold of 7 to 8 g/dL compared with higher hemoglobin levels) in hospitalized patients with coronary heart disease. (Grade: weak recommendation; low-quality evidence) ACP recommends against the use of erythropoiesis-stimulating agents in patients with mild to moderate anemia and congestive heart failure or coronary heart disease. (Grade: strong recommendation; moderate-quality evidence).

Congestive heart failure in rats is associated with increased collecting duct vasopressin sensitivity and vasopressin type 2 receptor reexternalization

A number of studies have shown that rats with congestive heart failure (CHF) have increased protein levels of the vasopressin (AVP)-regulated water channel aquaporin-2 (AQP2) even during conditions with unchanged circulating levels of AVP, suggesting an increase in the sensitivity of the AVP type 2 (V2) receptor in experimental CHF. The present study was aimed at investigating AVP signaling in rats with moderate CHF (left ventricular end diastolic pressure >10 mmHg; normal plasma AVP levels) induced by ligation of the left anterior descending coronary artery. Sham-operated rats were used as controls. Western blotting analyses revealed an increased abundance of AQP2 in renal cortex (+33 ± 9% of sham; P < 0.05) and in inner medulla (IM) (+54 ± 15% of sham; P < 0.05) in CHF rats compared with sham-operated controls. Dose-response studies on isolated collecting ducts (CDs) showed an increased accumulation of cAMP in response to AVP in CHF rats compared with controls. V2 receptor surface-binding studies in isolated IMCDs showed a marked and comparable AVP-induced V2 receptor internalization in response to AVP in both CHF and control rats. As expected V2 receptor surface binding remained low after AVP challenge in control rats. In contrast to this, V2 receptor surface binding returned to pre-AVP levels within 30 min in the CHF rats, indicating an obtained recycling ability of the V2 receptor in CHF. Together the results indicate the presence of an increased AVP sensitivity in the CDs from CHF rats, associated with an acquired recycling ability of the V2 receptor.

Low Atrial Fibrillatory Rate Is Associated With Poor Outcome in Patients With Mild to Moderate Heart Failure

Atrial fibrillatory rate (AFR) is a measure of atrial remodeling caused by atrial fibrillation (AF), and its acceleration negatively affects outcome of interventions for persistent AF. However, the prognostic value of AFR in patients with congestive heart failure (CHF) has not been studied. We sought to evaluate whether AFR can predict outcome in patients with mild to moderate (New York Health Association II-III) CHF. High-resolution 20-minute long Holter ECGs obtained from 169 CHF patients with AF at enrollment were analyzed. AFR was estimated using spatiotemporal QRST cancellation and time-frequency analysis. The patients were followed for a median of 44 months, with primary end point defined as total mortality and secondary end points as sudden death and heart failure death. Atrial signal quality was sufficient for AFR estimation in 142 patients (mean age 69±11 years, 101 male). Of those, 48 patients died during follow-up, including 18 because of CHF progression. Mean AFR was 390±60 fpm and decreased with age (r=-0.3, P<0.001). Patients with AFR ≤371 fpm (lower tertile) had 44% 3-year mortality as compared with 26% with higher AFR. Lower AFR was an independent predictor of all cause mortality (HR=1.99, 95% CI=1.09-3.63, P=0.025) and CHF death (HR=3.74, 95% CI=1.38-10.14, P=0.010) after adjustment for significant clinical covariates in multivariable Cox analysis. In CHF patients with AF, reduced AFR assessed using noninvasive approach is associated with increased risk of death because of heart failure progression, and may be considered a predictor of outcome.

Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials

Studies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality. We searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy. Of 3071 reports identified, 12 studies (n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62-0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72-0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67-0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69-1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials. The cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.

A Controller for a Miniature Intra‐Aortic Ventricular Assist Device

Two control algorithms have been developed for a minimally invasive axial-flow ventricular assist device (VAD) for placement in the descending aorta. The purpose of the device is to offload the left ventricle and to augment lower body perfusion in patients with moderate congestive heart failure. The VAD consists of an intra-aortic impeller with a built-in permanent magnet rotor and an extra-aortic stator. The control algorithms, which use pressure readings upstream and downstream of the VAD to determine the pump status, have been tested in a mock circulatory system under two conditions, namely with or without afterload sensitivity. The results give an insight into controller design for an intra-aortic blood pump working in series with the heart.

Usefulness of Short-Term Variability of QT Intervals as a Predictor for Electrical Remodeling and Proarrhythmia in Patients With Nonischemic Heart Failure

The high incidence of sudden cardiac death in heart failure (HF) reflects electrophysiologic changes in response to myocardial failure. We previously showed that short-term variability of QT intervals (STV(QT)) identifies latent repolarization disorders in patients with drug-induced or congenital long QT syndrome. This study sought to determine (1) if STV(QT) is increased in patients with dilated cardiomyopathy (DC) and moderate congestive HF and (2) if increased STV(QT) is associated with ventricular arrhythmia in patients with HF. Sixty patients (53 +/- 12 years of age, 14 women) with DC and moderate HF (New York Heart Association classes II to III) were compared to matched controls. Twenty patients had implantable cardiac defibrillators secondary to a history of ventricular tachycardia (VT). Two cardiologists blinded to diagnosis manually measured QT intervals. Beat-to-beat variability of repolarization was determined from Poincaré plots of 30 consecutive QT intervals as was STV(QT). QTc intervals were comparable in patients and controls (419 +/- 36 vs 415 +/- 32 ms, respectively, p >0.05), whereas STV(QT) was significantly higher in patients with HF (7.8 +/- 3 vs 4.1 +/- 2 ms, respectively, p <0.05). STV(QT) was more increased in patients with a history of VT compared to those without VT (10.1 +/- 2 vs 6.6 +/- 2 ms, respectively, p <0.05). Increased STV(QT) and decreased ejection fraction were associated with a history of VT; however, STV(QT) was the strongest indicator. In conclusion, the present study demonstrates for the first time that STV(QT) is increased in patients with DC with HF. Patients with DC and HF and implantable cardiac defibrillators for secondary prevention had the highest STV(QT). Thus, increased STV(QT) in the context of moderate HF may reflect a latent repolarization disorder and increased susceptibility to sudden death in patients with DC, which is not identified by a prolonged QT interval.

Aldosterone Receptor Antagonists

A 63-year-old woman is evaluated after a recent hospitalization for an acute myocardial infarction. She reports fatigue and exertional dyspnea after ambulating 25 m. Her left ventricular (LV) ejection fraction is 38%, and her medications include aspirin, clopidogrel, a loop diuretic, an angiotensin-converting enzyme inhibitor (ACE-I), and a β-adrenergic receptor antagonist. On physical examination, her blood pressure is 144/92 mm Hg, and her heart rate is 72 bpm. Her jugular venous pressure is 9 cm water, and bilateral inspiratory rales and 1+ peripheral edema are noted. The patient’s serum K+ is 4.5 mEq/L and creatinine is 1.2 mg/dL. She is diagnosed with hypertension and moderate congestive heart failure (CHF) with LV systolic dysfunction. Despite evidence from clinical trials demonstrating a morbidity and mortality advantage for selected patients treated with aldosterone receptor antagonists, these drugs are underused in clinical practice. The Randomized Aldactone Evaluation Study (RALES) and Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) established that spironolactone and eplerenone, respectively, increased survival in patients with severe CHF symptoms from LV systolic dysfunction occurring with minimal exertion or at rest (New York Heart Association [NYHA] class III or IV) or CHF after an acute myocardial infarction.1–3 As a result of these studies, aldosterone receptor antagonists were given an American Heart Association/American College of Cardiology class I recommendation for use, yet only 32% of eligible patients are routinely prescribed these drugs.4,5 This trend likely reflects clinicians’ persisting concerns over reports linking increased community-based spironolactone use with drug-induced deaths and hospitalizations.6 This association is drawn largely from population-based observational data demonstrating a temporal (and not causal) relationship between increased prescription rates of spironolactone and increased rates of hospital admission for the treatment of hyperkalemia and subsequent in-hospital deaths. Given that aldosterone receptor antagonists are often used …

Relationship between RANKL and neuroendocrine activation in elderly males with heart failure

The main cytokines regulating bone remodeling are the receptor activator of nuclear factor-κB ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG). Recent data have linked RANKL and OPG to cardiovascular disease as well. NT-pro-BNP and adiponectin are well-established biomarkers of heart failure reflecting neuroendocrine activation in this multi-complex disorder. The objective of this article was to investigate whether RANKL is associated with neuroendocrine activation in 75 elderly males with mild to moderate congestive heart failure (CHF) and left ventricular ejection fraction <40%. The control group consisted of 20 healthy male volunteers with matching age and body mass index (BMI). Serum RANKL (sRANKL), OPG, NT-pro-BNP, adiponectin, leptin, clinical, and echocardiography parameters were evaluated. In comparison to the control group, the CHF patients showed significantly increased sRANKL levels [126.8 (122.6) vs. 47.8 (44.4) pg/ml, P < 0.0001]. There was a significant relative risk of systolic CHF in elderly males associated with increased sRANKL above the calculated cut-off of 83 pg/ml [OR = 10.286 (95%CI 3.079-34.356), P < 0.0001; RR = 3.600 (95%CI = 1.482-8.747)]. In the CHF patients, the log-transformed values of sRANKL levels correlated positively with the log-transformed values of the serum NT-pro-BNP and adiponectin levels (P = 0.004, r = 0.326 and P = 0.037, r = 0. 241, respectively), while inversely correlated with the BMI and creatinine clearance (P = 0.015, r = -0.281 and P = 0.042, r = -0.236, respectively). In multivariate regression model, sRANKL was a significant determinant of NT-pro-BNP independent of age, BMI and creatinine clearance (P = 0.002, R (2) = 0.546). In conclusion, our study suggests that in elderly males with systolic heart failure sRANKL was significantly associated with parameters of neuroendocrine activation such as NT-pro-BNP and adiponectin. Further studies are needed to elucidate the potential role of sRANKL in the complex pathogenesis of heart failure.