Usefulness of the Mitral Regurgitation Severity Index to Assess the Severity of Chronic Mitral Regurgitation.

Existing metrics for grading mitral regurgitation (MR) are limited and fraught with high interobserver variability. We developed and evaluated a Doppler-based, semiquantitative novel index (Mitral Regurgitation Severity Index [MRSI]) of MR severity. In a total of 125 patients (70 in the derivation cohort and 55 in the validation cohort), MRSI was calculated as a ratio of time velocity integral of mitral inflow (continuous-wave Doppler-TVI MV) to the time velocity integral of the left ventricle outflow (pulse-wave Doppler-TVI LVOT). Inter-rater agreement for MRSI and predictive ability of the MRSI were then assessed. In the derivation cohort, MRSI differed significantly between patients with severe MR (2.6 ± 0.51) and mild-moderate (nonsevere) MR (1.4 ± 0.18) and a cutoff of ≥1.8 was associated with optimal diagnostic accuracy. In the validation cohort, MRSI exhibited excellent agreement between a level II and a level III reader with a mean difference of -0.14 (95% confidence limit of agreement: -0.80 to 0.53), correlation coefficient of 0.88 (p <0.001), and 16% CV; and using the cut point of 1.8, it exhibited good inter-rater reproducibility with a kappa coefficient of 0.72 (p <0.001). In conclusion, MRSI appears to be a simple, quantitative, practical, color-independent metric to differentiate severe MR from nonsevere MR.

Actinomycotic endocarditis of the eustachian valve: a rare case and a review of the literature.

Eustachian valve endocarditis caused by Actinomyces species is extremely rare. A literature review revealed only one reported case-caused by Actinomyces israelii in an intravenous drug abuser. Our patient, a 30-year-old woman who at first appeared to be in good health, presented with fever, a large mobile mass on the eustachian valve, and extensive intra-abdominal and pelvic masses that looked malignant. Histopathologic examination of tissue found in association with an intrauterine contraceptive device revealed filamentous, branching microorganisms consistent with Actinomyces turicensis. This patient was treated successfully with antibiotic agents. In addition to presenting a new case of a rare condition, we discuss cardiac actinomycotic infections in general and eustachian valve endocarditis in particular: its predisposing factors, clinical course, sequelae, and our approaches to its management.

Evaluation of lixivaptan in euvolemic and hypervolemic hyponatremia and heart failure treatment.

INTRODUCTION: Lixivaptan is a selective vasopressin type 2 (V2) receptor antagonist that induces aquaresis, the electrolytes sparing excretion of water. Its ability to correct hyponatremia has been demonstrated in experimental animal studies as well as in clinical trials in humans. Recently, three Phase III, double-blind, randomized, placebo-controlled studies have been completed. In two studies, patients with euvolemic hyponatremia were enrolled, one in the inpatient and the other in the outpatient setting and the third study involved patients with hypervolemic hyponatremia hospitalized for decompensated heart failure (HF). The trials confirmed the efficacy of lixivaptan in raising serum sodium but raised concern about its safety in patients hospitalized with decompensated HF. AREAS COVERED: The authors review original publications on lixivaptan and summarize their findings. Specifically, the authors present information regarding its structure, pharmacodynamics and kinetics, metabolism as well as its efficacy and safety in laboratory animals and human studies. Furthermore, the FDA website was accessed to obtain information presented at the September 13, 2012 meeting of the Cardiovascular and Renal Drugs Advisory Committee. EXPERT OPINION: The published data indicate that lixivaptan raises sodium levels in hyponatremic patients and supports its use in patients with euvolemic hyponatremia. However, the authors note that more safety data are still needed specifically in patients with decompensated HF.

Prevalence, determinants, and clinical significance of cardiac troponin-I elevation in individuals admitted for a hypertensive emergency.

Hypertensive emergencies (HEs) are frequently accompanied with the release of cardiac troponin I (cTnI); however, determinants and clinical significance of cTnI elevation are largely unknown. A retrospective analysis was performed on patients (n = 567) with a diagnosis of HE admitted to two tertiary care centers that primarily serve an inner-city population. Data on demographics, clinical variables, and cTnI were collected through chart review. Using regression analyses, predictors of cTnI elevation were studied and the impact of cTnI on all-cause mortality (data obtained through the Social Security Death Index) was determined. cTnI elevation was observed in 186 (32.3%) admissions with a mean peak cTnI level of 4.06 ± 14.6 ng/mL. Predictors of cTnI were age, history of hypercholesterolemia, blood urea nitrogen level, pulmonary edema, and requirement for mechanical ventilation. During a mean follow-up period of 3.1 years, there were 211 deaths (37%). Neither the presence nor the extent of cTnI elevation was associated with mortality, while age, history of coronary artery disease, and blood urea nitrogen level were predictive of mortality. cTnI elevation commonly occurs in the setting of HEs. Despite a high incidence of adverse clinical outcomes, cTnI elevation was not an independent predictor of mortality in this population.

Tolvaptan, hyponatremia, and heart failure.

Tolvaptan is the first FDA-approved oral V(2) receptor antagonist for the treatment of euvolemic and hypervolemic hyponatremia, in patients with conditions associated with free water excess such as heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone secretion. Tolvaptan inhibits the binding of arginine vasopressin to the V(2) receptors on the collecting ducts of the kidneys resulting in aquaresis, the electrolytes sparing excretion of water. This article reviews the accumulated experience with tolvaptan and all the major clinical trials that were conducted to study its safety and efficacy and concludes by summarizing clinicians' views of its current application in clinical practice.

The potential role for lixivaptan in heart failure and in hyponatremia.

INTRODUCTION: Hypervolemia and hyponatremia are common features in heart failure and have been associated with increased morbidity and mortality. Stimulation of arginine vasopressin (AVP) plays an important role in the development of both hypervolemia and hyponatremia. Lixivaptan is a selective vasopressin type 2 (V(2)) receptor antagonist that has been demonstrated to have the ability to induce aquaresis, the electrolyte sparing excretion of water, resulting in fluid removal as well as correction of hyponatremia. AREAS COVERED: This article describes the prevalence, pathophysiology and current treatment limitations of hyponatremia, highlights the importance of arginine vasopressin and the potential role of arginine vasopressin antagonists and reviews all available literature on lixivaptan, a selective V(2) receptor antagonist. EXPERT OPINION: The available experience of lixivaptan in heart failure, although limited, is encouraging. Its aquaretic effect provides the basis for its use to correct hypervolemia and hyponatremia in patients with heart failure, and the absence of neurhormonal stimulation provides positive signal for the exploration of its potential in improving outcomes.

Red cell distribution width and mortality in predominantly African-American population with decompensated heart failure.

INTRODUCTION: Red-cell distribution width (RDW) has been identified as a novel prognostic marker in heart failure patients. However, evidence is limited for its predictive value in the setting of patients hospitalized with decompensated heart failure (DHF) and no data are available for African Americans (AA). METHODS AND RESULTS: Data that included baseline characteristics, laboratory findings, and discharge medications were collected retrospectively on a total of 789 patients with DHF (mean age 62.7 ± 15.1 years, 50% males and 80% AA), admitted to an urban medical center between January 2007 and August 2007, 145 (18.38%) died during median follow-up of 573 days. Unadjusted and adjusted Cox-proportional hazard models were used to analyze predictive value of discharge RDW on mortality. There was a significant negative association between RDW and statin use, blood hemoglobin levels and mean corpuscular volume (MCV); whereas serum creatinine and blood urea nitrogen (BUN) increased with increasing RDW. A statistically significant graded increase in all-cause mortality with higher RDW quartiles (lowest vs highest quartile), independent of hemoglobin and creatinine levels, was found for all patients (adjusted hazard ratio [HR] 3.21; 95% confidence interval [CI]: 1.77-5.83, P < .05) for AAs (adjusted HR 2.92; 95% CI: 1.50-5.71, P < .05) and for non-AAs (adjusted HR-1.27, 95% CI: 1.03-1.55, P = 0.019; RDW evaluated as continuous variable). CONCLUSION: Discharge RDW is an independent predictor of all-cause mortality in predominantly AA patients hospitalized with DHF. Further research is warranted to delineate underlying pathophysiological mechanisms including the association between statin use and RDW.

Lixivaptan, a non-peptide vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia.

Lixivaptan (VPA-985), being developed by Biogen Idec and Cardiokine, under license from Wyeth (now part of Pfizer), is a non-peptide, selective vasopressin V2 receptor antagonist for the potential oral treatment of hyponatremia associated with heart failure. Arginine vasopressin, the native V2 receptor ligand, stimulates water reabsorption via activation of V2 receptors that are expressed in the collecting ducts of the kidney. In preclinical studies, lixivaptan displayed competitive antagonist activity at V2 receptors in vitro, and increased urine volume and decreased urine osmolality in rats and dogs. The therapeutic benefits of lixivaptan are being evaluated in patients with conditions that are associated with water excess and hyponatremia. Phase II clinical trials in patients with congestive heart failure, liver cirrhosis with ascites or syndrome of inappropriate antidiuretic hormone have demonstrated that, unlike traditional diuretics, lixivaptan increases water clearance without affecting renal sodium excretion or activating the neurohormonal system. Administration of lixivaptan in combination with the diuretic furosemide has been tested in rats as well as in trials in healthy volunteers, in which the two agents were well tolerated. Ongoing phase III trials will determine the role of lixivaptan in the management of hyponatremia, especially when associated with heart failure.

Valvular perforation in left-sided native valve infective endocarditis.

BACKGROUND: Left-sided native valve infective endocarditis (LNVIE) can result in mitral (MP) and aortic (AP) valve perforation, the prognostic significance of which remains poorly defined. HYPOTHESIS: Valvular perforation is associated with worse outcomes. METHODS: Retrospective review of patients with LNVIE during 1998-2005 was performed to examine characteristics and outcome predictors of LNVIE complicated by valve perforation. Patients were stratified as: group A: MP or AP detected by transesophageal echocardiography (TEE) or surgery; group B: no TEE evidence of MP or AP. RESULTS: A total of 123 patients were included (group A = 47, group B = 76). In group A, 35 patients (74.5%) had MP alone, 11 (23.4%) had AP alone, and 1 patient had both. Severe valvular insufficiency was encountered more in group A (85.1% versus 59.2%, p = 0.003), so was hemodialysis (40.4% versus 17.1%, p = 0.004) and indications for valvular surgery (93.6% versus 77.6%, p = 0.02). Group A had a higher rate of in-hospital death (31.9% versus 15.8%, p = 0.04). Among patients who had an indication for valvular surgery, the in-hospital mortality rate for those who underwent valvular surgery was 16.7% in group A, and 7.9% in group B (p = 0.4), compared to those who did not undergo surgery (71.4% versus 33.3%, p = 0.04). Amongst survivors, hospital stay was on average 9.2 d longer in group A (38.9 versus 29.7 d, p = 0.05). Univariate analysis revealed association between lower survival and valvular perforation (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.17-0.95), that was lost after adjusting for hemodialysis. CONCLUSIONS: Valve perforation complicating LNVIE is associated with hemodialysis, severe valvular insufficiency, and significant morbidity and mortality. Compared to conservative management, early surgical intervention is associated with improved survival.

Conivaptan and its role in the treatment of hyponatremia.

Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with increased morbidity and mortality. The recognition of the central role that arginin vasopressin plays in the pathogenesis of hyponatremia and the discovery that its actions are mediated by stimulation of V(1A) and V(2) receptors have led to the development of a new class of drugs, the arginin vasopressin antagonists. Conivaptan is a nonselective V(1A) and V(2) receptors antagonist that was the first of this class to be approved by the FDA for the management of euvolemic and hypervolemic hyponatremia. Its short-term safety and efficacy for the correction of hyponatremia have been established by multiple double-blind, randomized, controlled studies. Blocking the effects of arginin vasopressin on V(2) receptors produces aquaresis--the electrolyte-sparing excretion of water--an ideal approach to correct hypervolemic hyponatremia. The nonselectivity of conivaptan offers a theoretical advantage for its use in heart failure that may merit further exploration.