Raphael Bonita

Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction The ROSE Acute Heart Failure Randomized Trial

IMPORTANCE Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. OBJECTIVE To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 μg/kg/min) or low-dose nesiritide (0.005 μg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. INTERVENTIONS Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). MAIN OUTCOMES AND MEASURES Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). RESULTS Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. CONCLUSION AND RELEVANCE In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01132846.

Iodine: an environmental trigger of thyroiditis

Like most autoimmune diseases of humans, chronic lymphocytic (Hashimotos) thyroiditis results from the combination of a genetic predisposition and an environmental trigger. A body of clinical and epidemiologic evidence points to excessive ingestion of iodine as an environmental agent. In genetically determined thyroiditis in animals, iodine enrichment has been shown to increase the incidence and severity of disease. Its mechanism of action is still uncertain. Using a new animal model of autoimmune thyroiditis, the NOD.H2(h4) mouse, we have been able to show that iodine enhances disease in a dose-dependent manner. Immunochemical studies suggest that iodine incorporation in the thyroglobulin may augment the antigenicity of this molecule by increasing the affinity of its determinants for the T-cell receptor or the MHC-presenting molecule either altering antigen processing or by affecting antigen presentation.

Valvular Heart Disease in Osteogenesis Imperfecta: Presentation of a Case and Review of the Literature

Osteogenesis imperfecta (OI) is a rare inheritable disorder of connective tissue. While musculoskeletal abnormalities are well known, cardiovascular involvement is rare. Aortic root dilation is the most common cardiovascular manifestation. OI preferentially affects the left‐sided heart valves, for unclear reasons, leading to aortic and mitral regurgitation. Valve replacement surgery carries a unique set of issues in this population, and fewer than 40 cases have been reported. We report a case of chronic severe aortic regurgitation in a patient with OI complicated by the development of a flail aortic valve leaflet and presenting with a transient ischemic attack. The patient subsequently underwent successful combined bioprosthetic aortic valve replacement and coronary artery bypass grafting. We review the literature on valvular disease and other cardiovascular manifestations in OI and the related surgical considerations relevant to this patient population. (Echocardiography 2010;27:69‐73)

Kinetics of mononuclear cell infiltration and cytokine expression in iodine-induced thyroiditis in the NOD-H2h4 mouse.

Mononuclear cell infiltration of the thyroid gland is a common histologic feature of chronic lymphocytic thyroiditis. Although the infiltrating mononuclear cells have been implicated in the destruction of the thyroid, information concerning the progression of infiltration into the thyroid is limited. In this report, we examine the composition and kinetics of mononuclear cell infiltration in the thyroid and the expression of major histocompatibility complex class II (I-Ak), IL-12, and IFN-gamma in the thyroid of the NOD-H2h4 mouse, a model of spontaneous autoimmune thyroiditis accelerated by the administration of excess dietary iodine. Mice were given a low dose of 0.015% NaI in their drinking water for 2, 4, 6, 8, and 16 weeks, and thyroids were removed, serially sectioned, and stained in an avidin-biotin peroxidase assay. The thyroid infiltrate included CD4+ and CD8+ T cells, F4/80+ macrophages, and B220+ B cells. After 2 weeks of iodine treatment, CD4+ T cells were the first seen in the thyroid, followed by CD8+ T cells and F4/80+ macrophages. B220+ B cells entered the thyroid after 4 weeks of iodine treatment. IL-12 and IFN-gamma positive cells were located in the thyroid early in disease and were up-regulated in the focal accumulations of infiltrating cells. Thyrocytes clearly expressed I-Ak after 4 weeks of iodine treatment near the location of mononuclear cell infiltration.

Dynamic Changes in Lymphocyte GRK2 Levels in Cardiac Transplant Patients: A Biomarker for Left Ventricular Function

G protein‐coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme‐linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 signifi cantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end‐stage HF. Clin Trans Sci 2010; Volume #: 1–5

Cardiovascular Toxicities of Cancer Chemotherapy

Cancer chemotherapy has improved over the years with the advent of newer agents, including more targeted chemotherapeutic drugs, resulting in better patient survival. However, with continued use and patient exposure to these drugs, important cardiovascular adverse effects are becoming realized, such as left ventricular dysfunction and heart failure, myocardial ischemia, hypertension, arrhythmias, and pulmonary arterial hypertension. In this article, we review the most common cardiovascular toxicities and their related pathophysiology that occur with the use of these agents.

Photoplethysmographic Signal to Screen Sleep-Disordered Breathing in Hospitalized Heart Failure Patients: Feasibility of a Prospective Clinical Pathway.

OBJECTIVES The purpose of this study was to evaluate the plethysmographic signal-derived oxygen desaturation index (ODI) as an inpatient screening strategy to identify sleep-disordered breathing (SDB) in patients with congestive heart failure (CHF). BACKGROUND SDB is highly prevalent among patients hospitalized with CHF but is widely underdiagnosed. We evaluated overnight photoplethysmography as a possible screening strategy for hospitalized patients with CHF. METHODS Consecutively admitted heart failure patients with high clinical suspicion of SDB and ODI ≥5 were offered outpatient polysomnography (PSG), which was completed within 4 weeks of discharge. PSG was considered positive if the apnea hypoxia index (AHI) was ≥5. A Bland-Altman plot was used to assess agreement between ODI and AHI. Receiver-operator characteristics were determined for ODI ≥5 and AHI ≥5. RESULTS A screening questionnaire identified 246 of 282 consecutive patients with positive symptoms for SDB. Of these patients, 105 patients were offered further evaluation and 86 had ODI ≥5 (mean ODI 17 ± 17). Among these 86 patients, 68 underwent outpatient PSG within 4 weeks of discharge. PSG showed that 64 (94%) had SDB, with a mean AHI of 28. Inpatient ODI correlated well with PSG-derived AHI. The area under the curve was 0.82 for AHI ≥5. The Bland-Altman plot revealed no major bias. Matthews correlation coefficient revealed that the optimal cut-off for ODI is 5. CONCLUSIONS Screening hospitalized patients with heart failure using targeted inpatient ODI identifies a cohort of patients with a high prevalence of SDB. Our screening strategy provides a potentially cost-effective method for early detection and treatment of SDB.

Reporting of Clinical Trials: Publication, Authorship, and Trial Registration

Transparency is the foundation on which all of research integrity rests. The public trust from patients, providers, and policy makers depends on fidelity to the mandates of accountability and access. Two important foundational practices for maintaining transparency in research and the reporting of clinical trials discussed in this review concern manuscript authorship and clinical trial registry, recognizing recent controversies regarding honorary and ghost authorship in the publication of industry-sponsored studies.

Recurrent orthostatic syncope due to left atrial and left ventricular collapse after a continuous-flow left ventricular assist device implantation

Left ventricular assist devices (LVADs) have become an established treatment for patients with advanced heart failure as a bridge to transplantation or for permanent support as an alternative to heart transplantation. Continuous-flow LVADs have been shown to improve outcomes, including survival, and reduce device failure compared with pulsatile devices. Although LVADs have been shown to be a good option for patients with end-stage heart failure, unanticipated complications may occur. We describe dynamic left atrial and left ventricular chamber collapse related to postural changes in a patient with a recent continuous-flow LVAD implantation.

TREATMENT OF SLEEP DISORDERED BREATHING IN PATIENTS ADMITTED FOR DECOMPENSATED HEART FAILURE REDUCES 6 MONTHS HOSPITAL VISITS

Despite outcome improvement re-hospitalization of congestive heart failure (CHF) is high. Sleep disordered breathing (SDB) is common and under-diagnosed in CHF patients. We hypothesized that early recognition and treatment of SDB in hospitalized CHF patients will reduce hospital visits (combined end