Multiple Drug Regimen-Refractory Rosai-Dorfman-Destombes Disease Mimicking Relapsing Polychondritis Successfully Treated with Cobimetinib.

Rosai-Dorfman-Destombes disease (RDD) or sinus histiocytosis with massive lymphadenopathy is a rare non-Langerhans cell histiocytosis of unknown cause. The disease often manifests as painless bilateral cervical lymphadenopathy associated with systemic symptoms such as fever and weight loss. Extranodal disease is also frequent and can involve any organ, mostly the skin, nasal cavity, bone, and retro-orbital tissue. Swelling of cartilaginous tissues, such as the helix of the ear or laryngeal structures, may mimic the entity known as relapsing polychondritis. Although spontaneous remission is the most expected evolution, some cases require systemic treatment with prednisone, methotrexate or cytotoxic agents, with variable rates of success. In this respect, since somatic variants in the genes involved in the mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK) pathway have been observed to play a pathogenic role in RDD. Therefore, the use of therapies targeting these pathogenic variants appears to be a reasonable strategy. Here we present the case of a 37-year-old woman with RDD and extensive extranodal involvement that showed a rapid and complete response to the MEK inhibitor cobimetinib. LEARNING POINTS: Rosai-Dorfman-Destombes disease (RDD) may mimic the entity known as relapsing polychondritis but should be treated with drug therapy for the underlying disease.Mutations in MAPK/ERK pathway components should be determined in RDD with systemic involvement, although testing to determine every somatic mutation responsible for the disease is not available in all healthcare centres.MEK inhibitors like cobimetinib could be effective in RDD cases with severe and refractory systemic disease, even if molecular analysis has not been possible.

Clinical Prognosis of Right-Sided Infective Endocarditis not Associated with Cardiac Devices or Intravenous Drug use: a Cohort Study and Meta-Analysis.

Right-sided infective endocarditis (RSIE), classically associated with intravenous drug use or intracardiac devices, is considered a good-prognosis infective endocarditis (IE) form. However, predisposing factors and prognosis for "NODID" RSIE (NOt associated with cardiac Devices or Intravenous Drug use) remain unclear. The aim of this study was to evaluate predisposing factors and prognosis of NODID RSIE compared to other RSIE forms. A retrospective cohort study (January 2008-January 2019) was conducted in a reference center on 300 patients diagnosed with IE. Endocarditis-related events were defined as related to IE in mortality or open-heart surgery during follow-up. A review and meta-analysis of associated literature (January 2008-January 2019) were also performed. Fifty-seven patients presented RSIE (19%), 22 of which were NODID RSIE (39%). Use of intravascular catheters (23% vs 3%; p = 0.027) and congenital heart diseases (18% vs 0%; p = 0.019) were associated with NODID RSIE. This group had a higher in-hospital mortality (23% vs 3%; p = 0.027) and endocarditis-related event rates (41% vs 6%; p = 0.001) than non-NODID RSIE. Furthermore, NODID RSIE was independently associated with in-hospital endocarditis-related events (OR = 19.29; 95%CI:2.23-167.16; p = 0.007). Our meta-analysis evaluated four studies and identified 96 cases (30%) of NODID RSIE from 320 total RSIE cases. NODID RSIE patients demonstrated higher in-hospital mortality (RR = 2.81; 95%CI:1.61-4.90; p < 0.001; I2 = 0.0%) and necessity of open-heart surgery (RR = 13.89; 95%CI:4.14-46.60; p < 0.001; I2 = 0.0%) than non-NODID RSIE cases. Our study suggests that NODID RSIE has the highest endocarditis-related event rate and in-hospital mortality among RSIE cases and therefore should not be considered a good-prognosis IE.

Prevalence and incidence of Q-wave unrecognized myocardial infarction in general population: Diagnostic value of the electrocardiogram. The REGICOR study.

BACKGROUND: Diagnosis of unrecognized myocardial infarction (UMI) remains an open question in epidemiological and clinical studies, inhibiting effective secondary prevention of myocardial infarction. We aimed to determine the prevalence and incidence of Q-wave UMI in asymptomatic individuals aged 35 to 74years, and to ascertain the positive predictive value (PPV) of asymptomatic Q-wave to diagnose UMI. METHODS: Two population-based cross-sectional studies were conducted, in 2000 (with 10-year follow-up) and in 2005. A baseline electrocardiogram was obtained for each participant. Imaging techniques (echocardiography, cardiac magnetic resonance imaging, and myocardial perfusion single-photon emission computerized tomography) were used to confirm UMI in patients with asymptomatic Q-wave. RESULTS: The prevalence of confirmed Q-wave UMI in the 5580 participants was 0.18% (95% confidence interval [CI]: 0.10-0.33) and the incidence rate was 27.1 Q-wave UMI per 100,000person-years. The proportion of confirmed Q-wave UMI with respect to all prevalent MI was 8.1% (95% CI: 4.4-14.2). The PPV of asymptomatic Q-wave to diagnose Q-wave UMI was 29.2% (95% CI: 18.2-43.2%) overall, but much higher (75%, 95% CI: 40.9-92.9%) in participants with 10-year CHD risk ≥10%, compared to lower-risk participants. CONCLUSION: Opportunistic identification of asymptomatic Q-waves by routine electrocardiogram overestimates actual Q-wave UMI, which represents 8% to 13% of all myocardial infarction in the population aged 35 to 74years. This overestimation is particularly high in the population at low cardiovascular risk. In epidemiological studies and in clinical practice, diagnosis of a pathologic Q-wave in asymptomatic patients requires detailed analysis of imaging tests to confirm or rule out myocardial necrosis.

Plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1): an independent predictor of poor response to cardiac resynchronization therapy.

AIMS: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular structural remodelling. The aim of our study was to analyse MMP-2 and TIMP-1 levels as predictors of poor response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: A cohort of 42 CRT patients from our centre was prospectively evaluated at baseline and after 12-month follow-up. MMP-2 and TIMP-1 assays were performed prior to CRT implant. Cardiac resynchronization therapy responders were defined as patients who survived, were not transplanted, and increased their basal 6 min walking distance test (6MWDT) by >or=10% or improved their NYHA functional class. Overall, 25 patients (60%) were classed as responders. At 12-month follow-up, six patients (14.2%) had died and one (2.4%) patient had been transplanted. Compared with responders, non-responders had higher levels of TIMP-1 (277 +/- 59 vs. 216 +/- 46 ng/mL, P = 0.001), MMP-2 (325 +/- 115 vs. 258 +/- 56 ng/mL, P = 0.02), and creatinine (1.76 +/- 0.8 vs. 1.25 +/- 0.3 mg/dL, P = 0.01). In a multivariate analysis, TIMP-1 was the only independent predictor of non-response to CRT [OR 0.97, 95% (CI 0.96-0.99) P = 0.005]. TIMP-1>or=248 ng/mL predicted non-response with 71% sensitivity and 72% specificity. CONCLUSION: TIMP-1 is an independent predictor of non-response in patients treated with CRT.

Multiple aorto-right cavitary fistula: a rare complication of prosthetic valvular endocarditis in intravenous drug users.

Aorto-cavitary fistula is an infrequent complication in infective endocarditis as well as multiple fistula, being the most rare among intracardiac fistulas. The prognosis of infective endocarditis worsens if there are fistulas associated, exceeding the mortality over 40% despite aggressive surgical treatment. Although transoesophageal echocardiography offers a better sensitivity and specificity, sometimes transthoracic echocardiography is enough to obtain these infrequent pictures that we present.

Partial ventricular septal defect (Pacman Heart).

Complete ventricular septal defects (VSD) can be congenital (estimated prevalence 0.5% in live births) (Roguin N, et al. High prevalence of muscular ventricular septal defect in neonates. J Am Coll Cardiol 1995;26:1545-1548) or may be a complication of acute myocardial infarction (estimated incidence in the era of thrombolysis 0.2%) [Crenshaw BS, et al. Risk factors, angiographic patterns, and outcomes in patients with ventricular septal defect complicating acute myocardial infarction. GUSTO-I (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) Trial Investigators. Circulation 2000;101:27-32]. In this paper, we report two unique cases of partial VSD.

[Specialized care program for end-stage heart failure patients. Initial experience in a heart failure unit]. / Programa de atención especializada en la insuficiencia cardíaca terminal. Experiencia piloto de una unidad de insuficiencia cardíaca.

INTRODUCTION AND OBJECTIVES: End-stage heart failure is associated with very high morbidity and mortality. Palliative care has been little studied in affected patients. PATIENTS AND METHOD: Between January 1998 and December 2004, 61 patients with end-stage heart failure participated in a specialized advanced heart failure care program. The program included patient education on advanced heart failure, with day-care and home-care elements, and involved intravenous drug administration when necessary. RESULTS: The mean age of the study population was 64 (13) years (range 32-87 years), with 92% being male. Their mean ejection fraction was 23 (6%), mean systolic blood pressure 100 (16) mm Hg, mean blood sodium level 137 (4) mEq, mean creatinine level 1.7 (0.8) mg/dL, and mean hemoglobin level 12 (2) mg/dL. The number of hospitalizations, number of days in hospital per admission, and number of emergency room visits in the year before inclusion in the specialized heart failure care program were 5.7 (0.5), 53 (5), and 8.3 (1.1), respectively. After inclusion, these figures decreased significantly to 1.9 (0.2) (P=.0001), 19 (3) (P=.0001), and 1.2 (0.2) (P=.0001), respectively. During a mean follow-up period of 11 (10) months, 28 patients died (47%) and 23 (38%) underwent heart transplantation. In addition, use of the program led to a reduction in healthcare costs. CONCLUSIONS: Although mortality in end-stage heart failure patients remained very high, use of a specialized advanced heart failure care program decreased the number of hospitalizations, days per hospitalization, and emergency room visits, and reduced the cost of care.

[Impaired endothelium-dependent forearm vasodilation in idiopathic dilated cardiomyopathy is related to severe left ventricular dysfunction and elevated serum tumor necrosis factor levels]. / La disfunción endotelial periférica en la miocardiopatía dilatada idiopática se asocia con mayor disfunción ventricular y concentraciones plasmáticas elevadas de factor de necrosis tumoral.

INTRODUCTION AND OBJECTIVES: Endothelial dysfunction has been found in patients with idiopathic dilated cardiomyopathy (IDC), but its mechanism remains unknown. Our aim was to investigate whether forearm endothelium-dependent vasoreactivity correlates with cardiac disease severity or neurohormonal activation. PATIENTS AND METHOD: We studied 23 patients with IDC and 10 healthy sex- and age-matched controls using brachial artery ultrasound to assess flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NIV). In the IDC group, we determined plasma neurohormone and cytokine levels at the same time. RESULTS: FMD was significantly less in the IDC group compared with the control group [--0.06 (2.8)% vs 4.4 (4.6)%, respectively; P<.01], whereas NIV was similar in both groups [15.0 (6.4)% vs 14.0 (7.4)%, respectively; P=NS]. FMD was significantly less in patients with poorer left ventricular (LV) function and more severe LV dilatation, and in those with a higher tumor necrosis factor-alpha (TNF-alpha) level. NIV was similar in all patient subgroups. There was a significant inverse correlation between the TNF-alpha plasma level and FMD (r=-0.75; P<.01). No correlation was found between the plasma levels of other neurohormones and FMD. CONCLUSIONS: FMD, but not NIV, was impaired in patients with IDC compared with control subjects. In patients, there were significant associations between FMD impairment and the severity of LV dilatation, the severity of LV systolic dysfunction, and the plasma TNF-alpha level. The strongest correlation was observed between TNF-alpha plasma level and FMD. These data suggest that TNF-alpha may be implicated in endothelial dysfunction in patients with IDC.