The epidemiology and pathophysiology of heart failure.

Heart failure (HF) remains a major growing public health problem in the United States. Despite extensive understanding of the mechanism at the molecular level and innovations in therapy, HF carries high morbidity and mortality rates, with frequent hospital admissions. In the Medicare population, HF is the leading cause for hospitalization, accounting for more than1 million admissions per year. The authors provide a review of the epidemiology and pathophysiology of HF.

Improvement of cardiac functions by chronic metformin treatment is associated with enhanced cardiac autophagy in diabetic OVE26 mice.

OBJECTIVE: Autophagy is a critical cellular system for removal of aggregated proteins and damaged organelles. Although dysregulated autophagy is implicated in the development of heart failure, the role of autophagy in the development of diabetic cardiomyopathy has not been studied. We investigated whether chronic activation of the AMP-activated protein kinase (AMPK) by metformin restores cardiac function and cardiomyocyte autophagy in OVE26 diabetic mice. RESEARCH DESIGN AND METHODS: OVE26 mice and cardiac-specific AMPK dominant negative transgenic (DN)-AMPK diabetic mice were treated with metformin or vehicle for 4 months, and cardiac autophagy, cardiac functions, and cardiomyocyte apoptosis were monitored. RESULTS: Compared with control mice, diabetic OVE26 mice exhibited a significant reduction of AMPK activity in parallel with reduced cardiomyocyte autophagy and cardiac dysfunction in vivo and in isolated hearts. Furthermore, diabetic OVE26 mouse hearts exhibited aggregation of chaotically distributed mitochondria between poorly organized myofibrils and increased polyubiquitinated protein and apoptosis. Inhibition of AMPK by overexpression of a cardiac-specific DN-AMPK gene reduced cardiomyocyte autophagy, exacerbated cardiac dysfunctions, and increased mortality in diabetic mice. Finally, chronic metformin therapy significantly enhanced autophagic activity and preserved cardiac functions in diabetic OVE26 mice but not in DN-AMPK diabetic mice. CONCLUSIONS: Decreased AMPK activity and subsequent reduction in cardiac autophagy are important events in the development of diabetic cardiomyopathy. Chronic AMPK activation by metformin prevents cardiomyopathy by upregulating autophagy activity in diabetic OVE26 mice. Thus, stimulation of AMPK may represent a novel approach to treat diabetic cardiomyopathy.

Similar observed CABG related bleeding complications in patients with and without clopidogrel loading doses.

OBJECTIVE: Pretreatment with clopidogrel before percutaneous coronary intervention improves cardiovascular outcomes. However, some patients require elective coronary artery bypass graft (CABG) surgery instead, possibly increasing bleeding complications. We sought to assess the hemorrhagic complications and the length of hospital stay of stable patients receiving clopidogrel pretreatment that are referred for CABG. METHODS: Between March and August 2007, 493 patients underwent diagnostic catheterization; 54 patients underwent elective CABG and were stratified according to clopidogrel loading dose (n = 20) or not (n = 34). Incidences of major hemorrhagic events and median post-surgical hospital stay were compared between groups. RESULTS: TIMI Bleeding index was not significantly difference between the clopidogrel and not clopidogrel groups (mean difference 0.46; 95% CI -0.89 to 1.82; p = 0.5). The incidence of major TIMI bleeding (70% vs. 73.5%; p > 0.9), peak hemoglobin loss > 5 g/dL (60% vs. 38.2%; p = 0.2), and blood transfusion > 4 units (20% vs. 26.5%; p = 0.7) in clopidogrel vs. no-clopidogrel group were not statistically different. Interestingly, the post-surgical length of stay was longer for the no-clopidogrel group (median of 5 vs. 7 days; p = 0.006). CONCLUSION: There was no significant evidence of increased bleeding or need for blood transfusion during CABG in patients pretreated with clopidogrel. The current practice of clopidogrel pretreatment before percutaneous coronary intervention does not significantly increase the risk of hemorrhagic complications in stable patients provided they can wait for at least 7 days before CABG. In a single center retrospective study, clopidogrel pretreatment was not found to be associated with increased bleeding or need for blood transfusion during coronary artery bypass graft surgery, suggesting that clopidogrel pretreatment before percutaneous coronary intervention does not significantly increase the risk of hemorrhagic complication in stable patients provided they can wait for 7 days before the surgery.

Similar observed CABG related bleeding complications in patients with and without clopidogrel loading doses / Complicaciones hemorrágicas asociadas a cirugía de revascularización miocárdica en pacientes con o sin dosis de carga de clopidogrel

Objective: Pretreatment with clopidogrel before percutaneous coronary intervention improves cardiovascular outcomes. However, some patients require elective coronary artery bypass graft (CABG) surgery instead, possibly increasing bleeding complications. We sought to assess the hemorrhagic complications and the length of hospital stay of stable patients receiving clopidogrel pretreatment that are referred for CABG. Methods: Between March and August 2007, 493 patients underwent diagnostic catheterization; 54 patients underwent elective CABG and were stratified according to clopidogrel loading dose (n = 20) or not (n = 34). Incidences of major hemorrhagic events and median post-surgical hospital stay were compared between groups. Results: TIMI Bleeding Index was not significantly different between the clopidogrel and no-clopidogrel groups (mean difference 0.46; 95% CI -0.89 to 1.82; p = 0.5). The incidence of major TIMI bleeding (70% vs. 73.5%; p > 0.9), peak hemoglobin loss > 5 g/dL (60% vs. 38.2%; p = 0.2), and blood transfusion > 4 units (20% vs. 26.5%; p = 0.7) in clopidogrel vs. no-clopidogrel group were not statistically different. Interestingly, the post-surgical length of stay was longer for the no-clopidogrel group (median of 5 vs. 7 days; p = 0.006). Conclusion: There was no significant evidence of increased bleeding or need for blood transfusion during CABG in patients pretreated with clopidogrel. The current practice of clopidogrel pretreatment before percutaneous coronary intervention does not significantly increase the risk of hemorrhagic complications in stable patients provided they can wait for at least 7 days before CABG. In a single center retrospective study, clopidogrel pretreatment was not found to be associated with increased bleeding or need for blood transfusion during coronary artery bypass graft surgery, suggesting that clopidogrel pretreatment before percutaneous coronary intervention does not significantly increase the risk of hemorrhagic complications in stable patients provided they can wait for 7 days before the surgery.

Objetivo: El pretratamiento con clopidogrel antes de la intervención precutánea coronaria, mejora los resultados cardiovasculares. Sin embargo, algunos pacientes que requieren cirugía programada de puente aortocoronario (CABG), posiblemente incrementan las complicaciones de sangrado. Nosotros buscamos valorar las complicaciones hemorrágicas y la duración de la estancia hospitalaria de los pacientes estables que reciben el pretratamiento de clopidogrel y que son enviados a CABG. Métodos: Entre los meses de marzo y agosto de 2007, 493 pacientes tuvieron diagnóstico de cateterización; 54 pacientes tuvieron una CABG programada y fueron estratificados con base en la dosis cargada de clopidogrel (n = 20) o no cargada (n = 34), y se compararon las incidencias de mayores eventos hemorrágicos y la media de estancia post operatoria entre ambos grupos. Resultados: El Indice de Sangrado TIMI no arrojó una diferencia significativa entre los grupos con clopidogrel y sin clopidogrel (la diferencia principal 0.46; 95% CI - 0.89 a 1.82; p = 0.5). La incidencia de mayor sangrado TIMI (70 % vs. 73.5%; p > 0.9) máxima pérdida de hemoglobina > 5 g/dL (60% vs. 38.2%; p = 0.2) y transfusión de sangre > 4 unidades (20% vs. 26.5%; p = 0.7) entre los grupos con clopidogrel y sin clopidogrel no fue estadísticamente diferente. Pero es interesante que el periodo de permanencia post operatoria fue más largo en el grupo que no fue tratado con clopidogrel (media de cinco vs. siete días: p = 0.006). Conclusión: No hay una evidencia significativa de incremento de sangrado o necesidad de transfusión sanguínea durante la CABG en pacientes pretratados con clopidogrel. La práctica actual del pretratamiento clopidogrel antes de la intervención precutánea coronaria no incrementa significativamente el riesgo de complicaciones hemorrágicas en pacientes estables siempre y cuando puedan esperar al menos siete días antes de la CABG. En un estudio simple de retrospectiva, no se encontró que el pretratamiento con clopidogrel se asociara con el incremento de sangrado o la necesidad de transfusión sanguínea durante la cirugía de puente aortocoronario, sugiriendo que el pretratamiento con clopidogrel antes de la intervención precutánea coronaria, no incrementa significativamente el riesgo de complicaciones hemorrágicas en pacientes estables siempre y cuando puedan esperar siete días antes de la cirugía.

Papillary renal cell carcinoma with cutaneous metastases.

Cutaneous metastasis is a rare form of presentation of renal cell carcinoma (RCC). Case reports and case series of RCC with skin metastasis in the English literature from 1972 to 2008 were identified by searching the keywords "renal cell cancer," "papillary renal cell tumor," "skin metastasis," and "cutaneous metastasis" in the National Library of Medicine, PUBMED, OVID, and EMBASE search engines. Although a few cases of RCC with skin metastasis are reported in the literature, almost all are clear cell histologic type. We are reporting a unique case of papillary RCC with cutaneous metastases diagnosed at our institution along with a comprehensive literature review of papillary RCC etiology, clinical presentation, prognosis, diagnosis, and the treatment options that are currently available.

Use of simultaneous angioplasty and in situ thrombolysis with a specialized balloon catheter for peripheral interventions.

The treatment of acute limb ischemia is always challenging. Various techniques including balloon angioplasty, rheolytic thrombectomy, and prolonged localized infusion of thrombolytics are often used to achieve revascularization. However, some patients with suboptimal angiographic results may benefit from novel alternatives such as the Clearway irrigation balloon (Atrium, Hudson, NH, USA). This device allows simultaneous low-pressure balloon angioplasty and delivery of thrombolytics in situ in patients with arterial or venous thrombosis. This strategy may improve the acute angiographic results in complex acute limb ischemia cases.

The evaluation and monitoring of volume status in congestive heart failure.

The increasing prevalence of heart failure dictates that physicians effectively assess and treat congestion. The evaluation of volume status in the complex group of patients with heart failure is very challenging. Physical examination is at best challenging and not always helpful, confounded by body habitus and comorbidities. Weight monitoring has been shown to be helpful, especially in combination with remote monitoring or telephonic checks. Invasive methods such as pulmonary artery catheters provide significant information but have not been proven to be clinically effective. Noninvasive measures such as impedance cardiography and echocardiography provide additional information. The future of heart failure management may reside in implantable monitors, either alone or in combination with other intracardiac devices. These monitors can provide surrogates of pulmonary capillary wedge pressure and volume. They can also be followed remotely and provide information on the patient's status more frequently than office visits. This manuscript will review volume assessment including past, current, and future methods.

Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis and chronic renal failure: a case report.

UNLABELLED: Vitamin C is a precursor of oxalate and promoter of its absorption, potentially causing hyperoxaluria. Malabsorption causes Calcium (Ca) chelation with fatty acids, producing enteric hyperoxaluria. CASE: A 73-year-old man with both risk factors was hospitalized with serum creatinine of 8.4 mg/dL (versus 1.2 mg/dL four months earlier) (normal 0.6-1.3 mg/dL). Given his oxalate-rich diet, chronic diarrhea, and daily 680 mg vitamin C and furosemide, we postulated Ca oxalate-induced nephropathy, a diagnosis confirmed by documenting hyperoxaluria, and finding of diffuse intraluminal crystals and extensive interstitial fibrosis on biopsy. He was hemodialysed 6 times to remove excess oxalate. Two weeks off vitamin C, his creatinine spontaneously fell to 3.1 mg/dL. Three months later, on low oxalate diet and 100 mg vitamin B6, urine oxalate to creatinine ratio decreased from 0.084 to 0.02 (normal < 0.035), while creatinine fell and stayed at 1.8 mg/dL. CONCLUSION: 1) High-dose vitamin C can induce hyperoxaluric nephropathy and progressive renal failure, especially if aggravated by diarrhea, oxalate-rich diet, metabolic acidosis, and dehydration. 2) The diagnosis should be suspected in unexplained renal insufficiency when associated with these risk factors. 3) Since prompt treatment could avert end-stage renal disease, we recommend monitoring urinary oxalate in patients on high-dose vitamin C and renal biopsy if necessary.