Mohammad Sarraf

Cardiorenal Syndrome in Acute Decompensated Heart Failure

Renal dysfunction is highly prevalent in patients with heart failure. Furthermore, worsening renal function in patients with acute decompensated heart failure (ADHF), the so-called cardiorenal syndrome, impacts short and long-term morbidity and mortality. In recent years, more evidence has surfaced from clinical trials and heart failure registries that a complex cross-talk between the kidney and heart in patients with ADHF exists. Meanwhile, management of patients presenting with ADHF and concomitant renal dysfunction continues to be challenging. Therefore, understanding the interaction of the heart and kidneys is pivotal in tailoring therapy of these patients. We have extensively reviewed the pathophysiology of ADHF, the role of neurohoromones as well as other biomarkers and predictors of mortality in these patients based on the current evidence. Moreover, we have discussed the current and future pharmacologic and non-pharmacologic therapies for treatment of this deadly disease. The strength of the evidence is limited, however, due to a paucity of randomized controlled trials in this patient population. What is evident from current national statistics; however, are the poor results in treating the congestion of ADHF. In this regard, the role of secondary hyperaldosteronism is discussed in the diuretic section as well as diuretic resistance in ADHF. In conclusion, since renal function is the single most important prognostic factor in the outcome of patients with ADHF, a better understanding of the pathophysiology of the cardiorenal syndrome is needed to target therapy and ultimately improve the mortality of patients with ADHF.

A case of tuberous sclerosis complex that progressed to end-stage renal disease.

Background A 31-year-old woman with tuberous sclerosis complex presented with a 1 week history of subjective fever, chills, rigors, poor appetite and dizziness.Investigations Physical examination, urine and blood analysis, CT of the abdomen, chest and brain, and chest X-ray.Diagnosis End-stage renal disease, septic shock and urinary tract infection secondary to huge bilateral angiomyolipomas of the kidney associated with tuberous sclerosis complex.Management Antibiotic therapy, vasopressor treatment and bilateral nephrectomy, followed by hemodialysis while awaiting renal transplantation.

Arterial insulin resistance in Yucatan micropigs with diet-induced obesity and metabolic syndrome

AIMnMetabolic syndrome affects a large proportion of the population and increases cardiovascular disease risk. Because metabolic syndrome often co-exists clinically with atherosclerosis, it is difficult to distinguish the respective contributions of the components to vascular abnormalities. Accordingly, we utilized a porcine dietary model of metabolic syndrome without atherosclerosis to investigate early abnormalities of vascular function and signaling.nnnMETHODSnThirty-two Yucatan micropigs were fed either a high-fat, high-simple-sugar, high-calorie (HFHS) or standard chow diet (STD) for 6 months. Neither diet contained added cholesterol. Blood pressure and flow-mediated vasodilatation were assessed at baseline and 6 months. Aortas were harvested at 6 months to assess histology, insulin signaling, and endothelial nitric oxide (eNOS) phosphorylation.nnnRESULTSnHFHS pigs developed characteristics of metabolic syndrome including obesity, dyslipidemia, and insulin resistance, but without histologic evidence of atherosclerosis. Although arterial intima-media thickness did not differ between groups, vascular dysfunction in HFHS was manifest by increased blood pressure and impaired flow-mediated vasodilation of the femoral artery. Compared with STD, aortas from HFHS exhibited increased p85α expression and Ser307 IRS-1 phosphorylation, and blunted insulin-stimulated IRS-1-associated phosphatidylinositol (PI) 3-kinase activity. In the absence of insulin stimulation, aortic Akt Ser473-phosphorylation was greater in HFHS than in STD. With insulin stimulation, Akt phosphorylation increased in STD, but not HFHS. Insulin-induced Ser1177-phosphorylation of eNOS was decreased in HFHS, compared with STD.nnnCONCLUSIONSnPigs with metabolic syndrome develop early vascular dysfunction and aortic insulin signaling abnormalities, and could be a useful model for early human vascular abnormalities in this condition.

OUTCOMES FOR SURGICAL AND TRANSCATHETER AORTIC VALVE REPLACEMENT IN NONAGENARIANS

Transcatheter aortic valve replacement (TAVR) may offer extreme-age patients a treatment alternative to surgical aortic valve replacement (SAVR). We aim to describe outcomes of TAVR and SAVR in nonagenarians in a large nationwide inpatient sample (NIS).nnThe NIS was used to identify patients>90 year

ROSIGLITAZONE ALTERS CHARACTERISTICS OF ISCHEMIC VENTRICULAR FIBRILLATION IN PIGS

Background: Despite favorable metabolic effects of anti-diabetic thiazolidinedione drugs (TZDs), it is uncertain if TZDs reduce cardiovascular mortality. We previously showed that TZDs exert an off-target effect to block cardiac ATP-sensitive potassium (KATP) channels and may increase propensity for ischemic ventricular fibrillation (VF) in pigs. In this study, we tested the hypothesis that a TZD drug, rosiglitazone (ROSI), alters spectral characteristics of ischemic VF through effects on KATP channels.