Therapy of heart failure

The incidence and prevalence of heart failure is on the rise. It has become the single most expensive health care item in the United States and the number one discharge diagnosis in the elderly. The goals of therapy include both prevention and treatment of heart failure. In recent years research studies and randomized clinical trials have revolutionized the understanding of the pathophysiology and treatment of this disease. This article focuses on the medical management of chronic systolic heart failure based on the pathophysiology of the disease. Systolic heart failure is characterized by a decrease in left ventricular function and cardiac output, which results in activation of several neurohormonal compensatory systems. The long term effects of this neurohormonal activation leads to further deterioration of cardiac function. The use of hydralazine and nitrates to reduce the systemic vascular resistance was the first to show an improvement in mortality and morbidity. Then angiotensin converting enzyme inhibitors, by inhibiting the renin angiotensin system, demonstrated a greater improvement in mortality and morbidity. More recently the inhibition of the sympathetic stimulation with beta-blockers has been shown to have an additive effect on morbidity and mortality in combination with angiotensin-converting enzyme inhibitors. Digoxin and diuretics remain important for improving symptoms and decreasing hospitalizations but have not been shown to decrease mortality. The most recent advance in the treatment of cardiac failure is the demonstration that the aldosterone antagonists, spironolactone decreases morbidity and mortality.     

Interventional Cardiovascular Pharmacotherapy

In the last decade, a variety of novel anticoagulant and antiplatelet agents that improve outcomes in patients undergoing percutaneous coronary revascularization have emerged. During the next decade, continued refinements in catheter-based device technology should lead to further increases in the number of interventional procedures. The use of optimal antithrombotic strategies is pivotal in reducing adverse events among patients undergoing percutaneous coronary intervention (PCI). Our purpose is to review the current evidence regarding the efficacy of available adjunctive anticoagulant and antiplatelet agents in treating patients undergoing percutaneous coronary revascularization. It should be borne in mind that patients undergoing PCI in the midst of an acute coronary event require a different level of coagulation and platelet aggregation inhibition than low-risk patients undergoing elective PCI for stable angina pectoris. Similarly, generalizing antithrombotic regimen safety data to a wide spectrum of catheter-based therapeutic devices should be avoided. A level of anticoagulation that is safe and effective for angioplasty and stent placement may not be sufficient for devices with longer intracoronary dwell times such as brachytherapy catheters. In light of current evidence, activated clotting times should be targeted in the 200- to 250-second range during elective PCI and in the 250- to 300-second range when intervening on a higher-risk lesion, such as one with an angiographically visible thrombus or in patients presenting with an acute coronary syndrome (ACS).Low-dose enoxaparin sodium is an attractive antithrombin strategy in PCI because it is intrinsically adjusted for renal function, age, and concomitant glycoprotein (GP) IIb/IIIa antagonist use. Other low-molecular weight heparins have also been studied as adjunctive anticoagulants during cardiac catheterization. For example, in pilot studies, dalteparin sodium was shown to have a good safety profile when used alone or in combination with abciximab during PCI.A wealth of data supports the use of a GP IIb/IIIa antagonist in patients presenting with ACS, especially those with high-risk features such as elevated cardiac markers; the systematic use of GP IIb/IIIa inhibitors in this population is therefore encouraged. Overall, the use of GP IIb/IIIa inhibitors reduces the incidence of thrombotic complications following PCI, is associated with a mortality benefit, but has no impact on the risk of restenosis.     

Biochemical study on the hypoglycemic effects of onion and garlic in alloxan-induced diabetic rats.

The present study was carried out to investigate the effects of onion (Allium cepa Linn) and garlic (Allium sativum Linn) juices on biochemical parameters, enzyme activities and lipid peroxidation in alloxan-induced diabetic rats. Alloxan was administered as a single dose (120 mg/kg BW) to induce diabetes. A dose of 1 ml of either onion or garlic juices/100 g body weight (equivalent to 0.4 g/100 g BW) was orally administered daily to alloxan-diabetic rats for four weeks. The levels of glucose, urea, creatinine and bilirubin were significantly (p<0.05) increased in plasma of alloxan-diabetic rats compared to the control group. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and alkaline and acid phosphatases (AlP, AcP) activities were significantly (p<0.05) increased in plasma and testes of alloxan-diabetic rats, while these activities were decreased in liver compared with the control group. Brain LDH was significantly (p<0.05) increased. The concentration of thiobarbituric acid reactive substances and the activity of glutathione S-transferase in plasma, liver, testes, brain, and kidney were increased in alloxan-diabetic rats. Treatment of the diabetic rats with repeated doses of either garlic or onion juices could restore the changes of the above parameters to their normal levels. The present results showed that garlic and onion juices exerted antioxidant and antihyperglycemic effects and consequently may alleviate liver and renal damage caused by alloxan-induced diabetes.     

Functional and anatomical evaluation of the effect of nepafenac in prevention of macular edema after phacoemulsification in diabetic patients

AIM: To evaluate the effect of prophylactic administration of nepafenac in prevention of macular edema occurring in diabetic patients after phacoemulsification and to investigate the correlation between optical coherence tomography (OCT) foveal thickness and multifocal electroretinogram (MF-ERG) parameters. METHODS: The study included two groups. Group 1 included 50 diabetic patients with senile cataract (50 eyes, 30 females, 20 males, aged 55±7y) received nepafenac 0.1% eye drop. Group 2 included another 50 diabetic patients with senile cataract (50 eyes, 22 female, 28 males, aged 53.8±8y) did not receive nepafenac. All patients were followed up for 3mo postoperatively. OCT and MF-ERG were done preoperative and at 1wk, 1, 2 and 3mo. RESULTS: The mean foveal thickness was statistically significantly lower in Group 1. Five eyes in Group 2 developed clinical cystoid macular oedema (CMO) (10%), and no patients in Group 1 developed central macular thickening more than 50 μm. There were insignificant differences in MF-ERG amplitudes and latencies between the two groups except in the five eyes that developed CMO, there statistically significant reduction of MF-ERG amplitude with increase in foveal thickness. CONCLUSION: Perioperative nepafenac reduces the incidence of CMO following uncomplicated phacoemulsification significantly. Nepafenac has no side effects.     

A comprehensive non‐invasive framework for automated evaluation of acute renal transplant rejection using DCE‐MRI

The objective was to develop a novel and automated comprehensive framework for the non‐invasive identification and classification of kidney non‐rejection and acute rejection transplants using 2D dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). The proposed approach consists of four steps. First, kidney objects are segmented from the surrounding structures with a geometric deformable model. Second, a non‐rigid registration approach is employed to account for any local kidney deformation. In the third step, the cortex of the kidney is extracted in order to determine dynamic agent delivery, since it is the cortex that is primarily affected by the perfusion deficits that underlie the pathophysiology of acute rejection. Finally, we use an analytical function‐based model to fit the dynamic contrast agent kinetic curves in order to determine possible rejection candidates. Five features that map the data from the original data space to the feature space are chosen with a k‐nearest‐neighbor (KNN) classifier to distinguish between acute rejection and non‐rejection transplants. Our study includes 50 transplant patients divided into two groups: 27 patients with stable kidney function and the remainder with impaired kidney function. All of the patients underwent DCE‐MRI, while the patients in the impaired group also underwent ultrasound‐guided fine needle biopsy. We extracted the kidney objects and the renal cortex from DCE‐MRI for accurate medical evaluation with an accuracy of 0.97 ± 0.02 and 0.90 ± 0.03, respectively, using the Dice similarity metric. In a cohort of 50 participants, our framework classified all cases correctly (100%) as rejection or non‐rejection transplant candidates, which is comparable to the gold standard of biopsy but without the associated deleterious side‐effects. Both the 95% confidence interval (CI) statistic and the receiver operating characteristic (ROC) analysis document the ability to separate rejection and non‐rejection groups. The average plateau (AP) signal magnitude and the gamma‐variate model functional parameter α have the best individual discriminating characteristics. Copyright © 2013 John Wiley & Sons, Ltd.     

Could severity of mitral annular calcification predict other left sided structural or functional abnormalities?

ObjectiveThe prognostic value of MAC severity is important not only because it shares a common risk factors with vascular atherosclerotic changes but also through increasing the cardiovascular morbidity and mortality. This study was conducted in order to evaluate association between severity of MAC and left sided echocardiographic abnormalities mainly left sided valvular abnormalities as well as left atrial systolic and diastolic functional abnormalities.MethodsWe prospectively obtained 12-leads electrocardiograms and transthoracic echocardiograms (TTE) on patients scheduled for non-emergent echocardiographic assessment at tertiary care hospital. MAC was graded as mild, moderate and severe. LA linear dimensions, LA filling and emptying volumes and left atrium ejection fraction were done specifically in addition to commonly measured TTE parameters.ResultsFrom the 80 patients considered for the study, 47 patients had mild MAC, 29 patients had moderate MAC and 4 patients had severe MAC. Valvular affection through echo-doppler assessment that included mainly mitral stenosis, mitral incompetence, aortic sclerosis as well as aortic incompetence showed a highly significant statistical difference (p-values 0.00, 0.00, 0.00 and 0.00 respectively). There was a highly significant statistical difference between patients with different degrees of MAC and LA linear dimension (p-value 0.00), all LA filling and emptying volumes as well as LA ejection fractions with the exception of LA passive emptying volume and LA passive ejection fraction was insignificant.ConclusionsThere is a direct proportionate relationship between severity of MAC and associated left sided valvular affection, increase LA linear dimension as well as lower overall LA function.