Why is there a need to shift from CHADS2 score to the new evolved CHA2DS2-VASc score? Which one is better predictor of stroke risk?

The CHADS₂ scoring system is used to stratify stroke risk in patients with nonvalvular atrial fibrillation. Guidelines (Circulation 2006; ) recommend aspirin for patients with CHADS₂ scores of 0 (low risk), warfarin or aspirin for patients with scores of 1 (intermediate risk), and warfarin for patients with scores of ≥2 (high risk). CHADS₂, however, classifies many patients as intermediate risk, and clinicians struggle with committing these patients to long-term warfarin anticoagulation. In this study involving 74,000 patients with nonvalvular atrial fibrillation, Danish investigators compared CHADS₂ with a new system, CHA₂DS₂-VASc. CHA₂DS₂-VASc also classifies patients with scores of 0 as low risk, 1 as intermediate risk, and ≥2 as high risk .

Of 16,000 patients in the low-risk CHADS₂ category, 40% were categorized as intermediate risk and 22% as high risk by CHA₂DS₂-VASc. Of 24,000 patients categorized by CHADS₂ as intermediate risk, 93% were categorized as high risk by CHA₂DS₂-VASc. The 1-year event rate of hospital admission and death due to thromboembolism (e.g., stroke) per 100 person-years was 1.7, 4.8, and 12.3 for patients with low-, intermediate-, and high-risk CHADS₂ scores and 0.8, 2.0, and 8.8 for patients with low-, intermediate-, and high-risk CHA₂DS₂-VASc scores. Similar patterns were found during 5 to 10 years of follow-up. For both scoring systems and all risk categories, the estimated event rate was lower in patients treated with vitamin K antagonists (e.g., warfarin), except for patients with CHA₂DS₂-VASc scores of 0, in whom the event rate was unchanged.

Simple clinical risk score is required to help assess the risk of stroke in patients with atrial fibrillation. Atrial fibrillation increases the risk of stroke but this risk is not homogenous and depends on the presence of various stroke risk factors; hence, there isn’t one size which fits all. The older CHADS2 score which was described in 2001 includes five common stroke risk factors seen in non-warfarin arm in the historical trials. However in these trials the patients were not truly representative, because they only randomized <10% of the patients screened . Many of the stroke risk factors that we see in routine practice are not recorded properly or they are inadequately defined . hence we extended this in 2009 , including common risk factors that we see in our practice , including those seen in large observational trials . CHADS2 and CHA2DS2-VASc have 5 common risk factors, but why CHA2DS2-VASc is particularly good is because it reliably identifies patients at truly low risk of ischemic stroke; and these truly low risk are CHA2Ds2-VASc of zero in men and CHA2Ds2-VASc of one in females. These patients who are at truly low risk do not need any antithrombotic therapies. The next step is to offer anti-thrombotic therapy to those who have one or more stroke risk factors, in other words a CHA2DS2-VASc score of one in men and CHA2SS2-VASc of two in women and it really doesn’t matter whether the score 1, 2 or 8; we need to offer anti-thrombotic therapy to these patients, if we are serious about stroke prevention.

Final message

CHA₂DS₂-VASc is better than CHADS₂ at predicting which patients with nonvalvular atrial fibrillation are at high risk for thromboembolism. CHA₂DS₂-VASc also appears to be better at predicting which patients are truly at low risk. Broad use of the CHA₂DS₂-VASc scoring system could lower the number of patients treated with vitamin K antagonists who will not benefit from them and raise the number of patients treated with vitamin K antagonists who will.

The CAN-TREAT HFrEF + AF algorithm (Management of concomitant heart failure and reduced ejection fraction and atrial fibrillation)

The essence of Beta-Adrenoceptor Antagonists ( BAA) action in hypertension

The mechanism underlying the essential hypertension is complex and has not yet been completely defined, but it is evident that the activation of the SNS plays an important role in its pathogenesis.

Blockade of beta-AR interferes with the sympathetic regulation of the heart. The HR and contractility are only marginally affected by the BAA administration at rest, but it suppresses prominently the increases in HR and cardiac contractility induced by stress and/or physical exercises. The mechanism of antihypertensive effects of BAAs is like-wise unknown, even though a number of explanations have been proposed to play an essential role. They include the following effects:

-          Reduction of cardiac output

-          Central nervous system effects

-          Renin-angiotensin- aldosterone system inhibition

-          Reduction of plasma volume

-          Peripheral vascular resistance reduction

-          Improvement of vascular compliance

-          Baroreceptor resetting

-          Reduction of pressor response to exercise and stress-related catecholamines.

All these effects are possible proposition of a solution in the pursuit of finding the best treatment for the state of hypertension and its sequelae . 

Classification of cardiogenic shock according to Inotropic/vasopressor and mechanical circulatory support .(What are Pre-Shock, Mild-shock, profound and severe refractory cardiogenic shock ?)

Diabetes mediated vessels toxicity (How high blood sugar can damage the heart's vessels)

High levels of glucose can also damage extracellularly and increase the production of advanced glycosylation end-products (AGEs) in the circulation and on matrix proteins.

The AGEs directly affect cell function, arterial wall stiffness or gene expression of interacting cells. They are ligands for a number of scavenger receptors and the receptor for AGEs (RAGE). As reviewed by Goldberg and Dansky (2006), two lines

of evidence strongly support the theory that AGEs mediate diabetic complications:

-infusions of soluble RAGE, which is presumed to complex AGEs, reduce and stabilise atherosclerotic lesions, and inhibition of AGE formation reduces lesions; and diets enriched in AGEs promote lesions. Beyond AGEs, other mechanisms also link hyperglycaemia to oxidative stress and vascular dysfunction, as well as adverse effects on vascular smooth-muscle cells (Sundell, 2005) (Figure above).

-Finally, hyperglycaemia, at least at the experimental level, has also been shown to induce MMP expression in both endothelial cells and macrophages (Sundell, 2005).

As discussed above, such changes are likely to render the plaque less stable and more susceptible to rupture and hence luminal thrombosis.

Every 10% increase in hypertension treatment would lead to an additional 14,000 deaths annually prevented

Every 10% increase in treatment of elevated low-density lipoprotein cholesterol or aspirin prophylaxis would lead to 8000 deaths prevented in those aged <80 years, per year. Overall, the models suggest that optimal use of all of these interventions could prevent 50,000-100,000 deaths per year in those aged <80 years and 25,000-40,000 deaths per year in those aged <65 years.

2013 and 2014 review of evidence for possible beneficial effects of diuretics and dopamine in patients with decompensated heart failure(HF) and acute kidney injury ( AKI)

2013: Dictum;
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1-Diuretics: 
Loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid) have long been used to “convert” oliguric to nonoliguric AKI. However, it is most likely that oliguric patients who respond to diuretics have a lesser renal injury than those who do not, with an intrinsically more favorable outcome. Moreover there is evidence that “forced” diuresis may exacerbate hypovolemia and renal injury. Once dialysis is required, high dose furosemide does not alter the natural history of AKI.

2- Dopamine:
Dopaminergic agents (dopamine, fenoldopam) potentially confer renal protection by increasing renal blood flow (RBF), diuresis and saliuresis. By activating cyclic AMP they “turn off” the energy-dependent tubular sodium pump and thereby decrease tubular oxygen consumption; increased intratubular urine flow protects against tubular obstruction.In part this may be because there is very wide variability in dopamine pharmacokinetics, i.e. some patients given low dose dopamine may achieve high plasma levels, i.e. in the beta- or alpha-adrenergic range.

Unfortunately, in 2013, there is no compelling evidence that any pharmacologic intervention can definitively prevent or attenuate AKI and alter patient outcome. The current recommendation is that diuretic therapy, low dose dopamine, fenoldopam or atrial natriuretic peptide should NOT be used to prevent or treat AKI. The question is, where do we go from here?

2014 Dictums :
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The Heart Failure clinical Research Network , funded by the National Heart,Lung and blood Institute in the USA , addressed the possibility that low dose dopamine or low- dose nesiritide could safely augment the diuresis induced by loop diuretics in patients with decompensated HF. The trial , in 360 patients , showed no evidence that diuresis or decongestion was enhanced by such combined therapy or that renal function was better preserved .
The is that we should continue what we are doing maintain aggressive approach to diuretic therapy , and perhaps concern ourselves less when renal function transiently worsen .

Final Message :
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Despite more than thirty years of use as a renal vasodilator , low dose dopamine (2Mic/kg/m) has shown no evidence of benefit in patients with acute oliguric renal failure on the basis of its action on dopaminergic renal receptors . In fact , low -dose dopamine can have deleterious effects on hemodynamics ( decreased splanchnic blood flow ) immune function ( inhibition of T-cell lymphocyte function ) and endocrine function ( inhibition of thyroid _stimulating hormone release from the pituitary ) .
For more information read here ;>>>

Greet van den Berghe’s work shows neuroendocrine dysfunction as well as immunological modulation secondary to prolactin

-Reasons Dopamine is Bad

-Does not benefit the renal system

-Induces Natriuresis and Diuresis

-Shunts blood away from outer medulla, which is the region most prone to ischemic damage

-Possible induction of decreased splanchnic perfusion

-Decreases GI Motility

-Impairs ventilatory response to hypoxemia and hypercapnia

-Effects on anterior pituitary–decreases prolactin secretion.