Michael Y. Henein

Statins moderate coronary stenoses but not coronary calcification: Results from meta-analyses

INTRODUCTIONnCoronary artery stenoses have been shown in various trials to be moderated by treatment with statins. A similar effect on coronary artery calcification has not been demonstrated. We therefore undertook meta-analyses of trials examining the effect of statin treatment on coronary artery stenoses and coronary artery calcification.nnnMETHODSnLiterature searches identified five controlled trials suitable for inclusion in the analysis of the effect of statins (high dose versus either low dose or placebo) on coronary artery calcification and six trials suitable for inclusion in the analysis of the effect of statins on coronary artery stenoses.nnnRESULTSnAll trials reported substantial and significant reductions in LDL-C with statin treatment which results in net reductions of LDL-C in the CAC and coronary stenoses trials of 1.0 mmol/L and 0.9 mmol/L, respectively. Analysis of the CAC trials did not demonstrate any effect of statins on the progression of calcification. In contrast, in the coronary stenoses trials there was a consistent moderation of stenosis severity progression with statins (p<0.0001).nnnCONCLUSIONSnMeta-analyses of the available trials have demonstrated a significant moderation of coronary stenoses associated with the statin-induced reduction in LDL-C. In contrast, there was no effect on coronary calcification despite a similar reduction in LDL-C levels. This suggests that the pathogenesis of the two conditions may be different, if not in aetiology, then certainly in their development. It further suggests that statin use to moderate arterial calcification is not effective.

Arterial calcification : Friend or foe?

There is a significant relationship between the presence, extent and progression of coronary artery calcification (CAC) and cardiovascular (CV) events and mortality in both CV and renal patients and CAC scoring can provide improved predictive ability over risk factor scoring alone. There is also a close relationship between CAC presence and atherosclerotic plaque burden, with angiography studies showing very high sensitivity but poor specificity of CAC score for predicting obstructive disease. Nevertheless, there are objections to CAC screening because of uncertainties and lack of studies showing improved outcome. Furthermore, histopathology studies indicate that heavily calcified plaque is unlikely to result in a CV event, while the vulnerable plaque tends to be uncalcified or mixed, suggesting that calcification may be protective. This scenario highlights a number of paradoxes, which may indicate that the association between CAC and CV events is spurious, following from the adoption of CAC as a surrogate for high plaque burden, which itself is a surrogate for the presence of vulnerable plaque. Since studies indicate that arterial calcification is a complex, organised and regulated process similar to bone formation, there is no particular reason why it should be a reliable indicator of either the plaque burden or the risk of a future CV event. We suggest that it is time to divorce arterial calcification from atherosclerosis and to view it as a distinct pathology in its own right, albeit one which frequently coexists with atherosclerosis and is related to it for reasons which are not yet fully understood.

The predictive value of arterial and valvular calcification for mortality and cardiovascular events

A review of the predictive ability of arterial and valvular calcification has shown an additive effect of calcification in more than 1 location in predicting mortality and coronary heart disease, with mitral annual calcification being a particularly strong predictor. In individual arteries and valves there is a clear association between calcification presence, extent and progression and future cardiovascular events and mortality in asymptomatic, symptomatic and high risk patients, although adjustment for calcification in other arterial beds generally renders associations non-significant. Furthermore, in acute coronary syndrome, culprit plaque is normally not calcified. This would tend to reduce the validity of calcification as a predictor and suggest that the association with cardiovascular events and mortality may not be causal. The association with stroke is less clear; carotid and intracranial artery calcification show little predictive ability, with symptomatic plaques tending to be uncalcified.

Patterns of cardiac dysfunction coinciding with exertional breathlessness in hypertrophic cardiomyopathy

OBJECTIVEnThe commonest cause of breathlessness in hypertrophic cardiomyopathy (HCM) is left ventricular outflow tract (LVOT) obstruction which improves with its removal. However, in the absence of outflow tract obstruction, as in dilated cardiomyopathy, patients may be limited by similar symptoms, thus suggesting a potential common mechanism for the two conditions. We aimed to assess cardiac function at the time of symptoms in a group of unselected patients with HCM to identify other patterns of cardiac dysfunction which coincide with their breathlessness.nnnMETHODSnWe studied 37 HCM patients (aged 55 ± 15 years, 13 female) with septal thickness >15 mm and 17 controls (aged 58 ± 12 years, 12 female) using Doppler echocardiography, at rest and at peak dobutamine stress. Stress end points were symptoms, >20 mmHg drop in systolic blood pressure, arrhythmia, or maximum dobutamine dosage of 40 μg/kg/min.nnnRESULTSnAt rest: LV systolic function was maintained (EF 68 ± 7 v 76 ± 12%, respectively), LVOT velocity raised (p<0.005), lateral and septal long axis amplitude reduced (p<0.05 and p<0.005, respectively) and dyssynchronous and QRS duration was also broader (p<0.005) in patients compared to controls. At peak stress: Overall LVOT velocities were higher in patients than controls (4.3 ± 1.7 v 1.7 ± 1.0m/s, p<0.005, respectively) due to systolic anterior movement of the mitral valve and mitral regurgitation developing. In the 15 patients who did not develop significant LVOT obstruction (velocity <4m/s), LV ejection time increased and peak systolic amplitude did not increase. In the 10 patients with neither LVOT obstruction nor restrictive filling, QRS duration prolonged by 12 ms (p <0.05), post-ejection shortening worsened and peak systolic amplitude fell (p<0.005). Also, LV ejection time prolonged by 5s/min (p<0.05), filling time failed to increase as it did in controls (p<0.005) and Tei index was higher than controls (p<0.01).nnnCONCLUSIONnExertional breathlessness in HCM is associated with LV outflow tract obstruction and functional mitral regurgitation in almost two thirds of patients. The remaining one third have either resistant restrictive physiology or dyssynchronous cavity at fast heart rate. Despite similar exercise limiting breathlessness in the three groups, means of management should be quite different.

Non-invasive imaging in detecting myocardial viability: Myocardial function versus perfusion

Coronary artery disease (CAD) is the most prevalent and single most common cause of morbidity and mortality [1] with the resulting left ventricular (LV) dysfunction an important complication. The distinction between viable and non-viable myocardium in patients with LV dysfunction is a clinically important issue among possible candidates for myocardial revascularization. Several available non-invasive techniques are used to detect and assess ischemia and myocardial viability. These techniques include echocardiography, radionuclide images, cardiac magnetic resonance imaging and recently myocardial computed tomography perfusion imaging. This review aims to distinguish between the available non-invasive imaging techniques in detecting signs of functional and perfusion viability and identify those which have the most clinical relevance in detecting myocardial viability in patients with CAD and chronic ischemic LV dysfunction. The most current available studies showed that both myocardial perfusion and function based on non-invasive imaging have high sensitivity with however wide range of specificity for detecting myocardial viability. Both perfusion and function imaging modalities provide complementary information about myocardial viability and no optimum single imaging technique exists that can provide very accurate diagnostic and prognostic viability assessment. The weight of the body of evidence suggested that non-invasive imaging can help in guiding therapeutic decision making in patients with LV dysfunction.

Echocardiography in Heart Failure

It is generally accepted that Doppler echocardiography is the mainstay investigation for the diagnosis and management of patients with heart failure. Its noninvasive nature makes it patient friendly as well as a unique tool for repeat studies during various stages of the disease process. It provides detailed information, with high temporal resolution, on cardiac structure and function, which guide clinicians to the optimum management plan. Even if resting information fails to explain the patient’s symptoms, stress echo findings usually provide accurate explanation and guide toward direct management. We hereby discuss the use of echocardiography in heart failure in detail.

Right Heart Failure

Cardiac output is determined by the efficient left and right ventricular performance; therefore, one should always see the right ventricle as an important integral part of the overall cardiac pump function. A strong evidence supporting the role of the right ventricle in determining exercise tolerance as well as clinical outcome in patients with heart failure exists.