The Cardiac Cycle-Extra Reading

Question 1

Cheng, Circulation, 2011

Answer 1

1. Dynamic Left Ventricular Remodelling Occurs Naturally Over the Lifecourse
   - suggests that LV remodelling occurs naturally as we age but that extra factors can make this worse
   - the extent at which normal remodelling eventually leads to LV dysfunction is unclear
   - the most common form of LV remodelling is INCREASED LV MASS
   - LV mass increases are accelerated by obesity, hypertension and diabetes
   - the normal remodelling pattern seen with ageing is CONCENTRIC
   - rate of relative remodelling is faster in women because they see reduced cardiomyocyte dropout
   - recent data have linked: dyslipidaemia, physical inactivity and sleep apnoea with heart failure
   - family history of HF means greater odds of ECCENTRIC remodelling
2. Extra-Cardiac Predictors of Heart Failure Risk
   - suggests that there may be other body systems that can predict risk of heart failure
   - Adverse LV remodelling and cardiac dysfunction have been associated with pulmonary airflow obstruction and decreased renal function
   - Cross-sectional studies have associated abnormalities in serum creatinine, albumin and haemoglobin with increased risk of heart failure or worse outcomes
   - Renal dysfunction and anaemia particularly associated with HFREF (systolic dysfunction)
   - Pulmonary obstructive disease particular associated with HFPEF (diastolic dysfunction)
   - this evidence underscores the notion that progression to heart failure is likely a multi-organ process
3. Biomarkers of Left Ventricular Remodelling and Heart Failure
   - suggests that biological molecules can be used to identify that remodelling and heart failure is a risk or taking place
   - CRP, Fibrinogen and Plasminogen Inhibitors have all been associated with remodelling
   - RAAS and BNP are both predictors for heart failure
   - Recent studies have identified novel biomarks: Subclinical LV disease identified by increased levels of Adiponectin, Heart failure risk detected by Growth Differentiation Factor-15-could we use these to identify those at risk and treat them early?
   - Lots of research is currently being done to find common genetic variants that may underlie LV remodelling and therefore may provide a future therapeutic target

Question 2

Cubbon, Circulation, 2011

Answer 2

• Involved a comparison of 2 studies, 1993-1995 versus 2006-2009
• the 2006 study had 72% more people taking beta blockers with a simultaneous reduction in mortality from 12 to 8% between studies and a reduction in sudden death from 33 to 13%. So the reduction in sudden death was VERY SIGNIFICANT
• measurements of cardiac remodelling and electrical stability have also improved significantly in 15 years
• appears that ‘optimal therapy’ may have had a major impact on outcomes and symptoms in heart failure
• The MERIT-HF study also shows a 40% decline in sudden death with B-blockers
• a major electric feature in sudden death is ELECTRIC INHOMOGENEITY-electrical impulses not all combining as one-they become random
• BUT b-blockers aren’t so effective that they improve outcomes completely so new therapeutic targets are still needed

Question 3

Cubbon, Diabetes & Vasc Res, 2013

Answer 3

-Diabetics shown to have HF of an ischaemic aetiology and worse symptoms
-Diabetes associated with double crude and adjusted risk of total and cardiovascular mortality despite administration of optimal medical therapy
-in spite of advances in the management of HF, diabetes remains a major adverse prognostic feature despite patients receiving contemporary evidence based therapies
-Prevalence of diabetes in HF thought to be in excess of 25% so it is a major issue
-Diabetes impacts similarly upon mortality in ischaemic and non-ischaemic HF
-Multivariate analyses suggest that alterations in recognised prognostic factors such as renal function do not significantly account for diabetes detrimental effects
-Some studies have suggested that diabetes exerts its effects through diabetic cardiomyopathy caused by cardiac GLUCOTOXICITY-excess glucose causes problems to cardiac myocytes
^the effects of diabetes are not purely because of coronary artery disease causing ischaemia
-if the pattern of improving heart failure mortality is to continue to increase, then targeting the phenotype of diabetics appears increasingly necessary

Question 4

Sliwa, Circulation, 2011

Answer 4

-Much of the global CVD is borne by low-to-middle income countries-these countries see 80% of CVD deaths
-economic constraints limit the ability of these countries to deal with it
-it is predicted that non-communicable forms of CVD will be the leading cause of death and disability globally by 2020
-Hypertension is a highly modifiable antecedent for CVD yet is responsible for more deaths worldwide than any other factor
-differences in urban versus rural BP’s in low income countries represents the various stages of epidemiologial transition
-in low income countries the effects of CVD occur at a much younger age
-often risk predictor tools do not fully quantify risk as they are based on one ethnicity e.g Framingham is predominantly white-all ethnicities pose different risk of CVD
-So developing accurate ethnic and region specific tools to quantify CVD risk is a priority
-On a population based level, studies have shown that even modest reductions to dietary salt may substantially decrease CV events
-Epidemiological transition has contributed to the rise in CVD and will no doubt cause a sustained epidemic of non-communicable CVD
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