1. A 78-year-old woman is admitted to hospital with nausea, abdominal pain,
constipation and low mood with generalised musculoskeletal pain and
weakness. On examination she appears dehydrated.Blood tests demonstrate
a marked electrolyte abnormality.
Which of the following is most likely to be seen on her ECG?
a. Lengthening of the PR interval
b. Shortening of the QT interval
c. T wave inversion
d. Torsades de pointes
e. U waves
The correct answer is 'shortening of the QT interval'. The cluster of signs and
symptoms being described here is typical of hypercalcaemia - 'stones, bones, groans
and psychiatric moans'. This patient will most likely have been commenced on
intravenous fluids and, depending on severity, a bisphosphonate. The most
commonly seen ECG change in hypercalcaemia is shortening of the QT interval.
Lengthening of the PR interval may be seen in abnormalities with potassium levels.
Higher levels of potassium lead to progressive paralysis of the atria, lengthening the
PR interval. Severe hypokalaemia may also cause this change. This is not usually
seen with hypercalcaemia.
T wave inversion is seen in a number of problems, including hypokalaemia. It is not,
however, typically associated with hypercalcaemia.
Torsades de pointes may rarely be seen in hypocalcaemia, not hypercalcaemia. It is
more commonly associated with hypokalaemia and hypomagnesaemia.
U waves are small deflections immediately following the T wave and usually in the
same direction. They are most commonly seen with bradycardia and severe
hypokalaemia. There is a rarer association with hypocalcaemia - not hypercalcaemia.
Hypercalcaemia: features
Features
● 'bones, stones, groans and psychic moans'
● corneal calcification
● shortened QT interval on ECG
● hypertension
,2. An obese 45-year-old male, with known hyperlipidaemia and peripheral vascular
disease, presents with a right parietal ischaemic stroke. He reports trouble sleeping
and laying flat at night that began after a flu-like illness 3 months ago, and reports
some exertional dyspnoea. Which of the following investigations are most likely to
find the cause of the stroke?
a. Echocardiogram
b. CT brain with angiograph
c. Magnetic resonance imaging / Magnetic resonance angiography(MRI/MRA)
d. Carotid doppler of carotid vessels
e. CT Chest with contrast
The underlying diagnosis is a viral myocarditis precipitating a dilated
cardiomyopathy and causing a cardioembolic stroke. Previously, the enteroviruses
(including coxsackievirus) were the most common identified viruses. Currently,
parvovirus B-19 and human herpes virus 6 are considered the most common causes
of viral myocarditis. The echo may show reduced left ventricular ejection fraction,
myocardial dyssynchrony (myocardial segments contract at different points in time),
thinning of the left ventricular wall and a dilated left ventricle. Trouble sleeping and
laying flat at night and the exertional dyspnoea after a flu-like illness are key features
suggestive of a viral myocarditis.
CT brain and MRI/MRA will show the effect of the stroke, and not the cause. Carotid
doppler ultrasonography of the carotids will not show the cause, as the cause is
cardioembolic stroke.
Dilated cardiomyopathy
Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy,
accounting for 90% of cases.
Causes:
● idiopathic: the most common cause
● myocarditis: e.g. Coxsackie B, HIV, diphtheria, Chagas disease
● ischaemic heart disease
● peripartum
● hypertension
● iatrogenic: e.g. doxorubicin
, ● substance abuse: e.g. alcohol, cocaine
● inherited: either a familial genetic predisposition to DCM or a specific
syndrome e.g. Duchenne muscular dystrophy
○ around a third of patients with DCM are thought to have a genetic
predisposition
○ a large number of heterogeneous defects have been identified
○ the majority of defects are inherited in an autosomal dominant fashion
although other patterns of inheritance are seen
● infiltrative e.g. haemochromatosis, sarcoidosis
+ these causes may also lead to restrictive cardiomyopathy
● nutritional e.g. wet beriberi (thiamine deficiency)
Pathophysiology
● dilated heart leading to predominately systolic dysfunction
● all 4 chambers are dilated, but the left ventricle more so than right ventricle
● eccentric hypertrophy (sarcomeres added in series) is seen
Features
● classic findings of heart failure
● systolic murmur: stretching of the valves may result in mitral and tricuspid
regurgitation
● S3
● 'balloon' appearance of the heart on the chest x-ray
, 3. The neprilysin inhibitor, sacubitril, in combination with the angiotensin II receptor
blocker, valsartan, has been shown to reduce mortality, reduce hospitalisations and
improve symptoms in comparison to enalapril in the treatment of heart failure with
reduced ejection fraction. What is its mechanism of action in heart failure?
a. Improves myocardial contraction
b. Prevents the degradation of natriuretic peptides such as BNP and ANP
c. Reduces heart rate
d. Multiple inhibition of renin, angiotensinogen and aldosterone
e. Inhibition of vasopressin release therefore promoting diuresis
The correct answer is prevents the degradation of natriuretic peptides such as BNP
and ANP.
The natriuretic peptide system regulates the detrimental effects of the upregulation
of the renin-angiotensinogen-aldosterone system (RAAS) which occurs in heart
failure. Sodium and water retention and vasoconstriction caused by activation of the
RAAS, sympathetic nervous system and the action of vasopressin, lead to increased
ventricular preload and afterload and elevated wall stress which in turn lead to
production of BNP. BNP acts to promote natriuresis and vasodilation. Atrial stretch
leads to the production of ANP which has similar biological properties to BNP. Two
strategies have been employed to try and improve outcomes in heart failure via
modulation of this pathway. The first is the administration of exogenous natriuretic
peptides. Nesiritide, a recombinant human BNP, initially showed promising beneficial
effects on haemodynamics and natriuresis in patients with HF. However, in a
large-scale randomised controlled trial, it failed to improve outcomes though it did
improve dyspnoea. The second strategy is to inhibit the breakdown of natriuretic
peptides. ANP & BNP are inactivated by a membrane bound endopeptidase,
neprilysin, which is found in a number of tissues but in especially high
concentrations in the kidney. This led to the development of the neprilysin inhibitor,
sacubitril. Given in combination with the angiotensin II receptor blocker, valsartan, it
has been shown to reduce mortality, reduce hospitalisations and improve symptoms
in comparison to enalapril in the treatment of heart failure with reduced ejection
fraction.
Chronic heart failure: drug management
constipation and low mood with generalised musculoskeletal pain and
weakness. On examination she appears dehydrated.Blood tests demonstrate
a marked electrolyte abnormality.
Which of the following is most likely to be seen on her ECG?
a. Lengthening of the PR interval
b. Shortening of the QT interval
c. T wave inversion
d. Torsades de pointes
e. U waves
The correct answer is 'shortening of the QT interval'. The cluster of signs and
symptoms being described here is typical of hypercalcaemia - 'stones, bones, groans
and psychiatric moans'. This patient will most likely have been commenced on
intravenous fluids and, depending on severity, a bisphosphonate. The most
commonly seen ECG change in hypercalcaemia is shortening of the QT interval.
Lengthening of the PR interval may be seen in abnormalities with potassium levels.
Higher levels of potassium lead to progressive paralysis of the atria, lengthening the
PR interval. Severe hypokalaemia may also cause this change. This is not usually
seen with hypercalcaemia.
T wave inversion is seen in a number of problems, including hypokalaemia. It is not,
however, typically associated with hypercalcaemia.
Torsades de pointes may rarely be seen in hypocalcaemia, not hypercalcaemia. It is
more commonly associated with hypokalaemia and hypomagnesaemia.
U waves are small deflections immediately following the T wave and usually in the
same direction. They are most commonly seen with bradycardia and severe
hypokalaemia. There is a rarer association with hypocalcaemia - not hypercalcaemia.
Hypercalcaemia: features
Features
● 'bones, stones, groans and psychic moans'
● corneal calcification
● shortened QT interval on ECG
● hypertension
,2. An obese 45-year-old male, with known hyperlipidaemia and peripheral vascular
disease, presents with a right parietal ischaemic stroke. He reports trouble sleeping
and laying flat at night that began after a flu-like illness 3 months ago, and reports
some exertional dyspnoea. Which of the following investigations are most likely to
find the cause of the stroke?
a. Echocardiogram
b. CT brain with angiograph
c. Magnetic resonance imaging / Magnetic resonance angiography(MRI/MRA)
d. Carotid doppler of carotid vessels
e. CT Chest with contrast
The underlying diagnosis is a viral myocarditis precipitating a dilated
cardiomyopathy and causing a cardioembolic stroke. Previously, the enteroviruses
(including coxsackievirus) were the most common identified viruses. Currently,
parvovirus B-19 and human herpes virus 6 are considered the most common causes
of viral myocarditis. The echo may show reduced left ventricular ejection fraction,
myocardial dyssynchrony (myocardial segments contract at different points in time),
thinning of the left ventricular wall and a dilated left ventricle. Trouble sleeping and
laying flat at night and the exertional dyspnoea after a flu-like illness are key features
suggestive of a viral myocarditis.
CT brain and MRI/MRA will show the effect of the stroke, and not the cause. Carotid
doppler ultrasonography of the carotids will not show the cause, as the cause is
cardioembolic stroke.
Dilated cardiomyopathy
Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy,
accounting for 90% of cases.
Causes:
● idiopathic: the most common cause
● myocarditis: e.g. Coxsackie B, HIV, diphtheria, Chagas disease
● ischaemic heart disease
● peripartum
● hypertension
● iatrogenic: e.g. doxorubicin
, ● substance abuse: e.g. alcohol, cocaine
● inherited: either a familial genetic predisposition to DCM or a specific
syndrome e.g. Duchenne muscular dystrophy
○ around a third of patients with DCM are thought to have a genetic
predisposition
○ a large number of heterogeneous defects have been identified
○ the majority of defects are inherited in an autosomal dominant fashion
although other patterns of inheritance are seen
● infiltrative e.g. haemochromatosis, sarcoidosis
+ these causes may also lead to restrictive cardiomyopathy
● nutritional e.g. wet beriberi (thiamine deficiency)
Pathophysiology
● dilated heart leading to predominately systolic dysfunction
● all 4 chambers are dilated, but the left ventricle more so than right ventricle
● eccentric hypertrophy (sarcomeres added in series) is seen
Features
● classic findings of heart failure
● systolic murmur: stretching of the valves may result in mitral and tricuspid
regurgitation
● S3
● 'balloon' appearance of the heart on the chest x-ray
, 3. The neprilysin inhibitor, sacubitril, in combination with the angiotensin II receptor
blocker, valsartan, has been shown to reduce mortality, reduce hospitalisations and
improve symptoms in comparison to enalapril in the treatment of heart failure with
reduced ejection fraction. What is its mechanism of action in heart failure?
a. Improves myocardial contraction
b. Prevents the degradation of natriuretic peptides such as BNP and ANP
c. Reduces heart rate
d. Multiple inhibition of renin, angiotensinogen and aldosterone
e. Inhibition of vasopressin release therefore promoting diuresis
The correct answer is prevents the degradation of natriuretic peptides such as BNP
and ANP.
The natriuretic peptide system regulates the detrimental effects of the upregulation
of the renin-angiotensinogen-aldosterone system (RAAS) which occurs in heart
failure. Sodium and water retention and vasoconstriction caused by activation of the
RAAS, sympathetic nervous system and the action of vasopressin, lead to increased
ventricular preload and afterload and elevated wall stress which in turn lead to
production of BNP. BNP acts to promote natriuresis and vasodilation. Atrial stretch
leads to the production of ANP which has similar biological properties to BNP. Two
strategies have been employed to try and improve outcomes in heart failure via
modulation of this pathway. The first is the administration of exogenous natriuretic
peptides. Nesiritide, a recombinant human BNP, initially showed promising beneficial
effects on haemodynamics and natriuresis in patients with HF. However, in a
large-scale randomised controlled trial, it failed to improve outcomes though it did
improve dyspnoea. The second strategy is to inhibit the breakdown of natriuretic
peptides. ANP & BNP are inactivated by a membrane bound endopeptidase,
neprilysin, which is found in a number of tissues but in especially high
concentrations in the kidney. This led to the development of the neprilysin inhibitor,
sacubitril. Given in combination with the angiotensin II receptor blocker, valsartan, it
has been shown to reduce mortality, reduce hospitalisations and improve symptoms
in comparison to enalapril in the treatment of heart failure with reduced ejection
fraction.
Chronic heart failure: drug management
