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VOLUME 8 NUMBER 1 • MARCH 2011
CARDIOVASCULAR FOCUS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Females with acute coronary syndrome are
more likely to present with unstable angina
and are less likely to have ST-elevation myocar-
dial infarction. These women are again older
and have diabetes and hypertension more
often than their male counterparts. They also
experience more in-hospital complications
than males.
Females often present atypically with no
chest pain but rather with angina equivalents.
Females are often diagnosed late and are
treated less aggressively than males.
In summary, cardiovascular disease is a
common disease in females, with a high mor-
tality rate. Females often present atypically and
are treated differently from males.
Cardiotoxicity of anti-cancer agents,
particularly in breast cancer
Prevention, monitoring and treatment
‘Not all heart failure is the same’ was the
phrase used by Prof M Ewer from the Univer-
sity of Texas.
There are two types of cancer drug-related
cardiac failure. Type 1 is the typical anthracy-
cline-induced cardiac failure that is related to
cumulative dose and has clear changes on
myocardial biopsy. Type 2 is caused by cellu-
lar dysfunction. The drug trastuzumab is com-
monly responsible for this condition and it is
not associated with cumulative dose.
He also pointed out that one can have acute
cardiotoxicity with anthracyclines. This condi-
tion presents with chest pain, ECG changes
and raised troponins, and is a myopericarditis.
It is however not deemed to be of major clini-
cal importance.
Why is the heart damaged by chemother-
apy? Reasons include that the heart is sensitive
to theeffect of thesedrugs, it has nobiochemical
reserve, and is a terminally differentiated organ.
Prevention is the solution to this problem.
Firstly, one should recognise a high-risk patient.
Features of such a patient include cumulative
dose of anthracycline, previous cardiac disease,
hypertension, and the patient’s age, to name
but a few risk factors.
When treating such a patient, the maxi-
mum cumulative dose of anthracyclines should
be kept below 400 mg/m
2
, and drugs such
as epirubin and mitoxantrone should pref-
erentially be used. Angiotensin converting
enzyme inhibitors and beta-blockers should be
used concomitantly to protect the heart. The
patients should be followed up regularly and
it should be noted that LVEF is not a sensitive
screen for myocardial damage in this situation.
Direct thrombin inhibitors in atrial
fibrillation
This topic was discussed by Prof MD Ezekow-
itz, the principal investigator of the RELY trial.
There are currently three therapeutic groups
that can possibly prevent thrombo-embolism
in atrial fibrillation. These groups include the
anticoagulants, the anti-platelet agents and
the group of non-antithrombotic drugs.
The anticoagulants can be divided into
the coumarins, the factor Xa inhibitors, and
the direct thrombin inhibitors. Multiple trials
including AFASAK, BAATAF, CAFA, SPAF and
SPINAF have proven stroke risk reduction with
warfarin, which is currently the therapeutic
standard.
Xymalagatran (a direct thrombin inhibitor)
was shown to be non-inferior to warfarin in
stroke prevention. This drug, however, caused
a rise in the transaminases and was subse-
quently rejected by the FDA.
Dabigatran was consequently developed
and was shown in the RELY trial to be non-infe-
rior to warfarin and had no liver side effects.
This drug is a direct thrombin inhibitor in a pro-
drug form. It is converted to its active metabo-
lite by tissue esterases and is therapeutic within
two hours of administration.
The drug has a twice-daily dosage and is
mostly (80%) eliminated by the kidney. It has
interaction with proton pump inhibitors and
with drugs metabolised by p-glycoprotein. Side
effects of this drug include dyspepsia.
In the RELY trial, the bleeding complica-
tions were less than with warfarin in the lower
(110-mg) arm and the same as warfarin in
the 150-mg arm. This is therefore a drug that
might change our management of atrial fibril-
lation in the future.
Chronic pulmonary thrombo-
embolic disease
Three to 5% of patients with venous thrombo-
embolism develop chronic thrombo-embolic
pulmonary hypertension. These patients often
have no history of venous thrombo-embolism
and may present similarly to idiopathic pulmo-
nary hypertension. Risk factors for this disease
include: age, prior pulmonary embolism, anti-
cardiolipin antibodies and other pro-throm-
botic states.
The prognosis of this disease is a function of
the pulmonary arterial pressure, with mortality
rising once the pulmonary pressure is higher
than 30 mmHg. Surgery might reverse the pul-
monary hypertension associated with chronic
embolisation.
Pulmonary endarterctomy can be consid-
ered in patients with pulmonary arterial pres-
sures of more than 40 mmHg, a pulmonary
vascular resistance of more than 300, symp-
tomatic individuals with proximal emboli, and
absence of co-morbid disease. This procedure
is done under cardiac bypass and has a mortal-
ity rate of approximately 5%.
Complications of this procedure include:
reperfusion pulmonary oedema, haemorrhagic
pulmonary infarction, residual pulmonary
hypertension and subsequent development of
small-vessel pulmonary hypertension.
This surgery is, however, only indicated for
proximal disease. In distal disease, the goal is
to improve haemodynamics with prostacyclins,
sildenafil or bosentan.
Prof Rubin’s message with this talk was that
one should consider this condition in the dif-
ferential of pulmonary hypertension and that
surgical treatment can have benefit in these
patients.
Cardiovascular care of older adults:
challenging dynamics
Prof N Wenger, in her talk, eluded to the ‘Tsu-
nami of aging’, with 20% of the population
being older than 65 years. Cardiovascular dis-
ease also becomes more prevalent with older
age and has a worse outcome in the elderly. To
complicate matters further, there is a dispro-
portionate age-related therapeutic risk.
Prof Wenger suggested that the following
points should be kept in mind when treating
the elderly. Firstly, what is the outcome desired
for the individual? Is it quality of life, function-
ality, or simply avoiding an adverse outcome?
Secondly, one should evaluate cognition and
pharmacological interactions in the specific
patient when deciding on treatment goals.
Thirdly, adverse drug reactions should be kept
in mind as this makes up 30% of hospital
admissions. Fourthly, one should evaluate one’s
threshold for interventions. Finally, the specific
cardiovascular syndrome should be considered.
There are no simple answers when dealing
with elderly patients. Evaluating these princi-
ples can help the physician to develop a more
rational treatment plan for his/her patient.
Gideon Visagie, Department of Internal
Medicine, University of the Free State,
Bloemfontein
