KV Sahasranam MD, DM, FACC
Baby Memorial Hospital, Kozhikode, Kerala, India. PIN:
673004
Address for Correspondence: Prof. Dr. KV Sahasranam MD,
DM, FACC, Senior Consultant Cardiologist, Baby Memorial
Hospital, Kozhikode, Kerala, India. PIN: 673004. E-mail:
ramani2911@gmail.com
Keywords: heart failure, management
"The longer you look back, the further you can look
forward". - Sir Winston Churchill
The simplest definition of heart failure is "A condition in
which the heart fails to discharge its contents
adequately"[1]. Even though the prevalence is quoted at 4 - 20
/ 1000 population, in the elderly above 65 years, the figures
may exceed 100/1000. After the age of 45, it is found that the
relative incidence of heart failure which is approximately 1 -
5 /1000, double for each decade of life. As modernization
increases and healthcare improves over the years, the
prevalence of heart failure also increases due to the increase
in longevity of individuals.
The oldest case of heart failure in a mummy has been
identified in the remains of an Egyptian mummy - Nebiri, who
lived 3500 years ago in Egypt [2]. Atherosclerosis also has
been described in ancient Egyptian mummies that lived 3500
years ago. One study where 52 mummies had whole body
multislice computed tomography done showed definite evidence
of atherosclerosis or calcification of the coronary arteries.
These mummies belonged to the BC 1550 - 1580 period [3].
Some of the cardiac glosses of the Ebers papyrus (1536-1550
BC) seem to have described one of the earliest documented
observations of the syndrome of heart failure [4].
Hippocrates (460-370 BC) also had described cases of heart
failure as dropsy and dyspnea. Though this was not specific
for heart failure, his description of heart failure with
cardiac cirrhosis is classical [5].
A twelfth century description of heart failure from "The
Alexiad", a biography of the Byzantine Emperor Alexis I
Comnenus written by his daughter Anna Comnena describes the
symptoms of heart failure lucidly - "Every day it grew worse,
attacking him no longer at intervals, but relentlessly, with
no interruptions. He was unable to lie on either side, so weak
that every breath involved great effort. His condition was
serious, for never for one moment could he breathe freely he
was forced to sit upright in order to breathe at all: if by
chance, he did lie on his back or side, the suffocation was
awful to breathe in or exhale even a tiny stream of air became
impossible" [6].
Blood letting, either by venesection or leeches
(hirudinotherapy) was a popular treatment to alleviate the
symptoms from dropsy associated with heart failure [7]. The
medicinal leech
Hirudo medicinalis was used for this.
This type of treatment with leeches for bloodletting is said
to be known to ancient Egyptians and Greeks. It was also
popular during the middle ages.
In the early 19th century, Reginald Southey who was an English
physician introduced the Southey's tubes or cannula for
draining edema of the limbs. [8].
It was in the year 1785 that William Withering published
his account of 158 patients whom he treated with foxglove.
Withering had noticed that an old woman in Shropsire was using
the drug as a concoction to treat dropsy in some patients.
Withering soon zeroed in on the active ingredient in the
concoction and found that it was the foxglove plant. Thus was
born the era of digitalis treatment of heart failure,
revolutionizing the management of the disease [9].
The treatment of heart failure took a leap forward with the
introduction of organomercuial diuretics in 1920 and Thiazide
diuretics in 1958 [1]. Prior to 1980's the "Non
pharmacological Era" of heart failure management stressed
mainly on lifestyle modification like bed rest, positioning,
restriction of fluids, digitalis and diuretics which were just
coming in to the practice of managing heart failure.
Pharmacological Era of Heart Failure Management
In 1975, beta blockers, Alprenolol and Practolol were reported
to be tried in heart failure [10] ushering in an "Era of
Pharmacological Interventions" in the management of heart
failure. The initial observation of survival with the use of
beta blockers in heart failure was recorded as early as 1979
[11]. But it was only after the publication of the multicenter
randomized trial regarding the benefit of Metoprolol in 1993
were beta blockers officially approved for the management of
chronic congestive heart failure [12]. Soon trials established
the fact that Carvedilol, Metoprolol and Bisoprolol are the
three beta blockers which are effective in reducing mortality
in chronic congestive heart failure.
Concurrently, other studies also were ongoing and the
Vasodilator Heart Failure (ValHeft) trial published in 1986
heralded a new "Era of Neurohumoral interventions" when beta
blockers, Angiotensin Converting Enzyme inhibitors (ACEI) and
mineralocorticoid inhibitors changed the scenario in the
management of heart failure [13]. The publication of the
CONSENSUS study in 1987 was a landmark in the treatment of
heart failure where the emphasis shifted from symptomatic
management to a more rational management based on
pathophysiology.
Soon to follow were the use of Angiotensin Receptor Blockers
(ARB) in the management of heart failure after the publication
of the trial in 2001 [15]. Valsartan, Candesartan, Losartan,
Irbesartan and Telmisartan soon were alternate drugs
available. Though they were superior to placebo, they were not
better than ACE inhibitors in the management of congestive
heart failure. Studies have shown that the use of betablockers
with mineralocorticoid receptor antagonists when added to ACEI
resulted in incremental decreases in the risk of death by
30-35%.
The latest addition to the pharmacological therapy of heart
failure has been the introduction of Angiotensin-Neprilysin
inhibitors (ARNI) in heart failure [16]. The benefit of this
combination was excellent leading to premature stopping of
this trial.
Simultaneously, developments with other inotropic and
vasodilator therapy also occurred with the use in intravenous
Dobutamine [17], Milrinone [18], Nitroglycerine, Sodium
Nitroprusside and Nesiritide [19]. But intravenous inotropes,
unlike vasodilators, fell into disrepute owing to their
increasing side effects like arrhythmogenesis and are hardly
of use today.
A novel mechanism to tackle the heart rate in chronic heart
failure was discovered with the introduction of the I
f
or "funny channel" inhibitor Ivabradine [22]. It reduced the
risk of hospitalization and worsening of heart failure in
patients with stable symptomatic chronic heart failure
with left ventricular ejection fraction of 35% or
less who are in sinus rhythm with a resting heart rate of 70
bpm or more and either are on maximally tolerated doses of
beta blockers or have a contraindication for beta blocker
therapy.
Device Therapies in Heart Failure
The turn of the century saw the dawn of the "Device Era" in
the management of heart failure. Also known as
"Electrophysiologic Intervention" of heart failure, it
includes, pacemakers, Cardiac Resynchronization Therapy
devices (CRT) and Implantable Cardioverter Defibrillators
(ICD).
Cardiac Resynchronisation Therapy (CRT)
The development of mechanical asynchrony as a consequence of
electrical and conduction defects in a failing heart decreases
contractile cardiac performance, prolongs mitral regurgitation
thereby resulting in wasted cardiac work [21]. Restoration of
electrical synchrony could hence restore mechanical synchrony
and reduce mitral regurgitation. This was the basis of CRT.
Cazeau et al in 1994 performed the first biventricular pacing
in a case of dilated cardiomyopathy, successfully increasing
cardiac output and reducing pulmonary artery wedge pressure
[22]. Soon to follow were a series of observational studies
(without a control group) endorsing the improvement in
exercise capacity and quality of life [23]. The MIRACLE Trial
was a randomized double blind trial which showed improvement
in symptoms, quality of life and exercise capacity in the
treated arm of the study [24]. The left ventricular size was
reduced and the ejection fraction reduced.
In 2010, the Heart Failure Society of America (HFSA) laid down
guidelines for CRT therapy in heart failure [25]. The European
Society of Cardiology and the ACC/AHA also emphasized the
importance of devices in the management of heart failure and
published guidelines for the same in 2010 and 2012
respectively.
Implantable Cardiac Defibrillator (ICD)
It was in the 1970's that the first ICD use was reported [26].
The ICD was developed by Dr. Michel Mirowski and Dr. Morton
Mower. Initially, as has happened with most inventions and
discoveries in the past, they were widely criticized by the
medical fraternity for their impractical ideas. But
undeterred, the duo proceeded to develop the ICD and reported
the first implantation in 1973. The initial ICD was very large
needing thoracotomies to implant them. The advances in
technology have miniaturized them so much so that they can now
be implanted like a pacemaker and have an assortment of
sophisticated functions like atrial and ventricular
defibrillation, pacing for tachycardia and bradycardia,
storage of electrograms and biventricular pacing.
The landmark MADIT I and II trials published in 1996 and 2002
showed a remarkable decrease in risk of death in patients with
coronary disease and low ejection fraction [27,28]. Studies of
implantation of ICD in heart failure also showed a substantial
benefit in survival compared to treatment with anti arrhythmic
drugs for the prevention of sudden death due to
arrhythmias. Bardy et al showed that ICD implantation
reduced the risk of death by 23% whereas Amiodarone had no
benefit in prolonging survival in patients with heart failure
[29]. Soon guidelines on device therapy in heart failure were
published by the European Society of Cardiology [30] and the
ACC/AHA [31]. Both the introduction of CRT and ICD has to a
great extent revolutionized the modern management of heart
failure.
Emerging Therapies in Heart Failure
Other newer devices in the management of chronic heart
failure are Ventricular Assist devices like Left, Right and
Biventricular assist devices. Surgical options in the
management of heart failure are revascularization procedures
like Coronary Artery Bypass Surgery, Valvular surgery,
Ventricular restoration and heart transplantation. A
total artificial heart for orthotopic transplantation is being
intensely investigated and offers promises for the future.
Questions arise as to what the future holds for the management
of heart failure. It is well known that the heart is one of
the organs in the body with the minimum chances of
regeneration. The future holds plenty of scope for the use of
stem cells in the management of heart disease and chronic
heart failure. [32]. Improved left ventricular performance and
better exercise tolerance has been shown by intracoronary stem
cell infusion. Also the long term mortality was shown to be
decreased in a non randomized study [33]. However, the use of
stem cells in the treatment of heart failure has not received
widespread acceptance yet.
Gene therapy focuses on improving the function of the existing
myocytes in the heart by altering or influencing the
expression of specific genes and holds promises for the
future. Gene therapy is evolving a viable adjunct to the
treatment of heart failure using mechanical or pharmacological
methods. There are ongoing trials targeting various pathways
for rescuing the failing myocardium. The results have been
encouraging. [34]. The next decade may see the dawn of a new
era of stem cell and gene therapy in the management of chronic
heart failure.
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