Adaptive and Maladaptive Hypertrophy:

18th & 19th Century Views

Arnold M. Katz, MD, DMed (Hon.)Visiting Professor of Medicine and Physiology

Dartmouth CollegeHanover, New Hampshire

Professor of Medicine EmeritusUniversity of Connecticut School of Medicine

Farmington, Connecticut

Clinical Picture

Digitalis

Architecture of the Failing Heart

Heart FailureThe 18th & 19th Centuries

“Modern Echoes”

Heart Failure in the 19th Century

The respiration, always short, becomes hurried and laborious on the slightest exertion or mental emotion. The effort of ascending a staircase is particularly distressing. The patient stops abruptly, grasps at the first object that presentsitself and fixing the upper extremities in order to afford a fulcrum for the muscles of respiration, gasps with an aspect of extreme distress.

Incapable of lying down, he is seen for weeks, and even for months together, either reclining in the semi-erect posture supported by pillows, or sitting with the trunk bent forward and the elbows or fore-arms resting on the drawn-up knees. The latter position he assumes when attacked by a paroxysms of dyspnea - sometimes, however, extending the arms against the bed on either side, to afford a firmer fulcrum for the muscles of respiration.

JAMES HOPETreatise on the Diseases

of the Heart and Great Vessels (1832).

Heart Failure in the 19th Century

With eyes widely expanded and starting, eye-brows raised, nostrils dilated, a ghastly and haggard countenance, and the head thrown back at every inspiration, he casts around a hurried, distracted look of horror, of anguish, of supplication: now imploring, in plaintive moans, or quick broken accents, and half-stifled voice, the assistance already often lavished in vain: now upbraiding the impotency of medicine; and now in an agony of despair, drooping his head on his chest, and muttering a fervent invocation for death to put a period to his sufferings.

JAMES HOPETreatise on the Diseases

of the Heart and Great Vessels(1832).

Heart Failure in the 19th Century

For a few hours - perhaps only for a few minutes - he tastes an interval of delicious respite, which cheers him with the hope that the worst is over, and that his recovery is at hand. Soon that hope vanishes. From a slumber fraught with the horrors of a hideous dream, he starts up with a wild exclamation that “it is returning.” At length, after reiterated recurrences of the same attacks, the muscles of respiration, subdued by the efforts of which the instinct of self-preservation alone renders them capable, participate in the general exhaustion, and refuse to perform their function. The patient gasps, sinks, and expires.

JAMES HOPETreatise on the Diseases

of the Heart and Great Vessels. (1832)

Clinical Picture

Digitalis

Architecture of the Failing Heart

Heart FailureThe 18th & 19th Centuries

“[Digitalis] has a power over the motion of the heart, to a degree yet unobserved in any other medicine, [that] may be converted to salutary ends.”

Digitalis purpura

“In the year 1775, my opinion was asked concerning a family recipe for the cure of the dropsy. I was told that it had long been kept a secret by an old woman of Shropshire, who had sometimes made cures after the more regular practitioners had failed… The medicine was composed of some twenty or more herbs; but it was not very difficult for one conversant with these subjects to perceive that the active herb could be no other than Foxglove.”

William Withering An Account of the

Foxglove and Some of its Medical Uses (1785).

Discovery of Digitalis (1785)

A Modern Echo (1997)

The Digitalis Investigation Group. N Engl J Med.1997;336:525-32.

Does Digitalis Improve Prognosis in Heart Failure Patients Who Are in Sinus Rhythm?

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Clinical Picture

Digitalis

Architecture of the Failing Heart

Heart FailureThe 18th & 19th Centuries

Distinguished between enlarged hearts with increased cavity size

(eccentric hypertrophy, dilatation),and with increased wall thickness

(concentric hypertrophy, hypertrophy).

“So varied and so serious are the maladies of the heart that we often discover that it has suffered from an increase in its own bulk, combined with enlargement []. Nor do I mean here by increase of bulk dilatation of the cavities only, but thickening of the fibers and increase of density [that] makesthe base of the heart heavier than is normal...”

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JOANNIS MARIA LANCISIDe Aneurysmatibus, (1728)

Architectural Patterns of Cardiac Enlargement

It is necessary to distinguish two species of [cardiac enlargement]. In the first the heart is enlarged,its [walls] thickened, the energyof its action increased.

J.N. CORVISARTAn Essay on the

Organic Diseases and Lesions of the Heart and

Great Vessels (1812).

Concentric Hypertrophy(“Hypertrophy”)

Eccentric Hypertrophy(“Dilatation”)

Architectural Patterns of Cardiac Enlargement

In the second there is likewiseenlargement, but [also] thinningof the [walls] and diminution ofenergy in the action of the organ.

“Hypertrophy”

Architectural Patterns of Cardiac Enlargement

ConcentricHypertrophy

Normal EccentricHypertrophy

“Dilatation”

Dilatation Weakens the Heart

[That] the heart may be too big for its system is a melancholy fact; for when it becomes relaxed, it enlarges, and as it grows in bulk loses its power…

JOHN BELLThe Anatomy of the Human

Body. 2nd Ed. (1802).

Prognosis is Worse in Dilatation Than Hypertrophy

…the progress of hypertrophy is, in general, slow, tardy and chronic… frequently hypertrophy does not merit on its own account anything more than a secondary consideration.

Réné-Joseph-Hyacinthe Bertin

Treatise on the Diseases of the Heart and Great Vessels

(1833).

…considered in the abstract, dilatation of the heart has the effect to weaken the contractile power of the muscular substance…The muscular fibres lose in strength what they acquire in extent.

Hypertrophy, by adding

to the heart’s power… tends to maintain itself, while dilatation tends downwards.

JOHN MILNER FOTHERGILLThe Heart and Its Diseases. 2nd Ed.

(1879).

Prognosis is Worse in Dilatation Than Hypertrophy

If the dilatation… [has] reached a certain degree, and so far as to induce a morbid dyspnoea, the disease has a marked tendency to increase, unless the circulation be maintained in a state of complete repose.

Dilatation is Progressive

When dilatation has progressed so far as to occasion morbid dyspnea, it has a constant tendency to increase unless the circulation be kept tranquil by a very quiet life and judicious medical treatment. – JAMES HOPE

A Treatise on the Diseases of the Heart and Great Vessels (1832).

– FRANCOIS ARAN Practical Manual of the Diseases

of the Heart and Great Vessels (1843).

A Modern Echo (1985)

Pfeffer JM, Pfeffer MA & Braunwald E. Circ Res. 1985;57:84-95.

Effect of an ACE Inhibitor on “Remodeling”

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What is seen in the arm of blacksmiths, in the legs of dancers, is also seen in the heart… In proportion as the walls are thickened, its contractile power augments.

Hypertrophy is Compensatory

In [valvular heart disease], nature, to enable the heart to perform the additional labour thrown upon it, increases its strength by an addition of muscular fibre, and the heart thus becomes hypertrophied, in accordance with the general law, that muscular fibres become thickened and strengthened when there is additional power required from it.

– DOMINIC JOHN CORRIGAN Edinburgh Med Surg J (1832).

– FRANCOIS ARAN Practical Manual of the Diseases of the Heart and Great Vessels (1843).

A Modern Echo (1968)

Hood WP, Rackley CE & Rolett EL. Am J Cardiol. 1968;22:550-8.

Hypertrophy is Compensatory

Time After Onset QRS (sec)

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Pressure Overload(Aortic Stenosis)

Stress (dynes/cm2 x 103)Pressure (dynes/cm2 x 103)

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[Overload] excites a more forcible ventricular action… and hypertrophy is produced. The increased muscular growth for a certain period protects against the occurrence of dilatation. At length, hypertrophy reaches a point beyond which it cannot advance… The causes, however, persist and… can produce only dilatation [so that] from this period the progressive enlargement is due to augmentation of the cavities…

Hypertrophy Protects Against the Deleterious Effects of Dilatation

AUSTIN FLINTDiseases of the Heart

2nd Ed. (1870).

According to this view, hypertrophy becomes an important conservative provision, first, against over-accumulation of blood, and second, against the more serious form of enlargement, viz., dilatation.

Hypertrophy is a compensatory and beneficial condition, in fact, nature’s effort to meet a difficulty… Dilatation is the direct opposite of hypertrophy, inasmuch as it impairs the efficiency of the cardiac pump.

BYROM BRAMWELLDiseases of the Heart and

Thoracic Aorta (1884).

…[although] dilatation is usually bad, in regurgitant valvular lesions dilatation of the cavity… behind the affected orifice is beneficial, providing that it is just sufficient to accommodate the blood which is regurgitated at each systole.

Hypertrophy is Compensatory But Dilatation is Usually Deleterious

Hypertrophy Can Be Deleterious As Well As Compensatory

Hypertrophy [which] always occurs wherever a portion of the heart has been called upon to perform work beyond its normal capacity… may exist for many years, and the individual still continue to have relatively good health, but in the end it certainly leads to a so-called catastrophe through some of its sequels… which are of themselves full of danger to the patient.

It has frequently been said that the heart hypertrophies in order to establish a sort of compensation… This view would be correct if the hypertrophy remained stationary; but experience has shown that the excess of work imposed upon the heart finally deteriorates its fibres …

– LEOPOLD SCHROETTER Ziemssen’s Practice of Medicine (1876).

– CONSTANTIN PAUL Diseases of the Heart (1884).

A Modern Echo (1987-1988)

-MyosinHeavy Chain

-MyosinHeavy Chain

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Izumo S et al. J Clin Invest. 1987;79:970.Izumo S et al. Proc Nat Acad Sci. USA. 1988;85:339.

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Hypertrophy is Accompanied by Reversion to the Fetal Phenotype

1) “DEVELOPMENT”: Depends on the nature of the underlying abnormality.

2) “FULL COMPENSATION”: Allows the heart’s “vigor” to meet the increased hemodynamic demand. (ADAPTIVE HYPERTROPHY)

3) “BROKEN COMPENSATION”: Can result in acute dilatation

[pulmonary edema], but more commonly evolves slowly as

the result of “degeneration and weakening of the heart muscle.” (MALADAPTIVE HYPERTROPHY)

WILLIAM OSLERThe Principles and

Practice of Medicine (1892).

Adaptive and Maladaptive Hypertrophy

Three Stages in the Heart’s Response to Overload

JOHN MILNER FOTHERGILLThe Heart and Its Diseases. 2nd Ed.

(1879).

Hypertrophy and Dilatation Result from Different Mechanical Stresses

With increase in the distending force [as in aortic insufficiency], hypertrophy is always combined withdilatation of the cardiac chambers.

…in obstruction… without any increase in the distending force, as in aortic stenosis, there is pure hypertrophy, usually without dilatation.

Increased Systolic Stress

Increased Diastolic Stress

Increased Diastolic

Stress

Increased Diastolic

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Hypertrophy and Dilatation Result from Different Mechanical Stresses

IncreasedSystolicStress

IncreasedSystolicStress

Aortic stenosis(Hypertrophy)

Aortic stenosis(Hypertrophy)

Aortic insufficiency(Dilatation)

Aortic insufficiency(Dilatation)

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Strain imposed during diastolic phase

Yamamoto K et al. Circulation. 2001:103:1459-64.

A Modern Echo (2001)

Systolic and Diastolic Stress Activate Different Signaling Pathways

Strain

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Strain imposedduring thesystolic phase

Strain imposedduring thediastolic phase

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Clinical Picture

Digitalis

Architecture of the Failing Heart

Heart FailureThe 18th & 19th Centuries

“Modern Echoes”