CARDIOMYOPAT

HY
 CARDIOMYOPATHIES ARE INTRINSIC CARDIAC MUSCLE DISEASES THAT MAY BE GENETIC
(IDIOPATHIC) OR DUE TO WELL-DEFINED CAUSES
 THERE ARE TWO MAJOR GROUPS OF CARDIOMYOPATHIES:
• PRIMARY CARDIOMYOPATHIES INVOLVE PREDOMINANTLY THE HEART.
THEY MAY BE GENETIC OR ACQUIRED (E.G., VIRAL MYOCARDITIS,
ANTHRACYCLINE CARDIOTOXIC).
• SECONDARY CARDIOMYOPATHIES HAVE MYOCARDIAL INVOLVEMENT
AS A COMPONENT OF A SYSTEMIC OR MULTIORGAN DISORDER
(E.G. HEMOCHROMATOSIS, AMYLOIDOSIS).
 THERE ARE THREE GENERAL PATHOPHYSIOLOGIC CATEGORIES OF CARDIOMYOPATHY:
1) DILATED (90%)
2)HYPERTROPHIC
3)RESTRICTIVE (LEAST COMMON).
 DILATED CARDIOMYOPATHY
 DCM IS CHARACTERIZED MORPHOLOGICALLY AND FUNCTIONALLY BY
PROGRESSIVE CARDIAC DILATION AND CONTRACTILE (SYSTOLIC)
DYSFUNCTION, USUALLY WITH CONCOMITANT HYPERTROPHY
ETIOLOGY OF DILATED
CARDIOMYOPATHY
IDIOPATHIC
ALCOHOL
COBALT
POSTPARTUM
PATHOGENESIS OF DILATED
CARDIOMYOPATHY
1)GENETIC INFLUENCES
 DCM IS PROBABLY FAMILIAL IN UP TO 50% OF CASES, CAUSED BY MUTATIONS IN A DIVERSE
GROUP OF MORE THAN 20 GENES ENCODING PROTEINS INVOLVED IN THE CYTOSKELETON,
SARCOLEMMA, AND NUCLEAR ENVELOPE (E.G., LAMIN A/C).
 IN PARTICULAR, TRUNCATION MUTATIONS IN TTN, A GENE THAT ENCODES TITIN, MAY ACCOUNT
FOR APPROXIMATELY 10% TO 20% OF ALL CASES OF DCM
 IN THE GENETIC FORMS OF DCM, AUTOSOMAL DOMINANT INHERITANCE IS THE PREDOMINANT
PATTERN.
 X-LINKED, AUTOSOMAL RECESSIVE, AND MITOCHONDRIAL INHERITANCE OF DCM ARE LESS
COMMON.
 MITOCHONDRIAL GENE DELETIONS AFFECT
1)OXIDATIVE PHOSPHORYLATION
2)FATTY ACID Β-OXIDATION
 X-LINKED CARDIOMYOPATHY CAN ALSO BE ASSOCIATED WITH MUTATIONS AFFECTING THE
MEMBRANE ASSOCIATED DYSTROPHIN PROTEIN
2)MYOCARDITIS
 THE DETECTION OF THE GENETIC FINGERPRINTS OF COXSACKIE B AND OTHER VIRUSES
WITHIN MYOCARDIUM OF PATIENTS WITH DCM SUGGESTS THAT VIRAL MYOCARDITIS CAN
BE CAUSAL

3)ALCOHOL AND OTHER TOXINS;

 ALCOHOL ABUSE IS STRONGLY ASSOCIATED WITH THE DEVELOPMENT OF DCM, RAISING THE
POSSIBILITY THAT ETHANOL TOXICITY OR A SECONDARY NUTRITIONAL DISTURBANCE CAN
UNDERLIE MYOCARDIAL INJURY.
 ALCOHOL OR ITS METABOLITES (ESPECIALLY ACETALDEHYDE) HAVE A DIRECT TOXIC EFFECT
ON THE MYOCARDIUM.
 CHRONIC ALCOHOLISM MAY BE ASSOCIATED WITH THIAMINE DEFICIENCY,
 COBALT IS AN EXAMPLE OF A HEAVY METAL WITH CARDIOTOXICITY AND HAS CAUSED DCM
IN THE SETTING OF INADVERTENT TAINTING (E.G., IN BEER PRODUCTION).
 CARDIOTOXIC DRUGS USED FOR CHEMOTHERAPY ARE ALSO IMPORTANT CAUSES OF DCM.
3)CHILDBIRTH;
 PERIPARTUM CARDIOMYOPATHY CAN OCCUR LATE IN PREGNANCY OR UP TO 5 MONTHS
POSTPARTUM;
4) IRON OVERLOAD
 IN THE HEART CAN RESULT FROM EITHER HEREDITARY HEMOCHROMATOSIS OR FROM
MULTIPLE TRANSFUSIONS.
 DCM IS THE MOST COMMON MANIFESTATION OF SUCH IRON EXCESS
5)SUPRAPHYSIOLOGIC STRESS
 PATHOGENESIS OF ARRYTHMOGENIC
CARDIOMYOPATHY
 CLASSICAL ARRHYTHMOGENIC CARDIOMYOPATHY HAS AN AUTOSOMAL DOMINANT
INHERITANCE WITH A VARIABLE PENETRANCE;
 MANY OF THE CAUSAL MUTATIONS INVOLVE GENES ENCODING DESMOSOMAL JUNCTIONAL
PROTEINS AT THE INTERCALATED DISK (E.G., PLAKOGLOBIN) AS WELL AS PROTEINS THAT
INTERACT WITH THE DESMOSOME (E.G., THE INTERMEDIATE FILAMENT DESMIN).
 NAXOS SYNDROME IS A DISORDER CHARACTERIZED BY ARRHYTHMOGENIC
CARDIOMYOPATHY
 ETIOLOGY OF HYPERTROPHIC
CARDIOMYOPATHY
Aortic stenosis
Genetic
Hypertension
 HYPERTROPHIC CARDIOMYOPATHY
AND PATHOGENESIS
 HYPERTROPHIC CARDIOMYOPATHY (HCM) IS A COMMON (1 IN 500 PREVALENCE),
CLINICALLY HETEROGENEOUS, GENETIC DISORDER CHARACTERIZED BY MYOCARDIAL
HYPERTROPHY, POORLY COMPLIANT LEFT VENTRICULAR MYOCARDIUM LEADING TO
ABNORMAL DIASTOLIC FILLING, AND (IN ABOUT ONE-THIRD OF CASES) INTERMITTENT
VENTRICULAR OUTFLOW OBSTRUCTION
 IN MOST CASES, THE PATTERN OF TRANSMISSION IS AUTOSOMAL DOMINANT WITH
VARIABLE PENETRANCE
 HCM IS MOST COMMONLY CAUSED BY MUTATIONS IN ANY ONE OF SEVERAL GENES THAT
ENCODE SARCOMERIC PROTEINS;
 MUTATIONS CAUSING HCM ARE FOUND MOST COMMONLY IN THE GENES ENCODING
MYOSIN-BINDING PROTEIN C (MYBP-C) OR Β-MYOSIN HEAVY CHAIN (Β-MHC/MYH7) ,
FOLLOWED BY THE GENES CODING FOR CARDIAC TNI, TNT, AND Α-TROPOMYOSIN;
 ETIOLOGY OF RESTRICTIVE
CARDIOMYOPATHY
IDIOPATHIC
SARCOIDOSIS
AMYLOIDOSIS
RADIATION
 RESTRICTIVE CARDIOMYOPATHY AND
PATHOGENESIS
 RESTRICTIVE CARDIOMYOPATHY IS CHARACTERIZED BY A PRIMARY DECREASE IN VENTRICULAR
COMPLIANCE, RESULTING IN IMPAIRED VENTRICULAR DIASTOLIC FILLING.
 RESTRICTIVE CARDIOMYOPATHY CAN BE IDIOPATHIC OR ASSOCIATED WITH DISTINCT DISORDERS
THAT AFFECT THE MYOCARDIUM, PRINCIPALLY AMYLOIDOSIS,SARCOIDOSIS, RADIATION-INDUCED
FIBROSIS, METASTATIC TUMORS, OR THE ACCUMULATION OF METABOLITES FROM INBORN ERRORS
OF METABOLISM.

AMYLOIDOSIS
 AMYLOIDOSIS IS AN IMPORTANT FORM OF RESTRICTIVE CARDIOMYOPATHY RESULTING FROM THE
EXTRACELLULAR ACCUMULATION OF PROTEIN FIBRILS THAT FORM INSOLUBLE Β-PLEATED SHEETS
 THE AMYLOID DEPOSITS ARE LARGELY COMPOSED OF TRANSTHYRETIN, A NORMAL SERUM PROTEIN
SYNTHESIZED IN THE LIVER THAT TRANSPORTS THYROXINE AND RETINOL-BINDING PROTEIN.
 CARDIAC AMYLOIDOSIS MOST FREQUENTLY PRODUCES A RESTRICTIVE CARDIOMYOPATHY, BUT IT
CAN ALSO BE ASYMPTOMATIC, MANIFEST AS DILATION OR ARRHYTHMIAS, OR MIMIC ISCHEMIC OR
VALVULAR DISEASE.
GROSS FEATURES OF
DILATED
CARDIOMYOPATHY
HEART IS TYPICALLY
ENLARGED
HEAVY (2 TO 3 TIMES
NORMAL WEIGHT)
FLABBY DUE TO DILATION OF
ALL CHAMBERS
MURAL THROMBI DUE TO
STASIS OF BLOOD IN POORLY
CONTRACTILE CHAMBERS
CORONARY ARTERIES PATENT
 MICROSCOPIC
FEATURES OF
DILATED
CARDIOMYOPATHY
 VARIABLE MYOCYTE
HYPERTROPHY
 INTERSTITIAL FIBROSIS
 COLLAGEN IS HIGHLIGHTED
AS BLUE IN THIS MASSON
TRICHROME STAIN
MUSCLE CELLS ARE
HYPERTROPHIED WITH
ENLARGED NUCLEI
SOME MUSCLE CELLS ARE
ATTENUATED,STRETCHED
AND IRREGULAR
IN DILATED
CARDIOMYOPATHY CAUSED
BY TRUNCATING MUTATION
IN TITIN GENE MYOCYTES
MAY EXHIBIT
HYPERCHROMATIC, HIGHLY
DISTORTED ,BIZARRE NINJA
STARS LIKE NUCLEI
 GROSS AND
MICROSCOPIC
FEATURES OF
ARRYTHMOGENIC
CARDIOMYOPATHY
DILATION OF RIGHT
VENTRICLE
RIGHT VENTRICULAR WALL
IS SEVERLY ATTENUATED
DUE TO LOSS OF
MYOCYTES
RIGHT VENTRICULAR WALL
IS ACCOMPANIED BY
MASSIVE FATTY
INFILTRATION AND FOCAL
FIBROSIS
 HISTOLOGIC SECTION
OF THE RIGHT
VENTRICULAR FREE
WALL ,
DEMONSTRATING
REPLACEMENT OF
MYOCARDIUM (RED)
BY FIBROSIS (BLUE,
ARROW) AND FAT
(MASSON
TRICHROME STAIN)
 GROSS AND
MICROSCOPIC
FEATURES OF
HYPERTROPHIC
CARDIOMYOPATHY
 HEART IS THICK WALLED AND HEAVY
 MASSIVE MYOCARDIAL HYPERTROPHY
WITHOUT VENTRICULAR DILATION
 DISPROPORTIONATE THICKENING OF THE
VENTRICULAR SEPTUM RELATIVE TO THE LEFT
VENTRICLE FREE WALL, TERMED
ASYMMETRIC SEPTAL HYPERTROPHY
 ON LONGITUDINAL SECTIONING, THE
NORMALLY ROUND-TO-OVOID LEFT
VENTRICULAR CAVITY MAY BE COMPRESSED
INTO A “BANANA-LIKE” CONFIGURATION BY
BULGING OF THE VENTRICULAR SEPTUM
INTO THE LUMEN
 THE LEFT VENTRICULAR OUTFLOW TRACT
OFTEN EXHIBITS A FIBROUS ENDOCARDIAL
PLAQUE AND THICKENING OF THE ANTERIOR
MITRAL LEAFLET
MASSIVE MYOCYTE HYPERTROPHY,
WITH TRANSVERSE MYOCYTE
DIAMETERS FREQUENTLY GREATER
THAN 40 µM (NORMAL IS
APPROXIMATELY 15 µM)
HAPHAZARD DISARRAY OF BUNDLES
OF MYOCYTES, INDIVIDUAL
MYOCYTES, AND CONTRACTILE
ELEMENTS IN SARCOMERES WITHIN
CELLS (TERMED MYOFIBER DISARRAY)
 FIBROTIC NARROWING OF SMALL
INTRAMURAL ARTERIES
 INTERSTITIAL AND REPLACEMENT
FIBROSIS
 GROSS AND
MICROSCOPIC FEATURES
OF RESTRICTIVE
CARDIOMYOPATHY
GROSS;
 BI-ATRIAL DILATION COMMONLY
OBSERVED
 VENTRICLES ARE OF APPROXIMATELY
NORMAL SIZE
 CAVITIES ARE NOT DILATED

MICROSCOPY;
PATCHY OR DIFFUSE
INTERSTITIAL FIBROSIS
VARYING FROM MINIMAL TO
EXTENSIVE
RESTRICTIVE CARDIOMYOPATHY
DUE TO AMYLOIDOSIS
MICROSCOPIC FEATURES
 HYALINE EOSINOPHILIC DEPOSITS OF
AMYLOID MAY BE FOUND IN THE
INTERSTITIUM, CONDUCTION TISSUE,
VALVES, ENDOCARDIUM,
PERICARDIUM, AND SMALL
INTRAMURAL CORONARY ARTERIES
 HEMATOXYLIN AND EOSIN STAIN,
SHOWING AMYLOID APPEARING AS
AMORPHOUS PINK MATERIAL AROUND
MYOCYTE
CONGO RED STAIN
VIEWED UNDER
POLARIZED LIGHT, IN
WHICH AMYLOID
SHOWS
CHARACTERISTIC
APPLE-GREEN
BIREFRINGENCE
GROSS FEATURES IN AMYLOIDOSIS;
 THE HEART VARIES IN CONSISTENCY FROM NORMAL
TO FIRM AND RUBBERY
 THE CHAMBERS ARE USUALLY OF NORMAL SIZE BUT
CAN BE DILATED AND HAVE THICKENED WALLS
 SMALL, SEMITRANSLUCENT NODULES RESEMBLING
DRIPS OF WAX MAY BE SEEN ON THE ATRIAL
ENDOCARDIAL SURFACE
DIAGNOSIS OF DILATED CARDIOMYOPATHY

• CHEST X RAY – SHOWS SIGN OF CARDIOMEGALY

• ECG REVEALS: TACHYCARDIA , BRADYCARDIA AND DYSARRYTHMIAS
• ECHOCARDIOGRAPHY:VENTRICULAR DILATATION
NORMAL OR THIN WALLS
• AUSCULTATION: S3 HEART SOUND
 DIAGNOSIS OF HYPERTROPHIC
CARDIOMYOPATHY
• HISTORY AND PHYSICAL EXAMINATION
• ECG(ELECTROCARDIOGRAM)
• CARDIAC MRI
• CHEST X-RAY: INCREASE RATIO OF DISTANCE BETWEEN HEART
THORACIC CAGE
 DIAGNOSIS OF RESTRICTIVE
CARDIOMYOPATHY
• ECG: SHOWS TACHYCARDIA
• CHEST X-RAY : SHOW CARDIOMEGALY
• CT-SCAN AND MRI SCAN
 COMPLICATIONS OF DILATED
CARDIOMYOPATHY
• SYSTOLIC HEART FAILURE
• VALVE REGURGITATION
• ARRYTHMIAS
 COMPLICATIONS OF
HYPERRTROPHIC
CARDIOMYOPATHY
ARRYTHMIAS
STROKE
SUDDEN CARDIAC DEATH
 COMPLICATIONS OF RESTRICTIVE
CARDIOMYOPATHY
HEART FAILURE
ABNORMAL HEART RHYTHM
STROKE
SUDDEN CARDIAC DEATH
SYPHILIS
 -Syphilisis a chronic Sexually transmitted infections with varied
chronic clinical and pathologic manifestations

Etiology and pathogenesis

-Caused by Treponema pallidum subspecies pallidum
-Can be visualized by SILVER STAINS and IMMUNOFLUORESCENCE techniques
-Can readily cross the placenta and cause Congenital syphilis
Pathogenesis:
-Proliferative end arteritis affecting small blood vessels with a surrounding plasma
rich infiltrate is characteristic of all stages of syphilis
-Ischemia produced by vascular lesions

-Immune response to Treponema pallidum reduces the burden of bacteria and

lead to resolution of local lesions but does reliably eliminate the systemic
infections

-Infiltrating CD4+ T cells are Th1 cells that may activate the macrophages to kill
the bacteria
-Treponeme specific antibodies are detectable and these activate complement in
the lesion and opsonize the bacteria for phagocytosis by macrophages

-TprK protein in outer membrane accumulates structural diversity during the

course of infection though gene conversion between silent donor sites and tprk
gene and this antigenic diversity allows the organism to persist

-Syphilis is divided into three stages with distinct clinical and pathologic
manifestation
1) Primary syphilis
2) Secondary syphilis
3) Tertiary syphilis
Primary syphilis:
-Occurs approximately 3 weeks after infection
-Characterised by single firm , non tender ,raised ,red lesion(Chancre)
-Located on penis , cervix , vaginal wall or anus
-Chancres heals with or without therapy
-Spirochetes are plentiful in chancres and spread from there throughout the
body by hematologic and lymphatic dissemination
Secondary syphilis:
-Characterised by painless, superficial lesions of the skin and mucosal surfaces
-Occurs 2-10 weeks after the primary chancre in approximately 75% of
untreated people
-Skin lesions occurs frequently on palms or soles and may be maculopaplular ,
scaly , or pustular
-Moist areas of skin such as anogenital region, inner thighs, and axillae may
have broad based elevated plaques called condylomata lata
-Silver gray superficial erosions may form on the oral, pharyngeal, and genital
mucous membranes
-Lymphadenopathy, mild fever , malaise and weight loss are also common in
secondary syphilis

Secondary syphilis lasts for several weeks and then the person enters the latent
stage
 Tertiary Syphilis
Three main manifestation:
1)Cardiovascular syphilis
2)Neurosyphilis
3)Benign tertiary syphilis

-May be alone or in combination

-One third of untreated patients develop syphilis
-After latent period of 5 years or more
 CARDIOVASCULAR SYPHILIS
>80% manifested as Syphilitic aortitis
-Pathogenesis not known
-May be immune (low treponeme and intense inflammatory infiltrate )

Aortitis Progressive dilatation of aortic root and arch aortic

valve insufficiency and aneurysms
 NEUROSYPHILIS
Asymptomatic and Symptomatic

Asymptomatic- One third of neurosyphilis cases

CSF abnormalities- 1) Pleocytosis (increase number of inflammatory cells)
2) Increase protein levels
3)Decreased glucose
Confirmed – Antibodies against spirochetes in CSF
-Every tertiary syphilis patient should be tested for neurosyphilis even if
there is no neurological symptoms

Symptomatic-manifested as :1) Meningovascular diseas

2)Paretic syphilis
3)Tabes Dorsalis
- Increased risk in HIV due to impared cell mediated immunity

Meningovascular Neurosyphilis-Chronic meningitis involve base of brain

and cerebral convexities and spinal leptomeninges

-Associated with obliterative end arteritis (heubner arteritis) accompanied

by distinctive perivascular inflammatory reaction rich in plasma cells and
lymphocytes

Paretic Neurosyphilis-Invasion of brain by Treponema pallidum

-Insidious but progressive cognitive impairment
-Mood alterations(Delusion of grandeur) terminate as severe dementia
-Frontal lobe commonly involved
Tabes Dorsalis- Damage to sensory axons in dorsal roots
-loss of proprioception
-loss of pain sensation
-skin and joint damage (charcot joints )
-loss of deep tendon reflexes
 BENIGN TERTIARY SYPHILIS
-Gummas in bone , skin and mucous membrane
-Gummas are nodular lesions related to the development of delayed
hypersensitivity to bacteria
-Skeletal involvement causes pain,tenderness,swelling and pathologic
fractures
 CONGENITAL SYPHILIS
-Infect the baby by crossing the placenta and during childbirth in birth canal

Early disease (infantile syphilis)- first 2 years

-Still born
-Maculopapular rashes on palm and feet
-Snuffles

Late disease(tardive syphilis)->2 years

-Saddle nose(nasal bone destruction)
-Saber sinus (bend tibia)
-Hutchinson teeth (Teeth notched)
-Hearing loss ( eighth nerve damage)
Congenital Syphilis
 DIAGNOSIS
-Identify spirochetes in chancres
-Using dark field microscopy

Confirm- Serological tests for antibodies against Treponema pallidum

Non treponemal test-

Detect antibodies against cardiolipin
1)Rapid plasma reagin
2)VDRL
But these test are non specific as cardiolipin is also released due to
damage to other tissues of body
Treponemal test –
-Detects antibody against Treponema pallidum

1)Treponema Pallidum Particle agglutination test (TPPA)

-Fluorescent treponemal antibody test (FTA-ABS)
 TREATMENT

-Penicillin
Watch Jarisch herxheimer reaction

Spirochetes die and releases

lots of antigen

Immune system overdrive

Sudden fever , muscle and

joint pain last for few hours
to days