This document provides an overview of basic science and forensic pathology aspects of cardiomyopathies. It discusses cardiomyopathies in three sentences: Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilatation. The three main patterns are dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. Dilated cardiomyopathy is the most common and can result from genetic or acquired causes, while restrictive cardiomyopathy is the least frequent.
Pathology of Cardiomyopathies
Literally means “disease of the heart muscle”.
Term “cardiomyopathy” is used to describe heart disease resulting from an abnormality in the myocardium.
Diseases of the myocardium usually produce:
>abnormalities in cardiac wall thickness and chamber size.
>mechanical or electrical dysfunction
>associated with significant morbidity and mortality.
Pathology of Cardiomyopathies
Literally means “disease of the heart muscle”.
Term “cardiomyopathy” is used to describe heart disease resulting from an abnormality in the myocardium.
Diseases of the myocardium usually produce:
>abnormalities in cardiac wall thickness and chamber size.
>mechanical or electrical dysfunction
>associated with significant morbidity and mortality.
Cardiomyopathy
Definition
Abnormal structure or function of the myocardium.
Newer definitions require it to be unexplained by ischaemic, hypertensive, or valvular disease, with the term limited to myocardial diseases with known genetic, morphological, and/or functional characteristics.
It often leads to heart failure, and in rarer cases, sudden cardiac death.
Dilated cardiomyopathy (DCM)
Pathophysiology and epidemiology
Commonest cardiomyopathy. Exact prevalence unclear but probably more than 1/500. Can present at any age.
Features:
Dilated chambers.
Systolic dysfunction.
↓Cardiac output.
Causes:
Idiopathic
Familial, 2/3 of which are autosomal dominant.
Cardiovascular: ischaemia, HTN, valve disease. See 'Definition' above about why this isn't strictly speaking 'cardiomyopathy'.
Myocarditis: viral, Chagas disease.
Alcohol
Pregnancy: Peripartum cardiomyopathy.
Stress: Takotsubo cardiomyopathy.
Tachycardia: 'tachymyopathy', usually in chronic SVT such as atrial flutter or AF.
Multi-system disease: thyrotoxicosis, sarcoidosis, haemochromatosis.
Arteriosclerosis is the most common disease of the arteries; the term means “hardening of the arteries”.
It is the diffuse process whereby the muscle fibers and the endothelial lining of the walls of small arteries and arterioles become thickened.
ATHEROSCLEROSIS
Seminar Prepared by :-
Ali Abdulazeem
Shilan Adnan Abdulrahman
Alaa Shamil
Guldan Hameed
Internal Medicine
College of Medicine - University of Kirkuk
Atherosclerosis - Definition - Risk Factors - Lesser and Non Quantitated risk factors - Arterial wall - The development of Atherosclerosis - Many Features of the injury Hypothesis - The process of Atherogenesis - Pathogenesis in short - Morphology of Atheroma - Components of Atheromatous Plaque (MP) - Complications and clinical significance - Cardiovascular risk and its assessment.
Cardiomyopathy
Definition
Abnormal structure or function of the myocardium.
Newer definitions require it to be unexplained by ischaemic, hypertensive, or valvular disease, with the term limited to myocardial diseases with known genetic, morphological, and/or functional characteristics.
It often leads to heart failure, and in rarer cases, sudden cardiac death.
Dilated cardiomyopathy (DCM)
Pathophysiology and epidemiology
Commonest cardiomyopathy. Exact prevalence unclear but probably more than 1/500. Can present at any age.
Features:
Dilated chambers.
Systolic dysfunction.
↓Cardiac output.
Causes:
Idiopathic
Familial, 2/3 of which are autosomal dominant.
Cardiovascular: ischaemia, HTN, valve disease. See 'Definition' above about why this isn't strictly speaking 'cardiomyopathy'.
Myocarditis: viral, Chagas disease.
Alcohol
Pregnancy: Peripartum cardiomyopathy.
Stress: Takotsubo cardiomyopathy.
Tachycardia: 'tachymyopathy', usually in chronic SVT such as atrial flutter or AF.
Multi-system disease: thyrotoxicosis, sarcoidosis, haemochromatosis.
Arteriosclerosis is the most common disease of the arteries; the term means “hardening of the arteries”.
It is the diffuse process whereby the muscle fibers and the endothelial lining of the walls of small arteries and arterioles become thickened.
ATHEROSCLEROSIS
Seminar Prepared by :-
Ali Abdulazeem
Shilan Adnan Abdulrahman
Alaa Shamil
Guldan Hameed
Internal Medicine
College of Medicine - University of Kirkuk
Atherosclerosis - Definition - Risk Factors - Lesser and Non Quantitated risk factors - Arterial wall - The development of Atherosclerosis - Many Features of the injury Hypothesis - The process of Atherogenesis - Pathogenesis in short - Morphology of Atheroma - Components of Atheromatous Plaque (MP) - Complications and clinical significance - Cardiovascular risk and its assessment.
Etiopathogenesis and pharmacotherapy of CONGESTIVE CARDIAC FAILURE
a. the pathophysiology of selected disease states and the rationale for drug therapy;
b. the therapeutic approach to management of these diseases;
c. the controversies in drug therapy;
d. the importance of preparation of individualised therapeutic plans based on diagnosis;
e. needs to identify the patient-specific parameters relevant in initiating drug therapy,
and monitoring therapy (including alternatives, time-course of clinical and laboratory
indices of therapeutic response and adverse effects);
f. describe the pathophysiology of selected disease states and explain the rationale for
drug therapy;
g. summarise the therapeutic approach to management of these diseases including
reference to the latest available evidence;
h. discuss the controversies in drug therapy;
i. discuss the preparation of individualised therapeutic plans based on diagnosis; and
j. identify the patient-specific parameters relevant in initiating drug therapy, and
monitoring therapy (including alternatives, time-course of clinical and laboratory indices of therapeutic response and adverse effects).
Etiopathogenesis and pharmacotherapy of myocardial infraction
a. the pathophysiology of selected disease states and the rationale for drug therapy;
b. the therapeutic approach to management of these diseases;
c. the controversies in drug therapy;
d. the importance of preparation of individualised therapeutic plans based on diagnosis;
e. needs to identify the patient-specific parameters relevant in initiating drug therapy,
and monitoring therapy (including alternatives, time-course of clinical and laboratory
indices of therapeutic response and adverse effects);
f. describe the pathophysiology of selected disease states and explain the rationale for
drug therapy;
g. summarise the therapeutic approach to management of these diseases including
reference to the latest available evidence;
h. discuss the controversies in drug therapy;
i. discuss the preparation of individualised therapeutic plans based on diagnosis; and
j. identify the patient-specific parameters relevant in initiating drug therapy, and
monitoring therapy (including alternatives, time-course of clinical and laboratory indices of therapeutic response and adverse effects).
Cardiomyopathy literally means disease of the heart muscle but the term was originally coined to restrict its usage to myocardial disease of unknown cause.
it has three major types ,
Dilated Congestive cardiomyopathy( D.C.M)
Hypertrophic Asymetrical Cardiomyyopathy. (H.C.M)
Restrcitive Cardiomypathy ( R.C.M)
CAD is the commonest cause of deaths worldwide. Mortality rates have declined over the past four decades in western countries however this condition remains responsible for ~one-third of all deaths in individuals over age 35.
Mortality is on the rise in Low and middle income countries Tanzania being among. The 2016 Heart Disease and Stroke Statistics update of the AHA reported that 15.5 million people in the USA. have CHD.
The reported prevalence increases with age for both women and men. For those US people, the lifetime risk of developing CHD with ≥2 major risk factors is 37.5% for men and 18.3% for women.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists
Basic science and forensic pathology aspects of cardiomyopathies
1. Basic Science and Forensic
Pathology Aspects of
Cardiomyopathies
Luchenga Adam Mucheleng’anga
Clinical Fellow of Forensic Pathology
University of Toronto.
2. Disclaimer
This is not original work as it is book lifted from the
books listed at the end. This material is study notes
The PowerPoint is meant to ease the learning
process.
4. Basic Science of
Cardiomyopathies
• Cardiomyopathies
• Although the term cardiomyopathy
(literally, heart muscle disease) has
been historically applied to any
cardiac dysfunction resulting from a
myocardial abnormality, a more
nuanced definition is probably
appropriate.
• Thus stimulated by the recognition of
new phenotypes and the advent of
more sophisticated molecular
characterization—an expert panel has
suggested: “Cardiomyopathies are a
heterogeneous group of diseases of
the myocardium associated with
mechanical and/or electrical
dysfunction that usually (but not
invariably) exhibit inappropriate
ventricular hypertrophy or dilatation
and are due to a variety of causes that
frequently are genetic.
5. Basic Science of
Cardiomyopathies
• Cardiomyopathies
• Cardiomyopathies either are confined
to the heart or are part of generalized
systemic disorders, often leading to
cardiovascular death or progressive
heart failure-related disability.
• Thus, cardiomyopathies manifest as
failure of myocardial performance; this
can be mechanical (e.g., diastolic or
systolic dysfunction) leading to CHF, or
can culminate in life-threatening
arrhythmias.
• Primary cardiomyopathies can be
genetic or acquired diseases of
myocardium, whereas secondary
cardiomyopathies have myocardial
involvement as a component of a
systemic or multiorgan disorder.
6. Basic Science of
Cardiomyopathies
• Cardiomyopathies
• Cardiomyopathies either are confined to the heart or
are part of generalized systemic disorders, often
leading to cardiovascular death or progressive heart
failure-related disability.
• Thus, cardiomyopathies manifest as failure of
myocardial performance; this can be mechanical
(e.g., diastolic or systolic dysfunction) leading to CHF,
or can culminate in life-threatening arrhythmias.
• Primary cardiomyopathies can be genetic or acquired
diseases of myocardium, whereas secondary
cardiomyopathies have myocardial involvement as a
component of a systemic or multiorgan disorder.
7. Basic Science of Cardiomyopathies
• Cardiomyopathies
• A major advance in our understanding of
cardiomyopathies stems from the frequent
identification of underlying genetic causes, including
mutations in myocardial proteins involved in
contraction, cell-cell contacts, and the cytoskeleton.
• These, in turn, lead to abnormal contraction or
relaxation, or to dysregulated ion transport across
cell membranes.
• Although chronic myocardial dysfunction secondary
to ischemia, valvular abnormalities, or hypertension
can cause significant ventricular dysfunction, these
conditions should not be denoted as
cardiomyopathies.
8. Basic Science of Cardiomyopathies
• Cardiomyopathies
• Cardiomyopathies can be classified according to a variety of
criteria, including the underlying genetic basis of dysfunction;
inducing channelopathies, which may be included in
cardiomyopathies.
• However, we will confine our list of cardiomyopathies to
disorders that produce anatomic abnormalities in the heart.
• These fall into three pathologic patterns; Dilated
cardiomyopathy (including arrhythmogenic right ventricular
cardiomyopathy); Hypertrophic cardiomyopathy; and
Restrictive cardiomyopathy
9. Basic Science of Cardiomyopathies
• Cardiomyopathies
• Among the three major patterns, dilated
cardiomyopathy is most common (90% of
cases), and restrictive cardiomyopathy is the
least frequent.
• Within each pattern, there is a spectrum of
clinical severity, and in some cases clinical
features overlap among the groups.
• In addition, each of these patterns can be
caused by a specific identifiable cause, or can
be idiopathic.
12. Basic Science of
Cardiomyopathies
• Dilated Cardiomyopathy
• Dilated cardiomyopathy (DCM) is
characterized morphologically and
functionally by progressive cardiac
dilation and contractile (systolic)
dysfunction, usually with concomitant
hypertrophy.
• Many cases are familial, but the DCM
phenotype can result from diverse
causes, both primary and secondary.
13. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Pathogenesis.
By the time of diagnosis, DCM has typically
progressed to end-stage disease; the heart is dilated
and poorly contractile.
Unfortunately, at that point, even an exhaustive
evaluation frequently fails to suggest a specific
etiology.
Increasingly, familial (genetic) forms of DCM are
recognized, but the final pathology can also result
from various acquired myocardial insults; as this
implies, several different pathways can lead to DCM.
14.
15. Basic Science of Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• Genetic Influences.
• DCM is familial in at least 30% to 50% of cases,
in which it is caused by mutations in a diverse
group of more than 20 genes encoding proteins
involved in the cytoskeleton, sarcolemma, and
nuclear envelope (laminin A/C). In particular,
mutations in TTN, a gene that encodes titin (so-
called because it is the largest protein
expressed in humans), may account for
approximately 20% of all cases of DCM
16. Mutations in titin
account for
approximately 20% of
all dilated
cardiomyopathy.
Titin spans the
sarcomere and connects
the Z and M bands
thereby limiting the
passive range of motion
of the sarcomere as it
is stretched.
Titin also functions like
a molecular spring,
with domains that
unfold when the
protein is stretched and
refold when the tension
is removed, thereby
impacting the passive
elasticity of striated
muscle.
17. Basic Science of Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• Genetic Influences.
• In the genetic forms of DCM, autosomal dominant
inheritance is the predominant pattern; X-linked,
autosomal recessive, and mitochondrial inheritance
are less common.
• In some families there are deletions in mitochondrial
genes that result in defects in oxidative
phosphorylation; in others there are mutations in
genes encoding enzymes involved in β-oxidation of
fatty acids.
18. Basic Science of
Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• Genetic Influences.
• Mitochondrial defects typically manifest in the
pediatric population, while X-linked DCM typically
presents after puberty and into early adulthood.
• X-linked cardiomyopathy can also be associated
with mutations affecting the membrane-
associated dystrophin protein that couples
cytoskeleton to the extracellular matrix; recall
that dystrophin is mutated in the most common
skeletal myopathies (i.e., Duchenne and Becker
muscular dystrophies.
19. Basic Science of Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• Genetic Influences.
• Some patients and families with dystrophin
gene mutations have DCM as the primary
clinical feature.
• Interestingly, and probably resulting from the
common developmental origin of contractile
myocytes and conduction elements,
congenital abnormalities of conduction may
also be associated with DCM.
20. Basic Science of Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• Myocarditis.
• Sequential endomyocardial biopsies have
documented progression from myocarditis to
DCM.
• In other studies, 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.
21. Basic Science of Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• 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.
• Moreover, chronic alcoholism may be associated with
thiamine deficiency, which can lead to beriberi heart
disease (also indistinguishable from DCM).
22. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Pathogenesis.
Alcohol and other toxins.
Nevertheless, no morphologic features serve to distinguish
alcoholic cardiomyopathy from DCM of other causes.
In other cases, some other toxic insult can progress to eventual
myocardial failure.
Particularly important is myocardial injury caused by certain
chemotherapeutic agents, including doxorubicin (Adriamycin), and
even targeted cancer therapeutics (e.g., tyrosine kinase inhibitors).
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).
23. Basic Science of Cardiomyopathies
Dilated Cardiomyopathy
Pathogenesis.
Childbirth.
A special form of DCM, termed peripartum cardiomyopathy, can occur late in pregnancy or up to months
postpartum.
The mechanism underlying this entity is poorly understood but is probably multifactorial.
Pregnancy-associated hypertension, volume overload, nutritional deficiency, other metabolic
derangements, or an as yet poorly characterized immunological reaction have been proposed as causes.
24. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Pathogenesis.
Childbirth.
Recent work suggests that the primary defect is a microvascular
angiogenic imbalance within the myocardium leading to functional
ischemic injury.
Thus, peripartum cardiomyopathy can be elicited in mouse models by
increased levels of circulating antiangiogenic mediators including
vascular endothelial growth factor inhibitors (e.g., sFLT1, as occurs
with preeclampsia) or antiangiogenic cleavage products of the
hormone prolactin (which rises late in pregnancy).
25. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Pathogenesis.
Childbirth.
Proangiogenic approaches, including the
blockade of prolactin secretion by
bromocriptine, represent new therapeutic
strategies for treating this disease.
26. Basic Science of Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• 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, and
may be caused by interference with metal-dependent enzyme
systems or to injury from iron-mediated production of reactive
oxygen species.
27. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Pathogenesis.
Supraphysiologic stress
This can happen with persistent tachycardia, hyperthyroidism, or
even during development, as in the foetuses of insulin dependent
diabetic mothers.
Excess catecholamines, in particular, may result in multifocal
myocardial contraction band necrosis that can eventually progress
to DCM.
This can happen in individuals with pheochromocytomas, tumors
that elaborate epinephrine; use of cocaine or vasopressor agents
such as dopamine can have similar consequences.
28. Basic Science of
Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• Supraphysiologic stress
• Such “catecholamine effect” also
occurs in the setting of intense
autonomic stimulation, for example,
secondary to intracranial lesions or
emotional duress.
• Thus, takotsubo cardiomyopathy is
an entity characterized by left
ventricular contractile dysfunction
following extreme psychological
stress; affected myocardium may be
stunned or show multifocal
contraction band necrosis.
29. Basic Science of
Cardiomyopathies
• Dilated Cardiomyopathy
• Pathogenesis.
• Supraphysiologic stress
• For unclear reasons, the left
ventricular apex is most often affected
leading to “apical ballooning” that
resembles a “takotsubo,”
• Japanese for “fishing pot for trapping
octopus” (hence, the name).
• The mechanism of catecholamine
cardiotoxicity is uncertain, but likely
relates either to direct myocyte toxicity
due to calcium overload or to focal
vasoconstriction in the coronary
arterial macro- or microcirculation in
the face of an increased heart rate.
30. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Pathogenesis.
Supraphysiologic stress
Similar changes may be encountered in individuals who
have recovered from hypotensive episodes or have
been resuscitated from a cardiac arrest; in such cases,
the damage is a result of ischemia-reperfusion with
subsequent inflammation.
31. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Morphology
In DCM the heart is usually enlarged,
heavy (often weighing two to three times
normal), and flabby, due to dilation of all
chambers.
Mural thrombi are common and may be
a source of thromboemboli.
There are no primary valvular alterations; if
mitral (or tricuspid) regurgitation is present,
it results from left (or right) ventricular
chamber dilation (functional regurgitation).
32. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Morphology
Either the coronary arteries are free of
significant narrowing or the obstructions
present are insufficient to explain the
degree of cardiac dysfunction.
The histologic abnormalities in DCM are nonspecific and
usually do not point to a specific etiology.
Most muscle cells are hypertrophied with
enlarged nuclei, but some are attenuated,
stretched, and irregular.
33. Basic Science of
Cardiomyopathies
• Dilated Cardiomyopathy
• Morphology
• Interstitial and endocardial
fibrosis of variable degree is
present, and small
subendocardial scars may
replace individual cells or
groups of cells, probably
reflecting healing of previous
ischemic necrosis of myocytes
caused by hypertrophy-induced
imbalance between perfusion
and demand.
• Moreover, the severity of
morphologic changes may not
reflect either the degree of
dysfunction or the patient’s
prognosis.
34. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Clinical Features.
DCM can occur at any age, including in
childhood, but it most commonly affects
individuals between the ages of 20 and 50.
It presents with slowly progressive signs and
symptoms of CHF including dyspnea, easy
fatigability, and poor exertional capacity.
At the end stage, ejection fractions are
typically less than 25% (normal = 50% to 65%).
35. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Clinical Features.
Secondary mitral regurgitation and abnormal
cardiac rhythms are common, and embolism
from intracardiac thrombi can occur.
Death usually results from progressive cardiac
failure or arrhythmia, and can occur suddenly.
Although the annual mortality is high (10% to
50%), some severely affected patients respond
well to pharmacologic therapy.
36. Basic Science of
Cardiomyopathies
Dilated Cardiomyopathy
Clinical Features.
Cardiac transplantation is also increasingly
performed, and long-term ventricular assist
can be beneficial.
Interestingly, in some patients, relatively
short-term mechanical cardiac support can
induce durable improvement of cardiac
function.
37. Basic Science of
Cardiomyopathies
Arrhythmogenic Right Ventricular
Cardiomyopathy
Arrhythmogenic right ventricular
cardiomyopathy (ARVC) is an inherited
disease of myocardium causing right
ventricular failure and rhythm disturbances
(particularly ventricular tachycardia or
fibrillation) with sudden death.
Left-sided involvement with left-sided heart
failure may also occur.
38. Basic Science of
Cardiomyopathies
Arrhythmogenic Right Ventricular
Cardiomyopathy
Morphologically, the right ventricular
wall is severely thinned due to loss of
myocytes, accompanied by extensive
fatty infiltration and fibrosis.
Although myocardial inflammation may
be present, ARVC is not considered an
inflammatory cardiomyopathy.
Classical ARVC has autosomal dominant
inheritance with a variable penetrance.
39. Basic Science of
Cardiomyopathies
Arrhythmogenic Right Ventricular
Cardiomyopathy
The disease has been attributed to defective
cell adhesion proteins in the desmosomes that
link adjacent cardiac myocytes.
Naxos syndrome is a disorder characterized by
arrhythmogenic right ventricular
cardiomyopathy and hyperkeratosis of plantar
palmar skin surfaces specifically associated
with mutations in the gene encoding the
desmosome-associated protein plakoglobin.
40. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a common
(incidence, 1 in 500), 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.
It is the leading cause of left ventricular hypertrophy
unexplained by other clinical or pathologic causes.
The heart is thick-walled, heavy, and hyper-contracting, in
striking contrast to the flabby, hypo-contracting heart of
DCM.
41. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
HCM causes primarily diastolic dysfunction; systolic
function is usually preserved.
The two most common diseases that must be
distinguished clinically from HCM are deposition
diseases (e.g., amyloidosis, Fabry disease) and
hypertensive heart disease coupled with age-
related subaortic septal hypertrophy.
Occasionally, valvular or congenital subvalvular
aortic stenosis can also mimic HCM.
42. Basic Science of
Cardiomyopathies
• Hypertrophic Cardiomyopathy
• Pathogenesis.
• In most cases, the pattern of transmission is
autosomal dominant with variable
penetrance.
• HCM is caused by mutations in any one of
several genes that encode sarcomeric
proteins; there are more than 400 different
known mutations in nine different genes,
most being missense mutations.
• Mutations causing HCM are found most
commonly in the gene encoding β-myosin
heavy chain (β-MHC), followed by the genes
coding for cardiac TnT, α-tropomyosin, and
myosin-binding protein C (MYBP-C); overall,
these account for 70% to 80% of all cases.
43. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Pathogenesis.
Different affected families may have distinct
mutations involving the same protein.
For example, approximately 50 different
mutations of β-MHC are known to cause
HCM.
The prognosis of HCM varies widely and
correlates strongly with specific mutations.
44. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Pathogenesis.
Although it is clear that these genetic defects
are critical to the etiology of HCM, the
sequence of events leading from mutations to
disease is still poorly understood.
HCM is a disease caused by mutations in
proteins of the sarcomere.
45. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Pathogenesis.
Although such sarcomeric alterations have been thought to be
pathologic on the basis of abnormal cardiac contraction causing
a secondary compensatory hypertrophy, newer evidence
suggests that HCM may instead arise from defective energy
transferfrom its source of generation (mitochondria) to its site of
use (sarcomeres).
In addition, the interstitial fibrosis in HCM probably occurs
secondary to exaggerated responses of the myocardial
fibroblasts to the primary myocardial dysfunction.
46. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Pathogenesis.
In contrast, DCM is mostly associated with
abnormalities of cytoskeletal proteins, and can be
conceptualized as a disease of abnormal force
generation, force transmission, or myocyte signaling.
To complicate matters, mutations in certain genes, can
give rise to either HCM or DCM, depending on the site
and nature of the mutation.
47. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Morphology
The essential feature of HCM is massive myocardial
hypertrophy, usually without ventricular dilation.
The classic pattern involves disproportionate thickening of
the ventricular septum relative to the left ventricle free
wall (with a ratio of septum to free wall greater than
3 : 1), termed asymmetric septal hypertrophy.
In about 10% of cases, the hypertrophy is concentric
and symmetrical.
48. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Morphology
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.
Although marked hypertrophy can involve the entire
septum, it is usually most prominent in the
subaortic region.
The left ventricular outflow tract often exhibits a
fibrous endocardial plaque associated with thickening
of the anterior mitral leaflet.
49. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Morphology
Both findings result from contact of the
anterior mitral leaflet with the septum during
ventricular systole; they correlate with the
echocardiographic “systolic anterior motion”
of the anterior leaflet, with functional left
ventricular outflow tract obstruction during
mid-systole.
50. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Morphology
The most important histologic features of HCM
myocardium are:
Massive myocyte hypertrophy, with transverse
myocyte diameters frequently greater than 40 µm
(normal, approximately 15 µm);
Haphazard disarray of bundles of myocytes,
individual myocytes, and contractile elements in
sarcomeres within cells (termed myofiber disarray);
and Interstitial and replacement fibrosis.
51. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Clinical Features.
The central abnormality in HCM is reduced
stroke volume due to impaired diastolic
filling.
This is a consequence of a reduced chamber
size, as well as the reduced compliance of
the massively hypertrophied left ventricle.
In addition, approximately 25% of patients
with HCM have dynamic obstruction to the
left ventricular outflow.
52. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Clinical Features.
The compromised cardiac output in conjunction
with a secondary increase in pulmonary venous
pressure explains the exertional dyspnea seen
in these patients.
Auscultation discloses a harsh systolic ejection
murmur, caused by the ventricular outflow
obstruction as the anterior mitral leaflet moves
toward the ventricular septum during systole.
53. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Clinical Features.
Because of the massive hypertrophy, high left
ventricular chamber pressure, and frequently thick
walled intramural arteries, focal myocardial ischemia
commonly results, even in the absence of concomitant
coronary artery disease.
Major clinical problems in HCM are atrial fibrillation,
mural thrombus formation leading to embolization and
possible stroke, intractable cardiac failure, ventricular
arrhythmias, and, not infrequently, sudden death,
especially with certain specific mutations.
54. Basic Science of
Cardiomyopathies
Hypertrophic Cardiomyopathy
Clinical Features.
Indeed, HCM is one of the most common causes of
sudden, otherwise unexplained death in young
athletes.
The natural history of HCM is highly variable.
Most patients can be helped by pharmacologic
intervention (e.g., β-adrenergic blockade) to decrease
heart rate and contractility.
Some benefit can also be gained by reducing the septal
myocardial mass, thus relieving the outflow tract
obstruction.
This can be achieved either by surgical excision of
muscle or by carefully controlled septal infarction
through a catheter-based infusion of alcohol.
55. Basic Science of
Cardiomyopathies
Restrictive Cardiomyopathy
Restrictive cardiomyopathy is characterized by a primary
decrease in ventricular compliance, resulting in impaired
ventricular filling during diastole.
Because the contractile (systolic) function of the left
ventricle is usually unaffected, the functional abnormality
can be confused with that of constrictive pericarditis or
HCM.
Restrictive cardiomyopathy can be idiopathic or
associated with distinct diseases or processes that affect
the myocardium, principally radiation fibrosis,
amyloidosis, sarcoidosis, metastatic tumors, or the
deposition of metabolites that accumulate due to inborn
errors of metabolism.
56. Basic Science of
Cardiomyopathies
Restrictive Cardiomyopathy
The morphologic features are not
distinctive.
The ventricles are of approximately normal
size or slightly enlarged, the cavities are not
dilated, and the myocardium is firm and
noncompliant.
Bilatrial dilation is commonly observed.
57. Basic Science of
Cardiomyopathies
Restrictive Cardiomyopathy
Microscopically, there may be only patchy
or diffuse interstitial fibrosis, which can vary
from minimal to extensive.
Endomyocardial biopsy can often reveal a
specific etiology.
An important specific subgroup is
amyloidosis.
58. Basic Science of
Cardiomyopathies
• Restrictive Cardiomyopathy
• Several other restrictive conditions merit brief
mention.
• Endomyocardial fibrosis is principally a disease
of children and young adults in Africa and
other tropical areas, characterized by fibrosis
of the ventricular endocardium and
subendocardium that extends from the apex
upward, often involving the tricuspid and
mitral valves.
• The fibrous tissue markedly diminishes the
volume and compliance of affected chambers
and socauses a restrictive functional defect.
• Ventricular mural thrombi sometimes develop,
and indeed the endocardial fibrosis may result
from thrombus organization.
• The etiology is unknown.
59. Basic Science of
Cardiomyopathies
• Restrictive Cardiomyopathy
• Several other restrictive conditions merit
brief mention.
• Loeffler endomyocarditis also results
in endomyocardial fibrosis, typically
with large mural thrombi, with an
overall morphology similar to the
tropical disease.
• However, in addition to the cardiac
changes, there is often a peripheral
eosinophilia and eosinophilic
infiltrates in multiple organs, including
the heart.
• The release of toxic products of
eosinophils, especially major basic
protein, is postulated to initiate
endomyocardial necrosis, followed by
scarring of the necrotic area, layering
of the endocardium by thrombus, and
finally organization of the thrombus.
60. Basic Science of
Cardiomyopathies
• Restrictive Cardiomyopathy
• Many patients with Loeffler
endomyocarditis have a
myeloproliferative disorder
associated with chromosomal
rearrangements involving either
the platelet-derived growth factor
receptor (PDGFR)-α or -β genes.
• These rearrangements produce
fusion genes that encode
constitutively active PDGFR
tyrosine kinases.
• Treatment of such patients with
the tyrosine kinase inhibitor
imatinib has resulted in
hematologic remissions
associated with reversal of the
endomyocarditis, which is
otherwise often rapidly fatal.
61. Basic Science of
Cardiomyopathies
• Restrictive Cardiomyopathy
• Endocardial fibroelastosis is an
uncommon heart disease
characterized by fibroelastic
thickening that typically involves the
left ventricular endocardium.
• It is most common in the first 2 years
of life; in a third of cases, it is
accompanied by aortic valve
obstruction or other congenital
cardiac anomalies.
• Endocardial fibroelastosis may actually
represent a common morphologic
endpoint of several different insults
including viral infections (e.g.,
intrauterine exposure to mumps) or
mutations in the gene for tafazzin,
which affects mitochondrial inner
membrane integrity. Diffuse
involvement may be responsible for
rapid and progressive cardiac
decompensation and death.
63. Forensic Pathology Aspects
of Cardiomyopathies
• Cardiomyopathy
• Although many cases of
cardiomyopathy come to clinical
attention due to signs and
symptoms of heart failure, in
some individuals their first
symptom will be sudden death or
their symptoms will be so
insidious as to be ignored until
death occurs.
• This is particularly true for
hypertrophic cardiomyopathy
and right ventricular
cardiomyopathy, but can
occasionally be seen in cases of
dilated cardiomyopathy.
64. Forensic Pathology Aspects of Cardiomyopathies
Hypertrophic cardiomyopathy
Relatively common cardiac disease, said to occur in about 1 in 500
individuals in the general population, yet it remains a relatively uncommon
cause of sudden death when compared to its overall frequency.
Its etiology lies in mutations of one of a number of genes that produce
proteins necessary for the structural integrity, contractile function, or
regulation of the cardiac sarcomere.
Unfortunately, DNA analysis for hypertrophic cardiomyopathy is not widely
available and, as such, the autopsy diagnosis still relies on anatomic
features.
65. Forensic Pathology Aspects of Cardiomyopathies
Hypertrophic cardiomyopathy
The heart will exhibit either concentric or asymmetric left ventricular hypertrophy.
Asymmetric hypertrophy is said to be present when the interventricular septal
thickness is 1.3 times greater than that of the posterolateral free wall.
Left ventricular outflow tract obstruction is a feature of some cases, such that
hypertrophic cardiomyopathy has also been referred to as hypertrophic obstructive
cardiomyopathy (HOCM) and idiopathic hypertrophic subaortic stenosis (IHSS).
66. Forensic Pathology Aspects of Cardiomyopathies
Hypertrophic cardiomyopathy
Anatomic features that suggest the presence of outflow tract obstruction include
thickening of the anterior mitral valve leaflet and formation of a fibrous plaque,
reflecting a mirror image of the mitral valve leaflet, on the adjacent left ventricular
outflow tract endocardium.
Histologically, most cases will exhibit a fairly characteristic bizarre branching of
myocytes, particularly prominent in the interventricular septum.
It is very important that histologic sections of the interventricular septum and the left
ventricular free walls be taken perpendicular to the long axis of the heart in order to
properly demonstrate these myocytes.
67. Forensic Pathology Aspects of Cardiomyopathies
Hypertrophic cardiomyopathy
Another characteristic feature is the presence of thickened intramural coronary
arteries.
Each of these features can be present in variable degrees, such that the
diagnosis may be difficult.
Because hypertrophic cardiomyopathy is inherited as an autosomal dominant
disorder, when the diagnosis is established, it is important to recommend that
close family members undergo clinical testing for this disease.
68. Forensic Pathology Aspects of
Cardiomyopathies
• Hypertrophic cardiomyopathy
• A 43-year-old female collapsed and died suddenly in her
home.
• She had no significant past medical history, but a sibling had
died suddenly several years previously with an autopsy
diagnosis of “cardiac death of undetermined etiology.”
• At autopsy, the heart weight was 590 grams and there was
evidence of asymmetric hypertrophy of the left ventricle,
particularly prominent in the anterior portion of the
interventricular septum (Image). This produced left
ventricular outflow tract obstruction with thickening of the
anterior mitral valve leaflet and mirror image fibrous
thickening of the left ventricular outflow tract adjacent to
the anterior mitral valve leaflet (Image).
69. Evidence of asymmetric hypertrophy of the left ventricle, particularly
prominent in the anterior portion of the interventricular septum
70. Left ventricular outflow tract obstruction with thickening of the anterior mitral valve leaflet and mirror
image fibrous thickening of the left ventricular outflow tract adjacent to the anterior mitral valve leaflet
71. Forensic Pathology Aspects of
Cardiomyopathies
• Hypertrophic cardiomyopathy
• Another view of anterior mitral valve leaflet
thickening, from a different case, is shown in Image.
• Histologically, bizarre branching myocytes were
found throughout the left ventricular myocardium,
but were most prominent within the interventricular
septum (Image).
• Characteristic endothelial and medial thickening of
intramural coronary arteries was noted (Image).
• A diagnosis of hypertrophic cardiomyopathy was
made.
• Review of the histologic sections from the sibling
who died previously also revealed the characteristic
findings of hypertrophic cardiomyopathy.
72. Another view of anterior mitral valve leaflet thickening, from a different
case.
75. Forensic Pathology Aspects of Cardiomyopathies
Arrhythmogenic right ventricular cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy (also referred to as ARVD or
arrhythmogenic right ventricular dysplasia) is a relatively rare disorder that presents
pathologically as either paper-like thinning of the right ventricular myocardium
associated with replacement of the myocardium by a mixture of fibrous tissue and fat,
or as transmural fatty infiltration of the right ventricular myocardium extending from
the epicardium to the endocardium.
There may be evidence of patchy myocardial fibrosis and chronic inflammatory cell
infiltrates.
Occasionally, fatty infiltration will be found within the myocardium of the left ventricle.
76. Forensic Pathology Aspects of Cardiomyopathies
Arrhythmogenic right ventricular cardiomyopathy
In some cases, the diagnosis is relatively straightforward.
In others, assessing the degree of fatty infiltration as being abnormal can be challenging,
particularly in the elderly.
As such, referral to a cardiac pathologist is warranted.
Because arrhythmogenic right ventricular cardiomyopathy can be a familial disorder
(primarily autosomal dominant inheritance), family members should undergo clinical
examination for the disease when the diagnosis is made.
77. Forensic Pathology Aspects of Cardiomyopathies
• Arrhythmogenic right ventricular cardiomyopathy
• A 42-year-old female was found dead on a bed in a hotel room
that she had been cleaning.
• There was no known significant past medical history.
• At autopsy, there was transmural fatty infiltration and thickening
of the right ventricular myocardium (Image).
• Histologically, the fatty infiltration extended completely through
the myocardium to the endocardium (Image), with formation of
islands of myocardium completely surrounded by adipose tissue
(Image).
• A diagnosis of arrhythmogenic right ventricular cardiomyopathy
was made.
81. Forensic Pathology Aspects of Cardiomyopathies
Dilated cardiomyopathy
In cases of dilated cardiomyopathy, there is dilatation of all four cardiac
chambers, with predilection for more severe disease in the left
ventricle.
Although there will be left ventricular hypertrophy, ventricular
dilatation can produce a normal or even reduced free wall thickness.
The endocardium will exhibit variable degrees of fibrous thickening and
mural thrombi are often present.
82. Forensic Pathology Aspects of Cardiomyopathies
• Dilated cardiomyopathy
• The histologic changes are nonspecific, but include
endocardial fibrosis, interstitial fibrosis within the
myocardium, hypertrophy and/or actual thinning of
myocytes (as a result of ventricular dilatation), myocytolysis,
and occasional chronic inflammatory cell infiltrates.
• The diagnosis can only be made in the absence of
hypertension, coronary artery disease, and valvular disease.
• Silent or subclinical viral myocarditis is thought to be the
underlying cause of many cases of dilated cardiomyopathy.
83. Forensic Pathology Aspects of Cardiomyopathies
Dilated cardiomyopathy
So-called alcoholic cardiomyopathy is a form of dilated cardiomyopathy
that occurs in alcoholics, usually in the absence of alcoholic cirrhosis.
This is one of the more common reasons for a dilated cardiomyopathy
to come to the attention of a forensic pathologist.
Peripartum cardiomyopathy is a form of dilated cardiomyopathy of
unknown etiology arising in the third trimester of pregnancy or the first
6 months postpartum.
84. Forensic Pathology Aspects of
Cardiomyopathies
• Dilated cardiomyopathy
• A 35-year-old female, was found dead in bed.
• She had apparently felt unwell for an unspecified
number of days prior to her death.
• Her eighth child had been delivered 6 weeks
previously without complications.
• There was no clinical history of hypertension.
• At autopsy, the atrial and ventricular chambers
were dilated, and the myocardium was uniformly
pale in color (Image).
85. The atrial and ventricular chambers were dilated, and the myocardium
was uniformly pale in color.
86. Forensic Pathology
Aspects of
Cardiomyopathies
Dilated cardiomyopathy
There was increased trabeculation of the left
ventricle, such that it had a morphologic
appearance similar to that of the right ventricle.
Histologic examination of the myocardium
revealed variable degrees of myocardial fibrosis,
with some myocyte hypertrophy and occasional
chronic inflammatory cell infiltrates (Image).
The cause of death was attributed to peripartum
cardiomyopathy.
87. Variable degrees of myocardial fibrosis, with some myocyte hypertrophy
and occasional chronic inflammatory cell infiltrates
88. Forensic Pathology
Aspects of
Cardiomyopathies
Alcoholic cardiomyopathy
Alcohol and its metabolites are directly toxic to
the heart.
In addition, chronic ethanol abusers may have
some element of thiamine deficiency, raising the
possibility of additional cardiac pathology.
Although an association between chronic ethanol
abuse and dilated cardiomyopathy is known, a
mechanism is not, and the morphology of
alcoholic dilated cardiomyopathy is no different
than any other form of dilated cardiomyopathy.
89. Forensic Pathology Aspects of Cardiomyopathies
• Alcoholic cardiomyopathy
• A 65-year-old known alcoholic was found
collapsed in the hallway of his apartment
building.
• His buttocks were in the air and his pants
were around his ankles.
• There was no evidence of trauma on the
body.
• At autopsy, the only finding of note was a
prominent dilated cardiomyopathy (Image).
91. Forensic Pathology Aspects of Cardiomyopathies
• Alcoholic cardiomyopathy
• Toxicology showed only a negligible
amount of alcohol.
• His cause of death was attributed to
dilated cardiomyopathy arising as a
result of chronic ethanol abuse.
92. Forensic Pathology Aspects of Cardiomyopathies
• Myotonic dystrophy
• Myotonic dystrophy is an autosomal dominant disease of skeletal muscle
that can be associated with cardiomyopathy and occasionally with sudden
death.
• The pathologic appearance of the heart is actually quite nonspecific (in fact,
the heart can appear to be normal), with histologic abnormalities appearing
in skeletal muscle rather than cardiac myocytes.
• DNA hybridization is used to detect an increased number of repeats of a
trinucleotide sequence (CTG) in the gene that encodes myotonin protein
kinase.
• These studies can be performed on postmortem blood, ideally collected in a
tube containing EDTA, although definitive results become less likely with
increasing postmortem period.
93. Forensic Pathology Aspects of Cardiomyopathies
• Myotonic dystrophy
• A 45-year-old male collapsed and died suddenly while
carrying wood at his worksite.
• Although he was suspected to have myotonic
dystrophy, this diagnosis had never been confirmed.
• At autopsy, there was evidence of left ventricular
hypertrophy and slight dilatation, together with
dilatation of the right ventricle.
94. Forensic Pathology
Aspects of
Cardiomyopathies
• Myotonic dystrophy
• Histologically, the myocardium
appeared to be relatively unremarkable,
however, sections of skeletal muscle
exhibited some central nuclei (Image)
and nuclear chains (Image), as can be
seen in myotonic dystrophy.
• Ring fibers, which are most
characteristic of this disease, were not
seen.
• Postmortem DNA hybridization studies
were consistent with a diagnosis of
myotonic dystrophy.
97. Forensic Pathology Aspects of Cardiomyopathies
• Do
• Search for any past medical history or histologic findings
that might suggest the underlying etiology of a dilated
cardiomyopathy. Examine the right ventricle of the heart,
looking for evidence of hypertrophy, thinning, and/or
significant fatty infiltration.
• Consider the diagnosis of hypertrophic cardiomyopathy in
cases of concentric, as well as asymmetric, left ventricular
hypertrophy.
• Take histologic sections of the interventricular septum at
right angles to its long axis in order to identify the abnormal
myocytes seen in hypertrophic cardiomyopathy.
98. Forensic Pathology Aspects of Cardiomyopathies
• Do
• Look for evidence of intramural coronary artery
abnormalities as an additional histologic sign of
hypertrophic cardiomyopathy.
• Recommend clinical screening of a family when
you make a diagnosis of hypertrophic
cardiomyopathy or right ventricular
cardiomyopathy.
• Don’t
• Make a diagnosis of “cardiomyopathy” in the
presence of hypertension, significant coronary
artery disease, or valvular disease.
99. BOOKS
• Pathologic basis of disease
• ISBN 978-1-4557-2613-4
• I. Kumar, Vinay, 1944- editor. II. Abbas, Abul K., editor. III. Aster,
Jon C., editor.
100. BOOKS
• Forensic Pathology, Principles and Practice
• David Dolinak, M.D.
• Evan W. Matshes, M.D.
• Emma O. Lew, M.D.
101. BOOKS
• Atlas of Forensic Histopathology
Peter M. Cummings, M.D.
Darin P. Trelka M.D.
Kimberley M. Springer, M.D.