Cardiomyopathies Flashcards
What is the definition of cardiomyopathy?
It is defined as a myocardial disorder, in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease (CAD), hypertension, valvular disease and congenital heart disease (CHD) sufficient to cause the observed myocardial abnormality.
What are the main phenotypes of cardiomyopathies?
- Hypertrophic cardiomyopathy
- Dilated cardiomyopathy
- Arrhythmogenic right ventricular cardiomyopathy
- Restrictive cardiomyopathy
- Unclassified cardiomyopathies such as left ventricular noncompaction cardiomyopathy which is now considered an early stage or variant of dilated or non dilated left ventricular cardiomyopathy.
Classical scenario of cardiomyopathy? How do we understand which phenotype?
- Acute new onset of symptoms such as chest pain, palpitations, syncope, dyspnea on effect. All of which are non specific cardiologic symptoms.
- Incidental findings such as abnormal ECG or stress test.
- Family screening, specifically if there is a first degree relative with CM or a history of SCD.
Then we asses ventricular morphology and function using echocardiogram and ventricular scar/fatty replacement using MRI. These tools can help us asses which phenotype of CM.
How does genetic testing for cardiomyopathy mutation work?
If the genetist finds a pathogenic or likely pathogenic gene there is strong evidence of it being responsible for the onset of the disease. Variants of uncertain significance are genes that may or may not be connected to the onset of the disease. If no genetic variant is identified in the screening we must consider that the panel of genes was set up incorrectly.
What is Hypertrophic Cardiomyopathy? Etiology?
It’s defined as the presence of an increased left ventricular wall thickness with or without right ventricular hypertrophy, and/or an increase in left ventricular mass, that is not solely explained by an abnormal loading condition such as hypertension (afterload increase) or valve diseases (preload increase).
Most forms of HCM (40-60%) are caused by autosomal dominant gene mutations involving the mechanical architecture of the cardiac myocytes like MYBPC3 an MYH7. There may also be non sarcomeric variants which are phenocopies of the disease but are caused by other diseases such as metabolic or storage disease, amyloidosis and others.
What is the pathophysiology of HCM?
Conformation of myocardium is abnormal with myofiber disarray. Since they follow a heterogenous orientation, occupying the volume in a non-efficient way increase of ECM and decrease of fibers.
There are intra myocardial vessels which present increased thickness, we can also detect micro scarring and fibrosis.
How is HCM classified?
It is classified based on site of hypertrophy as it may be apical, neutral, sigmoidal or reverse curve.
It is also classified based on degree of obstruction.
- If it is non obstructive the margin of the septum is asymmetric but doesn’t bulge inside the cavity of the LV and is not invasive for outflow tract.
- if it is obstructive it causes hemodynamic changes. This causes a lower CO and syncope.
What are there mechanisms by which the left ventricular outflow obstruction may occur?
Structural : Obstruction may be frequently due to papillary
muscles displacement. Considering the asymmetric hypertrophy, it may lead to dislocation of these muscles, so that they result more anterior, tending to create the obstruction. Being an anatomical/structural problem, it can be treated only surgically.
Functional : It is not caused by the myocardial wall itself but by the suction of the anterior leaflet of the mitral valve during the systolic phase. The huge difference in pressure, instead of inducing the closure of the valve, causes the occlusion of the outflow of the left ventricle by the anterior mitral leaflet, also causing mitral valve regurgitation.
What is classical clinical presentation of HCM?
Dyspnea on effort, syncope, palpitations, chest pain on effort and cardiocirculatory arrest.
How is HCM diagnosed?
Physical examination : In most cases it is normal but in most severe cases there is systolic murmurs due to LVOT obstruction.
ECG : Increased LV voltages which is sign of hypertrophy, ST segment abnormalities and symmetric or asymmetric negative T waves.
BNP : May be increased because of diastolic function.
Echo : Gold standard diagnostic tool.
MRI : May indicated replacement fibrosis and show increased extracellular volume.
Arrhythmia monitoring exams : 48 h holter ECG but in case of paroxysmal arrhythmias we may opt for implantable loop recorders.
Genetic testing.
How does HCM evolve over time?
In most cases, 75%, it stays stable without major risk of HF and SCD. In 15% of cases it can cause adverse remodeling where it can evolve to maladaptive overt dysfunction, EF between less than 50% and it is a clear sign of end stage HCM.
How can we predict the risk of sudden death in patients with HCM?
The ESC recommends the use of its risk calculators based on large cohort studies made with patients affected by HCM. Data that needs to be inserted : age, maximal LV wall thickness, LA size, maximal LVOT gradient, family history of SCD, non sustained vtach, and unexplained syncope.
The American scoring system instead accounts for a number of more relevant risk factors such as 2 key factors like presence of apical aneurysm and presence of extensive Late Gadolinium Enhancement on MRI, cutoff is 15%.
What is late gadolinium enhancement CMR?
Late gadolinium enhancement (LGE) is a method where cardiovascular magnetic resonance (CMR) images are obtained after the administration of gadolinium contrast material that accumulates into a tissue with increased extra cellular space. This method is suggestive of fibrosis in both the left and right ventricles.
How is HCM treated?
In case of resting/provocable LVOTO with a gradient ≥50 mmHg (prognostic cutoff) and onset of symptoms, the 1st line drugs are beta-blockers able to reduce HR and prevent ventricular dilation.
If the patient is still symptomatic or intolerant to beta-blockers, we should consider calcium-antagonists such as Verapamil o Diltiazem.
If the patient is again still symptomatic, Disopyramide should be considered as anti-arrhythmic agent (Class I), which having also myorelaxant properties, has a key application in HCM and no other relevant diseases in cardiology.
Before considering the last option, which is the surgical septal reduction therapy, we may consider (Class IIa) a new drug called Mavacamten, which basically, targeting myosin, favors myocardial relaxation improving the diastolic function.
What is septal reduction therapy?
ASA = alcohol septal ablation, minimally invasive, hemodynamic procedure that is performed percutaneously which through a wire reaching the LAD coronary artery we deliver alcoholic agents which cause massive selective and local necrosis of myocytes in order to reduce the LV thickness. The main side effects are unwanted MI in different areas or AV block due to necrosis of septal myocytes.
Myectomy : Open heart surgery, directly remove the portion of septum in excess that causes obstruction.
What is dilated cardiomyopathy?
It’s defined as the presence of LV dilation and global or regional systolic dysfunction unexplained solely by abnormal loading conditions (e.g. CHD, hypertension, valve disease).
RV dilation or dysfunction may be present but they are not necessary for the diagnosis.
There is no disarray since the fibers present longitudinal and aligned but there are areas of replacement fibrosis causing contractile dysfunction and risk of arrhythmias. MRI shows an increase in LV volume with thinning of LV walls (opposite to HCM). Prevalence is much higher than HCM, also because it is the final common pathway of all the remaining cardiomyopathies including end-stage HCM.
