Instagram Threads

Bay Four

          Patterns, pearls and practical medicine

Cardiomyopathies

  • Defined as a condition in which heart muscle is structurally and functionally abnormal, in the absence of CAD, HTN, valvular disease, and congenital heart disease
  • Cardiomyopathies can coexist with ischaemic, valvular, and hypertensive disease however
  • Five main types
      • Hypertrophic cardiomyopathy (HCM, HOCM)
      • Dilated cardiomyopathy (DCM)
      • Arrhythmogenic right ventricular cardiomyopathy (ARVC)
      • Restrictive cardiomyopathy (RCM)
      • Non-dilated left ventricular cardiomyopathy (NDLVC)
  • All are descriptions with multiple causes, not a really a diagnosis
  • Underlying causes to consider: Ischaemic, inherited, inflammatory, infiltrative, idiopathic (the five I’s)
  • Don’t ignore unexplained elevated troponins or abnormal T waves – could be an underlying cardiomyopathy

The general approach

  • Imaging to identify phenotype and determine dysfunction (most commonly with CMR and echo)
  • Assess/treat symptoms – ask specifically about syncope
  • Family hx, incl of Sudden Cardiac Death (SCD) which can sometimes be reported as drowning or an RTA
  • Check for other signs associated with genetic causes of cardiomyopathies – learning difficulty, deafness, visual impairment, gait disturbance, sensory abnormalities, muscle weakness
  • Evaluate and mitigate prognostic risks (eg HF, CVA)
  • SCD (sudden cardiac death) risk stratification for all at diagnosis and often done every 1-2 years
  • Prevent complications – consider VTE prophylaxis, ICD
      • ICD advised for anyone with a cardiomyopathy who has sustained a cardiac arrest, syncope or haemodynamic compromise due to VF or VT (provided no reversible causes).
      • Consider ICD in anyone with a hx of VT (and see specific indications per type of cardiomyopathy)
  • Manage chronic disease
      • Lifestyle interventions
      • Supportive care (inotropes, pacing, mechanical, transplant, antiarrythmics)
      • Limit injury/prevent recurrence (immunosuppression, antivirals, anticoagulation etc)

Investigations

  • ECG (and often Holter). May see
      • Signs of LVH (in HCM)
      • AV block
      • Low voltage (occurs in amyloid, Friedrichs ataxia, certain gene variants eg PLN)
      • Features of ARVC incl ectopics
  • Bloods incl renal function, TFTs, HbA1C, NT-pro BNP, LFTs, CK (myopathies), CRP (myocarditis), haematinics (haemochromatosis), bone profile, troponin (in chronic inflammatory skeletal myopathies, trop T can be produced by peripheral muscle cells. Check Trop I instead)
  • Cardiac imaging
      • Echo for all
      • Cardiac MRI
        • Can look for scar, necrosis, oedema
        • Patterns of Late Gadolinium Enhancement (LGE) can point to specific diagnoses. Sarcoid, myocarditis, DCM, eosinophilic, amyloid, HCM and Fabry’s, CAD/MI all have specific appearances
        • Most useful in helping to diagnose NDLVC, ARCV, myocarditis, amyloid, sarcoid, haemochromatosis
      • Occasionally need cardiac CT of coronaries, angiography or PET (CTCA to rule out CAD which may mimic findings, or occur alongside the cardiomyopathy)
  • Endomyocardial biopsy can help with diagnosing type of myocarditis (though low sensitivity), infiltrative disease like sarcoid and presence of viruses. Rarely required however
  • Consider genetic testing (and cascade testing of family if monogenic cause found)
      • Monogenic cause can be found in around 40% of HCM and 30% of DCM, but genes play a larger role as often polygenic inheritance of multiple susceptible variants
      • No evidence to support medications in unaffected carriers
      • Most AD inherited, with incomplete penetrance
      • Lots of interplay between comorbidities and genetic risk – eg HTN, DM and obesity will often lead to more severe or earlier disease in those who are generically prone
  • Surveillance – regular Holter, echo, and CMR if progressive disease
  • Screening family members of patient – Echo and ECG for all 1st degree family members of patients with cardiomyopathy, and consider cascade genetic testing if indicated

Hypertrophic cardiomyopathy (HCM)

  • Defined as increased LV wall thickness in any location (with or without RV hypertrophy) generally >15mm in adults (or >13mm if 1st degree relative diagnosed), not explained by loading conditions (eg HTN or aortic stenosis)
  • Pathophysiology
      • Characterised by myocyte hypertrophy and disarray, interstitial fibrosis and medial hypertrophy of small vessels.
      • Macroscopically, hypertrophy is usually asymmetric and involves the basal intraventricular septum wall, although different patterns, such as apical or concentric hypertrophy, have also been described.
      • The hypertrophy, in combination with other structural changes seen in HCM (elongated mitral valve leaflets and papillary muscles abnormalities), contribute to obstruction of blood flow during systole and increased pressure gradient across the LV outflow track (LVOT)
      • However: no obstruction in 75% of cases
  • Prevalence 1:500
  • Often inherited AD. A genetic mutation can be identified in about 50% of HCM cases
  • Childhood HCM has more potential causes including metabolic syndromes and neuromuscular disorders (but most is still due to variants in the sarcomere protein genes)
  • Clinical features
      • The clinical spectrum and natural course of the condition is heterogeneous and ranges from complete absence of symptoms to HF symptoms or sudden death. Obstruction increases risk of death.
      • Many asymptomatic and often benign. Some develop symptoms years after diagnosis made and changes seen on ECG and echo
      • Can cause chest pain, SOB (oedema), palpitations. The most common symptom is breathlessness on exertion because of the underlying obstruction. Chest pain is less often seen and accompanies breathlessness
      • Some have heart failure – often in those with LV outflow tract obstruction, or if HCM diagnosed in childhood. Systolic dysfunction is very rare
      • SCD can occur (0.8% per year). See risk factors below.
      • AF occurs in around 20% (and they have a higher stroke risk than other patient with AF)
      • Risk of syncope is around 15% every 5 years and increases risk of death. Cause of syncope/presyncope could be related to:
          • Paradoxical arrythmia
          • Non-sustained VT
          • AF
          • Outflow tract obstruction
          • Something else (eg autonomic dysfunction)
      • Syncope can be precipitated by dehydration, vasodilation, arrhythmias and betablocker withdrawal
      • Small increased risk of IE
      • Around 30% have an abnormal BP response to exercise (either drops or fails to increase by 20mmHg)
      • Signs include a jerky pulse, forceful apex beat, systolic thrill at left sternal border, ejection systolic murmur that radiates throughout precordium, audible S4
      • Lots associated conditions including
          • Friedreich’s ataxia – neuromuscular symptoms, DM
          • Amyloidosis
          • Fabry’s disease – skin, renal, GI, neuro involvement
          • Myocarditis
          • Metabolic conditions incl glycogen storage diseases
      • Risk factors of SCD in HCM (An online calculator is available). Spontaneous VF is the biggest risk.
          • Extensive LGE on CMR
          • Extreme LVH (esp if max wall thickness >30mm)
          • Hx of non-sustained VT (NSVT occurs in 25% of HCM patients on holter), esp if exercise-associated
          • Unexplained syncope
          • Abnormal BP response
          • Family hx of SCD
          • Adolescent males
          • Larger LA size
          • LVOTO max gradient
          • LV apical aneurysm
          • LV EF <50%
  • Diagnosis
      • ECG can suggest LVH on ECG (with no sign of HTN or AS to explain it)
          • S wave depth in V1 + tallest R wave height in V5-V6 > 35 mm
          • ST depression and TWI in I, AVL and V5-6 (or TWI across all chest leads, esp in apical HCM)
          • ST elevation V1-V3
          • LAD
          • Can be dagger Qs (deep, narrow) in lateral/inferior leads
          • p-mitrale (bifed ps)
          • Signs of WPW (overlap)
      • Can also get TWI inferiorly, and upright T wave in AVR
      • Can get short PR, or AV block – and their presence may suggest specific causes
      • Echo
          • LV hypertrophy (LV wall > 15mm). Extreme concentric LVH with wall thickness >30mm suggests Pompe’s or Danon disease
          • Focal and symmetrical (cf. concentric hypertrophy of hypertensive cardiomyopathy)
          • MR very common
          • Can have a high EF, sometimes >80%, due to a very small LV cavity (and low SV). EF is not a good measure of LV impairment when hypertrophy present
          • Check for LV outflow tract obstruction – important as it increases risk of SCD. Do Valsalva during echo. If negative and symptoms, do stress echo to confirm. LVOTO usually defined a gradient of >30mmHg, however generally only treated if >50mmHg.
          • Mid-cavity obstruction is often more severe (and 25% also have an LV apical aneurysm, which carries an increased risk of VT and LV therombus)
      • CMR
          • Better than echo for evaluation in some circumstances (apical HCM, aneurysms, LV thrombi), and some aetiologies have specific appearances eg Fabry’s and Amyloidosis, metabolic syndromes
          • LGE is present in 65% on CMR (often patchy and mid-wall). In athletes’ heart, which can be a differential, should be no LGE (but this still doesn’t rule out HCM)
      • However – sometimes imaging normal and only family history and abnormal ECG
      • Genetic testing
          • AD monogenetic inheritance in around 50% of cases (a single variant will be found on genetic testing). Sporadic cases can also have a monogenic cause
          • Can be gene positive but phenotype negative (but needs annual review)
          • Especially important if HTN present
          • Consider testing relatives
  • Management
      • Often no specific treatment if asymptomatic and no arrhythmia
      • If symptomatic, can aim to reduce LV filling pressures with a betablocker or verapamil
      • Treat any angina (nitrates can be used with caution if no LVOTO). Ranolazine – very good for angina in HCM, and reduces ectopic burden
      • Generally avoid nitrates and diuretics (esp if syncope, though can use low dose diuretics for SOB if careful to avoid hypovolaemia
      • LV Outflow Tract Obstruction
          • Avoid dehydration and excess ETOH. Lose weight.
          • Avoid vasodilators like nitrates and sildenafil
          • Betablockers 1st line drugs (could also use verapamil or diltiazem instead)
          • 2nd line drugs include mavacamten (ATPase inhibitor, well tolerated) and disopyramide (anti-cholingegic, monitor QTC, avoid in glaucoma, BPH, long QT)
          • Treat consider surgery (ventricular septal mymectomy) or septal ablation – esp if severe symptoms, and syncope. Surgery can leads to AV block, LBBB, VSD and AR
          • If asymptomatic – usually don’t treat
          • Pacing sometimes considered
      • Consider ICD
          • Depending on risk of SCD and patient preference
          • Can use HCM risk of SCD calculator. Consider ICD if risk is 4-6% over 5 years. ICD recommended if risk is >6% over 5 years
      • Heart transplant for those with refractory symptoms
      • Treat AF with usual rate or rhythm control, which may improve symptoms of HF.
      • Ensure lifelong anticoagulation if any hx of AF (ignore CHADSVASC)
      • Treat HF as usual (perhaps with a lower threshold for a CRT device)
      • Exercise advice
          • Can usually safely exercise if asymptomatic and no obstruction
          • High intensity exercise / competition can be considered if genotype-positive but phenotype-negative (or if morphologically mild disease with no obstruction or exercise induced arrythmias)
          • A patient with an ICD fitted can continue to exercise intensely if there is no increase in shocks or adverse events
      • Pregnancy – most tolerate pregnancy well although gradient increases slightly during pregnancy

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

  • RV and / or dysfunction, characterised by specific ECG abnormalities and histopathology
  • Actually usually biventricular (in 70%)
  • Prevalence 1:2500 – so rare, but also one of the most common causes of SCD (especially in young athletes with the disease)
  • Usually presents in those aged 20-50 (most commonly mid-thirties), and more common in men. High intensity exercise can accelerate the disease
  • Features
      • Can present with frequent Ventricular Ectopics (found incidentally)
      • Risk of SCD and syncope
      • Biventricular failure
      • Arrhythmias
          • Risk of VT/VF is 4-10% per year and increased in men, those with RV dysfunction and prior VT
          • The biggest risk is that of fast VT ie >250bpm which can lead to arrest. Those with ARVC can often tolerate sustained VT without arrest if slower
      • ST changes with trop rise and normal coronaries
  • Four clusters
      • Cluster 1 very RV heavy, cluster 3 very LV heavy
      • Different genetic mutations and the ECGs are different
      • Can sometimes mimic DCM or NDLVC
  • Diagnosis
      • Genetics
          • Variants can be found in around 60% of those with ARVC.
          • Mostly AD inheritance – but penetrance varies according to age, gender and physical activity
          • Most variants code for the cardiac desmosome – PKP2, DSP, DSG2, DSC2, JUP
          • Also variants in DES, TMEM43, PLN
          • Those with DSP or DSG2 variants are more prone to HF
          • DSP cardiomyopathy (Desmoplakin gene varients) – LV predominance, recurrent myocarditis, female predisposition, and occasionally associated with Carvajal syndrome (palmoplantar keratoderma, tightly curled hair, more often AR inherited)
      • ECG
          • Anterior (V1-V3) TWI – but this can be normal
          • Delayed upstroke in S wave in V2
          • Epsilon wave (a small post-excitation deflection / wiggle found between the end of the QRS complex and the start of the T wave. Often overdiagnosed, but when present, there is often severe structural HD, so not a very useful finding)
          • QRS fragmentation, and QRS prolongation in V1-V3
          • Frequent VEs, and VT can occur usually in LBBB morphology
          • Small limb lead complexes
      • Echo and CMR
          • Often RMWA incl RV akinesia / dyskinesia or bulging
          • RV dilatation
          • Check for LV involvement with contrast enhanced CMR
      • Differentials / phenocopies (occasionally biopsy advised to exclude)
          • Myocarditis
          • Sarcoid
          • RV infarction
          • DCM
          • Chagas disease
          • Pulmonary HTN
          • Congenital heart disease with volume overload
          • Idiopathic RV outflow tract VT (This is more benign. Usually baseline ECG normal, no family hx, normal RV on imaging, single VT morphology, non-inducible VT)
          • Athletes heart – suggested by no RWMAs, normal RV, no frequent VEs, no inverted T waves in precordial leads
  • Management
      • Annual Holter advised
      • ARVC risk calculator
          • Gives risk of VF or VT within 5 years for those with confirmed diagnosis and no prior sustained ventricular arrhythmia
          • Input age, sex, hx of syncope, number of TWI in precordial and inferior leads, max PVC count in 24 hour Holter, prior non-sustained VT (ie lasting <30 secs), RV EF
      • ICD
          • Always if hx of arrest or syncopal VT as for other cardiomyopathies
          • Often advised if non-syncopal VT, RV EF <40%, LV EF <45%, high risk by the calculator above
          • Inserted quite frequently in this condition
      • Exercise
          • All can do low intensity exercise
          • All should avoid moderate or intense exercise
          • Should not do intense exercise even if gene positive but phenotype negative
      • Antiarrhythmics
          • Betablocker 1st line, amiodarone 2nd line (but caution using long term)
      • Ablation sometimes advised if drugs don’t work
      • No excess mortality in ARVC in pregnancy

Dilated cardiomyopathy (DCM)

  • LV dilatation and dysfunction (EF <50%) unexplained solely by abnormal loading conditions or CAD
  • LV dilatation defined as end-diastolic diameter of >58mm in men and >52mm in women
  • Isolated LV dilatation with normal EF is an early form of DCM
  • 2% prevalence
  • Genetics
      • Causative gene variants can be found in around 40% of patients overall (and 10-15% in chemo-induced, alcoholic or peripartum DCM), and in 20% of those with no family hx
      • Testing useful – helps predict prognosis, determine management, informs genetic counselling and have implications for relatives who might want screening
      • Sarcomeric – Titin gene truncating variants are present in 13.5% of those with alcoholic DCM, and also increase the risk of cancer therapy-induced cardiomyopathy and post-partum cardiomyopathy. They are associated with recovery of EF with standard HF treatments
      • LMNA (worse prognosis), RBM20
      • Dystrophin, emerin, Barth syndrome mutations are all x-linked
      • Rarely due to mitochondrial mutations or disease
      • Significant interplay between genetic risk and disease modifiers that may trigger or accelerate DCM eg pregnancy, HTN, ETOH, toxins (therefore identifying an acquired cause doesn’t exclude an inherited cause too, and vica versa)
  • Causes
      • Idiopathic (50%)
      • Ischaemic
      • Inherited – familial (cardiac phenotype), myotonic or muscular dystrophy, thalassemia, hemochromatosis
      • Drugs – ETOH, cocaine/stimulants, cobalt, chemotherapy, toxins, antipsychotics, anabolic steroids, ARVs
      • HTN
      • Post-myocarditis/infection (incl Chagas, HIV, Lyme, viruses, TB, fungi)
      • Takotsubo cardiomyopathy
      • CTD / autoimmune – SLE, sarcoid, chronic inflammation, thyroid disease, EGPA, RA, ILD
      • Pregnancy / peripartum
      • Nutritional deficiency – Thiamine (beri beri), selenium, zinc, copper or carnitine deficiencies
      • Friedreich’s ataxia
      • Metabolic – Phaeo, acromegaly, chronic hypocalcaemia or hypophosphataemia
  • Can progress through: subclinical, isolated ventricular dilation, arrythmias, hypokinesia, dilated CM with LV dilation and hypokinesia (can take years/decades)
  • DCM with disproportionate arrythmias – this can suggest causes such as inflammation/myocarditis, incl sarcoid, or genetic
  • CMR
      • Can detect presence of oedema which suggests myocarditis/inflammation
      • LGE can determine extent of fibrosis, correlates with prognosis, and give clues to cause. It is present in around 30% of patients with DCM
          • CAD can give specific patterns of fibrosis
          • Subepicardial fibrosis occurs post-myocarditis
          • Patchy fibrosis in sarcoid
          • Extensive inferolateral scar/fibrosis in dystrophinopathies
          • Septal mid wall LGE in LMNA carriers
          • Ring-like LGR in DSP and FLNC-truncating variant carriers
      • Dedicated T2 sequences can determine myocardial iron deposition and helps diagnose haemochromatosis
      • Can also be useful for well relatives of patients with DCM who carry certain gene variants
  • Management
      • Broadly as you would manage heart failure of any cause
      • ICD recommended if hx of arrest or VT with haemodynamic compromise
      • Consider ICD for:
          • EF <35%
          • Anyone with high-risk genes
            • LMNA, FLNC-truncating variants, EMD, TMEM43 represent the highest risk
            • DSP, RBM20, PLN also high risk
          • Consider if none of the above, but additional risk factors eg hx of VT or increased ventricular ectopics, syncope, significant LGE, other gene variants associated with DCM
      • Moderate or intense exercise can be considered in gene-positive, phenotype-negative people (unless high risk gene like LMNA or TMEM43), and in those with EF >50%, no symptoms and no arrythmias

Non-dilated left ventricular cardiomyopathy

  • Non-ischaemic LV scarring or fatty replacement (with or without RWMAs)
  • Often normal cavity size and well-preserved function
  • Often asymptomatic, but can present with AV block, arrhythmia, diastolic HF, syncope or arrest
  • Genetics
      • Genes variants conveying risk are similar to those in DCM, and incl DSP, LMNA, DES, FLNC, PLN, TMEM43, RBM20. All AD inherited.
      • If these genetic variants present, have a lower threshold for ICD for primary prevention
      • Desmoplakin (DSP) variants can cause a form with lots of fibrosis and episodic inflammation
  • ECG features can suggest a specific cause
      • Prolonged PR interval or AV block in neuromuscular causes of NDLVC and in sarcoidosis.
      • Prolonged PR interval, AF, ventricular ectopics, low voltage in laminopathies
      • Low QRS voltage in NDLVC caused by DSP and PLN variants
  • Holter advised annually due to risks of AV block and other arrythmias
  • CMR essential – see advice re: DCM. Can be ring-like scarring.

Restrictive cardiomyopathy

  • Often presents as HF with preserved EF
  • Restrictive pathophysiology, with normal or low ventricular volumes and normal ventricular wall thickness. Often bi-atrial dilatation.
  • Normal systolic function, severe diastolic dysfunction
  • Prognosis often worse than that of other cardiomyopathies (and is mostly determined by amount of restriction, not the cause). Main cause of death is HF in adults, and 5 year survival rate around 50%
  • Signs
      • Raised JVP
      • Low pulse volume
      • Increased heart rate as it progresses
      • Hepatomegaly, ascites, oedema
  • Causes
      • Amyloid (often LVH too)
      • Sarcoid
      • Haemochromatosis / iron overload
      • Glycogen storage diseases and lysosomal storage diseases (eg Fabry’s, Pompe’s, Danon)
      • Endomyocardial fibrosis
      • Hypereosinophilia
      • Carcinoid
      • Endocardial cancers or fibroelastosis
      • Malignancy
      • Drugs (eg chloroquine)
      • Friedreich’s ataxia
      • Cystinosis or hyperoxaluria
      • Generalised arterial calcification of infancy
      • Fibrosis – radiation, chemo, systemic sclerosis, inflammatory, DM
  • Investigations
      • CMR useful to diagnose differential of constrictive pericarditis, can determine amount of fibrosis and can help distinguish metabolic from inflammatory causes
      • Genetic tests
          • The most common gene variant implicated is TNN13
          • Other variants include TNNT2, ACTC1, MYH7, MYBPC3, TTN, TPM1, MYPN, MYL3, MYL2, DES, FLNC, and BAG3
      • Cardiac biopsy sometimes done in cases of suspected iron overload, storage disorders, mitochondrial cytopathies, amyloid, sarcoid
  • Management
      • Treat the cause
      • Maintenance of euvolaemia essential
      • AF occurs in 50% (always anticoagulated unless contraindication)

Related conditions

  • LV hypertrabeculation (LV non-compaction)
      • Prominent trabeculae and deep intertrabecular recesses, with LV wall thickening, and sometimes systolic dysfunction
      • Often familial
      • Can be transient in athletes or pregnancy
  • Inflammatory cardiomyopathy
      • Myocarditis associated with cardiac dysfunction
      • Progresses to DCM in around 30%
      • Differential is cardiac sarcoid and ARVC
  • Lamin cardiomyopathy
      • DCM with high incidence of heart block, with or without muscular dystrophy
      • Multiple phenotypes
      • Arrythmias precede the DCM, in those with normal LV function. Therefore important to diagnose early. High risk of SCD
      • Often family hx, and sometimes family members get a PPM and then die of an arrythmia
  • Takotsubo cardiomyopathy / syndrome
      • LV apical ballooning, with some local systolic dysfunction and oedema
      • Often cauases angina like chest pain, diffuse TWI, and sometimes mildly elevated trop
      • Most common in post menopausal women and opften preceded by stress
      • Often reverses
      • See MINOCA
  • Fabry’s disease
  • Cardiac amyloid
      • Can cause HFpEF, aortic stenosis, unexplained LVH
      • Mostly occurs in older patients
      • Also causes neuropathy, proteinuria, carpal tunnel
      • See Cardiac amyloidosis
  • Glycogen storage diseases
      • Incl Danon disease, Pompe’s disease, PRKAG2
      • Consider if short PR interval and increased ECG voltages, conduction disease in PRKAG2
      • See Glycogen storage diseases
  • RASopathies
      • Multisystemic diseases caused by variants in the RAS-mitogen-activated kinase (RAS-MAPK) cascade
      • Includes Noonan’s, Costello’s, and cardiofaciocuaneous syndromes
      • Can cause infant and childhood onset HCM (often with other congenital HD eg pulmonary stenosis)
  • Friedreich’s ataxia
      • AR inherited (GAA triplet repeat expansion in the frataxin (FTX) gene
      • Leads to HCM (often with HF), AF, neuromuscular symptoms, DM

 

Scroll to Top

Comments and corrections

Help us improve by reporting your comments and corrections.

Thank you!

Your comment has been sent. We review all submissions carefully.