Heart Muscle Diseases (Cardiomyopathies): Causes

Dilated (dilated) cardiomyopathy (DCM)

Etiology (causes)

In approximately 50% of cases, the cause of dilated cardiomyopathy is unknown (“primary/idiopathic cardiomyopathy”). Biographic Causes

  • Genetic burden-approximately 30% are genetic familial forms
    • X-linked recessive – mutations of the dystrophin gene.
    • Autosomal-dominant – associated with excitation conduction disorder as well as sick sinus syndrome.
    • Autosomal recessive – mutation of the genes of fatty acid oxidation.
    • Mutations of the mitochondrial DNA
    • Dilating course in mutations (primary or secondary).
    • Genetic diseases
      • Amyloidosis – in addition to acquired forms of amyloidosis (e.g., due to malignancy/malignant tumor), there are amyloidoses with mostly autosomal dominant inheritance; lead to accumulation of abnormally altered proteins in the interstitium, i.e., intercellular space
      • Barth syndrome – congenital defect of phospholipid metabolism (X-linked recessive inheritance); characterized by dilated cardiomyopathy (DCM; Myocardial disease associated with abnormal dilatation of the heart muscle, especially the left ventricle, myopathy of the skeletal muscle, neutropenia (reduction of neutrophil granulocytes in the blood), retarded growth, and organoaciduria; pathogenesis: Disruption of the respiratory chain in mitochondria (power plants of cells); affects only boys and occurs in early childhood.
      • Glycogen storage diseases – group of diseases with both autosomal dominant and autosomal recessive inheritance, in which the glycogen stored in body tissues can not or only incompletely degraded again or converted to glucose.
      • Hemochromatosis (iron storage disease, English : hematochromatosis; from Greek haima = blood, chroma = color) – autosomal recessive hereditary disease; men are much more often affected than women. In the disease, there is an increased absorption of iron in the upper small intestine
      • Hurler syndrome – genetic disease with autosomal recessive inheritance; most severe form of mucopolysaccharidosis type I (MPS I), a rare lysosomal storage disease with characteristic skeletal deformities and delayed motor and intellectual development.
      • Friedreich’s ataxia (FA; Friedreich’s disease) – genetic disorder with autosomal recessive inheritance; degenerative disease of the central nervous system leading, among other things, to motor dysfunction; most common inherited form of ataxia (movement disorder); disease generally sets in during childhood or early adulthood.
      • Fabry disease (synonyms: Fabry disease or Fabry-Anderson disease) – X-linked lysosomal storage disease due to a defect in the gene encoding the enzyme alpha-galactosidase A, resulting in progressive accumulation of the sphingolipid globotriaosylceramide in cells; mean age of manifestation: 3-10 years; early symptoms: Intermittent burning pain, decreased or absent sweat production, and gastrointestinal problems; if left untreated, progressive nephropathy (kidney disease) with proteinuria (increased excretion of protein in urine) and progressive renal failure (kidney weakness) and hypertrophic cardiomyopathy (HCM; disease of the heart muscle characterized by thickening of the heart muscle walls).
      • Gaucher disease – genetic disease with autosomal recessive inheritance; lipid storage disease due to the defect of the enzyme beta-glucocerebrosidase, which leads to the storage of cerebrosides mainly in the spleen and marrow-containing bones.
      • Hunter’s disease – X-linked recessive lysosomal storage disease from the group of mucopolysaccharidoses (MPS; of which seven forms are known); clinical picture: first nonspecific symptoms, such as frequent ENT infections, usually occur in early childhood; disease course is progressive and increasingly leads to severe physical and, in some cases, cognitive impairments: the spectrum of impairments ranges from early type A (mental retardation) to early type B (very mild manifestations with little or without mental developmental delay); in severe courses often early death of patients.
      • Niemann-Pick disease (synonyms: Niemann-Pick disease, Niemann-Pick syndrome, or sphingomyelin lipidosis) – genetic disorder with autosomal recessive inheritance; belongs to the group of sphingolipidoses, which in turn are classified as lysosomal storage diseases; main symptoms of Niemann-Pick disease type A are hepatosplenomegaly (enlargement of the liver and spleen) and psychomotor decline; no cerebral symptoms are observed in type B
      • Pompe disease – genetic disease with autosomal recessive inheritance; lysosomal storage disease leading to cardiomegaly and heart failure, neurological and muscular deficits.
      • Neurofibromatosis – genetic disease with autosomal dominant inheritance; belongs to the phakomatoses (diseases of the skin and nervous system); three genetically distinct forms are distinguished:
        • Neurofibromatosis type 1 (von Recklinghausen’s disease) – patients develop multiple neurofibromas (nerve tumors) during puberty, which often occur in the skin but also occur in the nervous system, orbita (eye socket), gastrointestinal tract (gastrointestinal tract), and retroperitoneum (space located behind the peritoneum on the back toward the spine); The appearance of café-au-lait spots (CALF; light brown macules/spots) and multiple benign (benign) neoplasms is typical
        • [Neurofibromatosis type 2 – characterized by bilateral (bilateral) acoustic neuroma (vestibular schwannoma) and multiple meningiomas (meningeal tumors).
        • Schwannomatosis – hereditary tumor syndrome]
      • Noonan syndrome – genetic disorder with autosomal recessive or autosomal dominant inheritance that resembles the symptoms of Turner syndrome (short stature, pulmonary stenosis or other congenital heart defects; Low-set or large ears, ptosis (drooping of the upper eyelid ), epicanthal fold (“Mongolian fold”), cubitus valgus/abnormal position of the elbow with increased radial deviation of the forearm to the upper arm).
      • Transthyretin (TTR)-associated familial amyloid cardiomyopathy – with autosomal dominant inheritance; TTR-associated systemic amyloidosis (ATTR) with predominantly cardiac involvement leading to a restrictive cardiomyopathy with chronic heart failure (cardiac insufficiency); manifestation: adulthood (usually after 30. Age); warning signs (red flags) are a bilateral carpal tunnel syndrome (compression syndrome (narrowing syndrome) of the median nerve in the region of the carpal canal) and typical ECG and echo changes; HFpEF (heart failure with preserved ejection fraction) with left ventricular hypertrophy (enlargement of the left ventricle).
      • Tuberous sclerosis – genetic disease with autosomal dominant inheritance, associated with malformations and tumors of the brain, skin lesions, and mostly benign tumors in other organ systems.
  • Pregnancy: pregnancy cardiomyopathy/peripartum cardiomyopathy.

The other cases are “secondary (acquired)/specific cardiomyopathies”. Here, the heart is affected as part of systemic diseases. Behavioral causes

  • Consumption of stimulants
    • Chronic alcohol abuse (alcohol abuse) → alcoholic cardiomyopathy (ACM) (genes have been identified that are associated with alcohol toxicity to the myocardium: most commonly, these were gene variants of the TTN gene that lead to premature termination of the amino acid chain of titin)
  • Drug use
    • Cocaine
    • Methamphetamine (“crystal meth”) → methamphetamine-associated cardiomyopathy (appearance of severe heart failure (heart failure)/NYHA stage III or IV)

Disease-related causes

  • Acromegaly – endocrinological disease caused by overproduction of the growth hormone somatotropin (STH), with marked enlargement of the phalanges or acra, such as the hands, feet, lower jaw, chin, nose and eyebrow ridges.
  • Amyloidosis – extracellular (“outside the cell”) deposits of amyloids (degradation-resistant proteins) that can lead to cardiomyopathy (heart muscle disease), neuropathy (peripheral nervous system disease), and hepatomegaly (liver enlargement), among other conditions.
  • Carnitine deficiency
  • Dermatomyositis – disease belonging to the collagenoses, which affects the skin and muscles and is associated mainly with diffuse pain on movement.
  • Diabetes mellitus
  • Endocarditis Löffler (endocarditis parietalis fibroplastica) – acute form of endocarditis (endocarditis), which mainly affects the right ventricle (heart chamber).
  • Endomyocardial fibrosis
  • Hyperthyroidism (hyperthyroidism)
  • Hyperparathyroidism (parathyroid hyperfunction).
  • Hypothyroidism (hypothyroidism)
  • Hypovitaminoses such as beri-beri (caused by vitamin B1 deficiency), pellagra (caused by niacin deficiency), scurvy (caused by vitamin C deficiency).
  • Infections – e.g. viral infections (common cause of congestive cardiomyopathy / heart muscle disease, in which the ventricles (lower chambers of the heart) enlarge (dilatation), but can not pump enough blood into the body; this then leads to heart failure (cardiac insufficiency)), Lyme disease
  • Kwashiorkor (protein deficiency disease).
  • Lyme disease
  • Muscular dystrophy (muscle weakness)
  • Myocarditis (inflammation of the heart muscle)
  • Pheochromocytoma – usually benign tumor that originates predominantly in the adrenal gland and can lead to crisis increases in blood pressure.
  • Polyarteritis nodosa (PAN) – autoimmune disease that leads to vasculitis (inflammation of blood vessels) with narrowing of the vascular lumen.
  • Rheumatoid arthritis
  • Sarcoidosis (synonyms: Boeck’s disease; Schaumann-Besnier’s disease) – systemic disease of connective tissue with granuloma formation (skin, lungs and lymph nodes).
  • Selenium deficiency
  • Scleroderma – group of autoimmune connective tissue diseases, which is one of the collagenoses.
  • Systemic lupus erythematosus (SLE) – group of autoimmune diseases in which there is the formation of autoantibodies; it belongs to the collagenoses.

Chemotherapies

Environmental pollution – intoxications (poisonings).

Other causes

Hypertrophic (enlarged) cardiomyopathy (HCM)

Pathogenesis (disease development)

HCM is the most common hereditary (inherited) heart disease. In 90% of cases, it runs in families (= familial hypertrophic cardiomyopathy, FHC). Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by end-systolic narrowing of the left ventricular outflow tract with an intraventricular pressure gradient and mitral regurgitation (leakiness of the mitral valve). Furthermore, diastolic function is impaired. This results in decreased diastolic distensibility of the ventricle (heart chamber). In particular, intracellular calcium proliferation and interstitial fibrosis (abnormal proliferation of connective tissue) play a role.

Etiology (causes)

Biographic causes

  • Genetic burden – autosomal dominant with age-dependent penetrance – approximately two-thirds of cases are distributed among the three most common genes for MYH7, MYBPC3, and TNNT2
    • Genetic risk dependent on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism; English : single nucleotide polymorphism):
        • Genes: MYBPC3 (20-40% of cases of FHC), MYH7 (30-40% of cases of FHC).
        • SNP: rs3218713 in the MYH7 gene.
          • Allele constellation: AG (causes familial hypertrophic cardiomyopathy).
          • Allele constellation: AA (causes familial hypertrophic cardiomyopathy).
        • SNP: rs3218714 in the MYH7 gene.
          • Allele constellation: CT (causes familial hypertrophic cardiomyopathy).
          • Allele constellation: TT (causes familial hypertrophic cardiomyopathy).
        • SNP: rs375882485 in the MYBPC3 gene.
          • Allele constellation: AG (causes familial hypertrophic cardiomyopathy).
          • Allele constellation: AA (causes familial hypertrophic cardiomyopathy).

Restrictive (limited) cardiomyopathy (RCM)

Etiology (causes)

The causes of restrictive cardiomyopathy are unknown. Familial clusters are observed. Biographic causes

  • Genetic factors

Arrhythmogenic right ventricular cardiomyopathy (ARVCM)

Etiology (Causes)

The causes of arrhythmogenic right ventricular cardiomyopathy are unknown. Familial clusters are observed (in 40% of cases).Mutations in proteins of the desmosomes (important for cell contact in the myocardium/cardiac muscle) are thought to lead to arrhythmogenic right ventricular cardiomyopathy. Biographic Causes

  • Genetic factors
    • Autosomal recessive
    • Autosomal dominant

Drugs that can cause myocarditis and/or cardiomyopathy