Valvular Heart Disease: Causes

Pathogenesis (development of disease)

The human heart is composed of two systems (left and right hearts), each consisting of an atrium (atrium cordis) and a ventricle (ventricle). Between the left atrium (atrium cordis sinistrum) and the left ventricle is the mitral valve as the inlet valve, and as the outlet valve from the ventricle is the aortic valve. Between the right atrium (atrium cordis dextrum) and the right ventricle is the tricuspid valve as the inlet valve, and as the outlet valve from the ventricle is the pulmonic valve. The pathogenesis of acquired valvular heart (HKF) defects is largely explained by inflammatory changes in the heart valves due to infections, immunologic diseases, and diseases of the endocardium and myocardium.

Etiology (Causes)

Biographic Causes

  • Genetic burden from parents, grandparents1+2+3 – 25 genes have now been found to have a statistically significant association with the development of congenital heart defects; at the same time, it has been pointed out that new mutations are most important in patients with syndromal heart defects
    • Genetic diseases
      • Ehlers-Danlos syndrome2+3+4+5 – group of genetic connective tissue disorders characterized by increased elasticity of the skin and unusual tearability of the same.
      • Marfan syndrome2+3+5 – genetic disease that can be inherited both autosomal dominant or occur sporadically (as a new mutation); systemic connective tissue disease characterized mainly by tall stature; 75% of these patients have an aneurysm (pathological (abnormal) bulge of the arterial wall)
  • Maternal gravidity (pregnancy): elevated blood glucose during organ development in the first trimester (third trimester): per 10 mg/dl increase in blood glucose resulted in an 8 percent increase in heart defects
  • Parents: alcohol consumption of parents6 before conception.

Behavioral causes

  • Overweight (BMI ≥ 25; obesity)4
  • Android body fat distribution4, that is, abdominal/visceral, truncal, central body fat (apple type) – high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)) is presentWhen waist circumference is measured according to the International Diabetes Federation (IDF, 2005) guideline, the following standard values apply:
    • Men < 94 cm
    • Women < 80 cm

    In 2006, the German Obesity Society published somewhat more moderate figures for waist circumference: < 102 cm for men.

Disease-related causes

Congenital malformations, deformities and chromosomal abnormalities (Q00-Q99).

  • Chromosomal defects, unspecified.
  • Ehlers-Danlos syndrome2+3+4+5 (see below “Biographical causes”).
  • Marfan syndrome2+3+5 (see below “Biographical Causes”).

Skin and subcutaneous (L00-L99).

  • Psoriasis (psoriasis) (twice the risk of aortic valve stenosis (aortic valve narrowing) compared with the reference population)

Cardiovascular system (I00-I99).

  • Atherosclerosis5 (arteriosclerosis, hardening of the arteries).
  • Endocarditis1+2+4+5 (endocarditis of the heart)
  • Arterial hypertension (high blood pressure)
    • Level of systolic blood pressure was log-linearly related to risk of mitral regurgitation in a large study
    • Study based on so-called Mendelian randomization (GRS; association/130 gene variants (SNP, single-nucleotide polymorphisms: increased systolic blood pressure levels): with each 20 mmHg increase in systolic blood pressure predictable by GRS, the risk of:
      • Aortic valve stenosis: 3.26-fold (odds ratio [OR] 3.26; 95% confidence interval [CI] 1.50-7.10, p=0.002).
      • Aortic valve regurgitation: 2.59-fold (OR 2.59; 95% CI 0.75-8.92, p=0.13).
      • Mitral valve regurgitation: 2.19-fold (OR 2.19; 95% CI 1.07- 4.47 p=0.03).
  • Cardiomyopathy2 (heart muscle disease), hypertrophic obstructive4 or dilated2
  • Myocarditis2 (inflammation of the heart muscle) → rupture or fibrosis of a papillary muscle (warty protrusion of the myocardium (heart muscle) into the interior of the heart, which is connected via chordae tendineae (tendon threads) to two of the leaflets of a leaflet valve between the atrium (atrium) and ventricle (heart chamber) (mitral and tricuspid valves)), dyscontraction

Infectious and parasitic diseases (A00-B99).

  • Rheumatic fever1+2+4+5
  • Infections, unspecified

Musculoskeletal system and connective tissue (M00-M99).

  • Autoimmune diseases, unspecified1
  • Systemic lupus erythematosus (SLE)1

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

  • Total cholesterol4
  • LDL cholesterol4

Increase in risk of developing aortic stenosis with each one standard deviation increase in plasma LDL cholesterol, total cholesterol, and triglyceride levels by 64%, 82%, and 55%, respectively. For triglycerides, the results were inconclusive. Drugs

  • Drugs, unspecified
  • Fluconazole (antifungal; antifungal) in the first trimester of pregnancy – increase in cardiac defects (cardiac septal defects: significant adjusted odds ratio of 1.81 (1.04-3.14))
  • Cytostatic therapy (anticancer drugs) with cardiotoxic drugs (drugs that damage the heart muscle) in childhood; demonstrated in a study of 1,853 patients with a cancer diagnosis who were followed up after an average of 22.6 years:
    • Pathologic valve findings in the form of regurgitation (blood does not take the usually intended path but flows back in the other direction) or stenosis (“valve narrowing”) in 28% of evaluable cases,
    • 7.4% of patients met criteria for myopathy (heart muscle disease),
    • 4.4% had a conduction or arrhythmia disorder, and
    • 3.8% showed evidence of coronary artery disease (CAD; disease of the coronary arteries)

Environmental exposure – intoxications (poisonings).

  • Outdoor temperatures for 10 days above 30 °C in weeks 2 to 8 of pregnancy (i.e., during the period of cardiac development) → increase in prevalence (disease incidence) of heart defects from 878.9 to 979.5 per 100,000 (mainly non-critical heart defects); for atrial septal defects (malformation of the heart in which the cardiac septum between the two atria of the heart is not completely closed) increase in prevalence of 37%.

1Mitral valve stenosis (mitral stenosis) 2Mitral valve insufficiency (mitral regurgitation) 3Mitral valve prolapse 4Aortic valve stenosis (aortic stenosis) 5Aortic valve insufficiency (aortic regurgitation) 6Inborn valvular heart disease