Heart Failure (Cardiac Insufficiency): Causes

Pathogenesis (development of disease)

A variety of conditions can trigger heart failure – see Etiology (causes) below. In Germany, 90% of heart failure is triggered by:

  • Hypertension (high blood pressure)
  • Coronary heart disease (CHD)

All diseases that cause heart failure lead to a constantly increased load or direct weakening of the myocardium (heart muscle). The blood can no longer adequately supply the organs with oxygen. Through the increased release of mediators (messenger substances), e.g. adrenaline, the body attempts to improve cardiac performance. Over time, however, the heart’s sensitivity to these agents decreases. Other messengers – such as renin, aldosterone – are thought to inhibit the excretion of fluid by the kidneys to maintain blood pressure despite poor cardiac output. However, the increased amount of fluid in the blood vessels puts even more strain on the weak heart. The heart increases in size, comparable to the muscle of an athlete. This increase in size weakens the heart even more, however, because the coronary vessels do not grow at the same rate, and thus an optimal oxygen supply is not guaranteed. This creates a vicious circle. Chronic heart failure (HF) classified according to pump function:

HF type HFrEF HFmrEF HFpEF
Criteria 1 Symptoms ± sign a Symptoms ± signs a Symptoms ± signs a
2 LVEF < 40 LVEF 40-49 % LVEF ≥ 50 %
3
  1. Increased serum concentrationnatriuretic peptide b
  2. At least 1 additional criterion:
    a. relevant structural heart disease (LVH and/or LAE).
    b. diastolic dysfunction (echocardiographic findings) c
  1. Increased serum concentrationnatriuretic peptide b
  2. At least 1 additional criterion:
    a. relevant structural heart disease (LVH and/or LAE).
    b. diastolic dysfunction c

Legend

  • HFrEF: “Heart Failure with reduced Ejection Fraction”; heart failure with reduced ejection fraction/ejection fraction (= systolic heart failure; synonym: isolated systolic dysfunction; systole is the tense and thus blood outflow phase of the heart).
  • HFmrEF: “Heart Failure mid-range Ejection Fraction”; “mid-range” heart failure [approximately 10-20% of patients].
  • HFpEF: “Heart Failure with preserved Ejection Fraction”; heart failure with preserved ejection fraction (= diastolic heart failure; synonym: diastolic dysfunction; diastole is the slackening and thus blood inflow phase).
  • LVEF: left ventricular ejection fraction; ejection fraction (also expulsion fraction) of the left ventricle during a heartbeat.
  • LAE: enlargement of the left atrium (left atrial volume index [LAVI] > 34 ml/m2.
  • LVH: left ventricular hypertrophy (left ventricular muscle mass index [LVMI] ≥ 115 g/m2 for men and ≥ 95 g/m2 for women).
  • A: signs may be absent in early stages of heart failure (esp. HFpEF) and in diuretic-treated patients
  • B: BNP > 35 pg/ml and/or NT-proBNP > 125 pg/ml.
  • C: decrease in e’ to < 9 cm/s and increase in E:e’ ratio to > 13 (value: < 8 is considered normal).

Furthermore, heart failure can be divided into:

  • Forward failure (“forward failure”) with decreased cardiac output (CV).
  • Backward failure (“backward failure”) in the presence of backpressure anterior to the insufficient ventricle – based on clinic and hemodynamics.

Men and women often suffer from different forms of heart failure:

  • Men often have a disorder of systolic function, which is an inability to pump blood out of the heart.
  • Women, on the other hand, are more likely to have a disorder of the diastolic form, that is, an impediment to the filling of the heart.

Both dysfunctions lead to the symptomatology of shortness of breath and exercise intolerance. Echocardiography is performed to distinguish these clinical pictures. Guideline-based treatment is required depending on the nature of the disorder.

Etiology (Causes)

Biographic Causes

  • Genetic disorders:
    • 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.
  • Premature infants (= birth before completion of the 37th week of pregnancy (SSW)).
    • Load of 60% of individual maximum: ejection fraction (ejection fraction) of adult preterm infants on average significantly 6.7% below that of controls (71.9% vs. 78.6%)
    • Load of 80% of individual maximum: 7.3% below that of controls (69.8% vs. 77.1%)
    • Cardiac output reserve (difference between cardiac index at the respective load level and cardiac index at rest); reserve at 40% load was 56.3% lower than that of controls (729 vs 1,669 ml/min/m2).
    • Limitation: small number of subjects
  • Age – increasing age:
    • The maximum incidence of heart failure is in the 8th decade of life.
    • Women: Early onset of menopause (40th to 45th year of life).
  • Hormonal factors – early onset of menopause (see age below).
  • Socioeconomic factors – the bottom fifth (quintile), living in the greatest poverty, is 61% more likely to develop chronic heart failure at older ages; this group is also 3.51 years (3.25-3.77 years) earlier in developing the disease

Behavioral causes

  • Nutrition
    • Consumption of “red” meat products (men); women over 50 years of age.
    • Low consumption of fruits and vegetables (women).
    • High intake of sodium and table salt
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Consumption of stimulants*
    • Alcohol (woman: > 40 g/day; man: > 60 g/day) – up to 7 alcoholic drinks per week in early middle age was associated with a lower risk of future heart failure
    • Tobacco (smoking) – study using the principle of Mendelian randomization demonstrated that genetic propensity to use tobacco products was associated with an approximately 30% higher risk of heart failure compared with genetic abstinence from smoking (odds ratio, OR 1.28)
  • Drug use
    • Cannabis (hashish and marijuana) (+ 10% risk increase).
  • Physical activity
    • Physical inactivity
  • Psycho-social situation
    • Sleep duration – longer sleep had a favorable effect, shorter sleep had an unfavorable effect: staying in bed longer reduced the risk by about a quarter per additional hour of sleep (OR 0.73)
  • Overweight (BMI ≥ 25; obesity* * ).
    • Independent risk factor for diastolic heart failure with preserved systolic function (Heart failure with preserved ejection fraction, HFpEF); systolic heart failure as a direct consequence of obesity is rare.
    • In adolescents (life stage marking the transition from childhood to adulthood), risk already increased with BMI in the high-normal range; at 22.5-25.0 kg/m², risk increased by 22% (adjusted hazard ratio, HR: 1.22)

Disease-related causes

  • Congenital or acquired heart defects* * .
  • Anorexia nervosa (anorexia nervosa)
  • Atherosclerosis* * (arteriosclerosis, hardening of the arteries)
  • Chronic obstructive pulmonary disease (COPD) – progressive (progressive), not fully reversible (reversible) obstruction (narrowing) of the airways.
  • Endocrinologic diseases and metabolic disorders – e.g., diabetes mellitus (insulin resistance)* * (approximately 25% of cases), hyperthyroidism (hyperthyroidism) or hypothyroidism (hypothyroidism); osteoporosis/low bone density is associated with heart failure
  • Inflammatory heart disease* – myocarditis (inflammation of the heart muscle), endocarditis (inflammation of the lining of the heart), pericarditis (inflammation of the pericardium).
  • Valvular heart disease:
    • With reduction of systolic ventricular function (= contraction, ejection): aortic or mitral regurgitation.
    • With normal LV function (left ventricular function): mitral stenosis, tricuspid regurgitation.
  • Cardiac arrhythmias* * (chronic heart failure: e.g., atrial fibrillation (VHF); acute heart failure: e.g., acute bradycardic or tachycardic arrhythmia).
  • High-output failure (inadequate blood (O2) supply to the periphery with increased cardiac output (HZV): e.g., anemia* (anemia), arteriovenous (AV) fistulae, hyperthyroidism (hyperthyroidism)/thyrotoxicosis).
  • Hypertension* * (high blood pressure) (normal LV function).
    • “Risers” in whom nocturnal blood pressure values exceeded diurnal values at 24-hour blood pressure measurement were most at risk: Hazard ratio (probability in a collective of occurrence of an event) was 1.48 (1.05 to 2.08) for cardiovascular disease and 2.45 (1.34 to 4.48) for chronic heart failure.
  • Insomnia (sleep disturbances) – patients suffering from severe sleep disturbances are 4.53 times more likely to have heart failure than individuals who do not have problems with sleep
  • Cardiomyopathy* /* * (heart muscle disease): dilated cardiomyopathy (reduced systolic ventricular function); hypertrophic cardiomyopathy (normal LV function).
  • Coronary artery disease (CAD)* /* *
  • Myocardial infarction* * (heart attack) (reduced systolic ventricular function; acute heart failure in massive myocardial infarction)Prognostic factors for the development of heart failure are ventricular size (end-diastolic volume, i.e., maximal filling) and ventricular mass. Note: Silent myocardial infarctions also significantly increase the risk of developing heart failure.
  • Myocardial ischemia (reduced blood flow to the heart muscle).
  • Renal insufficiency* * , chronic (chronic renal failure).
  • Obstructive sleep apnea syndrome (OSAS; pauses in breathing during sleep caused by obstruction of the airways, often occurring several hundred times per night), especially in the case of right heart failure (insufficient pumping of the right ventricle of the heart)
  • Vasculitides* * (inflammatory rheumatic diseases characterized by a tendency to inflammation of the (usually) arterial blood vessels) and other autoimmune diseases.

* The “cardiotoxic triad” of arterial hypertension, coronary heart disease, and diabetic cardiomyopathy conditions an unfavorable prognosis. * * Prognostically relevant factors; other prognostically relevant factors include: Respiratory disease, depression, and malignancies.

Laboratory diagnoses-laboratory parameters considered independent risk factors.

  • Total testosterone-estradiol ratio – a high testosterone-estradiol ratio is associated with an increased risk of heart failure
  • Glomerular filtration rate (GFR) ↓ – patients with moderately impaired renal function (> CKD stage 3 or a GFR < 60 ml/min/1.73m2) have a 3-fold higher risk of heart failure than patients with normal renal function (GFR > 90 ml/min/1.73m2)

Medications

  • Calcimimetic (etelcalcetide) → worsening heart failure.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs; non steroidal anti-inflammatory drugs, NSAID).
    • 19% increased risk of decompensated heart failureA significantly higher risk was associated with current use of diclofenac, etoricoxib, ibuprofen, indomethacin, ketorolac, naproxen, nimesulide, piroxicam, rofecoxib
    • Nonselective NSAIDs: ibuprofen, naproxen, and diclofenac increased risk by 15%, 19%, and 21%, respectively
    • COX-2 inhibitors rofecoxib and etoricoxib led to a 34% and 55% increase in risk, respectively.
    • Very high doses of
    • Greatest hazard for heart failure-related hospitalization was associated with ketoralac (odds ratio, OR: 1.94)
  • Note: “The indication of drugs that may adversely affect the clinical condition of patients with heart failure should be critically evaluated. These include, for example, class I and III antiarrhythmic agents, calcium channel blockers (except amlodipine, felodipine), and nonsteroidal anti-inflammatory drugs.” See Table 19: Selected drugs that may adversely affect the clinical condition of patients with HFrEF.