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Cardiac Hypertrophy

Cardiac hypertrophy refers to the condition of an enlarged heart due to heart muscle hypertrophy, i.e., heart muscle thickening. This condition interferes with heart function.


Presentation

Patients may present with symptoms characteristic for heart failure. These symptoms are very unspecific and do not allow for a confirmed diagnosis of CH. Also, the severity of symptoms is not necessarily proportional to cardiac enlargement and heart muscle thickening. In order to evaluate the latter and to verify the tentative diagnosis of CH, imaging techniques need to be applied.

Frequently experienced symptoms include general weakness, chest pressure or pain, palpitations, dyspnea and peripheral edema. While patients affected by mild to moderate CH show exercise-induced dyspnea, more severe cases may be associated with dyspnea when at rest. Additionally, dizziness and syncopes may be reported.

Severe Clinical Course
  • Despite the generally good prognosis of TT-CM, severe clinical courses have been reported due to the depressed LV function with cardiogenic shock or malignant tachyarrhythmias.[ncbi.nlm.nih.gov]
Heart Disease
  • However, like any good drama, activation of PGE2-EP4 signaling exerts both protective and detrimental effects in the ischemic heart disease.[ncbi.nlm.nih.gov]
  • These conditions accompany a variety of common cardiovascular diseases, e.g. hypertension, aortic and pulmonary artery stenosis, valvular heart disease and ischemic heart disease.[symptoma.com]
  • However, whether miR-96 is involved in heart diseases, particularly cardiac hypertrophy, remains unclear. In this study, we found that miR-96 is a negative regulator of cardiac hypertrophy.[ncbi.nlm.nih.gov]
  • Finally we summarize therapeutic approaches that target the IGF1-PI3K-Akt signaling pathway which are showing promise in preclinical models of heart disease. KEYWORDS: Exercise; Heart; IGF1-PI3K-Akt signaling[ncbi.nlm.nih.gov]
  • These results also suggest a strategy to modulate mTOR activity and facilitate the translational exploitation of HDAC inhibitors in heart disease. Copyright 2016, American Association for the Advancement of Science.[ncbi.nlm.nih.gov]

Workup

Clinical examination and auscultation of the patient will allow for the tentative diagnosis of heart insufficiency. Peripheral edema, heart murmurs and signs of pulmonary edema are frequently observed. Diagnosis may be supported by data obtained with the clinical history of the patient. They usually report symptoms to aggravate when doing exercise. Also, a medical history of hypertension is very common in CH patients.

Electrocardiographic and radiologic exams should follow. The former may reveal alterations characteristic for left or right ventricular hypertrophy. Electrocardiography is considered to be a specific diagnostic tool for CH, however, it is not used on large scale due to the costs involved. Chest X-rays show an enlarged heart and possibly pulmonary edema.

The method of choice to confirm CH and to evaluate its progress is echocardiography. Here, ventricular volumes, the thickness of ventricular walls and septum, valvular function and other parameters can be easily obtained. In order to calculate the mass of the left ventricle for the diagnosis of LVH, criteria published by Devereux and Reichek in 1977 are still applied [21].

Treatment

CH is a maladaptive response to one (or more) of several possible triggers, e.g., valvular heart disease, hypertension, pulmonary hypertension due to pulmonary embolism or emphysema, chronic bronchitis, other chronic inflammations, hyper- or hypothyreosis. In order to relieve the volume or pressure overload, these underlying diseases should be treated if at all possible. Some may require surgery, some may be manageable with drug therapy. If the underlying disease is merely a side effect of medication administered to treat other diseases, HIV infection, for instance, medication should be changed if possible. If there are no alternatives, possible benefits and consequences of cessation of therapy have to be considered. Unfortunately, tissue damage caused by previous myocardial infarction will not be reversible.

CH drug therapy aims at reducing myocardial contractility as well as preload and afterload. Therefore, beta- sympatholytic drugs, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers, and diuretics are applied. Positive inotropic drugs are not recommended for CH treatment since these compounds accelerate the progression of hypertrophy and thus may promote heart failure.

Furthermore, patients should be advised to adapt their lifestyle. They should stop smoking, reduce cholesterol intake and thus blood cholesterol levels, pay attention to blood glucose levels and blood pressure. Obesity and overweight are unfavorable prognostic factors and weight reduction may contribute largely to an improvement of their general condition. Alcohol consumption should be discontinued or at least reduced.

Prognosis

The long-term prognosis of CH depends on stage and degree of hypertrophy. The cardiothoracic ratio has been proposed as an objective parameter to assess the patients' long-term prognosis and the likelihood of congestive heart failure and death. In this line, a cardiothoracic ratio of less than 55% is associated with a more favorable prognosis and lower probabilities of lethal consequences. This parameter seems to be of greater prognostic value than electrocardiographic findings [20].

Etiology

Any pathological condition that results in biomechanical stress, i.e., in volume or pressure overload of the heart, may provoke CH. Such overloads are often caused by systemic diseases and indeed, general hypertension is the most common trigger of CH. This fact may also serve as an explanation for the observation that CH most frequently affects the left ventricle. However, hypertension may also be limited to the pulmonary circulation, in which case the right ventricle would try to compensate and become hypertrophic. Aortic and pulmonary artery stenosis, as well as valvular heart disease, may serve as examples for local triggers of cardiac overloads. Here, the precise location of the pathology determines which chambers will mainly be exposed to increased loads. Thus, CH may be considered as a protective reaction of the heart with the aim is to normalize cardiac output and wall loads. Unfortunately, this process negatively affects myocardial contractility and leaves CH patients susceptible to arrhythmias and heart failure. In this context, CH is a maladaptive process.

Intriguingly, CH is also observed in highly trained athletes. Here, cardiac enlargement is associated with adaptive hypertrophy and dilation and does increase rather than reduce myocardial contractility [11]. In athletes, CH is not accompanied by cardiovascular problems. Although this is not new and studies that were done decades ago already showed that mild to moderate hypertrophy of the left ventricle contributes to increased stroke volumes and improved oxygen consumption in athletes [12] [13], the precise difference between this adaptive and the above-mentioned maladaptive CH is not yet fully understood. Myosin isoform distribution, myofibrillar ATPase activity, intracellular signaling pathways as well as adrenergic signaling have been proposed as key factors in determining the fate of a hypertrophic heart [14] [15] [16]. Most likely, current research will reveal even more factors contributing to adaptive or maladaptive CH.

Epidemiology

The overall incidence of left ventricular hypertrophy, the most common form of CH, has been estimated to be about 15 to 20%. General condition, age, race and possibly gender seem to affect the individual risk for CH. In this context, overweight, obesity and hypertension predispose for CH. Interestingly, the prevalence of these risk factors coincides with the aforementioned overall incidence of CH. Incidence rates are higher among the elderly and among blacks. With regards to gender distribution, a trend towards more common detection of CH in women has been observed (overall incidence of 19% in women vs. 16% in men) [17].

Morbidity and mortality associated with CH are high. While maladaptive CH may result from ischemic heart disease or myocardial infarction, these diseases may also develop as a consequence of CH. Also, CH patients have a higher risk for arrhythmias, congestive heart failure, and sudden cardiac death.

Sex distribution
Age distribution

Pathophysiology

As per the definition of tissue hypertrophy, CH is the result of an elevated cardiomyocyte volume. Therefore, a hypertrophic heart is characterized by a thickening of ventricle walls and septum [18]. CH is a maladaptive intent to compensate for cardiac overload. Unfortunately, hypertrophy is only effective for limited periods of time during which progressively increasing loads often further aggravate the general condition of the heart. The final consequences are congestive heart failure and death, but important knowledge gaps remain regarding the transition of stage two CH to stage three CH.

Causative conditions expose cardiomyocytes to increased volume and pressure loads and trigger hypertrophy. Its aim is to improve the contractility and efficiency of the heart and it involves a plethora of changes in gene expression, transcriptional regulation, post-translational modification, protein synthesis, receptor signaling and signal transduction as well as intercellular signaling. Current research is focused on identifying and possibly modifying each single step. Overexpression of fetal genes whose mRNA and proteins are not detectable in healthy adults is mentioned here as an interesting feature of CH since these genes may serve as molecular markers of the disease [19].

Hypertrophy is also associated with re-organization of sarcomeric structure [20]. While volume overload evokes hypertrophy with longitudinal cell growth due to the respective addition of sarcomeres, pressure overload and reduced contractility due to prior myocardial infarction is associated with concentric hypertrophy, a parallel addition of sarcomeres and thus with transversal cell growth.

Prevention

Hypertension, hypercholesterolemia and diabetes mellitus predispose people for CH. While there are no specific recommendations to prevent CH, lifestyle modifications play an important role in preventing the aforementioned, underlying diseases. In this context, smoking should be avoided completely. Individuals following a sedentary lifestyle should include exercise in their routine. Regular physical activity contributes significantly to cardiovascular health. Half an hour daily may serve as a value of reference regarding the minimal amount of exercise. Food with high contents of cholesterol, other types of fat, sugar, and salt should be avoided and replaced with fruits and vegetables. Alcohol should be avoided.

Because even a healthy lifestyle is no guarantee for cardiovascular health, regular checkups are recommended. Blood pressure, serum cholesterol and glucose levels should be monitored. This particularly applies to patients with greater risks of developing the respective diseases since hereditary factors may play an important role in their etiology.

Summary

Cardiac hypertrophy (CH) is a condition that results from an increase in cardiomyocyte size and leads to overall thickening of the heart muscle and heart enlargement. CH may usually develop due to hereditary protein dysfunctions, but also due to chronic volume or pressure overloads as well as limited myocardial function after infarction or other cardiac diseases. These conditions accompany a variety of common cardiovascular diseases, e.g. hypertension, aortic and pulmonary artery stenosis, valvular heart disease and ischemic heart disease.

The body tries to compensate for reduced ejection fractions by augmenting the strength of the heart muscle. By raising the cardiomyocyte volume and thus by triggering concentric hypertrophy,the chances of thinner portions of the cardiac wall to be exposed to pressure loads are also avoided [1] [2] [3]. However, this comes at the cost of an increased risk for arrhythmias and heart failure [4] [5].

CH develops slowly and three stages can be distinguished to this end [6]. During the initial phase, there is an increased volume or pressure load that may result from a variety of conditions. This stage is followed by compensatory hypertrophy. Here, CH is able to compensate for the existing overload and cardiac output is normalized. However, this situation cannot be maintained and remodeling processes start. Ventricular dilation, progressive reduction of cardiac output and finally heart failure characterize the third stage of the disease. Altered ionic currents, particularly Ca2+ currents, lead to an increased rate of apoptosis [7] [8] [9] [10]. Functionally, these alterations manifest as arrhythmias and ventricular dysfunction.

CH has to be distinguished from cardiac dilation. Both conditions result in an overall enlargement of the heart, but while a thickened heart muscle accounts for the former, wall thinning and greater atrial and/or ventricular volumes are associated with the latter. However, both conditions may exist at the same time. For instance, such is the case during the third stage of CH.

Patient Information

Cardiac hypertrophy (CH) refers to the condition of an enlarged heart with a thickened muscle layer.

Causes

CH develops as a consequence of volume and pressure overloads or loss of functionality of the myocardium. These conditions result in reduced cardiac output. The body's oxygen demands can no longer be met. In order to improve heart function, to strengthen the heart, the heart muscle develops this adaptive mechanism of cardiac hypertrophy. While this strategy may work for some time, the heart will eventually be unable to resist to persisting volume and pressure overloads. This stage of CH is associated with dilation of cardiac chambers, reduction of cardiac output and finally heart failure.

Symptoms

Symptoms resemble those of cardiac insufficiency and are rather unspecific. Chest pain may be experienced as well as palpitations, breathing difficulties when physically active or even at rest and peripheral edema which manifests in form of swollen legs may be seen.

Diagnosis

Medical history, clinical examination, and auscultation may justify the tentative diagnosis of CH. However, imaging techniques need to be applied to confirm this diagnosis and to assess the precise condition of the heart. To this end, chest X-rays and echocardiography are the most commonly used methods to visualize heart and lungs. The physician may also carry out an electrocardiography to detect possible arrhythmias.

Treatment

Volume and pressure overloads are associated with a variety of cardiovascular diseases, e.g. valvular heart disease, hypertension, pulmonary embolism or emphysema, chronic bronchitis and thyroid problems. In order to relief the heart from overload, the underlying disease needs to be treated.

Direct treatment of CH consists in medication that aims at reducing myocardial contractility and cardiac overload. Therefore, beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers and diuretics may be prescribed.

References

Article

  1. Sandler H, Dodge HT. Left Ventricular Tension and Stress in Man. Circ Res. 1963; 13:91-104.
  2. Hood WP, Jr., Rackley CE, Rolett EL. Wall stress in the normal and hypertrophied human left ventricle. Am J Cardiol. 1968; 22(4):550-558.
  3. Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975; 56(1):56-64.
  4. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990; 322(22):1561-1566.
  5. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991; 114(5):345-352.
  6. Meerson FZ. On the mechanism of compensatory hyperfunction and insufficiency of the heart. Cor Vasa. 1961; 3:161-177.
  7. Bers DM. Cardiac excitation-contraction coupling. Nature. 2002; 415(6868):198-205.
  8. Armoundas AA, Wu R, Juang G, Marban E, Tomaselli GF. Electrical and structural remodeling of the failing ventricle. Pharmacol Ther. 2001; 92(2-3):213-230.
  9. Hill JA. Electrical remodeling in cardiac hypertrophy. Trends Cardiovasc Med. 2003; 13(8):316-322.
  10. Haunstetter A, Izumo S. Toward antiapoptosis as a new treatment modality. Circ Res. 2000; 86(4):371-376.
  11. Frey N, Olson EN. Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol. 2003; 65:45-79.
  12. Raskoff WJ, Goldman S, Cohn K. The "athletic heart". Prevalence and physiological significance of left ventricular enlargement in distance runners. Jama. 1976; 236(2):158-162.
  13. Bevegard BS, Shepherd JT. Regulation of the circulation during exercise in man. Physiol Rev. 1967; 47(2):178-213.
  14. Giusti R, Bersohn MM, Malhotra A, Scheuer J. Cardiac function and actomyosin ATPase activity in hearts of conditioned and deconditioned rats. J Appl Physiol Respir Environ Exerc Physiol. 1978; 44(2):171-174.
  15. Wilkins BJ, Dai YS, Bueno OF, et al. Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy. Circ Res. 2004; 94(1):110-118.
  16. Barki-Harrington L, Perrino C, Rockman HA. Network integration of the adrenergic system in cardiac hypertrophy. Cardiovasc Res. 2004; 63(3):391-402.
  17. Savage DD. Overall risk of left ventricular hypertrophy secondary to systemic hypertension. Am J Cardiol. 1987; 60(17):8I-12I.
  18. Liang F, Gardner DG. Mechanical strain activates BNP gene transcription through a p38/NF-kappaB-dependent mechanism. J Clin Invest. 1999; 104(11):1603-1612.
  19. Frey N, Olson EN. Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol. 2003; 65:45-79.
  20. Toyama S, Ishiyama T, Terada A, Yamagami T, Okamoto K, Yagi S. The prognosis of cardiac hypertrophy. Bull World Health Organ. 1963; 28(2):269-272.
  21. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation. 1977; 55(4):613-618.

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Last updated: 2018-06-22 04:15