Reversal of acromegalic cardiomyopathy in young but not in middle‐aged patients after 12 months of treatment with the depot long‐acting somatostatin analogue octreotide

European Journal of Endocrinology

Pivonello

Grasso

et al. 2011

Self Cite

Context: The most frequent cause of death in acromegaly is cardiomyopathy. Objective: To evaluate determinants of acromegalic cardiomyopathy. Design: Observational, open, controlled, retrospective study. Subjects: Two hundred and five patients with newly diagnosed active acromegaly (108 women and 97 men; median age 44 years) and 410 non-acromegalic subjects sex-and age-matched with the patients. Main outcome measures: Left ventricular (LV) mass index (LVMi), transmitral inflow early-to-atrial (E/A) peak velocity ratio, and LV ejection fraction (LVEF) were measured by Doppler echocardiography to determine the prevalence of LV hypertrophy (LVH), diastolic and systolic dysfunction. The role of age, estimated disease duration, body mass index, GH and IGF1 levels, systolic and diastolic blood pressure, lipid profile and glucose tolerance in determining different features of the acromegalic cardiomyopathy was investigated. Results: Compared with controls, the patients had lower E/A, LVEF, high-density lipoprotein (HDL)-cholesterol levels and higher LVMi, total-and low-density lipoprotein (LDL)-cholesterol, triglycerides, glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-R) and HOMA-b. The relative risk to develop mild (odds ratio (OR)Z1.67 (1.05-2.66); PZ0.027) or severe hypertension (ORZ1.58 (1.04-2.32); PZ0.027), arrhythmias (ORZ4.93 (1.74-15.9); PZ0.001), impaired fasting glucose/impaired glucose tolerance (ORZ2.65 (1.70-4.13); P!0.0001), diabetes (ORZ2.14 (1.34-3.40); PZ0.0009), LVH (ORZ11.9 (7.4-19.5); P!0.0001), diastolic (ORZ3.32 (2.09-5.31); P!0.0001) and systolic dysfunction (ORZ14.2 (6.95-32.2); P!0.0001), was higher in acromegaly. The most important predictor of LVH (tZ2.4, PZ0.02) and systolic dysfunction (tZK2.77, PZ0.006) was disease duration and that of diastolic dysfunction was patient's age (tZK3.3, PZ0.001). Patients with an estimated disease duration of O10 years had a relative risk to present cardiac complications three times higher than patients with estimated disease duration %5 years. Conclusions: The prevalence of different features of cardiomyopathy is 3.3-14.2 times higher in the acromegalic than in the non-acromegalic population. The major determinant of cardiomyopathy is disease duration.

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Study Protocolmentioning

confidence: 99%

See 1 more Smart Citation

Determinants of cardiac disease in newly diagnosed patients with acromegaly: results of a 10 year survey study

European Journal of Endocrinology

Pivonello

Grasso

et al. 2011

Self Cite

“…It should be noted that the cardiac effects of somatostatin analogues or surgery appear to be related not only to the strict biochemical control of acromegaly but also to patients' age and the duration of GH and IGF-I hypersecretion before intervention (Table 2). In a recent study including 22 patients successfully controlled for 1 year by octreotide-LAR, we observed the disappearance of LV hypertrophy in 100% of patients aged below 40 years and only in 50% of those aged above 40 years (59). In addition, LVEF at peak exercise significantly increased only in younger patients, being restored in 80% of young and in 50% of middle-aged patients (59).…”

Section: Effect Of Gh/igf-i Suppression On Cardiac Morphology and Permentioning

confidence: 99%

The heart: an end-organ of GH action

European Journal of Endocrinology

Vitale

Pivonello

et al. 2004

Several experimental and clinical studies have indicate that the heart is an end-organ of GH action. Patients with either childhood-or adulthood-onset GH deficiency (GHD) have abnormalities of cardiac structure and function, such as reduced cardiac mass, impaired diastolic filling and reduced left ventricular response at peak exercise. These cardiovascular abnormalities can be reversed, at least partially, after GH replacement therapy. On the other hand, the chronic overproduction of GH and IGF-I in acromegaly leads to the development of a specific cardiomyopathy. Concentric cardiac hypertrophy occurs in more than two-thirds of patients at diagnosis and is commonly associated with diastolic dysfunction. In later stages, impaired systolic function ending in heart failure can occur if GH/IGF-I excess is not controlled. Additionally, acromegalic cardiomyopathy is complicated by abnormalities of cardiac rhythm and cardiac valves. Successful control of acromegaly is accompanied by a decrease of the left ventricular mass and improvement of cardiac function. These beneficial effects appear earlier in young patients with short disease duration than in elderly patients. In conclusion, GH and IGF-I play a main role in the regulation of cardiac development and performance.European Journal of Endocrinology 151 S93-S101

“…Ageing and long duration of GH/IGF-I excess are main determinants of cardiac derangement and early diagnosis and effective treatment are essential to reserved the acromegalic cardiomyopathy [4]. In fact, younger patients respond better to treatment in terms of cardiac improvement than middleaged patients, provided that all had controlled GH and IGF-I levels [5].…”

mentioning

confidence: 99%

Left ventricular synchronicity in acromegaly

Grasso

2013

Endocrine

Self Cite

GH hypersecretion has a direct detrimental effect on the heart: a specific cardiomyopathy is a well-known consequence of acromegaly. The most common features of the acromegalic cardiomyopathy include concentric biventricular hypertrophy, left ventricular systolic and diastolic dysfunction, rhythm disturbances, and an increased prevalence of valve abnormalities [1]. Cardiac hypertrophy is present in about 20 % of young normotensive patients with short duration of the disease and in up to 90 % of hypertensive patients with long-term duration of the disease [2]. This evidence lends support to the concept that cardiac hypertrophy is an early event strongly worsening with the disease duration, and aggravated by hypertension. These cardiac complications are a major determinant of the shortened life expectancy of acromegalic patients. Indeed, patients with acromegaly display about 30 % enhanced mortality rate, in particular, cardiovascular disease represents the cause of death in 60 % of cases [3]. Ageing and long duration of GH/IGF-I excess are main determinants of cardiac derangement and early diagnosis and effective treatment are essential to reserved the acromegalic cardiomyopathy [4]. In fact, younger patients respond better to treatment in terms of cardiac improvement than middleaged patients, provided that all had controlled GH and IGF-I levels [5].Besides cardiac structure and function have been deeply investigated in acromegaly, left ventricular synchronicity has never been evaluated so far. In their study, Kırış et al.[6] describe left ventricular synchronicity in acromegaly.Left ventricular dyssynchrony (LVD), as defined by the standard deviation of time to peak systolic velocity by tissue Doppler imaging, reflects both electrical activation and the result of heterogeneity of contractile properties in the wall [7]. LVD is a common phenomenon in patients with heart failure, reduced left ventricular ejection fraction and wide QRS complexes, and it is associated with impairment of left ventricular systolic and diastolic function and adverse clinical outcomes [7,8]. However, nowadays LVD seems to be a marker of early left ventricular dysfunction even before of regional wall motion abnormality or overt systolic and diastolic abnormalities, and it seems to occur even when the left ventricular ejection fraction is relatively preserved and QRS duration is within the normal range [9]. Previous data suggest that factors other than ischemia might be involved, such as intramyocardial fibrosis or matrix changes that might affect electrical conduction [7].Later, it was shown that left ventricular synchronicity might be impaired also in patients who have narrow QRS complexes in disorders such as hypertension, diabetes mellitus, and hypo/hyperthyroidism [6].Moreover, few report recently demonstrated the relationship of left ventricular hypertrophy (LVH) and LVD in hypertensive patients, suggesting that hypertension impairs left ventricular function not only by influencing myocardial function, but also by impairing left vent...