Treatment of Growth Hormone Excess is Associated with Improvement in Abnormal Cardiac Phenotypes

Abstract

IntroductionCardiovascular disease is the leading cause of mortality in patients with growth hormone (GH) hypersecretion, termed acromegaly. The traditional manifestation of GH excess is cardiac hypertrophy, but a dilated phenotype with clinical heart failure exists. Prior studies have suggested that treatment of GH excess may lead to an improvement in early stage dysfunction, but have shown no benefit in dilated cardiomyopathy or advanced disease.HypothesisCorrection of GH excess in acromegaly will result in improvement in both a hypertrophic and dilated (DCM) cardiac phenotype, even in more advanced disease.MethodsA retrospective analysis was performed on all patients diagnosed with and treated for acromegaly at a single institution. Patients with abnormalities on baseline transthoracic echocardiogram were evaluated (n=50). Abnormalities were defined as an elevated left ventricular mass index, elevated left ventricular diastolic diameter, or reduced ejection fraction. Detailed histories were extracted, including age of diagnosis, treatment modality, IGF-1 levels, cardiovascular medications, and clinical outcomes. Where available, we compared pretreatment imaging to most recent findings to quantify changes in cardiac function.ResultsThe study cohort consisted of 21 patients (42%) with dilated cardiomyopathy, 25 patients (50%) with hypertrophic phenotype and 4 patients (8%) with ischemic cardiomyopathy. Hypertension (61%), diabetes mellitus (36%) and obstructive sleep apnea (48%) were the most common comorbidities. Successful treatment of acromegaly resulted in a clinically-relevant improvement in mean LV ejection fraction in the DCM cohort from 38% to 49% (p = 0.05) and mean LV diastolic diameter from 66 to 60 mm (p = 0.20). Additionally, an improvement in LV mass index was seen in the hypertrophic phenotype from 117 to 104 g/m2 (p = 0.05). Heart rate, QRS and QTC intervals were statistically unchanged.ConclusionsContrary to prior research, treatment of human growth hormone excess resulted in an improvement in dilated as well as hypertrophic phenotypes, though not necessarily independent of guideline-directed medical therapy. This highlights the importance of effective treatment of GH excess states in reducing the prevalent cardiovascular morbidity and mortality in patients with acromegaly. Cardiovascular disease is the leading cause of mortality in patients with growth hormone (GH) hypersecretion, termed acromegaly. The traditional manifestation of GH excess is cardiac hypertrophy, but a dilated phenotype with clinical heart failure exists. Prior studies have suggested that treatment of GH excess may lead to an improvement in early stage dysfunction, but have shown no benefit in dilated cardiomyopathy or advanced disease. Correction of GH excess in acromegaly will result in improvement in both a hypertrophic and dilated (DCM) cardiac phenotype, even in more advanced disease. A retrospective analysis was performed on all patients diagnosed with and treated for acromegaly at a single institution. Patients with abnormalities on baseline transthoracic echocardiogram were evaluated (n=50). Abnormalities were defined as an elevated left ventricular mass index, elevated left ventricular diastolic diameter, or reduced ejection fraction. Detailed histories were extracted, including age of diagnosis, treatment modality, IGF-1 levels, cardiovascular medications, and clinical outcomes. Where available, we compared pretreatment imaging to most recent findings to quantify changes in cardiac function. The study cohort consisted of 21 patients (42%) with dilated cardiomyopathy, 25 patients (50%) with hypertrophic phenotype and 4 patients (8%) with ischemic cardiomyopathy. Hypertension (61%), diabetes mellitus (36%) and obstructive sleep apnea (48%) were the most common comorbidities. Successful treatment of acromegaly resulted in a clinically-relevant improvement in mean LV ejection fraction in the DCM cohort from 38% to 49% (p = 0.05) and mean LV diastolic diameter from 66 to 60 mm (p = 0.20). Additionally, an improvement in LV mass index was seen in the hypertrophic phenotype from 117 to 104 g/m2 (p = 0.05). Heart rate, QRS and QTC intervals were statistically unchanged. Contrary to prior research, treatment of human growth hormone excess resulted in an improvement in dilated as well as hypertrophic phenotypes, though not necessarily independent of guideline-directed medical therapy. This highlights the importance of effective treatment of GH excess states in reducing the prevalent cardiovascular morbidity and mortality in patients with acromegaly.