Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. This review summaries the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS

Exercise Intolerance in Heart Failure with Preserved Ejection Fraction

Exercise intolerance represents a typical feature of heart failure with preserved ejection fraction (HFpEF), and is associated with a poor quality of life, frequent hospitalizations, and increased all-cause mortality. The cardiopulmonary exercise test is the best method to quantify exercise intolerance, and allows detection of the main mechanism responsible for the exercise limitation, influencing treatment and prognosis. Exercise training programs improve exercise tolerance in HFpEF. However, studies are needed to identify appropriate type and duration. This article discusses the pathophysiology of exercise limitation in HFpEF, describes methods of determining exercise tolerance class, and evaluates prognostic implications and potential therapeutic strategies

Testosterone deficiency independently predicts mortality in women with HFrEF: insights from the T.O.S.CA. registry

Aims Testosterone deficiency (TD) is associated with increased morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). However, data in women are scanty. The aim of this study was to investigate the prognostic impact of TD on women with HFrEF. Methods Among 480 patients prospectively enrolled in the T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, a prospective, multicentre, nationwide, observational study, 94 women were included in the current analysis. The TD was defined as serum testosterone levels lower than 25 ng/dl. Data regarding clinical status, echocardiography, exercise performance, cardiovascular hospitalization, and survival after an average follow-up of 36 months were analysed. Results Thirty patients (31.9%) displayed TD. TD was associated with lower tricuspid annular plane excursion (TAPSE) to pulmonary arterial systolic pressure PASP ratio (TAPSE/PASP) (P = 0.008), peak oxygen consumption (VO2 peak) (P = 0.03) and estimated glomerular filtration rate (P Conclusions One-third of women with HFrEF displays TD that impacts remarkably on their morbidity and mortality. TD is associated with a worse clinical profile including exercise capacity, right ventricular-pulmonary arterial coupling, and renal function. These findings lend support to an accurate profiling of women with HF, a problem often overlooked in clinical trials.</p

Multiple hormonal and metabolic deficiency syndrome predicts outcome in heart failure: the T.O.S.CA. registry

Aims Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients. Methods and Results The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of >_2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction <_45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37–2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28–3.83), P = 0.01], with a graded relation between HDs and cumulative events (P Conclusion MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target