Multiple hormonal and metabolic deficiency syndrome predicts outcome in heart failure: the T.O.S.CA. Registry
Antonio Cittadini1,2, Andrea Salzano3, Massimo Iacoviello4
1Department of Translational Medical Sciences, Federico II University, Via Sergio Pansini, 5, 80131 Naples, Italy.
Insights
Multiple hormonal and metabolic deficiency syndrome (MHDS) is common in chronic heart failure (CHF) and significantly increases mortality and hospitalizations. Addressing MHDS in CHF patients may offer a new therapeutic target for improving outcomes.
Area of Science:
- Cardiology
- Endocrinology
- Clinical Research
Background:
- Multiple hormonal and metabolic deficiency syndrome (MHDS) is increasingly recognized in chronic heart failure (CHF).
- However, large-scale observational data on MHDS's impact on CHF progression and patient outcomes are limited.
- The T.O.S.CA. Registry was established to investigate this association.
Purpose of the Study:
- To assess the impact of MHDS on morbidity and mortality in patients with chronic heart failure.
- To determine if MHDS is an independent predictor of adverse outcomes in CHF patients.
Main Methods:
- A prospective, multicentre observational study (T.O.S.CA. Registry) involving 480 CHF patients (ejection fraction ≤45%).
- Evaluation of thyroid hormones, IGF-1, testosterone, DHEA-S, insulin resistance, and diabetes.
- MHDS defined as ≥2 hormone deficiencies; primary endpoint was all-cause mortality or cardiovascular hospitalization.
Main Results:
- MHDS or diabetes was diagnosed in 77.5% of patients.
- MHDS was independently associated with a higher risk of the primary endpoint (HR 1.93; P<0.001).
- A graded relationship was observed between the number of hormone deficiencies and cumulative adverse events (P<0.01).
Conclusions:
- MHDS is a prevalent condition in CHF patients.
- MHDS is independently linked to increased mortality and cardiovascular hospitalizations.
- MHDS represents a potential therapeutic target for improving CHF patient outcomes.
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 < 0.01).
Conclusion:
MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target.
Trial Registration:
ClinicalTrials.gov identifier: NCT023358017.
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