Phd in ANGIO-CARDIO-THORACIC PATHOPHYSIOLOGY AND IMAGING

Thesis title: Prognostic Evaluation of Heart Failure in Women: Insight from the MECKI Score Database

Background: Heart failure is a multi-organ disease often associated with comorbidities. Heart failure in women assumes extremely peculiar characteristics. The pathophysiology of the damage is profoundly different; the endothelial dysfunction, the damage to the microcirculation and the comorbidities that cause chronic heart failure are in fact frequently associated with a type of decompensation that has a better ejection fraction than those in the male population. Symptoms are often vague and not "typical", which often delays diagnosis, bringing patients to the doctor's attention only belatedly. This aspect frequently leads to having a much older age than the male gender at diagnosis, which determines higher co-pathology degree and polypharmacy. In this situation, female patients are highly exposed to risk of iatrogenic damage and poor compensation and therapeutic unsuccess. Age is often a limiting factor also for enrollment in clinical trials, which therefore frequently have a gender-related bias. To identify the prognosis, it is necessary to take into account several variables. The cardiopulmonary test allows a comprehensive assessment of the patient during physical activity as physical exercise involves the cardiovascular, hematopoietic, sympathetic/parasympathetic, neuro-hormonal, respiratory and motor systems. The oxygen consumption at the peak and at the anaerobic threshold mainly depend on the cardiovascular and motor systems while the VE/VCO2 is an index not only of ventilatory efficiency and of the ventilation/perfusion mismatch of the lung, but also of activation of metabo- and chemoreceptors. The proposed risk scores are very numerous but mostly based on data obtained in male populations. Few use the cardiopulmonary exercise test. Among these, the Metabolic Exercise Cardiac Kidney Indexes -MECKI score- was obtained by evaluating about 80 variables of which 6 have independent prognostic significance: hemoglobin, natremia, renal function (MDRD), left ventricular ejection fraction (LVEF), oxygen consumption at the peak of the exercise [%] and VE/VCO2 slope. The MECKI score demonstrated in patients with systolic heart failure, considering the combined cardiovascular death, urgent heart transplant and LVAD as an end-point, AUC = 0.804 (0.754-0.852) at 1 year, 0.789 (0.750-0.828) at 2 years, 0.762 (0.726-0.799) at 3 years and 0.760 (0.724-0.796) at 4 years. Aim of the study: identify parameters and variables which could be associated to a different prognosis in men and women enrolled in the MECKI Score database. Thus, the objectives of the present study: 1) achievement in 2 years of at least 7000 cases with about 1400 cases of female gender; 2) evaluation of the prognosis in systolic heart failure in the female gender, differentiating by: a) etiology (ischemic non-ischemic), b) presence/absence of atrial fibrillation, c) presence of CRT, d) presence/absence of diabetes/hypertension/dyslipidemia; 3) evaluation in the female gender of the prognostic cut-offs of the variables that generate the MECKI score. Results: In reviewing the MECKI Score database, numerous, mostly expected, gender differences emerged which reinforce the initial hypothesis. In the population examined, there is no substantial difference in age, women have, although overweight, a lower BMI than men, a better LVEF, significant differences in renal function and hemoglobin concentration (these parameters are already corrected for sex); no difference in terms of natremia. Other differences were observed about pharmacological therapy among the two groups. Kaplan-Meier survival curves showed that the MECKI Score is accurate in predicting the risk also in the female population, as there are no overall differences in the prevalence of events in the two sexes at two years. Differences in survival curves begin to be observed over longer follow-up periods. Conclusions: gender-specific characteristics have a critical impact on heart failure in women and it should be valuable to concentrate future analysis for the identification of any specific subpopulation that have peculiarities that can impact on the prognosis. However, the MECKI Score maintains its prognostic power at two years follow up, even in the female population, guaranteeing appropriate clinical and therapeutic choices.