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Background Central apneas (CA) are a frequent comorbidity in patients with heart failure (HF) and are associated with worse prognosis. The clinical and prognostic relevance of CA in each sex is unknown. Methods and Results Consecutive outpatients with HF with either reduced or mildly reduced left ventricular ejection fraction (n=550, age 65±12 years, left ventricular ejection fraction 32%±9%, 21% women) underwent a 24‐hour ambulatory polygraphy to evaluate CA burden and were followed up for the composite end point of cardiac death, appropriate implantable cardioverter‐defibrillator shock, or first HF hospitalization. Compared with men, women were younger, had higher left ventricular ejection fraction, had lower prevalence of ischemic etiology and of atrial fibrillation, and showed lower apnea‐hypopnea index (expressed as median [interquartile range]) at daytime (3 [0–9] versus 10 [3–20] events/hour) and nighttime (10 [3–21] versus 23 [11–36] events/hour) (all P <0.001), despite similar neurohormonal activation and HF therapy. Increased chemoreflex sensitivity to either hypoxia or hypercapnia (evaluated in 356 patients, 65%, by a rebreathing test) was less frequent in women ( P <0.001), but chemoreflex sensitivity to hypercapnia was a predictor of apnea‐hypopnea index in both sexes. At adjusted survival analysis, daytime apnea‐hypopnea index ≥15 events/hour (hazard ratio [HR], 2.70; 95% CI, 1.06–7.34; P =0.037), nighttime apnea‐hypopnea index ≥15 events/hour (HR, 2.84; 95% CI, 1.28–6.32; P =0.010), and nighttime CA index ≥10 events/hour (HR, 5.01; 95% CI, 1.88–13.4; P =0.001) were independent predictors of the primary end point in women but not in men (all P >0.05), also after matching women and men for possible confounders. Conclusions In chronic HF, CA are associated with a greater risk of adverse events in women than in men.

Background Reduced left ventricular ejection fraction (LVEF) has been used as a key criterion for the management of mitral regurgitation (MR) in patients with heart failure (HF), including the decision about mitral valve repair. However, LVEF, not taking into account mitral regurgitant volume, may be an imprecise predictor of outcome in HF patients with MR. Conversely, the estimation of the forward volume through the LV outflow tract (LVOT) may be a better metric in this setting. In this regard, LVOT velocity time integral (LVOT-VTI), not relying on geometrical assumptions, has been shown to be more reproducible than the calculated stroke volume (i.e., LVOT-VTI * LVOT cross sectional area), at least in the acute setting. Objective To assess the prognostic significance of LVOT-VTI in a contemporary cohort of patients with chronic HF and significant MR. Methods Consecutive patients with chronic HF with reduced (≤40%) or mildly reduced (41-49%) LVEF and moderate-to-severe or severe MR, according to the latest European Society of Cardiology criteria, were selected and followed-up for the endpoint of cardiovascular death. Results 203 patients were enrolled in the study (74±11 years, 66% men, 47% ischemic etiology, HFrEF 86%, LVEF 31±9%, mean LVOT-VTI 21±6 cm). Most patients showed a NYHA class II (40%) or III (31%) and received beta-blockers (95%), ACE-inhibitors/ARBs or ARNI (77%), and mineralocorticoid receptor antagonists (82%). Seventy-seven patients (38%) had permanent atrial fibrillation and 46 (23%) a cardiac resynchronization therapy device. Over a median follow-up of 18 (7-33) months, 30 patients died, 24 of whom for a cardiovascular cause, and 10 underwent mitral valve repair/replacement. When stratified according to the optimal prognostic cut-off of LVOT-VTI, patients with a LVOT-VTI &lt;16 cm (n=36) showed the greater risk of cardiovascular death (Log Rank 18.2, p&lt;0.001, Figure). Similarly, patients with a LVEF &lt;33% (n=122) showed a higher risk of cardiovascular death (Log Rank 5.5, p=0.019). Nevertheless, at Cox regression analysis, a unit decrease in LVOT-VTI (hazard ratio, HR 0.87 [95%CI 0.79-0.95], p=0.002) but not in LVEF (p=0.729) was associated with a higher risk of cardiovascular death (Figure). Conclusion Left ventricular forward volume, noninvasively estimated through LVOT-VTI, but not LVEF, predicts the risk of cardiac death in patients with chronic HF and significant MR.

Background The echocardiographic evaluation of cardiac output relies on the product of the flow across the left ventricular outflow tract (LVOT), estimated through its velocity time integral (LVOT-VTI), and its cross-sectional area, estimated through the formula πr2. Considering the geometrical assumption behind such formula, LVOT-VTI has been proposed as a more reproducible surrogate of cardiac systolic function and showed prognostic value in the critical care setting. However, the role of such measure in patients with chronic heart failure (HF) remains unexplored. Objective To assess the clinical and prognostic significance of LVOT-VTI in a contemporary cohort of patients with chronic HF. Methods Outpatients with chronic HF with a LV ejection fraction &lt;50% were prospectively enrolled to undergo a clinical, echocardiographic, and biohumoral assessment, and were followed-up for the endpoint of all-cause death. Results Finally, 971 patients were enrolled (71±12 years, 72% men, 50% ischemic etiology, LVEF 35±9%). Most patients showed a NYHA class I-II (74%) and were treated with ACE-inhibitors/ARBs or ARNI (81%), beta-blockers (95%), and mineralocorticoid receptor antagonists (71%). Patients were distinguished in three subgroups according to LVOT-VTI tertiles &lt;19 (n=324), 19–24 (n=324), or ≥24 (n=323). Compared with the other two subgroups, patients with LVOT-VTI &lt;19 showed worse NYHA class, lower LVEF and tricuspid annular plane systolic excursion (TAPSE), and higher E/e', left atrial volume index (LAVi), estimated systolic pulmonary arterial pressure (sPAP), and NT-proBNP concentration (all p&lt;0.001). No differences were observed as for patients' age, HF etiology, and therapies (all p&gt;0.05). Over a median follow-up of 22 (9–34) months, 103 (11%) patients met the primary endpoint. LVOT-VTI significantly stratified the risk of death, observing 65 (20%), 21 (7%), and 17 (5%) events across the subgroups with values &lt;19, 19–24, or ≥24 (log-rank 33, p&lt;0.001). At multivariable regression analysis, LVOT-VTI &lt;19 (HR 2.06 [95% 1.21–3.49], p=0.008), but not LVEF &lt;30% (p=0.614) was an independent predictor of all-cause death in a model adjusted for age, sex, ischemic etiology, renal function, hemoglobin, E/e', LAVi, TAPSE, sPAP, and NT-proBNP. Conclusion LVOT-VTI is associated with disease severity and is a strong predictor of all-cause death in patients with chronic HF. Funding Acknowledgement Type of funding sources: None.

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