Obstructive (OA) and central apneas (CA) are highly prevalent breathing disorders that have a negative impact on cardiac structure and function; while OA promote the development of progressive cardiac alterations that can eventually lead to heart failure (HF), CA are more prevalent once HF ensues. Therefore, the early identification of the deleterious effects of apneas on cardiac function, and the possibility to detect an initial cardiac dysfunction in patients with apneas become relevant. Speckle tracking echocardiography (STE) imaging has become increasingly recognized as a method for the early detection of diastolic and systolic dysfunction, by the evaluation of left atrial and left and right ventricular global longitudinal strain, respectively. A growing body of evidence is available on the alterations of STE in OA, while very little is known with regard to CA. In this review, we discuss the current knowledge and gap of evidence concerning apnea-related STE alterations in the development and progression of HF.

Birk-Barel syndrome, alternatively known as KCNK9 imprinting syndrome, is caused by a missense mutation in the potassium two pore domain channel subfamily K member 9 (KCNK9) gene on chromosome 8q24.3. This syndrome demonstrates dominant inheritance and is imprinted with paternal silencing, where the paternally inherited allele is silenced, and the maternally inherited allele is active. Congenital hypotonia, palatal abnormalities, intellectual disability, severe feeding difficulties, and dysmorphic facial features characterize this sporadic genetic syndrome. To date, there are approximately 21 molecularly diagnosed individuals worldwide described in the literature. We describe the first known case of Puerto Rican ethnicity, a 16-month-old female born prematurely at 36-weeks with Birk-Barel syndrome, confirmed with whole-exome sequencing, and her response to non-invasive ventilation as a treatment for her sleep breathing disorder.

To assess the impact of sacubitril-valsartan on apneic burden in patients with heart failure with reduced ejection fraction (HFrEF), 51 stable HFrEF patients planned for switching from an ACE-i/ARB to sacubitril-valsartan were prospectively enrolled.
At baseline and after 6 months of treatment, all patients underwent echocardiography, 24-h cardiorespiratory monitoring, neurohormonal evaluation, and cardiopulmonary exercise testing. At baseline 29% and 65% of patients presented with obstructive and central apneas, respectively. After 6 months, sacubitril-valsartan was associated with a decrease in NT-proBNP, improvement in LV function, functional capacity and ventilatory efficiency. After treatment, the apnea-hypopnea index (AHI) decreased across the 24-h period (p < 0.001), as well as at daytime (p < 0.001) and at nighttime (p = 0.026), proportionally to baseline severity. When subgrouping according to the type of apneas, daytime, nighttime and 24-h AHI decreased in patients with central apneas (all p < 0.01). Conversely, in patients with obstructive apneas, the effect of drug administration was neutral at nighttime, with significant decrease only in daytime events (p = 0.007), mainly driven by reduction in hypopneas.
Sacubitril-valsartan on top of medical treatment is associated with a reduction in the apneic burden among a real-life cohort of HFrEF patients. The most marked reduction was observed for central apneas.

Cheyne-Stokes respiration (CSR) is believed to only occur in supine and sleeping conditions, and thus, CSR treatment is applied to those specific states. Although CSR has also been described in patients with heart failure (HF) during wakefulness, its persistence in an upright position is still unknown.
The purpose of this study was to assess the predictors, clinical correlates, and prognostic value of diurnal CSR in upright position.
Outpatients with systolic HF underwent a comprehensive evaluation, including short-term respiratory monitoring with a head-up tilt test to investigate the presence of upright CSR, assessment of chemoreflex response to hypoxia and hypercapnia, and 24-h cardiorespiratory recording. At follow-up, cardiac death was considered as the endpoint.
Of 574 consecutive patients (left ventricular ejection fraction 32 ± 9%; age 65 ± 13 years; 80% men), 195 (34%) presented supine CSR only, 82 (14%) presented supine and upright CSR, and 297 patients (52%) had normal breathing. Patients with upright CSR had the greatest apnea-hypopnea and central apnea index (at daytime and nighttime), the worst hemodynamic profile and exercise performance, increased plasma norepinephrine and N-terminal pro-B-type natriuretic peptide, and chemosensitivity to hypercapnia, which was the only independent predictor of upright CSR (odds ratio: 3.96; 95% confidence interval [CI]: 1.45 to 10.76; p = 0.007 vs. normal breathing; odds ratio: 4.01; 95% CI: 1.54 to 10.46; p = 0.004 vs. supine CSR). At 8-year follow-up, patients with upright CSR had the worst outcome (log-rank = 14.05; p = 0.001) and the presence of upright CSR independently predicted 8-year cardiac death (hazard ratio: 2.39; 95% CI: 1.08 to 5.29; p = 0.032).
Upright CSR in HF patients is predicted by increased chemosensitivity to hypercapnia and is associated with worse clinical conditions and with a greater risk of cardiac death.

Background: Although central apneas (CA) and obstructive apneas (OA) are highly prevalent in heart failure (HF), a comparison of apnea prevalence, predictors and clinical correlates in the whole HF spectrum, including HF with reduced ejection fraction (HFrEF), mid-range EF (HFmrEF) and preserved EF (HFpEF) has never been carried out so far. Materials and methods: 700 HF patients were prospectively enrolled and then divided according to left ventricular EF (408 HFrEF, 117 HFmrEF, 175 HFpEF). All patients underwent a thorough evaluation including: 2D echocardiography; 24-h Holter-ECG monitoring; cardiopulmonary exercise testing; neuro-hormonal assessment and 24-h cardiorespiratory monitoring. Results: In the whole population, prevalence of normal breathing (NB), CA and OA at daytime was 40, 51, and 9%, respectively, while at nighttime 15, 55, and 30%, respectively. When stratified according to left ventricular EF, CA prevalence decreased (daytime: 57 vs. 43 vs. 42%, p = 0.001; nighttime: 66 vs. 48 vs. 34%, p < 0.0001) from HFrEF to HFmrEF and HFpEF, while OA prevalence increased (daytime: 5 vs. 8 vs. 18%, p < 0.0001; nighttime 20 vs. 29 vs. 53%, p < 0.0001). In HFrEF, male gender and body mass index (BMI) were independent predictors of both CA and OA at nighttime, while age, New York Heart Association functional class and diastolic dysfunction of daytime CA. In HFmrEF and HFpEF male gender and systolic pulmonary artery pressure were independent predictors of CA at daytime, while hypertension predicted nighttime OA in HFpEF patients; no predictor of nighttime CA was identified. When compared to patients with NB, those with CA had higher neuro-hormonal activation in all HF subgroups. Moreover, in the HFrEF subgroup, patients with CA were older, more comorbid and with greater hemodynamic impairment while, in the HFmrEF and HFpEF subgroups, they had higher left atrial volumes and more severe diastolic dysfunction, respectively. When compared to patients with NB, those with OA were older and more comorbid independently from background EF. Conclusions: Across the whole spectrum of HF, CA prevalence increases and OA decreases as left ventricular systolic dysfunction progresses. Different predictors and specific clinical characteristics might help to identify patients at risk of developing CA or OA in different HF phenotypes.

Treatment-emergent central sleep apnea (TE-CSA) is defined as the emergence or persistence of central respiratory events during the initiation of positive airway pressure (PAP) without a back-up rate in obstructive sleep apnea (OSA) patients and after significant resolution of obstructive events. Previous studies have estimated a prevalence from 0.56 to 20.3%. The aim of this study was to establish the prevalence of TE-CSA in a Greek adult population.
One thousand fifty nine patients with newly diagnosed OSA, who were referred to the Sleep Disorders Center of Evangelismos Hospital of Athens over an 18-month period, were included in this study. A split-night polysomnography (PSG), or two formal overnight PSGs (diagnostic and continuous PAP (CPAP) titration study), were performed.
Patients with OSA were divided in two groups; the first group included 277 patients, who underwent two separate studies (diagnostic and CPAP titration study), and the second group 782 patients, who underwent split-night studies. The prevalence of TE-CSA in the first group was 2.53% (7 patients), and in the second group was 5.63% (44 patients).
The prevalence of TE-CSA in Greece was lower compared to most previous reported studies. The significant variation in the prevalence of TE-CSA between different centers throughout the world is mainly associated with the used diagnostic criteria as well as methodological and technical aspects.