VIDEO COLOR OCT ANGIOGRAPHY FOR MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To investigate the myopic macular neovascularization (mMNV) features on dynamic video-color optical coherence tomography (OCT) angiography (OCTA) and the diagnostic rate versus the static, four-segmentations visualization mode. DESIGN: Retrospective cohort study PARTICIPANTS: Fifty-four patients with mMNV METHODS: Sixty-two eyes with high myopia complicated by mMNV were included. Clinical charts, fluorescein angiography and structural OCT were used as standard reference to assess lesion activity. Static and video-color OCTA were then analysed and compared by two independent reviewers. MAIN OUTCOME MEASURES: Morphology description of mMNV on video-color OCTA and differences in the proportion of diagnosis between video-colour and static OCTA. RESULTS: 62 eyes from 54 patients (mean age 63,22 years) were enrolled. Thirty-four (55%) mMNV were active and 28 (45%) inactive. Twenty-two (65%) active mMNV presented on video-color OCTA as an interlacing vascular network in the outer retina and the choriocapillaris. A tapered form was the prevalent size (72,7%). In 3 eyes (9%) an abnormal and irregular vascular network (AVN) was disclosed and in 5 (15%) only some blood flow alteration. All the lesions extended both in the outer retinal and the choriocapillaris. Eleven (39%) inactive mMNV presented on video-color OCTA as an interlacing vascular network too, in the outer retina and the choriocapillaris. Eight (29%) had some AVN and 6 (21%) only some blood flow alteration. The diagnostic rate of video-color vs static OCTA was 95% (IC 95% 86% to 99%) vs 77% (IC 95% 86% to 99%, p= 0.0009), and shows an advantage in favour of video-colour OCTA of 15% (CI 95%, 3%-27%) and 22% (CI 95%, 7%-38%) in active and inactive lesions, respectively (p<0.026). Lesion extension within both the outer retina and the choriocapillaris was present in 90% and 69% of cases on dynamic OCTA and static OCTA, respectively, with a proportion difference of 20% (CI 95%, 10%-31%, p= 0.0005). Concordance between the two examiners was high: 0.95 (95%, CI 0.88 to 1.00) and 0.96 (0.91 to 1.00) for active and inactive lesions, respectively. CONCLUSIONS: Video color-enhanced OCTA may help in diagnosing mMNV and should be considered by clinicians in addition to structural OCT and static OCTA.

Muscle Strength and Phase Angle Are Potential Markers for the Efficacy of Multidisciplinary Weight-Loss Program in Patients with Sarcopenic Obesity.

Background/Objectives: Traditional weight-loss methods often result in the loss of both fat and muscle mass. For individuals with sarcopenic obesity (SO), additional muscle loss can exacerbate sarcopenia, leading to further declines in muscle strength and function, ultimately worsening quality of life. To mitigate this risk, weight-loss strategies should emphasize the preservation and building of muscle mass through adequate protein intake and tailored resistance training. This study aimed to evaluate changes in SO status following a 4-week multidisciplinary weight-loss intervention program in hospitalized patients with obesity. Methods: This study included adult patients with obesity (BMI > 30 kg/m2, aged 18-90 years). The SO diagnosis was performed using the handgrip strength (HGS) test and skeletal muscle mass (SMM) by bioelectrical impedance analysis (BIA) according to ESPEN/EASO-2022 guidelines. Results: A total of 2004 patients were enrolled, 64.8% female, with a mean age of 56 (±14) years and a BMI of 40.7 (±6.48) kg/m2. SO was present in 9.38% (188 patients) at baseline. At discharge, 80 patients (42.55%) were no longer classified as sarcopenic and showed significant improvements in HGS. The likelihood of resolving SO was not modified in patients with only phase angle (PhA) improvement (p-value = 0.141). Patients with HGS increment had a 65% probability to be No-SO at discharge and this probability, with the concomitant PhA increment, rose to 93% (p-value < 0.0001), indicating that functional changes and good nutrition status are crucial in improvement of SO. Muscle mass (MM) and SMMI remained unchanged in the studied cohort. Conclusions: Improvements in HGS and the PhA are potential markers for the efficacy of weight-loss programs tailored to patients with SO. These findings suggest that specific interventions focusing on these markers could be beneficial in managing SO patients.

Transcranial static magnetic stimulation for amyotrophic lateral sclerosis: a bicentric, randomised, double-blind placebo-controlled phase 2 trial.

Background: Enhanced glutamatergic transmission leading to motor neuron death is considered the major pathophysiological mechanism of amyotrophic lateral sclerosis (ALS). Motor cortex excitability can be suppressed by transcranial static magnetic stimulation (tSMS), thus tSMS can be evaluated as a potential treatment for ALS. The aim of present study was to investigate the efficacy and safety of tSMS in ALS. Methods: In this phase 2 trial, we randomly assigned ALS patients to receive daily tSMS or placebo stimulation over a period of 6 months. For each participant we calculated mean disease monthly progression rate (MPR) as the variation of the total ALS Functional Rating Scale-Revised (ALSRFS-R) score, before the beginning of the treatment (over a period of at least three months) and over the six-month treatment period. The primary efficacy outcome was the difference in MPR before and after the beginning of treatment. Secondary outcomes included safety and tolerability, compliance, and changes in corticospinal output. A long-term follow-up of 18 months was performed in all patients who completed the six-month treatment considering a composite endpoint event (tracheostomy or death). Trial registered at ClinicalTrials.gov, ID: NCT04393467, status: closed. Findings: Forty participants were randomly assigned to real (n = 21) or placebo stimulation (n = 19). Thirty-two participants (18 real and 14 placebo) completed the 6-month treatment. The MPR did not show statistically significant differences between the two arms during the pre-treatment (mean ± Standard deviation; Real: 1.02 ± 0.62, Sham: 1.02 ± 0.57, p-value = 1.00) and treatment period (Real: 0.90 ± 0.55, Sham: 0.94 ± 0.55, p-value = 0.83). Results for secondary clinical endpoints showed that the treatment is feasible and safe, being compliance with tSMS high. The change in corticospinal output did not differ significantly between the two groups. At the end of the long-term follow-up of 18 months, patients of real group had a statistically significant higher tracheostomy-free survival compared with patients of placebo group (Hazard Ratio = 0.27 95% Confidence interval 0.09-0.80, p-value = 0.019). Interpretation: tSMS did not modify disease progression during the 6 months of treatment. However, long-term follow-up revealed a substantial increase in tracheostomy free survival in patients treated with real stimulation supporting the evaluation of tSMS in larger and more prolonged studies. Funding: The "Fondazione 'Nicola Irti' per le opere di carità e di cultura", Rome, Italy, supported present study.

Cerebrospinal fluid and blood neurofilament light chain levels in amyotrophic lateral sclerosis and frontotemporal degeneration: A meta-analysis.

BACKGROUND AND PURPOSE: Neurofilament light chain (NFL) has been shown to be increased in amyotrophic lateral sclerosis (ALS) and, to a lesser extent, in frontotemporal dementia (FTD). A meta-analysis of NFL in ALS and FTD was performed. METHODS: Available studies comparing cerebrospinal fluid and blood NFL levels in ALS versus neurologically healthy controls (NHCs), other neurological diseases (ONDs) and ALS mimics, as well as in FTD and related entities (behavioural variant of FTD and frontotemporal lobar degeneration syndromes) versus NHCs, ONDs and other dementias were evaluated. RESULTS: In ALS, both cerebrospinal fluid and blood levels of NFL were higher compared to other categories. In FTD, behavioural variant of FTD and frontotemporal lobar degeneration syndromes, NFL levels were consistently higher compared to NHCs; however, several comparisons with ONDs and other dementias did not demonstrate significant differences. DISCUSSION: Amyotrophic lateral sclerosis is characterized by higher NFL levels compared to most other conditions. In contrast, NFL is not as good at discriminating FTD from other dementias.

Blood pressure variability assessed by office, home, and ambulatory measurements before and during antihypertensive drug treatment: a sub-analysis of the REVERENT randomized trial.

OBJECTIVES: Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10 weeks after initiating antihypertensive drug therapy. METHODS: Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses). RESULTS: Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53 ±â€Š10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24 h ABP 144 ±â€Š9, 138 ±â€Š10, and 143 ±â€Š10 mmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P  = 0.28; HBP: -0.2%, P  = 0.20; 24 h ABP: 1.1%, P  < 0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04-0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively ( P  < 0.05/< 0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64-73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04-0.27). CONCLUSION: These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements.

Sarcopenia Prevalence among Hospitalized Patients with Severe Obesity: An Observational Study.

Background: Sarcopenic obesity (SO) is the combination of excess fat, skeletal muscle and muscular strength/function deficit. The ESPEN/EASO have proposed new diagnostic criteria, but the SO prevalence in patients with severe obesity remains to be established. The aim of this study was to establish the SO prevalence in a large cohort of inpatients with obesity, considering sex, age, BMI, type, and number of concomitant diseases. Methods: Patient data of both genders aged between 18 and 90 years with a body mass index (BMI) of ≥30 kg/m2 underwent hospital evaluation including bioelectrical impedance analysis (BIA) and handgrip strength (HS). QoL scores were obtained by the Psychological General Well-Being Index questionnaire. The study was approved by the institutional Ethic Committee. Results: Among the 3858 patients, 444 (11.51%) exhibited a strength deficit, while 3847 (99.71%) had skeletal muscle mass deficit. The prevalence of SO was then 11.48%, with higher rates in women (12.39%), in individuals aged >70 years (27%), and in those reporting a 'poor' QoL (12.6%). No significant difference in SO prevalence was found when stratifying by BMI (30-40 kg/m2 vs. >40 kg/m2, p = 0.1710). In SO patients, osteoarticular diseases (57%), hypertension/heart failure (38%), type 2 diabetes mellitus (34%), and obstructive sleep apnea (32%) were the more frequent comorbidities. Conclusions: The application of ESPEN/EASO-SO criteria in a cohort of inpatients with severe obesity revealed 11.48% SO prevalence, which was associated with age (particularly > 70 years), gender (women), but not BMI, as determinants. Disease staging and QoL screening may improve the identification of SO high-risk patients.

Interventions aimed to increase average 24-h systolic blood pressure reduce blood pressure drops in patients with reflex syncope and orthostatic intolerance.

AIMS: Systolic blood pressure (SBP) drops recorded by 24-h ambulatory blood pressure (BP) monitoring (ABPM) identify patients with susceptibility to reflex syncope and orthostatic intolerance. We tested the hypothesis that treatments aimed to increase BP (reassurance, education, and lifestyle measures plus pharmacological strategies) can reduce SBP drops. METHODS AND RESULTS: This was a multicentre, observational proof-of-concept study performed in patients with reflex syncope and/or orthostatic intolerance and with SBP drops on a screening ABPM. Among 144 eligible patients, 111 underwent a second ABPM on average 2.5 months after start of treatment. Overall, mean 24-h SBP increased from 114.1 ± 12.1 to 121.4 ± 14.5 mmHg (P < 0.0001). The number of SBP drops <90 and <100 mmHg decreased by 61%, 46% during daytime, and by 48% and 37% during 24-h period, respectively (P < 0.0001 for all). The dose-response relationship between difference in 24-h average SBP increase and reduction in number of SBP drops reached a plateau around ∼15 mmHg increase of 24-h SBP. The reduction in SBP drop rate was consistent and significant in patients who underwent deprescription of hypotensive medications (n = 44) and in patients who received BP-rising drugs (n = 67). CONCLUSION: In patients with reflex syncope and/or orthostatic intolerance, an increase in average 24-h SBP, regardless of the implemented strategy, significantly reduced the number of SBP drops and symptom burden. A 13 mmHg increase in 24-h SBP appears to represent the optimal goal for aborting the maximal number of SBP drops, representing a possible target for future interventions. ClincalTrials.gov identifier: NCT05729724.

Development of a questionnaire on nutritional knowledge for the obese hospitalized patient: the NUTRIKOB questionnaire.

Introduction: Different approaches, involving different areas and figures, are useful for the rehabilitation of obese subjects through a multidisciplinary hospital path. A focal point of rehabilitation is represented by education on healthy eating by increasing the dietary knowledge patients. Few tools investigating food knowledge are available in Italy: therefore, the need has emerged to develop easy-to-use tools for clinical practice that allow to detect food knowledge to set up a more targeted food re-education. The following work aimed at building and validating a questionnaire capable of investigating the dietary knowledge of the population affected by obesity. Methods: A pool of experts carried out a review of the literature, gathering all the information necessary to select and construct the best set of questions and the format of the final project of the questionnaire. During statistical analysis the validity, reproducibility and stability of the questionnaire were investigate in a sample of 450 subjects with obesity. Results: Early analysis disclosed that 5 questions of the original questionnaire had no discriminating power. The successive validation phases were successful, confirming good content validity, stability and reproducibility over time. Discussion: The questionnaire has all the characteristics to be considered a valid tool for investigating dietary knowledge in the obese population. The psychometric tests confirmed a good internal consistency of the structure, a validity of the content, a good reproducibility and stability over time.

Long-term effects of GH therapy in adult patients with Prader-Willi syndrome: a longitudinal study.

Introduction: Prader-Willi syndrome (PWS) is a complex disorder resulting from the failure of expression of paternal alleles in the PWS region of chromosome 15. The PWS phenotype resembles that observed in the classic non-PWS GH deficiency (GHD), including short stature, excessive fat mass, and reduced muscle mass. To date, a small number of studies on the long-term effects of GH treatment are available in adult subjects with PWS. Methods: In this longitudinal study, 12 obese subjects with PWS (GHD/non-GHD 6/6) were treated for a median of 17 years, with a median GH dose of 0.35 mg/day. The median age was 27.1 years. Anthropometric, body composition, hormonal, biochemical, and blood pressure variables were analyzed in all subjects. Results: Waist circumference was significantly lower at the end of the treatment period (p-value=0.0449), while body mass index (BMI) did not differ significantly. Compared to the baseline, a highly significant reduction of Fat Mass % (FM%) was observed (p-value=0.0005). IGF-I SDS values significantly increased during GH therapy (p-value=0.0005). A slight impairment of glucose homeostasis was observed after GH therapy, with an increase in the median fasting glucose levels, while insulin, HOMA-IR, and HbA1c values remained unchanged. Considering GH secretory status, both subjects with and without GHD showed a significant increase in IGF-I SDS and a reduction of FM% after GH therapy (p-value= 0.0313 for all). Discussion: Our results indicate that long-term GH treatment has beneficial effects on body composition and body fat distribution in adults with PWS associated with obesity. However, the increase in glucose values during GH therapy should be considered, and continuous surveillance of glucose metabolism is mandatory during long-term GH therapy, especially in subjects with obesity.

Towards an individualized management of pubertal induction in girls with hypogonadism: insight into the best replacement outcomes from a large multicentre registry.

OBJECTIVE: An evidence-based pubertal induction scheme in hypogonadal girls is still to be established. Interestingly, literature data report a suboptimal uterine longitudinal diameter (ULD) in >50% of treated hypogonadal women, negatively influencing their pregnancy outcomes. This study aims to investigate auxological and uterine outcomes of pubertal induction in girls in the light of underlying diagnosis and therapeutic schemes used. DESIGN: Retrospective analysis of longitudinal data from a multicentric registry. METHODS: Auxological, biochemical, and radiological data were collected at baseline and during follow-up in 95 hypogonadal girls (chronological age > 10.9 years, Tanner stage ≤ 2) treated with transdermal 17ß-oestradiol patches for at least 1 year. Induction was started at a median dose of 0.14 mcg/kg/day with a 6-monthly increase and was considered completed for 49/95 patients who started progesterone with a concomitant oestrogen adult dose. RESULTS: At the end of induction, the achievement of the complete breast maturation was associated with a 17ß-oestradiol dose at progesterone introduction. ULD showed a significant correlation with a 17ß-oestradiol dosage. Final ULD was >65 mm in only 17/45 girls. At multiple regression analysis, pelvic irradiation represented the major determinant of reduced final ULD. After correction for uterine irradiation, ULD was associated with the 17ß-oestradiol dose at progesterone introduction. Final ULD was not significantly different from the one assessed after progesterone introduction. CONCLUSIONS: Our results provide evidence that progestins, hampering further changes in uterine volume and breast development, should be introduced only in the presence of a concomitant adequate 17ß-oestradiol dose and an appropriate clinical response.

Detection of impending reflex syncope by means of an integrated multisensor patch-type recorder.

We assessed the capability of an integrated multisensory patch-type monitor (RootiRx®) in detecting episodes of reflex (pre)syncope induced by tilt table test (TTT). Firstly, we performed an intrapatient comparison of cuffless systolic blood pressure (SBP), R-R interval (RRI) and variability (power spectrum analysis) obtained by means of the RootiRx® with those obtained with conventional methods (CONV) with validated finger pressure devices at baseline in supine position and repeatedly during TTT in 32 patients affected by likely reflex syncope. Secondly, the LF/HF values obtained with RootiRx® during TTT were analyzed in 50 syncope patients. Compared with baseline supine recordings, during TTT a decrement of median SBP was observed with CONV (-53.5 mmHg) but not with RootiRx® ®(-1 mmHg). Conversely, RRI reduction (CONV: 102 ms; RootiRx®: 127 ms) and RRI Low Frequency/High Frequency powers ratio (LF/HF) increase (CONV: 1.6; RootiRx®: 2.5) were similar. The concordance was good for RRI (0.97 [95% CI 0.96-0.98]) and fair for LF/HF ratio (0.69 [95% CI 0.46-0.83]). During the first 5 min of TTT the LF/HF ratio was higher in patients who later developed syncope than in no-syncope patients. This ratio was significantly different among patients with syncope, presyncope or without symptoms at the time of syncope (p value = 0.02). In conclusion, cuffless RootiRx® was unable to detect rapid drops of SBP occurring during impending reflex syncope and thus cannot be used as a diagnostic tool for hypotensive syncope. On the other hand, RRI mean values and LF/HF power ratios obtained with RootiRx® were consistent with those simultaneously obtained using conventional methods.

Effect of Continuous Positive Airway Pressure on Glucose and Lipid Profiles in Patients With Obstructive Sleep Apnoea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIM: Continuous Positive Airway Pressure (CPAP) is the most effective therapy for symptomatic obstructive sleep apnoea (OSA). However, uncertainty remains about the effectiveness of CPAP in improving OSA-related metabolic dysregulation. This meta-analysis of randomized controlled trials (RCTs) aimed to investigate whether CPAP, compared to other control treatments, could improve glucose or lipid metabolism in OSA patients. METHODS: Relevant articles were searched in three different databases (MEDLINE, EMBASE and Web of Science) from inception to 6th Feb 2022 through specific search terms and selection criteria. RESULTS: From a total of 5553 articles, 31 RCTs were included. CPAP modestly improved insulin sensitivity as determined by mean fasting plasma insulin and Homeostasis Model Assessment of Insulin Resistance reduction of 1.33mU/L and 0.287, respectively. In subgroup analyses pre-diabetic/type 2 diabetic patients as well as those with sleepy OSA showed a greater response to CPAP. Regarding lipid metabolism, CPAP was associated with a mean total cholesterol reduction of 0.064mmol/L. In subgroup analyses, the benefit was higher in patients that showed more severe OSA and oxygen desaturations at the baseline sleep study as well as in younger and obese subjects. Neither glycated haemoglobin nor triglycerides, HDL- and LDL-cholesterol were reduced by CPAP. CONCLUSION: CPAP treatment may improve insulin sensitivity and total cholesterol levels in OSA patients but with low effect size. Our results suggest that CPAP does not substantially improve metabolic derangements in an unselected OSA population, but the effect may be higher in specific subgroups of OSA patients.

Shedding Light on Latent Pulmonary Vascular Disease in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Among patients with heart failure with preserved ejection fraction (HFpEF), a distinct hemodynamic phenotype has been recently described, ie, latent pulmonary vascular disease (HFpEF-latentPVD), defined by exercise pulmonary vascular resistance (PVR) >1.74 WU. OBJECTIVES: This study aims to explore the pathophysiological significance of HFpEF-latentPVD. METHODS: The authors analyzed a cohort of patients who had undergone supine exercise right heart catheterization with cardiac output (CO) measured by direct Fick method, between 2016 and 2021. HFpEF-latentPVD patients were compared with HFpEF control patients. RESULTS: Out of 86 HFpEF patients, 21% qualified as having HFpEF-latentPVD, 78% of whom had PVR >2 WU at rest. Patients with HFpEF-latentPVD were older, with a higher pretest probability of HFpEF, and more frequently experienced atrial fibrillation and at least moderate tricuspid regurgitation (P < 0.05). PVR trajectories differed between HFpEF-latentPVD patients and HFpEF control patients (Pinteraction = 0.008), slightly increasing in the former and reducing in the latter. HFpEF-latentPVD patients displayed more frequent hemodynamically significant tricuspid regurgitation during exercise (P = 0.002) and had more impaired CO and stroke volume reserve (P < 0.05). Exercise PVR was correlated with mixed venous O2 tension (R2 = 0.33) and stroke volume (R2 = 0.31) in HFpEF-latentPVD patients. The HFpEF-latentPVD patients had had higher dead space ventilation during exercise and higher PaCO2 (P < 0.05), which correlated with resting PVR (R2 = 0.21). Event-free survival was reduced in HFpEF-latentPVD patients (P < 0.05). CONCLUSIONS: The results suggest that when CO is measured by direct Fick, few HFpEF patients have isolated latent PVD (ie, normal PVR at rest, becoming abnormal during exercise). HFpEF-latentPVD patients present with CO limitation to exercise, associated with dynamic tricuspid regurgitation, altered ventilatory control, and pulmonary vascular hyperreactivity, portending a poor prognosis.

Impact of severe secondary tricuspid regurgitation on rest and exercise hemodynamics of patients with heart failure and a preserved left ventricular ejection fraction.

Background: Both secondary tricuspid regurgitation (STR) and heart failure with preserved ejection fraction (HFpEF) are relevant public health problems in the elderly population, presenting with potential overlaps and sharing similar risk factors. However, the impact of severe STR on hemodynamics and cardiorespiratory adaptation to exercise in HFpEF remains to be clarified. Aim: To explore the impact of STR on exercise hemodynamics and cardiorespiratory adaptation in HFpEF. Methods: We analyzed invasive hemodynamics and gas-exchange data obtained at rest and during exercise from HFpEF patients with severe STR (HFpEF-STR), compared with 1:1 age-, sex-, and body mass index (BMI)- matched HFpEF patients with mild or no STR (HFpEF-controls). Results: Twelve HFpEF with atrial-STR (mean age 72 years, 92% females, BMI 28 Kg/m2) and 12 HFpEF-controls patients were analyzed. HFpEF-STR had higher (p < 0.01) right atrial pressure than HFpEF-controls both at rest (10 ± 1 vs. 5 ± 1 mmHg) and during exercise (23 ± 2 vs. 14 ± 2 mmHg). Despite higher pulmonary artery wedge pressure (PAWP) at rest in HFpEF-STR than in HFpEF-controls (17 ± 2 vs. 11 ± 2, p = 0.04), PAWP at peak exercise was no more different (28 ± 2 vs. 29 ± 2). Left ventricular transmural pressure and cardiac output (CO) increased less in HFpEF-STR than in HFpEF-controls (interaction p-value < 0.05). This latter was due to lower stroke volume (SV) values both at rest (48 ± 9 vs. 77 ± 9 mL, p < 0.05) and at peak exercise (54 ± 10 vs. 93 ± 10 mL, p < 0.05). Despite these differences, the two groups of patients laid on the same oxygen consumption isophlets because of the increased peripheral oxygen extraction in HFpEF-STR (p < 0.01). We found an inverse relationship between pulmonary vascular resistance and SV, both at rest and at peak exercise (R 2 = 0.12 and 0.19, respectively). Conclusions: Severe STR complicating HFpEF impairs SV and CO reserve, leading to pulmonary vascular de-recruitment and relative left heart underfilling, undermining the typical HFpEF pathophysiology.

Nocturnal hypoxia indexes are associated with left ventricular remodeling and diastolic dysfunction in obstructive sleep apnea patients.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) is associated with heart derangements detected at echocardiography as higher left ventricular mass index (LVMI), higher left ventricular end-diastolic diameter, lower left ventricular ejection fraction (LVEF), and impaired diastolic function. However, the currently used parameter to define OSA diagnosis and severity, the apnea/hypopnea index (AHI), poorly predicts cardiovascular damage, cardiovascular events, and mortality. Our study aimed to assess if other polygraphic indices of OSA presence and severity, in addition to AHI, might better predict echocardiographic cardiac remodeling. METHODS AND RESULTS: We enrolled two cohorts of individuals referred for suspected OSA to the outpatient facilities of the IRCCS Istituto Auxologico Italiano, Milano, and of the Clinica Medica 3, Padova. All patients underwent home sleep apnea testing and echocardiography. Based on the AHI the cohort was divided into no-OSA (AHI<15 events/hour) and moderate-severe OSA (AHI≥15 events/hour). We recruited 162 patients and found that compared to patients with no-OSA, those with moderate-severe OSA showed higher LV remodeling [left ventricular end-diastolic volume (LVEDV) 48.4 ± 11.5 ml/m2 vs. 54.1 ± 14.0 ml/m2, respectively, p = 0.005] and lower LVEF (65.3 ± 5.8% vs. 61.6 ± 7.8%, respectively, p = 0.002), whereas we could not find any difference in LVMI and early and late ventricular filling velocity ratio (E/A). At multivariate linear regression analysis two polygraphic hypoxic burden-related markers were independent predictors of LVEDV and E/A, i.e., the percentage of time with O2 saturation below 90% (ß = 0.222) and ODI (ß = -0.422), respectively. CONCLUSIONS: Our study shows that nocturnal hypoxia-related indexes were associated with left ventricular remodeling and diastolic dysfunction in OSA patients.

Impact of reboxetine plus oxybutynin treatment for obstructive sleep apnea on cardiovascular autonomic modulation.

The combination of noradrenergic (reboxetine) plus antimuscarinic (oxybutynin) drugs (reb-oxy) reduced obstructive sleep apnea (OSA) severity but no data are available on its effects on cardiac autonomic modulation. We sought to evaluate the impact of 1-week reb-oxy treatment on cardiovascular autonomic control in OSA patients. OSA patients were randomized to a double-blind, crossover trial comparing 4 mg reboxetine plus 5 mg oxybutynin to a placebo for OSA treatment. Heart rate (HR) variability (HRV), ambulatory blood pressure (BP) monitoring (ABPM) over 24 h baseline and after treatment were performed. Baroreflex sensitivity was tested over beat-to-beat BP recordings. 16 subjects with (median [interquartile range]) age 57 [51-61] years and body mass index 30 [26-36]kg/m2 completed the study. The median nocturnal HR was 65 [60-69] bpm at baseline and increased to 69 [64-77] bpm on reb-oxy vs 66 [59-70] bpm on placebo (p = 0.02). The mean 24 h HR from ABPM was not different among treatment groups. Reb-oxy administration was not associated with any modification in HRV or BP. Reb-oxy increased the baroreflex sensitivity and did not induce orthostatic hypotension. In conclusion, administration of reb-oxy did not induce clinically relevant sympathetic overactivity over 1-week and, together with a reduction in OSA severity, it improved the baroreflex function.

Phase angle (PhA) in overweight and obesity: evidence of applicability from diagnosis to weight changes in obesity treatment.

Phase angle (PhA) is a recently proposed marker of nutritional status in many clinical conditions. Its use in patients with obesity presents different critical concerns due to the higher variability of the two measured parameters (resistance, R, and reactance, Xc) that contribute to the determination of PhA. Controversial is the relation between PhA and BMI that might vary with graded levels of obesity due to the variation in fat and free fat mass. Obesity is frequently associated with metabolic, hepatic, cardiovascular and kidney diseases that introduce variations in PhA values, in relation to multimorbidity and severity degree of these diseases. It is reported that the improvement of clinical condition is associated with a positive change in PhA. Also, the treatment of obesity with weight loss might confirm this effect, but with different responses in relation to the type and duration of the intervention applied. In fact, the effect appears not only related to the percentage of weight loss but also the possible loss of free fat mass and the nutritional, metabolic and structural modifications that might follow each therapeutic approach to decrease body weight. We can conclude that the PhA could be used as marker of health status in patients with obesity supporting an appropriate weight loss intervention to monitor efficacy and fat free mass preservation.

An updated meta-analysis of hemodynamics markers of prognosis in patients with pulmonary hypertension due to left heart disease.

Pulmonary hypertension (PH) is associated with a poor prognosis in left heart disease (LHD). We sought to provide an updated analysis on the association of hemodynamic variables, such as pulmonary vascular resistance (PVR), pulmonary artery compliance (PAC), and diastolic pressure gradient (DPG), with prognosis in PH-LHD, through a systematic literature review. Sixteen articles were identified, including 9600 patients with LHD, heterogeneous in terms of age, sex, and etiology of cardiac disease. In this large population, PVR (hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.05-1.0), DPG (HR, 1.02; 95% CI: 1.01-1.02) and PAC (HR, 0.76; 95% CI: 0.69-0.84) were associated with an increased risk of adverse outcome, albeit with a less solid performance of DPG. Similar results were found when hemodynamic variables were analyzed according to the thresholds commonly applied in clinical practice, or subdividing cohorts according to the underlying LHD. Furthermore, cumulative metanalysis indicated that these results are consistently stable since 2018. Thus, PVR, DPG and PAC have an established prognostic value in PH-LHD. These results are consistent through the years and unlikely to change with further studies.