Blood pressure screening in Mata Sector, a rural area of Rwanda.

In rural sub-Saharan Africa, knowledge of non-communicable diseases such as high blood pressure (BP) is rather limited. This report provides information about a BP screening in Mata Sector, a rural region in Southern Province of Rwanda. Community-based, house-to-house screening was performed between February and July 2020 on more than 7000 inhabitants. The screening was conducted by a local team composed by 20 community health care workers, five community health care supervisors, and one nurse with hypertension surveillance training. BP and heart rate were recorded after 5 min of resting, using a validated automated oscillometric OMRON M6 IT-HEM-7322-E monitor with Intelli Wrap Cuff (HEM-FL31-E) technology. The mean of the second and third value was retained. BP was normal (<140/90 mm Hg) in 6340 (88%) and elevated in 863 (12%) participants with 95% of unawareness. Grade 1 (140-159/90-99 mm Hg) hypertensive BP readings were detected in 697 (81%), grade 2 (160-179/100-109 mm Hg) in 134 (16%), and grade 3 (≥180/≥110 mm Hg) in 32 (3.7%) individuals. The prevalence of hypertensive readings was significantly age-dependent. Additionally, a slightly greater proportion of participants with high BP (14% versus 11%) had a body mass index (BMI) ≥ 25.0 kg/m2. Also resting heart rate was higher in individuals with high BP (82 versus 77 beats/min). Although individuals identified with occasionally elevated BP values need further confirmatory measurements to establish the diagnosis of hypertension, these data suggest that high BP represents a noteworthy and preventable reason of concern within sub-Saharan Africa.

Assessment and management of exaggerated blood pressure response to standing and orthostatic hypertension: consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability.

Recent evidence suggests that an exaggerated blood pressure (BP) response to standing (ERTS) is associated with an increased risk of adverse outcomes, both in young and old individuals. In addition, ERTS has been shown to be an independent predictor of masked hypertension. In the vast majority of studies reporting on the prognostic value of orthostatic hypertension (OHT), the definition was based only on systolic office BP measurements. This consensus statement provides recommendations on the assessment and management of individuals with ERTS and/or OHT. ERTS is defined as an orthostatic increase in SBP at least 20 mmHg and OHT as an ERTS with standing SBP at least 140 mmHg. This statement recommends a standardized methodology to assess ERTS, by considering body and arm position, and the number and timing of BP measurements. ERTS/OHT should be confirmed in a second visit, to account for its limited reproducibility. The second assessment should evaluate BP changes from the supine to the standing posture. Ambulatory BP monitoring is recommended in most individuals with ERTS/OHT, especially if they have high-normal seated office BP. Implementation of lifestyle changes and close follow-up are recommended in individuals with ERTS/OHT. Whether specific antihypertensive treatment should be administered in hypertensive patients with ERTS/OHT is unknown. Thus, they should be managed as any other hypertensive patient. Standardized standing BP measurement should be implemented in future epidemiological and interventional studies.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic individuals.

A study protocol for evaluating aortic stiffness modifications in patients treated with endovascular aortic repair.

BACKGROUND: Arterial stiffness, particularly aortic stiffness (AoS), is associated with an increased risk of cardiovascular disease. Endovascular repair for abdominal (EVAR) and thoracic (TEVAR) aortic disease may increase AoS. This study protocol aims to assess changes in AoS before and after interventions for aortic disease. METHODS: Patients scheduled for EVAR or TEVAR during a three-year period will be enrolled. An indirect AoS indicator, carotid-to-femoral pulse wave velocity (cf-PWV) will be measured non-invasively using applanation tonometry and reported with others perioperative data before and after the endovascular treatment. Moreover, cardiological data will be collected through echocardiography. RESULTS: Fifty EVAR and 50 TEVAR will be enrolled. We will primarily analyze changes in cf-PWV. To ensure the reliability of our findings, we will also include supplementary data such as clinical information, morphological data, and functional echocardiographic data. CONCLUSIONS: By examining AoS modifications before and after endovascular aortic repair, this study aims to enhance our understanding of how arterial stiffness changes following endoprosthesis deployment. The findings from the applied protocol are expected to be informative for innovative graft designs with minimized mechanical mismatch with the aortic wall and with improved vascular hemodynamic, aligning with the current trend in improving patient outcomes. Moreover, understanding these modifications is important for predicting and improving long-term cardiovascular outcomes in patients undergoing such interventions.

Predictors of Psychological Well-Being and Quality of Life in Patients with Hypertension: A Longitudinal Study.

Previous research has highlighted the positive impact of greater health-related quality of life (Hr-QoL) and subjective well-being (SWB) on chronic diseases' severity and progression. There is a paucity of studies investigating the long-term trajectories of these variables among hypertensive patients. The present study aims to investigate the relationships between psychological variables (Type A and D personality, locus of control-LoC, self-esteem, and trait anxiety) with SWB and Hr-QoL in patients with hypertension and comorbid metabolic syndrome. A total of 185 volunteer patients (130 males, 70.3%; mean age 54 ± 10.93) were enrolled. Patients filled out measures of Hr-QoL and SWB, LoC, and self-esteem at three time points-Type A and D behaviors and anxiety measures only at baseline. Analyses were run through two-level hierarchical mixed models with repeated measures (Level 1) nested within participants (Level 2), controlling for sociodemographic and clinical confounders. Neither Hr-QoL nor SWB changed over time. Patients with greater self-esteem and internal LoC (and lower external LoC) increased their SWB and Hr-QoL up to 1-year follow-up. A greater Type A behavior and trait anxiety at baseline predicted a longitudinal increase in most of the dependent variables. Results suggest that it could be useful to tailor interventions targeting specific variables to increase Hr-QoL and SWB among hypertensive patients.

Prognostic Relevance of Short-Term Blood Pressure Variability. The Spanish ABPM Registry.

BACKGROUND: The prognostic relevance of short-term blood pressure (BP) variability in hypertension is not clearly established. We aimed to evaluate the association of short-term BP variability, with all-cause and cardiovascular mortality in a large cohort of patients with hypertension. METHODS: We selected 59 124 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry from 2004 to 2014 (median follow-up: 9.7 years). Systolic and diastolic BP SD and coefficient of variation from daytime and nighttime, weighted SD, weighted coefficient of variation, average real variability (mean of differences between consecutive readings), and BP variability ratio (ratio between systolic and diastolic 24-hour SD) were calculated through baseline 24-hour ambulatory BP monitoring. Association with all-cause and cardiovascular mortality were assessed by Cox regression models adjusted for clinical confounders and BP. RESULTS: Patients who died during follow-up had higher values of BP variability compared with those remaining alive. In adjusted models systolic and diastolic daytime and weighted SD and coefficient of variation, average real variability, as well as systolic nighttime SD and BP variability ratio were all significantly associated with all-cause and cardiovascular mortality. Hazard ratios for 1-SD increase in the systolic components ranged from 1.05 to 1.12 for all-cause mortality and from 1.07 to 1.17 for cardiovascular mortality. A daytime SD≥13 mm Hg, a nighttime and a weighted SD≥12 mm Hg, and an average real variability ≥10 mm Hg, all systolic, were independently associated with mortality. CONCLUSIONS: Short-term blood pressure variability shows a relatively weak but significant association with all-cause and cardiovascular mortality in patients with hypertension.

Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project).

PURPOSE: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. METHODS: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. RESULTS: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors. CONCLUSIONS: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.

ACHIEVE conference proceedings: implementing action plans to reduce and control hypertension burden in Africa.

The prevalence of hypertension, the commonest risk factor for preventable disability and premature deaths, is rapidly increasing in Africa. The African Control of Hypertension through Innovative Epidemiology, and a Vibrant Ecosystem [ACHIEVE] conference was convened to discuss and initiate the co-implementation of the strategic solutions to tame this burden toward achieving a target of 80% for awareness, treatment, and control by the year 2030. Experts, including the academia, policymakers, patients, the WHO, and representatives of various hypertension and cardiology societies generated a 12-item communique for implementation by the stakeholders of the ACHIEVE ecosystem at the continental, national, sub-national, and local (primary) healthcare levels.

Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial

BACKGROUND: In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction. METHODS: We conducted a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial of peak-flow triggered ASV in patients aged 18 years or older with heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%) who were stabilised on optimal medical therapy with co-existing sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥15 events/h of sleep), with concealed allocation and blinded outcome assessments. The trial was carried out at 49 hospitals in nine countries. Sleep-disordered breathing was stratified into predominantly OSA with an Epworth Sleepiness Scale score of 10 or lower or predominantly CSA. Participants were randomly assigned to standard optimal treatment alone or standard optimal treatment with the addition of ASV (1:1), stratified by study site and sleep apnoea type (ie, CSA or OSA), with permuted blocks of sizes 4 and 6 in random order. Clinical evaluations were performed and Minnesota Living with Heart Failure Questionnaire, Epworth Sleepiness Scale, and New York Heart Association class were assessed at months 1, 3, and 6 following randomisation and every 6 months thereafter to a maximum of 5 years. The primary endpoint was the cumulative incidence of the composite of all-cause mortality, first admission to hospital for a cardiovascular reason, new onset atrial fibrillation or flutter, and delivery of an appropriate cardioverter-defibrillator shock. All-cause mortality was a secondary endpoint. Analysis for the primary outcome was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01128816) and the International Standard Randomised Controlled Trial Number Register (ISRCTN67500535), and the trial is complete. FINDINGS: The first and last enrolments were Sept 22, 2010, and March 20, 2021. Enrolments terminated prematurely due to COVID-19-related restrictions. 1127 patients were screened, of whom 731 (65%) patients were randomly assigned to receive standard care (n=375; mean AHI 42·8 events per h of sleep [SD 20·9]) or standard care plus ASV (n=356; 43·3 events per h of sleep [20·5]). Follow-up of all patients ended at the latest on June 15, 2021, when the trial was terminated prematurely due to a recall of the ASV device due to potential disintegration of the motor sound-abatement material. Over the course of the trial, 41 (6%) of participants withdrew consent and 34 (5%) were lost to follow-up. In the ASV group, the mean AHI decreased to 2·8-3·7 events per h over the course of the trial, with associated improvements in sleep quality assessed 1 month following randomisation. Over a mean follow-up period of 3·6 years (SD 1·6), ASV had no effect on the primary composite outcome (180 events in the control group vs 166 in the ASV group; hazard ratio [HR] 0·95, 95% CI 0·77-1·18; p=0·67) or the secondary endpoint of all-cause mortality (88 deaths in the control group vs. 76 in the ASV group; 0·89, 0·66-1·21; p=0·47). For patients with OSA, the HR for all-cause mortality was 1·00 (0·68-1·46; p=0·98) and for CSA was 0·74 (0·44-1·23; p=0·25). No safety issue related to ASV use was identified. INTERPRETATION: In patients with heart failure and reduced ejection fraction and sleep-disordered breathing, ASV had no effect on the primary composite outcome or mortality but eliminated sleep-disordered breathing safely.

Single-Pill, Triple Antihypertensive Therapy in Rural Sub-Saharan Africa: Preliminary Experience.

INTRODUCTION: Worldwide, arterial hypertension is the foremost preventable and modifiable cardiovascular risk factor. In addition to lifestyle changes, recent international guidelines recommend single-pill, low-dose combinations as initial treatment strategy. We investigated whether this approach is feasible in a rural sub-Saharan Africa setting. METHODS: Diagnosis of hypertension was established over three sets of blood pressure measurements, performed according to the European Society of Hypertension recommendations by trained personnel, using a validated, automated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals with arterial hypertension, a once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at an appropriate dose. Patients were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. The treatment regimen was adjusted, if needed, at each outpatient clinic scheduled after 4, 8, 12, and 16 weeks. RESULTS: Seventy-nine patients (aged 61 [53-70] years; median and interquartile range) strictly adhered to the treatment schedule, while 19 individuals (70 [65-80] years) dropped out. Blood pressure was < 140/90 mmHg after 4 weeks in 44 (56%), after 8 weeks in 62 (78%), after 12 weeks in 69 (87%), and after 16 weeks in 74 (94%) participants. Excellent tolerance was reported. CONCLUSIONS: These results provide real-life evidence that hypertension management with a once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide as initial treatment is feasible and effective also in a rural sub-Saharan setting. Single-pill combinations should be made available also in rural and remote areas in low- and middle-income countries as a reliable first-line treatment strategy.

Right Atrial Remodeling and Outcome in Patients with Secondary Tricuspid Regurgitation.

BACKGROUND: In patients with secondary tricuspid regurgitation (STR), right atrial remodeling (RAR) is a proven marker of disease progression. However, the prognostic value of RAR, assessed by indexed right atrial volume (RAVi) and reservoir strain (RAS), remains to be clarified. Accordingly, the aim of our study is to investigate the association with outcome of RAR in patients with STR. METHODS: We enrolled 397 patients (44% men, 72.7 ± 13 years old) with mild to severe STR. Complete two-dimensional and speckle-tracking echocardiography analysis of right atrial and right ventricular (RV) size and function were obtained in all patients. The primary end point was the composite of death from any cause and heart failure hospitalization. RESULTS: After a median follow-up of 15 months (interquartile range, 6-23), the end point was reached by 158 patients (39%). Patients with RAS <13% and RAVi >48 mL/m2 had significantly lower survival rates compared to patients with RAS ≥13% and RAVi ≤48 mL/m2 (log-rank P < .001). On multivariable analysis, RAS <13% (hazard ratio, 2.11; 95% CI, 1.43-3.11; P < .001) and RAVi > 48 mL/m2 (hazard ratio, 1.49; 95% CI, 1.01-2.18; P = .04) remained associated with the combined end point, even after adjusting for RV free-wall longitudinal strain, significant chronic kidney disease, and New York Heart Association class. Secondary tricuspid regurgitation excess mortality increased exponentially with values of 18.2% and 51.3 mL/m2 for RAS and RAVi, respectively. In nested models, the addition of RAS and RAVi provided incremental prognostic value over clinical, conventional echocardiographic parameters of RV size and function and RV free-wall longitudinal strain. CONCLUSIONS: In patients with STR, RAR was independently associated with mortality and heart failure hospitalization. Assessment of RAR could improve risk stratification of patients with STR, potentially identifying those who may benefit from optimization of medical therapy and a closer follow-up.

Myocardial oxygen supply and demand imbalance predicts mortality in older nursing home residents: The PARTAGE study.

BACKGROUND: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. METHODS: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. RESULTS: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. CONCLUSIONS: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. TRIAL REGISTRATION: NCT00901355, registered on ClinicalTrials.gov website.

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.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3-13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of antihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8-103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063-1.378, P=0.004) and 1.150 (95% CI, 1.021-1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.

What about chronotropic incompetence in heart failure with mildly reduced ejection fraction? Clinical and prognostic implications from the Metabolic Exercise combined with Cardiac and Kidney Indexes score dataset.

AIMS: Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction, however no data on its clinical and prognostic impacts in heart failure with mildly reduced ejection fraction (HFmrEF) are available. Therefore, the study aims to investigate, in a large multicentre HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters. METHODS AND RESULTS: Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analysed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored. Chronotropic incompetence prevalence differed depending on the method (peak heart rate, pHR% vs. pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR% ≤ 65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 years. At multivariate analysis, both pHR% [hazard ratio 0.97 (0.95-0.99), P < 0.05] and pHRR% [hazard ratio 0.977 (0.961-0.993), P < 0.01] were associated with the primary endpoint. A pHR% ≤ 75% and a pHRR% ≤ 50% represented the most accurate cut-off values in predicting the outcome. CONCLUSION: The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies.

Chronotropic incompetence is an easy-to-obtain additive parameter for cardiovascular death risk stratification in heart failure with mildly reduced ejection fraction (HFmrEF). Peak heart rate and peak heart rate reserve are associated with exercise capacity in HFmrEF. Peak heart rate and peak heart rate reserve are associated with cardiovascular death in HFmrEF.

Adaptive servo-ventilation for sleep-disordered breathing in patients with heart failure with reduced ejection fraction (ADVENT-HF): a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial.

BACKGROUND: In patients with heart failure and reduced ejection fraction, sleep-disordered breathing, comprising obstructive sleep apnoea (OSA) and central sleep apnoea (CSA), is associated with increased morbidity, mortality, and sleep disruption. We hypothesised that treating sleep-disordered breathing with a peak-flow triggered adaptive servo-ventilation (ASV) device would improve cardiovascular outcomes in patients with heart failure and reduced ejection fraction. METHODS: We conducted a multicentre, multinational, parallel-group, open-label, phase 3 randomised controlled trial of peak-flow triggered ASV in patients aged 18 years or older with heart failure and reduced ejection fraction (left ventricular ejection fraction ≤45%) who were stabilised on optimal medical therapy with co-existing sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥15 events/h of sleep), with concealed allocation and blinded outcome assessments. The trial was carried out at 49 hospitals in nine countries. Sleep-disordered breathing was stratified into predominantly OSA with an Epworth Sleepiness Scale score of 10 or lower or predominantly CSA. Participants were randomly assigned to standard optimal treatment alone or standard optimal treatment with the addition of ASV (1:1), stratified by study site and sleep apnoea type (ie, CSA or OSA), with permuted blocks of sizes 4 and 6 in random order. Clinical evaluations were performed and Minnesota Living with Heart Failure Questionnaire, Epworth Sleepiness Scale, and New York Heart Association class were assessed at months 1, 3, and 6 following randomisation and every 6 months thereafter to a maximum of 5 years. The primary endpoint was the cumulative incidence of the composite of all-cause mortality, first admission to hospital for a cardiovascular reason, new onset atrial fibrillation or flutter, and delivery of an appropriate cardioverter-defibrillator shock. All-cause mortality was a secondary endpoint. Analysis for the primary outcome was done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01128816) and the International Standard Randomised Controlled Trial Number Register (ISRCTN67500535), and the trial is complete. FINDINGS: The first and last enrolments were Sept 22, 2010, and March 20, 2021. Enrolments terminated prematurely due to COVID-19-related restrictions. 1127 patients were screened, of whom 731 (65%) patients were randomly assigned to receive standard care (n=375; mean AHI 42·8 events per h of sleep [SD 20·9]) or standard care plus ASV (n=356; 43·3 events per h of sleep [20·5]). Follow-up of all patients ended at the latest on June 15, 2021, when the trial was terminated prematurely due to a recall of the ASV device due to potential disintegration of the motor sound-abatement material. Over the course of the trial, 41 (6%) of participants withdrew consent and 34 (5%) were lost to follow-up. In the ASV group, the mean AHI decreased to 2·8-3·7 events per h over the course of the trial, with associated improvements in sleep quality assessed 1 month following randomisation. Over a mean follow-up period of 3·6 years (SD 1·6), ASV had no effect on the primary composite outcome (180 events in the control group vs 166 in the ASV group; hazard ratio [HR] 0·95, 95% CI 0·77-1·18; p=0·67) or the secondary endpoint of all-cause mortality (88 deaths in the control group vs. 76 in the ASV group; 0·89, 0·66-1·21; p=0·47). For patients with OSA, the HR for all-cause mortality was 1·00 (0·68-1·46; p=0·98) and for CSA was 0·74 (0·44-1·23; p=0·25). No safety issue related to ASV use was identified. INTERPRETATION: In patients with heart failure and reduced ejection fraction and sleep-disordered breathing, ASV had no effect on the primary composite outcome or mortality but eliminated sleep-disordered breathing safely. FUNDING: Canadian Institutes of Health Research and Philips RS North America.

Wall Properties of Elastic and Muscular Arteries in Children and Adolescents at Increased Cardiovascular Risk.

BACKGROUND: Pulse wave velocity (PWV) assessment represents a simple method to estimate arterial distensibility. At present, carotid-femoral PWV (cf-PWV) is considered the gold standard method in the non-invasive evaluation of the elastic properties of the aorta. On the other hand, the mechanical properties of muscular arteries can be evaluated on the axillo-brachial-radia axis by estimating the carotid-radial PWV (cr-PWV). While a number of studies have addressed these issues in adults, limited information is available on the respective features of cf-PWV and cr-PWV and on their modulating factors in children and adolescents at increased cardiovascular risk. METHODS: The mechanical properties of the predominantly elastic (aorta) and muscular (axillo-brachial-radial axis) arteries were evaluated in a pediatric population characterized by either elevated blood pressure (BP) or excess body weight, and the main factors affecting cf-PWV and cr-PWV values in these individuals were investigated. RESULTS: 443 children and adolescents (median age 11.5 years, 43.3% females) were enrolled; 25% had BP values >90th percentile and 81% were excess weight. The cf-PWV values were significantly lower than the cr-PWV values: median (Q1-Q3) = 4.8 m/s (4.3-5.5) and 5.8 m/s (5.0-6.5), respectively (p < 0.001). The pubertal development (p < 0.03), systolic BP and diastolic BP z-scores (p = 0.002), heart rate (p < 0.001), and waist-to-height ratio (p < 0.005) were significantly associated with cf-PWV values. No significant association was found between BMI z-score and cf-PWV. Predictors of high cf-PWV (>95th percentile) were the heart rate (OR 1.07, 95%CI 1.04-1.10, p < 0.001) and waist-to-height ratio (OR 1.06, 95%CI 1.0-1.13, p = 0.04). The variables significantly related with cr-PWV values were diastolic BP z-score (p = 0.001), heart rate (p < 0.01), and HOMA index (p < 0.02). No significant association was found between the cr-PWV and BMI z-score or waist-to-height ratio. CONCLUSIONS: Systolic and diastolic BP values and central obesity are associated with aortic stiffness in a population of children and adolescents at increased cardiovascular risk. In contrast, diastolic BP, heart rate, and levels of insulin resistance appear to be related to distensibility of the upper limb vascular district.