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Introduction: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side. Methods: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures. Results: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%). Conclusions: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk.

Background: Visit-to-visit blood pressure (BP) variability associates with an increased risk of cardiovascular events. We investigated the role of seasonal BP modifications on the magnitude of BP variability and its impact on cardiovascular risk. Methods: In 25 390 patients included in the ONTARGET and TRANSCEND trials, the on-treatment systolic (S) BP values obtained by five visits during the first two years of the trials were grouped according to the month in which they were obtained. SBP differences between winter and summer months were calculated for BP variability quintiles (Qs), as quantified by the coefficient of variation (CV) of on-treatment mean SBP from the five visits. The relationship of BP variability with the risk of cardiovascular events and mortality was assessed by the Cox regression model. Results: SBP was approximately 4 mmHg lower in summer than in winter regardless of confounders. Winter/summer SBP differences contributed significantly to each SBP-CV quintile. Increase of SBP-CV from Q1 to Q5 was associated with a progressive increase in the adjusted hazard ratio (HR) of the primary endpoint of the trials, i.e. morbid and fatal cardiovascular events. This association was even stronger after removal of the effect of seasonality from the calculation of SBP-CV. A similar trend was observed for secondary endpoints. Conclusions: Winter/summer SBP differences significantly contribute to visit-to-visit BP variability. However, this contribution does not participate in the adverse prognostic significance of visit-to-visit BP variations, which seems to be more evident after removal of the BP effects of seasonality from visit-to-visit BP variations.

Background: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long-term follow-up. Methods: Consecutive HCM patients with S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this observational study. Baseline, procedural and follow-up data were regularly collected. Efficacy and safety were compared with a cohort of HCM patients implanted with a tv-ICD. Results: Seventy patients (64% males) were implanted with S-ICD at 41 ± 15 years, whereas 168 patients with tv-ICD at 49 ± 16 years. For S-ICD patients, mean ESC SCD risk score was 4,5 ± 1.9%: 25 (40%) at low-risk, 17 (27%) at intermediate and 20 (33%) at high-risk. Patients were followed-up for 5.1 ± 2.3 years. Two patients (0.6 per 100-person-years, vs 0.4 per 100 person-years with tv-ICD, p = 0.45) received an appropriate shock on VF, 17 (24%) were diagnosed with de-novo AF. Inappropriate shocks occurred in 4 patients (1.2 per 100-person-years, vs 0.9 per 100 person-years with tv-ICD, p = 0.74), all before Smart-Pass algorithm implementation. Four patients experienced device-related adverse events (1.2 per 100-person-years, vs 1 per 100 person-years with tv-ICD, p = 0.35%). Conclusions: S-ICDs were often implanted in patients with an overall low-intermediate ESC SCD risk, reflecting both the inclusion of additional risk markers and a lower decision threshold. S-ICDs in HCM patients followed for over 5 years showed to be effective in conversion of VF and safe. Greater scrutiny may be required to avoid overtreatment in patients with milder risk profiles.

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 an-tihypertensive 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.

Background and aims: The discordance between QRS voltages on electrocardiogram (ECG) and left ventricle (LV) wall thickness (LVWT) on echocardiogram (echo) is a recognized red flag (RF) of amyloid cardiomyopathy (AC) and can be measured by specific indexes. No head-to-head comparison of different ECG/echo indexes among subjects with echocardiographic suspicion of AC has yet been undertaken. The study aimed at evaluating the performance and the incremental diagnostic value of different ECG/echo indexes in this subset of patients. Methods: Electrocardiograms of subjects with LV hypertrophy, preserved ejection fraction and ≥ 1 echocardiographic RF of AC participating in the AC-TIVE study, an Italian prospective multicenter study, were independently analyzed by two cardiologists. Low QRS voltages and 8 different ECG/echo indexes were evaluated. Cohort specific cut-offs were computed. Results: Among 170 patients, 55 (32 %) were diagnosed with AC. Combination of low QRS voltages with interventricular septum ≥ 1,6 cm was the most specific (specificity 100 %, positive predictive value 100 %) ECG/echo index, while the ratio between the sum of all QRS voltages and LVWT <7,8 was the most sensitive and accurate (sensitivity 94 %, negative predictive value 97 %, accuracy 82 %). When the latter index was added to a model using easily-accessible clinical variables, the diagnostic accuracy for AC greatly increased (AUC from 0,84 to 0,95; p = 0,007). Conclusions: Among patients with non-dilated hypertrophic ventricles with normal ejection fraction and echocardiographic RF of AC, easily-measurable ECG/echo indexes, mainly when added to few clinical variables, can help the physician orient second level investigations. External validation of the results is warranted.

Background: Air pollution and obstructive sleep apnea (OSA) are both linked with cardiovascular co-morbidities and share similar pathophysiological mechanisms. A causal association between the two has been postulated. However, the results of the studies on this topic are conflicting mainly because of the lack of adjustment for important confounders such as seasonality and temperature. We aimed to evaluate if such an association exists in a highly polluted area like Lombardy region (Italy) when accounting for all confounders. Methods: Data of adult patients seen at the Sleep Disorder Centre in Milan from 2010 to 2020 were analysed and the main polygraphic data were retrieved. Air pollutant concentrations of the following pollutants NO2, O3, PM2.5, and PM10 were collected through monitoring stations. Results: A total of 3493 patients were included: males (2358, 67.5%) mean age 60.1 (SD = 14.3) years, BMI 29.2 (6.2) kg/m2, mean AHI 16.5 (18.1) events/h. After adjusting for all confounders, in the multivariable analysis, the only associations that remained significant were long-term exposure to O3 with indexes of OSA severity (AHI and ODI) but only in spring. Furthermore, a positive association was seen between long-term exposure to PM10 and ODI but in springtime only. Conclusion: The findings of the current study does not support an association between fine particulate matter and OSA severity.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.

The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged <70 years, high BMI was associated with an increased risk of MACE, whereas among the older subjects it was associated with lower risk. Compared to the group with normal weight/healthy metabolic status, the metabolically healthy participants aged <70 years who were overweight/obese had an increased risk of MACE with an adjusted hazard ratio of 3.81 (95% CI, 1.34-10.85, p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07-6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.

Background: We aimed to determine the influence of coronavirus disease 2019 (COVID-19) pandemic on blood pressure (BP) control assessed by ambulatory blood pressure monitoring (ABPM). Methods: Office BP and ABPM data from two visits conducted within a 9-15 months interval were collected from patients treated for hypertension. In the prepandemic group, both visits took place before, while in the pandemic group, Visit-1 was done before and Visit-2 during the pandemic period. Results: Of 1811 collected patients 191 were excluded because they did not meet the required ABPM time frames. Thus, the study comprised 704 patients from the pandemic and 916 from the prepandemic group. Groups did not differ in sex, age, duration of hypertension, frequency of first line antihypertensive drug use and mean 24 h BP on Visit-1. The prevalence of sustained uncontrolled hypertension was similar in both groups. On Visit-2 mean 24 h BP, daytime and nighttime systolic BP and diastolic BP were higher in the pandemic compared to the prepandemic group (P < 0.034). The prevalence of sustained uncontrolled hypertension on Visit-2 was higher in the pandemic than in the prepandemic group [0.29 (95% confidence interval (95% CI): 0.26-0.33) vs. 0.25 (95% CI: 0.22-0.28), P < 0.037]. In multivariable adjusted analyses a significant difference in BP visit-to-visit change was observed, with a more profound decline in BP between visits in the prepandemic group. Conclusions: This study using ABPM indicates a negative impact of the COVID-19 pandemic on BP control. It emphasizes the need of developing strategies to maintain BP control during a pandemic such as the one induced by COVID-19.

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.

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

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 and normotensive seated office BP. Whether antihypertensive treatment should be administered in the latter is unknown. Hypertensive patients with ERTS/OHT should be managed as any other hypertensive patient. Standardized standing BP measurement should be implemented in future epidemiological and interventional studies.

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

Objective:Ambulatory blood pressure monitoring (ABPM) plays an important role in the diagnosis of hypertension. However, methodological factors and the measurement conditions affect the results and may lead to incorrect classification of the patient. We performed a pilot study to evaluate the impact of oscillometric measurement artefacts on ABPM-derived variables.Methods:Four classes of artefacts have been detected: motor activity artefacts, cuff errors, cardiovascular arousals, and arrhythmias. The data consisted of uncorrected measurements (all data), corrected measurements (all artefact free data), and artefact affected data.Results:A total of 30 individuals (9 female/21 male), aged between 36 and 86 years, mean: 65.5 (standard deviation: 9.5) were included in the study. The average blood pressure (BP) was higher in artefacts-affected measurements compared the artefact-free measurements both for systolic (4.6 mmHg) and diastolic (1.3 mmHg) measurements. Further, artefact-affected systolic BP (SBP) was 6.4 mmHg higher than artefact-free measurements during daytime. Nocturnal measurements showed no artefact-depended differences. Individual comparisons yielded that 23% of the participants crossed the threshold for BP classification for either 24-h, daytime or nocturnal hypertension when comparing uncorrected and artefact-free measurements. Dipping classification changed within 24% of participants. BP variability was 21 and 12% higher for SPB and DBP, respectively, during daytime. These differences were even higher (27% for SBP and 21% for DPB) during night-time.Conclusion:The study reveals that measurement artefacts are frequently present during cuff-based ABPM and do relevantly affect measurement outcome. Exclusion of measurement artefacts is a promising approach to improving cuff-based ABPM accuracy.

Hypertension is the most common and preventable risk factor for cardiovascular disease (CVD), accounting for 20% of deaths worldwide. However, 2/3 of people with hypertension are undiagnosed, untreated, or under treated. A multi-pronged approach is needed to improve hypertension management. Elevated blood pressure (BP) in childhood is a predictor of hypertension and CVD in adulthood; therefore, screening and education programmes should start early and continue throughout the lifespan. Home BP monitoring can be used to engage patients and improve BP control rates. Progress in imaging technology allows for the detection of preclinical disease, which may help identify patients who are at greatest risk of CV events. There is a need to optimize the use of current BP control strategies including lifestyle modifications, antihypertensive agents, and devices. Reducing the complexity of pharmacological therapy using single-pill combinations can improve patient adherence and BP control and may reduce physician inertia. Other strategies that can improve patient adherence include education and reassurance to address misconceptions, engaging patients in management decisions, and using digital tools. Strategies to improve physician therapeutic inertia, such as reminders, education, physician-peer visits, and task-sharing may improve BP control rates. Digital health technologies, such as telemonitoring, wearables, and other mobile health platforms, are becoming frequently adopted tools in hypertension management, particularly those that have undergone regulatory approval. Finally, to fight the consequences of hypertension on a global scale, healthcare system approaches to cardiovascular risk factor management are needed. Government policies should promote routine BP screening, salt-, sugar-, and alcohol reduction programmes, encourage physical activity, and target obesity control.[GRAPHICS].

Introduction Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. Methods and analysis The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. Ethics and dissemination This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's

Objective:To develop scientific consensus recommendations for the optimal design and functions of different types of blood pressure (BP) measuring devices used in clinical practice for the detection, management, and long-term follow-up of hypertension.Methods:A scientific consensus meeting was performed by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability and STRIDE BP (Science and Technology for Regional Innovation and Development in Europe) during the 2022 Scientific Meeting of the ESH in Athens, Greece. Manufacturers were also invited to provide their feedback on BP device design and development. Thirty-one international experts in clinical hypertension and BP monitoring contributed to the development of consensus recommendations on the optimal design of BP devices.Statement:International consensus was reached on the requirements for the design and features of five types of BP monitors, including office (or clinic) BP monitors, ambulatory BP monitors, home BP monitors, home BP telemonitors, and kiosk BP monitors for public spaces. For each device type "essential" requirements (must have), and "optional" ones (may have) are presented, as well as additional comments on the optimal device design and features.Conclusions:These consensus recommendations aim at providing manufacturers of BP devices with the requirements that are considered mandatory, or optional, by clinical experts involved in the detection and management of hypertension. They are also directed to administrative healthcare personnel involved in the provision and purchase of BP devices so that they can recommend the most appropriate ones.

Unlabelled: A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study. Aim: of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death. Methods: Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men. Results: A significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P< 0.001 and women: beta 0,069, F 4.36, P<0.001. During follow-up 319 CV deaths occurred. Kaplan-Meier curves showed a significantly poorer survival rate in subjects with higher SUA (> 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P<0.0001). At multivariate Cox regression analysis in women LVH alone and the combination of higher SUA and LVH but not hyperuricemia alone, were associated with a higher risk of CV death, while in men hyperuricemia without LVH, LVH without hyperuricemia and their combination were all associated with a higher incidence of CV death. Conclusions: Our findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women.

Background: COVID-19 has been associated with a higher risk of post-acute complications. Our aim was to analyze and compare post-acute cardiovascular complications of COVID-19 survivors of the first and second/third pandemic waves in Lombardy, in both hospitalized and non-hospitalized COVID-19 patients. Methods and results: We included adults aged ≥40 years infected during the first and second/third waves of COVID-19 pandemic. The follow-up initiated 30 days after COVID-19 diagnosis and continued up to 9 months. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the post-acute cardiovascular outcomes were calculated against an inverse probability treatment weighted control group. Subgroup analysis were performed by age classes, sex, previous cardiovascular disease and stratified by COVID-19 hospitalization status to explore the impact of COVID-19 severity on outcomes. Compared to the control group, COVID-19 patients had an increased risk of hospitalization for any cardiovascular complications (HR 1st wave 1.53 95% CI: 1.38–1.69; HR 2nd/3rd wave 1.25 95% CI: 1.19–1.31) and for individual cardiovascular outcomes, although HRs were higher in COVID-19 group from the 1st pandemic wave. The results were confirmed in the subgroup analyses. Of note, the risk for any cardiovascular disease was also evident even among individuals who were not hospitalized during the acute phase of the infection. Conclusion: Our results provide evidence that COVID-19 is a risk factor for post-acute cardiovascular complications among different pandemic waves regardless of COVID-19 severity, age, sex and a history of cardiovascular diseases. Care strategies of people with COVID-19 should include cardiac monitoring.

Background: Echocardiographic surrogates of right ventricle–to–pulmonary artery (RV-PA) coupling have been reported to be associated with outcomes in patients with secondary tricuspid regurgitation (STR). However, pulmonary artery systolic pressure (PASP) is difficult to estimate using echocardiography in patients with severe STR. The aim of the present study was to evaluate the predictive power of a surrogate of RV-PA coupling obtained using right ventricular (RV) volumes measured on three-dimensional echocardiography. Methods: One hundred eight patients (mean age, 73 ± 13 years; 61% women) with moderate or severe STR were included. Results: At a median follow-up of 24 months (interquartile range, 2-48 months), 72 patients (40%) had reached the composite end point of death of any cause and heart failure hospitalization. RV-PA coupling was computed as the ratio between RV forward stroke volume (SV) (i.e., RV SV − regurgitant volume) and RV end-systolic volume (ESV). RV forward SV/ESV was significantly more related to the composite end point than RV ejection fraction (area under the curve, 0.85 [95% CI, 0.78-0.93] vs 0.73 [95% CI, 0.64-0.83], respectively; P = .03). A value of 0.40 was found to best correlate with outcome. On multivariate Cox regression, RV forward SV/ESV, tricuspid annular plane systolic excursion/PASP, and RV free wall longitudinal strain/PASP were all independently associated with the occurrence of the composite end point when added to a group of parameters including STR severity (severe vs moderate), atrial fibrillation, pulmonary arterial hypertension, right atrial volume, RV end-diastolic volume, and RV free wall longitudinal strain. RV forward SV/ESV < 0.40 (HR, 3.36; 95% CI, 1.49-7.56; P < .01) carried higher related risk than RV free wall longitudinal strain/PASP < −0.42%/mm Hg (HR, 3.1; 95% CI, 1.26-7.84; P = .01) and tricuspid annular plane systolic excursion/PASP < 0.36 mm/mm Hg (HR, 2.69; 95% CI, 1.29-5.58; P = .01). RV eject

Aims: The HFA-PEFF algorithm (Heart Failure Association-Pre-test assessment, Echocardiography and natriuretic peptide score, Functional testing in cases of uncertainty, Final aetiology) is a three-step algorithm to diagnose heart failure with preserved ejection fraction (HFpEF). It provides a three-level likelihood of HFpEF: low (score < 2), intermediate (score 2–4), or high (score > 4). HFpEF may be confirmed in individuals with a score > 4 (rule-in approach). The second step of the algorithm is based on echocardiographic features and natriuretic peptide levels. The third step implements diastolic stress echocardiography (DSE) for controversial diagnostic cases. We sought to validate the three-step HFA-PEFF algorithm against a haemodynamic diagnosis of HFpEF based on rest and exercise right heart catheterization (RHC). Methods and results: Seventy-three individuals with exertional dyspnoea underwent a full diagnostic work-up following the HFA-PEFF algorithm, including DSE and rest/exercise RHC. The association between the HFA-PEFF score and a haemodynamic diagnosis of HFpEF, as well as the diagnostic performance of the HFA-PEFF algorithm vs. RHC, was assessed. The diagnostic performance of left atrial (LA) strain < 24.5% and LA strain/E/E′ < 3% was also assessed. The probability of HFpEF was low/intermediate/high in 8%/52%/40% of individuals at the second step of the HFA-PEFF algorithm and 8%/49%/43% at the third step. After RHC, 89% of patients were diagnosed as HFpEF and 11% as non-cardiac dyspnoea. The HFA-PEFF score resulted associated with the invasive haemodynamic diagnosis of HFpEF (P < 0.001). Sensitivity and specificity of the HFA-PEFF score for the invasive haemodynamic diagnosis of HFpEF were 45% and 100% for the second step of the algorithm and 46% and 88% for the third step of the algorithm. Neither age, sex, body mass index, obesity, chronic obstructive pulmonary disease, or paroxysmal atrial fibrillation influenced the performance o

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, a

Background: Electrical stimulation has recently been introduced to treat patients with Obstructive sleep apnoea There are, however, few data on the effects of transcutaneous submental electrical stimulation (TES) on the cardiovascular system. We studied the effect of TES on cardiorespiratory variables in healthy volunteers during head-down-tilt (HDT) induced baroreceptor loading. Method: Cardiorespiratory parameters (blood pressure, heart rate, respiratory rate, tidal volume, airflow/minute ventilation, oxygen saturation, and end-tidal CO2/O2 concentration) were recorded seated, supine, and during head-down-tilt (50) under normoxic, hypercapnic (FiCO2 5%) and poikilocapnic hypoxic (FiO2 12%) conditions. Blood pressure (BP) was measured non-invasively and continuously (Finapres). Gas conditions were applied in random order. All participants were studied twice on different days, once without and once with TES. Results: We studied 13 healthy subjects (age 29 (12) years, six female, body mass index (BMI) 23.23 (1.6) kg·m−2). A three-way ANOVA indicated that BP decreased significantly with TES (systolic: p = 4.93E-06, diastolic: p = 3.48E-09, mean: p = 3.88E-08). Change in gas condition (systolic: p = 0.0402, diastolic: p = 0.0033, mean: p = 0.0034) and different postures (systolic: 8.49E-08, diastolic: p = 6.91E-04, mean: p = 5.47E-05) similarly impacted on BP control. When tested for interaction, there were no significant associations between the three different factors electrical stimulation, gas condition, or posture, except for an effect on minute ventilation (gas condition/posture p = 0.0369). Conclusion: Transcutaneous electrical stimulation has a substantial impact on the blood pressure. Similarly, postural changes and variations in inspired gas impact on blood pressure control. Finally, there was an interaction between posture and inspired gases that affects minute ventilation. These observations have implications on our understanding of integrated cardiorespira

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 1.33 mU/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 0.064 mmol/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.

Blood pressure is not a static parameter, but rather undergoes continuous fluctuations over time, as a result of the interaction between environmental and behavioural factors on one side and intrinsic cardiovascular regulatory mechanisms on the other side. Increased blood pressure variability (BPV) may indicate an impaired cardiovascular regulation and may represent a cardiovascular risk factor itself, having been associated with increased all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia incidence. Nonetheless, BPV was considered only a research issue in previous hypertension management guidelines, because the available evidence on its clinical relevance presents several gaps and is based on heterogeneous studies with limited standardization of methods for BPV assessment.The aim of this position paper, with contributions from members of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and from a number of international experts, is to summarize the available evidence in the field of BPV assessment methodology and clinical applications and to provide practical indications on how to measure and interpret BPV in research and clinical settings based on currently available data. Pending issues and clinical and methodological recommendations supported by available evidence are also reported. The information provided by this paper should contribute to a better standardization of future studies on BPV, but should also provide clinicians with some indications on how BPV can be managed based on currently available data.

Introduction: Variable D-dimer trends during hospitalization reportedly result in distinct in-hospital mortality. In this multinational case series from the first and second waves, we show the universality of such D-dimer trends. Methods: We reviewed 405 patients with COVID-19 during the first wave admitted to three institutions in the United States, Italy, and Colombia, and 111 patients admitted to the U.S. site during the second wave and 55 patients during the third wave. D-dimer was serially followed during hospitalization. Results: During the first wave, 66 (15%) patients had a persistently-low pattern, 33 (8%) had early-peaking, 70 (16%) had mid-peaking, 94 (22%) had fluctuating, 30 (7%) had late-peaking, and 112 (26%) had a persistently-high pattern. During the second and third waves, similar patterns were observed. D-dimer patterns were significantly different in terms of in-hospital mortality similarly in all waves. Patterns were then classified into low-risk patterns (persistently-low and early-peaking), where no deaths were observed in both waves, high-risk patterns (mid-peaking and fluctuating), and malignant patterns (late-peaking and persistently-high). Overall, D-dimer trends were associated with an increased risk for in-hospital mortality in the first wave (overall: HR: 1.73) and stayed the same during the second (HR: 1.67, p < 0.001) and the third (HR: 4.4, p = 0.001) waves. Conclusion: D-dimer behavior during COVID-19 hospitalization yielded universal categories with distinct mortality risks that persisted throughout all studied waves of infection. Monitoring D-dimer behavior may be useful in the management of these patients.

Background: Right heart failure (RHF) is associated with a dismal prognosis in patients with pulmonary hypertension (PH). Exercise right heart catheterization may unmask right heart maladaptation as a sign of RHF. We sought to (1) define the normal limits of right atrial pressure (RAP) increase during exercise; (2) describe the right heart adaptation to exercise in PH owing to heart failure with preserved ejection fraction (PH-HFpEF) and in pulmonary arterial hypertension (PAH); and (3) identify the factors associated with right heart maladaptation during exercise. Methods and results: We analyzed rest and exercise right heart catheterization from patients with PH-HFpEF and PAH. Right heart adaptation was described by absolute or cardiac output (CO)-normalized changes of RAP during exercise. Individuals with noncardiac dyspnea (NCD) served to define abnormal RAP responses (>97.5th percentile). Thirty patients with PH-HFpEF, 30 patients with PAH, and 21 patients with NCD were included. PH-HFpEF were older than PAH, with more cardiovascular comorbidities, and a higher prevalence of severe tricuspid regurgitation (P < .05). The upper limit of normal for peak RAP and RAP/CO slope in NCD were >12 mm Hg and ≥1.30 mm Hg/L/min, respectively. PH-HFpEF had higher peak RAP and RAP/CO slope than PAH (20 mm Hg [16-24 mm Hg] vs 12 mm Hg [9-19 mm Hg] and 3.47 mm Hg/L/min [2.02-6.19 mm Hg/L/min] vs 1.90 mm Hg/L/min [1.01-4.29 mm Hg/L/min], P < .05). A higher proportion of PH-HFpEF had RAP/CO slope and peak RAP above normal (P < .001). Estimated stressed blood volume at peak exercise was higher in PH-HFpEF than PAH (P < .05). In the whole PH cohort, the RAP/CO slope was associated with age, the rate of increase in estimated stressed blood volume during exercise, severe tricuspid regurgitation, and right atrial dilation. Conclusions: Patients with PH-HFpEF display a steeper increase of RAP during exercise than those

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 (R2 = 0.12 and 0.19, respectively). Conclusions: Severe STR complicating HFpEF impairs SV and CO reserve, leading to pulmonary vascular de-recruitment and relative

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.

Sleep-disordered breathing (SDB) comprises different diseases characterized by abnormal respiratory patterns during sleep including obstructive sleep apnea. SDB prevalence and impact in patients with chronic respiratory infections have been only marginally studied. The purpose of this narrative review is to report the prevalence and impact of SDB in chronic respiratory infections, including cystic fibrosis (CF), bronchiectasis and mycobacterial infections, and explore the possible pathophysiological mechanisms. Common pathophysiological mechanisms, underlying SDB onset in all chronic respiratory infections, include inflammation, which plays a central role, chronic nocturnal cough and pain, excessive production of mucous plugs, presence of obstructive and/or restrictive ventilatory impairment, upper airways involvement, and comorbidities, such as alteration of nutritional status. SDB may affect about 50% of patients with bronchiectasis. The severity of the disease, e.g., patients colonized with P. aeruginosa and frequent exacerbators, as well as comorbidities, such as chronic obstructive pulmonary disease and primary ciliary dyskinesia, may impact SDB onset. SDB may also frequently complicate the clinical course of both children and adults with CF, impacting the quality of life and disease prognosis, suggesting that their routine assessment should be incorporated into the clinical evaluation of patients from the first stages of the disease regardless of suggestive symptoms, in order to avoid late diagnosis. Finally, although the prevalence of SDB in patients with mycobacterial infections is uncertain, extrapulmonary manifestations, particularly nasopharyngeal locations, and concomitant symptoms, such as body pain and depression, may act as atypical predisposing factors for their development.

The author Lia Crotti would like to integrate her affiliation as follows, since in the original version of the article the university affiliation was not present. Affiliations. b Department of Cardiology, IRCCS Istituto Auxologico Italiano, Department of Cardiovascular, Neural and Metabolic Sciences, Ospedale San Luca, Milan, Italy. f Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy. The authors would like to apologise for any inconvenience caused.