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Objective: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA.Methods: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively.Results: The [HCO3-] level was normal in most patients (average 24.0 +/- 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030

A 70–year–old woman was admitted to our Intensive Care Unit (ICU) with high levels Hs–TnT. Coronaries were normal and ventriculography was suggestive for Takotsubo Syndrome (TS). In the acute phase she developed a cardiogenic shock and transthoracic echocardiography (TTE) showed a dilated left ventricle (LV) with iperkinesia of basal segments and biventricular apex and mid –ventricular akinesia, with a severely reduced left ventricular ejection fraction (LVEF 20%). Seven days after admission to Cardiac Rehabilitation Unit, a TTE showed LV apical hypertrophy (max thickness 18 mm), hypokinesia of hypertrophic segments, hypercontractility of basal segments and LVEF 55%. These features could have been suggestive for a coexisting apical hypertrophic cardiomyopathy (HCM). The EKG showed T wave inversions in precordial and inferior leads, not present at admission, this observation being against the presence of a pre–existing unknown HCM. Cardiac Magnetic Resonance (CMR) showed T1 and T2 mapping imagines for oedema in LV infero–lateral, basal segments and apical region, a subepicardial stria of late gadolinium enhancement in infero–lateral basal segment. These patterns were reported as suggestive for myocarditis rather than TS. Recent infectious or autoimmune diseases were excluded. Further TTE showed reversed LV parameters, normal kinesis of all segments, LVEF 66%, with a persistence of negative T waves at EKG. Discussion Our patient developed a classical TS with LV apical ballooning and hyperkinesia of basal segments with uncommon right ventricular hypokinesia. A peculiar finding was the transient apical LV thickness that was seen through TTE, mimicking an apical hypertrophic cardiomyopathy. Such a finding has already been described in few case reports; however, the nature and the physiopathology of that apical thickness was never proved. Through CMR we noted that, in the same region where TTE detected apical hypertrophy, there was a consistent amount of oedema which could be the reason of pseudo–hypertrophy findings. Our experience confirms the importance of integrating CMR in the diagnostic algorithm as already supported in consensus statements. In our case CMR played a key–role in the exclusion of a coexisting apical hypertrophic cardiomyopathy.

A 71–year–old patient with a history of prostatic cancer, recently underwent CABG and mitral valve replacement and during cardiac rehabilitation (CR) was diagnosed with a cryptogenic stroke while on treatment with oral anticoagulant and antiaggregants. It is worth mentioning that during hospitalization he suffered several feverish episodes without major organ involvement with the only exception of the one related to the chest scar infection. He was admitted to CR department with high fever (38.5 C) and hemocultures were positive for Staphylococcus epidermidis which was also isolated from the chest scar. The transthoracic echocardiogram executed at the admission did not show any pathological alteration. After 5 days of antibiotic therapy and optimized medical therapy, he had an ischemic stroke. NIHSS score was initially 10. Acute presentation of ischemic stroke was peculiar: he had left hemiparesis with Babinski sign, but a concomitant Broca‘s aphasia, thus suggesting multiple areas of cerebral ischemia. He was evaluated with a basal computerized tomography (CT) scan which didn’t show any sign of ischemic stroke and NIHSS score completely reversed after 30 minutes to 0: this was more suggestive for a transient ischemic attack rather than ischemic stroke but despite the negative CT scan, the subsequent cerebral magnetic resonance imaging showed ischemic signs localized in different vascular territories. Supra–aortic vessels were normal. Therefore, we performed a transesophageal echocardiography (TEE) which showed a peculiar vegetation over the mitral valve, presenting more as a filament rather than typical vegetation. Despite the absence of fever, negative PCR, negative procalcitonine and white blood cells within the normal limits, we performed hemocultures and Staphylococcus haemolyticus was isolated. Antibiotic therapy was immediately started; however, after three weeks of appropriate therapy the TEE exam showed an evolution of the valve’s lesion which required surgical revision. Conclusion This case highlights how ischemic stroke related to multiple ischemic foci may be the only sign of an underlying endocarditis that caused septic embolization. Indeed, the patient was completely asymptomatic, did not have fever, inflammatory markers were negative and only clinical investigations to understand the nature of his stroke allowed us to make the diagnosis of endocarditis.

Background Diagnostic criteria for ambulatory blood pressure monitoring (ABPM) in patients with suspected reflex syncope are lacking. Purpose We hypothesized that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM than control subjects and we aimed to define the SBP cut-off values that allow identification of patients with hypotensive susceptibility. Methods We compared ABPM data from reflex syncope patients and controls, matched by average 24-hour SBP, age, sex and hypertension. Patients with constitutional hypotension, orthostatic hypotension, predominant cardioinhibition or competing causes of syncope were excluded. Daytime and night-time SBP drops ( Results In the Derivation cohort, daytime SBP drops were significantly more common in 158 syncope patients than 329 controls. One or more daytime drop Conclusion SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope. Funding Acknowledgement Type of funding sources: None.

Background Exercise right heart catheterization (RHC) is considered the gold-standard test to diagnose heart failure with preserved ejection fraction (HFpEF). However, exercise RHC is an insufficiently standardized technique, and current hemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise hemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects. Methods We performed a systematic literature review following the PRISMA statement until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all hemodynamic variables were evaluated, stratified according to body position (supine/upright exercise). The PAWP / cardiac output (CO) slope during exercise was extrapolated. Results Twenty-seven studies were identified, providing data for 2180 HFpEF patients and 682 controls. At peak exercise, HfpEF cohorts showed a summary estimate of PAWP at peak which was twice as high as compared with control cohorts (30; 95% CI: 29–31 mmHg and 16; 95% CI: 15–17 mmHg, respectively), as well as of delta PAWP (15; 95% CI: 14–16 mmHg and 7; 95% CI: 6–8 mmHg, respectively), and of right atrial pressure (18; 95% CI: 16–19 mmHg and 8; 95% CI: 8–9 mmHg, respectively). These differences persisted after adjustment for age, sex, body mass index, body position. Additionally, summary estimates of PAWP at peak performed during supine exercise was slightly higher than that obtained in upright position only for HFpEF cohorts (supine position: 31; 95% CI: 30–32 mmHg vs upright position; 26; 95% CI: 25–27 mmHg, respectively, p-value Conclusions Despite methodological heterogeneity across centers, the hemodynamic profile of HFpEF patients is consistent across studies and characterized by a higher left and right filling pressure at rest compared with controls, enhanced by physical exercise. A PAWP/CO slope cut-off >2 mmHg/L/min seems to retain validity also for studies conducted in the supine position, potentially overcoming the need of different supine and upright PAWP cut-offs. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Background Obstructive sleep apnoea (OSA) is a well-known cardiovascular risk factor and is frequently associated with hypertension. The treatment of OSA with continuous positive airway pressure (CPAP) can resolve apnoeas, hypoxia, and sympathetic hyperactivation. Meta-analyses of randomised controlled trials (RCTs) show that CPAP treatment modestly reduces blood pressure (BP) with a pronounced heterogeneity among different OSA patient subgroups. Purpose To study the effects of CPAP treatment on BP changes, and to identify predictors of BP response to CPAP through analysis of individual patient data from published RCTs. Methods Study groups who had published RCTs on the effect of CPAP therapy on BP in OSA were invited to share the individual patient data (i.e. BP values, history of hypertension and antihypertensive drugs use). The outcomes of interest were the group-difference (BP at follow-up – BP at baseline) in office and out-of-office BP. Data analysis was performed with a one-step approach using a linear regression model, with treatment as covariate, including a random effect. An additional analysis was performed by stratifying patients in three subgroups: normotension, controlled hypertension and uncontrolled hypertension, based on BP at baseline, history of hypertension or treatment with antihypertensive drugs. Lastly, we evaluated the determinants of CPAP associated BP changes. Results Individual patient data from 34 parallel-group RCTs (n=7,456, 72% males, body mass index, BMI 31.9±14.8 kg/m2, age 58.6±10.9 years, apnoea-hypopnoea index, AHI 35.5±20.6 /hour) were analysed. The overall CPAP effect was larger for 24-BP compared to office BP measurements (Table 1), the highest reductions being observed for nocturnal BP. The stratified analysis showed a consistent BP lowering effect in the group of patients with uncontrolled hypertension whereas there was no significant BP change in those with controlled hypertension or in normotensives (figure 1). Higher BP levels at baseline and history of hypertension were independent predictors of BP reduction by CPAP for office and 24-BP measurements. Younger age and more severe nocturnal oxygen desaturations predicted a larger treatment effect on office BP only. Conclusions BP response to CPAP in OSA patients varies in different patient groups as a function of baseline BP, the greatest reduction being observed in younger patients with uncontrolled BP. Thus, our individual patient data meta-analysis indicates that younger patients with uncontrolled hypertension and more severe nocturnal oxygen desaturations measured by minimum SpO2 are likely to benefit the most from CPAP treatment in terms of BP reduction. Funding Acknowledgement Type of funding sources: None.

Background Left ventricular end-diastolic pressure (LVEDP) is the gold-standard for the assessment of LV filling pressure. For practical reasons, pulmonary artery wedge pressure (PAWP) is used as a surrogate for LVEDP. However, the interposition of the left atrium (LA) may account discrepancies between LVEDP and PAWP. The imprecision of both end-diastolic (or mid-A) and mean PAWP estimates for LVEDP has been widely described for cardiac catheterization at rest. PAWP measurement during exercise has been advocated to discriminate heart failure with preserved ejection fraction (HFpEF) from non-cardiac dyspnea, with an end-expiratory pathologic threshold ≥25 mmHg. However, a formal comparison of PAWP (either mid-A or mean PAWP) vs LVEDP during exercise has never been performed. Aim To compare LVEDP and PAWP during exercise. Methods We retrospectively analyzed consecutive patients with unexplained dyspnea and a normal LV ejection fraction, who had a clinical indication of right and left heart catheterization at rest and during exercise to assess unexplained dyspnea. Patients with mitral regurgitation ≥ moderate were excluded. Hemodynamic measurements were always taken at end-expiration. Results Forty-six consecutive patients were included in the analysis (80% with a peak mean PAWP ≥25 mmHg). We found a good correlation between both mid-A and mean PAWP on one side, and LVEDP on the other side (R2>0.55). At peak exercise, mid-A PAWP had no bias as compared with LVEDP, while mean PAWP slightly overestimated LVEDP by 1–2 mmHg. However, confidence intervals were quite large (Figure 1), suggesting imprecision of PAWP estimates for LVEDP in the individual patient. A disagreement between mean PAWP and LVEDP, using a threshold of ≥25 mmHg for both variables at peak exercise, was found in 11% of patients. In 4% of them, mean PAWP was ≥25 but LVEDP 2 mmHg/L/min, as an alternative parameter suggesting HFpEF. Conclusions In patients with unexplained exertional breathlessness, both mid-A and mean PAWP showed good correlation with LVEDP during exercise with minimal average bias, but their ability to estimate LVEDP was burdened by a relevant imprecision. Therefore, when in these patients peak PAWP is Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Background Although echocardiographic surrogates of right ventricular -arterial coupling (RVAC) have been reported to be associated with outcome in patients with moderate or severe secondary tricuspid regurgitation (STR), pulmonary artery systolic pressure (SPAP) is difficult to be estimated using echocardiography in patients with severe STR. Purpose Accordingly, we evaluated the predictive power of indexes of RVAC obtained using RV volumes measured using three-dimensional echocardiography (3DE). Methods We prospectively enrolled 180 patients with moderate or severe STR and complete two-dimensional, Doppler and 3DE data. The composite endpoint of death for any cause and heart failure hospitalization was used as primary outcome. Results After a median follow up of 24 months (IQR: 2–48), 72 patients (40%) reached the primary endpoint. Most of the echocardiographic parameters of RV function were associated with outcomes. Among the different parameters of RVAC, the receiver operating curve (ROC) analysis selected the ratio between (RV stroke volume [SV]-RegVol)/ RV End-systolic volume (ESV) (i.e. the RV forward SV/ESV) as the best predictor of the combined endpoint (AUC 0.80 [IC 95% 0.73–087]), with a threshold value of 0.49. Event-free survival of patients with RV forward SV/ESV higher and lower 0.49 has been performed (Figure 1). Multivariable Cox proportional hazards models were constructed (Figure 2). Adding sequentially the 3D-RVEF, TAPSE/SPAP and the forward RV SV/RV ESV on top of a basal model made of TR severity, New York Heart Association (NYHA) functional class and tricuspid anulus plane systolic excursion (TAPSE), the χ2 of the model increased from 40 to 43 (p=0.13) by adding 3D RVEF, from 43 to 46 (p=0.04) by adding TAPSE/SPAP, and from 46 to 51 (p=0.02) by adding RV forward SV/ESV. Severe TR (HR 3.53 [CI 95%: 1.84–6.78], p Conclusions The RV forward SV/ESV is an index of RVAC obtained by 3DE which is independent from SPAP and it is strongly associated with the occurrence of death or heart failure hospitalization in patients with STR. Funding Acknowledgement Type of funding sources: None.

Background Pulmonary hypertension (PH) is associated with a poor prognosis in patients with left heart disease (LHD). Several hemodynamic variables have been shown to predict outcome, including pulmonary vascular resistance (PVR), pulmonary artery compliance (PAC), and the diastolic pressure gradient (DPG). We sought to provide an updated analysis on the association of these variables with prognosis in PH-LHD. Methods We performed a systematic literature review including studies reporting association measurements between DPG and/or PVR and/or PAC and death in PH-LHD patients. These hemodynamic variables were extracted to estimate the pooled hazard ratio (HR) of adverse outcome for each one, and cumulative meta-analysis was performed to investigate temporal trends in the effects reported in the literature as well as the impact of sample size. Results 17 articles were identified, including 9716 patients with LHD, heterogeneous in terms of age, sex, and etiology of cardiac disease. In this large population, we found that PVR (HR, 1.09; 95% CI: 1.06–1.12), DPG (HR, 1.02; 95% CI: 1.01–1.02) and PAC (HR, 0.73; 95% CI: 0.76–0.81) were associated with an increased risk of adverse outcome, albeit with a less solid performance of DPG (Figure 1). 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 (either heart failure with preserved or reduced left ventricular ejection fraction, or valvular heart disease). Furthermore, cumulative metanalysis indicated that these results are consistently stable since 2018 (Figure 2). Conclusions Despite the heterogeneity of PH-LHD group and the intrinsic limitations of each variable, PVR, DPG, and PAC have an established prognostic value in PH-LHD. The strongest correlation with PVR and PAC supports their use in defining disease severity and identifying a subgroup of patients at higher risk of adverse outcome. We believe that these results are consistent through the years and unlikely to change with the addition of further studies. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Background Right heart failure (RHF) represents the final step of distinct diseases, such as pulmonary arterial hypertension (PAH) and pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF). RHF may be defined by the inability of the heart to maintain a normal cardiac output (CO) or to do so at the expense of high right atrial pressure (RAP), at rest or during exercise. However, exercise hemodynamic features suggestive of RHF, as well as their determinants, have still not been defined. Aim We sought to i. define the limits of normal of RAP increase during exercise; ii. describe the behavior of RAP during exercise in PAH and in PH-HFpEF, and its relation to right heart afterload and preload. Methods We retrospectively analyzed data from consecutive patients referred for suspicion of PH, who underwent both a resting and exercise right heart catheterization at two centers with identical methodology. We included patients with PH-HFpEF or PAH. Right heart adaptation to exercise was described either using absolute or CO-normalized RAP increase during exercise (RAP/CO slope), this latter representing the inverse of the Frank-Starling reserve. A control cohort of subjects with normal hemodynamics at rest and during exercise served to define abnormal increase in RAP, i.e. values of RAP and RAP/CO slope > mean ± 2 standard deviation of controls. Estimated stressed blood volume (eSBV), as a measure of effective preload, was computed using a commercially-available software. Results 80 patients were included in the analysis, of which 29 were PH-HFpEF, 30 PAH and 21 controls. HFpEF patients were older than PAH patients and with a higher burden of cardiovascular comorbidities (p Mean pulmonary artery pressure (PAP), pulmonary vascular resistance (PVR) and total vascular resistance (TPR) were higher in PAH than in PH-HFpEF both at rest and during exercise (p On average, PH-HFpEF had higher resting and peak RAP than PAH, as well as higher RAP/CO slope (Figure 1). The upper limit of normal of exercise RAP and of RAP/CO slope, as determined in control subject, was 12 mmHg and 1.55 mmHg/L/min. A higher rate of HFpEF patients, compared with PAH, had a RAP/CO slope and a peak RAP above normal limits (78% and 91% of PH-HFpEF vs 47% and 44% of PAH, respectively, p RAP/CO slope in the whole cohort was associated with eSBV but not with right ventricular afterload measures (PAP, TPR, PVR). Conclusions PH-HFpEF display more frequently a steeper increase of RAP during exercise than PAH patients in spite of similar CO, suggesting a more exhausted Frank-Starling reserve. The steep RAP increase during exercise seems to reflect a dysfunctional preload rather than an afterload-mismatch. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Case Presentation A 61–years–old woman was referred to our center after her 33 years old daughter suffered a sudden cardiac death. Cardiovascular risk factors: dyslipidemia and family history of ischemic cardiomyopathy. Diagnostic and Therapeutic Work Up Patient’s ECG was normal. Holter ECG showed frequent ventricular extrasystoles (2000/die) isolated and not premature, with LBB morphology, associated with not sustained ventricular tachycardias with LLB and low axis morphology (HR mean 140–170 beats/min). Exercise Stress Test did not show a clear correlation between physical activity and arrhythmias. Beta blocker therapy was started and was only partially effective in reducing ventricular arrhythmias, and a loop recorder was implanted. In 2019 a cardiac MRI with adenosine was performed, showing a mild globular shaped left ventricle with a non–specific linear distribution of LGE in the middle septum. Genetic analysis for channelopathies and cardiomyopathies resulted negative. In the last advanced echocardiogram (2022) with 3D reconstruction and strain analyses, characteristics suspected for arrhythmic mitral valve prolapse (MAD and curling of inferolateral wall) were identified. Accordingly, it has been decided to perform a second cardiac MRI to better characterize the underlying cardiac condition and to define the appropriate risk stratification algorithm. Conclusions Arrhythmic mitral valve prolapse is defined by ventricular arrhythmias in the absence of other known causes and it is present in up to 13% of sudden cardiac deaths in female patients. According to the recent consensus document by EHRA, sudden cardiac death risk stratification is complex and based firstly on the evaluation of arrhythmic burden, and secondly on symptoms and additional risk factors (i.e. MAD, left ventricle disfunction, flap redundancy, LGE in specific areas and so on). This case shows the importance of advanced imaging techniques and multimodal approach in ventricular arrhythmias evaluation.

Congenital heart disease can be associated with pulmonary hypertension (PH) development and heart right remodelling. Nevertheless, the adaptation of the pulmonary circulation and of the right heart can be extremely heterogeneous, so that an accurate diagnostic work up may be advisable when an intracardiac shunt is suspected. Case Presentation A 53 years old woman, with no relevant clinical history and asymptomatic, was incidentally found to have clinical, ECG and echocardiographic signs of PH, and was referred to our Center. Diagnostic and Therapeutic Work Up Echocardiography showed: normal left ventricle (LV 3D volumes 88/35 ml), mild left atrial dilatation (39 ml/m2); severe right chambers dilatation (RV 3D 347/124 ml, EF 3D 62%, AD 116 ml/m2), moderate tricuspid regurgitation with a regurgitant jet velocity of 2.9 m/s. Right heart catheterization showed normal pulmonary pressures at rest (mPAP 20, PAWP 5 mmHg), extremely high pulmonary blood flow (Qp 29 L/min, calculated with the direct Fick method), with normal pulmonary vascular resistance (PVR 0.5 WU). During the oxymetric run, a step up in hemoglobin saturation between superior vena cava and right atrium (from 74 to 97%) was found, with a Qp/Qs ratio of 5.5. During exercise, Qp reserve was normal, suggesting a normal contractile reserve function of RV despite the extreme dilatation. Additionally, the patient did not develop exercise PH and exercise capacity was normal, based on a measured oxygen consumption (VO2) at peak of 24 ml/kg/min (104% of predicted). Angio–CT of the chest was performed, confirming the presence of a sinus venosus atrial septal defect. The patient was then referred for surgical correction. Conclusion Echocardiography signs are useful to direct correctly diagnostic work up. A severe RV dilatation with normal systolic function in an asymptomatic middle age woman should raise the possibility of an intracardiac shunt. Despite a large intracardiac shunt with a high Qp/Qs ratio for decades, PVR was normal, confirming that individual predisposition may play a role in the development of PH in pre–tricuspid shunts. Exercise test showed an optimal RV reserve, suggesting a low cardiac surgery risk.

Background Right heart failure (RHF) represents the final step of distinct diseases, differently involving the pulmonary circulation, such as pulmonary arterial hypertension (PAH) and pulmonary hypertension (PH) due to heart failure with preserved ejection fraction (HFpEF). Exercise may unmask right heart maladaptation as a sign of RHF, but cut–offs for right atrial pressure (RAP) rise during exercise remain to be defined. We hypothesized that PH–HFpEF may present with worse right heart adaptation to exercise than PAH due to increased chamber stiffness and dysfunctional preload. Aim We sought to describe the behavior of RAP during exercise in PAH and in PH–HFpEF, and the mechanisms underlying right heart maladaptation. Methods We performed a retrospective analysis of data (2007–2021) obtained from patients with either PAH or PH–HFpEF who underwent a right heart catheterization at rest and during exercise. Right heart adaptation to exercise was described using either absolute or cardiac output (CO)–normalized RAP increase during exercise (RAP/CO slope). Patients with non–cardiac dyspnea (NCD) served to define RAP limits of normality. Estimated stressed blood volume (eSBV), as a measure of effective preload, was computed based on hemodynamics using a commercially–available software. Results Ninety–four patients were included (32 PH–HFpEF, 32 PAH and 30 NCD). The upper limit of normal for absolute peak RAP and RAP/CO slope were 12 mmHg and 1.55 mmHg/L/min. Compared with PH–HFpEF, PAH patients showed higher systolic, diastolic and mean pulmonary artery pressure (PAP) as well as higher indices of right ventricular afterload both at rest and during exercise, but lower filling pressures and similar CO (Figure 1).In particular, PH–HFpEF had higher peak RAP and higher RAP/CO slope than PAH (Figure 1,2). Additionally, 78% and 91% of PH–HFpEF, as compared with 47% and 44% of PAH had a RAP/CO slope and a peak RAP above normal, respectively (p Conclusions PH–HFpEF display worse right heart maladaptation to exercise than PAH, likely due to a combination of increased right heart stiffness and a more exhausted Frank–Starling reserve.

Echocardiography is the gatekeeper of the diagnostic workflow of pulmonary hypertension (PH). However, it lacks precision, and right heart catheterization (RHC) may be needed in selected cases. A morbidly obese 47–year–old woman (BMI= 58 Kg/m2) with dyspnea NYHA II was referred to our Center after a high probability of PH was found at echocardiography, this latter performed as a routine assessment before bariatric surgery. Despite a suboptimal acoustic window, the tricuspid regurgitant jet profile was well–defined, with an estimated systolic pulmonary artery pressure (PAP) of 100 mmHg. There were no overt echocardiographic signs of left heart disease. During RHC, mean PAP was just above normal values, with filling pressures at the upper limit of normal (Figure 1), high cardiac index (3.6 L/min/m2) and normal pulmonary vascular resistance (1.4 WU). The echocardiographic estimate of high systolic PAP was explained by an intraventricular RV pressure gradient of about 100 mmHg (Figure 2). Oximetry ruled out a significant intracardiac shunt. Since resting hemodynamics did not explain the patient’s symptoms, the patient pre–test probability of having heart failure with preserved ejection fraction (HFpEF) was intermediate–high, and PAWP was in a grey–zone. Accordingly, we performed an exercise RHC. The test eventually unmasked HFpEF, as witnessed by an abnormal increase of PAWP and LV end–diastolic pressure (Figure 1 panel C and D). Exercise capacity was mildly reduced (71% of predicted) due to peripheral limitation with normal cardiac and respiratory reserves. Transesophageal echocardiography was then performed. It showed a muscular obstruction below the infundibulum dividing the RV into a high–pressure apical portion and a low–pressure infundibulum (Figure 3). This rare congenital anomaly was also associated with a restrictive perimembranous ventricular septal defect. Double–chambered RV has been reported to present rarely in adults, but it might be a cause of false Doppler echocardiographic estimate of PAP. Based on a meticulous invasive hemodynamic characterization at rest and during exercise, integrated with cardiovascular imaging, we could perform such a diagnosis. This congenital anomaly did not fully explain the patient’s symptoms, which may better be attributed to cardiovascular complication of obesity (HFpEF). Accordingly, we referred the patient for bariatric surgery first, postponing the indication to cardiac surgery during the follow–up.

Background Clinicians need to identify patients with amyloid cardiomyopathy (AC) at an early stage, due to the availability of disease–modifying therapies. Some echocardiographic findings may rise the suspicion of AC, also in patients with mild or no symptoms, addressing second level diagnostic tests. Aim To investigate the prevalence of AC in consecutive patients ≥55 years undergoing clinically indicated, routine transthoracic echocardiogram in Italy and presenting echocardiographic signs suggestive of AC. Methods This is a prospective multicentric study conducted in Italy. It comprises two phases: 1) a recording phase consisting in a national survey on prevalence of possible echocardiographic red flags of AC in consecutive unselected patients ≥55 years undergoing routine echocardiogram (previously published) and 2) an AC diagnostic phase involving a diagnostic work–up for AC to investigate AC prevalence among patients with at least one echocardiographic red flag (herein presented). Patients that in Phase 1 presented an “AC suggestive” echocardiogram (i.e., at least one red flag of AC in hypertrophic, non–dilated left ventricles with preserved ejection fraction) underwent clinical evaluation, blood and urine tests and scintigraphy with bone tracer. Diagnosis of transthyretin related–AC (ATTR–AC) was made in presence of grade 2–3 Perugini uptake at scintigraphy and absence of monoclonal protein. The study was registered at ClinicalTrials.gov (#NCT04738266). Results Of the 5315 screened echocardiograms, 381 exams (7.2%) were classified as “AC suggestive” and proceeded to Phase 2. 217 patients completed Phase 2 investigations. Main reasons for the 164 non–entering patients into Phase 2 were death (n = 49) and refusal to participate (n = 66). A final diagnosis of AC was made in 62 patients with an estimated prevalence of 28,6% (95% CI: 22,5%–34,7%). ATTR–AC was diagnosed in 51 and AL–AC in 11 patients, ascertaining a prevalence of 23,5% (95% CI: 17,8%–29,2%) and 5,1% (95% CI: 2,2%–8,0%), respectively. Conclusion Among a cohort of consecutive unselected patients ≥55 years with echocardiographic findings suggestive of AC, the prevalence of AC ranged from 23% up to 35%. Although ATTR–AC was predominant, AL–AC was diagnosed in a significant number of cases. Echocardiography has a fundamental role in screening patients, raising the suspicion of disease and orienting diagnostic work–up for AC.

A 66–y.o. man with hypertrophic cardiomyopathy presented with residual exertional dyspnea NYHA III a few years after surgical myectomy, mitral valve repair and ICD implantation. Echocardiography showed residual mild septal hypertrophy and mitral regurgitation (MR), and a variable obstruction of left ventricular outflow tract (LVOT), witnessed by a pressure gradient ranging from 15 to 50–70 mmHg (Figure 1). Exercise echocardiography did not suggest exercise–induced LVOT obstruction (LVOTO) or functional MR. We thus performed a thorough invasive hemodynamic evaluation at rest and during exercise. LVOTO was present at rest, with a maximum pressure gradient of 90–100 mmHg and typical “spike–and–dome” configuration of the aortic pulse contour (Figure 2), with LV end–diastolic pressure (LVEDP) at the upper limit of normal (15 mmHg) and normal pulmonary hemodynamics. During exercise, we observed a paradoxical reduction of the LVOTO (30–40 mmHg at peak, Figure 2). Pulmonary hypertension developed during exercise, due to LV diastolic dysfunction, witnessed by a marked increase in pulmonary artery wedge pressure and LVEDP (up to 25 mmHg and 30 mmHg at peak, respectively). Cardiac output (CO) reserve was at the lower limits of normal, mainly due to chronotropic incompetence, responsible for a mildly reduced exercise capacity (peak oxygen consumption was 20 mL/Kg/min, 75% of predicted). Thus, cardiac catheterization confirmed the presence of a relevant LVOTO at rest, that was not directly related to exertional symptoms. These latter were mainly attributable to LV diastolic dysfunction and reduced CO reserve. These findings helped us driving treatment decision in a tailored way: beta–blockers were not uptitrated, because of their negative inotropic effect, and high–risk septal reduction therapies were excluded, since exertional symptoms were unrelated to LVOTO. However, an attempt to reduce LVOTO was done by DDD sequential pacing through the ICD. Pacing could induce mechanical dyssynchrony and reduce LVOTO by increasing the end–systolic LVOT diameter. The simultaneous echocardiographic monitoring highlighted an acute reduction of LVOT gradient from 50–70 mmHg to 20–30 mmHg (Figure 3). This case suggests that, in well–selected cases, patients’ management based on pathophysiological reasoning may help to define the etiopathogenetic mechanism underlying symptoms, and to drive treatment decision in a patient–centered way.

Constrictive physiology leads to exertional symptoms related to restrained diastolic filling and intracardiac/intrathoracic dissociation. However, these hemodynamic abnormalities might not be evident in some patients. A 55–year–old woman was referred to our center to perform a right and left cardiac catheterization because of “unexplained” dyspnea. Three years before she was found to have a large idiopathic pericardial effusion. Anti–inflammatory therapy did not result in any improvement. Since then, the patient complained dyspnea NYHA II–III, in the absence of any clinical and imaging sign of tamponade/pericardial constriction. At rest, there was no sign of constriction, but a relative hypovolemic status characterized by low pulmonary and filling pressures and cardiac output (CO) at the lower limits of normal. After a 500 mL saline load and passive legs raising, Kussmaul’s and “M” signs appeared on the right atrial pressure curve (Figure 1), the pulmonary artery wedge pressure (PAWP) – left ventricular end–diastolic pressure (LVEDP) gradient difference between expiration and inspiration was >5 mmHg (Figure 2), and ventricular systolic pressures went out of phase by 180°. Both right and left filling pressures as well as pulmonary pressures steeply increased in a concordant manner by about 10 mmHg after fluid load, in absence of a relevant increase in CO (Figure 3). Physical exercise performed thereafter showed an additional mild increase with a plateau pattern of all pressures, suggesting an upward–shift of the pressure/flow relationship (Figure 3). All these signs suggested a latent constrictive physiology. Despite this, the patient showed an optimal CO reserve coupled with a normal exercise capacity (peak oxygen consumption, VO2, 127% of predicted) that would have argued against our hypothesis. We then performed a diagnostic and evacuative pericardiocentesis. After the drainage of 130 ml of pericardial fluid, LV transmural pressure increased and CO at rest was fully normalized. Moreover, no hemodynamic sign of constriction could be observed even after a 1000 ml saline load. The patient reported disappearance of exertional breathlessness, objectivated by an increase in peakVO2 by 20% as compared with the previous test. Thus, our case underscores how subtle the hemodynamic impact of pericardial effusion can be, with the need of well–tailored diagnostic exams to explain otherwise “unexplained” patients’ symptoms, with potential therapeutic implications.

An 80–year–old man, diagnosed with idiopathic pulmonary arterial hypertension (PAH) in 2012 and treated with sildenafil, experienced his first hospitalization for heart failure in June 2019. He had several cardiovascular risk factors (overweight, hypertension, diabetes) and comorbidities (ischemic heart disease, and mild chronic obstructive pulmonary disease), whose progression was excluded. Since this event, he complained a progressive deterioration of the exertional dyspnea (NYHA III), with overt signs of fluid overload, right chambers dilation and high NTproBNP (1366 ng/L). However, the center taking care of this patient neither decided to fully re–evaluate him nor to escalate PAH–treatment due to his clinical profile (high suspicion of left heart disease, LHD). He then came to our pulmonary hypertension (PH) center where we decided to perform a cardiac catheterization, which showed the persistence of precapillary PH with high pulmonary vascular resistance, PVR (7.6 WU), low cardiac output, CO (2.2 L/min/m2), high right atrial pressure, RAP (12 mmHg). Pulmonary artery wedge pressure (PAWP) and left ventricular end–diastolic pressure (LVEDP) were at the upper limits of normal (13 mmHg and 16 mmHg, respectively) (Figure 1). Based on these “borderline” PAWP values, with an intermediate–high pre–test probability of left heart disease, we performed an exercise test with concomitant gas–exchange analysis on a cycle ergometer in the cath lab (Figure 2). Exercise induced a steep increase in pulmonary pressure (TPR 9 WU), unrelated to an exaggerate increase in PAWP or LVEDP (whose peak values reached 20 mmHg, with a PAWP/CO slope

Background Left ventricular end–diastolic pressure (LVEDP) approximates LV stiffness. Pulmonary artery wedge pressure (PAWP) reflects the hemodynamic load imposed by the left heart on the pulmonary circulation, with the interposition of the left atrium (LA). PAWP is frequently seen as a surrogate measure for LVEDP, but the two measures may not coincide. The imprecision of PAWP estimates for LVEDP and the disagreement between the two measures have been widely described for cardiac catheterization at rest. PAWP measurement during exercise has been advocated to discriminate heart failure with preserved ejection fraction (HFpEF) from non–cardiac dyspnea (NCD), with an end–expiratory pathologic threshold ≥25 mmHg. However, a formal comparison of PAWP vs LVEDP during exercise has never been performed. Aim. We sought to compare LVEDP and PAWP during exercise. Methods We retrospectively analyzed consecutive patients with unexplained dyspnea and a normal LV ejection fraction, who performed right and left heart catheterization at rest and during exercise. Results Forty–six consecutive patients were included in the analysis (80% with a peak PAWP ≥25 mmHg). We found a good correlation between both end–diastolic and mean PAWP on one side, and LVEDP on the other side (R2>0.55). End–expiratory, end–diastolic (mid–A) peak PAWP had no bias as compared with LVEDP, while mean PAWP slightly overestimated LVEDP by 1–2 mmHg. However, confidence intervals were quite large (Figure 1), suggesting imprecision of PAWP estimates for LVEDP. A disagreement between PAWP and LVEDP, using a threshold of ≥ 25 mmHg for both variables at peak exercise, was found in 11% of patients. In 4%, PAWP was ≥25 but LVEDP 2 mmHg/L/min, as an alternative parameter confirming HFpEF. Conclusions PAWP estimates for LVEDP during exercise bear a good correlation and a minimal bias, albeit being burdened by a relevant imprecision. In patients with unexplained exertional dyspnea and peak PAWP

Funding Acknowledgements Type of funding sources: None. Introduction – Non-invasive parameters used to assess right ventricular (RV) function, i.e. tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (FAC), RV ejection fraction (RVEF), and RV free-wall longitudinal strain (RVFWLS) have shown their prognostic implications. However, since they are extremely load dependent, they do not provide an accurate representation of the RV intrinsic performance. On the other end, invasive indices of RV-arterial coupling (RVAC) derived from pressure-volume loops are not routinely performed, rising the urgency for more feasible, and reliable non-invasive estimates of RVAC. Purpose – To: i. evaluate the prognostic value of echocardiography-derived RVAC surrogates: RVEF/systolic pulmonary artery pressure (sPAP), RVFWLS/sPAP, TAPSE/sPAP, FAC/sPAP, and RV stroke volume/end-systolic volume (SV/ESV), ii. identify the cut-off values associated to all-cause mortality; and iii. compare their prognostic value with that of classical parameters of RV function. Methods – We prospectively enrolled 366 patients with various cardiac diseases, undergoing clinically-indicated comprehensive two- and three-dimensional echocardiography. Results – During a mean follow-up of 7.6 ± 1 years, 80 (21.9%) patients died. At univariable Cox regression, most of the echocardiographic parameters were related to all-cause mortality. The echocardiographic parameters with significance at univariable analysis (p Conclusion – RVAC surrogates provide incremental prognostic value compared to standard RV functional measurements. RVEF/sPAP, with a cut-off value of 1.5, was the best parameter for risk stratification, and was independently related to all-cause mortality. Abstract Figure. Prognostic value of RVAC surrogates Abstract Figure. Kaplan-Meier curves survival probability

Funding Acknowledgements Type of funding sources: None. Introduction - A by-product of left atrial (LA) strain analysis is the automated measurement of LA maximal volume (LAVmax), which may decrease the time of echocardiography reporting, and increase the reproducibility of the LAVmax measurement. However, the automated measurement of LAVmax by two-dimensional speckle-tracking analysis (2DSTE) has never been validated. Purpose – Accordingly, we sought to: i. assess the feasibility of automated LAVmax measurement by 2DSTE; ii. compare the automated LAVmax by 2DSTE with conventional two-dimensional (2DE) biplane and three-dimensional echocardiography (3DE) measurements; and iii. evaluate the accuracy and reproducibility of the three echocardiography techniques. Methods – LAVmax (34­-197 mL) were prospectively obtained from 198/210 (feasibility 94%) consecutive patients with various cardiac diseases (median age 67 years, 126 men) by 2DSTE, 2DE and 3DE. Results – 2DE and 2DSTE measurements resulted in similar LAVmax values (bias = 1.5 mL, limits of agreement, LOA ± 7.5 mL), and slightly underestimated 3DE LAVmax (biases=-5 mL, LOA ± 17 mL, and -6 mL, LOA ± 16 mL, respectively). LAVmax by 2DSTE and 2DE were strongly correlated to those obtained by cardiac magnetic resonance (CMR) (r=.946, and r=.935, respectively; p Conclusion – Automated LAVmax measurement by 2DSTE is highly feasible, highly reproducible, and provided similar values to conventional 2DE calculations in consecutive patients with a wide range of LAVmax. Abstract Figure. Echocardiography and CMR correlations Abstract Figure. Echocardiography techniques correlations

Funding Acknowledgements Type of funding sources: None. Introduction — Atrial functional tricuspid regurgitation (A-FTR) is a recently defined phenotype of FTR associated with persistent/permanent atrial fibrillation. Differently from the classical ventricular form of FTR (V-FTR), patients with A-FTR might present with severely dilated right atrium (RA) and tricuspid annulus (TA), and with preserved right ventricular (RV) size and systolic function. However, the geometry and function of the RV, RA and TA in patients with A-FTR and V-FTR remain to be systematically evaluated. Purpose — Accordingly, we sought to: i. study the geometry and function of the RV, RA and TA in A-FTR by two- and three-dimensional transthoracic echocardiography; and ii. compare them with those found in V-FTR. Methods — We prospectively analysed 113 (44 men, age 68 ± 18 years) FTR patients (A-FTR = 55 and V-FTR = 58) that were compared to two groups of age- and sex-matched controls to develop the respective Z-scores. Results — The severity of FTR, and the degree of TA dilation were similar in A-FTR and V-FTR patients. The Z-scores of RV size were significantly larger, and those of RV function were significantly lower in V-FTR than in A-FTR (p 2), with similar RA maximal volumes (RAVmax) between A-FTR and V-FTR (p = 0.2). Whereas, the RA minimal volumes (RAVmin) were significantly larger in A-FTR than in V-FTR (p = 0.001). Conclusion — Despite similar degrees of FTR, RAVmax and TA size, A-FTR patients show larger RAVmin than V-FTR patients. Conversely, V-FTR patients show dilated, more elliptic and dysfunctional RV than A-FTR patients. Abstract Figure. A-FTR versus V-FTR Abstract Figure. Remodelling patterns in A-FTR and V-FTR

Funding Acknowledgements Type of funding sources: None. Background Severe tricuspid regurgitation (TR) is associated with excess mortality and morbidity. Therefore, assessment of TR severity is pivotal. Calculation of the effective regurgitant orifice area (EROA) and the regurgitant volume (RVol) using flow convergence method (PISA) by echocardiography are still the recommended parameters to define TR severity. However, the distortion of the proximal convergence zone related to the extent of valve leaflet tethering may result in smaller PISA radius and in underestimation of TR severity. Correcting for the angle of the leaflet tethering could reduce errors due to geometric assumption of a flat valvular plane and improve the accuracy of the calculations. Purpose: The aims of our study were (1) to evaluate whether taking into account the extent of leaflet tethering by applying the angle correction (AC) in the PISA formula improves the accuracy of the quantitative assessment of TR severity; (2) to assess the potential clinical impact of AC. Methods Forty-one patients with functional TR (73.5 ± 11.8 years,51% men,36% sinus rhythm,17% severe), underwent 2D and 3D echocardiography. We compared the RVol obtained by volumetric method (as reference) with the RVol by PISA with and without AC. TR RVol by volumetric method was calculated as: total RV stroke volume (RVSV) – left ventricular forward SV (LVSV), where RVSV was obtained by subtracting the end-systolic from end-diastolic RV volume measured by 3D echocardiography and LV SV was calculated by multiplying LV outflow area by velocity time integral (VTI) (Fig. 1). TR RVol by PISA was calculated as EROA x VTITR. Uncorrected EROA was calculated using the formula: 6.28 r2 xVa/ PeakVTR (r - PISA radius, Va, aliasing velocity, PeakVTR – TR peak velocity). The corrected EROA accounting for the PISA geometric distortion by leaflet tethering angle (α) was calculated as: 6.28 r2 x Va (α/180)/ PeakV TR (PISAac), where α was measured using a protractor generated by dedicated software. Results Application of AC to PISA method resulted in larger EROA and RVol (0.34± 0.38 cm2 vs 0.24± 0.24cm2 and, 25.2± 19.3 mL vs 18.6 ± 13.1mL, respectively). The percentage change in EROAac was over 40%. When compared to the volumetric method, RVol by corrected PISA method was significantly closer and correlated (bias -3.95mL, LOA ± 6.41 mL, r= .987; p< .001) than the conventional PISA without AC (bias -10.5 mL, LOA ± 15 mL, r= .975). Angle correction resulted in a change of TR severity in 32% of cases (Fig. 2) and in a greater concordance of TR severity grade with the volumetric method (75%, 31/41 with AC vs 52%, 22/41 without AC). Conclusions Angle-corrected PISA method that accounts for the extent of the leaflet tethering in TR provided significantly larger TR RVol that were closely correlated with the volumetric RVol by 3D echocardiography. A simple geometric angle correction of the proximal flow with PISA method reclassified up to 1/3 of patients with functional TR. Abstract Figure. Representation of study method Abstract Figure. Reclassification of TR severity

ObjectivePost-COVID-19 syndrome presents a health and economic challenge affecting ~10% of patients recovering from COVID-19. Accurate assessment of patients with post-COVID-19 syndrome is complicated by health anxiety and coincident symptomatic autonomic dysfunction. We sought to determine whether either symptoms or objective cardiopulmonary exercise testing could predict clinically significant findings.Methods113 consecutive military patients were assessed in a comprehensive clinical pathway. This included symptom reporting, history, examination, spirometry, echocardiography and cardiopulmonary exercise testing (CPET) in all, with chest CT, dual-energy CT pulmonary angiography and cardiac MRI where indicated. Symptoms, CPET findings and presence/absence of significant pathology were reviewed. Data were analysed to identify diagnostic strategies that may be used to exclude significant disease.Results7/113 (6%) patients had clinically significant disease adjudicated by cardiothoracic multidisciplinary team (MDT). These patients had reduced fitness (V̇O226.7 (±5.1) vs 34.6 (±7.0) mL/kg/min; p=0.002) and functional capacity (peak power 200 (±36) vs 247 (±55) W; p=0.026) compared with those without significant disease. Simple CPET criteria (oxygen uptake (V̇O2) >100% predicted and minute ventilation (VE)/carbon dioxide elimination (V̇CO2) slope 2slope ConclusionsIn a population recovering from SARS-CoV-2, there is reassuringly little organ pathology. CPET and functional capacity testing, but not reported symptoms, permit the exclusion of clinically significant disease.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Background: The impact of removing the upper airway lymphoid tissue and in particular, tonsillectomy, in adults with OSA has not been demonstrated in large populations. Aims: To compare the severity of OSA and the prevalence of cardiovascular, metabolic and respiratory co-morbidities between patients with OSA who had undergone previous tonsillectomy and those who had not. Methods: The 19,711 participants in this study came from the European sleep apnea database (ESADA) which comprises data from unselected adult patients aged 18–80 years with a history of symptoms suggestive of OSA referred to sleep centers throughout Europe. Results: There were no differences between the two groups in terms of sex ratio and age (146 patients with previous tonsillectomy vs. 19565 patients without). Patients who had undergone tonsillectomy had a lower body mass index (29.3 ± 5.2 kg/m2 vs 32.2 ± 6.6 kg/m2, p < 0.001), lower subjective sleep latency (17.1 ± 17.8 min vs 25.5 ± 30.4 min, p = 0.001), lower ODI (15.7 ± 18.3 events/hour vs 30.7 ± 26.1 events/hour, p < 0.001), and SpO2, European Respiratory Society, ERS, The ESADA network has previously received support from the European Union COST action B26 and the European Respiratory Society. We gratefully acknowledge unrestricted seeding grants from ResMed Inc and Philips Respironics Inc. for establishment of the organisation and the database. Excellent technical assistance in terms of centre monitoring and database maintenance was provided by Ann-Christin Lundquist, RN and Jeanette Norum, RN.

Summary Background Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes. Methods This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models. Findings Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays. Interpretation Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure. Funding International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.

Objective/Background: The Clinical Global Impression scale (CGI) reflects the clinician's assessment of the disease impact on patient's global functioning. We assessed predictors of CGI scale rating in patients with obstructive sleep apnea (OSA). Patients/Methods: Consecutive patients with suspected OSA (n = 7581) were identified in the European Sleep Apnea Database (ESADA). Anthropometrics, comorbidities, apnea severity obtained by polygraphy or polysomnography, and daytime sleepiness [Epworth Sleepiness Scale (ESS)] were assessed. The CGI 7-point scale was completed at the end of the diagnostic process (CGI-severity, ie, CGI-S) and, in a sub-population, at treatment follow-up (CGI-Improvement). Results: CGI-S was rated mild to moderate in 44% of patients. CGI rating at any given apnea intensity was worse in women than in men (p < 0.01). Patients undergoing polygraphy (n = 5075) were more frequently rated as severely ill compared to those studied with polysomnography (19.0% vs 13.0%, p < 0.001). In patients aged

Pulmonary arterial hypertension in primary myelofibrosis is common and associated with an altered angiogenic status