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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/m 2 ) and 12 HFpEF-controls patients were analyzed. HFpEF-STR had higher ( p < 0.01) right atrial pressure than HFpEF-controls both at rest (10 ± 1 vs. 5 ± 1 mmHg) and during exercise (23 ± 2 vs. 14 ± 2 mmHg). Despite higher pulmonary artery wedge pressure (PAWP) at rest in HFpEF-STR than in HFpEF-controls (17 ± 2 vs. 11 ± 2, p = 0.04), PAWP at peak exercise was no more different (28 ± 2 vs. 29 ± 2). Left ventricular transmural pressure and cardiac output (CO) increased less in HFpEF-STR than in HFpEF-controls (interaction p -value < 0.05). This latter was due to lower stroke volume (SV) values both at rest (48 ± 9 vs. 77 ± 9 mL, p < 0.05) and at peak exercise (54 ± 10 vs. 93 ± 10 mL, p < 0.05). Despite these differences, the two groups of patients laid on the same oxygen consumption isophlets because of the increased peripheral oxygen extraction in HFpEF-STR ( p < 0.01). We found an inverse relationship between pulmonary vascular resistance and SV, both at rest and at peak exercise ( R 2 = 0.12 and 0.19, respectively). Conclusions Severe STR complicating HFpEF impairs SV and CO reserve, leading to pulmonary vascular de-recruitment and relati, SCOPUS: ar.j, info:eu-repo/semantics/published

Aims: 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 haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects. Methods and results: We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise). The PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-seven studies were identified, providing data for 2180 HFpEF patients and 682 controls. At peak exercise, patients with HFpEF achieved higher PAWP (30 [29–31] vs. 16 [15–17] mmHg, P < 0.001) and mean right atrial pressure (P < 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, and body position. However, peak PAWP values were highly heterogeneous among the cohorts (I2 = 93%), with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls (3.75 [3.20–4.28] vs. 0.95 [0.30–1.59] mmHg/L/min, P value < 0.0001), even after adjustment for covariates (P = 0.007). Conclusions: Despite methodological heterogeneity, as well as heterogeneity of pooled haemodynamic estimates, the exercise haemodynamic profile of HFpEF patients is consistent across studies and characterized by a steep PAWP rise during exercise. More standardization of exercise haemodynamics may be advisable for a wider application in clinical practice.

Aims: 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 haemodynamic thresholds to define HFpEF are not universally accepted. We sought to describe the exercise haemodynamics profile of HFpEF cohorts reported in literature, as compared with control subjects. Methods and results: We performed a systematic literature review until December 2020. Studies reporting pulmonary artery wedge pressure (PAWP) at rest and peak exercise were extracted. Summary estimates of all haemodynamic variables were evaluated, stratified according to body position (supine/upright exercise). The PAWP/cardiac output (CO) slope during exercise was extrapolated. Twenty-seven studies were identified, providing data for 2180 HFpEF patients and 682 controls. At peak exercise, patients with HFpEF achieved higher PAWP (30 [29–31] vs. 16 [15–17] mmHg, P < 0.001) and mean right atrial pressure (P < 0.001) than controls. These differences persisted after adjustment for age, sex, body mass index, and body position. However, peak PAWP values were highly heterogeneous among the cohorts (I2 = 93%), with a relative overlap with controls. PAWP/CO slope was steeper in HFpEF than in controls (3.75 [3.20–4.28] vs. 0.95 [0.30–1.59] mmHg/L/min, P value < 0.0001), even after adjustment for covariates (P = 0.007). Conclusions: Despite methodological heterogeneity, as well as heterogeneity of pooled haemodynamic estimates, the exercise haemodynamic profile of HFpEF patients is consistent across studies and characterized by a steep PAWP rise during exercise. More standardization of exercise haemodynamics may be advisable for a wider application in clinical practice., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: Long scanning times impede cardiac magnetic resonance (CMR) clinical uptake. A “one-size-fits-all” shortened, focused protocol (eg, only function and late-gadolinium enhancement) reduces scanning time and costs, but provides less information. We developed 2 question-driven CMR and stress-CMR protocols, including tailored advanced tissue characterization, and tested their effectiveness in reducing scanning time while retaining the diagnostic performances of standard protocols. METHODS AND RESULTS: Eighty three consecutive patients with cardiomyopathy or ischemic heart disease underwent the tailored CMR. Each scan consisted of standard cines, late-gadolinium enhancement imaging, native T1-mapping, and extracellular volume. Fat/edema modules, right ventricle cine, and in-line quantitative perfusion mapping were performed as clinically required. Workflow was optimized to avoid gaps. Time target was <30 minutes for a CMR and [removed]30% (CMR: from 42±8 to 28±6 minutes; stress-CMR: from 50±10 to 34±6 minutes, both P[removed]45% of cases. Quality grading was similar between the 2 protocols. Tailored protocols did not require additional staff. CONCLUSIONS: Tailored CMR and stress-CMR protocols including advanced tissue characterization are accurate and timeeffective for cardiomyopathies and ischemic heart disease.

Purpose Current treatment of acromegaly restores a normal life expectancy in most cases. So, the study of persistent complications affecting patients' quality of life (QoL) is of paramount importance, especially motor disability and depression. In a large cohort of acromegalic patients we aimed at establishing the prevalence of depression, to look for clinical and sociodemographic factors associated with it, and to investigate the respective roles (and interactions) of depression and arthropathy in influencing QoL. Methods One hundred and seventy-one acromegalic patients (95 women and 76 men, aged 20-85 years) among those recruited in a cross-sectional Italian multicentric study were investigated. Each patient filled in three validated questionnaires: AcroQoL, WOMAC (measuring articular pain, stiffness and functionality), and AIMS (evaluating articular symptoms and depression). Results A very high (up to 28%) depression rate was detected in acromegalic subjects. Two patients showing pathological AIMS depression scores, committed suicide during the three years observational period. In our population poor psychological status was significantly associated with female sex. Furthermore, a significant strong correlation was found between AIMS depression score and WOMAC score. Both depression and arthropathy-related motor disability turned out to independently contribute with similar strength to the impairment of QoL. Conclusions We report a high prevalence of depression in acromegaly, which is associated with female sex and arthropathy. Both depression and arthropathy strongly and independently contribute to the impaired QoL of patients. Our study shows that assessment and monitoring of psychological status is mandatory in acromegaly, also suggesting an inexpensive tool for this assessment.

Exercise hemodynamics can differentiate heart failure with preserved ejection fraction (HFpEF) from noncardiac dyspnea. However, respiratory pressure swings may impact hemodynamic measurements, potentially leading to misdiagnosis of HFpEF. Moreover, threshold values for abnormal hemodynamic response indicative of HFpEF are not universally accepted. Thus, we sought to evaluate the impact of respiratory pressure swings on hemodynamic data interpretation as well as the concordance among 3 proposed exercise hemodynamic criteria for HFpEF: (1) end-expiratory pulmonary artery wedge pressure (PAWPexp) ≥25 mm Hg; (2) PAWPexp/cardiac output slope >2 mm Hg/L per minute; and (3) respiratory-averaged (avg) mean pulmonary artery pressure >30 mm Hg, total pulmonary resistanceavg >3 WU, PAWPavg ≥20 mm Hg.

Background: Exercise hemodynamics can differentiate heart failure with preserved ejection fraction (HFpEF) from noncardiac dyspnea. However, respiratory pressure swings may impact hemodynamic measurements, potentially leading to misdiagnosis of HFpEF. Moreover, threshold values for abnormal hemodynamic response indicative of HFpEF are not universally accepted. Thus, we sought to evaluate the impact of respiratory pressure swings on hemodynamic data interpretation as well as the concordance among 3 proposed exercise hemodynamic criteria for HFpEF: (1) end-expiratory pulmonary artery wedge pressure (PAWPexp) ≥25 mm Hg; (2) PAWPexp/cardiac output slope >2 mm Hg/L per minute; and (3) respiratory-averaged (avg) mean pulmonary artery pressure >30 mm Hg, total pulmonary resistanceavg>3 WU, PAWPavg≥20 mm Hg. Methods: Fifty-seven patients with unexplained dyspnea (70% women, 70±9 years) underwent exercise cardiac catheterization. The difference between end-expiratory and averaged hemodynamic values, as well as the concordance among the 3 hemodynamic definitions of HFpEF, were assessed. Results: End-expiratory hemodynamics measurements were higher than values averaged across the respiratory cycle. During exercise, a larger proportion of patients exceeded the threshold of 25 mm Hg for PAWPexprather than for PAWPavg(70% versus 53%, P<0.01). The concordance of 3/3 HFpEF exercise hemodynamic criteria was recorded in 70% of patients. PAWPexp/cardiac output slope identified HFpEF more frequently than the other 2 criteria (81% versus 64% to 69%), incorporating over 97% of abnormal responses to the latter. Patients with 3/3 positive criteria had worse clinical, gas-exchange, and hemodynamic profiles. Conclusions: Respiratory pressure swings impact on the exercise hemodynamic definitions of HFpEF that provide discordant results in 30% of patients. Equivocal diagnoses of HFpEF might be limited by adopting the most sensitive and inclusive criterion alone (ie, PAWPexp/cardiac output slop, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Acute exposure to high altitude (>2500 m) is known to induce a rise in blood pressure (BP) and the appearance of sleep related breathing alterations, in particular central sleep apneas and periodic breathing. Little information is available on whether this is the case in humans also for acute exposure to moderate altitude (between 1500 and 2500 m). Aim of this study was to evaluate the effects of acute exposure of healthy volunteers to moderate altitude on conventional and ambulatory BP as well as on the frequency and severity of breathing alterations during sleep. Methods: Forty-four healthy lowlanders underwent 24-hour ambulatory BP monitoring and nocturnal cardio-respiratory sleep study at sea level and during acute (1–2 days after arrival) exposure to moderate altitude (2035 m, Sestriere, Italy). The key variables investigated included average systolic and diastolic BP and heart rate over daytime, night-time and 24 h, the frequency of obstructive and central apneas/hypopnoeas and the behaviour of oxygen saturation during sleep. Results: Compared to sea level, during moderate altitude exposure mean systolic/diastolic BP increased significantly during daytime (respectively from 125.6 ± 10.9 to 130.6 ± 12.3, p = 0.0032 and from 78.8 ± 6.7 to 81.8 ± 7.7 mmHg, p = 0.0048) and during night-time (respectively from 102.4 ± 12.4 to 107.4 ± 12.7, p = 0.0028, and from 62.0 ± 8.2 to 65.8 ± 8.2 mmHg, p = 0.0014), with no change in nocturnal BP dipping. BP increase was more evident in participants aged over 40 years. Apnea-hypopnea index (AHI) increased from 1.60 (0.40–2.90) to 5.4 (2.90–10.60), p < 0.0001), mainly because of increasing frequency of hypopneas and central apneas, in particular in males aged over 40 years. No association was found between size of BP changes and AHI. Conclusion: Our results indicate that in healthy subjects even exposure to moderate altitude may induce significant, although mild, changes in ambulatory BP and in respiratory patt

Background Twenty-four-hour blood pressure variability (BPV) is independently related to cardiovascular outcomes, but limited and conflicting evidence is available on the relative prognostic importance of systolic and diastolic BPV. The aim of this study was to verify the hypothesis that the association of systolic and diastolic blood pressure variability over 24 h with cardiovascular mortality in untreated subjects is affected by age. Design and methods The study included 9154 untreated individuals assessed for hypertension between 1982 and 2002 in the frame of the Dublin Outcome Study, in which 24 h ambulatory blood pressure monitoring was obtained (age 54.1 +/- 14.3 years, 47% males). The association of short-term systolic and diastolic blood pressure variability with cardiovascular and all-cause mortality in the entire sample and separately in younger and older age subgroups was assessed over a median follow-up period of 6.3 years. Results Diastolic BPV was directly and independently related to cardiovascular mortality (adjusted hazard ratio (adjHR) for daytime standard deviation 1.16 (95% confidence interval 1.08-1.26)) with no significant differences among age groups. Conversely, systolic BPV was independently associated with cardiovascular mortality only in younger (<50 years) subjects (adjHR for daytime standard deviation 1.72 (95% confidence interval 1.33-2.23)), superseding the predictive value of diastolic BPV in this group. Conclusions Diastolic short-term BPV independently predicts CARDiovascular mortality in hypertensive subjects at all ages, while systolic BPV seems a particularly strong predictor in young adults. If confirmed, these findings might improve the understanding of the prognostic value of BPV, with new perspectives for its possible clinical application

Few studies have investigated the kinematic aspects of the body centre of mass motion, that is, its three-dimensional path during strides and their changes with child development. This study aimed to describe the three-dimensional path of the centre of mass in children while walking in order to disentangle the effect of age from that of absolute forward speed and body size and to define preliminary pediatric normative values. The three-dimensional path of the centre of mass during walking was compared across healthy children 5-6- years (n = 6), 7-8 years (n = 6), 9-10 years (n = 5), and 11-13 years of age (n = 5) and healthy adults (23-48 years, n = 6). Participants walked on a force-sensing treadmill at various speeds, and height normalization of speed was conducted with the dimensionless Froude number. The total length and maximal lateral, vertical, and forward displacements of the centre of mass path were calculated from the ground reaction forces during complete strides and were scaled to the participant's height. The centre of mass path showed a curved figure-of-eight shape. Once adjusted for speed and participants' height, as age increased, there was a decrease in the three-dimensional parameters and in the lateral displacement, with values approaching those of adults. At each step, lateral redirection of the centre of mass requires brisk transient muscle power output. The base of support becomes relatively narrower with increasing age. Skilled shortening of the lateral displacement of the centre of mass may therefore decrease the risk of falling sideways. The three-dimensional path of the centre of mass may represent maturation of neural control of gait during growth.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially w

Objective: Office and ambulatory blood pressure (BP) measurements are the main techniques to detect the effects of antihypertensive treatments in clinical trials, but the treatment-induced changes in these BP values can differ markedly. We performed a meta-analysis of clinical trials to quantify these differences and identified some of the associated factors. Methods: We conducted a MEDLINE search for randomized clinical trials (RCTs) on hypertensive patients treated with at least one antihypertensive drug that reported changes in both office and 24-h BP. Random-effects models were fitted to estimate the summary of the difference between the changes as quantified by either technique. The I2 and Cochrane's Q statistics were calculated to evaluate the heterogeneity between studies. Results: A total of 52 studies were included in our metaanalysis with about 9500 patients. The summary estimate D of SBP and DBP was -6.5 (95% confidence interval: -7.5 to -5.6) and -3.3 (95% confidence interval, -3.9 to -2.7), respectively. The difference was independent on the treatment duration and use of mono or combination treatment but for SBP it varied with the different treatment types in monotherapy, and it was greater in relation to baseline office BP and age. Allowing for the placebo effect also reduced the difference. Absolute on treatment BP values were at target for either pressure and the rate of controlled hypertensive individuals was similar (around one-third) for either measuring approach. Conclusion: Our meta-analysis confirms that overall treatment-induced reduction is markedly greater for office BP than for 24-h BP, but it also shows that the quantitative relationship between these two measuring approaches varies with demographic, clinical and therapeutic conditions as well as in relation to placebo correction.