Mueller maneuver attenuates left atrial phasic volumes and myocardial strain in healthy younger adults.

The left atrium (LA) is a key, but incompletely understood, modulator of left ventricular (LV) filling. Inspiratory negative intrathoracic pressure swings alter cardiac loading conditions, which may impact LA function. We studied acute effects of static inspiratory efforts on LA chamber function, LA myocardial strain, and LV diastolic filling. We included healthy adults (10 males/9 females, 24 ± 4 yr) and used Mueller maneuvers to reduce intrathoracic pressure to -30 cmH2O for 15 s. Over six repeated trials, we used echocardiography to acquire LA- and LV-focused two-dimensional (2-D) images, and mitral Doppler inflow and annular tissue velocity spectra. Images were analyzed for LA and LV chamber volumes, tissue relaxation velocities, transmitral filling velocities, and speckle tracking-derived LA longitudinal strain. Repeated measures were made at baseline, early Mueller, late Mueller, then early release, and late release. In the late Mueller compared with baseline, LV stroke volume decreased by -10 ± 4 mL (P < 0.05) and then returned to baseline upon release; this occurred with a -11 ± 9 mL (P < 0.05) end-diastolic volume reduction. Early diastolic LV filling was attenuated, reflected by decreased tissue relaxation velocity (-2 ± 2 cm/s, P < 0.05), E-wave filling velocity (-13 ± 14 cm/s, P < 0.05), and LA passive emptying volume (-5 ± 5 mL, P < 0.05), each returning to baseline with release. LA maximal volume decreased (-5 ± 5 mL, P < 0.05) during the Mueller maneuver, but increased relative to baseline following release (+4 ± 5 mL, P < 0.05), whereas LA peak positive longitudinal strain decreased (-6 ± 6%, P < 0.05) and then returned to baseline. Attenuated LA and in turn, LV filling may contribute to acute stroke volume reductions experienced during forceful inspiratory efforts.NEW & NOTEWORTHY In healthy younger adults, the Mueller maneuver transiently reduces left atrial filling and passive emptying during the reservoir and conduit phases, respectively. Corresponding reductions are seen in left atrial reservoir and conduit phase longitudinal myocardial strain and strain rate. However, left atrial pump phase active function and mechanics are largely preserved compared with baseline. Rapid changes in LA chamber volumes and myocardial strain with recurrent forceful inspiratory efforts and relaxation may reflect acute LA stress.

Pulmonary hemodynamic and right ventricular responses to brief and prolonged exercise in middle-aged endurance athletes.

Right ventricular (RV) function is closely coupled to pulmonary arterial (PA) hemodynamics and is believed to decline with prolonged exercise. A linear pressure-flow relationship is thought to exist between PA pressures and increasing exercise intensity in athletes, yet a paucity of directly measured pulmonary hemodynamic data exists supporting this contention. We sought to describe the PA pressure, PA wedge pressure (PAWP), and RV functional responses to brief and prolonged exercise in endurance-trained athletes. Twenty-one healthy athletes (54 ± 5 yr) underwent right heart catheterization to assess pulmonary hemodynamics during graded, submaximal exercise. Measurements were made at rest and during three stages of steady-state, semiupright cycle ergometry at heart rates of 100 beats/min (EX1), 130 beats/min (EX2), and 150 beats/min (EX3). Five athletes completed an additional 34 min at 130 beats/min for a total exercise time of 60 min [prolonged exercise (PLG)]. PA pressures and PAWP increased significantly at EX1 without a further rise at EX2, EX3, or PLG. PAWP adjusted for absolute work rate demonstrated a significant decline as exercise intensity increased from EX1 to EX2. The resistance compliance time constant decreased at EX1 without further changes at EX2, EX3, and prolonged exercise. RV function did not decline during PLG. After an initial rise in PA pressure and PAWP during early, nonsteady-state exercise, values remained constant despite increases in exercise intensity and duration. These data indicate that in healthy, middle-aged endurance-trained athletes, the PA and pulmonary venous/left atrial compartments rapidly accommodate high conduit flows produced during intensive and prolonged exercise while maintaining RV function. NEW & NOTEWORTHY The right ventricular (RV)-pulmonary arterial (PA) circulatory unit has not been well studied during prolonged exercise, and this study provides an ecological approach that reflects a typical bout of endurance training integrating a transition from rest to exercise with successive increases in intensity, progressing to steady-state, sustained exercise. We demonstrated a remarkably constant response of the PA and PA wedge pressure during incremental, steady-state exercise and that no changes occur in pulmonary pressures throughout prolonged exercise, concomitant to a preservation of RV performance.

How consumer physical activity monitors could transform human physiology research.

A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O2, and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing.

Clinical Validation of Non-Invasive Cardiac Output Monitoring in Healthy Pregnant Women.

OBJECTIVE: Non-invasive hemodynamic monitoring has the potential to be a valuable clinical tool for the screening and management of hypertensive disorders of pregnancy. The objective of this study was to validate the clinical utility of the non-invasive cardiac output monitoring (NICOM) system in pregnant women. METHODS: Twenty healthy pregnant women with a singleton pregnancy at 22 to 26 weeks' gestation were enrolled in this study. Measures of heart rate, stroke volume, and cardiac output were obtained through NICOM and compared with Doppler echocardiography. RESULTS: NICOM significantly overestimated measures of both stroke volume and cardiac output compared with Doppler echocardiography (95 ± 4 vs. 73 ± 4 mL, P < 0.0001; and 7.4 ± 0.2 vs. 5.6 ± 0.2 L/min, P < 0.0001; respectively). CONCLUSIONS: There is no gold standard for the measurement of cardiac output in the setting of pregnancy. However, once normal values have been established, NICOM has the potential to be a useful clinical tool for monitoring maternal hemodynamics in pregnant women. Further investigation regarding the validity of NICOM is required in larger populations of healthy and hypertensive pregnant women to determine whether this device is appropriate for maternal hemodynamic assessment during pregnancy.

The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults.

KEY POINTS: A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship. This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP. We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise-associated increases in PAWP. Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP. Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. ABSTRACT: The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp-time. The RpCp-time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp-time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non-athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8-10 min stages of cycle ergometry, at targeted heart-rates of 100 beats min(-1) (Light) and 120 beats min(-1) (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate exercise. RpCp-time decreased for Light exercise (0.39 ± 0.08 to 0.25 ± 0.08, P < 0.001) without any further change for Moderate exercise, and the decrease in RpCp-time was related to changes in PAWP (r(2)  = 0.26, P < 0.001). Changes in PASP (r(2)  = 0.43, P < 0.001), PADP (r(2)  = 0.47, P < 0.001) and mPAP (r(2)  = 0.50, P < 0.001) were linearly correlated with changes in PAWP, although they were not significantly related to changes in cardiac output. In healthy adults, exercise is associated with decreases in Cp and a resultant decline in RpCp-time, indicating increased pulsatile right ventricular afterload. Changes in RpCp-time, PASP, PADP and mPAP were systematically related to increases in PAWP.

Left atrial reservoir pressure-volume relations during exercise in healthy older adults.

The left atrium (LA) mediates cardiopulmonary interactions. During ventricular systole, the LA functions as a compliant reservoir that is coupled to the left ventricle (LV) and offloads volume from the pulmonary vasculature. We aimed to describe LA reservoir function using phasic relationships between pulmonary artery wedge pressure (PAWP) and LA volume events. We included healthy adults (7 M/6 F, 56 ± 8 yr) who were studied at rest and during semirecumbent cycle ergometry at a target of 100 beats/min heart rate. Right heart catheterization was performed to record the PAWP and two-dimensional (2-D) echocardiography was used to measure LA and LV volumes. We manually measured A-wave, x-trough, V-wave, and y-trough PAWP beat-by-beat, as well as minimal, maximal, and precontraction biplane LA volumes. Heart rate increased by 40 ± 7 beats/min with exercise; stroke volume and cardiac output also rose. Although all phasic PAWP measurements increased with exercise, the x-V pressure pulse during LA filling doubled from 4 ± 2 to 8 ± 4 mmHg (P = 0.001). LA minimal volume was unchanged but maximal volume increased from 39 ± 9 to 48 ± 9 mL (P < 0.001) with exercise, and so reservoir volume increased from 24 ± 5 to 32 ± 8 mL (P < 0.001). As such, calculated LA compliance decreased from 6.8 ± 3.4 to 4.8 ± 2.6 mL/mmHg (P = 0.029). The product of V-wave PAWP and LA maximal volume, a surrogate for LA wall stress, increased from 486 ± 193 to 953 ± 457 mmHg·mL (P < 0.001). In healthy older adults during submaximal exercise, the PAWP waveform shifts upward and its amplitude widens, LA filling increases, LA compliance decreases modestly, and LA wall stress may augment substantially.NEW & NOTEWORTHY We combined invasive estimates of left atrial pressure with noninvasive left atrial volume measurements made at rest and during exercise in healthy humans. Left atrial pressure and volume both increased with exercise, though the pressure increase was relatively greater, and calculated compliance decreased modestly while estimated peak wall stress nearly doubled. Our results demonstrate left atrial loading during exercise in healthy older adults and provide insight into how the left atrium mediates cardiopulmonary interactions.

Exercise and pulsatile pulmonary vascular loading in chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary disease (CTEPD) is characterized by organized nonresolving thrombi in pulmonary arteries (PA). In CTEPD with pulmonary hypertension (PH), chronic thromboembolic PH (CTEPH), early wave reflection results in abnormalities of pulsatile afterload and augmented PA pressures. We hypothesized that exercise during right heart catheterization (RHC) would elicit more frequent elevations of pulsatile vascular afterload than resistive elevations in patients with CTEPD without PH. The interdependent physiology of pulmonary venous and PA hemodynamics was also evaluated. Consecutive patients with CTEPD without PH (resting mean PA pressure ≤20 mmHg) undergoing an exercise RHC were identified. Latent resistive and pulsatile abnormalities of pulmonary vascular afterload were defined as an exercise mean PA pressure/cardiac output >3 WU, and PA pulse pressure to PA wedge pressure (PA PP/PAWP) ratio >2.5, respectively. Forty-five patients (29% female, 53 ± 14 years) with CTEPD without PH were analyzed. With exercise, 19 patients had no abnormalities (ExNOR), 26 patients had abnormalities (ExABN) of pulsatile (20), resistive (2), or both (4) elements of pulmonary vascular afterload. Exercise elicited elevations of pulsatile afterload (53%) more commonly than resistive afterload (13%) (p < 0.001). ExABN patients had lower PA compliance and higher pulmonary vascular resistance at rest and exercise and prolonged resistance-compliance time product at rest. The physiological relationship between changes in PA pressures relative to PAWP was disrupted in the ExABN group. In CTEPD without PH, exercise RHC revealed latent pulmonary vascular afterload elevations in 58% of patients with more frequent augmentation of pulsatile than resistive pulmonary vascular afterload.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 9: Summary of Current Status, Challenges, Opportunities, and Recommendations.

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada.

Dans ce chapitre final de l'ATLAS sur l'épidémiologie, le diagnostic et la prise en charge de la maladie cardiovasculaire chez les femmes de l'Alliance canadienne de santé cardiaque pour les femmes, nous présentons les points saillants de l'ATLAS au sujet de l'état actuel des soins cardiovasculaires offerts aux femmes, ainsi que des défis et des occasions dans ce domaine. Nous concluons par 12 recommandations concrètes sur les prochaines étapes à entreprendre pour donner suite aux progrès déjà réalisés afin de combler les lacunes dans les connaissances, en s'attaquant aux disparités qui subsistent dans les soins cardiovasculaires prodigués aux femmes, dans le but d'améliorer les résultats de santé des femmes au Canada.

Sex differences in pulmonary and systemic vascular function at rest and during exercise in healthy middle-aged adults.

Our aim was to conduct a sex-disaggregated analysis of pulmonary and systemic vascular function in healthy individuals both at rest and during submaximal exercise. Healthy individuals underwent right-heart catheterization at rest and during submaximal cycling. Hemodynamic data were collected in a control state and with moderate exercise. Pulmonary and systemic vascular variables including: compliance, resistance, and elastance were calculated, indexed to body surface area (BSA), adjusted for age and compared between male and female sex. Thirty-six individuals (18M/18F; 54 ± 7 vs. 58 ± 6 years, p = 0.04) were included. When adjusted for age and indexed to BSA, total pulmonary resistance (TPulmR) (516 ± 73 vs. 424 ± 118 WU m-2, p = 0.03) and pulmonary arterial elastance (PEa) (0.41 ± 0.1 vs. 0.32 ± 0.1 mmHg ml-1 m2, p = 0.03) were higher in females vs. males. Both pulmonary (Cpa) and systemic compliance (Csa) were lower in females vs. males however lost significance with adjustment for age. Systemic arterial elastance (SEa) was higher in females (1.65 ± 0.29 vs. 1.31 ± 0.24 mmHg ml-1, p = 0.05). Secondary analyses demonstrated significant correlations between age and PVR (r = 0.33, p = 0.05), TPulmR (r = 0.35, p = 0.04), Cpa (r = -0.48, p < 0.01), and PEa (r = 0.37, p = 0.03). During exercise, there were greater increases in TPulmR (p = 0.02) and PEa (p = 0.01) in females vs. males. In conclusion, TPulmR and PEa are significantly higher at rest and exercise in females vs. males. Cpa and Csa were lower in females, however this may have been confounded by age. Our results are consistent with the notion that indices of pulmonary and systemic vascular load are higher, related to both older age and female sex, independent of heart failure.

Alterations of pulmonary vascular afterload in exercise-induced pre- and post-capillary pulmonary hypertension.

Exercise imposes increased pulmonary vascular afterload based on rises in pulmonary artery (PA) wedge pressure, declines in PA compliance, and resistance-compliance time. In health, afterload stress stabilizes during steady-state exercise. Our objective was to examine alterations of these exercise-associated stresses in states of pre- and post-capillary pulmonary hypertension (PH). PA hemodynamics were evaluated at rest, 2 and 7 min of steady-state exercise at moderate intensity in patients who exhibited Pre-capillary (n = 22) and post-capillary PH (n = 22). Patients with normal exercise hemodynamics (NOR-HD) (n = 32) were also studied. During exercise in all groups, PA wedge pressure increased at 2 min, with no further change at 7 min. In post-capillary PH and NOR-HD, increases in PA diastolic pressure and diastolic pressure gradient remained stable at 2 and 7 min of exercise, while in pre-capillary PH, both continued to increase at 7 min. The behavior of the diastolic pressure gradient was linearly related to the duration of resistance-compliance time at rest (r2  = 0.843) and exercise (r2  = 0.760). Exercise resistance-compliance time was longer in pre-capillary PH associated with larger increases in diastolic pressure gradient. Conversely, resistance-compliance time was shortest in post-capillary PH compared to pre-capillary PH and NOR-HD and associated with limited increases in exercise diastolic pressure gradient. During steady-state, modest-intensity exercise-specific patterns of pulmonary vascular afterload responses were observed in pre- and post-capillary PH relative to NOR-HD. Longer resistance-compliance time related to greater increases in PA diastolic pressure and diastolic pressure gradients in pre-capillary PH, while shorter resistance-compliance time appeared to limit these increases in post-capillary PH.

Hemodynamic and Clinical Determinants of Left Atrial Enlargement in Liver Transplant Candidates.

New-onset heart failure is a frequent complication after orthotopic liver transplantation (OLT). Left atrial enlargement (LAE) may be a sign of occult left heart disease. Our primary objective was to determine invasive hemodynamic and clinical predictors of LAE and then investigate its effect on post-transplant outcomes. Of 609 subjects who received OLT between January 1, 2010, and October 1, 2018, 145 who underwent preoperative right-sided cardiac catheterization and transthoracic echocardiography were included. Seventy-eight subjects (54%) had pretransplant LAE. Those with LAE had significantly lower systemic vascular resistance with higher cardiac and stroke volume index (61.0 vs 51.7 ml/m2; p <0.001), but there was no difference in pulmonary artery wedge pressure. There was a linear relation between left atrial volume index and stroke volume index (R2 = 0.490, p<0.001), but not pulmonary artery wedge pressure. The presence of severe LAE was associated with a reduced likelihood (hazard ratio = 0.26, p = 0.033) of reaching the composite end point of new-onset systolic heart failure, heart failure hospitalization, or heart failure death within 12 months post-transplant. There was also a significant reduction in LAE after transplantation (p = 0.013). In conclusion, LAE was common in OLT recipients and was more closely associated with stroke volume than left heart filling pressures. The presence of LAE was associated with a reduced likelihood of reaching composite outcomes and tended to regress after transplant.

Hemodynamic reserve predicts early right heart failure after LVAD implantation.

BACKGROUND: Early right heart failure (RHF) remains a major source of morbidity and mortality after left ventricular assist device (LVAD) implantation, yet efforts to predict early RHF have proven only modestly successful. Pharmacologic unloading of the left ventricle may be a risk stratification approach allowing for assessment of right ventricular and hemodynamic reserve. METHODS: We performed a multicenter, retrospective analysis of patients who had undergone continuous-flow LVAD implantation from October 2011 to April 2020. Only those who underwent vasodilator testing with nitroprusside during their preimplant right heart catheterization were included (n = 70). Multivariable logistic regression was used to determine independent predictors of early RHF as defined by Mechanical Circulatory Support-Academic Research Consortium. RESULTS: Twenty-seven patients experienced post-LVAD early RHF (39%). Baseline clinical characteristics were similar between patients with and without RHF. Patients without RHF, however, achieved higher peak stroke volume index (SVI) (30.1 ± 8.8 vs 21.7 ± 7.4 mL/m2; p < 0.001; AUC: 0.78; optimal cut-point: 22.1 mL/m2) during nitroprusside administration. Multivariable analysis revealed that peak SVI was significantly associated with early RHF, demonstrating a 16% increase in risk of early RHF per 1 ml/m2 decrease in SVI. A follow up cohort of 10 consecutive patients from July 2020 to October 2021 resulted in all patients being categorized appropriately in regards to early RHF versus no RHF according to peak SVI. CONCLUSION: Peak SVI with nitroprusside administration was independently associated with post-LVAD early RHF while resting hemodynamics were not. Vasodilator testing may prove to be a strong risk stratification tool when assessing LVAD candidacy though additional prospective validation is needed.