Exercise intolerance in heart failure: The important role of pulmonary hypertension.

NEW FINDINGS: What is the topic of this review? This review concerns the negative impact of pulmonary hypertension (PH) on the pulmonary haemodynamic and gas exchange responses to exercise, considering the mechanisms by which PH plays a role in exercise intolerance in heart failure (HF) patients. What advances does it highlight? The hallmark limited pulmonary vascular 'reserve' and impaired pulmonary gas exchange responses to exercise in HF are worsened by the development of PH; these are key determinants of exercise intolerance. Even HF patients who present with 'normal' pulmonary vascular function experience exercise-induced PH, which plays a role in exercise intolerance. ABSTRACT: Patients with heart failure universally complain of exertional intolerance, but the underlying cause(s) of this intolerance may differ between patients with different disease phenotypes. Exercise introduces an impressive stress to the lungs, where elevations in venous return and cardiac output engender substantial increases in pulmonary blood volume and flow. Relative to healthy individuals, the pulmonary vascular reserve to accept this increase in pulmonary perfusion is compromised in heart failure, with a growing body of evidence suggesting that the development of pulmonary hypertension (PH), and in particular a precapillary component of PH, worsens the pulmonary haemodynamic response to exercise in these patients. Characterized by an exaggerated increase in pulmonary arterial pressure and an elevation in pulmonary vascular resistance, this dysfunctional pulmonary haemodynamic response plays a role in exercise intolerance, probably through an impairment of right ventricular function, underperfusion of the pulmonary circulation and a subsequent reduction in systemic blood flow and oxygen delivery. The hallmark abnormalities in ventilatory and pulmonary gas exchange that accompany heart failure, including a greater ventilatory equivalent for carbon dioxide, are also worsened by the development of PH. This raises the possibility that measures of exercise pulmonary gas exchange might help to 'describe' underlying PH in heart failure; however, several fundamental issues and questions need to be addressed before such gas exchange measures could truly be considered efficacious measures used to differentiate the type of PH and track the severity of PH in heart failure. exercise intolerance, heart failure, pulmonary gas exchange, pulmonary haemodynamics, pulmonary hypertension.

Exercise Intolerance in Heart Failure: Central Role for the Pulmonary System.

We propose that abnormalities of the pulmonary system contribute significantly to the exertional dyspnea and exercise intolerance observed in patients with chronic heart failure. Interventions designed to address the deleterious pulmonary manifestations of heart failure may, therefore, yield promising improvements in exercise tolerance in this population.

Pulmonary and respiratory muscle function in response to 10 marathons in 10 days.

PURPOSE: Marathon and ultramarathon provoke respiratory muscle fatigue and pulmonary dysfunction; nevertheless, it is unknown how the respiratory system responds to multiple, consecutive days of endurance exercise. METHODS: Nine trained individuals (six male) contested 10 marathons in 10 consecutive days. Respiratory muscle strength (maximum static inspiratory and expiratory mouth-pressures), pulmonary function (spirometry), perceptual ratings of respiratory muscle soreness (Visual Analogue Scale), breathlessness (dyspnea, modified Borg CR10 scale), and symptoms of Upper Respiratory Tract Infection (URTI), were assessed before and after marathons on days 1, 4, 7, and 10. RESULTS: Group mean time for 10 marathons was 276 ± 35 min. Relative to pre-challenge baseline (159 ± 32 cmH2O), MEP was reduced after day 1 (136 ± 31 cmH2O, p = 0.017), day 7 (138 ± 42 cmH2O, p = 0.035), and day 10 (130 ± 41 cmH2O, p = 0.008). There was no change in pre-marathon MEP across days 1, 4, 7, or 10 (p > 0.05). Pre-marathon forced vital capacity was significantly diminished at day 4 (4.74 ± 1.09 versus 4.56 ± 1.09 L, p = 0.035), remaining below baseline at day 7 (p = 0.045) and day 10 (p = 0.015). There were no changes in FEV1, FEV1/FVC, PEF, MIP, or respiratory perceptions during the course of the challenge (p > 0.05). In the 15-day post-challenge period, 5/9 (56%) runners reported symptoms of URTI, relative to 1/9 (11%) pre-challenge. CONCLUSIONS: Single-stage marathon provokes acute expiratory muscle fatigue which may have implications for health and/or performance, but 10 consecutive days of marathon running does not elicit cumulative (chronic) changes in respiratory function or perceptions of dyspnea. These data allude to the robustness of the healthy respiratory system.

Influence of Thoracic Fluid Compartments on Pulmonary Congestion in Chronic Heart Failure.

INTRODUCTION: Pulmonary congestion is a common finding of heart failure (HF), but it remains unclear how pulmonary and heart blood volumes (Vp and Vh, respectively) and extravascular lung water (EVLW) change in stable HF and affect lung function. METHODS: Fourteen patients with HF (age 68 ± 11 y, LVEF 33 ± 8%) and 12 control subjects (age 65 ± 9 y) were recruited. A pulmonary function test, thoracic computerized tomographic (CT) scan, and contrast perfusion scan were performed. From the thoracic scan, a histogram of CT attenuation of lung tissue was generated and skew, kurtosis, and full-width half-max (FWHM) calculated as surrogates of EVLW. Blood volumes were calculated from the transit time of the contrast through the great vessels of the heart. RESULTS: Patients with HF had greater Vp and Vh (Vp 0.55 ± 0.21 L vs 0.41 ± 0.13 L; Vh 0.53 ± 0.33 L vs 0.40 ± 0.15 L) and EVLW (skew 3.2 ± 0.5 vs 3.7 ± 0.7; kurtosis 19.4 ± 6.6 vs 25.9 ± 9.4; FWHM 73 ± 13 HU vs 59 ± 9 HU). Spirometric measures were decreased in HF (percentage of predicted: forced vital capacity 86 ± 17% vs 104 ± 9%; forced expiratory volume in 1 second 83 ± 20% vs 105 ± 11%; maximal mid-expiratory flow 82 ± 42% vs 115 ± 43%). Vp was associated with decreased expiratory flows, and EVLW was associated with decreased lung volumes. CONCLUSIONS: Congestion in stable patients with HF includes expanded Vp and Vh and increased EVLW associated with reductions in lung volumes and expiratory flows.

Pulmonary capillary reserve and exercise capacity at high altitude in healthy humans.

PURPOSE: We determined whether well-acclimatized humans have a reserve to recruit pulmonary capillaries in response to exercise at high altitude. METHODS: At sea level, lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary membrane conductance (DmCO), and pulmonary capillary blood volume (V c) were measured at rest before maximal oxygen consumption ([Formula: see text]) was determined in seven adults. Then, DLCO, DmCO and V c were measured pre- and post-exhaustive incremental exercise at 5150 m after ~40 days of acclimatization. RESULTS: Immediately after exercise at high altitude, there was an increase in group mean DmCO (14 ± 10%, P = 0.040) with no pre- to post-exercise change in group mean DLCO (46.9 ± 5.8 vs. 50.6 ± 9.6 ml/min/mmHg, P = 0.213) or V c (151 ± 28 vs. 158 ± 37 ml, P = 0.693). There was, however, a ~20% increase in DLCO from pre- to post-exercise at high altitude (51.2 ± 0.2 vs. 61.1 ± 0.2 ml/min/mmHg) with a concomitant increase in DmCO (123 ± 2 vs. 156 ± 4 ml/min/mmHg) and V c (157 ± 3 vs. 180 ± 8 ml) in 2 of the 7 participants. There was a significant positive relationship between the decrease in [Formula: see text] from sea level to high altitude and the change in DLCO and lung diffusing capacity for nitric oxide (DLNO) from rest to end-exercise at high altitude. CONCLUSION: These data suggest that recruitment of the pulmonary capillaries in response to exercise at high altitude is limited in most well-acclimatized humans but that any such a reserve may be associated with better exercise capacity.

Association of Cognitive Performance with Time at Altitude, Sleep Quality, and Acute Mountain Sickness Symptoms.

OBJECTIVE: It is well documented that cognitive performance may be altered with ascent to altitude, but the association of various cognitive performance tests with symptoms of acute mountain sickness (AMS) is not well understood. Our objective was to assess and compare cognitive performance during a high-altitude expedition using several tests and to report the association of each test with AMS, headache, and quality of sleep. METHODS: During an expedition to Mount Everest, 3 cognitive tests (Stroop, Trail Making, and the real-time cognitive assessment tool, an in-house developed motor accuracy test) were used along with a questionnaire to assess health and AMS. Eight team members were assessed pre-expedition, postexpedition, and at several time points during the expedition. RESULTS: There were no significant differences (P >.05) found among scores taken at 3 time points at base camp and the postexpedition scores for all 3 tests. Changes in the Stroop test scores were significantly associated with the odds of AMS (P <.05). The logistic regression results show that the percent change from baseline for Stroop score (ß = -5.637; P = .032) and Stroop attempts (ß = -5.269; P = .049) are significantly associated with the odds of meeting the criteria for AMS. CONCLUSIONS: No significant changes were found in overall cognitive performance at altitude, but a significant relationship was found between symptoms of AMS and performance in certain cognitive tests. This research shows the need for more investigation of objective physiologic assessments to associate with self-perceived metrics of AMS to gauge effect on cognitive performance.

Submaximal Exercise Pulmonary Gas Exchange in Left Heart Disease Patients With Different Forms of Pulmonary Hypertension.

BACKGROUND: We determined whether pulmonary gas exchange indices during submaximal exercise are different in heart failure (HF) patients with combined post- and pre-capillary pulmonary hypertension (PPC-PH) versus HF patients with isolated post-capillary PH (IPC-PH) or no PH. METHODS AND RESULTS: Pulmonary hemodynamics and pulmonary gas exchange were assessed during rest and submaximal exercise in 39 HF patients undergoing right heart catheterization. After hemodynamic evaluation, patients were classified as having no PH (n = 11), IPC-PH (n = 12), or PPC-PH (n = 16). At an equivalent oxygen consumption, end-tidal CO2 (PETCO2) and arterial oxygen saturation (SaO2) were greater in no-PH and IPC-PH versus PPC-PH patients (36.1 ± 3.2 vs. 31.7 ± 4.5 vs. 26.2 ± 4.7 mm Hg and 97 ± 2 vs. 96 ± 3 vs. 91 ± 1%, respectively). Conversely, dead-space ventilation (VD/VT) and the ventilatory equivalent for carbon dioxide (V˙(E)/V˙CO2 ratio) were lower in no-PH and IPC-PH versus PPC-PH patients (0.37 ± 0.05 vs. 0.38 ± 0.04 vs. 0.47 ± 0.03 and 38 ± 5 vs. 42 ± 8 vs. 51 ± 8, respectively). The exercise-induced change in V(D)/V(T), V˙(E)/V˙CO2 ratio, and PETCO2 correlated significantly with the change in mean pulmonary arterial pressure, diastolic pressure difference, and transpulmonary pressure gradient in PPC-PH patients only. CONCLUSIONS: Noninvasive pulmonary gas exchange indices during submaximal exercise are different in HF patients with combined post- and pre-capillary PH compared with patients with isolated post-capillary PH or no PH.

Differential effects of exercise intensity and tolerable duration on exercise-induced diaphragm and expiratory muscle fatigue.

We investigated the effect of exercise intensity and tolerable duration on the development of exercise-induced diaphragm and expiratory muscle fatigue. Ten healthy adults (25 ± 5 yr; 2 females) cycled to intolerance on three separate occasions: 1) 5% below critical power ( 0.05). In conclusion, the magnitude of exercise-induced diaphragm fatigue was greater after longer-duration severe exercise than after shorter-duration severe and heavy exercise. By contrast, the magnitude of exercise-induced expiratory muscle fatigue was unaffected by exercise intensity and tolerable duration.NEW & NOTEWORTHY Exercise-induced respiratory muscle fatigue contributes to limiting exercise tolerance. Accordingly, better understanding the exercise conditions under which respiratory muscle fatigue occurs is warranted. Although heavy-intensity as well as short- and long-duration severe-intensity exercise performed to intolerance elicit diaphragm and expiratory muscle fatigue, we find, for the first time, that the relationship between exercise intensity, exercise duration, and the magnitude of exercise-induced fatigue is different for the diaphragm compared with the expiratory muscles.

Effect of Ultra-Marathon Trail Running at Sea Level and Altitude on Alveolar-Capillary Function and Lung Diffusion.

INTRODUCTION: Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress-tolerability of the alveolar-capillary unit. This study examined the effect of ultra-marathon trail racing at different altitudes (ranging from <1000 m to between 1500 - 2700 m) on alveolar-capillary recruitment and lung diffusion. METHODS: Cardiac and lung function were examined before and after an ultra-marathon in 67 runners (age:41 ± 9y, BMI:23 ± 2 kg/m2, 10 females), and following 12-24 h of recovery in a subset (n = 27). Cardiac biomarkers (cTnI & BNP) were assessed from whole blood, while lung fluid accumulation (comet tails), stroke volume (SV) and cardiac output (Q) were quantified via echocardiography. Lung diffusing capacity for carbon monoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semi-recumbent cycling (20, 30, & 40 W). RESULTS: Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± .02 vs 0.13 ± .03 ng/ml; BNP: 20 ± 2 vs 112 ± 21 pg/ml, p < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, p < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 ml; 40 W: 93 ± 2 vs 88 ± 2 ml, p < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 l/min, p < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 l/min, p = 0.899). Resting DLco and Vc decreased after the race (p < 0.01), while Dm was unchanged (p = 0.465); however, during the three stages of exercise DLco, Vc and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL/min/mmHg; 83 ± 3 vs 73 ± 2 mL; 186 ± 6 vs 170 ± 7 mL/min/mmHg, respectively, p < 0.01). When corrected for alveolar volume and Q, DLco decreased from pre- to post-race (p < 0.01), and changes in DLco were similar for all ultra-marathon events (p > 0.05). CONCLUSIONS: Competing in an ultra-marathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar-capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultra-marathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures.

A possible role for systemic hypoxia in the reactive component of pulmonary hypertension in heart failure.

BACKGROUND: The mechanisms underlying the reactive component of pulmonary hypertension (PH) in heart failure (HF) are unclear. We examined whether resting systemic oxygen levels are related to pulmonary hemodynamics in HF. METHODS AND RESULTS: Thirty-nine HF patients underwent right heart catheterization. Subsequently, patients were classified as having: 1) no PH (n = 12); 2) passive PH (n = 10); or 3) reactive PH (n = 17). Blood was drawn from the radial and pulmonary arteries for the determination of PaO(2), SaO(2), PvO(2), SvO(2), and vasoactive neurohormones. PaO(2) and PvO(2) were lower in reactive PH versus no PH and passive PH patients (65.3 ± 8.6 vs 78.3 ± 11.4 mm Hg and 74.5 ± 14.0 mm Hg; 29.2 ± 4.1 vs 36.2 ± 2.8 mm Hg and 33.4 ± 2.3 mm Hg; P < .05). SaO(2) and SvO(2) were lower in reactive PH versus no PH patients (93 ± 3% vs 96 ± 3%; 51 ± 11% vs 68 ± 4%; P < .05), but not different versus passive PH patients. The transpulmonary pressure gradient (TPG) was inversely related to PaO(2), PvO(2), SaO(2), and SvO(2) in the reactive PH patients only (r ≤ -0.557; P < .05). Similarly, plasma endothelin-1 correlated with PaO(2), PvO(2), SvO(2) (r ≤ -0.495), and TPG (r = 0.662; P < .05) in reactive PH patients only. CONCLUSIONS: Systemic hypoxia may play a role in the reactive component of PH in HF, potentially via a hypoxia-induced increase in endothelial release of the vasoconstrictor endothelin-1.

Energy expenditure and intensity levels during a 6170-m summit in the Karakoram Mountains.

OBJECTIVE: Although the majority of high altitude studies have used doubly labeled water to assess energy expenditure (EE), minimal research has examined variation in intensity levels while participating in such an expedition. The purpose of this study was to use ambulatory monitoring technology to assess EE and time spent in moderate (3.0-6.0 METS), vigorous (6.0-9.0 METS), and very vigorous (>9.0 METS) intensities during an expedition to summit a 6170-m peak in Northern Pakistan. METHODS: Twelve men and 2 women were studied. Their EE was determined from galvanic skin response, heat flux, and biaxial accelerometry using a multisensor armband. Lake Louise Scores for altitude illness assessment were obtained each morning. RESULTS: Average daily total EE and number of steps taken was 4173 ± 848 kcal/d (range, 3332 to 4838 kcal/d) and 26,232 ± 7210 steps/d (range, 11,788 to 34,979 steps/d), respectively. On average, subjects spent approximately 7.7 h/d performing physical activity (>3.0 METS). Of this, subjects spent 399 ± 107, 61 ± 77, and 3 ± 10 min/d at moderate, vigorous, and very vigorous intensity levels, respectively, corresponding to 88%, 11%, and 1% of total physical activity time. During summit day, subjects climbed at an intensity equivalent to approximately 42% of their high altitude predicted maximal oxygen consumption at 5100 m). CONCLUSIONS: During a high altitude expedition, subjects predominantly exercise at a moderate intensity, with limited time spent at higher intensity levels. Use of accelerometer-based technology may provide more cost-effective and logistically easier means of assessing EE in extreme environments.

Pulmonary Capillary Recruitment Is Attenuated Post Left Ventricular Assist Device Implantation.

There is limited knowledge of pulmonary physiology and pulmonary function after continuous flow-left ventricular assist device (CF-LVAD) implantation. Therefore, this study investigated whether CF-LVAD influenced pulmonary circulation by assessing pulmonary capillary blood volume and alveolar-capillary conductance in addition to pulmonary function in patients with heart failure. Seventeen patients with severe heart failure who were scheduled for CF-LVAD implantation (HeartMate II, III, Abbott, Abbott Park, IL or Heart Ware, Medtronic, Minneapolis, MN) participated in the study. They underwent pulmonary function testing (measures of lung volumes and flow rates) and unique measures of pulmonary physiology using a rebreathe technique that quantified the diffusing capacity of the lungs for carbon monoxide (DLCO) and diffusing capacity of the lungs for nitric oxide before and 3 months after CF-LVAD implantation. After CF-LVAD, pulmonary function was not significantly changed (p >0.05). For lung diffusing capacity, alveolar volume (VA) was not changed (p = 0.47), but DLCO was significantly reduced (p = 0.04). After correcting for VA, DLCO/VA showed a trend toward reduction (p = 0.08). For the alveolar-capillary component, capillary blood volume (Vc) was significantly reduced (p = 0.04), and alveolar-capillary membrane conductance trended toward a reduction (p = 0.06). However, alveolar-capillary membrane conductance/Vc was not altered (p = 0.92). In conclusion, soon after CF-LVAD implantation, Vc is reduced likely because of pulmonary capillary derecruitment, which contributes to the decrease in lung diffusing capacity.

Does COVID-19 impair V̇o2peak in patients with cardiorespiratory disease? Insight from cardiopulmonary responses to maximal exercise pre- and post-illness.

Reduced exercise capacity has been suggested as a cardinal sequela of COVID-19. However, only cross-sectional approaches that either do not consider individuals with concomitant cardiorespiratory disease or account for exercise capacity before infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) support this assumption. Is reduced exercise capacity a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease? We retrospectively reviewed cardiopulmonary exercise testing (CPET) data collected across three hospitals between October 2018 and March 2022. Forty-two patients who completed a CPET before and after COVID-19 and 25 patients who performed two separate CPETs but did not contract COVID-19 (CTL) were included. Within each patient, the same test protocol was performed at the first and second CPETs. The time between CPETs was similar between the groups (COVID-19 489 ± 534 vs. CTL 534 ± 257 days, P = 0.662). The COVID-19 group performed the CPETs 312 ± 232 days before and 176 ± 110 days after infection. Exercise time, peak heart rate, peak systolic pressure, oxygen uptake (V̇o2) at anaerobic threshold, peak ventilation, and ventilatory efficiency were not different between the CPETs in both groups. Peak V̇o2 was reduced from before to after SARS-CoV-2 infection. However, the change in V̇o2peak from the first to the second CPET was not different between COVID-19 vs. CTL. Accounting for V̇o2peak before COVID-19 and including a group of control patients, we find limited evidence for reduced exercise capacity as a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease.NEW & NOTEWORTHY There is accumulating evidence that reduced exercise capacity is, or can be, an outcome following COVID-19. However, evidence to date relies upon cross-sectional approaches that either do not consider patients with concomitant cardiorespiratory disease or account for pre-infection exercise capacity data. Accounting for V̇o2peak before COVID-19 and including a group of control patients, we find limited evidence for reduced exercise capacity as a sequela of SARS-CoV-2 infection in patients with concomitant cardiorespiratory disease.

Pneumatic stenting in the surgical candidacy assessment for cough variant expiratory central airway collapse.

Expiratory Central Airway Collapse (ECAC) is a multifactorial, underdiagnosed entity that poses unique challenges. Airway stenting is used as a predictor for successful outcomes after central airway stabilization surgery via tracheobronchoplasty (TBP). This approach may pose suboptimal performance in certain ECAC variants. We hypothesize that Continuous Positive Airway Pressure (CPAP), used as a pneumatic stent, could be a non-invasive alternative to evaluate surgical candidacy in cough-predominant ECAC presentations. We report on a 67-year-old female with a history of chronic cough and confirmed ECAC. After optimization of medical therapy without significant relief and unsuccessful stent trial. We opted to perform CPAP trial during exercise, the patient exercised on a treadmill, and CPAP was applied at two levels (9 cmH2O, 11 cmH2O). The use of CPAP was associated with resolution of cough and a decrease in exercise-related perceived exertion. Applying CPAP during exercise may be a promising alternative to stent trials to determine patients' candidacy for surgical management of cough-predominant ECAC.

Lung "Comet Tails" in Healthy Individuals: Accumulation or Clearance of Extravascular Lung Water?

Parks, Jordan K, Courtney M. Wheatley-Guy, Glenn M. Stewart, Caitlin C. Fermoyle, Bryan J. Taylor, Jesse Schwartz, Briana Ziegler, Kay Johnson, Alice Gavet, Loïc Chabridon, Paul Robach, and Bruce D. Johnson. Lung "Comet Tails" in healthy individuals: accumulation or clearance of extravascular lung water? High Alt Med Biol. 24:230-233, 2023-Ultrasound lung comet tails (or B-lines) tend to be limited in number (<5) or absent under ultrasound examination, and the appearance of diffuse B-lines with lung sliding has been suggested to identify pulmonary edema. Clinical evaluation of B-lines has been utilized as a bedside test to assess pulmonary congestion in patients with heart failure. Exposure to altitude or prolonged exercise can alter fluid regulation and can lead to pulmonary congestion or edema. As such, B-lines have been utilized in the field to monitor for pathological lung fluid accumulation. However, ultrasound lung comet lines might not be as reliable for identifying extravascular lung water (EVLW) as previously thought in healthy individuals exercising at altitude where an increase in the number of ultrasound lung comets would reflect fluid buildup in the interstitial space of the alveoli and pulmonary capillaries. This report will focus on reviewing the literature and our data from a group of ultraendurance runners that completed the Ultra Trail Mont Blanc race that demonstrates that lung comet tails may not always be evidence of pathological fluid accumulation in healthy individuals and as such should be used to assess EVLW in concert with other diagnostic testing.

Inspiratory muscle weakness in cardiovascular diseases: Implications for cardiac rehabilitation.

Exercise limitation is a cardinal manifestation of many cardiovascular diseases (CVD) and is associated with poor prognosis. It is increasingly well understood that exercise-based cardiac rehabilitation (CR) is an intervention that portends favorable clinical outcomes, including improvements in exercise capacity. The etiology of exercise limitation in CVD is multifactorial but is typically governed by terminal sensations of pain, fatigue, and/or breathlessness. A known but perhaps underestimated complication of CVD that contributes to breathlessness and exercise intolerance in such patients is inspiratory muscle dysfunction. For example, inspiratory muscle dysfunction, which encompasses a loss in muscle mass and/or pressure generating capacity, occurs in up to ~40% of patients with chronic heart failure and is associated with breathlessness, exertional intolerance, and worse survival in this patient population. In this review, we define inspiratory muscle weakness, detail its prevalence in a range of CVDs, and discuss how inspiratory weakness impacts physiological function and clinical outcomes in patients with CVD often referred to CR. We also evaluate the available evidence addressing the effects of exercise-based CR with and without concurrent specific inspiratory muscle training (IMT) on inspiratory muscle function, general physiological function, and clinical outcomes in patients with CVD. Finally, we consider whether the assessment of global respiratory muscle function should become standard as part of the patient intake assessment for phase II CR programs, giving practical guidance on the implementation of such measures as well as IMT as part of phase II CR.

Sex-Specific Physiological Responses to Ultramarathon.

PURPOSE: Despite a growing body of literature on the physiological responses to ultramarathon, there is a paucity of data in females. This study assessed the female physiological response to ultramarathon and compared the frequency of perturbations to a group of race- and time-matched males. METHODS: Data were collected from 53 contestants of an ultramarathon trail race at the Ultra-Trail du Mont-Blanc (UTMB®) in 2018/19. Before and within 2 h of the finish, participants underwent physiological assessments, including blood sampling for biomarkers (creatine kinase-MB isoenzyme [CK-MB], cardiac troponin I [cTnI], brain natriuretic peptide [BNP], and creatinine [Cr]), pulmonary function testing (spirometry, exhaled NO, diffusing capacities, and mouth pressures), and transthoracic ultrasound (lung comet tails, cardiac function). Data from eight female finishers (age = 36.6 ± 6.9 yr; finish time = 30:57 ± 11:36 h:min) were compared with a group of eight time-matched males (age = 40.3 ± 8.3 yr; finish time = 30:46 ± 10:32 h:min). RESULTS: Females exhibited significant pre- to postrace increases in BNP (25.8 ± 14.6 vs 140.9 ± 102.7 pg·mL -1 ; P = 0.007) and CK-MB (3.3 ± 2.4 vs 74.6 ± 49.6 IU·L -1 ; P = 0.005), whereas males exhibited significant pre- to postrace increases in BNP (26.6 ± 17.5 vs 96.4 ± 51.9 pg·mL -1 ; P = 0.002), CK-MB (7.2 ± 3.9 vs 108.8 ± 37.4 IU·L -1 ; P = 0.002), and Cr (1.06 ± 0.19 vs 1.23 ± 0.24 mg·dL -1 ; P = 0.028). Lung function declined in both groups, but males exhibited additional reductions in lung diffusing capacities (DL CO = 34.4 ± 5.7 vs 29.2 ± 6.9 mL⋅min -1 ⋅mm Hg -1 , P = 0.004; DL NO = 179.1 ± 26.2 vs 152.8 ± 33.4 mL⋅min -1 ⋅mm Hg -1 , P = 0.002) and pulmonary capillary blood volumes (77.4 ± 16.7 vs 57.3 ± 16.1 mL; P = 0.002). Males, but not females, exhibited evidence of mild postrace pulmonary edema. Pooled effect sizes for within-group pre- to postrace changes, for all variables, were generally larger in males versus females ( d = 0.86 vs 0.63). CONCLUSIONS: Ultramarathon negatively affects a range of physiological functions but generally evokes more frequent perturbations, with larger effect sizes, in males compared to females with similar race performances.

The Effect of Preexercise Expiratory Muscle Loading on Exercise Tolerance in Healthy Men.

PURPOSE: Acute nonfatiguing inspiratory muscle loading transiently increases diaphragm excitability and global inspiratory muscle strength and may improve subsequent exercise performance. We investigated the effect of acute expiratory muscle loading on expiratory muscle function and exercise tolerance in healthy men. METHODS: Ten males cycled at 90% of peak power output to the limit of tolerance (TLIM) after 1) 2 × 30 expiratory efforts against a pressure-threshold load of 40% maximal expiratory gastric pressure (PgaMAX) (EML-EX) and 2) 2 × 30 expiratory efforts against a pressure-threshold load of 10% PgaMAX (SHAM-EX). Changes in expiratory muscle function were assessed by measuring the mouth pressure (PEMAX) and PgaMAX responses to maximal expulsive efforts and magnetically evoked (1 Hz) gastric twitch pressure (Pgatw). RESULTS: Expiratory loading at 40% of PgaMAX increased PEMAX (10% ± 5%, P = 0.001) and PgaMAX (9% ± 5%, P = 0.004). Conversely, there was no change in PEMAX (166 ± 40 vs 165 ± 35 cm H2O, P = 1.000) or PgaMAX (196 ± 38 vs 192 ± 39 cm H2O, P = 0.215) from before to after expiratory loading at 10% of PgaMAX. Exercise time was not different in EML-EX versus SHAM-EX (7.91 ± 1.96 vs 8.09 ± 1.77 min, 95% CI = -1.02 to 0.67, P = 0.651). Similarly, exercise-induced expiratory muscle fatigue was not different in EML-EX versus SHAM-EX (-28% ± 12% vs -26% ± 7% reduction in Pgatw amplitude, P = 0.280). Perceptual ratings of dyspnea and leg discomfort were not different during EML-EX versus SHAM-EX. CONCLUSION: Acute expiratory muscle loading enhances expiratory muscle function but does not improve subsequent severe-intensity exercise tolerance in healthy men.