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Classification of the total sample (n=156) according to the HFA-PEFF algorithm (A) and the H 2 FPEF score (B), along with corresponding rates of invasively defined heart failure with preserved ejection fraction (HFpEF inv). Sources of Funding This work was supported by grants from the National Institutes of Health (R01HL134893, R01-HL140224, and K24 HL153669 to Dr Ho, R01-HL142809 to Dr Malhotra, K23-HL138260 to Dr Nayor, and R01-HL131029 to Dr Lewis) and the American Heart Association (15GPSGC24800006 to Dr Lewis). Pulmonary capillary wedge pressure patterns during exercise predict exercise capacity and incident heart failure. [Extracted from the article]

Background: Peak oxygen consumption and oxygen pulse along with their respective percent predicted measures are gold standards of exercise capacity. To date, no studies have investigated the relationship between percent predicted peak oxygen pulse (%PredO 2 P) and ventricular-vascular response (VVR) and the association of %PredO 2 P with all-cause mortality in heart failure with preserved ejection fraction (HFpEF) patients., Objectives: The authors investigated the association between: 1) CPET measures of %PredO 2 P and VVR; and 2) %PredO 2 P and all-cause mortality in HFpEF patients., Methods: Our cohort of 154 HFpEF patients underwent invasive CPET and were grouped into %PredO 2 P tertiles. The association between percent predicted Fick components and markers of VVR (ie, proportionate pulse pressure, effective arterial elastance) was determined with correlation analysis. The Cox proportional hazards model was used to identify predictors of mortality., Results: The participants' mean age was 57 ± 15 years. Higher %PredO 2 P correlated with higher exercise capacity. In terms of VVR, higher %PredO 2 P correlated with a lower pressure for a given preload (effective arterial elastance r = -0.45, P  < 0.001 and proportionate pulse pressure r = -0.22, P  = 0.008). %PredO 2 P distinguished normal and abnormal percent predicted peak stroke volume and correlated positively with %PredVO 2 (r = 0.61, P  < 0.001). Participants had a median follow-up time of 5.6 years and 15% death. Adjusted for age and body mass index, there was a 5% relative reduction in mortality (HR: 0.95, 95% CI: 0.92-0.98, P  = 0.003) for every percent increase in %PredO 2 P., Conclusions: In HFpEF, %PredO 2 P is a VVR marker that can stratify invasive parameters such as percent predicted peak stroke volume. %PredO 2 P is an independent prognostic marker for all-cause mortality and those with higher %PredO 2 P exhibited longer survival., Competing Interests: Dr Malhotra was supported by the National Heart, Lung, and Blood Institute (R01HL142809, R01HL159514, and R01HL162928), the American Heart Association (22TPA969625), and the Wild Family Foundation. Dr Malhotra has received research funding from Angea Biotherapeutics and Amgen; and serves as a consultant for Myokardia/BMS, Renovacor, Epizon Pharma, and Third Pole. Dr Malhotra is a co-founder of Patch, Inc; is a co-inventor for a patent on pharmacologic BMP inhibitors (along with Mass General Brigham) for which he receives royalties; and has received royalties from UpToDate for scientific content authorship. Dr Nayor was supported by NIH grants K23-HL138260, R01-HL156975, and R01-HL131029 and by a Career Investment Award from the Department of Medicine, Boston University School of Medicine; and has received speaking honoraria from Cytokinetics. Dr Lewis has received research funding from the National Institutes of Health R01-HL 151841, R01-HL131029, R01-HL159514, American Heart Association 15GPSGC-24800006 and Amgen, Cytokinetics, Applied Therapeutics, AstraZeneca, and SoniVie; has received honoraria for advisory boards outside of the current study from Pfizer, Merck, Boehringer Ingelheim, NXT, American Regent, Cyclerion, Cytokinetics, and Amgen; and has received royalties from UpToDate for scientific content authorship related to exercise physiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Whether systemic oxygen levels (SaO 2 ) during exercise can provide a window into invasively derived exercise hemodynamic profiles in patients with undifferentiated dyspnea on exertion is unknown., Methods: We performed cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial blood gas sampling in individuals referred for dyspnea on exertion. Receiver operator analysis was performed to distinguish heart failure with preserved ejection fraction from pulmonary arterial hypertension., Results: Among 253 patients (mean ± SD, age 63 ± 14 years, 55% female, arterial O 2 [PaO 2 ] 87 ± 14 mmHg, SaO 2 96% ± 4%, resting pulmonary capillary wedge pressure [PCWP] 18 ± 4mmHg, and pulmonary vascular resistance [PVR] 2.7 ± 1.2 Wood units), there was no exercise PCWP threshold, measured up to 49 mmHg, above which hypoxemia was consistently observed. Exercise PaO 2 was not correlated with exercise PCWP (rho = 0.04; P = 0.51) but did relate to exercise PVR (rho = -0.46; P < 0.001). Exercise PaO 2 and SaO 2 levels distinguished left-heart-predominant dysfunction from pulmonary-vascular-predominant dysfunction with an area under the curve of 0.89 and 0.89, respectively., Conclusion: Systemic O 2 levels during exercise distinguish relative pre- and post-capillary pulmonary hemodynamic abnormalities in patients with undifferentiated dyspnea. Hypoxemia during upright exercise should not be attributed to isolated elevation in left heart filling pressures and should prompt consideration of pulmonary vascular dysfunction., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to evaluate hemodynamic correlates of inducible blood pressure (BP) pulsatility with exercise in heart failure with preserved ejection fraction (HFpEF), to identify relationships to outcomes, and to compare this with heart failure with reduced ejection fraction (HFrEF)., Background: In HFpEF, determinants and consequences of exercise BP pulsatility are not well understood., Methods: We measured exercise BP in 146 patients with HFpEF who underwent invasive cardiopulmonary exercise testing. Pulsatile BP was evaluated as proportionate pulse pressure (PrPP), the ratio of pulse pressure to systolic pressure. We measured pulmonary arterial catheter pressures, Fick cardiac output, respiratory gas exchange, and arterial stiffness. We correlated BP changes to central hemodynamics and cardiovascular outcome (nonelective cardiovascular hospitalization) and compared findings with 57 patients with HFrEF from the same referral population., Results: In HFpEF, only age (standardized beta = 0.593; P < 0.001), exercise stroke volume (standardized beta = 0.349; P < 0.001), and baseline arterial stiffness (standardized beta = 0.182; P = 0.02) were significant predictors of peak exercise PrPP in multivariable analysis (R = 0.661). In HFpEF, lower PrPP was associated with lower risk of cardiovascular events, despite adjustment for confounders (HR:0.53 for PrPP below median; 95% CI: 0.28-0.98; P = 0.043). In HFrEF, lower exercise PrPP was not associated with arterial stiffness but was associated with lower peak exercise stroke volume (P = 0.013) and higher risk of adverse cardiovascular outcomes (P = 0.004)., Conclusions: In HFpEF, greater inducible BP pulsatility measured using exercise PrPP reflects greater arterial stiffness and higher risk of adverse cardiovascular outcomes, in contrast to HFrEF where inducible exercise BP pulsatility relates to stroke volume reserve and favorable outcome., Competing Interests: Funding Support and Author Disclosures Dr Namasivayam is supported by a Clinical and Research Fellowship from the Division of Cardiology, Massachusetts General Hospital, Harvard Medical School; and is a recipient of the St. Vincent’s Clinic Travelling Fellowship Award. Dr Lewis is supported by the American Heart Association Award 15GPSGC24800006 and by the National Heart, Lung and Blood Institute Awards R01-HL 131029 and R01-HL151841. Dr Nayor is supported by National Institutes of Health/National Heart, Lung, and Blood Institute K23-HL138260. Dr Ho is supported by National Institutes of Health/National Heart, Lung, and Blood Institute R01-HL134893 and R01-HL140224. Dr Malhotra is supported by Transformation Project Award 18TPA34230025 from the American Heart Association and grant R01-HL142809 from the National Heart, Lung, and Blood Institute. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Background: Obesity has multifactorial effects on lung function and exercise capacity. The contributions of obesity-related inflammatory pathways to alterations in lung function remain unclear., Research Question: To examine the association of obesity-related inflammatory pathways with pulmonary function, exercise capacity, and pulmonary-specific contributors to exercise intolerance., Method: We examined 695 patients who underwent cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring at Massachusetts General Hospital between December 2006-June 2017. We investigated the association of adiponectin, leptin, resistin, IL-6, CRP, and insulin resistance (HOMA-IR) with pulmonary function and exercise parameters using multivariable linear regression., Results: Obesity-related inflammatory pathways were associated with worse lung function. Specifically, higher CRP, IL-6, and HOMA-IR were associated with lower percent predicted FEV 1 and FVC with a preserved FEV 1 /FVC ratio suggesting a restrictive physiology pattern (P ≤ 0.001 for all). For example, a 1-SD higher natural-logged CRP level was associated with a nearly 5% lower percent predicted FEV 1 and FVC (beta -4.8, s.e. 0.9 for FEV1; beta -4.9, s.e. 0.8 for FVC; P < 0.0001 for both). Obesity-related inflammatory pathways were associated with worse pulmonary vascular distensibility (adiponectin, IL-6, and CRP, P < 0.05 for all), as well as lower pulmonary artery compliance (IL-6 and CRP, P ≤ 0.01 for both)., Interpretation: Our findings highlight the importance of obesity-related inflammatory pathways including inflammation and insulin resistance on pulmonary spirometry and pulmonary vascular function. Specifically, systemic inflammation as ascertained by CRP, IL-6 and insulin resistance are associated with restrictive pulmonary physiology independent of BMI. In addition, inflammatory markers were associated with lower exercise capacity and pulmonary vascular dysfunction., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Arterial stiffness is thought to contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We sought to examine arterial stiffness in HFpEF and hypertension and investigate associations of arterial and left ventricular hemodynamic responses to exercise., Methods and Results: A total of 385 symptomatic individuals with an EF of ≥50% underwent upright cardiopulmonary exercise testing with invasive hemodynamic assessment of arterial stiffness and load (aortic augmentation pressure, augmentation index, systemic vascular resistance index, total arterial compliance index, effective arterial elastance index, and pulse pressure amplification) at rest and during incremental exercise. An abnormal hemodynamic response to exercise was defined as a steep increase in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO > 2 mm Hg/L/min). We compared rest and exercise measures between HFpEF and hypertension in multivariable analyses. Among 188 participants with HFpEF (mean age 61 ± 13 years, 56% women), resting arterial stiffness parameters were worse compared with 94 hypertensive participants (mean age 55 ± 15 years, 52% women); these differences were accentuated during exercise in HFpEF (all P ≤ .0001). Among all participants, exercise measures of arterial stiffness correlated with worse ∆PCWP/∆CO. Specifically, a 1 standard deviation higher exercise augmentation pressure was associated with 2.15-fold greater odds of abnormal LV hemodynamic response (95% confidence interval 1.52-3.05; P < .001). Further, exercise measures of systemic vascular resistance index, elastance index, and pulse pressure amplification correlated with a lower peak oxygen consumption., Conclusions: Exercise accentuates the increased arterial stiffness found in HFpEF, which in turn correlates with left ventricular hemodynamic responses. Unfavorable ventricular-vascular interactions during exercise in HFpEF may contribute to exertional intolerance and inform future therapeutic interventions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Respiratory tract infections (RTIs) are expensive for MCOs and cause significant morbidity among their members. Although awareness of resistance to antibiotics is increasing, antibiotic selection for community-acquired RTIs remains largely empiric. When making formulary decisions, Pharmacy and Therapeutics Committees may want to consider the spectrum of coverage that an antibiotic provides and its vulnerability to resistance development. Through appropriate formulary management and provider education, MCOs can promote successful clinical and economic outcomes. This article examines the current status of antibiotic therapy for community-acquired RTIs and encourages the incorporation of new parameters into MCO formulary decision processes.