Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach. / Ineficiência Ventilatória Comparável no Desempenho Máximo e Submáximo em Indivíduos com DPOC e ICC: Uma Abordagem Inovadora.

BACKGROUND: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E - V ˙ CO 2 ). Alternatively, a new approach for ventilatory efficiency ( η E V ˙ ) has been published. OBJECTIVE: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E - V ˙ CO 2 slope and intercept). METHODS: Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E - V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. RESULTS: The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E - V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). CONCLUSION: The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.

FUNDAMENTO: Atualmente, o excesso de ventilação tem sido fundamentado na relação entre ventilação-minuto/produção de dióxido de carbono ( V ˙ E − V ˙ CO 2 ). Alternativamente, uma nova abordagem para eficiência ventilatória ( η E V ˙ ) tem sido publicada. OBJETIVO: Nossa hipótese principal é que níveis comparativamente baixos de η E V ˙ entre insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) são atingíveis para um nível semelhante de desempenho aeróbico máximo e submáximo, inversamente aos métodos estabelecidos há muito tempo (inclinação V ˙ E − V ˙ CO 2 e intercepto). MÉTODOS: Ambos os grupos realizaram testes de função pulmonar, ecocardiografia e teste de exercício cardiopulmonar. O nível de significância adotada na análise estatística foi 5%. Assim, dezenove indivíduos elegíveis para DPOC e dezenove indivíduos elegíveis para ICC completaram o estudo. Com o objetivo de contrastar valores completos de V ˙ E − V ˙ CO 2 e η E V ˙ para o período de exercício (100%), correlações foram feitas com frações menores, como 90% e 75% dos valores máximos. RESULTADOS: Os dois grupos tiveram características correspondentes para a idade (62±6 vs 59±9 anos, p>.05), sexo (10/9 vs 14/5, p>0,05), IMC (26±4 vs 27±3 Kg m2, p>0,05), e pico V ˙ O 2 (72±19 vs 74±20 % pred, p>0,05), respectivamente. A inclinação V ˙ E − V ˙ CO 2 e intercepto foram significativamente diferentes para DPOC e ICC (207,2±1,4 vs 33,1±5,7 e 5,3±1,9 vs 1,7±3,6, p<0,05 para ambas), mas os valores médios da η E V ˙ foram semelhantes entre os grupos (10,2±3,4 vs 10,9±2,3%, p=0,462). As correlações entre 100% do período do exercício com 90% e 75% dele foram mais fortes para η E V ˙ (r>0,850 para ambos). CONCLUSÃO: A η E V ˙ é um método valioso para comparação entre doenças cardiopulmonares, com mecanismos fisiopatológicos até agora distintos, incluindo restrições ventilatórias na DPOC.

Ineficiência Ventilatória Comparável no Desempenho Máximo e Submáximo em Indivíduos com DPOC e ICC: Uma Abordagem Inovadora / Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach

Resumo Fundamento: Atualmente, o excesso de ventilação tem sido fundamentado na relação entre ventilação-minuto/produção de dióxido de carbono ( V ˙ E − V ˙ CO 2). Alternativamente, uma nova abordagem para eficiência ventilatória ( η E V ˙) tem sido publicada. Objetivo: Nossa hipótese principal é que níveis comparativamente baixos de η E V ˙ entre insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) são atingíveis para um nível semelhante de desempenho aeróbico máximo e submáximo, inversamente aos métodos estabelecidos há muito tempo (inclinação V ˙ E − V ˙ CO 2 e intercepto). Métodos: Ambos os grupos realizaram testes de função pulmonar, ecocardiografia e teste de exercício cardiopulmonar. O nível de significância adotada na análise estatística foi 5%. Assim, dezenove indivíduos elegíveis para DPOC e dezenove indivíduos elegíveis para ICC completaram o estudo. Com o objetivo de contrastar valores completos de V ˙ E − V ˙ CO 2 e η E V ˙ para o período de exercício (100%), correlações foram feitas com frações menores, como 90% e 75% dos valores máximos. Resultados: Os dois grupos tiveram características correspondentes para a idade (62±6 vs 59±9 anos, p>.05), sexo (10/9 vs 14/5, p>0,05), IMC (26±4 vs 27±3 Kg m2, p>0,05), e pico V ˙ O 2 (72±19 vs 74±20 % pred, p>0,05), respectivamente. A inclinação V ˙ E − V ˙ CO 2 e intercepto foram significativamente diferentes para DPOC e ICC (207,2±1,4 vs 33,1±5,7 e 5,3±1,9 vs 1,7±3,6, p<0,05 para ambas), mas os valores médios da η E V ˙ foram semelhantes entre os grupos (10,2±3,4 vs 10,9±2,3%, p=0,462). As correlações entre 100% do período do exercício com 90% e 75% dele foram mais fortes para η E V ˙ (r>0,850 para ambos). Conclusão: A η E V ˙ é um método valioso para comparação entre doenças cardiopulmonares, com mecanismos fisiopatológicos até agora distintos, incluindo restrições ventilatórias na DPOC.

Abstract Background: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E − V ˙ CO 2). Alternatively, a new approach for ventilatory efficiency ( η E V ˙) has been published. Objective: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E − V ˙ CO 2 slope and intercept). Methods: Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E − V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. Results: The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E − V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). Conclusion: The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.

Prognostic Value of Hemodynamic Gain Index in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Assessment of functional capacity in patients with heart failure with reduced ejection fraction (HFrEF) is essential for risk stratification, and it traditionally relied on cardiopulmonary exercise testing (CPET)-derived peak oxygen consumption (peak Vo2). OBJECTIVES: This study sought to investigate the prognostic value of alternative nonmetabolic exercise testing parameters in a contemporary cohort with HFrEF. METHODS: Medical records of 1,067 consecutive patients with chronic HFrEF who underwent CPET from December 2012 to September 2020 were reviewed for a primary outcome that was a composite of all-cause mortality, left ventricular assist device implantation, and/or heart transplantation. Multivariable Cox regression and log-rank testing were used to determine prognostic values of various exercise testing variables. RESULTS: The primary outcome was identified in 331 of 954 patients (34.7%) of the HFrEF cohort (median follow-up time, 946 days). After adjustment for demographics, cardiac parameters, and comorbidities, higher hemodynamic gain index (HGI) and peak rate-pressure product (RPP) were associated with greater event-free survival (adjusted HR per doubling: 0.76 and 0.36; 95% CI: 0.67-0.87 and 0.28-0.47; all P < 0.001, respectively). Moreover, HGI (area under the curve [AUC]: 0.69; 95% CI: 0.65-0.72) and peak RPP (AUC: 0.71; 95% CI: 0.68-0.74) were comparable to the standard peak Vo2 (AUC: 0.70; 95% CI: 0.66-0.73; P for comparison = 0.607 and 0.393, respectively) for primary outcome discrimination. CONCLUSIONS: HGI and peak RPP show good correlation with peak Vo2 in terms of prognostication and outcome discrimination in patients with HFrEF and may serve as suitable alternatives to CPET-derived prognostic variables.

Association of pulse pressure with death, myocardial infarction, and stroke among cardiovascular outcome trial participants.

Background: Prior evidence demonstrates that pulse pressure (PP), a surrogate marker of arterial stiffness, is an independent risk factor for mortality and major adverse cardiovascular (CV) events. Objectives: The study aimed to identify the association of PP with death, myocardial infarction, and stroke among participants enrolled in large CV outcome clinical trials and determine if this association was impacted by pre-existing CV disease, or specific CV risk factors. Methods: A total of 65,382 individuals, ages 19 to 98 years, that were enrolled in one of five CV outcome trials were analyzed. Baseline demographics, history, blood pressures, and medications were collected. Univariate and multivariable analyses were conducted to explore temporal patterns, risks, and adjusted survival rates. Results: Mean baseline PP was 52 ± 12 mmHg. For every 10 mmHg increase in PP, there was an increased risk of death, stroke, or myocardial infarction (hazard ratio (HR) 1.11, 95 % CI 1.08 to 1.14, p < 0.001). Similarly, a PP ≥ 60 mmHg demonstrated an HR of 1.27 (95 % CI 1.19 to 1.36, p < 0.001) compared with PP < 60 mmHg. A similar association existed for all subgroups analyzed except for participants with a history of stroke where increasing PP did not increase risk (HR 1.02, 95 % CI 0.95 to 1.10, p = 0.53). PP was a better predictor of adverse outcomes when compared to both systolic and diastolic blood pressures using the AIC and C-index. Conclusions: Among participants enrolled in CV outcome trials, baseline PP is associated with increased risk of death, myocardial infarction, and stroke for those with pre-existing CV disease and risk factors with the exception of a prior history of stroke.

Prognostic Role of Metabolic Exercise Testing in Heart Failure.

Heart failure is a clinical syndrome with significant heterogeneity in presentation and severity. Serial risk-stratification and prognostication can guide management decisions, particularly in advanced heart failure, when progression toward advanced therapies or end-of-life care is warranted. Each currently utilized prognostic marker carries its own set of challenges in acquisition, reproducibility, accuracy, and significance. Left ventricular ejection fraction is foundational for heart failure syndrome classification after clinical diagnosis and remains the primary parameter for inclusion in most clinical trials; however, it does not consistently correlate with symptoms and functional capacity, which are also independently prognostic in this patient population. Utilizing the left ventricular ejection fraction as the sole basis of prognostication provides an incomplete characterization of this condition and is prone to misguide medical decision-making when used in isolation. In this review article, we survey and exposit the important role of metabolic exercise testing across the heart failure spectrum, as a complementary diagnostic and prognostic modality. Metabolic exercise testing, also known as cardiopulmonary exercise testing, provides a comprehensive evaluation of the multisystem (i.e., neurological, respiratory, circulatory, and musculoskeletal) response to exercise performance. These differential responses can help identify the predominant contributors to exercise intolerance and exercise symptoms. Additionally, the aerobic exercise capacity (i.e., oxygen consumption during exercise) is directly correlated with overall life expectancy and prognosis in many disease states. Specifically in heart failure patients, metabolic exercise testing provides an accurate, objective, and reproducible assessment of the overall circulatory sufficiency and circulatory reserve during physical stress, being able to isolate the concurrent chronotropic and stroke volume responses for a reliable depiction of the circulatory flow rate in real time.

Appropriateness of Cardiovascular Disease Prevention Recommendations Obtained From a Popular Online Chat-Based Artificial Intelligence Model.

This study examines the appropriateness of artificial intelligence model responses to fundamental cardiovascular disease prevention questions.

National, regional, and urban-rural patterns in fixed-terrestrial broadband internet access and cardiac rehabilitation utilization in the United States.

Objective: Sparse patterns in fixed-terrestrial broadband internet access are predominantly observed among older adults and low income areas, which are interrelated factors also associated with low center-based cardiac rehabilitation (CR) utilization in the United States (US). Telehealth CR is proposed to increase CR utilization under an assumption that fixed-terrestrial broadband internet access is readily available nationwide and parallels CR utilization demand. We aimed to characterize national, geographical, and urban-rural patterns in fixed-terrestrial broadband internet access, CR eligibility rates, and center-based utilization throughout the US. Methods: Centers for Disease Control data were used to estimate CR eligibility rates and center-based utilization for 2017-2018 among Medicare fee-for-service beneficiaries aged ≥65 years. Census Bureau data for 2018 were used to estimate fixed-terrestrial broadband internet access among households of adults aged ≥65 years. Results: Southern states exhibited the highest percentage of households without broadband internet [median (IQR): 32% (24-39)] coupled with the highest CR eligibility rates [per 1,000 beneficiaries, median (IQR): 18 (15-21)] and lowest participation rates [percentage completing ≥1 session, median (IQR): 25% (17-33)]. Compared with urban areas, rural areas demonstrated significantly higher eligibility rates [15.5 (13.2-18.4) vs. 17.4 (14.5-21.0)], participation rates [30.6% (22.0-39.4) vs. 34.6% (22.6-48.3)], and percentage of households without broadband internet [23.8% (18.1-29.2) vs. 31.6% (26.5-37.6)], respectively. Conclusion: Overlapping patterns in fixed-terrestrial broadband internet access and CR eligibility rates and center-based utilization suggest telehealth CR policies need to account for the possibility that lack of broadband-quality internet access could be a barrier to accessing telehealth CR delivery models.

Geographical and Urban-Rural Disparities in Cardiac Rehabilitation Eligibility and Center-Based Use in the US.

This cross-sectional study analyzes county-level eligibility, participation, adherence, and completion rates for cardiac rehabilitation services among Medicare beneficiaries.

Individualized exercise prescription and cardiac rehabilitation following a spontaneous coronary artery dissection or aortic dissection.

Aims: Prescribed aerobic-based exercise training is a low-risk fundamental component of cardiac rehabilitation (CR). Secondary prevention therapeutic strategies following a spontaneous coronary artery dissection (SCAD) or aortic dissection (AD) should include CR. Current exercise guidance for post-dissection patients recommends fundamental training components including target heart rate zones are not warranted. Omitting fundamental elements from exercise prescriptions risks safety and makes it challenging for both clinicians and patients to understand and implement recommendations in real-world practice. We review the principles of exercise prescription for CR, focusing on translating guidelines and evidence from well-studied high-risk CR populations to support the recommendation that exercise testing and individualized exercise prescription are important for patients following a dissection. Methods and results: When patients self-perceive exercise intensity there is a tendency to underestimate intensities within metabolic domains that should be strictly avoided during routine exercise training following a dissection. However, exercise testing associated with CR enrolment has gained support and has not been linked to adverse events in optimally medicated post-dissection patients. Graded heart rate and blood pressure responses recorded throughout exercise testing provide key information for developing an exercise prescription. An exercise prescription that is reflective of medical history, medications, and cardiorespiratory fitness optimizes patient safety and yields improvements in blood pressure control and cardiorespiratory fitness, among other benefits. Conclusion: This clinical practice and education article demonstrates how to develop and manage a CR exercise prescription for post-acute dissection patients that can be safe and effective for maintaining blood pressure control and improving cardiorespiratory fitness pre-post CR.

Sinus Tachycardia: a Multidisciplinary Expert Focused Review.

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.

Influence of locomotor muscle group III/IV afferents on cardiovascular and ventilatory responses in human heart failure during submaximal exercise.

The purpose of this study is to determine the influence of locomotor muscle group III/IV afferent inhibition on central and peripheral hemodynamics at multiple levels of submaximal cycling exercise in patients with heart failure with reduced ejection fraction (HFrEF). Eleven patients with HFrEF and nine healthy matched controls were recruited. The participants performed a multiple stage [i.e., 30 W, 50%peak workload (WL), and a workload eliciting a respiratory exchange ratio (RER) of ∼1.0] exercise test with lumbar intrathecal fentanyl (FENT) or placebo (PLA). Cardiac output ([Formula: see text]tot) was measured via open-circuit acetylene wash-in technique and stroke volume was calculated. Leg blood flow ([Formula: see text]l) was measured via constant infusion thermodilution and leg vascular conductance (LVC) was calculated. Radial artery and femoral venous blood gases were measured. For HFrEF, stroke volume was higher at the 30 W (FENT: 110 ± 21 vs. PLA: 100 ± 18 mL), 50%peak WL (FENT: 113 ± 22 vs. PLA: 103 ± 23 mL), and RER = 1.0 (FENT: 119 ± 28 vs. PLA: 110 ± 26 mL) stages, whereas heart rate and systemic vascular resistance were lower with fentanyl than with placebo (all, P < 0.05). [Formula: see text]tot in HFrEF and [Formula: see text]tot, stroke volume, and heart rate in controls were not different between fentanyl and placebo (all, P > 0.19). During submaximal exercise, controls and patients with HFrEF exhibited increased leg vascular conductance (LVC) with fentanyl compared with placebo (all, P < 0.04), whereas no differences were present in [Formula: see text]l or O2 delivery with fentanyl (all, P > 0.20). Taken together, these findings provide support for locomotor muscle group III/IV afferents playing a role in integrative control mechanisms during submaximal cycling exercise in patients with HFrEF and older controls.NEW & NOTEWORTHY Patients with HFrEF exhibit severe exercise intolerance. One of the primary peripheral mechanisms contributing to exercise intolerance in patients with HFrEF is locomotor muscle group III/IV afferent feedback. However, it is unknown whether these afferents impact the central and peripheral responses during submaximal cycling exercise. Herein, we demonstrate that inhibition of locomotor muscle group III/IV afferent feedback elicited increases in stroke volume during submaximal exercise in HFrEF, but not in healthy controls.

Impact of left atrial strain mechanics on exercise intolerance and need for septal reduction therapy in hypertrophic cardiomyopathy.

AIMS: We sought to assess the relationship between left atrial (LA) strain mechanics and exercise intolerance, and to evaluate the prognostic impact of LA strain mechanics on clinical deterioration necessitating septal reduction therapy in hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: Consecutive HCM patients who underwent exercise stress echocardiography and cardiopulmonary exercise testing on the same day between October 2015 and April 2019 were enrolled prospectively. LA strain mechanics were analysed using speckle tracking echocardiography. LA stiffness was calculated as the ratio of E/e' ratio to LA reservoir strain. The study cohort was divided into four groups based on the quartile of percent-predicted peak VO2, and exercise intolerance was defined as the lowest quartile (≤51%). Of 532 patients studied (mean age: 51 ± 15 years, 42% female), 138 patients demonstrated exercise intolerance. As exercise capacity worsened, LA strain mechanics worsened along a continuum (P < 0.001). LA contractile strain with a cut-off of -13.9% was optimal at identifying exercise intolerance. On multivariable analysis, worse LA contractile strain was an independent predictor for exercise intolerance (P = 0.002). Of patients with left ventricular outflow tract obstruction, patients with LA stiffness worse than the median value (≥0.41) were significantly more likely to require septal reduction therapy than those with better LA stiffness (P = 0.026). CONCLUSION: Worse LA contractile strain was an independent predictor for exercise intolerance in HCM. Patients with worse LA stiffness had a higher probability of clinical deterioration necessitating septal reduction therapy.

Spontaneous coronary artery dissection: Principles of management.

Spontaneous coronary artery dissection (SCAD) is an acute noniatrogenic tear in the coronary arterial wall, leading to disruption of coronary blood flow and myocardial infarction. Previously considered rare, it is now recognized as a common cause of acute coronary syndrome, particularly in young women. Despite growing awareness of this disease, there is a paucity of data on acute and long-term therapy. This review summarizes the existing literature on treatment of SCAD and describes a comprehensive management strategy.

The obesity paradox in heart failure: What is the role of cardiorespiratory fitness?

The obesity paradox describes a survival benefit for higher body mass index in patients with heart failure. But other factors like cardiorespiratory fitness may play a role in heart failure development, severity, and survival. Although more research is needed to better understand the relationships between body mass index and fitness in patients with heart failure, evidence indicates that recommending weight loss and an exercise program is appropriate for most patients.

Invasive Hemodynamic and Metabolic Evaluation of HFpEF.

PURPOSE OF REVIEW: Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous condition of multiple causes, characterized by a clinical syndrome resulting from elevated left ventricular filling pressures, with an apparently unimpaired left ventricular systolic function. Although HFpEF has been long recognized as a distinct entity with significant morbidity for patients, its diagnosis remains challenging to this day. In recent years, few diagnostic algorithms have been postulated to aid in the identification of this condition. Invasive hemodynamic and metabolic evaluation is often warranted for the conclusive diagnosis and risk stratification of HFpEF, in patients presenting with undifferentiated DOE. RECENT FINDINGS: Rest and provoked hemodynamics remain the golden-standard diagnostic tool to unequivocally confirm the diagnosis of both established and incipient HFpEF, respectively. Cycle exercise hemodynamics is the paramount provocative maneuver to unveil this condition. Rapid saline loading does not offer a significant benefit over that of cycle exercise. Vasoactive agents can also uncover and confirm incipient HFpEF disease. The role of metabolic evaluation in patients presenting with idiopathic dyspnea on exertion (DOE) is of unparalleled value for those who have expertise in cardiopulmonary exercise test (CPET) interpretation; however, the average clinician who focuses solely on oxygen consumption will find it underwhelming. Invasive CPET stands alone as the ultimate diagnostic tool to discriminate between pulmonary, cardiovascular, and skeletal muscle disorders, and their respective contribution to DOE and exercise intolerance. SUMMARY: Several hemodynamic and metabolic parameters have demonstrated not only strong diagnostic value, but also predictive power in HFpEF. Additionally, these diagnostic methods have given rise to several therapeutic interventions that are now part of our clinical armamentarium. Regrettably, due to the heterogeneity and multicausality of HFpEF, none of the targeted interventions have been so far successful in decreasing the mortality burden of this prevalent condition.