Compared with traditional exercise tests, cardiopulmonary exercise testing (CPET) provides a thorough assessment of exercise integrative physiology involving the pulmonary, cardiovascular, muscular, and cellular oxidative systems. Due to the prognostic ability of key variables, CPET applications in cardiology have grown impressively to include all forms of exercise intolerance, with a predominant focus on heart failure with reduced or with preserved ejection fraction. As impaired cardiac output and peripheral oxygen diffusion are the main determinants of the abnormal functional response in cardiac patients, invasive CPET has gained new popularity, especially for diagnosing early heart failure with preserved ejection fraction and exercise-induced pulmonary hypertension. The most impactful advance has recently come from the introduction of CPET combined with echocardiography or CPET imaging, which provides basic information regarding cardiac and valve morphology and function. This review highlights modern CPET use as a single or combined test that allows the pathophysiological bases of exercise limitation to be translated, quite easily, into clinical practice.

Objectives The aim of this study was to characterize left atrial (LA) pathology in explanted hearts with transthyretin amyloid cardiomyopathy (ATTR-CM); LA mechanics using echocardiographic speckle-tracking in a large cohort of patients with ATTR-CM; and to study the association with mortality. Background The clinical significance of LA involvement in ATTR-CM is of great clinical interest. Methods Congo red staining and immunohistochemistry was performed to assess the presence, type, and extent of amyloid and associated changes in 5 explanted ATTR-CM atria. Echo speckle tracking was used to assess LA reservoir, conduit, contractile function, and stiffness in 906 patients with ATTR-CM (551 wild-type (wt)-ATTR-CM; 93 T60A-ATTR-CM; 241 V122I-ATTR-CM; 21 other). Results There was extensive ATTR amyloid infiltration in the 5 atria, with loss of normal architecture, vessels remodeling, capillary disruption, and subendocardial fibrosis. Echo speckle tracking in 906 patients with ATTR-CM demonstrated increased atrial stiffness (median [25th-75th quartile] 1.83 [1.15-2.92]) that remained independently associated with prognosis after adjusting for known predictors (lnLA stiff: HR: 1.23; 95% CI: 1.03-1.49; P = 0.029). There was substantial impairment of the 3 phasic functional atrial components (reservoir 8.86% [5.94%-12.97%]; conduit 6.5% [4.53%-9.28%]; contraction function 4.0% [2.29%-6.56%]). Atrial contraction was absent in 22.1% of patients whose electrocardiograms showed sinus rhythm (SR) “atrial electromechanical dissociation” (AEMD). AEMD was associated with poorer prognosis compared with patients with SR and effective mechanical contraction (P = 0.0018). AEMD conferred a similar prognosis to patients in atrial fibrillation. Conclusions The phenotype of ATTR-CM includes significant infiltration of the atrial walls, with progressive loss of atrial function and increased stiffness, which is a strong independent predictor of mortality. AEMD emerged as a distinctive phenotype identifying patients in SR with poor prognosis.

Aims Heart rate recovery (HRR) appears to be a robust prognostic marker in heart failure (HF). When using the 6 min walk test (6MWT) in HF, distance ambulated is generally the reference prognostic variable. We hypothesized that HRR after the 6MWT would be a better prognostic measure than distance ambulated. Methods and results A 6MWT and cardiopulmonary exercise testing (CPX) were randomly performed in 258 HF patients [216 HF with reduced EF (HFrEF) and 42 HF preserved EF (HFpEF)], after which HRR was measured. HRR was defined as the difference between heart rate at peak exercise and 1 min following test termination. Patients were assessed for major cardiac events during a mean follow‐up period of 22.8 ± 22.1 months. There were 50 major cardiac events during the tracking period. Univariate Cox regression analysis results identified HRR after both the 6MWT and CPX as a significant (P < 0.001) predictor of adverse events. Multivariate Cox regression analysis revealed that dichotomized HRR after the 6MWT and CPX was the strongest predictor of survival (χ2 61.1 and 53.8, respectively; P < 0.001), with LVEF (residual χ2 6.1, P < 0.05) adding significant prognostic value to the 6MWT model and ventilatory efficiency (the VE/VCO2 slope) (residual χ2 6.6, P < 0 .05) adding significant prognostic value to the CPX model. Conclusions HRR after the 6MWT is a powerful prognosticator that performs similarly to HRR after maximal exercise. If confirmed in subsequent studies, 6MWT HRR should replace 6MWT distance as the reference criterion 6MWT measure to consider when grading cardiovascular risk in HF patients.