Surveillance Stress Testing After Percutaneous Intervention for Patients With Multivessel or Left Main Coronary Disease.

BACKGROUND: The optimal surveillance strategy after percutaneous coronary intervention (PCI) for high-risk patients with multivessel or left main coronary artery disease (CAD) remains uncertain. OBJECTIVES: This study aims to determine the prognostic role of routine functional testing in patients with multivessel or left main CAD who underwent PCI. METHODS: The POST-PCI (Pragmatic Trial Comparing Symptom-Oriented Versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention) trial randomized high-risk PCI patients to routine functional testing at 1 year or standard care alone during follow-up. This analysis focused on participants with multivessel or left main CAD. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. RESULTS: Among 1,706 initially randomized patients, 1,192 patients with multivessel (n = 833) or left main (n = 359) were identified, with 589 in the functional testing group and 603 in the standard care group. Two-year incidences of primary outcome were similar between the functional testing group and the standard care group (6.2% vs 5.7%, respectively; HR: 1.09; 95% CI: 0.68-1.74; P = 0.73). This trend persisted in both groups of multivessel (6.2% vs 5.7%; HR: 1.09; 95% CI: 0.62-1.89; P = 0.78) and left main disease (6.2% vs 5.7%; HR: 1.09; 95% CI: 0.46-2.56; P = 0.85) (P for interaction = 0.90). Routine surveillance functional testing was associated with increased rates of invasive angiography and repeat revascularization beyond 1 year. CONCLUSIONS: In high-risk patients with multivessel or left main CAD who underwent PCI, there was no incremental clinical benefit from routine surveillance functional-testing compared with standard care alone during follow-up. (Pragmatic Trial Comparing Symptom-Oriented Versus Routine Stress Testing in High-Risk Patients Undergoing Percutaneous Coronary Intervention [POST-PCI]; NCT03217877).

Atrial fibrillation as a risk factor for exercise-induced pulmonary haemorrhage following a standardised exercise test.

BACKGROUND: Atrial fibrillation (AF) has been proposed as a risk factor for exercise-induced pulmonary haemorrhage (EIPH) due to increased pressure in the left atrium. OBJECTIVE: To evaluate if AF was associated with EIPH following a standardised exercise test (SET) to fatigue. STUDY DESIGN: Two-arm controlled experiment. METHODS: Ten untrained Standardbred mares mean (standard deviation [SD]) age 6 (2) years performed a SET on the treadmill in sinus rhythm (SR) (SET1) and 25-44 days after induction of self-sustained AF (SET2). AF was induced by tachypacing using a pacing device. Endoscopy, including tracheal wash and bronchoalveolar lavage (BAL), was performed 48-72 h before and 24 h after the two SETs. In addition, endoscopic grading of tracheal blood was performed 2 h after each SET. RESULTS: After SET1, none of the horses showed blood in the trachea, and two horses showed erythrophagocytosis. Following SET2, two horses had grade 1 blood in the trachea and free erythrocytes and erythrophagocytosis in the BAL, while another two horses had erythrophagocytosis in the BAL. In SET2, the overall performance on the treadmill was decreased with a lower maximum velocity (SET1 10.3 ± 0.8 m/s vs. SET2 8.9 ± 0.9 m/s, p = 0.004), a higher heart rate (284 ± 21 vs. 221 ± 18 bpm, p = 0.003) and more abnormal QRS complexes (p < 0.001) compared with SET1. CONCLUSIONS: Two horses showed signs of EIPH, resulting in visible blood in the trachea, when exercising in AF compared with SR. However, a possible link between EIPH, pulmonary pressure and AF needs to be further elucidated.

Hemodynamic parameters at rest predicting exercise capacity in patients supported with left ventricular assist device.

Left ventricular assist devices improve prognosis and quality of life, but exercise capacity remains limited in most patients after device implantation. Left ventricular assist device optimization through right heart catheterization reduces device-related complications. However, hemodynamic parameters associated with exercise capacity under optimized conditions. The aim of this study was to elucidate the predictors of exercise capacity from hemodynamic parameters at rest after left ventricular assist device optimization. We retrospectively reviewed 24 patients who underwent a ramp test with right heart catheterization, echocardiography and cardiopulmonary exercise testing more than 6 months after left ventricular assist device implantation. Pump speed was optimized to a lower setting that achieved right atrial pressure < 12 mmHg, pulmonary capillary wedge pressure < 18 mmHg, and cardiac index > 2.2 L/min/m2, then exercise capacity was assessed by cardiopulmonary exercise testing. After left ventricular assist device optimization, the mean right atrial pressure, pulmonary capillary wedge pressure, cardiac index, and peak oxygen consumption were 7 ± 5 mmHg, 10 ± 7 mmHg, 2.7 ± 0.5 L/min/m2, and 13.2 ± 3.0 mL/min/kg, respectively. Pulse pressure, stroke volume, right atrial pressure, mean pulmonary artery pressure, and pulmonary capillary wedge pressure were significantly associated with peak oxygen consumption. Multivariate linear regression analysis of factors predicting peak oxygen consumption revealed that pulse pressure, right atrial pressure, and aortic insufficiency remained independent predictors (ß = 0.401, p = 0.007; ß = - 0.558, p < 0.001; ß = - 0.369, p = 0.010, respectively). Our findings suggests that cardiac reserve, volume status, right ventricular function, and aortic insufficiency predict exercise capacity in patients with a left ventricular assist device.

The electrocardiographic manifestations of pectus excavatum before and after surgical correction.

BACKGROUND: Pectus excavatum (PEx) can cause cardiopulmonary limitations due to cardiac compression and displacement. There is limited data on electrocardiogram (ECG) alterations before and after PEx surgical repair, and ECG findings suggesting cardiopulmonary limitations have not been reported. The aim of this study is to explore ECG manifestations of PEx before and after surgery including associations with exercise capacity. METHODS: A retrospective review of PEx patients who underwent primary repair was performed. ECGs before and after surgical correction were evaluated and the associations between preoperative ECG abnormalities and cardiopulmonary function were investigated. RESULTS: In total, 310 patients were included (mean age 35.1 ± 11.6 years). Preoperative ECG findings included a predominant negative P wave morphology in V1, and this abnormal pattern significantly decreased from 86.9% to 57.4% (p < 0.001) postoperatively. The presence of abnormal P wave amplitude in lead II (>2.5 mm) significantly decreased from 7.1% to 1.6% postoperatively (p < 0.001). Right bundle branch block (RBBB) (9.4% versus 3.9%, p < 0.001), rsr' patterns (40.6% versus 12.9%, p < 0.001), and T wave inversion in leads V1-V3 (62.3% vs 37.7%, p < 0.001) were observed less frequently after surgery. Preoperative presence of RBBB (OR = 4.8; 95%CI 1.1-21.6) and T wave inversion in leads V1-3 (OR = 2.3; 95%CI 1.3-4.2) were associated with abnormal results in cardiopulmonary exercise testings. CONCLUSION: Electrocardiographic abnormalities in PEx are frequent and can revert to normal following surgery. Preoperative RBBB and T wave inversion in leads V1-3 suggested a reduction in exercise capacity, serving as a marker for the need for further cardiovascular evaluation of these patients.

Long-term outcomes of pulmonary embolism in children and adolescents.

ABSTRACT: Knowledge regarding the long-term consequences of pulmonary embolism (PE) in children is limited. This cohort study describes the long-term outcomes of PE in children who were followed-up at a single-center institution using a local protocol that included clinical evaluation, chest imaging, echocardiography, pulmonary function tests, and cardiopulmonary exercise tests at follow-up, starting 3 to 6 months after acute PE. Children objectively diagnosed with PE at age 0 to 18 years, who had ≥6 months of follow-up were included. Study outcomes consisted of PE resolution, PE recurrence, death, and functional outcomes (dyspnea, impaired pulmonary or cardiac function, impaired aerobic capacity, and post-PE syndrome). The frequency of outcomes was compared between patients with/without underlying conditions. In total, 150 patients were included; median age at PE was 16 years (25th-75th percentile, 14-17 years); 61% had underlying conditions. PE did not resolve in 29%, recurrence happened in 9%, and death in 5%. One-third of patients had at least 1 documented abnormal functional finding at follow-up (ventilatory impairments, 31%; impaired aerobic capacity, 31%; dyspnea, 26%; and abnormal diffusing capacity of the lungs to carbon monoxide, 22%). Most abnormalities were transient. When alternative explanations for the impairments were considered, the frequency of post-PE syndrome was lower, ranging between 0.7% and 8.5%. Patients with underlying conditions had significantly higher recurrence, more pulmonary function and ventilatory impairments, and poorer exercise capacity. Exercise intolerance was, in turn, most frequently because of deconditioning than to respiratory or cardiac limitation, highlighting the importance of physical activity promotion in children with PE.

Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

[Anatomical resection for non-small cell lung cancer: cardiopulmonary exercise testing in assessing the risk of respiratory complications]. / Anatomicheskie rezektsii po povodu nemelkokletochnogo raka legkogo: kardiorespiratornoe nagruzochnoe testirovanie v otsenke riska respiratornykh oslozhnenii.

OBJECTIVE: To assess the role of cardiopulmonary exercise testing in examination of patients with high risk of respiratory complications in anatomical resections for non-small cell lung cancer. MATERIAL AND METHODS: A non-randomized retrospective single-center study was devoted to immediate results of surgical treatment of patients with NSCLC between December 2020 and April 2021. Median age of patients was 65 (84; 30) years, male-to-female ratio - 129 (57%)/98 (43%). All patients were examined according to a unified algorithm recommended by the American (ATS) and European (ESTS) societies of thoracic surgeons. At the first stage, we analyzed airflow rate and performed non-invasive exercise tests (6-minute walk and/or stair test). Resections of lungs were performed in 231 patients, anatomic lung resections - in 227 patients (lobectomy - 199, bilobectomy - 4, segmentectomy - 17, pneumonectomy - 7). We excluded 4 patients who underwent non-anatomic lung resections (marginal resections). RESULTS: Among 236 patients referred for anatomical lung resections, 34 (14.4%) ones were selected for cardiopulmonary testing. Selection was based on low exercise tolerance and/or severe decrease in predictive respiratory parameters (FEV<50%). Patients were divided into 4 groups depending on peak oxygen consumption. There were 5 (2%), 10 (29.4%), 11 (32.3%) and 8 (23.5%) patients with extremely high, high, moderate and low risk of respiratory complications, respectively. Surgeries were performed for IA1 (n=6), IA2 (n=50), IA3 (n=37), IB (n=31), IIA (n=19), IIB (n=37), IIIA (n=25) and IIIB (n=4) stages. The overall incidence of postoperative complications was 23% (95% CI: 18-28.8). Complications Clavien-Dindo grade I, IIIA, IIIB, IVA, IVB and V prevailed in both groups. Median postoperative hospital-stay (6 (6; 8) vs. 7 (6; 8) days) and time of pleural drainage (4 (2; 5) vs. 3 (3; 4) days) were similar. Organ-sparing procedures prevailed in the main group (5 (26%) out of 19 (95% CI: 11.81-48.8) vs. 12 (6.7%) out of 180 (95% CI: 3.8-11.3)). Overall mortality (n=231) was 1.7% (95% CI: 0.7-4.4). Mortality throughout the first postoperative year was 24% (95% CI: 12.2-42.1) and 7.4% (95% CI: 4.2-11.3), respectively. CONCLUSION: Cardiopulmonary exercise testing makes it possible to objectively assess exercise tolerance and identify high-risk patients for respiratory complications. These data are valuable when planning the treatment of patients with non-small cell lung cancer.

Exercise ventilatory response after COVID-19: comparison between ambulatory and hospitalized patients.

Inefficient ventilatory response during cardiopulmonary exercise testing (CPET) has been suggested as a cause of post-COVID-19 dyspnea. It has been described in hospitalized patients (HOSP) with lung parenchymal sequelae but also after mild infection in ambulatory patients (AMBU). We hypothesize that AMBU and HOSP have different ventilatory responses to exercise, due to different etiologies. We analyzed CPET realized between July 2020 and May 2022 of patients with persisting respiratory symptoms 3 mo after COVID-19. Chest computed tomography (CT) scan, pulmonary function tests, quality of life, and respiratory questionnaires were collected. CPET data were specifically explored as a function of ventilation (V̇e) and time. Seventy-nine consecutive patients were included (42 AMBU and 37 HOSP, median: 54 [44-60] yr old, 57% female). Patients were hospitalized for a median of 20 [8-34] days, with pneumonia (41%) or acute respiratory distress syndrome (ARDS; 30%). Among HOSP, 12(32%) patients had abnormal values for spirometry and 18(51%) for carbon monoxide diffusing capacity (P < 0.001). CPET showed no differences between AMBU and HOSP in peak absolute O2 uptake (V̇o2) (1.59 [1.22-2.11] mL·min-1; P = 0.65). Tidal volume (VT) as a function of V̇e, was lower in AMBU than in HOSP (P < 0.01) toward the end of exercise. The slope of the V̇e-CO2 production was higher than normal in both groups (30.9 [26.1-34.3]; P = 0.96). In conclusion, the severity of COVID-19 did not influence the exercise capacity, but AMBU demonstrated a less efficient ventilatory response to exercise as compared with HOSP. CPET with exploration of data as a function of V̇e and throughout the exercise better unveil ventilatory inefficiency.NEW & NOTEWORTHY We evaluated the exercise ventilatory response in patients with persisting dyspnea after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. We found that despite similar peak power and peak absolute O2 uptake, tidal volume as a function of ventilation was lower in ambulatory than in hospitalized patients toward the end of exercise, reflecting ventilatory inefficiency. We call for evaluation of minute ventilation with the exploration of data throughout the exercise and not only peak data to better unveil ventilatory inefficiency.

Increasing frequency of dyspnea among patients referred for cardiac stress testing.

OBJECTIVE: To assess the frequency, change in prevalence, and prognostic significance of dyspnea among contemporary patients referred for cardiac stress testing. PATIENTS AND METHODS: We evaluated the prevalence of dyspnea and its relationship to all-cause mortality among 33,564 patients undergoing stress/rest SPECT-MPI between January 1, 2002 and December 31, 2017. Dyspnea was assessed as a single-item question. Patients were divided into three temporal groups. RESULTS: The overall prevalence of dyspnea in our cohort was 30.2%. However, there was a stepwise increase in the temporal prevalence of dyspnea, which was present in 25.6% of patients studied between 2002 and 2006, 30.5% of patients studied between 2007 and 2011, and 38.7% of patients studied between 2012 and 2017. There was a temporal increase in the prevalence of dyspnea in each age, symptom, and risk factor subgroup. The adjusted hazard ratio for mortality was higher among patients with dyspnea vs those without dyspnea both among all patients, and within each chest pain subgroup. CONCLUSIONS: Dyspnea has become increasingly prevalent among patients referred for cardiac stress testing and is now present among nearly two-fifths of contemporary cohorts referred for stress-rest SPECT-MPI. Prospective study is needed to standardize the assessment of dyspnea and evaluate the reasons for its increasing prevalence.

Six-month effects of supervised exercise on walking ability and health-related factors in peripheral arterial disease: a pilot study.

BACKGROUND: In peripheral arterial disease (PAD) patients with intermittent claudication (IC), the combination of aerobic and resistance exercises could counteract muscle loss and attenuate disease progression. This study analyzed the effects of six months of a combined exercise program on walking ability, lower limb body composition, cardiovascular risk factors, and Ankle-Brachial Index (ABI). METHODS: Twenty-three patients (age 63.2±1.5 years and ABI 0.58±0.07) with PAD and IC were allocated to a control group (CG) or a supervised exercise group (SUP). Ten patients underwent six months of treadmill walking combined with resistance exercises, three times a week. The CG (N.=13) received a recommendation for walking. All patients were measured at baseline (M0), after three months (M3), and six months (M6). RESULTS: During constant treadmill protocol, the claudication onset time/distance (COT/COD), absolute claudication time/distance (ACT/ACD), and number of pauses of overall patients significantly improved at M3 and M6. Between groups were found significant differences in COT and COD at M6 (P=0.005 and P=0.007, respectively); and in ACT and ACD at M3 (P=0.003 for both) and at M6 (P=0.005 and P=0.005, respectively), with major improvements in the SUP. Over the six months, a significant group effect was found in fat-free mass (P=0.041) and predicted muscle mass (P=0.039) of the lower ABI leg, with greater improvements in the SUP. CONCLUSIONS: A supervised exercise program that combines aerobic and resistance training improves PAD symptoms and has additional benefits for patients. Patients in the program showed improvements in walking ability, lower-limb body composition, perceived exertion, and heart rate during treadmill walking.

Screening of silent myocardial ischaemia using a stress test in rheumatoid arthritis patients: Association with traditional risk factors and disease activity.

INTRODUCTION: We aimed to screen the presence of silent myocardial ischaemia, in established rheumatoid arthritis (RA) patients, using a stress test then to evaluate its association with the disease activity and the cardiovascular (CV) risk factors and Heartscore. METHODS: It is a transversal study in a rheumatologic centre in Tunisia. One hundred three RA patients, asymptomatic for CV diseases, were submitted to a stress test. Demographic data, CV risk factors and disease characteristics were assessed and risk factors of silent myocardial ischaemia in RA patients were identified. RESULTS: There were 103 patients (sex-ratio = 0.3) with a mean age of 53 ± 10 years. The evaluation of the disease activity showed that the mean Disease Activity Score in 28 joints C-reactive protein, Clinical Disease Activity Index and Simplified Disease Activity Index were 3.9 ± 1.38, 17.17 ± 11.4 and 33.39 ± 26, respectively. The ischaemic ratio (CT/HDL) revealed that 42% of patients had a moderate to high myocardial ischaemic risk. HeartSCORE was high in 35% of cases. A silent myocardial ischaemia in the stress test was found in 11 patients (10.6%) and was associated with male sex (p = 0.03), advanced age (p = 0.04), erosive character (p = 0.05), the advanced age of the RA diagnosis (p = 0.01) and the ischaemic ratio (p = 0.05). No relationship was found with the majority of traditional CV risk factors nor with disease activity variables. CONCLUSION: Our results corroborated the hypothesis that the stress test could reveal subclinical CV dysfunction and supported the utility of the Heartscore as a screening tool.

Characteristics of cardiopulmonary exercise testing in patients with combined post- and pre-capillary pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension (PH) is a common and morbid complication of left heart disease (LHD), comprising two subtypes: (1) isolated post-capillary pulmonary hypertension (Ipc-PH) and (2) combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Knowledge regarding the physiological characteristics that distinguish Cpc-PH, which has a worse prognosis, from Ipc-PH remains limited. Therefore, this study aimed to assess the utility of cardiopulmonary exercise testing (CPET) variables in detecting Cpc-PH. METHODS AND RESULTS: Among 105 consecutive patients with LHD (age: 55 ± 13 years; male/female = 79/26) who underwent right heart catheterization and CPET, 45 (43%) were classified as PH-LHD (mean pulmonary artery pressure >20 mmHg). Ipc-PH (n = 24) was defined as pulmonary vascular resistance (PVR) ≤ 3 WU and Cpc-PH (n = 21) as PVR > 3 WU. Patients with Cpc-PH had a significantly lower peak partial pressure of carbon dioxide (PETCO2) (Non-PH/Ipc-PH/Cpc-PH = 38.2 ± 6.6 vs. 38.3 ± 6.0 vs 33.0 ± 4.4 mmHg, p = 0.006), higher VE vs. VCO2 slope (Non-PH/Ipc-PH/Cpc-PH = 33.0 [28.3, 36.6] vs. 32.5 [28.1, 37.8] vs. 40.6 [33.6, 46.1], p = 0.007), and lower ΔVO2/ΔWR (Non-PH/Ipc-PH/Cpc-PH = 8.5 ± 1.4 vs. 8.0 ± 1.7 vs. 6.8 ± 2.0 mL/min/watt, p = 0.001) than those with Ipc-PH and non-PH. Using multivariable logistic regression analysis, CPET variables were found to be independent predictors of Cpc-PH (lower peak PETCO2: odds ratio, 0.728 [95% confidence interval {CI}: 0.616-0.840], p = 0.003 and lower ΔVO2/ΔWR: odds ratio, 0.747 [95% CI: 0.575-0.872], p = 0.003). CONCLUSION: From our exploratory analysis, CPET variables, especially in the lower peak PETCO2 and lower ΔVO2/ΔWR, were associated with Cpc-PH in patients with left heart disease.

Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction: Implications for V˙/Q˙ Mismatch.

BACKGROUND: The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. RESEARCH QUESTION: Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? STUDY DESIGN AND METHODS: Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (Vdalv; Enghoff modification of the Bohr equation) and the alveolar-arterial Po2 difference (A-aDO2; alveolar gas equation), were also derived. The ventilation (V˙e)/CO2 elimination (V˙co2) slope was also calculated as the slope of the V˙e and V˙co2 relationship, which reflects ventilatory efficiency. RESULTS: Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vs NTG: 4.03 ± 2.18; P = .009) despite a clear decrease in pulmonary capillary wedge pressure at 20 W (PLC: 19.7 ± 8.2 vs NTG: 15.9 ± 7.4 mm Hg; P < .001). Moreover, Vdalv (PLC: 0.28 ± 0.07 vs NTG: 0.31 ± 0.08 L/breath; P = .01), A-aDO2 (PLC: 19.6 ± 6.7 vs NTG: 21.1 ± 6.7; P = .04), and V˙e/V˙co2 slope (PLC: 37.6 ± 5.7 vs NTG: 40.2 ± 6.5; P < .001) all increased at 20 W after a decrease in pulmonary capillary wedge pressure. INTERPRETATION: These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.

Predicting the Development of Renal Replacement Therapy Indications by Combining the Furosemide Stress Test and Chemokine (C-C Motif) Ligand 14 in a Cohort of Postsurgical Patients.

OBJECTIVES: Optimal timing of renal replacement therapy (RRT) initiation in severe acute kidney injury (AKI) remains controversial. Initiation of treatment early in the course of AKI may lead to some patients undergoing unnecessary RRT, whereas delayed treatment is associated with increased mortality. This study aims to investigate whether the combination of the furosemide stress test (FST) and AKI-associated biomarkers can predict the development of indications for RRT. DESIGN: Single-center, prospective, observational study. SETTING: University Hospital of Muenster, Germany. PATIENTS: Critically ill, postoperative patients with moderate AKI (Kidney Disease: Improving Global Outcomes stage 2) and risk factors for further progression (vasopressors and/or mechanical ventilation) receiving an FST. INTERVENTIONS: Sample collection and measurement of different biomarkers (chemokine [C-C motif] ligand 14 [CCL14], neutrophil gelatinase-associated lipocalin, dipeptidyl peptidase 3). MEASUREMENT AND MAIN RESULTS: The primary endpoint was the development of greater than or equal to one predefined RRT indications (hyperkalemia [≥ 6 mmol/L], diuretic-resistant hypervolemia, high urea serum levels [≥ 150 mg/dL], severe metabolic acidosis [pH ≤ 7.15], oliguria [urinary output < 200 mL/12 hr], or anuria). Two hundred eight patients were available for the primary analysis with 108 having a negative FST (urine output < 200 mL in 2 hr following FST). Ninety-eight patients (47%) met the primary endpoint, 82% in the FST negative cohort. At the time of inclusion, the combination of a negative FST test and high urinary CCL14 levels had a significantly higher predictive value for the primary endpoint with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.82-0.92) compared with FST or CCL14 alone (AUC, 0.79; 95% CI, 0.74-0.85 and AUC, 0.83; 95% CI, 0.77-0.89; p < 0.001, respectively). Other biomarkers showed lower AUCs. CONCLUSIONS: The combination of the FST with the renal biomarker CCL14 predicts the development of indications for RRT.

Hypertrophic Cardiomyopathy as an Unexpected Mimic of Inducible Laryngeal Obstruction: The Case for Cardiopulmonary Exercise Testing in Otolaryngology.

INTRODUCTION: Inducible laryngeal obstruction is a common and challenging cause of exertional dyspnea. We report a case of an unanticipated cardiac condition that presented with symptoms suggestive of inducible laryngeal obstruction. DISCUSSION: A 55-year-old man was evaluated for progressive exertional dyspnea and throat tightness, unexplained after multiple medical evaluations. Resting laryngeal examination was suspicious for laryngopharyngeal reflux and mild vocal fold adduction during quiet expiration. Given progressive and refractory symptoms, maximal cardiopulmonary exercise testing with intermittent laryngeal examination was performed. This study excluded laryngeal causes of exercise limitation and led to an unexpected diagnosis of persistent atrial flutter and hypertrophic cardiomyopathy. CONCLUSION: Cardiopulmonary exercise testing with laryngeal examination can identify unexpected and life-threatening mimics of inducible laryngeal obstruction that may be missed by unmonitored exercise challenges. Suspicion for inducible laryngeal obstruction at rest may not predict the true nature of exercise limitation on cardiopulmonary exercise testing.

Assessing Right Ventricle Pulmonary Artery Coupling and Uncoupling Using Echocardiography and Cardiopulmonary Exercise Test in Post Operative TOF Patients.

Right ventricular-pulmonary arterial (RV-PA) coupling is an important determinant in the development of right ventricular dilatation. RV-PA coupling is defined as the ratio of pulmonary arterial elastance (an index of arterial load) and right ventricular end-systolic elastance (an index of contractility). A retrospective study of postoperative 135 TOF patients who underwent for pulmonary valve replacement was conducted. RV-PA coupling was calculated noninvasively using Ea/Emax (cardiac magnetic resonance) = ventricular end-systolic volume/ventricular systolic volume, equation and patients were divided into coupling and uncoupling group and compared the results on the basis of echocardiography and cardiopulmonary exercise test. Lower tricuspid annular plane systolic excursion, percentage predictive peak VO2, VE/VCO2 at anaerobic threshold, (AT), VE/VCO2 at peak, Minute ventilation, (VE) Volume of Carbondioxide output, (VCO2) slope, volume of oxygen output (VO2) work rate (WR) slope, and WR at VO2 peak were identified as risk factors for uncoupling of RV-PA. In RV-PA coupling combination of echocardiography and cardiopulmonary exercise test revealed the most important modality to identify risk factor and may be useful for therapeutic decision making by identifying patients of especially high risk for inadequate therapy.

Exercise Oximetry Correlates Better With Exercise-Induced Lactate Increase, than Ankle Brachial Index or Walking Time, in Vascular Claudicants.

In claudication, the correlation between walking-induced biomarkers and indices of clinical severity (e.g., walking distance or ankle brachial index (ABI)), is fair. We hypothesized that a correlation would be observed between the clinical estimation of ischemia severity with exercise transcutaneous oximetry (Ex-TcpO2) and lactate increase. A prospective study was performed among 377 patients with arterial claudication. We recorded age, sex, ABI, body mass index (BMI), systolic arterial blood pressure (SBP), and glycemia. Capillary blood lactate was measured at rest and 3 min after a constant load treadmill test. We recorded maximum walking time (MWT), heart rate (HRmax), the sum of minimal decrease from oxygen values for buttocks, thighs and calves Ex-TcpO2 (DROPmin), as well as the amplitude of chest-TcpO2 decrease. A multilinear regression model was used to assess the variables associated with lactate increase. BMI, SBP, HRmax, the amplitude of decrease in chest-TcpO2 and DROPmin, but not age, sex, ABI, MWT, diabetes mellitus nor glycemia, were significantly associated to lactate increase in the model. Because it accounts for the severity and diffusion of lower-limb exercise-induced ischemia and detects exercise induced hypoxemia, TcpO2 may be preferable to ABI or MWT to estimate the metabolic consequences of walking in claudicants.

The safety of carotid stenosis during vasodilator pharmacologic stress testing.

BACKGROUND: While thousands of patients undergo stress testing annually, the risk of exercise and pharmacologic stress in patients with carotid artery disease has not been fully defined but is of concern as patients are at risk for cerebrovascular accidents and transient ischemic attacks. METHODS: All patients with either ultrasound or CTA evaluation of their carotid arteries from over a 10 year period who underwent stress testing within 180 days without intervening carotid intervention were reviewed for any adverse events within 24 hours of their stress test. The primary end point was any cerebrovascular event or syncope while the secondary endpoints included death, myocardial infarction, urgent angiography, urgent revascularization, or exaggerated hemodynamic response (systolic BP drop > 20 mmHg or systolic BP > 180 mmHg at peak stress). Patients were stratified into categories based on their level of carotid disease. Patients with severe carotid stenosis were propensity matched to those with mild or no stenosis. RESULTS: A total of 4457 patients underwent carotid ultrasound, 10,644 CTA, and 16,011 had stress testing during this time period with 514 having both a carotid evaluation and a stress test within 6 months. After propensity matching, 62 patients with severe carotid stenosis were matched to 170 patients with mild or no carotid stenosis. Incidentally, all patients with severe carotid stenosis underwent pharmacologic stress. There were no primary endpoints and only three secondary endpoints in two patients in the mild or no carotid stenosis group. The proportion of exaggerated hemodynamic response to stress was similar in both groups-21.0% in the carotid stenosis group vs 31.2% without (P = .17) having a significant drop in systolic BP, and 3.2% vs 4.7% (P = 1.0) having a significantly elevated systolic BP. CONCLUSION: In this study cohort there were few primary and secondary outcome events with no events occurring in patients with significant carotid stenosis. Additionally, there was no difference in exaggerated hemodynamic responses. While these results suggest that stress testing entails no demonstrable increased risk in patients with significant carotid stenosis, continued care should be taken given the limitations of the small size of this study.