Category Archives: Publications

Cardiorespiratory fitness assessed by cardiopulmonary exercise testing between different stages of pre-dialysis chronic kidney disease: A systematic review and meta-analysis.

Alexandrou ME; P Theodorakopoulou M; Boutou A; Pella E; Boulmpou A; Papadopoulos CE; Zafeiridis A;
Papagianni A; Sarafidis P;

Nephrology (Carlton, Vic.) [Nephrology (Carlton)] 2021 Jul 20. Date of Electronic Publication: 2021 Jul 20.

Aim: The burden of several cardiovascular risk factors increases in parallel to renal function decline. Exercise intolerance is common in patients with chronic kidney disease (CKD) and has been associated with increased risk of adverse outcomes. Whether indices of cardiorespiratory capacity deteriorate with advancing CKD stages is unknown.
Methods: We conducted a systematic review and meta-analysis of studies assessing cardiorespiratory capacity in adult patients with pre-dialysis CKD using cardiopulmonary exercise testing (CPET) and reporting data for different stages. Our primary outcome was differences in peak oxygen uptake (VO 2 peak) between patients with CKD Stages 2-3a and those with Stages 3b-5(pre-dialysis). Literature search was undertaken in PubMed, Web of Science and Scopus databases, and abstract books of relevant meetings. Quality assessment was undertaken with Newcastle-Ottawa-Scale.
Results: From 4944 records initially retrieved, six studies with 512 participants fulfilling our inclusion criteria were included in the primary meta-analysis. Peak oxygen uptake (VO 2 peak) was significantly higher in patients with CKD Stages 2-3a versus those with Stages 3b-5(pre-dialysis) [weighted-mean-difference, WMD: 2.46, 95% CI (1.15, 3.78)]. Oxygen consumption at ventilatory threshold (VO 2 VT) was higher in Stages 2-3a compared with those in Stages 3b-5(pre-dialysis) [standardized-mean-difference, SMD: 0.59, 95% CI (0.06, 1.1)], while no differences were observed for maximum workload and respiratory-exchange-ratio. A secondary analysis comparing patients with CKD Stages 2-3b and Stages 4-5(pre-dialysis), yielded similar results [WMD: 1.78, 95% CI (1.34, 2.22)]. Sensitivity analysis confirmed the robustness of these findings.
Conclusion: VO 2 peak and VO 2 VT assessed with CPET are significantly lower in patients in CKD Stages 3b-5 compared with Stages 2-3a. Reduced cardiorespiratory fitness may be another factor contributing to cardiovascular risk increase with advancing CKD.

Ventilatory efficiency in pulmonary vascular diseases.

Weatherald J; Philipenko B; Montani D; Laveneziana P;

European respiratory review : an official journal of the European Respiratory Society [Eur Respir Rev] 2021 Jul 20; Vol. 30 (161). Date of Electronic Publication: 2021 Jul 20 (Print Publication: 2021).

Cardiopulmonary exercise testing (CPET) is a frequently used tool in the differential diagnosis of dyspnoea. Ventilatory inefficiency, defined as high minute ventilation ( V’ E ) relative to carbon dioxide output ( V’ CO 2 ), is a hallmark characteristic of pulmonary vascular diseases, which contributes to exercise intolerance and disability in these patients. The mechanisms of ventilatory inefficiency are multiple and include high physiologic dead space, abnormal chemosensitivity and an altered carbon dioxide (CO 2 ) set-point. A normal V’ E / V’ CO 2 makes a pulmonary vascular disease such as pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) unlikely. The finding of high V’ E /V’ CO 2 without an alternative explanation should prompt further diagnostic testing to exclude PAH or CTEPH, particularly in patients with risk factors, such as prior venous thromboembolism, systemic sclerosis or a family history of PAH. In patients with established PAH or CTEPH, the V’ E / V’ CO 2 may improve with interventions and is a prognostic marker. However, further studies are needed to clarify the added value of assessing ventilatory inefficiency in the longitudinal follow-up of patients.

Exercise tolerance and quality of life in hemodynamically partially improved patients with chronic thromboembolic pulmonary hypertension treated with balloon pulmonary angioplasty.

Miura K; Katsumata Y; Kawakami T; Ikura H; Ryuzaki T; Shiraishi Y; Fukui S; Kawakami M; Kohno T; Sato K;
Fukuda K;

PloS one [PLoS One] 2021 Jul 23; Vol. 16 (7), pp. e0255180. Date of Electronic Publication: 2021 Jul 23 (Print Publication: 2021).

The efficacy of extensive balloon pulmonary angioplasty (BPA) beyond hemodynamic improvement in chronic thromboembolic pulmonary hypertension (CTEPH) patients has been verified. However, the relationship between extensive BPA in CTEPH patients after partial hemodynamic improvement and exercise tolerance or quality of life (QOL) remains unclear. We prospectively enrolled 22 CTEPH patients (66±10 years, females: 59%) when their mean pulmonary artery pressure initially decreased to <30 mmHg during BPA sessions. Hemodynamic and echocardiographic data, cardiopulmonary exercise testing, and QOL scores using the 36-item short form questionnaire (SF-36) were evaluated at enrollment (entry), just after the final BPA session (finish), and at the 6-month follow-up (follow-up). We analyzed whether extensive BPA improves exercise capacity and QOL scores over time. Moreover, the clinical characteristics leading to improvement were elucidated. The peak oxygen uptake (VO2) showed significant improvement at entry, finish, and follow-up (17.3±5.5, 18.4±5.9, and 18.9±5.3 mL/kg/min, respectively; P<0.001). Regarding the QOL, the physical component summary (PCS) scores significantly improved (32±11, 38±13, and 43±13, respectively; P<0.001), but the mental component summary scores remained unchanged. Linear regression analysis revealed that age and a low peak VO2 at entry were predictors of improvement in peak VO2, while low PCS scores and low TAPSE at entry were predictors of improvement in PCS scores. In conclusion, extensive BPA led to improved exercise tolerance and physical QOL scores, even in CTEPH patients with partially improved hemodynamics.

How to Assess Breathlessness in Chronic Obstructive Pulmonary Disease.

Lewthwaite H; Jensen D; Ekström M;

International journal of chronic obstructive pulmonary disease [Int J Chron Obstruct Pulmon Dis] 2021 Jun 03; Vol. 16, pp. 1581-1598. Date of Electronic Publication: 2021 Jun 03 (Print Publication: 2021).

Activity-related breathlessness is the most problematic symptom of chronic obstructive pulmonary disease (COPD), arising from complex interactions between peripheral pathophysiology (both pulmonary and non-pulmonary) and central perceptual processing. To capture information on the breathlessness experienced by people with COPD, many different instruments exist, which vary in applicability depending on the purpose and context of assessment. We reviewed common breathlessness assessment instruments, providing recommendations around how to assess the severity of, or change in, breathlessness in people with COPD in daily life or in response to exercise provocation. A summary of 14 instruments for the assessment of breathlessness severity in daily life is presented, with 11/14 (79%) instruments having established minimal clinically importance differences (MCIDs) to assess and interpret breathlessness change. Instruments varied in their scope of assessment (functional impact of breathlessness or the severity of breathlessness during different activities, focal periods, or alongside other common COPD symptoms), dimensions of breathlessness assessed (uni-/multidimensional), rating scale properties and intended method of administration (self-administered versus interviewer led). Assessing breathlessness in response to an acute exercise provocation overcomes some limitations of daily life assessment, such as recall bias and lack of standardized exertional stimulus. To assess the severity of breathlessness in response to an acute exercise provocation, unidimensional or multidimensional instruments are available. Borg’s 0-10 category rating scale is the most widely used instrument and has estimates for a MCID during exercise. When assessing the severity of breathlessness during exercise, measures should be taken at a standardized submaximal point, whether during laboratory-based tests like cardiopulmonary exercise testing or field-based tests, such as the 3-min constant rate stair stepping or shuttle walking tests. Recommendations are provided around which instruments to use for breathlessness assessment in daily life and in relation to exertion in people with COPD.

Cardiorespiratory Fitness After Open Repair for Acute Type A Aortic Dissection – A Prospective Study.

Norton EL; Rubenfire M; Fink S; Sitzmann J; Hobbs RD; Saberi S; Willer CJ; Yang B; Hornsby WE;

Seminars in thoracic and cardiovascular surgery [Semin Thorac Cardiovasc Surg] 2021 Jun 05. Date of Electronic Publication: 2021 Jun 05.

Objective: Cardiorespiratory fitness (as measured by peak oxygen consumption [VO 2peak ]) is an independent predictor of cardiovascular disease and all-cause mortality. Limited data exist on VO 2peak following repair for an acute type A aortic dissection (ATAAD) or proximal thoracic aortic aneurysm (pTAA). This study prospectively evaluated VO 2peak , functional capacity, and health-related quality of life (HR-QOL) following open repair.
Methods: Participants with a history of an ATAAD (n=21) or pTAA (n=43) performed cardiopulmonary exercise testing (CPX), six-minute walk testing, and HR-QOL at 3 (early) and 15 (late) months following open repair.
Results:   The median age at time of surgery was 55-years-old and 60-years-old in the ATAAD and pTAA groups, respectively. Body mass index significantly increased between early and late timepoints for both ATAAD (p=0.0245, 56% obese) and pTAA groups (p=0.0045, 54% obese). VO 2peak modestly increased by 0.8 mLO2•kg-1•min-1 within the ATAAD group (P=0.2312) while VO 2peak significantly increased by 2.2 mLO2•kg-1•min-1 within the pTAA group (P=0.0003). Anxiety significantly decreased in the ATAAD group whereas functional capacity and HR-QOL metrics (social roles and activities, physical function) significantly improved in the pTAA group (p values<0.05). There were no serious adverse events during CPX.
Conclusion: Cardiorespiratory fitness among the ATAAD group remained 36% below predicted normative values >1 year after repair. CPX should be considered post-operatively to evaluate exercise tolerance and blood pressure response to determine whether mild-to-moderate aerobic exercise should be recommended to reduce future risk of morbidity and mortality.


Preoperative Cardiopulmonary Exercise Test Associated with Postoperative Outcomes in Patients Undergoing Cancer Surgery: A Systematic Review and Meta-Analyses.

Steffens D; Ismail H; Denehy L; Beckenkamp PR; Solomon M; Koh C; Bartyn J;

Annals of surgical oncology [Ann Surg Oncol] 2021 Jun 08. Date of Electronic Publication: 2021 Jun 08.

Backgrounds: There is mixed evidence on the value of preoperative cardiorespiratory exercise test (CPET) to predict postoperative outcomes in patients undergoing a cancer surgical procedure. The purpose of this review was to investigate the association between preoperative CPET variables and postoperative complications, length of hospital stay, and quality of life in patients undergoing cancer surgery.
Methods: A search was conducted on MEDLINE, Embase, AMED, and Web of science from inception to April 2020. Cohort studies investigating the association between preoperative CPET variables, including peak oxygen uptake (peak VO 2 ), anaerobic threshold (AT), or ventilatory equivalent for carbon dioxide (V E /V CO2 ), and postoperative outcomes (complications, length of stay, and quality of life) were included. Risk of bias was assessed using the QUIPS tool. A random-effect model meta-analysis was performed whenever possible.
Results: Fifty-two unique studies, including 10,030 patients were included. Overall, most studies were rated as having low risk of bias. Higher preoperative peak VO 2 was associated with absence of postoperative complications (mean difference [MD]: 2.28; 95% confidence interval [CI]: 1.26-3.29) and no pulmonary complication (MD: 1.47; 95% CI: 0.49-2.45). Preoperative AT and V E /V CO2 also demonstrated some positive trends. None of the included studies reported a negative trend.
Conclusions: This systematic review and meta-analysis demonstrated a significant association between superior preoperative CPET values, especially peak VO 2 , and better postoperative outcomes. The assessment of preoperative functional capacity in patients undergoing cancer surgery has the potential to facilitate treatment decision making.

Cardiopulmonary Exercise Testing with Echocardiography to Identify Mechanisms of Unexplained Dyspnea.

Martens P; Herbots L; Verbrugge FH; Dendale P; Borlaug BA; Verwerft J;

Journal of cardiovascular translational research [J Cardiovasc Transl Res] 2021 Jun 10. Date of Electronic Publication: 2021 Jun 10.

Little data is available about the pathophysiological mechanisms of unexplained dyspnea and their clinical meaning. Consecutive patients with unexplained dyspnea underwent prospective standardized cardiopulmonary exercise testing with echocardiography (CPETecho). Patients were grouped as having normal exercise capacity (peak VO 2 > 80% with respiratory exchange [RER] > 1.05), reduced exercise capacity (peak VO 2 ≤ 80% with RER > 1.05), or a submaximal exercise test (RER ≤ 1.05). From 307 patients, 144 (47%) had normal and 116 (38%) reduced exercise capacity, and 47 (15%) had a submaximal exercise test. Patients with reduced versus normal exercise capacity had significantly more mechanisms for unexplained dyspnea (2.3±1.0 vs 1.5±1.0, respectively; p<0.001). Exercise PH (42%), low heart rate reserve (51%), low stroke volume reserve (38%), low diastolic reserve (18%), and peripheral muscle limitation (17%) were most common. Patients with more mechanisms for dyspnea displayed poorer peak VO 2 and had an increased risk for cardiovascular hospitalization (p=0.002). Patients with unexplained dyspnea display multiple coexisting mechanisms for exercise intolerance, which relate to the severity of exercise limitation and risk of subsequent cardiovascular hospitalizations.

Women Have Lower Mortality Than Men After Attending a Long-Term Medically Supervised Exercise Program.

de Souza E Silva CG; Nishijuka FA; de Castro CLB; Franca JF; Myers J; Laukkanen JA; de Araújo CGS

Journal of cardiopulmonary rehabilitation and prevention [J Cardiopulm Rehabil Prev] 2021 Jun 10. Date of Electronic Publication: 2021 Jun 10.

Purpose: Medically supervised exercise programs (MSEPs) are equally recommended for men and women with cardiovascular disease (CVD). Aware of the lower CVD mortality in women, we hypothesized that among patients attending a MSEP, women would also have better survival.
Methods: Data from men and women, who were enrolled in a MSEP between 1994 and 2018, were retrospectively analyzed. Sessions included aerobic, resistance, flexibility and balance exercises, and cardiopulmonary exercise test was performed. Date and underlying cause of death were obtained. Kaplan-Meier methods and Cox proportional hazards regression were used for survival analysis.
Results: A total of 2236 participants (66% men, age range 33-85 yr) attended a median of 52 (18, 172) exercise sessions, and 23% died during 11 (6, 16) yr of follow-up. In both sexes, CVD was the leading cause of death (39%). Overall, women had a more favorable clinical profile and a longer survival compared to men (HR = 0.71: 95% CI, 0.58-0.85; P < .01). When considering those with coronary artery disease and similar clinical profile, although women had a lower percentage of sex- and age-predicted maximal oxygen uptake at baseline than men (58 vs 78%; P < .01), after adjusting for age, women still had a better long-term survival (HR = 0.68: 95% CI, 0.49-0.93; P = .02).
Conclusion: Survival after attendance to a long-term MSEP was better among women, despite lower baseline cardiorespiratory fitness. Future studies should address whether men and women would similarly benefit when participating in an MSEP.

Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart.

Rieth AJ; Richter MJ; Tello K; Gall H; Ghofrani HA; Guth S; Wiedenroth CB; Seeger W; Kriechbaum SD; Mitrovic V; Schulze PC; Hamm CW;

Clinical research in cardiology : official journal of the German Cardiac Society [Clin Res Cardiol] 2021 Jun 10. Date of Electronic Publication: 2021 Jun 10.

Objective: We sought to explore whether classification of patients with heart failure and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) according to their left ventricular ejection fraction (LVEF) identifies differences in their exercise hemodynamic profile, and whether classification according to an index of right ventricular (RV) function improves differentiation.
Background: Patients with HFmrEF and HFpEF have hemodynamic compromise on exertion. The classification according to LVEF implies a key role of the left ventricle. However, RV involvement in exercise limitation is increasingly recognized. The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PASP) ratio is an index of RV and pulmonary vascular function. Whether exercise hemodynamics differ more between HFmrEF and HFpEF than between TAPSE/PASP tertiles is unknown.
Methods: We analyzed 166 patients with HFpEF (LVEF ≥ 50%) or HFmrEF (LVEF 40-49%) who underwent basic diagnostics (laboratory testing, echocardiography at rest, and cardiopulmonary exercise testing [CPET]) and exercise with right heart catheterization. Hemodynamics were compared according to echocardiographic left ventricular or RV function.
Results: Exercise hemodynamics (e.g. pulmonary arterial wedge pressure/cardiac output [CO] slope, CO increase during exercise, and maximum total pulmonary resistance) showed no difference between HFpEF and HFmrEF, but significantly differed across TAPSE/PASP tertiles and were associated with CPET results. N-terminal pro-brain natriuretic peptide concentration also differed significantly across TAPSE/PASP tertiles but not between HFpEF and HFmrEF.
Conclusion: In patients with HFpEF or HFmrEF, TAPSE/PASP emerged as a more appropriate stratification parameter than LVEF to predict clinically relevant impairment of exercise hemodynamics. Stratification of exercise hemodynamics in patients with HFpEF or HFmrEF according to LVEF or TAPSE/PASP, showing significant distinctions only with the RV-based strategy. All data are shown as median [upper limit of interquartile range] and were calculated using the independent-samples Mann-Whitney U test or Kruskal-Wallis test. PVR pulmonary vascular resistance; max maximum level during exercise.

Circulatory Response to Trauma of Surgical Operations

Clowes GH; Del Guercio LR;

Circulatory response to trauma of surgical operations. Metabolism. 1960;9:67-81. (NOTE THE DATE)

To determine the nature of the normal cardiovascular response of man to surgi­cal operations, thirteen patients making uncomplicated recoveries after thoraco­tomy for pulmonary surgery were studied by measuring cardiac output and arterial and venous pressure before, during and for one week after surgery. Arterial pH, blood gas and electrolytes were analyzed simultaneously. Through­ out the observations, arterial blood pres­sure was more or less constantly main­tained; but during the operation cardiac output fell an average of  33  per  cent with a decrease of  stroke  volume,  and the calculated peripheral arterial resist­ance rose. Venous pressure was elevated in all patients during the  induction of anesthesia and remained so to the end of the operation. Upon awakening and during extubation, the situation was promptly reversed.  Cardiac output rose to 130 per cent of the resting value; peripheral resistance fell below normal; and venous pressure returned to levels below 10 cm. of H20 . These changes persisted to the end of the first post­ operative week. Three patients, who recovered satisfactorily after cardiac operations,  followed a similar  pattern of circulatory response. Arterial pH and pCO2 were main­tained within normal limits in all pa­tients who recovered; however, all showed some degree of arterial oxygen desaturation postoperatively. Metabolic acidosis,  as  indicated   by  an  elevation of lactic acid, took  place  during  and after the operation but returned to pre­-operative values within three days. Sodium fell, on the average, to 129 mEq./L. on the second postoperative day.  Ionized calcium fell to 4.1 mg. per cent on the first day. Potassium remained unchanged. Three patients who recovered from open heart operations responded in the same fashion with a postoperative in­ crease in cardiac output.
Two patients died postoperatively. Both failed to show the normal post­ operative elevation of cardiac output; metabolic acidosis increased until re­spiratory compensation failed, and ar­terial pH fell below 7.3.