Sethi S;  (Hull York Medical School, Hull, UK.)
Ravindhran B; Long J; Gurung R;Huang C; Smith GE; Carradice D; Wallace T; Ibeggazene S; Chetter I; Pymer S;

Journal of vascular surgery [J Vasc Surg] 2023 Sep 13.
Date of Electronic Publication: 2023 Sep 13.

Introduction: A preoperative supervised exercise programme (SEP) improves cardiorespiratory fitness and perioperative outcomes for patients undergoing elective abdominal aortic aneurysm (AAA) repair. The aim of this study was to assess the effect of a preoperative SEP on long-term survival of these patients. A secondary aim was to consider long-term changes in cardiorespiratory fitness and quality of life.
Methods: Patients scheduled for open or endovascular AAA repair were previously randomized to either a 6-week preoperative SEP or standard management and a significant improvement in a composite outcome of cardiac, pulmonary, and renal complications was seen following SEP. For the current analysis, patients were followed up to five years post-surgery. The primary outcome for this analysis was all-cause mortality. Data were analysed on an intention to treat (ITT) and per protocol (PP) basis, with the latter meaning that patients randomised to SEP who did not attend any sessions, were excluded. The PP analysis was further interrogated using a complier average causal effect (CACE) analysis on an all or nothing scale, which adjusts for compliance. Additionally, patients who agreed to follow-up attended the research centre for cardiopulmonary exercise testing and/or provided QoL measures.
Results: ITT analysis demonstrated that the primary endpoint occurred in 24 of the 124 participants at five years, with 8 in the SEP group and 16 in the control group (p = 0.08). The PP analysis demonstrated a significant survival benefit associated with SEP attendance (4 vs. 16 deaths p = 0.01). CACE analysis confirmed a significant intervention effect (HR = 0.36; 95% CI: 0.16, 0.90; p = 0.02). There was no difference between groups for cardiorespiratory fitness measures and most QoL measures.
Conclusion: These novel findings suggest a long-term mortality benefit for patients attending a SEP prior to elective AAA repair. The underlying mechanism remains unknown, and this merits further investigation.

Agostoni P;  (Centro Cardiologico Monzino, IRCCs, Milan, Italy.)
Pluchinotta FR; Salvioni E; et al.

European journal of heart failure [Eur J Heart Fail] 2023 Sep 13.
Date of Electronic Publication: 2023 Sep 13.

Aims: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF).
Methods and Results: 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow-up of 1490 days). We analyzed clinical, laboratory, ECG, echocardiographic, exercise, and survival data from HFimpEF (n = 1504) and pHFrEF (n = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: LVEF 44.0[41.0-47.0] vs. 29.7[24.1-34.5]%, BNP 122[65-296] vs. 373[152-888] pg/mL, hemoglobin 13.5[12.2-14.6] vs. 13.7[12.5-14.7] g/dL, renal function by MDRD 72.0[56.7-89.3] vs. 70.4[54.5-85.3] mL/min, peakVO ₂ 62.2[50.7-74.1] vs. 52.6[41.8-64.3]%pred, VE/VCO ₂ slope 30.0[26.9-34.4] vs. 32.1[28.0-38.0] in HFimpEF and pHFrEF, respectively (p < 0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person-years for HFimpEF and pHFrEF, respectively (p < 0.001). Kaplan-Meier analysis showed that HFimpEF had better a long-term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan-Meier curves showed the same prognosis.
Conclusions: HFimpEF represents a peculiar group of HF patients whose clinical, laboratory, ECG, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.

Ariyaratnam JP; Elliott AD; Mishima RS; Kadhim K; McNamee O; Kuklik P; Emami M; Malik V; Fitzgerald JL; Gallagher C; Lau DH; Sanders P;

JACC. Heart failure [JACC Heart Fail] 2023 Aug 21.
Date of Electronic Publication: 2023 Aug 21.

Background: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. We hypothesize that patients with symptomatic AF but without overt clinical HF commonly exhibit subclinical HFpEF according to established hemodynamic criteria.
Objectives: The authors sought to use invasive hemodynamics to investigate the prevalence and implications of subclinical HFpEF in AF ablation patients.
Methods: Consecutive symptomatic AF ablation patients were prospectively recruited. Diagnosis of subclinical HFpEF was undertaken by invasive assessment of left atrial pressure (LAP). Participants had HFpEF if the baseline mean LAP was >15 mm Hg and early HFpEF if the mean LAP was >15 mm Hg after a 500-mL fluid challenge. LA compliance was assessed invasively by monitoring the LAP and LA diameter during direct LA infusion of 15 mL/kg normal saline. LA compliance was calculated as Δ LA diameter/ΔLAP. LA cardiomyopathy was further studied with exercise echocardiography and electrophysiology study. Functional impact was evaluated using cardiopulmonary exercise testing and the AF Symptom Severity questionnaire.
Results: Of 120 participants, 57 (47.5%) had HFpEF, 31 (25.8%) had early HFpEF, and 32 (26.7%) had no HFpEF. Both HFpEF and early HFpEF were associated with lower LA compliance compared with those without HFpEF (P < 0.001). Participants with HFpEF and early HFpEF also displayed decreased LA emptying fraction (P = 0.004), decreased LA voltage (P = 0.001), decreased VO _2peak (P < 0.001), and increased AF symptom burden (P = 0.002) compared with those without HFpEF.
Conclusions: Subclinical HFpEF is common in AF ablation patients and is characterized by a LA cardiomyopathy, decreased cardiopulmonary reserve and increased symptom burden. The diagnosis of HFpEF may identify patients with AF with the potential to benefit from novel HFpEF therapies. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921).
Competing Interests: Funding Support and Author Disclosures Drs Ariyaratnam, Mishima, Kadhim, Emami, Malik, and Fitzgerald are supported by Postgraduate Scholarships from the University of Adelaide. Dr Elliott is supported by a Future Leader Fellowship from the National Heart Foundation of Australia. Dr Gallagher is supported by a Postdoctoral Fellowship from the University of Adelaide. Dr Lau is supported by a Mid-career fellowship from The Hospital Research Foundation. Dr Sanders is supported by a Practitioner Fellowship from the National Health and Medical Research Council of Australia. Dr Lau reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Abbott Medical, Bayer, Biotronik, BMS Pfizer, Boehringer Ingelheim, Medtronic, and MicroPort CRM. Dr Sanders has served on the advisory board of Medtronic, Abbott Medical, Boston-Scientific, Pacemate, and CathRx. Dr Sanders reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Medtronic, Boston-Scientific, and Abbott Medical; and reports that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott Medical, Boston Scientific, and Microport CRM. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Pezzuto B; Agostoni P;

Journal of clinical medicine [J Clin Med] 2023 Aug 23; Vol. 12 (17).
Date of Electronic Publication: 2023 Aug 23.

Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis if left untreated. Despite remarkable achievements in understanding disease pathophysiology, specific treatments, and therapeutic strategies, we are still far from a definitive cure for the disease, and numerous evidences have underlined the importance of early diagnosis and treatment to improve the prognosis. Cardiopulmonary exercise testing (CPET) is the gold standard for assessing functional capacity and evaluating the pathophysiological mechanisms underlying exercise limitation. As effort dyspnea is the earliest and one of the main clinical manifestations of PAH, CPET has been shown to provide valid support in early detection, differential diagnosis, and prognostic stratification of PAH patients, being a useful tool in both the first approach to patients and follow-up. The purpose of this review is to present the current applications of CPET in pulmonary hypertension and to propose possible future utilization to be further investigated.

Rischard FP; Bernardo RJ; Vanderpool RR; Kwon DH; Acharya T; Park MM; Katrynuik A; Insel M; Kubba S; Badagliacca R; Larive AB; Naeije R;Garcia JGN; Beck GJ; Erzurum SC; Hassoun PM; Hemnes AR; Hill NS; Horn EM; Leopold JA; Rosenzweig EB; Tang WHW; Wilcox JD;

Circulation. Heart failure [Circ Heart Fail] 2023 Sep 04, pp. e010555.
Date of Electronic Publication: 2023 Sep 04.

Background: Normative changes in right ventricular (RV) structure and function have not been characterized in the context of treatment-associated functional recovery (RV functional recovery [RVFnRec]). The aim of this study is to assess the clinical relevance of a proposed RVFnRec definition.
Methods: We evaluated 63 incident patients with pulmonary arterial hypertension by right heart catheterization and cardiac magnetic resonance imaging at diagnosis and cardiac magnetic resonance imaging and invasive cardiopulmonary exercise testing following treatment (≈11 months). Sex, age, ethnicity matched healthy control subjects (n=62) with 1-time cardiac magnetic resonance imaging and noninvasive cardiopulmonary exercise testing were recruited from the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) project. We examined therapeutic cardiac magnetic resonance imaging changes relative to the evidence-based peak oxygen consumption (VO _2peak )>15 mL/(kg·min) to define RVFnRec by receiver operating curve analysis. Afterload was measured as mean pulmonary artery pressure, resistance, compliance, and elastance.
Results: A drop in RV end-diastolic volume of -15 mL best defined RVFnRec (area under the curve, 0.87; P =0.0001) and neared upper 95% CI RV end-diastolic volume of controls. This cutoff was met by 22 out of 63 (35%) patients which was reinforced by freedom from clinical worsening, RVFnRec 1 out of 21 (5%) versus no RVFnRec 17 out of 42, 40% (log-rank P =0.006). A therapy-associated increase of 0.8 mL/mm Hg in compliance had the best predictive value of RVFnRec (area under the curve, 0.76; [95% CI, 0.64-0.88]; P =0.001). RVFnRec patients had greater increases in stroke volume, and cardiac output at exercise.
Conclusions: RVFnRec defined by RV end-diastolic volume therapeutic decrease of -15 mL predicts exercise capacity, freedom from clinical worsening, and nears normalization. A therapeutic improvement of compliance is superior to other measures of afterload in predicting RVFnRec. RVFnRec is also associated with increased RV output reserve at exercise.

Chaudhry S; Kumar N; Arena R; Verma S;

Current opinion in cardiology [Curr Opin Cardiol] 2023 Sep 08.
Date of Electronic Publication: 2023 Sep 08.

Purpose of Review: Cardiopulmonary exercise testing (CPET) is the gold standard for directly assessing cardiorespiratory fitness (CRF) and has a relatively new and evolving role in evaluating atherosclerotic heart disease, particularly in detecting cardiac dysfunction caused by ischemic heart disease. The purpose of this review is to assess the current literature on the link between cardiovascular (CV) risk factors, cardiac dysfunction and CRF assessed by CPET.
Recent Findings: We summarize the basics of exercise physiology and the key determinants of CRF. Prognostically, several studies have been published relating directly measured CRF by CPET and outcomes allowing for more precise risk assessment. Diagnostically, this review describes in detail what is considered healthy and abnormal cardiac function assessed by CPET. New studies demonstrate that cardiac dysfunction on CPET is a common finding in asymptomatic individuals and is associated with CV risk factors and lower CRF. This review covers how key CPET parameters change as individuals transition from the asymptomatic to the symptomatic stage with progressively decreasing CRF. Finally, a supplement with case studies with long-term longitudinal data demonstrating how CPET can be used in daily clinical decision making is presented.
Summary: In summary, CPET is a powerful tool to provide individualized CV risk assessment, monitor the effectiveness of therapeutic interventions, and provide meaningful feedback to help patients guide their path to improve CRF when routinely used in the outpatient setting.

Darwen C; MBryan A; Quraishi-Akhtar T; Moore J;

BJA open [BJA Open] 2023 Feb 23; Vol. 5, pp. 100124.
Date of Electronic Publication: 2023 Feb 23 (Print Publication: 2023).

Background: Blood lactate concentration in the postoperative period is a marker of physiological stress and a predictor of complications and mortality. Cardiopulmonary exercise testing (CPET) is a common preoperative risk stratification tool. We aimed to investigate the association between preoperative CPET results and postoperative lactate concentration with postoperative mortality after major noncardiac surgery.
Methods: We analysed data from patients undergoing major noncardiac surgery in a tertiary UK centre between 2007 and 2014 who had preoperative CPET and postoperative lactate measurements. Univariate and multivariate analyses were performed to assess the association between lactate concentration, CPET results, or both and mortality.
Results: We analysed data from 1075 patients. A mean lactate concentration >2 mM in the first 12, 24, and 48 h after surgery was associated with odds ratios (ORs) and 95% confidence intervals (CIs) for 30-day mortality of 3.9 (2.1-7.3; P <0.005), 4.5 (2.4-8.4; P <0.005), and 6.1 (3.3-11.5; P <0.005), respectively. The dichotomous CPET variable, ventilatory equivalence for CO ₂ ( V̇ E/ V̇ _co2 ; cut-off 34), was associated with increased risk of 30-day mortality (OR 2.5; 95% CI: 1.3-4.8; P <0.005). In a multivariable model, hyperlactataemia and poor V̇ E/ V̇ _co2 retained their significant associations with 30- and 90-day mortality when adjusted for age, BMI, and surgical risk. When looking at the combined effect of the dichotomous hyperlactataemia in the first 24 h (cut-off 2 mM) and preoperative V̇ E/ V̇ _co2 , the OR for 30-day mortality was 11.53 (95% CI: 4.6-28.8; P ≤0.005).
Conclusions: Our study suggests that postoperative hyperlactataemia and preoperative poor V̇ E/ V̇ _co2 are independently associated with an increased risk of mortality after major noncardiac surgery.

Baracchini N; Zaffalon D; Merlo M; Baschino S; Barbati G; Pezzuto B; Capovilla TM; Rossi M; Carriere C; Agostoni P; Sinagra G;

International journal of cardiology [Int J Cardiol] 2023 Aug 08, pp. 131252.
Date of Electronic Publication: 2023 Aug 08.

Background: Cardiopulmonary exercise testing (CPET) is a recognized tool for prognostic stratification in patients with dilated cardiomyopathy (DCM). Given the lack of data currently available, the aim of this study was to test the prognostic value of repeating CPET during the follow-up of patients with DCM.
Methods: This multicenter, retrospective study, analyzed DCM patients who consecutively performed two echocardiographies and CPETs during clinical stability. The study end-point was a composite of death from all causes, heart transplantation, left ventricular assist device implantation, life-threatening ventricular arrhythmias or hospitalization for heart failure.
Results: 216 DCM patients were enrolled (52 years, 78% male, NYHA I-II 82%, LVEF 32%, 94% on ACE inhibitors/ARNI, 95% on beta-blockers). The interval between CPETs was 15 months. During a median follow-up of 38 months from the second CPET, 102 (47%) patients experienced the study end-point. Among them, there was stability of echocardiographic values but a significant worsening of functional capacity. Among the 173 patients (80%) who did not show echocardiographic left ventricular reverse remodeling (LVRR), the 1-year prevalence of the study-end point was higher in patients who worsened vs patients who maintained stable their functional capacity at CPET (38 vs. 15% respectively, p-value: 0.001). These results were consistent also when excluding life-threatening ventricular arrhythmias from the composite end-point.
Conclusion: In clinically stable DCM patients with important depression of LVEF, the repetition of combined echocardiography and CPET might be recommended. When LVRR fails, 1-year repetition of CPET could identify higher-risk patients.

Gronningsaeter L; Estensen ME; Skulstad H; Langesaeter E; Edvardsen E;

Hypertension in pregnancy [Hypertens Pregnancy] 2023 Dec; Vol. 42 (1), pp. 2245054.

Aims: To objectively study cardiorespiratory fitness (CRF) and physical activity (PA) and to evaluate limiting factors of exercise intolerance associated with poor CRF after severe pre-eclampsia.
Methods: In this single-centre, cross-sectional study, CRF was measured as peak oxygen uptake (VO _2peak ) during a cardiopulmonary exercise test (CPET) on a treadmill in women 7 years after severe pre-eclampsia. Ninety-six patients and 65 controls were eligible to participate. Cardiac output (CO) was measured by impedance cardiography. PA was measured using accelerometers.
Results: In 62 patients and 35 controls (mean age 40 ± 3 years), the VO _2peak (in mL·kg-1·min-1) values were 31.4 ± 7.2 and 39.1 ± 5.4, respectively (p<0.01). In the patients, the COpeak was (9.6 L·min-1), 16% lower compared to controls (p<0.01). Twelve patients (19%) had a cardiac limitation to CPET. Twenty-three (37%) patients and one (3%) control were classed as unfit, with no cardiopulmonary limitations. The patients demonstrated 25% lower PA level (in counts per minute; p<0.01) and 14% more time being sedentary (p<0.01), compared with the controls. Twenty-one patients (34%) compared with four (17%) controls did not meet the World Health Organization’s recommendations for PA (p=0.02). Body mass index and PA level accounted for 65% of the variability in VO _2peak .
Conclusion: Significantly lower CRF and PA levels were found in patients on long-term follow-up after severe pre-eclampsia. CPET identified cardiovascular limitations in one third of patients. One third appeared unfit, with adiposity and lower PA levels. These findings highlight the need for clinical follow-up and exercise interventions after severe pre-eclampsia.