De Biase N; (Department of Clinical and Experimental Medicine, University of Pisa, Italy.)
Mazzola M; Del Punta L; Di Fiore V;De Carlo M; Giannini C; Costa G; Paneni F; Mengozzi A; Nesti L; Gargani L; Masi S; Pugliese NR;

European journal of heart failure [Eur J Heart Fail] 2023 Sep 01.
Date of Electronic Publication: 2023 Sep 01.

Aims: Degenerative aortic valve stenosis with preserved ejection fraction (ASpEF) and heart failure with preserved ejection fraction (HFpEF) display intriguing similarities. This study aimed to provide a non-invasive, comparative analysis of ASpEF versus HFpEF at rest and during exercise.
Methods and Results: We prospectively enrolled 148 patients with HFpEF and 150 patients with degenerative moderate-to-severe ASpEF, together with 66 age- and sex-matched healthy controls. All subjects received a comprehensive evaluation at rest and 351/364 (96%) performed a combined cardiopulmonary exercise stress echocardiography test. Patients with ASpEF eligible for transcatheter aortic valve replacement (n = 125) also performed cardiac computed tomography (CT). HFpEF and ASpEF patients showed similar demographic distribution and biohumoral profiles. Most patients with ASpEF (134/150, 89%) had severe high-gradient aortic stenosis; 6/150 (4%) had normal-flow, low-gradient ASpEF, while 10/150 (7%) had low-flow, low-gradient ASpEF. Both patient groups displayed significantly lower peak oxygen consumption (VO ₂ ), peak cardiac output, and peak arteriovenous oxygen difference compared to controls (all p < 0.01). ASpEF patients showed several extravalvular abnormalities at rest and during exercise, similar to HFpEF (all p < 0.01 vs. controls). Epicardial adipose tissue (EAT) thickness was significantly greater in ASpEF than HFpEF and was inversely correlated with peak VO ₂ in all groups. In ASpEF, EAT was directly related to echocardiography-derived disease severity and CT-derived aortic valve calcium burden.
Conclusion: Functional capacity is similarly impaired in ASpEF and HFpEF due to both peripheral and central components. Further investigation is warranted to determine whether extravalvular alterations may affect disease progression and prognosis in ASpEF even after valve intervention, which could support the concept of ASpEF as a specific sub-phenotype of HFpEF.

Ogura A;  (Cardiovascular Stroke Renal Project (CRP), Hyogo, Japan.)
Izawa KP; Tawa H; Wada M;Kanai M; Kubo I; Makihara A; Yoshikawa R; Matsuda Y;

The American journal of cardiology [Am J Cardiol] 2023 Sep 07; Vol. 205, pp. 387-392.
Date of Electronic Publication: 2023 Sep 07.

Patients with heart disease have a low anaerobic threshold (AT), and the determinants of AT may differ, depending on the severity of renal dysfunction. This study aimed to verify the determinants of AT for each stage of renal function in patients with heart disease. We consecutively enrolled 250 patients with heart disease who underwent cardiopulmonary exercise testing in our institution. The patients were divided into 3 groups by their estimated glomerular filtration rate (eGFR): <45, 45 to 59, and ≥60 ml/min/1.73 m ² . A multivariate linear regression analysis was performed to evaluate the independent determinants of AT for each group. In total, 201 patients were analyzed. AT decreased with the deterioration of renal function (eGFR <45, 10.9 ± 2.1 vs eGFR 45 to 59, 12.4 ± 2.5 vs eGFR ≥60, 14.0 ± 2.6 ml/min/kg, p <0.001). In the eGFR <45 group, left ventricular ejection fraction and hemoglobin were significantly associated with AT (β = 0.427, p = 0.006 and β = 0.488, p = 0.002, respectively). In the eGFR 45 to 59 and ≥60 groups, ΔP _ET O ₂ (end-tidal oxygen partial pressure from rest to AT) showed a significant association with AT (β = 0.576, p <0.001 and β = 0.308, p = 0.003, respectively). The determinants of AT depended on the stage of renal dysfunction in patients with heart disease. In conclusion, in the eGFR <45 group, the determinants of AT were left ventricular ejection fraction and hemoglobin, whereas in the eGFR 45 to 59 and eGFR ≥60 groups, the determinant of AT was ΔP _ET O ₂ .

Triantafyllidi H;  (Department of Cardiology,  National and Kapodistrian University of Athens,  Greece.)
Benas D; Iliodromitis E;

International journal of cardiology [Int J Cardiol] 2023 Sep 12, pp. 131356.
Date of Electronic Publication: 2023 Sep 12.

No abstract available

Schwendinger F; (University of Basel, Basel, SWITZERLAND.)
Wagner J; Knaier R; Infanger D; Rowlands AV;Hinrichs T; Schmidt-Trucksäss A;

Medicine and science in sports and exercise [Med Sci Sports Exerc] 2023 Sep 13.
Date of Electronic Publication: 2023 Sep 13.

Purpose: Accelerometer-assessed physical activity (PA) can be summarised using cut-point-free or population-specific cut-point-based outcomes. We aimed to: 1) examine the interrelationship between cut-point-free (intensity gradient [IG] and average acceleration [AvAcc]) and cut-point-based accelerometer metrics, 2) compare the association between cardiorespiratory fitness (CRF) and cut-point-free metrics to that with cut-point-based metrics in healthy adults aged 20 to 89 years and patients with heart failure, and 3) provide age-, sex-, and CRF-related reference values for healthy adults.
Methods: In the COmPLETE study, 463 healthy adults and 67 patients with heart failure wore GENEActiv accelerometers on their non-dominant wrist and underwent cardiopulmonary exercise testing. Cut-point-free (IG: distribution of intensity of activity across the day; AvAcc: proxy of volume of activity) and traditional (moderate-to-vigorous and vigorous activity) metrics were generated. The ‘interpretablePA’ R-package was developed to translate findings into clinical practice.
Results: IG and AvAcc yield complementary information on PA with both IG (p = 0.009) and AvAcc (p < 0.001) independently associated with CRF in healthy individuals (adjusted R2 = 73.9%). Only IG was independently associated with CRF in patients with heart failure (p = 0.043, adjusted R2 = 38.4%). The best cut-point-free and cut-point-based model had similar predictive value for CRF in both cohorts. We produced age- and sex-specific reference values and percentile curves for IG, AvAcc, moderate-to-vigorous PA, and vigorous PA for healthy adults.
Conclusions: IG and AvAcc are strongly associated with CRF and, thus, indirectly with the risk of non-communicable diseases and mortality, in healthy adults and patients with heart failure. However, unlike cut-point-based metrics, IG and AvAcc are comparable across populations. Our reference values provide a healthy age- and sex-specific comparison that may enhance the translation and utility of cut-point-free metrics in clinical practice.
Competing Interests: Conflict of Interest and Funding Source: The COmPLETE study was funded by the Swiss National Science Foundation (Grant no. 182815). AVR is supported by the Lifestyle Theme of the Leicester NHR Leicester Biomedical Research Centre and NIHR Applied Research Collaborations East Midlands (ARC-EM). The authors declare that they have no competing interests. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sports Medicine.

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.