Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy.

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.

mPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

BACKGROUND: Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. METHODS: In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). RESULTS: One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. CONCLUSIONS: In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Heart failure with preserved ejection fraction: relevance of a dedicated dyspnoea clinic.

BACKGROUND AND AIMS: Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous presentation. This study provides an in-;depth description of haemodynamic and metabolic alterations revealed by systematic assessment through cardiopulmonary exercise testing combined with exercise echocardiography (CPETecho) within a dedicated dyspnoea clinic. METHODS AND RESULTS: Consecutive patients (n = 297), referred to a dedicated dyspnoea clinic using a standardized workup including CPETecho, with HFpEF diagnosed through a H2FPEF score ≥6 or HFA-PEFF score ≥5, were evaluated. A median of four haemodynamic/metabolic alterations was uncovered per patient: impaired stroke volume reserve (73%), impaired chronotropic reserve (72%), exercise pulmonary hypertension (65%), and impaired diastolic reserve (64%) were the most frequent cardiac alterations. Impaired peripheral oxygen extraction and a ventilatory limitation were present in 40% and 39%, respectively. In 267 patients (90%), 575 further diagnostic examinations were recommended (median of two tests per patient). Cardiac magnetic resonance imaging, coronary or amyloidosis workup, ventilation-perfusion scanning, and pulmonology referral were each recommended in approximately one out of three patients. In 293 patients (99%), 929 cardiovascular drug optimizations were performed (median of 3 modifications per patient). In 110 patients (37%), 132 cardiovascular interventions were performed, with ablation as the most frequent procedure. CONCLUSION: Holistic workup of HFpEF patients within a multidisciplinary, dedicated dyspnoea clinic, including systematic implementation of CPETecho reveals various haemodynamic/metabolic alterations, leading to further diagnostic testing and potential treatment changes in the majority of cases.

Lifelong endurance exercise and its relation with coronary atherosclerosis.

AIMS: The impact of long-term endurance sport participation (on top of a healthy lifestyle) on coronary atherosclerosis and acute cardiac events remains controversial. METHODS AND RESULTS: The Master@Heart study is a well-balanced prospective observational cohort study. Overall, 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile, were included. Peak oxygen uptake quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on computed tomography coronary angiography. Analyses were corrected for multiple cardiovascular risk factors. The median age was 55 (50-60) years in all groups. Lifelong and late-onset athletes had higher peak oxygen uptake than non-athletes [159 (143-177) vs. 155 (138-169) vs. 122 (108-138) % predicted]. Lifelong endurance sports was associated with having ≥1 coronary plaque [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.17-2.94], ≥ 1 proximal plaque (OR 1.96, 95% CI 1.24-3.11), ≥ 1 calcified plaques (OR 1.58, 95% CI 1.01-2.49), ≥ 1 calcified proximal plaque (OR 2.07, 95% CI 1.28-3.35), ≥ 1 non-calcified plaque (OR 1.95, 95% CI 1.12-3.40), ≥ 1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39-5.65), and ≥1 mixed plaque (OR 1.78, 95% CI 1.06-2.99) as compared to a healthy non-athletic lifestyle. CONCLUSION: Lifelong endurance sport participation is not associated with a more favourable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum.

Exercise-induced myocardial T1 increase and right ventricular dysfunction in recreational cyclists: a CMR study.

PURPOSE: Although cardiac troponin I (cTnI) increase following strenuous exercise has been observed, the development of exercise-induced myocardial edema remains unclear. Cardiac magnetic resonance (CMR) native T1/T2 mapping is sensitive to the pathological increase of myocardial water content. Therefore, we evaluated exercise-induced acute myocardial changes in recreational cyclists by incorporating biomarkers, echocardiography and CMR. METHODS: Nineteen male recreational participants (age: 48 ± 5 years) cycled the 'L'étape du tour de France" (EDT) 2021' (175 km, 3600 altimeters). One week before the race, a maximal graded cycling test was conducted to determine individual heart rate (HR) training zones. One day before and 3-6 h post-exercise 3 T CMR and echocardiography were performed to assess myocardial native T1/T2 relaxation times and cardiac function, and blood samples were collected. All participants were asked to cycle 2 h around their anaerobic gas exchange threshold (HR zone 4). RESULTS: Eighteen participants completed the EDT stage in 537 ± 58 min, including 154 ± 61 min of cycling time in HR zone 4. Post-race right ventricular (RV) dysfunction with reduced strain and increased volumes (p < 0.05) and borderline significant left ventricular global longitudinal strain reduction (p = 0.05) were observed. Post-exercise cTnI (0.75 ± 5.1 ng/l to 69.9 ± 41.6 ng/l; p < 0.001) and T1 relaxation times (1133 ± 48 ms to 1182 ± 46 ms, p < 0.001) increased significantly with no significant change in T2 (p = 0.474). cTnI release correlated with increase in T1 relaxation time (p = 0.002; r = 0.703), post-race RV dysfunction (p < 0.05; r = 0.562) and longer cycling in HR zone 4 (p < 0.05; r = 0.607). CONCLUSION: Strenuous exercise causes early post-race cTnI increase, increased T1 relaxation time and RV dysfunction in recreational cyclists, which showed interdependent correlation. The long-term clinical significance of these changes needs further investigation. TRIAL REGISTRATION NUMBERS AND DATE: NCT04940650 06/18/2021. NCT05138003 06/18/2021.

The effect of intravenous ferric carboxymaltose on cardiac reverse remodelling following cardiac resynchronization therapy-the IRON-CRT trial.

AIMS: Iron deficiency is common in heart failure with reduced ejection fraction (HFrEF) and negatively affects cardiac function and structure. The study the effect of ferric carboxymaltose (FCM) on cardiac reverse remodelling and contractile status in HFrEF. METHODS AND RESULTS: Symptomatic HFrEF patients with iron deficiency and a persistently reduced left ventricular ejection fraction (LVEF <45%) at least 6 months after cardiac resynchronization therapy (CRT) implant were prospectively randomized to FCM or standard of care (SOC) in a double-blind manner. The primary endpoint was the change in LVEF from baseline to 3-month follow-up assessed by three-dimensional echocardiography. Secondary endpoints included the change in left ventricular end-systolic (LVESV) and end-diastolic volume (LVEDV) from baseline to 3-month follow-up. Cardiac performance was evaluated by the force-frequency relationship as assessed by the slope change of the cardiac contractility index (CCI = systolic blood pressure/LVESV index) at 70, 90, and 110 beats of biventricular pacing. A total of 75 patients were randomized to FCM (n = 37) or SOC (n = 38). At baseline, both treatment groups were well matched including baseline LVEF (34 ± 7 vs. 33 ± 8, P = 0.411). After 3 months, the change in LVEF was significantly higher in the FMC group [+4.22%, 95% confidence interval (CI) +3.05%; +5.38%] than in the SOC group (-0.23%, 95% CI -1.44%; +0.97%; P < 0.001). Similarly, LVESV (-9.72 mL, 95% CI -13.5 mL; -5.93 mL vs. -1.83 mL, 95% CI -5.7 mL; 2.1 mL; P = 0.001), but not LVEDV (P = 0.748), improved in the FCM vs. the SOC group. At baseline, both treatment groups demonstrated a negative force-frequency relationship, as defined by a decrease in CCI at higher heart rates (negative slope). FCM resulted in an improvement in the CCI slope during incremental biventricular pacing, with a positive force-frequency relationship at 3 months. Functional status and exercise capacity, as measured by the Kansas City Cardiomyopathy Questionnaire and peak oxygen consumption, were improved by FCM. CONCLUSIONS: Treatment with FCM in HFrEF patients with iron deficiency and persistently reduced LVEF after CRT results in an improvement of cardiac function measured by LVEF, LVESV, and cardiac force-frequency relationship.

Predictors of poor outcome in critically ill patients with COVID-19 pneumonia treated with extracorporeal membrane oxygenation.

INTRODUCTION: We aimed to identify risk factors associated with ICU mortality in critically ill patients with COVID-19 pneumonia treated with Extracorporeal membrane oxygenation (ECMO). We also aimed to assess protocol violations of the local eligibility criteria of ECMO initiation. METHODS: All 31 consecutive adult patients with confirmed COVID-19 pneumonia admitted to ICU and treated with ECMO from March 13th 2020 to 8 December 2021 were enrolled. Eligibility criteria for ECMO initiation were: P/F-ratio<50 mmHg >3 hours, P/F-ratio<80 mmHg >6 hours or pH<7.25 + PaCO2>60 mmHg >6 hours, despite maximal protective invasive ventilation. Primary outcome was ICU mortality. Univariate logistic regression analyses were performed to identify predictors of ICU mortality. RESULTS: 12 out of 31 patients (38.7%) did not survive ECMO treatment in ICU. Half of the non-survivors suffered from acute kidney failure compared to 3 out of 19 survivors (15.79%) (p = .04). Half of the non-survivors required CRRT treatment versus 1 patient in the survivor group (5.3%) (p < .01). Higher age (2.45 (0.97-6.18), p = .05), the development of AKI (5.33 (1.00-28.43), p = .05), need of CRRT during ICU stay (18.00 (1.79-181.31), p = .01) and major bleeding during ECMO therapy (0.51 (0.19-0.89), p < .01) were identified to be predictors of ICU mortality. CONCLUSION: Almost 60% of patients could be treated successfully with ECMO with sustained results at 3 months. Predictors for ICU mortality were development of AKI and need of CRRT during ICU stay, higher age category and major bleeding. Inadvertent ECMO allocation was noted in almost one in five patients.

Iron Deficiency Is Associated With Impaired Biventricular Reserve and Reduced Exercise Capacity in Patients With Unexplained Dyspnea.

BACKGROUND: Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear. METHODS AND RESULTS: Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography in a tertiary care dyspnea clinic. ID was defined as ferritin of <300 µg/L and a transferrin saturation of <20% and its impact on peak oxygen uptake (peakVO2), biventricular response to exercise, and peripheral oxygen extraction was assessed. Of 272 patients who underwent cardiopulmonary exercise testing with echocardiography, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO2 (14.6 ± 7.6 mL/kg/minvs 17.8 ± 8.8 mL/kg/min; P = .009) and maximal workload (89 ± 50 watt vs 108 ± 56 watt P = .047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (P < .05) and depressed RV function by tricuspid s' (P = .004), tricuspid annular plane systolic excursion (P = .034), and RV end-systolic pressure-area ratio (P = .038), with more RV-pulmonary artery uncoupling measured by tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure ratio (P = .023). RV end-systolic pressure-area ratio change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09 ± 0.72 mm Hg/cm2 vs 2.58 ± 1.14 mm Hg/cm2; P < .001). ID was associated with impaired peripheral oxygen extraction (peakVO2/peak cardiac output; P = .036). Cardiopulmonary exercise testing with echocardiography resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio of >14, with equal distribution in patients with (28.6%) or without ID (25.4%, P = .611). None of these findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea. CONCLUSIONS: In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with decreased exercise capacity, diminished biventricular contractile reserve, and decreased peripheral oxygen extraction.

Cardiac dysfunction rather than aortic valve stenosis severity drives exercise intolerance and adverse haemodynamics.

AIMS: To study the impact of heart failure with preserved ejection fraction (HFpEF) vs. aortic stenosis (AS) lesion severity on left ventricular (LV) hypertrophy, diastolic dysfunction, left atrial (LA) dysfunction, haemodynamics, and exercise capacity. METHODS AND RESULTS: Patients (n = 206) with at least moderate AS (aortic valve area ≤0.85 cm/m2) and discordant symptoms underwent cardiopulmonary exercise testing with simultaneous echocardiography. The population was stratified according to the probability of underlying HFpEF by the heavy, hypertension, atrial fibrillation, pulmonary hypertension, elder, filling pressure (H2FPEF) score [0-5 (AS/HFpEF-) vs. 6-9 points (AS/HFpEF+)] and AS severity (Moderate vs. Severe). Mean age was 73 ± 10 years with 40% women. Twenty-eight patients had Severe AS/HFpEF+ (14%), 111 Severe AS/HFpEF- (54%), 13 Moderate AS/HFpEF+ (6%), and 54 Moderate AS/HFpEF- (26%). AS/HFpEF+ vs. AS/HFpEF- patients, irrespective of AS severity, had a lower LV global longitudinal strain, impaired diastolic function, reduced LV compliance, and more pronounced LA dysfunction. The pulmonary arterial pressure-cardiac output slope was significantly higher in AS/HFpEF+ vs. AS/HFpEF- (5.4 ± 3.1 vs. 3.9 ± 2.2 mmHg/L/min, respectively; P = 0.003), mainly driven by impaired cardiac output and chronotropic reserve, with signs of right ventricular pulmonary arterial uncoupling. AS/HFpEF+ vs. AS/HFpEF- was associated with a lower peak aerobic capacity (11.5 ± 3.7 vs. 15.9 ± 5.9 mL/min/kg, respectively; P < 0.0001) but did not differ between Moderate and Severe AS (14.7 ± 5.5 vs. 15.2 ± 5.9 mL/min/kg, respectively; P = 0.6). CONCLUSION: A high H2FPEF score is associated with a reduced exercise capacity and adverse haemodynamics in patients with moderate to severe AS. Both exercise performance and haemodynamics correspond better with intrinsic cardiac dysfunction than AS severity.

Exercise pulmonary hypertension by the mPAP/CO slope in primary mitral regurgitation.

AIMS: Exercise-induced pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure over cardiac output (mPAP/CO) slope >3 mmHg/L/min, has important diagnostic and prognostic implications. The aim of this study is to investigate the value of the mPAP/CO slope in patients with more than moderate primary mitral regurgitation (MR) with preserved ejection fraction and no or discordant symptoms. METHODS AND RESULTS: A total of 128 consecutive patients were evaluated with exercise echocardiography and cardiopulmonary testing. Clinical outcome was defined as the composite of mitral valve intervention, new-onset atrial fibrillation, cardiovascular hospitalization, and all-cause mortality. The mean age was 63 years, 61% were male, and the mean LVEF was 66 ± 6%. The mPAP/CO slope correlated with peak VO2 (r = -0.52, P < 0.001), while the peak systolic pulmonary artery pressure (sPAP) did not (r = -0.06, P = 0.584). Forty-six per cent (n = 59) had peak exercise sPAP ≥60 mmHg, and 37% (n = 47) had mPAP/CO slope >3 mmHg/L/min. Event-free survival was 55% at 1 year and 46% at 2 years, with reduced survival in patients with mPAP/CO slope >3 mmHg/L/min (hazard ratio, 4.9; 95% confidence interval, 2.9-8.2; P < 0.001). In 53 cases (41%), mPAP/CO slope and peak sPAP were discordant: patients with slope >3 mmHg/L/mmHg and sPAP <60 mmHg (n = 21) had worse outcome vs. peak sPAP ≥60 mmHg and normal slope (n = 32, log-rank P = 0.003). The mPAP/CO slope improved predictive models for outcome, incremental to resting and exercise sPAP, and peak VO2. CONCLUSION: Exercise PH defined by the mPAP/CO slope >3 mmHg/L/min is associated with decreased exercise capacity and a higher risk of adverse events in significant primary MR and no or discordant symptoms. The slope provides a greater prognostic value than single sPAP measures and peak VO2.

The Oxygen Cascade According to HFpEF Likelihood: A Focus on Sex Differences.

Background: Women are at greater risk for heart failure with preserved ejection fraction (HFpEF). Objectives: The aim of the study was to compare sex differences in the pathophysiology of exertional breathlessness in patients with high vs low HFpEF likelihood. Methods: This cohort study evaluated consecutive patients (n = 1,936) with unexplained dyspnea using cardiopulmonary exercise testing and simultaneous echocardiography and quantified peak oxygen uptake (peak VO2) and its determinants. HFpEF was considered likely when the H2FPEF or HFA-PEFF score was ≥6 or ≥5, respectively. Sex differences were evaluated with the Student's t-test or Mann-Whitney U test and determinants of exercise capacity with a multivariable linear regression. Results: The cohort included 1,963 patients (49% women and 28% [n = 555] with a high HFpEF likelihood). HFpEF likelihood did not impact the magnitude of sex differences in peak VO2 and its determinants. Overall, women had lower peak VO2 (mean difference -4.4 mL/kg/min [95% CI: -3.7 to -5.1 mL/kg/min]) secondary to a reduced O2 delivery (-0.5 L/min [95% CI: -0.4 to -0.6 L/min]) and less oxygen extraction (-2.9 mL/dL [95% CI: -2.5 to -3.2 mL/dL]). Reduced O2 delivery was due to lower hemoglobin (-1.2 g/dL [95% CI: -0.9 to -1.5 g/dL]) and smaller stroke volume (-15 mL [95% CI: -14 to -17 mL]). Women demonstrated increased mean pulmonary artery pressure/cardiac output slope (+0.5 mm Hg/L/min [95% CI: 0.3-0.7 mm Hg/L/min]) and left ventricular ejection fraction (+1% [95% CI: 1%-2%]), while they had smaller left ventricular end-diastolic volumes (-9 mL/m2 [95% CI: -8 to -11 mL/m2]) and mass (-12 g/m2 [95% CI: -9 to -14 g/m2]) and more often iron deficiency (55% vs 33%; P < 0.001). Conclusions: Women with unexplained dyspnea had significantly lower peak VO2, regardless of HFpEF likelihood, attributed to both lower peak exercise O2 delivery and extraction. This suggests that physiologic sex differences, and not HFpEF likelihood, are an important factor contributing to functional limitations in females with exertional breathlessness.

Low rates of myocardial fibrosis and ventricular arrhythmias in recreational athletes after SARS-CoV-2 infection.

Introduction: High rates of cardiac involvement were reported in the beginning of the coronavirus disease 2019 (COVID-19) pandemic. This led to anxiety in the athletic population. The current study was set up to assess the prevalence of myocardial fibrosis and ventricular arrhythmias in recreational athletes with the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: Consecutive adult recreational athletes (≥18 years old, ≥4 h of mixed type or endurance sports/week) underwent systematic cardiac evaluation after a prior confirmed COVID-19 infection. Evaluation included clinical history, electrocardiogram (ECG), 5-day Holter monitoring, and cardiac magnetic resonance (CMR) imaging with simultaneous measurement of high-sensitive cardiac Troponin I. Data from asymptomatic or mildly symptomatic athletes (Group 1) were compared with those with moderate to severe symptoms (Groups 2-3). Furthermore, a comparison with a historical control group of athletes without COVID-19 (Master@Heart) was made. Results: In total, 35 athletes (18 Group 1, 10 female, 36.9 ± 2.2 years, mean 143 ± 20 days following diagnosis) were evaluated. The baseline characteristics for the Group 1 and Groups 2-3 athletes were similar. None of the athletes showed overt myocarditis on CMR based on the updated Lake Louise criteria for diagnosis of myocarditis. The prevalence of non-ischemic late gadolinium enhancement [1 (6%) Group 1 vs. 2 (12%) Groups 2-3; p = 0.603] or ventricular arrhythmias [1 Group 1 athlete showed non-sustained ventricular tachycardia (vs. 0 in Groups 2-3: p = 1.000)] were not statistically different between the groups. When the male athletes were compared with the Master@Heart athletes, again no differences regarding these criteria were found. Conclusion: In our series of recreational athletes with prior confirmed COVID-19, we found no evidence of ongoing myocarditis, and no more detection of fibrosis or ventricular arrhythmias than in a comparable athletic pre-COVID cohort. This points to a much lower cardiac involvement of COVID-19 in athletes than originally suggested.

Clinical Significance of Exercise Pulmonary Hypertension With a Negative Diastolic Stress Test for Suspected Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.

Determining optimal noninvasive parameters for the prediction of left ventricular remodeling in chronic ischemic patients.

OBJECTIVES: DOPPLER-CIP aims to determine the optimal noninvasive parameters (myocardial function, perfusion, ventricular blood flow, cell integrity) and methodology (ergometry, echocardiography, scintigraphy, MRI) in a given ischemic substrate that best predicts the impact of an intervention (or the lack thereof) on adverse morphological ventricular remodeling and functional recovery. Moreover, the relative predictive value of each of these parameters, in respect to the cost of extracting this information in order to enable optimization of cost-effectiveness for improved health care, will be determined by this project. DESIGN: DOPPLER-CIP is a multi-center registry study. All patients with ischemic heart disease included in this study undergo at least two noninvasive stress imaging examinations at baseline. The presence/or absence of left ventricular (LV) remodeling will be assessed after a follow-up of 2 years, during which all cardiac events will be registered. RESULTS: 676 patients were included. Currently, baseline data analysis is almost finished and the follow-up is ongoing. CONCLUSIONS: After completion, DOPPLER-CIP will provide evidence-based guidelines toward the most effective use of cardiac imaging in the chronically ischemic heart disease patient. The study will generate information, knowledge, and insight into the new imaging methodologies and into the pathophysiology of chronic ischemic heart disease.

Aortic Valve Replacement: Totally Endoscopic versus Mini-Sternotomy.

(1) Background: The development of totally endoscopic aortic valve replacement has the potential to enhance clinical results compared to mini-sternotomy. To our knowledge, no comparison between these two techniques has been conducted before. Therefore, the objective of this retrospective study is to examine the results after both totally endoscopic and mini-sternotomy approaches. (2) Methods: This study covered all elective patients who underwent isolated aortic valve replacement, either totally endoscopically (n = 392) or through a mini-sternotomy (n = 323), between 2013 and 2021. Multivariable analysis was used to account for baseline variations between the two groups. All data were retrospectively gathered and analysed. The primary objective of this study was the one-year mortality rate. (3) Results: The mean aortic cross-clamping and cardiopulmonary bypass times were significantly longer in the totally endoscopic approach (cross-clamping: 43.73 ± 13.71 min and 61.93 ± 16.76 min, p-value < 0.001; CPB time: 64.86 ± 23.02 min and 93.23 ± 23.67 min, p-value < 0.001). However, perioperative bleeding was lower (706.40 ± 542.77 mL and 444.50 ± 515.84 mL, p-value < 0.001). The primary objective, one-year survival, did not significantly differ between both groups (Mini-AVR: 94.5% vs TEAVR: 93.3%, p-value = 0.520). (4) Conclusions: Our results show that totally endoscopic aortic valve replacement has comparable clinical results compared to aortic valve replacement through mini-sternotomy.

Impact of Estimated Left Atrial Pressure on Cardiac Resynchronization Therapy Outcome.

BACKGROUND: We investigated the impact of baseline left atrial (LA) strain data and estimated left atrial pressure (LAP) by applying the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) guidelines on cardiac resynchronization therapy (CRT) outcomes. METHODS: Datasets of 219 CRT patients were retrospectively analysed. All patients had full echocardiographic diastolic function assessment before CRT and were classified based on the guideline algorithm into normal LAP (nLAP = 40%), elevated LAP (eLAP = 49%) and indeterminate LAP (iLAP = 11%). All relevant baseline characteristics were analysed. CRT-induced left ventricular (LV) reverse remodeling was measured as the relative change of LV end-systolic volume (LVESV) at 12 ± 6 months after CRT compared to baseline. Patients were followed up for all-cause mortality for a mean of 4.8 years [interquartile range (IQR): 2.7-6.0 years]. RESULTS: At follow-up, CRT resulted in more pronounced reduction of LVESV in patients with nLAP than in patients with eLAP. In univariate analysis, nLAP was associated with LV reverse remodelling (p < 0.001), as well as long-term survival after CRT (p < 0.01). However, multivariable analysis showed that only the association between nLAP and LV reverse remodelling after CRT is independent (p < 0.01). Adding LA strain analysis to the guideline algorithm improved the feasibility of LAP estimation without affecting the association between estimated LAP and CRT outcome. CONCLUSION: Normal LAP before CRT, estimated using the 2016 ASE/EACVI guideline algorithm, is associated with LV reverse remodelling and long-term survival after CRT. Albeit non-independent, it can serve as a non-invasive imaging-based predictor of effective therapy. Furthermore, the inclusion of LA reservoir strain in the guideline algorithm can enhance the feasibility of LAP estimation without affecting the association between LAP and CRT outcome.

Pulmonary hypertension during exercise underlies unexplained exertional dyspnoea in patients with Type 2 diabetes.

AIMS: To compare the cardiac function and pulmonary vascular function during exercise between dyspnoeic and non-dyspnoeic patients with Type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Forty-seven T2DM patients with unexplained dyspnoea and 50 asymptomatic T2DM patients underwent exercise echocardiography combined with ergospirometry. Left ventricular (LV) function [stroke volume, cardiac output (CO), LV ejection fraction, systolic annular velocity (s')], estimated LV filling pressures (E/e'), mean pulmonary arterial pressures (mPAPs) and mPAP/COslope were assessed at rest, low- and high-intensity exercise with colloid contrast. Groups had similar patient characteristics, glycemic control, stroke volume, CO, LV ejection fraction, and E/e' (P > 0.05). The dyspnoeic group had significantly lower systolic LV reserve at peak exercise (s') (P = 0.021) with a significant interaction effect (P < 0.001). The dyspnoeic group also had significantly higher mPAP and mPAP/CO at rest and exercise (P < 0.001) with significant interaction for mPAP (P < 0.009) and insignificant for mPAP/CO (P = 0.385). There was no significant difference in mPAP/COslope between groups (P = 0.706). However, about 61% of dyspnoeic vs. 30% of non-dyspnoeic group had mPAP/COslope > 3 (P = 0.009). The mPAP/COslope negatively predicted V̇O2peak in dyspneic group (ß = -1.86, 95% CI: -2.75, -0.98; multivariate model R2:0.54). CONCLUSION: Pulmonary hypertension and less LV systolic reserve detected by exercise echocardiography with colloid contrast underlie unexplained exertional dyspnoea and reduced exercise capacity in T2DM.

Three-dimensional echocardiography of the athlete's heart: a comparison with cardiac magnetic resonance imaging.

Three-dimensional echocardiography (3DE) is the most accurate cardiac ultrasound technique to assess cardiac structure. 3DE has shown close correlation with cardiac magnetic resonance imaging (CMR) in various populations. There is limited data on the accuracy of 3DE in athletes and its value in detecting alterations during follow-up. Indexed left and right ventricular end-diastolic volume (LVEDVi, RVEDVi), end-systolic volume, ejection fraction (LVEF, RVEF) and left ventricular mass (LVMi) were assessed by 3DE and CMR in two-hundred and one competitive endurance athletes (79% male) from the Pro@Heart trial. Sixty-four athletes were assessed at 2 year follow-up. Linear regression and Bland-Altman analyses compared 3DE and CMR at baseline and follow-up. Interquartile analysis evaluated the agreement as cardiac volumes and mass increase. 3DE showed strong correlation with CMR (LVEDVi r = 0.91, LVEF r = 0.85, LVMi r = 0.84, RVEDVi r = 0.84, RVEF r = 0.86 p < 0.001). At follow up, the percentage change by 3DE and CMR were similar (∆LVEDVi r = 0.96 bias - 0.3%, ∆LVEF r = 0.94, bias 0.7%, ∆LVMi r = 0.94 bias 0.8%, ∆RVESVi r = 0.93, bias 1.2%, ∆RVEF r = 0.87 bias 0.4%). 3DE underestimated volumes (LVEDVi bias - 18.5 mL/m2, RVEDVi bias - 25.5 mL/m2) and the degree of underestimation increased with larger dimensions (Q1vsQ4 LVEDVi relative bias - 14.5 versus - 17.4%, p = 0.016; Q1vsQ4 RVEDVi relative bias - 17 versus - 21.9%, p = 0.005). Measurements of cardiac volumes, mass and function by 3DE correlate well with CMR and 3DE accurately detects changes over time. 3DE underestimates volumes and the relative bias increases with larger cardiac size.

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

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 VO2 > 80% with respiratory exchange [RER] > 1.05), reduced exercise capacity (peak VO2 ≤ 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 VO2 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.