Cardiopulmonary Profiling of Athletes with Post-Exertional Malaise after COVID-19 Infection-A Single-Center Experience.

(1) Background: Cardiopulmonary exercise testing (CPET) has been suggested by the European Society of Cardiology (ESC) for assessing the exercise limitations of apparently healthy individuals, but data on elite athletes regarding this test are scarce. (2) Methods: We analyzed CPET in elite (n = 43, 21.9 ± 3.7 years) and recreational (n = 40, 34.7 ± 13.0 years) athletes with persistent subjective exercise intolerance and post-exertional malaise (PEM) after COVID-19 infection. The primary outcome was the point prevalence of the adequate cardiopulmonary response (ACPR), defined by the presence of all of the following ESC criteria for apparently healthy individuals: (1) >100% of predicted peak oxygen consumption (predVO2peak), (2) VE/VCO2 < 30, (3) no exercise oscillatory ventilation (EOV), and (4) heart rate recovery of ≥12 beats/minute 1 min after exercise termination (HRR1). Results: ACPR occurred more frequently in elite athletes than in recreational athletes (70.0% vs. 39.5%; p = 0.005), mainly driven by the lower VE/VCO2 (<30: 97.7% vs. 65%, p < 0.001). Elite (11.6%) and recreational athletes (22.5%) showing a plateau of O2 pulse did not display ACPR. Conclusions: ACPR was not observed in all recreational and elite athletes with PEM. In particular, perturbed VE/VCO2 and the plateauing of O2 pulse are suitable for quantifying exercise limitations and may identify a high-risk population with long-COVID-19 syndrome who require their training intensities to be adapted.

Increased Dead Space Ventilation as a Contributing Factor to Persistent Exercise Limitation in Patients with a Left Ventricular Assist Device.

(1) Background: The exercise capacity of patients with a left ventricular assist device (LVAD) remains limited despite mechanical support. Higher dead space ventilation (VD/VT) may be a surrogate for right ventricular to pulmonary artery uncoupling (RV-PA) during cardiopulmonary exercise testing (CPET) to explain persistent exercise limitations. (2) Methods: We investigated 197 patients with heart failure and reduced ejection fraction with (n = 89) and without (HFrEF, n = 108) LVAD. As a primary outcome NTproBNP, CPET, and echocardiographic variables were analyzed for their potential to discriminate between HFrEF and LVAD. As a secondary outcome CPET variables were evaluated for a composite of hospitalization due to worsening heart failure and overall mortality over 22 months. (3) Results: NTproBNP (OR 0.6315, 0.5037-0.7647) and RV function (OR 0.45, 0.34-0.56) discriminated between LVAD and HFrEF. The rise of endtidal CO2 (OR 4.25, 1.31-15.81) and VD/VT (OR 1.23, 1.10-1.40) were higher in LVAD patients. Group (OR 2.01, 1.07-3.85), VE/VCO2 (OR 1.04, 1.00-1.08), and ventilatory power (OR 0.74, 0.55-0.98) were best associated with rehospitalization and mortality. (4) Conclusions: LVAD patients displayed higher VD/VT compared to HFrEF. Higher VD/VT as a surrogate for RV-PA uncoupling could be another marker of persistent exercise limitations in LVAD patients.

The cardiorespiratory optimal point as a discriminator of lesion severity in adults with congenital heart disease.

BACKGROUND: Peak oxygen consumption (VO2peak), which depends on maximal exertion and is reduced in adults with congenital heart disease (ACHD), is associated with lesion severity. The lowest ventilatory equivalent for oxygen (the minimum value of VE/VO2) reflects the cardiorespiratory optimal point (COP) as best possible respiration-circulatory interaction and may discriminate between lesion types without the need for maximal exertion. However, data on COP in ACHD is scarce. METHODS: We retrospectively analyzed stable ACHD with moderate (N.=13) and severe lesions (N.=17) reporting to our outpatient clinic undergoing cardiopulmonary exercise testing. The primary outcome of the study was the difference of COP between moderate and severe lesions. Secondary outcomes were between group differences of the submaximal variable exercise oxygen uptake efficiency slope (OUES) and peak O2 pulse (O2pulsemax) as a surrogate for peripheral oxygen extraction and stroke volume increase during exercise. RESULTS: The group of severe lesions displayed higher COP (29.5±7.0 vs. 25.2±6.2, P=0.028) as well as lower O2pulsemax (13.3±8.4 vs. 14.9±3.4 mL/beat/kg 102, P=0.038). VO2peak (17.4±6.5 vs. 20.8±8.5 mL/kg/min, P=0.286) and OUES (1.5±0.7 vs. 1.8±0.9, P=0.613) showed a trend towards lower values in severe lesions. COP was a better between group discriminator than O2pulsemax (area under the curve 73.8% vs. 72.4%). CONCLUSIONS: As a submaximal variable, COP discriminated between moderate and severe lesions and may prove beneficial in a highly vulnerable population that is often unable to undergo exertional testing.

Epicardial adipose tissue and obstructive coronary artery disease in acute chest pain: the EPIC-ACS study.

Aims: We tested the hypothesis that epicardial adipose tissue (EAT) quantification improves the prediction of the presence of obstructive coronary artery disease (CAD) in patients presenting with acute chest pain to the emergency department. Methods and results: Within this prospective observational cohort study, we included 657 consecutive patients (mean age 58.06 ± 18.04 years, 53% male) presenting to the emergency department with acute chest pain suggestive of acute coronary syndrome between December 2018 and August 2020. Patients with ST-elevation myocardial infarction, haemodynamic instability, or known CAD were excluded. As part of the initial workup, we performed bedside echocardiography for quantification of EAT thickness by a dedicated study physician, blinded to all patient characteristics. Treating physicians remained unaware of the results of the EAT assessment. The primary endpoint was defined as the presence of obstructive CAD, as detected in subsequent invasive coronary angiography. Patients reaching the primary endpoint had significantly more EAT than patients without obstructive CAD (7.90 ± 2.56 mm vs. 3.96 ± 1.91 mm, P < 0.0001). In a multivariable regression analysis, a 1 mm increase in EAT thickness was associated with a nearby two-fold increased odds of the presence of obstructive CAD [1.87 (1.64-2.12), P < 0.0001]. Adding EAT to a multivariable model of the GRACE score, cardiac biomarkers and traditional risk factors significantly improved the area under the receiver operating characteristic curve (0.759-0.901, P < 0.0001). Conclusion: Epicardial adipose tissue strongly and independently predicts the presence of obstructive CAD in patients presenting with acute chest pain to the emergency department. Our results suggest that the assessment of EAT may improve diagnostic algorithms of patients with acute chest pain.

Higher BNP/NT-pro BNP levels stratify prognosis equally well in patients with and without heart failure: a meta-analysis.

AIMS: The initial and dynamic levels of B-type natriuretic peptide (BNP) and N-terminal-prohormone BNP (NT-proBNP) are routinely used in clinical practice to identify patients with acute and chronic heart failure. In addition, BNP/NT-proBNP levels might be useful for risk stratification in patients with and without heart failure. We performed a meta-analysis to investigate, whether the value of BNP/NT-proBNP as predictors of long-term prognosis differentiates in cohorts with and without heart failure. METHODS AND RESULTS: We systematically searched established scientific databases for studies evaluating the prognostic value of BNP or NT-proBNP. Random effect models were constructed. Data from 66 studies with overall 83 846 patients (38 studies with 46 099 patients with heart failure and 28 studies with 37 747 patients without heart failure) were included. In the analysis of the log-transformed BNP/NT-proBNP levels, an increase in natriuretic peptides by one standard deviation was associated with a 1.7-fold higher MACE rate (hazard ratio [95% confidence interval]: 1.74[1.58-1.91], P < 0.0001). The effect sizes were comparable, with a substantial overlap in the confidence intervals, when comparing studies involving patients with and without heart failure (1.75[1.54-2.0], P < 0.0001 vs. 1.74[1.47-2.06], P < 0.0001). Similar results were observed when stratifying by quartiles of BNP/NT-proBNP. In studies using pre-defined cut-off-values for BNP/NT-proBNP, elevated levels were associated with the long-term prognosis, independent of the specific cut-off value used. CONCLUSIONS: BNP/NT-proBNP levels are predictors for adverse long-term outcome in patients with and without known heart failure. Further research is necessary to establish appropriate thresholds, especially in non-heart failure cohorts.

Epicardial adipose tissue is a robust measure of increased risk of myocardial infarction - a meta-analysis on over 6600 patients and rationale for the EPIC-ACS study.

BACKGROUND: Epicardial adipose tissue (EAT) surrounds the heart and the coronary vessels. EAT produces pro- and anti-inflammatory cytokines. Several studies have already documented the association of EAT and cardiovascular risk factors as well as coronary artery disease manifestations. Currently computed tomography (CT) is considered the gold standard for measurement of 3-dimensional volume of EAT. In addition, echocardiography might be an easy accessible alternative in particular in an emergency setting. METHODS: We performed a metaanalysis of existing studies describing the differences of EAT in patients with and without myocardial infarction. We used established databases and were searching for "epicardial adipose tissue" or "pericardial adipose tissue" and "myocardial infarction", "coronary events", or "acute coronary syndrome". We included over 6600 patients from 7 studies. Random effect models were calculated and all analyses were performed by using the Review Manager 5.3. RESULTS: Patients with myocardial infarction had 37% (confidence interval [0.21-0.54], P value <.001)] higher measures of EAT compared to patients without myocardial infarction. Comparing studies using echocardiography vs CT for assessment of EAT thickness, similar relative differences in EAT with wide overlap of confidence intervals were observed (for echocardiography: 0.4 [0.04-0.76], for CT: 0.36 [0.16-0.57], P value <.001 for both). CONCLUSIONS: Patients with myocardial infarction have more EAT as compared to patients without myocardial infarction independently of the used imaging modality. Further prospective studies are needed to evaluate, how quantification of EAT in clinical routine can improve patients management.

Implications of Alterations in Pre-test Probability in the 2019 Update of ESC Guidelines for Chronic Coronary Syndromes on Diagnostic Accuracy of Pharmacological Stress-Echocardiography: A Retrospective Cohort Study.

BACKGROUND: With the 2019 update of European Society of Cardiology (ESC) guidelines for chronic coronary syndromes, the pre-test probabilities (PTPs) based on age, sex, and symptoms have undergone major revisions. We aimed to determine implications of these alterations on diagnostic accuracy of dobutamine stress echocardiography (DSE). METHODS: We retrospectively included consecutive patients undergoing pharmacological stress-echocardiography for evaluation of suspected obstructive coronary artery disease. DSE was performed as non-invasive imaging test and was indicated by individual treating physician's decision. Sensitivity, specificity, positive and negative predictive value as well as accuracy were assessed for detection of obstructive coronary artery disease, defined as revascularization therapy following DSE. RESULTS: We included 206 patients (mean age 63.2 ± 12.4 years, 59.7% male). 51% of the cohort had a PTP of < 15% according to both scores. 9.2% of patients with PTP < 15% according to the original Diamond and Forrester score had a PTP > 15% according to 2019 ESC guidelines, predominantly due to the accountancy of dyspnea. In contrast, 13.6% of patient had a PTP ≥ 15% according to the original Diamond and Forrester score, while PTP was assessed below this threshold by updated guidelines. The differences in patient selection according to updated guidelines did not alter the diagnostic accuracy of DSE (68% for both). CONCLUSIONS: Changes in assessment of PTP according to updated ESC guidelines from 2019 led to a relevant reclassification of patients with suspected coronary artery disease, ultimately changing the group of patients appropriate for DSE for evaluation of myocardial ischemia. Comparing the diagnostic performance in appropriate PTP groups, however, led to similar results.

Utilization of IVUS improves all-cause mortality in patients undergoing invasive coronary angiography.

Background and aims: Available data suggest that the use of IVUS for guidance of percutaneous coronary interventions (PCIs) improves the prognosis of patients undergoing complex interventions. We aimed to examine how the utilization of intravascular ultrasound (IVUS) affects patient survival irrespective of procedure complexity. Methods: The present analysis is based on the longitudinal ECAD registry of consecutive patients undergoing coronary angiography between 2004 and 2019. The incidence of death due to any cause was evaluated during a mean follow-up of 3.4 years. Cox regression analysis was used to determine the association of IVUS utilization with incident mortality. Results: Overall, data from 30,814 coronary angiography exams (mean age 64.9 ± 12.5 years, 70.3% male) were included, among which 4991 procedures (16.2%) were guided by IVUS. Utilization of IVUS was associated with a 35% reduction in mortality, independent of traditional risk factors (0.64(0.58-0.71), p < 0.0001). The effect of IVUS on mortality was equally present in patients undergoing IVUS-guided coronary interventions (0.75[0.67-0.84], p < 0.0001) as well as purely diagnostic coronary angiography exams (0.62[0.56-0.72], p < 0.0001). In patients without coronary intervention, IVUS utilization led to a higher frequency of aspirin (82.6% vs. 61.9% for IVUS vs. no IVUS, p < 0.0001) and statin therapy (74.9% vs. 62.5%, p < 0.0001). Conclusions: In a large longitudinal registry cohort of patients undergoing invasive coronary angiography, IVUS utilization was associated with lower long-term mortality. The beneficial role of IVUS utilization on survival was equally present for coronary interventions and diagnostic coronary angiograms. Our results support the use of intravascular imaging for decision making in interventional cardiology.

Comparison of Lipoprotein(a)-Levels in Patients ≥70 Years of Age With Versus Without Aortic Valve Stenosis.

Although lipoprotein(a) (Lp[a]) is linked with aortic valve calcification and clinical aortic valve stenosis (AVS) in middle-aged cohorts, patients aged ≥70 years represent a majority of patients with AVS, in which mechanisms leading to AVS may differ. We sought to determine whether Lp(a) distinguishes patients ≥70 years with and without AVS. We matched 484 patients ≥70 years with AVS, scheduled for transcatheter aortic valve implantation with 484 patients without AVS by age group and gender. Lp(a) levels were compared in patients with and without AVS and stratified by presence and absence of clinical coronary artery disease (CAD) manifestation. A total of 968 patients (mean age 80 ± 5 years, 48% women) were included. When comparing patients with and without AVS, no difference in Lp(a) was observed (AVS: 17 [8; 56] mg/dl, no AVS: 18.5 [8.5; 57] mg/dl, p = 0.56). In contrast, patients with clinical CAD manifestation had higher Lp(a) levels than those without clinical CAD manifestation (coronary artery disease: 19 [9; 60] mg/dl, no coronary artery disease 15 [7; 44] mg/dl, p = 0.0006). In regression analysis, no significant association of Lp(a) with AVS was observed in unadjusted (OR [95% CI]: 0.98 [0.91 to 1.06], p = 0.59) and risk factor-adjusted models (0.98 [0.90 to 1.06], p = 0.57). However, Lp(a) was independently associated with clinical CAD manifestation (unadjusted: 1.14 [1.04 to 1.24], p = 0.003, risk factor adjusted: 1.17 [1.07 to 1.27], p = 0.0006). In conclusion, in a large cohort of patients ≥70 years, Lp(a) was associated with clinical CAD manifesation, but not with AVS. Our results suggest that in patients over 70 years, the development of AVS is not influenced by Lp(a).

Pericoronary fat volume but not attenuation differentiates culprit lesions in patients with myocardial infarction.

BACKGROUND AND AIMS: We aimed to determine the association of pericoronary adipose tissue (PCAT) volume and attenuation with culprit lesions in the underlying coronary segment in patients with acute myocardial infarction. METHODS: In patients with myocardial infarction, PCAT volume and attenuation surrounding the following segments were manually traced from non-contrast CT imaging: LM, proximal and mid-segment of LAD, RCA, and LCX. PCAT volume and attenuation surrounding culprit and non-culprit lesions were compared. Odds ratios (OR) and 95% confidence intervals (CI) were calculated per 1 standard deviation increase in PCAT volume/attenuation. RESULTS: We included 46 subjects (mean age 64.4 ±â€¯16.4 years, 71% male) with acute myocardial infarction. PCAT volume around the right coronary artery was higher compared to left coronary segments, while PCAT attenuation decreased from proximal to distal segments. PCAT volume surrounding culprit lesions was higher compared to segments without culprit lesion (4.90 ±â€¯3.07 ml vs. 2.33 ±â€¯2.63 ml, p < 0.0001), whereas the attenuation was not different (-84.8 ±â€¯9.4 HU vs. -84.2 ±â€¯9.9 HU, p = 0.77). In univariate regression analysis, PCAT volume was significantly associated with the probability of presence of culprit lesions (OR [95% CI]: 3.10 [1.84-5.22], p < 0.0001). Associations remained stable upon adjustment for risk factors (3.34 [1.81-6.15], p < 0.0001). PCAT attenuation was not relevantly different around culprit lesions (unadjusted: 0.94 [0.63-1.40], p = 0.77, risk factor adjusted: 1.00 [0.61-1.64], p = 0.996). CONCLUSIONS: In patients with acute myocardial infarction, PCAT volume is strongly and independently associated with culprit lesions in the underlying coronary segments, whereas PCAT attenuation does not relevantly differentiate surrounding coronary segments with and without culprit lesions.

Epicardial Adipose Tissue Thickness Independently Predicts Severe Aortic Valve Stenosis.

BACKGROUND AND AIM OF THE STUDY: Epicardial fat tissue (EAT) is associated with coronary as well as aortic valve calcification. The study aim was to determine whether EAT thickness is different in patients with and without aortic valve stenosis (AVS). METHODS: A cohort of 200 consecutive patients with severe AVS and 200 matched patients without AVS were included retrospectively in the study. EAT thickness was quantified, using transthoracic echocardiography, as the space between the epicardial wall of the myocardium and the visceral layer of the pericardium. Unadjusted and risk factor-adjusted logistic regression analysis was used to determine the association of EAT thickness with the presence of AVS. RESULTS: Overall, 400 patients (182 males, 218 females; mean age 79.6 ± 6.5 years) were included in the study. EAT thickness was significantly higher in patients with severe AVS (7.4 ± 0.3 mm versus 5.8 ± 0.2 mm; p <0.0001 for patients with and without AVS, respectively). In logistic regression analysis, an increase in EAT by one standard deviation was associated with a two-fold increased occurrence of AVS (OR [95%CI]: 2.10 [1.65-2.68]; p <0.0001). Associations remained stable upon adjustment for age, gender and traditional cardiovascular risk factors (2.08 [1.59-2.72]; p <0.0001). Body mass index (BMI) -specific subgroup analysis showed that the link between EAT and AVS was independent of BMI (1.78 [1.15-2.75], 2.62 [1.71- 4.02], and 2.22 [1.36- 3.62], for BMI <25 kg/m2, 25-30 kg/m2, and >30kg/ m2, respectively). EAT, in addition to traditional cardiovascular risk factors, significantly improved the area under the receiver operating characteristic curve (from 0.70 to 0.76; p = 0.003). CONCLUSIONS: EAT thickness is significantly associated with severe AVS, independent of traditional risk factors. While further studies are needed to confirm these results, the present findings support the hypothesis that EAT may influence sclerosis of the aortic valve.

Cardiac computed tomography-derived epicardial fat volume and attenuation independently distinguish patients with and without myocardial infarction.

BACKGROUND AND OBJECTIVE: Epicardial adipose tissue (EAT) volume is associated with coronary plaque burden and adverse events. We aimed to determine, whether CT-derived EAT attenuation in addition to EAT volume distinguishes patients with and without myocardial infarction. METHODS AND RESULTS: In 94 patients with confirmed or suspected coronary artery disease (aged 66.9±14.7years, 61%male) undergoing cardiac CT imaging as part of clinical workup, EAT volume was retrospectively quantified from non-contrast cardiac CT by delineation of the pericardium in axial images. Mean attenuation of all pixels from EAT volume was calculated. Patients with type-I myocardial infarction (n = 28) had higher EAT volume (132.9 ± 111.9ml vs. 109.7 ± 94.6ml, p = 0.07) and CT-attenuation (-86.8 ± 5.8HU vs. -89.0 ± 3.7HU, p = 0.03) than patients without type-I myocardial infarction, while EAT volume and attenuation were only modestly inversely correlated (r = -0.24, p = 0.02). EAT volume increased per standard deviation of age (18.2 [6.2-30.2] ml, p = 0.003), BMI (29.3 [18.4-40.2] ml, p<0.0001), and with presence of diabetes (44.5 [16.7-72.3] ml, p = 0.0002), while attenuation was higher in patients with lipid-lowering therapy (2.34 [0.08-4.61] HU, p = 0.04). In a model containing volume and attenuation, both measures of EAT were independently associated with the occurrence of type-I myocardial infarction (OR [95% CI]: 1.79 [1.10-2.94], p = 0.02 for volume, 2.04 [1.18-3.53], p = 0.01 for attenuation). Effect sizes remained stable for EAT attenuation after adjustment for risk factors (1.44 [0.77-2.68], p = 0.26 for volume; 1.93 [1.11-3.39], p = 0.02 for attenuation). CONCLUSION: CT-derived EAT attenuation, in addition to volume, distinguishes patients with vs. without myocardial infarction and is increased in patients with lipid-lowering therapy. Our results suggest that assessment of EAT attenuation could render complementary information to EAT volume regarding coronary risk burden.