Exercise, cancer, and the cardiovascular system: clinical effects and mechanistic insights.

Cardiovascular diseases and cancer are the leading causes of death in the Western world and share common risk factors. Reduced cardiorespiratory fitness (CRF) is a major determinant of cardiovascular morbidity and cancer survival. In this review we discuss cancer- induced disturbances of parenchymal, cellular, and mitochondrial function, which limit CRF and may be antagonized and attenuated through exercise training. We show the impact of CRF on cancer survival and its attenuating effects on cardiotoxicity of cancer-related treatment. Tailored exercise programs are not yet available for each tumor entity as several trials were performed in heterogeneous populations without adequate cardiopulmonary exercise testing (CPET) prior to exercise prescription and with a wide variation of exercise modalities. There is emerging evidence that exercise may be a crucial pillar in cancer treatment and a tool to mitigate cardiotoxic treatment effects. We discuss modalities of aerobic exercise and resistance training and their potential to improve CRF in cancer patients and provide an example of a periodization model for exercise training in cancer.

Relevance of Cardiovascular Exercise in Cancer and Cancer Therapy-Related Cardiac Dysfunction.

PURPOSE OF THE REVIEW: Cancer therapy-related cardiac dysfunction (CTRCD) has been identified as a threat to overall and cancer-related survival. Although aerobic exercise training (AET) has been shown to improve cardiorespiratory fitness (CRF), the relationship between specific exercise regimens and cancer survival, heart failure development, and reduction of CTRCD is unclear. In this review, we discuss the impact of AET on molecular pathways and the current literature of sports in the field of cardio-oncology. RECENT FINDINGS: Cardio-oncological exercise trials have focused on variations of AET intensity by using moderate continuous and high intensity interval training, which are applicable, safe, and effective approaches to improve CRF. AET increases CRF, reduces cardiovascular morbidity and heart failure hospitalization and should thus be implemented as an adjunct to standard cancer therapy, although its long-term effect on CTRCD remains unknown. Despite modulating diverse molecular pathways, it remains unknown which exercise regimen, including variations of AET duration and frequency, is most suited to facilitate peripheral and central adaptations to exercise and improve survival in cancer patients.

Current Therapies and Future Horizons in Cardiac Amyloidosis Treatment.

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid. RECENT FINDINGS: The current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial fibrillation and valvular disease remains a challenge in CA, driven by technical difficulties and uncertain outcomes. Tafamidis is the first ATTR-stabilizer approved with a rapidly growing rate of clinical use. In parallel, various new therapeutic classes are in late-stage clinical trials including silencers, antibodies and genetic therapy. Managing CA is a critical challenge for future heart failure care. This review delineates the current standard-of-care and scientific landscape of CA therapy.

(Non)-Exertional Variables of Cardiopulmonary Exercise Testing in Heart Failure with and Without Cardiac Amyloidosis.

PURPOSE OF REVIEW: Cardiac amyloidosis (CA) constitutes an important etiology of heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF). Since patients with CA show early exhaustion, we aimed to investigate whether non-exertional variables of cardiopulmonary exercise testing (CPET) provide additional information in comparison to traditional peak oxygen consumption (VO2peak). RECENT FINDINGS: We retrospectively investigated CPET variables of patients with HFpEF and HFmrEF with (n = 21) and without (n = 21, HF) CA at comparable age and ejection fraction. Exertional and non-exertional CPET variables as well as laboratory and echocardiographic markers were analyzed. The primary outcome was the difference in CPET variables between groups. The secondary outcome was rehospitalization in patients with CA during a follow-up of 24 months. Correlations between CPET, NTproBNP, and echocardiographic variables were calculated to detect patterns of discrimination between the groups. HF patients with CA were inferior to controls in most exertional and non-exertional CPET variables. Patients with CA were hospitalized more often (p = 0.002), and rehospitalization was associated with VE/VCO2 (p = 0.019), peak oxygen pulse (p = 0.042), the oxygen equivalent at the first ventilatory threshold (p = 0.003), circulatory (p = 0.024), and ventilatory power (p < .001), but not VO2peak (p = 0.127). Higher performance was correlated with lower E/e' and NTproBNP as well as higher resting heart rate and stroke volume in CA. Patients with CA displayed worse non-exertional CPET performance compared to non-CA HF patients, which was associated with rehospitalization. Differences between correlations of resting echocardiography and CPET variables between groups emphasize different properties of exercise physiology despite comparable ejection fraction.

Moderate Continuous and Modified High-Intensity Interval Training in Patients With Left Ventricular Assist Devices: The Prospective Train-the-LVAD Trial.

BACKGROUND: High-intensity interval training (HIIT) of 4 minutes at 80%-90% of peak oxygen consumption (VO2peak) has been shown to be feasible in patients with left ventricular assist devices (LVADs). The effect of shorter bouts of HIIT, which reduce the anaerobic burden, has not been investigated compared to moderate continuous training (MCT). METHODS AND RESULTS: We conducted a prospective, monocentric study (NCT05121077) randomizing patients with LVADs into 20 minutes of MCT (n = 10) or short bouts (≤ 90 seconds) of HIIT (n = 10) following cardiopulmonary exercise testing at 50%-60% and 80%-90% of VO2peak. Each of the 18 supervised sessions (3×/week, t0-t1) included 10 minutes of strengthening training. The primary outcome was the increase of VO2peak in the 2 groups between t0 and t1. Secondary outcomes were changes in the 12-item Kansas City Cardiomyopathy Questionnaire, the 6-minute walk distance and the percentage of VO2peak at the first ventilatory threshold. VO2peak significantly increased with HIIT (13.0 ± 4.6mL/kg/min vs 14.6 ± 4.3mL/kg/min; P = 0.037), but not with MCT (11.8 ± 3.3mL/kg/min vs 13.1 ± 3.3mL/kg/min; P = 0.322), without between-group differences (P = 0.853). Secondary outcomes improved from t0-t1 in MCT and HIIT, without differences between the groups. CONCLUSIONS: Short bouts of HIIT are feasible, and they improved VO2peak and functional parameters in patients in this pilot prospective study.

Exercise oscillatory ventilation in patients with advanced heart failure with and without left ventricular assist device.

BACKGROUND: Exercise oscillatory ventilation (EOV), indicating pathological fluctuations on pulmonary arterial pressure, is associated with mortality in patients with heart failure (HF). Whether left ventricular assist device (LVAD)-induced ventricular unloading can reverse EOV and may prevent short-term rehospitalization has not been investigated. METHODS: We performed a retrospective single-center in- and outpatient analysis of patients with (n = 20, LVAD) and without (n = 27, HF) circulatory support and reduced ejection fraction (EF, 22.8 ± 7.9%). The association of cardiopulmonary exercise testing (CPET) variables and 3 months-rehospitalization (3MR) as a primary outcome was analyzed. Furthermore, CPET variables were compared regarding the presence of EOV (+/-). RESULTS: Lower VO2peak (11.6 ± 4.9 ml/kg/min vs. 14.4 ± 4.3 ml/kg/min, p = 0.039), lower increase of PETCO2 (CI = 0.049-1.127; p = 0.068), and higher VE/VCO2 (43.8 ± 9.5 vs. 38.3 ± 10.6; p = 0.069) were associated with 3MR. Flattening of O2 pulse (CI = 0.139-2.379; p = 0.487) had no impact on 3MR. EOV was present in 59.5% (n = 28/47) of patients, without a significant difference between LVAD and HF patients (p = 0.959). Patients with HF/EOV+ demonstrated significantly lower VO2peak compared with HF/EOV- (p = 0.039). LVAD/EOV+ displayed significantly lower EF (p = 0.004) and fewer aortic valve opening than LVAD/EOV- (p = 0.027). CONCLUSIONS: Lower VO2peak , but not EOV, was associated with 3MR. EOV occurred at a similar rate in LVAD and HF patients, which may illustrate insufficient unloading during exercise in chronic LVAD therapy and may contribute to the limited exercise capacity following LVAD implantation. Simultaneous CPET and right heart catheterization studies are needed to elucidate whether EOV may serve as a non-invasive predictor of insufficient LV unloading necessitating LVAD reprograming.

Outpatient Management of Oligosymptomatic Patients with respiratory infection in the era of SARS-CoV-2: Experience from rural German general practitioners.

BACKGROUND: Covid-19 is causing a pandemic and forces physicians to restructure their work. We want to share our experience in the outpatient management of potentially-infected patients with special consideration of altered national test strategies during the crisis. METHODS: We analysed patients with respiratory symptoms reporting to our three rural general practitioner (GP) offices in North Rhine-Westphalia, Germany, from 27.01-20.04.2020 (n = 489 from a total of 6090 patients). A history of symptoms was taken at the doorstep following a specific questionnaire. Patients with respiratory symptoms were examined in a separated isolation area, while the others were allowed to enter the office. We applied the first recommended algorithm of the German Robert Koch Institute (RKI) to test suspected patients and compared our results with an adapted, more liberal version of the RKI, which is currently applied in Germany. RESULTS: Eighty patients (16.36%, mean age: 47.03 years+ - 18.08) were sent to a nasopharyngeal smear. Five patients (6.25%) proved to be positive, four of whom had established risk factors for COVID-19. Overall, the most common symptoms were cough (83.75%), sore throat (71.25%), as well as myalgia and fatigue (66.25%). The most common diagnoses were rhinopharyngitis (37.22%) and acute bronchitis (30.27%). A sore throat was more common in positively-tested patients (80% vs. 12%). Applying the first RKI test strategy yielded 6.25% of positive tests (n = 80), while the more liberal later RKI recommendation would have achieved 1.36% positive tests from 369 patients. No positive test was missed by applying the conservative strategy. None of our employees called in sick during this period, which emphasises the efficacy and safety of our screening methods. CONCLUSION: A clinical distinction between ordinary respiratory infections and COVID-19 is not possible in a low-prevalence population. Our model to prevent unprotected physical contact, screen patients in front of the office with protective equipment, and examine respiratory infections in separated areas works in the GP setting without overt health risks for employees. Thus, this approach should be used as a GP standard to uphold patient care without major health risks for the personnel. Large multi-centre studies are necessary to work out the most suitable test strategy.

Expression of the zinc importer protein ZIP9/SLC39A9 in glioblastoma cells affects phosphorylation states of p53 and GSK-3ß and causes increased cell migration.

Zinc importer proteins (ZIPs) have been proven as important molecular regulators in different cancers. As a member of the solute carrier family, ZIP9/SLC39A9 is overexpressed in prostate and breast cancer and affects B-cell receptor signaling. Here, we present data indicating that changes in intracellular zinc levels in glioblastoma cells can cause enhanced cell survival and cell migration, both hallmarks of the disease process. In particular, treatment of human glioblastoma cells with sublethal doses of cell-permeable heavy metal (Zn2+ > Fe2+ > Mn2+) chelator (N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN)) induced ZIP9 expression. Either TPEN treatment or expression of ZIP9 cDNA causes enhanced migration behavior of glioblastoma cells. Compared to untreated glioblastoma cells TPEN treatment or expression of ZIP9 results in activation of the tumor suppressor p53 by phosphorylation at serine residue 46 (Ser46) and in inactivation of the migration relevant glycogen synthase kinase 3 beta (GSK-3ß) by phosphorylation at serine residue 9 (Ser9). Whilst p53 activation affects cell survival in response to TPEN, GSK-3ß inactivation directly affects glioblastoma cell migration. Therefore, ZIP9 expression could regulate the migratory behavior of glioblastoma cells, so that ZIP9 may be of biological, but not of clinical relevance for glioblastomas, since in GBM tumor tissues, ZIP9 expression is not significantly increased compared to normal brain.

Fixation of supracondylar femoral fractures following total knee arthroplasty: is there any difference comparing angular stable plate fixation versus rigid interlocking nail fixation?

INTRODUCTION: Literature does not provide any reliable comparison between angular stable plate fixation and rigid nail fixation for stabilization of supracondylar periprosthetic femoral fractures. Thus, the purpose of this study was to compare these two implants in clinical practice relating to fracture healing, functional results and treatment-related complications. PATIENTS AND METHODS: In this retrospective study (level IV), clinical and radiographic records of 86 patients (62 female and 24 male, average age: 75.6) with supracondylar periprosthetic femoral fractures between 1996 and 2010 were analyzed. 48 patients underwent lateral plate fixation by an angular stable plate system (LISS), whereas 38 patients were stabilized by a rigid interlocking nail device. RESULTS: Sixty-four (76 %) patients returned to their pre-injury activity level and were satisfied with their clinical outcome. We had an overall Oxford outcome score of 2.21, with patients following angular stable plate fixation of 2.22, and patients after rigid nail fixation of 2.20. Successful fracture healing within 6 months was achieved in 74 (88 %) patients. Comparing between plate fixation and nail fixation, statistical analysis did not reveal any significant differences. Overall, we had a relatively high rate of fracture healing and a satisfactory functional outcome with both implants. Both methods of fixation showed similar results relating to the functional outcome and individual satisfaction of the patients. However, with regards to fracture healing and treatment-related complications, intramedullary nail fixation showed slight advantages.

Heart failure classification based on resting ejection fraction does not display a unique exercise response pattern.

BACKGROUND: Heart failure with preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) ejection fraction (EF) remains a controversial categorization. Whether these three categories reflect a distinct pattern of exercise limitation in cardiopulmonary exercise testing (CPET) needs to be investigated. We aimed to analyze whether CPET variables differ between all heart failure categories (HF). METHODS: We analyzed CPET variables of stable HFpEF (n = 123), HFmrEF (n = 31), and HFrEF (n = 153; 74 patients with and 79 patients without left ventricular assist device, LVAD) patients. The association between HF and peak oxygen consumption (VO2peak) was used as a primary outcome, while the association between HF, oxygen uptake efficiency slope (OUES), and increase of O2 pulse (ΔO2 pulse) were analyzed as secondary outcomes. RESULTS: VO2peak displayed a consistent decline across all HF categories (19.8 ml ± 6.2/kg/min vs. 17.5 ± 7.9 ml/kg/min vs. 13.7 ± 4.0 ml/kg/min, p < 0.001). OUES only showed differences between HFpEF and HFrEF (1.8 ± 0.6 vs. 1.4 ± 0.5, p < 0.001) as well as HFmrEF and HFrEF (1.9 ± 0.9 vs. 1.4 ± 0.5, p = 0.004). ΔO2 pulse differed between HFpEF and HFrEF (7.7 ± 3.5 ml/beat/kg*100 vs. 5.5 ± 3.0 ml/beat/kg*100, p < 0.001) as well as HFpEF and HFmrEF (7.7 ± 3.5 ml/beat/kg*100 vs. 6.3 ± 4.1 ml/beat/kg*100, p = 0.049). Outcome variables did not differ between HFrEF with and without LVAD support (VO2peak: p = 0.364, OUES: p = 0.129, ΔO2 pulse: p = 0.564). CONCLUSIONS: HF did not display a distinct CPET profile. Thus, EF-based categorization does not entirely reflect exercise limitations. CPET variables could contribute to better characterize HF phenotypes.

The controversial role of beta-blockers in heart failure with preserved ejection fraction.

Beta-blocker (BB) therapy is a main pillar in treating patients with heart failure and reduced ejection fraction and has shown a prognostic benefit. However, evidence for application of BB in heart failure with preserved ejection fraction (HFpEF), especially in the absence of coronary artery disease, atrial fibrillation or arterial hypertension, is scarce. HFpEF is characterized by elevations in left atrial pressure and reduced compliance of the left ventricle leading to a hampered increase of cardiac output (CO) during exercise, which results in exertional dyspnea. This may be due to either a limited increase in stroke volume or reduced chronotropy during physical activity. We critically discuss the pathophysiological background of HFpEF, current data on BB in heart failure therapy, as well as the potential benefits and harms of BB therapy in HFpEF. Furthermore, we argue that non-cardio selective BB with peripheral activity to reduce afterload may be more suitable in this population than cardio-selective BB. Although preliminary data on BB in HFpEF are available, multicenter prospective trials to assess a reduction of cardiovascular morbidity are warranted. Future trials need to focus on phenotyping HFpEF patients and assess who may benefit most from tailored BB therapy.

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.

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.

Betablockers reduce oxygen pulse increase and performance in heart failure patients with preserved ejection fraction.

BACKGROUND: Beta blockers (BB) reduce chronotropic response and exercise capacity in heart failure with preserved ejection fraction (HFpEF). To analyze the influence of BB on exercise performance and O 2 pulse increase as a surrogate for stroke volume in HFpEF. METHODS: We retrospectively analyzed the influence of BB intake (yes: n = 48/no: n = 51) on peak oxygen uptake (VO 2peak), oxygen uptake efficiency slope (OUES), and increase of O 2 pulse in HFpEF patients undergoing cardiopulmonary exercise testing (CPET). Associations of outcome variables and risk category of the algorithm of the Heart Failure Association of the European Society of Cardiology (HFA-PEFF score) were calculated. RESULTS: Patients on BB showed lower VO 2peak (p = .003) and OUES (p = .002), with a dominant effect in the high-risk (p = .020; 0.002), but not in the low risk-group (p = .434; p = .499). In the intermediate group BB showed a trend towards lower VO 2peak (p = .078) and lower values for OUES (p = .020). Patients on BB also demonstrated a lower increase of O 2 pulse during exercise (p = .002), without differences between HFA-PEFF risk groups (low: p = .322, intermediate: p = .269, high: p = .313). CONCLUSIONS: BB reduce exercise capacity and O 2 pulse increase in HFpEF patients. Direct quantification of O 2 pulse increase may help to improve the discrimination of HFpEF 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.

Diastolic exercise stress testing in heart failure with preserved ejection fraction: The DEST-HF study.

AIMS: Pulmonary capillary wedge pressure (PAWP) ≥25 mmHg during bicycle ergometry is recommended to uncover occult heart failure with preserved ejection fraction. We hypothesized that PAWP increase would differ in available diastolic stress tests and that the margin of PAWP ≥25 mmHg would only be reliably achieved through ergometry. METHODS AND RESULTS: We conducted a prospective, single-arm study in patients with an intermediate risk for heart failure with preserved ejection fraction according to the ESC HFA-PEFF score. A total of 19 patients underwent four stress test modalities in randomized order: leg raise, fluid challenge, handgrip, and bicycle ergometry. The primary outcome was the difference (Δ) between resting and exercise PAWP in each modality. Secondary outcomes were differences (Δ) in mean pulmonary artery pressure (mPAP), cardiac output (CO), as well as the ratios between mPAP and PAWP to CO. Compared to resting values, passive leg raise (Δ7.7 ± 8.0 mmHg, p = 0.030), fluid challenge (Δ9.2 ± 6.4 mmHg, p = 0.003), dynamic handgrip (Δ9.6 ± 7.5 mmHg, p = 0.002), and bicycle ergometry (Δ22.3 ± 5.0 mmHg, p < 0.001) uncovered increased PAWP during exercise. Amongst these, bicycle ergometry also demonstrated the highest ΔmPAP (27.2 ± 7.1 mmHg, p < 0.001), ΔCO (3.3 ± 2.6 L/min, p < 0.001), ΔmPAP/CO ratio (2.3 ± 2.0 mmHg/L/min, p < 0.001), and ΔPAWP/CO ratio (2.2 ± 1.4 mmHg/L/min, p < 0.001) compared to other modalities. PAWP ≥25 mmHg was only reliably achieved in bicycle ergometry (31.1 ± 3.9 mmHg). In all other modalities only 10.5% of patients achieved PAWP ≥25 mmHg (handgrip 18.4 ± 6.6 mmHg, fluid 18.1 ± 5.6 mmHg, leg raise 16.5 ± 7.0 mmHg). CONCLUSIONS: We demonstrate that bicycle ergometry exhibits a distinct haemodynamic response with higher increase of PAWP compared to other modalities. This finding needs to be considered for valid detection of exercise PAWP ≥25 mmHg when non-bicycle tests remain inconclusive.

Phosphodiesterase-5 inhibitors for left ventricular assist device implantation complicated by right ventricular failure.

AIMS: Phosphodiesterase-5 inhibitors (PDE5I) are frequently implemented after left ventricular assist device (LVAD) implantation to improve haemodynamics in patients with early postoperative right ventricular (RV) failure. It is unknown if long-term PED5I therapy beyond the early post-operative period provides any clinical benefit in stable outpatients, who have recovered from post-operative RV failure under univentricular device support. This study aimed to investigate the impact of PDE5I discontinuation on RV function and cardiopulmonary exercise capacity in patients on durable LVAD support. METHODS AND RESULTS: We enrolled 31 clinically stable LVAD recipients on long-term oral PDE5I therapy. The mean age was 53 years, and 90% were male. Patients discontinued PDE5I and underwent cardiopulmonary exercise testing, echocardiography, LVAD interrogation, and biomarker analysis at baseline and 4 weeks after PDE5I withdrawal. At 4 weeks, no significant changes were observed in echocardiographic indices of RV morphology and function but an increase in peak tricuspid regurgitation velocity (2.1 vs. 2.4 m/s, P = 0.01). Peak oxygen consumption (11.4 vs. 11.8 mL/min/kg, P = 0.52), minute ventilation/carbon dioxide production slope (33 vs. 35, P = 0.56), N-terminal pro-brain natriuretic peptide (1455 vs. 1399 pg/mL, P = 0.55), flow and power readings of the device, and quality of life (Kansas City Cardiomyopathy Questionnaire score 78.3% vs. 77.5%, P = 0.62) exhibited no significant changes. We observed an increase in 6-min walking distance (346 vs. 364 m, P = 0.03). Two patients were hospitalized for non-cardiac reasons (subtherapeutic INR, driveline infection). No patient was hospitalized for cardiac decompensation. CONCLUSIONS: In LVAD patients with a history of early post-operative RV failure, discontinuation of long-term PDE5I therapy was not associated with deterioration of RV function, exercise capacity, and quality of life. PDE5I should be critically evaluated until more evidence regarding the net clinical benefit of this pharmacologic intervention becomes available.

Erectile dysfunction and quality of life in patients under left ventricular assist device support - an unspoken issue.

Background: Multiple domains of quality of life (QoL) such as erectile function are not sufficiently investigated among left ventricular assist-device (LVAD) patients. We aimed to evaluate the prevalence of erectile dysfunction (ED) and its association with QoL and depression. Methods: This is a prospective, single-center, cross-sectional study. We included adult male LVAD patients who were clinically stable after at least 3 months post-implantation. Erectile function was assessed with the International Index of Erectile Function (IIEF-5) questionnaire with a score of ≤21 being confirmatory for ED. QoL and depression were estimated with the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Patient Health Questionnaire depression scale (PHQ-8), respectively. Results: The study included 56 patients, of whom 45 (80 %) met criteria for ED, a prevalence much higher than previously reported in patients with established cardiovascular disease or conservatively treated heart failure. Patients with ED were older and had lower 6-minute walking distance. ED was not associated with comorbidities and heart failure medications but with less frequent use of diuretics and phosphodiesterase-5 inhibitors. There was a correlation between erectile function and depression as well as QoL. Conclusions: These findings underscore that ED deserves special attention and should be included in a multi-targeted approach to address suboptimal QoL outcomes after LVAD implantation.

Reduced physical activity and weight gain are associated with an increase of depressive symptoms during the COVID-19 pandemic. A general practitioners' prospective observational study.

OBJECTIVES: We aimed to assess associations between depressive symptoms, lifestyle, and somatic symptoms during the COVID-19 pandemic. DESIGN: A prospective, observational study using a self-designed questionnaire. SETTING: Three general practitioners' (GP) offices in rural Germany. PARTICIPANTS: 271 adult patients without manifest cardiovascular or pulmonary disease with (n = 82) and without (n = 189) hypertension reporting to our GP offices. MAIN OUTCOME MEASURES: The reported increase of depressive symptoms (loneliness, sleeplessness, joylessness, listlessness) prior to the first documented case in Germany on 27.01.2020 (t0) as opposed to patients' health perception during the Corona pandemic (t1) was the primary outcome measure. The secondary outcome measures were changes in physical activity (PA), dyspnea and angina in the two groups. RESULTS: Out of 271 patients (50.8 ± 16.8 years, 55.1% females), 1.5% were tested positive for COVID-19. Overall, listlessness (8.5%, p = 0.001), sleeplessness (5.2%, p = 0.001) and joylessness (4.2%, p = 0.003) were increased. Dyspnea significantly increased (9.2%, p < 0.001) and employment status worsened (6.5%, p < 0.001). There were significant associations between the increase of depressive symptoms, weight increase (p = 0.017), and reduction in physical activity (p = 0.046). However, after adjusting for age, hypertensive patients did not show more depressive symptoms (p = 0.704), dyspnea (p = 0.063) or angina (p = 0.432), nor was there any difference in PA (p = 0.906) compared to healthy individuals. CONCLUSIONS: We demonstrate an association between the deterioration of depressive symptoms, weight gain, and reduced physical activity during COVID-19, both in hypertensives and healthy controls. Hypertension is no driver of symptom deterioration during the pandemic. The trial was registered in the German Clinical Trials Registry (DRKS00022157).

Vital capacity and valvular dysfunction could serve as non-invasive predictors to screen for exercise pulmonary hypertension in the elderly based on a new diagnostic score.

Introduction: Exercise pulmonary hypertension (exPH) has been defined as total pulmonary resistance (TPR) >3 mm Hg/L/min and mean pulmonary artery pressure (mPAP) >30 mm Hg, albeit with a considerable risk of false positives in elderly patients with lower cardiac output during exercise. Methods: We retrospectively analysed patients with unclear dyspnea receiving right heart catheterisation at rest and exercise (n=244) between January 2015 and January 2020. Lung function testing, blood gas analysis, and echocardiography were performed. We elaborated a combinatorial score to advance the current definition of exPH in an elderly population (mean age 67.0 years±11.9). A stepwise regression model was calculated to non-invasively predict exPH. Results: Analysis of variables across the achieved peak power allowed the creation of a model for defining exPH, where three out of four criteria needed to be fulfilled: Peak power ≤100 Watt, pulmonary capillary wedge pressure ≥18 mm Hg, pulmonary vascular resistance >3 Wood Units, and mPAP ≥35 mm Hg. The new scoring model resulted in a lower number of exPH diagnoses than the current suggestion (63.1% vs. 78.3%). We present a combinatorial model with vital capacity (VCmax) and valvular dysfunction to predict exPH (sensitivity 93.2%; specificity 44.2%, area under the curve 0.73) based on our suggested criteria. The odds of the presence of exPH were 2.1 for a 1 l loss in VCmax and 3.6 for having valvular dysfunction. Conclusion: We advance a revised definition of exPH in elderly patients in order to overcome current limitations. We establish a new non-invasive approach to predict exPH by assessing VCmax and valvular dysfunction for early risk stratification in elderly patients.