Aortic arch blood flow measurements as a predictor of successful ECMO weaning in cardiogenic shock.

Objective: Acute cardiogenic shock is a life-threatening condition with mortality rates of up to 50%. If conventional therapy fails, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy has emerged to a promising alternative for temporary cardiac and respiratory support in specialized centers. However, it is only a bridge to recovery, final decision, heart transplantation or the permanent implantation of a left ventricular assist device. Therefore, the identification of the optimum weaning time point is challenging, and standardized weaning protocols are rare. Methods: In this explorative pilot study, we evaluated the potential benefit of blood flow measurements in the aortic arch using an ultrasonic cardiac output monitor (USCOM) for the primary endpoint of successful VA-ECMO weaning. 12 patients under VA-ECMO therapy for acute cardiogenic shock and a hemodynamic condition which qualified for a stepwise weaning process were included in this study. Main exclusion criterion was the presence of additional venting therapy for left ventricular unloading, e.g. Impella. Statistical comparisons were performed using the Mann-Whitney test and corrected for multiple testing by the Holm-Sidak method. Results: Peak velocity of flow in the aortic arch showed a positive correlation with weaning success independent of ECMO flow (weaning success vs. failure: 0.75 vs. 0.35 m/s (low ECMO support), p = 0.049), whereas we identified only a trend for mean pressure gradient, minute distance and stroke volume index. Conclusion: We hypothesize, that USCOM might provide an additive benefit to conventional strategies in its ability to predict successful VA-ECMO weaning and prevent pulmonary congestion. Larger upcoming trials are required to address this relevant topic and provide standardized treatment protocols for optimized weaning in the future.

The association of off-hour vs. on-hour intensive care unit admission time with mortality in patients with cardiogenic shock: a retrospective multi-centre analysis.

AIMS: Studies have shown a so-called off-hour effect for many different diseases, but data are scarce concerning cardiogenic shock. We therefore assessed the association of off-hour vs. on-hour intensive care unit admission with 30-day mortality in patients with cardiogenic shock. METHODS AND RESULTS: In total, 1720 cardiogenic shock patients (666 admitted during off-hours) from two large university hospitals in Germany were included in retrospect. An admission during off-hours was associated with increased 30-day mortality compared to an admission during on-hours [crude mortality 48% vs. 41%, HR 1.17 (1.03-1.33), P = 0.017]. This effect remained significant after propensity score matching (P = 0.023). Neither patients with a combined SCAI stage D and E (P = 0.088) or C (P = 0.548) nor those requiring cardiopulmonary resuscitation (P = 0.114) had a higher mortality at off-hour admission. In contrast, those without veno-arterial extracorporeal membrane oxygenation [HR 1.17 (1.00-1.36), P = 0.049], without acute myocardial infarction [HR 1.27 (1.02-1.56), P = 0.029] or a with combined SCAI stage A and B [HR 2.23 (1.08-4.57), P = 0.025] had an increased mortality at off-hour admission. CONCLUSION: Our study showed an increased mortality in patients with cardiogenic shock admitted during off-hours, especially in those with a milder onset of disease. This stresses the importance of a thorough workup of each patient, especially at times of limited resources, the menace of underestimating the severity of cardiogenic shock, and the need for an improved 24×7 available risk stratification.

Long-Term Follow-Up of Patients With Elevated Aldosterone-to-Renin Ratio but Negative Confirmatory Test: The Progression of Primary Aldosteronism Phenotypes.

BACKGROUND: About 10% of patients with arterial hypertension have a positive screening test for primary aldosteronism (PA) and 50% to 70% of them have a negative confirmatory test: the appropriate follow-up of these patients is currently unknown. We investigated the incidence of PA in patients with previous negative confirmatory testing, after at least a 2-year follow-up. METHODS: One hundred eighty-four patients with a previously elevated aldosterone-to-renin ratio followed by a negative confirmatory test were recruited in 2 hypertension centers (Torino and Munich). We repeated the screening test for PA and, if positive, the confirmatory test (seated saline infusion test or captopril challenge test). Primary end point of the study was the incidence of newly diagnosed overt PA, as defined by a positive confirmatory test. RESULTS: After a mean follow-up of 5 years, 20% of patients developed overt PA. When subtype diagnosis was offered systematically, one-third of patients displayed unilateral PA. Patients who developed PA showed worsening of blood pressure control and a higher rate of cardiac organ damage, despite similar implementation of antihypertensive therapy, compared with patients without PA. A mild progression of autonomous aldosterone secretion was evident even in patients without confirmed PA but with relatively stable control of blood pressure levels over time. CONCLUSIONS: About one-fifth of patients with a negative confirmatory test develop overt PA over time. A clinical follow-up of patients with a negative confirmatory test is advisable, along with the repetition of PA investigation, primarily in patients with worsening of blood pressure control.

Cardiac deceleration capacity is associated with severity of inflammation in COVID-19.

PURPOSE: In this pilot study, we investigated the cardiac autonomic activity of coronavirus disease 2019 (COVID-19)-infected hospitalized patients. COVID-19 is characterized by cough, fever, and dyspnea, which in some severe cases can lead to hypoxia, respiratory failure, and shock. Since breathing disorders and pulmonary diseases are tightly linked to autonomic dysfunction, we analyzed the cardiac autonomic activity by measuring the deceleration capacity (DC) in COVID-19 patients. METHODS: In 14 adults (4 men and 10 women) with a median age of 63.5 years and positive for SARS-CoV-2 by polymerase chain reaction (PCR) with severe symptoms requiring hospital treatment, a high-resolution digital 30 min electrocardiogram (ECG) in Frank leads configuration was performed in a resting supine position within the first 48 h after hospital admission. DC was assessed using validated software and associated with several markers of inflammation and clinical course. RESULTS: The study revealed a significant association between reduced DC (≤ 2.5 ms) and older age (74 years) in COVID-19 patients, compared to those with a higher DC > 2.5 ms (56.5 years). However, the duration of hospitalization was similar for both groups. There was a nonsignificant trend towards a higher maximum viral load in patients with reduced DC. Further, patients with a DC ≤ 2.5 ms showed higher levels of inflammatory markers such as C-reactive protein (CRP) and procalcitonin (PCT), as well as leukocytosis, compared to patients with a DC > 2.5 ms. Also, the COVID-19-severity marker ferritin was significantly elevated in patients with lower DC. Other markers associated with COVID-19, such as lactate dehydrogenase (LDH) and creatine kinase (CK), exhibited comparable levels in both groups. CONCLUSIONS: Reduced DC (≤ 2.5 ms) was significantly associated with older age, increased inflammatory markers, and elevated ferritin in patients with COVID-19. These findings suggest that DC might serve as a valuable indicator for predicting the risk of severe inflammation in COVID-19 and possibly complications associated with this disease, such as heart failure. Further studies are needed to confirm these observations and clarify the clinical significance of DC in COVID-19 and other infectious diseases.

Digital Transformation in the Diagnostics and Therapy of Cardiovascular Diseases: Comprehensive Literature Review.

BACKGROUND: The digital transformation of our health care system has experienced a clear shift in the last few years due to political, medical, and technical innovations and reorganization. In particular, the cardiovascular field has undergone a significant change, with new broad perspectives in terms of optimized treatment strategies for patients nowadays. OBJECTIVE: After a short historical introduction, this comprehensive literature review aimed to provide a detailed overview of the scientific evidence regarding digitalization in the diagnostics and therapy of cardiovascular diseases (CVDs). METHODS: We performed an extensive literature search of the PubMed database and included all related articles that were published as of March 2022. Of the 3021 studies identified, 1639 (54.25%) studies were selected for a structured analysis and presentation (original articles: n=1273, 77.67%; reviews or comments: n=366, 22.33%). In addition to studies on CVDs in general, 829 studies could be assigned to a specific CVD with a diagnostic and therapeutic approach. For data presentation, all 829 publications were grouped into 6 categories of CVDs. RESULTS: Evidence-based innovations in the cardiovascular field cover a wide medical spectrum, starting from the diagnosis of congenital heart diseases or arrhythmias and overoptimized workflows in the emergency care setting of acute myocardial infarction to telemedical care for patients having chronic diseases such as heart failure, coronary artery disease, or hypertension. The use of smartphones and wearables as well as the integration of artificial intelligence provides important tools for location-independent medical care and the prevention of adverse events. CONCLUSIONS: Digital transformation has opened up multiple new perspectives in the cardiovascular field, with rapidly expanding scientific evidence. Beyond important improvements in terms of patient care, these innovations are also capable of reducing costs for our health care system. In the next few years, digital transformation will continue to revolutionize the field of cardiovascular medicine and broaden our medical and scientific horizons.

Impact of Preparticipating Hypohydration on Cardiopulmonary Exercise Capacity in Ambitious Recreational Athletes.

BACKGROUND: Heat induces a thermoregulatory strain that impairs cardiopulmonary exercise capacity. The aim of the current study is to elucidate the effect of isolated dehydration on cardiopulmonary exercise capacity in a model of preparticipating hypohydration. METHODS: Healthy recreational athletes underwent a standardised fluid deprivation test. Hypohydration was assessed by bioelectrical impedance analysis (BIA) and laboratory testing of electrolytes and retention parameters in the blood and urine. The participants underwent cardiopulmonary exercise testing (CPET) with a cycle ramp protocol. Each participant served as their own control undergoing CPET in a hypohydrated [HYH] and euhydrated [EUH] state. RESULTS: Fluid deprivation caused a mild (2%) but significant reduction of body water (38.6 [36.6; 40.7] vs. 39.4 [37.4; 41.5] %; p < 0.01) and an increase of urine osmolality (767 [694; 839] vs. 537 [445; 629] mosm/kg; p < 0.01). Hypohydration was without alterations of electrolytes, serum osmolality or hematocrit. The oxygen uptake was significantly lower after hypohydration (-4.8%; p = 0.02 at ventilatory threshold1; -2.0%; p < 0.01 at maximum power), with a corresponding decrease of minute ventilation (-4% at ventilatory threshold1; p = 0.01, -3.3% at maximum power; p < 0.01). The power output was lower in hypohydration (-6.8%; p < 0.01 at ventilatory threshold1; -2.2%; p = 0.01 at maximum power). CONCLUSION: Isolated hypohydration causes impairment of workload as well as peak oxygen uptake in recreational athletes. Our findings might indicate an important role of hypohydration in the heat-induced reduction of exercise capacity.

Evaluation of a Standardized Training and Adherence Surveillance Programme to Overcome Quality-of-Life Impairments and Enhance Compliance in Patients Treated with Wearable Cardioverter Defibrillator.

Background: Treatment with wearable cardioverter defibrillators (WCD) is a non-invasive, transient therapy option for prevention of sudden cardiac death (SCD) in patients with temporary contraindications for implantation of a permanent cardioverter defibrillator. Due to the constant risk of fatal arrhythmias, compliance is the fundamental requirement for effectiveness of a WCD, but this might be hindered by the poor quality-of-life (QoL) during WCD therapy. In this retrospective single-center study, we examined if a standardized WCD training and adherence surveillance programme could enhance compliance and QoL. Methods: All patients with a prescription for WCD treatment from January 2017 to August 2019 were included and received a standardized WCD training programme. QoL was validated using the modified EQ-5D-3L questionnaire. The findings were compared to a historical, previously published, retrospective cohort from our center (WCD prescription period 03/2012-02/2016), not receiving the additional training programme. Endpoints comprised therapy adherence, arrhythmic episodes, and dimensions of QoL. Results: Ninety-two patients underwent WCD treatment in the study cohort for a median of 49 days. Median daily wear time was enhanced in the study cohort (historical cohort vs study cohort 21.9 vs 23.3 hours/per day, p<0.01) and artefact alarms occurred less frequently (67.9% vs 48.9%, p 0.01). Major restrictions in QoL in the study cohort were found in mobility (48%), daily routine (44%), and sleep (49%), but the dimensions pain (36% vs 4%, p<0.01), mental health (43% vs 29%, p 0.03), and restrictions in daily routine (48% vs 30%, p 0.04) improved. Conclusion: A standardized training and adherence surveillance programme might have beneficial effects on compliance and QoL. As these findings are essential for therapy success, they might potentially lead to a reduction in arrhythmic deaths in upcoming WCD trials.

Comparable Analysis of Acute Changes in Vascular Tone after Coffee versus Energy Drink Consumption.

Caffeinated beverages are popular throughout the world, especially due to their stimulating effects on body physiology. However, short- and long-term outcome studies have shown variable results on general health. In this pilot study, we exposed a cohort of 23 healthy individuals to 240 mg of caffeine either in the form of coffee or energy drinks and performed repetitive pulse wave analyses. This experimental approach was chosen to investigate the acute effects of caffeine consumption on vascular tone depending on the form of caffeine intake. Our data indicate that energy drinks, in contrast to coffee, might negatively impact systolic blood pressure and pulse wave velocity. This issue needs special attention in the light of cardiovascular health as the observed effects have been associated with an increased risk of cardiovascular events upon persistent exposure.

Manual Compression versus Suture-Mediated Closure Device Technique for VA-ECMO Decannulation.

Background: The impact of devices for vessel closure on the safety and efficacy of cannula removal in VA-ECMO patients is unknown. Methods: We retrospectively analyzed 180 consecutive patients weaned from VA-ECMO after cardiac arrest or cardiogenic shock from January 2012 to June 2020. In the first period (historical technique group), from January 2012 to December 2018, primary decannulation strategy was manual compression. In the second period (current technique group), from January 2019 to June 2020, decannulation was performed either by a conventional approach with manual compression or by a suture-mediated closure device technique. Results: A femoral compression system was necessary in 71% of patients in the historical group compared to 39% in the current technique group (p < 0.01). Vascular surgery was performed in 12% in the historical cohort and 2% in the current technique cohort, which indicated a clear trend, albeit it did not reach significance (p = 0.07). Conclusion: We illustrated that a suture-mediated closure device technique for VA-ECMO decannulation was feasible, safe, and may have reduced the need of surgical interventions compared to manual compression alone.

Differences in Cell-Intrinsic Inflammatory Programs of Yolk Sac and Bone Marrow Macrophages.

BACKGROUND: Tissue-resident macrophages have mixed developmental origins. They derive in variable extent from yolk sac (YS) hematopoiesis during embryonic development. Bone marrow (BM) hematopoietic progenitors give rise to tissue macrophages in postnatal life, and their contribution increases upon organ injury. Since the phenotype and functions of macrophages are modulated by the tissue of residence, the impact of their origin and developmental paths has remained incompletely understood. METHODS: In order to decipher cell-intrinsic macrophage programs, we immortalized hematopoietic progenitors from YS and BM using conditional HoxB8, and carried out an in-depth functional and molecular analysis of differentiated macrophages. RESULTS: While YS and BM macrophages demonstrate close similarities in terms of cellular growth, differentiation, cell death susceptibility and phagocytic properties, they display differences in cell metabolism, expression of inflammatory markers and inflammasome activation. Reduced abundance of PYCARD (ASC) and CASPASE-1 proteins in YS macrophages abrogated interleukin-1ß production in response to canonical and non-canonical inflammasome activation. CONCLUSIONS: Macrophage ontogeny is associated with distinct cellular programs and immune response. Our findings contribute to the understanding of the regulation and programming of macrophage functions.

Hospitalization for COVID-19 is associated with significant changes in body composition.

BACKGROUND & AIMS: COVID-19 is a severe viral infection of the respiratory tract and has become a worldwide pandemic. Months after the initial infection several people report persistent limitations in daily life. Previous studies have identified body composition as a predictor of clinical progression in cases of COVID-19. However, body impedance measurements were limited to baseline and not repeated in serial measurements. In this study we analyzed the impact of a moderate oxygen-dependent COVID-19 infection on body composition during hospitalization. METHODS: We enrolled 12 consecutive patients hospitalized due to an oxygen-dependent SARS-CoV-2 infection. Body impedance analysis was performed within 24 h of admission and repeated on day 3 ± 1 as well as on the day of discharge. Endpoints were any significant changes in body composition. RESULTS: Median age of enrolled patients was 70.6 years with a BMI of 30.8 kg/m2. Patients were hospitalized for 14 days. Median oxygen demand was 3 l/min, 2 patients required mechanical ventilation. Body water and fat remained unchanged during the study period. We observed a significant decrease of phase angle (-0.6, p < 0.01) and body cell mass (-2.3%, p < 0.01) with an increase in extracellular mass on day 3. Values returned to baseline along recovery. CONCLUSION: We found a significant reduction in body cell mass and phase angle during the active infection with slow regression towards hospital discharge. Future studies are needed to clarify if nutrition and training programs during and after COVID-19 might limit these changes and have a positive impact on clinical course and rehabilitation.

Impact of moderate altitude exposure on cardiovascular risk.

Acute exposure to extreme altitude increases arterial stiffness by activation of the sympathetic and endothelin system as well as hypoxia-induced reactive oxygen species production. Beyond a certain individual threshold, these physiological adaptations represent a relevant cardiovascular risk factor. In this pilot study we investigated to what extent temporary exposure to moderate altitude, as present during hiking, skiing or in aeroplanes, leads to changes in vascular tone. Pulse wave parameters of 8 healthy individuals were assessed with a BR-102 plus pulse wave analyser (Schiller, Germany) at baseline (521 m) and after 24 h exposure to moderate altitude (2650 m). We identified a significant increase in heart rate (61 vs. 68/min, p = 0.021) as well as changes in central (35.6 vs. 41.4 mmHg, p = 0.024) and peripheral pulse pressure (44.7 vs. 52.6 mmHg, p = 0.006). Amplitudes of forward (21.6 vs. 25.4 mmHg, p = 0.012) and backward pulse waves (15.3 vs. 17.6 mmHg, p = 0.043) were significantly elevated. Pulse wave velocity showed no significant change from 5.8 m/s at baseline to 6.1 m/s at moderate altitude (p = 0.056). We show that temporary exposure to moderate altitude leads to mild changes in vascular tone reflected by pulse pressure and pulse wave amplitude in healthy adults. Although the observed effects were mild in our study, it indicates that adaptation capacity is of crucial importance and any restrictions by disease or simply with the process of ageing demand increased awareness, even in moderate altitude.

[Update 2021: COVID-19 from the perspective of cardiology]. / Update 2021: COVID-19 aus Sicht der Kardiologie.

More than one year ago COVID-19 emerged to a rapidly expanding global pandemic. Along with a growing number of individuals infected with SARS-CoV-2, we gained substantial knowledge on development, progression and treatment of the disease. In the light of increasing worldwide infection rates during the current "third wave", we will give a short update on COVID-19 from a cardiological point-of-view.

Obesity, Nutrition and Heart Rate Variability.

Heart rate variability (HRV) represents the activity and balance of the autonomic nervous system and its capability to react to internal and external stimuli. As a measure of general body homeostasis, HRV is linked to lifestyle factors and it is associated with morbidity and mortality. It is easily accessible by heart rate monitoring and gains interest in the era of smart watches and self-monitoring. In this review, we summarize effects of weight loss, training, and nutrition on HRV with a special focus on obesity. Besides weight reduction, effects of physical activity and dietary intervention can be monitored by parameters of HRV, including its time and frequency domain components. In the future, monitoring of HRV should be included in any weight reduction program as it provides an additional tool to analyze the effect of body weight on general health and homeostasis. HRV parameters could, for example, be monitored easily by implementation of an electrocardiogram (ECG) every two to four weeks during weight reduction period. Indices presumibly showing beneficial changes could be a reduction in heart rate and the number of premature ventricular complexes as well as an increase in standard deviation of normal-to-normal beat intervals (SDNN), just to name some.

Treatment of acute cardiac tamponade: A retrospective analysis of classical intermittent versus continuous pericardial drainage.

BACKGROUND: Acute cardiac tamponade is a life-threatening pathology in modern cardiology as catheter-based interventions become increasingly relevant. Pericardiocentesis is usually the primary treatment of choice. However, protocols for handling of draining pigtail catheters are very variable due to limit data and require further investigation. METHODS: We retrospectively analyzed 52 patients with acute cardiac tamponade requiring immediate pericardiocentesis from January 2017 to August 2020. Patients were treated with a classical approach of intermittent manual aspiration or continuous pericardial drainage using a redon drainage system. RESULTS: Mean age of patients was 74 years in both groups. Most common causes for cardiac tamponade were percutaneous coronary interventions in about 50% and transaortic valve implantations in 25% of all cases. 28 patients were treated with classic intermittent drainage from 2017 to 2020. 24 patients were treated with continuous drainage from December 2018-2020. Compared to classical intermittent drainage treatment, continuous drainage was associated with a lower rate of a surgical intervention or cardiac re-tamponade and a lower mortality at 5 days (HR 0.2, 95% CI 0.1-0.9, log-rank p = 0.03). Despite a longer total drainage time under continuous suction, drainage volumes were comparable in both groups. CONCLUSION: Acute cardiac tamponade can be efficiently treated by pericardiocentesis with subsequent continuous negative pressure drainage via a pigtail catheter. Our retrospective analysis shows a significantly lower mortality, a decreased rate of interventions and lower rates of cardiac re-tamponade without any relevant side effects when compared to classical intermittent manual drainage. These findings require further investigations in larger, randomized trials.

Synthesis, DNA-binding and antiproliferative properties of diarylquinolizinium derivatives.

A series of ten 2,7- and 2,8-diarylquinolizinium derivatives was synthesized and their DNA-binding and cytotoxic properties were investigated. Except for one nitro-substituted derivative all tested diarylquinolizinium ions bind to DNA with sufficient affinity (2 × 104 M-1-2 × 105 M-1). It was shown with photometric, fluorimetric and polarimetric titrations as well as with flow-LD analysis that the ligands bind mainly by intercalation to duplex DNA, however, depending on the ligand-DNA ratio, groove binding and backbone association were also observed with some derivatives. The biological activity was further investigated with tests of cytotoxicity and antiproliferative properties towards non-tumor cells and selected cancer cells, along with cell cycle analysis and an annexin-V assay. Notably, substrates that carry donor-functionalities in the 4-position of the phenyl substituents revealed a strong, and in some cases selective, antiproliferative activity as quantified by the growth inhibition, GI50, at very low micromolar and even submicromolar level both in leukemia and solid tumors.

Two populations of self-maintaining monocyte-independent macrophages exist in adult epididymis and testis.

Macrophages are the principal immune cells of the epididymis and testis, but their origins, heterogeneity, development, and maintenance are not well understood. Here, we describe distinct populations of epididymal and testicular macrophages that display an organ-specific cellular identity. Combining in vivo fate-mapping, chimeric and parabiotic mouse models with in-depth cellular analyses, we found that CD64hiMHCIIlo and CD64loMHCIIhi macrophage populations of epididymis and testis arise sequentially from yolk sac erythro-myeloid progenitors, embryonic hematopoiesis, and nascent neonatal monocytes. While monocytes were the major developmental source of both epididymal and testicular macrophages, both populations self-maintain in the steady-state independent of bone marrow hematopoietic precursors. However, after radiation-induced macrophage ablation or during infection, bone marrow-derived circulating monocytes are recruited to the epididymis and testis, giving rise to inflammatory macrophages that promote tissue damage. These results define the layered ontogeny, maintenance and inflammatory response of macrophage populations in the male reproductive organs.

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives.

A small series of five novel berberine derivatives was synthesized by the Cu-catalyzed click reaction of 9-propargyladenine with 9-O-(azidoalkyl)berberine derivatives. The association of the resulting berberine-adenine conjugates with representative quadruplex-forming oligonucleotides 22AG dA(G3TTA)3G3 and a2 d(ACAG4TGTG4)2 was examined with photometric and fluorimetric titrations, thermal DNA denaturation analysis, and CD spectroscopy. The results from the spectrometric titrations indicated the formation of 2:1 or 1:1 complexes (ligand:G4-DNA) with log K b values of 10-11 (2:1) and 5-6 (1:1), which are typical for berberine derivatives. Notably, a clear relationship between the binding affinity of the ligands with the length of the alkyl linker chain, n, was not observed. However, depending on the structure, the ligands exhibited different effects when bound to the G4-DNA, such as fluorescent light-up effects and formation of ICD bands, which are mostly pronounced with a linker length of n = 4 (with a2) and n = 5 (with 22AG), thus indicating that each ligand-G4-DNA complex has a specific structure with respect to relative alignment and conformational flexibility of the ligand in the binding site. It was shown exemplarily with one representative ligand from the series that such berberine-adenine conjugates exhibit a selective binding, specifically a selectivity to quadruplex DNA in competition with duplex DNA, and a preferential thermal stabilization of the G4-DNA forms 22AG and KRAS. Notably, the experimental data do not provide evidence for a significant effect of the adenine unit on the binding affinity of the ligands, for example, by additional association with the loops, presumably because the adenine residue is sterically shielded by the neighboring triazole unit.