Effects of cardiovascular risk factors and pre-existing diseases on the short-term outcome of Takotsubo syndrome.

BACKGROUND: The effects of cardiovascular risk factors (CVRF) on the development of most acute cardiac conditions are well established; however, little is known about the frequency and effects of CVRF in Takotsubo syndrome (TTS) patients. OBJECTIVE: The aim of our study was to compare the frequency of CVRF and pre-existing diseases (PD) of TTS patients to ST-elevation myocardial infarction (STEMI) patients and analyze their effects on short-term outcome. METHODS: We analyzed the frequency of CVRF (hypertension, hyperlipidemia, type II diabetes mellitus, smoking, chronic kidney disease, family history) as well as somatic and psychiatric PD at admission in TTS patients and compared them with STEMI patients. Their effect on short-term outcome was calculated using a combined endpoint of cardiogenic shock, cardiopulmonary resuscitation, mechanical ventilation, and/or in-hospital death. RESULTS: In total, 150 TTS and 155 STEMI patients were included in our study. We observed a higher frequency of psychiatric (30% vs. 7%, p < 0.001), neurological (5% vs. 0%, p = 0.01), and pulmonary (18% vs. 5%, p < 0.001) PD in TTS patients as compared to STEMI patients. There were less smokers (47% vs. 61%, p = 0.03) and patients with hyperlipidemia (24% vs. 51%, p < 0.001) in the TTS cohort than in the STEMI cohort. None of the CVRF or PD behaved as an independent predictor for adverse short-term outcome in TTS patients. CONCLUSION: Psychiatric, neurological, and pulmonary pre-existing diseases are more common in TTS than in STEMI patients. Interestingly, PD and CVRF do not seem to have any impact on the short-term outcome of TTS patients.

Improvement of Symptoms and Cardiac Magnetic Resonance Abnormalities in Patients with Post-Acute Sequelae of SARS-CoV-2 Cardiovascular Syndrome (PASC-CVS) after Guideline-Oriented Therapy.

Cardiac magnetic resonance (CMR) studies reported CMR abnormalities in patients with mild-moderate SARS-CoV-2 infection, suggesting ongoing myocardial inflammation. Patients (n = 278, 43 ± 13 years, 70.5% female) with post-acute sequelae of SARS-CoV-2 cardiovascular syndrome (PASC-CVS) were included prospectively into the Vienna POSTCOV Registry between March 2021 and March 2023 (clinicaltrials.gov NCT05398952). Clinical, laboratory, and CMR findings were recorded. Patients with abnormal CMR results were classified into isolated chronic pericardial (with/without pleural) effusion, isolated cardiac function impairment, or both (myopericarditis) groups. Medical treatment included a nonsteroidal anti-inflammatory agent (NSAID) for pericardial effusion and a condition-adapted maximal dose of heart failure (HF) treatment. Three months after medical therapy, clinical assessment and CMR were repeated in 82 patients. Laboratory analyses revealed normal hematological, inflammatory, coagulation, and cardiac biomarkers. CMR abnormalities were found in 155 patients (55.8%). Condition-adapted HF treatment led to a significant increase in the left ventricular ejection fraction (LVEF) in patients with initially reduced LVEF (from 49 ± 5% to 56 ± 4%, p = 0.009, n = 25). Low-moderate doses of NSAIDs for 3 months significantly reduced pericardial effusion (from 4/3;5.75/mm to 2/0;3/mm, median/interquartile ranges/p < 0.001, n = 51). Clinical symptoms improved markedly with a decrease in CMR abnormalities, which might be attributed to the maintenance of NSAID and HF medical treatment for PASC-CVS.

A CircRNA-miRNA-mRNA Network for Exploring Doxorubicin- and Myocet-Induced Cardiotoxicity in a Translational Porcine Model.

Despite the widespread use of doxorubicin (DOX) as a chemotherapeutic agent, its severe cumulative cardiotoxicity represents a significant limitation. While the liposomal encapsulation of doxorubicin (Myocet, MYO) reduces cardiotoxicity, it is crucial to understand the molecular background of doxorubicin-induced cardiotoxicity. Here, we examined circular RNA expression in a translational model of pigs treated with either DOX or MYO and its potential impact on the global gene expression pattern in the myocardium. This study furthers our knowledge about the regulatory network of circRNA/miRNA/mRNA and its interaction with chemotherapeutics. Domestic pigs were treated with three cycles of anthracycline drugs (DOX, n = 5; MYO, n = 5) to induce cardiotoxicity. Untreated animals served as controls (control, n = 3). We applied a bulk mRNA-seq approach and the CIRIquant algorithm to identify circRNAs. The most differentially regulated circRNAs were validated under cell culture conditions, following forecasting of the circRNA-miRNA-mRNA network. We identified eight novel significantly regulated circRNAs from exonic and mitochondrial regions in the porcine myocardium. The forecasted circRNA-miRNA-mRNA network suggested candidate circRNAs that sponge miR-17, miR-15b, miR-130b, the let-7 family, and miR125, together with their mRNA targets. The identified circRNA-miRNA-mRNA network provides an updated, coherent view of the mechanisms involved in anthracycline-induced cardiotoxicity.

Renin Trajectories and Outcome in Stable Heart Failure with Reduced Ejection Fraction (HFrEF) on Contemporary Therapy: A Monocentric Study from an Austrian Tertiary Hospital Outpatient Clinic.

Introduction: The renin-angiotensin system (RAS) is the main target of neurohumoral therapy in heart failure with reduced ejection fraction (HFrEF) effectively reducing mortality. Reasonably, renin might serve as a biomarker for risk prediction and therapy response. Renin indeed bears some additional value to clinical risk models, albeit the effect is not pronounced. Whether assessing renin trajectories can overcome the weaknesses of single renin measurements has not been reported. Methods: A total of 505 patients with stable HFrEF were enrolled prospectively and followed through routine clinical visits. Active plasma renin concentration was documented up to 5 years. Changes in renin were analyzed throughout the disease course, and survival was compared for different renin trajectories within the first year. Results: Baseline renin levels were not related to all-cause mortality (crude HR for an increase of 100 µiE/ml: 1.01 (95% CI: 0.99-1.02), p = 0.414) but associated with unplanned HF hospitalizations (crude HR: 1.01 (95% CI: 1.00-1.02), p = 0.015). Renin increased during the disease course from baseline to 1-year and 2-year FUP (122.7 vs. 185.6 µIU/ml, p = 0.039, and 122.7 vs. 258.5 µIU/ml, p = 0.001). Both survival and unplanned HF hospitalization rates were comparable for different renin trajectories at 1-year FUP (p = 0.546, p = 0.357). Conclusions: Intriguingly, renin is not a good biomarker to indicate prognosis in HF, while renin trajectories over a 1-year period do not have an additional value. Rapid physiologic plasma renin variations, but also opposing effects of angiotensinogen-derived metabolites under presence of RAS blockade, might obscure the predictive ability of renin.

Determinants of trust in times of crises: A cross-sectional study of 3,065 German-speaking adults from the D-A-CH region.

Interpersonal trust declined worldwide during the COVID-19 pandemic; strategies are needed to restore it. We surveyed 3,065 quota-sampled German-speaking adults residing in the D-A-CH region. Using multinomial logistic regression models and backward elimination for variable selection, we calculated multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95% CIs) to appraise correlates of interpersonal trust using the Interpersonal Trust Short Scale (KUSIV3). Participants with high levels of interpersonal trust (top KUSIV3 tertile (T3)) tended to be older, male, residents of Switzerland, university degree holders, and workers with higher income and work satisfaction (all Pdiff<0.01) compared to those in the lowest KUSIV3 tertile (T1). Optimism was most strongly associated with high interpersonal trust (ORT3vsT1 = 5.75, 95%CI = 4.33-7.64). Also significantly associated with high interpersonal trust were: Having voted in the last national election (for the opposition, OR = 1.39, 95%CI = 1.02-1.89 or the governing party, OR = 1.61, 95%CI = 1.23-2.11) versus non-voters; perspective taking (ORT3vsT1 = 1.46, 95%CI = 1.11-1.91); being more extraverted (ORT3vsT1 = 1.99, 95%CI = 1.53-2.59) and more agreeable (ORT3vsT1 = 1.95, 95% CI = 1.46-2.61); and scoring higher on complexity thinking (ORT3vsT1 = 1.32, 95%CI = 1.01-1.72). Participants scoring significantly lower for interpersonal trust did not regularly participate in religious meetings (OR = 0.61, 95%CI = 0.44-0.84, versus participation at least monthly); were more conscientious (ORT3vsT1 = 0.68, 95%CI = 0.51-0.91) or current smokers (OR = 0.68; 95%CI = 0.53-0.87, versus never smoking); had sleep problems >5 times a week (OR = 0.48; 95%CI = 0.36-0.66, versus none); and scored high on conspiracy belief (ORT3vsT1 = 0.53; 95%CI = 0.41-0.69). Results differed minimally by gender and country. These findings may be helpful in devising targeted strategies to strengthen interpersonal trust and social engagement in European societies, especially during times of crises.

Identification of Gene Expression Signatures for Phenotype-Specific Drug Targeting of Cardiac Fibrosis.

We have designed translational animal models to investigate cardiac profibrotic gene signatures. Domestic pigs were treated with cardiotoxic drugs (doxorubicin, DOX, n = 5 or Myocet®, MYO, n = 5) to induce replacement fibrosis via cardiotoxicity. Reactive interstitial fibrosis was triggered by LV pressure overload by artificial isthmus stenosis with stepwise developing myocardial hypertrophy and final fibrosis (Hyper, n = 3) or by LV volume overload in the adverse remodeled LV after myocardial infarction (RemoLV, n = 3). Sham interventions served as controls and healthy animals (Control, n = 3) served as a reference in sequencing study. Myocardial samples from the LV of each group were subjected to RNA sequencing. RNA-seq analysis revealed a clear distinction between the transcriptomes of myocardial fibrosis (MF) models. Cardiotoxic drugs activated the TNF-alpha and adrenergic signaling pathways. Pressure or volume overload led to the activation of FoxO pathway. Significant upregulation of pathway components enabled the identification of potential drug candidates used for the treatment of heart failure, such as ACE inhibitors, ARB, ß-blockers, statins and diuretics specific to the distinct MF models. We identified candidate drugs in the groups of channel blockers, thiostrepton that targets the FOXM1-regulated ACE conversion to ACE2, tyrosine kinases or peroxisome proliferator-activated receptor inhibitors. Our study identified different gene targets involved in the development of distinct preclinical MF protocols enabling tailoring expression signature-based approach for the treatment of MF.

[Long COVID-A New Challenge in Medicine: Focus on Pregnancy and Breastfeeding]. / Long COVID ­ eine neue Herausforderung in der Medizin: Fokus auf Schwangerschaft und Stillzeit.

Long COVID (coronavirus disease) has been described as a new multi-organ disease, which appears to be more prevalent in women than in men. Pregnant and breastfeeding women are a special subgroup of patients to consider with long COVID, as only scarce data have been collected to date. Menstrual changes are commonly observed during or after COVID-19; some studies also attribute slight changes of cycle length to previous inoculation against the virus. Pregnant women who have a symptomatic infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are at a higher risk for adverse outcomes and pregnancy-associated complications. Moreover, more and robust data are required to evaluate vertical transmission. COVID vaccines are the most effective tool against the pandemic, as they prevent infection, but also appear to be able to ease long COVID symptoms. Vaccines have been proven safe and effective in both pregnant and breastfeeding women. This article aims to present current data on long COVID in pregnant and breastfeeding women and elucidate risk factors and possible treatment options.

Comparison of High-Sensitivity C-Reactive Protein vs C-reactive Protein for Cardiovascular Risk Prediction in Chronic Cardiac Disease.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) is a biomarker used for risk prediction for cardiovascular disease by assessing low concentration of inflammation. Measurements of regular CRP have become very sensitive with a lower detection limit of 0.3 mg/L. This study aimed to compare and explore the association between CRP and hs-CRP. METHODS: Data from 607 consecutive patients referred for cardiovascular risk assessment with hs-CRP were reviewed retrospectively. In total, 570 patients were included in the analysis and classified into 3 (low-, medium-, and high-risk) groups (hs-CRP cutoff: <1, 1-3, >3 mg/L). Correlation between hs-CRP and CRP was assessed with the kappa statistic and visualized with a Bland-Altman plot. The association between hs-CRP and occurrence of the composite outcome (acute myocardial infarction, stroke, coronary intervention [percutaneous coronary intervention or bypass surgery], or death) was determined with Cox regression analysis and visualized with Kaplan-Meier curves. RESULTS: A total number reclassification occurred in 8.6% of the cases for CRP risk groups, which demonstrates an agreement of 91.4% (kappa 0.87; P < 0.001). The correlation between CRP and hs-CRP was significant (P < 0.001), Spearman regression R2 = 0.98. A Bland-Altman plot displayed an average difference of 0.19 mg/L (95%CI, 0.17 to 0.23) between the CRP and hs-CRP. Cardiovascular events were more likely to occur in patients who were older, with hs-CRP or CRP >3 mg/L and a history of coronary artery disease. CONCLUSIONS: The usual laboratory tests for CRP values in the lower range highly correlate with the hs-CRP tests and can therefore replace the costlier hs-CRP measurements.

Sacubitril/valsartan is well tolerated in patients with longstanding heart failure and history of cancer and improves ventricular function: real-world data.

BACKGROUND: Sacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalizations due to heart failure in patients with reduced ejection fraction (HFrEF) when compared to enalapril. Data about sacubitril/valsartan in patients with a history of cancer are scarce, as these patients were excluded from the pivotal trial, PARADIGM-HF. The aim of the current study was to assess tolerability of sacubitril/valsartan in patients with a history of cancer. METHODS: We identified 225 patients at our heart failure out-patient unit who fulfilled the indication criteria to receive sacubitril/valsartan. Out of these, 9.3% (n = 21) had a history of histologically confirmed cancer. Oncologic surgery was performed in 16 (76.2%) patients, 11 (52.4%) patients received previous antineoplastic therapy and 9 patients (42.9%) radiation. RESULTS: Sacubitril/valsartan was withdrawn in 3 of 21 patients (14.3%) because of dizziness (n = 2) or pruritus (n = 1). After a median follow-up of 12 months (range 1-34 months), NYHA functional class improved significantly from NYHA 3 to NYHA 2 (mean -0.6, p = 0.006) and left ventricular ejection fraction as assessed by echocardiography increased significantly from 26.8 ± 5.4% to 39.2 ± 10% (mean + 12%, CI 95% [8.4-16.4], p = 0.0004). NT-proBNP was significantly reduced (baseline median 2774 pg/ml, range 1441 - 12,982 vs follow-up 1266 pg/ml, range 199-6324, p = 0.009). There was no significant change in creatinine levels (1.18 ± 0.4 vs 1.22 ± 0.4 mg/dl; mean + 0.005 mg/dl, CI 95% [-0.21- 0.12], p = 0.566). CONCLUSIONS: In our pilot study we show that sacubitril/valsartan is generally well tolerated in patients with HFrEF and history of cancer. Importantly, even patients with long-standing cardiotoxicity induced heart failure can be treated and up-titrated with sacubitril/valsartan to usual target dosages, leading to improvement in LV function and biomarkers. Larger studies are needed to confirm these findings in cancer patients with cardiotoxicity.