Pre-existing Cardiac Disease Research Articles

Not Just CTEPH: A Narrative Review on the Spectrum Approach to Postpulmonary Embolism Conditions.

Three mutually exclusive entities can underlie a postpulmonary embolism syndrome (PPES): not obstructed postpulmonary embolism syndrome (post-PE dyspnea), chronic thromboembolic pulmonary disease (CTEPD), and chronic thromboembolic pulmonary hypertension (CTEPH). Cardiorespiratory impairment in CTEPH and CTEPD underlies respiratory and hemodynamic mechanisms, either at rest or at exercise. Gas exchange is affected by the space effect, the increased blood velocity, and, possibly, intracardiac right to left shunts. As for hemodynamic effects, after a period of compensation, the right ventricle dilates and fails, which results in retrograde and anterograde right heart failure. Little is known on the pathophysiology of post-PE dyspnea, which has been reported in highly comorbid with lung and heart diseases, so that a "two-hit" hypothesis can be put forward: it might be caused by the acute myocardial damage caused by pulmonary embolism in the context of preexisting cardiac and/or respiratory diseases. More than one-third of PE survivors develops PPES, with only a small fraction (3-4%) represented by CTEPH. A value of ≈3% is a plausible estimate for the incidence of CTEPD. Growing evidence supports the role of CTEPD as a hemodynamic phenotype intermediate between post-PE dyspnea and CTEPH, but it still remains to be ascertained whether it constantly underlies exercise-induced pulmonary hypertension and if it is a precursor of CTEPH. Further research is needed to improve the understanding and the management of CTEPD and post-PE dyspnea.

Investigation of 5-fluorouracil cardiotoxicity in combinational therapy: Influence of risk factors and demographics in a Pakistani population.

5-Fluorouracil (5-FU) is a chemotherapeutic agent used to treat various types of cancers. Although widely used, it has consistently been attributed to cardiotoxicities after administration. The purpose of this study was to assess the parameters and predictors of cardiotoxicities associated with various 5-FU-based chemotherapeutic protocols in patients with GI/colorectal cancer, as well as the correlation of these cardiotoxic events with age, sex, cumulative dose, and risk factors such as obesity, hypertension, and family history of cardiac diseases. A prospective study consisting of 396 patients of both sexes was conducted in the oncology ward of Nishtar Hospital in Multan, Pakistan. Patients were grouped according to the therapeutic protocol they received (5-FU monotherapy or in combination, with different dosing regimens). Electrocardiography and serum troponin levels were used to assess 5-FU-induced cardiotoxicity. In cases where cardiotoxicity was detected, 5-FU treatment was interrupted; nitroglycerin, nitrates, and calcium channel blockers were administered; and cardiac monitoring was initiated. 5-FU was discontinued in all cases of acute myocardial infarction. Of the 396 patients, 28.5% reported different cardiotoxic symptoms after receiving various 5-FU-containing protocols. 35% had anginal pain, 13% suffered a myocardial infarction, 11% developed hypertension, and 10% presented heart failure. Patients receiving 5-FU combination therapy showed cardiotoxic events that were significantly different from those on 5-FU monotherapy. Based on the ECG results, only the QTc-d interval increased significantly (p < 0.001) after therapy. 68% of the patients had troponin levels > 2 ng/mL at the end of treatment. Pre-existing cardiac diseases, treatment duration, smoking, and obesity were found to be influential components in the development of cardiotoxicity, and patients with cancer should be closely monitored during 5-FU chemotherapy.

Predictive value of changes in basal myocardial 18F-fluorodeoxyglucose uptake for cardiotoxicity in locally advanced esophageal cancer patients receiving definitive radiotherapy

To investigate the predictive value of changes in segmental myocardial 18F-fluorodeoxyglucose (FDG) uptake for major adverse cardiac events (MACEs) in patients with locally advanced esophageal cancer undergoing definitive radiation therapy (RT). Between August 2012 and January 2019, 482 patients with stages II and III esophageal cancer from 2 institutions were enrolled and divided into the training (n = 285) and external validation (n = 197) cohorts. All patients underwent 18F-FDG positron emission tomography within 1 week before treatment and within 3 months of treatment. Myocardial delineation was performed using the Carimas software based on the American Heart Association 17-segment model and was automatically divided into basal, middle, and apical regions. The main endpoint was the occurrence of MACEs, including unstable angina, myocardial infarction, coronary revascularization, hospitalization for heart failure or urgent visits, and cardiac death. Analyses included competing risk and Cox regression. Model performance was assessed using the area under the receiver operating characteristic curve and Brier score. Thirty-four patients (11.9%) developed MACEs at a median follow-up of 78 months. The basal region (median, 19.44 Gy) of the myocardium received the highest radiation dose, followed by the middle (median, 13.02 Gy) and apical regions (median, 9.32 Gy). Multivariate analysis showed that the change ratio in pretreatment and posttreatment basal myocardial mean standardized uptake value (SUV) remained significant after adjusting for age, pre-existing cardiac disease, and dosimetric parameters. The area under the receiver operating characteristic curves and Brier scores demonstrated favorable predictive accuracies of models integrating variables with significant differences in the multivariate analysis when predicting MACEs in the training and validation cohorts. The basal change ratio of mean SUV was an independent predictor of MACEs in patients with locally advanced esophageal cancer receiving definitive RT. Changes in basal myocardial FDG uptake are promising biomarkers for predicting radiation-induced cardiotoxicity.

Unexpected Infective Endocarditis: Towards a New Alert for Clinicians.

Despite the clear indications and worldwide application of specific guidelines, the recognition of Infective Endocarditis (IE) may be challenging in day-to-day clinical practice. Significant changes in the epidemiological and clinical profile of IE have been observed, including variations in the populations at risk and an increased incidence in subjects without at-risk cardiac disease. Emergent at-risk populations for IE particularly include immunocompromised patients with a comorbidity burden (e.g., cancer, diabetes, dialysis), requiring long-term central venous catheters or recurrent healthcare interventions. In addition, healthy subjects, such as skin-contact athletes or those with piercing implants, may be exposed to the transmission of highly virulent bacteria (through the skin or mucous), determining endothelial lesions and subsequent IE, despite the absence of pre-existing at-risk cardiac disease. Emergent at-risk populations and clinical presentation changes may subvert the conventional paradigm of IE toward an unexpected clinical scenario. Owing to its unusual clinical context, IE might be overlooked, resulting in a challenging diagnosis and delayed treatment. This review, supported by a series of clinical cases, analyzed the subtle and deceptive phenotypes subtending the complex syndrome of unexpected IE. The awareness of an unexpected clinical course should alert clinicians to also consider IE diagnosis in patients with atypical features, enhancing vigilance for preventive measures in an emergent at-risk population untargeted by conventional workflows.

Urogeriatric thinking using the example of antiandrogen therapy for prostate cancer

The geriatric patient is defined by an age of over 75years and multimorbidity or by an age of over 80years. These patients exhibit aparticular vulnerability, which, in the incidence of side effects or complications, leads to aloss of autonomy. Treatment sequalae, once they have arisen, can no longer be compensated. It is important to recognize and document treatment requirements among geriatric patients with the help of screening instruments such as the Identification of Seniors at Risk (ISAR) and Geriatric8 (G8) scores. If a treatment requirement is identified, oncologic treatment should not be commenced uncritically but rather a focus placed on identification of functional deficits relevant to treatment, ideally using a geriatric assessment but at least based on adetailed medical history. These deficits can then be presented in astructured, examiner-independent, and forensically validated manner using special assessments. A planned treatment requires not only consideration of survival gains, but also knowledge of specific side effects and, in geriatric patients in particular, their impact on everyday life. These considerations should be compared with the patient's individual risk profile in order to prevent side effects from negating the effect of the treatment, for example by worsening the patient's self-help status. With regard to androgen deprivation in prostate cancer-which often is used uncritically-it is important to consider possible side effects such as osteoporosis, sarcopenia, anemia, and cognitive impairment in terms of apossible fall risk; an increase in cardiovascular mortality and the triggering of ametabolic syndrome on the basis of preexisting cardiac diseases or risk constellations; and to carry out acareful risk-benefit analysis.

COVID-19 in patients with pre-existing cardiovascular disease: a series of cases during the fourth epidemiologic wave in Mexico City

SARS-CoV-2 infection induces an immune response that causes excessive inflammation damaging cardiac tissue and vascular endothelium. The objective of this study is to review a series of cases of hospitalized patients with pre-existing cardiac disease to describe the clinical behavior and highlight the low frequency of morbidity and mortality. Retrospective study of 17 patients with a confirmed diagnosis of COVID-19 by polymerase chain reaction test or antigen test, a history of cardiovascular disease with or without comorbidities, and a history of at least one dose of the vaccine for COVID-19, during the period between December 30, 2021 and March 17, 2022 at the Ignacio Chávez National Institute of Cardiology in Mexico City. The most frequent cardiac pathology was acute myocardial infarction (31.25%) and the most common arrhythmia was atrial fibrillation (25%). The median number of days of hospital stay was 10 days (interquartile range: 4-14). Regarding the outcomes, 94% of the patients were discharged due to clinical improvement, and only one patient died during his hospitalization. It is crucial to continue investigating SARS-CoV-2 effects in patients pre-existing heart disease and in those with persistent symptoms after infection. This will allow the development of more effective strategies for the treatment and prevention of cardiovascular complications associated with COVID-19.

SARS-CoV-2 pathogenesis in an angiotensin II–induced heart-on-a-chip disease model and extracellular vesicle screening

Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II-treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs.

Baseline Cardiac Parameters as Biomarkers of Radiation Cardiotoxicity in Lung Cancer: An NI-HEART Analysis

BackgroundRadiation-induced cardiotoxicity poses a significant challenge in lung cancer management because of the close anatomical proximity of the heart to the lungs, compounded by a high prevalence of cardiovascular risk factors among patients. ObjectivesThe aim of this study was to assess the predictive value of routinely available clinical and imaging-based cardiac parameters in identifying “high risk” patients for major adverse cardiac events (MACE) and mortality following radiation therapy (RT). MethodsThe medical records of patients who underwent definitive RT for non–small cell lung cancer using modern planning techniques at a single center between 2015 and 2020 were retrospectively reviewed. Cardiac events were verified by cardiologists, and mortality data were confirmed with the national registry. Cardiac substructures were autosegmented on RT planning scans for retrospective structure and dose analysis, and their correlation with clinical factors was examined. Fine-Gray models were used to analyze relationships while considering the competing risk for death. ResultsAmong 478 patients included in the study, 77 (16%) developed 88 MACE, with a median time to event of 16.3 months. A higher burden of pre-existing cardiac diseases was associated with an increased cumulative incidence of MACE (55% [95% CI: 12%-20%] vs 16% [95% CI: 35%-71%]; P < 0.001). Left atrial and left ventricular enlargement on RT planning scans was associated with cumulative incidence of atrial arrhythmia (14% [95% CI: 9%-20%] vs 4% [95% CI: 2%-8%]; P = 0.001) and heart failure (13% [95% CI: 8%-18%] vs 6% [95% CI: 3%-10%]; P = 0.007) at 5 years, respectively. However, myocardial infarction was not associated with the presence of coronary calcium (4.2% [95% CI: 2%-7%] vs 0% [95% CI: 0%-0%]; P = 0.094). No cardiac imaging metrics were found to be both clinically and statistically associated with survival. ConclusionsThe present findings suggest that cardiac history and RT planning scan parameters may offer potential utility in prospectively evaluating cardiotoxicity risk following RT for patients with lung cancer.

Cardiotoxicity from bruton tyrosine kinase inhibitors (BTKi)—an analysis of an administrative health claims database

BackgroundFirst generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials.ObjectiveGiven paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients.MethodsWe performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum’s de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death from the time of index presciption were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding.ResultsA total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19–90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32–90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs. 150 (30–870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.013), hypertension (6.3%-vs-25%, p = NS), sudden cardiac arrest/death (0% vs. 1.5%, p = NS) in the acalabrutinib group compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib.ConclusionsThere was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients.

Respiratory Support Practices for Bronchiolitis in the Pediatric Intensive Care Unit

Admissions to the pediatric intensive care unit (PICU) due to bronchiolitis are increasing. Whether this increase is associated with changes in noninvasive respiratory support practices is unknown. To assess whether the number of PICU admissions for bronchiolitis between 2013 and 2022 was associated with changes in the use of high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) and to identify factors associated with HFNC and NIV success and failure. This cross-sectional study examined encounter data from the Virtual Pediatric Systems database on annual PICU admissions for bronchiolitis and ventilation practices among patients aged younger than 2 years admitted to 27 PICUs between January 1, 2013, and December 31, 2022. Use of HFNC and NIV was defined as successful if patients were weaned to less invasive support (room air or low-flow nasal cannula for HFNC; room air, low-flow nasal cannula, or HFNC for NIV). The main outcome was the number of PICU admissions for bronchiolitis requiring the use of HFNC, NIV, or IMV. Linear regression was used to analyze the association between admission year and absolute numbers of encounters stratified by the maximum level of respiratory support required. Multivariable logistic regression was used to analyze factors associated with HFNC and NIV success and failure (defined as not meeting the criteria for success). Included in the analysis were 33 816 encounters for patients with bronchiolitis (20 186 males [59.7%]; 1910 patients [5.6%] aged ≤28 days and 31 906 patients [94.4%] aged 29 days to <2 years) treated at 27 PICUs from 2013 to 2022. A total of 7615 of 15 518 patients (49.1%) had respiratory syncytial virus infection and 1522 of 33 816 (4.5%) had preexisting cardiac disease. Admissions to the PICU increased by 350 (95% CI, 170-531) encounters annually. When data were grouped by the maximum level of respiratory support required, HFNC use increased by 242 (95% CI, 139-345) encounters per year and NIV use increased by 126 (95% CI, 64-189) encounters per year. The use of IMV did not significantly change (10 [95% CI, -11 to 31] encounters per year). In all, 22 381 patients (81.8%) were successfully weaned from HFNC to low-flow oxygen therapy or room air, 431 (1.6%) were restarted on HFNC, 3057 (11.2%) were escalated to NIV, and 1476 (5.4%) were escalated to IMV or extracorporeal membrane oxygenation (ECMO). Successful use of HFNC increased from 820 of 1027 encounters (79.8%) in 2013 to 3693 of 4399 encounters (84.0%) in 2022 (P = .002). In all, 8476 patients (81.5%) were successfully weaned from NIV, 787 (7.6%) were restarted on NIV, and 1135 (10.9%) were escalated to IMV or ECMO. Success with NIV increased from 224 of 306 encounters (73.2%) in 2013 to 1335 of 1589 encounters (84.0%) in 2022 (P < .001). In multivariable logistic regression, lower weight, higher Pediatric Risk of Mortality III score, cardiac disease, and PICU admission from outside the emergency department were associated with greater odds of HFNC and NIV failure. Findings of this cross-sectional study of patients aged younger than 2 years admitted for bronchiolitis suggest there was a 3-fold increase in PICU admissions between 2013 and 2022 associated with a 4.8-fold increase in HFNC use and a 5.8-fold increase in NIV use. Further research is needed to standardize approaches to HFNC and NIV support in bronchiolitis to reduce resource strain.

Impact of Arterial Hypotension During Spinal Anesthesia for Cesarean Delivery on the Newborn at Kouba Hospital

Introduction: Spinal anesthesia is commonly used for cesarean deliveries but can lead to maternal hypotension, a frequent complication that may adversely affect the fetus. The objective of this study was to determine the incidence of post-spinal hypotension for cesarean delivery and identify associated risk factors. Methods: This was a prospective descriptive study conducted at Kouba Hospital over one month. Inclusion criteria were patients admitted for scheduled or emergency cesarean under spinal anesthesia after informed consent, without absolute contraindication to spinal anesthesia, baseline blood pressure ≥100 mmHg, and heart rate ≤100 bpm. Patients were excluded if hypotensive, vagotonic, had pre-existing cardiac disease, or received general anesthesia. All patients received 8 mg 0.5% bupivacaine, 2.5 μg sufentanil, and 100 μg intrathecal morphine with standard monitoring and 250 ml fluid preloading. Hypotension was defined as ≥20% decrease from baseline blood pressure. Data collected included demographics, obstetric history, and anesthetic/surgical details. Analysis was done using EPI Info software. Results: 42 parturients were included, mostly ASA II, with mean BMI 26.5±4.1 kg/m2 and gestational age 37.4±2.1 weeks. 50% had a history of hypotension in previous cesareans, and 68% underwent emergency cesarean. Sensory block reached T4 level on average. Hypotension incidence was 80%, with 40% requiring additional fluids and mean 15±10 mg ephedrine. Despite hypotension, most neonates had satisfactory Apgar scores. High BMI, emergency cesarean, and previous hypotension history were significantly associated with increased hypotension risk. Discussion: The high 80% hypotension incidence aligns with literature reports of 70-90%, likely exacerbated by using isobaric/hypobaric rather than hyperbaric bupivacaine. Identified risk factors were consistent with published data. Prompt management likely prevented major neonatal consequences. Conclusion: Intraoperative hypotension is frequent after spinal anesthesia for cesarean delivery. Guidelines recommend a standardized approach with fluid loading, vasopressors, and lateral tilt positioning to prevent maternal and fetal complications. Larger studies are needed to further characterize risk factors.

Affected by Surgery, Healed by Medicine a Successful Story

ABSTRACT Infective endocarditis (IE) is relatively less common in children compared to adults but can result in significant morbidity and mortality. The epidemiology of IE has shifted in recent years, from rheumatic heart disease (less prevalence) to congenital heart disease (increased survival) and an increase in the use of central venous catheters in children with chronic illness. Children with no preexisting cardiac disease can be affected rarely. We present a case of a 13-year-old boy with no cardiac disease, presented with a fever. He had a history of surgery for hypospadias 3 weeks before presentation. He was diagnosed with IE according to modified Duke criteria. The blood cultures grew methicillin-resistant Staphylococci aureus. The case was surgically deferred in view of his clinical condition and was managed medically. We emphasize the importance of having a high index of suspicion for endocarditis in children with fever even without cardiac disease.

A Pragmatic Study of Cardiovascular Disease During Long-Term COVID-19

BackgroundMany patients diagnosed with COVID-19 have persistent cardiovascular symptoms, but whether this represents a true cardiac process is unclear. This study assessed whether symptoms associated with long COVID among patients referred for cardiovascular evaluation are associated with objective abnormalities on cardiac testing to explain their clinical presentation. MethodsA retrospective cohort study of 40,462 unique patients diagnosed with COVID-19 at our tertiary referral was conducted and identified 363 patients with persistent cardiovascular symptoms a minimum of 4 weeks after polymerase chain reaction confirmed COVID-19 infection. Patients had no cardiovascular symptoms prior to COVID-19 infection. Each patient was referred for cardiovascular evaluation at a tertiary referral center. The incidence and etiology of abnormalities on cardiovascular testing among patients with long COVID symptoms are reported here. The cohort was subsequently divided into 3 categories based on the dominant circulating severe acute respiratory syndrome coronavirus 2 variant at the time of initial infection for further analysis. ResultsAmong 40,462 unique patients diagnosed with COVID-19 at our tertiary referral center from April 2020 to March 2022, 363 (0.9%) patients with long COVID were evaluated by Cardiology for possible cardiac sequelae from COVID and formed the main study cohort. Of these, 229 (63%) were vaccinated and 47 (12.9%) had severe initial infection, receiving inpatient treatment for COVID prior to developing long COVID symptoms. Symptoms were associated with a cardiac cause in 85 (23.4%), of which 52 (14.3%) were attributed to COVID; 39 (10.7%) with new cardiac disease from COVID, and 13 (3.6%) to worsening of pre-existing cardiac disease after COVID infection. The median troponin change in 45 patients with troponin measurements within 4 weeks of acute infection was +4 ng/dL (9 to 13 ng/dL). Among the total cohort with long COVID, 83.7% were diagnosed during the pre-Delta phase, 13.2% during the Delta phase, and 3.1% during the Omicron phase of the pandemic. There were 6 cases of myocarditis, 11 rhythm disorders, 8 cases of pericarditis, 5 suspected cases of endothelial dysfunction, and 33 cases of autonomic dysfunction. ConclusionThis pragmatic retrospective cohort study suggests that patients with long COVID referred for cardiovascular evaluation infrequently have new, objective cardiovascular disease to explain their clinical presentation. A multidisciplinary, patient-centered approach is warranted for symptom management along with conservative use of diagnostic testing.

Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice.

Thyroid hormones (THs) are known to have various effects on the cardiovascular system. However, the impact of TH levels on preexisting cardiac diseases is still unclear. Pressure overload due to arterial hypertension or aortic stenosis and aging are major risk factors for the development of structural and functional abnormalities and subsequent heart failure. Here, we assessed the sensitivity to altered TH levels in aged mice with maladaptive cardiac hypertrophy and cardiac dysfunction induced by transverse aortic constriction (TAC). Mice at the age of 12 months underwent TAC and received T4 or anti-thyroid medication in drinking water over the course of 4 weeks after induction of left ventricular pressure overload. T4 excess or deprivation in older mice had no or only very little impact on cardiac function (fractional shortening), cardiac remodeling (cardiac wall thickness, heart weight, cardiomyocyte size, apoptosis, and interstitial fibrosis), and mortality. This is surprising because T4 excess or deprivation had significantly changed the outcome after TAC in young 8-week-old mice. Comparing the gene expression of deiodinases (Dio) 2 and 3 and TH receptor alpha (TRα) 1 and the dominant-negative acting isoform TRα2 between young and aged mice revealed that aged mice exhibited a higher expression of TRα2 and Dio3, while expression of Dio2 was reduced compared with young mice. These changes in Dio2 and 3 expressions might lead to reduced TH availability in the hearts of 12-month-old mice accompanied by reduced TRα action due to higher TRα2. In summary, our study shows that low and high TH availability have little impact on cardiac function and remodeling in older mice with preexisting pressure-induced cardiac damage. This observation seems to be the result of an altered expression of deiodinases and TRα isoforms, thus suggesting that even though cardiovascular risk is increasing with age, the response to TH stress may be dampened in certain conditions.

Machine-Learning Based Risk Assessment for Cancer Therapy-Related Cardiac Adverse Events Among Breast Cancer Patients.

The study aims to develop machine-learning models to predict cardiac adverse events in female breast cancer patients who receive adjuvant therapy. We selected breast cancer patients from a retrospective dataset of the Taipei Medical University Clinical Research Database and Taiwan Cancer Registry between January 2004 and December 2020. Patients were monitored at the date of prescribed chemo- and/or -target therapies until cardiac adverse events occurred during a year. Variables were used, including demographics, comorbidities, medications, and lab values. Logistics regression (LR) and artificial neural network (ANN) were used. The performance of the algorithms was measured by the area under the receiver operating characteristic curve (AUC). In total, 1321 patients (an equal 15039 visits) were included. The best performance of the artificial neural network (ANN) model was achieved with the AUC, precision, recall, and F1-score of 0.89, 0.14, 0.82, and 0.2, respectively. The most important features were a pre-existing cardiac disease, tumor size, estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), cancer stage, and age at index date. Further research is necessary to determine the feasibility of applying the algorithm in the clinical setting and explore whether this tool could improve care and outcomes.

Association between left ventricular systolic function parameters and myocardial injury, organ failure and mortality in patients with septic shock

BackgroundLeft ventricular ejection fraction (LVEF) is inconsistently associated with poor outcomes in patients with sepsis. Newer parameters such as LV longitudinal strain (LVLS), mitral annular plane systolic excursion (MAPSE) and LV longitudinal wall fractional shortening (LV-LWFS) may be more sensitive indicators of LV dysfunction, but are sparsely investigated. Our objective was to evaluate the association between five traditional and novel echocardiographic parameters of LV systolic function (LVEF, peak tissue Doppler velocity at the mitral valve (s´), LVLS, MAPSE and LV-LWFS) and outcomes in patients admitted to the Intensive Care Unit (ICU) with septic shock.MethodsA total of 152 patients admitted to the ICU with septic shock from two data repositories were included. Transthoracic echocardiograms were performed within 24 h of ICU admission. The primary outcome was myocardial injury, defined as high-sensitivity troponin T ≥ 45 ng/L on ICU admission. Secondary outcomes were organ support-free days (OSFD) and 30-day mortality. We also tested for the prognostic value of the systolic function parameters using multivariable analysis.ResultsLVLS, MAPSE and LV-LWFS, but not LVEF and s´, differed between patients with and without myocardial injury. After adjustment for age, pre-existing cardiac disease, Simplified Acute Physiology (SAPS3) score, Sequential Organ Failure Assessment (SOFA) score, plasma creatinine and presence of right ventricular dysfunction, only MAPSE and LV-LWFS were independently associated with myocardial injury. None of the systolic function parameters were associated with OSFD or 30-day mortality.ConclusionsMAPSE and LV-LWFS are independently associated with myocardial injury and outperform LVEF, s´ and LVLS. Whether these parameters are associated with clinical outcomes such as the need for organ support and short-term mortality is still unclear.Trial registration NCT01747187 and NCT04695119.

Correlation of head injury with ECG and echo changes.

Abnormal electrocardiogram (ECG) findings can be seen in traumatic brain injury (TBI) patients. ECG may be an inexpensive tool to identify patients at high risk for developing cardiac dysfunction after TBI. This study aimed to examine abnormal ECG findings after isolated TBI and their association with true cardiac dysfunction based on echocardiogram. This prospective observational study examined the data from adult patients with isolated and non-operated TBI between 2020 and 2021. Patients aged <18 years and >65 years with and presence of extracranial injuries including orthopedic, chest, cardiac, abdominal, and pelvis, pre-existing cardiac disease, patients who have undergone cardiothoracic surgery, with inotrope drugs, acute hemorrhage, and brain death were excluded from the study. We examined data from 100 patients with isolated TBI who underwent ECG and echocardiographic evaluation. ECG changes among 53% of mild cases showed a heart rate of 60-100/min, and 2% of cases showed more than 100/min. Prolonged pulse rate (PR) interval was observed in 8%, 11%, and 16% of mild, moderate, and severe cases, while no changes in PR interval were observed in 65% of cases. A prolonged QRS pattern was observed in 5%, 7%, and 15% of mild, moderate, and severe cases. A normal QRS complex was observed in 71% of cases. Prolonged QTc was observed in 3%, 10%, and 15% of cases in mild, moderate, and severe cases, respectively. Repolarization abnormalities, but not ischemic-like ECG changes, are associated with cardiac dysfunction after isolated TBI. 12-lead ECG may be an inexpensive screening tool to evaluate isolated TBI patients for cardiac dysfunction.

MRNA vaccines for COVID-19 are safe and clinically effective in patients with cardiac amyloidosis

IntroductionAmyloidosis is a rare disease in which malformed proteins are deposited in tissues occurring mostly commonly in older age. These deposits can lead to severe organ dysfunction e.g. in the myocardium with great impact on prognosis. The Covid-19 pandemic has caused excess mortality worldwide since 2020. Risk factors for a severe course include pre-existing cardiac diseases like heart failure and advanced age. Therefore, vaccination against Sars-CoV2 viruses is highly recommended for patients with cardiac amyloidosis. However, since there are no specific data on mRNA vaccines in patients with cardiac amyloidosis, some patients have concerns about cardiac adverse events following immunization (AEFI), such as myocarditis. PurposeThe purpose of the study is to assess the safety and efficacy of mRNA vaccines in patients with cardiac amyloidosis. MethodsPatients of the Amyloidosis Center Charité Berlin (ACCB) were assessed about the vaccination, its tolerability and clinical effectiveness. To date, we included 62 patients (54 men) with a median age of 82,5 years (range 37 to 92). 46 patients had wtATTR amyloidosis, ten patients had hATTR amyloidosis, and six patients had AL amyloidosis. The mean systolic left ventricular function was 51% (range 30 to 62) with a mean global strain of −11,5% (range −18,5 to −3,1). The mean NT-pro-BNP was 1145 ng/l (range 24 to 48297). Results59 patients were triple vaccinated and three patients so far are double vaccinated. Three of the patients were unvaccinated. 171 of the vaccine doses administered were mRNA vaccines and eight doses were a viral vector-vaccine. None of the patients reported severe side effects. Thirteen patients reported feeling of pressure and pain at the injection site after vaccination and four patients had fever of maximum two days, eight patients reported lower general condition of maximum five days. One patient reported malaise for 14 days after each vaccination, which resolved spontaneously. There was no clinical or laboratory evidence of suspected vaccine-induced myocarditis. Five patients reported of a COVID-19 breakthrough infection, all of which with a mild course of disease. None of the patients had symptoms of worsening heart failure in temporal relation to the vaccination.Most of the vaccinations (103) were performed at an official vaccination center, 59 were performed at a general practitioner. ConclusionIn patients with cardiac amyloidosis, mRNA vaccines for COVID-19 are safe with respect to severe cardiac adverse events and show effective protection against clinically relevant SARS-CoV2 infection.

INVASIVE HEMODYNAMIC MONITORING WITH PULMONARY ARTERY CATHETER IN SEPSIS-ASSOCIATED CARDIOGENIC SHOCK.

Background: Both sepsis-induced cardiomyopathy and worsening of preexisting cardiac disease can contribute to circulatory shock in septic patients. The early use of pulmonary artery catheter (PAC) could play a pivotal role in the management of sepsis-associated cardiogenic shock. In this study, we aimed to evaluate the impact of early invasive hemodynamic monitoring with PAC in patients with sepsis-associated cardiogenic shock. Method: We performed a retrospective study using the National Inpatient Sample data from January 2017 to December 2019. The early use of PAC was defined as the use of PAC within 2 days from the admission. We performed the multivariable logistic regression analysis to investigate the association between the early use of PAC and in-hospital mortality in patients with sepsis-associated cardiogenic shock and sepsis without cardiogenic shock, respectively. Results: There was no difference in in-hospital mortality between PAC and no PAC groups in sepsis without cardiogenic shock (adjusted odds ratio [aOR] = 1.05, 95% confidence interval [CI] = 0.82-1.35, P = 691). On the other hand, the early use of PAC was independently associated with lower in-hospital mortality in patients with sepsis-associated cardiogenic shock (aOR = 0.58, 95% confidence interval [CI] = 0.46-0.72, P < 0.001). The use of PAC was also associated with increased use of mechanical circulatory support in those with sepsis-associated cardiogenic shock (aOR = 12.26, 95% CI = 9.37-16.03, P < 0.001). For patients with sepsis-associated cardiogenic shock, the use of PAC after 2 days of admission was associated with significantly higher in-hospital mortality and decreased use of mechanical circulatory support. Conclusion: The use of pulmonary artery catheters in sepsis-associated cardiogenic shock was associated with significantly lower in-hospital mortality and increased use of mechanical circulatory supports in patients with sepsis-associated cardiogenic shock.

The Role of Serum Monocytes and Tissue Macrophages in Driving Left Ventricular Systolic Dysfunction and Cardiac Inflammation Following Subarachnoid Hemorrhage.

Neurocardiogenic injury is common after aneurysmal subarachnoid hemorrhage (aSAH) despite low prevalence of preexisting cardiac disease. Potential mechanisms include autonomic dysregulation due to excess catecholamines as well as systemic inflammation. Understanding how inflammation contributes to cardiac dysfunction may aid in identifying novel therapeutic strategies. Here, we investigated serum leukocytes as predictors of left ventricular systolic dysfunction in patients with aSAH. We also investigated increased cardiac macrophages in an animal model of SAH and whether immunomodulatory treatment could attenuate this inflammatory response. We retrospectively analyzed 256 patients with aSAH admitted to University of Illinois Hospital between 2013 and 2019. Our inclusion criteria included patients with aSAH receiving an echocardiogram within 72h of admission. Our primary outcome was echocardiographic evidence of systolic dysfunction. We performed multinomial regression and receiver operating curve analysis. We also used the endovascular perforation model of SAH in male Sprague-Dawley rats to assess for myocardial inflammation. Two days after surgery, hearts were collected and stained for the macrophage marker Iba-1. We compared the presence and morphology of macrophages in cardiac tissue isolated from SAH animals and sham controls treated with and without the immunomodulatory agent fingolimod. Of 256 patients with aSAH, 233 (91.0%) underwent echocardiography within 72h of admission. Of 233, 81 (34.7%) had systolic dysfunction. Patients had baseline differences in the presence of hypertension, alcohol use, and admission Glasgow Coma Scale and Hunt-Hess score. On multivariable analysis, total leukocytes (odds ratio 1.312, p < 0.001), neutrophils (odds ratio 1.242, p = 0.012), and monocytes (odds ratio 6.112, p = 0.008) were independent predictors of reduced systolic function, whereas only monocytes (odds ratio 28.014, p = 0.030) predicted hyperdynamic function. Within the rodent heart, there were increased macrophages after SAH relative to controls, and this was attenuated by fingolimod treatment (p < 0.0001). Increased serum leukocytes are associated with abnormal left ventricular systolic function following aSAH. The strongest independent predictor of both reduced and hyperdynamic systolic function was increased monocytes. Increased cardiac macrophages after experimental SAH can also be targeted by using immunomodulatory drugs.