Doxorubicin-induced acute cardiotoxicity is associated with increased oxidative stress, autophagy, and inflammation in a murine model.

Drug-induced cardiotoxicity is a life-threatening side effect of doxorubicin (DOX) treatment that impacts patient prognosis and survival. In the majority of cases, the acute clinical form often remains asymptomatic, with few patients presenting rather nonspecific electrocardiographic abnormalities. While chronic toxicity has been more widely studied, the alterations appearing in acute cardiotoxicity are much less investigated. Thus, our in vivo study aimed to evaluate the process of DOX-induced acute myocardial toxicity by investigating oxidative stress and autophagy markers as mechanisms of myocardial toxicity in correlation with echocardiography and electrocardiography findings. Our results show that both autophagy and oxidative homeostasis were disrupted as soon as 7 days after DOX treatment, alterations that occurred even before the significant increase of NT-proBNP, a clinical marker for cardiac suffering. Moreover, we found a large number of alterations in the electrocardiography and echocardiography of treated rats. These findings suggest that DOX-induced myocardial toxicity started early after treatment initiation, possibly marking the initial phase of the unfolding process of cardiac damage. Further studies are required to completely decipher the mechanisms of DOX-induced cardiotoxicity.

The Effectiveness of Antiplatelet Therapy and the Factors Influencing It in Patients with Acute Coronary Syndrome before and during the COVID-19 Pandemic.

Background and Objectives: Dual antiplatelet therapy (DAPT) is essential in the treatment of patients with acute coronary syndrome (ACS). The objective of this study was to evaluate the effectiveness of antiplatelet medication in our practice and to investigate the factors that influence it. Materials and Methods: A prospective cohort observational study was conducted, in which 193 patients with ACS were enrolled. The patients were stented in the catheterization laboratory between May 2019 and October 2020, before and during the COVID-19 pandemic, and were receiving DAPT. Their platelet functions were tested using a Multiplate Analyzer. In addition to this, clinical data, demographics, laboratory tests, and cardiovascular risk factors were also analyzed. Results: 43.46% of the patients treated with aspirin were found to be resistant to it. This phenomenon was more common in men (48.17% vs. 31.48%, p = 0.036), and it was associated with being under the age of 50 (OR: 2.08; 95% CI: 1.11-3.90) and weighing over 70 kg (OR: 3.00; 95% CI: 1.21-7.40). Most of the patients treated with clopidogrel were in the optimal treatment window, while about half of the patients treated with ticagrelor had an exaggerated pharmacological response. Among the laboratory parameters, leukocytosis and platelet count were found to be determinants of platelet reactivity for both the aspirin and ticagrelor treatments. Conclusions: Many patients treated with antiplatelet agents are outside of the treatment window. The results obtained showed that low doses of gastro-resistant aspirin tablets are ineffective, and their efficacy can be influenced by various clinical and laboratory factors. Patients receiving ticagrelor have significantly reduced platelet reactivity, influenced only by certain laboratory indicators. The pandemic significantly influenced the results of the platelet aggregation tests only in patients treated with clopidogrel.

Electrocardiographic Patterns in Patients with Neurally Mediated Syncope.

The baseline electrocardiogram (ECG) is less informative in neurally mediated syncope (NMS) than in arrhythmic syncope. However, some of the ECG patterns present in NMS can have diagnostic and prognostic value in such patients. Electrocardiographic documentation of a syncopal spell and thus identification of the ECG changes can be performed during tilt table test (TTT) or during prolonged ECG monitoring. This work reviews the specific ECG patterns in NMS, which are primarily related to the cardioinhibitory reflex. In addition, there are other ECG findings present in patients with NMS that are being analyzed, such as increased heart rate variability as well as specific QRS voltage patterns. In addition to the diagnostic and prognostic value, these ECG patterns in NMS may help improving the selection of patients for pacemaker implant.

Cardiac Amyloidosis with Discordant QRS Voltage between Frontal and Precordial Leads.

Among the different types, immunoglobulin light chain (AL) cardiac amyloidosis is associated with the highest morbidity and mortality. The outcome, however, is significantly better when an early diagnosis is made and treatment initiated promptly. We present a case of cardiac amyloidosis with left ventricular hypertrophy criteria on the electrocardiogram. After 9 months of follow-up, the patient developed low voltage in the limb leads, while still maintaining the Cornell criteria for left ventricular hypertrophy as well. The relative apical sparing by the disease process, as well as decreased cancellation of the opposing left ventricular walls could be responsible for this phenomenon. The discordance between the voltage in the frontal leads and precordial leads, when present in conjunction with other findings, may be helpful in raising the clinical suspicion of cardiac amyloidosis.

Usefulness of the Electrocardiogram in a Patient Presenting with Right-Sided Pneumothorax and Presyncope.

We present the case of a 71-year-old man with history of smoking, pulmonary emphysema, hypertension, multivessel coronary artery disease and prior coronary artery bypass graft surgery who presented with spontaneous right-sided pneumothorax associated with phasic changes of the QRS amplitude on the electrocardiogram. While several case reports have described QRS amplitude changes associated with left-sided pneumothorax, reports of phasic ECG changes in right-sided pneumothorax are exceedingly rare. Such changes, when present in a patient with sudden onset chest pain and dyspnea, should prompt a diagnostic workup for possible pneumothorax.

Isolated very low QRS voltage predicts response to tilt-table testing in patients with neurally mediated syncope.

BACKGROUND: A number of patients with neurally mediated syncope (NMS) have isolated QRS complexes of very low voltage (≤0.3 mV) in the frontal plane leads on the 12-lead electrocardiogram (ECG). HYPOTHESIS: The aim of this study was to assess the importance of QRS voltage in predicting response to tilt-table testing (TTT) in patients with suspected NMS. METHODS: We included 216 patients (age: 49 ± 20 years, 103 men) with suspected NMS who had either a positive or negative response to TTT (n = 91 TTT+, and n = 125 TTT-). The QRS voltage was measured in mV on 12-lead ECGs performed within 3 days of the TTT. The lowest QRS voltage (QRSmin), as well as the voltage in each of the 12 leads was also determined. RESULTS: Very low voltage (QRSmin  ≤ 0.3 mV) in the frontal leads was significantly more prevalent in the TTT+ group than in the TTT- group (74 vs 22%, respectively; P  < .001). Patients in the TTT+ group had significantly lower QRSmin when compared to patients in the TTT- group. QRSmin predicted a positive tilt-table test in a multivariate model that also included patient gender, height, history of presyncope, QRS duration, and left ventricular end-diastolic diameter indexed to height. ROC analysis showed that QRSmin of ≥0.3 mV discriminated between TTT+ and TTT- patients with a sensitivity of 78% and specificity of 68%. CONCLUSION: Isolated very low QRS voltage in the frontal leads predicts a positive response to TTT in patients with suspected NMS.

Isolated very low QRS voltage in the frontal leads predicts recurrence of neurally mediated syncope.

BACKGROUND: The study was prompted by our observation that some patients with neurally mediated syncope (NMS) have an isolated QRS complex, of very low voltage (≤0.3 mV cutoff), in 1 of the frontal leads on the 12-lead electrocardiogram. OBJECTIVE: To prospectively evaluate whether the presence of isolated very low voltage (VLV) predicts recurrence of NMS. METHODS: We included 205 patients (aged 50 ± 17 years) with a median of 3 syncopal episodes. Tilt testing was performed in all patients and was positive in 87 (42%). The patients were followed for a median of 14 months. RESULTS: VLV in frontal leads was present in 92 patients (45%). During the follow-up period 60 patients experienced recurrence of syncope. The actuarial total syncope recurrence rate at 1 year was 32% (95% confidence interval [CI 23%-44%) in patients with isolated VLV in frontal plane leads, and 14% (95% CI 8%-24%) in patients without VLV (log-rank test P < .0001). The significant relationship between the presence of isolated VLV in the frontal leads and syncope recurrence was retained in Cox multivariate analysis that included the history of presyncope and syncope as well as the left ventricular end-diastolic diameter. The presence of isolated VLV in frontal leads was associated with a 3-fold increase of the risk of recurrent syncope. CONCLUSIONS: Isolated very low QRS voltage in the frontal leads predicts recurrence of NMS independent of clinical factors that predict recurrence of syncope in such patients. This phenomenon may help generate new diagnostic tools and insights into the pathogenesis of NMS.

Severity of esophageal injury predicts time to healing after radiofrequency catheter ablation for atrial fibrillation.

BACKGROUND: The delivery of radiofrequency (RF) energy to the posterior left atrium creates a risk of injury to the adjacent esophagus. Esophageal endoscopy (EGD) is used to screen patients at risk for esophageal thermal injury after RF ablation. OBJECTIVE: The purpose of this study was to analyze the macroscopic features of the severity of esophageal injuries induced by RF ablation to the left atrium as seen by EGD and evaluate the association of these descriptions with the time elapsed until complete healing. METHODS: This study analyzed 219 patients undergoing RF ablation for atrial fibrillation. Esophageal temperature probes were used during each ablation, and EGD was performed in cases with intraesophageal temperature ≥39°C. Repeat EGD was obtained at 10 days to evaluate for healing in all cases demonstrating esophageal injury. Serial endoscopies were repeated every 2 weeks until complete healing was documented. Lesions were classified according to severity as superficial or deep ulceration; size and shape were also noted. RESULTS: We found 37.4% of patients (82 of 219) with esophageal intraluminal temperatures ≥39°C. Of these, 22 patients (27%) were identified with esophageal injury, with 68% being superficial ulcerations and 32% deep. On repeat EGD at 10 days, only 29% of deep ulcerations were healed, as compared with 87% of the superficial injuries (P = .0136). No difference in healing was found when analyzed for size or shape. CONCLUSIONS: The macroscopic severity of esophageal lesions detected on endoscopy the day after RF ablation can predict the time to resolution, with severe, deep ulcerations requiring a longer time to heal.

Impact of tricuspid regurgitation and prior coronary bypass surgery on the geometry of the coronary sinus: a rotational coronary angiography study.

INTRODUCTION: The coronary sinus (CS) is often distorted in patients with advanced cardiomyopathy, making CS cannulation difficult. The objective of this study was to examine the impact of the underlying cardiac pathology on the variability of the CS anatomy, using rotational coronary venous angiography (RCVA). METHODS AND RESULTS: Seventy-nine patients undergoing RCVA for cardiac resynchronization therapy (CRT) were evaluated: age 63 +/- 15 years, 43% with prior coronary artery bypass grafting (CABG). Aspects of the CS anatomy which could impact cannulation were examined: the CS ostial angle, the posterior displacement of the CS away from the atrioventricular groove, a measure of CS curvature, and the presence of stenoses and aneurysmal dilatations. The CS ostial angle was variable (65-151 degrees, mean 119 +/- 19 degrees, <90 degrees in 8 patients) and decreased significantly (P = 0.0022) with increasing severity of tricuspid regurgitation (TR), reaching 94 +/- 18 degrees in patients with severe TR. The posterior displacement of the CS was significantly more accentuated in patients with prior CABG when compared with the patients without CABG (7.1 +/- 3.7 vs 4.5 +/- 2.8 mm; P = 0.0246). The decrease in luminal diameter at the CS-great cardiac vein (GCV) junction was 2.0 +/- 1.0 mm, being more pronounced in patients with prior CABG versus nonCABG (26 vs 20%; P = 0.042). Stenoses and aneurysmal dilatations of the CS-GCV were encountered in 4 (5%) and 6 (8%) of patients, respectively, all of them with prior CABG, representing 12% and 18% of the CABG group. CONCLUSION: The CS anatomy in patients undergoing CRT is variable, and is impacted by the severity of the underlying TR and history of a prior CABG.

Risk factors for symptomatic gallstones in patients with liver cirrhosis: a case-control study.

OBJECTIVES: Liver cirrhosis is a well-documented risk factor for the formation of gallstones. In cirrhotic patients, gallstones are almost always "silent," and surgery is rarely required. When indicated (symptoms or complications), cholecystectomy implies a high morbidity risk in these patients, especially in the advanced stages of cirrhosis. The aim of this study was to estimate the risk factors for symptom development in cirrhotic patients with gallstones to identify the subgroup of patients at risk of undergoing surgery. METHODS: A total of 140 patients with liver cirrhosis and gallstones were studied: 97 with asymptomatic and 43 with symptomatic gallstone disease. The risk factors for gallstone formation (age, gender, family history, parity, obesity, diabetes mellitus, hyperlipoproteinemia) and the characteristics of liver cirrhosis (etiology, duration, Child class, hypersplenism), gallstones (duration, number, size), and gallbladder (size, wall thickness) were assessed in all patients. In 12 patients (four symptomatic, eight asymptomatic), gallbladder emptying was also evaluated by ultrasound. The association of asymptomatic and symptomatic gallstones with all these parameters was statistically evaluated by Student's t, Mann-Whitney, and chi(2) tests, as well as by means of multiple logistic regression. The causal relationship between these characteristics and gallstone symptoms was also examined by means of the KDD (knowledge discovery from databases) method, with an algorithm for learning Bayesian networks. RESULTS: Advanced age, female gender, viral etiology of cirrhosis, family history of gallstones, and duration of gallstone disease were significantly associated with symptomatic gallstone disease. The number or size of gallstones and the size or emptying of the gallbladder did not differ in symptomatic versus asymptomatic patients. Male gender and alcoholic cirrhosis were inversely correlated with symptom presence. In the multivariate analysis, family history (p = 0.0098) and advanced age (p = 0.0422) were positively correlated and male gender (p = 0.0049) and alcoholic etiology of cirrhosis (p = 0.0116) negatively correlated with symptom presence. These relationships (except for age) were also evidenced by the KDD method. CONCLUSIONS: The risk of gallstones becoming symptomatic is significantly lower in men and in alcoholic cirrhosis. In cirrhotic women, and especially in the presence of a positive family history and of advanced age, the risk of developing symptoms and undergoing surgery was significantly greater.