Stroke and presence of patent foramen ovale in sickle cell disease.

Sickle cell disease (SCD) is an inherited monogenic hemoglobinopathy characterized by formation of sickle erythrocytes under conditions of deoxygenation. Sickle erythrocytes can lead to thrombus formation and vaso-occlusive episodes that may result in hemolytic anemia, pain crisis and multiple organ damage. Moreover, SCD is characterized by endothelial damage, increased inflammatory response, platelet activation and aggravation, and activation of both the intrinsic and the extrinsic coagulation pathways. Cerebrovascular events constitute an important clinical complication of SCD. Children with SCD have a 300-fold higher risk of acute stroke and by the age of 45 about 25% of patients have suffered an overt stoke. Management and prevention of stroke in patients with SCD is not well defined. Moreover, the presence of patent foramen ovale (PFO) increases the risk of the occurrence of an embolic cerebrovascular event. The role of PFO closure and antiplatelet or anticoagulation therapy has not been well investigated. Moreover, during COVID-19 pandemic and taking into account the increased rates of thrombotic events and the difficulties in blood transfusion, management of SCD patients is even more challenging and difficult, since data are scarce regarding stroke occurrence and management in this specific population in the COVID-19 era. This review focuses on pathophysiology of stroke in patients with SCD and possible treatment strategies in the presence of PFO.

Verapamil-sensitive idiopathic left ventricular tachycardia and concomitant atrioventricular nodal reentrant tachycardia.

We describe the case of a young patient with runs of repetitive monomorphic left ventricular tachycardia. He was diagnosed with verapamil-sensitive, idiopathic left ventricular tachycardia (ILVT) and underwent an electrophysiological study, in which dual atrioventricular (AV) nodal physiology was evident, with an AV nodal reentrant tachycardia (AVNRT) being easily and reproducibly induced. Both the AVNRT and the ILVT were successfully ablated using high-density electroanatomical mapping and an open-irrigation catheter. In conclusion, verapamil-sensitive ILVT might coexist with AVNRT. In case of invasive therapy, a thorough electrophysiological evaluation is mandatory to exclude or treat other co-existing reentrant supraventricular arrhythmias.

Safety and tolerability of regadenoson compared with dipyridamole in myocardial perfusion imaging in patients scheduled to undergo medium to high-risk noncardiac surgery: a randomized controlled study.

OBJECTIVE: Regadenoson is the first Food and Drug Administration-approved selective A2A adenosine receptor agonist used in myocardial perfusion imaging. Its main benefits are its simplified and brief protocol, along with the ability to be administered safely in patients with asthma or chronic obstructive pulmonary disease of moderate severity. This study aims to identify any potential benefits of regadenoson, regarding the frequency of adverse reactions and its tolerability, over dipyridamole. METHODS: This is a randomized controlled study of 200 patients scheduled for medium to high-risk noncardiac surgery, of whom 100 were stressed with regadenoson (study group) and the rest with dipyridamole (control group). RESULTS: A greater proportion of adverse reactions was recorded in the regadenoson group as compared to the dipyridamole group (53 vs. 36%; P = 0.023), though the duration of most adverse reactions was shorter in the regadenoson group. Dyspnea (P < 0.001) and gastrointestinal disturbances (P = 0.001) were significantly more frequent in the regadenoson group. The use of aminophylline in patients who developed any adverse events was similar in the two groups (P > 0.05). When multiple regression analyses were performed, differences in adverse reactions between the two groups were no longer significant (odds ratio = 1.96; 95% confidence interval, 0.88-3.25; P = 0.11). CONCLUSION: In our group of patients scheduled for myocardial perfusion imaging for preoperative assessment, the two agents, regadenoson and dipyridamole, have no significant differences in the frequency of mild adverse reactions and in aminophylline use, with regadenoson also having the advantage of faster symptom resolution. Nevertheless, dipyridamole can be considered as a well-tolerated and low-cost alternative.

The Effect of Dobutamine Stress Testing on Vortex Formation Time in Patients Evaluated for Ischemia.

Vortex formation time (VFT) is a dimensionless index used to quantify duration of vortex ring formation during diastole. We sought to investigate the effect of pharmaceutical stress on VFT in patients evaluated for ischemia. For this purpose, a standard dobutamine stress echo (DSE) protocol was performed in 50 consecutive patients, and VFT was calculated at rest and at peak. VFT was calculated from echocardiography measurements using a previously developed mathematical equation. VFTi was calculated as the percentage of change of VFTpeak, compared with VFTrest. Mean VFTrest was 2.46 (0.73) and mean VFTpeak 1.67 (0.57) with mean VFTi - 30.0% (19.8). In 14 (28%) patients, an ischemic response (DSE+) was documented. VFTi was significantly lower in DSE+ patients a finding which remained significant in the multivariate analysis after adjusting for age, sex, hypertension, diabetes, history of coronary artery disease, and relative increase of heart rate during stress. Graphical Abstract.

Cardiovascular Disease in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by venous, arterial or microvascular thrombosis or obstetric events in the presence of persistently positive antiphospholipid antibodies and constitutes a major cause of cardiovascular events in young people. Τhis review highlights the pathophysiology of cardiovascular complications in patients with APS and possible treatment options. Patients with APS have endothelial dysfunction, accelerated endothelial proliferation and intimal hyperplasia, atherogenesis, platelet activation, inflammatory products secretion and coagulation-fibrinolytic dysregulation. Cardiovascular complications include accelerated atherosclerosis, acute coronary syndrome, Libman-Sacks endocarditis, cardiomyopathy and venous, arterial or intracardiac thrombi. Moreover, pulmonary hypertension and peripheral microvascular dysfunction are common findings. Management of these patients is not well documented. The role of primary thrombosis prevention remains controversial in individuals with positive antiphospholipid antibodies. Treatment of traditional cardiovascular risk factors according to current guidelines for the prevention of cardiovascular disease in the general population is recommended for primary prevention of APS. Anticoagulation therapy with unfractionated or low-molecular-weight heparin overlapped with a vitamin K antagonist remains the mainstay of the treatment for APS patients with venous thrombosis, whereas direct oral anticoagulants are not yet recommended. Data are scarce regarding the secondary arterial thrombosis prevention and it is not clear whether dual or triple antithrombotic therapy is necessary. To date, it is recommended to follow current guidelines for the management of acute coronary syndrome in the general population. New treatment targets are promising options for patients with catastrophic APS.

Methylmalonic acid and vitamin B12 in patients with heart failure.

OBJECTIVE: Vitamin B12 deficiency among patients with heart failure (HF) may have been underestimated. High serum levels of methylmalonic acid (MMA) have been identified in several studies as an early indicator of vitamin B12 deficiency. Furthermore, MMA seems to constitute a biomarker of oxidative stress and mitochondrial dysfunction. There are scarce data regarding vitamin B12 and MMA in patients with HF. The aim of this study was to investigate vitamin B12 and MMA serum levels in patients with HF. METHODS: One hundred five consecutive patients admitted to our hospital with symptoms and signs of acute decompensated HF were included in the study. Demographic and clinical characteristics as well as comorbidities and medical treatment before hospital admission were recorded. Transthoracic echocardiography was performed in all patients. Blood samples were collected during the first 24 hours of hospitalization and measured for complete blood count, biochemical profile, vitamin B12, N-terminal prohormone of brain natriuretic peptide, and MMA levels. Finally, 51 healthy individuals constituted the control group. RESULTS: A total of 43.8% of patients with HF had elevated MMA levels, but only 10.5% had overt vitamin B12 deficiency, defined as serum cobalamin levels below 189 pg/ml. Mean MMA level was higher in patients with HF than in controls (33.0 ± 9.6 vs. 19.3 ± 6.3 ng/ml; p < 0.001). This difference remained significant when adjusted for age, sex, vitamin B12, and folate serum levels and kidney function (B = 14.7 (9.6-19.7); p < 0.001). MMA levels were higher in patients with acutely decompensated chronic HF than in those with newly diagnosed acute HF (34.7 ± 10.5 vs. 30.7 ± 7.8 ng/ml; p = 0.036). Correlation analysis revealed significantly negative correlation between MMA and vitamin B12 levels only in patients without comorbidities. CONCLUSION: Patients with HF have elevated MMA levels, independent of age, gender, HF category, or comorbidities, possibly indicating subclinical vitamin B12 deficiency. Further research is needed to investigate subclinical vitamin B12 deficiency in patients with HF and/or to clarify whether MMA constitutes a biomarker of oxidative stress.

Stress ECHO beyond coronary artery disease. Is it the holy grail of cardiovascular imaging?

Stress echocardiography (SE) is a very useful method in clinical practice, because it offers important information of both the patient's functional status and hemodynamic changes during stress. Therefore, SE provides strong diagnostic and prognostic data in a wide spectrum of cardiovascular diseases. This review summarizes the clinical applications of SE in conditions beyond coronary artery disease (CAD) and highlights practical recommendations and key issues for each condition that need further investigation. SE is an established method for the evaluation of symptomatic and asymptomatic patients with valvular heart disease (VHD) and cardiomyopathies, and provides important information regarding prognosis and management of patients with congenital heart disease, pulmonary hypertension or diastolic dysfunction. Moreover, when one or multiple VHD and cardiomyopathy or CAD coexist in one patient, SE is a very useful clinical tool for the evaluation of etiology and symptomatology.

Biomarkers of Myocardial Injury and Inflammation after Permanent Pacemaker Implantation: The Lead Fixation Type Effect.

BACKGROUND: Permanent pacemaker implantation is accompanied by minor myocardial damage, indicated by elevated serum levels of cardiac biomarkers. Aim of this prospective study was to comparably investigate the lead fixation type effect on the extent of myocardial injury and inflammation following pacemaker implantation, and to assess the possible clinical implications. METHODS: Cardiac troponin I (cTnI) and C-reactive protein (CRP) were measured at baseline, 6 and 24h after implantation in 101 patients, categorized into the active and passive lead fixation group. Patients were followed up for clinical adverse events or abnormal pacing parameters at 24h, 7 and 30 days post-procedure. RESULTS: cTnI increased at 6h post-procedure (p<0.05) in 23.8% of patients, and returned to baseline after 24h. The passive group demonstrated significantly higher cTnI at 6h compared to the active group (p=0.006). CRP increased significantly at 6h, and maintained an upward trend after 24h (p<0.01) in both groups. The active group demonstrated significantly higher CRP at 6h compared to the passive group. We did not identify an association of positive biomarkers with adverse events. CONCLUSION: cTnI and CRP can increase early after permanent pacemaker implantation, indicating mechanical myocardial injury and inflammation. The extent of these biomarkers elevation depends on the lead fixation type, and is not related to worse short-term prognosis.

The role of thyroid hormones in acute coronary syndromes: Prognostic value of alterations in thyroid hormones.

The prognosis of acute coronary syndromes (ACS) is affected by many factors. Normal thyroid homeostasis is known to alter during various critical illnesses, a condition that has been shown to correlate with the severity of the disease and increased mortality. The purpose of this article is to review literature to emphasize the considerable association of thyroid function with the cardiovascular system and summarize all existing evidence with regard to the role of thyroid hormones alterations during ACS. The electronic databases of PubMed, Medline, Scopus, and Cochrane were searched for relevant literature and studies. Alterations in thyroid hormone plasma concentrations, especially low triiodothyronine (T3) levels, represent a hormonal imbalance that is not uncommon among patients suffering an acute coronary event. Many studies have identified this abnormal thyroid hormonal status to be related to worse prognosis. Although further large-scale clinical trials are needed, the low T3 syndrome manifesting in patients during ACS might be useful in prognostic stratification.

Effect of gender on the prognostic value of dobutamine stress myocardial contrast echocardiography.

BACKGROUND: Dobutamine stress contrast echo (DSCE) has a well-established prognostic value in the context of coronary artery disease (CAD). However, data regarding its prognostic capability separately in men and women are scarce. The aim of the current study was to assess gender-related differences in the prognostic performance of DSCE. METHODS: DSCE was performed in 2645 consecutive patients, who were classified into two groups depending on gender. Follow-up lasted 57.1±10.1 months. End points included all-cause mortality, cardiac death, late revascularization, and hospitalizations. Survival analysis was performed comparing men and women. RESULTS: Of the 2645 patients (59.3±8.7 years), 69.1% were men. DSCE was positive in 23.4% of male patients, while in females, the respective percentage was 14.3%. There was statistically significant difference between the two groups with regard to end point occurrence (11.6% vs. 6.1%, p<0.05). Multivariate analysis revealed that the DSCE response was the strongest predictor of adverse outcomes (Exp(B)=51.9, p<0.05) in both groups. The predictive model including DSCE results along with clinical data performed well without significant differences between males and females (C-index 0.93 vs. 0.87 respectively, p=NS). CONCLUSION: DSCE has a strong prognostic value for patients with known or suspected CAD, regardless of patient gender. This makes DSCE an attractive screening option for women in whom CAD assessment can be challenging.

Ranolazine and its Antiarrhythmic Actions.

Ranolazine, a newly introduced, FDA-approved antianginal agent, has more recently been shown to have additional beneficial antiarrhythmic actions attributed to its inhibitory effect on both peak and late sodium current. The first clinical evidence of ranolazine's antiarrhythmic efficacy has been provided by the MERLIN-TIMI 36 trial, which showed that ranolazine may suppress both supraventricular and ventricular arrhythmias in patients with non-ST-segment elevation acute coronary syndrome. An interesting observation of available studies is that ranolazine seems to be more effective in pathological conditions, such as heart failure, ischemia, tachyarrhythmias or long QT3 syndrome, and has little effect on normal myocytes. Importantly, the drug may have an antiarrhythmic effect without causing proarrhythmia. The mechanisms involved in the antiarrhythmic action of ranolazine, experimental and clinical data for its antiarrhythmic efficacy in suppressing atrial fibrillation and ventricular tachyarrhythmias, are herein reviewed. Current data from small randomized trials indicate that further larger randomized controlled trials are needed that will examine the antiarrhythmic effects of ranolazine and its potential use in patients with arrhythmias.