Case report: Sodium-glucose cotransporter 2 inhibitors induce left ventricular reverse remodeling in anthracycline-related cardiac dysfunction-a case series.

Purpose: To describe the efficacy and safety of sodium-glucose cotransporter 2 inhibitors as a specific treatment for anthracycline-related cardiac dysfunction in a small real-world population. Methods: Seven patients with anthracycline-related cardiac dysfunction were clinically and echocardiographically evaluated before and after the introduction of sodium-glucose cotransporter 2 inhibitors. Results: After a median period of 24 weeks with uninterrupted sodium-glucose cotransporter 2 inhibitors treatment, a significant clinical improvement was observed with at least one New York Heart Association Functional Class (NHYA FC) improvement in all patients (median NYHA FC: I vs. III, p < 0.010). A noteworthy left ventricular reserve remodeling (median left ventricular end diastolic volume indexed: 53 vs. 82.5 ml/m2, p = 0.018; median left ventricular ejection fraction: 50% vs. 40%, p = 0.17) was also observed. Sodium-glucose cotransporter 2 inhibitors therapy was well tolerated by every patients; no cases of discontinuation or relevant side effects were observed. Conclusion: Sodium-glucose cotransporter 2 inhibitors induce a significant clinical improvement and left ventricular reserve remodeling in patients affected by anthracycline-related cardiac dysfunction.

Cardiac Implantable Electronic Devices Infection Assessment, Diagnosis and Management: A Review of the Literature.

The use of increasingly complex cardiac implantable electronic devices (CIEDs) has increased exponentially in recent years. One of the most serious complications in terms of mortality, morbidity and financial burden is represented by infections involving these devices. They may affect only the generator pocket or be generalised with lead-related endocarditis. Modifiable and non-modifiable risk factors have been identified and they can be associated with patient or procedure characteristics or with the type of CIED. Pocket and systemic infections require a precise evaluation and a specialised treatment which in most cases involves the removal of all the components of the device and a personalised antimicrobial therapy. CIED retention is usually limited to cases where infection is unlikely or is limited to the skin incision site. Optimal re-implantation timing depends on the type of infection and on the results of microbiological tests. Preventive strategies, in the end, include antibiotic prophylaxis before CIED implantation, the possibility to use antibacterial envelopes and the prevention of hematomas. The aim of this review is to investigate the pathogenesis, stratification, diagnostic tools and management of CIED infections.

Novel SCN5A Frameshift Mutation in Brugada Syndrome Associated With Complex Arrhythmic Phenotype.

In this case report, we characterize a novel inherited frameshift mutation c.4700_4701del (p.Phe1567Cysfs*221) in a single copy of the SCN5A gene and its association with Brugada syndrome (BrS). The proband experienced a life-threatening ventricular arrhythmia successfully treated with DC-shock and he also suffered from supraventricular tachycardia. Ajmaline test confirmed the BrS diagnosis. No other mutation nor low frequency variants in the other 23 analyzed genes were detected. The same mutation was found in the father and sister, who were both diagnosed with BrS. We hypothesize that this mutation could be responsible for BrS and potentially linked to supraventricular tachycardias. Further studies are needed to confirm this observation and to assess the clinical relevance of this mutation, in terms of risk-stratification.

SCN5A Nonsense Mutation and NF1 Frameshift Mutation in a Family With Brugada Syndrome and Neurofibromatosis.

In this case series, we report for the first time a family in which the inherited nonsense mutation [c. 3946C > T (p.Arg1316*)] in the SCN5A gene segregates in association with Brugada syndrome (BrS). Moreover, we also report, for the first time, the frameshift mutation [c.7686delG (p.Ile2563fsX40)] in the NF1 gene, as well as its association with type 1 neurofibromatosis (NF1), characterized by pigmentary lesions (café au lait spots, Lisch nodules, freckling) and cutaneous neurofibromas. Both of these mutations and associated phenotypes were discovered in the same family. This genetic association may identify a subset of patients at higher risk of sudden cardiac death who require the appropriate electrophysiological evaluation. This case series highlights the importance of genetic testing not only to molecularly confirm the pathology but also to identify asymptomatic family members who need clinical examinations and preventive interventions, as well as to advise about the possibility of avoiding recurrence risk with medically assisted reproduction.

Reversibility of Left Ventricle Longitudinal Strain Alterations Induced by Adjuvant Therapy in Early Breast Cancer Patients.

Left ventricular ejection fraction (LV-EF), despite its high feasibility, is not sensitive enough to detect early and subtle LV systolic dysfunction during oncologic treatments. Therefore, we used systolic global longitudinal strain (GLS) by speckle tracking echocardiography to verify whether early LV systolic dysfunction induced by adjuvant therapy in early breast cancer patients at low risk for cardiotoxicity can be reversed. Thirty patients (aged 53 ± 11 y) with no previous cardiac and oncologic disease who were receiving adjuvant trastuzumab and taxane (group HER2+, n = 15) or taxane only (group HER2-, n = 15), after treatment with anthracyclines, were studied. LV-EF and GLS were measured at baseline, after anthracyclines (end of week 7 or 8), short term after trastuzumab and/or taxane (end of week 18) and after completion of therapy. Significant LV systolic dysfunction was defined as a relative reduction in GLS of >10% with respect to baseline values. Mean and individual LV-EFs did not change significantly during the oncologic treatment and after completion of therapy, although GLS varied significantly. In particular, during the course of therapy, four patients in the trastuzumab-docetaxel HER2+ subgroup and two patients in the taxane HER2- subgroup had a relative decrease (>10%) in GLS. However, after the end of adjuvant treatment, strain modification was fully or partially reversible. Speckle tracking echocardiography is more sensitive than LV-EF in recognizing subtle myocardial impairment during adjuvant chemotherapy. However, in patients at low risk for cardiotoxicity, these alterations may be reversible and not associated with clinically significant cardiotoxicity or late development of decreased LV-EF.

Cancer therapy-induced cardiotoxicity: role of ultrasound deformation imaging as an aid to early diagnosis.

In the last decade, ultrasound deformation imaging, based on both Doppler and speckle tracking echocardiography techniques, has emerged as a more sensitive tool to identify subtle and subclinical left ventricular systolic dysfunction in several clinical settings compared with ejection fraction. In this article, we review the evidence relative to the application of ultrasound deformation imaging to the oncologic field for detection of left ventricular systolic dysfunction induced by cardiotoxic treatments with the aim of verifying whether this approach may actually help in early diagnosis of chemotherapy-induced cardiotoxicity.

On-treatment platelet reactivity in patients with chronic obstructive pulmonary disease undergoing percutaneous coronary intervention.

Patients with chronic obstructive pulmonary disease (COPD) show a poor prognosis after myocardial infarction (MI) and percutaneous coronary intervention (PCI). We evaluated on-treatment platelet reactivity (PR) and several gene polymorphisms related to PR in 130 patients undergoing PCI with and without COPD. Those with concomitant COPD showed higher on-treatment PR values both at the time of PCI and 1 month after. This finding may contribute to explain the poor prognosis of COPD patients after MI and PCI.

Coagulation factors and recurrence of ischemic and bleeding adverse events in patients with acute coronary syndromes.

In the last years, management and prognosis of patients with acute coronary syndromes (ACS) are significantly improved. Nowadays antithrombotic (antiplatelet plus anticoagulant drugs) therapy represents the main treatment of ACS patients. Anticoagulant drugs are particularly helpful in the acute phase of ACS, whereas in the chronic phase are maintained only in selected cases. Many studies demonstrate that exists a significant variability in the coagulation factor levels between patients affected by ACS. This variation on coagulation factors levels is due to environmental (smoking, inflammation, sex, oral contraceptive, triglycerides, diabetes mellitus) and genetic determinants. Particularly several gene polymorphisms have been selected and clearly associated with significant variations in the coagulation factors values. The heightened levels of tissue factor, factor VII and fibrinogen are related with a "hypercoagulable status" and with a higher occurrence of ischemic complications after ACS and/or PCI. On the contrary, less data are available regarding the relationship between coagulation factors levels (or their gene polymorphisms) and bleeding complications. Recently, new anticoagulant drugs have been developed. They show less side effects and a better tolerability and, probably, their selected use in patients with a "hypercoagulable status" may improve the clinical outcome after ACS. In this review we analyze the current available data and we discuss how this finding may be useful for planning future studies to optimize the treatment of ACS patients.

Kounis-Zavras syndrome presenting with ventricular arrhythmias and cardiogenic shock.

In this case report we describe a case of the Kounis-Zavras syndrome (coincidental occurrence of chest pain and allergic reactions accompanied by clinical and laboratory findings of cardiac ischemia). A 34-year-old woman presented to the emergency unit with severe chest pain from 2 h. She reported a medical history of asthma. On arrival, her heart rate was 125 beats/min and her systolic blood pressure (SBP) was 70 mmHg. A repeated electrocardiogram displayed dynamic changes with ST-segment elevation in D1-aVL leads and ST-segment depression in infero-posterior leads. Two episodes of ventricular fibrillation were observed. The coronary artery angiography showed multivessel coronary vasospasms. Intracoronary nitroglycerin was used to alleviate the coronary vasospasms. Contemporaneously, the patient's husband came to the hospital reporting a history of ketorolac consumption some hours before the onset of the acute event for headache symptoms. This crucial information permitted us to suppose it was a case of allergic myocardial infarction during anaphylactic shock due to ketorolac. Betametasone, chlorphenamine, and ranitidine were administered and progressively a full recovery of SBP and of clinical status was observed. .

The in vitro effects of verbascoside on human platelet aggregation.

Preliminary in vitro and animal studies have shown that verbascoside, a phenolic compound, may have several favourable biological activities, including an influence on endothelial function and on platelet aggregation. We sought to evaluate the effects of verbascoside, biotechnologically produced from plant cell cultures, on human platelet aggregation (PA). The blood from 40 aspirin-naïve volunteers with at least one cardiovascular risk factor was preincubated in vitro with verbascoside (1 and 2 mg/dL) and aspirin (100 µM). The blood from 20 patients with a prior diagnosis of coronary heart disease who were chronically assuming aspirin was preincubated in vitro with verbascoside (1 and 2 mg/dL). PA is measured with a light transmission aggregometry and multiplate analyzer. As compared to reference, preincubation with verbascoside resulted in a significant inhibition of adenosine diphosphate (ADP) and arachidonic acid (AA)-induced PA (p < 0.01 for both). Verbascoside 2 mg/dL did not show a stronger effect as compared to verbascoside 1 mg/dL (p = 0.4). As expected, the in vitro addition of aspirin reduced AA induced PA (p < 0.01), but not that induced by ADP (p = 0.5). The addition of verbascoside to the blood of aspirin-treated patients did not improve the values of PA after AA stimulus (p = 0.8), whereas it ensured a stronger inhibition after ADP stimulus (p < 0.01). Verbascoside in vitro affects PA by mildly inhibiting aggregation, triggered both by ADP and AA. These preliminary data, while intriguing, require confirmation in subjects receiving verbascoside orally in order to determine whether these findings are clinically relevant.

Thrombin generation assay: a new tool to predict and optimize clinical outcome in cardiovascular patients?

Antithrombotic therapy (including antiplatelet and anticoagulant drugs) is the cornerstone of the current medical treatment of patients with acute coronary syndromes (ACS). This therapy and particularly the new antiplatelet and anticoagulant drugs have significantly reduced the ischemic risk, but have increased bleeding complications. Recently, several studies have emphasized the negative prognostic impact on long-term mortality of these bleeding adverse events. Thus, new assays to estimate the bleeding risk and the efficacy of these antithrombotic drugs are clearly in demand. Regarding the anticoagulant drugs, new promising data have emerged about the thrombin generation assay (TGA). TGA measures the ability of plasma to generate thrombin. TGA may be used to check coagulation function, to value risk of thrombosis and to compare the efficacy of different anticoagulants employed in clinical management of patients with ACS. The TGA result is a curve which describes the variation of thrombin's amount during the activation of the coagulation cascade. All available anticoagulant drugs influence the principal parameters generated by TGA and so it is possible to evaluate the effects of the medical treatment. In this review we provide a brief description of the assay and we summarize the principals of previous studies by analyzing the relationship between anticoagulant drugs and TGA. Moreover, a brief summary of its ability to predict ischemic and bleeding risks has been provided.