Chiara Cavallino

Novel biomarkers in the diagnosis of acute coronary syndromes: the role of circulating miRNAs

Cardiovascular disease, in particular acute coronary syndromes (ACS), is still one of the leading causes of death in industrialized countries. ACS including ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris (UA) are associated with lower mortality if diagnosed early. The diagnosis is based on clinical symptoms, ECG and circulating biomarker-level changes. Recent studies have shown that there are alternatives to the known biomarkers such as ultrasensitive troponin I or T and creatine kinase Mb; there are, in fact, novel biomarkers such as miRNAs. These are 22-nucleotide-long non-coding RNAs that regulate gene expression at post-transcriptional level. Several recent studies have shown that miRNAs play a physiological role in cardiovascular homeostasis and in the pathogenesis of cardiovascular disease. Expression-pattern studies of myocardial tissue reveal that several miRNAs are up- or down-regulated during myocardial infarction. The purpose of the present review is to highlight the state of the art and future views on this topic.

Prevalence of ventricular arrhythmias in patients with cardiac resynchronization therapy without back-up ICD: a single-center experience.

Aims Current guidelines recommend cardiac resynchronization therapy (CRT) in selected heart failure patients, but do not precisely clarify when a back-up implantable cardioverter defibrillator (ICD) should be associated (CRT-D). In this study we evaluate the occurrence of ventricular arrhythmias in a population of patients implanted with biventricular pacemaker without a back-up ICD (CRT-P). Methods We performed a retrospective analysis on 84 patients (55 men, mean age 74 ± 7 years), implanted with a CRT-P since April 2000. Patients had in 31% an underlying coronary artery disease, in 56% an idiopatic dilated cardiomyopathy and in 13% a valvular disease. An upgrade to CRT-P was performed from previous conventional pacemakers in 36% of cases. Baseline New York Heart Association (NYHA) functional class was II in 25%, III in 63% and IV in 12%. Mean left ventricular ejection fraction was 29.8 ± 8.8% with two-dimensional echo. During follow-up, occurrence of ventricular arrhythmias was assessed clinically and through the pacemaker stored data at the scheduled check-up. Results During a mean follow-up of 29 months (range 2–127 months), telemetry interrogation revealed unsustained ventricular tachyarrhythmias in 11 of 84 patients (13.1%). Only one patient experienced an episode of sustained ventricular tachycardia. An upgrading to a CRT-D was performed in two patients; one of these patients died suddenly 15 months after the upgrade. Death occurred in 20 of 84 patients (23.8%): 15 for refractory heart failure and five for noncardiac causes. Conclusion Our data show that CRT-P may be well tolerated in selected patients even during a long-term follow-up; and that an upgrade to CRT-D may not be enough to prevent sudden death.

Aortic counterpulsation in cardiogenic shock during acute myocardial infarction

Intra-aortic balloon counterpulsation is the most widely used form of mechanical hemodynamic support in the setting of cardiogenic shock due to ST-segment elevation myocardial infarction (STEMI). Intra-aortic balloon pump (IABP) is also strongly recommended (class 1b) in the current European guidelines for treatment of STEMI. The evidence of a possible benefit of IABP in this setting is based mainly on registry data and a few randomized trials. Cardiogenic shock and subsequent death due to STEMI result from three factors: hemodynamic deterioration, occurrence of multiorgan dysfunction and systemic inflammatory response. IABP does not cause an immediate improvement in blood pressure, but the recent SHOCK II trial shows positive effects on multiorgan dysfunction. Some experimental and clinical studies have indicated that IABP results in hemodynamic benefits as a result of afterload reduction and diastolic augmentation with improvement of coronary perfusion. However, the effect on cardiac output is modest and may not be sufficient to reduce mortality. Furthermore we can say that the use of IABP before coronary revascularization in the setting of STEMI complicated with cardiogenic shock may make the interventional procedure safer by improving left ventricular unloading. The purpose of the present review is to clarify the state of the art on this topic.

Pharmacological Adjuvant Therapies in Primary Coronary Interventions: Bivalirudin

The direct thrombin inhibitor bivalirudin has gained popularity in cardiovascular medicine over the past decade because, in comparison with unfractionated heparin, it guarantees a predictable dose-related degree of anticoagulation with a low immunogenic profile and, possibly, with reduced rates of major bleeding complications. In the past bivalirudin has been frequently employed in the management of patients with heparin-induced thrombocytopenia. The REPLACE-2, ACUITY and ISAR-REACT4 studies demonstrated bivalirudin non-inferiority in comparison with unfractionated heparin in terms of ischemic end-points with a reduction of the bleeding rate also in patients acute coronary syndrome without ST elevation. Finally the results of the HORIZONS-AMI study positioned this drug as a first choice anticoagulant during percutaneous coronary interventions in patients with ST-elevation myocardial infarction. In fact the bivalirudin alone regimen, compared to unfractionated heparin plus GP2b3a inhibitors, decreased in-hospital bleeding rates and short and long term mortality. Given the body of clinical evidence, bivalirudin is likely to contend to GP2b3a inhibitors the leading place among the proposed anticoagulation strategies in the setting of acute coronary syndromes. The duration of the bivalirudin infusion after PCI and the optimal oral antiplatelet regimen associated to bivalirudin are important issues to be solved in future randomized controlled studies.

Intracoronary vs intravenous bivalirudin bolus in ST-elevation myocardial infarction patients treated with primary angioplasty.

Background: Intracoronary bolus administration may provide high local bivalirudin concentration without changing the global dose, potentially offering a more favorable antithrombotic effect in the infarct related artery (IRA). Objectives: The purpose of this study was to investigate the feasibility and safety of intracoronary bolus administration of bivalirudin followed by the standard intravenous infusion in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). Methods: In 245 consecutive patients treated with primary PCI, bivalirudin bolus was given directly in the IRA, followed by a standard intravenous infusion. Clinical reperfusion markers, postprocedural coronary flow indexes, and bleeding events of the intracoronary group were compared with a propensity score-matched cohort of primary PCI patients (n=245) treated with the standard bivalirudin protocol of intravenous bolus and infusion. Results: Higher rates of ⩾70% ST-segment resolution (72.7% vs 60.0%, p=0.004), lower postprocedural peak CK-MB levels (188.3±148.7 vs 242.1±208.1 IU/dl, p=0.025) and better Thrombolysis in Myocardial Infarction (TIMI) frame count values (14.7 vs 17.9, p=0.001) were observed in the IC bolus group compared with the standard intravenous bolus group. Rates of bleeding were similar between groups. Only three cases of acute stent thrombosis were observed, all in the intravenous bolus group (p=0.25). Conclusions: Intracoronary bivalirudin bolus administration during primary PCI is safe and improves ST-segment resolution, postprocedural coronary flow and enzymatic infarct size compared with the standard intravenous route.

Giant bronchial artery aneurysm treated by coil embolization and Amplatzer placement.

To the Editor Bronchial artery aneurysm (BAA) is a rare but lifethreatening disorder. Until the past decade, it was treated by surgery; now selective embolism is the treatment of first choice, although in the literature only some case descriptions can be found. We present a case of an asymptomatic and casual finding of a giant BAA that was treated successfully with coil embolization and Amplatzer device.

[Giant aneurysm of the right coronary artery: an unusual treatment].

Coronary artery aneurysm (CAA) is an uncommon disease observed in only 0.15-4.9% of patients undergoing coronary angiography. CAA are defined as dilated coronary artery sections exceeding by 1.5 times the diameter of normal adjacent segments or of the patients largest coronary vessel. Occasionally, CAA enlarge enough to be called giant CAA. We report the case of a 78-year-old man, with known chronic ischemic cardiomyopathy and a history of prior coronary artery bypass surgery (with a left internal mammary artery graft to the left anterior descending coronary artery and saphenous venous graft to the obtuse marginal branch), who was referred to our cardiology department for progressive dyspnea. Echocardiography showed severe mitral regurgitation suggesting replacement; coronary angiography revealed three-vessel coronary artery disease, left internal mammary artery patency, saphenous vein graft occlusion and an aneurysm of the mid right coronary artery. Cardiac magnetic resonance confirmed this finding, showing a giant CAA (65 x 75 mm) with a large endoluminal thrombus. Treatment is not standardized and may include medical therapy, percutaneous treatment and surgical intervention; our patient underwent percutaneous coil embolization. One-month angiographic follow-up showed successful obliteration. The patient underwent surgical mitral valve replacement without any complications. At 9-month clinical follow-up, he was asymptomatic; transthoracic echocardiography showed an ejection fraction of 44% without prosthetic mitral regurgitation.

Stable Ventricular Fibrillation in a Heterotopic Heart Transplant Recipient

We present an unusual case of ventricular fibrillation in a conscious patient symptomatic for chest pain and shortness of breath. Almost 20 years ago he underwent heterotopic cardiac transplantation for the treatment of severe idiopathic cardiomyopathy. In the precyclosporine era, this technique was extremely useful because of the high rate of graft rejection in which the maintenance of the native heart could prevent patient death. To date, with the improvements in immunosuppressive therapy, it is generally reserved to a specific subset of conditions. A coronary angiography and a cardiac MRI confirmed the diagnosis. Six months follow-up ECG was unchanged suggesting the persistence of a double heart rhythm in the same body.

Out-of-hospital cardiac arrest: always coronary angiography?

ABSTRACT Introduction: Out-of-hospital cardiac arrest (OHCA) remains one of the principle challenges in the setting of critical care medicine and emergency cardiology. Areas covered: Long-term survival rates even after successful resuscitation are variable but increasing in the recent years; due to the improvement of base and advanced cardiac life support techniques an increasing number of resuscitated patients are admitted to the hospital. Recent data suggested that patients surviving to hospital discharge after OHCA presented long-term outcome similar to patients with ST-elevation myocardial infarction. However, limited and incompletely clear data are available in the literature about the selection and risk stratification of patients to be subjected to coronary angiography, particularly in patients who have unfavorable clinical features in whom procedures may be futile and may affect public reporting of morality. Recently the ESC and AHA addressed appropriate treatments for ST-elevation myocardial infarction (STEMI) patients with out-of-hospital cardiac arrest. Expert commentary: Immediate coronary intervention in the setting of OHCA appears to be associated with better survival to discharge; the documentation of an occluded coronary artery in medium 25% of patients without signs of STEMI at ECG helps to explain why early angiography can improve outcomes. In the treatment of OHCA we can find some ethical issues; for example a combination of comorbidities with advanced age and prolonged ischemia indicated by severe lactic acidosis may signify a high enough chance of multiorgan failure or anoxic brain injury and where the benefit of coronary reperfusion therapy appears minimal.

Ranolazine : Effects on Ischemic Heart

Coronary artery disease is the major cause of mortality and morbidity in the industrialized countries; in the United States of America and in Europe, it is responsible for one of every six deaths per year. In the setting of ischemic heart disease, angina pectoris and chest pain, in particular, are the major causes of emergency department accesses. Angina pectoris is a clinical syndrome characterized by discomfort typically in the chest, neck, chin and left arm induced by physical exertion, emotional stress and cold and is relieved by rest or by taking of nitrates. The main targets of treatment of angina pectoris are to improve quality of life by reducing the frequency and the severity of symptoms, to increase functional capacity and to improve prognosis. Ranolazine is a recent antianginal drug with unique methods of action. It was approved by the US Food and Drug Administration in 2006 as add-on therapy in patients symptomatic for stable angina. With the inhibition of the late sodium current, Ranolazine protects against ion deregulation, prevents cellular calcium overload and the subsequent increase in diastolic tension without impacting heart rate and blood pressure. Short term clinical trials and patent research show that add on therapy with Ranolazine in patients with chronic stable angina significantly improves exercise duration, exercise time to angina and reduces the use of nitro glycerine. Long term clinical trials showed no significant differences in the rate of cardiovascular death and myocardial infarction in patients with non-ST segment elevation acute coronary syndromes but a reduction in terms of recurrent ischemia. Ranolazine is generally well tolerated and even if it increases the duration of QTc interval it is not associated with atrial and ventricular arrhythmias. Therefore Ranolazine represents a good therapeutic approach in patients with chronic stable angina still symptomatic, while on optimal anti-ischemic therapy, or intolerant to traditional anti-ischemic drugs.