rationale for the use of high dose sustained release isosorbide 5 mononitrate in ischemic heart disease and chronic heart failure

Isosorbide-5-mononitrate is one of the two pharmacologically active metabolites of isosorbide dinitrate. At variance from its parent drug, it has a longer elimination half-life, no metabolic first-pass, and greater bioavailability, allowing once-daily administration as standard or as sustained-release formulations. Several trials have shown that isosorbide-5-mononitrate, in the form of sustained-released capsules administered once daily at doses ranging between 50 and 100 mg, is an effective symptomatic drug for the treatment of stable angina and chronic heart failure (CHF), and is now indicated for these conditions by American and European guide- lines. In particular, at 80 mg once-daily sustained-release isosorbide-5-mononitrate has been shown to have trough plasma levels below the minimum therapeutic concentration (100 ng/mL), ensuring a nitrate-free period as sufficient as to avoid nitrate tolerance. This 80 mg dosage is the only high dose sustained-release formulation of isosorbide-5-mononitrate currently marketed in Italy. Isosorbide-5-mononitrate also exerts positive hemodynamic effects (reduction in filling pressure and systemic vascular resistance, with increase in cardiac output) in heart failure in as- sociation with standard medical therapy and hydralazine, with a positive impact on patient prog- nosis. (Heart International 2007; 3: 98-111

Atrial flutter: from ECG to electroanatomical 3D mapping

Atrial flutter is a common arrhythmia that may cause significant symptoms, including palpitations, dyspnea, chest pain and even syncope. Frequently it’s possible to diagnose atrial flutter with a 12-lead surface ECG, looking for distinctive waves in leads II, III, aVF, aVL, V1,V2. Puech and Waldo developed the first classification of atrial flutter in the 1970s. These authors divided the arrhythmia into type I and type II. Therefore, in 2001 the European Society of Cardiology and the North American Society of Pacing and Electrophysiology developed a new classification of atrial flutter, based not only on the ECG, but also on the electrophysiological mechanism. New developments in endocardial mapping, including the electroanatomical 3D mapping system, have greatly expanded our understanding of the mechanism of arrhythmias. More recently, Scheinman et al, provided an updated classification and nomenclature. The terms like common, uncommon, typical, reverse typical or atypical flutter are abandoned because they may generate confusion. The authors worked out a new terminology, which differentiates atrial flutter only on the basis of electrophysiological mechanism

Multiorgan paradoxical embolism consequent to acute pulmonary thromboembolism with patent foramen ovale: a case report

Paradoxical embolism is defined as a systemic arterial embolism requiring the passage of a venous thrombus into the arterial circulatory system through a right-to-left shunt. It is a relatively rare phenomenon, representing about 2% of all cases of arterial embolism. We report a case of a 79-years-old woman admitted to hospital because of dyspnea and lower left limb pain. CT scan revealed multiple thrombi to kidney, lower limb and superior mesenteric artery during acute pulmonary embolism. Echocardiogram documented a patent foramen ovale with a right-to-left shunt. The patient was treated with thrombolytic therapy and heparin with progressive improvement of symptoms and resolution of pulmonary embolism and peripheral thrombosis. Patent foramen ovale closure was not performed because a life-long anticoagulation therapy was necessary, a tunnel-type patent foramen ovale may increases difficulty in realizing device implantation and there are no clear evidence-based guidelines to date addressing treatment in presence of a patent foramen ovale

Riparazione valvolare mitralica percutanea: la Mitraclip

L'insufficienza mitralica (IM) è la valvulopatia cardiaca più comune, con una prevalenza stimata nella popolazione generale, aggiustata per età e sesso, pari all'1.7%, ma con un marcato incremento con l'aumentare dell'età, potendo colpire fino al 13.2% della popolazione al di sopra di 75 anni. La prevalenza non trascurabile dell'IM e l'importante impatto prognostico di questa malattia nei pazienti (pz.) affetti, sia nella sua forma degenerativa primitiva (IMP) che nella sua forma secondaria/funzionale (IMF), risultante dalla dilatazione e disfunzione del ventricolo sinistro (Vsx) nei pz con scompenso, ha portato all'elaborazione di nuove strategie di trattamento percutaneo minimamente invasivo, per consentire il trattamento di un maggior numero di pz. affetti. Fra esse la più frequentemente usata è la riparazione valvolare mitralica percutanea tramite impianto di clip con sistema Mitraclip (Abbott Laboratories, Menlo Park, California, USA). Considerato l'alto tasso di prevalenza di IM e di SC nella popolazione generale, la prognosi infausta di queste malattie, e l'alto tasso di comorbilità presente nei soggetti affetti da SC, che spesso rende i pz. stessi ineleggibili al trattamento chirurgico convenzionale, la riparazione valvolare percutanea mediante Mitraclip potrebbe rappresentare per molti individui un beneficio non solo sintomatologico, ma anche prognostico, andando ad interrompere il circolo vizioso che si crea fra disfunzione del Vsx e sovraccarico di volume, mediato proprio dall'IM stessa. In questa revisione della letteratura verranno discussi gli aspetti principali della riparazione valvolare mitralica percutanea con Mitraclip e l'importante impatto prognostico da essa derivante

Irreversible proteasome inhibition with carfilzomib as first line therapy in patients with newly diagnosed multiple myeloma: Early in vivo cardiovascular effects.

Patients who experienced cardiovascular side effects during cancer therapy with carfilzomib for multiple myeloma had relapsed multiple myeloma, so have be previously treated with other cancer therapies. The present is a single center cohort study to evaluate early cardiovascular effects of administration of irreversible proteasome inhibitor carfilzomib in naïve patients. We included 24 patients and collected cardiovascular side effects, echocardiographic parameters and endothelial function at baseline and after 4 cycles. At early follow up we observed increase in blood arterial pressure values (mean change in systolic pressure of 10 mmHg (P-value  0.01; diastolic arterial pressure and mean arterial pressure of 3.3 mmHg and 5.4 mmHg, both P-value  0.01). Reactive hyperemia PAT index was reduced in the whole cohort by a mean of 0.46 points (P-value  0.01); diastolic function was changed: E-wave-deceleration-time (EDT) was reduced by 49,96 ± 31 ms, P-value  0.05 and early diastolic tissue Doppler velocity (e') by a mean value of 1.46 cm/s, P - value 0.04. At early follow up we did not observe events of grade 3 or 4. We observe correlation between events and endothelial dysfunction at baseline and age (OR 1.9, CI 95% 0.05-5.804, P- value: 0.038 for RHI1.67; OR 1,4, CI 95%0.99-2.56, P- value: 0.04 for age). Our results suggest that therapy with carfilzomib when used as first line therapy is responsible for increase in systemic blood pressure, alteration of endothelium-mediated vascular dilatation and early myocardial diastolic dysfunction

Diagnostic value of the head-up tilt test and the R-test in patients with syncope

The diagnostic value of the head-up tilt test (HUTT) in discovering vasovagal syndrome depends on the pre-test probability. An accurate anamnesis and clinical examination screens the patients indicated for the HUTT. In patients with unexplained syncope, the R-test is an alternative procedure to discover its cause. In our study, we evaluated the diagnostic significance of the HUTT in a group of 211 patients and of the R-test in a subgroup of 45 patients with negative HUTT results and with negative traditional Holter ECG monitoring (24 hr)

Spasmogenic Effects of the Proteasome Inhibitor Carfilzomib on Coronary Resistance, Vascular Tone and Reactivity

Background: Carfilzomib (CFZ) is a new proteasome inhibitor used for the treatment of multiple myeloma. Besides heart failure, angina and myocardial ischemia occurred following administration of CFZ, which is not contraindicated in patients with recent myocardial infarction/unstable angina excluded from the safety trials. Aimof Study: To test the effects of CFZ (10−9 to 10−7 mol/L) on vascular tone and reactivity in the isolated rabbit heart and aorta. Methods and Results: CFZ administered by bolus injection to the isolated heart increased coronary perfusion pressure (CPP) at all tested concentrations and mildly raised left ventricular pressure and heart rate, only at the highest concentration. Addition of CFZ directly into the organ bath increased the basal tone of isolated aortic strips with contraction plateau reached after 10 min. This spasmogenic effect doubled following ablation of the endothelium. Pretreatment with CFZ amplified the vasospastic action exerted by KCl, noradrenaline (NA) and angiotensin II (A) on aortic strips, and impaired vasodilation following administration of nitroglycerin (NTG) and nifedipine (NFP) on the contraction plateau induced by KCl, NA and A. Aortic strips pretreatedwith CFZ exhibited impaired relaxation, as compared to untreated strips, following administration of acetylcholine (Ach), an endothelium- dependent vasodilating agent, on the plateau of NA contraction (p b 0.05). Conclusions: CFZ increased CPP, resting vasoconstricting tone and the spasmogenic effect of different agents. Preincubation with CFZ decreased the anti-spasmogenic activity of NTG and NFP, as well as reduced by over 50% the vasodilating effect of Ach, suggesting that CFZ can impair vasodilation via an endothelium dependent mechanism. Further studies are warranted to establish its clinical safety in patients with known CAD and prior history of coronary spasm

Erythropoietin: a new perspective in cardiovascular therapy

Erythropoietin is a hormone produced by the kidney, which regulates proliferation, differentiation and maturation of red cells. Recombinant human EPO (rH-EPO) is well known to correct anaemia in patients with chronic renal failure in terminal stage. However, recent studies showed the existence of several not haematopoietic effects of erythropoietin. EPO receptors have been found to be expressed in several tissues, included the cardiovascular system. An increase in cardiac systolic function has been observed in patients with chronic heart failure treated with EPO. Other beneficial effects appear to be related to the pro-angiogenic properties on endothelial cells and could be useful for treatment of ischemic heart disease. These findings suggest that EPO could provide potential therapeutic benefits in the management of cardiovascular diseases beyond anaemia correction. This review focuses its attention on the pleiotropic effects of EPO and its future promising applications in cardiovascular pathology

Peripartum Cardiomyopathy

which left ventricular dysfunction and symptoms of heart failure occur in the peripartum period in previously healthy women. Incidence of PPCM ranges from 1 in 1300 to 1 in 15,000 pregnancies. The etiology of PPCM is unknown, but viral, autoimmune, and idiopathic causes may contribute. The diagnostic criteria are onset of heart failure in the last month of pregnancy or in the first 5 months postpartum, absence of determinable cause for cardiac failure, and absence of a demonstrable heart disease before the last month of pregnancy. Risk factors for PPCM include advanced maternal age, multiparity, African race, twinning, gestational hypertension, and long-term tocolysis. The clinical presentation of patients with PPCM is similar to that of patients with dilated cardiomyopathy. Echocardiography is central to diagnosis. Early diagnosis and initiation of treatment are essential to optimize pregnancy outcome. Treatment is similar to medical therapy for other forms of dilated cardiomyopathy. About half the patients of PPCM recover without complications. The prognosis is poor in patients with persistent cardiomyopathy. Persistence of disease after 6 months indicates irreversible cardiomyopathy and portends worse survival