Pasquale Assennato

Hsp60 and heme oxygenase-1 (Hsp32) in acute myocardial infarction.

Heat shock proteins (Hsps) are produced in response to various stressors, including ischemia-reperfusion, and they can exit cells and reach the blood. In this pilot study, we determined serum levels of Hsp60 and heme-oxygenase-1 (HO-1; also named Hsp32) in subjects with acute myocardial infarction (AMI) to assess their clinical significance and potential prognostic value. We also performed a bioinformatics analysis of the 2 molecules in search of structural clues on the mechanism of their release from cells. We studied 40 patients consecutively admitted for AMI (male:female patient ratio=20:20, mean age: 64 ± 13 years) and 40 matched controls. A blood sample was drawn for biochemical analyses within 24 h of symptoms onset, and Hsp60 and HO-1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA). All patients were followed up for 6 months to register adverse post-AMI cardiovascular events. A multivariate analysis demonstrated that elevated Hsp60 (P=0.0361), creatine phosphokinase-muscle brain (CK-MB) (P=0.0446), and troponin (P=0.0490) were predictive of post-AMI adverse events. In contrast, increased HO-1 showed a significant association with less severity of coronary artery diseases (P=0.0223). These findings suggest that Hsp60 and HO-1 play distinct roles in the pathogenesis of AMI and subsequent AMI-related pathology. The possibility that these proteins differ in their roles and mechanisms of action in AMI and post-AMI pathology was supported also by the bioinformatics estimates of probability of their localization in various subcellular compartments. The results clear the way for subsequent investigation on the pathogenetic role and clinical significance of Hsp60 and HO-1 in AMI.

Plasma endothelin-1 levels in patients with angina pectoris and normal coronary angiograms

BACKGROUND Some patients with typical angina and electrocardiographic evidence of ischemia have normal coronary angiograms. These patients have a reduced coronary flow reserve and abnormal endothelium-dependent vasodilator responses; this syndrome is known as microvascular angina. Among endothelium-derived peptides, endothelin-1 (ET-1) is a potent vasoconstrictor and an important modulator of microvascular function. METHODS Plasma ET-1 was measured in 13 patients with typical angina, instrumental evidence of ischemia, and normal arteriograms and in 20 normal control subjects. RESULTS Mean concentration of ET-1 was 2.89+/-1.24 pmol/L in patients with angina and normal angiograms and 1.99+/-0.81 pmol/L in normal control subjects (p < 0.02). Plasma levels of ET-1 values were significantly higher in patients with angina, positive exercise test results for ischemia, and normal coronary arteriograms compared with the group of patients with no clinical or instrumental evidence of ischemia. CONCLUSIONS This is consistent with the hypothesis that in patients with microvascular angina, an endothelial dysfunction in the coronary vascular area caused by impaired endothelium-derived ET-1 could play an active role in the disease process.

Cardiac changes in subclinical and overt hyperthyroid women: retrospective study.

BACKGROUND This retrospective and descriptive 4-year study was undertaken to describe cardiac changes in subclinical and overt hyperthyroidism. METHODS We revised the charts of 386 consecutive cardiopathic women whose blood samples were referred to the Radioimmunoassay Laboratory to evaluate thyroid function from 1 January 1997 through 31 December 2000. RESULTS After excluding women because euthyroid or hypothyroid, or taking amiodarone and women with hypertension, rheumatic disease, myocardial infarction, a total of 31 hyperthyroid women were thus selected for the study: 19 with subclinical hyperthyroidism and 12 with overt hyperthyroidism. The prevalence of atrial fibrillation did not differ between subclinical (48%) and overt (67%) hyperthyroid women, as well as left atrial dimension; the latter was larger in hyperthyroid (27.8+/-7.8 cm(2)/m(2)) than in control women (18.9+/-2.8 cm(2)/m(2)) (P<0.001). In the subclinical and overt hyperthyroidism, the heart rate (HR) was increased and left ventricular end diastolic (LVED) volume was reduced; in addition, only in overt hyperthyroidism, left ventricular (LV) mass was increased. A significant correlation between LV mass and free triiodothyronine was found. CONCLUSION HR increase and LVED decrease, both in subclinical and overt hyperthyroidism, indicate a global impairment of diastolic heart performance, complicated in overt hyperthyroidism by LV concentric hypertrophy. So, in our opinion, subclinical hyperthyroidism, far from being considered a simple laboratory finding, in clinical practice should be taken into serious consideration.

Vasospastic angina and scombroid syndrome: a case report

Abstract Scombroid syndrome is a fish poisoning characterised by the onset of symptoms compatible with a pseudoallergic reaction; it is rarely also responsible of signs and symptoms of acute coronary syndromes, as demonstrated in this case report.

Troponin I/ejection fraction ratio: a new index to differentiate Takotsubo cardiomyopathy from myocardial infarction.

– Transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid-segments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution; a stressful trigger is often, but not always, present; – Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture; – New ECG abnormalities (either ST-segment elevation and/or T wave inversion) or modest elevation in cardiac troponin; and – Absence of pheochromocytoma or myocarditis.

Heart Failure and Mechanical Circulatory Assist Devices

During the last 20 years, the management of heart failure has significantly improved by means of new pharmacotherapies, more timely invasive treatments and device assisted therapies. Indeed, advances in mechanical support, namely with the development of more efficient left ventricular assist devices (LVAD), and the total artificial heart have reduced mortality and morbidity in patients with end-stage heart failure awaiting for transplantation. However, the transplant cannot be the only solution, due to an insufficient number of available donors, but also because of the high number of patients who are not candidates for severe comorbidities or advanced age. New perspectives are emerging in which the VAD is no longer conceived only as a “Bridge to Transplant”, but is now seen as a destination therapy. In this review, the main VAD classification, current basic indications, functioning modalities, main limitations of surgical VAD and the total artificial heart development are described.

Angiographic Evaluation of Coronary Microvascular Dysfunction in Patients with Heart Failure and Preserved Ejection Fraction.

The aim of this study was to evaluate myocardial perfusion and coronary blood flow through validated angiography indices to assess whether there is greater MVD in patients with microvascular angina and HFPEF compared to those who do not have.

G-protein-coupled receptor kinase 5 polymorphism and Takotsubo cardiomyopathy.

Background Takotsubo cardiomyopathy (TTC) is an increasingly reported clinical syndrome that mimics acute myocardial infarction without obstructive coronary artery disease and is characterized by transient systolic dysfunction of the apical and/or mid-segments of the left ventricle. The syndrome mainly occurs in postmenopausal women with high adrenergic state conditions. Nowadays, the pathophysiology of TTC is not yet known and the possibility of a genetic predisposition is controversial. Aims The purpose of this study was to assess the genetic susceptibility to TTC through analysis of the L41Q polymorphism of the G-protein-coupled receptor kinase 5 (GRK5). Methods and results In a cohort of 20 patients enrolled in two tertiary Italian centers with diagnosis of TTC, accordingly to the commonly accepted Mayo Clinic criteria and in 22 healthy individuals (control) we have evaluated the polymorphism in GRK5 gene. The TTC patients had a mean age of 65 ± 9 years and 19 of 20 were women. The presence of one or two L41 alleles of GRK5 was significantly more frequent in TTC group than in the control group (40 vs. 8%, P = 0.0372). Conclusion In our study, we have found a significant difference in the frequency of GRK5 polymorphism between TTC patients and controls, supporting a genetic predisposition to this cardiac syndrome.

Non-responders to cardiac resynchronization therapy: Insights from multimodality imaging and electrocardiography. A brief review

BACKGROUND Cardiac resynchronization therapy (CRT) is a successful strategy for heart failure (HF) patients. The pre-requisite for the response is the evidence of electrical dyssynchrony on the surface electrocardiogram usually as left bundle branch block (LBBB). Non-response to CRT is a significant problem in clinical practice. Patient selection, inadequate delivery and sub-optimal left ventricle lead position may be important causes. OBJECTIVES In an effort to improve CRT response multimodality imaging (especially echocardiography, computed tomography and cardiac magnetic resonance) could play a decisive role and extensive literature has been published on the matter. However, we are so far from routinary use in clinical practice. Electrocardiography (with respect to left ventricle capture and QRS narrowing) may represent a simple and low cost approach for early prediction of potential non-responder, with immediate practical implications. CONCLUSION This brief review covers the current recommendations for CRT in HF patients with particular attention to the potential benefits of multimodality imaging and electrocardiography in improving response rate.

STEMI patients and nonculprit lesions: To treat or not to treat? and when? A review of most recent literature.

Patients with ST segment elevation myocardial infarction and multivessel disease represent a high percentage of ischemic patient with a worse outcome than patient with single coronary artery disease. Therefore, initial management of these patients is of high importance, but unfortunately this is not clarified yet. We analyze the available literature trying to afford current doubts to determine which way of revascularization is to be preferred.