Maria Aurora Morales

Prognostic value of dobutamine-atropine stress echocardiography early after acute myocardial infarction

OBJECTIVES The aim of this multicenter, multinational, prospective, observational study was to assess the relative value of myocardial viability and induced ischemia early after uncomplicated myocardial infarction. BACKGROUND Dobutamine-atropine stress echocardiography allows evaluation of rest function (at baseline), myocardial viability (at low dose) and residual ischemia (peak dose, up to 40 micrograms with atropine up to 1 mg) in one test. METHODS Dobutamine-atropine stress echocardiography was performed 12 +/- 5 days (mean +/- SD) after a first uncomplicated acute myocardial infarction in 778 patients (677 men; mean age 58 +/- 10 years) with technically satisfactory rest echocardiographic study results. Patients were followed-up for 9 +/- 7 months. RESULTS Dobutamine-atropine stress echocardiographic findings were positive for myocardial ischemia in 436 of patients (56%) and negative in 342 (44%). During follow-up, there were 14 cardiac-related deaths (1.8% of the total cohort), 24 (2.9%) nonfatal myocardial infarctions and 63 (8%) hospital readmissions for unstable angina. One hundred seventy-four patients (22%) underwent coronary revascularization (bypass surgery or coronary angioplasty). Spontaneous events occurred in 61 of 436 patients with positive and 40 of 342 patients with negative findings on dobutamine-atropine stress echocardiography (14% vs. 12%, p = 0.3). When only spontaneously occurring events were considered, the most important predictor was myocardial viability (chi-square 9.7). Using the Cox proportional hazards model, only the presence of myocardial viability (hazard ratio [HR] 2.0, p < 0.002) and age (HR 1.03, p < 0.001) were predictive of spontaneously occurring events. When only hard cardiac events were considered, age was the strongest predictor (chi-square 3.6, p = 0.056), followed by wall motion score index (WMSI) at peak dose (chi-square 3.3, p = 0.06) and remote ischemia (chi-square 2.25, p = 0.1). When cardiac death was considered, WMSI at peak dose was the best predictor (HR 9.2, p < 0.0001). CONCLUSIONS During dobutamine stress, echocardiographic recognition of myocardial viability is more prognostically important than echocardiographic recognition of myocardial ischemia for predicting unstable angina, whereas WMSI at peak stress was the best predictor of cardiac-related death. Different events can be recognized with different efficiency by various stress echocardiographic variables.

Bleomycin in the setting of lung fibrosis induction: From biological mechanisms to counteractions.

Bleomycin (BLM) is a drug used to treat different types of neoplasms. BLMs most severe adverse effect is lung toxicity, which induces remodeling of lung architecture and loss of pulmonary function, rapidly leading to death. While its clinical role as an anticancer agent is limited, its use in experimental settings is widespread since BLM is one of the most widely used drugs for inducing lung fibrosis in animals, due to its ability to provoke a histologic lung pattern similar to that described in patients undergoing chemotherapy. This pattern is characterized by patchy parenchymal inflammation, epithelial cell injury with reactive hyperplasia, epithelial-mesenchymal transition, activation and differentiation of fibroblasts to myofibroblasts, basement membrane and alveolar epithelium injuries. Several studies have demonstrated that BLM damage is mediated by DNA strand scission producing single- or double-strand breaks that lead to increased production of free radicals. Up to now, the mechanisms involved in the development of pulmonary fibrosis have not been fully understood; several studies have analyzed various potential biological molecular factors, such as transforming growth factor beta 1, tumor necrosis factor alpha, components of the extracellular matrix, chaperones, interleukins and chemokines. The aim of this paper is to review the specific characteristics of BLM-induced lung fibrosis in different animal models and to summarize modalities and timing of in vivo drug administration. Understanding the mechanisms of BLM-induced lung fibrosis and of commonly used therapies for counteracting fibrosis provides an opportunity for translating potential molecular targets from animal models to the clinical arena.

C-type natriuretic peptide and its relation to non-invasive indices of left ventricular function in patients with chronic heart failure.

C-type natriuretic peptide (CNP) significantly increases in chronic heart failure (CHF) patients as a function of clinical severity. Aim of this study was to evaluate in CHF patients the relationship between circulating CNP concentrations and echo-Doppler conventional indices of left ventricular (LV) function as well as less load independent parameters as dP/dt. LV ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) and LV dP/dt were evaluated together with plasma CNP levels in 38 patients with CHF and in 63 controls. CNP levels resulted significantly higher in CHF patients than in controls (7.19+/-0.59 pg/ml vs. 2.52+/-0.12 pg/ml, p<0.0001). A significant correlation between dP/dt and CNP levels (r=-0.61, p<0.0001) was observed. A good correlation with EF (r=-0.55, p<0.001) and a less significant relation with LVEDD (r=0.316, p<0.05) were also reported. When patients were divided according to dP/dt values a very significant difference in CNP levels was observed: Group I (<600, n=25) vs. Group II (>600, n=13): 8.46+/-0.69 and 4.75+/-0.75 pg/ml, respectively, p<0.001. This is the first study that reports a correlation between CNP and dP/dt in CHF patients, thus suggesting a possible role on cardiac contractility.

The role of cardiac fat in insulin resistance.

Purpose of reviewTo evaluate the relationship between cardiac fat accumulation and insulin resistance. We discuss the current knowledge regarding the different techniques for measuring, in vivo in humans, cardiac fat deposition, the effects of systemic and myocardial insulin resistance and the clinical relevance of the relation between atherosclerosis and cardiac fat in conditions of insulin resistance. Recent findingsIn humans, fat accumulates mainly around the heart, as epicardial, perivascular and intrathoracic fat, but also inside the cardiomyocytes. All these cardiac fat depots have been shown to be markers of cardiac lipotoxicity, mitochondrial dysfunction, inflammation and local and systemic insulin resistance as well as of atherosclerosis and cardiac dysfunction. SummaryAlthough cardiac fat is associated with impairment in heart metabolism and cardiac dysfunction, the interplay among cardiac fat accumulation, insulin resistance and cardiac dysfunction remains to be fully established.

Innate inflammation in myocardial perfusion and its implication for heart failure.

Heart failure is characterized by a chronic inflammatory status, with high circulating levels of inflammatory cytokines significantly correlated with deterioration of functional capacity, cardiac performance, and coronary flow reserve—the latter occurring even with normal systemic endothelial function. Impaired coronary flow reserve in heart failure is poorly related to systemic inflammation levels and somewhat matched by a reduction in myocardial contractile reserve. Both coronary flow and myocardial functional reserve can be imaged noninvasively and can be useful clinically for disease severity titration, diagnostic anticipation, and prognostic stratification. Coronary microcirculatory dysfunction can be a trigger of disease and a potential target for therapeutic intervention in heart failure patients. Clinical observational studies showed a striking beneficial effect of endogenous adenosine accumulation on symptoms, exercise capacity, and left ventricular function in chronic heart failure, but this needs to be confirmed in prospective randomized large‐scale trials.

Inappropriateness of Cardiovascular Radiological Imaging Testing; A Tertiary Care Referral Center Study

Aims Radiological inappropriateness in medical imaging leads to loss of resources and accumulation of avoidable population cancer risk. Aim of the study was to audit the appropriateness rate of different cardiac radiological examinations. Methods and Principal Findings With a retrospective, observational study we reviewed clinical records of 818 consecutive patients (67±12 years, 75% males) admitted from January 1-May 31, 2010 to the National Research Council – Tuscany Region Gabriele Monasterio Foundation cardiology division. A total of 940 procedures were audited: 250 chest x-rays (CXR); 240 coronary computed tomographies (CCT); 250 coronary angiographies (CA); 200 percutaneous coronary interventions (PCI). For each test, indications were rated on the basis of guidelines class of recommendation and level of evidence: definitely appropriate (A, including class I, appropriate, and class IIa, probably appropriate), uncertain (U, class IIb, probably inappropriate), or inappropriate (I, class III, definitely inappropriate). Appropriateness was suboptimal for all tests: CXR (A = 48%, U = 10%, I = 42%); CCT (A = 58%, U = 24%, I = 18%); CA (A = 45%, U = 25%, I = 30%); PCI (A = 63%, U = 15%, I = 22%). Top reasons for inappropriateness were: routine on hospital admission (70% of inappropriate CXR); first line application in asymptomatic low-risk patients (42% of CCT) or in patients with unchanged clinical status post-revascularization (20% of CA); PCI in patients either asymptomatic or with miscellaneous symptoms and without inducible ischemia on non-invasive testing (36% of inappropriate PCI). Conclusion and Significance Public healthcare system – with universal access paid for with public money – is haemorrhaging significant resources and accumulating avoidable long-term cancer risk with inappropriate cardiovascular imaging prevention.

The role of wearable sensors and wireless technologies for the assessment of heart rate variability in anorexia nervosa

PurposeBradycardia and abnormal cardiac autonomic function are related to increased mortality in anorexia nervosa (AN). The aim of this study was to assess heart rate (HR) and HR variability of young adolescents with AN as compared to controls by means of wearable sensors and wireless technologies.MethodThe ECG signal was recorded in 27 AN girls and 15 healthy girls at rest using a wearable chest strap. The tachogram, the mean intervals between R peaks (meanRR), the root mean square of successive differences (RMSSD), the power of low-frequency (LF) and high-frequency (HF) bands and the LF/HF ratio were assessed.ResultsAll AN girls showed a reduced HR and an increased meanRR and RMSSD. An HF increase, a LF decrease, and a LF/HF reduction indicated a prevalence of the parasympathetic on sympathetic activity.ConclusionsThe instruments used in this pilot study were feasible, unobtrusive and extremely suitable in AN subjects who are burdened by high incidence of cardiovascular mortality; their application could open to new approaches of vital signs monitoring in hospitals as well as in home settings.

Altered expression of connexin 43 and related molecular partners in a pig model of left ventricular dysfunction with and without dipyrydamole therapy.

Gap junctions (GJ) mediate electrical coupling between cardiac myocytes, allowing the spreading of the electrical wave responsible for synchronized contraction. GJ function can be regulated by modulation of connexon densities on membranes, connexin (Cx) phosphorylation, trafficking and degradation. Recent studies have shown that adenosine (A) involves Cx43 turnover in A1 receptor-dependent manner, and dipyridamole increases GJ coupling and amount of Cx43 in endothelial cells. As the abnormalities in GJ organization and regulation have been described in diseased myocardium, the aim of the present study was to assess the regional expression of molecules involved in GJ regulation in a model of left ventricular dysfunction (LVD). For this purpose the distribution and quantitative expression of Cx43, its phosphorylated form pS368-Cx43, PKC phosphorylated substrates, RhoA and A receptors, were investigated in experimental models of right ventricular-pacing induced LVD, undergoing concomitant dipyridamole therapy or placebo, and compared with those obtained in the myocardium from sham-operated minipigs. Results demonstrate that an altered pattern of factors involved in Cx43-made GJ regulation is present in myocardium of a dysfunctioning left ventricle. Furthermore, dipyridamole treatment, which shows a mild protective role on left ventricular function, seems to act through modulating the expression and activation of these factors as confirmed by in vitro experiments on cardiomyoblastic cell line H9c2 cells.

ECG and GSR measure and analysis using wearable systems: Application in anorexia nervosa adolescents

The objective of this study was to test the feasibility of using wearable sensors and wireless technology to measure the autonomic function and stress level in the ambulatory setting. Autonomic function was studied acquiring ECG tracings by means of a wearable sensorized chest strap. Galvanic skin response (GSR) was measured as an indicator of stress level by two electrodes positioned on the palm of the non dominant hand and a wireless acquisition module in a wrist support. Data were acquired in a group of young adolescents with anorexia nervosa (AN) as compared to controls in resting conditions. From ECG the tachogram, the mean RR intervals (meanRR), the root mean square of successive differences (RMSSD) the power of low frequency (LF) and high frequency (HF) bands and the LF/HF ratio were assessed. From GSR mean, median, variance, standard deviation, area under the curve of the sampled signal and delta between maximum and minimum conductance values were computed. All AN patients showed reduced HR and increased meanRR and RMSSD. HF increase, LF decrease and LF/HF reduction were suggestive of prevalence of parasympathetic over sympathetic activity. Additionally, AN showed a decreased GSR variance, standard deviation and delta value with respect to controls. The results of this study show that wearable sensors used in this study were feasible, unobtrusive and therefore extremely suitable for young patients providing the means for future monitoring in the home setting which may be preferable in this population burdened by high cardiovascular morbidity and mortality.

Dipyridamole in Heart Failure due to Dilated Cardiomyopathy: A Pilot Study

Introduction: Dipyridamole (DIP) might be beneficial in heart failure (HF). It has been reported to improve symptoms in observational, small-scale studies. The PRoFESS study for secondary prevention of stroke observed a reduction in the risk of HF with acetylsalicylic acid (ASA) plus DIP in comparison with clopidogrel. The present pilot study was aimed at assessing the clinical effects of DIP and ASA in dilated cardiomyopathy. Materials and Methods: Nineteen outpatients with nonischemic HF, New York Heart Association (NYHA) Class II, ejection fraction (EF) <40%, were randomized to ASA 25 mg, or ASA 25 mg plus DIP 200 mg (ASA + DIP), twice daily. They were evaluated at baseline and after 6 months for symptoms, EF, and exercise capacity through 6-min walk test. Results: Eleven subjects were in the ASA group and 8 in the ASA + DIP. Dyspnea improved, without differences between the two arms: n = 6/5/0/0 for NYHA I/II/III/IV in ASA, n = 4/3/1/0 in ASA + DIP. EF increased in both groups (ASA: from 34 [28-35%] to 40 [32-46%]; ASA + DIP from 32.5 [25.75-34%] to 36 [31.5-46%]). No change in meters walked or points in the Borg scale was observed. In a similar population, an adequately powered study would need to recruit 38 subjects. Conclusion: The study, although underpowered, did not show any difference between the two treatment strategies. While this appears in contrast with previous studies, the strict inclusion criteria, the randomized, double-blind design, and the clinical end-points give strength to our findings. A properly sized trial would be within the capabilities of a single center.