Francisco Gonçalves

Left ventricular dysfunction in human immunodeficiency virus (HIV)-infected patients

We evaluated left ventricular function by echocardiography in a prospective study that included 98 consecutive human immunodeficiency virus (HIV)-infected patients and 40 HIV-seronegative normal controls. When compared with controls, HIV patients showed increased isovolumic relaxation time (101+/-18 ms versus 71+/-10 ms; p<0.0001) and left ventricular diastolic diameters (51+/-6 mm versus 47+/-3 mm; p<0.0005), and decreased fractional shortening (31+/-6% versus 37+/-2%; p<0.0001). Diastolic dysfunction was the most frequent finding (63% of the patients). We found depressed ejection fraction in 31 (32%) patients. Only 8 (8%) patients had symptomatic congestive heart failure. Left ventricular dysfunction was not attributable to intravenous drug abuse or to therapy. It was less severe in earlier stages of the infection (fractional shortening: acquired immunodeficiency syndrome=30%+/-6%, asymptomatic HIV-seropositives 34%+/-5%; p<0.005) and in HIV-2-infected patients. Patients with opportunistic infections (all aetiologies mixed) had more frequent congestive heart failure than those without infections (16% of the patients with versus 4% of the patients without infections; p<0.05). The fact that even asymptomatic HIV-seropositives had signs of left ventricular dysfunction (fractional shortening: asymptomatic HIV-seropositives=34%+/-5%; controls=37%+/-2%; p<0.05) favours the hypothesis of the HIV being one of the causes of these abnormalities.

The magnitude of the variation in glycemia: a new parameter for risk assessment in acute coronary syndrome?

INTRODUCTION AND OBJECTIVES The aim was to evaluate the relationship between the magnitude of the variation in the level of glycemia during hospitalization and in-hospital and long-term mortality and postdischarge endpoints in two groups of patients with acute coronary syndrome: those with and those without a previous diagnosis of diabetes. METHODS The study included 1210 patients admitted for acute coronary syndrome between May 2004 and July 2007. The study population was divided in two subgroups: patients with a previous diagnosis of diabetes (n=386) and nondiabetics (n=824). Each subgroup was further divided into four smaller groups according to the quartile of glycemia variation: diabetics (Q1: <46 mg/dl; Q2: 46-88 mg/dl; Q3: 88-164 mg/dl; Q4: >or=164 mg/dl) and nondiabetics (Q1: <14 mg/dl; Q2: 14-30 mg/dl; Q3: 30-60 mg/dl; Q4: >or=60 mg/dl). Patients were followed up for an average of 18 months after the occurrence of the acute coronary syndrome. RESULTS In diabetic patients, there was no relationship between the magnitude of the glycemia variation and in-hospital or postdischarge endpoints. In nondiabetics, no significant difference was observed in in-hospital mortality or morbidity, but statistically significant clinical differences were found during follow-up. Multivariate regression analysis showed that Q4 versus Q1, age >or=70 years, and previous antiplatelet or angiotensin-converting enzyme inhibitor therapy were independent predictors of postdischarge endpoints in the nondiabetic group. CONCLUSIONS In nondiabetic acute coronary syndrome patients, the magnitude of the variation in glycemia observed during hospitalization was a strong independent predictor of postdischarge clinical endpoints.

Nicotine Nasal Inhalation, Atrial Fibrillation and Seizures

Accessible online at: www.karger.com/journals/crd Dear Sir, Nicotine is currently used in therapeutics as a means of promoting smoking cessation. Buccal administration, transdermal administration and oral and nasal inhalation have been used. The possibility exists, not only of the transference of nicotine dependence, but also of the abuse of nicotine, especially for preparations with a more rapid onset of effects. The abuse of nicotine may lead to the development of serious clinical effects. A 45-year-old male Caucasian patient was admitted to the emergency service unit after having developed syncope and generalized seizures. The patient was found to have tachycardia (heart rate 170/min), which was shown to correspond to atrial fibrillation, and was initially treated with intravenous amiodarone (300 mg) and digoxin (0.5 mg). He was in a state of agitation. Blood pressure was 153/67 mm Hg. Bilateral mydriasis was noted with a slow pupillary light reflex. Heart and pulmonary sounds were normal, and so was the remaining neurological examination. A cerebral computed tomography scan was normal. Normal values for blood gases, hemoglobin, leukocytes, platelets, plasma sodium, potassium and urea with a slight elevation of plasma glucose (the patient was receiving a glucose-containing serum) were found. The following values for plasma enzymes were measured: creatine kinase 234 units/l, creatine kinase MB fraction 5 units/l, lactate dehydrogenase 251 units/l, myoglobin 445 ng/ml, and troponin I 0.07 ng/ml. The patient had a history of heavy tobacco smoking, but no other diseases were known to exist. For some months, he had been on a program to stop smoking with the substitution of tobacco by inhaled nicotine. The patient had developed a syndrome of nicotine abuse, and in the emergency room he used his personal inhaler several times before being convinced to stop. He confirmed that he had used the inhaler prior to the syncope for an undetermined number of times. The patient refused electrical cardioversion, and was continued to be treated with intravenous amiodarone, returning to sinus rhythm after some hours of therapy. A week later, he was examined once again. The physical examination was normal, and so was a transthoracic echocardiogram. The diagnosis of inhaled nicotine abuse associated with atrial fibrillation and seizures was established. The association between atrial fibrillation and the administration of nicotine has previously been described [1–3]. As far as we are aware of, this is the first report of an association between inhaled nicotine abuse and atrial fibrillation. It may be concluded that the nasal administration of nicotine has the potential for drug abuse, which may be dangerous given the fact that nicotine can produce relatively serious clinical effects.

Zidovudine therapy and left ventricular function and mass in human immunodeficiency virus-infected patients

Human immunodeficiency virus-infected (HIV) patients frequently present left ventricular dysfunction. Its etiology is not elucidated but zidovudine has been postulated as a possible cause factor. This study is an attempt to clarify this issue by evaluating the effect of zidovudine therapy on left ventricular function in these patients. We prospectively studied by echocardiographic examination 11 consecutive HIV-infected patients who were assigned for zidovudine therapy. We excluded patients that had a history or a physical examination suggestive of ischemic, rheumatic, congenital, or hypertensive heart disease. Patients with diabetes mellitus, excessive ethanol intake and patients on potentially cardiodepressant drugs were also excluded. Echocardiographic examination was performed immediately before the initiation of zidovudine therapy and 1 and 3 months later. Left ventricular diameters, mass and fractional shortening showed no significant difference from baseline, at 1 or 3 months after the initiation of zidovudine therapy. Our results suggest that zidovudine therapy has no effect on left ventricular diameters, mass or fractional shortening during a short term.

Comparative analysis and meta-analysis of major clinical trials with oral factor Xa inhibitors versus warfarin in atrial fibrillation

Objectives A comparative analysis of three major clinical trials with factor Xa inhibitor oral anticoagulant (XOAC) drugs versus warfarin in atrial fibrillation—Rocket-AF (rivaroxaban), Aristotle (apixaban) and Engage AF Timi 48 (edoxaban; two different doses and sets of data)—was carried out. Methods Data were extracted from the original reports (study level) and a meta-analysis was carried out. Results When compared with warfarin, XOAC therapy was associated with a decrease in haemorrhagic stroke, with a similar pattern for all regimens and meta-analysis showing a risk ratio of 0.488 (95% CI 0.396 to 0.601). Regarding total mortality, a favourable pattern was seen for all four regimens and meta-analysis showed a risk ratio of 0.892 (95% CI 0.840 to 0.947). Major bleeding and gastrointestinal bleeding provided two examples regarding which heterogeneity would seem to exist, when XOAC drugs are compared with warfarin. In what concerns the incidence of myocardial infarction, the primary end point (stroke plus systemic embolism) and ischaemic stroke, the situation is less clear. These results are inconsistent with a putative ‘group effect’ for all the seven parameters under study, and for some of them it would probably be best to look at each of the individual trial data rather than at the meta-analysis data (which seem to lack a clear biological meaning). Conclusions Apixaban, rivaroxaban and edoxaban have shown interesting effects, when compared with warfarin in clinical trials, in patients with atrial fibrillation, particularly with regard to haemorrhagic stroke and to the mortality rate. No other consistent conclusions concerning a putative ‘group effect’ can be reached at the present stage. Concerns regarding adherence to therapy, possible drug interactions, cost and current absence of antidotes may be taken into consideration when choosing an anticoagulant drug.

Can We Improve Outcomes in Patients With Previous Coronary Artery Bypass Surgery Admitted for Acute Coronary Syndrome

INTRODUCTION AND OBJECTIVES Prognosis and in-hospital management of patients with acute coronary syndrome (ACS) and a history of coronary artery bypass graft (CABG) surgery are still debated. The objective of this study was to characterize ACS patients with a CABG and to compare their in-hospital and postdischarge outcomes with those of patients without a CABG. METHODS This ongoing prospective observational study included 1,495 consecutive patients admitted for ACS to a coronary care unit and followed up for a mean of 19 months. There were two groups: group A (n=73), with CABGs; and group B (n=1,223), without CABGs. RESULTS Group A patients were more often male (86.3% versus 69.1%; P=.002), and more frequently had a history of diabetes, myocardial infarction and heart failure. Group B patients more frequently had ST-elevation myocardial infarction, and had a higher median ejection fraction (53% [interquartile range, 47%-60%] vs. 50% [42%-55%]; P< .01) and peak troponin-I concentration. There was no difference in the use of invasive techniques. Regarding medication, Group B patients were more likely to receive dual antiplatelet therapy at discharge. No significant difference was observed in in-hospital mortality (9.5% versus 5.9%; P=.2) or mortality at 1 month, 6 months or 1 year (9.8% versus 9.1%; log-rank test, P=.87) and the cumulative major adverse cardiac event rate was equally low in both groups. The presence of a CABG was associated with more readmissions for unstable angina (11.3% vs. 3.1%; P< .01). CONCLUSIONS In our ACS patients, the presence of a CABG had no significant influence on short- or medium-term outcomes, such as all-cause mortality and adverse cardiac events.

Depression predicts mortality and hospitalization in heart failure: A six-years follow-up study.

BACKGROUND The aim of this study is to evaluate the prevalence of depressive symptoms (DS) and its relation on hospitalization for cardiovascular (CV) causes and all-cause mortality risk among outpatients with HF. METHODS A prospective study was conducted on 130 adult outpatients with HF. The Beck Depression Inventory Scale-second edition (BDI-II) was used to screen for DS. All-cause mortality and hospitalization for CV causes were registered over 6 years. Logistic regression and multinomial logistic regression analysis were used to evaluate the independent prognostic value of DS on mortality and hospitalization for CV causes after adjustment for clinical risk factors. RESULTS During a mean follow-up of 6 years, 44% of patients were classified as having DS. Sixty-two participants died for all causes, representing 61% of those with DS and 37% of those without (p=0.006); Forty-nine participants (38%) were hospitalized for CV causes, representing 49% of those with DS and 29% of those without (p=0.027). Logistic regression analysis indicated that DS predicted all-cause mortality (OR: 2.905; 95% CI:1.228-6.870; p=0.006) and multinomial logistic regression indicated that DS were predictive of hospitalization for CV causes (OR: 3.169; 95% CI: 1.230-8.164; p=0.027). These associations were independent of conventional risk factors. LIMITATIONS Only outpatient sample; measure of DS only at baseline; cause of death was not known. CONCLUSION This study, first held in a portuguese population, showed that DS are independent predictors of death and hospitalization for CV causes among HF patients and its impact persists over 6 years.

Platelet aggregation at discharge, A useful tool in acute coronary syndromes?

INTRODUCTION Inhibition of platelet aggregation appears two hours after the first dose of clopidogrel, becomes significant after the second dose, and progresses to a steady-state value of 55% by day seven. Low response to clopidogrel has been associated with increased risk of stent thrombosis and ischemic events, particularly in the context of stable heart disease treated by percutaneous coronary intervention. OBJECTIVE To stratify medium-term prognosis of an acute coronary syndrome (ACS) population by platelet aggregation. METHODS We performed a prospective longitudinal study of 70 patients admitted for an ACS between May and August 2009. Platelet function was assessed by ADP-induced platelet aggregation using a commercially available kit (Multiplate(®) analyzer) at discharge. The primary endpoint was a combined outcome of mortality, non-fatal myocardial infarction, or unstable angina, with a median follow-up of 136.0 (79.0-188.0) days. RESULTS The median value of platelet aggregation was 16.0U (11.0-22.5U) with a maximum of 41.0U and a minimum of 4.0U (normal value according to the manufacturer: 53-122U). After ROC curve analysis with respect to the combined endpoint (AUC 0.72), we concluded that a value of 18.5U conferred a sensitivity of 75.0% and a specificity of 68% to that result. We therefore created two groups based on that level: group A - platelet aggregation <18.5U, n=44; and group B - platelet aggregation ≥18.5U, n=26. The groups were similar with respect to demographic data (age 60.5 [49.0-65.0] vs. 62.0 [49.0-65.0] years, p=0.21), previous cardiovascular history, and admission diagnosis. There were no associations between left ventricular ejection fraction, GRACE risk score, or length of hospital stay and platelet aggregation. The groups were also similar with respect to antiplatelet, anticoagulant, proton pump inhibitor (63.6 vs. 46.2%, p=0.15) and statin therapy. The variability in platelets and hemoglobin was also similar between groups. Combined event-free survival was higher in group A (96.0 vs. 76.7%, log-rank p<0.01). Platelet aggregation higher than 18.5U was an independent predictor of the combined event (HR 6.75, 95% CI 1.38-32.90, p=0.02). CONCLUSION In our ACS population platelet aggregation at discharge was a predictor of medium-term prognosis.

Relaxin serum levels in acute heart failure are associated with pulmonary hypertension and right heart overload

Despite the promising results of serelaxin as a new potential acute heart failure (HF) therapy, its clinical use preceded the understanding of the endogenous relaxin system in HF. We aimed to evaluate relaxin circulating levels in a population of acute HF and their association with clinical and echocardiographic parameters.

Antithrombotic therapy in nonvalvular atrial fibrillation: A narrative review

Atrial fibrillation (AF) is an important and potentially modifiable cause of stroke. It has been known since 1989 that oral anticoagulant drugs, such as warfarin, lead to a dramatic decrease in stroke associated with AF. The best risk-benefit ratio is obtained with intensity of oral anticoagulant treatment for an INR of 2-3, even in the elderly. Given the risks of anticoagulant therapy, including bleeding, individual thromboembolic risk must be assessed in patients with AF. In 2009, dabigatran was shown to be a reasonable alternative to vitamin K antagonists, establishing itself as a major alternative to warfarin in AF patients. Rivaroxaban and apixaban have subsequently also been shown to be alternatives to warfarin. When there are contraindications to vitamin K antagonists, antiplatelet agents can produce a therapeutic effect, although much less than oral anticoagulants. Apixaban may be a better alternative to aspirin in this setting. Patients with low-risk atrial fibrillation (no risk factors) have not been the subjects of specific clinical trials. It is unclear what would be the best therapeutic choice for these patients.