Immune Checkpoint Inhibitors and Scleroderma: Data from the European Pharmacovigilance Database.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can be commonly associated with the occurrence of immune-related adverse drug reactions (irADRs), which can involve any tissue and organ. ICI-induced skin toxicities are common irADRs and they can be a consequence of a rheumatologic ADR, such as in the case of scleroderma. A recent literature review reported that scleroderma and scleroderma mimics represent a group of disorders with significant morbidity that have been described during ICIs' use. OBJECTIVE AND METHODS: Considering the clinical significance of scleroderma cases, the present study aimed to analyze the occurrence of these events in patients receiving ICIs by describing data from individual case safety reports (ICSRs) retrieved from the European spontaneous reporting system, EudraVigilance (EV). RESULTS: Until February 2023, 70 ICSRs with at least one ICI as the suspected drug and at least one preferred term (PT) related to scleroderma cases were retrieved from the EV. Pembrolizumab was reported as suspected in 41 ICSRs, nivolumab in 25 ICSRs, ipilimumab in 8 ICSRs and atezolizumab in 3 ICSRs. Patients who experienced scleroderma cases were adults, and no differences were found in terms of sex distribution. Scleroderma cases were mainly classified as serious, while the outcome was mainly reported as favorable. The most reported PTs were scleroderma and morphea. CONCLUSIONS: Considering the seriousness of ICI-induced scleroderma cases and the recent marketing authorization of some ICIs, we believe that further high-quality clinical studies should be conducted on this topic to better estimate the impact of these events in patients with cancer.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and the reporting of falls and fractures: an european pharmacovigilance analysis.

Background: The risk of falls and bone fractures with sodium-glucose co-transporter-2 (SGLT2) inhibitors has been characterized by conflicting evidence. Therefore, we decided to investigate the reporting probability of falls and fractures by comparing SGLT2 inhibitors with DPP4 inhibitors. Methods A retrospective, pharmacovigilance study of the European database of Individual Case Safety Reports (ICSRs) was conducted. Disproportionality analyses (Reporting Odds Ratio, ROR) were conducted to compare the reporting probability of falls or fracture between treatments. Results A total of 507 ICSRs reporting at least one fall or fracture with SGLT2 inhibitors were identified. The most reported SGLT2 inhibitor was canagliflozin (N = 188; 36.9%), followed by empagliflozin (N = 176; 34.5%), and dapagliflozin (N = 143; 28.0%). A total of 653 events related to fall or bone fracture were reported. Fall was the most reported event (N = 333; 51.0%). Among fractures (N = 320; 49.0%), the most reported were foot fractures (N = 40; 6.1%) and hip fractures (N = 32; 4.9%). SGLT2 inhibitors were associated with a lower reporting probability of fall than DPP4 inhibitors (ROR, 0.66; 95%CI, 0.57-0.78). The lower reporting probability of fall was also observed when the single SGLT2 inhibitor was compared to DPP4 inhibitors: dapagliflozin (ROR, 0.67; 95%CI, 0.53-0.83), canagliflozin (ROR, 0.56; 95%CI, 0.45-0.70), and empagliflozin (ROR, 0.77; 95%CI, 0.63-0.94). For fractures, canagliflozin showed a slightly significant increased reporting when compared with DPP4 inhibitors (not confirmed in the sensitivity analysis), whereas all other comparison showed no statistically significant difference. Conclusion SGLT2 inhibitors were associated with a lower reporting probability of fall than DPP4 inhibitors, in accordance with the reassuring evidence about the safety profile of these drugs. Future researches will help to confirm their long-term safety profile.

COVID-19 Vaccines and Atrial Fibrillation: Analysis of the Post-Marketing Pharmacovigilance European Database.

Atrial fibrillation (AF) has been described in COVID-19 patients. Recently, some case reports and US pharmacovigilance analyses described AF onset as a rare adverse event following COVID-19 vaccination. The possible correlation is unclear. We systematically analyzed the reports of AF related to COVID-19 vaccines collected in the European pharmacovigilance database, EudraVigilance (EV), from 2020 to November 2022. We carried out descriptive and disproportionality analyses. Moreover, we performed a sensitivity analysis, excluding the reports describing other possible alternative AF causes (pericarditis, myocarditis, COVID-19, or other drugs that may cause/exacerbate AF). Overall, we retrieved 6226 reports, which represented only 0.3% of all those related to COVID-19 vaccines collected in EV during our study period. AF reports mainly referred to adults (in particular, >65 years old), with an equal distribution in sex. Reports were mainly related to tozinameran (54.04%), elasomeran (28.3%), and ChAdOx1-S (14.32%). The reported AF required patient hospitalization in 35% of cases and resulted in a life-threatening condition in 10% of cases. The AF duration (when reported) was highly variable, but the majority of the events had a short duration (moda = 24 h). Although an increased frequency of AF reporting with mRNA vaccines emerges from our study, other investigations are required to investigate the possible correlation between COVID-19 vaccination and the rare AF occurrence.

Immune-related adverse events and immune checkpoint inhibitors: a focus on neurotoxicity and clinical management.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) represent an innovative therapeutic approach of oncologic diseases. In Europe, this therapeutic class currently includes eight agents: ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab, durvalumab and dostarlimab. Despite their proved clinical benefits, they can induce immune-related adverse events (irADRs), that can also involve the nervous system. AREAS COVERED: Despite their rarity, neurological irADRs related to ICI-treatments can lead to serious and dangerous complications, highlighting the importance of a strict monitoring of patients. This review aims to summarize the safety profile of ICIs, focusing on their possible neurotoxicity and their management. EXPERT OPINION: Considering the clinical relevance of ICIs-induced irADRs and that the underlying mechanisms are still not completely understood, the use of ICIs requires extensive safety monitoring. Before to prescribe immunotherapy, oncologists should identify possible individual risk factors that may favor the onset of irADRs. Oncologists and general practitioners should inform and educate patients about the specific toxicities of immunological checkpoint inhibitors, including nervous ones. They should be carefully monitored at least 6 months after the end of treatment. ICIs-related nervous toxicities require a multidisciplinary management, in which neurologists and clinical pharmacologists should participate.

Do immune checkpoint inhibitors share the same pharmacological feature in the risk of cardiac arrhythmias?

BACKGROUND: Despite the available evidence showing an association between cardiac arrhythmia and Immune Checkpoint Inhibitors (ICIs), few studies have compared this risk between ICIs. OBJECTIVES: We aim to evaluate Individual Case Safety Reports (ICSRs) of ICIs-induced cardiac arrhythmias and compare the reporting frequency of cardiac arrhythmias among ICIs. METHODS: ICSRs were retrieved from the European Pharmacovigilance database (Eudravigilance). ICSRs were classified based on the ICI reported (pembrolizumab, nivolumab, atezolizumab, ipilimumab, durvalumab, avelumab, cemiplimab, and dostarlimab). If more than one ICI was reported, the ICSR was classified as a combination of ICIs. ICSRs of ICI-related arrhythmias were described and the reporting frequency of cardiac arrhythmias was assessed by applying the reporting odds ratio (ROR) and its 95 % confidence interval (95 %CI). RESULTS: A total of 1262 ICSRs were retrieved, of which 147 (11.65 %) were related to combinations of ICIs. A total of 1426 events of cardiac arrhythmias were identified. The three most reported events were atrial fibrillation, tachycardia, and cardiac arrest. Ipilimumab was associated with a reduced reporting frequency of cardiac arrhythmias compared to all other ICIs (ROR 0.71, 95 %CI 0.55-0.92; p = 0.009). Anti-PD1 was associated with a higher reporting frequency of cardiac arrhythmias than anti-CTLA4 (ROR 1.47, 95 %CI 1.14-1.90; p = 0.003). CONCLUSION: This study is the first comparing ICIs for the risk of cardiac arrhythmias. We found that ipilimumab was the only ICI associated with a reduced reporting frequency. Further high-quality studies are needed to confirm our results.

Nuclear assessment of right ventricle.

For many years, the right ventricle (RV) has been considered a passive chamber with a relatively insignificant role in the overall functionality of the heart. More recently, the role of performance of RV in the clinical presentation and long-term prognosis of multiple pathological states, such as congenital heart diseases, chronic heart failure, pulmonary hypertension, and chronic obstructive pulmonary disease. Despite echocardiography and cardiac magnetic resonance are the 2 most commonly used imaging techniques for noninvasive assessment of RV, nuclear imaging provides new opportunities for comprehensive evaluation of RV from a single study, because it can assess right ventricular perfusion and metabolism as well as morphology and ejection fraction. In this review, we summarize the application of radionuclide techniques (nuclear cardiology) for evaluation of the RV, focusing on its emerging role in the assessment of right ventricular perfusion and metabolism.

Prevalence and severity of asymptomatic coronary and carotid artery disease in patients with abdominal aortic aneurysm.

We evaluated the prevalence and severity of occult coronary artery disease (CAD) and cerebrovascular disease (CeVD) in patients with abdominal aortic aneurysm (AAA). We studied 100 consecutive patients with no history of CAD, normal electrocardiogram, normal systolic function, and no angina or dyspnea. All patients underwent carotid Doppler study and invasive coronary angiography. Significant CAD was observed in 61% of patients. In all, 51% of patients with significant CAD showed either left main (n = 7), 3-vessel (n = 17), or proximal left anterior descending (n = 7) CAD, corresponding to 31% of the total cohort. Cerebrovascular disease was detected in 53% of patients, and in 38% of them was significant (peak systolic flow velocity ≥125 <230 cm/s). In 36% of patients with CeVD either left main (n = 5), 3-vessel (n = 11), or proximal left anterior descending (n = 3) CAD was observed. Severe asymptomatic CAD is prevalent in AAA, and 31% of patients fulfill indications for coronary revascularization.

Prognostic role of transthoracic echocardiography in patients affected by heart failure and reduced ejection fraction.

Heart failure with reduced ejection fraction is a common and malignant condition, which recognizes a lot of causes and that carries a poor long-term prognosis. All patients with reduced left ventricular ejection fraction, both asymptomatic and symptomatic, should be evaluated with transthoracic echocardiography as a depth analysis of first level, due to its characteristics of accuracy, availability, safety and low costs. In fact, echocardiography is an essential tool to establish not only the diagnosis, but also the aetiology and the understanding pathophysiology of heart failure. Moreover, by the new more sensitive and more specific echocardiographic technologies, such as tissue Doppler imaging or strain rate or speckle tracking or three-dimensional echocardiography, it is possible to identify other recognized high-risk parameters associated with adverse outcome, which are useful to guide therapy and follow-up management of heart failure patients. Therefore, this review would underline the prognostic role of some echocardiographic parameters in the evaluation and management of patients with heart failure and reduced ejection fraction.

Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis.

OBJECTIVES: The purpose of this paper was to assess whether statins reduce all-cause mortality and cardiovascular (CV) events in elderly people without established CV disease. BACKGROUND: Because of population aging, prevention of CV disease in the elderly is relevant. In elderly patients with previous CV events, the use of statins is recommended by guidelines, whereas the benefits of these drugs in elderly subjects without previous CV events are still debated. METHODS: Randomized trials comparing statins versus placebo and reporting all-cause and CV mortality, myocardial infarction (MI), stroke, and new cancer onset in elderly subjects (age ≥ 65 years) without established CV disease were included. RESULTS: Eight trials enrolling 24,674 subjects (42.7% females; mean age 73.0 ± 2.9 years; mean follow up 3.5 ± 1.5 years) were included in analyses. Statins, compared with placebo, significantly reduced the risk of MI by 39.4% (relative risk [RR]: 0.606 [95% confidence interval (CI): 0.434 to 0.847]; p = 0.003) and the risk of stroke by 23.8% (RR: 0.762 [95% CI: 0.626 to 0.926]; p = 0.006). In contrast, the risk of all-cause death (RR: 0.941 [95% CI: 0.856 to 1.035]; p = 0.210) and of CV death (RR: 0.907 [95% CI: 0.686 to 1.199]; p = 0.493) were not significantly reduced. New cancer onset did not differ between statin- and placebo-treated subjects (RR: 0.989 [95% CI: 0.851 to 1.151]; p = 0.890). CONCLUSIONS: In elderly subjects at high CV risk without established CV disease, statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term.

The prognostic value of normal stress cardiac magnetic resonance in patients with known or suspected coronary artery disease: a meta-analysis.

BACKGROUND: Ischemia detection with stress cardiac magnetic resonance (CMR) is typically based on induction of either myocardial perfusion defect or wall motion abnormality. Single-center studies have shown the high value of stress CMR for risk stratification. The aim of this study was to define the prognostic value of stress CMR for prediction of adverse cardiac events in patients with known or suspected coronary artery disease. METHODS AND RESULTS: Studies published between January 1985 and April 2012 were identified by database search. We included studies using stress CMR to evaluate subjects with known or suspected coronary artery disease and providing primary data on clinical outcomes of nonfatal myocardial infarction or cardiac death with a follow-up time ≥3 months. Total of 14 studies were finally included, recruiting 12 178 patients. The negative predictive value for nonfatal myocardial infarction and cardiac death of normal CMR was 98.12% (95% confidence interval, 97.26-98.83) during a weighted mean follow-up of 25.3 months, resulting in estimated event rate after a negative test equal to 1.88% (95% confidence interval, 1.17-2.74). The corresponding annualized event rate after a negative test was 1.03%. Comparable negative predictive values for major coronary events were obtained in studies considering the absence of inducible perfusion defect compared with those evaluating the absence of inducible wall motion abnormality (98.39% versus 97.31%, respectively; P=0.227 by meta-regression analysis). CONCLUSIONS: Stress CMR has a high negative predictive value for adverse cardiac events, and the absence of inducible perfusion defect or wall motion abnormality shows a similar ability to identify low-risk patients with known or suspected coronary artery disease.

Prevalence and severity of asymptomatic coronary and carotid artery disease in patients with lower limbs arterial disease.

OBJECTIVES: Lower limbs arterial disease (LLAD) portends high risk of cardiovascular events. Yet, the prevalence of significant occult coronary artery (CAD) and cerebrovascular (CVD) disease in patients without CAD and CVD has not been widely investigated. The purpose of this study was to evaluate the prevalence and severity of CAD and CVD in patients with LLAD of the lower extremities. METHODS: From January 2008 through December 2011 we studied 200 consecutive patients admitted for symptomatic LLAD, with normal global and regional systolic function, no symptoms of angina or dyspnea. During hospital admission all patients underwent carotid Doppler study and invasive angiography. RESULTS: Significant CAD was observed in 110 of 200 (55%) patients. Fifty-eight (53%) patients with significant CAD showed either left main (n = 7), 3 vessels (n = 35) or proximal left anterior descending (n = 16) CAD, corresponding to 29% of total cohort. CVD was detected in 86(43%) patients (69% with concomitant CAD), including 30(35%) with severe and 15(17%) with significant disease. In thirty-two (37%) patients with CVD either left main (n = 4), 3 vessels (n = 18) or proximal left anterior descending (n = 10) CAD was observed. The percent of patients with left main, 3 vessel or proximal left anterior descending stenosis among those with CVD was significantly higher (37%; p = 0.03) compared to those without CVD. CONCLUSIONS: Severe asymptomatic CAD and CVD are quite prevalent in LLAD, and 29% of patients fulfill indications for coronary revascularization. Cost-effective strategies to detect occult CAD or CVD in LLAD patients need to be investigated in large multicenter studies.

Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries: a digital reactive hyperemia study.

BACKGROUND: To assess endothelial function (EF) in type 2 diabetic patients with angiographically normal coronaries compared to diabetic patients with obstructive coronary artery disease (CAD) and to non-diabetic patients, with and without CAD. METHODS: One hundred eighty-three patients undergoing coronary angiography were divided in: group 1 with diabetes mellitus (DM) and CAD (n = 58); group 2 with DM without CAD (n = 58); group 3 with CAD without DM (n = 31) and group 4 without CAD and DM (n = 36). EF was assessed by reactive hyperemia index (RHI) using a fingertip peripheral arterial tonometry and compared to values obtained in 20 healthy volunteers. RESULTS: RHI was significantly lower in patients with DM compared to patients without DM (1.69 ± 0.38 vs 1.84 ± 0.44; p = 0.019). RHI was comparable among groups 1, 2 and 3, each value being significantly lower compared to group 4 (2 ± 0.44; p<0.001 vs group 1; p<0.005 vs group 2; p<0.002 vs group 3). At multivariate analysis DM and CAD were significant predictors of endothelial dysfunction (ED) (OR = 2.29; p = 0.012; OR = 2.76; p = 0.001, respectively), whereas diabetic patients (n = 116) CAD and glycated haemoglobin (HbA1c) were independent significant predictors of ED (OR = 3.05; p = 0.009; OR = 1.96; p = 0.004, respectively). Diabetic patients with ED (n = 67) had higher levels of HbA1c than diabetic patients with normal endothelial function (7.35 ± 0.97 vs 6.87 ± 0.90; p = 0.008) and RHI inversely correlated to HbA1c (p = 0.02; r = -0.210). CONCLUSIONS: Diabetic patients with and without CAD show significantly impaired peripheral vascular function compared to non-diabetic patients without CAD. ED in diabetic patients without CAD is comparable to that of patients with CAD but without DM. HbA1c is a weak independent predictor of ED.

[Endothelial function as a marker of pre-clinical atherosclerosis: assessment techniques and clinical implications]. / Funzione endoteliale quale marker di aterosclerosi subclinica: metodiche di valutazione ed applicazioni cliniche.

Endothelium plays a key role in maintenance of vascular homeostasis. Cardiovascular risk factors promote development of endothelial dysfunction, characterized by increased vasoconstriction and by procoagulant/pro-inflammatory endothelial activities. In coronary artery, endothelium-dependent dilation improves blood flow, while the occurrence of endothelial dysfunction reduces myocardial perfusion, so new methods have been developed for assessment of endothelial function in coronary and peripheral arteries. The quantitative angiography with intracoronary infusion of acetylcholine remains the "gold standard" to assess the endothelium-dependent vasodilatation. The use of this technique is restricted to patients who have a clinical indication for coronary angiography, so new imaging methods have been considered for noninvasive diagnosis of coronary microvascular disease, such as magnetic resonance imaging phase contrast and positron emission tomography. The advent of new techniques has facilitated testing of endothelial dysfunction in peripheral arteries with non-invasive methods. This review presents available in-vivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic tools include local vasodilatation by venous occlusion plethysmography and assessment of flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, laser Doppler flowmetry. The possibility to detect endothelial dysfunction as an early marker of atherosclerosis makes these instruments useful for early stratification of patients at risk for cardiovascular events. Aim of this review is to summarize the characteristics of non-invasive assessment of endothelial function in order to optimize cardiovascular risk management.

A meta-analysis reporting effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients without heart failure.

OBJECTIVES: The goal of the study was to assess the effects of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) on the composite of cardiovascular (CV) death, myocardial infarction (MI), and stroke, and on all-cause death, new-onset heart failure (HF), and new-onset diabetes mellitus (DM) in high-risk patients without HF. BACKGROUND: ACE-Is reduce CV events in high-risk patients without HF whereas the effects of ARBs are less certain. METHODS: Twenty-six randomized trials comparing ARBs or ACE-Is versus placebo in 108,212 patients without HF were collected in a meta-analysis and analyzed for the risk of the composite outcome, all-cause death, new-onset HF, and new-onset DM. RESULTS: ACE-Is significantly reduced the risk of the composite outcome (odds ratio [OR]: 0.830 [95% confidence interval (CI): 0.744 to 0.927]; p = 0.001), MI (OR: 0.811 [95% CI: 0.748 to 0.879]; p < 0.001), stroke (OR: 0.796 [95% CI: 0.682 to 0.928]; p < 0.004), all-cause death (OR: 0.908 [95% CI: 0.845 to 0.975]; p = 0.008), new-onset HF (OR: 0.789 [95% CI: 0.686 to 0.908]; p = 0.001), and new-onset DM (OR: 0.851 [95% CI: 0.749 to 0.965]; p < 0.012). ARBs significantly reduced the risk of the composite outcome (OR: 0.920 [95% CI: 0.869 to 0.975], p = 0.005), stroke (OR: 0.900 [95% CI: 0.830 to 0.977], p = 0.011), and new-onset DM (OR: 0.855 [95% CI: 0.798 to 0.915]; p < 0.001). CONCLUSIONS: In patients at high CV risk without HF, ACE-Is and ARBs reduced the risk of the composite outcome of CV death, MI, and stroke. ACE-Is also reduced the risk of all-cause death, new-onset HF, and new-onset DM. Thus, ARBs represent a valuable option to reduce CV mortality and morbidity in patients in whom ACE-Is cannot be used.

[Endothelial dysfunction in type 2 diabetic patients with normal coronary arteries. A peripheral arterial tonometry study]. / Evidenza di disfunzione endoteliale in pazienti diabetici di tipo 2 con arterie coronariche angiograficamente normali. Studio con tonometria arteriosa digitale.

AIM: to evaluate endothelial function (EF) in diabetic and non-diabetic patients without CAD by peripheral artery tonometry (PAT) technique. METHODS: a cohort of 94 patients (55 men and 39 postmenopausal women; mean age 63 +/- 9 years) undergoing coronary angiography was divided into 2 groups: 58 patients with DM and (group 1) and 36 patients without DM. Endothelial dysfunction (ED) was assessed by digital pulse amplitude, using a fingertip peripheral arterial tonometry (PAT). As a measure of ED, reactive hyperemia index (RHI) was calculated as the ratio of the digital pulse volume during reactive hyperemia following 5 min ischemia and its basal value. RESULTS: prevalence of cardiovascular risk factors was similar between the two groups. RHI values were significantly lower in diabetic patients compared to non-diabetics (1.72 +/- 0.34 vs 2.00 +/- 0.44; p < 0.005) and they correlated with levels of glycosylated hemoglobin (p = 0.05; r = -0.266). CONCLUSION: despite similar level of other risk factors, EF was much more impaired in diabetic patients than in non-diabetics. These evidences further support the impact of DM on cardiovascular risk.

Implantable cardioverter defibrillator to prevent sudden cardiac death in a patient with systemic sclerosis: A clinical case.

Ventricular arrhythmias are frequent in patients with systemic sclerosis and may result in sudden cardiac death. We report the case of a patient with systemic sclerosis and recent syncopes in whom induction of unstable sustained ventricular tachycardia of 2 different morphologies accompanied by syncopal event was demonstrated at the electrophysiological study. He was then implanted a 3rd generation implantable cardioverter defibrillator and remained thereafter asymptomatic. We suggest that aggressive testing is warranted in systemic sclerosis patients with suspected malignant arrhythmias to identify candidates for defibrillator implantation and prevent sudden deaths.

N-terminal pro-b-type natriuretic peptide and left atrial function in patients with congestive heart failure and severely reduced ejection fraction.

AIMS: Amino-terminal portion of pro-B-type natriuretic peptide (NT-pro-BNP) is a valuable diagnostic and prognostic marker in congestive heart failure (CHF). In CHF patients, elevation of natriuretic peptide levels correlate with decreased left ventricular (LV) ejection fraction (EF) and increased left atrial (LA) volumes, but a correlation with LA function that is a determinant of haemodynamic and clinical status in CHF with independent prognostic value has never been investigated. Aim of this study was to evaluate the relationship between cardiac neurohormonal activation and LA function in patients with CHF due to dilated cardiomyopathy. METHODS AND RESULTS: One hundred and one patients (86% males; mean age, 64 ± 11 years) with dilated ischaemic or non-ischaemic cardiomyopathy, LV EF ≤45% (mean LV EF, 33 ± 8%), and New York Heart Association class II-IV underwent transthoracic echocardiography to evaluate LA fractional active and total emptying from M- and B-Mode images, and, on the same day, venous blood sample collection to dose NT-pro-BNP. By univariate analyses, NT-pro-BNP significantly correlated to age, LA dimensions, LA function indexes, EF, and functional class. At multivariate analysis, LV EF and M- or B-Mode indexes of LA function were the only independent predictors of NT-pro-BNP values. A NT-pro-BNP cut-off of 1480 pg/mL identified LA dysfunction with 89% specificity and 54% sensitivity. CONCLUSION: In CHF patients with severely impaired systolic function, NT-pro-BNP levels reflect LA and LV dysfunction. These data should prompt studies to investigate the relationship between changes of LA function and NT-pro-BNP levels and their clinical value as prognostic and therapeutic targets in CHF.

Molecular imaging of atherosclerosis in translational medicine.

Functional characterization of atherosclerosis is a promising application of molecular imaging. Radionuclide-based techniques for molecular imaging in the large arteries (e.g. aorta and carotids), along with ultrasound and magnetic resonance imaging (MRI), have been studied both experimentally and in clinical studies. Technical factors including cardiac and respiratory motion, low spatial resolution and partial volume effects mean that noninvasive molecular imaging of atherosclerosis in the coronary arteries is not ready for prime time. Positron emission tomography imaging with fluorodeoxyglucose can measure vascular inflammation in the large arteries with high reproducibility, and signal change in response to anti-inflammatory therapy has been described. MRI has proven of value for quantifying carotid artery inflammation when iron oxide nanoparticles are used as a contrast agent. Macrophage accumulation of the iron particles allows regression of inflammation to be measured with drug therapy. Similarly, contrast-enhanced ultrasound imaging is also being evaluated for functional characterization of atherosclerotic plaques. For all of these techniques, however, large-scale clinical trials are mandatory to define the prognostic importance of the imaging signals in terms of risk of future vascular events.

Prognostic role of myocardial single photon emission computed tomography in the elderly.

The increase in average life expectancy will move the burden of coronary artery disease (CAD) to older patients. Myocardial perfusion imaging by single photon emission computed tomography (SPECT) has been extensively validated for diagnosis and prognostic evaluation in large population series. Yet, its use is usually limited in elderly patients in whom, despite increased absolute cardiovascular risk, diagnostic and therapeutic work-up is often underperformed. American College of Cardiology/American Heart Association guidelines recommend exercise ECG testing as the initial noninvasive method for assessment of CAD in patients with a normal or near-normal resting ECG, regardless of age. However, a considerable proportion of elderly patients is unable to reach an adequate workload during the exercise test and the majority of those undergoing for standard exercise treadmill score are classified as intermediate risk. In elderly patients, SPECT imaging may provide valuable diagnostic and prognostic information for clinical management. In particular, normal or near normal SPECT identifies elderly patients at low risk of major adverse cardiac events at the short-term follow-up.

Cardiovascular effects of antiretroviral drugs: clinical review.

In HIV infected patients an increased occurence of cardiac events has been demontrated from the introduction of highly active antiretroviral therapy (HAART). Antiretroviral drugs' regimens are, in fact, associated with several metabolic side effects, such as dyslipidemia, impaired glucose metabolism and abnormal body fat distribution, that increase the cardiovascular risk of HIV subjects. In addition, HIV infection itself, the chronic inflammatory status and the relevant presence in this population of some of the traditional cardiovascular risk factors contribute to an higher incidence of cardio and cerebrovascular events. In last years several studies showed the occurence of carotid vascular impairment in patients in treatment with protease inhibitors (PI). Similarly the DAD Study reported an increase of 26% of the risk of myocardial infarction in patients on HAART and that this risk is indipendently associated with longer exposure to PI, even after multivariate adjustments. A correct evaluation of the metabolic status before starting HAART and an adeguate control of the drugs-related metabolic abnormalities may reduce the incidence of cardiac events and still improve HIV patients prognosis. This review will focus on the metbolic effects of antiretroviral drugs and to the contribution of combination antiretroviral therapy on cardiovascular risk.