Molecular imaging of inflammation and intraplaque vasa vasorum: A step forward to identification of vulnerable plaques?

Current developments in cardiovascular biology and imaging enable the noninvasive molecular evaluation of atherosclerotic vascular disease. Intraplaque neovascularization sprouting from the adventitial vasa vasorum has been identified as an independent predictor of intraplaque hemorrhage and plaque rupture. These intraplaque vasa vasorum result from angiogenesis, most likely under influence of hypoxic and inflammatory stimuli. Several molecular imaging techniques are currently available. Most experience has been obtained with molecular imaging using positron emission tomography and single photon emission computed tomography. Recently, the development of targeted contrast agents has allowed molecular imaging with magnetic resonance imaging, ultrasound and computed tomography. The present review discusses the use of these molecular imaging techniques to identify inflammation and intraplaque vasa vasorum to identify vulnerable atherosclerotic plaques at risk of rupture and thrombosis. The available literature on molecular imaging techniques and molecular targets associated with inflammation and angiogenesis is discussed, and the clinical applications of molecular cardiovascular imaging and the use of molecular techniques for local drug delivery are addressed

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Clinical outcomes of implantable cardioverter-defibrillator therapy in noncompaction cardiomyopathy: a systematic review and meta-analysis

A subgroup of patients with noncompaction cardiomyopathy (NCCM) is at increased risk of ventricular arrhythmias and sudden cardiac death (SCD). In selected patients with NCCM, implantable cardioverter-defibrillator (ICD) therapy could be advantageous for preventing SCD. Currently, there is no complete overview of outcome and complications after ICD therapy in patients with NCCM. This study sought to present an overview using pooled data of currently available studies. Embase, MEDLINE, Web of Science, and Cochrane databases were searched and returned 915 studies. After a thorough examination, 12 studies on outcome and complications after ICD therapy in patients with NCCM were included. There were 275 patients (mean age 38.6 years; 47% women) with NCCM and ICD implantation. Most of the patients received an ICD for primary prevention (66%). Pooled analysis demonstrates that the appropriate ICD intervention rate was 11.95 per 100 person-years and the inappropriate ICD intervention rate was 4.8 per 100 person-years. The cardiac mortality rate was 2.37 per 100 person-years. ICD-related complications occurred in 10% of the patients, including lead malfunction and revision (4%), lead displacement (3%), infection (2%), and pneumothorax (2%). Patients with NCCM who are at increased risk of SCD may significantly benefit from ICD therapy, with a high appropriate ICD therapy rate of 11.95 per 100 person-years and a low cardiac mortality rate of 2.37 per 100 person-years. Inappropriate therapy rate of 4.8 per 100 person-years and ICD-related complications were not infrequent and may lead to patient morbidity

Impact of sex on timing and clinical outcome of septal myectomy for obstructive hypertrophic cardiomyopathy

Background: Sex disparities are common in hypertrophic cardiomyopathy (HCM). Previous research has shown that at time of myectomy, women are older, have greater impairment of diastolic function and more advanced cardiac remodeling. The clinical impact of these differences is unknown. Method: This study included 162 HCM patients (61% men) who underwent septal myectomy. Time to treatment was calculated in relation to symptom onset and diagnosis. Pre- and post-operative echocardiographic data were collected. Sex differences were assessed at baseline and in time-to-event survival analyses for the composite endpoint of all-cause mortality, cardiac transplantation, re-intervention and aborted sudden cardiac death. Results: Women were generally older at time of myectomy (57 vs. 49 years, p 0.05), but a shorter time since diagnosis compared to men (2.6 [1.2–7.0] vs. 4.3 [2.4–8.3] years, p = 0.02). Mean wall thickness and left atrial diameter were the same for men and women, but were higher in women when correcting for body surface area (absolute: 20 vs. 19 mm, 48 vs 46 mm, p ≥ 0.05; corrected: 9.7 vs. 11.2 mm/m2, 23.4 vs. 26.3 mm/m2, p 0.05). Conclusion: In conclusion, although women present later in life and seem to have more advanced disease on echocardiography, time until myectomy was similar and clinical outcomes after myectomy are favourable for both men and women

Noninvasive imaging of the vulnerable atherosclerotic plaque

Atherosclerosis is an inflammatory disease, complicated by progressively increasing atherosclerotic plaques that eventually may rupture. Plaque rupture is a major cause of cardiovascular events, such as unstable angina, myocardial infarction, and stroke. A number of noninvasive imaging techniques have been developed to evaluate the vascular wall in an attempt to identify so-called vulnerable atherosclerotic plaques that are prone to rupture. The purpose of the present review is to systematically investigate the accuracy of noninvasive imaging techniques in the identification of plaque components and morphologic characteristics associated with plaque vulnerability, assessing their clinical and diagnostic value

Correlation of carotid artery atherosclerotic lesion echogenicity and severity at standard US with intraplaque neovascularization detected at contrast-enhanced US

To correlate echogenicity and severity of atherosclerotic carotid artery lesions at standard ultrasonography (US) with the degree of intraplaque neovascularization at contrast material-enhanced (CE) US

Incidence of recovery of contractile function following revascularization in patients with ischemic left ventricular dysfunction.

Contractile function in patients with ischemic left ventricular (LV) dysfunction may improve after myocardial revascularization. Currently, the incidence of contractile function recovery after revascularization in these patients is unclear. The aim of this study was to assess the incidence of function improvement after myocardial revascularization in patients with ischemic LV dysfunction. A total of 258 consecutive patients (aged 59 +/- 12 years) with severely depressed LV ejection fractions (EFs) due to chronic coronary artery disease and heart failure symptoms were studied. All patients underwent radionuclide ventriculography and 2-dimensional echocardiography at rest before and 3 to 6 months after revascularization. At baseline, 1,330 segments (32%) were normal and 2,775 segments (68%) were dysfunctional. Improvement after revascularization occurred in 736 of the 2,775 dysfunctional segments (27%). Overall, LVEF improved from 29 +/- 7 to 32 +/- 9 (p /=5% postrevascularization) was present in 101 patients (39%). Improvement of LVEF after revascularization was frequently observed in patients with a more severely impaired baseline LVEF. At least 3 segments with improvement of function were needed for an improvement of LVEF of >/=5%

Why do patients with ischemic cardiomyopathy and a substantial amount of viable myocardium not always recover in function after revascularization?

In patients with ischemic cardiomyopathy and a substantial amount of dysfunctional but viable myocardium, myocardial revascularization may improve left ventricular ejection fraction. The aim of this study was to evaluate why not all patients with a substantial amount of viable tissue recover in function after revascularization