Federica Papetti

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke

Objective: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO. Methods: Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates. Results: Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%–26%) in those with 0 to 3 points to 73% (95% CI: 66%–79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%–28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%–4%) in the highest. Conclusion: Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.

Remodelling of the left ventricle in athlete's heart: a three dimensional echocardiographic and magnetic resonance imaging study.

Intensive long term athletic training is associated with morphological cardiac changes, which have extensively been described as “athlete’s heart”. These changes are considered to be physiological adaptations to increased haemodynamic overload induced by chronic and intensive exercise.1,2 For many years, morphological assessment of athlete’s heart and its differentiation from pathological cardiac conditions have been based on two dimensional and M mode echocardiography. The formulas used with these methods are based on geometric assumptions and are possible causes of inaccuracy. The objective of our study was, therefore, to validate and assess the pattern of left ventricular (LV) remodelling in a population of highly trained athletes by using three different techniques—conventional two dimensional echocardiography, three dimensional echocardiography, and magnetic resonance imaging (MRI)—and to explore the potential advantages and limitations of these techniques. Thirty subjects were studied: 18 male top level athletes, who were members of the Italian Olympic rowing team (> 3 consecutive years’ long term exercise), and 12 untrained sedentary male subjects. All subjects signed an informed consent form. Each patient underwent two dimensional echocardiography (Sonos 5500; Philips). LV mass was calculated by the Devereux formula, and LV volumes and ejection fraction (EF) were calculated by the modified Simpson’s rule. Three dimensional echocardiography was performed with a Philips Sonos 7500 equipped with the X-Matrix probe (2–4 MHz). Images were acquired by the “full volume” technique, which consists of a wide angle three dimensional pyramid built on four smaller …

Recurrent stroke predictors differ in medically treated patients with pathogenic vs other PFOs

Objective: To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score. Methods: Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of ≤6 points, n = 677). We tested 15 clinical, 5 radiologic, and 3 echocardiographic variables for associations with stroke recurrence using Cox survival models with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant. Results: Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA. For all other predictors, effects were significantly different in the 2 RoPE score categories. For the low RoPE score group, but not the high RoPE score group, older age and antiplatelet (vs warfarin) treatment predicted recurrence. Conversely, echocardiographic features (septal hypermobility and a small shunt) and a prior (clinical) stroke/TIA were significant predictors in the high but not low RoPE score group. Conclusion: Predictors of recurrence differ when PFO relatedness is classified by the RoPE score, suggesting that patients with CS and PFO form a heterogeneous group with different stroke mechanisms. Echocardiographic features were only associated with recurrence in the high RoPE score group.

Neuroimaging findings in cryptogenic stroke patients with and without patent foramen ovale.

Background and Purpose— Patent foramen ovale (PFO) and cryptogenic stroke are commonly associated but some PFOs are incidental. Specific radiological findings associated with PFO may be more likely to indicate a PFO-related cause. We examined whether specific radiological findings are associated with PFO among subjects with cryptogenic stroke and known PFO status. Methods— We analyzed the Risk of Paradoxical Embolism(RoPE) Study database of subjects with cryptogenic stroke and known PFO status, for associations between PFO and: (1) index stroke seen on imaging, (2) index stroke size, (3) index stroke location, (4) multiple index strokes, and (5) prior stroke on baseline imaging. We also compared imaging with purported high-risk echocardiographic features. Results— Subjects (N=2680) were significantly more likely to have a PFO if their index stroke was large (odds ratio [OR], 1.36; P=0.0025), seen on index imaging (OR, 1.53; P=0.003), and superficially located (OR, 1.54; P<0.0001). A prior stroke on baseline imaging was associated with not having a PFO (OR, 0.66; P<0.0001). Finding multiple index strokes was unrelated to PFO status (OR, 1.21; P=0.161). No echocardiographic variables were related to PFO status. Conclusions— This is the largest study to report the radiological characteristics of patients with cryptogenic stroke and known PFO status. Strokes that were large, radiologically apparent, superficially located, or unassociated with prior radiological infarcts were more likely to be PFO-associated than were unapparent, smaller, or deep strokes, and those accompanied by chronic infarcts. There was no association between PFO and multiple acute strokes nor between specific echocardiographic PFO features with neuroimaging findings.

Transesophageal Echocardiography in Cryptogenic Stroke and Patent Foramen Ovale: Analysis of Putative High-Risk Features From the Risk of Paradoxical Embolism Database

Background—Patent foramen ovale (PFO) is associated with cryptogenic stroke (CS), although the pathogenicity of a discovered PFO in the setting of CS is typically unclear. Transesophageal echocardiography features such as PFO size, associated hypermobile septum, and presence of a right-to-left shunt at rest have all been proposed as markers of risk. The association of these transesophageal echocardiography features with other markers of pathogenicity has not been examined. Methods and Results—We used a recently derived score based on clinical and neuroimaging features to stratify patients with PFO and CS by the probability that their stroke is PFO-attributable. We examined whether high-risk transesophageal echocardiography features are seen more frequently in patients more likely to have had a PFO-attributable stroke (n=637) compared with those less likely to have a PFO-attributable stroke (n=657). Large physiologic shunt size was not more frequently seen among those with probable PFO-attributable strokes (odds ratio [OR], 0.92; P=0.53). The presence of neither a hypermobile septum nor a right-to-left shunt at rest was detected more often in those with a probable PFO-attributable stroke (OR, 0.80; P=0.45; OR, 1.15; P=0.11, respectively). Conclusions—We found no evidence that the proposed transesophageal echocardiography risk markers of large PFO size, hypermobile septum, and presence of right-to-left shunt at rest are associated with clinical features suggesting that a CS is PFO-attributable. Additional tools to describe PFOs may be useful in helping to determine whether an observed PFO is incidental or pathogenically related to CS.

The Risk of Paradoxical Embolism (RoPE) Study: initial description of the completed database

Background Detecting a benefit from closure of patent foramen ovale in patients with cryptogenic stroke is hampered by low rates of stroke recurrence and uncertainty about the causal role of patent foramen ovale in the index event. A method to predict patent foramen ovale-attributable recurrence risk is needed. However, individual databases generally have too few stroke recurrences to support risk modeling. Prior studies of this population have been limited by low statistical power for examining factors related to recurrence. Aims The aim of this study was to develop a database to support modeling of patent foramen ovale-attributable recurrence risk by combining extant data sets. Methods We identified investigators with extant databases including subjects with cryptogenic stroke investigated for patent foramen ovale, determined the availability and characteristics of data in each database, collaboratively specified the variables to be included in the Risk of Paradoxical Embolism database, harmonized the variables across databases, and collected new primary data when necessary and feasible. Results The Risk of Paradoxical Embolism database has individual clinical, radiologic, and echocardiographic data from 12 component databases, including subjects with cryptogenic stroke both with (n = 1925) and without (n = 1749) patent foramen ovale. In the patent foramen ovale subjects, a total of 381 outcomes (stroke, transient ischemic attack, death) occurred (median follow-up 2·2 years). While there were substantial variations in data collection between studies, there was sufficient overlap to define a common set of variables suitable for risk modeling. Conclusion While individual studies are inadequate for modeling patent foramen ovale-attributable recurrence risk, collaboration between investigators has yielded a database with sufficient power to identify those patients at highest risk for a patent foramen ovale-related stroke recurrence who may have the greatest potential benefit from patent foramen ovale closure.

Patent foramen ovale and its embolic implications

This study investigates the usefulness of the echocardiographic characteristics of patent foramen ovale (PFO) in the stratification of stroke recurrence risk in patients with acute ischemic cerebral disease. Shunting at rest and a highly mobile fossa ovalis membrane are more frequently detected in stroke patients with PFO as the only identifiable cause of embolism. For PFO patients with both rest patency and membrane mobility > 6.5 mm, the risk of stroke/transient ischemic attack recurrence was 7.6% (95% CI, 0-18.0) at 12 months and 12.5% (95% CI, 0-26.1) at 24 months (p = 0.05). The association of both rest patency and high membrane mobility seems to identify those stroke patients with PFO at higher risk for further brain embolism.

Harmonic imaging with Levovist for transthoracic echocardiographic reconstruction of left ventricle in patients with post-ischemic left ventricular dysfunction and suboptimal acoustic windows

BACKGROUND Attempts to perform transthoracic 3-dimensional echocardiography (3DE) are often encumbered by poor definition of chamber borders in adult patients who have technically suboptimal acoustic windows. METHODS To assess whether harmonic imaging (HI) and contrast agents can facilitate transthoracic 3DE assessment of the left ventricle, we used fundamental imaging (FI), HI alone, and HI coupled with the echo-enhancing contrast agent Levovist in 15 consecutive patients with post-ischemic left ventricular (LV) dysfunction and technically difficult windows. Dynamic 3DE image data sets were obtained at 5-degree angles (36 slices) from a transthoracic apical view. From these data a total of 240 myocardial segments were analyzed with the use of dynamic short-axis paraplane slices at basal, middle, and apical LV levels (standard 16 segment model). For border definition, each segment was scored in random sequence on the following scale by 2 independent investigators: 0 = not seen, 1 = suboptimal visualization, and 2 = well defined. RESULTS Our results showed a significant increase in the number of well-visualized segments when harmonic mode combined with Levovist injection was compared with FI and HI alone. CONCLUSION Harmonic imaging alone improves LV assessment by 3DE when compared with FI. Contrast imaging in which Levovist is added to HI further improves the capability of transthoracic tomographic 3DE in the visualization of LV myocardial segments. This could allow 3DE by transthoracic windows to be used more widely in adults for the evaluation of LV volume and function.

Short-term evolution (9 months) of aortic atheroma in patients with or without embolic events: a follow-up transoesophageal echocardiographic study

AIMS The influence of clinical risk factors and therapeutic options on aortic plaque changes is unknown. In this study, we have evaluated aortic atheroma (AA) evolution in patients with and without embolic events. METHODS AND RESULTS We enrolled 83 patients (mean age 67.9+/-8.6 years). All patients were studied with transoesophageal echocardiography at baseline and 9 months after enrolment. Baseline atherosclerotic plaques were defined as uncomplicated (between 1 and 3.9 mm) and complicated aortic plaques (>or=4 mm). To minimize sub-millimetre errors in plaque evolution, AA progression was defined as an increase in maximal plaque thickness>or=1 mm. Similarly, regression was defined as a decrease in maximal thickness of atheromatous plaque>or=1 mm. Aortic plaques were classified as uncomplicated in 20.5% and complicated in 79.5% of patients. Fifty-five plaques (47.8%), both complicated and uncomplicated, remained unchanged. Conversely, 16 plaques (13.9%) increased (mean plaque thickness from 3.94+/-1.39 to 5.56+/-1.41 mm, P<0.001) and 44 (38.3%) decreased (mean plaque thickness from 5.25+/-1.52 to 3.79+/-1.53 mm, P<0.001). Multinomial logistic regression procedure suggests that statins increase the probability of plaque thickness reduction (OR 5.92, 95% CI 1.27-27.7, P=0.024) and decrease the probability of plaque progression (OR 0.03, 95% CI 0.01-0.28, P=0.002). CONCLUSION This study suggests that statins may reduce the risk of AA progression.

p53 codon 72 polymorphism and coronary artery disease: evidence of association with left ventricular ejection fraction.

Introduction:Recently, there has been a surge of interest on the possible relationship between p53 polymorphism and coronary atherosclerosis. The authors have investigated the possible association of p53 codon 72 polymorphism with left ventricular ejection fraction (LVEF) in subjects with and without coronary artery disease (CAD). Methods:The authors have studied 198 subjects admitted consecutively to Valmontone Hospital for CAD and 129 subjects admitted for cardiovascular diseases without CAD. Fifty-nine subjects admitted for CAD to Division of Cardiac Surgery of Tor Vergata University were also studied. All subjects were from the white population. The p53 polymorphism was evaluated using the restriction fragment length polymorphism polymerase chain reaction. Results:p53 codon 72 polymorphism is a significant independent predictor of LVEF in subjects with CAD but not in subjects with cardiovascular disease without CAD. In subjects with CAD, LVEF is significantly lower in subjects carrying the *Pro variant than in *Arg/*Arg subjects. This effect is more evident in subjects with a positive history of infarction. Conclusions:Our study points to a significant relationship of p53 codon 72 polymorphism with cardiac function in subjects with CAD.