Abcd2

Abcd2 and stroke risk

Cardiac papillary fibroelastoma: A comprehensive

 

Cardiac papillary fibroelastoma: A comprehensive

analysis of 725 cases

Ramesh M. Gowda, MD,a Ijaz A. Khan, MD, FACP, FACC,b Chandra K. Nair, MD, FACP, FACC,b

Nirav J. Mehta, MD,b Balendu C. Vasavada, MD, FACC,a and Terrence J. Sacchi, MD, FACCa Omaha, Neb, and

Brooklyn, NY

 

(Am Heart J 2003;146:404–10.)

 

Seven hundred twenty-five cases of CPF were identified. Males comprised 55% of

patients. Highest prevalence was in the 8th decade of life. The valvular surface was the predominant locations of tumor.

The most commonly involved valve was the aortic valve, followed by the mitral valve. The left ventricle was the predominant

nonvalvular site involved. No clear risk factor for development of CPF has been reported. Size of the tumor varied

from 2 mm to 70 mm. Clinically, CPFs have presented with transient ischemic attack, stroke, myocardial infarction, sudden

death, heart failure, presyncope, syncope, pulmonary embolism, blindness, and peripheral embolism. Tumor mobility

was the only independent predictor of CPF-related death or nonfatal embolization. Symptomatic patients should be

treated surgically because the successful complete resection of CPF is curative and the long-term postoperative prognosis

is excellent. The symptomatic patients who are not surgical candidates could be offered long-term oral anticoagulation,

although no randomized controlled data are available on its efficacy. Asymptomatic patients could be treated surgically if

the tumor is mobile, as the tumor mobility is the independent predictor of death or nonfatal embolization. Asymptomatic

patients with nonmobile CPF could be followed-up closely with periodic clinical evaluation and echocardiography, and

receive surgical intervention when symptoms develop or the tumor becomes mobile.

 

Additional pearls from this review:

 

1. 

Cardiac

papillary fibroelastomas (CPF), the second most

common primary cardiac tumors, are benign endocardial

papillomas predominantly affecting the cardiac

valves, and account for three fourths of all cardiac valvular

tumors. They consist of a small, highly papillary,

pedunculated and avascular tumor, covered by a single

layer of endothelium, containing variable amounts of

fine elastic fibrils arranged in whorls in a hyaline

stroma.

2.

Although CPF are rare and histologically benign

tumors, they may result in life-threatening complications,

such as stroke, acute valve dysfunction, embolism,

and sudden death.

3.

The most common clinical presentation was of transient

ischemic attack or stroke (n 120 patients). The

other manifestations were angina (n 49 patients),

myocardial infarction (n 28 patients), sudden death

(n 21 patients), heart failure (n 24 patients), presyncope

or syncope (n 12 patients), pulmonary

embolism (n 3 patients), blindness (n 7 patients),

mesenteric ischemia (n 2 patients), peripheral emboli

(n 3 patients), and renal infarction (n 1 patient).

In patients with mitral valve tumors, stroke was

the most common clinical presentation, but in patients

with aortic valve tumors, sudden death and myocardial

infarction were the 2 most common presentations. In

a large number of patients, tumors were identified as

incidental findings at autopsy (n 209 patients) or at

surgery for other cardiac reasons (n 9 patients).

4.

The major immunophenotypic

difference between CPF and cardiac myxoma was the

frequent presence of muscle-specific actin in the stellate

cells of the stroma in cardiac myxoma but not in

CPF.

5. 

Because most CPF are located in the left heart (95%),

systemic embolism in particular is frequent. In a majority

of CPF cases with embolism, the cerebral arteries,

including retinal arteries, are affected, and transient

ischemic attack, stroke, and sudden visual loss have

been reported

6.

The classic

diastolic tumor plop, which is heard in one third of

patients with atrial myxoma, has not been described

with CPF, except in 1 case where a tricuspid valve

CPF was associated with a tumor plop.46

7. Diferential diagnostic analysis:

Cardiac myxoma

is a predominant left atrial tumor, and is usually attached

to the atrial septum by a stalk. Histologically,

myxoma differs from CPF by presence of polygonal

 

myxoma cells and blood vessels within papillae.125

The papillae of CPF are devoid of blood vessels. Calretinin

staining may be a useful way to distinguish between

myxoma and CPF.218 Cardiac fibroma, which is

a separate entity, frequently demonstrates calcification

and cystic degeneration. Cardiac rhabdomyomas are

predominant myocardial neoplasms seen in infants and

children.214 Metastatic tumors of the heart are more

frequent than the primary tumors.1 Unlike CPF, malignant

tumors commonly involve the pericardium and

myocardium, and are usually accompanied by systemic

symptoms. However, with both primary and metastatic

tumors, the clinical course may be complicated by emboli.

Ljevak J, Mismas A, Bazina A, et al.
An infrequent type of stroke with an unusual cause and successful therapy: basilar artery occlusion caused by a cardiac papillary fibroelastoma recanalized 12 hours after onset [In Process Citation]
Intern Med (Japan), 2013, 52(2) p277-9

 

take home points: Again, BA can be recanalized later than other vessels; this tumor type is very sensitive to lysis

Etiology and treatment of ischaemic stroke in patients with (sup)-thalassemia major.

Eur J Neurol 2011 Dec;18(12):1426-8    (ISSN: 1468-1331)

 

BACKGROUND AND PURPOSE: Although hypercoagulability-induced thromboembolism is generally accepted as cause of cerebral ischaemia in thalassemic patients, cardiogenic embolism has been recently suggested as another possible stroke etiology. METHODS: We present four adult (sup)-thalassemia major patients with manifest cardiac involvement who suffered territorial strokes. RESULTS: In the presence of siderotoxic cardiomyopathy and arrhythmia, we assumed cardiogenic embolism as etiology of stroke and initiated oral anticoagulation as preventive medication. Two of our patients were the first (sup)-thalassemia major patients who underwent successful thrombolysis with rtPA. CONCLUSIONS: Cardioembolism seems to be the cause of stroke in cases of (sup)-thalassemia major. Thrombolysis can be applied in the setting of acute brain ischaemia in such high risk patients. [ 2011 The Author(s). European Journal of Neurology 2011 EFNS.].

 

Comment:  Take home points

1.  Thal cases can be cardioembolic not just hypercoagulable and may benefit from anticoagulation

2.  Thrombolysis might help in some cases

anticoagulation in acute stroke

Lancet Neurology 2013 published a metaanalysis of studies showing no benefit of anticoagulation in acute stroke.  However, like Freddy Krueger, the debate will not die.  Below is an excerpt from the editorial by Hart et al.  that lays out some of the remaining points of contention.

A meta-analysis of 24 trials involving 23 748 patients with acute stroke found that early anticoagulation compared with no anticoagulation reduced recurrent ischaemic stroke and venous thromboembolism at the cost of increased intracranial and extracranial haemorrhage, with no overall reduction in death or disability.² Consequently, guidelines for stroke management now recommend that anticoagulants should not be used for the management of acute stroke caused by common cerebrovascular disorders (including atrial fibrillation).³ Nonetheless, the question remains: are there acute stroke patients at high risk of thrombotic events and low risk of bleeding who might yet benefit from early anticoagulant therapy?

In this issue of The Lancet Neurology, William Whiteley and colleagues⁴ report the results of a pooled individual patient-level analysis of the five largest randomised trials that have tested heparins in patients with acute ischaemic stroke. The authors developed risk prediction models to identify acute stroke patients The analyses by Whiteley and colleagues provide no support for the use of anticoagulants in the management of patients with acute stroke, but the results must be interpreted with caution. First, despite careful efforts by the investigators to derive the best risk-prediction models, they were only modestly predictive of thromboembolic and bleeding events (C-statistics in the order of 0·6), thereby reducing the quality of the evidence and limiting the strength of the conclusions. Second, the conclusion must necessarily be restricted to the subgroups common to the trial databases; for example, the presence of large artery atherosclerosis was not considered.⁵ Third, uncertainty remains regarding the role of heparins in patients with uncommon conditions resulting in acute brain ischaemia. These include patients with acute cerebral venous thrombosis, small-to-moderate brain infarcts due to cerebral arterial dissection, aseptic embolism from prosthetic cardiac valves, mobile left ventricular thrombi, and aortic arch plaque with protruding overlying thrombi.

The balance between risks and benefits of heparins also remains unclear for patients with acute transient ischaemic attack or minor ischaemic strokes who were poorly represented in the randomised trials. These patients have a low risk of secondary haemorrhagic transformation because they do not have substantial areas of acute brain necrosis. A randomised trial that assessed the combination of clopidogrel plus aspirin in patients with acute transient ischaemic attack found a benefit of the intensive antiplatelet therapy,⁶ and other trials testing dual antiplatelet therapy in patients with acute ischaemic attack or minor ischaemic stroke are ongoing.⁷ Whether early anticoagulation provides benefit for these patients needs to be assessed.

Recently introduced novel oral anticoagulants that selectively target thrombin (dabigatran etexilate) or factor Xa (rivaroxaban, apixaban) are attractive candidates for acute stroke treatment because they work rapidly (within 2–3 h) after oral administration. The most important advantage of the novel oral anticoagulants over warfarin is the sharply decreased risk of intracerebral haemorrhage seen during long-term treatment in patients with atrial fibrillation.⁸ If the novel oral agents are associated with a similarly low risk of secondary brain haemorrhage after acute stroke, the balance between risks and benefits of early anticoagulation might be altered in favour of treatment, making this a priority for future research.

Despite multiple randomised trials testing heparins in patients with acute ischaemic stroke, and also the rigorous efforts by Whiteley and colleagues to identify subsets of patients defined by thromboembolic and bleeding risk that might benefit from early anticoagulation, the value of this approach has not been established for any patient group.⁴ However, promising early data with the use of combined antiplatelet therapy and the emergence of novel oral anticoagulants with a rapid onset of action and low risk of intracranial haemorrhage means that anticoagulant therapies for patients with acute brain ischaemia remains a fruitful area for future clinical research.

Hemorrhagic transformation in patients with acute ischaemic stroke and an indica

Hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation; Marsh EB, Llinas RH, Hillis AE, Gottesman RF; European Journal of Neurology (Mar 2013)

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. METHODS: Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. RESULTS: Age [odds ratio (OR) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 8) occurred in the anticoagulated group. CONCLUSIONS: The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR.

MR Rescue NEJM 2013

Background
Whether brain imaging can identify patients who are most likely to benefit from
therapies for acute ischemic stroke and whether endovascular thrombectomy improves
clinical outcomes in such patients remains unclear.
Methods
In this study, we randomly assigned patients within 8 hours after the onset of largevessel,
anterior-circulation strokes to undergo mechanical embolectomy (Merci
Retriever or Penumbra System) or receive standard care. All patients underwent
pretreatment computed tomography or magnetic resonance imaging of the brain.
Randomization was stratified according to whether the patient had a favorable
penumbral pattern (substantial salvageable tissue and small infarct core) or a nonpenumbral
pattern (large core or small or absent penumbra). We assessed outcomes
using the 90-day modified Rankin scale, ranging from 0 (no symptoms) to 6 (dead).
Results
Among 118 eligible patients, the mean age was 65.5 years, the mean time to enrollment
was 5.5 hours, and 58% had a favorable penumbral pattern. Revascularization
in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality
was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate
differed across groups. Among all patients, mean scores on the modified Rankin
scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P = 0.99).
Embolectomy was not superior to standard care in patients with either a favorable
penumbral pattern (mean score, 3.9 vs. 3.4; P = 0.23) or a nonpenumbral pattern
(mean score, 4.0 vs. 4.4; P = 0.32). In the primary analysis of scores on the 90-day
modified Rankin scale, there was no interaction between the pretreatment imaging
pattern and treatment assignment (P = 0.14).
Conclusions
A favorable penumbral pattern on neuroimaging did not identify patients who would
differentially benefit from endovascular therapy for acute ischemic stroke, nor was
embolectomy shown to be superior to standard care. (Funded by the National Institute
of Neurological Disorders

 

Blogger comment:  key point here is mean time to vascularization has to be less than 8 hours.  MR rescue should be done within six or preferably four hours.

IMS 3 article

Endovascular Therapy after Intravenous
t-PA versus t-PA Alone for Stroke
Joseph P. Broderick, M.D., Yuko Y. Palesch, Ph.D., Andrew M. Demchuk, M.D., et al NEJM 2013

 

BACKGROUND
Endovascular therapy is increasingly used after the administration of intravenous tissue
plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic
stroke, but whether a combined approach is more effective than intravenous t-PA
alone is uncertain.
METHODS
We randomly assigned eligible patients who had received intravenous t-PA within
3 hours after symptom onset to receive additional endovascular therapy or intravenous
t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified
Rankin scale score of 2 or less (indicating functional independence) at 90 days
(scores range from 0 to 6, with higher scores indicating greater disability).
RESULTS
The study was stopped early because of futility after 656 participants had undergone
randomization (434 patients to endovascular therapy and 222 to intravenous t-PA
alone). The proportion of participants with a modified Rankin score of 2 or less at
90 days did not differ significantly according to treatment (40.8% with endovascular
therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage
points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National
Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe
stroke, or ≥20, indicating severe stroke]), nor were there significant differences for
the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8
percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0
percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and
intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively;
P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage
within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83).
CONCLUSIONS
The trial showed similar safety outcomes and no significant difference in functional
independence with endovascular therapy after intravenous t-PA, as compared with
intravenous t-PA alone. (Funded by the National Institutes of Health and others;
ClinicalTrials.gov number, NCT00359424.)

 

Blogger comment

 

There's a lot of issues with the studies:

IMS III:

1) IMS III only included patients that arrived in <3 hours and could get IV tPA.

2) Patients that are not candidates for IV tPA (recent surgery, coumadin, etc) undergo endovascular mechanical thrombectomy.

3) 5197 patients were screened for IMS III, but only 656 patients randomized, which typically means the confined scope of a PRCT does not generalize to the real world.

4) For most of IMS III, noncontrast CT was the only imaging (CTA was only added later) which means there were likely a significant number of patients withOUT an occlusion that were randomized in the study (in the Ciccone study, 10% of patients did not have an occlusion!).

5) IMS III included a hodge-podge of endovascular treatments including EKOS, which no one uses, and IA tPA, which is rarely used now that we have mechanical thrombectomy devices.

6) The study was halted because of futility, thus the number of patients studied was not enough for the study to be adequately powered to demonstrate a difference.

7) IMS III was a comparison of IV tPA versus IV tPA plus endovascular therapy. What the study shows is maybe IV tPA is our best treatment. However, the way we practice, and most high-volume stroke centers are the same, is we give IV tPA to eligible candidates and only perform endovascular therapy in patients that are not eligible for IV tPA, or who receive IV tPA and the IV tPA does not work.

8)  Current devices in past year are much more effective and current protocols stress earlier door to needle.

Synthesis trial

SYNTHESIS N Engl J Med 2013

Background
In patients with ischemic stroke, endovascular treatment results in a higher rate of
recanalization of the affected cerebral artery than systemic intravenous thrombolytic
therapy. However, comparison of the clinical efficacy of the two approaches is
needed.
Methods
We randomly assigned 362 patients with acute ischemic stroke, within 4.5 hours
after onset, to endovascular therapy (intraarterial thrombolysis with recombinant
tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a
combination of these approaches) or intravenous t-PA. Treatments were to be given
as soon as possible after randomization. The primary outcome was survival free of
disability (defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6, with
0 indicating no symptoms, 1 no clinically significant disability despite symptoms,
and 6 death) at 3 months.
Results
A total of 181 patients were assigned to receive endovascular therapy, and 181 intravenous
t-PA. The median time from stroke onset to the start of treatment was
3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA (P<0.001).
At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the
intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for
age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% confidence
interval, 0.44 to 1.14; P = 0.16). Fatal or nonfatal symptomatic intracranial
hemorrhage within 7 days occurred in 6% of the patients in each group, and there
were no significant differences between groups in the rates of other serious adverse
events or the case fatality rate.
Conclusions
The results of this trial in patients with acute ischemic stroke indicate that endovascular
therapy is not superior to standard treatment with intravenous t-PA. (Funded
by the Italian Medicines Agency, ClinicalTrials.gov number, NCT00640367.)

 

Blogger comment-- endovascular v tpa does not represent real world since current protocol is patients get iv if eligible and both if iv does not work,and endovascular alone if not eligible for iv. Also hodgepodge of old interventional methods were used.

SYNTHESIS (Italian Study):

1) This study only randomized patients that arrived in < 4.5 hours and were eligible candidates for IV tPA. For same reasons as above, this is a very narrow scope of patients.

2) This study was a comparison of IV tPA versus IA tPA (additional devices could be used). IA tPA is rarely used as an endovascular therapy now that we have mechanical devices.

3) No CTA was allowed in this study. Only noncontrast head CT. 10% of patients randomized to IA therapy had no occlusion on angiogram, and these patients because the protocol dictated, were given IA tPA anyways even if they had no occlusion!

4) In his presentation, Ciccone showed that the time-to-treatment was significantly different: >60 minutes longer in the IA treatment arm of the study.

5) It is not clear how many patients were screened to arrive at the final enrollment of 362.