Thrombophilia Testing

Connors provides an excellent review and guide to the use of thrombophilia testing (N Engl J Med 2017;377:1177-87. DOI: 10.1056/NEJMra1700365).

Occult Cancer in Patients with Unprovoked Venous Thromboembolism

van Es et al report a meta-analysis and systematic review examining the prevalence of occult cancer detection in the first year after unprovoked pulmonary thromboembolism (Ann Intern Med. 2017;167:410-417. doi:10.7326/M17-0868).

Abstract

Background

Screening for cancer in patients with unprovoked
venous thromboembolism (VTE) often is considered, but clinicians
need precise data on cancer prevalence, risk factors, and
the effect of different types of screening strategies.
Purpose: To estimate the prevalence of occult cancer in patients
with unprovoked VTE, including in subgroups of different ages
or those that have had different types of screening.

Data Sources

MEDLINE, EMBASE, and the Cochrane Central
Register of Controlled Trials up to 19 January 2016.
Study Selection: Prospective studies evaluating cancer screening
strategies in adults with unprovoked VTE that began enrolling
patients after 1 January 2000 and had at least 12 months of
follow-up.

Data Extraction

2 investigators independently reviewed abstracts
and full-text articles and independently assessed risk of
bias.

Data Synthesis

10 eligible studies were identified. Individual
data were obtained for all 2316 patients. Mean age was 60 years;
58% of patients received extensive screening. The 12-month period
prevalence of cancer after VTE diagnosis was 5.2% (95% CI,
4.1% to 6.5%). The point prevalence of cancer was higher in
patients who had extensive screening than in those who had
more limited screening initially (odds ratio [OR], 2.0 [CI, 1.2 to
3.4]) but not at 12 months (OR, 1.4 [CI, 0.89 to 2.1]). Cancer
prevalence increased linearly with age and was 7-fold higher in
patients aged 50 years or older than in younger patients (OR, 7.1
[CI, 3.1 to 16]).

Limitation

Variation in patient characteristics and extensive
screening strategies; unavailability of long-term mortality data.
Conclusion: Occult cancer is detected in 1 in 20 patients within
a year of receiving a diagnosis of unprovoked VTE. Older age is
associated with a higher cancer prevalence. Although an extensive
screening strategy initially may detect more cancer cases
than limited screening, whether this translates into improved patient
outcomes remains unclear.

Bromocriptine Peripartum Cardiomyopathy

Hilfiker-Kleiner et al published a randomized clinical trial of 1 week versus 8 week bromocriptine in patients with peripartum cardiomyopathy (European Heart Journal (2017) 38, 2671–2679 doi:10.1093/eurheartj/ehx355). There is an accompanying editorial: European Heart Journal (2017) 38, 2680–2682 doi:10.1093/eurheartj/ehx428. Change in LVEF as assessed by cardiac magnetic resonance imaging was the primary endpoint.

Abstract

Aims

An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental
and first clinical observations suggested beneficial effects of the prolactin release inhibitor bromocriptine in PPCM.

Methods and results

In this multicentre trial, 63 PPCM patients with left ventricular ejection raction (LVEF) _50%) was
present in 52% of the 1W- and in 68% of the 8W-groupwith no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6months tended to be lower.No patient in the study needed heart transplantation, LV assist device or died.

Conclusion

Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group.

Athletes Heart

Pelliccia et al provide an excellent comprehensive review of assessment and diagnostic issues of Athletes heart (European Heart Journal (2017) 0, 1–27 doi:10.1093/eurheartj/ehx532). The diagnostic approach to discrimination from hypertrophc cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, LV non-compaction and other pathologies is useful.

Physical Activity and Mortality and Cardiovascular Events: PURE Study

S A Lear et al report on the PURE study: a prospective cohort study examining the effect of physical activity on mortality and cardiovascular outcomes(Lancet http://dx.doi.org/10.1016/S0140-6736(17)31634-3).

ABSTRACT

Background

Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels.

Methods

In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 ears. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering.

Findings

Between Jan 1, 2003, and Dec 31, 2010, 168 916 participants were enrolled, of whom 141 945 completed the IPAQ. Analyses were limited to the 130 843 participants without pre-existing CVD. Compared with low physical activity
(750 minutes per week) were associated with graded reduction in mortality (hazard ratio 0·80, 95% CI 0·74–0·87 and 0·65, 0·60–0·71; p<0·0001 for trend), and major CVD (0·86, 0·78–0·93; p<0·001 for trend). Higher physical activity was associated with lower risk of CVD and mortality in high-income, middle-income, and low-income countries. The adjusted population attributable fraction for not meeting the physical activity guidelines was 8·0% for mortality
and 4·6% for major CVD, and for not meeting high physical activity was 13·0% for mortality and 9·5% for major CVD. Both recreational and non-recreational physical activity were associated with benefits.

Interpretation

Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle-income, and high-income countries. Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD in middle age.

Patent Foramen Ovale and Cryptogenic Stroke

Three papers appeared in the September 14 issue of the New England Journal of Medicine:

• N Engl J Med 2017;377:1011-21. DOI: 10.1056/NEJMoa1705915
• N Engl J Med 2017;377:1022-32. DOI: 10.1056/NEJMoa1610057
• N Engl J Med 2017;377:1033-42. DOI: 10.1056/NEJMoa1707404

and an accompanying editorial: DOI: 10.1056/NEJMe1709637

There appears to be reduced risk of stroke as well as increased risk of atrial fibrillation.

Mas et al report an open label randomized clinical trial in patients with recent stroke and PFO (with either atrial septal aneurysm or large inter-atrial shunt: compared PFO closure versus antiplatelet therapy versus anticoagulation.

ABSTRACT

BACKGROUND

Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy.

METHODS

In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3.

RESULTS

A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P = 0.02). The number of serious adverse events did not differ significantly between the treatment groups (P = 0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone.

CONCLUSIONS

Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation.

Saver et al report on the long term (10 year) outcomes of the RESPECT study.

ABSTRACT

BACKGROUND

Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown.

METHODS

In a multicenter, randomized, open-label trial, with blinded adjudication of endpoint events, we randomly assigned patients 18 to 60 years of age who had
a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory.

RESULTS

We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P = 0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI,0.18 to 0.79; P = 0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group than in the medical-therapy group.

CONCLUSIONS

Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was
associated with a lower rate of recurrent ischemic strokes than medical therapy
alone during extended follow-up

Søndergaard et at report the REDUCE trial comparing PFO closure with antiplatelet therapy in patients with cryptogenic stroke.

ABSTRACT

BACKGROUND

The efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infarctions.

METHODS

In this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet- only group). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24-month incidence of new brain infarction, which was a composite of clinical ischemic stroke or silent brain infarction
detected on imaging.

RESULTS

We enrolled 664 patients (mean age, 45.2 years), of whom 81% had moderate or large interatrial shunts. During a median follow-up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet-only group (hazard ratio, 0.23; 95% confidence interval [CI], 0.09 to 0.62; P = 0.002). The incidence of new brain infarctions was significantly lower in the PFO closure group than in the antiplatelet-only group (22 patients [5.7%] vs. 20 patients [11.3%]; relative risk, 0.51; 95% CI, 0.29 to 0.91; P = 0.04), but the incidence of silent brain infarction did not differ significantly between the study groups P = 0.97). Serious adverse events occurred in 23.1% of the patients in the PFO closure group and in 27.8% of the patients in the antiplatelet-only group (P = 0.22). Serious device-related adverse events occurred in 6 patients (1.4%) in the PFO closure group, and atrial fibrillation occurred in 29 patients (6.6%) after PFO closure.

CONCLUSIONS

Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation.