Mohammad Khalid Mojadidi

Transcatheter Patent Foramen Ovale Closure After Cryptogenic Stroke: An Updated Meta-Analysis of Randomized Trials

Paradoxical embolism from a patent foramen ovale (PFO) mediated right-to-left shunt is a well-described mechanism of ischemic stroke [(1)][1]. In a patient level meta-analysis of the earlier 3 randomized trials, percutaneous PFO closure was superior to medical therapy for secondary prevention of

Patent foramen ovale: Unanswered questions.

The foramen ovale is a remnant of the fetal circulation that remains patent in 20-25% of the adult population. Although long overlooked as a potential pathway that could produce pathologic conditions, the presence of a patent foramen ovale (PFO) has been associated with a higher than expected frequency in a variety of clinical syndromes including cryptogenic stroke, migraines, sleep apnea, platypnea-orthodeoxia, deep sea diving associated decompression illness, and high altitude pulmonary edema. A unifying hypothesis is that a chemical or particulate matter from the venous circulation crosses the PFO conduit between the right and left atria to produce a variety of clinical syndromes. Although observational studies suggest a therapeutic benefit of PFO closure compared to medical therapy alone in patients with cryptogenic stroke, 3 randomized controlled trials (RCTs) did not confirm the superiority of PFO closure for the secondary prevention of stroke. However, meta-analyses of these RCTs demonstrate a significant benefit of PFO closure over medical therapy alone. Similarly, observational studies provide support for PFO closure for symptomatic relief of migraines. But one controversial randomized study failed to replicate the results of the observational studies while another two demonstrated a partial benefit. The goal of this review is to discuss the clinical conditions associated with PFO and provide internists and primary care physicians with current data on PFO trials, and clinical insight to help guide their patients who are found to have a PFO on echocardiographic testing.

Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1 152 407 subjects

Objectives To perform an updated meta-analysis to evaluate the long-term cardiovascular and cerebrovascular outcomes among migraineurs. Setting A meta-analysis of cohort studies performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources The MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for relevant articles. Participants A total of 16 cohort studies (18 study records) with 394 942 migraineurs and 757 465 non-migraineurs were analysed. Primary and secondary outcome measures Major adverse cardiovascular and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non-specified), myocardial infarction (MI) and all-cause mortality. The outcomes were reported at the longest available follow-up. Data analysis Summary-adjusted hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard model. The risk of bias was assessed by the Newcastle-Ottawa Scale. Results Migraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95% confidence interval [CI] 1.26 to 1.60, P<0.001, I2=40%) driven by a higher risk of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P<0.001, I2=72%) and MI (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I2=59%). There was no difference in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10, P=0.38, I2=91%), with a considerable degree of statistical heterogeneity between the studies. The presence of aura was an effect modifier for stroke (adjusted HR aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31, P interaction=0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12 to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, Pinteraction<0.001). Conclusion Migraine headache was associated with an increased long-term risk of cardiovascular and cerebrovascular events. This effect was due to an increased risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to severe degree of heterogeneity for the outcomes, which was partly explained by the presence of aura. PROSPERO registration number CRD42016052460.

Evolution of acute ischemic stroke therapy from lysis to thrombectomy: Similar or different to acute myocardial infarction?

Acute ischemic stroke remains a major global cause of death, permanent disability, and dementia. For nearly two decades, intravenous tissue plasminogen activator (tPA) has been the only recommended therapy, albeit administered within the recommended time window (i.e., <4.5h). However, intravenous tPA is associated with modest recanalization rates, with a majority of patients having poor functional outcomes despite timely administration. Endovascular therapy has recently been introduced as adjunctive management of acute ischemic stroke. First generation endovascular thrombectomy devices have failed to improve outcomes compared with intravenous tPA. However, recent randomized trials utilizing stent retrievers demonstrated that these devices improve functional outcomes in patients with acute ischemic stroke secondary to large-artery occlusion. Introduction of stent retrieves has begun a new era for acute ischemic stroke therapy. This comprehensive review discusses the evolution of acute ischemic stroke therapy over the last two decades, with emphasis on recent randomized trials evaluating stent retrievers. Additionally, similarities and differences between the evolution of therapy in ST elevation myocardial infarction and acute ischemic stroke will be highlighted.

Identification and Quantification of Patent Foramen Ovale–Mediated Shunts: Echocardiography and Transcranial Doppler

Once deemed benign, patent foramen ovale (PFO)-mediated right-to-left shunting has now been linked to stroke, migraine, and hypoxemia. Contrast transesophageal echocardiography is considered the standard technique for identifying a PFO, allowing visualization of the atrial septal anatomy and differentiation from non-PFO right-to-left shunts. Transthoracic echocardiography is the most common method for PFO imaging, being cost-effective, but has the lowest sensitivity. Transcranial Doppler is highly sensitive but is unable to differentiate cardiac from pulmonary shunts; it is the best method to quantitate shunt severity, being more sensitive than transthoracic or transesophageal echocardiography so is our preferred screening method for PFO.

Staged versus index procedure complete revascularization in ST‐elevation myocardial infarction: A meta‐analysis

BACKGROUND Complete revascularization of patients with ST-elevation myocardial infarction and multivessel coronary artery disease reduces adverse events compared to infarct-related artery only revascularization. Whether complete revascularization should be done as multivessel intervention during index procedure or as a staged procedure remains controversial. METHOD We performed a meta-analysis of randomized controlled trials comparing outcomes of multivessel intervention in patients with ST-elevation myocardial infarction and multivessel coronary artery disease as staged procedure versus at the time of index procedure. Composite of death or myocardial infarction was the primary outcome. Mantel-Haenszel risk ratios were calculated using random effect model. RESULTS Six randomized studies with a total of 1126 patients met our selection criteria. At a mean follow-up of 13 months, composite of myocardial infarction or death (7.2% vs 11.7%, RR: 1.66, 95%CI: 1.09-2.52, P = 0.02), all cause mortality (RR: 2.55, 95%CI: 1.42-4.58, P < 0.01), cardiovascular mortality (RR: 2.8, 95%CI: 1.33-5.86, P = 0.01), and short-term (<30 days) mortality (RR: 3.54, 95%CI: 1.51-8.29, P < 0.01) occurred less often in staged versus index procedure multivessel revascularization. There was no difference in major adverse cardiac events (RR: 1.14, 95%CI: 0.88-1.49, P = 0.33), repeat myocardial infarction (RR: 1.14, 95%CI: 0.68-1.92, P = 0.61), and repeat revascularization (RR: 0.92, 95%CI: 0.66-1.28, P = 0.62). CONCLUSION In patients with ST-elevation myocardial infarction and multivessel coronary artery disease, a strategy of complete revascularization as a staged procedure compared to index procedure revascularization results in reduced mortality without an increase in repeat myocardial infarction or need for repeat revascularization.

Percutaneous coronary intervention or coronary artery bypass grafting for unprotected left main coronary artery disease

Recent trials comparing PCI with CABG for unprotected left main disease yielded discrepant evidence.

Intravenous β-blockers for patients undergoing primary percutaneous coronary intervention: A meta-analysis of randomized trials

BACKGROUND The efficacy and safety of intravenous β-blockers in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) are not well known. METHODS Electronic databases were searched for randomized trials that compared intravenous β-blocker use with routine care or placebo in patients with STEMI undergoing primary PCI. Summary estimates risk ratios (RR) were constructed using DerSimonian and Laird model. RESULTS Four randomized trials with 1149 Killip class I or II STEMI patients were included. Intravenous β-blockers were associated with a reduction in the risk of ventricular arrhythmias during hospitalization (RR 0.42, 95% confidence interval [CI] 0.26-0.69, P=0.001). The risk of cardiogenic shock (RR 0.78, 95% CI 0.31-1.97, P=0.61), bradycardia (RR 1.54, 95% CI 0.35-6.81, P=0.57), all-cause mortality (RR 0.71, 95% CI 0.19-3.17, P=0.72), and cardiovascular mortality (RR 0.93, 95% CI 0.35-2.48, P=0.88) during hospitalization was similar in both groups. There was a trend towards a lower risk of future heart failure hospitalizations with intravenous β-blockers (RR 0.32, 95% CI 0.10-1.05, P=0.06). CONCLUSION Intravenous β-blockers, in STEMI patients (Killip class I or II) undergoing primary PCI, appear to be safe. Intravenous β-blockers were associated with a reduced risk of ventricular arrhythmias. Due to the small number of patients, the impact on other outcomes could not be determined. Therefore, future trials are recommended to establish the efficacy of intravenous β-blockers in primary PCI.

Meta-Analysis of Aspirin Versus Dual Antiplatelet Therapy Following Coronary Artery Bypass Grafting

Although aspirin monotherapy is considered the standard of care after coronary artery bypass grafting (CABG), more recent evidence has suggested a benefit with dual antiplatelet therapy (DAPT) after CABG. We performed a meta-analysis of observational studies and randomized controlled trials comparing outcomes of aspirin monotherapy with DAPT in patients after CABG. Subgroup analyses were conducted according to surgical technique (i.e., on vs off pump) and clinical presentation (acute coronary syndrome vs no acute coronary syndrome). Random effects overall risk ratios (RR) were calculated using the DerSimonian and Laird model. Eight randomized control trials and 9 observational studies with a total of 11,135 patients were included. At a mean follow-up of 23 months, major adverse cardiac events (10.3% vs 12.1%, RR 0.84, confidence interval [CI] 0.71 to 0.99), all-cause mortality (5.7% vs 7.0%, RR 0.67, CI 0.48 to 0.94), and graft occlusion (11.3% vs 14.2%, RR 0.79, CI 0.63 to 0.98) were less with DAPT than with aspirin monotherapy. There was no difference in myocardial infarction, stroke, or major bleeding between the 2 groups. In conclusion, DAPT appears to be associated with a reduction in graft occlusion, major adverse cardiac events, and all-cause mortality, without significantly increasing major bleeding compared with aspirin monotherapy in patients undergoing CABG.

Early Invasive Strategy and In‐Hospital Survival Among Diabetics With Non‐ST‐Elevation Acute Coronary Syndromes: A Contemporary National Insight

Background There are limited data on the merits of an early invasive strategy in diabetics with non‐ST‐elevation acute coronary syndrome, with unclear influence of this strategy on survival. The aim of this study was to evaluate the in‐hospital survival of diabetics with non‐ST‐elevation acute coronary syndrome treated with an early invasive strategy compared with an initial conservative strategy. Methods and Results The National Inpatient Sample database, years 2012–2013, was queried for diabetics with a primary diagnosis of non‐ST‐elevation acute coronary syndrome defined as either non‐ST‐elevation myocardial infarction or unstable angina (unstable angina). An early invasive strategy was defined as coronary angiography±revascularization within 48 hours of admission. Propensity scores were used to assemble a cohort managed with either an early invasive or initial conservative strategy balanced on >50 baseline characteristics and hospital presentations. Incidence of in‐hospital mortality was compared in both groups. In a cohort of 363 500 diabetics with non‐ST‐elevation acute coronary syndrome, 164 740 (45.3%) were treated with an early invasive strategy. Propensity scoring matched 21 681 diabetics in both arms. Incidence of in‐hospital mortality was lower with an early invasive strategy in both the unadjusted (2.0% vs 4.8%; odds ratio [OR], 0.41; 95% CI, 0.39–0.42; P<0.0001) and propensity‐matched models (2.2% vs 3.8%; OR, 0.57; 95% CI, 0.50–0.63; P<0.0001). The benefit was observed across various subgroups, except for patients with unstable angina (P interaction=0.02). Conclusions An early invasive strategy may be associated with a lower incidence of in‐hospital mortality in patients with diabetes. The benefit of this strategy appears to be superior in patients presenting with non‐ST‐elevation myocardial infarction compared with unstable angina.