Rebecca Fox

Spontaneous Coronary Artery Dissection : Prevalence of Predisposing Conditions Including Fibromuscular Dysplasia in a Tertiary Center Cohort

OBJECTIVES We sought to evaluate the prevalence of fibromuscular dysplasia (FMD) and other predisposing conditions among spontaneous coronary artery dissection (SCAD) patients. BACKGROUND Spontaneous coronary artery dissection is considered rare. However, we observed many young women with SCAD and concomitant FMD. METHODS Spontaneous coronary artery dissection patients were identified prospectively and retrospectively at Vancouver General Hospital over the past 6 years. Coronary angiograms were meticulously reviewed by 2 senior interventional cardiologists. Identified patients were contacted for prospective evaluation at our SCAD clinic, and screening for FMD of renal, iliac, and cerebrovascular arteries was performed with computed tomography angiography or magnetic resonance angiography, if not already screened during the index angiogram. Potential predisposing and precipitating conditions for SCAD were extracted from clinical history. RESULTS We identified 50 patients with nonatherosclerotic SCAD from April 2006 to March 2012. Average age was 51.0 years, and almost all were women (98.0%). All presented with myocardial infarction (MI), 30.0% had ST-segment elevation, and 70.0% had non-ST-segment elevation MI. Only 1 was postpartum, and 2 were involved in intense isometric exercises. Emotional stress was reported in 26.0% before the MI. Twelve percent had >1 dissected coronary artery. Most SCAD patients had FMD of ≥1 noncoronary territory (86.0%): 25 of 43 (58.1%) renal, 21 of 43 (48.8%) iliac, and 20 of 43 (46.5%) cerebrovascular (6 of 43, 14.0% had intracranial aneurysm). Five had incomplete FMD screening. CONCLUSIONS Nonatherosclerotic SCAD predominantly affects women, and most have concomitant FMD. We suspect these patients have underlying coronary FMD that predisposed them to SCAD, but this requires proof from histology or intracoronary imaging of the affected coronary arteries.

Quality of Life after Late Invasive Therapy for Occluded Arteries

BACKGROUND The open-artery hypothesis postulates that late opening of an infarct-related artery after myocardial infarction will improve clinical outcomes. We evaluated the quality-of-life and economic outcomes associated with the use of this strategy. METHODS We compared percutaneous coronary intervention (PCI) plus stenting with medical therapy alone in high-risk patients in stable condition who had a totally occluded infarct-related artery 3 to 28 days after myocardial infarction. In 951 patients (44% of those eligible), we assessed quality of life by means of a battery of tests that included two principal outcome measures, the Duke Activity Status Index (DASI) (which measures cardiac physical function on a scale from 0 to 58, with higher scores indicating better function) and the Medical Outcomes Study 36-Item Short-Form Mental Health Inventory 5 (which measures psychological well-being). Structured quality-of-life interviews were performed at baseline and at 4, 12, and 24 months. Costs of treatment were assessed for 458 of 469 patients in the United States (98%), and 2-year cost-effectiveness was estimated. RESULTS At 4 months, the medical-therapy group, as compared with the PCI group, had a clinically marginal decrease of 3.4 points in the DASI score (P=0.007). At 1 and 2 years, the differences were smaller. No significant differences in psychological well-being were observed. For the 469 patients in the United States, cumulative 2-year costs were approximately

Incidental atherosclerotic renal artery stenosis diagnosed at cardiac catheterization: no difference in kidney function with or without stenting.

7,000 higher in the PCI group (P<0.001), and the quality-adjusted survival was marginally longer in the medical-therapy group. CONCLUSIONS PCI was associated with a marginal advantage in cardiac physical function at 4 months but not thereafter. At 2 years, medical therapy remained significantly less expensive than routine PCI and was associated with marginally longer quality-adjusted survival. (ClinicalTrials.gov number, NCT00004562.)

The Effects of Aspirin and Clopidogrel Response on Myonecrosis After Percutaneous Coronary Intervention: A BRIEF-PCI (Brief Infusion of Intravenous Eptifibatide Following Successful Percutaneous Coronary Intervention) Trial Substudy

BACKGROUND The long-term kidney function of patients with atherosclerotic renal artery stenosis (ARAS) diagnosed incidentally at the time of cardiac catheterization is not well described despite the increasingly common practice of assessing these vessels at the time of cardiac investigation. METHODS This is a retrospective analysis of a cohort identified prospectively at the time of non-emergent coronary angiography. Those with >or=50% ARAS were managed medically and underwent stenting if recommended by their nephrologist and/or cardiologist. Longitudinal regression analysis was used to compare the annualized change in estimated glomerular filtration rate (GFR) in stented and unstented patients. Cox regression analysis was used to determine the predictors of a decline in GFR by >or=25%. RESULTS Of 140 patients, 67 (48%) were stented, mostly for preservation of kidney function (70.1%) and/or resistant hypertension (53.7%). Median follow-up time was 943 days. Stented patients were younger, had higher systolic blood pressure and more severe ARAS. The adjusted rate of change in GFR was -1.49 (95% CI -2.33 to -0.65) ml/min/1.73 m(2)/year in the unstented group, and -1.48 (95% CI -2.34 to -0.62) ml/min/1.73 m(2)/year in the stented group (p = 0.99). A decline of GFR >or=25% occurred in 42 (30%) patients; no patient required dialysis. Only the presence of cereberovascular disease was associated with this outcome (hazard ratio 2.52, 95% CI 1.56-5.41). CONCLUSION We were unable to demonstrate a benefit or harm of renal artery stenting for ARAS, thus further increasing the uncertainty of the significance of these lesions and how they are best managed.

Characterizing the spectrum of in-stent restenosis: Implications for contemporary treatment

OBJECTIVES The purpose of this study was to evaluate the effects of aspirin and clopidogrel response on myonecrosis after percutaneous coronary intervention (PCI) with glycoprotein (GP) IIb/IIIa blockade. BACKGROUND Aspirin and clopidogrel resistance is increasingly recognized, but its effects on PCI outcomes with GP IIb/IIIa blockade are unknown. METHODS This was a prospective, pre-specified substudy of the BRIEF-PCI (Brief Infusion of Intravenous Eptifibatide Following Successful Percutaneous Coronary Intervention) trial, which randomized 624 patients to 18-h or <2-h eptifibatide infusion after uncomplicated PCI. To be eligible, patients must have been pre-treated with aspirin (>or=5 days) and clopidogrel (75 mg/day >or=5 days, 300 mg loading >or=6 h, or 600 mg loading >or=2 h) and must not have received GP IIb/IIIa inhibitors within 48 h. Verify-Now Aspirin and Clopidogrel (P2Y(12)) assays were performed at baseline before PCI. Patients with aspirin reaction unit (ARU) >or=550 were labeled as aspirin resistant. Clopidogrel low-responders were defined as those in the lowest quartile of platelet inhibition. The primary end point was the prevalence of myonecrosis within 24 h after PCI. RESULTS We enrolled 209 patients into our substudy, of which 185 had aspirin response assessed, 198 had clopidogrel response assessed, and 174 had both assessed. There were 4.9% who were aspirin resistant. Clopidogrel low-responders were defined as those in the lowest quartile with platelet inhibition <19%. Only 1.1% had both aspirin resistance and low clopidogrel response. There was no difference in myonecrosis prevalence among aspirin-resistant compared with aspirin-sensitive patients (11.1% vs. 27.8%, p = 0.259) or among clopidogrel low-responders compared with clopidogrel responders (23.5% vs. 29.3%, p = 0.433). CONCLUSIONS Aspirin and clopidogrel response did not affect myonecrosis prevalence amongst patients who received eptifibatide for PCI.

Molecular Screening of Familial Hypercholesterolemia in the Icelandic Population

BACKGROUND Reports addressing treatment of in-stent restenosis (ISR) are principally derived from clinical trials. OBJECTIVES To characterize the spectrum of ISR in an unselected population, and to explore clinical and angiographic factors determining management. METHODS During a prespecified six-month period before the introduction of drug-eluting stents, consecutive cases of ISR that were identified during clinically driven cardiac catheterization at five hospitals offering all approved treatment modalities for ISR were prospectively registered. RESULTS ISR was identified in 363 patients; 301 (84%) had one ISR lesion and 62 (16%) had multiple lesions. Unstable clinical presentations accounted for 51%, including 15% with ST-elevation myocardial infarction. The median interval (25th, 75th percentiles) from stent insertion to angiographic diagnosis of ISR was eight months (Q1,Q3: 4,15), with a median stented length of 18 mm (Q1,Q3: 15,28). The majority of lesions (60%) displayed a diffuse ISR pattern (Mehran types 2 and 3). ISR type was independent of time to re-presentation, diabetes, arterial territory and total stent length. Treatment included percutaneous coronary intervention (PCI) alone (n=139 [38%]), PCI with brachytherapy (n=105 [29%]), medical therapy (n=60 [17%]) and coronary artery bypass graft surgery (n=59 [16%]). Medical therapy was associated with small vessel size and recurrent ISR, and coronary artery bypass graft surgery was associated with multiple lesions, as well as diffuse, occlusive and recurrent ISR. For patients treated percutaneously, PCI treatment alone was more common for focal restenosis and after ST-elevation myocardial infarction, and brachytherapy was the more common treatment for diffuse and recurrent ISR, and stable angina. CONCLUSIONS These data provide a benchmark description of the spectrum of ISR with which the impact of drug-eluting stents may be compared and better understood.

Comprehensive genetic testing for female and male infertility using next-generation sequencing

Familial hypercholesterolemia (FH) is a monogenic disease characterized by a lifelong exposure to high LDL-C levels that can lead to early onset coronary heart disease (CHD). The main causes of FH identified to date include loss-of-function mutations in LDLR or APOB, or gain-of-function mutations in PCSK9. Early diagnosis and genetic testing of FH suspects is critical for improved prognosis of affected individuals as lipid lowering treatments are effective in preventing CHD related morbidity and mortality. In the present manuscript, we developed a comprehensive next generation sequencing (NGS) panel which we applied on two different resources of FH in the Icelandic population: 62 subjects from 23 FH families with known or unknown culprit mutations, and a population-based sampling of 315 subjects selected for total cholesterol levels above the 95th percentile cut-point. The application of the NGS panel revealed significant diagnostic yields in identifying pathogenic LDLR mutations in both family and population-based genetic testing.

Primary stenting versus balloon angioplasty in occluded coronary arteries: the Total Occlusion Study of Canada (TOSCA).

PurposeTo develop a comprehensive genetic test for female and male infertility in support of medical decisions during assisted reproductive technology (ART) protocols.MethodsWe developed a next-generation sequencing (NGS) gene panel consisting of 87 genes including promoters, 5′ and 3′ untranslated regions, exons, and selected introns. In addition, sex chromosome aneuploidies and Y chromosome microdeletions were analyzed concomitantly using the same panel.ResultsThe NGS panel was analytically validated by retrospective analysis of 118 genomic DNA samples with known variants in loci representative of female and male infertility. Our results showed analytical accuracy of > 99%, with > 98% sensitivity for single-nucleotide variants (SNVs) and > 91% sensitivity for insertions/deletions (indels). Clinical sensitivity was assessed with samples containing variants representative of male and female infertility, and it was 100% for SNVs/indels, CFTR IVS8-5T variants, sex chromosome aneuploidies, and copy number variants (CNVs) and > 93% for Y chromosome microdeletions. Cost analysis shows potential savings when comparing this single NGS assay with the standard approach, which includes multiple assays.ConclusionsA single, comprehensive, NGS panel can simplify the ordering process for healthcare providers, reduce turnaround time, and lower the overall cost of testing for genetic assessment of infertility in females and males, while maintaining accuracy.