Amir Ahmadi

Coronary plaque quantification and fractional flow reserve by coronary computed tomography angiography identify ischaemia-causing lesions

Abstract Aims Coronary plaque characteristics are associated with ischaemia. Differences in plaque volumes and composition may explain the discordance between coronary stenosis severity and ischaemia. We evaluated the association between coronary stenosis severity, plaque characteristics, coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT), and lesion-specific ischaemia identified by FFR in a substudy of the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). Methods and results Coronary CTA stenosis, plaque volumes, FFRCT, and FFR were assessed in 484 vessels from 254 patients. Stenosis >50% was considered obstructive. Plaque volumes (non-calcified plaque [NCP], low-density NCP [LD-NCP], and calcified plaque [CP]) were quantified using semi-automated software. Optimal thresholds of quantitative plaque variables were defined by area under the receiver-operating characteristics curve (AUC) analysis. Ischaemia was defined by FFR or FFRCT ≤0.80. Plaque volumes were inversely related to FFR irrespective of stenosis severity. Relative risk (95% confidence interval) for prediction of ischaemia for stenosis >50%, NCP ≥185 mm3, LD-NCP ≥30 mm3, CP ≥9 mm3, and FFRCT ≤0.80 were 5.0 (3.0–8.3), 3.7 (2.4–5.6), 4.6 (2.9–7.4), 1.4 (1.0–2.0), and 13.6 (8.4–21.9), respectively. Low-density NCP predicted ischaemia independent of other plaque characteristics. Low-density NCP and FFRCT yielded diagnostic improvement over stenosis assessment with AUCs increasing from 0.71 by stenosis >50% to 0.79 and 0.90 when adding LD-NCP ≥30 mm3 and LD-NCP ≥30 mm3 + FFRCT ≤0.80, respectively. Conclusion Stenosis severity, plaque characteristics, and FFRCT predict lesion-specific ischaemia. Plaque assessment and FFRCT provide improved discrimination of ischaemia compared with stenosis assessment alone.

Do Plaques Rapidly Progress Prior to Myocardial Infarction?: The Interplay Between Plaque Vulnerability and Progression

There is a common misperception in the cardiology community that most acute coronary events arise from ruptures of mildly stenotic plaques. This notion has emanated from multiple studies that had measured the degree of angiographic luminal narrowing in culprit plaques months to years before myocardial infarction. However, angiographic studies within 3 months before myocardial infarction, immediately after myocardial infarction with thrombus aspiration or fibrinolytic therapy, and postmortem pathological observations have all shown that culprit plaques in acute myocardial infarction are severely stenotic. Serial angiographic studies also have demonstrated a sudden rapid lesion progression before most cases of acute coronary syndromes. The possible mechanisms for such rapid plaque progression and consequent luminal obstruction include recurrent plaque rupture and healing and intraplaque neovascularization and hemorrhage with deposition of erythrocyte-derived free cholesterol. Moreover, recent intravascular and noninvasive imaging studies have demonstrated that plaques which result in coronary events have larger plaque volume and necrotic core size with greater positive vessel remodeling compared with plaques, which remain asymptomatic during several years follow-up, although these large atheromatous vulnerable plaques may angiographically seem mild. As such, it is these vulnerable plaques which are more prone to rapid plaque progression or are those in which plaque progression is more likely to become clinically evident. Therefore, in addition to characterizing plaque morphology, inflammatory activity, and severity, detection of the rate of plaque progression might identify vulnerable plaques with an increased potential for adverse outcomes.

Association of Coronary Stenosis and Plaque Morphology With Fractional Flow Reserve and Outcomes

IMPORTANCE Obstructive coronary lesions with reduced luminal dimensions may result in abnormal regional myocardial blood flow as assessed by stress-induced myocardial perfusion imaging or a significant fall in distal perfusion pressure with hyperemia-induced vasodilatation (fractional flow reserve [FFR] ≤0.80). An abnormal FFR has been demonstrated to identify high-risk lesions benefitting from percutaneous coronary intervention while safely allowing revascularization to be deferred in low-risk lesions, resulting in a decrease in the number of revascularization procedures as well as substantially reduced death and myocardial infarction. While FFR identifies hemodynamically significant lesions likely to produce ischemia-related symptoms, it remains less clear as to why it might predict the risk of acute coronary syndromes, which are usually due to plaque rupture and coronary thrombosis. OBSERVATIONS Although the atherosclerotic plaques with large necrotic cores (independent of the degree of luminal stenosis) are known to be associated with vulnerability to rupture and acute coronary syndromes, emerging evidence also suggests that they may induce greater rates of ischemia and reduced FFR compared with non-lipid-rich plaques also independent of the degree of luminal narrowing. It is proposed that the presence of large necrotic cores within the neointima may be associated with the inability of the vessel to dilate and may predispose to ischemia and abnormal FFR. CONCLUSIONS AND RELEVANCE Having a normal FFR requires unimpaired vasoregulatory ability and significant luminal stenosis. Therefore, FFR should identify lesions that are unlikely to possess large necrotic core, rendering them safe for treatment with medical therapy alone. Further studies are warranted to determine whether revascularization decisions in patients with stable coronary artery disease could be improved by assessment of both plaque composition and ischemia.

Sex-based Prognostic Implications of Nonobstructive Coronary Artery Disease: Results from the International Multicenter CONFIRM Study

PURPOSE To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution. MATERIALS AND METHODS Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models. RESULTS At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03). CONCLUSION When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

The effects of intravitreal bevacizumab on patients with macular edema secondary to branch retinal vein occlusion

OBJECTIVE To evaluate the effect of intravitreal bevacizumab on visual acuity (VA) and central retinal thickness (CRT) in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). DESIGN Retrospective review. PARTICIPANTS The study included 42 patients with ME secondary to BRVO who received intravitreal injections of bevacizumab in 2 referral-based retinal practices in Vancouver, B.C., between November 2005 and July 2006. METHODS We performed a retrospective review of consecutive patients with ME secondary to BRVO. All of the patients in this study had nonischemic BRVOs. Patients were all treated with at least 1 bevacizumab injection and were seen at 6- to 8-week intervals for VA testing. Most of the patients also underwent optical coherence tomography (OCT) 2 months and 6 months after treatment. VA and OCT measurements at each follow-up time point were compared with the baseline values. RESULTS A total of 42 eyes from 42 patients with ME secondary to BRVO were reviewed. The mean VA improved from 20/280 at baseline to 20/180 at first follow-up session (p < 0.04; average follow-up = 42 days) and remained at a similar level, 20/170, through the eighth follow-up session (p < 0.04; average follow-up = 356). The CRT was reduced from a mean of 451 microm (388-512 microm) at baseline to 358 microm (298-418 microm) at 2 months (p < 0.02) and to 400 microm (335-465 microm) at 6 months postinjection (p < 0.068). CONCLUSIONS We found a significant improvement in VA and CRT in patients with ME secondary to BRVO after intravitreal bevacizumab injection(s). No complications or serious side effects were observed. Intravitreal bevacizumab appears to have an emerging role as either a primary or an adjuvant treatment modality in the setting of ME secondary to BRVO.

Prognostic Determinants of Coronary Atherosclerosis in Stable Ischemic Heart Disease: Anatomy, Physiology, or Morphology?

Risk stratification in patients with stable ischemic heart disease is essential to guide treatment decisions. In this regard, whether coronary anatomy, physiology, or plaque morphology is the best determinant of prognosis (and driver an effective therapeutic risk reduction) remains one of the greatest ongoing debates in cardiology. In the present report, we review the evidence for each of these characteristics and explore potential algorithms that may enable a practical diagnostic and therapeutic strategy for the management of patients with stable ischemic heart disease.

CT Assessment of Myocardial Perfusion and Fractional Flow Reserve

Coronary computed tomography angiography (CTA) offers a non-invasive method to detect coronary plaque and stenosis. However, to date, CTA has been most useful as a method of ruling out coronary artery disease (CAD) among patients with low to intermediate pretest probability of significant CAD. The reduced specificity of CTA for detecting physiologically significant stenosis is a known limitation of this technique, particularly since some patients require additional functional testing following CTA. Therefore, intense interest has focused on the development of methods to determine the functional significance of anatomical lesions identified by CTA. This article will discuss two emerging methods: stress myocardial perfusion imaging using CT, or CT perfusion, and computer simulation of fractional flow reserve.

Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? Results from the multinational coronary CT angiography evaluation for clinical outcome: an international multicenter registry (CONFIRM).

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p<0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p>0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.

Predictive Value of Age-and Sex-Specific Nomograms of Global Plaque Burden on Coronary Computed Tomography Angiography for Major Cardiac Events

Background— Age-adjusted coronary artery disease (CAD) burden identified on coronary computed tomography angiography predicts major adverse cardiovascular event (MACE) risk; however, it seldom contributes to clinical decision making because of a lack of nomographic data. We aimed to develop clinically pragmatic age- and sex-specific nomograms of CAD burden using coronary computed tomography angiography and to validate their prognostic use. Methods and Results— Patients prospectively enrolled in phase I of the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes) were included (derivation cohort: n=21,132; 46% female) to develop CAD nomograms based on age–sex percentiles of segment involvement score (SIS) at each year of life (40–79 years). The relationship between SIS age–sex percentiles (SIS%) and MACE (all-cause death, myocardial infarction, unstable angina, and late revascularization) was tested in a nonoverlapping validation cohort (phase II, CONFIRM registry; n=3030, 44% female) by stratifying patients into 3 SIS% groups (⩽50th, 51–75th, and >75th) and comparing annualized MACE rates and time to MACE using multivariable Cox proportional hazards models adjusting for Framingham risk and chest pain typicality. Age–sex percentiles were well fitted to second-order polynomial curves (men: R2=0.86±0.12; women: R2=0.86±0.14). Using the nomograms, there were 1576, 965, and 489 patients, respectively, in the ⩽50th, 51–75th, and >75th SIS% groups. Annualized event rates were higher among patients with greater CAD burden (2.1% [95% confidence interval: 1.7%–2.7%], 3.9% [95% confidence interval: 3.0%–5.1%], and 7.2% [95% confidence interval: 5.4%–9.6%] in ⩽50th, 51–75th, and >75th SIS% groups, respectively; P<0.001). Adjusted MACE risk was significantly increased among patients in SIS% groups above the median compared with patients below the median (hazard ratio [95% confidence interval]: 1.9 [1.3–2.8] for 51–75th SIS% group and 3.4 [2.3–5.0] for >75th SIS% group; P<0.01 for both). Conclusions— We have developed clinically pragmatic age- and sex-specific nomograms of CAD prevalence using coronary computed tomography angiography findings. Global plaque burden measured using SIS% is predictive of cardiac events independent of traditional risk assessment. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443637.

Post-vaccination myositis and myocarditis in a previously healthy male

BackgroundThe immunological literature has been redefining clinical phenomena as hypotheses emerge regarding causal links between triggers, immunologic manifestations, and their specific inflammatory cascades. Of late, autoimmune manifestations that appear to be caused by an external adjuvant have been grouped into a complex syndrome referred to as autoimmune/inflammatory syndrome induced by adjuvants (ASIA). This syndrome may present with diverse clinical problems, which may include neurocognitive impairment, inflammatory musculoskeletal changes, and constitutional symptoms. There is evidence in the literature linking vaccines to different auto-immune manifestations. Vaccines have not traditionally been reported to trigger ASIA, although reports are emerging linking the human papilloma virus and hepatitis B vaccines to it.Case presentationWe report the first suspected case of ASIA in a previously healthy patient who received the Fluad seasonal influenza vaccine, which contains the MF59 adjuvant. He presented to hospital with profound weakness and was diagnosed with severe rhabdomyolysis. He also had elevated troponin-I and extensive cardiac investigations enabled the diagnosis of myocarditis. His infectious and rheumatologic work-ups were negative. He responded well to conservative management and did not require immune suppressive therapy.ConclusionGiven the benefits of the influenza vaccine, and the low incidence of clinically significant complications, we encourage ongoing seasonal influenza immunization. However, ongoing surveillance is required to evaluate the occurrence of rare adverse events, including ASIA.