Reversible Myocardial Ischemia Research Articles

Seizure and regadenoson: An underestimated concern

For 15 years, regadenoson, a selective adenosine 2A (A2A) receptor agonist, has been largely used as a pharmacologic stress agent in myocardial perfusion studies. It acts by increasing coronary blood flow. It has been shown to be non-inferior to adenosine for the detection of reversible myocardial ischemia. Regadenoson has several advantages, including less serious adverse effects, better tolerance and easier practical administration. However, specific adverse effects on the central nervous system, although rarely reported, can provocoke seizure through A2A receptor activation. We report here a case of regadenoson-associated-seizure and review the relevant literature. A 73-year-old male with a past medical history of hypertension, atrial fibrillation, stroke, hemodialysis and type 2 diabetes was referred for evaluation of hypokinesia of the apical segments. He had an unique episode of epilepsia in 2008. Less than one minute after regadenoson injection, he had a partial tonic-clonic seizure of the right upper and lower limbs, which lasted for 30seconds and resolved spontaneously. This case report is a reminder that this under-diagnosed adverse effect must be taken into consideration when using regadenoson for cardiac stress testing.

Efficacy and safety evaluation of Ginkgo biloba dropping pill (GBDP) on stable angina pectoris complicated with depression: A placebo-controlled, randomized, double-blind, multicenter study

BackgroundStable angina pectoris (SAP) is a clinical condition characterized by reversible and temporary myocardial ischemia and hypoxia. A majority of SAP patients also experience depressive disorders, which adversely affect their disease prognosis and overall quality of life. However, the clinical utility of existing antidepressants is constrained by their side effects. Ginkgo biloba dropping pill (GBDP), a Chinese patented medication, has demonstrated efficacy in the treatment of both coronary heart disease and mental disorders. This prospective, randomized, double-blind, multicenter clinical trial aimed to assess the effectiveness and safety of GBDP as an adjuvant therapy for SAP complicated by depression. MethodsParticipants were randomly assigned in a 1:1 ratio to receive either GBDP or a placebo (5 pills, three times a day) in addition to standard therapy for a duration of 12 weeks. The Seattle Angina Questionnaire (SAQ) was administered every 4 weeks during the treatment, and angina event frequency was assessed weekly. The 36-item Short-Form (SF-36) and Hamilton Depression Scale (HAMD) scores were measured both before and after the treatment. ResultsOut of the 72 patients, 68 (n = 34 per group) completed the entire study. At the first visit (4 weeks ± 3 days), the SAQ-Angina Stability score in the GBDP group was significantly higher than that in the placebo group (p < 0.05). While the average weekly frequency of angina episodes in the placebo group notably increased after 12 weeks of treatment (p < 0.05), it displayed an improving trend in the GBDP group (p > 0.05). By the endpoint, each subcategory score of SF-36 in the GBDP group exhibited significant improvement compared to baseline (p < 0.05). The comparison of score improvement between the two groups revealed that the SF-PCS score of the GBDP group was higher than that of the placebo group (p < 0.05). HAMD scores in both groups significantly increased after treatment (p < 0.05). No discernible difference in the incidence of adverse reactions was observed between the two groups (p > 0.05). ConclusionIn patients with SAP complicated by depression, GBDP, when combined with standard treatment, rapidly and safely alleviates angina pectoris symptoms. It demonstrates therapeutic potential in enhancing the quality of life and alleviating depressive symptoms.

Nourin miRNAs: novel biomarkers highly expressed in unstable angina patients with normal ECG and negative hs-troponin and dropped post percutaneous coronary intervention

Abstract Background We recently reported that Nourin-dependent miR-137 and miR-106b can identify reversible myocardial ischemia in chest pain patients with a confirmed diagnosis of chronic stable chronic artery disease (CAD) and unstable angina (UA). These patients showed normal resting ECG and hs-cTnI below the clinical decision (&amp;lt;99th of URL). Normal, low-grade, baseline expression levels of Nourin miRNAs were detected in healthy subjects and in non-cardiac chest pain patients with hs-cTnI &amp;lt;99th URL. Purpose 1) To confirm the upregulation of Nourin miRNAs in chest pain patients with normal resting ECG and hs-cTnI &amp;lt; 99th URL, who are suspected of having UA; 2) whether Nourin miRNA expression levels change after relieving myocardial ischemia by PCI; and 3) whether there is an association between severity of chest of pain and Nourin miRNA expression levels prior to PCI. Methods This study enrolled 36 consecutive chest pain patients with normal resting ECGs and hs-cTnI &amp;lt;99th URL, from two large referral centers in Egypt. All enrolled patients had a single vessel disease with significant coronary stenosis (&amp;gt;70%) during diagnostic coronary angiography that was treated by PCI using standard techniques. The gene expression levels of miR-137 and miR-106b were measured in serum samples collected prior to PCI, as well as 12 hours and 24 hours post PCI. The angina class was evaluated at presentation, discharge, and after 4 weeks to verify angina relief. Results All patients (n=36) underwent successful PCI. Gene expression levels of miR-137 and miR-106b were significantly upregulated prior to PCI (mean ± SD: miR-137 = 355±150 and miR-106b =317±122) compared to healthy subjects (n=16) who showed minimal expression levels ranged from 0.615 to 1.05 (P &amp;lt;0.0001). Levels of both biomarkers dropped by 50% (12 hours) and 65% (24 hours) post PCI (P &amp;lt;0.05) (Figure 1). The expression levels of Nourin miRNAs did not associate with the Canadian class levels of angina severity. All patients were asymptomatic at discharge, while 84% remained asymptomatic after 4 weeks. Conclusions This study: 1) confirms that Nourin miR-137 and miR-106b can identify myocardial ischemia in patients presenting with unstable angina; 2) confirms that these two novel molecular biomarkers are elevated during myocardial ischemia, in the absence of myocardial injury; and 3) for the first time, we report a significant drop of Nourin miRNA expression levels post PCI, with myocardial ischemia relief.

Evaluating hs-cTnI serum levels and cTnI gene expression compared with cardiac nuclear scan in patients with angina pectoris.

Exercise stress can cause reversible myocardial ischemia in people with coronary artery disease (CAD). On the other hand, the new troponin biomarker with high sensitivity can detect faster and small amounts of troponin in blood circulation. The present study aimed to investigate the serum troponin level following exercise stress and the result of nuclear heart scans as the gold standard. For this purpose, 93 patients with stable angina and no history of known CAD and organic disease were included in this cross-sectional study. The serum level of the highly sensitive cardiac troponin I (hs-cTnI) was measured 75 minutes after the peak of the exercise test and reached at least 85% of the maximum heart rate. It was compared with the rate of reversible myocardial ischemia based on the nuclear heart scan, the three-month prognosis and the persistence of chest pain were investigated. Also, the expression level of the cTnI gene was evaluated by real-time PCR technique. The results showed that the average age of the patients was 58.9+12.4 years, and 62 (66.66%) patients were female. Reversible myocardial ischemia was observed in 31 patients. The relationship between hs-cTI level and the rate of reversible ischemia cases was significant (p = 0.0041). Also, the cTnI gene expression showed the same results as the serum level. According to the heart nuclear scan report, the hs-cTnI value above 1.6ng/dl had a specificity of 72% and sensitivity of 66%, a positive predictive value of 53%, and a negative predictive value of 78%. There was no significant relationship between hs-cTnI level and prognosis and the continuation of chest pain in patients after three months. Generally, the serum level of high-sensitivity cardiac troponin was higher after exercise in the group with reversible myocardial ischemia.

Wireless Single-Lead versus Standard 12-Lead ECG, for ST-Segment Deviation during Adenosine Cardiac Stress Scintigraphy.

Wearable wireless electrocardiographic (ECG) monitoring is well-proven for arrythmia detection, but ischemia detection accuracy is not well-described. We aimed to assess the agreement of ST-segment deviation from single- versus 12-lead ECG and their accuracy for the detection of reversible ischemia. Bias and limits of agreement (LoA) were calculated between maximum deviations in ST segments from single- and 12-lead ECG during 82Rb PET-myocardial cardiac stress scintigraphy. Sensitivity and specificity for reversible anterior-lateral myocardial ischemia detection were assessed for both ECG methods, using perfusion imaging results as a reference. Out of 110 patients included, 93 were analyzed. The maximum difference between single- and 12-lead ECG was seen in II (-0.019 mV). The widest LoA was seen in V5, with an upper LoA of 0.145 mV (0.118 to 0.172) and a lower LoA of -0.155 mV (-0.182 to -0.128). Ischemia was seen in 24 patients. Single-lead and 12-lead ECG both had poor accuracy for the detection of reversible anterolateral ischemia during the test: single-lead ECG had a sensitivity of 8.3% (1.0-27.0%) and specificity of 89.9% (80.2-95.8%), and 12-lead ECG a sensitivity of 12.5% (3.0-34.4%) and a specificity of 91.3% (82.0-96.7%). In conclusion, agreement was within predefined acceptable criteria for ST deviations, and both methods had high specificity but poor sensitivity for the detection of anterolateral reversible ischemia. Additional studies must confirm these results and their clinical relevance, especially in the light of the poor sensitivity for detecting reversible anterolateral cardiac ischemia.

Prevalence of Coronary Artery Disease in Asymptomatic type 2 Diabetes Mellitus Patients with Invasive Correlation in North India.

Type 2 diabetes mellitus (T2DM) is the risk factor for coronary artery disease (CAD). In this study, we assessed the prevalence of CAD in asymptomatic T2DM patients and its correlation with invasive testing in treadmill testing (TMT)-positive cases. A total of 90 patients with asymptomatic T2DM were recruited and subjected to TMT TMT-positive patients were subjected to coronary angiography (CAG). At baseline, the mean duration of T2DM (years) was 4.87 ± 4.04 with mean levels of HbA1c (%) of 7.96 ± 1.02. TMT was positive in 28 patients (31.1%) for reversible myocardial ischaemia (RMI), and among them, 16 patients consented to CAG, of which 14 required coronary angioplasty and the remaining two (7.1%) had to undergo coronary artery bypass grafting (CABG). The remaining 12 TMT positives (42.9%) were managed medically. To conclude, there is a high prevalence of silent CAD in T2DM. They need regular screening to detect the same and prevent the morbidity and mortality associated with overt CAD. Hence, it is important to screen people with type 2 diabetes, to prevent the morbidity and mortality associated with overt CAD.

Regadenoson Stress Testing: A Comprehensive Review With a Focused Update.

Regadenoson is a pharmacological stress agent that has been widely used since its approval by the Food and Drug Administration (FDA) in 2008. For many years, dipyridamole and adenosine, which are non-selective adenosine receptor agonists, were more popular. However, these agents are less preferred now due to their undesirable adverse effects as compared to regadenoson. In the ADVANCE (ADenoscan Versus regAdenosoN Comparative Evaluation) phase 3 clinical trial, regadenoson demonstrated non-inferiority to adenosine for detecting reversible myocardial ischemia. This review summarizes the clinical utilities of regadenoson as the most widely used pharmacological stress agent. Moreover, the use of regadenoson has been documented in specific patient populations. Although regadenoson has established safety and efficacy in most patients with chronic diseases, there are equivocal results in the literature for other chronic diseases. It is warranted to highlight that the use of regadenoson has not been studied in patients of low socioeconomic class; it is a condition that carries a significant burden on the cardiovascular system.

T-wave inversion in the precordial leads: сardiac and non-cardiac causes

The T-wave inversion (TWI) is a common electrocardiographic finding. Causes for TWI are numerous and sometimes TWI may appear in life-threatening conditions. The aim of this review was to provide an up-to-date analysis of TWI, including i) definition and prevalence; ii) causes, and iii) differential diagnosis in benign TWI, reversible myocardial ischemia of the left ventricular anterior wall; takotsubo cardiomyopathy; subarachnoid hemorrhage; pulmonary embolism; right ventricular arrhythmogenic cardiomyopathy; and "cardiac memory". The review presents practical electrophysiological criteria, which allow suspecting in time a life-threatening condition to choose an up-to-date treatment.

Changes in ventricular depolarisation vectors during exercise caused by regional myocardial ischaemia

Research at the Aga Khan University for several years has been directed to find a reliable, low-cost, portable, non-invasive method for identification of coronary artery disease, its location and extent. A new method has been devised to measure the magnitude and direction of cardiac electrical vectors in three perpendicular planes during physical exercise to identify reduction in myocardial excitability as the electrophysiological marker of hypoxia. This report shows that changes in electrical forces due to exercise-induced regional hypoxia serve as indicators of reversible myocardial ischaemia. Changes in the magnitude and direction of vectors at stages of the Bruce protocol were measured in healthy volunteers, and patients undergoing the same exercise protocol for distribution of a radioactive tracer injected intravenously at peak exercise and after recovery (myocardial perfusion scan). Alterations in the magnitude and direction of resultant vectors during exercise were scored to enable analysis. Analysis identified slow progression of myocardial depolarisation as the electrophysiological marker of regional hypoxia relative to physical work. Compared with myocardial perfusion scan the sensitivity and specificity of electrical vectors for identification of ischaemia were 88% and 71%, respectively. Accuracy of ischaemia shown by electrical vectors is being assessed in patients undergoing elective coronary angiography.

Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis.

Capillary derecruitment distal to a coronary stenosis is implicated as the mechanism of reversible perfusion defect and potential myocardial ischemia during coronary hyperemia; however, the underlying mechanisms are not defined. We tested whether pericyte constriction underlies capillary derecruitment during hyperemia under conditions of stenosis. In vivo two-photon microscopy (2PM) and optical microangiography (OMAG) were used to measure hyperemia-induced changes in capillary diameter and perfusion in wild-type and pericyte-depleted mice with femoral artery stenosis. OMAG demonstrated that hyperemic challenge under stenosis produced capillary derecruitment associated with decreased RBC flux. 2PM demonstrated that hyperemia under control conditions induces 26 ± 5% of capillaries to dilate and 19 ± 3% to constrict. After stenosis, the proportion of capillaries dilating to hyperemia decreased to 14 ± 4% (P = 0.05), whereas proportion of constricting capillaries increased to 32 ± 4% (P = 0.05). Hyperemia-induced changes in capillary diameter occurred preferentially in capillary segments invested with pericytes. In a transgenic mouse model featuring partial pericyte depletion, only 14 ± 3% of capillaries constricted to hyperemic challenge after stenosis, a significant reduction from 33 ± 4% in wild-type littermate controls (P = 0.04). These results provide for the first time direct visualization of hyperemia-induced capillary derecruitment distal to arterial stenosis and demonstrate that pericyte constriction underlies this phenomenon in vivo. These results could have important therapeutic implications in the treatment of exercise-induced ischemia. NEW & NOTEWORTHY In the setting of coronary arterial stenosis, hyperemia produces a reversible perfusion defect resulting from capillary derecruitment that is believed to underlie cardiac ischemia under hyperemic conditions. We use optical microangiography and in vivo two-photon microscopy to visualize capillary derecruitment distal to a femoral arterial stenosis with cellular resolution. We demonstrate that capillary constriction in response to hyperemia in the setting of stenosis is dependent on pericytes, contractile mural cells investing the microcirculation.

Влияние дозы окситоцина на развитие обратимой ишемии миокарда у рожениц разных возрастных групп во время операции кесарева сечения

Влияние дозы окситоцина на развитие обратимой ишемии миокарда у рожениц разных возрастных групп во время операции кесарева сечения

High prevalence of undiagnosed COPD among patients evaluated for suspected myocardial ischaemia

ObjectiveChronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) are leading causes of global morbidity and mortality. Despite the well-known comorbidity between COPD and CAD, the presence of COPD...

Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy.

Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hs-cTnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8-11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (>14 ng/L). Patients with hs-cTnT >14 ng/L had increased LV mass (144 ± 40 g vs 116 ± 34 g; P < 0.001) and volume (179 ± 80 mL vs 158 ± 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 ± 14 vs 62 ± 11; P = 0.006) and global longitudinal strain (14.1 ± 3.4% vs 16.9 ± 3.2%; P < 0.001), and more reversible perfusion defects (P = 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD.

Association between plasma ceramides and inducible myocardial ischemia in patients with established or suspected coronary artery disease undergoing myocardial perfusion scintigraphy

BackgroundRecent studies have suggested that specific plasma ceramides are independently associated with major adverse cardiovascular events in patients with coronary artery disease (CAD), but it is currently unknown whether plasma ceramide levels are associated with stress-induced reversible myocardial ischemia. MethodsWe measured six previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1)] in 167 consecutive patients with established or suspected CAD who underwent either exercise or dypiridamole myocardial perfusion scintigraphy (MPS) for various clinical indications. Plasma ceramide levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay both at baseline and after MPS. ResultsSeventy-eight patients had inducible myocardial ischemia on stress MPS. Women had significantly higher circulating levels of basal and post-stress Cer(d18:1/16:0) and Cer(d18:1/18:0) compared to men, whereas all other plasma ceramides did not differ between the sexes. Of the six measured plasma ceramides, basal Cer(d18:1/24:1) showed the strongest association with the presence of stress-induced myocardial perfusion defects in univariate analysis (unadjusted-odds ratio 1.48 per 1-SD increment, 95% confidence interval 1.08–2.04). Notably, after adjustment for age, sex, smoking, dyslipidemia, hypertension, diabetes, prior history of CAD, left ventricular ejection fraction, and type of stress testing (exercise vs. dypiridamole), all measured ceramides, except for plasma Cer(d18:1/24:0), were independently associated with the presence of inducible myocardial ischemia. ConclusionsDistinct plasma ceramides are positive and independent predictors of stress-induced myocardial perfusion defects in patients with established or suspected CAD referred for clinically indicated MPS. Further research is needed to examine whether distinct plasma ceramides could be a useful therapeutic target for treatment and management of CAD.

Effects of Verapamil and Pinacidil on Extracellular K+, pH, and the Incidence of Ventricular Fibrillation during 60 Minutes of Ischemia.

Ca++-channel antagonist verapamil and ATP-sensitive K+-channel opener pinacidil are known to decrease the rise in extracellular K+ ([K+]e) level and pH (pHe) that occurs during reversible acute myocardial ischemia and to lessen the accompanying activation delay. Verapamil is also known to decrease the incidence of ventricular tachycardia (VT)/fibrillation (VF) during acute myocardial ischemia; however, the effects of ATP-sensitive K+-channel opener on the incidence of VT/VF are controversial. We studied, in an in vivo pig model, the effects of verapamil and pinacidil on the changes in [K+]e level and pHe, local activation, and the incidence of VT/VF during 60 minutes of ischemia. Thirty-one pigs were divided into 2 groups: a verapamil group (9 control pigs and 8 verapamil-treated pigs) and pinacidil group (5 control pigs and 9 pinacidil-treated pigs). In the verapamil group, VF developed in 1 of the 9 control pigs, whereas no VF developed in 8 verapamil-treated pigs. In the pinacidil group, VF developed in 3 of the 5 control pigs and all 9 pinacidil-treated pigs. Under verapamil treatment (versus the control condition), onset of the second rise in [K+]e level was delayed, and the maximum rise in [K+]e level was decreased. Under pinacidil treatment (versus the control condition), time to the onset of VT/VF was shorter than that under the control condition, and VT/VF developed at lower [K+]e level and higher pHe. In conclusion, VF may develop at a lesser [K+]e rise and pHe fall in the presence of pinacidil during acute myocardial ischemia.

CARDIAC TROPONIN T CONCENTRATIONS MEASURED WITH A HIGH-SENSITIVITY ASSAY AND REVERSIBLE MYOCARDIAL ISCHEMIA IN PATIENTS WITH SUSPECTED STABLE ANGINA: A DOPPLER-CIP SUBSTUDY

Cardiac troponin T measured with high sensitivity assays (hs-cTnT) have been associated with reversible myocardial ischemia, but whether hs-cTnT concentrations are related to the presence of reversible ventricular hypokinesia or perfusion defects in patients with suspected stable angina is unknown

Alternative interventions for refractory angina

### Learning objectives Refractory angina (RA) is conventionally defined as a chronic condition (≥3 months in duration) characterised by angina caused by coronary insufficiency in the setting of coronary artery...

Traditional and Alternative Therapies for Refractory Angina.

Refractory angina (RFA) is an unfavourable condition that is characterized with persistent angina due to reversible myocardial ischemia in patients with coronary artery disease that remains uncontrollable despite an optimal combination of pharmacological agents and revascularization. Despite significant advances in revascularization techniques and agents used in pharmacological therapy, there is still a significant population suffering from RFA and the global prevalence is even increasing. Anti- anginal treatment and secondary risk-factor modification are the traditional approaches for this group of patients. Furthermore, now there is still a large number of alternative treatment options. In order to review traditional and alternative treatment strategies in patients with RFA, we searched Pubmed for articles in English using the search terms "pharmacological therapy, refractory angina", "alternative therapy, refractory angina" between inception to June 2016. We also went through separately for each alternative treatment modality on Pubmed. To identify further articles, we handsearched related citations in review articles and commentaries. We also included data from the European Society of Cardiology (2013), and the Canadian Society of Cardiology/ Canadian Pain Society (2012) guidelines. Data show that besides traditional pharmacological agents, such as nitrates, beta- blockers or calcium channel blockers, novel antiischemic drugs and if symptoms persist, several non- invasive and/ or invasive alternative strategies may be considered. Impact of some pharmacological agents, such as rho- kinase inhibitors, and novel alternative treatment modalities, such as coronary sinus reducers, stem cell therapy, gene and protein therapy, on outcomes are still under investigation.

P.1.012 - N-acylethanolamines attenuate Toll-like receptor (TLR)3-induced neuroinflammation, nociceptive and anxiety-like behaviour in rats

Increased circulating osteoprotegerin (OPG) levels have been associated with the prevalence and severity of coronary artery disease and the risk of cardiovascular death. OPG is a cytokine of the tumor necrosis factor receptor superfamily and is expressed in various cell types in the body, including osteoblasts, inflammatory cells, vascular smooth muscle cells/endothelial cells and cardiomyocytes. The main sources determining OPG levels in the circulation however, are not well understood, and whether reversible myocardial ischemia influences OPG levels are not known. Accordingly, OPG levels were measured in 198 patients referred for exercise stress testing and myocardial perfusion imaging (MPI). In addition OPG levels were measured in 8 healthy control subjects performing a maximal bicycle stress test. Plasma samples were collected before, immediately after, 1.5 h and 4.5 h after exercise stress testing with MPI. OPG levels at baseline were not different in patient with reversible myocardial ischemia (n = 19) and patients without reversible ischemia (n = 179) (4.7 [3.6–5.5] pmol/L vs. 4.3 [3.4–5.2] pmol/L, p = 0.21), and there was an increase in OPG levels immediately after exercise regardless of whether or not the patient had reversible ischemia on MPI (absolute increase: 0.2 [0–0.55] pmol/L vs. 0.3 [0–0.5] pmol/L, p = 0.72). OPG levels also increased immediately after stress in the 8 control subjects (3.5 (3.2–3.8) pmol/L at baseline to 3.8 (3.5–4.7), p = 0.008). In conclusion, OPG levels increase acutely during exercise stress testing, but this increase is likely caused by mechanisms other than myocardial ischemia.

A Prospective Natural History Study of Coronary Atherosclerosis Using Fractional Flow Reserve

BackgroundIn patients with coronary artery disease, clinical outcome depends on the extent of reversible myocardial ischemia. Whether the outcome also depends on the severity of the stenosis as determined by fractional flow reserve (FFR) remains unknown. ObjectivesThis study sought to investigate the relationship between FFR values and vessel-related clinical outcome. MethodsWe prospectively studied major adverse cardiovascular events (MACE) at 2 years in 607 patients in whom all stenoses were assessed by FFR and who were treated with medical therapy alone. The relationship between FFR and 2-year MACE was assessed as a continuous function. Logistic and Cox proportional hazards regression models were used to calculate the average decrease in the risk of MACE per 0.05-U increase in FFR. ResultsMACE occurred in 272 (26.5%) of 1,029 lesions. Target lesions with diameter stenosis ≥70% were more often present in the MACE group (p < 0.01). Median FFR was significantly lower in the MACE group versus the non-MACE group (0.68 [interquartile range: 0.54 to 0.77] vs. 0.80 [interquartile range: 0.70 to 0.88]; p < 0.01). The cumulative incidence of MACE significantly increased with increasing FFR quartiles. An average decrease in MACE per 0.05-unit increase in FFR was statistically significant even after adjustment for all clinical and angiographic features (odds ratio: 0.81; 95% confidence interval: 0.76 to 0.86]). The strongest increase in MACE occurred for FFR values between 0.80 and 0.60. In multivariable Cox regression analysis, FFR was significantly associated with MACE up to 2 years (hazard ratio: 0.87; 95% confidence interval: 0.83 to 0.91]). ConclusionsIn patients with stable coronary disease, stenosis severity as assessed by FFR is a major and independent predictor of lesion-related outcome. (FAME II - Fractional Flow Reserve [FFR] Guided Percutaneous Coronary Intervention [PCI] Plus Optimal Medical Treatment [OMT] Verses OMT; NCT01132495)