Seattle Angina Pectoris Questionnaire and Canadian Cardiovascular Society Angina Categories in the Assessment of Total Coronary Atherosclerotic Burden.

The patient reported angina measurement with the Seattle Angina Questionnaire (SAQ) has shown to have prognostic implications and became an endpoint in clinical trials. Our objective was to study physician-reported and SAQ severity with the total coronary atherosclerotic burden as assessed by 4 angiographic scores. We prospectively analyzed data of consecutive patients scheduled for coronary angiography or percutaneous coronary intervention. The Canadian Cardiovascular Society (CCS) angina categories was used as physician-reported angina. SAQ domains were categorized as severe (0 to 24), moderate 25 to 75 and mild angina (>75). All angina assessments were done before coronary angiography. Gensini, Syntax, Friesinger, and Sullivan angiographic scores were used for total atherosclerotic burden quantification: 261 patients were included in the present analysis. The median age was 66.0 (59.0 to 71.8) years, 53.6% were male and 43.7% had diabetes. The median SYNTAX score was 6.0 (0 to 18.0). The worse the symptoms of CCS categories, the more severe was the atherosclerotic burden in all angiographic scores: SYNTAX (p = 0.01); Gensini (p <0.01); Friesinger (p = 0.02) and Sullivan (p = 0.03). Conversely, SAQ domains were not able to discriminate the severity of CAD in any of the scores. The only exception was the severe SAQ quality of life that had worse Gensini score than the mild SAQ quality of life (p = 0.04). In conclusion, CCS angina categories are related to the total atherosclerotic burden in coronary angiography, by all angiographic scores. SAQ domains should be used as a measure of patient functionality and quality of life but not as a measure of CAD severity.

Combined stress myocardial CT perfusion and coronary CT angiography as a feasible strategy among patients presenting with acute chest pain to the emergency department.

BACKGROUND: A combined approach of myocardial CT perfusion (CTP) with coronary CT angiography (CTA) was shown to have better diagnostic accuracy than coronary CTA alone. However, data on cost benefits and length of stay when compared to other perfusion imaging modalities has not been evaluated. Therefore, we aim to perform a feasibility study to assess direct costs and length of stay of a combined stress CTP/CTA and use SPECT myocardial perfusion imaging (SPECT-MPI) as a benchmark, among chest pain patients at intermediate-risk for acute coronary syndrome (ACS) presenting to the emergency department (ED). METHODS: This is a prospective two-arm clinical trial (NCT02538861) with 43 patients enrolled in stress CTP/CTA arm (General Electric Revolution CT) and 102 in SPECT-MPI arm. Mean age of the study population was 65 â€‹± â€‹12 years; 56% were men. We used multivariable linear regression analysis to compare length of stay and direct costs between the two modalities. RESULTS: Overall, 9 out of the 43 patients (21%) with CTP/CTA testing had an abnormal test. Of these 9 patients, 7 patients underwent invasive coronary angiography and 6 patients were found to have obstructive coronary artery disease. Normal CTP/CTA test was found in 34 patients (79%), who were discharged home and all patients were free of major adverse cardiac events at 30 days. The mean length of stay was significantly shorter by 28% (mean difference: 14.7 â€‹h; 95% CI: 0.7, 21) among stress CTP/CTA (20 â€‹h [IQR: 16, 37]) compared to SPECT-MPI (30 â€‹h [IQR: 19, 44.5]). Mean direct costs were significantly lower by 44% (mean difference: $1535; 95% CI: 987, 2082) among stress CTA/CTP ($1750 [IQR: 1474, 2114] compared to SPECT-MPI ($2837 [IQR: 2491, 3554]). CONCLUSION: Combined stress CTP/CTA is a feasible strategy for evaluation of chest pain patients presenting to ED at intermediate-risk for ACS and has the potential to lead to shorter length of stay and lower direct costs.

Long-Term (3 Years) Outcomes of Ranolazine Therapy for Refractory Angina Pectoris (from the Ranolazine Refractory Registry).

Ranolazine is approved for patients with chronic stable angina but has not been formally studied in patients with refractory angina pectoris (RAP). Patients with RAP have limited therapeutic options and significant limitations in their quality of life. The Ranolazine Refractory Angina Registry was designed to evaluate the safety, tolerability, and effectiveness of ranolazine in RAP patients in order to expand treatment options for this challenging patient population. Using an extensive prospective database, we enrolled 158 consecutive patients evaluated in a dedicated RAP clinic. Angina class, medications, major adverse cardiac events including death, myocardial infarction, and revascularization were obtained at 12, 24, and 36 months. At 3 years, 95 (60%) patients remained on ranolazine. A ≥2 class improvement in angina was seen in 48% (38 of 80 patients with known Canadian Cardiovascular Society class) of those who remained on ranolazine. Discontinuation due to side effects, ineffectiveness, cost, and progression of disease were the principle reasons for discontinuation, but primarily occurred within the first year. In conclusion, ranolazine is an effective antianginal therapy at 3-year follow-up in patients with RAP and may reduce cardiac readmission.

Comparison of NICE and ESC proposed strategies on new onset chest pain and the contemporary clinical utility of pretest probability risk score.

AIMS: Patients with de novo chest pain are usually investigated non-invasively. The new UK-National Institute for Health and Care Excellence (NICE) guidelines recommend CT coronary angiography (CTCA) for all patients, while European Society of Cardiology (ESC) recommends functional tests. We sought to compare the clinical utility and perform a cost analysis of these recommendations in two UK centres with different primary investigative strategies. METHODSRESULTS: We compared two groups of patients, group A (n=667) and group B (n=654), with new onset chest pain in two neighbouring National Health Service hospitals, each primarily following either ESC (group A) or NICE (group B) guidance. We assessed the clinical utility of each strategy, including progression to invasive coronary angiography (ICA) and revascularisation. We present a retrospective cost analysis in the context of UK tariff for stress echo (£176), CTCA (£220) and ICA (£1001). Finally, we sought to identify predictors of revascularisation in the whole population.Baseline characteristics in both groups were similar. The progression to ICA was comparable (9.9% vs 12.0%, p=0.377), with similar requirement for revascularisation (4.0% vs 5.0%.; p=0.532). The average cost of investigations per investigated patient was lower in group A (£279.66 vs £325.77), saving £46.11 per patient. The ESC recommended risk score (RS) was found to be the only predictor of revascularisation (OR 1.05, 95% CI 1.04 to 1.06; p<0.001). CONCLUSION: Both NICE and ESC-proposed strategies led to similar rates of ICA and need for revascularisation in discrete, but similar groups of patients. The SE-first approach had a lower overall cost by £46.11 per patient, and the ESC RS was the only variable correlated to revascularisation.

Cost-effectiveness of the coronary sinus Reducer and its impact on the healthcare burden of refractory angina patients.

AIMS: The coronary sinus Reducer is a percutaneous device proven to improve angina symptoms in refractory angina (RA). We evaluated its potential cost-effectiveness and impact on the healthcare resource use. METHODS AND RESULTS: Angina-related healthcare resource usage and quality-of-life data were collected for 215 consecutive RA patients undergoing Reducer implantation in Belgium, the Netherlands, and Italy. Costs were assessed from each country's healthcare system perspective. Data from the date of RA diagnosis to Reducer implantation [Standard-of-Care (SoC)-period] and from Reducer implantation to follow-up (Reducer-period) were compared: during Reducer-period, a significant reduction in angina-driven hospitalizations, outpatient visits, coronary angiograms, and percutaneous coronary interventions per patient-year was observed, translating into significantly reduced costs per patient-year. To assess cost-effectiveness, costs and utilities of 1-year SoC were compared with those of 1-year Reducer-period. Assumptions on Reducer efficacy duration were further explored with modelled projections. Reducer was associated with higher quality-adjusted life years (QALYs: 0.665 vs. 0.580, P < 0.001) and incremental costs, yielding incremental cost-effectiveness ratios (ICERs) of 53 197, 34 948, 63 146 €/QALY gained in Belgium, the Netherlands, and Italy, respectively. Under both the assumptions of 2 and 3 years Reducer effect duration with a 30%-year efficacy decrease, the device yielded ICERs in the range of 1977-20 796 €/QALY gained. CONCLUSION: In patients with RA, Reducer device decreases healthcare resource use and related costs. In a limited 1-year timeframe, Reducer is consistently cost-effective according to a range of cost-effectiveness thresholds. Under the explored assumptions, the device yields cost-effectiveness ratios suggesting high value from all the considered perspectives.

Clinical Use of CT-Derived Fractional Flow Reserve in the Emergency Department.

OBJECTIVES: This study sought to examine the feasibility, safety, clinical outcomes, and costs associated with computed tomography-derived fractional flow reserve (FFRCT) in acute chest pain (ACP) patients in a coronary computed tomography angiography (CTA)-based triage program. BACKGROUND: FFRCT is useful in determining lesion-specific ischemia in patients with stable ischemic heart disease, but its utility in ACP has not been studied. METHODS: ACP patients with no known coronary artery disease undergoing coronary CTA and coronary CTA with FFRCT were studied. FFRCT ≤0.80 was considered positive for hemodynamically significant stenosis. RESULTS: Among 555 patients, 297 underwent coronary CTA and FFRCT (196 negative, 101 positive), whereas 258 had coronary CTA only. The rejection rate for FFRCT was 1.6%. At 90 days, there was no difference in major adverse cardiac events (including death, nonfatal myocardial infarction, and unexpected revascularization after the index visit) between the coronary CTA and FFRCT groups (4.3% vs. 2.7%; p = 0.310). Diagnostic failure, defined as discordance between the coronary CTA or FFRCT results with invasive findings, did not differ between the groups (1.9% vs. 1.68%; p = NS). No deaths or myocardial infarction occurred with negative FFRCT when revascularization was deferred. Negative FFRCT was associated with higher nonobstructive disease on invasive coronary angiography (56.5%) than positive FFRCT (8.0%) and coronary CTA (22.9%) (p < 0.001). There was no difference in overall costs between the coronary CTA and FFRCT groups ($8,582 vs. $8,048; p = 0.550). CONCLUSIONS: In ACP, FFRCT is feasible, with no difference in major adverse cardiac events and costs compared with coronary CTA alone. Deferral of revascularization is safe with negative FFRCT, which is associated with higher nonobstructive disease on invasive angiography.

Optimizing the Assessment of Patient Clinical Risk at the Time of Cardiac Stress Testing.

Due to a marked temporal decline in inducible myocardial ischemia over recent decades, most diagnostic patients now referred for cardiac stress testing have nonischemic studies. Among nonischemic patients, however, long-term risk is heterogeneous and highly influenced by a variety of clinical parameters. Herein, we review 8 factors that can govern long-term clinical risk: coronary risk factor burden; patient symptoms; exercise capacity and exercise test responses; the need for pharmacologic stress testing; autonomic function; musculoskeletal status; subclinical atherosclerosis; and psychosocial risk. To capture the clinical benefit provided by both assessing myocardial ischemia and these additional parameters, the authors propose that a cardiac stress tests report have an additional component beyond statements as to the likelihood of obstructive coronary artery disease and/or magnitude of ischemia. This added component could be a comment section designed to make referring physicians aware of aspects of long-term risk that may influence clinical management and potentially lead to changes in the intensity of risk factor management, frequency of follow-up, need for further testing, or other management decisions. In this manner, the increasingly frequent normal stress test result might more commonly influence treatment recommendations and even patient behavior, thus leading to improvement in patient outcomes even in the setting of normal stress test results.

Impact of baseline calibration on semiquantitative assessment of myocardial perfusion reserve by adenosine stress MRI.

In this study, we sought to investigate the impact of baseline calibration, which is used in quantitative cardiac MRI perfusion analysis to correct for surface coil inhomogeneity and noise, on myocardial perfusion reserve index (MPRI) and its contribution to previously reported paradoxical low MPRI < 1.0 in patients with unobstructed coronary arteries. Semiquantitative perfusion analysis was performed in 20 patients with unobstructed coronary arteries undergoing stress/rest perfusion CMR and in ten patients undergoing paired rest perfusion CMR. The following baseline calibration settings were compared: (1) baseline division, (2) baseline subtraction and (3) no baseline calibration. In uncalibrated analysis, we observed ~ 20% segmental dispersion of signal intensity (SI)-over-time curves. Both baseline subtraction and baseline division reduced relative dispersion of t0-SI (p < 0.001), but only baseline division corrected for dispersion of peak-SI and maximum upslope also (p < 0.001). In the assessment of perfusion indices, however, baseline division resulted in paradoxical low MPRI (1.01 ± 0.23 vs. 1.63 ± 0.38, p < 0.001) and rest perfusion index (RPI 0.54 ± 0.07 vs. 0.94 ± 0.12, p < 0.001), respectively. This was due to a reversed ratio of blood-pool and myocardial baseline-SI before the second perfusion study caused by circulating contrast agent from the first injection. In conclusion, baseline division reliably corrects for inhomogeneity of the surface coil sensitivity profile facilitating comparisons of regional myocardial perfusion during hyperemia or at rest. However, in the assessment of MPRI, baseline division can lead to paradoxical low results (even MPRI < 1.0 in patients with unobstructed coronary arteries) potentially mimicking severely impaired perfusion reserve. Thus, in the assessment of MPRI we propose to waive baseline calibration.

Long-term statin persistence is poor among high-risk patients with dyslipidemia: a real-world administrative claims analysis.

BACKGROUND: A decade ago, statin persistence was < 50% after 1 year, and recent short-term analyses have revealed very little progress in improving statin persistence, even in patients with a prior cardiovascular (CV) event. Data on longer-term statin persistence are lacking. We measured long-term statin persistence in patients with high CV risk. METHODS: This retrospective administrative claims analysis of the Optum Research Database included patients aged ≥ 45 years with diabetes and/or atherosclerotic CV disease (ASCVD) who had a statin prescription filled in 2010. It included an elevated triglycerides (TG) cohort of patients with index date in 2010 and TG ≥ 150 mg/dL (n = 23,181) and a propensity-matched comparator cohort with TG < 150 mg/dL and high-density lipoprotein cholesterol > 40 mg/dL (n = 23,181). Both cohorts were followed for ≥ 6 months up to March 2016. RESULTS: The probability of remaining on a prescription fill for index statin therapy was 47% after 1 year and 19% after 5 years in both cohorts. Statin persistence was worse among women than men, and among younger versus older patients (P < 0.001 for all comparisons). After 5 years, the probability of remaining on a prescription fill for index statin was < 25% across all subgroups assessed including patients with and without baseline revascularization, heart failure, peripheral artery disease and renal disease. Similar results were observed in a subcohort analysis of patients with TG 200-499 mg/dL. CONCLUSIONS: Long-term statin persistence after 5 years is alarmingly low (< 25%) and is a public health concern.

Comparison of outcomes in emergency department patients with suspected cardiac chest pain: two-centre prospective observational study in Southern China.

BACKGROUND: Hong Kong (HK) and Guangzhou (GZ) are cities in China with different healthcare systems. This study aimed to compare 30-day and 6-month mortality and characteristics of patients with suspected cardiac chest pain admitted to two emergency departments (ED) in HK and GZ. METHODS: A prospective observational study enrolled patients with suspected cardiac chest pain presenting to EDs in the Prince of Wales Hospital (PWH), HK and the Second Affiliated Hospital of Guangzhou Medical University (AHGZMU),GZ. The primary outcome was 30-day and 6-month mortality. RESULTS: In total, 996 patients were recruited, 407 cases from GZ and 589 cases from HK.The 30-day and 6-month mortality of chest patients were 3.7% and 4.7% in GZand 0.3% and 1.9% in HK, respectively. Serum creatinine level (Cr) was an independent factor for 30-day mortality whilst Cr and systolic blood pressure (SBP) were independent factors for 6-month mortality. In Cox regression analysis, unadjusted and adjusted hazard ratios for 30-day and 6-month mortality in GZ were significantly increased. CONCLUSION: The 30-day and 6-month mortality of patients with suspected cardiac chest pain in Guangzhou were higher than in Hong Kong due to due to different baseline clinical characteristics of patients and different distributions of diagnoses, which were associated with different healthcare systems. Serum creatinine and SBP were independent factors for 30-day and 6-month mortality.

Cost-effectiveness of a management strategy based on exercise echocardiography versus exercise electrocardiography in patients presenting with suspected angina during long term follow up: A randomized study.

INTRODUCTION: Exercise ECG (Ex-ECG) is advocated by guidelines for patients with low - intermediate probability of coronary artery disease (CAD). However, there are no randomized studies comparing Ex-ECG with exercise stress echocardiography (ESE) evaluating long term cost-effectiveness of each management strategy. METHODS: Accordingly, 385 patients with no prior CAD and low-intermediate probability of CAD (mean pre-test probability 34%), were randomized to undergo either Ex-ECG (194 patients) or ESE (191 patients). The primary endpoint was clinical effectiveness defined as the positive predictive value (PPV) for the detection of CAD of each test. Cost-effectiveness was derived using the cumulative costs incurred by each diagnostic strategy during a mean of follow up of 3.0 years. RESULTS: The PPV of ESE and Ex-ECG were 100% and 64% (p = 0.04) respectively for the detection of CAD. There were fewer clinic (31 vs 59, p < 0.01) and emergency visits (14 vs 30, p = 0.01) and lower number of hospital bed days (8 vs 29, p < 0.01) in the ESE arm, with fewer patients undergoing coronary angiography (13.4% vs 6.3%, p = 0.02). The overall cumulative mean costs per patient were £796 for Ex-ECG and £631 for ESE respectively (p = 0.04) equating to a >20% reduction in cost with an ESE strategy with no difference in the combined end-point of death, myocardial infarction, unplanned revascularization and hospitalization for chest pain between ESE and Ex-ECG (3.2% vs 3.7%, p = 0.38). CONCLUSION: In patients with low to intermediate pretest probability of CAD and suspected angina, an ESE management strategy is cost-effective when compared with Ex-ECG during long term follow up.

Design and Rationale of the RIPCORD 2 Trial (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?): A Randomized Controlled Trial to Compare Routine Pressure Wire Assessment With Conventional Angiography in the Management of Patients With Coronary Artery Disease.

BACKGROUND: Investigation of anginal chest pain has traditionally involved either assessment of the coronary anatomy by angiography or noninvasive testing for reversible ischemia. Invasive pressure wire assessment at the time of angiography offers information on both anatomy and physiology. Fractional flow reserve-guided percutaneous coronary intervention is associated with lower resource utilization and improved clinical outcome compared with angiographic guidance alone. However, the value of routine fractional flow reserve of all major coronary vessels at the time of diagnostic angiography has not been established in a randomized trial despite persuasive observational data. A change in practice to routine fractional flow reserve assessment of all major vessels during diagnostic angiography would require evidence not just of clinical benefit but also of cost effectiveness. This randomized trial aims to test that strategy. METHODS AND RESULTS: RIPCORD 2 (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?) is an 1100 patient prospective, multicenter, randomized trial. Participants are randomized, after initial coronary angiography, and in equal proportion, to assessment and management according to (1) conventional angiography only or (2) additional routine pressure wire assessment in all epicardial vessels of sufficient size to be amenable to revascularization. The primary economic outcome measure will be a comparison of healthcare costs at 1 year. The primary quality-of-life outcome measure analysis will compare patient-reported quality-of-life scores at 1 year. Secondary outcome measures include clinical events at 1 year, management strategy (optimal medical therapy with or without revascularization), and angina status at 1 year according to Canadian Cardiovascular Society angina grade. CONCLUSIONS: The aim of the RIPCORD 2 trial is to assess whether a strategy of routine fractional flow reserve-guided assessment and management of all major coronary arteries will be associated with more effective resource utilization, improved quality of life, and better clinical outcome, compared with angiographic guidance alone. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02892903.

Value of Myocardial Perfusion Assessment With Coronary Computed Tomography Angiography in Patients With Recent Acute-Onset Chest Pain.

OBJECTIVES: The authors sought to perform a randomized controlled trial to evaluate the clinical efficacy of combined examination with coronary computed tomography angiography (CTA) and computed tomography perfusion imaging (CTP) compared to coronary CTA alone. BACKGROUND: Stress myocardial CTP may increase diagnostic specificity when added to coronary CTA in patients suspected of having ischemic heart disease. METHODS: Patients recently hospitalized for acute-onset chest pain, who had acute coronary syndrome had been ruled out by normal electrocardiograms, normal troponin levels, and relief of symptoms, and who had a clinical indication for outpatient noninvasive testing, were screened for inclusion in the CATCH-2 (CArdiac cT in the treatment of acute CHest pain 2) trial (NCT02014311). Patients were randomized 1:1 to examination with coronary CTA or coronary CTA+CTP. The primary endpoint was the frequency of coronary revascularization among patients referred for invasive coronary angiography (ICA) based on index computed tomography evaluation. Secondary endpoints were invasive procedural complications at index-related ICA, post-index cardiac death, hospital admittance because of recurrence of chest pain, unstable angina pectoris, or acute myocardial infarction, ICA, and revascularization. RESULTS: Among 300 patients allocated to the coronary CTA+CTP group, 41 (14%) were referred for ICA compared with 89 (30%) allocated to coronary CTA (p < 0.0001). The primary endpoint occurred in 50% of coronary CTA+CTP patients versus 48% of invasively examined patients (p = 0.85). The total number of revascularizations was significantly lower in the coronary CTA+CTP group compared to the coronary CTA group (n = 20 [7%] vs. n = 42 [14%]; p = 0.0045). At median follow-up of 1.5 years, the occurrence of secondary endpoints was similar in the 2 groups. CONCLUSIONS: A post-discharge diagnostic strategy of coronary CTA+CTP safely reduces the need for invasive examination and treatment in patients suspected of having ischemic heart disease. (CArdiac cT in the treatment of acute CHest pain 2-Myocardial CT Perfusion [CATCH2]; NCT02014311).

[Innovative therapies for the treatment of refractory angina: the Reducer, a percutaneous device to narrow the coronary sinus]. / Terapie innovative per il trattamento dell'angina refrattaria: il Reducer, dispositivo percutaneo di restringimento del seno coronarico venoso.

Refractory angina is a chronic condition characterized by the presence of disabling symptoms due to severe obstructive coronary artery disease that is not improved by a combination of medical therapy and percutaneous or surgical revascularization. Mortality rates associated with this condition are quite low in clinically stable patients on optimal medical therapy, but rehospitalization rates remain high. This mandates the need for new therapies targeting an improvement of symptoms in this population, taking into account also the potential impact in terms of healthcare and costs. The increase in coronary sinus pressure seems to reduce myocardial ischemia leading to a redistribution of blood flow to the ischemic territories. The coronary sinus Reducer is a percutaneous implantable device, made of a stainless steel hourglass-shaped stent, designed to achieve controlled narrowing of the coronary sinus and to increase its upstream pressure. In various studies, the Reducer was safely implanted percutaneously via the right jugular vein in patients with refractory angina who were not amenable to revascularization and was associated with an improvement in anginal symptoms and ischemia. These results support further evaluation of the Reducer as an alternative treatment for patients with chronic refractory angina who are not candidates for coronary revascularization.

Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease.

OBJECTIVES: This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease. BACKGROUND: Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation. METHODS: We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia. RESULTS: All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn. CONCLUSIONS: Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

[Comparative Assessment of Effects of Isosorbide Dinitrate, Isosorbide-5-Mononitrate and Nicorandil on the Frequency of Angina Attacks and Vasoregulating Endothelial Function in Patients With Ischemic Heart Disease].

AIM: to compare effects of isosorbide dinitrate, isosorbide-5-mononitrate and nicorandil on frequency of angina attacks and vasoregulating endothelial function in patients with ischemic heart disease (IHD). MATERIAL AND METHODS. In 117 patients with stable II-III functional class angina we analyzed frequency of angina attacks, exercise tolerance, data of 24-hour Holter ECG monitoring and brachial artery Doppler study. RESULTS. Patients with IHD had impaired endothelium-dependent vasodilation in the form of reduced endothelial response to increase of "shear stress" during test with reactive hyperemia. Long-term therapy with isosorbide dinitrate, isosorbide-5-mononitrate, and nicorandil was associated with normalization of endothelium-dependent vasodilation of the brachial artery. This effect was more pronounced during therapy with nicorandil.

Clinical characteristics and outcomes of patients with angina and heart failure in the CHARM (Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity) Programme.

AIMS: To investigate the relationship between angina pectoris and fatal and non-fatal clinical outcomes in heart failure with reduced and preserved ejection fraction (HF-REF and HF-PEF, respectively). METHODS AND RESULTS: Of 7599 patients in the CHARM program, 5408 had ischaemic heart disease; 3855 had HF-REF (ejection fraction ≤45%) and 1553 had HF-PEF. These patients were separated into three groups: no history of angina, previous angina, and current angina. Three coronary outcomes were examined: fatal or non-fatal myocardial infarction (MI); MI or hospitalization for unstable angina (UA); and MI, UA or coronary revascularization. The composite heart failure outcome of cardiovascular death or heart failure hospitalization (HFH) was also analysed, along with its components and all-cause mortality. New York Heart Association functional class was worse in both HF-REF and HF-PEF patients with current angina compared with patients without angina (P < 0.001 and P = 0.005 respectively), despite similar clinical examination findings and ejection fraction. Patients with current angina had a higher risk of all three coronary outcomes (adjusted hazard ratios ranging from 1.8-3.1) than those without angina but did not have a higher risk of heart failure outcomes or all-cause mortality. CONCLUSION: In patients with heart failure current angina is associated with significantly more functional limitation and a higher risk of coronary events, across the spectrum of left ventricular ejection fraction.

Increased monomeric CRP levels in acute myocardial infarction: a possible new and specific biomarker for diagnosis and severity assessment of disease.

BACKGROUND: Monomeric CRP (mCRP) plays an important role in the process of atherosclerotic plaque rupture. Recently, it has been reported that mCRP was associated with acute myocardial infarction (AMI). OBJECTIVES: The aim of this study was to examine whether mCRP is increased in AMI patients and to investigate the possibility of using circulating mCRP as a biomarker for AMI diagnosis and severity assessment of disease. METHODS: A mCRP monoclonal antibody was generated and verified for its specificity. Immunofluorescence was used to assess the localization of mCRP in the infarcted myocardium. Furthermore, 101 AMI, 38 unstable angina pectoris (UAP) and 41 stable angina pectoris (SAP) patients were enrolled, and 43 healthy volunteer were recruited as controls in the study. Venous blood samples were collected to measure the circulating mCRP, cardiac Troponin T and hs-CRP levels. RESULTS: Significantly increased mCRP levels were observed in the infarcted myocardium of model mice. In addition, significantly increased plasma mCRP levels were also detected in AMI patients (20.96 ± 1.64 ng/ml) compared to those with UAP, SAP or in control patients (all 0 ng/ml, p < 0.001). ROC analysis revealed that circulating mCRP had considerable diagnostic accuracy for AMI with an AUC of 0.928 (95% confidence interval 0.887-0.969). Furthermore, nine patients (9/101, 8.91%) in AMI group died before the 30-day follow-up, and their plasma mCRP concentration was significantly higher than those in surviving patients (36.70 ± 10.26 vs. 19.41 ± 1.43 ng/ml, P = 0.002). CONCLUSIONS: These results indicate that mCRP is increased in AMI and that circulating mCRP might be a potential biomarker for diagnosis and severity assessment of disease in AMI.