Stress echocardiography for left ventricular diastolic dysfunction detection in patients with non-severe chronic obstructive pulmonary disease: a cross-sectional study.

AIM: To assess whether the simultaneous performance of exercise stress echocardiography and cardio-pulmonary testing (ESE-CPET) may facilitate the timely diagnosis of subclinical left ventricular diastolic dysfunction (LVDD) in patients with non-severe chronic obstructive pulmonary disease (COPD), preserved left ventricular systolic function, and exertional dyspnea or exercise intolerance. METHODS: This cross-sectional study, conducted between May 2017 and April 2018, involved 104 non-severe COPD patients with exertional dyspnea and preserved ejection fraction who underwent echocardiography before CPET and 1-2 minutes after peak exercise. Based on the peak E/e' ratio, patients were divided into the group with stress-induced LVDD - E/e'>15 and the group without stress-induced LVDD. We assessed the association between LVDD and the following CPET variables: minute ventilation, peak oxygen uptake (VO2), ventilatory efficiency, heart rate reserve, and blood pressure. RESULTS: During ESE-CPET, stress-induced LVDD occurred in 67/104 patients (64%). These patients had lower work load, peak VO2, O2 pulse, and minute ventilation (VE), and higher VE/VCO2 slope than patients without stress-induced LVDD (35.18±10.4 vs 37.01±11.11, P<0.05). None of the CPET variables correlated with E/e'. CONCLUSION: Combined ESE-CPET may distinguish masked LVDD in patients with non-severe COPD with exertional dyspnea and preserved left ventricular systolic function. None of the CPET variables was a predictor for subclinical LVDD.

Darapladib for preventing ischemic events in stable coronary heart disease.

BACKGROUND: Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2. METHODS: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). RESULTS: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). CONCLUSIONS: In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).

Positive Stress Electrocardiography in Patients With Non-obstructive Coronary Disease.

Introduction The episodes of myocardial ischemia in patients with non-obstructive coronary disease are extremely variable in provoking factors and presentation. Purpose We investigated the significance of coronary blood flow velocity and epicardial diameter as correlates of a positive electrocardiographic exercise stress test (ExECG) in hospitalized patients with unstable angina and non-obstructive coronary artery disease. Methods The study was a single-center cohort retrospective. ExECG was performed and analyzed in a group of 79 patients with non-obstructive coronary disease (coronary stenoses < 50%). Thirty-one percent of the patients (n=25) were diagnosed with slow coronary flow phenomenon, SCFP; 40.5% (n=32) - patients with hypertensive disease, left ventricular hypertrophy (LVH), and slow epicardial flow; 27.8% (n=22) with hypertension, left ventricular hypertrophy and normal coronary flow. The patients were hospitalized in University Hospital "Alexandrovska," Sofia in the period 2006-2008. Results The frequency of positive ExECG is increased as a trend was associated with smaller epicardial diameters and pronounced delay in epicardial coronary flow. In the subgroup with SCFP, the risk for a positive ExECG test was determined by slower coronary flow (36.5±7.7 frames vs. 30.3±4.4 frames, p=0.044) and borderline significant by epicardial lumen diameters (3.3±0.8 mm vs. 4.1±1.0 mm, p=0.051) and greater myocardial mass (92.8±12.6 g/m2 vs. 82.9±8.6 g/m2, p=0.054). In cases of left ventricular hypertrophy, which included both patients with the normal and slow epicardial flow, there were no statistically significant correlates of an abnormal exercise stress ECG test. Conclusions In patients with non-obstructive coronary atherosclerosis and predominantly slow epicardial coronary flow, the provoking of ischemia at an electrocardiographic exercise stress test is associated with the lower epicardial flow velocity at rest and with the smaller epicardial diameter. In SCFP, the risk for an abnormal stress test is determined by slower coronary flow, smaller epicardial lumen diameter, and greater myocardial mass. The presence and size of the plaque burden are not associated with a greater risk of a positive ExECG in these patients.

Left Ventricular Diastolic Function: Comparison of Slow Coronary Flow Phenomenon and Left Ventricular Hypertrophy in the Absence of Obstructive Coronary Disease.

Background An interplay of myocardial structural abnormalities and coronary arterial dysfunction underlies the worsening left ventricular compliance. The conventionally used angina drugs have demonstrated a beneficial effect on both angina and coronary flow in cases with microvascular dysfunction and non-obstructive coronary disease. Despite that, vasoactive therapy only partially affects diastolic function in this patient population. Purpose This retrospective study was planned to evaluate the association of myocardial mass, delayed epicardial coronary flow, and vasoactive drugs with parameters of diastolic function in two cohorts with preserved left ventricular function and non-obstructive coronary disease in patients with slow coronary flow phenomenon (SCFP) and patients with the hypertensive disease and left ventricular hypertrophy. Material and methods The epicardial coronary flow was evaluated in 48 patients with unstable angina in the absence of coronary stenosis >50%, by applying the methods of corrected thrombolysis in myocardial infraction frame count (cTFC). The abnormalities in the left ventricular function were assessed by echocardiography using PW-Doppler of the diastolic mitral inflow and tissue Doppler imaging. Twenty-one (43.8%) patients were diagnosed with SCFP, and twelve patients (25%) had slow epicardial coronary flow, hypertensive disease, and ventricular hypertrophy (SFLVH). The remaining 15 (31.3%) were patients with ventricular hypertrophy, hypertension, and non-delayed epicardial coronary flow (NFLVH). Results The patients with SFLVH showed reduced peak early diastolic lateral mitral annular velocity (e'L) when compared to SCFP (7.1±1.9cm/s vs 8.6±2.1 cm/s, p=0.045) and NFLVH (7.1±1.9 cm/s vs 8.7±1.8 cm/s, p=0.018). A borderline significant difference was observed for the peak early diastolic septal mitral annular velocity (e'S) between the patients with SFLVH and SCFP ( 7.0±1.3 cm/s vs 8.3±2.1 cm/s, p=0.057). The ratio of mitral diastolic inflow velocity to early diastolic velocity of the mitral annulus (E/e') in the SFLVH group was a tendency higher than E/e' of the patients with SCFP (9.8±3.1 vs. 8.2±2.1, p=0.084) and NFLVH (9.8±3.1 vs. 7.8±1.5, p=0.051) .In the group with left ventricular hypertrophy, E/e' >10 was more frequently observed in patients with a marked delay in the epicardial flow (33.1 ± 13.1 frames vs. 25.4 ± 11.8 frames, p=0.011) and higher left ventricular mass (146.9 ± 17.7 g/m2 vs. 126.1 ± 121.5 g/m2, p=0.027). Conclusions Patients with microvascular angina represent a diverse population. The echocardiographic parameters of left ventricular relaxation (e') and end-diastolic pressure (E/e') are abnormally altered in the population with left ventricular hypertrophy compared to SCFP. The delayed epicardial flow further impairs diastolic function in hypertensive patients with hypertrophy and non-obstructive coronary disease.

Total Testosterone as a Specific Marker of Acute Kidney Injury in Male Patients With Myocardial Infarction.

Aim The aim of the present study was to assess the significance of total testosterone (T) as a marker of acute kidney injury (AKI) in patients with acute myocardial infarction (MI). Patients and methods The study was a retrospective, single-center cohort study that included 55 consecutive male patients diagnosed with acute MI who were admitted to the Cardiology Clinic of Alexandrovska University Hospital (Sofia, Bulgaria) between July 2011 and December 2013. The plasma total T levels, measured at admission, the peak levels of myocardial necrosis markers, high-sensitive C-reactive protein (hsCRP), and the left ventricular ejection fraction (LVEF) were analyzed in relation to the incidence of AKI. Results The occurrence of AKI was positively predicted by reduced EF (OR=0.825; CI=0.724-0.942; P=0.004), advanced age (OR=1.077; CI=1.038-1.151; P=0.029), and low levels of total T (OR=0.837; CI=0.707-0.990; P=0.037). Reduced systolic function (OR=0.861; 95% CI=0.758-0.978; P=0.022 for EF) and marginally age (OR=1.094; 95% CI=1.000-1.197; P=0.051) contributed to the incidence of AKI in a multivariate model. Total T was not an independent factor (OR=0.841; 95% CI=0.669-1.058; P=0.139) for AKI. The total T levels were significantly inversely correlated with the peak of hsCRP (r= -0.153; P=0.009) and showed a tendency to inverse relation with the SYNTAX score (r= -0.235; P=0.083). Conclusion The total T levels are significantly inversely related to the peak of hsCRP and as a tendency to the SYNTAX score in male patients with acute MI. A low level of plasma total T is not an independent marker of AKI in acute MI. Advanced age and low EF are independent factors for AKI discrimination in a small cohort of patients with acute MI.

Association of High Density Cholesterol With Hyperemic Epicardial Flow and Frame Count Reserve in Patients With Moderate Coronary Lesions and Slow Coronary Flow.

Background Patients with microvascular angina and non-obstructive coronary atherosclerotic disease have an elevated risk of adverse events and all-cause mortality compared with individuals without ischaemic heart disease. The diagnosis coronary microvascular dysfunction in this setting relies on the detection of impaired coronary flow at rest or on calculation of coronary flow reserve. Previous studies demonstrate that the coronary flow reserve assessed by the corrected thrombolysis in myocardial infarction method - the frame count reserve is an objective quantitative alternative to other widely used invasive methods for microvascular status evaluation. Purpose We assessed the significance of clinical, hemodynamic, angiographic variables and therapy with reference to FCR in a small group of patients with up to moderate atherosclerotic coronary lesions and slow coronary flow. Materials and methods: Frame count reserve was evaluated in 15 patients without flow-limiting (>50%) coronary stenoses admitted with unstable angina. Frame count reserve was calculated by dividing the baseline corrected thrombolysis in myocardial infarction frame count (cTFC) by the cTFC assessed after intracoronary infusion of 100 µg of the calcium channel blocker - verapamil. Results The values of frame count reserve correlate positively with the levels of high density cholesterol (r= 0.900, p=0.001), inversely coronary flow after the application of verapamil - cTFCv (r= - 0.534, p=0.049). cTFCv was positively related with the levels of high density lipoproteins (r = - 0.645; p= 0.044) and was negatively influenced by the presence of atherosclerotic lesions at quantitative angiography (42.8±19.1 (n=8) vs 23±5.4 (n=7), p=0.029).The therapy with ß-blocker and long-acting nitrate was associated with insignificantly higher frame count reserves after intracoronary verapamil compared to the continuous intake only of ß-blocker or ß-blocker and verapamil (2.1±0.78 vs 1.34±0.14 vs 1.70±0.70, p=NS). Conclusions Higher high-density lipoproteins relate to higher frame count reserves evaluated using verapamil. The improved blood flow after this microvascular vasodilator is consistently positively related to high-density cholesterol and the lack of atherosclerosis at conventional coronary angiography. The combined intake of micro- and macrovascular vasodilator could be associated with higher frame count reserves compared to therapy with ß-blocker and one vasodilating drug.

Coronary Flow in Patients With Myocardial Bridges, Coronary Fistulae in the Setting of Unstable Non-Obstructive Coronary Disease.

Оbjective Our aim was to describe the difference in epicardial coronary flow at baseline on background anti-ischaemic therapy and following intracoronary glyceryl trinitrate in patients with acute coronary syndrome and non-obstructive coronary disease with and without myocardial bridges and coronary artery fistulae. Materials and methods Coronary flow was characterized in a group of 88 patients with coronary stenoses <50% diagnosed with acute coronary syndrome using the corrected Thrombolysis in Myocardial Infarction frame count (cTFC) method at coronary angiography at baseline and after the application of 200 µg glyceryl trinitrate. Results Тhe patients with myocardial bridges and coronary artery fistulae accounted for 4.4% (n=4) and 2.2% (n=2), respectively, of the patients with acute coronary syndrome. Sixty-two (70%) of all patients demonstrated slow progression of the contrast media (cTFC>25 frames) in at least one coronary artery. Coronary flow was similarly impaired in the patients with myocardial bridges, coronary artery fistulae, and those without coronary anomalies and variants. After the intracoronary infusion of glyceryl trinitrate, the epicardial flow improved in the patients with myocardial bridges and to a lesser degree in the cases with coronary fistulae. Most of the patients who responded to glyceryl trinitrate were on background therapy with calcium channel blockers. Conclusion The epicardial coronary flow of patients with non-obstructive coronary disease with myocardial bridges and acute coronary syndrome showed less impairment compared to baseline in response to intracoronary glyceryl trinitrate applied at background anti-ischaemic therapy that included calcium channel blockers.

Autonomic dysfunction, cardio-pulmonary exercise testing and masked heart failure with preserved ejection fraction in non-severe chronic obstructive pulmonary disease.

BACKGROUND: Autonomic dysfunction (AD) and cardiopulmonary exercise testing (CPET) parameters have been associated with masked heart failure with preserved ejection fraction (HFpEF) in the general population. Their clinical significance for masked HFpEF in chronic obstructive pulmonary disease (COPD) is however elusive. AIM: The aim of the study was to determine the prevalence, correlation and clinical significance of AD and CPET with masked HFpEF, in non-severe COPD patients, complaining of exertional dyspnoea, without clinically overt cardio-vascular (CV) comorbidities. METHODS AND RESULTS: We applied CPET and echocardiography in 68 COPD subjects. Echocardiography was performed before CPET and 1-2 min after peak exercise. Patients were divided into two groups: patients with and without masked HFpEF. Peak E/e' - 15 was applied as a cut-off. Chronotropic incompetence (CI) was assumed if both failure to reach the target heart rate (HR) on exercise and diminished heart rate reserve <80% occurred. Abnormal HR recovery (HRR) was taken if the decline is <12 beats within the first minute after exercise cessation. Univariate regression showed association between masked HFpEF, HRR, VO2, VO2 at AT, oxygen pulse and VE/VCO2 slope. The multivariate regression demonstrated HRR as the only independent predictor of masked HFpEF - (OR 10.28; 95% CI (3.55-29.80)). CONCLUSION: Abnormal HRR is the only independent predictor of masked HFpEF in non-severe COPD patients. Despite of being associated with masked HFpEF, the lower VO2, lower oxygen pulse, higher VE/VCO2 slope and lower exercise load seem to be the consequences, rather than the triggers for it.

The 'right way' to the left chamber in non-severe COPD: Echocardiographic predictors for stress-induced left ventricular diastolic dysfunction.

OBJECTIVE: Dyspnea is a major complaint of both chronic obstructive pulmonary disease (COPD) and heart failure with preserved ejection fraction (HFpEF). It often remains underdiagnosed in COPD patients when only echocardiography at rest is performed. The aim of this study was to evaluate the predictive value of cardiopulmonary and echocardiographic parameters at rest for the diagnosis of HFpEF in non-severe COPD patients who complain of exertional dyspnea and have no overt cardiovascular disease. METHODS: A total of 104 COPD patients underwent echocardiography before cardiopulmonary exercise testing (CPET) and 1-2 minutes after peak exercise. The patients were divided into 2 groups based on peak E/e' measurements: patients with masked HFpEF-stress and left ventricular diastolic dysfunction (LVDD; E/e'>15), and patients without masked HFpEF (without stress LVDD). CPET and echocardiographic parameters at rest were measured and the predictive value for stress E/e' was analyzed. RESULTS: Stress LVDD occurred in 67 of 104 patients (64%). These patients achieved a lower work load, lower 'VO2 consumption, lower minute ventilation, and higher 'VE/'VCO2 slope in comparison with patients without stress LVDD. None of the CPET values correlated with stress E/e'. The best independent predictors for stress LVDD were right atrium volume index (RAVI), right ventricle (RV) parasternal diameter, and RV E/A >0.75. The combination of these echocardiographic parameters predicted HFpEF with an accuracy of 91.2%. CONCLUSION: There is a high prevalence of stress LVDD in non-severe COPD patients with exertional dyspnea who remain free of overt cardiovascular disease. RAVI, RV parasternal diameter, and RV E/A >0.75 were the only independent predictors of stress LVDD.

Echocardiographic predictors of stress induced right ventricular diastolic dysfunction in non-severe chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary vasculopathy, right heart structural and functional abnormalities occur even in normoxemic chronic obstructive pulmonary disease (COPD) patients. Despite being associated with functional limitation, exacerbations, and disease progression, their detection and proper management is still delayed. AIM: Our aim was to establish the frequency of stress-induced right ventricular diastolic dysfunction (RVDD) in non-severe COPD patients, free of overt cardiovascular disease, who complain of exertional dyspnea and to look for echocardiographic predictors of it. MATERIALS AND METHODS: We applied cardio-pulmonary exercise testing (CPET) in 104 non-severe, COPD patients. A ramp protocol was performed. Echocardiography was done before and 1-2 min after peak exercise. Cut-off values for stress induced RVDD were E/e' >6. Receiver operating curves were constructed for echo parameters at rest to determine if any of them may discriminate stress induced RV E/e'>6 or <6. Uni- and multivariable linear regression analysis was also performed to assess the predictive power of each of them. A p-value < 0.05 was considered significant. RESULTS: A total of 78% of the patients had stress-induced RVDD. Right atrium volume index (RAVI) (cut-off >20.55 ml/m2; sensitivity - 86%; specificity - 86%), RV wall thickness (RVWT) (cut-off >5.25 mm; sensitivity - 100%; specificity - 63%), and RV E/A ratio at rest (cut-off >1.05; sensitivity - 79.7%; specificity - 90.5%) were the best predictors of stress RV E/e. In univariate regression analysis E/A showed the highest OR 19.73 (95% CI - 18.52-21.01); followed by RAVI - OR 3.82; (95% CI - 2.04-7.14). CONCLUSION: There is a high prevalence of stress-induced RVDD in non-severe COPD patients with exertional dyspnea, free of overt cardiovascular disease. RAVI, RVWT, E/A, and E/e' ratio at rest may be used as predictors for stress RVDD and may facilitate patients' risk stratification and proper management.