Abnormalities Of Coronary Microcirculation Research Articles

The Role of Circulating Biomarkers in Patients with Coronary Microvascular Disease

Coronary microvascular disease (CMD) comprises a spectrum of conditions characterized by the functional and structural abnormalities of coronary microcirculation, affecting vessels typically smaller than 500 μm. Despite its clinical significance as a contributor to myocardial ischemia, CMD frequently remains underdiagnosed due to the limitations of current diagnostic approaches. Invasive testing, including coronary reactivity assessment, is considered the gold standard, but it is resource-intensive and not always accessible. Non-invasive methods, such as positron emission tomography (PET) and transthoracic Doppler echocardiography (TTDE), offer alternatives but are limited by varying accuracy and accessibility. Amid these diagnostic challenges, there is increasing interest in circulating biomarkers as adjuncts in CMD evaluation. Biomarkers associated with endothelial dysfunction, inflammation, and oxidative stress, detectable through routine blood tests, may assist in CMD diagnosis, risk stratification, and therapeutic monitoring. These biomarkers can offer insights into CMD pathogenesis and enable early, non-invasive screening to identify patients who may benefit from more invasive investigations. This narrative review examines studies assessing biomarkers in CMD patients with diagnoses confirmed through invasive techniques. Our objective is to focus on circulating biomarkers linked to the invasive evaluation of coronary microcirculation, aiming to advance the understanding of the underlying mechanisms of this prevalent condition and enhance diagnostic accuracy and the clinical management of affected patients.

Coronary Microvascular Dysfunction: Insights on Prognosis and Future Perspectives.

Coronary microvascular dysfunction (CMD) comprises a wide spectrum of structural and/or functional abnormalities of coronary microcirculation that can lead to myocardial ischemia. Emerging evidence has indicated that CMD is a relevant cause of morbidity and mortality and is associated with a high risk of major adverse cardiovascular events (MACEs) and heart failure with preserved ejection fraction as well as poor quality of life. This review aims to elucidate briefly the pathogenesis and diagnostic modalities of CMD and to shed light on contemporary evidence on the prognostic impact of CMD. Finally, we will provide an overview of novel emerging therapeutic strategies for CMD.

Invasive assessment of coronary microvascular dysfunction with MACEs: a meta-analysis

Abstract Aims Although obstructive coronary artery disease (CAD) is considered a prerequisite for myocardial ischemia, it is established that abnormalities of coronary microcirculation may restrict myocardial perfusion in the absense of CAD. Coronary microvascular dysfunction (CMD) is likely associated with elevated risk for MACEs. We performed a meta-analysis of randomized controlled trials to determine the prognostic value of CMD, assessed by invasive techniques, in predicting cardiovascular endpoints in patients without epicardial CAD. Methods and results We identified all studies between 1 January 2000 and 1 December 2023, where coronary flow was invasively measured and clinical outcomes were reported. We included RCTs and all prospective and retrospective studies with a control group, which measured coronary flow reserve (CFR) and/or index of microcirculatory resistance (IMR), as assessed invasively. The endpoints were all-cause mortality and MACEs, including cardiovascular death, myocardial infarction, hospitalization for heart failure (HF) and coronary revascularization. Twenty-five articles enrolling a total of 9.800 subjects (mean age: 55.5±10.6 years) were included with a mean follow-up period of 37 months were eventually deemed eligible for our final analysis. Of these, 3.421 (34,9%) patients had CFR<2.5 and/or IMR>25, indicating CMD, while 6.379 (65,1%) subjects were found without CMD. The analysis of the pooled results demonstrated that the presence of CMD depicted by abnormal CFR and/or IMR was associated with a substantially higher risk for all-cause mortality during a median follow-up period of 3.2 years. The odds ratio for all-cause mortality in patients with CMD compared with those without CMD was 2.31 (95% CI: 1.62 - 2.54, p<0.01). A similar effect of abnormal CFR and IMR was also observed for cardiovascular morality (HR 2.47, 95% CI: 1.81 - 3.38, p<0.01). In addition, the composite of revascularization was also assessed in the total of the selected studies. In particular, the pooled analysis demonstrated a positive association of CMD with a higher future risk for revascularization (HR 1.87, 95% CI: 1.33 – 2.62, p<0.01). The composite of hospitalization for heart failure was also assessed. In addition, the pooled analysis demonstrated a positive association between CMD and hospitalization for HF (HR 2.50, 95% CI: 1.63 - 3.85, p<0.01).A similar effect of abnormal CMD was also observed for myocardial infraction (HR 1.73, 95% CI: 1.33 - 2.24). Elevated IMR (>40) seems to be to be prognostically more relevant than abnormal CFR in the setting of acute myocardial infarction. Conclusions CMD is associated with a nearly 3-fold increase in mortality and a 2-fold increase in major adverse cardiac events. Impaired coronary flow is strongly associated with increased risk of all-cause mortality and MACEs. Future studies and randomized controlled trials are needed to identify strategies to diagnose and treat CMD.

Determinants of right ventricular - pulmonary arterial uncoupling in hypertrophic cardiomyopathy

Abstract Background Right ventricular (RV) – pulmonary arterial (PA) coupling, assessed by echocardiography, is a non-invasive surrogate on how the RV is adapted to an increased afterload in the pulmonary circulation. In cases of exhaustion of compensatory RV remodeling, the ratio decreases and there is RV-PA uncoupling. Our objective was to identify what are the determinants of this parameter in patients with hypertrophic cardiomyopathy (HCM). Methods This prospective cohort study enrolled patients with HCM without obstructive epicardial coronary artery disease, that underwent a comprehensive evaluation. Echocardiography was used to assess RV-PA coupling as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP). In addition, coronary flow reserve in the left anterior descending artery (CFR_LAD) was also evaluated: diastolic coronary flow velocity was measured in basal conditions and in hyperemia and CFR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. This was used as a surrogate marker of coronary microvascular dysfunction. Cardiac magnetic resonance (CMR) was also performed to evaluate RV function (volumes and ejection fraction), and the extent of late gadolinium enhancement (LGE) in the left ventricle (LV). Results We enrolled 62 patients, with a mean age of 55 (15) years, 64% males. In 64% it was an asymmetrical septal hypertrophy phenotype, in 31% an apical hypertrophy, and in 27%, it was an obstructive HCM. Mean TAPSE/PASP was 0.556 (0.23) and median was 0.50. All patients had a normal LV ejection fraction. Univariable linear regression analysis showed that age, maximal wall thickness, E/E’, indexed left atrial volume (LAVi), CFR-LAD, %LGE and % hypoperfusion (by CMR) were correlated with RV-PA uncoupling. The HCM phenotype or the presence of obstruction were not associated with uncoupling. Multivariable stepwise linear regression analysis showed that the independent predictors of RV-PA uncoupling were age (b-estimate: - 0.180, p=0.009), LAVi (b-estimate: -0.645, p=<0.001), CFR-LAD (b-estimate: 0.183, p=0.011) and %LGE (b-estimate: -0.270, p=<0.001). Conclusion In patients with HCM, the presence of coronary microcirculation abnormalities and the extent of LGE in the LV are independent predictors of RV-PA uncoupling.

Evaluation of regional myocardial perfusion in methamphetamine abusers using real-time myocardial contrast echocardiography.

To evaluate the feasibility of assessing regional myocardial perfusion using real-time myocardial contrast echocardiography(MCE) at rest for detecting coronary microcirculation abnormalities in methamphetamine abusers.Materialand methods: Twenty-two male methamphetamine abusers (11 without chest pain, 11 with chest pain), free of ascertainedcoronary artery disease, were enrolled in this study. A control group of 22 age-matched male healthy participants was studiedfor comparison. Standard 2D, flow and tissue Doppler echo with measurements of cardiac morphologic and functional indicators,MCE with measurements of regional myocardial perfusion were performed, respectively. Compared to healthyparticipants, methamphetamine abusers had higher blood pressure, greater left ventricular mass index and more impaireddiastolic function, with preserved cardiac sizes and systolic function. Methamphetamine abusers with chest pain had a fasterheart rate than those without chest pain and healthy participants. MCE in methamphetamine abusers, especially with chestpain, had significant longer contrast agent arrival times, less functional capillary blood volumes, slower microvascular flowvelocities and less myocardial perfusion than healthy participants (p<0.05). Moreover, along with the increases of dosage andduration of use (from group A to group C, group A: 1-2 g/day, <2 years; group B: 2-3 g/day, 2-5 years; group C: >3 g/day, >5years) the reductions in the myocardial perfusion indices were more significant (p<0.01). The cutoff value with 5.1 dB2/s ofthe myocardial perfusion at the left ventricular apex had a sensitivity of 87.5%, specificity of 75.2% and accuracy of 81.9% fordifferentiating methamphetamine abusers from normal subjects. Real-time MCE can effectively detect coronarymicrocirculation abnormalities in methamphetamine abusers at rest and myocardial perfusion is significantly reduced in methamphetamineabusers. This finding may be involved in the occurrence and development of cardiac damage.

GW29-e1815 The evaluation of left ventricular systolic function in different types of ischemic heart disease by two-dimensional speckle-tracking echocardiography

Coronary microvascular dysfunction (CMD) induced by abnormalities of coronary microcirculation and obstructive coronary artery disease (CAD) with epicardial coronary stenosis are two types of ischemic heart disease. Both CMD and obstructive CAD can induce ventricular remodeling, eventually

Myocardial perfusion echocardiography and coronary microvascular dysfunction.

Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking.

THU0176 Subclinical myocardial dysfunction in primary antiphospholipid syndrome assessed by speckle tracking echocardiography

BackgroundBackground. Measurement of myocardial deformation or Global longitudinal strain (GLS) by speckle tracking echocardiography (STE) is useful for detection of microvascular damage and myocardial contractility impairment in patients with ischemic...

Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests

IntroductionMicrocirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome.MethodsForty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up.ResultsNineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests.ConclusionsA-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases.

Coronary Flow Reserve in Patients with Diabetes Mellitus and Prediabetes

Abnormalities of coronary microcirculation have been reported in patients with diabetes mellitus (DM) even in the presence of normal coronary arteries. It is unknown when the microvascular effects on coronary arteries begin to appear in the DM disease course. Coronary flow reserve (CFR), determined by pharmacological stress transthoracic Doppler echocardiography, is a reliable indicator of coronary microvascular function. We sought to determine the coronary microvascular function of prediabetic patients compared to DM patients and normal population. Seventy-four subjects with normal coronary arteries were enrolled. DM and prediabetes were diagnosed according to American Diabetes Association criteria. All subjects had Doppler recordings of the left anterior descending artery with adenosine infusion at a rate of 0.014 mg/kg per minute. The demographical characteristics and laboratory findings of the three groups were similar (DM group: n = 25, mean age 62 ± 7 years, 19 females; prediabetic group: n = 25, mean age 64 ± 12 years, 21 females; control group: n = 24, mean age 63 ± 7 years, 15 females) except fasting glucose levels. CFR values of the three groups were significantly different (DM group: CFR = 1.75 ± 0.50; prediabetic group: CFR = 2.24 ± 0.43; control group: CFR = 2.38 ± 0.32, P < 0.001). CFR values of DM group were lower than those of prediabetic and control groups (DM vs. prediabetic: P < 0.001, DM vs. control: P < 0.001). However, CFR levels of prediabetic group were not different from those of the control group (P = 0.481). DM was an independent factor predictive of CFR < 2 (OR, 22.69; 95% CI, 6.47-79.51; P < 0.001). Coronary microvascular function seems to be normal in the prediabetic state, but dysfunction appears after DM becomes overt.

Quantification of coronary microvascular resistance using angiographic images for volumetric blood flow measurement: in vivo validation

Structural coronary microcirculation abnormalities are important prognostic determinants in clinical settings. However, an assessment of microvascular resistance (MR) requires a velocity wire. A first-pass distribution analysis technique to measure volumetric blood flow has been previously validated. The aim of this study was the in vivo validation of the MR measurement technique using first-pass distribution analysis. Twelve anesthetized swine were instrumented with a transit-time ultrasound flow probe on the proximal segment of the left anterior descending coronary artery (LAD). Microspheres were injected into the LAD to create a model of microvascular dysfunction. Adenosine (400 μg·kg(-1)·min(-1)) was used to produce maximum hyperemia. A region of interest in the LAD arterial bed was drawn to generate time-density curves using angiographic images. Volumetric blood flow measurements (Q(a)) were made using a time-density curve and the assumption that blood was momentarily replaced with contrast agent during the injection. Blood flow from the flow probe (Q(p)), coronary pressure (P(a)), and right atrium pressure (P(v)) were continuously recorded. Flow probe-based normalized MR (NMR(p)) and angiography-based normalized MR (NMR(a)) were calculated using Q(p) and Q(a), respectively. In 258 measurements, Q(a) showed a strong correlation with the gold standard Q(p) (Q(a) = 0.90 Q(p) + 6.6 ml/min, r(2) = 0.91, P < 0.0001). NMR(a) correlated linearly with NMR(p) (NMR(a) = 0.90 NMR(p) + 0.02 mmHg·ml(-1)·min(-1), r(2) = 0.91, P < 0.0001). Additionally, the Bland-Altman analysis showed a close agreement between NMR(a) and NMR(p). In conclusion, a technique based on angiographic image data for quantifying NMR was validated using a swine model. This study provides a method to measure NMR without using a velocity wire, which can potentially be used to evaluate microvascular conditions during coronary arteriography.

Elevated circulating soluble form of CD40 ligand in patients with cardiac syndrome X

Background The presence of effort induced angina, positive exercise stress test responses and angiographically normal coronary arteries defines cardiac syndrome X (CSX). Its pathogenesis, although mostly attributed to endothelial dysfunction and coronary microcirculation abnormalities, is incompletely understood. The soluble CD40 ligand (sCD40L) has multiple autocrine, paracrine and endocrine actions that may lead to endothelial dysfunction and atherothrombosis. We sought to investigate the relationship among sCD40L levels and ischemic burden in patients with CSX and whether sCD40L levels are increased in patients with CSX compared to control subjects. Methods We assessed 30 prospectively enrolled patients with CSX and 28 apparently healthy subjects matched for coronary risk factors. All CSX patients and control subjects underwent myocardial perfusion scintigraphy. The summed difference score is taken to be an index of ischemic burden. This was classified as mildly, moderately and severely abnormal. White blood cells, sCD40L and C-reactive protein (CRP) concentrations were measured at peak exercise. Results At peak exercise, sCD40L levels were significantly greater in CSX patients than in the control group ( P = 0.008). Similarly, white blood cell count and CRP levels were higher in patients with CSX than in normal controls ( P = 0.02). After multivariable adjustment, sCD40L ( P = 0.03) was the only independent predictor of severe ischemic burden in CSX patients. Conclusions The present study showed for the first time that sCD40L is associated with ischemic burden in patients with CSX. The potential role of this inflammatory molecule in the pathogenesis of CSX deserves investigation in future studies.

Primary Coronary Microvascular Dysfunction

Myocardial ischemia is usually caused by abnormalities of epicardial coronary arteries. In the past 30 years, however, several studies have shown that abnormalities in coronary microcirculation may also cause or contribute to myocardial ischemia in several conditions. Accordingly, Camici and Crea1 have recently proposed a classification of coronary microvascular dysfunction (CMVD) based on the clinical setting in which it occurs (eg, obstructive coronary artery disease [CAD], cardiomyopathy, and systemic diseases) (Table 1). In these various conditions, CMVD can be caused by specific mechanisms related to the underlying disease. View this table: Table 1. Classification of CMVD According to its Pathogenetic Mechanisms (Derived From Camici and Crea 1 ) In a number of patients who present with angina attacks in the absence of any apparent cardiac or systemic disease, CMVD has been suggested to be the unique cause of symptoms. This condition is known as microvascular angina (MVA)2 and can be better defined as primary MVA to distinguish it from MVA occurring in the setting of specific diseases, which can be defined as secondary MVA. In clinical practice, primary MVA is usually suspected, by exclusion, in patients with sufficiently typical chest pain in whom, despite abnormalities of the ECG and/or stress test results indicative of myocardial ischemia, arteriography surprisingly fails to show fixed or dynamic obstructions in epicardial coronary arteries.3 Primary MVA, however, includes heterogeneous groups of patients, with different pathogenetic and pathophysiological mechanisms of CMVD, who might have different clinical implications and need different diagnostic and therapeutic approaches. In several previous studies, however, patients with different characteristics of chest pain, possibly related to different mechanisms of CMVD or even to nonischemic or noncardiac causes, have often been considered together, usually under the general descriptive term of chest pain with normal coronary arteries, which may have contributed to generate contrasting results …

Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients

Plasma concentration of asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide synthase, is considered a novel risk factor for endothelial dysfunction associated with enhanced atherosclerosis. Coronary microcirculation abnormalities have been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs or symptoms of coronary artery disease (CAD). The aim of the study was to compare the ERA and control groups with ADMA, intima-media thickness (IMT) and coronary flow reserve (CFR) levels. It assessed whether ERA patients have more cardiovascular risk (endothelial dysfunction and coronary microvascular abnormalities), and evaluated whether any difference in IMT/CFR between ERA and controls can be explained by any difference in ADMA levels between the groups. The study involved 25 ERA patients (female/male 21/4; mean age 52.04 +/- 14.05 years; disease duration <or=12 months) and 25 healthy volunteers with no history or current signs of CAD or other traditional risk factors. Dipyridamole trans-thoracic stress echocardiography was preformed to evaluate CFR, and carotid ultrasound to measure the IMT of the common carotid arteries. Blood samples were obtained in order to assess ADMA levels before the patients had received any biological or non-biological DMARDs, or steroid therapy. CFR was significantly reduced in the ERA patients (2.5 +/- 0.5 vs 3.5 +/- 0.8; P <0.01). In particular, 6/25 (24%) had a CFR of <2 consistent with potentially dangerous coronary flow impairment. Common carotid IMT was significantly greater in the ERA patients, although still within the normal range (0.68 +/- 0.1 vs 0.56 +/- 0.11 mm; P <0.01). There was a significant correlation between CFR and plasma ADMA levels in the ERA population (r = -0.53; P <0.01). IMT was negatively associated with CFR (P <0.05). Plasma ADMA levels were significantly higher in the ERA patients. A statistically significant negative effect of ADMA levels on CFR value was observed. The effect of ADMA levels on IMT is not significant.

Prognosis for Coronary Stenoses in Patients With Diabetes and Silent Myocardial Ischemia

Silent myocardial ischemia (SMI) is common in patients with diabetes (1–4). The prognostic value of SMI, evidenced by exercise electrocardiogram (ECG) stress test (5) and thallium 201 myocardial scintigraphy (6), as well as their association (7) in asymptomatic diabetic patients, has recently been demonstrated. About 50% of the patients with SMI exhibit angiographically normal coronary arteries (1,2). In these patients, endothelial dysfunction and abnormalities of coronary microcirculation may be involved (8). So far, the respective roles played by these functional disorders, by the demonstrated silent coronary stenoses, or by both in the poor prognosis of SMI are still unknown. The aim of this …

Overview of gender aspects of cardiac syndrome X.

Cardiac syndrome X, a condition defined by the presence of angina-like chest pain, a positive response to stress testing and normal coronary arteriograms, has been shown to occur in approximately 20--30% of angina patients undergoing coronary arteriography. The prevalence of syndrome X is significantly higher in women compared to men. In the majority of patients with chest pain and normal coronary arteriograms, symptoms are likely to be non-cardiac in origin. However, myocardial ischaemia may be the pathogenic mechanism in a proportion of syndrome X patients. Indeed, the clinical characteristics, the ischaemic electrocardiographic findings and the presence of myocardial perfusion defects during stress testing are similar in syndrome X and coronary artery disease patients. Moreover, coronary sinus oxygen saturation abnormalities and pH changes, as well as myocardial lactate production and alterations of cardiac high energy phosphate are seen during stress testing in patients with syndrome X and appear to endorse an ischaemic origin of symptoms in at least a proportion of these individuals. Patients with chest pain and normal coronary arteries have abnormal vasodilatory coronary blood flow responses and an increased sensitivity of the coronary microcirculation to vasoconstrictor stimuli (microvascular angina). Microvascular endothelial dysfunction appears to be responsible for these coronary microcirculation abnormalities. Given the high prevalence of peri- and post-menopausal women in cardiac syndrome X, it has been hypothesized that oestrogen deficiency may play a major role in the pathogenesis of this condition. Oestrogen vasoactive properties involve endothelium-dependent effects and, in postmenopausal women, forearm vasodilatation induced by acetylcholine is potentiated by the acute local administration of intravenous oestradiol. This suggests that endothelium-dependent responses in the peripheral circulation may be modulated by steroid hormones. Impairment of endothelial function in post-menopausal women with syndrome X has been reported by various groups and it could be hypothesized that oestrogen deficiency may contribute to the development of microvascular angina through endothelial dysfunction and that exogenous oestrogen administration may have a beneficial effect in syndrome X patients. This article reviews current knowledge regarding the role of oestrogen deficiency in the pathogenesis of syndrome X and the potential therapeutic role of oestrogen replacement therapy in women with chest pain and normal coronary arteriograms

Cardiac troponins in congestive heart failure

Background We sought to assess the release of cardiac troponins in congestive heart failure (CHF). Methods and Results We performed a computer-assisted search of the English language literature (MEDLINE database) followed by a manual search of the reference list of pertinent articles retrieved. Studies evaluating the release of cardiac troponins (T and I) in patients with CHF were screened for review. Studies investigating cardiac troponins in patients with ischemic coronary syndromes that reported the rate of CHF were also selected. Available data on the release of cardiac troponins in ischemic and nonischemic CHF were summarized. Possible mechanisms of cell death in the progression to end-stage CHF were discussed. Conclusions Cardiac troponins were detected in patients with advanced CHF. These markers correlated with the severity of CHF and suggest an association with worse prognosis. Possible mechanisms for the release of cardiac troponins T and I in advanced CHF may include the following: ventricular remodeling, presence of coronary artery disease in CHF, abnormalities of coronary microcirculation, and reduced coronary reserve. Further studies will be necessary to elucidate the actual mechanism and determine the clinical significance of cardiac troponins in CHF. (Am Heart J 1999;138:646-53.)

Limited myocardial contractile reserve and chronotropic incompetence in patients with chronic Chagas’ disease: Assessment by dobutamine stress echocardiography

ObjectivesTo determine whether dobutamine stimulation in patients with Chagas’ disease may uncover abnormal contractile responses as seen in ischemic myocardium.BackgroundSegmental left ventricular (LV) dysfunction in the absence of coronary atherosclerosis is frequently seen in patients with chronic Chagas’ heart disease. Myocardial ischemia and coronary microcirculation abnormalities have been found in animal models and in humans with Chagas’ disease. In addition, chagasic sera may contain autoantibodies against human beta-adrenergic receptors.MethodsTwo groups of patients with Chagas’ disease were studied by echocardiography: group 1 (n = 12) without and group 2 (n = 14) with LV segmental wall motion abnormalities (mostly apical aneurysm). Ten normal subjects served as control subjects. We performed qualitative assessment of wall motion and quantitative evaluation of LV cavity under baseline conditions and after dobutamine stimulation.ResultsPatients with Chagas’ disease exhibited a blunted inotropic and chronotropic response to dobutamine stimulation. After dobutamine, fractional area change in Chagas’ group 1 (54.7 ± 6.6%; SD) and in group 2 (35.1 ± 12.1%) were significantly lower than control group (66.7 ± 2.5%; p < 0.001). In addition, in 6 of 14 group 2 patients, dobutamine induced a biphasic response with improvement at low dose and deterioration at peak dose, as seen in patients with coronary artery disease. Although the three groups had similar basal mean heart rates and attained a similar mean peak dobutamine doses, both groups of patients with Chagas’ disease had a significantly blunted mean heart rate effect after dobutamine (p < 0.0001).ConclusionsThus, dobutamine stimulation unmasks a chronotropic incompetence and a blunted myocardial contractile response in chagasic patients, even in those with no overt manifestation of heart disease.