Effects of remote ischemic preconditioning on coronary blood flow and microcirculation.

This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative flow ratio (QFR) and index of microcirculatory resistance (IMR). We randomly divided 129 patients undergoing coronary angiography (CAG) into RIPC and control groups. Following the first CAG, we randomly divided the patients further into the unilateral upper limb and lower limb groups for four cycles of ischemia/reperfusion circulation; subsequently, we performed the second CAG. During each CAG, contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and IMR (in patients with cardiac syndrome X) were calculated and compared. We measured 253 coronary arteries in 129 patients. Compared to the control group, the average cQFR of the RIPC group increased significantly after RIPC. Additionally, 23 patients with cardiac syndrome X (IMR > 30) were included in this study. Compared to the control group, IMR and the difference between cQFR and fQFR (cQFR-fQFR) both decreased significantly after receiving RIPC. The application of RIPC can increase coronary blood flow and improve coronary microcirculation function.

Echocardiographic assessment of primary microvascular angina and primary coronary microvascular dysfunction.

There is an increasing interest in the role of echocardiography in the evaluation of primary microvascular angina, which is attributed to primary coronary microvascular dysfunction. Valid echocardiographic techniques are expected to facilitate the diagnosis and follow-up of these patients and would be valuable for research purposes and therapy evaluation. However, adequate echocardiographic data are lacking, and the interpretation of the limited available literature is hindered by the previous addition of microvascular angina under more inclusive entities, such as cardiac syndrome X. In experienced hands, the assessment of primary coronary microvascular dysfunction in patients with suspected primary microvascular angina, using multiple echocardiographic techniques is feasible, relatively inexpensive, and safe. Exclusion of obstructive epicardial coronary artery disease is, however, a prerequisite for diagnosis. Two-dimensional transthoracic echocardiography, routine stress echocardiography, and speckle-tracking echocardiography indirectly assess primary coronary microvascular dysfunction by evaluating potential impairment in myocardial function and lack diagnostic sensitivity and specificity. Conversely, certain echocardiographic techniques, including Doppler-derived coronary flow velocity reserve and myocardial contrast echocardiography, assess some coronary microvascular dysfunction parameters and have exhibited diagnostic and prognostic potentials. Doppler-derived coronary flow velocity reserve is the best studied and only guideline-approved echocardiographic technique for documenting coronary microvascular dysfunction in patients with suspected microvascular angina. Myocardial contrast echocardiography, by comparison, can detect heterogeneous and patchy myocardial involvement by coronary microvascular dysfunction, which is an advantage over the common practice of coronary flow velocity reserve assessment in a single vessel (commonly the left anterior descending artery) which only reflects regional microvascular function. However, there is no consensus regarding the diagnostic criteria, and expertise performing this technique is limited. Echocardiography remains underexplored and inadequately utilized in the setting of microvascular angina and coronary microvascular dysfunction. Appraisal of the current echocardiographic literature regarding coronary microvascular dysfunction and microvascular angina is important to stay current with the progress in its clinical recognition and create a basis for future research and technological advancements.

Phenotype-based management of coronary microvascular dysfunction.

40-70% of patients undergoing invasive coronary angiography with signs and symptoms of ischemia are found to have no obstructive coronary artery disease (INOCA). When this heterogeneous group undergo coronary function testing, approximately two-thirds have demonstrable coronary microvascular dysfunction (CMD), which is independently associated with adverse prognosis. There are four distinct phenotypes, or subgroups, each with unique pathophysiological mechanisms and responses to therapies. The clinical phenotypes are microvascular angina, vasospastic angina, mixed (microvascular and vasospastic), and non-cardiac symptoms (reclassification as non-INOCA). The Coronary Vasomotor Disorders International Study Group (COVADIS) have proposed standardized criteria for diagnosis. There is growing awareness of these conditions among clinicians and within guidelines. Testing for CMD can be done using invasive or non-invasive modalities. The CorMicA study advocates the concept of 'functional angiography' to guide stratified medical therapy. Therapies broadly fall into two categories: those that modulate cardiovascular risk and those to alleviate angina. Management should be tailored to the individual, with periodic reassessment for efficacy. Phenotype-based management is a worthy endeavor for both patients and clinicians, aligning with the concept of 'precision medicine' to improve prognosis, symptom burden, and quality of life. Here, we present a contemporary approach to the phenotype-based management of patients with INOCA.

Myocardial perfusion by CMR coronary sinus flow shows sex differences and lowered perfusion at stress in patients with suspected microvascular angina.

BACKGROUND: Patients with chest pain may have normal coronary arteries and suffer from microvascular angina (MVA). The aim of this study was to determine if patients with suspected MVA have lower global myocardial perfusion (global MP) during adenosine stress compared with healthy controls and coronary artery disease (CAD) patients and to determine if there are sex differences in global MP. METHODS: Twenty-three patients with suspected MVA (66 ± 11 years), 19 CAD patients (69 ± 5 years) with stress-induced ischaemia and 24 healthy controls (61 ± 10 years) underwent cardiac magnetic resonance (CMR) including coronary sinus flow measurements and first-pass perfusion at rest and during adenosine stress. Global MP was quantified as coronary sinus flow normalized to left ventricular mass. RESULTS: Global perfusion was lower during stress in patients with suspected MVA (2.9 ± 1.0 ml/min/g) compared with healthy volunteers (3.7 ± 1.1 ml/min/g, p = 0.018), but higher compared with CAD patients (2.0 ± 0.9 ml/min/g, p = 0.019). Female controls had higher global MP than male controls both at rest (1.0 ± 0.3 vs. 0.7 ± 0.2 ml/min/g, p = 0.003) and during stress (4.4 ± 1.0 vs. 3.1 ± 0.6 ml/min/g, p = 0.001). Furthermore, females with suspected MVA showed higher global MP than males with suspected MVA (3.3 ± 1.0 vs. 2.4 ± 0.7, p = 0.04). CONCLUSIONS: Patients with suspected MVA have lower global MP at stress than healthy volunteers but higher than patients with CAD. Furthermore, there seems to be a sex difference in global MP at stress both in healthy volunteers and in patients with suspected MVA, with higher global MP in females, which implies a need for sex-specific normal limits when assessing quantitative MP.

Longitudinal myocardial function is more compromised in cardiac syndrome X compared to insignificant CAD: Role of stress echocardiography and calcium scoring.

BACKGROUND AND AIM: The aim of this study was to assess the nature of myocardial dysfunction in the cardiac syndrome X (CSX) and insignificant coronary artery disease (ICAD) using dobutamine stress echocardiography (DSE) and coronary calcium scoring (CAC). METHODS: We prospectively studied 35 consecutive patients who complained of exertional angina, had ≥1 mm ST shift on exercise stress test but normal or no obstructive CAD (<50%) on angiography. Patients were divided into CSX (n = 27) with normal arteries and ICAD (n = 8) with insignificant stenosis. RESULTS: CSX patients had more females, lower calcium score and less prevalent cardiac risk factors compared to ICAD (p < 0.05 for all). At peak stress, MAPSE and TAPSE failed to increase in both groups. LV septal and lateral s' increased in the two groups but the increment increase was less in CSX than ICAD (p < 0.05) while other diastolic indices did not differ between groups (p > 0.05 for all). CAC correlated modestly with LV and RV systolic velocities: septal s' (r = -0.65, p < 0.001) lateral s' (r = -0.35, p = 0.04) and right s' (r = -0.53, p = 0.005) in CSX, while in ICAD patients only with RV s' (r = -0.58, p = 0.02). On multivariate model, only septal s' OR 1.816 (1.1090-3.820, p = 0.04) proved the most powerful independent predictor of CAC. CONCLUSIONS: Compromised LV longitudinal systolic velocities were more pronounced and calcium score as a surrogate for atherosclerosis was lower in CSX than ICAD. These findings strengthen the evidence for different pathogenesis of CSX compared to ICAD, with microvascular disease in the former and calcification in the latter.

Diagnostic approach for coronary microvascular dysfunction in patients with chest pain and no obstructive coronary artery disease.

A large number of studies has demonstrated that abnormalities of coronary microcirculation may be responsible for both acute and chronic cardiac ischemic syndromes. In clinical practice the microvascular origin of myocardial ischemia and angina is usually considered in patients who are found to have normal or near-normal coronary arteries at angiography. In this article, we review the diagnostic approach to patients with suspected coronary microvascular dysfunction as a cause of ischemic syndromes and also suggest a classification of chronic and acute microvascular coronary ischemic syndrome, including myocardial infarction with normal coronary arteries.

Comparison of subfoveal choroidal thickness and retinal nerve fiber layer thickness in patients with coronary slow flow phenomenon and microvascular angina: Optical coherence tomography based study.

BACKGROUND: The aim of this study was to evaluate and compare the subfoveal choroidal thickness (SFCT) and peripapillary retinal nerve fiber layer thickness (pRNFLT) in patients with microvascular angina (MA), coronary slow flow phenomenon (CSFP) and healthy controls. METHODS: Thirty-two consecutive patients with MA, 35 consecutive patients with CSFP and 40 age and sex-matched controls were enrolled. SFCT, average pRNFLT and four quadrants of pRNFLT were measured by spectral domain- optical coherence tomography (SD-OCT). RESULTS: The mean SCFT in patients with CSFP (267.57 ± 30.61 µm) was significantly thinner than those of patients with MA (288.84 ± 28.25 µm) and control (291.21 ± 31.75 µm) (p = 0.002) while SFCT of patients with MA were similar with those of controls. Patients with CSFP had thinner superior and inferior pRNFLT compared to patients with MA and controls (p < 0.001 and p = 0.005, respectively) while there were no significant differences in average pRNFLT, nasal and temporal quadrant of pRNFLTs among three groups. In the multivariate linear regression analyses, the presence of CSFP was found negatively correlated with SFCT and superior pRNFLT. CONCLUSION: Patients with CSFP had thinner SFCT, superior and inferior quadrants of pRNFLT proposing the presence of a generalized endothelial dysfunction and increased microvascular resistance in these patients.

Long-Term Prognosis of Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance.

OBJECTIVES: This study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD). BACKGROUND: Patients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI <1.4. The prognosis of CMD as determined by MPRI is unknown. METHODS: Chest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke. RESULTS: A total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI >1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p < 0.001). CONCLUSIONS: Stress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.

Utility of discovery approach using proteomics to create a biomarker profile for coronary microvascular dysfunction.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is a complex disease, difficult to diagnose and often requires advanced imaging. We used mass spectrometry (MS) using discovery approach to search for serum proteins as potential biomarkers in these patients. METHODS: We used serum samples from 10 patients with CMD and 10 with normal coronary flow reserve (CFR) admitted to an observation unit where acute myocardial infarction was excluded. We identified CMD using 82Rb positron emission tomography/computed tomography as CFR <2 in response to regadenoson, in the absence of coronary calcification or regional perfusion defects. We used MS to identify potential protein biomarkers that were differentially expressed in cases and controls. RESULTS: Baseline characteristics were not different between cases and controls, except for beta-blocker use and which was higher in cases, and mean (SD) CFR which was lower in cases [1.19 (0.23) and 2.78 (0.78) in cases and controls respectively; p < 0.01]. We identified 5345 peptides corresponding to 209 proteins, and identified 197 proteins by peptides with suitable properties to infer relative quantitation values. While the calculated values for some proteins (e.g. vascular cell adhesion molecule-1, apolipoprotein C and Von Willebrand Factor) indicate fold-differences between groups, these are most likely a result of high values in only 1-2 patients and are not statistically significant. CONCLUSION: Mass spectrometry using discovery approach may not be an adequate method for quantitative assessment of serum proteins in CMD patients. Future MS studies should evaluate other approaches including tissue samples or serial measurements.

Microvascular Angina Diagnosed by Absolute PET Myocardial Blood Flow Quantification.

PURPOSE OF REVIEW: The aim of this review is to provide an update on the use of positron emission tomography (PET) with myocardial blood flow (MBF) quantification for the diagnosis and management of patients with microvascular disease. RECENT FINDINGS: It is now recognized that a large proportion of patients with classical angina and non-obstructive epicardial disease are suffering from microvascular angina. Microvascular angina shares several key features with epicardial coronary disease, including many risk factors. Clinical criteria for the diagnosis of microvascular angina were recently proposed and PET imaging is called to play a central role in evaluation of these patients. Indeed, PET allows non-invasive measurements of MBF and flow reserve, which are altered in microvascular dysfunction. Furthermore, PET with flow quantification provides independent prognostic information and has the potential to monitor response to therapy in microvascular disease. PET with MBF quantification allows detection of microvascular dysfunction and plays a key role in the investigation of patients with suspected microvascular angina.

Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Function and CT Coronary Angiogram (CorCTCA) study.

Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA). OBJECTIVES: Our research has 2 objectives. The first is to undertake a diagnostic study, and the second is to undertake a nested, clinical trial of stratified medicine. DESIGN: A prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03477890) will be performed. All-comers referred for clinically indicated CTCA for investigation of suspected coronary artery disease (CAD) will be screened in 3 regional centers. Following informed consent, eligible patients with angina symptoms are enrolled before CTCA and remain eligible if CTCA excludes obstructive CAD. Diagnostic study: Invasive coronary angiography involving an interventional diagnostic procedure (IDP) to assess for disease endotypes: (1) angina due to obstructive CAD (fractional flow reserve ≤0.80); (2) microvascular angina (coronary flow reserve <2.0 and/or index of microvascular resistance >25); (3) microvascular angina due to small vessel spasm (acetylcholine); (4) vasospastic angina due to epicardial coronary spasm (acetylcholine); and (5) noncoronary etiology (normal coronary function). The IDP involves direct invasive measurements using a diagnostic coronary guidewire followed by provocation testing with intracoronary acetylcholine. The primary outcome of the diagnostic study is the reclassification of the initial CTCA diagnosis based on the IDP. Stratified medicine trial: Participants are immediately randomized 1:1 in the catheter laboratory to therapy stratified by endotype (intervention group) or not (control group). The primary outcome of the trial is the mean within-subject change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and certainty), and clinical utility (impact on treatment and investigations). Health status assessments include quality of life, illness perception, anxiety-depression score, treatment satisfaction, and physical activity. Participants who are not randomized will enter a follow-up registry. Health and economic outcomes in the longer term will be assessed using electronic patient record linkage. VALUE: CorCTCA will prospectively characterize the prevalence of disease endotypes in INOCA and determine the clinical value of stratified medicine in this population.

Right ventricular mechanics and exercise capacity in patients with microvascular angina: The impact of microvascular function.

OBJECTIVES: We planned to assess the right ventricular mechanics in subjects with typical chest pain and angiographically normal coronary arteries (microvascular angina [MVA]) and to search for an association between right ventricular mechanics, coronary flow reserve, and exercise tolerance. METHODS: Seventy-one patients with MVA (mean age of 48.5 ± 7.9 years, 63% female) and 30 healthy control subjects were recruited. Right ventricular mechanics were calculated utilizing speckle tracking imaging. The exercise capacity was assessed by metabolic equivalents (METs). Coronary flow reserve (CFR) was calculated as the ratio between hyperemic (in response to intravenous adenosine) diastolic peak flow velocity and the basal diastolic peak velocity. RESULTS: Coronary flow reserve (a surrogate marker of microvascular dysfunction) was diminished in MVA patients compared with the control group (2.41 ± 0.35 vs 3.35 ± 0.5; P < .03). Patients with lower right ventricular global longitudinal strain (RVGLS) and right ventricular global longitudinal strain rate (RVGLSr) had a considerably lower CFR (P < .001) and a significantly lower MET (P < .001) than patients with normal RV mechanics. Right ventricular global longitudinal strain and RVGLSr were significantly correlated with both CFR and METs in subjects with MVA. Receiver operating characteristic (ROC) curve analysis demonstrated that RVGLS ≤ -14.5 was the best cutoff value for the prediction of impaired exercise tolerance in patients with MVA. CONCLUSION: We suggested that impaired right ventricular mechanics in subjects with microvascular angina was associated with reduced exercise capacity. Moreover, right ventricular mechanics is significantly correlated with coronary flow reserve. Henceforth, right ventricular mechanics might be of value for both risk stratification and follow-up in cases with microvascular dysfunction.

Assessment of the relationship between coronary flow rates and myocardial perfusion abnormality in patients with nonobstructive coronary artery disease: an observational study in cardiac syndrome X and coronary slow flow.

OBJECTIVES: In this study, we evaluated and compared the level of myocardial ischaemia caused by cardiac syndrome X (CSX) and coronary slow flow (CSF) with single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI), and determined if changes in the level of myocardial ischaemia exist in CSF and CSX cases according to thrombolysis in myocardial infarction frame count (TFC). MATERIALS AND METHODS: The study population consisted of 66 patients with CSF and 78 angiographically normal patients (36 of them with CSX and 42 of them healthy controls). The coronary flow rates of all patients were documented using TFC. Subsequently, all patients were evaluated with SPECT-MPI and categorized into the following groups according to their results: patients with CSF, patients with CSX, and patients with normal coronary arteries. Finally, we investigated whether a relationship existed between the SPECT-MPI and TFC results from these three groups. RESULTS: All ischaemia scores for MPI were significantly higher in the CSF group than in the CSX and control groups (P < 0.05). TFC was significantly associated with the severity of ischaemia in the CSF patients. There was a significant positive correlation between the summon difference score (SDS) and mean TFC value (P < 0.05) as well as between the SDS and each individual coronary TFC value in the CSF patients (P < 0.05). The number of vessels involved in CSF was positively correlated with the SDS. CONCLUSION: CSF is associated with more severe myocardial ischaemia than CSX. The level of myocardial ischaemia on SPECT-MPI was correlated with the TFC and the number of affected coronary vessels in patients with CSF. These results suggest that CSF is a more serious clinical entity than CSX, and that the clinical severity of CSF appears to increase as the coronary flow rate decreases.

'Acute micro-coronary syndrome': detailed coronary physiology in a patient with Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TC), otherwise known as stress cardiomyopathy, is characterised by acute, transient left ventricular systolic dysfunction with apical ballooning in the absence of obstructive epicardial coronary stenosis. The presentation of TC mimics that of acute myocardial infarction. More recently there has been a shift towards thinking of TC as a 'microvascular acute coronary syndrome'. Our case is of an 82-year-old woman who presented with TC mimicking acute anterior ST elevation myocardial infarction in the context of sepsis. Slow flow noted in the left anterior descending artery prompted us to perform coronary physiology. Her fractional flow reserve was 0.91, with an index of myocardial resistance of 117 and a coronary flow reserve of 1.6. In combination these results are indicative of microvascular coronary dysfunction in the absence of significant epicardial stenosis.

Coronary Microvascular Dysfunction by Myocardial Contrast Echocardiography in Nonelderly Patients Referred for Computed Tomographic Coronary Angiography.

BACKGROUND: Microvascular dysfunction (MVD) is a potential cause of chest pain in younger individuals. The authors hypothesized that nonelderly patients referred for computed tomographic angiography (CTA) but without significant stenosis would have a high prevalence of MVD by myocardial contrast echocardiography (MCE). Secondary aims were to test whether the presence of nonobstructive coronary artery disease (CAD) or reduced brachial flow-mediated dilation (FMD) predicted MVD. METHODS: Subjects ≤60 years of age undergoing CTA were recruited if they had either no evidence of coronary plaque or evidence of mild CAD (<50% stenosis) and at least one high-risk plaque feature. Subjects underwent quantitative perfusion imaging using MCE at rest and during regadenoson vasodilator stress. MVD was defined as global or segmental delay of microvascular refill (≥2 sec) during regadenoson. FMD of the brachial artery was also performed. RESULTS: Of the 29 patients in whom MCE could be performed, 12 (41%) had MVD. These subjects, compared with those with normal microvascular function, had lower hyperemic perfusion (mean, 236 ± 68 vs 354 ± 161 intensity units/sec; P = .02) and microvascular flux rate (mean, 1.6 ± 0.4 vs 2.5 ± 0.9 sec-1; P = .002) on quantitative MCE. The degree of FMD was not significantly different in those with or without MVD (mean, 11 ± 4% vs 9 ± 4%; P = .32), and there was a poor correlation between results on stress MCE and FMD. Only eight of the 29 subjects were classified as having nonobstructive CAD. There were no groupwise differences in the prevalence of MVD function in those with versus without CAD (43% vs 38% for negative and positive findings on CTA, respectively, P = .79). CONCLUSIONS: MVD is a common finding in the nonelderly population referred for CTA for evaluation of possible CAD but without obstructive stenosis. Neither the presence of noncritical atherosclerotic disease nor abnormal FMD increases the likelihood for detecting MVD in this population.

Retinal microvascular changes in microvascular angina: Findings from the Australian Heart Eye Study.

OBJECTIVE: Microvascular changes in microvascular angina are poorly understood due to difficulties in imaging the coronary microcirculation in vivo. The retinal microvasculature may reflect changes in coronary microcirculation. We assessed microvascular changes in the retina in patients with microvascular angina and compared them with patients with angiographically proven coronary artery disease. METHODS: We performed retinal photography and coronary angiography on 915 patients. Retinal vessel calibers were measured using a validated computer-assisted method; coronary artery disease was graded from coronary angiograms. Microvascular angina was defined as angina with <25% stenosis in all coronary epicardial arteries. RESULTS: A total of 139 patients (15.2%) had microvascular angina, while 776 (84.8%) had coronary artery disease. Participants with microvascular angina and coronary artery disease had similar retinal arteriolar and venular calibers. After adjustment for age, ethnicity, mean arterial pressure, diabetes, current smoking, body mass index, and fellow vessel caliber, women with smaller venules were threefold more likely to have microvascular angina than women with larger venules (multivariable-adjusted odds ratio 3.54, 95% confidence interval 1.35 to 9.24, P < 0.01). This difference was not observed in men. CONCLUSIONS: Microvascular angina in women was associated with microvascular changes distinct from those in coronary artery disease.

Physical training improves myocardial perfusion but not left ventricular function response to exercise in patients with microvascular angina.

BACKGROUND: Patients with primary microvascular angina (PMA) commonly exhibit abnormal left ventricular function (LVF) during exercise, potentially owing to myocardial ischemia. Herein, we investigated in PMA patients the effect of the reduction of myocardial perfusion disorders, by using aerobic physical training, upon LVF response to exercise. METHODS: Overall, 15 patients (mean age, 53.7±8.9 years) with PMA and 15 healthy controls (mean age, 51.0±9.4 years) were studied. All subjects were subjected to baseline resting and exercise ventriculography, myocardial perfusion scintigraphy (MPS), and cardiopulmonary testing. PMA group members then participated in a 4-month physical training program and were reevaluated via the same methods applied at baseline. RESULTS: Baseline left ventricular ejection fraction (LVEF) determinations by ventriculography were similar for both groups (PMA, 67.7±10.2%; controls, 66.5±5.4%; P=0.67). However, a significant rise in LVEF seen in control subjects during exercise (75.3±6.2%; P=0.0001) did not materialize during peak exercise in patients with PMA (67.7±10.2%; P=0.47). Of the 12 patients in the PMA group who completed the training program, 10 showed a significant reduction in reversible perfusion defects during MPS. Nevertheless, LVEF at rest (63.5±8.7%) and at peak exercise (67.3±15.9%) did not differ significantly (P=0.30) in this subset. CONCLUSIONS: In patients with PMA, reduced left ventricular inotropic reserve observed during exercise did not normalize after improving myocardial perfusion through aerobic physical training.