Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial.

BACKGROUND: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management. METHODS AND RESULTS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive-assigned women revascularized versus 81.2% of invasive-assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive-assigned women and 74.8% of invasive-assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4-year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline-directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77-1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76-1.14]; P=0.49), with no significant sex-by-treatment-group interactions. CONCLUSIONS: Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial. REGISTRATION: URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.

Microvascular Dysfunction Is Associated With Impaired Myocardial Work in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Multimodality Study.

Background Two-dimensional speckle tracking echocardiography has been shown to correlate with microvascular dysfunction, a hallmark of hypertrophic cardiomyopathy (HCM). We hypothesized that there is an association between myocardial work and left ventricular ischemia, with incremental value to global longitudinal strain, in patients with HCM. Methods and Results We performed a prospective assessment of patients with HCM, undergoing 2-dimensional speckle tracking echocardiography and stress perfusion cardiac magnetic resonance. Results were stratified according to obstructive or nonobstructive HCM and the presence of significant replacement fibrosis (late gadolinium enhancement ≥15% of left ventricular mass). Seventy-five patients with HCM (63% men, age 55±15 years) were evaluated, 28% with obstructive HCM (mean gradient 89±60 mm Hg). Perfusion defects were found in 90.7%, involving 22.5±16.9% of left ventricular mass, and 38.7% had late gadolinium enhancement ≥15%. In a multivariable analysis, a lower global work index (r=-0.519, ß-estimate -10.822; P=0.001), lower global work efficiency (r=-0.379, ß-estimate -0.123; P=0.041), and impaired global constructive work (r=-0.532, ß-estimate -13.788; P<0.001) significantly correlated with ischemia. A segmental analysis supported these findings, albeit with lower correlation coefficients. A global work index cutoff ≤1755 mm Hg% was associated with hypoperfusion with a sensitivity of 88% and a specificity of 71%, while the best cutoff for global longitudinal strain (>-15.5%) had a sensitivity of 64% and a specificity of 57%. The association between myocardial work and perfusion defects was significant independently of late gadolinium enhancement ≥15% and obstructive HCM. Conclusions Impaired myocardial work was significantly correlated with the extent of ischemia in cardiac magnetic resonance, independently of the degree of left ventricular hypertrophy or fibrosis, with a higher predictive power than global longitudinal strain.

Outcomes in Pregnant Women with Valvular Heart Disease from Portuguese-Speaking African Countries Treated in Portugal through an International Agreement of Health Cooperation.

Aims: We performed a clinical audit of maternal and fetal outcomes in pregnant women with valvular heart disease (VHD) from Portuguese-speaking African countries who were transferred for their care, during a twenty-year period, through a memorandum of agreement of international cooperation. Methods and results: A retrospective analysis of 81 pregnancies in 45 patients with VHD (median age 24, interquartile range 22-29 years) from 2000 to 2020 was performed. The main outcome measures were maternal cardiovascular and fetal outcomes. History of rheumatic heart disease was present in 60 (74.1%) pregnancies. Most were in New York Heart Association (NYHA) functional class I or II; at the first evaluation, 35 (43.2%) were on cardiac medication and 49 (60.5%) were anticoagulated. Forty-eight pregnancies had at least one valvular prosthesis, including 38 mechanical heart valves. During pregnancy, deterioration in NYHA functional class occurred in 35 (42.0%), and eight (9.9%) patients required initiation or intensified cardiac medication. Mechanical valve thrombosis complicated four (4.9%) pregnancies, all cases on heparin, and resulted in one maternal death. Haemorrhagic complications happened in 7 (8.6%) anticoagulated patients, in the immediate postpartum or puerperal period. The 81 pregnancies resulted in 56 (69.1%) live births, while miscarriage and fetal malformations occurred in 19 (23.5%) and 12 (14.8%) pregnancies, respectively. In multivariate analysis, vitamin K antagonist therapy was the only independent predictor of an unsuccessful pregnancy (p = 0.048). Conclusion: In a high-income country, successful pregnancy was possible with low rate of maternal events in women with VHD transferred from five low-middle income countries in Africa. The use of anticoagulation with a vitamin K antagonist was associated with an unsuccessful pregnancy.

Role of cardiovascular magnetic resonance in the clinical evaluation of left ventricular hypertrophy: a 360° panorama.

Left ventricular hypertrophy (LVH) is a frequent imaging finding in the general population. In order to identify the precise etiology, a comprehensive diagnostic approach should be adopted, including the prevalence of each entity that may cause LVH, family history, clinical, electrocardiographic and imaging findings. By providing a detailed evaluation of the myocardium, cardiovascular magnetic resonance (CMR) has assumed a central role in the differential diagnosis of left ventricular hypertrophy, with the technique of parametric imaging allowing more refined tissue characterization. This article aims to establish a parallel between pathophysiological features and imaging findings through the broad spectrum of LVH entities, emphasizing the role of CMR in the differential diagnosis.

Cardiovascular complications of treatment for prostate cancer.

Prostate cancer, an androgen-dependent disease, is one of the leading causes of mortality in men. It can present as localised disease, locally advanced or distant metastatic disease. Treatment options for patients with prostate cancer include surgery, chemotherapy, brachytherapy, radiation therapy and hormonal therapy. There are multiple treatment options for each stage of the disease, but hormone therapy is usually reserved for advanced stages. Cardiovascular disease is the leading cause of death in patients with prostate cancer and both diseases share common risk factors. Hormone therapy improves prognosis in patients with more advanced disease, albeit at the cost of cardiovascular toxicity. Hormone therapy can be achieved with the use of agonists and antagonists of gonadotropin-releasing hormone receptors, androgen receptor blockers and enzyme inhibitors of androgen synthesis. Drug-specific cardiotoxicity caused by treatments for prostate cancer has not been fully elucidated. Cardiovascular disease in patients with prostate cancer is mainly managed via an ABCDE approach, a strategy to optimise common risk factors. With newer agents improving the prognosis for patients with prostate cancer, cardiovascular toxicity will have a greater impact on the outcomes of these patients. This article reviews cardiovascular risks associated with therapy for prostate cancer with a focus on hormonal therapy.

Associations between perfusion defects, tissue changes and myocardial deformation in hypertrophic cardiomyopathy, uncovered by a cardiac magnetic resonance segmental analysis.

BACKGROUND: Microvascular dysfunction is an often overlooked feature of hypertrophic cardiomyopathy (HCM). Our aim was to assess the association between microvascular dysfunction, wall thickness, tissue characteristics and myocardial deformation in HCM patients, by analyzing individual myocardial segments. METHODS: Prospective assessment including cardiac magnetic resonance to assess wall thickness, T1 and T2 mapping, extracellular volume, late gadolinium enhancement (LGE) and stress perfusion. Results were stratified according to the 16 American Heart Association segments. RESULTS: Seventy-five patients were recruited (1200 segments), 63% male, mean age 54.6±14.8 years, maximal wall thickness of 20.22±4.6 mm. Among the 424 segments (35%) with perfusion defects, 24% had defects only in the endocardial layer and 12% in both endocardial and epicardial layers. Perfusion defects were more often detected in hypertrophied segments (64%). Among the 660 segments with normal wall thickness, 19% presented perfusion defects. Independently of wall thickness, segments with perfusion defects had a higher T1 (ß-estimate 30.28, p<0.001), extracelluar volume (ß-estimate 1.50, p<0.001) and T2 (ß-estimate 0.73, p<0.001) and had late gadolinium enhancement more frequently (odds ratio 4.16, p<0.001). Higher values of circumferential strain (lower deformation) and lower values of radial strain were found in segments with perfusion defects (ß-estimate 2.76, p<0.001; and ß-estimate -10.39, p<0.001, circumferential and radial strain, respectively). CONCLUSION: While microvascular dysfunction was more prevalent in more hypertrophied segments, it also had a major presence in segments without hypertrophy. In this segmental analysis, we found an association between the presence of ischemia and tissue abnormalities, replacement fibrosis as well as impaired strain, independently of the segmental wall thickness.

Index of microcirculatory resistance in the assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Coronary microvascular dysfunction (CMD) is one of the most important pathophysiological features in hypertrophic cardiomyopathy (HCM). The index of microcirculatory resistance (IMR) is an invasive method to assess the coronary microcirculation. The aim was to assess CMD in patients with HCM by IMR. METHODS: Adult patients with HCM without epicardial coronary artery disease underwent cardiac catheterization for the assessment of CMD by IMR (normal cut-off value ≤22.0) and coronary flow reserve (CFR) (normal cut-off value ≥2). Cardiovascular magnetic resonance (CMR) was performed to assess the ischemic burden by perfusion imaging during regadenoson-induced hyperemia, and the extent of myocardial fibrosis was assessed by late gadolinium enhancement (LGE), native T1 mapping and extracellular volume (ECV). RESULTS: Fourteen patients were enrolled with a mean age of 62.8±6.2years, 8 (57.1%) males, of whom 9 (64.3%) had obstructive HCM. Using IMR, CMD was detected in 4 (29%) patients. Among four patients with an IMR>22.0, all had non-obstructive HCM and two had angina. CFR<2 was reported in eight patients (57%). Concordance between IMR and CFR (both normal or both abnormal) was verified in 6 patients (43%). Among four patients with IMR>22.0, perfusion defects were found in two of the three patients who underwent stress CMR. Increased ECV (>28%) was documented in two of the patients with IMR>22 and in three of the patients with IMR≤22.0. LGE was >15% in 2 of the patients with IMR>22 and in 4 with IMR≤22.0. CONCLUSIONS: IMR assessment in HCM is feasible and safe. Patients with abnormal IMR seemed to have more significant tissue abnormalities on CMR.

Blunted coronary flow velocity reserve is associated with impairment in systolic function and functional capacity in hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction constitutes an important pathophysiological feature in hypertrophic cardiomyopathy (HCM). We aimed to assess the association between impaired coronary flow velocity reserve (CFVR) and ventricular systolic function and functional capacity. METHODS: Eighty-three patients with HCM were enrolled in this prospective cohort study. Patients underwent echocardiogram to evaluate ventricular performance and CFVR in the left anterior descending artery (LAD) and posterior descending artery (PD). Diastolic coronary flow velocity was measured in basal conditions and in hyperemia. CFVR was calculated as the ratio of hyperemic and basal peak diastolic flow velocities. Functional capacity was evaluated by cardiopulmonary exercise testing (CPET). The link between CFVR and biventricular systolic function and peak VO2 was studied. RESULTS: Age was 55.0(14.4)years, 50 patients (60%) were male; 59 patients (71%) had nonobstructive HCM. Mean CFVR LAD was 1.81(0.49) and CFVR PD was 1.73(0.55). Lower CFVR PD was associated with impaired global longitudinal strain (GLS) 2D (ß-estimate:-3.240,95%CI:-4.634;-1.846, p < 0.001), GLS 3D (ß-estimate:-2.559,95%CI:-3.932;-1.186, p < 0.001) and area strain (ß-estimate:-3.044,95%CI:-5.373;-0.716, p = 0.011). Lower values of CFVR PD related to worse global work index (ß-estimate:267.824,95%CI:75.964;459.683, p = 0.007), global constructive work (ß-estimate:217.300,95%CI:38.750;395.850, p = 0.018) and global work efficiency (ß-estimate:5.656,95%CI:2.229;9.084, p = 0.002). Impaired CFVR LAD (ß-estimate:2.826, 95%CI:0.913;4.739, p = 0.004) and CFVR PD (ß-estimate:2.801,95%CI:0.657;4.945, p = 0.011) were associated with lower TAPSE. Lower values of CFVR LAD (ß-estimate:2.580, 95%CI:0.169;4.991, p = 0.036) and CFVR PD (ß-estimate:3.163, 95%CI: 0.721;5.606, p = 0.012) were associated with worse peak VO2. CONCLUSION: Lower CFVR was associated with impairment in biventricular systolic function parameters and functional capacity assessed by pVO2.

Strain patterns in primary mitral regurgitation due to rheumatic heart disease and mitral valve prolapse.

OBJECTIVE: Left atrial (LA) and left ventricular (LV) remodelling are the adaptive changes that occur in primary mitral regurgitation (MR) and are related to its clinical outcomes. Despite the pathophysiological differences in MR in rheumatic heart disease (RHD) and mitral valve prolapse (MVP), whether the pattern of LV and LA remodelling is different between the two conditions remains unknown. Hence, we compared the LA and LV strain pattern in MR due to RHD, the predominant etiology in developing countries topatients with MVP and age and sex-matched controls. METHODS: A total of 50 patients of severe MR which included 30 MVP MR and 20 RHD MR were assessed by strain imaging by speckle tracking echocardiography (STE) and were compared with age and sex-matched controls. 2D STE was used for LA and 3D STE was used for LV strain analysis. LA and LV strain parameters were compared between MVP MR and RHD MR groups. RESULTS: 30 patients with MVP and 20 with RHD were studied. 60% (n = 30) were symptomatic. Mean GLS was -17.2 ± 4.4% compared to -20 ± 3.2% among controls and mean LA strain was 17.35 ± 10.3% compared to 51.34 ± 11.5% among controls which were significantly lower (both p < 0.01). No significant difference in LA strain and GLS was found between MVP and RHD subgroups (LA strain 20.45 ± 11.9% and 14.63 ± 8.85%; p = 0.08; GLS - 18.25 ± 4.3% and-16.2 ± 4.6%; p = 0.12). PALS in the RHD group was lower compared to MVP(p = 0.08) which showed a trend towards significance. LV strain parameters showed no significant difference among the MVP and RHD groups. CONCLUSION: LA and LV strain parameters showed no significant difference in MR due to either RHD or MVP. There was a trend towards lower LA strain in RHD which needs validation with large multicentric studies. The current strain parameters from MVP with the prognostic value may be applied to MR of RHD etiology, pending confirmation of our results by other groups.

Myocardial work is associated with significant left ventricular myocardial fibrosis in patients with hypertrophic cardiomyopathy.

Late gadolinium enhancement on cardiac magnetic resonance adds prognostic information in patients with hypertrophic cardiomyopathy. Whether Myocardial work, a new parameter on transthoracic echocardiographic, can be associated with significant fibrosis in hypertrophic cardiomyopathy patients is unknown. In a single-centre prospective evaluation of hypertrophic cardiomyopathy patients in whom transthoracic echocardiographic and cardiac magnetic resonance were performed, Myocardial work and related indices were calculated from global longitudinal strain and from estimated left ventricular pressure curves. The extent of late gadolinium enhancement was quantitatively assessed. Late gadolinium enhancement ≥ 15% was chosen to define significant fibrosis. Logistic regression analysis was used to find the variables associated with late gadolinium enhancement ≥ 15% and cut-off values were determined. Among the forty-six patients analysed mean age was 56 ± 15 years, 28 (61%) were male patients and the mean left ventricular ejection fraction by transthoracic echocardiographic was 67 ± 8%. Global constructive work and global work index were significantly related to late gadolinium enhancement ≥ 15%, while global longitudinal strain nearly reached statistical significance. A cut-off ≤ 1550 mmHg% of global constructive work was associated with significant fibrosis with a sensitivity of 91% and a specificity of 84%, while the best cut-off for global longitudinal strain (> - 15%) had a sensitivity of 67% and a specificity of 76%. In our study cohort, global constructive work was associated with significant left ventricular myocardial fibrosis in cardiac magnetic resonance, suggesting its utility in patients who may not be able to have a cardiac magnetic resonance study.

The Impact of Ischemia Assessed by Magnetic Resonance on Functional, Arrhythmic, and Imaging Features of Hypertrophic Cardiomyopathy.

Aims: The aim of the study is to investigate the association between the degree of ischemia due to coronary microvascular dysfunction (CMD) and the left ventricular (LV) tissue characteristics, systolic performance, and clinical manifestations in hypertrophic cardiomyopathy (HCM). Methods and Results: This prospective study enrolled 75 patients with HCM without obstructive epicardial coronary artery disease. Each patient underwent cardiovascular magnetic resonance (CMR) including parametric mapping, perfusion imaging during regadenoson-induced hyperemia, late gadolinium enhancement (LGE) and three-dimensional longitudinal, circumferential, and radial strains analysis. Electrocardiogram, 24-h Holter recording, and cardiopulmonary exercise testing (CPET) were performed to assess arrhythmias and functional capacity. In total, 47 (63%) patients were men with the mean age of 54.6 (14.8) years, 51 (68%) patients had non-obstructive HCM, maximum wall thickness (MWT) was 20.2 (4.6) mm, LV ejection fraction (LVEF) was 71.6 (8.3%), and ischemic burden was 22.5 (16.9%) of LV. Greater MWT was associated with the severity of ischemia (ß-estimate:1.353, 95% CI:0.182; 2.523, p = 0.024). Ischemic burden was strongly associated with higher values of native T1 (ß-estimate:9.018, 95% CI:4.721; 13.315, p < 0.001). The association between ischemia and LGE was significant in following subgroup analyses: MWT 15-20 mm (ß-estimate:1.941, 95% CI:0.738; 3.143, p = 0.002), non-obstructive HCM (ß-estimate:1.471, 95% CI:0.258; 2.683, p = 0.019), women (ß-estimate:1.957, 95% CI:0.423; 3.492, p = 0.015) and age <40 years (ß-estimate:4.874, 95% CI:1.155; 8.594, p = 0.016). Ischemia in ≥21% of LV was associated with LGE >15% (AUC 0.766, sensitivity 0.724, specificity 0.659). Ischemia was also associated with atrial fibrillation or flutter (AF/AFL) (OR-estimate:1.481, 95% CI:1.020; 2.152, p = 0.039), but no association was seen for non-sustained ventricular tachycardia. Ischemia was associated with shorter time to anaerobic threshold (ß-estimate: -0.442, 95% CI: -0.860; -0.023, p = 0.039). Conclusion: In HCM, ischemia associates with morphological markers of severity of disease, fibrosis, arrhythmia, and functional capacity.