Left-ventricular outflow tract acceleration time is associated with symptoms in patients with obstructive hypertrophic cardiomyopathy

AIMS: Not all obstructive hypertrophic cardiomyopathy (HCM) patients are symptomatic. The relation between obstructive HCM and symptoms is not well understood. The hypothesis of this study is that left-ventricular outflow tract (LVOT) acceleration time (AT) is associated with symptoms. METHODS: We included 187 patients (61% men, mean age 55 ± 14 years) with obstructive HCM, defined as a maximal wall thickness ≥ 15 mm and a resting or provoked LVOT peak gradient ≥ 30 mmHg. Peak velocity (PV), left-ventricular (LV) ejection time (ET), and AT (the time between LVOT flow onset and the moment of PV) were measured on continuous-wave (CW) Doppler tracings. Logistic and Cox proportional hazard regression analyses were used to evaluate the relation between symptoms [New York Heart Association (NYHA) class ≥ II] and echocardiographic measurements, including AT. Reproducibility was assessed using the intraclass correlation coefficient (ICC). RESULTS: Symptomatic patients were more often female and had higher mean AT values. Logistic regression demonstrated a significant association between AT and symptomatic status (odds ratio 1.31 per 10 ms, p < 0.01) after adjustment for sex, negative inotropes, PV, LVOT diameter, and diastolic dysfunction. AT was independently associated with symptoms and septal reduction during follow-up (hazard ratio 1.09 per 10 ms, p < 0.05). The ICC was 0.98 with a mean difference of 0.28 ± 8.4 ms. CONCLUSION: In obstructive HCM patients, increased AT is significantly related to symptoms after adjustment for sex, negative inotropes, PV, LVOT diameter, and diastolic dysfunction, and is associated with the symptomatic status during follow-up. AT represents an easily measured echocardiographic variable with excellent inter-reader reproducibility. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40477-020-00513-3) contains supplementary material, which is available to authorized users

Prognostic stratification of obese patients by stress ^99mTc- tetrofosmin myocardial perfusion imaging

Obesity is a major heath problem associated with increased cardiovascular mortality. There are currently no data to support a role for stress imaging techniques in the risk stratification of obese patients. The aim of this study was to assess the independent value of stress 99mTc-tetrofosmin SPECT in predicting mortality and hard cardiac events in obese patients. Methods: We studied 265 patients with a body mass index greater than 30 kg/m2 by exercise or dobutamine stress 99mTc-tetrofosmin myocardial perfusion tomography. Endpoints during follow-up were cardiac death and death of any cause. Results: The mean patient age (±SD) was 59 ± 10 y, and 110 of the patients were men (42%). The mean body mass index was 37 ± 7 kg/m2. Scan findings were normal in 113 patients (43%). Myocardial perfusion abnormalities were fixed in 62 patients (23%) and reversible in 90 patients (34%). During a mean follow-up period of 5.5 ± 2 y, 41 patients (15%) died. Death was considered cardiac in 22 patients (8%). Nonfatal myocardial infarction occurred in 20 patients (7.5%). The annual cardiac death rate was 0.6% in patients with normal perfusion and 3.3% in patients with abnormal perfusion. Patients with a multiple-vessel distribution of abnormalities had a higher cardiac death rate than did patients with a single-vessel distribution (4.1%vs. 2.5%, P &lt; 0.05). The annual mortality rate was 1.3% in patients with normal perfusion and 4.2% in patients with abnormal perfusion. In a multivariate analysis, perfusion abnormalities were independently predictive of cardiac mortality (risk ratio, 3.2; 95% confidence interval, 1.5-6.7) and overall mortality (risk ratio, 2.7; 95% confidence interval, 1.4-4.3). Conclusion: Stress 99mTc-tetrofosmin myocardial perfusion imaging is a useful tool for predicting cardiac and overall mortality in obese patients.</p

Prognostic stratification of obese patients by stress ^99mTc- tetrofosmin myocardial perfusion imaging

Obesity is a major heath problem associated with increased cardiovascular mortality. There are currently no data to support a role for stress imaging techniques in the risk stratification of obese patients. The aim of this study was to assess the independent value of stress 99mTc-tetrofosmin SPECT in predicting mortality and hard cardiac events in obese patients. Methods: We studied 265 patients with a body mass index greater than 30 kg/m2 by exercise or dobutamine stress 99mTc-tetrofosmin myocardial perfusion tomography. Endpoints during follow-up were cardiac death and death of any cause. Results: The mean patient age (±SD) was 59 ± 10 y, and 110 of the patients were men (42%). The mean body mass index was 37 ± 7 kg/m2. Scan findings were normal in 113 patients (43%). Myocardial perfusion abnormalities were fixed in 62 patients (23%) and reversible in 90 patients (34%). During a mean follow-up period of 5.5 ± 2 y, 41 patients (15%) died. Death was considered cardiac in 22 patients (8%). Nonfatal myocardial infarction occurred in 20 patients (7.5%). The annual cardiac death rate was 0.6% in patients with normal perfusion and 3.3% in patients with abnormal perfusion. Patients with a multiple-vessel distribution of abnormalities had a higher cardiac death rate than did patients with a single-vessel distribution (4.1%vs. 2.5%, P &lt; 0.05). The annual mortality rate was 1.3% in patients with normal perfusion and 4.2% in patients with abnormal perfusion. In a multivariate analysis, perfusion abnormalities were independently predictive of cardiac mortality (risk ratio, 3.2; 95% confidence interval, 1.5-6.7) and overall mortality (risk ratio, 2.7; 95% confidence interval, 1.4-4.3). Conclusion: Stress 99mTc-tetrofosmin myocardial perfusion imaging is a useful tool for predicting cardiac and overall mortality in obese patients.</p

Association of ischemia on stress ^99mTc-tetrofosmin myocardial perfusion imaging with all-cause mortality in patients with diabetes mellitus

Stress myocardial perfusion imaging is a useful method for evaluation of coronary artery disease (CAD) in patients with diabetes mellitus. However, its role in predicting all-cause mortality is not well defined. The aim of this study was to determine whether myocardial ischemia on stress myocardial perfusion imaging can predict all causes of death in patients with diabetes mellitus. Methods: We studied 297 patients with diabetes mellitus and known or suspected CAD by exercise or dobutamine stress 99mTc-tetrofosmin myocardial perfusion tomographic imaging. Ischemia was defined as reversible perfusion abnormalities. The endpoints were death from any cause and hard cardiac events (cardiac death and nonfatal myocardial infarction). Results: An abnormal scan was detected in 179 (60%) patients. Myocardial perfusion abnormalities were fixed in 76 (26%) patients and were reversible in 103 (35%) patients. During a mean follow-up of 6 ± 2.1 y, 80 (27%) patients died. Nonfatal myocardial infarction occurred in 14 (5%) patients. The annual mortality rate was 2.5% in patients with normal perfusion, 4.5% in patients with fixed defects, and 6% in patients with ischemia. The annual cardiac death rate was 4.2% in patients with ischemia and 2.6% in patients with fixed defects. In patients with normal perfusion, the annual cardiac death rate was 0.9% during the 5 y after the stress test. In a Cox multivariate analysis model, predictors of death were age, history of heart failure, peripheral vascular disease, and reversible perfusion defects. Conclusion: Myocardial ischemia on stress 99mTc-tetrofosmin myocardial perfusion imaging is associated with an increased risk of all-cause mortality during long-term follow-up among patients with diabetes mellitus. Patients with normal perfusion have a lower mortality rate and may require less frequent follow-up stress perfusion imaging.</p

Risk stratification of patients with angina pectoris by stress ^99mTc-tetrofosmin myocardial perfusion imaging

Angina pectoris is a major symptom associated with myocardial ischemia. The aim of this study was to find whether stress myocardial perfusion imaging can independently predict mortality in patients with angina. Methods: We studied 455 patients with stable angina pectoris by exercise or dobutamine stress 99mTc-tetrofosmin myocardial perfusion tomographic imaging. An abnormal finding was defined as a reversible or fixed perfusion abnormality. The endpoint during follow-up was death from any cause. Results: Mean age was 60 ± 10 y. There were 266 men (58% of the patients). Myocardial perfusion was normal in 137 patients (30%). Perfusion abnormalities were reversible in 167 patients and fixed in 151 patients. During a mean follow-up of 6 ± 1.7 y, 93 patients (20%) died. The annual mortality rate was 1.5% in patients with normal perfusion and 4.5% in patients with abnormal perfusion. Patients with a multivessel distribution of perfusion abnormalities had a higher annual death rate than patients with abnormalities in a single-vessel distribution (5.1% vs. 3.7%). In a multivariate analysis model, independent predictors of death were age (risk ratio, 1.05; 95% confidence interval [CI], 1.03-1.08), the male sex (risk ratio, 2.1; CI, 1.3-3.4), diabetes (risk ratio, 2.2; CI, 1.4-3.5), heart failure (risk ratio, 2.7; CI, 1.6-4.5), smoking (risk ratio, 1.7; CI, 1.1-2.6), reversible perfusion abnormalities (risk ratio, 1.9; CI, 1.1-2.8), and fixed perfusion abnormalities (risk ratio, 2; CI, 1.2-3.1). Conclusion: Stress 99mTc-tetrofosmin myocardial perfusion imaging provides independent information for predicting mortality in patients with stable angina pectoris. Both reversible and fixed defects are associated with an increased risk of death. The extent of stress perfusion abnormalities is a major determinant of mortality. Patients with normal perfusion have a low mortality rate during long-term follow-up.</p

Prognostic stratification using dobutamine stress ^99mTc- tetrofosmin myocardial perfusion SPECT in elderly patients unable to perform exercise testing

Information on the prognostic value of noninvasive stress imaging techniques in the elderly is relatively scarce. This study assessed the prognostic value of dobutamine stress 99mTc-tetrofosmin SPECT for the prediction of mortality and cardiac events in elderly patients. Methods: Clinical information and SPECT results were analyzed for 272 consecutive patients ≥ 65 y old (mean age, 71 ± 5 y; range, 65-87 y) with limited exercise capacity. Follow-up was complete in 270 patients (99.3%); 23 underwent revascularization within 60 d of the scintigraphy and were excluded. Abnormal findings were defined as the presence of a fixed or reversible perfusion defect. A summed stress score was obtained to estimate the extent and severity of perfusion defects. The incremental prognostic value of SPECT over clinical data was evaluated according to 3 multivariate models, which included any SPECT abnormality, the presence of a fixed or reversible defect, and the summed stress score. Results: During the follow-up (3.3 ± 1.4 y), 59 patients died (29 cardiac deaths), 16 had a nonfatal infarction, and 49 underwent late revascularization. Abnormal scan findings were present for 140 patients (57%). The annual event rates for total mortality, cardiac death, and cardiac death or nonfatal infarction were, respectively, 3.2%, 0.2%, and 0.7% when scan findings were normal and, respectively, 9.5%, 4.3%, and 8% when scan findings were abnormal (all P &lt; 0.0001). Multivariate analysis showed that abnormal scan findings, the presence of a fixed or reversible defect, and the summed stress score provided incremental prognostic information over clinical data. The presence of abnormal scan findings was independently associated with an increased risk for total mortality, cardiac death, and cardiac death or nonfatal infarction (respectively, hazard ratio 3.4 [95% CI, 1.8-6.5], 12.1 [95% CI, 2.9-51.5], and 9.0 [95% CI, 2.8-29.6]). Conclusion: Dobutamine stress 99mTc-tetrofosmin SPECT provides incremental prognostic information for the prediction of total mortality and cardiac events in elderly patients.</p

Biomechanical response of ultrathin slices of hypertrophic cardiomyopathy tissue to myosin modulator mavacamten

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disorder of the heart, but effective treatment options remain limited. Mavacamten, a direct myosin modulator, has been presented as novel pharmacological therapy for HCM. The aim of this study was to analyze the biomechanical response of HCM tissue to Mavacamten using living myocardial slices (LMS). LMS (n = 58) from patients with HCM (n = 10) were cultured under electromechanical stimulation, and Verapamil and Mavacamten were administered on consecutive days to evaluate their effects on cardiac biomechanics. Mavacamten and Verapamil reduced contractile force and dF/dt and increased time-to-relaxation in a similar manner. Yet, the time-to-peak of the cardiac contraction was prolonged after administration of Mavacamten (221.0 ms (208.8 – 236.3) vs. 237.7 (221.0 – 254.7), p = 0.004). In addition, Mavacamten prolonged the functional refractory period (FRP) (330 ms (304 − 351) vs. 355 ms (313 − 370), p = 0.023) and better preserved twitch force with increasing stimulation frequencies, compared to Verapamil. As such, Mavacamten reduced (hyper-)contractility and prolonged contraction duration of HCM LMS, suggesting a reduction in cardiac wall stress. Also, Mavacamten might protect against the development of ventricular tachyarrhythmias due to prolongation of the FRP, and improve toleration of tachycardia due to better preservation of twitch force at tachycardiac stimulation frequencies.</p

Impact of diabetes mellitus on prediction of clinical outcome after coronary revascularization by ¹⁸F-FDG SPECT in patients with ischemic left ventricular dysfunction

Nuclear imaging using 18F-FDG is an established method for the noninvasive assessment of myocardial viability. Data on the value of 18F-FDG imaging in patients with diabetes mellitus are scarce. The aim of this study was to assess whether, in patients with diabetes mellitus and ischemic left ventricular (LV) dysfunction, 18/F-FDG imaging can predict improvement of LV function and heart failure symptoms after coronary revascularization. Methods: A total of 130 consecutive patients with ischemic LV dysfunction who were already scheduled for surgical revascularization were studied; 34 of the patients had diabetes mellitus. All patients underwent radionuclide ventriculography to assess left ventricular ejection fraction (LVEF), resting 2-dimensional echocardiography to identify dysfunctional myocardial tissue, and dual-isotope 18F-FDG/99m/Tc- tetrofosmin SPECT after oral administration of acipimox. Nine to 12 mo after coronary revascularization, radionuclide ventriculography and echocardiography were repeated. An improvement in LVEF by at least5% was considered significant. Results: 18F-FDG SPECT demonstrated that 610 (50%) of 1,212 dysfunctional segments were viable. Patients with and without diabetes mellitus had a comparable number of dysfunctional but viable segments per patient. Also, the number of patients with a substantial amount of dysfunctional but viable myocardium (≥ viable segments) was comparable between the groups with and without diabetes mellitus. The presence of substantial viability on 18F-FDG SPECT was predictive of improvement in LVEF and heart failure symptoms postoperatively (sensitivity and specificity of 82% and 89%, respectively, in patients with diabetes and 83% and 93%, respectively, in patients without diabetes; not statistically significant). Conclusion: 18F-FDG SPECT is practical for routine assessment of myocardial viability in patients with ischemic LV dysfunction with or without diabetes mellitus. Patients with substantial myocardial viability on 18F-FDG SPECT have a high probability of improvement of LV function and symptoms after coronary revascularization, irrespective of the absence or presence of diabetes mellitus.</p

Impact of diabetes mellitus on prediction of clinical outcome after coronary revascularization by ¹⁸F-FDG SPECT in patients with ischemic left ventricular dysfunction

Nuclear imaging using 18F-FDG is an established method for the noninvasive assessment of myocardial viability. Data on the value of 18F-FDG imaging in patients with diabetes mellitus are scarce. The aim of this study was to assess whether, in patients with diabetes mellitus and ischemic left ventricular (LV) dysfunction, 18/F-FDG imaging can predict improvement of LV function and heart failure symptoms after coronary revascularization. Methods: A total of 130 consecutive patients with ischemic LV dysfunction who were already scheduled for surgical revascularization were studied; 34 of the patients had diabetes mellitus. All patients underwent radionuclide ventriculography to assess left ventricular ejection fraction (LVEF), resting 2-dimensional echocardiography to identify dysfunctional myocardial tissue, and dual-isotope 18F-FDG/99m/Tc- tetrofosmin SPECT after oral administration of acipimox. Nine to 12 mo after coronary revascularization, radionuclide ventriculography and echocardiography were repeated. An improvement in LVEF by at least5% was considered significant. Results: 18F-FDG SPECT demonstrated that 610 (50%) of 1,212 dysfunctional segments were viable. Patients with and without diabetes mellitus had a comparable number of dysfunctional but viable segments per patient. Also, the number of patients with a substantial amount of dysfunctional but viable myocardium (≥ viable segments) was comparable between the groups with and without diabetes mellitus. The presence of substantial viability on 18F-FDG SPECT was predictive of improvement in LVEF and heart failure symptoms postoperatively (sensitivity and specificity of 82% and 89%, respectively, in patients with diabetes and 83% and 93%, respectively, in patients without diabetes; not statistically significant). Conclusion: 18F-FDG SPECT is practical for routine assessment of myocardial viability in patients with ischemic LV dysfunction with or without diabetes mellitus. Patients with substantial myocardial viability on 18F-FDG SPECT have a high probability of improvement of LV function and symptoms after coronary revascularization, irrespective of the absence or presence of diabetes mellitus.</p