Does diabetes increase the risk of cardiovascular events in patients with negative treadmill stress echocardiography?

Cardiovascular morbidity and mortality rates are considered to be high in patients with diabetes despite negative stress test results; however, little data are available to support this supposition. We compared the long-term cardiovascular events between patients with diabetes and those without diabetes with negative treadmill stress echocardiography and evaluated the predictors for cardiovascular events in patients with diabetes. A total of 1,243 consecutive patients (mean age, 56 ± 10 years; non-diabetics: diabetics, 975:268; mean follow-up of 5 years) with negative treadmill stress echocardiography were evaluated. Clinical data were examined, and major adverse cardiovascular events (MACEs, a composite of coronary revascularization, acute myocardial infarction, and cardiovascular death) were compared between the non-diabetic and diabetic groups. In the population matched by clinical characteristics, the diabetic and non-diabetic groups had similar occurrence of MACEs (non-diabetics vs. diabetics = 5% versus 7%; p = 0.329) and event-free survival. MACEs in the diabetic group were associated with elevated early diastolic velocity of the mitral inflow/mitral annulus (E/e') ratio, indicative of diastolic dysfunction. The absence of statin and dipeptidyl peptidase-4 inhibitor use and use of sulfonylureas were also predictors of more MACEs. In conclusion, long-term cardiovascular events in patients with diabetes and negative stress echocardiography were comparable to those in patients without diabetes. However, appropriate monitoring of diastolic dysfunction, statin use, and individualized antidiabetic drug selection are required to reduce the cardiovascular risk in patients with diabetes.

Full-blown cardiac manifestations in ankylosing spondylitis.

Ankylosing spondylitis often involves a heart, such as aortic or mitral regurgitation, conduction disorder, or cardiomyopathy. We present a 34-year-old male patient with ankylosing spondylitis who has severe aortic regurgitation, mild mitral stenosis, and a conduction disturbance of the left bundle branch block, identified using multimodal images.

Evolutionary change mimicking apical hypertrophic cardiomyopathy in a patient with takotsubo cardiomyopathy.

In this report, we introduce a case of thickening of the involved left ventricular apical segment on echocardiography and deep T-wave inversions in precordial leads on electrocardiography transiently seen in the course of recovery from biventricular takotsubo cardiomyopathy, mimicking apical hypertrophic cardiomyopathy. This result suggests that the echocardiographic finding of transient myocardial edema can be identified by cardiac magnetic resonance imaging in takotsubo cardiomyopathy. Additionally, it persisted a few weeks after full functional recovery. We believe that this case will contribute in part toward clarifying the pathophysiology of takotsubo cardiomyopathy.

Breast Cancer and Therapy-Related Cardiovascular Toxicity.

The global incidence of breast cancer is on the rise, a trend also observed in South Korea. However, thanks to the rapid advancements in anticancer therapies, survival rates are improving. Consequently, post-treatment health and quality of life for breast cancer survivors are emerging as significant concerns, particularly regarding treatment-related cardiotoxicity. In this review, we delve into the cardiovascular complications associated with breast cancer treatment, explore surveillance protocols for early detection and diagnosis of late complications, and discuss protective strategies against cardiotoxicity in breast cancer patients undergoing anticancer therapy, drawing from multiple guidelines.

Assessing Cardiovascular Risk with Coronary Artery Calcium and Carotid Intima-Media Thickness in Patients with Negative Stress Echocardiography.

Background: The role of treadmill stress echocardiography (TSE) in symptomatic patients may be limited. We evaluated whether carotid intima-media thickness (cIMT) and coronary artery calcium (CAC) scores can predict cardiovascular (CV) outcomes in patients with negative TSE. Methods: Patients who had negative TSE and measured cIMT or CAC scoring were enrolled and followed up. The primary CV outcome was defined as a composite of acute coronary syndrome, coronary revascularization, heart failure, stroke, and CV death. Results: Overall, 1095 patients participated. The median follow-up duration was 5.8 years. Patients with increased cIMT and CAC scores experienced a high incidence of primary CV outcomes (normal vs. increased group on cIMT and CAC scoring: 4.4% vs. 20.0% and 0.4% vs. 25.0%, respectively, p < 0.001). In the Cox proportional hazard model, increased cIMT and CAC scores were associated with increased primary CV outcomes (adjusted hazard ratio [95% confidence interval], p-value for increased cIMT and increased CAC scores = 2.939 [1.241-6.960], p = 0.014 and 45.192 [5.497-371.505], p < 0.001, respectively). Conclusions: Patients with increased cIMT and CAC scores have poor CV outcomes even though they have negative TSE results, and therefore, they should be carefully monitored.

Double-chambered left ventricle with a thrombus in an asymptomatic patient: A case report.

BACKGROUND: Double-chambered left ventricle (DCLV) is an extremely rare congenital disease in which the left ventricle (LV) is divided by abnormal muscle tissue. Due to its rarity, there is a lack of data on the disease, including its diagnosis, treatment, and prognosis. Accordingly, we report a case in which DCLV was diagnosed and followed up. CASE SUMMARY: A 45-year-old man presented to our hospital due to abnormal findings on an electrocardiogram recorded during a health check. He had no specific cardiac symptoms, comorbidities or relevant past medical history. Echocardiography revealed that the LV was divided into two by muscle fibers. There were no findings of ischemia on coronary angiography and coronary computed tomography angiography performed to exclude differential diagnoses. After comprehensive analysis of the images, DCLV was diagnosed. As it seemed to be asymptomatic DCLV, we decided the patient was to be observed without administering any medication. However, follow-up echocardiography revealed a thrombus in the accessory chamber (AC). Anticoagulant medication was initiated, the thrombus resolved, and the patient is currently undergoing follow-up without any specific symptoms. CONCLUSION: Asymptomatic, uncomplicated DCLV was diagnosed through multimodal imaging; however, a thrombus in the AC occurred during the follow-up. The findings highlight that multimodal imaging is essential in diagnosing DCLV, and that anticoagulation is important in its management.

Global burden of ADHD medication-associated cardiovascular disease, 1967-2023: A comparative analysis using the WHO pharmacovigilance database.

BACKGROUND: Despite the widespread use of attention-deficit hyperactivity disorder (ADHD) medications and their known sympathomimetic effects on the cardiovascular system, cardiovascular risk assessment of these medications using comprehensive global data is limited. This study investigated the association between individual ADHD medications and cardiovascular disease (CVD) using global pharmacovigilance data. METHODS: Reports from the World Health Organization international pharmacovigilance database were utilized (1967-2023; total reports, n=131,255,418). Reporting odds ratios (ROR), and information components (IC) were calculated to evaluate the association between each medication and specific CVDs. RESULTS: We identified 13,344 CVD cases related to ADHD medications out of 146,489 cases of all reports on ADHD medications. Cumulative reports on ADHD medications have shown a steady increase, notably in adults since 2010. ADHD medications were associated with a higher risk of CVD overall (ROR [95 % CI], 1.60 [1.58-1.63]; IC [IC0.25], 0.63 [0.60]), with a higher association observed in females than in males. Among specific CVDs, all drugs were associated with an increased risk of torsade de pointes/QT prolongation, cardiomyopathy, and myocardial infarction. Conversely, heart failure, stroke, and cardiac death/shock were exclusively associated with amphetamines. Lisdexamfetamine showed a weaker association with all CVDs compared to amphetamines, and methylphenidate exhibited the lowest overall association with CVD. Atomoxetine had the second-highest association with torsade de pointes/QT prolongation. CONCLUSIONS: The associations between CVDs and ADHD medications vary, with amphetamines posing a higher risk, while lisdexamfetamine and methylphenidate exhibit better safety profiles.

Cancer therapy-related cardiac dysfunction and the role of cardiovascular imaging: systemic review and opinion paper from the Working Group on Cardio-Oncology of the Korean Society of Cardiology.

Cardio-oncology is a critical field due to the escalating significance of cardiovascular toxicity as a side effect of anticancer treatments. Cancer therapy-related cardiac dysfunction (CTRCD) is a prevalent condition associated with cardiovascular toxicity, necessitating effective strategies for prediction, monitoring, management, and tracking. This comprehensive review examines the definition and risk stratification of CTRCD, explores monitoring approaches during anticancer therapy, and highlights specific cardiovascular toxicities linked to various cancer treatments. These include anthracyclines, HER2-targeted agents, vascular endothelial growth factor inhibitors, immune checkpoint inhibitors, chimeric antigen receptor T-cell therapies, and tumor-infiltrating lymphocytes therapies. Incorporating the Korean data, this review offers insights into the regional nuances in managing CTRCD. Using systematic follow-up incorporating cardiovascular imaging and biomarkers, a better understanding and management of CTRCD can be achieved, optimizing the cardiovascular health of both cancer patients and survivors.

Impact on clinical outcomes of renin-angiotensin system inhibitors against doxorubicin-related toxicity in patients with breast cancer and hypertension: A nationwide cohort study in South Korea.

BACKGROUND: Although doxorubicin (DOX) is a commonly used potent chemotherapeutic agent in patients with breast cancer, its cardiotoxic effect is a concern, particularly in patients with hypertension. Antihypertensive renin-angiotensin system (RAS) inhibitors may potentially play a role in preventing overt heart failure (HF) due to DOX toxicity. This study aimed to evaluate whether the use of RAS inhibitors improves clinical outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy. METHODS: A total of 54,344 female patients who were first diagnosed with breast cancer and initiated into DOX therapy between 2008 and 2015 were recruited from a nationwide Korean cohort. Patients were divided into two groups: with and without hypertension (HT, n = 10,789; non-HT, n = 43,555), and the RAS inhibitor group (n = 1,728) was sub-classified from the HT group. Two propensity score-matched cohorts were constructed to compare the clinical outcomes between non-HT and HT groups and between non-HT and RAS inhibitor groups. The primary outcome was the composite of HF and death. RESULTS: After propensity score matching, the HT group had a higher risk for HF (adjusted hazard ratio [HR] = 1.30, 95% confidence intervals [95% CI] = 1.09-1.55) compared to the non-HT group, but there was no significant difference in primary outcome between the two groups. The RAS inhibitor group had a lower risk for primary outcome (adjusted HR = 0.78, 95% CI = 0.65-0.94) and death (adjusted HR = 0.81, 95% CI = 0.66-0.99) compared to the non-HT group. CONCLUSIONS: Hypertension is a risk factor for HF in patients with breast cancer undergoing DOX chemotherapy. However, the RAS inhibitors used to treat hypertension may contribute to decreased mortality and improved clinical outcomes.

Differential Cardiovascular Outcomes of Each Antihypertensive Drug Class in Patients With Hypertension and Breast Cancer Undergoing Doxorubicin-Containing Chemotherapy.

PURPOSE: The preemptive use of renin-angiotensin system (RAS) inhibitors may reduce doxorubicin (DOX)-related cardiotoxicity. Using the national insurance claims data of Korea, this study compared cardiovascular (CV) outcomes following the use of four major antihypertensive drug classes in patients with hypertension and breast cancer who underwent DOX-containing chemotherapy. METHODS: A total of 4,722 patients with hypertension and breast cancer who underwent DOX-containing chemotherapy were included. The outcomes were compared between patients who used RAS inhibitors, calcium channel blockers (CCBs), beta-blockers (BBs), and thiazide and thiazide-like diuretics (TDs). The primary outcome was a composite of incident heart failure and serious ventricular arrhythmias, including ventricular tachycardia and fibrillation, ischemic heart disease, and stroke. RESULTS: In the propensity score-matched population, there were no significant differences in the primary outcome between RAS inhibitor and CCB users; however, patients with diabetes who used CCBs had a worse primary outcome than those who used RAS inhibitors (adjusted hazard ratio [aHR], 1.93; 95% confidence interval [CI], 1.06-3.51). BB and TD users had a worse primary outcome compared with RAS inhibitor (aHR, 1.88; 95% CI, 1.30-2.71 in BB users and aHR, 2.55; 95% CI, 1.37-4.75 in TD users) or CCB (aHR, 1.54; 95% CI, 1.09-2.16 in BB users and aHR, 2.08; 95% CI, 1.13-3.82 in TD users) users. CONCLUSION: RAS inhibitors are preferred for the treating hypertension and improving CV outcomes in patients with hypertension and breast cancer undergoing DOX-containing chemotherapy, particularly in patients with comorbid diabetes. However, CCBs are equivalent to RAS inhibitors and are more favorable than BBs and TDs in terms of improving CV outcomes.

Sodium-glucose cotransporter-2 inhibitors improve clinical outcomes in patients with type 2 diabetes mellitus undergoing anthracycline-containing chemotherapy: an emulated target trial using nationwide cohort data in South Korea.

Novel hypoglycemic agents, sodium-glucose cotransporter 2 inhibitors (SGLT2i), have shown protective effects against anthracycline (AC)-induced cardiotoxicity and exhibit partial anticancer effects in animal models. However, clinical evidence for this is scarce. This study aimed to evaluate whether SGLT2i improve the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) undergoing AC-containing chemotherapy. A total of 81,572 patients who underwent AC chemotherapy between 2014 and 2021 were recruited from a nationwide Korean cohort. Patients were classified into three groups: patients with T2DM taking SGLT2i (n = 780) and other hypoglycemic agents excluding SGLT2i (non-SGLT2i; n = 3,455) during AC chemotherapy, and the non-DM group (n = 77,337). The clinical outcome was a composite of heart failure hospitalization, acute myocardial infarction, ischemic stroke, and death. After propensity score matching, 779 SGLT2i users were compared with 7800 non-DM patients and 2,337 non-SGLT2i users. The SGLT2i group had better composite outcomes compared with the non-DM group (adjusted hazard ratio [HR] = 0.35, 95% confidence interval [95% CI] = 0.25-0.51) and compared with the non-SGLT2i group (adjusted HR = 0.47, 95% CI = 0.32-0.69). In conclusion, SGLT2i may contribute to improving clinical outcomes in patients with T2DM undergoing AC-containing chemotherapy, through an emulated target trial using Korean nationwide cohort data.

Adherence and clinical outcomes for twice-daily versus once-daily dosing of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: Is dosing frequency important?

BACKGROUND: Twice-daily dosing of non-vitamin K antagonist oral anticoagulants (NOACs) may reduce drug adherence compared with once-daily dosing of NOACs in patients with atrial fibrillation (AF), thus worsening clinical outcomes. We evaluated adherence to apixaban and dabigatran requiring twice-daily dosing compared with edoxaban or rivaroxaban with a once-daily dosing regimen and the subsequent clinical outcomes in patients with AF. METHODS: Adherence to each NOAC and outcomes were compared between patients who were diagnosed with AF and initiated NOACs between 2016 and 2017 using Korean claims data. High adherence was defined as the proportion of days covered (PDC) of the index NOAC ≥80%. The clinical outcomes included stroke, acute myocardial infarction, death, and composite outcome. RESULTS: A total of 33,515 patients were analyzed (mean follow-up, 1.7 ± 1.3 years). The proportion of patients with high adherence to NOACs was 95%, which did not significantly differ according to the dosing regimen. The mean PDC for NOACs was as high as ~96%, which was the highest for apixaban users, intermediate for edoxaban or rivaroxaban users, and lowest for dabigatran users, regardless of the dosing regimen. Adverse outcomes in low adherence patients for each NOAC were higher than that of high adherence patients, regardless of the dosing frequency. CONCLUSIONS: Adherence between once- and twice-daily dosing NOACs in patients with AF was high and similar among both dosing regimens. Patients with low NOAC adherence had poorer clinical outcomes, regardless of the dosing frequency.

APACHE II score, rather than cardiac function, may predict poor prognosis in patients with stress-induced cardiomyopathy.

While the disease course of stress-induced cardiomyopathy (SIC) is usually benign, it can be fatal. The prognostic factors to predict poorer outcome are not well established, however. We analyzed the Acute Physiology And Chronic Health Evaluation (APACHE) II score to assess its value for predicting poor prognosis in patients with SIC. Thirty-seven consecutive patients with SIC were followed prospectively during their hospitalization. Clinical factors, including APACHE II score, coronary angiogram, echocardiography and cardiac enzymes at presentation were analyzed. Of the 37 patients, 27 patients (73%) were women. The mean age was 66.1 ± 15.6 yr, and the most common presentation was chest pain (38%). Initial echocardiographic left ventricular ejection fraction (EF) was 42.5% ± 9.3%, and the wall motion score index (WMSI) was 1.9 ± 0.3. Six patients (16%) expired during the follow-up period of hospitalization. Based on the analysis of characteristics and clinical factors, the only predictable variable in prognosis was APACHE II score. The patients with APACHE II score greater than 20 had tendency to expire than the others (P = 0.001). Based on present study, APACHE II score more than 20, rather than cardiac function, is associated with mortality in patients with SIC.

Uptake of F-18 FDG and ultrasound analysis of carotid plaque.

OBJECTIVES: To elucidate the relation between the echolucent plaque on carotid ultrasound and acute inflammation on F-18 FDG carotid PET/CT. METHODS: Thirty nine patients (M:F ratio = 23:16, mean age = 63 ± 11 years) that underwent coronary angiography and carotid ultrasound were divided into three groups-echolucent plaque (n = 22), calcified (n = 10), and no plaque(n = 7). All the patients underwent F-18 FDG carotid PET/CT. The mean standardized uptake values (SUV), namely target to background ratio (TBR) on 180 minutes delayed F-18 FDG carotid PET/CT images were compared with levels of serum inflammatory markers and lipid profiles, and in terms of the presence of carotid plaque on carotid US. RESULTS: 180 minutes TBR of carotid arterial wall at echolucent plaque, calcified plaque, and no plaque were 1.40 ± 0.05, 1.23 ± 0.03, 1.17 ± 0.03 in both carotid artery. TBR of carotid arterial walls for echolucent plaque were significantly larger than TBR for calcified, and no plaque respectively at the both side of carotid artery (P < .05). Serum HDL levels were found to be inversely correlated with F-18 FDG uptake at both carotid arteries (r = -0.43, P = .005) on 180 minutes delayed phase images. Also serum hs-CRP levels were found to be correlated with F-18 FDG TBR values of right carotid arteries (r = 0.41, P = .04). CONCLUSIONS: Our results show that F-18 FDG carotid PET/CT can depict metabolically active atherosclerotic plaques, and suggest that F-18 FDG carotid PET/CT can be used as a noninvasive imaging modality for functional evaluation of atherosclerosis.

Coronary sinus endocarditis in a hemodialysis patient: A case report and review of literature.

BACKGROUND: Infective endocarditis is more common in hemodialysis patients than in the general population and is sometimes difficult to diagnose. Isolated coronary sinus (CS) vegetation is extremely rare and has a good prognosis, but complicated CS vegetation may have a poorer clinical course. We report a case of CS vegetation accidentally found via echocardiography in a hemodialysis patient with undifferentiated shock. The CS vegetation may have been caused by endocardial denudation due to tricuspid regurgitant jet and subsequent bacteremia. CASE SUMMARY: A 91-year-old man with dyspnea and hypotension was transferred from a nursing hospital. He was on regular hemodialysis and had a history of severe grade of tricuspid regurgitation. There was no leukocytosis or fever upon admission. Repetitive and sequential blood cultures revealed absence of microorganism growth. Chest computed tomography showed lung consolidation and a large pleural effusion. A mobile band-like mass on the CS, suggestive of vegetation, was observed on echocardiography. We diagnosed him with infective endocarditis involving the CS, pneumonia, and septic shock based on echocardiographic, radiographic, and clinical findings. Infusion of broad-spectrum antibiotics, fluid resuscitation, inotropic support, and ventilator care were performed. However, the patient died from uncontrolled infection and septic shock. CONCLUSION: CS vegetation can be fatal in hemodialysis patients with impaired immune systems, especially when it delays the diagnosis.

Estimation of coronary flow velocity reserve using transthoracic Doppler echocardiography and cold pressor test might be useful for detecting of patients with variant angina.

PURPOSE: The cold pressor test (CPT) has been used to detect variant angina, but its sensitivity in predicting vasospasm is low. The aim of this study was to determine whether estimates of the coronary flow velocity reserve (CFVR) in the distal left anterior descending coronary artery (dLAD) using transthoracic echocardiography (TTE) and CPT are useful tool to predict variant angina. METHODS: 65 patients (mean age = 52 +/- 10 years; male:female = 41:24) who had normal coronary artery on angiography and underwent acetylcholine provocation test were enrolled and divided into the spasm group (n = 31) and the no spasm group (n = 34). During CPT, the peak (PDV) and mean diastolic flow velocity (MDV) of the dLAD were estimated using TTE with a high-frequency transducer, and electrocardiography, blood pressures, heart rate, and symptoms were monitored every 30 seconds. CPT%PDV and CPT%MDV were defined as the percentage changes in PDV and MDV during CPT, respectively. RESULTS: CPT%PDV was 4.99 +/- 23.62% in the spasm group and 52.75 +/- 24.78% in the no spasm group (P < 0.001). CPT%MDV was 6.83 +/- 23.81% in the spasm group and 50.22 +/- 27.83% in the no spasm group (P < 0.001). CPT%PDV<31.1% had a sensitivity of 93.5% and a specificity of 82.4% in predicting variant angina (95% confidence interval [CI]: 0.939-0.979, P < 0.001). CPT%MDV<30.55% had a sensitivity of 90% and a specificity of 76.5% in predicting variant angina (95% CI: 0.884-0.950, P < 0.001). CONCLUSION: The measurement of changes in the coronary flow velocity of the dLAD using TTE and CPT might be useful for the estimation of endothelial dysfunction in patients with variant angina.

Clinical outcomes of discordant exercise electrocardiographic and echocardiographic findings compared with concordant findings in patients with chest pain and no history of coronary artery disease: An observational study.

The aim of this study was to evaluate comparative clinical outcomes of discordant electrocardiographic (ECG) and echocardiographic (Echo) findings compared with concordant findings during treadmill exercise echocardiography in patients with chest pain and no history of coronary artery disease (CAD).A total of 1725 consecutive patients who underwent treadmill echocardiography with chest pain and no history of CAD were screened. The patients were classified into 4 groups: ECG-/Echo- (negative ECG and Echo), ECG+/Echo- (positive ECG and negative Echo), ECG-/Echo+, and ECG+/Echo+. Concomitant CAD was determined using coronary angiography or coronary computed tomography. Major adverse cardiac events (MACEs) were defined as a composite of coronary revascularization, acute myocardial infarction, and death.MACEs were similar between ECG-/Echo- and ECG+/Echo- groups. Compared with ECG+/Echo- group, ECG-/Echo+ group had more MACEs (adjusted hazard ratio [HR] adjusted by clinical risk factors [95% confidence interval {CI}], 3.57 [1.75-7.29], P < .001). Compared with ECG+/Echo+ group, ECG-/Echo+ group had lower prevalence of concomitant CAD and fewer MACEs (HR, 0.49 [0.29-0.81], P = .006).Positive exercise Echo alone during treadmill exercise echocardiography had worse clinical outcomes than positive ECG alone, and the latter had similar outcomes to both negative ECG and Echo. Positive exercise Echo alone also had better clinical outcomes than both positive ECG and Echo. Therefore, exercise Echo findings might be superior for predicting clinical outcomes compared with exercise ECG findings. Additional consideration of ECG findings on positive exercise Echo will also facilitate better prediction of clinical outcomes.