Prediction of longitudinal clinical outcomes after acute myocardial infarction using a dynamic machine learning algorithm.

Several regression-based models for predicting outcomes after acute myocardial infarction (AMI) have been developed. However, prediction models that encompass diverse patient-related factors over time are limited. This study aimed to develop a machine learning-based model to predict longitudinal outcomes after AMI. This study was based on a nationwide prospective registry of AMI in Korea (n = 13,104). Seventy-seven predictor candidates from prehospitalization to 1 year of follow-up were included, and six machine learning approaches were analyzed. Primary outcome was defined as 1-year all-cause death. Secondary outcomes included all-cause deaths, cardiovascular deaths, and major adverse cardiovascular event (MACE) at the 1-year and 3-year follow-ups. Random forest resulted best performance in predicting the primary outcome, exhibiting a 99.6% accuracy along with an area under the receiver-operating characteristic curve of 0.874. Top 10 predictors for the primary outcome included peak troponin-I (variable importance value = 0.048), in-hospital duration (0.047), total cholesterol (0.047), maintenance of antiplatelet at 1 year (0.045), coronary lesion classification (0.043), N-terminal pro-brain natriuretic peptide levels (0.039), body mass index (BMI) (0.037), door-to-balloon time (0.035), vascular approach (0.033), and use of glycoprotein IIb/IIIa inhibitor (0.032). Notably, BMI was identified as one of the most important predictors of major outcomes after AMI. BMI revealed distinct effects on each outcome, highlighting a U-shaped influence on 1-year and 3-year MACE and 3-year all-cause death. Diverse time-dependent variables from prehospitalization to the postdischarge period influenced the major outcomes after AMI. Understanding the complexity and dynamic associations of risk factors may facilitate clinical interventions in patients with AMI.

Early menopause is associated with abnormal diastolic function and poor clinical outcomes in women with suspected angina.

Early identification of women at high risk for cardiovascular diseases (CVD), with subsequent monitoring, will allow for improved clinical outcomes and generally better quality of life. This study aimed to identify the associations between early menopause, abnormal diastolic function, and clinical outcomes. This retrospective study included 795 menopausal women from is a nationwide, multicenter, registry of patients with suspected angina visiting outpatient clinic. The patients into two groups: early and normal menopause (menopausal age ≤ 45 and > 45 years, respectively). If participants met > 50% of the diastolic function criteria, they were classified as having normal diastolic function. Multivariable-adjusted Cox models were used to test associations between menopausal age and clinical outcomes including the incidence of major adverse cardiovascular events (MACE), over a median follow-up period of 771 days. Early menopause was associated with increased waist circumference (p = 0.001), diabetes prevalence (p = 0.003), obstructive coronary artery disease (p = 0.005), abnormal diastolic function (p = 0.003) and greater incidences of MACE, acute coronary syndrome, and hospitalization for heart failure. In patients with abnormal diastolic function, early menopause increased MACE risk significantly, with no significant difference in normal diastolic function. These findings highlight early menopause and abnormal diastolic function as being potential risk markers in women for midlife CVD events.

Sex differences of sequential changes in coronary blood flow and microvascular function in patients with suspected angina.

AIMS: This study evaluated the sex differences of sequential changes in coronary blood flows and microvascular function in patients with suspected angina but with no obstructed coronary arteries. METHODS: A total of 202 consecutive patients who experienced chest pain but had no significant coronary artery stenosis and who underwent adenosine stress echocardiography were included in the study. Coronary blood flow (CBF) velocities were measured at 1, 2, and 3 min after adenosine infusion. RESULTS: The mean age was 61 years, and 138 (68%) were women. Approximately 40% of patients had coronary microvascular dysfunction (CMD, coronary flow velocity reserve < 2.3), with women exhibiting higher CMD prevalence. The left ventricular (LV) mass index was similar between men and women, while women exhibited higher baseline rate pressure products (RPP). At baseline, coronary blood flow velocities were similar between the sexes. However, CBF velocities in women gradually increased during the examination; and in men, the increase was abrupt and steep during the early stages of examination (p = 0.015 for interaction between time and sex), even with similar RPP in stress. Coronary flow velocity reserve was steadily lower in women compared to men (1 min, 2.09 ± 0.86 vs 2.44 ± 0.87; 2 min, 2.39 ± 0.72 vs 2.63 ± 0.85; 3 min, 2.45 ± 0.70 vs 2.68 ± 0.73). CONCLUSIONS: In patients with suspected angina but with no obstructed coronary arteries, CMD was especially prevalent among women. Women exhibited higher oxygen consumption, while exhibiting slower and gradual increases in CBF velocities. Conversely, men exhibited faster and steeper increases in CBF velocities even with similar RPP in stress.

Role of cardiac imaging in management of heart failure.

The significant advancement in cardiac imaging in recent years led to improved diagnostic accuracy in identifying the specific causes of heart failure and also provided physicians with guidelines for appropriately managing patients with heart failure. Diseases that were once considered rare are now more easily detected with the aid of cardiac imaging. Various cardiac imaging techniques are used to evaluate patients with heart failure, and each technique plays a distinct yet complementary role. This review aimed to discuss the comprehensive role of different types of cardiac imaging in the management of heart failure.

Gender disparities in prevalence by diagnostic criteria, treatment and mortality of newly diagnosed acute myocardial infarction in Korean adults.

Acute myocardial infarction (AMI) is highly prevalent and remains the leading cause of mortality. Particularly in women, under-recognition and management of AMI have been raised. The aim of this study was to investigate the long-term trends of prevalence, treatment methodologies, and mortality of AMI by gender. The subjects of this study were patients hospitalized for AMI according to the Korean National Health Insurance Claims Database from 2002 to 2018. Total 633,097 AMI patients were hospitalized, 40% women. The incidence of AMI has been increasing since 2011, with a lower incidence in women. Overall, 53.1% of patients underwent CAG, with a lower tendency in women than in men (39.8% vs. 62.3%). Furthermore, fewer women underwent PCI than men (77.5% vs. 85.8% in 2018, p < 0.0001). Of the 336,463 AMI patients undergoing CAG, women were undertreated with a lower prescription rate of beta-blockers or statins at discharge. When adjusted for age, women showed higher 7-day mortality but lower 1-year mortality relative to men. According to the Korean National Health Insurance Claims Database, women with AMI have been under-recognized, underdiagnosed, and undertreated in terms of revascularization or medical therapy for years suggesting that efforts to close the gender gap are necessary.

Serial changes of layer-specific myocardial function according to chemotherapy regimen in patients with breast cancer.

Aims: Chemotherapy-induced cardiotoxicity (CIC) is a significant complication, meanwhile myocardial damage might differ depending on chemotherapy agents and their timing. The aim of this study was to evaluate serial changes of layer-specific myocardial function in patients with breast cancer and their differences by the development time of CIC and chemotherapy agent. Methods and results: A total of 105 consecutive patients with breast cancer (age: 52.3 ± 9.3 years) were enrolled. Chemotherapy-induced cardiotoxicity occurred in 20 (19%) patients during 6 months. Endocardial and midmyocardial functions decreased in patients with or without CIC, with patients with CIC showing greater decreases during follow-up. Global longitudinal strain (GLS) change at 3 months was the most sensitive parameter to detect CIC. When new development of CIC was analysed at 6 months, GLS was reduced earlier than the decrease of left ventricular ejection fraction. In patients with CIC who were treated with anthracycline-based regimen for 3 months, endocardial GLS markedly decreased at 3 months and continued to decrease until 6 months. Patients with CIC who received trastuzumab therapy after anthracycline therapy showed further reduction in endocardial GLS at the 6-month follow-up, which was not shown in patients with CIC who received taxane therapy subsequently. Conclusion: Myocardial function assessed by strain decreased in all patients with breast cancer receiving chemotherapy. The endocardial layer was the most vulnerable to chemotherapy-induced myocardial damage. Functional impairment was more profound in patients with CIC who received sequential anthracycline-trastuzumab chemotherapy. Thus, early evaluation of left ventricular function might be necessary for all patients with breast cancer to detect CIC.

Impact of cardiovascular disease and risk factors on fatal outcomes in patients with COVID-19 according to age: a systematic review and meta-analysis.

OBJECTIVE: Previous studies that evaluated cardiovascular risk factors considered age as a potential confounder. We aimed to investigate the impact of cardiovascular disease (CVD) and its risk factors on fatal outcomes according to age in patients with COVID-19. METHODS: A systematic literature review and meta-analysis was performed on data collected from PubMed and Embase databases up to 11 June 2020. All observational studies (case series or cohort studies) that assessed in-hospital patients were included, except those involving the paediatric population. Prevalence rates of comorbid diseases and clinical outcomes were stratified by mean patient age in each study (ranges: <50 years, 50-60 years and ≥60 years). The primary outcome measure was a composite fatal outcome of severe COVID-19 or death. RESULTS: We included 51 studies with a total of 48 317 patients with confirmed COVID-19 infection. Overall, the relative risk of developing severe COVID-19 or death was significantly higher in patients with risk factors for CVD (hypertension: OR 2.50, 95% CI 2.15 to 2.90; diabetes: 2.25, 95% CI 1.89 to 2.69) and CVD (3.11, 95% 2.55 to 3.79). Younger patients had a lower prevalence of hypertension, diabetes and CVD compared with older patients; however, the relative risk of fatal outcomes was higher among the former. CONCLUSIONS: The results of the meta-analysis suggest that CVD and its risk factors (hypertension and diabetes) were closely related to fatal outcomes in COVID-19 for patients across all ages. Although young patients had lower prevalence rates of cardiovascular comorbidities than elderly patients, relative risk of fatal outcome in young patients with hypertension, diabetes and CVD was higher than in elderly patients. PROSPERO REGISTRATION NUMBER: CRD42020198152.

Rationale and Study Design of Differences in Cardiopulmonary Exercise Capacity According to Coronary Microvascular Dysfunction and Body Composition in Patients with Suspected Heart Failure with Preserved Ejection Fraction.

Coronary microvascular dysfunction (CMD) is one of the mechanisms of myocardial ischemia and left ventricular (LV) diastolic dysfunction, which is closely related to heart failure with preserved ejection fraction (HFpEF). Frailty, associated with sarcopenia, is often accompanied by HFpEF. In the present study, we aim to evaluate the relationship between CMD, body composition, and cardiopulmonary exercise capacity in patients with suspected HFpEF. We will enroll patients experiencing chest symptoms (chest pain or dyspnea) with an indication of non-obstructive coronary artery disease (<50% stenosis) on coronary angiography and preserved LV ejection fraction (≥50%) on echocardiography. All patients will undergo body composition analysis and adenosine stress echocardiography with the evaluation of coronary artery blood flow and maximal oxygen consumption by cardiopulmonary exercise test. LV end-diastolic pressure will be assessed using coronary angiography. Coronary flow reserve (CFR) is defined as the ratio of the peak to the baseline mean diastolic velocity of coronary blood flow. A CFR <2.3 is defined as coronary microvascular dysfunction. The correlation of CFR and body composition with LV diastolic function and cardiopulmonary exercise capacity will be assessed. This trial will suggest the specific phenotypes of HFpEF according to body composition and CMD and the specific management of the different phenotypes of HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04822649.

Effect of Anti-Inflammatory Drugs on Clinical Outcomes in Patients With Malignant Pericardial Effusion.

BACKGROUND: Pericardiocentesis (PCC) with extended catheter drainage has become a relatively safe procedure to control pericardial effusion (PE), but little is known about long-term outcomes after PCC in malignant PE. OBJECTIVES: This study evaluated the effects of anti-inflammatory agents on long-term outcomes after effective drainage of PE in active cancer patients. METHODS: From May 2007 to December 2018, 445 patients with malignant PE who underwent echocardiography-guided PCC were enrolled. Clinical, laboratory, echocardiographic and procedural findings, and clinical outcome data were collected. Use of anti-inflammatory agents including colchicine, nonsteroidal anti-inflammatory drugs, or steroids after PCC was also analyzed. Colchicine was administered in a dose of 0.6 mg orally, twice a day for 2 months. The primary outcome was defined as a composite of all-cause death and re-PCC or pericardial window operation due to recurred PE. RESULTS: The procedure was successful in 97.0% of the cases, with 1 procedure-related death. During the follow-up of 2 years, 26.1% of patients developed recurrent PE, and 46.0% developed constrictive pericarditis. The colchicine treatment group showed a significantly lower risk of composite events (adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [CI]: 0.49 to 0.87; p = 0.003) as well as all-cause death (aHR: 0.60; 95% CI: 0.45 to 0.81; p = 0.001) than did the noncolchicine group. On propensity score matching, colchicine after PCC was consistently associated with a lower composite events (aHR: 0.55; 95% CI: 0.37 to 0.82; p = 0.003). CONCLUSIONS: In cancer patients with malignant PE, PCC with extended drainage can be an appropriate therapeutic option and shows low complication rate. Patients receiving colchicine after successful PCC showed significant improvement in clinical outcome.

Clinical characteristics and long-term outcomes of peripartum takotsubo cardiomyopathy and peripartum cardiomyopathy.

AIMS: Although some peripartum-associated cardiomyopathy patients present with features that are clinically and echocardiographically similar to those of takotsubo cardiomyopathy (TCM), little is known about the diagnosis and clinical course of peripartum TCM. METHODS AND RESULTS: In a tertiary hospital in Seoul, Korea, we searched the hospital database to find cardiomyopathy cases that were associated with pregnancy from January 1995 to May 2019. Applying the published diagnostic criteria, we sought peripartum cardiomyopathy (PPCM) and peripartum TCM patients for comparison. Of 31 pregnancy-associated cardiomyopathy patients, 10 cases of peripartum TCM and 21 cases of PPCM were found. Maternal near-miss death was significantly more common in the peripartum TCM group than in the PPCM group (100.0% vs. 57.1%, P = 0.030). Complete recovery was observed with all peripartum TCM cases, while 23.8% of the PPCM cases had residual left ventricular dysfunction. One death and one heart transplantation occurred in the PPCM group, while neither occurred in the peripartum TCM group. There was no difference between the two groups in terms of the rate of major adverse clinical events at 3 years of follow-up [PPCM group: 26.3% (5/19) vs. TCM group: 33.3% (3/9), P = 0.750]. CONCLUSIONS: One-third of pregnancy-associated cardiomyopathy patients had peripartum TCM. With contemporary supportive care, both PPCM and peripartum TCM patients had a low mortality rate and excellent long-term outcomes.

Effect of sarpogrelate and high-dose statin on the reduction of coronary spasm in vasospastic angina: A two by two factorial, pilot randomized study.

BACKGROUND: Vasospastic angina (VSA) is characterized by coronary spasm, which can be aggravated by vasoactive substances such as serotonin. Hypothesis Sarpogrelate, a selective serotonin receptor antagonist, and high-dose statin have some effects on the reduction of coronary spasm in patients with VSA. METHODS: We recruited 100 patients with angiographically confirmed VSA, and randomly assigned them into four groups: sarpogrelate with high-dose statin (Group A, n = 25), sarpogrelate with low-dose or no statin (Group B, n = 25), placebo with high-dose statin (Group C, n = 25), and placebo with low-dose or no statin (Group D, n = 25). The primary endpoint was the remission of coronary spasm on 1-year follow-up provocation test. RESULTS: The most common site of coronary spasm was left anterior descending artery (42%). Most patients (96%) took calcium channel blockers, and 46% were treated with vasodilators. Overall, 40% of patients reported no chest pain at 1 year, and 23% showed complete remission of coronary spasm on 1-year follow-up provocation test. No difference was observed in symptomatic and angiographically complete remission rate between the sarpogrelate and the placebo group. Although the apolipoprotein B level at the 1-year follow-up was significantly lower in the high-dose statin group, symptomatic and angiographic outcomes were not different according to statin intensity. Distal thrombolysis in myocardial infarction (TIMI) flow on initial provocation test was independently associated with angiographically complete remission. CONCLUSIONS: Sarpogrelate or high-dose statin did not significantly improve the angiographic remission rate in patients with VSA. Distal TIMI flow on initial provocation test could predict the complete remission of coronary spasm at follow-up.

Natural history of spontaneous isolated celiac artery dissection after conservative treatment.

OBJECTIVE: Optimal treatment of spontaneous isolated celiac artery dissection (SICAD) is not well established because the natural history of this rare disease is poorly understood. We analyzed the natural history of patients who underwent conservative treatment. METHODS: The study included 28 patients with SICAD from December 2008 to January 2017. Our institutional policy of first-line treatment for SICAD patients was conservative, and invasive procedures were reserved for unstable complications such as severe persistent pain, significant organ malperfusion, rapid aneurysmal change, and rupture or concealed rupture. Demographics, clinical features, morphologic characteristics on computed tomography, treatment modalities, and follow-up results of these patients were retrospectively reviewed. RESULTS: Mean age was 52 years, and 89% of patients were male; 86% presented with pain, mostly abdominal, and 14% of cases were detected incidentally on abdominal imaging. None of these patients had unstable complications on admission, and all underwent initial conservative treatment. During the follow-up period (22 ± 20 months), aneurysmal change and propagation of thrombosis were noted in one patient and two patients, respectively, all of whom were managed conservatively without adverse clinical events. No difference in clinical and morphologic outcomes was noted between patients who were treated with antihypertensive therapy and those who were not. Patients with intramural hematoma on initial images showed dynamic vascular remodeling (partial to complete resorption) during the follow-up period compared with patients who had dominant intimal flap on initial images. CONCLUSIONS: The clinical course of patients with SICAD was benign. Even progressive vascular changes during follow-up did not require invasive treatment. Antihypertensive therapy might not modify the clinical course. The short-term results of conservative management are encouraging, but further evaluation with long-term follow-up in a large population is needed.

Nonsyndromic Peripheral Pulmonary Artery Stenosis Is Associated With Homozygosity of RNF213 p.Arg4810Lys Regardless of Co-occurrence of Moyamoya Disease.

BACKGROUND: Peripheral pulmonary arterial stenosis (PPAS) in childhood is frequently associated with other syndromes; however, PPAS in adolescents and adults is rare and its etiology is not well understood. We report the clinical characteristics of adult-onset nonsyndromic PPAS associated with the p.Arg4810Lys variant of the RNF213 gene. METHODS: We recently encountered an index case of severe pulmonary hypertension with multiple PPAS and intra- and extracranial arteriopathy. Because of a family history of Moyamoya disease (MMD), genetic analysis was performed, and revealed that this patient was homozygous for RNF213 p.Arg4810Lys. We searched for PPAS by reviewing the pulmonary hypertension registry and the MMD registry, and found four more cases of PPAS. Clinical features of the five patients and their families were analyzed. RESULTS: Mean age at diagnosis of pulmonary hypertension was 26 years, and the male to female ratio was 4:1. Genetic analysis of four patients revealed that all these patients were homozygous for the RNF213 p.Arg4810Lys variant. Pulmonary angiograms showed a string of beads pattern and/or diffuse stenosis of peripheral pulmonary arteries. Notably, three patients had MMD, whereas two patients did not. The three MMD patients had multiple stenoses of extracranial arteries other than the pulmonary artery. CONCLUSIONS: PPAS in segmental or subsegmental arteries in adulthood with multiple extracranial vasculopathies was found to be associated with homozygosity for RNF213 p.Arg4810Lys. RNF213 variant-associated vasculopathy should be categorized as a discrete disease entity of adulthood-onset PPAS regardless of the presence of MMD.