Higher Risk Of Cardiac Events Research Articles

Prognostic Value of Coronary Flow Capacity by 82Rb PET in Patients With Suspected Coronary Artery Disease and Normal Myocardial Perfusion at Semiquantitative Imaging Analysis.

Coronary flow capacity (CFC) is a measure that integrates hyperemic myocardial blood flow and myocardial flow reserve to quantify the pathophysiological impact of coronary artery disease on vasodilator capacity. We assessed the prognostic value of CFC derived from 82Rb positron emission tomography/computed tomography in patients with suspected coronary artery disease and normal myocardial perfusion imaging. We studied 1967 patients with suspected coronary artery disease and normal myocardial perfusion at the semiquantitative analysis of stress/rest cardiac 82Rb positron emission tomography/computed tomography imaging. Coronary artery calcium scores were calculated and categorized into 3 groups: 0, 0.1 to 99.9, and ≥100. Patients were classified as having myocardial steal, severely reduced CFC, moderately reduced CFC, mildly reduced CFC, minimally reduced CFC, or normal flow using previously defined thresholds. The outcome end points were myocardial infarction and cardiac death, whichever occurred first. During a mean time of 41±27 months, 49 events occurred (2.5% cumulative event rate, with an annualized event rate of 0.5% person-years). At multivariable Cox analysis, coronary artery calcium score categories and impaired CFC resulted as independent predictors of events (both P<0.001). The annualized event rate was higher in patients with impaired CFC compared with those with normal CFC (P<0.05). Kaplan-Meier analysis showed that patients with impaired CFC were at the highest risk of events. In patients with suspected coronary artery disease and normal myocardial perfusion, impaired CFC is associated with a higher risk of cardiac events. Evaluating CFC can help identify patients' candidates for additional therapies to prevent future events.

Prognostic parameters predict cardiac events in Brugada syndrome: a meta-analysis

Abstract Background Brugada syndrome (BrS) is recognized as a cause of sudden cardiac death (SCD), ventricular tachycardia or ventricular fibrillation (VT/VF). However, the prognosis varies among the patients with Brugada electrocardiograph (ECG) pattern. Furthermore, there is no prognostic tool to predict the worsening cardiac outcomes in BrS. Objectives Primary outcome was to assess the association between risks including patient history, ECG pattern, electrophysiology study (EPS) findings and cardiac events which is identified as VT/VF or SCD. Method We performed a meta-analysis of prospective and retrospective cohort studies which assessed the risks and cardiac events in patients with BrS. Pooled hazard ratios (HRs) was analyzed by using Random-effect model. Result A total of 27 studies involving 15,990 BrS patients. Of these, 17 were retrospective studies and 10 were prospective studies. In univariate analysis, the risks including male, aborted SCD, QRS duration≥120 msec, fragmented QRS (multiple spikes within the QRS complex in lead V1-V3), late potential (positive terminal filtered QRS complex of signal-averaged ECG), sinus node dysfunction or inducibility of ventricular tachyarrhythmias during EPS associated with a higher risk of cardiac events in BrS. In multivariate analysis, higher risks of cardiac events were associated in BrS patients with history of syncope (HR 2.65, 95% confidence interval (CI): 1.68-4.19, I2 = 54 %, p-value &amp;lt;0.001), family history of SCD (HR 2.64, 95%CI:1.39-5.01, I2 = 0%, p-value = 0.003), prior VF (HR 14.52, 95%CI: 3.36-62.84, I2 = 62%, p-value &amp;lt;0.001), type 1 Brugada ECG pattern (HR 2.07, 95%CI: 1.13-3.79, I2 = 0%, p-value = 0.018), spontaneous type 1 ECG pattern (HR 1.91, 95%CI: 1.01-3.61, I2 = 58%, p-value = 0.046), early repolarization pattern (HR 2.78, 95%CI: 1.9-4.07, I2 = 0%, p-value &amp;lt; 0.001) and history of atrial fibrillation before BrS diagnosis (HR 1.82, 95%CI: 1.03-3.23, I2 = 49%, p-value = 0.039) (Table 1). Conclusion Our findings suggest that patient history, ECG pattern, EPS findings can predict the cardiac events. Introducing a risk prediction model could aid in early management of BrS.

Cardiovascular disease in thymic cancer patients.

Cancer patients may have increased risk for adverse cardiac events, but our understanding of cardiovascular risk in thymic cancer patients is not clear. We sought to characterize baseline cardiometabolic risk factors before thymic cancer diagnosis and the potential association between cancer treatment and subsequent cardiac events. This was a retrospective cohort study evaluating patients with thymic cancer from 2003 to 2020 compared to age- and sex-matched controls without cancer. Baseline cardiovascular risk factors, cancer characteristics, and incidence of cardiac events were collected from the health information exchange. Multivariable regression was used to examine the impact of cardiovascular risk factors and cancer therapies. We compared 296 patients with pathology-confirmed thymic cancer to 2,960 noncancer controls. Prior to cancer diagnosis, thymic cancer patients (TCPs) had lower prevalence of hypertension, dyslipidemia, and diabetes mellitus and similar rates of obesity, tobacco use, and pre-existing cardiovascular disease (CVD) compared to controls. After diagnosis, high-risk TCPs (>2 cardiovascular risk factors or pre-existing CVD) had higher risk for cardiac events (HR 3.73, 95% CI 2.88-4.83, p < 0.001). In the first 3 years after diagnosis, TCPs had higher incidence of cardiac events (HR 1.38, 95% CI 1.01-1.87, p = 0.042). High-risk TCPs who received radiotherapy or chemotherapy had higher risk of cardiac events (HR 4.99, 95% CI 2.30-10.81, p < 0.001; HR 6.24, 95% CI 2.84-13.72, p < 0.001). Compared to noncancer controls, TCPs experienced more cardiac events when adjusted for risk factors. Patients with multiple cardiovascular risk factors receiving radiotherapy or chemotherapy had higher incidence of cardiac events.

Reduced Fetuin-A Levels Are Associated With Exercise Intolerance and Predict the Risk of Adverse Outcomes in Patients With Heart Failure: The Role of Cardiac-Hepatic-Peripheral Interaction.

Exercise intolerance in heart failure arises from multifactorial pathophysiological mechanisms. Hepatokines, liver-synthesized molecules, regulate systemic metabolisms in peripheral tissues. We previously identified the hepatokine fetuin-A as being linked to liver hypoperfusion in heart failure. Here, we investigated the role of fetuin-A in connecting cardiac-hepatic-peripheral interaction. We conducted a prospective study involving 202 consecutive hospitalized patients (mean age, 56.8 years; 76.2% men) with heart failure who underwent cardiopulmonary exercise testing. We measured the serum concentration of fetuin-A by ELISA. Correlation analysis revealed a negative association between fetuin-A levels and the ratio of minimum minute ventilation to carbon dioxide production, its slope, and a tendency toward a positive correlation with peak oxygen uptake. Patients with impaired exercise tolerance exhibited lower fetuin-A levels. During a median follow-up of 1045 days, 18.3% experienced cardiac events, including 4 cardiac deaths and 33 cases of worsening heart failure. Classification and regression tree analysis identified a high-risk subgroup with lower fetuin-A (<24.3 mg/L) and impaired exercise tolerance (peak oxygen uptake<14.2 mL/kg per min). Kaplan-Meier analysis revealed that this subgroup had the highest risk of cardiac events. In a multivariable Cox proportional hazard model, the combination of lower fetuin-A and exercise intolerance was independently associated with increased risks of cardiac events. Reduced circulating fetuin-A levels were associated with exercise intolerance in heart failure patients. Fetuin-A could emerge as a target implicated in exercise capacity connecting cardiac-hepatic-peripheral interaction and as a valuable biomarker for predicting prognosis when combined with peak oxygen uptake.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease

Background and aimsPatients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. Methods and resultsWe evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52–69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan–Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326–2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017–5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391–2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997–6.105; p < 0.001]). ConclusionsThe FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD. Clinical trialsThe study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124–12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html.

Non-dilated left ventricular cardiomyopathy vs. dilated cardiomyopathy: clinical background and outcomes.

Non-dilated left ventricular cardiomyopathy (NDLVC) was proposed as a new category of cardiomyopathy that included patients with non-left ventricular (LV) dilatation, LV wall motion abnormality, or LV scar. However, the clinical background and event rates of NDLVC were unclear. The aim of this study was to examine the characteristics and event rates of patients with NDLVC and reduced LV ejection fraction (NDLVC-REF) in comparison with those with dilated cardiomyopathy (DCM). We retrospectively included 363 patients with newly diagnosed non-ischaemic cardiomyopathy and reduced LV ejection fraction (<50%) between December 2004 and January 2018. Patients who did not have LV dilatation (LV dimension index of ≦31mm/m2 in men and ≦34mm/m2 in women) were categorized as NDLVC-REF (n=80, 22.2%), and the remaining patients were categorized as DCM. Cardiac events were defined as sudden cardiac death and rehospitalization for heart failure. Patients with NDLVC-REF had a higher prevalence of atrial fibrillation and a higher LV ejection fraction than those with DCM at baseline. LV ejection fraction was higher and LV end-diastolic diameter was smaller in patients with NDLVC-REF than in those with DCM at all time points after diagnosis. During the median follow-up period of 68.8months (interquartile range: 33.0-93.7months), 44 patients experienced cardiac events. The Kaplan-Meier curves showed no significant differences in the probability of cardiac events among NDLVC-REF and DCM patients (P=0.349). However, patients with NDLVC-REF and LV dilatation after diagnosis (14%) had a higher risk of cardiac events than those with NDLVC-REF without LV dilatation (P=0.049). There was no significant difference in the incidence of cardiac events between NDLVC-REF and DCM. Among NDLVC-REF patients, 18% of patients who showed LV dilatation after diagnosis had poor outcomes. Therefore, both NDLVC-REF and DCM patients may require equivalent attention to follow-up and regular assessment of LV function.

Liposomal-Associated Phospholipase A 2 Is More Effective in Predicting Cardiac Risk in Law Enforcement Than Framingham Risk Score and Coronary Artery Calcium Score Calculation.

To clarify the methods for identifying officers at high risk for cardiac events. This retrospective review included 3330 patient charts. Classic cardiovascular risk factors, coronary artery calcium (CAC) scores, and endothelial inflammatory biomarker levels were compared between civilians and law enforcement officers (LEOs). The Framingham Risk Score (FRS) was compared with risk assessment using inflammatory biomarkers. The FRS failed to identify more than 90% of LEOs at high risk of cardiovascular events. Similarly, the use of the CAC score was ineffective. Inflammatory biomarker analysis measuring the lipoprotein-associated phospholipase A 2 activity was the most reliable method for identifying LEOs at high risk of cardiovascular events. The use of the standard FRS and CAC scores is less effective than that of inflammatory biomarkers in identifying LEOs at high risk of cardiovascular events.

The Longitudinal Relationship between Frailty, Loneliness and Cardiovascular Disease: A Prospective Cohort Study

ObjectivesPrevious studies had reported that frailty and loneliness were associated with increased risk of cardiovascular disease (CVD). The aim of present study was to evaluate the combined effect of frailty and loneliness on the risk of CVD. MethodsA total of 9,674 participants from the China Health and Retirement Longitudinal Study were included. Multivariate Cox proportional hazards regression model was used to explore the associations between frailty, loneliness and new-onset CVD, stroke and cardiac events. ResultsDuring the 7-year follow-up, a total of 1,758 respondents experienced CVD (including 584 stroke and 1,324 cardiac events). Compared to those without loneliness or frailty, individuals with loneliness alone, or with frailty alone, or with both loneliness and frailty were significantly associated with increased risk of CVD, with corresponding HRs (95%CIs) were 1.21(1.07–1.37), 1.57(1.32–1.86) and 1.78(1.52–2.10), respectively. Similarly, participants with loneliness alone, or with frailty alone, or with both loneliness and frailty were associated with higher risk of cardiac events. The significant associations were consistent in age subgroups (participants aged less or more than 60 years). ConclusionOur study indicated that there was a combined effect of effect of frailty and loneliness on the risk of CVD, stroke and cardiac events. These findings highlighted the importance of identifying loneliness and frailty, and intervening much earlier both in older and younger population.

Epicardial and Pericoronary Adipose Tissue, Coronary Inflammation, and Acute Coronary Syndromes

Vascular inflammation is recognized as the primary trigger of acute coronary syndrome (ACS). However, current noninvasive methods are not capable of accurately detecting coronary inflammation. Epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT), in addition to their role as an energy reserve system, have been found to contribute to the development and progression of coronary artery calcification, inflammation, and plaque vulnerability. They also participate in the vascular response during ischemia, sympathetic stimuli, and arrhythmia. As a result, the evaluation of EAT and PCAT using imaging techniques such as computed tomography (CT), cardiac magnetic resonance (CMR), and nuclear imaging has gained significant attention. PCAT-CT attenuation, which measures the average CT attenuation in Hounsfield units (HU) of the adipose tissue, reflects adipocyte differentiation/size and leukocyte infiltration. It is emerging as a marker of tissue inflammation and has shown prognostic value in coronary artery disease (CAD), being associated with plaque development, vulnerability, and rupture. In patients with acute myocardial infarction (AMI), an inflammatory pericoronary microenvironment promoted by dysfunctional EAT/PCAT has been demonstrated, and more recently, it has been associated with plaque rupture in non-ST-segment elevation myocardial infarction (NSTEMI). Endothelial dysfunction, known for its detrimental effects on coronary vessels and its association with plaque progression, is bidirectionally linked to PCAT. PCAT modulates the secretory profile of endothelial cells in response to inflammation and also plays a crucial role in regulating vascular tone in the coronary district. Consequently, dysregulated PCAT has been hypothesized to contribute to type 2 myocardial infarction with non-obstructive coronary arteries (MINOCA) and coronary vasculitis. Recently, quantitative measures of EAT derived from coronary CT angiography (CCTA) have been included in artificial intelligence (AI) models for cardiovascular risk stratification. These models have shown incremental utility in predicting major adverse cardiovascular events (MACEs) compared to plaque characteristics alone. Therefore, the analysis of PCAT and EAT, particularly through PCAT-CT attenuation, appears to be a safe, valuable, and sufficiently specific noninvasive method for accurately identifying coronary inflammation and subsequent high-risk plaque. These findings are supported by biopsy and in vivo evidence. Although speculative, these pieces of evidence open the door for a fascinating new strategy in cardiovascular risk stratification. The incorporation of PCAT and EAT analysis, mainly through PCAT-CT attenuation, could potentially lead to improved risk stratification and guide early targeted primary prevention and intensive secondary prevention in patients at higher risk of cardiac events.

Pharmacogenomic evaluation of CYP2C19 alleles linking low clopidogrel response and the risk of acute coronary syndrome in Indians.

Clopidogrel is an antiplatelet drug widely prescribed to prevent atherothrombotic events in coronary artery disease patients. However, there is evidence to suggest that the effectiveness of clopidogrel varies owing to genetic diversity in CYP2C19. This heterogeneity in South Asians, who are also known to have high risk of cardiac events than other population groups, highlights the importance of investigating CYP2C19 variants to estimate the risk proportion in the groups. Given the high prevalence and genetic heterogeneity, the population-based case control was conducted in a cohort of 1191 subjects comprising 645 acute coronary syndrome (ACS) cases (unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction) and 546 healthy controls of South Asian Indian origin. The metabolization status of CYP2C19 was assessed using *2, *3 and *17 variants in the stated cohorts to determine the prevalence of metabolization and its association with phenotypes. The results suggest a possible genetic association between studied CYP2C19 polymorphisms and ACS, since there was a higher proportion of intermediate and poor metabolizers present in the studied cohorts. The association analyses revealed that the *2 allele of CYP2C19 confers a significant risk for ACS, while the *17 allele provides protection. These findings contribute to the understanding of CYP2C19 genetic variants and their impact on clopidogrel response in South Asian Indians. Additionally, they underline the significance of assessing CYP2C19 variations in patients receiving clopidogrel therapy in order to improve therapeutic outcomes.

Type 3 long QT syndrome: Is the effectiveness of treatment with beta-blockers population-specific?

BackgroundThe efficacy of beta-blocker treatment in type 3 long QT syndrome (LQT3) remains debated. ObjectivesThe purpose of this study was to test the hypothesis that beta-blocker use is associated with cardiac events (CEs) in a French cohort of LQT3 patients. MethodsAll patients with a likely pathogenic/pathogenic variant in the SCN5A gene (linked to LQT3) were included and followed-up. Documented ventricular tachycardia/ventricular fibrillation, torsades de pointes, aborted cardiac arrest, sudden death, and appropriate shocks were considered as severe cardiac events (SCEs). CEs also included syncope. ResultsWe included 147 patients from 54 families carrying 23 variants. Six of the patients developed symptoms before the age of 1 year and were analyzed separately. The 141 remaining patients (52.5% male; median age at diagnosis 24.0 years) were followed-up for a median of 11 years. The probabilities of a CE and an SCE from birth to the age of 40 were 20.5% and 9.9%, respectively. QTc prolongation (hazard ratio [HR] 1.12 [1.0–1.2]; P = .005]) and proband status (HR 4.07 [1.9–8.9]; P <.001) were independently associated with the occurrence of CEs. Proband status (HR 8.13 [1.7–38.8]; P = .009) was found to be independently associated with SCEs, whereas QTc prolongation (HR 1.11 [1.0–1.3]; P = .108) did not reach statistical significance. The cumulative probability of the age at first CE/SCE was not lower in patients treated with a beta-blocker. ConclusionIn agreement with the literature, proband status and lengthened QTc were associated with a higher risk of CEs. Our data do not show a protective effect of beta-blocker treatment.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease

Abstract Background Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. Although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. Purpose To investigate the relationship between noninvasive liver fibrosis score and the future risk of cardiac events. Methods Among 13,368 patients with NAFLD diagnosed using ultrasonography, 4,071 patients were evaluated. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index (cut-off value of 1.30 and 2.67) and NAFLD fibrosis score (NFS) (cut-off values of -1.455 and 0.676), respectively. The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. Results The median age of the evaluated patients was 61 [52–69] years, and 2,201 [54.1%] were male. After a median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan–Meier survival analysis demonstrated that MACE increased progressively with theFIB4 index (log-rank, p &amp;lt; 0.001) and NFS (log-rank, p &amp;lt; 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (compared to the group [reference] with low FIB4 index values, hazard ratio [HR] was 1.860 for the group with intermediate FIB4 index values [95% confidence interval (CI), 1.326–2.610; p&amp;lt;0.001] and 3.325 for the group with high FIB4 index values [95% CI, 2.017–5.479; p&amp;lt;0.001]), and the higher the NFS, the higher the risk for MACE (compared to the group [reference] with low NFSvalues, HR was 1.938 for the group with intermediate NFS values [95% CI, 1.391–2.699; p&amp;lt;0.001] and 3.492 for the group with high NFSvalues [95% CI, 1.997–6.105; p&amp;lt;0.001]). Conclusions The FIB4 index and NFS impacted the predictability of MACE in patients with NAFLD.Kaplan–Meier analysis for MACE

Peak VO2 and VE/VCO2 exhibit differential prognostic capacity for predicting cardiac events

Abstract Background Cardiopulmonary exercise testing (CPET) are commonly used to assess the functional capacity of patients with heart failure. While both peak oxygen uptake (VO2) and ventilatory efficiency (VE/CO2) are significant prognostic factors in heart failure, their values may not always be concordant. Methods This retrospective study included 688 patients who underwent both CPET and supine bicycle echocardiography (SBE) simultaneously. The primary endpoint of the study was defined as heart failure hospitalization or cardiac death. The patients were categorized into subgroups based on their VO2 and VE/VCO2 slope values. Results After median follow-up of 89 months, 111 (16.4%) patients developed cardiac events. The mean age and ejection fraction were 58 years and 59%. In multivariate analysis, both VO2 and VE/VCO2 remained powerful predictors of cardiac events after adjusting for age, ejection fraction, baseline or exercise E/e’, and peak TR velocity. Subgroup analysis revealed that Group III (VO2 &amp;gt;20 and VE/VCO2 &amp;gt;30) and IV (VO2 &amp;lt;20 and VE/VCO2 &amp;gt;30) had a significantly higher risk of cardiac events, with hazard ratios of 3.38 (CI 1.36-8.40) and 8.40 (CI 3.86-18.34), respectively, compared to Group I (VO2 &amp;gt;20 and VE/VCO2 &amp;lt;30). Group II (VO2 &amp;lt;20 and VE/VCO2 &amp;lt;30) had a non-significantly increased risk of cardiac events with a hazard ratio of 2.04 (CI 0.80-5.21) compared to Group I (Fig). Conclusion Both VO2 and VE/VCO2 slope were found to be excellent predictors of cardiac events in patients who underwent CPET and SBE. However, there is a slight difference between the two parameters, and poorer ventilatory inefficiency was found to be more associated with a worsened prognosis. The study suggests that the risk stratification using the VE/VCO2 slope and peak VO2 values can provide valuable information for clinicians in managing patients with heart failure.

Genetic factors predisposing to arrhythmic events and QTc prolongation during follow-up in long QT patients with unaffected QTc at initial presentation: Swedish experience

Abstract Background Patients carrying genetic variants associated with long QT syndrome (LQTS) who initially present with normal QTc (concealed LQTS) is a large and growing group of patients. Long-term progression of QTc interval and risk factors associated with arrhythmic events in this patient group remain poorly described. Purpose 1) To assess the prevalence of concealed LQTS among patients with genetically verified LQTS; 2) To explore genetic factors associated with QTc prolongation and arrhythmic events in patients with concealed LQTS. Methods Adult LQTS patients (LQT1-3) from three cardiogenetic clinics in Sweden were included in a prospective register. Digital ECGs recorded for any reason both in-hospital and in outpatient settings, were retrieved from ECG archives. Concealed LQTS was defined as QTcB &amp;lt; 460 ms in men or &amp;lt;470 ms in women at initial presentation. The proportion of patients exhibiting QTcB above 480, 490 and 500 ms thresholds at any time during follow-up (FU) was assessed. Ventricular arrhythmias (VA) were defined as torsades de pointes, appropriate ICD shock, aborted cardiac arrest or sudden cardiac death. Cardiac events (CE) were defined as VA or syncope. The risk of CE and VA by the age of 60 years associated with LQTS genotype, KCNH2 pore region mutations and KCNQ1 membrane-spanning mutations was assessed using Kaplan Meier survival curve analysis and Cox regression analysis adjusted for sex, proband status and beta blocker use. Results 1). Out of 211 LQTS patients, 89 (42%) had concealed LQTS (52 (58%) women, 22 (25%) probands, 16 (18%) had CE by the time of diagnosis). Median age at diagnosis was 39 [IQR 22-55] years, age at the end of FU 47 [31-62] years. Concealed LQTS prevalence did not differ between genotypes: LQT1 – 59/141 (42%), LQT2 – 25/57 (44%), LQT3 – 5/13 (39%). 2). LQT1 patients were least and LQT3 patients were most prone to develop QTc prolongation during FU (Table). 3). VA were reported in 3 (3.5%) patients and in all cases preceded by syncope. None of the LQT1 patients experienced VA during FU. Both VA events among LQT2 patients were reported in carriers of KCNH2 pore region mutations (log rank p=0.023). 4). Patients with LQT2 were at higher risk to develop CE than LQT1 patients (HRadj=3.04 95%CI 1.22-7.55). Among LQT1 patients, carriers of mutations affecting membrane-spanning KCNQ1 channel region tended to have higher risk of CE (log rank p=0.018, HRadj=3.99 95%CI 0.80-19.89). Conclusions Concealed LQTS patients represent a significant proportion of the LQTS population and are similarly distributed between the most common LQTS genotypes. These patients have low risk of VA, which is confined to LQT3 patients and LQT2 patients carrying KCNH2 pore region mutations. Concealed LQT1 patients are at the lowest risk of CE and VA and have the lowest risk of experiencing QTc prolongation during FU. Carriers of mutations affecting KCNQ1 membrane-spanning region represent the high-risk LQT1 group with regard to CE.Concealed LQTS patients characteristicsRisk of VA in concealed LQTS by genotype

The prognostic impact of follow-up cardiac Metaiodobenzylguanidine imaging: relation to differential trajectories in left ventricular ejection fraction after acute decompensation

Abstract Background Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure (HF). Recently, the trajectory of left ventricular ejection fraction (LVEF) has been focused in patients with reduced LVEF admitted for acute decompensated heart failure (ADHF). We sought to prospectively investigate the prognostic value of the follow-up cardiac MIBG imaging in ADHF patients with reduced LVEF, in relation to LVEF trajectory. Methods We prospectively studied 145 ADHF patients with reduced LVEF&amp;lt;40%. The cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the delayed image at the discharge and 6 months’ follow-up (6FUP). HF recovered LVEF (HFrecEF) was defined as those with a second measurement of LVEF at 6FUP of ≥ 40% with a 10-point increase from baseline LVEF, according to the previous report. Furthermore, in the present study, HFrecEF was classified into the two groups; patients with partial recovery of LVEF (≥40%, &amp;lt;50%) (HFparEF) and complete recovery of LVEF (≥50%) (HFcorEF). The endpoint was a cardiac event (CE) defined as a composite of cardiac death and unplanned hospitalization for worsening HF. Results At 6 months after the discharge, HFrecEF was observed in 97 (67%) of 145 study patients and the remaining 48 (33%) patients did not have HFrecEF (HFnorEF). In the subgroup of HFrecEF, 43 (30%) patients had HFparEF and 54 (37%) patients had HFcorEF. Late HMR at 6FUP in HFcorEF patients was significantly greater than those in HFparEF and HFnorEF patients, which was also observed at the discharge with non-significant difference. The change of late HMR significantly correlated with the improvement in LVEF (r=0.33, p&amp;lt;0.001). During a follow-up period of 4.3 ± 2.6 years, 28 patients in HFnorEF, 11 patients in HFparEF and 4 patients in HFcorEF had CEs, respectively. Kaplan-Meier analysis revealed that HFnorEF patients had a significantly higher risk of cardiac events than those with HFparEF and HFcorEF. (58.3% vs 25.6% vs 7.4% P &amp;lt; 0.0001). Patients with lower late HMR at 6FUP had a greater risk of CEs than those with higher late HR at 6FUP in HFrecEF, especially in HFparEF, which was not observed in HFnorEF subgroup. Conclusion The follow-up MIBG imaging after the discharge could provide the additional prognostic information in ADHF patients with recovered LV function.

Abstract 13795: Reduced Fetuin-A Levels Are Associated With Exercise Intolerance in Patients With Heart Failure and Predict the Risk of Adverse Outcomes

Background: Impaired exercise tolerance is a feature of heart failure (HF) and predicts adverse outcomes in patients with HF. Hepatokines are proteins synthesized and secreted by the liver, which regulate systemic metabolisms of peripheral tissues. However, the clinical impact of hepatokines on exercise capacity has not been well understood. Aims: Our objective was to investigate the relevance of a hepatokine, Fetuin-A, in relation to exercise capacity in HF. Methods and Results: We conducted a prospective study involving 120 consecutive hospitalized patients (mean 57.3 years old, 75.0% male) with HF who underwent cardiopulmonary exercise testing. The serum concentration of Fetuin-A was measured by an enzyme-linked immunosorbent assay. Patients with impaired exercise tolerance (peak oxygen uptake (VO 2 ) &lt; 14.0 mL/kg/m) exhibited lower Fetuin-A levels than those without ( Figure A ). Correlation analysis revealed that Fetuin-A was positively correlated with peak VO 2 and negatively correlated with minute ventilation to carbon dioxide production ratio and its slope. We then followed up patients and found 12 composites of cardiac events that included 5 cardiac death and 7 worsening HF. Based on classification and regression tree to determine the cut-off of Fetuin-A, Kaplan-Meier analysis revealed that patients with lower Fetuin-A levels (&lt; 22.2 ng/mL) and impaired exercise tolerance had the highest risk of cardiac events ( Figure B ). In a multivariable Cox proportional hazard model, the presence of both lower Fetuin-A and exercise intolerance was independently associated with an increased risk of cardiac events (hazard ratio, 18.8; P = 0.009). Conclusions: Reduced Fetuin-A levels were associated with exercise intolerance in patients with HF, and those with decreased levels of both Fetuin-A and peak VO 2 were at the highest risk of adverse outcomes.

Myocardial strain is associated with adverse cardiac events in patients treated with chimeric antigen receptor (CAR) T-cell therapy.

Cardiovascular events, including heart failure and arrhythmias, following chimeric antigen receptor (CAR) T-cell therapy are increasingly recognized. Although global longitudinal strain (GLS) has demonstrated prognostic utility for other cancer therapy-related cardiac dysfunction, less is known regarding the association of GLS with adverse cardiac events following CAR T-cell therapy. To determine the association of baseline GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy. Patients who had an echocardiogram within 6 months prior to receiving CAR T-cell therapy were retrospectively identified. Clinical data and cardiac events were collected via chart review. Echocardiograms were analyzed offline for GLS, left ventricular ejection fraction, and Doppler parameters. Multivariable logistic regression was used to determine the association between adverse cardiovascular events and echocardiographic parameters. Among 75 CAR T-cell therapy patients (mean age 63.9, 34.7% female), nine patients (12%) experienced cardiac events (CEs) including cardiovascular death, new/worsening heart failure, and new/worsening arrhythmia within 1 year of treatment. In univariable models, higher baseline GLS (OR 0.78 [0.63, 0.96], p = .021) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.40 [1.08, 1.81], p = .012) was associated with a higher risk of CE. After adjusting for age and LDH, higher baseline GLS (OR 0.65 [0.48-0.88], p = <.01) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.56 [1.06, 2.29], p = .024) was associated with a higher risk of CE. Lower GLS and higher mitral E/e' on a baseline echocardiogram were associated with higher risk for CEs in patients receiving CAR T-cell therapy.

Protocol: Can coronary artery calcium score identified on thoracic planning CT scans be used and actioned to identify cancer survivors at high risk of cardiac events: A feasibility study in cancer survivors undergoing radiotherapy in Australia

IntroductionA coronary artery calcium (CAC) CT scan can identify calcified plaque and predict risk of future cardiac events. Cancer survivors undergoing thoracic radiotherapy routinely undergo a planning CT scan, which...

Added value of coronary artery calcium score to myocardial perfusion 15O-water PET scans to identify patients at high risk of cardiac events

Abstract Funding Acknowledgements Type of funding sources: None. Background Coronary artery calcium (CAC) is a marker of atherosclerosis and a well-known cardiovascular risk predictor for both asymptomatic and symptomatic patients. In patients at intermediate risk of coronary artery disease, myocardial perfusion imaging (MPI) is performed. Within MPI methods, 15O-water PET is considered a gold standard. However, MPI provides information only about perfusion lacking information about the atherosclerotic process within coronary arteries. Nevertheless, calcium scoring CT (CSCT) scans are not routinely performed in combination with MPI scans. Purpose The aim of this study was to assess the added value of CSCT to myocardial perfusion 15O-water PET scan in prediction of long-term major adverse cardiac events (MACE). Methods We included 572 patients who underwent subsequent myocardial perfusion 15O-water – PET scan and a dedicated CSCT scan between 2008 and 2014. The endpoint was a MACE defines as a composite of all-cause death, myocardial infarction, late and urgent revascularisation (PCI or CABG), and unstable angina. The follow-up data were tracked from the date of PET scan until 1st February 2019. A hyperaemic MBF ≤ 2.3 ml/min/g in 2 adjacent segments was considered indicative of myocardial ischemia. This cut-off value was predefined in a comparable population and published previously. Manual scoring of CSCT scans was performed according to the Agatston method. We employed a previously described 6-point scale reflecting patient risk groups (0; 1–10; 11–100; 101–400; 401–1000; &amp;gt;1000 Agatston score (AS)). Results During the median follow up of 6.6 (interquartile range 4.5–7.8) years, 16.6% of patients experienced an end-point event. Event-free survival curves stratified by CAC risk groups are presented in Figure 1. Patients with CAC 0 were at lowest risk compared with all other groups (for all risk groups log-rank P &amp;lt; 0.001, and for CAC 1-100 log rank P = 0.004). Patients with CAC&amp;gt;1000 were at the highest risk of MACE compared with all groups except from patients with CAC 401–1000 (log-rank P=0.394). Based on multivariable Cox regression analysis of associations with MACE between CAC and myocardial perfusion defects, increasing CAC was associated with an increased risk of MACE, which was significant for patients with CAC 1-10 (adjusted hazard ratio (HR) 3.75, 95% CI 1.35–10.4, P = 0.11), CAC 11–100 (adjusted HR 4.12, 95% CI 1.71–9.93 P = 0.002), CAC 101–400 (adjusted HR 4.74, 95% CI 1.98– 11.3, P &amp;lt; 0.001), CAC 401–1000 (adjusted HR 8.43, 95% CI 3.38–20.98, P &amp;lt; 0.001), CAC &amp;gt;1000 (adjusted HR 11.17, 95% CI 4.55–27.43, P &amp;lt; 0.001) compared with patients with CAC 0 (Figure 2). Conclusions CAC scoring improved identification of patients at higher risk of long-term MACE, independently from ischemic information acquired with a 15O-water PET scan. Therefore, we suggest routinely performing CSCT scans in addition to results of MPI scan to determine patients of higher cardiovascular risk.

Prediction of outcome by 82Rb PET/CT in patients with ischemia and nonobstructive coronary arteries

BackgroundThe purpose of this study was to assess the prognostic value of cardiac 82Rb positron emission tomography (PET)/computed tomography (CT) imaging in patients with myocardial ischemia of nonobstructive coronary arteries (INOCA). MethodsWe retrospectively evaluated 311 INOCA patients who underwent rest stress 82Rb PET/CT. Cardiac end points were cardiac death, myocardial infarction, or late coronary revascularization. A parametric survival model was also used to identify how the variables influenced time to event. ResultsDuring a median follow-up of 37 months (range 6–108), 23 (7%) cardiac events occurred. In patients with events total perfusion defect (TPD) was higher and myocardial flow reserve (MFR) lower compared to those without events (both P < .001). At multivariable Cox analysis, increased TPD (i.e., ≥ 5%) and reduced MFR (i.e., < 2) were predictors of events (both P < .001). At Weibull survival analysis, the highest probability of cardiac events and risk acceleration were observed in patients with both increased TPD and reduced MFR. Annualized event rate was higher in patients with reduced MFR compared to those with preserved MFR (P < .001). ConclusionIn patients with INOCA, the combined evaluation of myocardial perfusion and coronary vascular function by 82Rb PET/CT is able to identify those at higher risk of cardiac events.