Experienced Cardiac Events Research Articles

PET/CT-derived coronary calcium score may predict cardiac complications in anthracycline-treated patients with lymphoma

AbstractAnthracycline-mediated cardiotoxicity is a common concern after lymphoma therapy, particularly in patients with high cardiovascular risk (CVR). In noncancer populations, coronary artery calcium scoring (CACS) effectively identifies individuals who may benefit from aggressive CVR modification to lower the risk of cardiovascular events. Emerging evidence suggests that CACS can also predict cancer therapy-related cardiotoxicity, potentially identifying candidates for cardioprotective strategies. Our study aimed to evaluate whether CACS obtained from pretreatment positron emission tomography (PET)/computed tomography (CT) scans could stratify cardiac event risk in patients with lymphoma receiving anthracycline-based chemotherapy. We enrolled 358 consecutive patients with lymphoma treated between 2012 and 2022, calculating the CACS from their pretreatment PET/CT. We reviewed medical records to identify pre-existing cardiac conditions, CVR, and posttreatment cardiac events, including coronary events, heart failure (HF), and arrhythmias. Logistic and Cox regression models were used to assess associations between CVR, CACS categories (CACS = 0, CACS 1-400, CACS >400), and new cardiac events. At a median follow-up of 27 months (95% confidence interval [CI], 22.3-31.7) in patients without cardiac history, 10% experienced posttreatment cardiac events (HF, 14; arrhythmias, 9; coronary event, 1; combination, 8). Patients with a CACS >0 had more events (21 total, 20% vs 11 total, 5.4% for CACS = 0; P < .001). Elevated CACS was independently associated with HF (CACS 1-400: odds ratio [OR], 3.73; 95% CI, 1.21-11.43; P = .022; CACS >400: OR, 5.43; 95% CI, 1.47-20.03; P = .011) and any cardiac event (CACS 1-400: OR, 2.48; 95% CI, 1.02-6.04; P = .045; CACS >400: OR, 3.28; 95% CI, 0.91-10.68; P = .029). CACS may effectively stratify patients with lymphoma at risk of cardiac complications, thereby identifying a group poised to benefit from targeted preventive strategies.

Visual coronary artery calcium assessment on routine chest CT can readily and cheaply identify liver transplant recipients with a low cardiac risk

Abstract Background Peri- and postoperative cardiac complications play an important role in survival of patients after liver transplantation (LT). However, the optimal approach for cardiac risk prediction in these patients has been debated on. LT recipients routinely receive non-gated computed tomography (CT) of the abdomen and chest to follow-up on their liver diseases. This study analyzed whether performance of coronary artery calcium (CAC) assessment on freely available scans can enhance cardiac risk stratification of LT recipients. Methods Consecutive LT recipients from 2008-2023 were included and analyzed retrospectively. CAC was scored visually on non-gated CT on a semi-quantitative ordinal scale and stratified in two groups according to CAC severity. Peri-operative (≤90 days) and post-operative all-cause mortality and cardiac events were analyzed. Furthermore, all-cause mortality and cardiac events were analyzed and compared between the groups with a Kaplan Meier curve and Cox proportional hazard regression. Results A total of 149 patients were included with a median age of 58 years. The median follow-up time was 5 years. The majority (74%) of patients had no or mild CAC. None of these patients died perioperatively due to cardiac causes, or experienced peri-operative cardiac events. The post-operative 10-year survival of LT recipients with no or mild calcifications was significantly better (p&amp;lt;0.01) than patients with severe CAC. The 10-year cardiac event-free survival was significantly better in patients with no or mild CAC (p&amp;lt;0.01) and the incidence increased &amp;gt;4-fold from only 4% in patients with no-mild CAC to 18% in patients with severe CAC. Of interest, severe CAC was a significant predictor of cardiac events (HR 4.6, p=0.02), while classical cardiovascular risk factors e.g. diabetes were not. Conclusion CAC assessment on routinely available non-gated CT can readily enhance peri- and postoperative cardiac risk stratification of LT recipients, as it identifies a selection of low-risk individuals for having peri- and post-operative cardiac events and all-cause mortality. Thereby, reducing test burden for the patients and saving healthcare expenses.

CTG repeat length underlying cardiac events and sudden death in myotonic dystrophy type 1.

Myotonic dystrophy Type 1 (DM1) is caused by the expansion of CTG repeats (CTGn) in the DM1 protein kinase (DMPK) gene, while it remains unclear whether CTGn may be associated with the incidence of cardiac events or sudden death in Japan as well as Europe. The aim of this study was to investigate the association between CTGn and cardiac involvements. This cohort study included patients with DM1 who were retrospectively recruited from nine Japanese hospitals specializing in neuromuscular diseases. A total of 496 patients with DM1 who underwent a genetic test in the DMPK gene were analysed. Patients with congenital form or under 15 years old were excluded and patients were assigned into the quartiles. When we compared the incidence of cardiac events including advanced/complete atrioventricular block, pacemaker implantation, and ventricular tachycardias or mortality among four groups, patients with 1300 or longer CTGn experienced composite cardiac events [hazard ratio (HR): 3.19, 95% confidence interval (CI): 1.02-9.99, P = 0.014] more frequently and had significantly higher mortality rate (HR: 6.79, 95% CI: 2.05-22.49, P < 0.001) than those under 400 CTGn while the rate of sudden death was not significantly different. Regarding the cardiac events and mortality in patients with DM1, patients with 1300 or longer CTGn are at especially high risk.

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.

Association between remnant cholesterol and the risk of cardiovascular disease in Chinese population

ObjectivesPrevious genetic, observational, and clinical intervention studies reported that circulating levels of remnant cholesterol was associated with cardiovascular disease (CVD). However, whether remnant cholesterol can predict CVD events in Chinese population was not well characterized. Study designThis was a prospective cohort study. MethodsWe used the data of 9456 Chinese adults aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS). Estimated remnant cholesterol was calculated as total cholesterol minus high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. Cox proportional hazard models and restricted cubic spline models were used to assess the relationships between remnant cholesterol levels and CVD, stroke and cardiac events. ResultsDuring 7 years of follow-up, a total of 886 (9.37 %) respondents experienced CVD, 392 (4.15 %) experienced stroke and 544 (5.75 %) experienced cardiac events. In multivariable-adjusted analyses, the adjusted hazard ratios (95 % confidence interval) for the highest versus lowest quartile of remnant cholesterol were 1.14 (1.02-1.32) for CVD and 1.43 (1.12-1.82) for stroke, and each 1-SD increase of log-transformed remnant cholesterol (2.93 mg/dl) was associated with 5 % and 11 % increased risk of the CVD and stroke, respectively. Remnant cholesterol was not associated with increased risk of cardiac events. ConclusionElevated remnant cholesterol levels were positively associated with CVD and stroke in Chinese adult population, suggesting that remnant cholesterol could be considered as a preferential predictor and treatment target of CVD in Chinese population.

Diverse Phenotypic Manifestations in a Family with a Novel RYR2 E4107A Variant.

Cardiac ryanodine receptor (RyR2) gain-of-function mutations cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Conversely, RyR2 loss-of-function mutations cause a new disease entity, termed calcium release deficiency syndrome (CRDS), which may include RYR2-related long QT syndrome (LQTS). Importantly, unlike CPVT, patients with CRDS do not always exhibit exercise- or epinephrine-induced ventricular arrhythmias, which precludes a diagnosis of CRDS. Here we report a boy and his father, who both experienced exercise-induced cardiac events and harbor the same RYR2 E4107A variant. In the boy, an exercise stress test (EST) and epinephrine provocation test (EPT) did not induce any ventricular arrhythmias. QTc was slightly prolonged (QTc: 474 ms), and an EPT induced QTc prolongation (QTc-baseline: 466 ms, peak: 532 ms, steady-state: 527 ms). In contrast, in his father, QTc was not prolonged (QTc: 417 ms), and neither an EST nor EPT induced QTc prolongation. However, an EST induced multifocal premature ventricular contraction (PVC) bigeminy and bidirectional PVC couplets. Thus, they exhibited distinct clinical phenotypes: the boy exhibited LQTS (or CRDS) phenotype, whereas his father exhibited CPVT phenotype. These findings suggest that, in addition to the altered RyR2 function, other unidentified factors, such as other genetic, epigenetic, and environmental factors, and aging, may be involved in the diverse phenotypic manifestations. Considering that a single RYR2 variant can cause both CPVT and LQTS (or CRDS) phenotypes, in cascade screening of patients with CPVT and CRDS, an EST and EPT are not sufficient and genetic analysis is required to identify individuals who are at increased risk for life-threatening arrhythmias.

Predicting Adverse Cardiac Events After Radiotherapy for Locally Advanced Non–Small Cell Lung Cancer

BackgroundRadiotherapy may cause grade ≥3 cardiac events, necessitating a better understanding of risk factors. The potential predictive role of imaging biomarkers with radiotherapy doses for cardiac event occurrence has not been studied. ObjectivesThe aim of this study was to establish the associations between cardiac substructure dose and coronary artery calcium (CAC) scores and cardiac event occurrence. MethodsA retrospective cohort analysis included patients with locally advanced non–small cell lung cancer treated with radiotherapy (2006-2018). Cardiac substructures, including the left anterior descending coronary artery, left main coronary artery, left circumflex coronary artery, right coronary artery, and TotalLeft (left anterior descending, left main, and left circumflex coronary arteries), were contoured. Doses were measured in 2-Gy equivalent units, and visual CAC scoring was compared with automated scoring. Grade ≥3 adverse cardiac events were recorded. Time-dependent receiver-operating characteristic modeling, the log-rank statistic, and competing-risk models were used to measure prediction performance, threshold modeling, and the cumulative incidence of cardiac events, respectively. ResultsOf the 233 eligible patients, 61.4% were men, with a median age of 68.1 years (range: 34.9-90.7 years). The median follow-up period was 73.7 months (range: 1.6-153.9 months). Following radiotherapy, 22.3% experienced cardiac events, within a median time of 21.5 months (range: 1.7-118.9 months). Visual CAC scoring showed significant correlation with automated scoring (r = 0.72; P < 0.001). In a competing-risk multivariable model, TotalLeft volume receiving 15 Gy (per 1 cc; HR: 1.38; 95% CI: 1.11-1.72; P = 0.004) and CAC score >5 (HR: 2.51; 95% CI: 1.08-5.86; P = 0.033) were independently associated with cardiac events. A model incorporating age, TotalLeft CAC (score >5), and volume receiving 15 Gy demonstrated a higher incidence of cardiac events for a high-risk group (28.9%) compared with a low-risk group (6.9%) (P < 0.001). ConclusionsAdverse cardiac events associated with radiation occur in more than 20% of patients undergoing thoracic radiotherapy within a median time of <2 years. The present findings provide further evidence to support significant associations between TotalLeft radiotherapy dose and cardiac events and define CAC as a predictive risk factor.

Decreased vector magnitudes may help identify events in patients with Long QT syndrome.

All Long QT syndrome (LQTS) patients are at elevated risk for channelopathy-induced delayed myocardial repolarization and consequently potentially life-threatening cardiac events with 90% of initial cardiac events occurring between preteen and 40years old. Utilizing ECG and derived vectorcardiographic parameters, including T wave Vector Magnitude (TwVM) measurement data, this study attempts to determine whether TwVM from baseline ECGs is effectively predictive of future cardiac events for genotype-positive LQTS patients. Verified carriers of established LQTS disease-causing genotypes were selected from University of Minnesota patient encounters between 2010 and 2020 for inclusion in this retrospective study. Baseline and predictive ECG and derived vectorcardiographic parameter evaluation, clinical data, and statistical analysis were compared between patients with and patients without cardiac events. First recorded ECG was at presentation to our hospital and final ECG is defined as ECG just prior to cardiac event (event defined below in Methods) or the most final documented ECG before cut-off year of 2020 for the event-free group. Of 41 participants, 15 experienced cardiac events and 26 did not. While many baseline electrocardiographic parameter measurements did not show significant differences between patient groups, vectorcardiographic parameters at baseline, specifically the QRS vector magnitude (QRSVM) and azimuth of the spatial ventricular gradient, showed significance. Additionally, final vectorcardiographic parameters, particularly the QRSVM, TwVM, and azimuth of the spatial ventricular gradient showed significant differences between patient groups. Final T-wave frontal axis was significantly larger in those without cardiac events. Significant Kaplan-Meier curve separation between patient groups was noted based on a QRSVM of 1.43mV or lower, with additional consideration to patient age, genotype, and beta blocker use. This study shows evidence of ECG and derived vectorcardiographic parameters, including TwVM, being effective in early prediction of cardiac events in genotype-positive LQTS patients.

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.

Novel methods for enhancing ECG visualization research

All Long QT syndrome (LQTS) patients are at elevated risk for channelopathy-induced delayed myocardial repolarization and consequently potentially life-threatening cardiac events with 90% of initial cardiac events occurring between preteen and 40 years old. Utilizing ECG and derived vectorcardiographic parameters, including T wave Vector Magnitude (TwVM) measurement data, this study attempts to determine whether TwVM from baseline ECGs is effectively predictive of future cardiac events for genotype-positive LQTS patients.Verified carriers of established LQTS disease-causing genotypes were selected from University of Minnesota patient encounters between 2010 and 2020 for inclusion in this retrospective study. Baseline and predictive ECG and derived vectorcardiographic parameter evaluation, clinical data, and statistical analysis were compared between patients with and patients without cardiac events. First recorded ECG was at presentation to our hospital and final ECG is defined as ECG just prior to cardiac event (event defined below in Methods) or the most final documented ECG before cut-off year of 2020 for the event-free group.Of 41 participants, 15 experienced cardiac events and 26 did not. While many baseline electrocardiographic parameter measurements did not show significant differences between patient groups, vectorcardiographic parameters at baseline, specifically the QRS vector magnitude (QRSVM) and azimuth of the spatial ventricular gradient, showed significance. Additionally, final vectorcardiographic parameters, particularly the QRSVM, TwVM, and azimuth of the spatial ventricular gradient showed significant differences between patient groups. Final T-wave frontal axis was significantly larger in those without cardiac events. Significant Kaplan-Meier curve separation between patient groups was noted based on a QRSVM of 1.43 mV or lower, with additional consideration to patient age, genotype, and beta blocker use.This study shows evidence of ECG and derived vectorcardiographic parameters, including TwVM, being effective in early prediction of cardiac events in genotype-positive LQTS patients.

Cardiac impacts of postoperative radiotherapy for breast cancer in Japanese patients.

Radiotherapy for breast cancer has attracted attention in Western countries because radiation to the heart can cause cardiac events. The purposes of this study were to evaluate the relationship between radiotherapy after breast-conserving surgery and the frequency of cardiac events in Japanese patients and to investigate the risk factors of cardiac events after postoperative radiotherapy in those patients. Female patients who received postoperative radiotherapy following breast-conserving surgery between 2007 and 2012 at our hospital were evaluated. In this study, we estimated the cumulative incidence of cardiac events including angina pectoris, myocardial infarction, ischemic heart disease, heart failure and cardiomyopathy after radiotherapy. Of 311 eligible patients, 7.1% of the patients had a smoking history, 20.3% of the patients were obese and 22.2% of the patients had hypertension. The median follow-up period was 118months (interquartile range, 102-132months). Twelve patients (3.9%) experienced cardiac events after treatment. The mean time to cardiac events was 126months. The 10-year cumulative incidences of cardiac events after treatment were 4.2% and 4.3% for patients with left-sided and right-sided breast cancer, respectively, without a significant difference. Multivariate analysis showed that only hypertension was a risk factor for cardiac events (hazard ratio = 16.67, P = 0.0003). In conclusion, postoperative radiotherapy for breast cancer did not increase the incidence of cardiac events. Since at least 2007, postoperative radiotherapy for breast cancer has been safely performed without effects on the heart.

Long-Term Treatment with Pacritinib on a Compassionate Use Basis in Patients with Advanced Myelofibrosis

Long-Term Treatment with Pacritinib on a Compassionate Use Basis in Patients with Advanced Myelofibrosis

Clinical Significance of the Head-Up Tilt Test in Improving Prognosis in Patients with Possible Neurally Mediated Syncope.

Simple SummarySeveral diseases can cause syncope, which is commonly known as fainting; however, syncope triggered by a reflex mechanism, also termed neurally mediated syncope (NMS), is one of the most common forms. While NMS is considered a benign disease, it can cause critical clinical events, such as severe trauma due to syncope. The head-up tilt test (HUTT) is one of the modalities for the diagnosis of NMS. The clinical significance of HUTT in the prognosis of NMS, such as recurrence rate of syncope and mortality, are still to be elucidated. This research aimed to clarify the value of HUTT for the diagnosis of NMS, and to investigate the prognosis of patients with NMS by analyzing the data of 101 patients with syncope and their close long-term (four years at the longest) follow-up. Furthermore, as insertable cardiac monitors (ICMs) are considered effective in patients with syncope, this study also aimed to evaluate the usefulness of ICM in patients with negative HUTT results. Finally, our research contributes to the improvement of the clinical management for patients with syncope.Syncope is commonly encountered in daily clinical practice. Depending on its etiology (benign or life-threatening conditions or environmental triggers), syncope can be neurally mediated (reflex), cardiac, or orthostatic. Furthermore, neurologic disease can cause symptoms that mimic syncope. However, there is limited research on neurally mediated syncope (NMS), which is considered a benign disorder, and close follow-ups are rarely performed. NMS can cause serious clinical events, including severe trauma and car accidents. The head-up tilt test (HUTT) is the gold standard for diagnosing NMS; however, its clinical significance remains unknown, and its relevance to NMS prognosis requires further research. This retrospective study aimed to assess the clinical significance of the HUTT for NMS. We reviewed the charts of 101 patients who underwent HUTT at Tokai University Hospital in Japan between January 2016 and March 2019. During the HUTT, 72 patients (69.2%) experienced syncope. Patients were followed up for 886.1 ± 457.7 days (interquartile range: 518–1293 days). The syncope recurrence rate was 16.9%; however, no significant difference was observed between the two groups (HUTT positive vs. negative) (13.8% vs. 18.1%, p = 0.772). Four of 29 (13.9%) and two of 72 (2.8%) patients in the negative and positive HUTT groups, respectively, experienced cardiac events (p = 0.019). Negative HUTT results may assist in anticipating unexpected clinical events within a few years. A negative HUTT result may allow us to reconsider the NMS diagnosis based on clinical information. Close outpatient follow-up of patients with negative HUTT results is warranted.

Impact of red blood cell distribution width and mean platelet volume in patients with ST-segment elevation myocardial infarction.

The complete blood cell count is one of the most frequently ordered laboratory tests, and many parameters, including red blood cell distribution width (RDW) and mean platelet volume (MPV), are available. The purpose of this study was to investigate the usefulness of the combination of RDW and MPV in patients with ST-segment elevation myocardial infarction (STEMI). Patients with STEMI who underwent primary percutaneous coronary intervention were retrospectively enrolled (n = 229). The association between RDW as well as MPV and cardiovascular events was investigated. The median age was 67years, and males made up 85% of the sample. Median RDW was 13.6%, and median MPV was 8.2 fL. During a median follow-up period of 528days (IQR 331.5-920.5), 41 patients died or experienced major adverse cardiac and cerebrovascular events (MACCEs). Patients with RDW ≧ 13.7% had more deaths or MACCEs with marginal significance (p = 0.0799). Patients with MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0283). Patients with RDW ≧ 13.7% and MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0185). MPV was significantly associated with death or adverse events in patients with STEMI who were treated with primary PCI. RDW had only a weak association with death or adverse events. The results of the combination of MPV and RDW were similar to those of MPV.

The Plasma Level of B-Type Natriuretic Peptide is a Useful Predictor of Cardiac Events for Out-Clinic Patients with Asymptomatic Heart Failure

Purpose: The circulating level of B-type Natriuretic Peptide (BNP) is recognized as a biomarker of ventricular dysfunction. In the field of primary prevention, BNP is a useful predictor of cardiac death, heart failure, cerebral infarction, and atrial fibrillation. On the other hand, the predictive value of BNP has not been fully elucidated in patients with coronary artery disease and/or those who are prone to atherosclerosis. Methods: We analyzed 679 patients (average age, 65.3 years; 29.2% women) with asymptomatic heart failure (ACC/AHA stage A to B) undergoing total risk management for cardiovascular disease prevention in the Kitasato Registry for Cardiovascular Disease Prevention. The mean follow-up period was 8.4 years (range, 73–3686 days) for all study patients. Results: Among all patients, 54.0% had coronary artery disease, 54.2% had hypertension, 55.7% had dyslipidemia, 31.2% had diabetes mellitus, and 15.5% had atrial fibrillation. The baseline level of plasma BNP was 47.5 (63.8) [mean (SD)] pg/mL. The plasma BNP level correlated with age and the serum creatinine level. The presence of coronary artery disease or atrial fibrillation significantly affected the plasma level of BNP (P &lt;0.05, P &lt;0.01; respectively). Plasma BNP levels were significantly higher in the event group than in the event-free group [80.4 (123.3) vs. 43.4 (50.8) pg/mL, P &lt;0.0001]. Of all patients, 59 experienced cardiac events and 10 died during the study period. In the multivariate analysis, plasma BNP level, age, and diabetes mellitus were identified as predictive factors. The Cox proportional hazards model showed that the plasma BNP level was an independent predictor of cardiac death. The event-free rate was significantly higher in patients with BNP of 40 pg/mL or less than in those with BNP of 40pg/mL or more. Conclusions: In the present long-term follow-up study, we found that the plasma level of BNP of patients who are in a stable condition was a useful prognostic marker. Circulating levels of plasma BNP could be an independent predictor of cardiac events in patients with asymptomatic heart failure.

Radiation and cardiotoxicity: A retrospective analysis of a midwest population.

e12616 Background: The most common female malignancy diagnosed in the US is breast cancer. Early breast cancer therapy is often treated with radiation therapy; one of the unfortunate side effects of radiotherapy in the past has been cardiotoxicity, especially coronary artery disease. Recent usage of dose reduction techniques have helped reduce these effects. Here, we present our analysis of breast cancer patients that received radiation therapy and the likelihood of cardiotoxicity. Methods: An IRB-approved retrospective study was performed utilizing ICD codes to analyze patients diagnosed with biopsy-confirmed breast cancer between January 1, 2014 and December 31, 2017. 478 of 1618 de-identified patients qualified for this study. Statistical analysis was performed with SAS v9.4. Descriptive statistics were computed for all study variables. Continuous variables were described with measures of central tendency (mean, median) and dispersion (range, standard deviation). Categorical variables were summarized as frequencies and percentages. Comparisons between categorical variables were compared with the Chi-Square test (or Fisher’s Exact) where appropriate. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival were assessed with Cox proportional hazards regression analyses. All significance is assumed at the p &lt; 0.05 level. Results: Of the 478 eligible patients, heart failure (HF), HF hospitalizations, acute coronary syndrome and overall cardiac events were compared among breast cancer patients. Patients who received radiation experienced HF 6.02% compared to 4.61% without radiation (p = 0.574). HF hospitalization was recorded as 2.27% in radiotherapy compared to 1.23% in non-radiotherapy patients (p = 0.686). Patients who radiation experienced ACS 2.27% of the time as compared to 1.21% in patients who were not treated with radiation. Of note, 9.25% receiving radiation experienced cardiac events compared to 4.24% in patients without radiation (p = 0.068). While results were not statistically significant, the trend of elevated cardiac events in breast cancer patients receiving radiation is noteworthy. Conclusions: Per our study, although statistically insignificant, radiation therapy may result in higher incidence of cardiac events in breast cancer patients. Further large-scale, prospective studies should be performed to confirm the aforementioned trends with respect to survival outcomes in urban and rural populations.

P5029Inducibility of ventricular tachyarrhythmias by up to two extrastimuli does not predict future cardiac events in asymptomatic Brugada patients: results from long-term follow-up

Abstract Background Most recent consensus conference report recommends Implantable Cardioverter Defibrillator (ICD) implantation for asymptomatic Brugada patients with spontaneous or fever-induced type-1 ECG (A-BrS) and inducible ventricular tachyarrhythmias (VTs) by up to two extrastimuli as class IIb indication. However, the validity of the inducible VTs by up to two extrastimuli in A-BrS is still unknown. Purpose To evaluate the validity of the inducibility by up to two extrastimuli in A-BrS in a large Japanese cohort of BrS (The Japan Idiopathic Ventricular Fibrillation Study [J-IVFS]). Methods A total of 193 consecutive A-BrS patients performed programmed electrical stimulation (PES) with non-aggressive uniform protocol (mean age 50±13 years, 180 males) were enrolled. PES protocol was using 2 basic pacing cycles and the order of introduction of up to 2 ventricular extra-stimuli from right ventricular apex [RVA] first, then right ventricular outflow tract [RVOT], 3 ventricular extra-stimuli from RVA then RVOT down to the minimum of 200ms. Clinical outcomes during the follow-up period were compared between A-BrS patients with and without inducible VTs by up to two extrastimuli. Results Thirty-five A-BrS (18%) had inducible VTs by up to two extrastimuli. During a mean follow-up period of 101±48 months, 7 A-BrS experienced cardiac events (sudden cardiac death [SCD] or VTs, 0.4%/yr). None of the 7 A-BrS had inducible VTs by up to two extrastimuli. The incidences of cardiac events tended to be higher in A-BrS without inducible VTs by up to two extrastimuli than in those with inducible VTs (p=0.10), as determined by the Kaplan-Meier method. In the A-BrS, the annual incidences of cardiac events in A-BrS with family history of SCD, inferolateral J wave, wide QRS duration &gt;90msec in lead V2, or inducible VT/VF by 3 extrastimuli were 0.7, 0.7, 0.6, and 0.3%/yr, respectively. Conclusions Our large-scaled multicentre study with long-term follow-up revealed the inducibility of ventricular tachyarrhythmias by up to two extrastimuli does not predict future cardiac events in A-BrS, even using non-aggressive uniform protocol. Rather, other parameters such as family history of SCD or inferolateral J wave might be helpful for risk assessment in A-BrS.

Prognostic impact of mitral L-wave in patients with hypertrophic cardiomyopathy without risk factors for sudden cardiac death.

Hypertrophic cardiomyopathy (HCM) with severe diastolic dysfunction is a major cause of heart failure and sudden cardiac death (SCD) associated with lethal arrhythmia. Although various risk factors for cardiac events have been reported in HCM patients, previous studies have reported that some HCM patients exhibit either no risk or a low risk of SCD experienced cardiac events. The mid-diastolic transmitral flow velocity curve (mitral L-wave) is an echocardiographic index of left ventricular compliance, and it has been reported as one of the parameters of advanced diastolic dysfunction assessed noninvasively. However, little is known about the association between the mitral L-wave and long-term clinical outcomes in HCM patients without SCD risk factors. Between July 2005 and February 2016, 112 patients were diagnosed with HCM and 96 patients without risk factors were enrolled. After excluding 3 patients whom we could not detect L-wave more than once, 93 patients (mean age 57.7 ± 13.1years, 33 females) were divided into the following two groups, according to the presence or absence of the mitral L-wave: Group L (+) (with the mitral L-wave) and Group L (-) (without the mitral L-wave). The correlations between the mitral L-wave and rates of cardiac events were investigated. The mitral L-wave was present in 14 (15.1%) patients [Group L]. During the follow-up period [4.7 (2.9-7.5) years], patients experienced 7 cardiac events. Kaplan-Meier survival analysis showed that the event-free rate was significantly lower in Group L (+) than in Group L (-) (log-rank P = 0.002). Additionally, in multivariate analysis, L-wave positivity was identified as independent predictors of cardiac events. Existence of the mitral L-wave can predict cardiac events, even in HCM patients without SCD risk factors.

Independent Prognostic Value of Pulmonary Diffusing Capacity in Nonsmoking Patients with Chronic Heart Failure.

The diffusing capacity of the lung for carbon monoxide (DLCO) is indicative of the alveolar-capillary membrane function. A reduced DLCO is associated with poor prognosis in chronic heart failure (HF). However, the significance of DLCO as an independent prognostic predictor has not been established. Here, we aimed to determine the prognostic value of DLCO in patients with chronic HF.We enrolled 214 patients (139 females, mean age: 63 ± 16 years, left ventricular ejection fraction [LVEF]: 45 ± 21%) with stable chronic HF who underwent pulmonary function tests. Only never smokers were included in the analysis because smoking can decrease DLCO.During a median follow-up period of 2.1 years, 52 patients (24.3%) experienced cardiac events, including unplanned HF admissions, left ventricular assist device (LVAD) implantations, all-cause deaths, and cardiopulmonary arrests (CPAs). The median percent predicted DLCO (%DLCO) was 87.3%. In a Cox regression analysis, a %DLCO of ≤87.3% was independently associated with the cardiac events, even after adjusting for age, sex, systolic blood pressure (SBP), LVEF, anemia, brain natriuretic peptide, estimated glomerular filtration rate (eGFR), and prior HF admission (hazard ratio [HR]: 1.87, 95% confidence interval: 1.03-3.53, P = 0.030).A reduced DLCO is an independent predictor of poor prognosis in nonsmoking patients with chronic HF.

Treatment of advanced colorectal cancer in a patient with cardiotoxic reactions to 5-fluorouracil and capecitabine using suboptimal doses

A 32-year-old female with stage IV colorectal cancer and metastasis to the liver experienced cardiotoxic reactions after treatment with 5-fluorouracil and its oral prodrug capecitabine even at two-thirds the recommended...