Significant Cardiac Events Research Articles

A Case of Coronary Artery Aneurysm Occurring After Drug-Coated Balloon Intervention for De Novo Chronic Total Occlusion

AbstractDrug-coated balloons (DCBs) have been proposed as a viable alternative to drug-eluting stents (DES) for managing chronic total occlusion (CTO), reducing adverse reactions associated with DES. However, adverse events after DCB treatment are rarely reported. We present a case of coronary artery aneurysm (CAA) formation after DCB treatment. A 55-year-old active smoker presented with exertional chest pain and positive ischemic response on the exercise stress test. Diagnostic coronary angiography revealed CTO in the mid-left anterior descending (mid-LAD) coronary artery with collateral circulation arising from the contralateral side. The patient underwent DCB treatment using a paclitaxel-coated balloon after predilatation with a noncutting balloon and a semi-compliant balloon. The final angiogram showed minimal recoil, type B coronary dissection nonflow limiting, and thrombolysis in myocardial infarction (TIMI) grade 3 flow. A follow-up coronary angiogram at 6 months revealed a fusiform aneurysm at the treated lesion with DCB. Despite the asymptomatic nature of the patient, good distal flow in the LAD, and the patient achieving a TIMI grade 3 flow, a decision was made to observe and closely monitor the patient. Despite potential risks, DCB remains a viable alternative to DES in CTO cases. Our case suggests that, although CAA occurred, it did not lead to significant adverse cardiac events. Further research is needed to understand the predictors and long-term outcomes of CAA.

A retrospective review of intramuscular olanzapine and parenteral benzodiazepine coadministration in the emergency department.

Acute agitation is a common presenting symptom in medical and mental health emergencies that may require pharmacologic intervention. There is a manufacturer recommendation against intramuscular coadministration of olanzapine with parenteral (intramuscular or intravenous) benzodiazepines despite a deficiency of high-quality evidence. The purpose of this study was to contribute to available literature regarding intramuscular olanzapine and parenteral benzodiazepine use in acutely agitated patients in the emergency department (ED). This was a single-center retrospective chart review of adult ED patients who received intramuscular olanzapine and a parenteral benzodiazepine within 2 hours. The composite primary endpoint evaluated the occurrence of cardiac or respiratory compromise within 2 hours of medication administration. Secondary endpoints mirrored the primary endpoint within 30 minutes and evaluated the occurrence of cardiac arrest or desaturation in the ED outside the 2-hour window. One hundred eleven patients were included in the analysis, 64 (57.7%) of whom had documented vitals or oxygen status within 2 hours of medication administration. The composite primary endpoint occurred in 8 patients (12.5%), with only 1 patient requiring intervention with intravenous fluids. The secondary composite endpoint occurred in 2 (9.5%) of 21 patients with documented vitals or oxygen status within 30 minutes of treatment, neither of which required intervention. There were no identified events of intubation or significant cardiac events. Until better evidence is available, this combination therapy should, at minimum, include appropriate patient monitoring. Future studies should investigate risk factors for serious adverse effects.

Prognostic Significance of Hemodynamics in Patients With Transposition of the Great Arteries and Systemic Right Ventricle.

Patients with transposition of the great arteries (TGA) and systemic right ventricle often confront significant adverse cardiac events. The prognostic significance of invasive hemodynamic parameters in this context remains uncertain. Our hypothesis is that the aortic pulsatility index and hemodynamic profiling utilizing invasive measures provide prognostic insights for patients with TGA and a systemic right ventricle. This retrospective multicenter cohort study encompasses adults with TGA and a systemic right ventricle who underwent cardiac catheterization. Data collection, spanning from 1994 to 2020, encompasses clinical and hemodynamic parameters, including measured and calculated values such as pulmonary capillary wedge pressure, aortic pulsatility index, and cardiac index. Pulmonary capillary wedge pressure and cardiac index values were used to establish 4 distinct hemodynamic profiles. A pulmonary capillary wedge pressure of ≥15 mm Hg indicated congestion, termed wet, while a cardiac index <2.2 L/min per m2 signified inadequate perfusion, labeled cold. The primary outcome comprised a composite of all-cause death, heart transplantation, or the requirement for mechanical circulatory support. Of 1721 patients with TGA, 242 individuals with available invasive hemodynamic data were included. The median follow-up duration after cardiac catheterization was 11.4 (interquartile range, 7.5-15.9) years, with a mean age of 38.5±10.8 years at the time of cardiac catheterization. Among hemodynamic parameters, an aortic pulsatility index <1.5 emerged as a robust predictor of the primary outcome, with adjusted hazard ratios of 5.90 (95% CI, 3.01-11.62; P<0.001). Among the identified 4 hemodynamic profiles, the cold/wet profile was associated with the highest risk for the primary outcome, with an adjusted hazard ratio of 3.83 (95% CI, 1.63-9.02; P<0.001). A low aortic pulsatility index (<1.5) and the cold/wet hemodynamic profile are linked with an elevated risk of adverse long-term cardiac outcomes in patients with TGA and systemic right ventricle.

Randomized Trial of Patiromer on Efficacy to Reduce Episodic Hyperkalemia in Patients with ESKD Treated With Hemodialysis

Individuals with end-stage kidney disease (ESKD) maintained on hemodialysis (HD) carry a high risk of cardiac arrhythmias. This risk is heightened by episodic hyperkalemia. The purpose of the study was to investigate whether patiromer administered daily reduced episodes of hyperkalemia in those with ESKD who receive HD, and to explore whether prescription of patiromer reduced the number of significant arrhythmia events. This was a prospective, randomized, open-label trial. Eligible patients with ESKD on HD were identified. Participants were randomized 1:1 to patiromer versus usual care. Those randomized to patiromer were administered the medication daily, and the dose was titrated based on serum potassium concentrations at the start of weeks 1, 2, and 3. All participants received 7-day continuous cardiac monitors at baseline and at week4. Of the 33 participants who were randomized, 1 withdrew due to adverse symptoms, and 1 withdrew due to pregnancy, leaving 31 in our analytic cohort. The mean age of randomized participants was 56 years, 55% were male, 81% were Black, and 10% were Hispanic/Latino. In week 4, the number of episodes of serum potassium≥ 5.5 mEq/l was 13 in the patiromer group and 41 in the control group; with median number of episodes of hyperkalemia in the patiromer group significantly lower than that of control group (0 vs. 3, P= 0.024). In week 4 continuous cardiac monitors, 6 participants had > 1000/24 h premature ventricular contractions, 5 had no sustained ventricular tachycardia (VT), 3 had atrial fibrillation, and 1 had bradycardia, with no significant differences between the groups. Patiromer administered daily reduced the frequency of hyperkalemia in study participants with ESKD who receive thrice-weekly HD. Larger studies are needed to determine whether patiromer reduces significant cardiac events.

A roadmap for modelling radiation-induced cardiac disease.

Cardiac risk mitigation is a major priority in improving outcomes for cancer survivors as advances in cancer screening and treatments continue to decrease cancer mortality. More than half of adult cancer patients will be treated with radiotherapy (RT); therefore it is crucial to develop a framework for how to assess and predict radiation-induced cardiac disease (RICD). Historically, RICD was modelled solely using whole heart metrics such as mean heart dose. However, data over the past decade has identified cardiac substructures which outperform whole heart metrics in predicting for significant cardiac events. Additionally, non-RT factors such as pre-existing cardiovascular risk factors and toxicity from other therapies contribute to risk of future cardiac events. In this review, we aim to discuss the current evidence and knowledge gaps in predicting RICD and provide a roadmap for the development of comprehensive models based on three interrelated components, (1) baseline CV risk assessment, (2) cardiac substructure radiation dosimetry linked with cardiac-specific outcomes and (3) novel biomarker development.

The Impact of Regorafenib on Cardiac Function in Metastatic Colorectal Cancer Patients a Retrospective Cohort Study

Introduction: Metastatic colorectal cancer (mCRC) poses significant clinical challenges, necessitating the exploration of novel treatment modalities. Regorafenib, a multi-kinase inhibitor, has emerged as a promising therapeutic option for refractory mCRC. However, concerns regarding its potential cardiotoxic effects warrant comprehensive evaluation of its impact on cardiac function parameters in this patient population. Methods: The purpose of this retrospective cohort research was to find out how regorafenib affected cardiac function measures in patients with metastatic colorectal cancer (mCRC) at the Pakistan Institute of Medical Sciences (PIMS) in Islamabad. 78 adult patients in all, having histologically proven mCRC, who were treated with regorafenib between January 2023 and March 2024 were included in the analysis. Baseline characteristics, treatment details, cardiac function parameters, and incidence of cardiac events were retrospectively analyzed. Statistical analyses were performed to assess changes in cardiac function parameters and identify predictors of cardiac toxicity associated with regorafenib therapy. Results: Following regorafenib therapy, there was a significant decrease in left ventricular ejection fraction (LVEF), alterations in diastolic function indices, and an incidence of clinically significant cardiac events (12%), including heart failure, arrhythmias, and myocardial infarction. Subgroup analyses identified older age, male sex, pre-existing hypertension, longer treatment duration, and higher cumulative doses of regorafenib as potential predictors of cardiac toxicity. Conclusion: This study underscores the potential cardiotoxic effects of regorafenib in mCRC patients and highlights the importance of personalized cardiac monitoring and risk management strategies during treatment. Further research is warranted to validate these findings and inform evidence-based approaches to optimize the cardiovascular safety of regorafenib in clinical practice.

Diabetes Mellitus and Peripartum Cardiomyopathy: A Nationwide Study

BackgroundThe relationship between diabetes mellitus-(DM) and peripartum-cardiomyopathy(PPCM) remains uncertain. This study aims to clarify the connection between DM and PPCM to predict cardiovascular-outcomes using data from the National Readmission Database(NRD). Methods and ResultsWe analyzed data from 2016-2020 and identified 20,865 hospitalizations for PPCM, with 10.02% (2,091 cases) of them diagnosed with DM. PPCM patients with DM had a higher mean age (36 years,SD-7.6 vs 32 years,SD-6.7;p=0.000). Baseline-comorbidities were shown in Figure1. DM in PPCM has been identified as a predictor for acute-kidney-injury(AKI)[OR 2.38,95%CI 2.01-2.82,p=0.000], and major-adverse-cardiac-and-cerebrovascular-events(MACCE)[OR 1.65,95%-CI 1.32-2.05,p=0.000]. However, it is not associated with an increased risk of death[OR 1.7,95%-CI 1.00-2.99,p=0.048],Stroke[OR 1.24,95%-CI 0.65-2.36,p=0.512],Myocardial infraction[OR 1.56,95%-CI 1.00-2.43,p = 0.051],Suddencardiac-arrest[OR 1.12,95%-CI 0.74-1.69,p=0.603), or the necessity for Mechanical-cardiac-support[OR 1.01,95%-CI 0.59-1.72, p=0.967], Figure-2. Moreover, PPCM patients with DM exhibit an extended mean hospital stay(7.2-vs-5.7 days,p<0.000) and infaltion adjusted-cost of hospitalization ($1,02,690-vs-$84,507,p<0.00). Interestingly, these patients had a lower 30-day non-elective readmission rate (2.3% vs. 8.9%). The top three primary causes of non-elective readmission in the DM group were heart-failure, acute pericarditis, and acute kidney injury. ConclusionsOur findings show that not only do PPCM patients with DM present a higher mean age and increased baseline comorbidities, but they are also at a greater risk for acute kidney injury and significant cardiac and cerebrovascular events. Additionally, these patients undergo extended average hospital stays and incur higher infaltion adjusted hospitalization expenses.

OUTCOMES OF ROTATIONAL ATHERECTOMY IN CALCIFIED PROXIMAL LEFT ANTERIOR DESCENDING (LAD) LESIONS IN THE CONTEXT OF TRIPLE VESSEL DISEASE

Percutaneous coronary intervention (PCI) has become more complex with the advancement of medical devices. One such device is the rotational atherectomy (RA), which uses a rotating diamond-coated burr to modify calcified lesions. This makes it easier to deliver balloons and stents to specific lesions. However, there is a lack of literature regarding the success of RA in calcified proximal 'left anterior descending (LAD) lesions' following PCI. To address this gap, a study was conducted to evaluate the clinical outcomes of RA in calcified proximal LAD lesions in triple vessel disease (TVD). The study included 112 patients who underwent PCI using RA between February 2022 and November 2022 at Lady Reading Hospital, Peshawar. Data was collected using a standard report structure, including operative and follow-up details and medical and demographic features. Retrospective data was collected using medical records and interviews with patients or doctors. The ethical committee approved the study. The participants had an average age of 68.4± 0.45 years, with 85 men (75.8%) and 40 (35.7%) with diabetes mellitus. The technical success rate was 97.6%, with 20 individuals (17.8%) experiencing significant adverse cerebral and cardiac events while hospitalized. At 1.5 years, 25 (22.3%) TVFs had occurred. Independent variables such as current smoking, chronic renal disease, history of cerebrovascular attack, left ventricle ejection fraction, and left central disease were assessed to predict TVF. Based on the results, the investigation showed that rotational atherectomy in calcified proximal LAD lesions had promising success rates.

The role of TBX20 truncating variants in dilated and left ventricular non-compaction cardiomyopathy

Abstract Background The genetic cause of dilated cardiomyopathy (DCM) remains unexplained in a considerable proportion of cases. TBX20, the T-Box transcription factor 20 gene, has been linked to cardiac septal defects. Although only a few case reports have described an association between TBX20 and DCM/left ventricular non-compaction (LVNC), there are no case-control studies available, and TBX20 is still considered a gene with limited evidence for these phenotypes. Objectives This study sought to investigate the relationship between truncating variants in TBX20 (TBX20tv) and the development of DCM and LVNC. Methods TBX20 was sequenced using massive parallel sequencing in 7,463 unrelated probands with DCM/LVNC and 22,773 probands with other diagnoses (e.g., hypertrophic or arrhythmogenic cardiomyopathy, channelopathies, or aortic diseases) as internal controls. It was tested for enrichment and cosegregation of TBX20tv in DCM/LVNC, and clinical characteristics and outcomes in carriers were analyzed. Results Twenty-four probands with 22 TBX20tv were identified. Variant frequencies were significantly higher in patients with DCM/LVNC (24/7,463; 0.29%) than in internal controls (2/22,773; 0.008%) or controls from the gnomAD database (4/124,098; 0.003%), with an OR of 70.18 (CI95%: 9.48 to 519.8; p &amp;lt;0.0001) and 95.61 (CI95%: 33.06-276.55; p &amp;lt;0.0001), respectively. Cosegregation was studied in 21 families, identifying 57 carriers, of whom 43 (75.4%) had cardiac involvement. A combined LODs score of 4.41 was obtained, which is indicative of very strong segregation. Regarding clinical characteristics, the mean age at diagnosis was 37 years old, and 50% of carriers were female. Forty-six percent developed left-ventricular dysfunction, which was moderate to severe in half of the cases. Three carriers received a heart transplant, and another carrier died due to heart failure. Congenital heart defects were present in 16 patients (28.1%). Valvular involvement was the most frequent congenital abnormality (5 cases had bicuspid aortic valve, and another 5 had mitral valve defects), followed by heart septal defects (3 atrial and 3 ventricular); coronary anomalies (2) and aortic coarctation (2) were also detected. In some patients, these defects presented as complex congenital heart disease. Conclusions TBX20tv are associated with the development of dilated and non-compaction cardiomyopathy, and the presence of congenital heart defects is also common. Although some carriers, particularly younger ones, may not present the phenotype, nearly half of them experience ventricular dysfunction, and significant cardiac events, such as cardiac death or transplantation, are not uncommon. Therefore, the TBX20 gene should be routinely included in genetic testing panels for DCM and LVNC.

Association of coronary computed tomographic angiography parameters defined in patients with acute coronary syndrome with risk of long-term significant cardiac events

Association of coronary computed tomographic angiography parameters defined in patients with acute coronary syndrome with risk of long-term significant cardiac events

Major cardiovascular events and associated factors among routine hemodialysis patients with end-stage renal disease at tertiary care hospital in Somalia.

Cardiovascular complications are the most significant cause of death in patients undergoing routine hemodialysi (HD) with end-stage renal disease (ESRD). The main objective of this study is to determine the significant cardiac events and risk factors in patients undergoing routine hemodialysis in Somalia. We carried out a cross-sectional retrospective study in a single dialysis center in Somalia. Two hundred out of 224 were included. All of them had ESRD and were on hemodialysis during the study period between May and October 2021. The records of all patients were reviewed, and the following parameters were analyzed socio-demographic factors, risk factors for cardiovascular disease, and the presence of cardiovascular diseases. The mean age was 54 ± 17.5 years (range 18-88 years), and 106 (53%) patients were males. The prevalence of a cardiovascular disease among hemodialysis patients was 29.5%. Moreover, the distribution of cardiovascular diseases was different; heart failure was the most common, about 27.1%, followed by coronary artery disease (17%), pericarditis and pericardial-effusion (13.6%), dysrhythmia (10.2%), cerebrovascular-accident (8.5%), and peripheral vascular disease (3.4%). About 176 (88%) participants had at least one modifiable cardiovascular risk factor. The most common modifiable cardiovascular risk factor was hypertension (n = 45, 25.1%), followed by anemia (n = 28, 15.6%) and diabetes (n = 26, 14.5%). Younger (18-30) participants were six times less likely to have cardiovascular events among hemodialysis than older age 0.4 (0.11-1.12). Low prevalence rate of cardiovascular complications was confirmed in ESRD patients receiving hemodialysis in the main HD center in Somalia. Diabetes, anemia, and hypertension were the highest significant risk factors for CVD in HD patients with ESRD in Somalia.

PO-02-047 OUTCOMES OF CARDIOVASCULAR IMPLANTABLE ELECTRONIC DEVICE REMOVAL WITHOUT REIMPLANTATION IN PEDIATRIC PATIENTS

Patients with cardiovascular implantable electronic device (CIED) may no longer meet indications for pacing during follow up. This population represents a challenge for physicians since no guidelines stipulate acceptable indication for CIED removal without reimplantation. Little is known about the risk of significant cardiac events in children who undergo CIED removal. The present study aims to investigate the outcomes in a population having undergone CIED removal without immediate reimplantation before the age of 18 years at our institution. We retrospectively searched for consecutive patients <18 years of age who underwent CIED removal at the Hospital for Sick Children from Jan 2007 to Dec 2022. The primary outcome of significant cardiac event was defined as symptomatic bradycardia with documented high grade atrioventricular block (AVB) or sinus pause, syncope of presumed cardiac origin, ventricular arrhythmia with hemodynamic compromise, or sudden death of presumed arrhythmic etiology. Of 667 patients who underwent CIED implantation at our institution during the study period, a total of 14 (2.1%) patients (9 males [64.3%]) underwent explantation without immediate reimplantation. The majority of patients (N=9; 64.3%) had structural heart disease, with the most common indication for implantation being post-op AVB (N=5; 35.7%) followed by sinus node dysfunction (SND, N=4; 28.6%). During a median follow-up of 2.2 years (IQR 0.4–6.7), significant cardiac event occurred in 3 (21.4%) patients aged 13.5 years (IQR 6.4–17.9) at a median of 0.7 years (IQR 0.6–3.2) after explantation. Two patients had recurrence of their post-operative AVB 7 and 8 months after explantation respectively, both presenting with self-resolving syncope and documented prolonged pause on implantable loop recorder (ILR). One patient known for left atrial isomerism who had been paced for SND developed new complete AVB 3.2 years after his device has been explanted, which represented a new indication for pacing. There were no aborted or sudden death during the 48.7 patient-years of follow-up. In a small cohort of pediatric patients, CIED explantation without reimplantation was a safe practice that required careful patient selection. An ILR should be considered at the time of explant to facilitate monitoring over time. Further studies are required to identify predictive factors for cardiac events in this specific population.

Prognostic value of fibrinogen-to-albumin ratio combined with coronary calcification score in patients with suspected coronary artery disease

ObjectiveThe aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs.BackgroundThe fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD.MethodsWe used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 < CACS ≤ 400, and CACS > 400).Results4946 patients [62(55–71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard β = 0.066, P < 0.001) was positively associated with FAR in patients with chest pain.Compared to ones with FAR-L, FAR-H had an increased risk for MACCEs (adjusted HR 1.371(1.053–1.786) P = 0.019). Multivariate Cox regression showed that age (adjusted HR 1.015 95% CI 1.001–1.028;p = 0.03), FAR (adjusted HR 1.355 95% CI 1.042–1.763;p = 0.023),FBG (adjusted HR 1.043 95% CI 1.006–1.083;p = 0.024) and CACS (adjusted HR 1.470 95% CI 1.250–1.727;p < 0.001) were the independent risk factors for MACCEs. The FAR and CACS significantly improved MACCEs risk stratification, contributing to substantial net reclassification improvement ( NRI 0.122, 95% CI 0.054–0.198, P < 0.001) and integrated discrimination improvement(IDI 0.011, 95% CI 0.006–0.017, P < 0.001).ConclusionFAR was an independent risk factor for MACCEs. The results showed that CACS was positively associated with FAR in patients with suspected CAD. A higher level of FAR and heavier coronary calcification burden was associated with worse outcomes among patients with suspected CAD. FAR and CACS improved the risk identification of patients with suspected CAD, leading to a significant reclassification of MACCEs.

CARDIAC COMPUTED TOMOGRAPHY (CT) FOR ACUTE CHEST PAIN: SYSTEMATIC REVIEW

Background: Coronary CT angiography (CCTA), a non-invasive approach for detecting anatomic atherosclerotic disease, is a potential diagnostic tool for patients with chest discomfort.CCTA has several benefits over other modalities (such as physiologic testing), including better accuracy in diagnosing obstructive coronary artery disease, identification of high-risk disease, and detection of subclinical atherosclerosis. Objective: When opposed to stress testing, coronary CT angiography (CCTA) offers several advantages, including improved accuracy in detecting obstructive coronary disease. The studys goal was to conduct a systematic review and meta-analysis comparing CCTA to other standard-of-care (SOC) techniques in the assessment of patients suffering from acute chest discomfort. Methods: Authors began with recognizing the important examination proof that spots light on the significance of cardiac computed tomography for acute chest pain among patients presenting to the emergency department. We led electronic writing look in the accompanying data sets: Ovid Medline (2010 to present), Ovid Medline Daily Update, Ovid Medline in process and other non-filed references, Ovid Embase (2010 to present), The Cochrane Library (latest issue) and Web of Science. Just examinations in English language will be incorporated. The precise selection was acted in close collaboration with a clinical examination curator. Results: Ten studies with a total of 6285 patients were included in the study.The trials employed diverse definitions and methods for SOC, but they all used physiologic testing. There were no significant differences between the groups in terms of all-cause mortality (RR 0.48, 95 percent CI 0.17 to 1.36, p=0.17), MI (RR 0.82, 95 percent CI 0.49 to 1.39, p=0.47), or MACE (RR 0.98, 95 percent CI 0.67 to 1.43, p=0.92). However, the CCTA arm had substantially higher incidence of ICA (RR 1.32, 95 percent CI 1.07 to 1.63, p=0.01) and revascularization (RR 1.77, 95 percent CI 1.35 to 2.31, p0.0001). Conclusion: CCTA is related with similar significant adverse cardiac events as other SOC methods, but greater rates of revascularization in individuals with acute chest pain.

Radiation-Induced Acute Cardiotoxicity in Women with Left Sided Breast Cancer: Results from a Phase II Prospective Clinical Trial

<h3>Purpose/Objective(s)</h3> Women with left sided breast cancer (BC) who receive adjuvant radiotherapy (RT) have increased risk of subsequent cardiac events, which may be mitigated by maintaining mean heart dose (MHD) below a threshold of 3 Gy. We hypothesized that early MRI evaluation of cardiac functional changes can identify acute cardiac insult and predict for the risk of long-term cardiac complications. Here we report the findings of a phase II prospective clinical trial evaluating RT-related LV structure and function using cardiac MRI in women with left sided BC treated with adjuvant RT. <h3>Materials/Methods</h3> Patients with left sided BC were enrolled into a single institutional phase II study. After informed consent, patients were allocated for breast RT with free breathing (FB) or with deep inspiratory breath hold (DIBH) delivery, if the predicted MHD was ≤3 Gy (≤ 5 Gy, if also regional nodal RT) or > 3 Gy (> 5 Gy, if regional nodal RT), respectively, on initial FB planning. Cardiac MRI was performed at baseline (pre-RT), and at 16 and 52 weeks. Cardiac toxicity was defined as change in the indexed LV end diastolic volume (LVEDVi), LV ejection fraction (LVEF), indexed LV end systolic volume (LVESVi) and indexed LV mass (LV MASSi). Estimation of multiple serum cardiac biomarkers were also done at the three time points. Continuous variables were expressed as mean ± standard deviation, and ANOVA analysis was used to identify correlation between changes in cardiac parameters from baseline to 16 and 52 weeks, when compared to cardiac radiation dosimetric data. <h3>Results</h3> Of the 69 participants, 25 received RT with FB technique. 44 received RT with DIBH, of which 23 also had received adjuvant chemotherapy (CT) prior to RT. For the FB, DIBH (no CT), and DIBH (with CT) cohorts, MHD was 1.70 ± 0.93 Gy, 1.93 ± 1.30 Gy, and 2.26 ± 1.15 Gy and mean LV dose was 2.47 ± 1.48 Gy, 3.18 ± 1.93 Gy, and 3.23 ± 1.82 Gy, respectively. Evaluation of LVEDVi, LVEF, LVESVi, and LV MASSi showed no statistical difference between the 3 treatment arms. No statistical correlation was noted between LVEF changes (≥ 5% and ≥ 10% from baseline) and the cardiac dosimetric data; all p values > 0.1. Prior CT did not measurably impact cardiac function. <h3>Conclusion</h3> In this prospective study, no significant post-RT cardiac events were demonstrable by functional imaging. This supports the significance of maintaining MHD ≤ 3 Gy to minimize or prevent RT related cardiac toxicity in women with left sided BC. Our observation warrants further investigation in a large prospective setting to evaluate late cardiac events. Analysis of serum cardiac biomarkers is currently ongoing.

Long QT syndrome-associated calmodulin mutations and their interactions with the Kv7.1 voltage-gated potassium channel

Abstract Introduction Calmodulin (CaM) is a highly conserved mediator of calcium (Ca2+) dependent signalling. Its flexible structure allows CaM to bind and modulate many targets, including cardiac ion channels. Genotyping has revealed several CaM mutations associated with congenital disorders of heart rhythm, known as long QT-syndrome (LQTS). LQTS patients suffer from prolonged ventricular recovery times (QT-interval) which increases their risk of significant cardiac events. Loss of function KV7.1 mutations are the largest cause of LQTS, accounting for &amp;gt;50% of cases. CaM facilitates Ca2+-sensitivity to KV7.1 in producing IKs, Kv7.1 mutations which reduce CaM binding promote LQTS pathology. However, the effects of LQTS-associated CaM mutations on Kv7.1 function remain unknown. Purpose To determine the biophysical consequences of congenital LQTS-associated CaM mutations and how they alter modulation of Kv7.1 in producing the ventricular repolarising IKs current. Methods WT and mutant CaM proteins were recombinantly expressed and purified for biophysical characterisation. Using circular dichroism, secondary structures and thermostability of proteins were quantified. Isothermal titration calorimetry was used to quantitatively measure interactions between CaM proteins and binding sites of KV7.1 (Helix B). NMR was employed to study the conformations of target-bound WT and mutant proteins. Whole cell currents were determined using voltage clamp electrophysiology in HEK cells. Results Mutations significantly changed the thermostability and secondary structure distributions of CaM, and also caused site-dependent increases in susceptibility to protease digestion. CaM interacted with Helix B (KV7.1) via both Ca2+-dependent and independent mechanisms. Ca2+ dependent binding to Helix B was much higher affinity than Ca2+-independent binding, with &amp;gt;2000-fold reduction in dissociation constant measured. LQTS-CaM variants reduced Helix B affinity with the largest reductions found in EF-hand IV mutants. These mutants also adopted most distinct conformations when Helix B-bound. Calmodulation of the KV7.1 channel produced larger (IKs) currents without altering channel activation kinetics. IKs exhibited Ca2+-sensitivity, in response to increased cytosolic Ca2+, larger currents were generated. Modulation by CaM mutants reduced current density at systolic Ca2+-concentrations (1000 nM), within physiological time periods (0.35 s), revealing a direct QT-prolonging modulatory effect. Conclusions Provided here are mechanistic insights as to how LQTS-associated CaM variants contribute to electrical disease of the heart. Mutations in the highly conserved structure of CaM disrupt protein conformation and perturb complex formation with KV7.1. This results in aberrant Ca2+-sensitivity of Kv7.1, reducing IKs generation. This ultimately decreases the repolarisation capacity of cells and would extend the QT interval of myocytes. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Intermediate Basic Science Research Fellowship

Drug-Coated Balloon Angioplasty for Carotid Artery In-Stent Restenosis: Case Series

Objectives: Few case reports have demonstrated promising results of drug-coated balloons (DCBs) as an emerging management for carotid artery in-stent restenosis (CAISR). Herein, we report 6 cases of CAISR which were treated with a DCB with or without new stent deployment. Background: Carotid artery in-stent restenosis is a high-risk condition with an estimated incidence rate that varies widely from 6% to 40%. Several strategies are available now for the management of the CAISR including conventional balloon angioplasty, plaque modification balloon angioplasty, and new stent placement. Methods: A retrospective review of consecutive patients with a diagnosis of severe CAISR at Baylor Scott & White The Heart Hospital Plano from 2011 to 2021 was performed. This study was approved by the Baylor Scott & White Research Institute institutional review board. Results: Six patients underwent DCB angioplasty with or without stent placement under an embolic protection device. Resolution of CAISR was achieved in all cases with 0% to 10% residual stenosis in all cases. Following the procedure, 1 patient had a brief episode of syncope with balloon inflation with immediate recovery on deflation of the balloon. There were otherwise no significant neurological or cardiac events prior to discharge. All patients were asymptomatic at their follow-up visit with no neurological or cardiac events reported at 12, 24, and 36 months following the procedure. Conclusion: While CAISR treatment remains a challenging condition, our study shows that the use of DCB with or without stent placement is a feasible and promising treatment option when compared with other conventional treatment options. Clinical Impact Carotid artery in-stent restenosis treatment remains a challenging condition. Our study shows that the use of drug coated balloon with or without stent placement is a feasible and promising treatment option when compared with current conventional treatment options.

Cardiovascular events in patients referred to computerized tomography angiography with moderate coronary artery stenosis

Objectives: Cardiovascular diseases are the most critical causes of mortality in the modern world. Additionally, most acute coronary events result from sudden thrombosis leading to atherosclerotic plaque rupture. Computerized tomography (CT) angiography can identify the characteristics and quantity of plaques. This study investigated the relationship between plaque and moderate coronary stenosis.&#x0D; Methods: This study was a retrospective diagnostic study comprising 91 patients who had been referred to CT angiography at Afshar Hospital in Yazd City, Iran, from 2017 to 2018 and undergone coronary angiography CT while bearing moderate coronary artery stenosis. Using the CT report, location, plaque density, the extent of stenosis, and vein involved were all extracted and recorded. The patients were followed up for one year from the time of the CT scan using the MACE questionnaire. Ultimately, data was analyzed using SPSS software version 22 through Chi-square, Fisher's exact test, and t-test.&#x0D; Results: The results revealed the mean age of the patients to be 62.76±1.08 years; 39 (42.9%) women and 52 (57.1%) men. Based on the obtained results, the most common involved vessel, location of stenosis in CT angiography, and plate density included the left anterior descending artery with 75.8%, the middle part of the left anterior descending artery with 29.7%, mixed density with 54.9% and one segment with 62.6% frequency. Also, according to the significant adverse cardiac event (MACE) questionnaire results, the frequency distribution of cardiovascular events in the studied patients did not exhibit any evidence of cardiovascular events in the patients' one-year follow-up.&#x0D; Conclusions: There was no evidence of cardiovascular events in the patients with moderate coronary artery stenosis during a 1-year follow-up.

Cardiopulmonary Toxicity Following Intensity-Modulated Proton Therapy (IMPT) Versus Intensity-Modulated Radiation Therapy (IMRT) for Stage III Non-Small Cell Lung Cancer

IntroductionIntensity-modulated proton therapy (IMPT) has the potential to reduce radiation dose to normal organs when compared to intensity-modulated radiation therapy (IMRT). We hypothesized that IMPT is associated with a reduced rate of cardiopulmonary toxicities in patients with Stage III NSCLC when compared with IMRT. MethodsWe analyzed 163 consecutively treated patients with biopsy-proven, stage III NSCLC who received IMPT (n = 35, 21%) or IMRT (n = 128, 79%). Patient, tumor, and treatment characteristics were analyzed. Overall survival (OS), freedom-from distant metastasis (FFDM), freedom-from locoregional relapse (FFLR), and cardiopulmonary toxicities (CTCAE v5.0) were calculated using the Kaplan-Meier estimate. Univariate cox regressions were conducted for the final model. ResultsMedian follow-up of surviving patients was 25.5 (range, 4.6-58.1) months. Median RT dose was 60 (range, 45-72) Gy [RBE]. OS, FFDM, and FFLR were not different based on RT modality. IMPT provided significant dosimetric pulmonary and cardiac sparing when compared to IMRT. IMPT was associated with a reduced rate of grade more than or equal to 3 pneumonitis (HR 0.25, P = .04) and grade more than or equal to 3 cardiac events (HR 0.33, P = .08). Pre-treatment predicted diffusing capacity for carbon monoxide less than equal to 57% (HR 2.8, P = .04) and forced expiratory volume in the first second less than equal to 61% (HR 3.1, P = .03) were associated with an increased rate of grade more than or equal to 3 pneumonitis. ConclusionsIMPT is associated with a reduced risk of clinically significant pneumonitis and cardiac events when compared with IMRT without compromising tumor control in stage III NSCLC. IMPT may provide a safer treatment option, particularly for high-risk patients with poor pretreatment pulmonary function.

Anomalous Coronary Artery Presenting with S-T Elevation Myocardial Infarction: A Case Report

Background: Coronary artery anomalies are very rare congenital conditions. Rarely occurring but potentially fatal abnormalities of the coronary vasculature, abnormalities of the coronary arteries can cause significant cardiac events such as myocardial ischemia (S-T Segment elevation MI) and cardiac arrest.&#x0D; Case Presentation: We are presenting a case of a 60 years old hypertensive female patient who presented with ST-segment elevation in all precordial leads.&#x0D; Management &amp; Results: On angiography, a giant right coronary artery was seen, and no Left coronary artery origin was not appreciated. Hence, Multidimensional CT angiography was done that showed dilated and ectatic left main coronary artery circulation originating from the pulmonary artery just above the pulmonary valve. The patient was declared a high-risk surgical candidate, was advised medical therapy, including beta blockers, dual antiplatelet, and antihyperlipidemic medications, and was advised to restrict physical activity.&#x0D; Conclusion: The rare presentation of an aberrant coronary artery is myocardial infarction with ST-segment elevation, and it might be difficult for doctors and cardiologists to determine the true reason without intervention. To optimize the care of these patients, traditional CAA and MDCT must be integrated with the clinical presentation of the patients.