bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the impact of heart failure treatment on cancer growth
Authors: Civati C , Goovaerts B , Van Berlo B , Segers V , De Keulenaer G
Published: October 2024

Background

Heart failure (HF) is associated with systemic alterations that extend beyond the cardiovascular system. The dysregulation of physiological pathways induced by HF, encompassing inflammatory or neurohormonal pathways, may foster an environment conducive to cancer growth and the spead of metastases. It is unknown whether these alterations are attenuated when HF is treated, and whether certain therapies for HF may yield more significant effects than others.

Purpose

This study aims to investigate whether myocardial infarction (MI)-induced left ventricular (LV) dysfunction promotes breast cancer growth and triggers the development of lung metastases. Additionally, it compares the potential impact of different therapeutic strategies for LV dysfunction on cancer development.

Methods

Myocardial infarction (MI) was induced in 11-week-old female BALB/c mice by ligation of the left anterior descending (LAD) coronary artery, leading to LV dysfunction and significant dilation within four weeks. Starting 2 weeks after surgery, mice with ejection fraction (EF) < 40% received daily oral gavage of vehicle or one of three drugs: carvedilol (10 mg/kg), enalapril (20 mg/kg), or empagliflozin (15 mg/kg). Four weeks post-surgery, 2x105 4T1 metastatic breast cancer cells were injected into the 4th mammary fat pad. Tumor volume was measured every two days, starting eight days after injection. Weekly echocardiographic assessments monitored cardiac function until the end of the experiment. Tumors were excised on day 22 after injection. Mice were euthanised on day 28 for post-mortem analysis. MCM2 proliferation staining was performed on lung tissue to quantify metastases.

Results

Among the HF treatments, only empagliflozin (n=11) induced a significant decrease in both left ventricular end-diastolic and end-systolic volume (Fig. 1.A; p=0.0043; Fig. 1.B; p=0.0186) compared to the vehicle group (n=11). Tumor weight and volume (Fig. 1.C-D) were not different in the HF/vehicle group (n=15) and the sham-operated group (n=13). Carvedilol (n=14) led to a small reduction in tumor weight (Fig. 1.C; p=0.1264), while empagliflozin (n=11) exhibited a significant reduction in both tumor weight (Fig. 1.C; p=0.0306) and volume (Fig. 1.D; p=0.0268). In addition, carvedilol (n=13) significantly reduced lung metastases (Fig. 1.E; p=0.0347) compared to the HF/vehicle group (n=13). Enalapril (n=10) and empagliflozin (n=9) did not significantly impact the development of lung metastases.

Conclusion

Despite the absence of increased cancer growth post-MI, our findings indicate that specific treatments for HF—namely, carvedilol and empagliflozin—attenuate cancer growth post-MI. Furthermore, carvedilol demonstrated potential in reducing metastatic spread. Additional research is required to uncover the underlying mechanisms both in the presence and absence of HF, and to explore the molecular impact that HF treatments have on various stages of cancer progression.Figure 1
Machine learning and traditional analysis of the interaction between cardiovascular diseases and hematological malignancies
Authors: Caller T , Fardman A , Sharon E , Naftali-Shani N , Leor J , Maor E , Itkin T
Published: October 2024

Background

Cardiovascular diseases and clonal hematopoiesis of indetermine potential (CHIP), the premalignant state of hematological cancers, exhibit reciprocal interactions. While the presence of CHIP confer a risk for heart failure, it is unclear if cardiovascular diseases are associated with elevated risk hematological cancers.

Purpose

To determine the association between cardiovascular diseases (CVD) and cardiovascular risk, and hematological cancer.

Methods

We evaluated 27,231 adults, free of CVD and cancer, who participated in preventive healthcare program between 2000-2018. Each participant underwent a complete physical evaluation, blood test and exercise stress test at baseline. CVD was defines as ischemic heart disease, stroke, atrial fibrillation or hypertension. Then, we used machine learning and traditional survival analysis to evaluate the association between CVD and hematological cancer. For machine learning, we used the random forest method using Curat package in r, and incorporated all continuous variables gathered into the model (70% training, 30% test). For survival analysis, we first matches each CVD patient to a control patient by propensity scores to balance for age, sex, smoking, diabeles mellitus, renal function, body mass index and length of follow-up. Then, we compared the CVD and non-CVD patients using cox proportional hazard regression.

Results

Using machine learning, we found that the strongest predictors for hematological cancer in our cohort are low eGFR, age, high atherosclerosis cardiovascular disease score (ASCVD) and BMI. Of note, systolic and diastolic blood pressure were also strong predictors of hematological cancer (Figure A). Then, we matched 5500 CVD patients to controls with median follow-up of 9.2 years (Interquartile range 5-15 years). During follow-up, 1380 developed cancer. Of them, 186 developed hematological cancer. We used cox proportional hazard regression and Kaplan Mayer method to determine the risk and hazard ratio of developing hematological cancer (Figure B-C). Compared with subjected without CVD, patients with CVD were 91% more likely to develop cancer during follow-up, and 62% more likely to develop hematological cancer (Figure C, HR=1.61. 95%CI 1.21-2.16). Moreover, the 10-year risk to develop hematological cancer was 1.9% for patients with CVD and 1.0% for individuals without CVD (Figure D). Notably, the increased incidence of hematological cancers included 38% increase in cases of leukemia but only 11% increase in cases of lymphoma.

Conclusions

Using machine learning and traditional analysis we show that CVD risk and CVD were associated with increased incidence of hematological cancer. Understanding this relationship could lead to advances in cardiovascular and cancer treatment and could ultimately help to improve patient outcomes.
Adverse cardiovascular events in patients with cancer: a biomarker-enhanced clinical risk score
Authors: Kraler S , Liberale L , Nopp S , Englisch C , Grilz E , Akhmedov A , Lapikova-Bryhinska T , Carbone F , Suter T M , Von Eckardstein A , Pabinger I , Luescher T F , Montecucco F , Ay C , Moik F
Published: October 2024

Background/Introduction

Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but reliable tools for cardiovascular risk prediction remain unavailable (1).

Purpose

To assess a broad panel of cardiovascular biomarkers and clinical risk factors and to provide a novel risk score for the prediction of MACE in cancer patients.

Methods

Among 2’192 patients with newly diagnosed or recurrent cancer, a broad panel of cardiovascular biomarkers, including NT-proBNP, P-/E-/L-selectins, ICAM-1, VCAM-1, sLOX-1, CRP, and Lp(a) were measured by blinded study personnel. Patients were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death (2,3). Uni- and multivariable competing risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with MACE, and a risk score was developed.

Results

Beyond clinical risk factors, ICAM-1, P-/E-/L-selectins and NT-proBNP levels were independently linked to 2-year MACE risk, though shape of associations differed markedly. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age ≥60 years, and +2 points for ASCVD history, yielding a bootstrapped C-statistic of 0.76 (95%CI:0.71-0.81). Implementation of cardiovascular biomarkers conferred improved performance (0.83, 95%CI:0.78-0.88). A simplified model, solely informed by clinical variables and readily available NT-proBNP (+1 point for NT-proBNP≥230pg/mL), achieved similar performance (0.80, 95%CI:0.74-0.86), with a cumulative 2-year MACE incidence of 0% in low- and 11.0% in high-risk patients.

Conclusions

Cancer patients are at substantial MACE risk. The herein presented first-of-its-kind risk score, integrating traditional cardiovascular risk factors and biomarkers, including NT-proBNP, effectively predicts 2-year MACE and 5-year cardiovascular death.
Double product derived from exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) in patients with a history of breast cancer and radiotherapy (RXT) exposure and MACE
Authors: Garzon-Dangond J , Gomez-Ardila M F , Tellez-Garcia E , Daryanani A E , Peethambaram P P , Thicke L A , Stan D L , Villarraga H R
Published: October 2024

Background

Breast cancer survivorship has markedly improved in the last two decades due to improved therapies. Among these, adjuvant chest radiotherapy stands out as an integral part of the current treatment. Chest radiotherapy can trigger accelerated atherosclerosis, which, coupled with cardiovascular (CV) risk factors common to this population, can lead to increased rates of coronary artery disease (CAD). ESC 2022 guidelines have established both Exercise Stress Echocardiography (ESE) and Dobutamine Stress Echocardiography (DSE) as cost-efficient and reliable tools for screening this patient population. Recommendations include ESE or DSE 5 years after radiotherapy as a screening tool. Double product (DP), an index common to both tests, parallels myocardial oxygen consumption. It has been used to predict major adverse cardiovascular events (MACE) in other cohorts.

Purpose

We sought to evaluate if DP could be used as a prognostic indicator for MACE (myocardial infarction, stroke, cardiovascular death, and heart failure) in this population.

Methods

Breast cancer patients treated with adjuvant radiotherapy from 2000 to 2022 were included. ESE or DSE was done after a mean of 5.4 years (1Q-2.2, 3Q-7.5) post-radiotherapy. Uni and multivariable adjusted Cox regression models were performed to evaluate the association between DP quartiles achieved and the risk of MACE in DSE and ESE groups. MACE-free survival among different quartiles was plotted with the Kaplan Meier method.

Results

696 patients were included, with a mean age of 65 (SD 10.0) and 72 (SD 9.4) in ESE and DSE respectively. 61% of patients had ESE. In ESE, we observed increased rates of MACE in the 1st quartile when compared to the other quartiles (Figure 1a). On the other hand, univariate and multivariate Cox models established that for every increase of 1000 units of DP achieved during ESE, there is a risk-reduction of 9% [HR=0.91 (0.86-0.95); p=<0.01] in the future incidence of MACE, thus establishing DP as a protective marker. Additionally, advanced age was shown to be a major risk factor as well [HR=4.58 (1.91-10.9); p=<0.01].

In the DSE cohort however, the development of MACE was equally distributed across DP quartiles even after adjusting for existing comorbidities (Figure 1b). Cox analysis did not establish DP as a prognostic tool in this cohort (Table 1).

Conclusion

DP is established as an excellent prognostic tool for the detection of MACE in patients who underwent ESE. Patients who achieve higher DP quartiles during these tests have lower future rates of MACE. Regarding DSE, DP is not a good prognostic tool. This could be explained by higher burden of cardiovascular risk factors in this patient population. ESE should be recommended when possible.
Can the presence of aortic or coronary artery calcifications in the standard of care baseline CT or PET-CT scan of patients with Hodgkin or non-Hodgkin lymphoma be used as a predictor of MACE?
Authors: Gomez Ardila M , Daryanani A , Garzon-Dangond J M , Tellez-Garcia E , Ricaurte-Carmona C , Cerhan J R , Foley T A , Villarraga H R
Published: October 2024

Background

Major adverse cardiovascular events (MACE), commonly defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and heart failure, represent a significant cause of mortality among patients with cancer.  With increased rates of both cancer and cancer survivorship, the identification of new predictive markers for the development of MACE in this population is crucial for implementing effective preventive and risk-mitigation strategies.

Purpose

To determine whether the presence of calcifications in the coronary arteries (CAC) or aorta (CA) of lymphoma patients, as reported in standard-of-care PET-CT (Positron Emission Tomography-Computed Tomography) or chest CT (Computed Tomography) scan, can predict the occurrence of MACE.

Methods

A Retrospective analysis was conducted on a cohort of patients diagnosed with Hodgkin or non-Hodgkin lymphoma and treated with anthracycline-based chemotherapy. Patients were diagnosed from January 1, 2013, and followed through to June 30, 2023. The reference point for the study was the radiologist’s report of the PET-CT or chest CT conducted before the initiation of anthracycline therapy. Patients who did not undergo a PET-CT or CT before the start of treatment, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CA and CAC was associated with the development of MACE. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression.

Results

326 patients were included with a mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was reported in 75 patients (23%) and CA in 18 (6%). In the univariate regression model, a statistically significant association was found between the presence of both CA and CAC with the risk of MACE. CAC showed a stronger association with the development of MACE than CA (HR: 3.7 [1-7.9], p=0.0005 vs HR: 2.9 [1- 8.5], p=0.050). In multivariable analysis CAC emerged as the strongest predictor of MACE (HR: 2.9 [1.3 – 6.4], p=0.01), after accounting for hypertension, diabetes, dyslipidemia, and GFR <60 (Table 1), while the association with CA attenuated (HR: 2.01 [0.7-6.5], p=0.2010) and was no longer significant (Table 2).

Conclusion

CAC in the standard-of-care PET/-CT scans was a predictor of MACE in lymphoma patients treated with anthracyclines, while the association with CA weakened in multivariable analyses and was likely underpowered given the small number of patients with CA. If replicated, this finding warrants closer surveillance of this group of patients and can be considered as a non-invasive cardiovascular risk marker.
New onset of left ventricular dysfunction and diastolic dysfunction are uncommon in patients with her2+ breast cancer after completion of cancer therapy
Authors: Osataphan N , Huang F , Yu C , Nardi Agmon I , Sooriyakanthan M , Abdel-Qadir H , Amir E , Thavendiranathan P
Published: October 2024

Background

Cardiotoxicity from anthracyclines and trastuzumab is common among patients with breast cancer during therapy. However, there are limited data on new onset of cardiotoxicity (systolic or diastolic dysfunction) after completion of therapy. This knowledge has implications to guide long-term follow-up.

Purpose

The aim of this study was to evaluate the incidence of cancer therapy related cardiac systolic dysfunction (CTRCD) and diastolic dysfunction (DD) in women with HER2+ breast cancer after completion of cancer therapy and compare to incidence during cancer therapy.

Methods

We conducted a prospective cohort study of women with HER2+ breast cancer who were treated with sequential anthracycline and trastuzumab therapy, with or without radiation therapy (The EMBRACE-MRI trial, NCT02306538). Comprehensive surveillance echocardiograms were performed at baseline and every 3 months during treatment, early post-trastuzumab, then at years 1, 2, and 3 post trastuzumab completion. CTRCD was defined as a reduction in 3D-left ventricular ejection fraction (LVEF) by ≥ 10% from baseline to < 55%. Diastolic dysfunction was defined as per the American Society of Echocardiography guidelines.

Results

A total of 136 female patients, with a mean age of 51.1 ± 9.2 years were recruited. Among them, 15.4% had hypertension, 3.7% had diabetes mellitus, and 10.3% had dyslipidemia. The mean cumulative doxorubicin equivalent dose was 203.9 ± 12.5 mg/m2, 120 patients received radiation therapy with the mean heart dose of 170.8 ± 75.9 cGy. During cancer treatment, 27 out of 136 patients (19.9%) developed CTRCD. In long-term follow-up, due to death or interruption due to the COVID-19 pandemic, follow-up was available in 128 patients at 1 year, 117 at 2 years and 111 at 3 years. 5 of the 27 patients still had persistent LV dysfunction (3 at 1 year, 1 at 2 year and 1 at 3 year), however, there were no new diagnosis of CTRCD post completion of therapy. Of 129 patients with baseline normal or indeterminate diastolic function, new DD was identified in 25/129 patients (19.4%) during cancer treatment (17 grade I, 2 grade II, 6 unable to grade). After completion of cancer therapy, 5 patients had persistent DD. In patients with no DD during therapy and completed 3 year follow-up, 5 patients developed new DD after therapy (2 grade I, 3 unable to grade). Figure 1 illustrates the percentage of patients with new CTRCD or new diastolic dysfunction at each timepoint. None of the patients developed clinical heart failure.

Conclusion

Although both CTRCD and diastolic dysfunction are common during sequential therapy with anthracyclines and trastuzumab in women with HER2+ breast cancer, new onset after treatment completion is rare during a careful follow-up. These findings have implications for long-term surveillance.
Prospective screening and proposed treatment algorithm for immune checkpoint inhibitor induced myositis in neoadjuvant-treated rectal cancer patients: data from the phase II CHINOREC trial
Authors: Zirnbauer R , Hametner S , Bergler-Klein J , Kuehrer I , Kulu A , Ammon D , Kabiljo J , Stift A , Schmid R , Laengle F , Machold K , Lambrechts D , Blueml S , Bergmann M , Laengle J
Published: October 2024

Background

Myositis is an infrequent (<1%) but potentially life-threatening (case fatality rate 40-50%) immune-related adverse event (irAEs) of immune checkpoint inhibitors (ICI), such as ipilimumab (IPI) and nivolumab (NIVO). The true incidence is likely to be underestimated and may not be representative for curative neoadjuvant treatment approaches in gastrointestinal (GI) cancers, especially in combination with chemoradiotherapy (CRT). Currently, the summary of product characteristics (SmPC) does not suggest any pre-emptive screening or surveillance.

Methods

The CHINOREC study is an ongoing prospective, randomized, open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with intermediate to locally advanced rectal cancer (LARC) receive either neoadjuvant CRT alone or in combination with a single dose of IPI and 3 cycles of NIVO, following surgical resection. Patients are monitored at baseline and throughout the whole study period for myotoxicity biomarkers, including cardiac troponin T (cTnT) and cardiac troponin I (cTnI).

Findings

From 06/2020 to 11/2023, 80 patients have been enrolled of whom 50 patients were randomized to the CRT+IPI/NIVO arm. Six patients (12%) developed biopsy-verified myositis. Myositis treatment was promptly implemented using a pragmatic step-up approach. Patients received glucocorticoids (GC) with concomitant intravenous immunoglobulin (IVIG). If myotoxicity biomarkers did not improve, patients received infliximab (INFLIXI) and/or plasma exchange (PLEX). Although all patients had strikingly elevated cTnT (median peak 284 ng/L, 95% CI 39-3097), cTnI levels remained largely normal, correlating with a negative cardiac magnetic resonance (CMR). All patients underwent successful tumor surgery without any major surgical complication. As of today, all patients' creatine kinase (CK) and myoglobin (MB) levels have normalized and they are tumor free without any major sequela.

Interpretation

Longitudinal biomarker screening (cTnT/cTnI) for ICI-induced myotoxicities is pivotal in curative neoadjuvant-treated cancer patients to initiate an early counter treatment in a holistic step-up approach, without compromising oncological principles.
Echocardiographic variables may improve baseline risk prediction of cancer therapy related cardiac dysfunction
Authors: Ruane L , Prasad S , Atherton J
Published: October 2024

Background

Baseline prediction of cancer therapy related cardiac dysfunction (CTRCD) in clinical practice is difficult, despite many known cancer and cardiovascular risk factors. Risk scores exist, including the HFA-ICOS score which is recommended by the 2022 European Society of Cardiology (ESC) Cardio-Oncology guidelines. Validation of such risk scores is required though, and identification of alternative risk factors that may improve risk prediction is needed.

Purpose

To assess the accuracy of the HFA-ICOS score for predicting CTRCD, and identify new risk factors with a focus on baseline echocardiography.

Methods

Echocardiograms and medical records were assessed for a cohort of breast cancer patients receiving trastuzumab or an anthracycline, who underwent serial echocardiographic monitoring. CTRCD was defined according to the 2022 ESC Cardio-Oncology guidelines. Baseline risk factors and echocardiography were compared between CTRCD and non-CTRCD groups, and the accuracy of the HFA-ICOS score in predicting CTRCD assessed.

Results

Data from 258 patients were analysed with CTRCD occurring in 23 (9%). 135 were low risk, 85 moderate-risk, 31 high-risk and 8 very high-risk according to the HFA-ICOS score with a trend of increasing rates of CTRCD with each risk category: 5%, 12%, 10%, 25%, respectively. The sensitivity and specificity of a combined moderate/high/very high-risk group was 70% and 54% (AUC 0.618, 95% CI 0.5-0.73). Only three individual baseline variables were associated with CTRCD in this cohort; ejection fraction 50-54%, (18% vs 2%, p=0.0027), borderline/abnormal average global longitudinal strain <-18, (43% vs 19%, p=0.04) and combination anthracycline plus trastuzumab, (45% vs 22%, p=0.0392). Left atrial volume index >34mL/m² was also higher in the CTRCD group (38% vs 23%) although not statistically significant. A simplified risk score using only these variables yielded a sensitivity and specificity of 74% and 53%, respectively (AUC 0.633, 95% CI 0.52-0.75).

Conclusion

Baseline prediction of CTRCD remains difficult in clinical practice. Although HFA-ICOS risk categories correlate with CTRCD diagnosis, the overall sensitivity is only moderate. Echocardiographic variables may further enhance risk prediction to enable development of targeted monitoring strategies.HFA-ICOS risk score categoriesROC curves
Cardioprotective role of statins in breast cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis
Authors: Lingamsetty S S P , Kritya M , Huang W , Fatima S R , Gewehr D M , Doma M , Pastrana S H , Hemdanieh M , Naji Z , Kuhar K , Martignoni F
Published: October 2024

Background

Statins may have cardioprotective effects in patients undergoing cardiotoxic chemotherapy regimens. Yet, their role in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity in patients with breast cancer remains unclear.

Purpose

To perform a systematic review and meta-analysis to evaluate the efficacy of statins in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity among patients with breast cancer.

Methods

We systematically searched PubMed, Embase, and Cochrane databases until January 2024 for studies comparing the efficacy of statin therapy versus no statin therapy in breast cancer patients receiving either anthracyclines, trastuzumab, or both. Cardiotoxicity was defined as per the definition of each individual study. A random-effects model was used to assess pooled risk ratios (RR) and mean differences (MD) with corresponding 95% confidence intervals. Statistical analyses were performed using Review Manager version 5.4.1.

Results

We included five studies, of which two were randomised trials. The pooled population comprised 1,839 anthracyclines and/or trastuzumab-treated patients with breast cancer, of whom 864 (47%) received statin therapy. In the pooled analyses, cardiotoxicity was significantly lower in the statin therapy group as compared with the no statin therapy group (RR 0.45; 95% CI 0.27 to 0.72; p=0.001; Figure 1A), additionally statin therapy was associated with a significantly lower reduction in left ventricular ejection fraction as compared with no statin therapy (MD 4.11%; 95% CI 2.68 to 5.53; p<0.00001; Figure 1B).

Conclusion

In this meta-analysis, statin therapy in anthracyclines and/or trastuzumab-treated patients with breast cancer was associated with lower cardiotoxicity and decline in left ventricular ejection fraction.
SLC4A3 anion exchanger mutations associated to sudden death : short or long QT syndrome?
Authors: Benbekhti S B , Maury P M , Placide L P , Delsarte L D , Massin F M , Granier M G , Probst V P , Pasquie J L P
Published: October 2024

Introduction

SLC4A3 gene codes for an (Cl-/HCO3-) exchanger present on the surface of cardiomyocytes (AE3 channel) is involved in maintaining the physiological acid-base gradient of the cardiomyocyte at rest. Loss of function of the SLC4A3 gene leading to an increase in intracellular pH has. been reported to be responsible for short QT syndrome (SQT).

Methods

The aim of our study was to characterize the genotype-phenotype relationships of SLC4A3 mutations identified in the French databases (Paris, Nantes and Lyon) in patients with sudden death. Through systematic exome sequencing we identified 3 new SLC4A3 variants in 3 families with a history of sudden death in two universitary hospitals.

Results

Family 1. The c.3209G>C variant (p.Gly1070Ala) in the SLC4A3 gene was identified in a 7-yo boy with VF at sleep but admitted in encephalic death. EKG showed short QT (QTc 280ms). Clinical examination, blood tests, TTE and autopsy were normal. There was no family history of sudden death. His mother had EKG evidence of SQT and was carrier the SLC4A3 mutation. She was implanted with an ICD. His two older brothers and the rest of the family had no mutation or pathological ECG and were asymptomatic.

Family 2. The c.1027C>T (p.Arg343Cys) mutation in the SLC4A3 gene was identified in a 29-year-old man who presented with sudden death at sleep (VF). Clinical examination, blood tests, TTE and autopsy were normal. A maternal uncle died suddenly while sleeping. His two brothers (30 and 27 yo) are both carriers of the SLC4A3 mutation and exhibit SQT (QTc 320 and 330 ms respectively). TEE, Holter monitoring and stress test were normal in both. Both brothers were treated with hydroquinidine. Over a 2-year follow-up they had no symptom nor AF.

Family 3. The c.1022C>G (p.Thr341Arg) mutation was identified in the SLC4A3 gene in a 54-yoman who presented with VF during shower but admitted in encephalic death. There was no family history of sudden death. Clinical examination, blood tests and echocardiography as well as coronary angiogram were normal. The initial ECG showed a prolonged QT interval (QTc 520 ms). QTc decreased to 480 ms in the 48 following hours. His parents and his sister as well as his 18 yo daughter have normal QTc values. We are awaiting the genetic results.

Conclusion

Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 has been recently reported to cause short QT syndrome but it seems that in rare cases it may also be responsible for LQTS. Further patients are needed to confirm these data. In order to understand the underlying electrophysiological mechanisms, we plan to characterize the cellular impact of these new mutations through IPS.
Risk assessment using DEVI and CARPREG -1 score to predict maternal adverse cardiac cvents in pregnancies with valvular heart disease: external validation study from MPAC registry
Authors: Gnanaraj J P , Anne Princy S , Anju S , Keepanasseril A
Published: October 2024

Background

Even though many risk assessment tools in pregnant women with valvular heart disease (VHD) are available, validation studies are few that assess their performance in diverse settings, which is needed prior to the application of routine clinical practice.

Objectives

To validate and establish the clinical utility of two risk stratification tools – DEVI (VHD-specific tool) and CARPREG-I in predicting adverse cardiac events in pregnant patients with VHD.

Methods

This cohort study involved consecutive pregnancies complicated with VHD enrolled in the prospective MPAC registry from July 2016 to December 2019(1). The ability to discriminate those with and without adverse cardiac outcomes was assessed using the area under the curve for both the DEVI and CARPREG-1 scores. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis.

Results Among 1029 pregnancies complicated with heart disease in the MPAC registry cohort, 604(52.3%) with valvular heart disease were included in this analysis. One or more composite adverse cardiac events occurred in 70 (11.6%) pregnancies during antenatal or the early postpartum period. Mitral regurgitation was the most common lesion (67.7%). In assessing the pregnancy outcomes, those who continued past 20 weeks were included, with the majority (92.0%) delivered at term, and the cesarean rates were 33.6% (n=203). The most common adverse event was heart failure (n=32, 5.3%), most of which (68.6%) occurred in the postnatal period. There were 11 maternal deaths (1.8%) during the study period, six among those with mechanical heart valves (four prosthetic valve thrombosis), two among those with severe mitral stenosis and pulmonary hypertension and two with severe mitral regurgitation and infective endocarditis.

The area under the receiver operating characteristic curve (AUC) was 0.766, with 95% confidence intervals (CI) 0.703- 0.828 for DEVI and 0.703 (95%CI 0.644- 0.763) for CARPREG-I models. Calibration plots suggested that the DEVI score overestimates risk at higher probabilities, whereas the CARPREG-I score underestimates the risk at most probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 60%.

Conclusion

In this external validation study in pregnant women with primary rheumatic VHD, DEVI and CARPREG-I scores showed good discrimination ability and clinical utility across various probabilities. Both can be used to classify those who develop adverse cardiac outcomes during pregnancy and childbirth. However, both models need recalibration to improve the agreement between the predicted and observed events prior to routine application in diverse clinical settings.Figure 1.a and b ROC and Decision Curves
Severity of pulmonary hypertension and pregnancy outcomes: newer insights from the M-PAC registry
Authors: Gnanaraj J P , Anne Princy S , Anju Surendran S , Meena Suresh T S , Kalaivani K , Kanmani K , Nandakumaran M , Ashok Viktor A V , Rani D R , Prathap Kumar G , Rajasekar Ramesh D , Elavarasi E , Elangovan C , Nageswaran P M , Arul A S
Published: October 2024

Background

Pregnancy outcomes in women with pulmonary hypertension remain suboptimal. Pregnant women with pulmonary hypertension (PH) are placed in the modified WHO category IV, regardless of the severity or etiology of PH. Earlier studies have indicated that pregnancy outcomes may differ based on the etiology, with more favourable outcomes observed with PH related to left to right shunts. However, it is possible that the pregnancy outcomes may vary based on the severity of PH also.

Purpose

To analyse pregnancy outcomes in women with PH and investigate differences based on disease severity.

Methods

M-PAC Registry, is a single center prospective study of pregnancies in women with heart diseases, conducted between July 2016 and December 2019 in a low-and middle-income country from South Asia, whose methodology and outcomes have been published(1). The current study analysed pregnancies with PH enrolled in the M-PAC registry. The tricuspid regurgitation velocity obtained during transthoracic echocardiography, was used to estimate right ventricular systolic pressure (RVSP). Based on the estimated RVSP, PH was classified into three groups; mild (36-45 mm of Hg), moderate (46-64 mm of Hg) and severe (≥ 65 mm of Hg). The differences in the maternal and foetal outcomes among the groups were analysed.

Results

Of the 1029 pregnancies complicated by heart disease enrolled in the M-PAC registry, 352(34.2%)had PH. Among these 352 pregnancies, 186(52.8%) had mild, 73 (20.7%) had moderate and 93 (26.5%) had severe PH.

Adverse maternal cardiac events occurred in 77 pregnancies (21.8%), with heart failure in 53(15.1%) and mortality in 10(2.8%). The composite adverse foetal event rate was 38.6%, foetal loss at 9.7%, low birth weight at 28.9%, and preterm labour at 7.1%. The mean (±standard deviation) RVSP was higher in pregnancies with adverse maternal outcome (58.81±16.9 vs 51.16±15.9; P < 0.001) or adverse foetal outcome (58.10±17.3 vs 49.52±14.9; P < 0.001)compared to those without.

When comparing the three groups, pregnancies with mild PH exhibited significantly lower rates of adverse maternal and fetal events compared to those with severe and moderate PH (Fig-1 and Table-1). Mild PH was associated with outcomes similar to those without PH in the M-PAC registry.

Conclusion

The severity of PH significantly correlated with the adverse pregnancy outcomes. Women with mild PH tend to experience pregnancy outcomes comparable to those without PH, suggesting that pregnancy should not be deemed contraindicated in this subgroup. Therefore, re-evaluation of the placement of PH within the modified World Health Organization (mWHO) classification is warranted, considering the severity of PH.Figure 1:Pregnancy Outcomes & PH SeverityTable-1 PH Severity & Pregnacny Outcomes
The relationship between coronary flow reserve and the TyG index in patients with gestational diabetes mellitus
Authors: Bugday I , Ozyildirim S , Barman H A , Dogan O , Aydin I , Ozkan F , Abbasov Y , Ersanli M K , Dogan S M
Published: October 2024

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder characterized by glucose intolerance during pregnancy. The triglyceride glucose (TyG) index, a marker of insulin resistance, and coronary flow reserve (CFR), a measure of coronary microvascular function, are emerging as potential indicators of cardiovascular risk.

This study aims to investigate the association between CFR and the TyG index in GDM patients.

This cross-sectional study of 87 GDM patients and 36 healthy controls was conducted. The participants underwent clinical assessments, blood tests, and echocardiographic evaluations. The TyG index was calculated as ln(triglycerides × fasting glucose/2). CFR was measured using Doppler echocardiography during rest and hyperemia induced by dipyridamole.

The study included 87 individuals in the GDM group and 36 individuals in the control group. There was no significant difference in age between the two groups (34.1 ± 5.3 years for GDM vs. 33.1 ± 4.9 years for the control, p = 0.364). The TyG index was significantly higher in the GDM group compared to the controls (p < 0.001) and CFR was lower in the GDM group (p < 0.001) as shown in Figure 1a and 1b. A negative and significant correlation between the TyG index and CFR was observed, which was demonstrated in Figure 2 (r = −0.624, p < 0.001). Linear regression revealed the TyG index as an independent predictor of reduced CFR.

The study findings reveal a significant association between the TyG index and CFR in GDM patients, suggesting their potential role in assessing cardiovascular risk.TyG index and CFR of the groupsTyG and CFR correlation analysis
Characterization of left atrial function during cardiac (reverse) remodeling induced by pregnancy
Authors: Ferreira A F , Anjos S , Azevedo M J , Morais J , Saraiva F A , Diaz S O , Sousa C , Machado A P , Leite-Moreira A , Sampaio-Maia B , Ramalho C , Barros A S , Falcao-Pires I
Published: October 2024

Introduction

The hemodynamic overload in pregnancy leads to cardiovascular remodeling, characterized by enlargement of left atrial (LA) and ventricular (LV) volumes associated with impaired LV relaxation, maintaining preserved systolic function. These changes are reversible during postpartum. Few scientific evidence has been published about LA function yet.

Purpose

To assess the changes in LA function through two-dimensional speckle tracking echocardiography analysis during pregnancy and its recovery up to 1 year after delivery and to determine potential predictors of its progression.

Methods

This prospective cohort study included volunteer pregnant women (healthy, obese and/or hypertensive and/or with gestational diabetes) recruited in two tertiary centers between 2019 and 2021. Women were evaluated by transthoracic echocardiography at the 1st trimester [1T, 10-15 weeks, baseline], 3rd trimester [3T, 30-35 weeks, peak of cardiac remodeling] of pregnancy as well as at the 1st, 6th and 12th month after delivery (during RR). Generalized linear mixed-effects models evaluated the extent of RR, including the variation of left atrial strain and its potential predictors.

Results

We included 130 pregnant women with a median age of 33 [30,36] years, 39,2% multiparas. Fifty-four (41.5%) were diagnosed with at least one cardiovascular risk factor. A significant enlargement of LA volume (24 [22, 28]mL/m2 to 29 [25, 33]mL/m2, p<0.001) associated with the increase of E/e’ (5.85 [5.08, 6.36] to 6.70 [5.67, 7.82], p<0.001) was observed from 1T to 3T, both recovering as soon as 1 month after delivery (LA volume: 29 [25, 33]mL/m2 to 24 [20, 27] mL/m2, p<0.001; E/e’: 6.70 [5.67, 7.82] to 5.70 [4.82, 6.47], p<0.001). Regarding LA function, a significant reduction of LA strain was verified from 1T to 3T (35 [31, 41]% to 31 [29, 36]%, p<0.001), recovering 6 months postpartum (31 [29, 36]% to 33 [30, 38]%, p=0.035). Systemic vascular resistance seemed to be an independent predictor of lower LA strain (-3.83 [-6.40, -1.25], p=0.004). The presence of cardiovascular risk factors (-0.80 [-2.28, 0.68], p=0.287), smoking habits (-1.26 [-2.82, 0.30], p=0.112), parity (-0.33 [-1.93, 1.27], p=0.684) and age (-0.11 [-0.29, 0.08], p=0.257) showed a non-significant impact in LA strain.

Conclusion

Despite the recovery in diastolic function and LA volume 1 month after delivery, the LA function only significantly improved 6 months later. Systemic vascular resistance was revealed as an independent predictor of LA strain.
The effect of HIV seropositivity on inpatient outcomes in atrial tachyarrhythmias: a US population analysis
Authors: Brown D , Dixon B , Cummings S , Simpson T , Henry D , Folkes J , Piplani S , Gallippi V , Sedaghati M , Radulovic M
Published: October 2024

Background

With the advent of antiretroviral therapy, the life expectancy of persons living with HIV(PLHIV) has been significantly prolonged and we are now seeing this group increasingly affected by chronic conditions. Atrial fibrillation is the most common sustained tachyarrhythmias in adults and commonly coexists with atrial flutter. HIV-1 especially has been shown to possess a specific cardiac tropism in which chronic immune activation and inflammation may lead to cytotoxicity and death of cardiac myocytes. It has also been associated with left atrial enlargement, which may increase arrhythmia generation and propagation. The effect of HIV on outcomes in atrial tachyarrhythmias have been poorly studied, so we therefore wanted to explore this influence on in-patient outcomes.

Purpose

To assess the effect of HIV seropositivity on inhospital outcomes of patients admitted with atrial fibrillation/flutter (AF)

Method

The study uses data from the HCUP-NIS database, which includes billing information from hospitals across the US. The study population included patients admitted with a principal diagnosis of atrial fibrillation or atrial flutter in 2020. Patients with HIV positivity were identified using ICD-10 codes. Multivariate regression was used to analyze outcomes while adjusting for confounders. They were classified into two groups: AF-only (AF-O) and AF with HIV (AF-H).

Results

A total of 400,715 patients were admitted with a primary diagnosis of atrial fibrillation/flutter in 2020, 1175 were PLHIV. Patients in the AF-H group were more likely to be younger, non-Caucasian, tobacco smokers, have lower median income, be uninsured, have HFrEF and CKD. They however had lower rates of HFpEF than persons in the AF-O group. After adjusting for hospital level confounders, the in-hospital mortality rate was similar between the two groups (aOR 0.46 95% CI 0.05-3.98, p=0.48). The rates of ischemic stroke/systemic embolization, major bleeding, in hospital respiratory failure, length of stay and total hospital charges were also not significantly different

Conclusion

The study suggests that AF patients with HIV have similar in-hospital mortality rates as patients without. There are significant differences in the economic and ethnic makeup of the two groups but these did not significantly influence the outcomes of interest. Larger cohorts will be needed to confirm these findings definitively, especially as more persons with HIV continue surviving past the sixth decade of life.
Reduction of aortic stiffness in newly diagnosed persons with HIV-infection: modifiable vascular dysfunction after antiretroviral therapy?
Authors: Robbertse P S , Doubell A F , Herbst P G
Published: October 2024

Background

People living with HIV (PLWH) are at an increased risk of cardiovascular disease (CVD), which is underestimated by contemporary risk stratification systems[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD. Aortic stiffness, as measured with pulse wave velocity (PWV), is a validated predictor of CVD [2,3] and has been shown to be elevated in PLWH at the time of HIV diagnosis compared to HIV-uninfected persons[4].

Purpose

To prospectively assess the influence of contemporary antiretroviral therapy (ART) on aortic stiffness in a group of newly diagnosed PLWH in a low- to middle-income setting.

Methods

A group of ART naïve PLWH with modest cardiovascular risk and free from known CVD, was recruited at the time of HIV diagnosis from the Western Cape Province of South Africa. Aortic stiffness was measured using carotid-femoral PWV on a commercially available device that simultaneously measured the carotid and femoral waveforms on a supine patient in a temperature-controlled room utilising established methodology[4]. The algorithmically-calculated time delay between the upstroke of the carotid and femoral wave-forms provided the transit time (TT). Carotid femoral path distance (path length) was measured using surface anatomy. PWV was calculated as direct path length divided by TT. Aortic distensibility was expressed according to the Bramwell-Hill equation as 3.57/PWV(squared)[5]. ART was initiated and PWV was re-evaluated 9 months later.

Results

Seventy-three participants completed follow-up and were included. The cohort was relatively young (mean age 32±7 years) with good female representation (n=33, 45%). Most received tenofovir/lamivudine/dolutegravir (n=71, 97%) Half of the group smoked cigarettes. Two participants were controlled hypertensives, and two participants had metabolic syndrome. A significant decrease in PWV (with scaling factor of 0.8) was observed at 9 months of ART (5.93 ±1.0 vs. 5.69 ±1.0 m/s; p=0.01). Aortic distensibility increased significantly as well (0.20 [IQR: 0.16 to 0.26] vs. 0.21 [IQR: 0.19 to 0.27] mmHg-1; p=0.02).

Conclusion

Improvement in aortic stiffness was observed in a group of newly diagnosed PLWH after 9 months of ART-initiation. This provides evidence of a modifiable component of vascular dysfunction and, in turn, cardiovascular risk with the use of contemporary ART at 9 months. It is unknown if this effect will be sustained long-term. The use of aortic stiffness (alone or in combination with other parameters) as a predictor of cardiovascular outcomes in the ART era requires further study.Abstract figureAbstract table
Aerobic exercise capacity improvement of patients with human immunodeficiency virus one year post-treatment initiation by integrase inhibitors
Authors: Triantafyllidi H , Birmpa D , Benas D , Fragkou P , Protopapas K , Kavvatha D , Papadopoulos A , Antoniadou A
Published: October 2024

Background

Infection by Human Immunodeficiency Virus (HIV) leads to chronic inflammation and subsequently to the early development of cardiovascular (CV) disease in young adults. Initiation of antiretroviral therapy (ART) usually leads to patient’s body weight and blood pressure increase. Cardiopulmonary exercise test (CPET) evaluates aerobic exercise capacity and subsequently cardiovascular and respiratory function. Aim of this study is the investigation of any treatment-induced changes in aerobic exercise capacity in treatment naïve young HIV patients’ at 1-year post HIV treatment initiation by different ART agents.

Methods

We studied 46 recently diagnosed and treatment naïve young HIV patients (37+10 years, 87% males, 62% smokers) at baseline and 1-year post ART initiation (integrase or protease inhibitors). Twenty-six (26) patients were randomly treated by the newer integrase inhibitor Dolutegravir (Group A, mean age=36+9 years, 100% males, 77% smokers) while 19 patients by the older protease inhibitor Darunavir/Cobicistat (Group B, mean age=37+10 years, 90% males, 47% smokers). All patients were submitted in CPET at baseline and 1-year post ART initiation. We estimated any changes in body mass index (BMI), systolic blood pressure (SBP) and CPET parameters (peak VO2, Oxygen pulse, WorkLoad, VE/VCO2) at 1-year post ART initiation.

Results

At baseline and 1-year re-evaluation, we found no differences between groups regarding age, BMI and CPET parameters. In the whole HIV population, we found an increase in body weight (76+12 vs. 82+15kg, p<0.001), SΒΡ (124+12 vs. 132+14mmHg, p<0.001), WorkLoad (176+35 vs. 186+35watt, p<0.001) and peak VO2 (2171+437 vs. 2299+491ml/min, p=0.03) at 1-year re-evaluation. In Group A, body weight (p<0.001), SBP (p=0.07), WorkLoad (p=0.006) and peak VO2 (p=0.01) were increased while in Group B, body weight (p<0.001), SBP (p=0.001) και WorkLoad (p=0.01) were also increased.

Conclusions

Aerobic exercise capacity is improved 1-year post-treatment initiation by the newer integrase inhibitor Dolutegravir in treatment-naïve HIV patients despite the adverse BMI and SBP increase. The newer Dolutegravir probably exhibits a more favorable CV profile in HIV patients compared to the older Darunavir/Cobicistat.Re-evaluation 1-year post ART initiation