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JACC. Advances Apr 2024There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle.
BACKGROUND
There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle.
OBJECTIVES
The purpose of this study was to compare the incidence of atrial arrhythmias, thromboembolic events, cardiac transplantation, and death following Fontan palliation in patients with uRV vs uLV.
METHODS
The Alliance for Adult Research in Congenital Cardiology conducted a multicenter retrospective cohort study on patients with total cavopulmonary connection Fontan palliation across 12 centers in North America. All components of the composite outcome, that is, atrial arrhythmias, thromboembolic events, cardiac transplantation, and death, were reviewed and classified by a blinded adjudicating committee. Time-to-event analyses were performed that accounted for competing risks.
RESULTS
A total of 384 patients were followed for 10.5 ± 5.9 years. The composite outcome occurred in 3.7 vs 1.7 cases per 100 person-years for uRV (N = 171) vs uLV (N = 213), respectively ( < 0.001). In multivariable analyses, uRV conferred a >2-fold higher risk of the composite outcome (HR: 2.17, 95% CI: 1.45-3.45, < 0.001). In secondary analyses of components of the primary outcome, uRV was significantly associated with a greater risk of cardiac transplantation or death (HR: 9.09, 95% CI: 2.17-38.46, < 0.001) and atrial arrhythmias (HR: 2.17, 95% CI: 1.20-4.00, = 0.010) but not thromboembolic events (HR: 1.64, 95% CI: 0.86-3.16, = 0.131).
CONCLUSIONS
Fontan patients with uRV vs uLV morphology have a higher incidence of adverse cardiovascular events, including atrial arrhythmia, cardiac transplantation, and all-cause mortality.
PubMed: 38939676
DOI: 10.1016/j.jacadv.2024.100871 -
JACC. Advances Apr 2024Managing patients with atrial fibrillation (AF) and worsening renal function (WRF) remains a clinical challenge due to the need of dose adjustment of non-vitamin K...
BACKGROUND
Managing patients with atrial fibrillation (AF) and worsening renal function (WRF) remains a clinical challenge due to the need of dose adjustment of non-vitamin K antagonist oral anticoagulants.
OBJECTIVES
To determine the incidence of WRF in patients with AF treated with edoxaban, the association of WRF with clinical outcomes, and predictors of WRF and clinical outcomes in these patients.
METHODS
This is a subanalysis of the Edoxaban Treatment in routiNe clinical prActice for patients with non-valvular Atrial Fibrillation in Europe study (NCT02944019), an observational study of edoxaban-treated patients with AF. WRF was defined as a ≥25% reduction in creatinine clearance between baseline and 2 years.
RESULTS
Of the 9,054 patients included (69% of the total 13,133 enrolled), most did not experience WRF (90.3%) during the first 2 years of follow-up. WRF occurred in 9.7% of patients. Patients with WRF had significantly higher rates of all-cause death (3.88%/y vs 1.88%/y; < 0.0001), cardiovascular death (2.09%/y vs 0.92%/y; < 0.0001), and major bleeding (1.51%/y vs 0.98%/y; = 0.0463) compared with those without WRF. Rates of intracranial hemorrhage (0.18%/y vs 0.18%/y) and of any stroke/systemic embolic events were low (0.90%/y vs 0.69%/y; = 0.3161) in both subgroups. The strongest predictors of WRF were a high CHADS-VASc score, high baseline creatinine clearance, low body weight, and older age. Most predictors of WRF were also predictors of clinical outcomes.
CONCLUSIONS
WRF occurred in approximately 10% of edoxaban-treated AF patients. Rates of death and major bleeding were significantly higher in patients with WRF than without. Stroke events were low in both subgroups.
PubMed: 38939675
DOI: 10.1016/j.jacadv.2024.100880 -
JACC. Advances Apr 2024Adult congenital heart disease (ACHD) patients have significant morbidity and rise in cardiac admissions. Their outcome with high-dose influenza vaccination is unknown...
BACKGROUND
Adult congenital heart disease (ACHD) patients have significant morbidity and rise in cardiac admissions. Their outcome with high-dose influenza vaccination is unknown in comparison to those without ACHD.
OBJECTIVES
The purpose of this study was to compare all-cause mortality or cardiopulmonary hospitalizations in self-identified ACHD versus non-ACHD patients receiving high- or low-dose influenza vaccination within the INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure trial.
METHODS
We prospectively included ACHD patients in the INVESTED (INfluenza Vaccine to Effectively Stop cardioThoracic Events and Decompensated heart failure) trial. The primary endpoint was all-cause death or hospitalization for cardiovascular or pulmonary causes.
RESULTS
Of the 272 ACHD patients, 132 were randomly assigned to receive high-dose trivalent and 140 to standard-dose quadrivalent influenza vaccine. Compared to the non-ACHD cohort (n = 4,988), ACHD patients were more likely to be younger, women, smokers, have atrial fibrillation, and have a qualifying event of heart failure. The primary outcome was 49.8 events versus 42.8 events per 100 person-years (adjusted HR: 1.17; 95% CI: 0.95-1.45; = 0.144) in the ACHD group and non-ACHD group, respectively. The interaction between ACHD status and randomized treatment effect was not significant for the primary outcome ( = 0.858). Vaccine-related adverse events were similar in both groups.
CONCLUSIONS
Patients who self-identify as being ACHD had similar primary outcome of all-cause death or hospitalization for cardiovascular or pulmonary causes compared to non-ACHD cohort. High-dose influenza vaccination was similar to standard-dose influenza vaccination on the primary outcome in patients who self-identify as ACHD.
PubMed: 38939662
DOI: 10.1016/j.jacadv.2024.100897 -
JACC. Advances Apr 2024A treatment strategy for congenital heart defects with moderate to severe pulmonary arterial hypertension (PAH) has not been established.
BACKGROUND
A treatment strategy for congenital heart defects with moderate to severe pulmonary arterial hypertension (PAH) has not been established.
OBJECTIVES
The purpose of this study was to identify patients in whom a treat and repair strategy was considered and to examine pretreatment variables associated with successful defect repair.
METHODS
Patients with atrial or ventricular septal defect and PAH (pulmonary vascular resistance [PVR] ≥ 5 Wood units) eligible for the treat and repair strategy were included. Hemodynamics among pretreatment, pre-repair, and post-defect repair were compared. Clinical outcomes in patients with or without defect repair were also compared. Clinical outcomes included all-cause death, hospitalization for worsening pulmonary hypertension, and lung transplantation.
RESULTS
Among 25 eligible for the treat and repair strategy, 20 underwent successful repair (repaired group) and 5 did not have a repair (unrepaired group). In the repaired group, PVR significantly decreased from 9.6 ± 2.6 WU at pretreatment to 5.0 ± 3.4 pre-repair (ß coefficient -4.6 [95% CI: -5.9 to -3.3]). The pulmonary to systemic blood flow ratio (Qp/Qs) increased from 1.5 ± 0.6 at pretreatment to 2.4 ± 1.3 pre-repair (ß coefficient 0.9 [95% CI: 0.4-1.38]). In the unrepaired group, pretreatment PVR decreased with treatment; however, PVR remained elevated. Qp/Qs did not change between pretreatment and post-treatment. The repaired group had a better prognosis than the unrepaired group (HR 0.092 [95% CI: 0.009-0.905]). Pretreatment mean pulmonary artery pressure, PVR, Qp/Qs, and arterial oxygen saturations were associated with undergoing defect repair.
CONCLUSIONS
In this small cohort, a treat and repair strategy was successfully used in a significant proportion of the patients with congenital heart defects with moderate to severe PAH.
PubMed: 38939653
DOI: 10.1016/j.jacadv.2024.100887 -
JACC. Advances May 2024For infants with single ventricle heart disease, the time after stage 2 procedure (S2P) is believed to be a lower risk period compared with the interstage period;...
BACKGROUND
For infants with single ventricle heart disease, the time after stage 2 procedure (S2P) is believed to be a lower risk period compared with the interstage period; however, significant morbidity and mortality still occur.
OBJECTIVES
This study aimed to identify risk factors for mortality or transplantation referral between S2P surgery and the first birthday.
METHODS
Retrospective cohort analysis of infants in the National Pediatric Cardiology Quality Improvement Collaborative who underwent staged single ventricle palliation from 2016 to 2022 and survived to S2P. Multivariable logistic regression and classification and regression trees were performed to identify risk factors for mortality and transplantation referral after S2P.
RESULTS
Of the 1,455 patients in the cohort who survived to S2P, 5.2% died and 2.3% were referred for transplant. Overall event rates at 30 and 100 days after S2P were 2% and 5%, respectively. Independent risk factors for mortality and transplantation referral included the presence of a known genetic syndrome, shunt type at stage 1 procedure (S1P), tricuspid valve repair at S1P, longer time to extubation and reintubation after S1P, ≥ moderate tricuspid regurgitation prior to S2P, younger age at S2P, and the risk groups identified in the classification and regression tree analysis (extracorporeal membrane oxygenation after S1P and longer S2P cardiopulmonary bypass time without extracorporeal membrane oxygenation).
CONCLUSIONS
Mortality and transplantation referral rates after S2P to 1 year of age remain high ∼7%. Many of the identified risk factors after S2P are similar to those established for interstage factors around the S1P, whereas others may be unique to the period after S2P.
PubMed: 38939642
DOI: 10.1016/j.jacadv.2024.100934 -
JACC. Advances May 2024
PubMed: 38939636
DOI: 10.1016/j.jacadv.2024.100922 -
Oncology Letters Aug 2024Tumor lysis syndrome (TLS) is a rare but serious complication in patients with solid tumors. It is characterized by a complex array of metabolic disturbances and...
Tumor lysis syndrome in a patient with advanced lung squamous cell carcinoma undergoing combined therapy with a programmed cell death protein 1 inhibitor and first‑line chemotherapy: A case report.
Tumor lysis syndrome (TLS) is a rare but serious complication in patients with solid tumors. It is characterized by a complex array of metabolic disturbances and clinical symptoms, resulting from the release of cellular contents into the bloodstream after tumor cell lysis. The present study reports the case of a patient with advanced lung squamous cell carcinoma (SCC) who developed TLS following combined treatment with PD-1 inhibitors and first-line chemotherapy. The treatment strategy included intravenous fluid replacement, urine alkalinization, uric acid reduction, renal protection and electrolyte stabilization, leading to the normalization of laboratory values. After one cycle of the combined therapy, the patient achieved a partial response, classified using the Response Evaluation Criteria in Solid Tumours 1.1 criteria. To the best of our knowledge, this is the first reported case of TLS in a patient with advanced lung SCC receiving concurrent PD-1 inhibitor and chemotherapy treatment. Given the increasing use of PD-1 inhibitors, it is essential to remain vigilant about the potential for TLS in solid tumors. Prompt intervention in high-risk patients, ongoing monitoring after treatment, and early detection of TLS are vital to improve patient adherence, ensure continuity of care and enhance outcomes.
PubMed: 38939620
DOI: 10.3892/ol.2024.14513 -
JACC. Advances May 2023Bleeding events are frequently applied as safety end points for randomized controlled trials (RCTs) investigating the effect of antithrombotic agents in patients with...
BACKGROUND
Bleeding events are frequently applied as safety end points for randomized controlled trials (RCTs) investigating the effect of antithrombotic agents in patients with coronary artery disease. However, whether a bleeding event is a valid surrogate for death remain uncertain.
OBJECTIVES
This study aimed to assess the correlation between the treatment effect on bleeding events and mortality.
METHODS
Multiple databases were searched to identify RCTs studying antithrombotic agents for patients with coronary artery disease through August 2022. Major and minor bleeding events were defined in included trials, mostly defined with BARC (Bleeding Academic Research Consortium) or TIMI (Thrombolysis In Myocardial Infarction) criteria. Trial-level correlations between nonfatal bleeding events and mortality were assessed. We performed subgroup analyses by the definitions of bleeding (BARC vs TIMI criteria), study year, and follow-up duration. We used a cutoff with a lower limit of 95% confidence interval of R >0.72 as a strong correlation and with an upper limit of 95% confidence interval of R <0.50 as a weak correlation.
RESULTS
A total of 48 RCTs with 181,951 participants were analyzed. Overall, trial-level R for major and minor bleeding were 0.09 (95% CI: 0.00-0.26) and 0.09 (95% CI: 0.00-0.27) for all-cause or cardiovascular death, respectively. When confined to major bleeding, R were 0.03 (95% CI: 0.00-0.13) and 0.01 (95% CI: 0.00-0.05), respectively. All of the subgroup analyses did not show any significant correlations.
CONCLUSIONS
We demonstrated a trial-defined bleeding event may not be a valid surrogate for mortality in RCTs investigating the effect of antithrombotic agents for coronary artery disease.
PubMed: 38939598
DOI: 10.1016/j.jacadv.2023.100276 -
Frontiers in Public Health 2024Ozone pollution is associated with cardiovascular disease mortality, and there is a high correlation between different pollutants. This study aimed to assess the...
BACKGROUND
Ozone pollution is associated with cardiovascular disease mortality, and there is a high correlation between different pollutants. This study aimed to assess the association between ozone and cardiovascular disease deaths and the resulting disease burden in Nanjing, China.
METHODS
A total of 151,609 deaths from cardiovascular disease were included in Nanjing, China from 2013 to 2021. Daily data on meteorological and air pollution were collected to apply a generalized additional model with multiple pollutants to perform exposure-response analyses, stratification analysis, and evaluation of excess deaths using various standards.
RESULTS
In the multi-pollutant model, an increase of 10 μg/m in O was significantly associated with a 0.81% (95%CI: 0.49, 1.12%) increase in cardiovascular disease deaths in lag05. The correlation weakened in both the single-pollutant model and two-pollutant models, but remained more pronounced in females, the older group, and during warm seasons. From 2013 to 2021, the number of excess deaths attributed to ozone exposure in cardiovascular disease continued to rise with an increase in ozone concentration in Nanjing. If the ozone concentration were to be reduced to the WHO standard and the minimum level, the number of deaths would decrease by 1,736 and 10,882, respectively.
CONCLUSION
The risk of death and excess deaths from cardiovascular disease due to ozone exposure increases with higher ozone concentration. Reducing ozone concentration to meet WHO standards or lower can provide greater cardiovascular disease health benefits.
Topics: Ozone; Humans; Cardiovascular Diseases; China; Female; Male; Air Pollutants; Environmental Exposure; Air Pollution; Middle Aged; Aged; Seasons; Adult; Rivers
PubMed: 38939565
DOI: 10.3389/fpubh.2024.1353384 -
Oncoimmunology 2024The need for reliable biomarkers to predict clinical benefit from anti-PD1 treatment in metastatic melanoma (MM) patients remains unmet. Several parameters have been...
The need for reliable biomarkers to predict clinical benefit from anti-PD1 treatment in metastatic melanoma (MM) patients remains unmet. Several parameters have been considered in the tumor environment or the blood, but none has yet achieved sufficient accuracy for routine clinical practice. Whole blood samples from MM patients receiving second-line anti-PD1 treatment (NCT02626065), collected longitudinally, were analyzed by flow cytometry to assess the immune cell subsets absolute numbers, the expression of immune checkpoints or ligands on T cells and the functionality of innate immune cells and T cells. Clinical response was assessed according to Progression-Free Survival (PFS) status at one-year following initiation of anti-PD1 (responders: PFS > 1 year; non-responders: PFS ≤ 1 year). At baseline, several phenotypic and functional alterations in blood immune cells were observed in MM patients compared to healthy donors, but only the proportion of polyfunctional memory CD4+ T cells was associated with response to anti-PD1. Under treatment, a decreased frequency of HVEM on CD4+ and CD8+ T cells after 3 months of treatment identified responding patients, whereas its receptor BTLA was not modulated. Both reduced proportion of CD69-expressing CD4+ and CD8+ T cells and increased number of polyfunctional blood memory T cells after 3 months of treatment were associated with response to anti-PD1. Of upmost importance, the combination of changes of all these markers accurately discriminated between responding and non-responding patients. These results suggest that drugs targeting HVEM/BTLA pathway may be of interest to improve anti-PD1 efficacy.
Topics: Humans; Melanoma; Male; Receptors, Immunologic; Female; Middle Aged; Aged; Programmed Cell Death 1 Receptor; Receptors, Tumor Necrosis Factor, Member 14; Immune Checkpoint Inhibitors; Adult; Treatment Outcome; CD8-Positive T-Lymphocytes
PubMed: 38939518
DOI: 10.1080/2162402X.2024.2372118