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ESMO Open Aug 2023Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Trastuzumab deruxtecan (T-DXd) has been shown to benefit progression-free survival and overall survival in patients with metastatic breast cancer (mBC) after progression on ≥1 human epidermal growth factor receptor 2 (HER2)-targeted therapies. However, interstitial lung disease (ILD) and cardiotoxicity are the most significant toxicities associated with T-DXd. Therefore, we conducted a systematic review and meta-analysis to assess the incidence and severity of these toxicities in mBC patients treated with T-DXd.
MATERIALS AND METHODS
We searched PubMed, Cochrane, and Scopus databases, and conferences websites for randomized clinical trials and nonrandomized studies of intervention including HER2-low or HER2-positive mBC patients who received at least one dose of T-DXd. Statistical analysis was carried out using R software.
RESULTS
We included 15 studies comprising 1970 patients with a mean follow-up of 13.3 months. Median age ranged from 53 to 59 years, 61.9% were non-Asian, and 67.4% had hormone receptor-positive mBC. In a pooled analysis, the incidence of ILD was 11.7% [222 patients; 95% confidence interval (CI) 9.1% to 15.0%]. Patients receiving T-DXd dose of 6.4 mg/kg developed a significantly higher rate of ILD (22.7%) compared to those receiving a dose of 5.4 mg/kg (9.3%) (P < 0.01). Most cases of ILD (80.2%; 174/217 patients) were mild (grade 1 or 2). Grade 3 or 4 ILD was reported in 29 patients (13.4%), and grade 5 in 14 patients (6.4%). The incidence of decreased left ventricular ejection fraction (LVEF) was 1.95% (95% CI 0.65% to 3.73%), and the QT interval (QTi) prolongation was 7.77% (95% CI 2.74% to 20.11%). Most patients were asymptomatic, but four had LV dysfunction and heart failure (0.26%).
CONCLUSIONS
In this meta-analysis of 1970 patients with mBC, treatment with T-DXd was associated with a 11.7% incidence of ILD, 7.7% incidence of prolonged QTi, and 1.9% incidence of reduced LVEF. Early detection and management of T-DXd-related toxicity by a multidisciplinary team may ultimately improve patient outcomes.
Topics: Humans; Middle Aged; Female; Breast Neoplasms; Cardiotoxicity; Incidence; Stroke Volume; Ventricular Function, Left; Lung Diseases, Interstitial
PubMed: 37481956
DOI: 10.1016/j.esmoop.2023.101613 -
Heart Failure Reviews Nov 2023The role of lipoprotein(a) [Lp(a)] as a possible causal risk factor for atherosclerotic artery disease and aortic valve stenosis has been well established. However, the... (Review)
Review
The role of lipoprotein(a) [Lp(a)] as a possible causal risk factor for atherosclerotic artery disease and aortic valve stenosis has been well established. However, the information on the association between Lp(a) levels and heart failure (HF) is limited and controversial. The main objective of the present study was to assess the association between Lp(a) levels and HF. This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect studies that evaluated the association between Lp(a) levels and HF. Eight studies, including 73,410 patients, were eligible for this research. Seven prospective or retrospective cohorts and one cross-sectional study were analyzed. Five studies analyzed populations without HF; another three included patients with HF or left ventricular dysfunction. The endpoints evaluated varied according to the study analyzed, including incident HF, HF hospitalizations, and decreased left ventricular ejection fraction. Lp(a) levels were also analyzed in different ways, including analysis of Lp(a) as a continuous or categorical variable (distinct cut-off points or percentiles). Globally, the studies included in this review found predominantly positive results. Data on some relevant subgroups, such as HF of ischemic or non-ischemic etiology or HF with or without left ventricular dysfunction, was poorly reported. This systematic review suggests that there would be a positive relationship between Lp(a) levels and HF. Given the complexity and heterogeneity of HF, new studies should be developed to clarify this topic.
PubMed: 37466712
DOI: 10.1007/s10741-023-10333-2 -
European Urology Focus Nov 2023Erectile dysfunction (ED) is associated with an increased risk of cardiovascular morbidity and mortality. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Erectile dysfunction (ED) is associated with an increased risk of cardiovascular morbidity and mortality.
OBJECTIVE
To systematically review and analyze the cardiac structure and function in men with ED assessed with echocardiography.
EVIDENCE ACQUISITION
We performed a systematic review and meta-analysis according to the guideline of the Preferred Reporting Items for Systematic Reviews and Meta-analyses. We searched PubMed and the Cochrane Library on June 2, 2022, and included studies evaluating cardiac structure and function using echocardiography in men with ED compared with controls without ED. The Newcastle-Ottawa Quality Assessment Scale was used for assessing the quality of studies. We analyzed the mean differences in left ventricular ejection fraction (LVEF), the ratio of early transmitral filling velocity to early diastolic mitral annular velocity (E/e'), ratio of the early to late diastolic transmitral flow velocity (E/A), isovolumic relaxation time (IVRT), and left ventricular mass index (LVMi) in a random-effect model computed using means and standard deviations. The review was preregistered with PROSPERO (CRD42022337183). We received no funding.
EVIDENCE SYNTHESIS
We included ten studies with 763 men diagnosed with ED (mean age: 55.6 yr) and 358 control men (mean age: 54.4 yr). E/e' was significantly worse in men with ED than in controls (mean absolute difference = 1.17, 95% confidence interval or CI [0.68, 1.65], p < 0.005). No significant differences were observed in LVEF, E/A, IVRT, or LVMi (-0.06, 95% CI [-1.06, 0.95], p = 0.91; -0.06, 95% CI [-0.24, 0.13], p = 0.55; 11.76, 95% CI [-0.88, 24.39], p = 0.07; and 4.37, 95% CI [-2.91, 11.65], respectively). The studies exhibited heterogeneity regarding study populations, reported echocardiography data, and variations in adjustments for confounding factors.
CONCLUSIONS
Left ventricle diastolic dysfunction, as assessed by E/e', was more frequent in men with ED than in matched controls without ED. The results imply that echocardiography may be useful in the cardiovascular evaluation of men with ED to help identify myocardial impairment.
PATIENT SUMMARY
This study reviewed for the first time previous research on cardiac structure and function in men with erectile dysfunction (ED), as assessed by echocardiography. We found that men with ED, compared with men without ED, had a higher ratio of early transmitral filling velocity to early diastolic mitral annular velocity , indicating a potentially higher rate of impaired diastolic function-a potential early indicator of heart disease. Identification of early signs of heart problems in men with ED may help initiate necessary lifestyle modifications or preventative therapies before the development of heart disease. However, more research is required to determine the clinical utility of using echocardiography as a risk assessment method.
Topics: Male; Humans; Middle Aged; Erectile Dysfunction; Ventricular Function, Left; Stroke Volume; Ventricular Dysfunction, Left; Diastole
PubMed: 37355365
DOI: 10.1016/j.euf.2023.06.001 -
The American Journal of Cardiology Nov 2023Heart failure (HF) is often categorized by left ventricular (LV) ejection fraction (LVEF). A new category of HF characterized by supra-normal LVEF (>65%), named HF with... (Review)
Review
Heart failure (HF) is often categorized by left ventricular (LV) ejection fraction (LVEF). A new category of HF characterized by supra-normal LVEF (>65%), named HF with supra-normal ejection fraction (HFsnEF), has been recently proposed. Some studies reported that patients with supra-normal LVEF might have an increased risk of long-term major adverse cardiovascular events and U-shaped mortality patterns. Currently, the prognosis of HFsnEF is not well established but seems to be associated with an increased risk of long-term major adverse cardiovascular events. It has been reported that HFsnEF is more prevalent in women and is associated with higher prevalence of nonischemic HF, higher blood urea nitrogen plasma levels, lower levels of natriuretic peptides, and to be less likely treated with β blockers. The pathophysiology of HFsnEF would be associated with microvascular dysfunction because of microvascular inflammation or reduced coronary flow reserve, and low stroke volume index with smaller cardiac chamber dimensions and concentric LV geometry. In this study, we systematically reviewed published data on patients with s supra-normal LV function and reported its definition, proposed pathophysiology, phenotypes, diagnostic strategy, and prognosis.
Topics: Humans; Female; Ventricular Function, Left; Stroke Volume; Heart Failure; Prognosis; Inflammation; Ventricular Dysfunction, Left
PubMed: 37734305
DOI: 10.1016/j.amjcard.2023.08.169 -
Cells Nov 2023There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past... (Review)
Review
There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.
Topics: Humans; Heart Ventricles; Epigenesis, Genetic; Ventricular Dysfunction, Right; Myocardium; Ventricular Function, Right
PubMed: 38067121
DOI: 10.3390/cells12232693 -
Frontiers in Cardiovascular Medicine 2023Left ventricular dysfunction and cardiomyopathy are well documented adverse effects associated with chemotherapy agents. Limited information exists regarding the impact... (Review)
Review
BACKGROUND
Left ventricular dysfunction and cardiomyopathy are well documented adverse effects associated with chemotherapy agents. Limited information exists regarding the impact of chemotherapeutic agents on the integrity and function of the right ventricle (RV).
OBJECTIVES
The current metanalysis compared pre- chemotherapy versus post- chemotherapy RV parameters measured on 2D echocardiography in patients receiving anthracycline and/or trastuzumab across all breast cancer patients.
METHODS
A systematic search across PubMed, EMBASE and Cochrane databases were performed from inception of the databases until November 2021 for relevant studies. We used the inverse variance method with a random effect model and DerSimonian and Laird method of Tau2 generation to calculate mean difference [MD] with 95% confidence interval [CI]. The analysis was carried out using RevMan Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).
RESULTS
Fifteen studies, constituting total of 644 patients, met the inclusion criteria, with most studies having a follow up period of less than 12 months from initiation of chemotherapy. Anthracycline and/or Trastuzumab chemotherapy resulted in a statistically significant reduction in right ventricular ejection fraction (RVEF) at follow-up [MD: 2.70, 95% CI: 0.27 to 5.13, -value- 0.03, - 71%, -value < 0.05]. Treatment with Anthracycline and/or Trastuzumab chemotherapy resulted in a significant reduction in RV fractional area change (RVFAC) at follow-up [MD: 3.74, 95% CI: 1.33 to 6.15, -value < 0.01, - 68%, -value < 0.05]. RV free wall longitudinal strain (RVFWLS) was lower at baseline, while LVEF was significantly reduced at follow-up [MD: -1.00, 95% CI: -1.86 to -0.15, -value < 0.05, - 0%, -value-0.40], [MD: 4.04, 95% CI: 2.08 to 6.01, -value < 0.01, - 91%, -value < 0.05], respectively. However, treatment with Anthracycline and/or Trastuzumab chemotherapy had no statistically significant effect on Tricuspid annular plane systolic excursion (TAPSE) at follow-up [MD: 0.53, 95% CI: -0.11 to 1.17, -value-0.11, - 98%, -value < 0.05].
CONCLUSIONS
Chemotherapy with anthracyclines and trastuzumab negatively affects right ventricular function leading to decline in RVEF, RVFAC, RVFWLS and LVEF.
PubMed: 37600030
DOI: 10.3389/fcvm.2023.1103941 -
EClinicalMedicine Aug 2023Right ventricular dysfunction (RVD) is associated with adverse outcomes of acute pulmonary embolism (PE). However, there are no studies describing the long-term,...
BACKGROUND
Right ventricular dysfunction (RVD) is associated with adverse outcomes of acute pulmonary embolism (PE). However, there are no studies describing the long-term, full-spectrum right ventricular parameters on morphology, pressure and function at certain follow-up time points after PE onset. More exploration of right ventricular function would provide useful clues for long-term management of patients with PE.
METHODS
For this systematic review and meta-analysis, we completed a literature search in Pubmed, EMBASE and WebofScience (from Jan 1st, 1998 to April 20th, 2023). Studies of patients with acute PE followed-up longer than 3 months with right ventricle assessment and written in English-language were included. Right ventricular function was assessed by either echocardiography or computed tomographic pulmonary angiography (CTPA). The primary outcome was structural and functional parameters of the right ventricle, and the secondary outcomes were functional assessments [New York Heart Association (NYHA) functional classification and 6-min walk test distance (6 MWD)], at each follow-up time points. Random effect meta-analyses were performed using R software (PROSPERO: CRD42023433332).
FINDINGS
A total of 33 studies (3920 patients) were included in the final analysis. The 3-month, 6-month and 1-year prevalence of right ventricular dysfunction (RVD) was 0.34 [95% confidence interval (CI) 0.21-0.48, I = 96%], 0.26 (95% CI 0.17-0.36, I = 93%) and 0.34 (95% CI 0.19-0.48, I = 94%), respectively. Pooled tricuspid annulus plane systolic excursion (TAPSE), right ventricular to left ventricular diameter (RV/LV) ratio and pulmonary artery systolic pressure (PASP) at 1-year was 21.80 mm (95% CI 20.08-23.52, I = 93%), 0.64 (95% CI 0.48-0.81, I = 92%) and 27.33 mmHg (95% CI 18.88-35.78) (I = 96%), respectively. The proportion of NYHA III-IV was 0.06 (95% CI 0.0-0.12) and the pooled 6 MWD was 462.98 m (95% CI 447.55-478.41) over 1 year. Patients treated with thrombolysis had lower prevalence of RVD (1-year 0.17 and 0.07 in systemic thrombolysis and catheter-directed thrombolysis, respectively) than those treated with anticoagulation therapy alone (1-year 0.24) but the pooled risk ratio (RR) was not statistically significant.
INTERPRETATION
Although the conclusion of this study may be limited by its high heterogeneity from varied study designs, inclusion criteria and definition of RVD of each study, our findings suggested that persistent RVD and functional impairment were of considerable high prevalence during long-term follow-up after acute PE. Treatment strategy may influence the prevalence of long-term RVD.
FUNDING
This study is supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-061). The National Key Research and Development Program of China (2016YFC0905600). National High Level Hospital Clinical Research Funding (2022-NHLHCRF-LX-01-02-03). CAMS Institute of Respiratory Medicine Grant for Young Scholars (2023-ZF-8).
PubMed: 37638233
DOI: 10.1016/j.eclinm.2023.102153 -
Diabetologia Apr 2024Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of... (Meta-Analysis)
Meta-Analysis Review
Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016-October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al's risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment.Registration PROSPERO ID CRD42022368035.
Topics: Adult; Humans; Heart Failure; Diabetes Mellitus, Type 2; Stroke Volume; Prognosis; Disease Progression
PubMed: 38334818
DOI: 10.1007/s00125-023-06068-2 -
American Journal of Obstetrics &... Aug 2023Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes. Fetal cardiac dysfunction may be 1 part of the pathophysiology of pregnancies... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes. Fetal cardiac dysfunction may be 1 part of the pathophysiology of pregnancies complicated by intrahepatic cholestasis of pregnancy. This systematic review and meta-analysis aimed to evaluate the association between intrahepatic cholestasis of pregnancy and fetal cardiac dysfunction.
DATA SOURCES
Systematic searches were performed on the databases of Medline, Embase, and Cochrane Library (up to March 2, 2023) for studies evaluating fetal cardiac function in pregnancies complicated by intrahepatic cholestasis of pregnancy in addition to the reference lists of included studies.
STUDY ELIGIBILITY CRITERIA
Studies were eligible for inclusion if they assessed the fetal cardiac function by fetal echocardiography in women with intrahepatic cholestasis of pregnancy (mild or severe) and compared with fetuses of healthy pregnant women. The studies published in English were included.
METHODS
The quality of the retrieved studies was assessed using the Newcastle-Ottawa Scale. Data on fetal myocardial performance index, E wave/A wave peak velocities ratio, and PR interval were pooled for the meta-analysis using random-effects models. The results were presented as weighted mean differences and 95% confidence intervals. This meta-analysis was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42022334801).
RESULTS
A total of 14 studies were included in this qualitative analysis. Of note, 10 studies that reported data on fetal myocardial performance index, E wave/A wave peak velocities ratio, and PR interval were included in the quantitative analysis and showed a significant association between intrahepatic cholestasis of pregnancy and fetal cardiac dysfunction. Significantly higher fetal left ventricular myocardial performance index values (weighted mean difference, 0.10; 95% confidence interval, 0.04-0.16) and longer fetal PR intervals (weighted mean difference, 10.10 ms; 95% confidence interval, 7.34-12.86) were revealed in pregnancies complicated by intrahepatic cholestasis of pregnancy. Compared with the situation in pregnancies complicated by mild intrahepatic cholestasis of pregnancy, PR intervals were even longer in pregnancies complicated by severe intrahepatic cholestasis of pregnancy (weighted mean difference, 5.98 ms; 95% confidence interval, 0.20-11.77). There was no significant difference in fetal E wave/A wave peak velocities ratio between the group with intrahepatic cholestasis of pregnancy and the healthy pregnant group (weighted mean difference, 0.01; 95% confidence interval, -0.03 to 0.05).
CONCLUSION
Our findings supported the idea that intrahepatic cholestasis of pregnancy is associated with overall impaired fetal myocardial performance and impaired fetal cardiac conduction system. However, current evidence about the association between fetal cardiac dysfunction and intrahepatic cholestasis of pregnancy-induced stillbirth is lacking. Further studies are needed to reveal the relationship between fetal cardiac dysfunction and adverse perinatal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy.
Topics: Pregnancy; Female; Humans; Pregnancy Complications; Stillbirth; Cholestasis, Intrahepatic; Fetus
PubMed: 37023984
DOI: 10.1016/j.ajogmf.2023.100952 -
Cureus Aug 2023The commonest cause of hepatic illness globally is non-alcoholic fatty liver disease (NAFLD). This multisystemic disease affects extrahepatic organs, including the... (Review)
Review
The commonest cause of hepatic illness globally is non-alcoholic fatty liver disease (NAFLD). This multisystemic disease affects extrahepatic organs, including the heart. It causes cardiac remodeling and a disruption of the systolic and diastolic functioning of the left ventricle. Numerous studies have investigated the connection between NAFLD and left ventricular diastolic dysfunction (LVDD). The results, nevertheless, are often contradictory. This systematic review looked at the relationship between NAFLD and LVDD generally and among different patient groups since it is a topic of interest. A thorough search approach was used to locate relevant publications published between 2003 and 2023 using major medical databases. Studies were chosen based on the pre-established eligibility criteria; the studies selected then underwent a critical evaluation using standardized quality assessment tools. For the systematic review, 13 articles were chosen, comprising nine cross-sectional studies, three narrative reviews, and one meta-analysis. There were a total of 13,341 NAFLD patients in these studies. Data extraction and qualitative synthesis from the selected research articles were conducted to determine the relationship between NAFLD and LVDD in various patient categories. We found a significant association between NAFLD and LVDD. Therefore, patients with NAFLD should be treated early to avoid complications since they are more likely to develop cardiac dysfunction in the future.
PubMed: 37674936
DOI: 10.7759/cureus.43013