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ESC Heart Failure Jun 2024Anthracycline chemotherapy (AC) for breast cancer can cause cancer therapy-related cardiac dysfunction (CTRCD) with resultant heart failure, traditionally defined as a...
AIMS
Anthracycline chemotherapy (AC) for breast cancer can cause cancer therapy-related cardiac dysfunction (CTRCD) with resultant heart failure, traditionally defined as a reduction in left ventricular (LV) ejection fraction on echocardiography. In recent years, global longitudinal systolic strain (GLS) has been used to identify subclinical cardiac dysfunction prior to development of overt CTRCD. Recent harmonized guidelines have incorporated GLS into definitions for CTRCD to identify cardiac dysfunction and inform decisions regarding cardioprotective strategies.
METHODS AND RESULTS
We evaluated subclinical dysfunction in breast cancer patients treated with AC and determined the echocardiographic and patient factors associated with significant GLS changes. One hundred fourteen HER2 negative patients treated with AC were prospectively recruited and underwent serial echocardiograms (LVEF and LVGLS) at three time points (prior to AC, 3 months, and 1 year). CTRCD was defined as an asymptomatic reduction in LVEF of 10% or symptomatic drop of 5% to LVEF <53%. Subclinical LV dysfunction was defined as a reduction of ≥10% in GLS compared with baseline, recognizing that this cut off identified an 'at risk cohort' rather than patients with established CTRCD. No participant demonstrated CTRCD by reduction in LVEF. Forty-three patients (38%) demonstrated a ≥10% relative reduction in GLS at 12 months; 20/43 (47%) had a reduced absolute GLS to <16%, and were older, had hypertension, increased LV mass, lower baseline e' velocity and GLS. GLS ≥20.5% at baseline yielded a sensitivity of 79% and specificity of 87% for a normal GLS (i.e., ≥16%) at 1 year despite a ≥10% reduction from baseline.
CONCLUSIONS
We present a stepwise evaluation for subclinical LV dysfunction using both a relative reduction in GLS combined with an absolute reduction in GLS. We believe our findings may re-stratify patients with a high baseline GLS into a lower risk group despite transient relative GLS decrements ≥10%.
PubMed: 38887181
DOI: 10.1002/ehf2.14884 -
BMJ Open Diabetes Research & Care Jun 2024Oxidative stress is known to affect left ventricular functions negatively. There is a strong bidirectional connection between diabetes mellitus (DM) and oxidative... (Observational Study)
Observational Study
INTRODUCTION
Oxidative stress is known to affect left ventricular functions negatively. There is a strong bidirectional connection between diabetes mellitus (DM) and oxidative stress. In parallel, left ventricular dysfunction is observed more frequently, even in patients with DM without other risk factors. In this context, the objective of this study is to comparatively investigate the potential relationship between oxidative stress and subclinical left ventricular dysfunction (SCLVD) assessed by Myocardial Performance Index (MPI) in patients with and without DM.
RESEARCH DESIGN AND METHODS
The sample of this observational cross-sectional single-center study consisted of 151 patients who were evaluated for oxidative stress and SCLVD by tissue Doppler echocardiography. Patients' total oxidant status (TOS), total antioxidant status (TAS), and Oxidative Stress Index (OSI) values were calculated. The effects of oxidative stress and DM on MPI were analyzed.
RESULTS
There were 81 patients with DM (mean age: 46.17±10.33 years) and 70 healthy individuals (mean age: 45.72±9.04 years). Mean TOS and OSI values of the DM group were higher than healthy individuals (5.72±0.55 vs 5.31±0.50, p = <0.001; and 4.92±1.93 vs 1.79±0.39, p = <0.001; respectively). The mean TAS value of the DM group was significantly lower than the healthy group (1.21±0.40 vs 3.23±0.51, p = <0.001). There was a significant correlation between OSI and MPI mitral in the DM group (R 0.554, p = <0.001) but not in the healthy group (R -0.069, p=0.249).
CONCLUSIONS
Both oxidative stress and myocardial dysfunction were found to be more common in patients with DM. The study's findings indicated the negative effect of oxidative stress on myocardial functions. Accordingly, increased oxidative stress caused more significant deterioration in MPI in patients with DM compared with healthy individuals.
Topics: Humans; Oxidative Stress; Female; Male; Middle Aged; Ventricular Dysfunction, Left; Cross-Sectional Studies; Adult; Case-Control Studies; Antioxidants; Diabetes Mellitus; Biomarkers; Ventricular Function, Left; Echocardiography, Doppler; Diabetes Mellitus, Type 2; Prognosis; Follow-Up Studies
PubMed: 38886070
DOI: 10.1136/bmjdrc-2024-004153 -
JCI Insight Jun 2024Parasympathetic dysfunction after chronic myocardial infarction (MI) is known to predispose ventricular tachyarrhythmias (VT/VF). VT/VF after MI is more common in males...
Parasympathetic dysfunction after chronic myocardial infarction (MI) is known to predispose ventricular tachyarrhythmias (VT/VF). VT/VF after MI is more common in males than females. The mechanisms underlying the decreased vagal tone and the associated sex difference in the occurrence of VT/VF after MI remain elusive. In this study, using optogenetic approaches, we found that responses of glutamatergic vagal afferent neurons were impaired following chronic MI in male mice, leading to reduced reflex efferent parasympathetic function. Molecular analyses of vagal ganglia demonstrated reduced glutamate levels, accompanied by decreased mitochondrial function and impaired redox status in infarcted males vs. sham animals. Interestingly, infarcted females demonstrated reduced vagal sensory impairment, associated with greater vagal ganglia glutamate levels and decreased vagal mitochondrial dysfunction and oxidative stress compared to infarcted males. Treatment with 17β-estradiol mitigated this pathological remodeling and improved vagal neurotransmission in infarcted male mice. These data suggest that a decrease in efferent vagal tone following MI results from reduced glutamatergic afferent vagal signaling that may be due to impaired redox homeostasis in the vagal ganglia, which subsequently leads to pathological remodeling in a sex-dependent manner. Importantly, estrogen prevents pathological remodeling and improves parasympathetic function following MI.
PubMed: 38885308
DOI: 10.1172/jci.insight.181042 -
Journal of Thoracic Disease May 2024Little is known about the role of complement activation in acute pulmonary embolism (PE). We investigated whether complement activation is associated with the severity...
BACKGROUND
Little is known about the role of complement activation in acute pulmonary embolism (PE). We investigated whether complement activation is associated with the severity of acute PE, along with the associated prothrombotic state, systemic inflammation and neutrophil extracellular traps (NETs) formation.
METHODS
We studied 109 normotensive, non-cancer PE patients (aged 58.1±15.0 years). On admission prior to initiation of anticoagulation, plasma soluble complement components, i.e., C3a and sC5b-9, were measured with enzyme-linked immunosorbent assay (ELISA), along with thrombin generation, fibrinolysis proteins (plasminogen, antiplasmin, plasminogen activator inhibitor-1), factor VIII (FVIII) activity, and fibrin clot properties, including clot permeability (K, a measure of clot density) and clot lysis time (CLT). Moreover, we determined inflammatory markers and citrullinated histone H3, a specific marker of NETs formation.
RESULTS
Patients in the lower tertile of C3a (≤1.45 ng/mL, n=37) had lower simplified Pulmonary Embolism Severity Index (sPESI) values and were less likely to have right ventricular (RV) dysfunction compared to the remaining subjects. The former subgroup also had 13% lower FVIII activity, but not fibrinogen, interleukin-6, fibrinolysis proteins, and thrombin generation. Plasma C3a levels correlated inversely with K and positively with CLT indicating formation of denser and poorly lysable clots in subjects with elevated C3a. Despite a positive association between C3a and sC5b-9, the latter parameter was solely associated with higher FVIII, but not with other variables.
CONCLUSIONS
We showed that in acute PE enhanced complement activation characterizes patients with poorer short-term prognosis who display prothrombotic fibrin clot properties and elevated FVIII, which supports the involvement of complement proteins in acute thromboembolism.
PubMed: 38883666
DOI: 10.21037/jtd-24-171 -
Indian Heart Journal Jun 2024Acute pulmonary embolism (APE) is the third most common cause of vascular death. Data on APE from India and other low-and middle-income countries is sparse.
BACKGROUND
Acute pulmonary embolism (APE) is the third most common cause of vascular death. Data on APE from India and other low-and middle-income countries is sparse.
OBJECTIVES
Study the clinical characteristics, prognostic factors, in-hospital mortality (IMH) and 12 months mortality of patients with APE in India.
METHODS
We prospectively enrolled 186 consecutive patients diagnosed with APE between November 2016 and November 2021 in Madras Medical College Pulmonary Embolism Registry (M-PER). All patients had electrocardiography and echocardiography. High risk patients and selected intermediate risk patients underwent fibrinolysis.
RESULTS
75 % of our patients were below 50 years of age. 35 % were women. The mean time to presentation from symptom onset was 6.04 ± 10.01 days. 92 % had CT pulmonary angiography. Intermediate risk category (61.3 %) was the more common presentation followed by high risk (26.9 %). Electrocardiography showed S1Q3T3 pattern in 56 %. 76 % had right ventricular dysfunction and 12.4 % had right heart thrombi(RHT) by echocardiography. 50.5 % received fibrinolysis. Patients with RHT received fibrinolysis more frequently (78.3 % vs 46.6 %; p = 0.007). In-hospital mortality (IHM) was 15.6 %. Systemic arterial desaturation and need for mechanical ventilation independently predicted IHM. Ten patients (5.3 %) were lost to follow up. One year mortality was 26.7 % (47/176). One year mortality of patients discharged alive was similar among high, intermediate and low risk groups(14.8 % vs 1.9 % vs 10.5 %; p = 0.891).
CONCLUSIONS
Patients with PE are often young and present late in India. The in-hospital and 12 months mortality were high. Low and intermediate risk groups had a high post discharge mortality similar to high risk patients.
PubMed: 38878966
DOI: 10.1016/j.ihj.2024.06.008 -
Renal Failure Dec 2024Recent accumulating evidence has recently documented a significant prevalence of right ventricular dysfunction (RVD) in end-stage renal disease (ESRD) patients....
AIMS
Recent accumulating evidence has recently documented a significant prevalence of right ventricular dysfunction (RVD) in end-stage renal disease (ESRD) patients. Tricuspid annular plane systolic excursion (TAPSE)/pulmonary-artery systolic pressure (PASP) ratio assessed with echocardiography might be a useful clinical index of right ventricular (RV) -pulmonary arterial (PA) coupling. The current study aimed to investigate the value of the TAPSE/PASP ratios in patients on maintenance hemodialysis (MHD).
METHODS
We studied 83 times echocardiographic tests from 68 patients with MHD. The associations of TAPSE/PASP ratios with echocardiography variables, clinical characteristics, and biochemical parameters were analyzed, as well as the associations of TAPSE/PASP ratios with odds of all-cause mortality, cardiovascular disease (CVD) events and frequent intermittent dialysis hypotension (IDH).
RESULTS
Correlation analysis showed TAPSE/PASP ratios positively correlated with LVEF and negatively correlated with E/A and E/e' values. For clinical and biochemical parameters, TAPSE/PASP ratios negatively correlated with BNP, NT-proBNP, age, CRP, and average interdialysis weight gain (ΔBW) and positively correlated with albumin. Logistic regression analysis, which induced the TAPSE/PASP ratio as a continuous variable (per 0.1 mm/mmHg increase), identified that the TAPSE/PASP ratio was associated with decreased CVD events (OR 0.386 [95% CI 0.231-0.645], < 0.001) and frequent IDH odds (OR 0.571 [95% CI 0.397-0.820], = 0.002). Moreover, the TAPSE/PASP ratio independently predicted CVD events (adjusted HR 0.539 [95% CI 0.391-0.743], < 0.001) during a follow-up period of 12 months.
CONCLUSIONS
RVD, assessed by echocardiography TAPSE/PASP ratio, was found to be associated with increased risks of CVD events and frequent IDH in patients with MHD.
Topics: Humans; Male; Female; Renal Dialysis; Ventricular Dysfunction, Right; Middle Aged; Aged; Kidney Failure, Chronic; Echocardiography; Cardiovascular Diseases; Retrospective Studies; Pulmonary Artery; Logistic Models; Tricuspid Valve
PubMed: 38874087
DOI: 10.1080/0886022X.2024.2364766 -
Frontiers in Pharmacology 2024Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart...
Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats. Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment. GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects.
PubMed: 38873418
DOI: 10.3389/fphar.2024.1402138 -
Journal of the Saudi Heart Association 2024Sickle Cell Disease (SCD) is not a hematologic disease that occurs in isolation; it results in multi-organ complications. There is growing evidence of vascular stiffness...
BACKGROUND
Sickle Cell Disease (SCD) is not a hematologic disease that occurs in isolation; it results in multi-organ complications. There is growing evidence of vascular stiffness as its underlying cause. This study aimed to investigate the relationship between endothelial stiffness and LV dysfunction in SCD patients and to explore its pathophysiology, particularly regarding the depletion of vasodilators such as Nitric Oxide (NO).
METHODOLOGY
32 patients with established criteria for SCD and 40 healthy control subjects were selected for this case-control study. Comprehensive clinical assessment and assessment of endothelial function using Brachial Flow-mediated dilation (FMD) were performed, along with serum NO measurement, which was followed by diagnosis and echocardiographic assessment using 3D speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI).
RESULTS
Collected SCD cases showed echocardiographic features of Systo-diastolic dysfunction with reduced FMD compared to controls, denoting endothelial dysfunction in those patients. LDH showed a marked elevation, while serum NO showed a significant reduction in cases compared with controls. We also noted a positive correlation between FMD on the one hand and measures of ventricular dysfunction and level of serum NO on the other hand, the latter proving that reduction of NO is responsible for reduced endothelial function.
CONCLUSION
We present the first report to date to outline the role of vascular stiffness as measured by brachial FMD in the induction of left ventricular dysfunction in SCD. We recommend that more research be conducted regarding possible strategies to replenish serum NO stores to delay microvascular injury and, in turn, ventricular dysfunction in SCD.
PubMed: 38873326
DOI: 10.37616/2212-5043.1369 -
Frontiers in Cardiovascular Medicine 2024Right ventricular (RV) fibrosis represents both adaptive and maladaptive responses to the overloaded RV condition. Its role in pulmonary hypertension (PH) associated...
Right ventricular fibrosis in adults with uncorrected secundum atrial septal defect and pulmonary hypertension: a cardiovascular magnetic resonance study with late gadolinium enhancement, native T1 and extracellular volume.
INTRODUCTION
Right ventricular (RV) fibrosis represents both adaptive and maladaptive responses to the overloaded RV condition. Its role in pulmonary hypertension (PH) associated with secundum atrial septal defect (ASD), which is the most common adult congenital heart disease (CHD), remains poorly understood.
METHODS
We enrolled 65 participants aged ≥18 years old with uncorrected secundum ASD who had undergone clinically indicated right heart catheterization (RHC), divided into the non-PH group ( = 7), PH group ( = 42), and Eisenmenger syndrome (ES) group ( = 16). We conducted cardiovascular magnetic resonance (CMR) studies with late gadolinium enhancement (LGE) imaging, native T1 mapping, and extracellular volume (ECV) measurement to evaluate the extent and clinical correlates of RV fibrosis.
RESULTS
LGE was present in 94% of the population and 86% of the non-PH group, mostly located at the right ventricular insertion point (RVIP) regions. LGE in the septal and inferior RV region was predominantly observed in the ES group compared to the other groups ( = 0.031 and < 0.001, respectively). The mean LGE scores in the ES and PH groups were significantly higher than those in the non-PH group (3.38 ± 0.96 vs. 2.74 ± 1.04 vs. 1.57 ± 0.79; = 0.001). The ES and PH groups had significantly higher degrees of interstitial RV fibrosis compared to those in the non-PH group, indicated by native T1 (1,199.9 ± 68.9 ms vs. 1,131.4 ± 47.8 ms vs. 1,105.4 ± 44.0 ms; < 0.001) and ECV (43.6 ± 6.6% vs. 39.5 ± 4.9% vs. 39.4 ± 5.8%; = 0.037). Additionally, native T1 significantly correlated with pulmonary vascular resistance ( = 0.708, < 0.001), RV ejection fraction ( = -0.468, < 0.001) and peripheral oxygen saturation ( = -0.410, = 0.001).
CONCLUSION
In patients with uncorrected secundum ASD, RV fibrosis may occur before the development of PH and progressively intensify alongside the progression of PH severity. A higher degree of RV fibrosis, derived from CMR imaging, correlates with worse hemodynamics, RV dysfunction, and poorer clinical conditions.
PubMed: 38873272
DOI: 10.3389/fcvm.2024.1395382 -
Frontiers in Cardiovascular Medicine 2024Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly...
BACKGROUND
Cardiac systolic dysfunction is a poor prognostic marker in light-chain (AL) cardiomyopathy, a primary interstitial disorder; however, its pathogenesis is poorly understood.
PURPOSE
This study aims to analyze the effects of extracellular volume (ECV) expansion, a surrogate marker of amyloid burden on myocardial blood flow (MBF), myocardial work efficiency (MWE), and left ventricular (LV) systolic dysfunction in AL amyloidosis.
METHODS
Subjects with biopsy-proven AL amyloidosis were prospectively enrolled (April 2016-June 2021; Clinicaltrials.gov ID NCT02641145) and underwent cardiac magnetic resonance imaging (MRI) to quantify rest MBF by perfusion imaging, LV ejection fraction (LVEF) by cine MRI, and ECV by pre- and post-contrast T1 mapping. The MWE was estimated as external cardiac work from the stroke volume and mean arterial pressure normalized to the LV myocardial mass.
RESULTS
Rest MBF in 92 subjects (62 ± 8 years, 52 men) with AL amyloidosis averaged 0.87 ± 0.21 ml/min/g and correlated with MWE ( = 0.42; < 0.001). Rest MBF was similarly low in subjects with sustained hematologic remission after successful AL amyloidosis therapy ( = 21), as in those with recently diagnosed AL amyloidosis. Both MBF and MWE decreased by ECV tertile ( < 0.01 for linear trends). The association of ECV with MWE comprised a direct effect (84% of the total effect; < 0.001) on MWE from adverse interstitial remodeling assessed by ECV and an indirect effect (16% of the total effect; < 0.001) mediated by MBF. There was a significant base-to-apex gradient of rest MBF in subjects with higher amyloid burden.
CONCLUSIONS
In AL amyloidosis, both MBF and MWE decrease as cardiac amyloid burden and ECV expansion increase. Both structural and vascular changes from ECV expansion and myocardial amyloid burden appear to contribute to lower MWE.
PubMed: 38873265
DOI: 10.3389/fcvm.2024.1371810