PURPOSE OF REVIEWAdvances in cancer treatments have resulted in significant improvements in survival. Anthracycline chemotherapeutics play a major role in the treatment of hematologic malignancies ...and solid tumors; however, there is a risk of anthracycline cardiomyopathy in survivors. This focused review will provide a historical context on anthracycline cardiomyopathy and will also review pathophysiologic mechanisms of cardiotoxicity, dosage recommendations, prognosis, and outcomes.
RECENT FINDINGSAnthracycline inhibition of topoisomerase 2β in cardiomyocytes is believed to be the dominant mechanism of anthracycline-related cardiotoxicity. Emerging data suggest that downregulation of the RNA-binding protein quaking 5 may also be contributing. There is continued lack of agreement regarding what dosage of anthracycline is associated with the highest risk of cardiotoxicity.
SUMMARYOngoing research into the mechanisms of anthracycline cardiotoxicity is warranted to allow for the development of targeted preventive therapies. A consensus definition of anthracycline cardiomyopathy will facilitate analyses of existing data and allow for the conduction of prospective clinical trials in this area.
New anti-neoplastic drugs have improved survival of cancer patients but have also been associated with chemotherapy-induced cardiomyopathy (CCMP), ultimately requiring orthotopic heart ...transplantation (OHT). We conducted this study to describe the clinical characteristics and outcomes of patients with CCMP treated with OHT and compare them with outcomes of patients with other forms of non-ischemic cardiomyopathy (NICMP).
We retrospectively identified 232 CCMP patients and 8,890 NICMP patients from the International Society of Heart and Lung Transplantation Registry who underwent OHT between January 2000 and December 2008. Survival rates were calculated using the Kaplan-Meier method. Categoric characteristics and outcomes groups were compared using the χ(2) and Fisher exact test. Comparisons for continuous variables were made using Wilcoxon-Mann-Whitney test. Multivariable analyses of predictors of survival were performed using Cox proportional hazard regression analysis.
Short-term and long-term post-transplant survival of the 232 CCMP patients was similar to the 8,890 NICMP patients (p = 0.19). Survival (95% confidence interval) at 1, 3, and 5 years was, respectively, 86% (0.81-0.91), 79% (0.76-0.87), and 71% 0.73-0.85) in the CCMP patients and 87% (0.86-0.88), 81% (0.82-0.84), and 74% (0.80-0.81) in the NICMP patients (p = 0.19). Compared with NICMP patients, CCMP patients had higher rates of post-OHT infection (22% vs 14%, p = 004) and malignancies (5% vs 2%, p = 0.006), but neither affected survival. There was only 1 malignancy recurrence in the CCMP patients and no differences in post-OHT death due to malignancies between the groups. Importantly, CCMP patients were twice as likely as NICMP patients to require right ventricular assist devices before OHT (5.6% vs 2.3%, p = 0.0021).
Patients with CCMP selected for OHT are younger, have less comorbidity, and are more likely to require biventricular mechanical support pre-OHT than other NICMP patients who receive allografts. Despite the higher incidence of malignancy and infection in CCMP patients who have received a heart transplant, their survival is comparable to those who receive allografts for other cardiomyopathies.
Objective
We aimed to develop a risk prediction model using a machine learning to predict survival and graft failure (GF) 5 years after orthotopic heart transplant (OHT).
Methods
Using the ...International Society of Heart and Lung Transplant (ISHLT) registry data, we analyzed 15,236 patients who underwent OHT from January 2005 to December 2009. 342 variables were extracted and used to develop a risk prediction model utilizing a gradient-boosted machine (GBM) model to predict the risk of GF and mortality 5 years after hospital discharge. After excluding variables missing at least 50% of the observations and variables with near zero variance, 87 variables were included in the GBM model. Ten fold cross-validation repeated 5 times was used to estimate the model’s external performance and optimize the hyperparameters simultaneously. Area under the receiver operator characteristic curve (AUC) for the GBM model was calculated for survival and GF 5 years post-OHT.
Results
The median duration of follow-up was 5 years. The mortality and GF 5 years post-OHT were 27.3% (
n
= 4161) and 28.1% (
n
= 4276), respectively. The AUC to predict 5-year mortality and GF is 0.717 (95% CI 0.696–0.737) and 0.716 (95% CI 0.696–0.736), respectively. Length of stay, recipient and donor age, recipient and donor body mass index, and ischemic time had the highest relative influence in predicting 5-year mortality and graft failure.
Conclusion
The GBM model has a good accuracy to predict 5-year mortality and graft failure post-OHT.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
5.
DOBUTAMINE INDUCED EOSINOPHILIC CARDIOMYOPATHY Love, William T; Narichania, Aalap; Hardaway, Brian W
Journal of the American College of Cardiology,
04/2016, Volume:
67, Issue:
13
Journal Article
Peer reviewed
Open access
LVAD induced right heart failure was considered, but the presence of peripheral eosinophilia and new fever without evidence of infection raised concern for dobutamine induced eosinophilic ...cardiomyopathy.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Many advanced heart failure patients have both a left ventricular assist device (LVAD) and an implantable cardioverter‐defibrillator (ICD). This study examines incidence, clinical impact, ...and management of LVAD‐related EMI.
Methods
We performed a three‐center retrospective analysis of transvenous ICD implanted patients with LVAD implanted between January 1, 2005 and December 31, 2020. The primary outcome was EMI after LVAD implantation, categorized as LVAD‐related noise or telemetry interference.
Results
The rate of LVAD‐related EMI among the 737 patients (mean age 58.6 ± 12.8 years) studied was 5.0%. Telemetry interference (1.5%) compromised ICD interrogation in all patients. This was resolved successfully with use of a metal shield, encased wand, radiofrequency tower, different ICD programmer or by increasing distance between ICD programmer and LVAD (n = 6). ICD replacement was required to reestablish successful communication in three patients. LVAD‐related noise (3.5%) led to oversensing (n = 4), inappropriate mode switches (n = 4), noise reversion (n = 3), inhibition of pacing (n = 2), inappropriate detection as atrial fibrillation (AF) (n = 2) and inappropriate detection as ventricular tachycardia (VT) and/or ventricular fibrillation (VF) (n = 2). This noise interference persisted (n = 3), resolved spontaneously (n = 16), resolved with programming change (n = 6) or required lead revision (n = 1).
Conclusions
EMI from LVAD impacts ICD function, although, the incidence rate is low. Physicians implanting both, LVAD in patients with ICD (more common) or ICD in patients with LVAD, should be aware of possible interferences. Telemetry failure not resolved by metal shielding was overcome by ICD generator replacement to a different manufacturer. In most cases, LVAD‐related noise resolves spontaneously.
Full text
Available for:
BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV ...is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.
Clonal haematopoiesis, which is highly prevalent in older individuals, arises from somatic mutations that endow a proliferative advantage to haematopoietic cells. Clonal haematopoiesis increases the ...risk of myocardial infarction and stroke independently of traditional risk factors
. Among the common genetic variants that give rise to clonal haematopoiesis, the JAK2
(JAK2
) mutation, which increases JAK-STAT signalling, occurs at a younger age and imparts the strongest risk of premature coronary heart disease
. Here we show increased proliferation of macrophages and prominent formation of necrotic cores in atherosclerotic lesions in mice that express Jak2
selectively in macrophages, and in chimeric mice that model clonal haematopoiesis. Deletion of the essential inflammasome components caspase 1 and 11, or of the pyroptosis executioner gasdermin D, reversed these adverse changes. Jak2
lesions showed increased expression of AIM2, oxidative DNA damage and DNA replication stress, and Aim2 deficiency reduced atherosclerosis. Single-cell RNA sequencing analysis of Jak2
lesions revealed a landscape that was enriched for inflammatory myeloid cells, which were suppressed by deletion of Gsdmd. Inhibition of the inflammasome product interleukin-1β reduced macrophage proliferation and necrotic formation while increasing the thickness of fibrous caps, indicating that it stabilized plaques. Our findings suggest that increased proliferation and glycolytic metabolism in Jak2
macrophages lead to DNA replication stress and activation of the AIM2 inflammasome, thereby aggravating atherosclerosis. Precise application of therapies that target interleukin-1β or specific inflammasomes according to clonal haematopoiesis status could substantially reduce cardiovascular risk.
Full text
Available for:
GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
PDF
