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ASAIO Journal (American Society For... Jun 2024Right ventricular (RV) dysfunction (RVD) after orthotopic heart transplantation (OHT) is a common cause of morbidity and mortality. Impella RP Flex was recently approved...
Right ventricular (RV) dysfunction (RVD) after orthotopic heart transplantation (OHT) is a common cause of morbidity and mortality. Impella RP Flex was recently approved for RV support as a temporary mechanical circulatory device. We present the first case of its use in managing RVD in a patient after OHT. Here, a 40 year old male patient with familial dilated cardiomyopathy and factor V Leiden mutation presented with Society for Cardiovascular Angiography & Interventions (SCAI) stage B cardiogenic shock. Hemodynamics at admission were indicative of need for intra-aortic balloon pump (IABP) support. Hemodynamics improved and patient underwent OHT. Postoperative day (POD) 1, IABP support was changed to 1:2 and eventually removed. Hemodynamics deteriorated quickly, requiring pharmacologic RV support and diuresis, but refractory RV failure persisted. Impella RP Flex was chosen due to the patient's small size and was placed via the right internal jugular vein on POD 12. The procedure was well tolerated, with the patient ambulatory the following day (POD 13). Impella was removed on POD 25 after 13 days of support. Patient achieved normal kidney, intrinsic rhythm improved sinus rhythm, and ultimately discharged on POD 50. Impella RP flex has emerged as a promising future indication as single or biventricular support postcardiac transplantation.
PubMed: 38905611
DOI: 10.1097/MAT.0000000000002253 -
Frontiers in Genetics 2024Previous studies have shown that Alzheimer's disease (AD) can cause myocardial damage. However, whether there is a causal association between AD and non-ischemic...
The causal effect of Alzheimer's disease and family history of Alzheimer's disease on non-ischemic cardiomyopathy and left ventricular structure and function: a Mendelian randomization study.
BACKGROUND
Previous studies have shown that Alzheimer's disease (AD) can cause myocardial damage. However, whether there is a causal association between AD and non-ischemic cardiomyopathy (NICM) remains unclear. Using a comprehensive two-sample Mendelian randomization (MR) method, we aimed to determine whether AD and family history of AD (FHAD) affect left ventricular (LV) structure and function and lead to NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).
METHODS
The summary statistics for exposures [AD, paternal history of AD (PH-AD), and maternal history of AD (MH-AD)] and outcomes (NICM, HCM, DCM, and LV traits) were obtained from the large European genome-wide association studies. The causal effects were estimated using inverse variance weighted, MR-Egger, and weighted median methods. Sensitivity analyses were conducted, including Cochran's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier, MR Steiger test, leave-one-out analysis, and the funnel plot.
RESULTS
Genetically predicted AD was associated with a lower risk of NICM [odds ratio (OR) 0.9306, 95% confidence interval (CI) 0.8825-0.9813, = 0.0078], DCM (OR 0.8666, 95% CI 0.7752-0.9689, = 0.0119), and LV remodeling index (OR 0.9969, 95% CI 0.9940-0.9998, = 0.0337). Moreover, genetically predicted PH-AD was associated with a decreased risk of NICM (OR 0.8924, 95% CI 0.8332-0.9557, = 0.0011). MH-AD was also strongly associated with a decreased risk of NICM (OR 0.8958, 95% CI 0.8449-0.9498, = 0.0002). Different methods of sensitivity analysis demonstrated the robustness of the results.
CONCLUSION
Our study revealed that AD and FHAD were associated with a decreased risk of NICM, providing a new genetic perspective on the pathogenesis of NICM.
PubMed: 38903751
DOI: 10.3389/fgene.2024.1379865 -
BMJ Case Reports Jun 2024Mid-aortic syndrome (MAS) is a rare vascular disease that usually leads to renovascular hypertension. With the predominant manifestations being intractable arterial...
Mid-aortic syndrome (MAS) is a rare vascular disease that usually leads to renovascular hypertension. With the predominant manifestations being intractable arterial hypertension and lower extremity arterial insufficiency, it has rarely been associated with dilated cardiomyopathy. We report a young girl with congestive heart failure, where the cause was initially attributed to dilated cardiomyopathy. A repeated echocardiogram 6 months later brought the physician's suspicion of MAS because of the abnormal colour of Doppler from the subcostal view. Further assessment using CT angiography revealed discrete thoracic coarctation at the level of T10, with the narrowest diameter of 2.1 mm, thus confirming the diagnosis. Her inflammatory markers and connective tissue screening were negative. She underwent successful stenting of coarctation of the aorta, which later caused improvement in her cardiac function. We highlighted the importance of looking for treatable causes of dilated cardiomyopathy and vigilant clinical and echocardiogram assessment with high suspicion to diagnose MAS.
Topics: Humans; Cardiomyopathy, Dilated; Female; Aortic Coarctation; Computed Tomography Angiography; Echocardiography; Stents; Diagnosis, Differential; Syndrome; Heart Failure
PubMed: 38901852
DOI: 10.1136/bcr-2024-259981 -
Advanced Drug Delivery Reviews Jun 2024Every year, more than a million people in the United States undergo chemotherapy or radiation therapy for cancer, as estimated by the CDC. While chemotherapy has been an... (Review)
Review
Every year, more than a million people in the United States undergo chemotherapy or radiation therapy for cancer, as estimated by the CDC. While chemotherapy has been an instrumental tool for treating cancer, it also causes severe adverse effects. The more commonly acknowledged adverse effects include hair loss, fatigue, and nausea, but a more severe and longer lasting side effect is cardiotoxicity. Cardiotoxicity, or heart damage, is a common complication of cancer treatments. It can range from mild to severe, and it can affect some patients temporarily or others permanently, even after they are cured of cancer. Dexrazoxane is the only FDA-approved drug for treating anthracycline induced cardiotoxicity, but it also has drawbacks and adverse effects. There is no other type of chemotherapy induced cardiotoxicity that has an approved treatment option. In this review, we discuss the pathophysiology of chemotherapeutic-induced cardiotoxicity, methods and guidelines of diagnosis, methods of treatment and mitigation, and current drug delivery approaches in therapeutic development.
PubMed: 38901637
DOI: 10.1016/j.addr.2024.115361 -
Free Radical Biology & Medicine Jun 2024Doxorubicin (Dox) use is limited by Dox-induced cardiotoxicity. TANK-blinding kinase 1 (TBK1) is an important kinase involved in the regulation of mitophagy, but the...
Doxorubicin (Dox) use is limited by Dox-induced cardiotoxicity. TANK-blinding kinase 1 (TBK1) is an important kinase involved in the regulation of mitophagy, but the role of TBK1 in cardiomyocytes in chronic Dox-induced cardiomyopathy remains unclear. Cardiomyocyte-specific Tbk1 knockout (Tbk1) mice received Dox (6 mg/kg, injected intraperitoneally) once a week for 4 times, and cardiac assessment was performed 4 weeks after the final Dox injection. Adenoviruses encoding Tbk1 or containing shRNA targeting Tbk1, or a TBK1 phosphorylation inhibitor were used for overexpression or knockdown of Tbk1, or inhibit phosphorylation of TBK1 in isolated primary cardiomyocytes. Our results revealed that moderate Dox challenge decreased TBK1 phosphorylation (with no effect on TBK1 protein levels), resulting in compromised myocardial function, obvious mortality and overt interstitial fibrosis, and the effects were accentuated by Tbk1 deletion. Dox provoked mitochondrial membrane potential collapse and oxidative stress, the effects of which were exacerbated and mitigated by Tbk1 knockdown, specific inhibition of phosphorylation and overexpression, respectively. However, Tbk1 (Ser172A) overexpression did not alleviate these effects. Further scrutiny revealed that TBK1 exerted protective effects on mitochondria via SQSTM1/P62-mediated mitophagy. Tbk1 overexpression mediated cardioprotective effects on Dox-induced cardiotoxicity were cancelled off by Sqstm1/P62 knockdown. Moreover, TBK1-mitophagy-mitochondria cascade was confirmed in heart tissues from dilated cardiomyopathy patients. Taken together, our findings denoted a pivotal role of TBK1 in Dox-induced mitochondrial injury and cardiotoxicity possibly through its phosphorylation and SQSTM1/P62-mediated mitophagy.
PubMed: 38901499
DOI: 10.1016/j.freeradbiomed.2024.06.009 -
Kidney & Blood Pressure Research Jun 2024A hereditary condition primarily affecting the kidneys and heart has newly been identified: the RRAGD-associated Autosomal Dominant Kidney Hypomagnesemia with... (Review)
Review
BACKGROUND
A hereditary condition primarily affecting the kidneys and heart has newly been identified: the RRAGD-associated Autosomal Dominant Kidney Hypomagnesemia with Cardiomyopathy (ADKH-RRAGD). This disorder is characterized by renal loss of magnesium and potassium, coupled with varying degrees of cardiac dysfunction. These range from arrhythmias to severe dilated cardiomyopathy, which may require heart transplantation. Mutations associated with RRAGD significantly disrupt the non-canonical branch of the mTORC1 pathway. This disruption hinders the the nuclear translocation and transcriptional activity of the transcription factor EB (TFEB) a crucial regulator of lysosomal and autophagic function.
SUMMARY
All identified RRAGD variants compromise kidney function, leading to hypomagnesemia and hypokalemia of various severity. The renal phenotype for most of the variants (i.e. S76L, I221K, P119R, P119L), typically manifests in the second decade of life occasionally preceded by childhood symptoms of dilated cardiomyopathy. In contrast, the P88L variant is associated to dilated cardiomyopathy manifesting in adulthood. To date, the T97P variant has not been linked to cardiac involvement. The most severe manifestations of ADKH-RRAGD, particularly concerning electrolyte imbalance and heart dysfunction requiring transplantation in childhood appear to be associated with the S76L, I221K, P119R variants.
KEY MESSAGES
This review aims to provide an overview of the clinical presentation for ADKH-RRAGD, aiming to enhance o awareness, promote early diagnosis and facilitate proper treatment. It also reports on the limited experience in patient management with diuretics, magnesium and potassium supplements, metformin, or calcineurin- and SGLT2-inhibitors.
PubMed: 38901414
DOI: 10.1159/000539889 -
The New Zealand Medical Journal Jun 2024The prevalence of heart failure in New Zealand is increasing. A small number of select patients with predicted poor short-term survival are candidates for advanced heart...
AIMS
The prevalence of heart failure in New Zealand is increasing. A small number of select patients with predicted poor short-term survival are candidates for advanced heart failure therapies such as transplantation and durable mechanical circulatory support (MCS). The aim of our study was to introduce left ventricular assist devices (LVADs) to the wider clinicians and highlight their role in managing patients with advanced heart failure in New Zealand.
METHOD
A retrospective audit of all ventricular assist device (VAD) recipients from January 2005 to December 2022 was conducted. Data were collated using electronic medical and paper records. The primary outcome was survival to transplantation or successful explant of VAD.
RESULTS
Thirty-nine patients received VADs; 32 were male and seven female. Mean age was 45 years (range 10-64 years). Most recipients were NZ European (25), six were Māori, four were Pacific peoples and four were of other ethnicities. The majority of LVADs were implanted for those with dilated cardiomyopathy (67%). At the time of data collection, 24 (62%) had survived to heart transplantation, seven (18%) died while on VAD support, five from right ventricular failure and two from strokes, one patient had their VAD explanted due to recovery and seven (18%) VAD recipients continue on support awaiting transplant.
CONCLUSION
This audit has provided an opportunity to inform New Zealand clinicians of our durable MCS programme and the expanding role of VAD support in patients with advanced heart failure. The programme will need to continue to audit and report its practice in order to provide equitable allocation of this very limited resource to a growing population in need.
Topics: Humans; Heart-Assist Devices; Male; Female; New Zealand; Heart Failure; Middle Aged; Adult; Retrospective Studies; Adolescent; Young Adult; Child; Heart Transplantation
PubMed: 38901048
DOI: 10.26635/6965.6444 -
ASAIO Journal (American Society For... Jun 2024This case report explores the successful use of the Impella 5.5 (Abiomed Inc., Danvers, MA) device in a 22 kg, 0.89 body surface area (BSA) pediatric patient with...
This case report explores the successful use of the Impella 5.5 (Abiomed Inc., Danvers, MA) device in a 22 kg, 0.89 body surface area (BSA) pediatric patient with longstanding dilated cardiomyopathy and elevated pulmonary vascular resistance. The article details the device selection, management, and outcome demonstrating the feasibility and potential benefits of the Impella 5.5 as a device within the pediatric population.
PubMed: 38896844
DOI: 10.1097/MAT.0000000000002256 -
Diagnostics (Basel, Switzerland) Jun 2024Non-ischemic dilated cardiomyopathy (DCM) represents a significant cause of heart failure, defined as the presence of left ventricular (LV) dilatation and systolic... (Review)
Review
Non-ischemic dilated cardiomyopathy (DCM) represents a significant cause of heart failure, defined as the presence of left ventricular (LV) dilatation and systolic dysfunction unexplained solely by abnormal loading conditions or coronary artery disease. Cardiac resynchronization therapy (CRT) has emerged as a cornerstone in the management of heart failure, particularly in patients with DCM. However, identifying patients who will benefit the most from CRT remains challenging. Speckle tracking echocardiography (STE) has garnered attention as a non-invasive imaging modality that allows for the quantitative assessment of myocardial mechanics, offering insights into LV function beyond traditional echocardiographic parameters. This comprehensive review explores the role of STE in guiding patient selection and optimizing outcomes in CRT for DCM. By assessing parameters such as LV strain, strain rate, and dyssynchrony, STE enables a more precise evaluation of myocardial function and mechanical dyssynchrony, aiding in the identification of patients who are most likely to benefit from CRT. Furthermore, STE provides valuable prognostic information and facilitates post-CRT optimization by guiding lead placement and assessing response to therapy. Through an integration of STE with CRT, clinicians can enhance patient selection, improve procedural success rates, and ultimately, optimize clinical outcomes in patients with DCM. This review underscores the pivotal role of STE in advancing personalized management strategies for DCM patients undergoing CRT.
PubMed: 38893704
DOI: 10.3390/diagnostics14111178 -
Diagnostics (Basel, Switzerland) Jun 2024The benefit of prophylactic implantable cardioverter defibrillators (ICDs) in patients with severe systolic dysfunction of non-ischemic origin is still unclear, and the...
Right Bundle Branch Block Predicts Appropriate Implantable Cardioverter Defibrillator Therapies in Patients with Non-Ischemic Dilated Cardiomyopathy and a Prophylactic Implantable Cardioverter Defibrillator.
The benefit of prophylactic implantable cardioverter defibrillators (ICDs) in patients with severe systolic dysfunction of non-ischemic origin is still unclear, and the identification of patients at risk for sudden cardiac death remains a major challenge. We retrospectively reviewed all consecutive patients with non-ischemic dilated cardiomyopathy (NICM) who underwent prophylactic ICD implantation between 2008 and 2020 in two tertiary centers. Our main goal was to identify the predictors of appropriate ICD therapies (anti-tachycardia pacing [ATP] and/or shocks) in this cohort of patients. A total of 224 patients were included. After a median follow-up of 51 months, 61 patients (27.2%) required appropriate ICD therapies. Patients with appropriate ICD therapies were more frequently men (87% vs. 69%, = 0.006), of younger age (59 years, (53-65) vs. 64 years, (57-70); = 0.02), showed more right bundle branch blocks (RBBBs) (15% vs. 4%, = 0.007) and less left bundle branch blocks (LBBBs) (26% vs. 47%, = 0.005) in the ECG, and had higher left ventricular end-diastolic (100 mL/m, (90-117) vs. 86, (71-110); = 0.011) and systolic volumes (72 mL/m, (59-87) vs. 61, (47-81), = 0.05). In a multivariate competing-risks regression analysis, RBBB (HR 2.26, CI 95% 1.02-4.98, = 0.043) was identified as an independent predictor of appropriate ICD therapies. RBBBs may help to identify patients with NICM at high risk of ventricular arrhythmias and requiring ICD intervention.
PubMed: 38893699
DOI: 10.3390/diagnostics14111173