Browsing by Subject "Cardiomyopathy"

Now showing 1 - 10 of 29
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    30-minute CMR for common clinical indications: a Society for Cardiovascular Magnetic Resonance white paper
    (BMC, 2022-03-01) Raman, Subha V.; Markl, Michael; Patel, Amit R.; Bryant, Jennifer; Allen, Bradley D.; Plein, Sven; Seiberlich, Nicole; Medicine, School of Medicine
    Background: Despite decades of accruing evidence supporting the clinical utility of cardiovascular magnetic resonance (CMR), adoption of CMR in routine cardiovascular practice remains limited in many regions of the world. Persistent use of long scan times of 60 min or more contributes to limited adoption, though techniques available on most scanners afford routine CMR examination within 30 min. Incorporating such techniques into standardize protocols can answer common clinical questions in daily practice, including those related to heart failure, cardiomyopathy, ventricular arrhythmia, ischemic heart disease, and non-ischemic myocardial injury. BODY: In this white paper, we describe CMR protocols of 30 min or shorter duration with routine techniques with or without stress perfusion, plus specific approaches in patient and scanner room preparation for efficiency. Minimum requirements for the scanner gradient system, coil hardware and pulse sequences are detailed. Recent advances such as quantitative myocardial mapping and other add-on acquisitions can be incorporated into the proposed protocols without significant extension of scan duration for most patients. Conclusion: Common questions in clinical cardiovascular practice can be answered in routine CMR protocols under 30 min; their incorporation warrants consideration to facilitate increased access to CMR worldwide.
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    A Case Report of Postheart Transplant Epicardial Adipose Deposition in a Patient With Dunnigan Syndrome
    (American College of Physicians, 2022) Bajpai, Vatsal; Damera, Nihanth; Pattisapu, Anish; Oral, Elif; Bateman, Pantila; Rao, Roopa A.; Medicine, School of Medicine
    Dunnigan syndrome is a rare genetic disorder that is a type of familial partial lipodystrophy. In some patients, severe cardiomyopathy and heart transplantation have been reported in this syndrome. Here, we describe a 40-year-old patient with Dunnigan syndrome who underwent heart transplantation for end-stage heart failure. Post-transplantation, routine imaging showed an accumulation of epicardial adipose tissue around the heart. In general, in Dunnigan syndrome, epicardial fat accumulation is not different compared with that of the general population. This is the first case report of exaggerated accumulation of adipose tissue around the heart causing subtle pericardial tamponade physiology.
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    Adjuvants in COVID-19 vaccines: innocent bystanders or culpable abettors for stirring up COVID-heart syndrome
    (Sage, 2024-02-04) Kanuri, Sri Harsha; Sirrkay, Prapthi Jayesh; Medicine, School of Medicine
    COVID-19 infection is a multi-system clinical disorder that was associated with increased morbidity and mortality. Even though antiviral therapies such as Remdesvir offered modest efficacy in reducing the mortality and morbidity, they were not efficacious in reducing the risk of future infections. So, FDA approved COVID-19 vaccines which are widely administered in the general population worldwide. These COVID-19 vaccines offered a safety net against future infections and re-infections. Most of these vaccines contain inactivated virus or spike protein mRNA that are primarily responsible for inducing innate and adaptive immunity. These vaccines were also formulated to contain supplementary adjuvants that are beneficial in boosting the immune response. During the pandemic, clinicians all over the world witnessed an uprise in the incidence and prevalence of cardiovascular diseases (COVID-Heart Syndrome) in patients with and without cardiovascular risk factors. Clinical researchers were not certain about the underlying reason for the upsurge of cardiovascular disorders with some blaming them on COVID-19 infections while others blaming them on COVID-19 vaccines. Based on the literature review, we hypothesize that adjuvants included in the COVID-19 vaccines are the real culprits for causation of cardiovascular disorders. Operation of various pathological signaling events under the influence of these adjuvants including autoimmunity, bystander effect, direct toxicity, anti-phospholipid syndrome (APS), anaphylaxis, hypersensitivity, genetic susceptibility, epitope spreading, and anti-idiotypic antibodies were partially responsible for stirring up the onset of cardiovascular disorders. With these mechanisms in place, a minor contribution from COVID-19 virus itself cannot be ruled out. With that being said, we strongly advocate for careful selection of vaccine adjuvants included in COVID-19 vaccines so that future adverse cardiac disorders can be averted.
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    Amyloid seeding of transthyretin by ex vivo cardiac fibrils and its inhibition
    (National Academy of Sciences, 2018-07-17) Saelices, Lorena; Chung, Kevin; Lee, Ji H.; Cohn, Whitaker; Whitelegge, Julian P.; Benson, Merrill D.; Eisenberg, David S.; Pathology and Laboratory Medicine, School of Medicine
    Each of the 30 human amyloid diseases is associated with the aggregation of a particular precursor protein into amyloid fibrils. In transthyretin amyloidosis (ATTR), mutant or wild-type forms of the serum carrier protein transthyretin (TTR), synthesized and secreted by the liver, convert to amyloid fibrils deposited in the heart and other organs. The current standard of care for hereditary ATTR is liver transplantation, which replaces the mutant TTR gene with the wild-type gene. However, the procedure is often followed by cardiac deposition of wild-type TTR secreted by the new liver. Here we find that amyloid fibrils extracted from autopsied and explanted hearts of ATTR patients robustly seed wild-type TTR into amyloid fibrils in vitro. Cardiac-derived ATTR seeds can accelerate fibril formation of wild-type and monomeric TTR at acidic pH and under physiological conditions, respectively. We show that this seeding is inhibited by peptides designed to complement structures of TTR fibrils. These inhibitors cap fibril growth, suggesting an approach for halting progression of ATTR.
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    Apical Sparing Pattern of Longitudinal Strain and Positive Bone Scintigraphy in Metastatic Myocardial Calcification
    (Elsevier, 2020-04-22) Zhang, Kathleen W.; Sadhu, Justin S.; Miller, Brent W.; Brennan, Daniel C.; Bierhals, Andrew J.; Chen, Jie-Fu; Lin, Chieh-Yu; Vader, Justin M.; Medicine, School of Medicine
    An apical sparing pattern of longitudinal strain and positive radionuclide bone scintigraphy are believed to be specific for the diagnosis of transthyretin cardiac amyloidosis. We report on a young woman with apical sparing of longitudinal strain and positive bone scintigraphy who was found to have metastatic myocardial calcification at autopsy.
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    Cardiomyopathy in Duchenne Muscular Dystrophy and the Potential for Mitochondrial Therapeutics to Improve Treatment Response
    (MDPI, 2024-07-09) Gandhi, Shivam; Sweeney, H. Lee; Hart, Cora C.; Han, Renzhi; Perry, Christopher G. R.; Pediatrics, School of Medicine
    Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene, resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with the development of cardiomyopathy—the leading cause of death—inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge. There is no cure for DMD; treatment is aimed at delaying disease progression and alleviating symptoms. A comprehensive understanding of the pathophysiological mechanisms is crucial to the development of targeted treatments. While established hypotheses of underlying mechanisms include sarcolemmal weakening, upregulation of pro-inflammatory cytokines, and perturbed ion homeostasis, mitochondrial dysfunction is thought to be a potential key contributor. Several experimental compounds targeting the skeletal muscle pathology of DMD are in development, but the effects of such agents on cardiac function remain unclear. The synergistic integration of small molecule- and gene-target-based drugs with metabolic-, immune-, or ion balance-enhancing compounds into a combinatorial therapy offers potential for treating dystrophin deficiency-induced cardiomyopathy, making it crucial to understand the underlying mechanisms driving the disorder.
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    Cardiovascular Research in Friedreich Ataxia: Unmet Needs and Opportunities
    (Elsevier, 2022-07-13) Payne, R. Mark; Pediatrics, School of Medicine
    Friedreich Ataxia (FRDA) is an autosomal recessive disease in which a mitochondrial protein, frataxin, is severely decreased in its expression. In addition to progressive ataxia, patients with FRDA often develop a cardiomyopathy that can be hypertrophic. This cardiomyopathy is unlike the sarcomeric hypertrophic cardiomyopathies in that the hypertrophy is associated with massive mitochondrial proliferation within the cardiomyocyte rather than contractile protein overexpression. This is associated with atrial arrhythmias, apoptosis, and fibrosis over time, and patients often develop heart failure leading to premature death. The differences between this mitochondrial cardiomyopathy and the more common contractile protein hypertrophic cardiomyopathies can be a source of misunderstanding in the management of these patients. Although imaging studies have revealed much about the structure and function of the heart in this disease, we still lack an understanding of many important clinical and fundamental molecular events that determine outcome of the heart in FRDA. This review will describe the current basic and clinical understanding of the FRDA heart, and most importantly, identify major gaps in our knowledge that represent new directions and opportunities for research.
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    A Case for Inclusion of Genetic Counselors in Cardiac Care
    (Wolters Kluwer, 2016-03) Arscott, Patricia; Caleshu, Colleen; Kotzer, Katrina; Kreykes, Sarah; Kruisselbrink, Teresa; Orland, Kate; Rigelsky, Christina; Smith, Emily; Spoonamore, Katherine; Larsen Haidle, Joy; Marvin, Monica; Ackerman, Michael J.; Hadi, Azam; Mani, Arya; Ommen, Steven; Cherny, Sara; Department of Medicine, IU School of Medicine
    Recent advances in genetic testing for heritable cardiac diseases have led to an increasing involvement of the genetic counselor in cardiology practice. We present a series of cases collected from a nationwide query of genetics professionals regarding issues related to cost and utilization of genetic testing. Three themes emerged across cases: (1) choosing the most appropriate genetic test, (2) choosing the best person to test, and (3) interpreting results accurately. These cases demonstrate that involvement of a genetic counselor throughout the evaluation, diagnosis, and continuing management of individuals and families with inherited cardiovascular conditions helps to promote the efficient use of healthcare dollars.
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    Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen
    (Springer, 2023) Coelho, Teresa; Waddington Cruz, Márcia; Chao, Chi-Chao; Parman, Yeşim; Wixner, Jonas; Weiler, Markus; Barroso, Fabio A.; Dasgupta, Noel R.; Jung, Shiangtung W.; Schneider, Eugene; Viney, Nicholas J.; Dyck, P. James B.; Ando, Yukio; Gillmore, Julian D.; Khella, Sami; Gertz, Morie A.; Obici, Laura; Berk, John L.; Medicine, School of Medicine
    Introduction: Hereditary transthyretin (ATTRv) amyloidosis is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic deposition of transthyretin (TTR) amyloid fibrils. ATTRv amyloidosis occurs in both males and females. Eplontersen (ION-682884), a ligand-conjugated antisense oligonucleotide designed to degrade hepatic TTR mRNA, is being evaluated for the treatment of ATTRv amyloidosis with polyneuropathy (ATTRv-PN) in the phase 3, international, multicenter, open-label NEURO-TTRansform study (NCT04136184). To describe the study population of this pivotal trial, here we report the baseline characteristics of patients enrolled in the NEURO-TTRansform study. Methods: Patients eligible for NEURO-TTRansform were 18-82 years old with a diagnosis of ATTRv-PN and Coutinho stage 1 (ambulatory without assistance) or stage 2 (ambulatory with assistance) disease; documented TTR gene variant; signs and symptoms consistent with neuropathy associated with ATTRv; no prior liver transplant; and New York Heart Association (NYHA) functional class I or II. Results: The NEURO-TTRansform study enrolled 168 patients across 15 countries/territories (North America, 15.5%; Europe, 38.1%; South America/Australia/Asia, 46.4%). At baseline, the study cohort had a mean age of 52.8 years, 69.0% of patients were male, and 78.0% of patients were White. The V30M variant was most prevalent (60.1% of patients), and prevalence varied by region. Overall, 56.5% and 17.3% of patients had received previous treatment with tafamidis or diflunisal, respectively. A majority of patients (79.2%) had Coutinho stage 1 disease (unimpaired ambulation) and early (before age 50) disease onset (53.0%). Time from diagnosis to enrollment was 46.6 (57.4) months (mean [standard deviation]). Most patients had a baseline polyneuropathy disability (PND) score of I (40.5%) or II (41.1%), and the mean modified Neuropathy Impairment Score + 7 (mNIS + 7) was 79.0. Conclusion: The recruited population in the ongoing NEURO-TTRansform study has global representation characteristic of contemporary clinical practice.
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    Clinical Genetic and Genomic Testing in Congenital Heart Disease and Cardiomyopathy
    (MDPI, 2024-04-26) Pidaparti, Mahati; Geddes, Gabrielle C.; Durbin, Matthew D.; Pediatrics, School of Medicine
    Congenital heart disease (CHD) and cardiomyopathies are the leading cause of morbidity and mortality worldwide. These conditions are often caused by genetic factors, and recent research has shown that genetic and genomic testing can provide valuable information for patient care. By identifying genetic causes, healthcare providers can screen for other related health conditions, offer early interventions, estimate prognosis, select appropriate treatments, and assess the risk for family members. Genetic and genomic testing is now the standard of care in patients with CHD and cardiomyopathy. However, rapid advances in technology and greater availability of testing options have led to changes in recommendations for the most appropriate testing method. Several recent studies have investigated the utility of genetic testing in this changing landscape. This review summarizes the literature surrounding the clinical utility of genetic evaluation in patients with CHD and cardiomyopathy.