Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report an autopsy case of a pedigree of familial amyloidotic polyneuropathy (FAP) with a mutation of isoleucine-50 transthyretin (ATTR Ser50Ile). A 47-year-old man started developing severe diarrhea and weight loss at age 41 years, followed by urinary incontinence, autonomic-nervous-system abnormalities and serious heart failure; the diagnosis of FAP (ATTR Ser50Ile) was made on the basis of genetic, histochemical and immunohistochemical analysis. Six years after the initial symptoms, he died of septic shock. Autopsy revealed suppurative peritonitis, perforation of the sigmoid colon and marked systemic amyloid deposition. The total amount of amyloid deposited in the heart was greatly increased and was much lower in the thyroid gland and kidneys compared with amyloid deposits in ordinary FAP (ATTR Val30Met). Amyloid deposition in peripheral vessel walls was prominent, particularly in lymphatics and veins. His elder sister, 54 years old, started to develop orthostatic hypotension at age 49 years, followed by dysesthesia, diarrhea and severe congestive heart failure. Endomyocardial biopsy revealed severe TTR-amyloid deposition; ultrastructural examination demonstrated that amyloid fibrils were deposited disproportionately and extended radially around microvessels.
 ...
PMID:Familial amyloidotic polyneuropathy (ATTR Ser50Ile): the first autopsy case report. 1083 37

Cardiac failure in transthyretin (TTR) amyloidosis patients has been shown to be caused by different mutations in the TTR gene. In the present case, a 73-year-old man from Northern Sweden was evaluated for heart failure. Amyloid deposits were found in subcutaneous fat and in intestinal biopsies. The presence of a variant form of TTR was detected in the plasma by electrospray ionisation mass spectrometry (ESI-MS). The mutation was located by single-strand conformation polymorphism (SSCP) analysis of the TTR gene where a band shift was seen in exon 2. Direct sequencing of exon 2 revealed a single base-pair substitution (G1724T). This transversion results in an amino acid substitution at codon 45, alanine to serine (ATTR Ala45Ser). Mass spectrometry analysis excluded that the variant is a polymorphism, since no similar shift in molecular weight has been present in more than 200 control samples. Congo red and immunostaining of duodenum biopsy specimens confirmed the presence of systemic ATTR amyloidosis, and clinical examination, including echocardiography, found evidence of a restrictive cardiomyopathy. He had 10 years previously been operated for a bilateral carpal tunnel syndrome, but otherwise no symptoms were present that could be attributed to his systemic amyloidosis. No axonal polyneuropathy was noted at nerve conduction studies. This novel mutation is the second amyloidogenic TTR mutation found in the Swedish population.
 ...
PMID:Heart failure caused by a novel amyloidogenic mutation of the transthyretin gene: ATTR Ala45Ser. 1084 18

There are few reports of combined heart and liver transplantation (CHLT) for familial amyloidotic polyneuropathy (FAP). The technique for the operation remains to be defined. Four CHLTs were performed for amyloidogenic transthyretin-related (variant Glu89Gln-ATTR Glu89Gln) cardiomyopathy in our center. Patients 1 and 4 had no serious involvement of other organs, whereas patients 2 and 3 had evident peripheral neuropathy and gastrointestinal motility alterations. Patient 3 also had high-grade orthostatic hypotension. All four patients underwent cardiac and sequential hepatic transplantation with organs procured from the same donor. Venovenous bypass was used in patients 1 and 4 who experienced uncomplicated procedures. The amyloidotic liver of patient 4 was successfully utilized for a domino procedure to treat a patient with hepatocellular carcinoma on cirrhosis. The cardiac performance of patients 1 and 4 remains normal; there has been no progression of amyloidosis at 42 and 1 months after transplantation. Patient 2 had no intraoperative complications but experienced postoperative bleeding, renal failure, sepsis, and heart failure, and finally died of multiorgan failure 2 months after transplant. In patient 3, right hemicolectomy was required intraoperatively due to intestinal ischemia, without significant hemodynamic instability, while extracardiac symptoms of amyloidosis gradually worsened postoperatively. In conclusion, CHLT for ATTR Glu89Gln may be performed even in patients with advanced disease. However, the most compromised patients are more likely to display intraoperative risks, postoperative complications, and worsening of extracardiac, extrahepatic symptoms.
 ...
PMID:Combined heart and liver transplantation in four adults with familial amyloidosis: experience of a single center. 1511 Jun 20

Amyloidosis is the term for specific pathological peptide deposits in various tissues. Amyloid substances may be the manifestation of the following nosological units: AL-amyloidosis, AA-amyloidosis, ATTR-amyloidosis, beta2-microglobulin amyloidosis and possibly othr familiar forms of amyloidosis. The most frequent symptoms of amyloidosis are: 1. proteinuria with nephrotic syndrome, 2. cardiac failure with restrictive cardiomyopathy, 3. unexplicable hepatomegaly, 4. idiopathic peripheral polyneuropathy, 5. haemorrhagic manifestations and symptoms of increased fragility of the capillaries while the number of thrombocytes is normal, 6. periorbital haematomas and 7. macroglossia. Diagnostic and therapeutic procedures differ according to the type of amyloidosis and are analyzed in detail in the text.
 ...
PMID:[Clinical manifestations of AL-amyloidosis and some other types of amyloidosis]. 1563 67

We report two new amyloidogenic transthyretin (TTR) variants detected in the Swedish population. One variant was previously unknown, while the other has been described in a French family. In Swedish patients, both variants have caused late-onset cardiac amyloidosis characterised by heart failure. In both cases, the diagnosis was determined by the detection of amyloid deposits in skin and/or rectal biopsies and identification of TTR mutations by genetic analysis. The index case of the previously unknown mutation (ATTR His88Arg) was a 66-year-old Swedish man, who sought medical attention for increasing dyspnea. Echocardiographic examination disclosed a restrictive cardiomyopathy, and subsequent examinations disclosed TTR amyloidosis. The patient is alive with moderate symptoms one year after the onset of disease. The index case for the new Swedish mutation (ATTR Gly53Glu) is a woman who sought medical attention at the age of 57 because of increasing dyspnea. Echocardiographic examination disclosed a hypertrophic cardiomyopathy with diastolic impairment. The diagnosis of systemic amyloidosis was made by fat aspiration biopsy and histopathology. The patient developed severe intractable heart failure, with pulmonary effusion and ascites. She died four years after the onset of her disease of intractable heart and kidney failure. Post mortem examination of biopsy specimens and blood revealed TTR amyloid deposits and the ATTR Gly53Glu mutation was detected.
 ...
PMID:Cardiomyopathy in Swedish patients with the Gly53Glu and His88Arg transthyretin variants. 1619 74

Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment.
 ...
PMID:[Cardiac amyloidosis]. 1834 65

Amyloidosis is an infiltrative disease characterized by deposition of amyloid fibrils within the extracellular tissue of one or multiple organs. Involvement of the heart, cardiac amyloidosis, is recognized as a common cause of restrictive cardiomyopathy and heart failure. The two major types of cardiac amyloidosis are cardiac amyloid light-chain (AL) and transthyretin-related cardiac amyloidosis (ATTR, mutant and wild types) (Nat Rev Cardiol 2010;7:398-408). While early recognition of cardiac amyloidosis is of major clinical importance, so is the ability to differentiate between subtypes. Indeed, both prognosis and therapeutic options vary drastically depending on the subtype. While endomyocardial biopsy with immunostaining is considered the gold standard, advances in imaging provide an attractive non-invasive alternative. Currently, electrocardiography, echocardiography, and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy. Yet, none of these modalities can effectively differentiate the cardiac amyloid subtypes. Recent data with (99m)Tc-phosphate derivatives, previously used as bone seeking radioactive tracers, have shown promising results; these radiotracers selectively bind ATTR, but not AL subtype, and can differentiate subtypes with high diagnostic accuracy. This review will initially present the non-radionuclide imaging techniques and then focus on the radionuclide imaging techniques, particularly (99m)Tc-DPD and (99m)Tc-PYP, mechanism of action, performance and interpretation of the study, diagnostic accuracy, prognostic value, future clinical perspective, and outlook.
...
PMID:Role of imaging in the diagnosis and management of patients with cardiac amyloidosis: state of the art review and focus on emerging nuclear techniques. 2434 27

Transthyretin amyloidosis (ATTR) is either a hereditary disease related to a mutation in the transthyretin gene that leads to neuropathy and/or cardiomyopathy or an acquired disease of the elderly that leads to restrictive cardiomyopathy. The prevalence of this disease is higher than once thought and awareness is likely to increase amongst physicians and in particular cardiologists. Until recently there have been no treatment options for this disease except to treat the heart failure with diuretics and the neuropathy symptomatically. However, there are several emerging pharmacologic therapies designed to slow or stop the progression of ATTR. This article reviews novel therapeutic drugs that work at different points in the pathogenesis of this disease attempting to change its natural history and improve outcomes.
...
PMID:Novel drugs targeting transthyretin amyloidosis. 2446 60

Transthyretin-cardiac amyloidoses (ATTR-CA) are an underdiagnosed but increasingly recognized cause of heart failure. Extracellular deposition of fibrillary proteins into tissues due to a variety of inherited transthyretin mutations in ATTRm or due to advanced age in ATTRwt eventually leads to organ failure. In the heart, amyloid deposition causes diastolic dysfunction, restrictive cardiomyopathy with progressive loss of systolic function, arrhythmias, and heart failure. While traditional treatments have consisted of conventional heart failure management and supportive care for systemic symptoms, numerous disease-modifying therapies have emerged over the past decade. From organ transplantation to transthyretin stabilizers (diflunisal, tafamidis, AG-1), TTR silencers (ALN-ATTR02, ISIS-TTR(Rx)), and degraders of amyloid fibrils (doxycycline/TUDCA), the potential for effective transthyretin amyloid therapy is greater now than ever before. In light of these multiple agents under investigation in human clinical trials, clinicians should be familiar with the systemic cardiac amyloidoses, their differing pathophysiology, natural histories, and unique treatment strategies.
...
PMID:Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. 2540 61

Hereditary transthyretin amyloidosis (ATTR) is a rare worldwide autosomal dominant disease caused by the systemic deposition of an amyloidogenic variant of transthyretin (TTR), which is usually derived from a single amino acid substitution in the TTR gene. More than 100 mutations have been described, with V30M being the most prevalent. Each variant has a different involvement, although peripheral neuropathy and cardiomyopathy are the most common. Orthotopic liver transplantation (OLT) was implemented as the inaugural disease-modifying therapy because the liver produces the circulating unstable TTR. In this review, we focus on the results and long-term outcomes of OLT for ATTR after more than 2063 procedures and 23 years of experience. After successful OLT, neuropathy and organ impairment are not usually reversed, and in some cases, the disease progresses. The overall 5-year survival rate is approximately 100% for V30M patients and 59% for non-ATTR V30M patients. Cardiac-related death and septicemia are the main causes of mortality. Lower survival is related to malnutrition, a longer duration of disease, cardiomyopathy, and a later onset (particularly for males). Deposits, which are composed of a mixture of truncated and full-length TTR (type A) fibrils, have been associated with posttransplant myocardial dysfunction. A higher incidence of early hepatic artery thrombosis of the graft has also been documented for these patients. Liver-kidney/heart transplantation is an alternative for patients with advanced renal disease or heart failure. The sequential procedure, in which ATTR livers are reused in patients with liver disease, reveals that neuropathy in the recipient may appear as soon as 6 years after OLT, and ATTR deposits may appear even earlier. Long-term results of trials with amyloid protein stabilizers or disrupters, silencing RNA, and antisense oligonucleotides will highlight the value and limitations of liver transplantation.
 ...
PMID:Liver transplantation in transthyretin amyloidosis: issues and challenges. 2548 46


1 2 3 4 5 Next >>