Transthyretin cardiac amyloidosis: A treatable form of heart failure with a preserved ejection fraction.
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SUBMITTER: Griffin JM
PROVIDER: S-EPMC7297649 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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Transthyretin cardiac amyloidosis: A treatable form of heart failure with a preserved ejection fraction.
Griffin Jan M JM Maurer Mathew S MS
Trends in cardiovascular medicine 20191217 1
Cardiac amyloidosis (CA) is considered a rare disease with poor prognosis and limited therapeutic options. However, non-biopsy diagnostic modalities as well as emerging therapies are challenging this long-held belief. Radionuclide bone scintigraphy is increasingly being used in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CA). As such, it is expected that the number of patients diagnosed with ATTR-CA will continue to rise. Emerging therapies decrease the progressive morbidity and ...[more]
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Project description:Heart failure with preserved ejection fraction (HFpEF) comprises half of the heart failure population. A specific, but underdiagnosed, cause for HFpEF is transthyretin-derived (ATTR) amyloidosis. This article reviews the clinical characteristics of cardiac ATTR amyloidosis. The clinical suspicion of cardiac ATTR amyloidosis is strong if pronounced left ventricular hypertrophy is present in the absence of hypertension. Scintigraphy with a diphosphonate tracer is a diagnostic tool for the early detection of cardiac ATTR amyloidosis with high sensitivity and specificity. First treatment options for ATTR amyloidosis recently emerged, and showed a reduction in morbidity and mortality, especially if treatment was started in the early stages of disease. In light of these results, screening for ATTR amyloidosis in the general HFpEF population with left ventricular hypertrophy might be useful.
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Project description:Heart Failure with Preserved Ejection Fraction (HFpEF) is one of the most frequent causes of heart failure in the world's population (about 19-55%), and is commonly associated with a high rate of hospitalization (almost 70-80%) and with increased mortality (40-50% in a 5-year timeframe). The elderly are more often affected, with higher rates of hospitalizations than young people, and currently almost 70% of the population aged 65 years old has HFpEF. An increase in cardiomyocyte stiffness, thus resulting in diastolic dysfunction, increased filling pressures and heart failure with preserved ejection fraction are characteristics features of the disease. In addition, among the various causes of HFpEF, cardiac amyloidosis (CA) can provoke diastolic dysfunction and increased wall stiffness directly from intercellular deposition of insoluble proteic substances and their toxic activity. Totally, almost 30 different proteins are able to form deposits, but the most frequently involved are transthyretin and misfolded monoclonal immunoglobulin light chains, which bring to two clinical conditions called transthyretin amyloidosis (ATTR) and light-chain amyloidosis (AL). Although there has been increasing attention on ATTR-CA in recent years, the actual prevalence remains underestimated, especially in people of advanced age, as well as its real impact as a cause of HFpEF, and only data derived from autoptic exams are currently available. Moreover, CA itself often mimics HFpEF, and some conflicting data on the use of predictive scores are described in the literature. The close relationship between HFpEF and CA, especially in older population and the main pathophysiological mechanisms which bond these two conditions are described in this focused review. The need to screen red flags for ATTR-CA in elderly patients with HFpEF is urgently advised, because a prompt recognition of the disease can optimize the approach to the disease with an early therapeutic, life-saving choice.
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Project description:ObjectivesThis study prospectively evaluated endomyocardial biopsies in patients with heart failure with preserved ejection fraction (HFpEF) to identify histopathologic phenotypes and their association with clinical characteristics.BackgroundMyocardial tissue analysis from a prospectively defined HFpEF cohort reflecting contemporary comorbidities is lacking.MethodsPatients with HFpEF (EF ≥50%) referred to the Johns Hopkins HFpEF Clinic between August 2014 and September 2018 were enrolled for right heart catheterization and endomyocardial biopsy. Clinical features, echocardiography, hemodynamics, and tissue histology were determined and compared with controls (unused donor hearts) and HF with reduced EF (HFrEF).ResultsOf the 108 patients enrolled, median age was 66 years (25th to 75th percentile: 57 to 74 years), 61% were women, 57% were African American, 62% had a previous HF hospitalization, median systolic blood pressure was 141 mm Hg (25th to 75th percentile: 125 to 162 mm Hg), body mass index (BMI) was 37 kg/m2 (25th to 75th percentile: 32 to 45 kg/m2), and 97% were on a loop diuretic. Myocardial fibrosis and myocyte hypertrophy were often present (93% and 88%, respectively); however, mild in 71% with fibrosis and in 52% with hypertrophy. Monocyte infiltration (CD68+ cells/mm2) was greater in patients with HFpEF versus controls (60.4 cells/mm2 [25th to 75th percentile: 36.8 to 97.8] vs. 32.1 cells/mm2 [25th to 75th percentile: 22.3 to 59.2]; p = 0.02) and correlated with age and renal disease. Cardiac amyloidosis (CA) was diagnosed in 15 (14%) patients (HFpEF-CA: 7 patients with wild-type transthyretin amyloidosis [ATTR], 4 patients with hereditary ATTR, 3 patients with light-chain amyloidosis, and 1 patient with AA (secondary) amyloidosis), of which 7 cases were unsuspected. Patients with HFpEF-CA were older, with lower BMI, higher left ventricular mass index, and higher N-terminal pro-B-type natriuretic peptide and troponin I levels.ConclusionsIn this large, prospective myocardial tissue analysis of HFpEF, myocardial fibrosis and hypertrophy were common, CD68+ inflammation was increased, and CA prevalence was 14%. Tissue analysis in HFpEF might improve precision therapies by identifying relevant myocardial mechanisms.
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Project description:ImportanceHeart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized.ObjectiveTo examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening.Design, setting, and participantsThis population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort).ExposuresMedical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis.Main outcomes and measuresThe ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex.ResultsA total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002).Conclusions and relevanceIn this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.
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Project description:BackgroundHeart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an underestimated phenotype. We aim to evaluate the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction.MethodsThis meta-analysis was conducted according to PRISMA guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar to locate studies whose primary objective was to analyze the prevalence of transthyretin amyloidosis in heart failure preserved ejection fraction.ResultsOf 271 studies initially identified, 5 studies comprising 670 patients were included in the final analysis. The prevalence of transthyretin amyloidosis was 11%. Patients with transthyretin amyloid cardiomyopathy were more likely to be males (RR 1.38; 95% CI 1.09 to 1.75; P<0.01; I2=37%), and more likely to have low voltage criteria on ECG (RR 2.98; 95% CI 1.03 to 8.58; P=0.04; I2=75%) compared with transthyretin negative group. They also have higher SMD of age (SMD 0.73; 95% CI 0.48 to 0.97; P<0.01; I2=0%), and NT-proBNP (SMD 0.48; 95% CI 0.02 to 0.93; P=0.04; I2=36%) compared with transthyretin negative group. On reported echocardiogram, they have higher SMD of mass index (SMD 0.77; 95% CI 0.27 to 1.27; P<0.01; I2=65%), posterior wall thickness (SMD 0.92; 95% CI 0.62 to 1.21; P<0.01; I2=0%), and septal wall thickness (SMD 1.49; 95% CI 0.65 to 2.32; P<0.01; I2=87%) compared with transthyretin negative group.ConclusionTransthyretin amyloidosis affects 11% of HFpEF patients. Therefore, screening HFpEF patients at risk of cardiac amyloidosis is warranted.
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