Subject(s)
Amyloidosis , Aortic Valve Stenosis , Heart Failure , Heart Valve Prosthesis , Transcatheter Aortic Valve Replacement , Humans , Transcatheter Aortic Valve Replacement/adverse effects , Prealbumin/genetics , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/surgery , Amyloidosis/complications , Amyloidosis/diagnosis , Electrocardiography , Treatment Outcome , Risk FactorsABSTRACT
AIMS: The role of necroptosis in dilated cardiomyopathy (DCM) remains unclear. Here, we examined whether phosphorylation of mixed lineage kinase domain-like protein (MLKL), an indispensable event for execution of necroptosis, is associated with the progression of DCM. METHODS AND RESULTS: Patients with DCM (n = 56, 56 ± 15 years of age; 68% male) were enrolled for immunohistochemical analyses of biopsies. Adverse events were defined as a composite of death or admission for heart failure or ventricular arrhythmia. Compared with the normal myocardium, increased signals of MLKL phosphorylation were detected in the nuclei, cytoplasm, and intercalated discs of cardiomyocytes in biopsy samples from DCM patients. The phosphorylated MLKL (p-MLKL) signal was increased in enlarged nuclei or nuclei with bizarre shapes in hypertrophied cardiomyocytes. Nuclear p-MLKL level was correlated negatively with septal peak myocardial velocity during early diastole (r = -0.327, P = 0.019) and was correlated positively with tricuspid regurgitation pressure gradient (r = 0.339, P = 0.023), while p-MLKL level in intercalated discs was negatively correlated with mean left ventricular wall thickness (r = -0.360, P = 0.014). During a median follow-up period of 3.5 years, 10 patients (18%) had adverse events. To examine the difference in event rates according to p-MLKL expression levels, patients were divided into two groups by using the median value of nuclear p-MLKL or intercalated disc p-MLKL. A group with high nuclear p-MLKL level (H-nucMLKL group) had a higher adverse event rate than did a group with low nuclear p-MLKL level (L-nucMLKL group) (32% vs. 4%, P = 0.012), and Kaplan-Meier survival curves showed that the adverse event-free survival rate was lower in the H-nucMLKL group than in the L-nucMLKL group (P = 0.019 by the log-rank test). Such differences were not detected between groups divided by a median value of intercalated disc p-MLKL. In δ-sarcoglycan-deficient (Sgcd-/- ) mice, a model of DCM, total p-MLKL and nuclear p-MLKL levels were higher than in wild-type mice. CONCLUSION: The results suggest that increased localization of nuclear p-MLKL in cardiomyocytes is associated with left ventricular diastolic dysfunction and future adverse events in DCM.
Subject(s)
Cardiomyopathy, Dilated , Heart Failure , Ventricular Dysfunction, Left , Animals , Female , Male , Mice , Heart Ventricles , Myocardium/pathology , Protein Kinases , Middle Aged , AgedABSTRACT
Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.
Subject(s)
Amyloid Neuropathies, Familial/diagnosis , Amyloid Neuropathies, Familial/genetics , Heart Diseases/diagnosis , Heart Diseases/genetics , Mutation/genetics , Prealbumin/genetics , Adult , Early Diagnosis , Female , Humans , Male , Middle AgedABSTRACT
A 56-year-old postmenopausal woman with out-of-hospital cardiac arrest caused by acute myocardial infraction was successfully resuscitated by intensive treatments and recovered without any neurological disability. She was diagnosed as having familial hypercholesterolemia (FH) based on a markedly elevated low-density lipoprotein cholesterol (LDL-C) level and family history of premature coronary artery disease. Genetic testing in her family members showed that a variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene (c.2004Cï¼A, p.S668R), which had been previously reported as having uncertain significance, was associated with FH, indicating that the variant is a potential candidate for the FH phenotype. Next-generation sequencing analysis for the proband also showed that there was a heterozygous mutation of the ATP-binding cassette sub-family G member 5 ( ABCG5) gene (c.1166Gï¼A, R389H), which has been reported to increase LDL-C level and the risk of cardiovascular disease. She was also diagnosed as having type 1 CD36 deficiency based on a lack of myocardial uptake of 123I-labeled 15-(p-iodophenyl)-3-R,S-methyl-pentadecanoic acid in scintigraphy and the absence of CD36 antigen in both monocytes and platelets in flow cytometry. She had a homozygous mutation of the CD36 gene (c.1126-5_1127delTTTAGAT), which occurs in a canonical splice site (acceptor) and is predicted to disrupt or distort the normal gene product. To our knowledge, this is the first report of a heterozygous FH phenotype caused by possibly oligogenic variants of the PCSK9 and ABCG5 genes complicated with type I CD36 deficiency caused by a novel homozygous mutation. Both FH phenotype and CD36 deficiency might have caused extensive atherosclerosis, leading to acute myocardial infarction in the present case.
Subject(s)
Hyperlipoproteinemia Type II , Myocardial Infarction , ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , Blood Platelet Disorders , Female , Genetic Diseases, Inborn , Humans , Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/genetics , Lipoproteins/genetics , Middle Aged , Myocardial Infarction/complications , Myocardial Infarction/genetics , Phenotype , Proprotein Convertase 9/genetics , Receptors, LDL/geneticsABSTRACT
Sarcoidosis is a systemic inflammatory disease characterized by the formation of noncaseating epithelioid granulomas. Multiple organs, including the lung, eyes, and skin, are involved in this disorder, and cardiac involvement is a major cause of morbidity and mortality in patients with this disorder. We present the case history of a 22-year-old man with neurosarcoidosis complicated by abrupt onset of cardiac tamponade. Cardiac tamponade is a rare but potentially fatal manifestation of sarcoidosis, which is treatable with glucocorticoid therapy. Including the present case, previously reported cases of sarcoidosis with cardiac tamponade are reviewed to delineate its clinical characteristics.
Subject(s)
Cardiac Tamponade/etiology , Central Nervous System Diseases/complications , Pericardial Effusion/surgery , Pericardiocentesis/methods , Sarcoidosis/complications , Bundle-Branch Block/diagnosis , Bundle-Branch Block/etiology , Cardiac Tamponade/diagnosis , Central Nervous System Diseases/drug therapy , Central Nervous System Diseases/pathology , Dyspnea/diagnosis , Dyspnea/etiology , Electrocardiography/methods , Humans , Male , Mobility Limitation , Muscular Diseases/etiology , Pericardial Effusion/diagnosis , Pericardial Effusion/etiology , Prednisolone/administration & dosage , Prednisolone/therapeutic use , Sarcoidosis/drug therapy , Sarcoidosis/pathology , Steroids/administration & dosage , Steroids/therapeutic use , Tomography, X-Ray Computed/methods , Treatment Outcome , Young AdultABSTRACT
Nonalcoholic fatty liver disease has been reported to be potentially linked to cardiovascular disease. Fatty liver index (FLI) is a noninvasive and simple predictor of nonalcoholic fatty liver disease. However, little is known about the relationship between FLI and cardiac function, especially in a general population. We investigated the relationships of FLI with echocardiographic parameters in 185 subjects (men/women: 79/106) of the Tanno-Sobetsu Study, a population-based cohort, who were not being treated with any medication and who underwent echocardiography. FLI was negatively correlated with high-density lipoprotein cholesterol and peak myocardial velocity during early diastole (e'; r = -0.342, p <0.001), an index of left ventricular (LV) diastolic function, and ratio of peak mitral velocities during early and late diastole (E/A) and was positively correlated with age, systolic and diastolic blood pressures, creatinine, uric acid, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, ratio of mitral to myocardial early diastolic peak velocity (E/e'), left atrial volume index and LV mass index. No significant correlation was found between FLI and LV ejection fraction. Stepwise multivariable regression analysis showed that FLI was independently and negatively associated with e' after adjustment of age, gender, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, and high-sensitivity C-reactive protein. Conversely, e' was independently and negatively associated with FLI after adjustment of age, gender, systolic blood pressure, and LV ejection fraction. In conclusion, elevated FLI is independently associated with LV diastolic dysfunction in a general population without medication. FLI would be a novel marker of LV diastolic dysfunction as an early sign of myocardial injury.
Subject(s)
Fatty Liver/diagnosis , Ventricular Dysfunction, Left/diagnosis , Aged , Blood Flow Velocity , Body Mass Index , Cohort Studies , Echocardiography , Fatty Liver/blood , Fatty Liver/physiopathology , Female , Humans , Male , Middle Aged , Triglycerides/blood , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/physiopathology , Waist Circumference , gamma-Glutamyltransferase/bloodABSTRACT
BACKGROUND: There are a lot of reports of the renal failure and heart failure due to coarctation of the aorta. However, there are no case reports in which revascularization dramatically improved left ventricular function in patients with progressive decline in left ventricular function. Herein, we present a rare case in which the left ventricular function was dramatically improved by surgical treatment for progressive left ventricular dysfunction due to atypical coarctation of the aorta. CASE PRESENTATION: A 58-year-old man underwent left axillary artery-bilateral femoral artery bypass at another hospital for atypical coarctation of the aorta due to Takayasu's arteritis. Approximately 10 years later, he was re-hospitalized for heart failure, and the left ventricular ejection fraction gradually decreased to 28%. Computed tomography showed severe calcification and stenosis at the same site from the peripheral thoracic descending aorta to the lower abdominal aorta of the renal artery, and aortography showed delayed bilateral renal artery blood flow. An increase in plasma renin activity was also observed. Despite the administration of multiple antihypertensive drugs, blood pressure control was insufficient. We decided to perform surgical treatment to improve progressive cardiac dysfunction due to increased afterload and activated plasma renin activity. Descending thoracic aorta-abdominal aorta bypass and revascularization of the bilateral renal arteries via the great saphenous vein grafts were performed. Postoperative blood pressure control was improved, and the dose of antihypertensive drugs could be reduced. Plasma renin activity decreased, and transthoracic echocardiography 1.5 years later showed an improvement in contractility with a left ventricular ejection fraction of 58%. CONCLUSION: In atypical coarctation of the aorta in patients with decreased bilateral renal blood flow, heart failure due to renal hypertension, and progressive decrease in left ventricular contractility, descending thoracic aorta-abdominal aortic bypass and bilateral renal artery recirculation can be extremely effective.
Subject(s)
Aorta, Abdominal , Aortic Coarctation , Heart Failure , Takayasu Arteritis , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Aorta, Abdominal/diagnostic imaging , Aorta, Abdominal/surgery , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aortic Coarctation/complications , Aortic Coarctation/diagnostic imaging , Aortic Coarctation/surgery , Heart Failure/etiology , Heart Failure/surgery , Humans , Male , Middle Aged , Positron Emission Tomography Computed Tomography , Renal Circulation , Stroke Volume , Takayasu Arteritis/complications , Takayasu Arteritis/surgery , Ventricular Function, LeftABSTRACT
Background: Takayasu arteritis (TA) is a large vessel vasculitis of unknown etiology characterized by chronic inflammatory changes of the aorta and its major branches. Complications such as anastomotic aneurysm and valve detachment have been reported in active TA patients who received aortic valve replacement and graft replacement of aorta. Case Summary:A 61-year-old man with a history of emergency aortic valve replacement and patch closure of the noncoronary sinus of Valsalva due to acute heart failure induced by acute aortic regurgitation and ruptured sinus of Valsalva 4 years ago was referred for exertional dyspnea. Dilatation of the sinus of Valsalva together with protrusion of the right sinus of Valsalva and ostial stenosis of the left coronary artery were newly found by computed tomography (CT). A Bentall operation with concomitant coronary artery bypass grafting was successfully performed with a composite graft. Diagnosis of TA was made on the basis of histological analyses of the resected sinus of Valsalva, though other arterial manifestations were not detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography. Three months later, a follow-up study revealed left coronary ostial pseudoaneurysm at the anastomotic site together with strong 18F-FDG uptake, leading to commencement of steroid therapy. Eight months later, disappearance of left coronary ostial pseudoaneurysm was found by a follow-up CT scan. Conclusion: This is a rare TA case in whom spontaneous resolution of coronary anastomotic aneurysm by steroid therapy was found without reconstructive surgery.
ABSTRACT
BACKGROUND: The 6-min walk test (6MWT) provides prognostic information for patients with interstitial lung disease (ILD). Parameter determined by Doppler echocardiography after the 6MWT (6 MW stress echocardiography) is shown to be a predictor of future development of pulmonary hypertension in patients with connective tissue disease. However, the clinical utility of 6 MW stress echocardiography in predicting cardiopulmonary events in patients with ILD remains unknown. We examined whether parameters determined by 6 MW stress echocardiography independent predictors of adverse events in patients with ILD. METHODS: Echocardiographic examinations were performed in 68 consecutively enrolled patients with ILD (age, 65 ± 10 years, 65% men). A pressure gradient of tricuspid regurgitation (TRPG) and pulmonary vascular resistance (PVRecho) calculated using the following formula [PVRecho = (peak velocity of TR × 10/time-velocity integral of right ventricular outflow (RVOT-VTI)) + 0.16] were measured at baseline and at post 6MWT. Data for parameters of pulmonary functional tests and for 6MWT were collected. RESULTS: During a mean follow-up period of 22 ± 12 months, 22 patients experienced cardiopulmonary events. In univariate analysis, %VC, TRPG, PVRecho, TRPG post 6MWT, and PVRecho post 6MWT were significantly associated with cardiopulmonary events. Multivariate analysis using the Cox proportional hazards model indicated that %VC [hazard ratio (HR): 0.97, p = 0.009] and PVRecho post 6MWT (HR: 1.77, p = 0.004) were independent predictors of cardiopulmonary events in patients with ILD. CONCLUSIONS: In addition to parameters of pulmonary function tests, increased PVRecho post 6MWT is a significant predictor of cardiopulmonary events in patients with ILD. A 6 MW stress echocardiography is useful in assessing the risk of adverse events in patients with ILD.
Subject(s)
Hypertension, Pulmonary , Lung Diseases, Interstitial , Aged , Echocardiography, Stress , Female , Humans , Hypertension, Pulmonary/diagnostic imaging , Lung Diseases, Interstitial/complications , Lung Diseases, Interstitial/diagnostic imaging , Male , Middle Aged , Prognosis , WalkingSubject(s)
Cardiomyopathies/etiology , Heart Failure/etiology , Immunoglobulin Light-chain Amyloidosis/etiology , Immunoglobulin kappa-Chains/analysis , Multiple Myeloma/complications , Myocardium/immunology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers/analysis , Bortezomib/therapeutic use , Cardiomyopathies/diagnosis , Cardiomyopathies/immunology , Cardiomyopathies/therapy , Dexamethasone , Female , Heart Failure/diagnosis , Heart Failure/therapy , Humans , Immunoglobulin Light-chain Amyloidosis/diagnosis , Immunoglobulin Light-chain Amyloidosis/immunology , Immunoglobulin Light-chain Amyloidosis/therapy , Middle Aged , Multiple Myeloma/diagnosis , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Myocardium/pathology , Treatment OutcomeABSTRACT
A 14-year-old girl with cardiopulmonary arrest was referred to our hospital. She had received an injection of inactivated influenza vaccine 7 days before the referral. Her cardiac rhythm was pulseless wide QRS tachycardia, and mechanical circulatory support was immediately begun. Results of endomyocardial biopsy showed that there was massive infiltration of CD3- and CD68-positive cells and various degrees of cardiomyocyte necrosis in all of 3 endomyocardial specimens, whereas infiltration of eosinophils or giant cells was not observed. A histologic diagnosis of lymphocytic myocarditis was made. Acute myocarditis is a rare but potentially fatal complication of the influenza vaccination.
Subject(s)
Hemodynamics/physiology , Influenza Vaccines/adverse effects , Influenza, Human/immunology , Myocarditis/physiopathology , Shock, Cardiogenic/etiology , Vaccination/adverse effects , Acute Disease , Adolescent , Female , Humans , Myocarditis/complications , Shock, Cardiogenic/physiopathologyABSTRACT
Bundle Sheath Defective 2, BSD2, is a stroma-targeted protein initially identified as a factor required for the biogenesis of ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO) in maize. Plants and algae universally have a homologous gene for BSD2 and its deficiency causes a RuBisCO-less phenotype. As RuBisCO can be the rate-limiting step in CO2 assimilation, the overexpression of BSD2 might improve photosynthesis and productivity through the accumulation of RuBisCO. To examine this hypothesis, we produced BSD2 overexpression lines in Arabidopsis. Compared with wild type, the BSD2 overexpression lines BSD2ox-2 and BSD2ox-3 expressed 4.8-fold and 8.8-fold higher BSD2 mRNA, respectively, whereas the empty-vector (EV) harbouring plants had a comparable expression level. The overexpression lines showed a significantly higher CO2 assimilation rate per available CO2 and productivity than EV plants. The maximum carboxylation rate per total catalytic site was accelerated in the overexpression lines, while the number of total catalytic sites and RuBisCO content were unaffected. We then isolated recombinant BSD2 (rBSD2) from E. coli and found that rBSD2 reduces disulfide bonds using reductants present in vivo, for example glutathione, and that rBSD2 has the ability to reactivate RuBisCO that has been inactivated by oxidants. Furthermore, 15% of RuBisCO freshly isolated from leaves of EV was oxidatively inactivated, as compared with 0% in BSD2-overexpression lines, suggesting that the overexpression of BSD2 maintains RuBisCO to be in the reduced active form in vivo. Our results demonstrated that the overexpression of BSD2 improves photosynthetic efficiency in Arabidopsis and we conclude that it is involved in mediating RuBisCO activation.
Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Photosynthesis/genetics , Arabidopsis/growth & development , Arabidopsis/metabolism , Arabidopsis/physiology , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/physiology , Escherichia coli , Gene Expression Regulation, Plant , Recombinant Proteins , Ribulose-Bisphosphate Carboxylase/metabolismABSTRACT
Although the benefit of updated therapeutic regimens, including bortezomib, on the survival of immunoglobulin light chain (AL) amyloidosis patients with heart failure (HF) has been reported, predictors of mortality in the patients treated with the updated therapy remain unclear. We retrospectively enrolled AL amyloidosis patients who had severe HF at the time of diagnosis and received the updated therapy, including bortezomib (n = 19, 61 ± 6 years old, 68% male). Severe HF was defined as the presence of both NYHA functional class III or IV and BNP > 200 pg/ml or NT-pro-BNP > 900 pg/ml. One-year mortality rate during follow-up after commencement of the treatment was 37%. Left ventricular morphological parameters and indexes of left ventricular diastolic function on admission were similar in the non-survivors and survivors. However, non-survivors had higher incidences of atrial fibrillation and ventricular tachycardia, higher serum total bilirubin levels (1.34 ± 0.55 vs. 0.61 ± 0.29 mg/dl), higher right atrial volume index (RAVI 49.7 ± 29.9 vs. 27.3 ± 6.8 ml/m2), lower tricuspid annular peak velocities during systole (RVs' 8.0 ± 1.8 vs. 11.6 ± 3.7 cm/sec) and late diastole (RVa' 3.4 ± 0.9 vs. 11.4 ± 5.3 cm/sec), and larger inferior vena cava dimension (22.7 ± 6.4 vs. 16.3 ± 4.9 mm) than those in survivors. Kaplan-Meier curve analyses showed that larger RAVI and lower RVs' and RVa', but not left ventricular systolic/diastolic dysfunction, predicted higher mortality during 1-year follow-up. The present results suggest that the presence of right-sided heart abnormality on admission is associated with high 1-year mortality in AL amyloidosis patients with severe HF under the updated therapeutic regimens.
Subject(s)
Heart Failure/diagnosis , Heart Failure/mortality , Immunoglobulin Light-chain Amyloidosis/complications , Ventricular Dysfunction, Right/physiopathology , Aged , Atrial Fibrillation/etiology , Bilirubin/blood , Bortezomib/therapeutic use , Echocardiography , Electrocardiography , Female , Heart Failure/physiopathology , Heart Failure/therapy , Humans , Immunoglobulin Light-chain Amyloidosis/physiopathology , Japan , Kaplan-Meier Estimate , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Prognosis , Regression Analysis , Retrospective Studies , Stroke Volume , Ventricular Function, LeftSubject(s)
Heart Neoplasms/chemically induced , Lymphoma/chemically induced , Methotrexate/adverse effects , Rheumatic Fever/drug therapy , Aged, 80 and over , Antirheumatic Agents/adverse effects , Biopsy , Diagnosis, Differential , Female , Heart Atria , Heart Neoplasms/diagnosis , Heart Ventricles , Humans , Lymphoma/diagnosis , Magnetic Resonance Imaging, Cine/methods , Myocardium/pathology , Tomography, X-Ray Computed/methodsABSTRACT
Takayasu arteritis (TA) is a large vessel vasculitis of unknown aetiology characterized by chronic inflammatory changes of the aorta and its major branches. We report the active TA case who had severe heart failure due to acute myocardial infarction and aortic regurgitation. Bentall procedure was successfully performed, but he had severely depressed left ventricular function and muscle wasting together with vascular inflammation. The treatment with tocilizumab, an interleukin-6 receptor monoclonal antibody, in addition to prednisolone and standard heart failure therapy led to prompt remission of TA activity and improvement of left ventricular function and muscle wasting. Taken together with possible involvement of interleukin-6 in the pathogenesis of heart failure and muscle wasting, inhibition of interleukin-6 receptor signalling by tocilizumab may be a safe and reasonable approach in the treatment of active TA with heart failure and muscle wasting.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Takayasu Arteritis/drug therapy , Aged , Antibodies, Monoclonal, Humanized/adverse effects , Heart Failure/complications , Humans , Male , Muscular Diseases/complications , Severity of Illness Index , Takayasu Arteritis/complications , Treatment OutcomeABSTRACT
The etiology of peripartum cardiomyopathy (PPCM) remains unestablished, but the involvement of abnormal autoimmunity has been suggested. We report a case of PPCM that was triggered by postpartum thyroiditis. Despite the presence of myocardial damage indicated by cardiac magnetic resonance imaging, the patient's cardiac function completely recovered with the addition of bromocriptine to standard therapies. We discuss the role of thyroid hormones in the development of PPCM through aggravation of a prolactin-dependent antiangiogenic effect, and we argue that more attention should be paid to postpartum thyroiditis as a novel risk factor for PPCM.
Subject(s)
Autoimmunity , Cardiomyopathies/complications , Heart Failure/etiology , Peripartum Period , Postpartum Period , Pregnancy Complications, Cardiovascular , Thyroiditis/complications , Adult , Cardiomyopathies/diagnosis , Cardiomyopathies/immunology , Echocardiography , Electrocardiography , Female , Heart Failure/diagnosis , Heart Failure/immunology , Humans , Magnetic Resonance Imaging, Cine , Pregnancy , Radiography, Thoracic , Thyroid Hormones/blood , Thyroiditis/blood , Thyroiditis/immunologyABSTRACT
Which combination of clinical parameters improves the prediction of prognosis in patients with pulmonary arterial hypertension (PAH) remains unclear. We examined whether combined assessment of pulmonary vascular resistance and right ventricular function by echocardiography is useful for classifying risks in PAH. In 41 consecutive patients with PAH (mean age of 48.9 ± 17.3 years, 31 females), a 6-min walk test, pulmonary function test, and echocardiography were performed at baseline and during PAH-specific therapies. The study endpoint was defined as a composite of cardiovascular death and hospitalization for PAH and/or right ventricular failure. During a follow-up period of 9.2 ± 8.7 months, 18 patients reached the endpoint. Multivariate regression analysis showed that the ratio of tricuspid regurgitation pressure gradient to the time-velocity integral of the right ventricular outflow tract (TRPG/TVI) and tricuspid annular plane systolic excursion (TAPSE) during PAH-specific treatment were independent prognostic predictors of the endpoint. Using cutoff values indicated by receiver operating characteristic analysis, the patients were divided into four subsets. Multivariate analyses by Cox's proportional hazards model adjusted for age, sex and body mass index indicated that subset 4 (TRPG/TVI ≥ 3.89 and TAPSE ≤ 18.9 mm) had a significantly higher event risk than did subset 1 (TRPG/TVI < 3.89 and TAPSE > 18.9 mm): HR = 25.49, 95% CI 4.70-476.97, p < 0.0001. Combined assessment of TRPG/TVI and TAPSE during adequate PAH-specific therapies enables classification of risks for death and/or progressive right heart failure in PAH.
Subject(s)
Echocardiography/methods , Pulmonary Arterial Hypertension/epidemiology , Pulmonary Artery/physiopathology , Pulmonary Wedge Pressure/physiology , Risk Assessment , Vascular Resistance/physiology , Female , Follow-Up Studies , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Prognosis , Pulmonary Arterial Hypertension/classification , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Artery/diagnostic imaging , ROC Curve , Retrospective Studies , Risk Factors , Systole , Ventricular Function, Left/physiology , Ventricular Function, Right/physiologyABSTRACT
BACKGROUND: Fatty acid-binding protein 4 (FABP4), which is expressed in both adipocytes and macrophages, is secreted from the cells and acts as an adipokine. An elevated circulating FABP4 level is associated with insulin resistance and atherosclerosis.MethodsâandâResults:We investigated the causative association between FABP4 level and progression of atherosclerosis in subjects of the Tanno-Sobetsu Study, a population-based cohort. In 281 subjects without medication (male/female: 109/172) in the year 2010 or 2013, the carotid intima-media thickness (CIMT) assessed using carotid ultrasonography was significantly correlated with age, adiposity, blood pressure, renal dysfunction and levels of cholesterol, triglycerides, fasting glucose, HbA1c and FABP4 (r=0.331, P<0.001). Multiple regression analysis demonstrated that age, sex and FABP4 concentration were independent predictors of CIMT. A total of 78 (male/female: 29/49) of the 156 subjects in 2010 underwent carotid ultrasonography again in 2013. The change in CIMT each year during that 3-year period (mean±SD: 3.8±22.3 µm/year) was positively correlated with basal levels of high-sensitivity C-reactive protein (hsCRP) (r=0.231, P=0.046) and FABP4 (r=0.267, P=0.018) in 2010. After adjustment for age, sex and hsCRP level, the basal FABP4 level was independently associated with the change in CIMT per year. CONCLUSIONS: FABP4 concentration is an independent predictor of the progression of carotid atherosclerosis.
Subject(s)
Carotid Artery Diseases/epidemiology , Disease Progression , Fatty Acid-Binding Proteins/blood , Adipokines/blood , Aged , Atherosclerosis/blood , Carotid Artery Diseases/diagnosis , Carotid Artery Diseases/pathology , Carotid Intima-Media Thickness , Female , Humans , Insulin/blood , Male , Middle Aged , PrognosisABSTRACT
BACKGROUND: Sleep-disordered breathing (SDB) is highly prevalent in patients with diabetes mellitus (DM) and heart failure (HF) and contributes to poor cardiovascular outcomes. Enlarged glycemic variability (GV) is a risk factor of cardiac events independently of average blood glucose level, but the influence of SDB on GV is uncertain. In this study, we examined whether the impact of SDB on GV is modified by the presence of DM with or without HF. METHODS AND RESULTS: Two hundred three patients (67.5±14.1 [SD] years old, 132 males) who were admitted to our institute for examination or treatment of DM and/or HF underwent continuous glucose monitoring and polysomnography. Both HbA1c (8.0±2.0 vs. 5.7±0.4%) and mean amplitude of glycemic excursion (MAGE, median: 95.5 vs. 63.5 mg/dl) were significantly higher in a DM group (n = 100) than in a non-DM group (n = 103), but apnea-hypopnea index (AHI: 29.0±22.7 vs. 29.3±21.5) was similar in the two groups. AHI was correlated with log MAGE in the non-DM group but not in the DM group, and multivariate regression analysis revealed that AHI was an independent variable for log MAGE in the non-DM group but not in the DM group. We then divided the non-DM patients into two subgroups according to BNP level (100 pg/ml). AHI was positively correlated with log MAGE (r = 0.74, p<0.001) in the non-DM low-BNP subgroup, but such a correlation was not found in the non-DM high-BNP subgroup. Continuous positive airway pressure (CPAP) reduced MAGE from 75.3 to 53.0 mg/dl in the non-DM group but did not reduce MAGE in the DM group. CONCLUSION: Severity of SDB was associated with higher GV, but DM as well as HF diminished the contribution of SDB to GV. Treatment with CPAP was effective for reduction of GV only in patients without DM.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/complications , Sleep Apnea Syndromes/complications , Aged , Blood Glucose Self-Monitoring , Continuous Positive Airway Pressure , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Male , Multivariate Analysis , Natriuretic Peptide, Brain/metabolism , Regression Analysis , Respiration , Sleep , Sleep Apnea Syndromes/physiopathology , Sleep Apnea Syndromes/therapyABSTRACT
A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML. In January 2014, he was admitted to the Dept. of Cardiovascular, Renal and Metabolic Medicine at our hospital because of heart failure. After examinations of cardiac function, he was diagnosed with constrictive pericarditis. Therefore, pericardiolysis was performed by the Dept. of Cardiovascular Surgery at our hospital. Pathologic findings showed hyaline-like fibrous tissue proliferation in the pericardium, which was diagnosed as fibrous pericarditis induced by nilotinib. We report a case of chronic myelogenous leukemia that developed fibrous pericarditis owing to nilotinib use.